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COVID-19: To have and to hold ... in quarantine
Tips for marriage survival during a pandemic
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
Tips for marriage survival during a pandemic
Tips for marriage survival during a pandemic
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
The Diagnosis and Management of Cutaneous T-Cell Lymphomas (FULL)
John Zic, MD. Let’s start by defining cutaneous T-cell lymphomas (CTCLs) and how they differ from other non-Hodgkin lymphomas. We also should discuss classification, which can be very confusing and epidemiology as it relates to the veteran population. Then I think we should dive into challenges with diagnosis and when should a VA or any provider consider mycosis fungoides (MF) and Sézary syndrome—the 2 most common variants of CTCLs.
I like to define the primary CTCLs as malignancies of the T-cell where the primary organ of involvement is the skin. However, this disease can spread to lymph nodes and visceral organs and the blood compartment in more advanced patients. Alejandro, could you provide some highlights about how CTCLs are classified?
Alejandro Ariel Gru, MD. Lymphomas are divided in the general hematology/oncology practice as Hodgkin and non-Hodgkin lymphomas. Traditionally all lymphomas that occur on the skin are non-Hodgkin lymphoma subtypes. That has specific connotations in terms of diagnosis, prognosis, and therapy. Because the T cells are one of the main residents of the subtypes of lymphocytes you encounter on the skin, most lymphomas that occur on the skin are derived of T-cell origin. B-cell lymphomas, in general, tend to be relatively uncommon or more infrequent.
There are 3 main subtypes of CTCL that present on the skin.1 MF is, by far, the most common subtype of CTCL. The disease tends to present in patients who are usually aged > 60 years and is more frequent in white males. It’s a lymphoma that is particularly relevant to the veteran population. The second subtype has many similarities to MF but shows substantial peripheral blood involvement and is referred to as Sézary syndrome. The third group is encompassed under the term CD30-positive lymphoproliferative disorders. This group includes 2 main subtypes: primary cutaneous anaplastic large-cell lymphoma and lymphomatoid papulosis. Some cases of MF develop progression to what we call large cell transformation, which implies cytologic transformation to a more aggressive lymphoma.
There are other cutaneous lymphomas that are far less common. Some are indolent and others can be more aggressive, but they represent < 5% of all CTCL subtypes.
Lauren Pinter-Brown, MD. That was a great summary about these non-Hodgkin lymphomas. In the veteran population, it’s wise to remember that there are many kinds of non-Hodgkin lymphomas. Because of the action that they have seen, some people, such as Vietnam veterans, might be more susceptible to non-Hodgkin lymphomas than others.
John Zic. That’s a good point because certainly non-Hodgkin lymphomas are listed as one of the potential disease associations with exposure to Agent Orange.
I’d like to move on to epidemiology and the incidence of MF and Sézary syndrome. An article that came out of Emory University in 2013 is one of the more up-to-date articles to examine the incidence and survival patterns of CTCL.2 The authors looked at patients from 2005 to 2008 and identified 2,273 patients in the Surveillance, Epidemiology, and End Results registry. They estimated that the incidence of MF in the US population is about 5.5 per 1,000,000 per year, which certainly makes it a rare disease. The incidence of Sézary syndrome was 0.1 per 1,000,000 per year, which comes out to about 1 per 10 million per year.
However, the MF incidence needs to be contrasted to the estimated incidence in the veteran population. In 2016, Larisa Geskin and colleagues from Columbia University and the Bronx US Department of Veterans Affairs (VA) Medical Center examined the VA database of patients with diagnoses of MF and Sézary syndrome.3 They combined them, but I have a feeling that the amount of Sézary syndrome patients was much less than those with MF. They estimated an incidence per million of 62 to 79 cases per 1,000,000 per year. The conclusion of Dr. Geskin’s study stated that the incidence of CTCL in the veteran population appears to be anywhere from 6 to 8 times higher. But if we use the most recent US incidence rates, it’s more than 10 times higher.
Those of you who have worked with veterans, either at the VA or in your private practice, do you have any ideas about why that might be?
Lauren Pinter-Brown. As you previously discussed, this is an illness of older people, and Vietnam veterans now are in their 60s and 70s. They may account for a lot of these diagnoses.
John Zic. That’s a good point. There’s quite a bit of talk about exposure to Agent Orange. But honestly, we really don’t know the cause of any of the CTCLs. We have not been able to identify a single cause. There are some risk factors. A 2014 article from the Journal of the National Cancer Institute looked at 324 cases of CTCL and compared it with 17,000 controls.4 They showed some interesting risk factors, such as body mass index (BMI) > 30 and smoking > 40 years. Similar to previous European studies, they showed that occupations like being a farmer, a painter, a woodworker, or a carpenter may carry additional risk.I wonder whether or not veterans were more likely to have some of these risk factors that this epidemiologic study picked up in addition to exposures that they may have encountered during their active-duty service. Interestingly, a decreased risk factor for developing MF was moderate physical activity. Clearly though, there are a large number of patients with CTCL in the veteran population.
I’d like to turn now to some of the challenges with diagnosis. Marianne, could you share some of your experience with early-stage disease and about how long it took them to be diagnosed?
Marianne Tawa, RN, MSN, ANP. Speaking specifically about early-stage disease, patients often share a history of waxing and waning rash that may not be particularly itchy. Confounding the picture, the distribution of early patch or plaque stage CTCL rash frequently occurs in covered areas. Many patients miss out on complete skin examinations by providers, thus early-stage CTCL may not be appreciated in a timely manner.
In certain scenarios, it may take upward of 5 to 7 years before the CTCL diagnosis is rendered. This is not because the patient delayed care. Nor is it because a skin biopsy was not performed. The progression of the disease and meeting the classic features of histology under the microscope can require clinical observation over time and repeated skin biopsies. We recommend patients refrain from topical steroid applications for 2 to 4 weeks prior to skin biopsy if we have a strong suspicion of CTCL. Many patients will report having a chronic eczematous process. Some patients may have a history of parapsoriasis, and they’re on the continuum for CTCL. That’s a common story for CTCL patients.
John Zic. What is the role of a skin biopsy in the diagnosis of CTCL? We see many patients who have had multiple skin biopsies who often wonder whether or not the diagnosis was missed by either the clinician or the pathologist.
Alejandro Ariel Gru. That is a great area of challenge in terms of pathologic diagnosis of early MF. A study led by Julia Scarisbrick, from an international registry data (PROCLIPI) on the early stages of the disease, showed a median delay of diagnosis of early MF of approximately 36 months.5 For all physicians involved in the diagnosis and care of patients with MF, the delay is probably significantly higher than that. We’ve seen patients who have lived without a diagnosis for a period of 10 or sometimes 15 years. That suggests that many cases are behaving in an indolent fashion, and patients are not progressing through the ‘natural’ stages of the disease and remain at the early stage. There also is the potential that other chronic inflammatory conditions, particularly psoriasis or parapsoriasis, can be confused with this entity. The diagnosis of certain types of parapsoriasis, can belong to the same spectrum of MF and can be treated in a similar way than patients with early stage MF are, such as phototherapy or methotrexate.
The diagnosis of MF relies on a combination of clinical, pathologic, and immunophenotypic findings where it is desired or preferred that at least 2 biopsies are done from different sides of the body. In addition to having a good clinical history that supports the diagnosis, a history of patches, plaques, and sometimes tumors in advanced stages in particular locations that are covered from the light (eg, trunk, buttocks, upper thighs, etc) combined with specific histopathologic criteria are capital to establish an accurate diagnosis.
In the biopsies, we look particularly for a lymphoid infiltrate that shows extension to the epidermis. We use the term epidermotropism to imply that these abnormal or neoplastic lymphocytes extend into the epidermis. They are also cytologically atypical. We see variations in the nucleus. In the size, we see a different character of the chromatin where they can be hyperchromatic. We also look for immunophenotypic aberrations, and particularly we analyze for patterns of expression of T-cell markers. Most cases of MF belong to a subset of T cells that are called CD4-positive or T-helper cells. We look for a patterned ratio of the CD4 and CD8 between the epidermis and an aberrant loss of the CD7 T-cell marker. Once we establish that we can see significant loss of these markers, we can tell where there is something wrong with that T-cell population, and likely belong to a neoplastic category.
In addition, we also rely on the molecular evaluation and search of a clonal population of T cells, by means of a T-cell receptor gene rearrangement study. Ideally, we like to see the establishment of a single clone of T cells that is matched in different biopsy sites. Proving that the same clone is present in 2 separate biopsies in 2 separate sites is the gold standard for diagnosis.6
John Zic. To recap, a biopsy is indicated for patients who have patches or plaques (that are slightly raised above the skin) in sun-protected areas that are fixed; rather than completely go away in the summer and come back in the winter, they are fixed if they have been present > 6 to 12 months. Many of these patients are diagnosed with eczema, psoriasis, allergic contact dermatitis, and other skin diseases before the clinician starts to think about other diagnoses, such as CTCL.
I agree that I would not rule out the diagnosis with 1 biopsy that does not show classic histologic changes. Also, I think that it’s important to alert the pathologist that you’re considering a diagnosis of T-cell lymphoma, either MF or some of the other subtypes, because that will certainly alert them to look a little closer at the infiltrating cells and perhaps do some of the other testing that was mentioned. Once we establish the MF diagnosis, staging studies may be indicated.
Lauren Pinter-Brown. Early stage would be patients with patches or plaques. Stage IA would be < 10% body surface area, and stage IB would be > 10%. I don’t perform scans for early-stage patients, but I do a very thorough physical and perform blood tests. For patients that have more advanced disease, such as tumors, erythroderma, or Sézary syndrome, I would conduct the same thorough examination and blood tests and scan the patient either with a computed tomography (CT) or a positron emission tomography (PET)/CT to detect adenopathy. We have to recognize that most of the adenopathy that is detected in these patients is peripheral, and we can feel it on physical examination.
John Zic. Do you prefer one imaging modality over the other? CT scan with IV contrast vs PET/CT?
Lauren Pinter-Brown. I tend to use PET/CT because it illuminates extranodal sites as well. I have to admit that sometimes it’s a problem to get that approved with insurance.
John Zic. In the federal system, many PET/CT scans are performed at other facilities. That would be an extra step in getting approval.
You mentioned Sézary syndrome. We should consider a diagnosis of Sézary syndrome when you have a patient with erythroderma, which means that they have > 80% of the skin covered in redness and scaling.
Lauren Pinter-Brown. The first step is to do a complete blood count (CBC) and see if there’s a lymphocytosis. Sometimes that really isn’t very sensitive, so my go-to test is flow cytometry. We are looking for an abnormal population of cells that, unlike normal T cells, often lack certain T-cell antigens. The most common would be CD7. We can confirm that this is a clone by T-cell gene rearrangement, and often in Sézary we like to compare the gene rearrangement seen in blood with what might be seen in the skin biopsy to confirm that they’re the same clone.
John Zic. That’s an excellent point. I know there are specific criteria to meet significant blood involvement. That is a topic of conversation among CTCL experts and something that might be changing over the next few years. But I think as it stands right now, having a lymphocytosis or at least an elevated CD4 count along with having a clone in the blood matching the clone in the skin are the first 2 steps in assessing blood involvement. However, the flow cytometry is very important. Not all medical centers are going to do flow cytometry—looking specifically for a drop of the CD7 or CD26 antigen among the CD4 population. But that is one of the major criteria that we look for in those patients with suspected blood involvement.
Marianne Tawa. Additionally, we would advise obtaining flow cytometry on patients that look like they have a robust skin burden with lots of patches, plaques, or tumors. We also perform lactate dehydrogenase (LDH) with staging.
John Zic. What do you usually tell patients with early-stage disease, those that have patches and plaques?
Marianne Tawa. For patients with stage IA disease, we are very optimistic about their prospects. We explain that the likelihood that early-stage disease will progress to a more advanced stage or rare variant is unlikely. This is very much a chronic disease, and the goal is to manage appropriately, palliate symptoms, and preserve quality of life (QOL).
Lauren Pinter-Brown. I often refer to a landmark paper by Youn H. Kim and colleagues that shows us that patients with IA disease who are at least treated usually have a normal lifespan.7 I encourage patients by sharing that data with them.
John Zic. Sean Whittaker and colleagues in the United Kingdom identified 5 risk factors for early-stage patients that may put them at higher risk for progressing: aged > 60 years; having a variant called folliculotropic MF; having palpable lymph nodes even if they’re reactive on biopsy, having plaques, and male sex.8 For staging of lymph nodes, what’s your usual approach when you see a patient with palpable lymph nodes?
Lauren Pinter-Brown. Many patients, particularly those with advanced skin disease, may have palpable lymph nodes that are reacting to their skin disease and on pathology would be dermatopathic. That would not change my management. I pay attention to the quality of the lymph node—if it’s very firm, if it’s > 2 cm, if it is persistent—before I biopsy. These patients have a higher incidence of wound infection after excisional biopsy. If the patient has pathologic lymph node involvement and effacement of the node with malignant cells, I would change my management. I do need to know that sort of information.
John Zic. Alejandro, as a hematopathologist can you comment on the debate about whether or not we actually do need an excisional biopsy or whether or not we can get a core lymph node biopsy to give you all the information that you need to grade it?
Alejandro Ariel Gru. There are 2 main modalities of biopsies we typically see for lymph nodes for evaluation and staging for involvement of CTCL. One is the traditional excisional biopsy that for the most part requires surgery with general anesthesia and has all the major implications that that type of procedure has. Many centers are looking at less invasive types of procedures, and needle core biopsies have become one of the most common forms of biopsy for all lymphoma subtypes. Excisional biopsies have the advantage of being able to see the whole lymph node, so you can determine and evaluate the architecture very well. Whereas needle core biopsies typically use a small needle to obtain a small piece of the tissue.
The likelihood of a successful diagnosis and accurate staging was compared recently in the British Journal of Dermatology.9 They were able to perform accurate staging in needle core biopsies of patients with MF. However, this is still a matter of debate; many people feel they are more likely to get enough information from an excisional biopsy. As we know, excisional biopsies sometimes can be hard, particularly if the large lymph node is located in an area that is difficult to access, for example, a retroperitoneal lymph node.
There are many staging categories that are used in the pathologic evaluation of lymph node involvement. On one hand, we could see the so-called dermatopathic changes, which is a reactive form of lymphadenopathy that typically happens in patients who have skin rashes and where there is no evidence of direct involvement by the disease (although there are some patients who can have T-cell clones by molecular methods). The patients who have clonal T cells perhaps might not do as well as the ones who do not. On the other hand, we have patients for whom the whole architecture of the lymph node is effaced or replaced by neoplastic malignant cells. Those patients are probably going to need more aggressive forms of therapy.10
John Zic. The type of lymph node biopsy has been a hot topic. If patients have palpable lymph nodes in the cervical, axillary, and inguinal area, I don’t know if it’s a consensus, but the recommendation right now is to consider performing a lymph node biopsy of the cervical lymph nodes first, axillary second, and inguinal lymph nodes third. That might have to do with the complication rates for those different areas.
I’d like to switch to a discussion to more advanced disease. CTCL tumors are defined as a dome-shaped nodule > 1 cm. They don’t have to be very big before we label it a tumor, and the disease is considered more advanced. For patients with a few tumors, what does your prognosis discussion sound like?
Marianne Tawa. Certainly, the prognosis discussion can become slightly more complicated when you move into the realm of tumor-stage development. This is especially true if a CTCL patient has lived with and managed indolent patches or plaques for several years. We approach these patients with optimism and with the goal of managing their tumors, whether it be with a skin-directed option, such as localized radiation or a host of approved systemic therapies. Patients presenting with or developing tumor-stage disease over time will require additional staging workup compared with early-stage disease staging practice. Patients are counseled on imaging use in tumor-stage disease and why flow cytometry may be requested to rule in or rule out accompanying peripheral blood involvement. Patients are exposed to a myriad of pictures, stories, and survival statistics from Internet research. It becomes our task to inform them of their unique presentation and tailored treatment plan, which thankfully may produce more favorable responses than those presented online.
Lauren Pinter-Brown. One thing that we focus on is the idea that a statistic regarding prognosis isn’t predictive for an individual patient. When patients go online, we caution them that many of the statistics are really old. There’s been a lot of new therapies in the past 10 years. Just looking at my patients, my feeling is that their prognosis has continued to improve over the decades that I’ve been involved in this area.
We have to take the statistics with a grain of salt, though certainly someone that has Sézary syndrome or someone that has nodal involvement or tumors is not going to fare as well as the patients that we talked about with stage I disease. However, if we all continue to do our jobs and have more and more treatment options for patients, that’s certainly going to change over time as it has with other non-Hodgkin lymphomas.
John Zic. We’ve all treated advanced patients with disease and some, of course, have died of the disease. When patients die of advanced CTCL, what are the things that lead to their demise?
Lauren Pinter-Brown. Probably the most common would be infections because their skin barrier has been broken. As the disease advances, their immune system also deteriorates. We may contribute to that sometimes with some of the therapies that we use, although we try and be judicious. First and foremost, the primary cause of death remains infection and sometimes inanition.
Marianne Tawa. I agree, infection or just the unfortunate progression of their lymphoma through the various armamentarium of treatments would be the 2 reasons.
John Zic. Let’s dive into therapy. I want to start with early stage. While, I don’t think there’s a role for systemic anticancer agents, certainly the IV agents for most patients with early-stage disease Marianne, you mentioned phototherapy. What are the types of phototherapy that you offer?
Marianne Tawa. We would start out with narrow band UVB therapy for patients with > 10% body surface area involvement. When applying topical corticosteroids to wider surface areas of the patient’s body is no longer feasible or effective, we recommend the initiation of narrow band UVB phototherapy. This is preferred because of its lessor adverse effect (AE) profile as far as nonmelanoma skin cancer risk. Patients commence narrow band UVB 3 times per week, with a goal of getting the patient into remission over a matter of months and then slowly tapering the phototherapy so that they get to a maintenance of once weekly.
Realizing that narrow band UVB may not penetrate deeper plaques or effectively reach folliculotropic variant of CTCL, we would employ PUVA, (psoralen and UVA). Patients are expected to protect their eyes with UVA glasses and remain out of the sun 24 hours following PUVA treatments. The cost of the methoxsalen can be an issue for some patients. Nonmelanoma skin cancer risks are increased in patients undergoing long-term PUVA treatments. Routine skin cancer surveillance is key.
There are monetary, time, and travel demands for patients receiving phototherapy. Thus, many CTCL patients are moving toward home-based narrow band UVB units supervised by their treating dermatologist. Other skin-directed treatment options, aside from topical corticosteroids and phototherapy, would include topical nitrogen mustard, imiquimod, and localized or total skin electron beam radiation.
John Zic. Here in Nashville, some of our veterans travel hundreds of miles to get to our center. It’s not practical for them to come here for the narrow band UVB phototherapy. Veterans can get approval through the VA Choice programs to have phototherapy performed by a local dermatologist closer to home. We also have had many veterans who choose to get home narrow band UVB phototherapy, which can be quite effective. Narrow band UVB phototherapy is among the most effective therapies for patients with generalized patches in particular, and maybe some with just a few plaques.
Medium potency topical steroids are not as helpful as superpotent topical steroids such as clobetasol, dipropionate ointment, or betamethasone dipropionate ointment. Usually, I tell patients to apply it twice a day for 8 weeks. You must be careful because these high-potency topical steroids can cause thinning of the skin, but it’s rarely seen, even in patients that may use them for 8 weeks if they’re applying them just to their patches and thin plaques. There are a few other topicals. There’s bexarotene gel, which is a topical retinoid, and mechlorethamine or nitrogen mustard gel that are available as topicals. Both of those can be helpful if patients have < 10% body surface area of patches or plaques because they can apply that at home.
Because of the excellent prognosis for patients in early stages, this is an area we want to try to avoid doing harm. For patients with advanced disease, what are some of the decisions that you think about in recommending a patient to get radiation therapy?
Lauren Pinter-Brown. I use radiation therapy sparingly and primarily for patients who either have only 1 tumor and the rest of their disease is patch and plaque or for patients who have very large tumors that are either cosmetically unacceptable or creating infection or pain. I treat people with systemic therapies primarily to prevent the formation of tumors.
John Zic. There probably is a role for total skin electron beam radiotherapy in patients who have failed multiple other skin-directed therapies and are progressing and then perhaps a role for more advanced patients who have multiple tumors where you’re trying to get some control of the disease. Are there any other situations where you might consider total skin electron beam?
Marianne Tawa. Yes, those are 2 scenarios. A third scenario would be in patients preparing for stem cell transplant. We typically do a modified 12 Gy regimen of total skin electron beam for palliation and up to 24 Gy regimen for patients who are in earnest preparing for a stem cell transplant.
John Zic. Systemic therapies also treat this disease. There are 2 oral agents. One is bexarotene capsules, a retinoid that binds to the RXR receptor and has a multitude of effects on different organ systems. It is probably the best tolerated oral agent we have. The other FDA-approved agent is vorinostat, a histone deacetylase inhibitor, but it has more gastrointestinal AEs than does bexarotene. Bexarotene has AEs as well, including hypertriglyceridemia and central hypothyroidism, which can throw a curveball to unsuspecting primary care physicians who might check thyroid function studies in these patients.
We certainly need to know about those AEs. There are many patients who have tumor-stage disease that can have radiotherapy to several tumors, then go on a drug like bexarotene capsules and may be able to maintain the remission for years. In my experience, it’s a drug that patients usually stay on. They can be weaned to a very low dose, but I’ve had several patients who come off of bexarotene only to suffer relapses.
Lauren, what are some of the things that you think about when you declare someone as having failed bexarotene or vorinostat and you’re thinking about IV therapies?
Lauren Pinter-Brown. Patient comorbidities and the particular compartment of their body that is involved are important factors. Do they have blood involvement, or not? Do they have nodal involvement, or not? Another concern is both acute and chronic toxicities that need to be discussed with the patient to determine an acceptable QOL. Finally, the schedule that you’re giving the drug. Some people may not be able to come in frequently. There are a lot of variables that go into making an individual decision at a particular time for a specific patient who will be using parenteral therapies.
John Zic. If we have a patient with advanced MF, tumors, and perhaps lymph node involvement, what are some of the systemic options that you would consider?
Lauren Pinter-Brown. With nodal involvement, an attractive option is something like IV romidepsin because we know that it treats peripheral T-cell lymphomas, which are aggressive nodal T-cell lymphomas. It’s FDA approved and also treats CTCL. Another is brentuximab vedotin if there is significant CD30 expression. It also is FDA approved for CTCL and has a long track record of treating certain peripheral T-cell lymphomas like anaplastic large cell.
John Zic. When would the stem cell transplant discussion start at your institution?
Lauren Pinter-Brown. It starts earlier for a younger patient because even though we do have lots of treatment if someone is aged 20 or30 years, I don’t really have any illusions that I have enough treatment options for them to live a normal lifespan if they have advanced disease. It’s a possibility for any patient when I see that the future options are dwindling, and that I am not going to be able to control the patient’s disease for much longer. Having said that, patients who have tumor-stage disease are among those that don’t do quite as well with allogeneic transplantation; ironically, patients with Sézary syndrome or erythroderma might do a little bit better.
John Zic. Before considering a stem cell transplant for patients with Sézary syndrome, that is erythroderma with significant blood involvement, what other treatment options would you offer?
Marianne Tawa. For low blood-burden disease, we might look at extracorporeal photopheresis as monotherapy or in combination with interferon or bexarotene. For patients with higher blood burden we might recommend low-dose alemtuzumab, especially if they have abundant CD52 expression. We also consider the newly FDA-approved anti-CCR4 antibody treatment, mogamulizumab, for patients presenting with Sézary syndrome. It is generally well tolerated but does have the potential for producing infusion reactions or drug rash.
Romidepsin has efficacy in blood, lymph node, and skin compartments. The primary considerations for patients considering romidepsin are prolonged infusion times and QOL AEs with gastrointestinal and taste disturbances and fatigue.
John Zic. Both of you have brought up an excellent point. This is a disease that while we do not have a good chance of curing, we have a pretty fair chance of controlling, especially if it’s early stage. The data from the stem cell transplant literature indicate that stem cell transplant may be one of the few modalities that we have that may offer a cure.11
Lauren Pinter-Brown. There are patients who are cured with allogeneic transplants; and the very first allogeneic transplants were performed well over 20 years ago. Many patients, even some in my practice, who were among those patients and continue to do extremely well without any evidence of disease. Sometimes when people have allogeneic transplantation, their disease relapse may be in a more indolent form that’s much easier to deal with than their original disease. Even if they’re not cured, the fact that the aggressive disease seems to be at bay may make them much easier to treat.
John Zic. Those are excellent points. You brought up photopheresis as a treatment modality for patients with evolving or early Sézary syndrome and patients with erythrodermic MF can also respond. We have a lot of experience with that at the Nashville VA medical center. We’re one of the few VA hospitals in the US that has a photopheresis unit. But the modality is available at many academic medical centers because it’s a treatment for graft-vs-host disease.
We tend to also consider photopheresis in patients who may have had an excellent response to another systemic agent. There are some data that patients who received photopheresis, after total skin electron beam therapy vs those who received chemotherapy after radiation, had a longer disease-free survival.12
I’d like to end with a discussion of something that’s very important, which is managing QOL issues for patients with CTCL. Itch is among some of the worst symptoms that can cause suffering in patients. But it is sometimes not a problem at all for patients who have a few patches or plaques. That’s one reason why they might ignore their rash. Certainly, as the disease progresses, especially those patients with erythroderma, the itch can be intractable and can have a major impact on their life. What are some approaches to managing itch at your institutions?
Lauren Pinter-Brown. One thing to be aware of is that the itch is not usually mediated by histamine, though people will often put the patients on a lot of antihistamines. I don’t find those to be the most effective treatments. I think of the itch in these patients as more of a neuropathic condition and would tend to treat more with things that you might use for neuropathy, such as gabapentin or doxepin or antidepressants. There’s a whole host of other treatments, such as aprepitant, something that I would use as an antiemetic, that might also be helpful for pruritus in this patient population.
John Zic. That’s my experience as well. I have found gabapentin to be helpful for patients with itch, though not universally.
Marianne Tawa. I consider itch a huge QOL concern for a large majority of our patients with a CTCL diagnosis. It’s on par with pain. In early-stage disease, pruritus levels improve as the cutaneous burden is reduced with skin-directed therapies such as, topical corticosteroid or phototherapy.
SSRI agents could also be considered for select patients. The antiemetic agent, aprepitant has been useful for addressing itch in a subset of our patients with Sézary syndrome. Patients will also seek out complementary modalities such acupuncture, hypnosis, and guided imagery.
John Zic. Because the disease itself affects the skin and can lead to dryness, patients often suffer with dry skin. When I trained in Chicago, that was the foundation of our treatment, making sure that patients are using a super fatted soap such as Dove (Unilever, London, United Kingdom) or Cetaphil (Galderma Laboratories; Fort Worth, TX), making sure that they’re lubricating their skin frequently with something perhaps in the wintertime as thick as petroleum jelly. And then in the summertime perhaps with Sarna lotion (Crown Laboratories; Johnson City, TN), which has menthol. It’s important to note that when the patient’s skin is infected, the itch can skyrocket. Being aware and monitoring the skin for signs of infection such as crusting and impetigo-like findings can be helpful.
I also wanted to touch on fatigue. Patients can have fatigue for many reasons. Sometimes it’s because the itch is interfering with their sleep. How do you approach managing fatigue?
Lauren Pinter-Brown. There have been many studies about cancer fatigue, and it appears that one of the cheapest and easiest modalities is for patients to walk. We often suggest that our patients go on walks, however much they can do, because that has been seen over and over again in studies of cancer fatigue to be beneficial.
John Zic. Do you have any advice for nurses that might be helping to manage patients in a cutaneous lymphoma clinic?
Marianne Tawa. As this is a rare disease, nursing encounters with patients carrying a diagnosis of CTCL in both oncology and dermatology settings may be few and far between. I recommend nurses familiarize themselves with articles published on CTCL topics found in both dermatology and oncology peer review journals. Another avenue for gaining insight and education would be through continuing education courses. Resources can also be found for nurses, patients, and caregivers through advocacy foundations such as the Cutaneous Lymphoma Foundation (www.clfoundation.org) and the Lymphoma Research Foundation ([email protected]).
John Zic. Is there anything else that anyone would like to add to our discussion?
Lauren Pinter-Brown. One thing that we touched upon, but I was concerned that we didn’t emphasize, was the use of flow cytometry as a diagnostic tool in a patient with erythroderma. Sometimes biopsies of patients with erythroderma are not diagnostic, so clinicians need to be aware that there are other ways of diagnosing patients—nodal biopsy or flow cytometry. They should not only think of it as a staging tool but sometimes as a diagnostic tool.
Alejandro Ariel Gru. I agree. Particularly in patients who have Sézary syndrome or MF with peripheral blood involvement, sometimes the findings on the biopsy show a dissociation between how impressive the clinical presentation of the patient might be and how very few findings you might encounter on the skin biopsy. Therefore, relying on flow cytometry as a diagnostic tool is capital. Lauren, you briefly mentioned the criteria, which is looking for an abnormal CD4 to CD8 ratio of > 10%, abnormal loss of CD7, > 40%, or abnormal loss of CD26 of > 30%.
In addition, there are new markers that are now undergoing validation in the diagnosis of Sézary syndrome. One is KIR3DL2, which is a natural killer receptor that has been shown to be significantly upregulated in Sézary syndrome and appears to be both more sensitive and specific. With that also comes therapies that target the KIR3DL2 molecule.
John Zic. One of the first things we teach our dermatology residents to work up patients with erythroderma is that they shouldn’t expect the skin biopsy to help them sort out the cause of the erythroderma. As you mentioned, Lauren, the flow cytometry of peripheral blood should always be accompanied by a CBC with differential and platelets. And if the patients do have lymph nodes, consider a biopsy because sometimes that’s where you can make the firmest diagnosis of a T-cell lymphoma.
Acknowledgmentszz
The participants and Federal Practitioner would like to thank Susan Thornton, CEO of the Cutaneous Lymphoma Foundation for helping to arrange this roundtable discussion.
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John Zic, MD. Let’s start by defining cutaneous T-cell lymphomas (CTCLs) and how they differ from other non-Hodgkin lymphomas. We also should discuss classification, which can be very confusing and epidemiology as it relates to the veteran population. Then I think we should dive into challenges with diagnosis and when should a VA or any provider consider mycosis fungoides (MF) and Sézary syndrome—the 2 most common variants of CTCLs.
I like to define the primary CTCLs as malignancies of the T-cell where the primary organ of involvement is the skin. However, this disease can spread to lymph nodes and visceral organs and the blood compartment in more advanced patients. Alejandro, could you provide some highlights about how CTCLs are classified?
Alejandro Ariel Gru, MD. Lymphomas are divided in the general hematology/oncology practice as Hodgkin and non-Hodgkin lymphomas. Traditionally all lymphomas that occur on the skin are non-Hodgkin lymphoma subtypes. That has specific connotations in terms of diagnosis, prognosis, and therapy. Because the T cells are one of the main residents of the subtypes of lymphocytes you encounter on the skin, most lymphomas that occur on the skin are derived of T-cell origin. B-cell lymphomas, in general, tend to be relatively uncommon or more infrequent.
There are 3 main subtypes of CTCL that present on the skin.1 MF is, by far, the most common subtype of CTCL. The disease tends to present in patients who are usually aged > 60 years and is more frequent in white males. It’s a lymphoma that is particularly relevant to the veteran population. The second subtype has many similarities to MF but shows substantial peripheral blood involvement and is referred to as Sézary syndrome. The third group is encompassed under the term CD30-positive lymphoproliferative disorders. This group includes 2 main subtypes: primary cutaneous anaplastic large-cell lymphoma and lymphomatoid papulosis. Some cases of MF develop progression to what we call large cell transformation, which implies cytologic transformation to a more aggressive lymphoma.
There are other cutaneous lymphomas that are far less common. Some are indolent and others can be more aggressive, but they represent < 5% of all CTCL subtypes.
Lauren Pinter-Brown, MD. That was a great summary about these non-Hodgkin lymphomas. In the veteran population, it’s wise to remember that there are many kinds of non-Hodgkin lymphomas. Because of the action that they have seen, some people, such as Vietnam veterans, might be more susceptible to non-Hodgkin lymphomas than others.
John Zic. That’s a good point because certainly non-Hodgkin lymphomas are listed as one of the potential disease associations with exposure to Agent Orange.
I’d like to move on to epidemiology and the incidence of MF and Sézary syndrome. An article that came out of Emory University in 2013 is one of the more up-to-date articles to examine the incidence and survival patterns of CTCL.2 The authors looked at patients from 2005 to 2008 and identified 2,273 patients in the Surveillance, Epidemiology, and End Results registry. They estimated that the incidence of MF in the US population is about 5.5 per 1,000,000 per year, which certainly makes it a rare disease. The incidence of Sézary syndrome was 0.1 per 1,000,000 per year, which comes out to about 1 per 10 million per year.
However, the MF incidence needs to be contrasted to the estimated incidence in the veteran population. In 2016, Larisa Geskin and colleagues from Columbia University and the Bronx US Department of Veterans Affairs (VA) Medical Center examined the VA database of patients with diagnoses of MF and Sézary syndrome.3 They combined them, but I have a feeling that the amount of Sézary syndrome patients was much less than those with MF. They estimated an incidence per million of 62 to 79 cases per 1,000,000 per year. The conclusion of Dr. Geskin’s study stated that the incidence of CTCL in the veteran population appears to be anywhere from 6 to 8 times higher. But if we use the most recent US incidence rates, it’s more than 10 times higher.
Those of you who have worked with veterans, either at the VA or in your private practice, do you have any ideas about why that might be?
Lauren Pinter-Brown. As you previously discussed, this is an illness of older people, and Vietnam veterans now are in their 60s and 70s. They may account for a lot of these diagnoses.
John Zic. That’s a good point. There’s quite a bit of talk about exposure to Agent Orange. But honestly, we really don’t know the cause of any of the CTCLs. We have not been able to identify a single cause. There are some risk factors. A 2014 article from the Journal of the National Cancer Institute looked at 324 cases of CTCL and compared it with 17,000 controls.4 They showed some interesting risk factors, such as body mass index (BMI) > 30 and smoking > 40 years. Similar to previous European studies, they showed that occupations like being a farmer, a painter, a woodworker, or a carpenter may carry additional risk.I wonder whether or not veterans were more likely to have some of these risk factors that this epidemiologic study picked up in addition to exposures that they may have encountered during their active-duty service. Interestingly, a decreased risk factor for developing MF was moderate physical activity. Clearly though, there are a large number of patients with CTCL in the veteran population.
I’d like to turn now to some of the challenges with diagnosis. Marianne, could you share some of your experience with early-stage disease and about how long it took them to be diagnosed?
Marianne Tawa, RN, MSN, ANP. Speaking specifically about early-stage disease, patients often share a history of waxing and waning rash that may not be particularly itchy. Confounding the picture, the distribution of early patch or plaque stage CTCL rash frequently occurs in covered areas. Many patients miss out on complete skin examinations by providers, thus early-stage CTCL may not be appreciated in a timely manner.
In certain scenarios, it may take upward of 5 to 7 years before the CTCL diagnosis is rendered. This is not because the patient delayed care. Nor is it because a skin biopsy was not performed. The progression of the disease and meeting the classic features of histology under the microscope can require clinical observation over time and repeated skin biopsies. We recommend patients refrain from topical steroid applications for 2 to 4 weeks prior to skin biopsy if we have a strong suspicion of CTCL. Many patients will report having a chronic eczematous process. Some patients may have a history of parapsoriasis, and they’re on the continuum for CTCL. That’s a common story for CTCL patients.
John Zic. What is the role of a skin biopsy in the diagnosis of CTCL? We see many patients who have had multiple skin biopsies who often wonder whether or not the diagnosis was missed by either the clinician or the pathologist.
Alejandro Ariel Gru. That is a great area of challenge in terms of pathologic diagnosis of early MF. A study led by Julia Scarisbrick, from an international registry data (PROCLIPI) on the early stages of the disease, showed a median delay of diagnosis of early MF of approximately 36 months.5 For all physicians involved in the diagnosis and care of patients with MF, the delay is probably significantly higher than that. We’ve seen patients who have lived without a diagnosis for a period of 10 or sometimes 15 years. That suggests that many cases are behaving in an indolent fashion, and patients are not progressing through the ‘natural’ stages of the disease and remain at the early stage. There also is the potential that other chronic inflammatory conditions, particularly psoriasis or parapsoriasis, can be confused with this entity. The diagnosis of certain types of parapsoriasis, can belong to the same spectrum of MF and can be treated in a similar way than patients with early stage MF are, such as phototherapy or methotrexate.
The diagnosis of MF relies on a combination of clinical, pathologic, and immunophenotypic findings where it is desired or preferred that at least 2 biopsies are done from different sides of the body. In addition to having a good clinical history that supports the diagnosis, a history of patches, plaques, and sometimes tumors in advanced stages in particular locations that are covered from the light (eg, trunk, buttocks, upper thighs, etc) combined with specific histopathologic criteria are capital to establish an accurate diagnosis.
In the biopsies, we look particularly for a lymphoid infiltrate that shows extension to the epidermis. We use the term epidermotropism to imply that these abnormal or neoplastic lymphocytes extend into the epidermis. They are also cytologically atypical. We see variations in the nucleus. In the size, we see a different character of the chromatin where they can be hyperchromatic. We also look for immunophenotypic aberrations, and particularly we analyze for patterns of expression of T-cell markers. Most cases of MF belong to a subset of T cells that are called CD4-positive or T-helper cells. We look for a patterned ratio of the CD4 and CD8 between the epidermis and an aberrant loss of the CD7 T-cell marker. Once we establish that we can see significant loss of these markers, we can tell where there is something wrong with that T-cell population, and likely belong to a neoplastic category.
In addition, we also rely on the molecular evaluation and search of a clonal population of T cells, by means of a T-cell receptor gene rearrangement study. Ideally, we like to see the establishment of a single clone of T cells that is matched in different biopsy sites. Proving that the same clone is present in 2 separate biopsies in 2 separate sites is the gold standard for diagnosis.6
John Zic. To recap, a biopsy is indicated for patients who have patches or plaques (that are slightly raised above the skin) in sun-protected areas that are fixed; rather than completely go away in the summer and come back in the winter, they are fixed if they have been present > 6 to 12 months. Many of these patients are diagnosed with eczema, psoriasis, allergic contact dermatitis, and other skin diseases before the clinician starts to think about other diagnoses, such as CTCL.
I agree that I would not rule out the diagnosis with 1 biopsy that does not show classic histologic changes. Also, I think that it’s important to alert the pathologist that you’re considering a diagnosis of T-cell lymphoma, either MF or some of the other subtypes, because that will certainly alert them to look a little closer at the infiltrating cells and perhaps do some of the other testing that was mentioned. Once we establish the MF diagnosis, staging studies may be indicated.
Lauren Pinter-Brown. Early stage would be patients with patches or plaques. Stage IA would be < 10% body surface area, and stage IB would be > 10%. I don’t perform scans for early-stage patients, but I do a very thorough physical and perform blood tests. For patients that have more advanced disease, such as tumors, erythroderma, or Sézary syndrome, I would conduct the same thorough examination and blood tests and scan the patient either with a computed tomography (CT) or a positron emission tomography (PET)/CT to detect adenopathy. We have to recognize that most of the adenopathy that is detected in these patients is peripheral, and we can feel it on physical examination.
John Zic. Do you prefer one imaging modality over the other? CT scan with IV contrast vs PET/CT?
Lauren Pinter-Brown. I tend to use PET/CT because it illuminates extranodal sites as well. I have to admit that sometimes it’s a problem to get that approved with insurance.
John Zic. In the federal system, many PET/CT scans are performed at other facilities. That would be an extra step in getting approval.
You mentioned Sézary syndrome. We should consider a diagnosis of Sézary syndrome when you have a patient with erythroderma, which means that they have > 80% of the skin covered in redness and scaling.
Lauren Pinter-Brown. The first step is to do a complete blood count (CBC) and see if there’s a lymphocytosis. Sometimes that really isn’t very sensitive, so my go-to test is flow cytometry. We are looking for an abnormal population of cells that, unlike normal T cells, often lack certain T-cell antigens. The most common would be CD7. We can confirm that this is a clone by T-cell gene rearrangement, and often in Sézary we like to compare the gene rearrangement seen in blood with what might be seen in the skin biopsy to confirm that they’re the same clone.
John Zic. That’s an excellent point. I know there are specific criteria to meet significant blood involvement. That is a topic of conversation among CTCL experts and something that might be changing over the next few years. But I think as it stands right now, having a lymphocytosis or at least an elevated CD4 count along with having a clone in the blood matching the clone in the skin are the first 2 steps in assessing blood involvement. However, the flow cytometry is very important. Not all medical centers are going to do flow cytometry—looking specifically for a drop of the CD7 or CD26 antigen among the CD4 population. But that is one of the major criteria that we look for in those patients with suspected blood involvement.
Marianne Tawa. Additionally, we would advise obtaining flow cytometry on patients that look like they have a robust skin burden with lots of patches, plaques, or tumors. We also perform lactate dehydrogenase (LDH) with staging.
John Zic. What do you usually tell patients with early-stage disease, those that have patches and plaques?
Marianne Tawa. For patients with stage IA disease, we are very optimistic about their prospects. We explain that the likelihood that early-stage disease will progress to a more advanced stage or rare variant is unlikely. This is very much a chronic disease, and the goal is to manage appropriately, palliate symptoms, and preserve quality of life (QOL).
Lauren Pinter-Brown. I often refer to a landmark paper by Youn H. Kim and colleagues that shows us that patients with IA disease who are at least treated usually have a normal lifespan.7 I encourage patients by sharing that data with them.
John Zic. Sean Whittaker and colleagues in the United Kingdom identified 5 risk factors for early-stage patients that may put them at higher risk for progressing: aged > 60 years; having a variant called folliculotropic MF; having palpable lymph nodes even if they’re reactive on biopsy, having plaques, and male sex.8 For staging of lymph nodes, what’s your usual approach when you see a patient with palpable lymph nodes?
Lauren Pinter-Brown. Many patients, particularly those with advanced skin disease, may have palpable lymph nodes that are reacting to their skin disease and on pathology would be dermatopathic. That would not change my management. I pay attention to the quality of the lymph node—if it’s very firm, if it’s > 2 cm, if it is persistent—before I biopsy. These patients have a higher incidence of wound infection after excisional biopsy. If the patient has pathologic lymph node involvement and effacement of the node with malignant cells, I would change my management. I do need to know that sort of information.
John Zic. Alejandro, as a hematopathologist can you comment on the debate about whether or not we actually do need an excisional biopsy or whether or not we can get a core lymph node biopsy to give you all the information that you need to grade it?
Alejandro Ariel Gru. There are 2 main modalities of biopsies we typically see for lymph nodes for evaluation and staging for involvement of CTCL. One is the traditional excisional biopsy that for the most part requires surgery with general anesthesia and has all the major implications that that type of procedure has. Many centers are looking at less invasive types of procedures, and needle core biopsies have become one of the most common forms of biopsy for all lymphoma subtypes. Excisional biopsies have the advantage of being able to see the whole lymph node, so you can determine and evaluate the architecture very well. Whereas needle core biopsies typically use a small needle to obtain a small piece of the tissue.
The likelihood of a successful diagnosis and accurate staging was compared recently in the British Journal of Dermatology.9 They were able to perform accurate staging in needle core biopsies of patients with MF. However, this is still a matter of debate; many people feel they are more likely to get enough information from an excisional biopsy. As we know, excisional biopsies sometimes can be hard, particularly if the large lymph node is located in an area that is difficult to access, for example, a retroperitoneal lymph node.
There are many staging categories that are used in the pathologic evaluation of lymph node involvement. On one hand, we could see the so-called dermatopathic changes, which is a reactive form of lymphadenopathy that typically happens in patients who have skin rashes and where there is no evidence of direct involvement by the disease (although there are some patients who can have T-cell clones by molecular methods). The patients who have clonal T cells perhaps might not do as well as the ones who do not. On the other hand, we have patients for whom the whole architecture of the lymph node is effaced or replaced by neoplastic malignant cells. Those patients are probably going to need more aggressive forms of therapy.10
John Zic. The type of lymph node biopsy has been a hot topic. If patients have palpable lymph nodes in the cervical, axillary, and inguinal area, I don’t know if it’s a consensus, but the recommendation right now is to consider performing a lymph node biopsy of the cervical lymph nodes first, axillary second, and inguinal lymph nodes third. That might have to do with the complication rates for those different areas.
I’d like to switch to a discussion to more advanced disease. CTCL tumors are defined as a dome-shaped nodule > 1 cm. They don’t have to be very big before we label it a tumor, and the disease is considered more advanced. For patients with a few tumors, what does your prognosis discussion sound like?
Marianne Tawa. Certainly, the prognosis discussion can become slightly more complicated when you move into the realm of tumor-stage development. This is especially true if a CTCL patient has lived with and managed indolent patches or plaques for several years. We approach these patients with optimism and with the goal of managing their tumors, whether it be with a skin-directed option, such as localized radiation or a host of approved systemic therapies. Patients presenting with or developing tumor-stage disease over time will require additional staging workup compared with early-stage disease staging practice. Patients are counseled on imaging use in tumor-stage disease and why flow cytometry may be requested to rule in or rule out accompanying peripheral blood involvement. Patients are exposed to a myriad of pictures, stories, and survival statistics from Internet research. It becomes our task to inform them of their unique presentation and tailored treatment plan, which thankfully may produce more favorable responses than those presented online.
Lauren Pinter-Brown. One thing that we focus on is the idea that a statistic regarding prognosis isn’t predictive for an individual patient. When patients go online, we caution them that many of the statistics are really old. There’s been a lot of new therapies in the past 10 years. Just looking at my patients, my feeling is that their prognosis has continued to improve over the decades that I’ve been involved in this area.
We have to take the statistics with a grain of salt, though certainly someone that has Sézary syndrome or someone that has nodal involvement or tumors is not going to fare as well as the patients that we talked about with stage I disease. However, if we all continue to do our jobs and have more and more treatment options for patients, that’s certainly going to change over time as it has with other non-Hodgkin lymphomas.
John Zic. We’ve all treated advanced patients with disease and some, of course, have died of the disease. When patients die of advanced CTCL, what are the things that lead to their demise?
Lauren Pinter-Brown. Probably the most common would be infections because their skin barrier has been broken. As the disease advances, their immune system also deteriorates. We may contribute to that sometimes with some of the therapies that we use, although we try and be judicious. First and foremost, the primary cause of death remains infection and sometimes inanition.
Marianne Tawa. I agree, infection or just the unfortunate progression of their lymphoma through the various armamentarium of treatments would be the 2 reasons.
John Zic. Let’s dive into therapy. I want to start with early stage. While, I don’t think there’s a role for systemic anticancer agents, certainly the IV agents for most patients with early-stage disease Marianne, you mentioned phototherapy. What are the types of phototherapy that you offer?
Marianne Tawa. We would start out with narrow band UVB therapy for patients with > 10% body surface area involvement. When applying topical corticosteroids to wider surface areas of the patient’s body is no longer feasible or effective, we recommend the initiation of narrow band UVB phototherapy. This is preferred because of its lessor adverse effect (AE) profile as far as nonmelanoma skin cancer risk. Patients commence narrow band UVB 3 times per week, with a goal of getting the patient into remission over a matter of months and then slowly tapering the phototherapy so that they get to a maintenance of once weekly.
Realizing that narrow band UVB may not penetrate deeper plaques or effectively reach folliculotropic variant of CTCL, we would employ PUVA, (psoralen and UVA). Patients are expected to protect their eyes with UVA glasses and remain out of the sun 24 hours following PUVA treatments. The cost of the methoxsalen can be an issue for some patients. Nonmelanoma skin cancer risks are increased in patients undergoing long-term PUVA treatments. Routine skin cancer surveillance is key.
There are monetary, time, and travel demands for patients receiving phototherapy. Thus, many CTCL patients are moving toward home-based narrow band UVB units supervised by their treating dermatologist. Other skin-directed treatment options, aside from topical corticosteroids and phototherapy, would include topical nitrogen mustard, imiquimod, and localized or total skin electron beam radiation.
John Zic. Here in Nashville, some of our veterans travel hundreds of miles to get to our center. It’s not practical for them to come here for the narrow band UVB phototherapy. Veterans can get approval through the VA Choice programs to have phototherapy performed by a local dermatologist closer to home. We also have had many veterans who choose to get home narrow band UVB phototherapy, which can be quite effective. Narrow band UVB phototherapy is among the most effective therapies for patients with generalized patches in particular, and maybe some with just a few plaques.
Medium potency topical steroids are not as helpful as superpotent topical steroids such as clobetasol, dipropionate ointment, or betamethasone dipropionate ointment. Usually, I tell patients to apply it twice a day for 8 weeks. You must be careful because these high-potency topical steroids can cause thinning of the skin, but it’s rarely seen, even in patients that may use them for 8 weeks if they’re applying them just to their patches and thin plaques. There are a few other topicals. There’s bexarotene gel, which is a topical retinoid, and mechlorethamine or nitrogen mustard gel that are available as topicals. Both of those can be helpful if patients have < 10% body surface area of patches or plaques because they can apply that at home.
Because of the excellent prognosis for patients in early stages, this is an area we want to try to avoid doing harm. For patients with advanced disease, what are some of the decisions that you think about in recommending a patient to get radiation therapy?
Lauren Pinter-Brown. I use radiation therapy sparingly and primarily for patients who either have only 1 tumor and the rest of their disease is patch and plaque or for patients who have very large tumors that are either cosmetically unacceptable or creating infection or pain. I treat people with systemic therapies primarily to prevent the formation of tumors.
John Zic. There probably is a role for total skin electron beam radiotherapy in patients who have failed multiple other skin-directed therapies and are progressing and then perhaps a role for more advanced patients who have multiple tumors where you’re trying to get some control of the disease. Are there any other situations where you might consider total skin electron beam?
Marianne Tawa. Yes, those are 2 scenarios. A third scenario would be in patients preparing for stem cell transplant. We typically do a modified 12 Gy regimen of total skin electron beam for palliation and up to 24 Gy regimen for patients who are in earnest preparing for a stem cell transplant.
John Zic. Systemic therapies also treat this disease. There are 2 oral agents. One is bexarotene capsules, a retinoid that binds to the RXR receptor and has a multitude of effects on different organ systems. It is probably the best tolerated oral agent we have. The other FDA-approved agent is vorinostat, a histone deacetylase inhibitor, but it has more gastrointestinal AEs than does bexarotene. Bexarotene has AEs as well, including hypertriglyceridemia and central hypothyroidism, which can throw a curveball to unsuspecting primary care physicians who might check thyroid function studies in these patients.
We certainly need to know about those AEs. There are many patients who have tumor-stage disease that can have radiotherapy to several tumors, then go on a drug like bexarotene capsules and may be able to maintain the remission for years. In my experience, it’s a drug that patients usually stay on. They can be weaned to a very low dose, but I’ve had several patients who come off of bexarotene only to suffer relapses.
Lauren, what are some of the things that you think about when you declare someone as having failed bexarotene or vorinostat and you’re thinking about IV therapies?
Lauren Pinter-Brown. Patient comorbidities and the particular compartment of their body that is involved are important factors. Do they have blood involvement, or not? Do they have nodal involvement, or not? Another concern is both acute and chronic toxicities that need to be discussed with the patient to determine an acceptable QOL. Finally, the schedule that you’re giving the drug. Some people may not be able to come in frequently. There are a lot of variables that go into making an individual decision at a particular time for a specific patient who will be using parenteral therapies.
John Zic. If we have a patient with advanced MF, tumors, and perhaps lymph node involvement, what are some of the systemic options that you would consider?
Lauren Pinter-Brown. With nodal involvement, an attractive option is something like IV romidepsin because we know that it treats peripheral T-cell lymphomas, which are aggressive nodal T-cell lymphomas. It’s FDA approved and also treats CTCL. Another is brentuximab vedotin if there is significant CD30 expression. It also is FDA approved for CTCL and has a long track record of treating certain peripheral T-cell lymphomas like anaplastic large cell.
John Zic. When would the stem cell transplant discussion start at your institution?
Lauren Pinter-Brown. It starts earlier for a younger patient because even though we do have lots of treatment if someone is aged 20 or30 years, I don’t really have any illusions that I have enough treatment options for them to live a normal lifespan if they have advanced disease. It’s a possibility for any patient when I see that the future options are dwindling, and that I am not going to be able to control the patient’s disease for much longer. Having said that, patients who have tumor-stage disease are among those that don’t do quite as well with allogeneic transplantation; ironically, patients with Sézary syndrome or erythroderma might do a little bit better.
John Zic. Before considering a stem cell transplant for patients with Sézary syndrome, that is erythroderma with significant blood involvement, what other treatment options would you offer?
Marianne Tawa. For low blood-burden disease, we might look at extracorporeal photopheresis as monotherapy or in combination with interferon or bexarotene. For patients with higher blood burden we might recommend low-dose alemtuzumab, especially if they have abundant CD52 expression. We also consider the newly FDA-approved anti-CCR4 antibody treatment, mogamulizumab, for patients presenting with Sézary syndrome. It is generally well tolerated but does have the potential for producing infusion reactions or drug rash.
Romidepsin has efficacy in blood, lymph node, and skin compartments. The primary considerations for patients considering romidepsin are prolonged infusion times and QOL AEs with gastrointestinal and taste disturbances and fatigue.
John Zic. Both of you have brought up an excellent point. This is a disease that while we do not have a good chance of curing, we have a pretty fair chance of controlling, especially if it’s early stage. The data from the stem cell transplant literature indicate that stem cell transplant may be one of the few modalities that we have that may offer a cure.11
Lauren Pinter-Brown. There are patients who are cured with allogeneic transplants; and the very first allogeneic transplants were performed well over 20 years ago. Many patients, even some in my practice, who were among those patients and continue to do extremely well without any evidence of disease. Sometimes when people have allogeneic transplantation, their disease relapse may be in a more indolent form that’s much easier to deal with than their original disease. Even if they’re not cured, the fact that the aggressive disease seems to be at bay may make them much easier to treat.
John Zic. Those are excellent points. You brought up photopheresis as a treatment modality for patients with evolving or early Sézary syndrome and patients with erythrodermic MF can also respond. We have a lot of experience with that at the Nashville VA medical center. We’re one of the few VA hospitals in the US that has a photopheresis unit. But the modality is available at many academic medical centers because it’s a treatment for graft-vs-host disease.
We tend to also consider photopheresis in patients who may have had an excellent response to another systemic agent. There are some data that patients who received photopheresis, after total skin electron beam therapy vs those who received chemotherapy after radiation, had a longer disease-free survival.12
I’d like to end with a discussion of something that’s very important, which is managing QOL issues for patients with CTCL. Itch is among some of the worst symptoms that can cause suffering in patients. But it is sometimes not a problem at all for patients who have a few patches or plaques. That’s one reason why they might ignore their rash. Certainly, as the disease progresses, especially those patients with erythroderma, the itch can be intractable and can have a major impact on their life. What are some approaches to managing itch at your institutions?
Lauren Pinter-Brown. One thing to be aware of is that the itch is not usually mediated by histamine, though people will often put the patients on a lot of antihistamines. I don’t find those to be the most effective treatments. I think of the itch in these patients as more of a neuropathic condition and would tend to treat more with things that you might use for neuropathy, such as gabapentin or doxepin or antidepressants. There’s a whole host of other treatments, such as aprepitant, something that I would use as an antiemetic, that might also be helpful for pruritus in this patient population.
John Zic. That’s my experience as well. I have found gabapentin to be helpful for patients with itch, though not universally.
Marianne Tawa. I consider itch a huge QOL concern for a large majority of our patients with a CTCL diagnosis. It’s on par with pain. In early-stage disease, pruritus levels improve as the cutaneous burden is reduced with skin-directed therapies such as, topical corticosteroid or phototherapy.
SSRI agents could also be considered for select patients. The antiemetic agent, aprepitant has been useful for addressing itch in a subset of our patients with Sézary syndrome. Patients will also seek out complementary modalities such acupuncture, hypnosis, and guided imagery.
John Zic. Because the disease itself affects the skin and can lead to dryness, patients often suffer with dry skin. When I trained in Chicago, that was the foundation of our treatment, making sure that patients are using a super fatted soap such as Dove (Unilever, London, United Kingdom) or Cetaphil (Galderma Laboratories; Fort Worth, TX), making sure that they’re lubricating their skin frequently with something perhaps in the wintertime as thick as petroleum jelly. And then in the summertime perhaps with Sarna lotion (Crown Laboratories; Johnson City, TN), which has menthol. It’s important to note that when the patient’s skin is infected, the itch can skyrocket. Being aware and monitoring the skin for signs of infection such as crusting and impetigo-like findings can be helpful.
I also wanted to touch on fatigue. Patients can have fatigue for many reasons. Sometimes it’s because the itch is interfering with their sleep. How do you approach managing fatigue?
Lauren Pinter-Brown. There have been many studies about cancer fatigue, and it appears that one of the cheapest and easiest modalities is for patients to walk. We often suggest that our patients go on walks, however much they can do, because that has been seen over and over again in studies of cancer fatigue to be beneficial.
John Zic. Do you have any advice for nurses that might be helping to manage patients in a cutaneous lymphoma clinic?
Marianne Tawa. As this is a rare disease, nursing encounters with patients carrying a diagnosis of CTCL in both oncology and dermatology settings may be few and far between. I recommend nurses familiarize themselves with articles published on CTCL topics found in both dermatology and oncology peer review journals. Another avenue for gaining insight and education would be through continuing education courses. Resources can also be found for nurses, patients, and caregivers through advocacy foundations such as the Cutaneous Lymphoma Foundation (www.clfoundation.org) and the Lymphoma Research Foundation ([email protected]).
John Zic. Is there anything else that anyone would like to add to our discussion?
Lauren Pinter-Brown. One thing that we touched upon, but I was concerned that we didn’t emphasize, was the use of flow cytometry as a diagnostic tool in a patient with erythroderma. Sometimes biopsies of patients with erythroderma are not diagnostic, so clinicians need to be aware that there are other ways of diagnosing patients—nodal biopsy or flow cytometry. They should not only think of it as a staging tool but sometimes as a diagnostic tool.
Alejandro Ariel Gru. I agree. Particularly in patients who have Sézary syndrome or MF with peripheral blood involvement, sometimes the findings on the biopsy show a dissociation between how impressive the clinical presentation of the patient might be and how very few findings you might encounter on the skin biopsy. Therefore, relying on flow cytometry as a diagnostic tool is capital. Lauren, you briefly mentioned the criteria, which is looking for an abnormal CD4 to CD8 ratio of > 10%, abnormal loss of CD7, > 40%, or abnormal loss of CD26 of > 30%.
In addition, there are new markers that are now undergoing validation in the diagnosis of Sézary syndrome. One is KIR3DL2, which is a natural killer receptor that has been shown to be significantly upregulated in Sézary syndrome and appears to be both more sensitive and specific. With that also comes therapies that target the KIR3DL2 molecule.
John Zic. One of the first things we teach our dermatology residents to work up patients with erythroderma is that they shouldn’t expect the skin biopsy to help them sort out the cause of the erythroderma. As you mentioned, Lauren, the flow cytometry of peripheral blood should always be accompanied by a CBC with differential and platelets. And if the patients do have lymph nodes, consider a biopsy because sometimes that’s where you can make the firmest diagnosis of a T-cell lymphoma.
Acknowledgmentszz
The participants and Federal Practitioner would like to thank Susan Thornton, CEO of the Cutaneous Lymphoma Foundation for helping to arrange this roundtable discussion.
John Zic, MD. Let’s start by defining cutaneous T-cell lymphomas (CTCLs) and how they differ from other non-Hodgkin lymphomas. We also should discuss classification, which can be very confusing and epidemiology as it relates to the veteran population. Then I think we should dive into challenges with diagnosis and when should a VA or any provider consider mycosis fungoides (MF) and Sézary syndrome—the 2 most common variants of CTCLs.
I like to define the primary CTCLs as malignancies of the T-cell where the primary organ of involvement is the skin. However, this disease can spread to lymph nodes and visceral organs and the blood compartment in more advanced patients. Alejandro, could you provide some highlights about how CTCLs are classified?
Alejandro Ariel Gru, MD. Lymphomas are divided in the general hematology/oncology practice as Hodgkin and non-Hodgkin lymphomas. Traditionally all lymphomas that occur on the skin are non-Hodgkin lymphoma subtypes. That has specific connotations in terms of diagnosis, prognosis, and therapy. Because the T cells are one of the main residents of the subtypes of lymphocytes you encounter on the skin, most lymphomas that occur on the skin are derived of T-cell origin. B-cell lymphomas, in general, tend to be relatively uncommon or more infrequent.
There are 3 main subtypes of CTCL that present on the skin.1 MF is, by far, the most common subtype of CTCL. The disease tends to present in patients who are usually aged > 60 years and is more frequent in white males. It’s a lymphoma that is particularly relevant to the veteran population. The second subtype has many similarities to MF but shows substantial peripheral blood involvement and is referred to as Sézary syndrome. The third group is encompassed under the term CD30-positive lymphoproliferative disorders. This group includes 2 main subtypes: primary cutaneous anaplastic large-cell lymphoma and lymphomatoid papulosis. Some cases of MF develop progression to what we call large cell transformation, which implies cytologic transformation to a more aggressive lymphoma.
There are other cutaneous lymphomas that are far less common. Some are indolent and others can be more aggressive, but they represent < 5% of all CTCL subtypes.
Lauren Pinter-Brown, MD. That was a great summary about these non-Hodgkin lymphomas. In the veteran population, it’s wise to remember that there are many kinds of non-Hodgkin lymphomas. Because of the action that they have seen, some people, such as Vietnam veterans, might be more susceptible to non-Hodgkin lymphomas than others.
John Zic. That’s a good point because certainly non-Hodgkin lymphomas are listed as one of the potential disease associations with exposure to Agent Orange.
I’d like to move on to epidemiology and the incidence of MF and Sézary syndrome. An article that came out of Emory University in 2013 is one of the more up-to-date articles to examine the incidence and survival patterns of CTCL.2 The authors looked at patients from 2005 to 2008 and identified 2,273 patients in the Surveillance, Epidemiology, and End Results registry. They estimated that the incidence of MF in the US population is about 5.5 per 1,000,000 per year, which certainly makes it a rare disease. The incidence of Sézary syndrome was 0.1 per 1,000,000 per year, which comes out to about 1 per 10 million per year.
However, the MF incidence needs to be contrasted to the estimated incidence in the veteran population. In 2016, Larisa Geskin and colleagues from Columbia University and the Bronx US Department of Veterans Affairs (VA) Medical Center examined the VA database of patients with diagnoses of MF and Sézary syndrome.3 They combined them, but I have a feeling that the amount of Sézary syndrome patients was much less than those with MF. They estimated an incidence per million of 62 to 79 cases per 1,000,000 per year. The conclusion of Dr. Geskin’s study stated that the incidence of CTCL in the veteran population appears to be anywhere from 6 to 8 times higher. But if we use the most recent US incidence rates, it’s more than 10 times higher.
Those of you who have worked with veterans, either at the VA or in your private practice, do you have any ideas about why that might be?
Lauren Pinter-Brown. As you previously discussed, this is an illness of older people, and Vietnam veterans now are in their 60s and 70s. They may account for a lot of these diagnoses.
John Zic. That’s a good point. There’s quite a bit of talk about exposure to Agent Orange. But honestly, we really don’t know the cause of any of the CTCLs. We have not been able to identify a single cause. There are some risk factors. A 2014 article from the Journal of the National Cancer Institute looked at 324 cases of CTCL and compared it with 17,000 controls.4 They showed some interesting risk factors, such as body mass index (BMI) > 30 and smoking > 40 years. Similar to previous European studies, they showed that occupations like being a farmer, a painter, a woodworker, or a carpenter may carry additional risk.I wonder whether or not veterans were more likely to have some of these risk factors that this epidemiologic study picked up in addition to exposures that they may have encountered during their active-duty service. Interestingly, a decreased risk factor for developing MF was moderate physical activity. Clearly though, there are a large number of patients with CTCL in the veteran population.
I’d like to turn now to some of the challenges with diagnosis. Marianne, could you share some of your experience with early-stage disease and about how long it took them to be diagnosed?
Marianne Tawa, RN, MSN, ANP. Speaking specifically about early-stage disease, patients often share a history of waxing and waning rash that may not be particularly itchy. Confounding the picture, the distribution of early patch or plaque stage CTCL rash frequently occurs in covered areas. Many patients miss out on complete skin examinations by providers, thus early-stage CTCL may not be appreciated in a timely manner.
In certain scenarios, it may take upward of 5 to 7 years before the CTCL diagnosis is rendered. This is not because the patient delayed care. Nor is it because a skin biopsy was not performed. The progression of the disease and meeting the classic features of histology under the microscope can require clinical observation over time and repeated skin biopsies. We recommend patients refrain from topical steroid applications for 2 to 4 weeks prior to skin biopsy if we have a strong suspicion of CTCL. Many patients will report having a chronic eczematous process. Some patients may have a history of parapsoriasis, and they’re on the continuum for CTCL. That’s a common story for CTCL patients.
John Zic. What is the role of a skin biopsy in the diagnosis of CTCL? We see many patients who have had multiple skin biopsies who often wonder whether or not the diagnosis was missed by either the clinician or the pathologist.
Alejandro Ariel Gru. That is a great area of challenge in terms of pathologic diagnosis of early MF. A study led by Julia Scarisbrick, from an international registry data (PROCLIPI) on the early stages of the disease, showed a median delay of diagnosis of early MF of approximately 36 months.5 For all physicians involved in the diagnosis and care of patients with MF, the delay is probably significantly higher than that. We’ve seen patients who have lived without a diagnosis for a period of 10 or sometimes 15 years. That suggests that many cases are behaving in an indolent fashion, and patients are not progressing through the ‘natural’ stages of the disease and remain at the early stage. There also is the potential that other chronic inflammatory conditions, particularly psoriasis or parapsoriasis, can be confused with this entity. The diagnosis of certain types of parapsoriasis, can belong to the same spectrum of MF and can be treated in a similar way than patients with early stage MF are, such as phototherapy or methotrexate.
The diagnosis of MF relies on a combination of clinical, pathologic, and immunophenotypic findings where it is desired or preferred that at least 2 biopsies are done from different sides of the body. In addition to having a good clinical history that supports the diagnosis, a history of patches, plaques, and sometimes tumors in advanced stages in particular locations that are covered from the light (eg, trunk, buttocks, upper thighs, etc) combined with specific histopathologic criteria are capital to establish an accurate diagnosis.
In the biopsies, we look particularly for a lymphoid infiltrate that shows extension to the epidermis. We use the term epidermotropism to imply that these abnormal or neoplastic lymphocytes extend into the epidermis. They are also cytologically atypical. We see variations in the nucleus. In the size, we see a different character of the chromatin where they can be hyperchromatic. We also look for immunophenotypic aberrations, and particularly we analyze for patterns of expression of T-cell markers. Most cases of MF belong to a subset of T cells that are called CD4-positive or T-helper cells. We look for a patterned ratio of the CD4 and CD8 between the epidermis and an aberrant loss of the CD7 T-cell marker. Once we establish that we can see significant loss of these markers, we can tell where there is something wrong with that T-cell population, and likely belong to a neoplastic category.
In addition, we also rely on the molecular evaluation and search of a clonal population of T cells, by means of a T-cell receptor gene rearrangement study. Ideally, we like to see the establishment of a single clone of T cells that is matched in different biopsy sites. Proving that the same clone is present in 2 separate biopsies in 2 separate sites is the gold standard for diagnosis.6
John Zic. To recap, a biopsy is indicated for patients who have patches or plaques (that are slightly raised above the skin) in sun-protected areas that are fixed; rather than completely go away in the summer and come back in the winter, they are fixed if they have been present > 6 to 12 months. Many of these patients are diagnosed with eczema, psoriasis, allergic contact dermatitis, and other skin diseases before the clinician starts to think about other diagnoses, such as CTCL.
I agree that I would not rule out the diagnosis with 1 biopsy that does not show classic histologic changes. Also, I think that it’s important to alert the pathologist that you’re considering a diagnosis of T-cell lymphoma, either MF or some of the other subtypes, because that will certainly alert them to look a little closer at the infiltrating cells and perhaps do some of the other testing that was mentioned. Once we establish the MF diagnosis, staging studies may be indicated.
Lauren Pinter-Brown. Early stage would be patients with patches or plaques. Stage IA would be < 10% body surface area, and stage IB would be > 10%. I don’t perform scans for early-stage patients, but I do a very thorough physical and perform blood tests. For patients that have more advanced disease, such as tumors, erythroderma, or Sézary syndrome, I would conduct the same thorough examination and blood tests and scan the patient either with a computed tomography (CT) or a positron emission tomography (PET)/CT to detect adenopathy. We have to recognize that most of the adenopathy that is detected in these patients is peripheral, and we can feel it on physical examination.
John Zic. Do you prefer one imaging modality over the other? CT scan with IV contrast vs PET/CT?
Lauren Pinter-Brown. I tend to use PET/CT because it illuminates extranodal sites as well. I have to admit that sometimes it’s a problem to get that approved with insurance.
John Zic. In the federal system, many PET/CT scans are performed at other facilities. That would be an extra step in getting approval.
You mentioned Sézary syndrome. We should consider a diagnosis of Sézary syndrome when you have a patient with erythroderma, which means that they have > 80% of the skin covered in redness and scaling.
Lauren Pinter-Brown. The first step is to do a complete blood count (CBC) and see if there’s a lymphocytosis. Sometimes that really isn’t very sensitive, so my go-to test is flow cytometry. We are looking for an abnormal population of cells that, unlike normal T cells, often lack certain T-cell antigens. The most common would be CD7. We can confirm that this is a clone by T-cell gene rearrangement, and often in Sézary we like to compare the gene rearrangement seen in blood with what might be seen in the skin biopsy to confirm that they’re the same clone.
John Zic. That’s an excellent point. I know there are specific criteria to meet significant blood involvement. That is a topic of conversation among CTCL experts and something that might be changing over the next few years. But I think as it stands right now, having a lymphocytosis or at least an elevated CD4 count along with having a clone in the blood matching the clone in the skin are the first 2 steps in assessing blood involvement. However, the flow cytometry is very important. Not all medical centers are going to do flow cytometry—looking specifically for a drop of the CD7 or CD26 antigen among the CD4 population. But that is one of the major criteria that we look for in those patients with suspected blood involvement.
Marianne Tawa. Additionally, we would advise obtaining flow cytometry on patients that look like they have a robust skin burden with lots of patches, plaques, or tumors. We also perform lactate dehydrogenase (LDH) with staging.
John Zic. What do you usually tell patients with early-stage disease, those that have patches and plaques?
Marianne Tawa. For patients with stage IA disease, we are very optimistic about their prospects. We explain that the likelihood that early-stage disease will progress to a more advanced stage or rare variant is unlikely. This is very much a chronic disease, and the goal is to manage appropriately, palliate symptoms, and preserve quality of life (QOL).
Lauren Pinter-Brown. I often refer to a landmark paper by Youn H. Kim and colleagues that shows us that patients with IA disease who are at least treated usually have a normal lifespan.7 I encourage patients by sharing that data with them.
John Zic. Sean Whittaker and colleagues in the United Kingdom identified 5 risk factors for early-stage patients that may put them at higher risk for progressing: aged > 60 years; having a variant called folliculotropic MF; having palpable lymph nodes even if they’re reactive on biopsy, having plaques, and male sex.8 For staging of lymph nodes, what’s your usual approach when you see a patient with palpable lymph nodes?
Lauren Pinter-Brown. Many patients, particularly those with advanced skin disease, may have palpable lymph nodes that are reacting to their skin disease and on pathology would be dermatopathic. That would not change my management. I pay attention to the quality of the lymph node—if it’s very firm, if it’s > 2 cm, if it is persistent—before I biopsy. These patients have a higher incidence of wound infection after excisional biopsy. If the patient has pathologic lymph node involvement and effacement of the node with malignant cells, I would change my management. I do need to know that sort of information.
John Zic. Alejandro, as a hematopathologist can you comment on the debate about whether or not we actually do need an excisional biopsy or whether or not we can get a core lymph node biopsy to give you all the information that you need to grade it?
Alejandro Ariel Gru. There are 2 main modalities of biopsies we typically see for lymph nodes for evaluation and staging for involvement of CTCL. One is the traditional excisional biopsy that for the most part requires surgery with general anesthesia and has all the major implications that that type of procedure has. Many centers are looking at less invasive types of procedures, and needle core biopsies have become one of the most common forms of biopsy for all lymphoma subtypes. Excisional biopsies have the advantage of being able to see the whole lymph node, so you can determine and evaluate the architecture very well. Whereas needle core biopsies typically use a small needle to obtain a small piece of the tissue.
The likelihood of a successful diagnosis and accurate staging was compared recently in the British Journal of Dermatology.9 They were able to perform accurate staging in needle core biopsies of patients with MF. However, this is still a matter of debate; many people feel they are more likely to get enough information from an excisional biopsy. As we know, excisional biopsies sometimes can be hard, particularly if the large lymph node is located in an area that is difficult to access, for example, a retroperitoneal lymph node.
There are many staging categories that are used in the pathologic evaluation of lymph node involvement. On one hand, we could see the so-called dermatopathic changes, which is a reactive form of lymphadenopathy that typically happens in patients who have skin rashes and where there is no evidence of direct involvement by the disease (although there are some patients who can have T-cell clones by molecular methods). The patients who have clonal T cells perhaps might not do as well as the ones who do not. On the other hand, we have patients for whom the whole architecture of the lymph node is effaced or replaced by neoplastic malignant cells. Those patients are probably going to need more aggressive forms of therapy.10
John Zic. The type of lymph node biopsy has been a hot topic. If patients have palpable lymph nodes in the cervical, axillary, and inguinal area, I don’t know if it’s a consensus, but the recommendation right now is to consider performing a lymph node biopsy of the cervical lymph nodes first, axillary second, and inguinal lymph nodes third. That might have to do with the complication rates for those different areas.
I’d like to switch to a discussion to more advanced disease. CTCL tumors are defined as a dome-shaped nodule > 1 cm. They don’t have to be very big before we label it a tumor, and the disease is considered more advanced. For patients with a few tumors, what does your prognosis discussion sound like?
Marianne Tawa. Certainly, the prognosis discussion can become slightly more complicated when you move into the realm of tumor-stage development. This is especially true if a CTCL patient has lived with and managed indolent patches or plaques for several years. We approach these patients with optimism and with the goal of managing their tumors, whether it be with a skin-directed option, such as localized radiation or a host of approved systemic therapies. Patients presenting with or developing tumor-stage disease over time will require additional staging workup compared with early-stage disease staging practice. Patients are counseled on imaging use in tumor-stage disease and why flow cytometry may be requested to rule in or rule out accompanying peripheral blood involvement. Patients are exposed to a myriad of pictures, stories, and survival statistics from Internet research. It becomes our task to inform them of their unique presentation and tailored treatment plan, which thankfully may produce more favorable responses than those presented online.
Lauren Pinter-Brown. One thing that we focus on is the idea that a statistic regarding prognosis isn’t predictive for an individual patient. When patients go online, we caution them that many of the statistics are really old. There’s been a lot of new therapies in the past 10 years. Just looking at my patients, my feeling is that their prognosis has continued to improve over the decades that I’ve been involved in this area.
We have to take the statistics with a grain of salt, though certainly someone that has Sézary syndrome or someone that has nodal involvement or tumors is not going to fare as well as the patients that we talked about with stage I disease. However, if we all continue to do our jobs and have more and more treatment options for patients, that’s certainly going to change over time as it has with other non-Hodgkin lymphomas.
John Zic. We’ve all treated advanced patients with disease and some, of course, have died of the disease. When patients die of advanced CTCL, what are the things that lead to their demise?
Lauren Pinter-Brown. Probably the most common would be infections because their skin barrier has been broken. As the disease advances, their immune system also deteriorates. We may contribute to that sometimes with some of the therapies that we use, although we try and be judicious. First and foremost, the primary cause of death remains infection and sometimes inanition.
Marianne Tawa. I agree, infection or just the unfortunate progression of their lymphoma through the various armamentarium of treatments would be the 2 reasons.
John Zic. Let’s dive into therapy. I want to start with early stage. While, I don’t think there’s a role for systemic anticancer agents, certainly the IV agents for most patients with early-stage disease Marianne, you mentioned phototherapy. What are the types of phototherapy that you offer?
Marianne Tawa. We would start out with narrow band UVB therapy for patients with > 10% body surface area involvement. When applying topical corticosteroids to wider surface areas of the patient’s body is no longer feasible or effective, we recommend the initiation of narrow band UVB phototherapy. This is preferred because of its lessor adverse effect (AE) profile as far as nonmelanoma skin cancer risk. Patients commence narrow band UVB 3 times per week, with a goal of getting the patient into remission over a matter of months and then slowly tapering the phototherapy so that they get to a maintenance of once weekly.
Realizing that narrow band UVB may not penetrate deeper plaques or effectively reach folliculotropic variant of CTCL, we would employ PUVA, (psoralen and UVA). Patients are expected to protect their eyes with UVA glasses and remain out of the sun 24 hours following PUVA treatments. The cost of the methoxsalen can be an issue for some patients. Nonmelanoma skin cancer risks are increased in patients undergoing long-term PUVA treatments. Routine skin cancer surveillance is key.
There are monetary, time, and travel demands for patients receiving phototherapy. Thus, many CTCL patients are moving toward home-based narrow band UVB units supervised by their treating dermatologist. Other skin-directed treatment options, aside from topical corticosteroids and phototherapy, would include topical nitrogen mustard, imiquimod, and localized or total skin electron beam radiation.
John Zic. Here in Nashville, some of our veterans travel hundreds of miles to get to our center. It’s not practical for them to come here for the narrow band UVB phototherapy. Veterans can get approval through the VA Choice programs to have phototherapy performed by a local dermatologist closer to home. We also have had many veterans who choose to get home narrow band UVB phototherapy, which can be quite effective. Narrow band UVB phototherapy is among the most effective therapies for patients with generalized patches in particular, and maybe some with just a few plaques.
Medium potency topical steroids are not as helpful as superpotent topical steroids such as clobetasol, dipropionate ointment, or betamethasone dipropionate ointment. Usually, I tell patients to apply it twice a day for 8 weeks. You must be careful because these high-potency topical steroids can cause thinning of the skin, but it’s rarely seen, even in patients that may use them for 8 weeks if they’re applying them just to their patches and thin plaques. There are a few other topicals. There’s bexarotene gel, which is a topical retinoid, and mechlorethamine or nitrogen mustard gel that are available as topicals. Both of those can be helpful if patients have < 10% body surface area of patches or plaques because they can apply that at home.
Because of the excellent prognosis for patients in early stages, this is an area we want to try to avoid doing harm. For patients with advanced disease, what are some of the decisions that you think about in recommending a patient to get radiation therapy?
Lauren Pinter-Brown. I use radiation therapy sparingly and primarily for patients who either have only 1 tumor and the rest of their disease is patch and plaque or for patients who have very large tumors that are either cosmetically unacceptable or creating infection or pain. I treat people with systemic therapies primarily to prevent the formation of tumors.
John Zic. There probably is a role for total skin electron beam radiotherapy in patients who have failed multiple other skin-directed therapies and are progressing and then perhaps a role for more advanced patients who have multiple tumors where you’re trying to get some control of the disease. Are there any other situations where you might consider total skin electron beam?
Marianne Tawa. Yes, those are 2 scenarios. A third scenario would be in patients preparing for stem cell transplant. We typically do a modified 12 Gy regimen of total skin electron beam for palliation and up to 24 Gy regimen for patients who are in earnest preparing for a stem cell transplant.
John Zic. Systemic therapies also treat this disease. There are 2 oral agents. One is bexarotene capsules, a retinoid that binds to the RXR receptor and has a multitude of effects on different organ systems. It is probably the best tolerated oral agent we have. The other FDA-approved agent is vorinostat, a histone deacetylase inhibitor, but it has more gastrointestinal AEs than does bexarotene. Bexarotene has AEs as well, including hypertriglyceridemia and central hypothyroidism, which can throw a curveball to unsuspecting primary care physicians who might check thyroid function studies in these patients.
We certainly need to know about those AEs. There are many patients who have tumor-stage disease that can have radiotherapy to several tumors, then go on a drug like bexarotene capsules and may be able to maintain the remission for years. In my experience, it’s a drug that patients usually stay on. They can be weaned to a very low dose, but I’ve had several patients who come off of bexarotene only to suffer relapses.
Lauren, what are some of the things that you think about when you declare someone as having failed bexarotene or vorinostat and you’re thinking about IV therapies?
Lauren Pinter-Brown. Patient comorbidities and the particular compartment of their body that is involved are important factors. Do they have blood involvement, or not? Do they have nodal involvement, or not? Another concern is both acute and chronic toxicities that need to be discussed with the patient to determine an acceptable QOL. Finally, the schedule that you’re giving the drug. Some people may not be able to come in frequently. There are a lot of variables that go into making an individual decision at a particular time for a specific patient who will be using parenteral therapies.
John Zic. If we have a patient with advanced MF, tumors, and perhaps lymph node involvement, what are some of the systemic options that you would consider?
Lauren Pinter-Brown. With nodal involvement, an attractive option is something like IV romidepsin because we know that it treats peripheral T-cell lymphomas, which are aggressive nodal T-cell lymphomas. It’s FDA approved and also treats CTCL. Another is brentuximab vedotin if there is significant CD30 expression. It also is FDA approved for CTCL and has a long track record of treating certain peripheral T-cell lymphomas like anaplastic large cell.
John Zic. When would the stem cell transplant discussion start at your institution?
Lauren Pinter-Brown. It starts earlier for a younger patient because even though we do have lots of treatment if someone is aged 20 or30 years, I don’t really have any illusions that I have enough treatment options for them to live a normal lifespan if they have advanced disease. It’s a possibility for any patient when I see that the future options are dwindling, and that I am not going to be able to control the patient’s disease for much longer. Having said that, patients who have tumor-stage disease are among those that don’t do quite as well with allogeneic transplantation; ironically, patients with Sézary syndrome or erythroderma might do a little bit better.
John Zic. Before considering a stem cell transplant for patients with Sézary syndrome, that is erythroderma with significant blood involvement, what other treatment options would you offer?
Marianne Tawa. For low blood-burden disease, we might look at extracorporeal photopheresis as monotherapy or in combination with interferon or bexarotene. For patients with higher blood burden we might recommend low-dose alemtuzumab, especially if they have abundant CD52 expression. We also consider the newly FDA-approved anti-CCR4 antibody treatment, mogamulizumab, for patients presenting with Sézary syndrome. It is generally well tolerated but does have the potential for producing infusion reactions or drug rash.
Romidepsin has efficacy in blood, lymph node, and skin compartments. The primary considerations for patients considering romidepsin are prolonged infusion times and QOL AEs with gastrointestinal and taste disturbances and fatigue.
John Zic. Both of you have brought up an excellent point. This is a disease that while we do not have a good chance of curing, we have a pretty fair chance of controlling, especially if it’s early stage. The data from the stem cell transplant literature indicate that stem cell transplant may be one of the few modalities that we have that may offer a cure.11
Lauren Pinter-Brown. There are patients who are cured with allogeneic transplants; and the very first allogeneic transplants were performed well over 20 years ago. Many patients, even some in my practice, who were among those patients and continue to do extremely well without any evidence of disease. Sometimes when people have allogeneic transplantation, their disease relapse may be in a more indolent form that’s much easier to deal with than their original disease. Even if they’re not cured, the fact that the aggressive disease seems to be at bay may make them much easier to treat.
John Zic. Those are excellent points. You brought up photopheresis as a treatment modality for patients with evolving or early Sézary syndrome and patients with erythrodermic MF can also respond. We have a lot of experience with that at the Nashville VA medical center. We’re one of the few VA hospitals in the US that has a photopheresis unit. But the modality is available at many academic medical centers because it’s a treatment for graft-vs-host disease.
We tend to also consider photopheresis in patients who may have had an excellent response to another systemic agent. There are some data that patients who received photopheresis, after total skin electron beam therapy vs those who received chemotherapy after radiation, had a longer disease-free survival.12
I’d like to end with a discussion of something that’s very important, which is managing QOL issues for patients with CTCL. Itch is among some of the worst symptoms that can cause suffering in patients. But it is sometimes not a problem at all for patients who have a few patches or plaques. That’s one reason why they might ignore their rash. Certainly, as the disease progresses, especially those patients with erythroderma, the itch can be intractable and can have a major impact on their life. What are some approaches to managing itch at your institutions?
Lauren Pinter-Brown. One thing to be aware of is that the itch is not usually mediated by histamine, though people will often put the patients on a lot of antihistamines. I don’t find those to be the most effective treatments. I think of the itch in these patients as more of a neuropathic condition and would tend to treat more with things that you might use for neuropathy, such as gabapentin or doxepin or antidepressants. There’s a whole host of other treatments, such as aprepitant, something that I would use as an antiemetic, that might also be helpful for pruritus in this patient population.
John Zic. That’s my experience as well. I have found gabapentin to be helpful for patients with itch, though not universally.
Marianne Tawa. I consider itch a huge QOL concern for a large majority of our patients with a CTCL diagnosis. It’s on par with pain. In early-stage disease, pruritus levels improve as the cutaneous burden is reduced with skin-directed therapies such as, topical corticosteroid or phototherapy.
SSRI agents could also be considered for select patients. The antiemetic agent, aprepitant has been useful for addressing itch in a subset of our patients with Sézary syndrome. Patients will also seek out complementary modalities such acupuncture, hypnosis, and guided imagery.
John Zic. Because the disease itself affects the skin and can lead to dryness, patients often suffer with dry skin. When I trained in Chicago, that was the foundation of our treatment, making sure that patients are using a super fatted soap such as Dove (Unilever, London, United Kingdom) or Cetaphil (Galderma Laboratories; Fort Worth, TX), making sure that they’re lubricating their skin frequently with something perhaps in the wintertime as thick as petroleum jelly. And then in the summertime perhaps with Sarna lotion (Crown Laboratories; Johnson City, TN), which has menthol. It’s important to note that when the patient’s skin is infected, the itch can skyrocket. Being aware and monitoring the skin for signs of infection such as crusting and impetigo-like findings can be helpful.
I also wanted to touch on fatigue. Patients can have fatigue for many reasons. Sometimes it’s because the itch is interfering with their sleep. How do you approach managing fatigue?
Lauren Pinter-Brown. There have been many studies about cancer fatigue, and it appears that one of the cheapest and easiest modalities is for patients to walk. We often suggest that our patients go on walks, however much they can do, because that has been seen over and over again in studies of cancer fatigue to be beneficial.
John Zic. Do you have any advice for nurses that might be helping to manage patients in a cutaneous lymphoma clinic?
Marianne Tawa. As this is a rare disease, nursing encounters with patients carrying a diagnosis of CTCL in both oncology and dermatology settings may be few and far between. I recommend nurses familiarize themselves with articles published on CTCL topics found in both dermatology and oncology peer review journals. Another avenue for gaining insight and education would be through continuing education courses. Resources can also be found for nurses, patients, and caregivers through advocacy foundations such as the Cutaneous Lymphoma Foundation (www.clfoundation.org) and the Lymphoma Research Foundation ([email protected]).
John Zic. Is there anything else that anyone would like to add to our discussion?
Lauren Pinter-Brown. One thing that we touched upon, but I was concerned that we didn’t emphasize, was the use of flow cytometry as a diagnostic tool in a patient with erythroderma. Sometimes biopsies of patients with erythroderma are not diagnostic, so clinicians need to be aware that there are other ways of diagnosing patients—nodal biopsy or flow cytometry. They should not only think of it as a staging tool but sometimes as a diagnostic tool.
Alejandro Ariel Gru. I agree. Particularly in patients who have Sézary syndrome or MF with peripheral blood involvement, sometimes the findings on the biopsy show a dissociation between how impressive the clinical presentation of the patient might be and how very few findings you might encounter on the skin biopsy. Therefore, relying on flow cytometry as a diagnostic tool is capital. Lauren, you briefly mentioned the criteria, which is looking for an abnormal CD4 to CD8 ratio of > 10%, abnormal loss of CD7, > 40%, or abnormal loss of CD26 of > 30%.
In addition, there are new markers that are now undergoing validation in the diagnosis of Sézary syndrome. One is KIR3DL2, which is a natural killer receptor that has been shown to be significantly upregulated in Sézary syndrome and appears to be both more sensitive and specific. With that also comes therapies that target the KIR3DL2 molecule.
John Zic. One of the first things we teach our dermatology residents to work up patients with erythroderma is that they shouldn’t expect the skin biopsy to help them sort out the cause of the erythroderma. As you mentioned, Lauren, the flow cytometry of peripheral blood should always be accompanied by a CBC with differential and platelets. And if the patients do have lymph nodes, consider a biopsy because sometimes that’s where you can make the firmest diagnosis of a T-cell lymphoma.
Acknowledgmentszz
The participants and Federal Practitioner would like to thank Susan Thornton, CEO of the Cutaneous Lymphoma Foundation for helping to arrange this roundtable discussion.
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8. Benton EC, Crichton S, Talpur R, et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sézary syndrome. Eur J Cancer. 2013; 49(13):2859-2868.
9. Battistella M, Sallé de Chou C, de Bazelaire C, et al. Lymph node image-guided core-needle biopsy for cutaneous T-cell lymphoma staging. Br J Dermatol. 2016;175(6):1397-1400.
10. Johnson WT, Mukherji R, Kartan S, Nikbakht N, Porcu P, Alpdogan O. Allogeneic hematopoietic stem cell transplantation in advanced stage mycosis fungoides and Sézary syndrome: a concise review. Chin Clin Oncol. 2019;8(1):12.
11. Johnson WT, Mukherji R, Kartan S, Nikbakht N, Porcu P, Alpdogan O. Allogeneic hematopoietic stem cell transplantation in advanced stage mycosis fungoides and Sézary syndrome: a concise review. Chin Clin Oncol. 2019;8(1):12.
12. Wilson LD, Jones GW, Kim D, et al. Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol. 2000;43(1 Pt 1):54-60.
1. Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-1714.
2. Imam MH, Shenoy PJ, Flowers CR, Phillips A, Lechowicz MJ. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States. Leuk Lymphoma. 2013;54(4):752-759.
3. Del Guzzo C, Levin A, Dana A, et al. The incidence of cutaneous T-Cell lymphoma in the veteran population. Abstract 133. J Invest Dermatol. 2016;136(5 suppl 1):S24.
4. Aschebrook-Kilfoy B, Cocco P, La Vecchia C, et al. Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sèzary syndrome: the InterLymph Non-Hodgkin lymphoma subtypes project. J Natl Cancer Inst Monogr. 2014;48:98-105.
5. Scarisbrick JJ, Quaglino P, Prince HM, et al. The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients. Br J Dermatol. 2018. [Epub ahead of print.]
6. Thurber SE, Zhang B, Kim YH, Schrijver I, Zehnder J, Kohler S. T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides. J Am Acad Dermatol. 2007;57(5):782-790.
7. Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol. 1996;132(11):1309-1313.
8. Benton EC, Crichton S, Talpur R, et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sézary syndrome. Eur J Cancer. 2013; 49(13):2859-2868.
9. Battistella M, Sallé de Chou C, de Bazelaire C, et al. Lymph node image-guided core-needle biopsy for cutaneous T-cell lymphoma staging. Br J Dermatol. 2016;175(6):1397-1400.
10. Johnson WT, Mukherji R, Kartan S, Nikbakht N, Porcu P, Alpdogan O. Allogeneic hematopoietic stem cell transplantation in advanced stage mycosis fungoides and Sézary syndrome: a concise review. Chin Clin Oncol. 2019;8(1):12.
11. Johnson WT, Mukherji R, Kartan S, Nikbakht N, Porcu P, Alpdogan O. Allogeneic hematopoietic stem cell transplantation in advanced stage mycosis fungoides and Sézary syndrome: a concise review. Chin Clin Oncol. 2019;8(1):12.
12. Wilson LD, Jones GW, Kim D, et al. Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol. 2000;43(1 Pt 1):54-60.
COVID-19: Addressing the mental health needs of clinicians
SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.
Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.
Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.
Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
Current research studies on COVID-19
Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.1 In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.2
The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.3
Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.
The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.4
These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.
Future studies will become more critical in addressing this issue.
Risks to clinicians, families prevail
According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.5
Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.
A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.6 We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.7 Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.
Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.
Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition from the field at a time when we most need all hands on deck.8
Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.
Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.9 Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.10
Potential solutions for improving care
COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.9 Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.10
A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.11 Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.
We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.14 This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.
For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.15
Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.
Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.16
Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.17 The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.18
These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.
In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.
The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.
We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.
Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.
References
1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.
2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.
3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.
4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.
5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.
6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.
7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.
8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.
9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.
10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.
11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.
12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.
13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.
14. Xiao H et al. Med Sci Monit. 2020;26:e923549.
15. Bergus GR et al. Acad Med. 2001;76:1148-52.
16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.
17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”
18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”
SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.
Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.
Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.
Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
Current research studies on COVID-19
Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.1 In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.2
The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.3
Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.
The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.4
These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.
Future studies will become more critical in addressing this issue.
Risks to clinicians, families prevail
According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.5
Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.
A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.6 We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.7 Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.
Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.
Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition from the field at a time when we most need all hands on deck.8
Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.
Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.9 Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.10
Potential solutions for improving care
COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.9 Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.10
A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.11 Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.
We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.14 This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.
For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.15
Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.
Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.16
Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.17 The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.18
These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.
In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.
The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.
We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.
Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.
References
1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.
2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.
3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.
4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.
5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.
6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.
7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.
8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.
9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.
10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.
11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.
12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.
13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.
14. Xiao H et al. Med Sci Monit. 2020;26:e923549.
15. Bergus GR et al. Acad Med. 2001;76:1148-52.
16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.
17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”
18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”
SARS-CoV-2 and the disease it causes, COVID-19, continues to spread around the world with a devastating social and economic impact. Undoubtedly, health care workers are essential to overcoming this crisis. If these issues are left unaddressed, low morale, burnout, or absenteeism could lead to the collapse of health care systems.
Historically, the health care industry has been one of the most hazardous environments in which to work. Employees in this industry are constantly exposed to a complex variety of health and safety hazards.
Particularly, risks from biological exposure to diseases such as tuberculosis, HIV, and currently COVID-19 are taking a considerable toll on health care workers’ health and well-being. Health care workers are leaving their families to work extra shifts, dealing with limited resources, and navigating the chaos. On top of all that, they are sacrificing their lives through these uncertain times.
Despite their resilience, health care workers – like the general population – can have strong psychological reactions of anxiety and fear during a pandemic. Still, they are required to continue their work amid uncertainty and danger.
Current research studies on COVID-19
Several studies have identified the impact of working in this type of environment during previous pandemics and disasters. In a study of hospital employees in China during the SARS epidemic (2002-2003), Ping Wu, PhD, and colleagues found that 10% of the participants experienced high levels of posttraumatic stress.1 In a similar study in Taiwan, researchers found that 17.3% of employees had developed significant mental health symptoms during the SARS outbreak.2
The impact of COVID-19 on health care workers seems to be much worse. A recent study from China indicates that 50.4% of hospital employees showed signs of depression, 44.6% had anxiety, and 34% had insomnia.3
Another recent cross-sectional study conducted by Lijun Kang, PhD, and associates evaluated the impact on mental health among health care workers in Wuhan, China, during the COVID-19 outbreak. This was the first study on the mental health of health care workers. This study recruited health care workers in Wuhan to participate in the survey from Jan. 29 to Feb. 4, 2020. The data were collected online with an anonymous, self-rated questionnaire that was distributed to all workstations. All subjects provided informed consent electronically prior to participating in the survey.
The survey questionnaire was made up of six components: primary demographic data, mental health assessment, risks of direct and indirect exposure to COVID-19, mental health care services accessed, psychological needs, and self-perceived health status, compared with that before the COVID-19 outbreak. A total of 994 health care workers responded to this survey, and the results are fascinating: 36.9% had subthreshold mental health distress (mean Patient Health Questionnaire–9 score, 2.4), 34.4% reported mild disturbances (mean PHQ-9, 5.4), 22.4% had moderate (mean PHQ-9, 9.0), and 6.2% reported severe disturbance (mean PHQ-9, 15.1). In this study, young women experienced more significant psychological distress. Regarding access to mental health services, 36.3% reported access to psychological materials, such as books on mental health; 50.4% used psychological resources available through media, such as online self-help coping methods; and 17.5% participated in counseling or psychotherapy.4
These findings emphasize the importance of being equipped to ensure the health and safety of health care workers through mental health interventions, both at work and in the community during this time of anxiety and uncertainty.
Future studies will become more critical in addressing this issue.
Risks to clinicians, families prevail
According to a recent report released by the Centers for Disease Control and Prevention, more than 9,000 health care workers across the United States had contracted COVID-19 as of mid-April, and 27 had died since the start of the pandemic.5
Health care workers are at risk around the globe, not only by the nature of their jobs but also by the shortage of personal protective equipment (PPE). In addition, the scarcity of N95 masks, respirators, and COVID-19 testing programs is causing the virus to spread among health care workers all over the world.
A study published recently by Celso Arango, MD, PhD, reported that 18% of staff at a hospital in Madrid had been infected with COVID-19. Dr. Arango speculated that transmission might be attributable to interactions with colleagues rather than with patients.6 We know, for example, that large proportions of people in China reportedly carried the virus while being asymptomatic.7 Those findings might not be generalizable, but they do suggest that an asymptomatic person could be a cause of contagion among professionals. Therefore, early screening and testing are critical – and should be priorities in health care settings.
Another problem clinicians can encounter is that, when they are called on to deal with very agitated patients, they might not get enough time to put on PPE. In addition, PPE can easily break and tear during the physical restraint process.
Working long hours is also putting a significant strain on health care workers and exposes them to the risk of infection. Also, health care workers not only worry about their safety but also fear bringing the virus to their families. They can also feel guilty about their conflicting feelings about exposing themselves and their families to risk. It is quite possible that, during this COVID-19 pandemic, health care workers will face a “care paradox,” in which they must choose between patients’ safety and their own. This care paradox can significantly contribute to a feeling of burnout, stress, and anxiety. Ultimately, this pandemic could lead to attrition from the field at a time when we most need all hands on deck.8
Further, according to a World Health Organization report on mental health and psychosocial consideration during the COVID-19 outbreak, some health care workers, unfortunately, experience avoidance by their family members or communities because of stigma, fear, and anxiety. This avoidance threatens to make an already challenging situation far worse for health care workers by increasing isolation.
Even after acute outbreak are over, the effects on health care workers can persist for years. In a follow-up study 13-26 months after the SARS outbreak, Robert G. Maunder, MD, and associates found that Toronto-area health care workers reported significantly higher levels of burnout, psychological distress, and posttraumatic stress. They were more likely to have reduced patient contact and work hours, and to have avoided behavioral consequences of stress.9 Exposure to stressful work conditions during a pandemic also might put hospital employees at a much higher risk of alcohol and substance use disorders.10
Potential solutions for improving care
COVID-19 has had a massive impact on the mental health of health care workers around the globe. Fortunately, there are evidence-based strategies aimed at mitigating the effects of this pandemic on health care workers. Fostering self-efficacy and optimism has been shown to improve coping and efficiency during disasters.9 Higher perceived workplace safety is associated with a lower risk of anxiety, depression, and posttraumatic stress among health care workers, while a lack of social support has been linked to adverse behavioral outcomes.10
A recent study found that, among Chinese physicians who cared for COVID-19 victims, more significant social support was associated with better sleep quality, greater self-effectiveness, and less psychological distress.11 Positive leadership and a professional culture of trust, and openness with unambiguous communication have been shown to improve the engagement of the medical workforce.12,13 Psychiatrists must advocate for the adoption of these practices in the workplace. Assessing and addressing mental health needs, in addition to the physical health of the health care workforce, is of utmost importance.
We can accomplish this in many ways, but we have to access our health care workers. Similar to our patient population, health care workers also experience stigma and anxiety tied to the disclosure of mental health challenges. This was reported in a study conducted in China, in which a specific psychological intervention using a hotline program was used for the medical team.14 This program provided psychological interventions/group activities aimed at releasing stress and anxiety. However, initially, the implementation of psychological interventions encountered obstacles.
For example, some members of the medical staff declined to participate in group or individual psychological interventions. Moreover, nurses showed irritability, unwillingness to join, and some staff refused, stating that “they did not have any problems.” Finally, psychological counselors regularly visited the facility to listen to difficulties or stories encountered by staff at work and provide support accordingly. More than 100 frontline medical staff participated and reported feeling better.15
Currently, several U.S. universities/institutes have implemented programs aimed at protecting the health and well-being of their staff during the COVID-19 pandemic. For instance, the department of psychiatry and behavioral health at Hackensack Meridian Health has put comprehensive system programs in place for at 16 affiliated medical centers and other patient care facilities to provide support during the COVID-19 crisis. A 24/7 team member support hotline connecting team members with a behavioral health specialist has become available when needed. This hotline is backed up by social workers, who provide mental health resources. In addition, another service called “Coping with COVID Talks” is available. This service is a virtual psychoeducational group facilitated by psychologists focusing on building coping skills and resilience.
Also, the consultation-liaison psychiatrists in the medical centers provide daily support to clinicians working in ICUs. These efforts have led to paradoxical benefits for employers, further leading to less commuting, more safety, and enhanced productivity for the clinician, according to Ramon Solhkhah, MD, MBA, chairman of the psychiatry department.16
Some universities, such as the University of North Carolina at Chapel Hill, have created mental health/telehealth support for health care workers, where they are conducting webinars on coping with uncertainty tied to COVID-19.17 The University of California, San Francisco, also has been a leader in this effort. That institution has employed its psychiatric workforce as volunteers – encouraging health care workers to use digital health apps and referral resources. Also, these volunteers provide peer counseling, phone support, and spiritual counseling to their health care workers.18
These approaches are crucial in this uncertain, challenging time. Our mental health system is deeply flawed, understaffed, and not well prepared to manage the mental health issues among health care workers. Psychiatric institutes/facilities should follow comprehensive and multifaceted approaches to combat the COVID-19 crisis. Several preventive measures can be considered in coping with this pandemic, such as stress reduction, mindfulness, and disseminating educational materials. Also, increased use of technology, such as in-the-moment measures, development of hotlines, crisis support, and treatment telepsychiatry for therapy and medication, should play a pivotal role in addressing the mental health needs of health care workers.
In addition, it is expected that, as a nation, we will see a surge of mental health needs for illnesses such as depression and PTSD, just as we do after “natural disasters” caused by a variety of reasons, including economic downturns. After the SARS outbreak in 2003, for example, health care workers showed symptoms of PTSD. The COVID-19 pandemic could have a similar impact.
The severity of mental health challenges among clinicians cannot be predicted at this time, but we can speculate that the traumatic impact of COVID-19 will prove long lasting, particularly among clinicians who served vulnerable populations and witnessed suffering, misery, and deaths. The long-term consequences might range from stress and anxiety to fear, depression, and PTSD. Implementation of mental health programs/psychological interventions/support will reduce the impact of mental health issues among these clinicians.
We must think about the best ways to optimize mental health among health care workers while also come up with innovative ways to target this at-risk group. The mental health of people who are saving lives – our frontline heroes – should be taken into consideration seriously around the globe. We also must prioritize the mental health of these workers during this unprecedented, challenging, and anxiety-provoking time.
Dr. Malik and Mr. Van Wert are affiliated with Johns Hopkins University, Baltimore. Dr. Kumari, Dr. Afzal, Dr. Doumas, and Dr. Solhkhah are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. All six authors disclosed having no conflicts of interest. The authors would like to thank Vinay Kumar for his assistance with the literature review and for proofreading and editing this article.
References
1. Wu P et al. Can J Psychiatry. 2009;54(5):302-11.
2. Lu YC et al. Psychother Psychosom. 2006;75(6):370-5.
3. Lai J et al. JAMA Netw Open. 2020;3(3):e203976.
4. Kang L et al. Brain Behav Immun. 2020 Mar 30. doi: 10.1016/j.bbi.2020.03.028.
5. Centers for Disease Control and Prevention COVID-19 Response Team. MMWR. 2020 Apr 17;69(15):477-81.
6. Arango C. Biol Psychiatry. 2020 Apr 8. doi: 10.1016/j.biopsych.2020.04.003.
7. Day M. BMJ. 2020 Apr 2. doi: 10.1136/bmj.m1375.
8. Kirsch T. “Coronavirus, COVID-19: What happens if health care workers stop showing up?” The Atlantic. 2020 Mar 24.
9. Maunder RG et al. Emerg Infect Dis. 2006;12(12):1924-32.
10. Wu P et al. Alcohol Alcohol. 2008;43(6):706-12.
11. Brooks SK et al. BMC Psychol. 2016 Apr 26;4:18.
12. Smith BW et al. Am J Infect Control. 2009; 37:371-80.
13. Chen Q et al. Lancet Psychiatry. 2020 Apr 1;7(14):PE15-6.
14. Xiao H et al. Med Sci Monit. 2020;26:e923549.
15. Bergus GR et al. Acad Med. 2001;76:1148-52.
16. Bergeron T. “Working from home will be stressful. Here’s how employees (and employers) can handle it.” roi-nj.com. 2020 Mar 23.
17. UNChealthcare.org. “Mental Health/Emotional Support Resources for Coworkers and Providers Coping with COVID-19.”
18. Psych.ucsf.edu/coronoavirus. “Resources to Support Your Mental Health During the COVID-19 Outbreak.”
COVID-19 and pregnancy: Is miscarriage a risk?
- Are you treating pregnant patients with COVID-19? Take this brief survey: https://www.surveymonkey.com/r/CDZ7VFK
- Enroll your patients in PRIORITY: Pregnancy Coronavirus Outcomes Registry
- Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection JAMA. April 30, 2020
- Are you treating pregnant patients with COVID-19? Take this brief survey: https://www.surveymonkey.com/r/CDZ7VFK
- Enroll your patients in PRIORITY: Pregnancy Coronavirus Outcomes Registry
- Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection JAMA. April 30, 2020
- Are you treating pregnant patients with COVID-19? Take this brief survey: https://www.surveymonkey.com/r/CDZ7VFK
- Enroll your patients in PRIORITY: Pregnancy Coronavirus Outcomes Registry
- Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection JAMA. April 30, 2020
COVID-19 in the era of loneliness
The natural state of human beings is to live together and function as organized groups. The beginnings of communities have primeval origins; evolutionarily, societies that worked together were more productive, efficient and—probably most important—safer. Thousands of years of evolution have ingrained these behaviors as part of our genetic constitution and developmental process. Social integration and acceptance thus are an integral part of basic human behavior and provide a sense of protection, pleasure, and purpose in life.
Unfortunately, the social isolation necessary to address the coronavirus disease 2019 (COVID-19) pandemic is preventing this integration, and is likely to worsen what some have called an epidemic of loneliness. As mental health clinicians, we need to use technology to strengthen our patients’ social support systems.
Loneliness: A growing problem
Changes in society over the last few decades have led to increased isolation. In the last 50 years, there has been a rise in single-person households in the United States. This is most common in large cities, where the prevalence is approximately 40%.1 The average number of confidants or the size of an American’s social network reduced by more than one-third from 1985 to 2009.2 In a study published in 2018, the health service company Cigna used the UCLA Loneliness Scale to survey >20,000 American adults.3 Nearly half of respondents reported always feeling alone (46%) or left out (47%), and individuals age 18 to 22 were the loneliest age group and claimed to be in worse health than older age groups. Furthermore, the results suggested that people who felt lonelier were more likely to have poor sleep and be less physically active. Americans who lived with others were less likely to report feeling lonely, except for single parents living only with their children. The results also showed that people who engage in meaningful interactions with others had lower loneliness scores and perceived that they were in better overall health.3
Studies have consistently demonstrated a link between loneliness and health problems such as cardiovascular disease, substance use disorders (SUDs), and mood disorders. A 2010 meta-analysis of 148 prospective studies with 308,849 participants found that the influence of social relationships on the risk of mortality is comparable to well-established risk factors for mortality such as smoking and alcohol consumption.4 These findings were confirmed in a 2015 meta-analysis that included 70 studies with 3.4 million participants followed for an average of 7 years. 5
Loneliness has been identified as a social determinant of health and is considered by many to be epidemic in proportion in developed countries. According to a 2019 Business Insider survey, almost 20% of US health care leaders planned to address social isolation in the next 12 months.6
Increased vulnerability during COVID-19 isolation
The forced quarantines and social distancing imposed by the COVID-19 crisis are likely to further exacerbate the loneliness epidemic. Hopefully, this increased isolation will not last more than several months, and its effect on chronic medical illnesses will be minor. However, for patients with mental illness, this further isolation, in conjunction with rising societal anxiety and fear of the potentially devastating financial consequences, could worsen their illness, and might even lead to suicidal ideation or behavior.
Individuals with SUDs are particularly vulnerable to the social limitations required by COVID-19. While social isolation is essential to limit the spread of COVID-19, this restriction poses unique challenges for these patients because connection and social support are important aspects of achieving and maintaining sobriety.7
Continue to: A call to action
A call to action
As mental health clinicians, we need to proactively engage with our patients to develop a plan to strengthen their social support systems. This may mean suggesting that they stay in contact with their network of people via video conferencing or by using the phone. We need to identify high-risk patients and continue to provide treatment via telepsychiatry. This is especially necessary to prevent relapse among patients with SUDs or mood disorders, and to minimize the risk of suicide.
We are ethically required to provide an atmosphere of trust, safety, and social inclusion by using resources, such as telehealth, video conferencing, and other online tools, to ameliorate the short- and long-term impact of COVID-19 isolation. Providing avenues that are easily accessible, are supportive, and maintain standards of care are essential. These resources should be implemented as early as possible to avoid negative outcomes regarding both COVID-19 and mental health.
There is also a significant risk that once circumstances improve, there will be a surge in the number of patients seeking a higher level of mental health care. Our actions and preparedness today will define the trajectory of our patients’ mental health in the future, potentially for years to come. While presently we are forced to be reactive, hopefully what is borne out of this crisis will translate into proactive measures for future crises.
Let this brief commentary serve as a call to action. As society finds ways to work from home, mental health clinicians need to lead the charge to use these same technologies to increase our patients’ social interactions. If we do not find ways to address the mental health burden of the COVID-19 pandemic, who will? We are all part of the mental health community, and we need to continue to function as an organized group, as has been the natural state of human beings for thousands of years.
Bottom Line
The social isolation required to limit the spread of the coronavirus disease 2019 pandemic is likely to increase loneliness, particularly among vulnerable patients with mood disorders and/or substance use disorders. As mental health clinicians, we need to work to strengthen our patients’ social support systems using resources such as video conferencing and other technologies.
Related Resources
- Cacioppo S, Grippo AJ, London S, et al. Loneliness: clinical import and interventions. Perspect Psychol Sci. 2015;10(2):238-249.
- Geriatric loneliness with Dr. Steven Wengel. Psychcast (podcast). https://www.mdedge.com/podcasts/psychcast/geriatricloneliness-dr-steven-wengel. Published April 1, 2020.
1. Howe N. Millennials and the loneliness epidemic. Forbes. https://www.forbes.com/sites/neilhowe/2019/05/03/millennials-and-the-loneliness-epidemic/. Published May 3, 2019. Accessed April 10, 2020.
2. The Economist. All the lonely people: loneliness is a serious public-health problem. https://www.economist.com/international/2018/09/01/loneliness-is-a-serious-public-health-problem. Published September 1, 2018. Accessed April 10, 2020.
3. Cigna. New Cigna study reveals loneliness at epidemic levels in America. https://www.cigna.com/newsroom/news-releases/2018/new-cigna-study-reveals-loneliness-at-epidemic-levels-in-america. Published May 1, 2018. Accessed April 10, 2020.
4. Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. PLoS Med. 2010;7(7):e1000316.
5. Holt-Lunstad J, Smith TB, Baker M, et al. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015;10(2):227-237.
6. Finley D. How increased social distancing for the coronavirus could spur a loneliness epidemic. Business Insider. https://www.businessinsider.com/coronavirus-could-spur-loneliness-epidemic-2020-3. Published March 16, 2020. Accessed April 10, 2020.
7. Roy L. Addiction treatment facilities: are they prepared for the COVID-19 coronavirus outbreak? Forbes. https://www.forbes.com/sites/lipiroy/2020/03/16/addiction-treatment-facilities-are-they-prepared-for-covid-19/#555149b544ea. Published March 16, 2020. Accessed April 10, 2020.
The natural state of human beings is to live together and function as organized groups. The beginnings of communities have primeval origins; evolutionarily, societies that worked together were more productive, efficient and—probably most important—safer. Thousands of years of evolution have ingrained these behaviors as part of our genetic constitution and developmental process. Social integration and acceptance thus are an integral part of basic human behavior and provide a sense of protection, pleasure, and purpose in life.
Unfortunately, the social isolation necessary to address the coronavirus disease 2019 (COVID-19) pandemic is preventing this integration, and is likely to worsen what some have called an epidemic of loneliness. As mental health clinicians, we need to use technology to strengthen our patients’ social support systems.
Loneliness: A growing problem
Changes in society over the last few decades have led to increased isolation. In the last 50 years, there has been a rise in single-person households in the United States. This is most common in large cities, where the prevalence is approximately 40%.1 The average number of confidants or the size of an American’s social network reduced by more than one-third from 1985 to 2009.2 In a study published in 2018, the health service company Cigna used the UCLA Loneliness Scale to survey >20,000 American adults.3 Nearly half of respondents reported always feeling alone (46%) or left out (47%), and individuals age 18 to 22 were the loneliest age group and claimed to be in worse health than older age groups. Furthermore, the results suggested that people who felt lonelier were more likely to have poor sleep and be less physically active. Americans who lived with others were less likely to report feeling lonely, except for single parents living only with their children. The results also showed that people who engage in meaningful interactions with others had lower loneliness scores and perceived that they were in better overall health.3
Studies have consistently demonstrated a link between loneliness and health problems such as cardiovascular disease, substance use disorders (SUDs), and mood disorders. A 2010 meta-analysis of 148 prospective studies with 308,849 participants found that the influence of social relationships on the risk of mortality is comparable to well-established risk factors for mortality such as smoking and alcohol consumption.4 These findings were confirmed in a 2015 meta-analysis that included 70 studies with 3.4 million participants followed for an average of 7 years. 5
Loneliness has been identified as a social determinant of health and is considered by many to be epidemic in proportion in developed countries. According to a 2019 Business Insider survey, almost 20% of US health care leaders planned to address social isolation in the next 12 months.6
Increased vulnerability during COVID-19 isolation
The forced quarantines and social distancing imposed by the COVID-19 crisis are likely to further exacerbate the loneliness epidemic. Hopefully, this increased isolation will not last more than several months, and its effect on chronic medical illnesses will be minor. However, for patients with mental illness, this further isolation, in conjunction with rising societal anxiety and fear of the potentially devastating financial consequences, could worsen their illness, and might even lead to suicidal ideation or behavior.
Individuals with SUDs are particularly vulnerable to the social limitations required by COVID-19. While social isolation is essential to limit the spread of COVID-19, this restriction poses unique challenges for these patients because connection and social support are important aspects of achieving and maintaining sobriety.7
Continue to: A call to action
A call to action
As mental health clinicians, we need to proactively engage with our patients to develop a plan to strengthen their social support systems. This may mean suggesting that they stay in contact with their network of people via video conferencing or by using the phone. We need to identify high-risk patients and continue to provide treatment via telepsychiatry. This is especially necessary to prevent relapse among patients with SUDs or mood disorders, and to minimize the risk of suicide.
We are ethically required to provide an atmosphere of trust, safety, and social inclusion by using resources, such as telehealth, video conferencing, and other online tools, to ameliorate the short- and long-term impact of COVID-19 isolation. Providing avenues that are easily accessible, are supportive, and maintain standards of care are essential. These resources should be implemented as early as possible to avoid negative outcomes regarding both COVID-19 and mental health.
There is also a significant risk that once circumstances improve, there will be a surge in the number of patients seeking a higher level of mental health care. Our actions and preparedness today will define the trajectory of our patients’ mental health in the future, potentially for years to come. While presently we are forced to be reactive, hopefully what is borne out of this crisis will translate into proactive measures for future crises.
Let this brief commentary serve as a call to action. As society finds ways to work from home, mental health clinicians need to lead the charge to use these same technologies to increase our patients’ social interactions. If we do not find ways to address the mental health burden of the COVID-19 pandemic, who will? We are all part of the mental health community, and we need to continue to function as an organized group, as has been the natural state of human beings for thousands of years.
Bottom Line
The social isolation required to limit the spread of the coronavirus disease 2019 pandemic is likely to increase loneliness, particularly among vulnerable patients with mood disorders and/or substance use disorders. As mental health clinicians, we need to work to strengthen our patients’ social support systems using resources such as video conferencing and other technologies.
Related Resources
- Cacioppo S, Grippo AJ, London S, et al. Loneliness: clinical import and interventions. Perspect Psychol Sci. 2015;10(2):238-249.
- Geriatric loneliness with Dr. Steven Wengel. Psychcast (podcast). https://www.mdedge.com/podcasts/psychcast/geriatricloneliness-dr-steven-wengel. Published April 1, 2020.
The natural state of human beings is to live together and function as organized groups. The beginnings of communities have primeval origins; evolutionarily, societies that worked together were more productive, efficient and—probably most important—safer. Thousands of years of evolution have ingrained these behaviors as part of our genetic constitution and developmental process. Social integration and acceptance thus are an integral part of basic human behavior and provide a sense of protection, pleasure, and purpose in life.
Unfortunately, the social isolation necessary to address the coronavirus disease 2019 (COVID-19) pandemic is preventing this integration, and is likely to worsen what some have called an epidemic of loneliness. As mental health clinicians, we need to use technology to strengthen our patients’ social support systems.
Loneliness: A growing problem
Changes in society over the last few decades have led to increased isolation. In the last 50 years, there has been a rise in single-person households in the United States. This is most common in large cities, where the prevalence is approximately 40%.1 The average number of confidants or the size of an American’s social network reduced by more than one-third from 1985 to 2009.2 In a study published in 2018, the health service company Cigna used the UCLA Loneliness Scale to survey >20,000 American adults.3 Nearly half of respondents reported always feeling alone (46%) or left out (47%), and individuals age 18 to 22 were the loneliest age group and claimed to be in worse health than older age groups. Furthermore, the results suggested that people who felt lonelier were more likely to have poor sleep and be less physically active. Americans who lived with others were less likely to report feeling lonely, except for single parents living only with their children. The results also showed that people who engage in meaningful interactions with others had lower loneliness scores and perceived that they were in better overall health.3
Studies have consistently demonstrated a link between loneliness and health problems such as cardiovascular disease, substance use disorders (SUDs), and mood disorders. A 2010 meta-analysis of 148 prospective studies with 308,849 participants found that the influence of social relationships on the risk of mortality is comparable to well-established risk factors for mortality such as smoking and alcohol consumption.4 These findings were confirmed in a 2015 meta-analysis that included 70 studies with 3.4 million participants followed for an average of 7 years. 5
Loneliness has been identified as a social determinant of health and is considered by many to be epidemic in proportion in developed countries. According to a 2019 Business Insider survey, almost 20% of US health care leaders planned to address social isolation in the next 12 months.6
Increased vulnerability during COVID-19 isolation
The forced quarantines and social distancing imposed by the COVID-19 crisis are likely to further exacerbate the loneliness epidemic. Hopefully, this increased isolation will not last more than several months, and its effect on chronic medical illnesses will be minor. However, for patients with mental illness, this further isolation, in conjunction with rising societal anxiety and fear of the potentially devastating financial consequences, could worsen their illness, and might even lead to suicidal ideation or behavior.
Individuals with SUDs are particularly vulnerable to the social limitations required by COVID-19. While social isolation is essential to limit the spread of COVID-19, this restriction poses unique challenges for these patients because connection and social support are important aspects of achieving and maintaining sobriety.7
Continue to: A call to action
A call to action
As mental health clinicians, we need to proactively engage with our patients to develop a plan to strengthen their social support systems. This may mean suggesting that they stay in contact with their network of people via video conferencing or by using the phone. We need to identify high-risk patients and continue to provide treatment via telepsychiatry. This is especially necessary to prevent relapse among patients with SUDs or mood disorders, and to minimize the risk of suicide.
We are ethically required to provide an atmosphere of trust, safety, and social inclusion by using resources, such as telehealth, video conferencing, and other online tools, to ameliorate the short- and long-term impact of COVID-19 isolation. Providing avenues that are easily accessible, are supportive, and maintain standards of care are essential. These resources should be implemented as early as possible to avoid negative outcomes regarding both COVID-19 and mental health.
There is also a significant risk that once circumstances improve, there will be a surge in the number of patients seeking a higher level of mental health care. Our actions and preparedness today will define the trajectory of our patients’ mental health in the future, potentially for years to come. While presently we are forced to be reactive, hopefully what is borne out of this crisis will translate into proactive measures for future crises.
Let this brief commentary serve as a call to action. As society finds ways to work from home, mental health clinicians need to lead the charge to use these same technologies to increase our patients’ social interactions. If we do not find ways to address the mental health burden of the COVID-19 pandemic, who will? We are all part of the mental health community, and we need to continue to function as an organized group, as has been the natural state of human beings for thousands of years.
Bottom Line
The social isolation required to limit the spread of the coronavirus disease 2019 pandemic is likely to increase loneliness, particularly among vulnerable patients with mood disorders and/or substance use disorders. As mental health clinicians, we need to work to strengthen our patients’ social support systems using resources such as video conferencing and other technologies.
Related Resources
- Cacioppo S, Grippo AJ, London S, et al. Loneliness: clinical import and interventions. Perspect Psychol Sci. 2015;10(2):238-249.
- Geriatric loneliness with Dr. Steven Wengel. Psychcast (podcast). https://www.mdedge.com/podcasts/psychcast/geriatricloneliness-dr-steven-wengel. Published April 1, 2020.
1. Howe N. Millennials and the loneliness epidemic. Forbes. https://www.forbes.com/sites/neilhowe/2019/05/03/millennials-and-the-loneliness-epidemic/. Published May 3, 2019. Accessed April 10, 2020.
2. The Economist. All the lonely people: loneliness is a serious public-health problem. https://www.economist.com/international/2018/09/01/loneliness-is-a-serious-public-health-problem. Published September 1, 2018. Accessed April 10, 2020.
3. Cigna. New Cigna study reveals loneliness at epidemic levels in America. https://www.cigna.com/newsroom/news-releases/2018/new-cigna-study-reveals-loneliness-at-epidemic-levels-in-america. Published May 1, 2018. Accessed April 10, 2020.
4. Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. PLoS Med. 2010;7(7):e1000316.
5. Holt-Lunstad J, Smith TB, Baker M, et al. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015;10(2):227-237.
6. Finley D. How increased social distancing for the coronavirus could spur a loneliness epidemic. Business Insider. https://www.businessinsider.com/coronavirus-could-spur-loneliness-epidemic-2020-3. Published March 16, 2020. Accessed April 10, 2020.
7. Roy L. Addiction treatment facilities: are they prepared for the COVID-19 coronavirus outbreak? Forbes. https://www.forbes.com/sites/lipiroy/2020/03/16/addiction-treatment-facilities-are-they-prepared-for-covid-19/#555149b544ea. Published March 16, 2020. Accessed April 10, 2020.
1. Howe N. Millennials and the loneliness epidemic. Forbes. https://www.forbes.com/sites/neilhowe/2019/05/03/millennials-and-the-loneliness-epidemic/. Published May 3, 2019. Accessed April 10, 2020.
2. The Economist. All the lonely people: loneliness is a serious public-health problem. https://www.economist.com/international/2018/09/01/loneliness-is-a-serious-public-health-problem. Published September 1, 2018. Accessed April 10, 2020.
3. Cigna. New Cigna study reveals loneliness at epidemic levels in America. https://www.cigna.com/newsroom/news-releases/2018/new-cigna-study-reveals-loneliness-at-epidemic-levels-in-america. Published May 1, 2018. Accessed April 10, 2020.
4. Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. PLoS Med. 2010;7(7):e1000316.
5. Holt-Lunstad J, Smith TB, Baker M, et al. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015;10(2):227-237.
6. Finley D. How increased social distancing for the coronavirus could spur a loneliness epidemic. Business Insider. https://www.businessinsider.com/coronavirus-could-spur-loneliness-epidemic-2020-3. Published March 16, 2020. Accessed April 10, 2020.
7. Roy L. Addiction treatment facilities: are they prepared for the COVID-19 coronavirus outbreak? Forbes. https://www.forbes.com/sites/lipiroy/2020/03/16/addiction-treatment-facilities-are-they-prepared-for-covid-19/#555149b544ea. Published March 16, 2020. Accessed April 10, 2020.
COVID-19: A psychiatry resident’s perspective
During these unprecedented times, venturing into the unknown of the coronavirus disease 2019 (COVID-19) pandemic, a feeling of impending doom prevails. Almost all of us have been restricted to our homes. Although the physical dimensions of what we call home may vary, the meaning of this restriction is fairly universal. No matter how our sociodemographics differ, with no guidance for this situation from anything even remotely comparable in the past, our lives have been transformed into a work in progress.
During this pandemic, I have observed a wide range of human emotions and behavior—many of them familiar and predictable, some abysmal, and some inspiring.
’Why should I care?’
On December 31, 2019, health officials in China informed the World Health Organization about a pneumonia-like presentation in a group of people in Wuhan. On January 7, 2020, a novel coronavirus was identified as the cause, and the first death was reported a few days later. In the following days and weeks the disease rapidly spread, as did the growing sense that this was not a typical virus.
While these events occurred, the rest of the world was in what I call a ”Why should I care?” mode. Most humans tend to suffer from this indifference. This has been observed repeatedly through the years, such as when the Ebola outbreak occurred in Africa in 2014-2016. It was only when cases started to develop in Europe and the United States that other countries started to pay attention. A similar phenomenon has been observed every time we’ve faced a global outbreak (avian influenza, Middle East respiratory syndrome, etc.).
When are we going to learn? It is time to realize that global borders are more porous than we think, and human interactions cannot be blocked by any wall. When a catastrophic event, outbreak, or disaster starts in any part of the world, it is naive to assume that we will not be affected. We will eventually be affected—the only question is how, when, and to what extent? We are always all in this together.
An abundance of ignorance and stupidity
Within a few weeks of the first reports from China, cases of COVID-19 were reported in South Korea, Italy, Spain, Germany, and many other countries. Slowly, COVID-19 reached the United States, which as of mid-April had the highest number of cases worldwide. When COVID-19 hit the United States, the response was that of shock and anger. How could this happen to us? Why is the government not doing anything?
Amidst this pandemonium, ignorance and stupidity of the highest degree were commonplace. This was not restricted to any particular country or region. Almost 2 months into the pandemic, the Ministry of Tourism in my home country of Nepal declared Nepal a ”coronavirus-free zone” and took measures to bring in tourists, focusing specifically on China, where COVID-19 had already killed hundreds. In India, some people were drinking cow urine in hopes of warding off the virus. In the United Sates, thousands of young people flocked to beaches for Spring Break, disregarding measures for social distancing. ”If I get corona, I get corona,” one young man said in an interview that went viral. Personally, I have encountered people who responded to this pandemic by saying the disease was ”cooties” or ”just a flu,” and dismissing it with ”If I die from this, I die.”
Continue to: Rising panic and fear
Rising panic and fear
For most people, seeing COVID-19 at their doorstep triggered a panic, and sent many into a frenzy of buying and hoarding. Once again, we proved that people everywhere are equally stupid, as toilet paper began to vanish from stores across the globe. And yet, this again was a moment when some people began to experience a false sense of immunity: ”I have enough food, money, and toilet paper to last me for 2 years. Why should I be worried?”
When the numbers of COVID-19 deaths in Europe were first reported, the fear became palpable. In Italy and Spain, towns were locked down, and tens of thousands of people (mostly older adults) have died. It was truly heartbreaking to see people alone and at their weakest with no family members allowed to be by their side.
A glimmer of hope
Despite all of this, there were superheroes—the nurses, physicians, allied health professionals, first responders, store workers, restaurant workers, delivery personnel, and others who didn’t have the option of staying home, or who volunteered to help people in need. In moments like this, the actions of these individuals give us hope, reminding us that the human spirit is resilient, and that we will get through this.
A rotation in the emergency department during COVID-19
As a psychiatry resident, it is unlikely that my peers and I face the same risks as our colleagues in other medical specialities. But those of us who happened to be in medical rotations during this time have had the chance to experience this very closely. My personal experience, albeit a brief one, of working in an emergency department with suspected COVID-19 patients has been sobering. Watching nurses and physicians walk into a room wearing personal protective equipment, fearful inside but with a reassuring smile for a scared patient, definitely was one of the most compelling moments of my life. Living in a distant land, with my daughter, wife, parents, and extended family back home in Nepal, has made this even more challenging.
We will overcome this as we have overcome previous challenges in the past. There will be death and chaos, but we will prevail. The only thing is to ask ourselves: How do we want to continue living when this is over?
During these unprecedented times, venturing into the unknown of the coronavirus disease 2019 (COVID-19) pandemic, a feeling of impending doom prevails. Almost all of us have been restricted to our homes. Although the physical dimensions of what we call home may vary, the meaning of this restriction is fairly universal. No matter how our sociodemographics differ, with no guidance for this situation from anything even remotely comparable in the past, our lives have been transformed into a work in progress.
During this pandemic, I have observed a wide range of human emotions and behavior—many of them familiar and predictable, some abysmal, and some inspiring.
’Why should I care?’
On December 31, 2019, health officials in China informed the World Health Organization about a pneumonia-like presentation in a group of people in Wuhan. On January 7, 2020, a novel coronavirus was identified as the cause, and the first death was reported a few days later. In the following days and weeks the disease rapidly spread, as did the growing sense that this was not a typical virus.
While these events occurred, the rest of the world was in what I call a ”Why should I care?” mode. Most humans tend to suffer from this indifference. This has been observed repeatedly through the years, such as when the Ebola outbreak occurred in Africa in 2014-2016. It was only when cases started to develop in Europe and the United States that other countries started to pay attention. A similar phenomenon has been observed every time we’ve faced a global outbreak (avian influenza, Middle East respiratory syndrome, etc.).
When are we going to learn? It is time to realize that global borders are more porous than we think, and human interactions cannot be blocked by any wall. When a catastrophic event, outbreak, or disaster starts in any part of the world, it is naive to assume that we will not be affected. We will eventually be affected—the only question is how, when, and to what extent? We are always all in this together.
An abundance of ignorance and stupidity
Within a few weeks of the first reports from China, cases of COVID-19 were reported in South Korea, Italy, Spain, Germany, and many other countries. Slowly, COVID-19 reached the United States, which as of mid-April had the highest number of cases worldwide. When COVID-19 hit the United States, the response was that of shock and anger. How could this happen to us? Why is the government not doing anything?
Amidst this pandemonium, ignorance and stupidity of the highest degree were commonplace. This was not restricted to any particular country or region. Almost 2 months into the pandemic, the Ministry of Tourism in my home country of Nepal declared Nepal a ”coronavirus-free zone” and took measures to bring in tourists, focusing specifically on China, where COVID-19 had already killed hundreds. In India, some people were drinking cow urine in hopes of warding off the virus. In the United Sates, thousands of young people flocked to beaches for Spring Break, disregarding measures for social distancing. ”If I get corona, I get corona,” one young man said in an interview that went viral. Personally, I have encountered people who responded to this pandemic by saying the disease was ”cooties” or ”just a flu,” and dismissing it with ”If I die from this, I die.”
Continue to: Rising panic and fear
Rising panic and fear
For most people, seeing COVID-19 at their doorstep triggered a panic, and sent many into a frenzy of buying and hoarding. Once again, we proved that people everywhere are equally stupid, as toilet paper began to vanish from stores across the globe. And yet, this again was a moment when some people began to experience a false sense of immunity: ”I have enough food, money, and toilet paper to last me for 2 years. Why should I be worried?”
When the numbers of COVID-19 deaths in Europe were first reported, the fear became palpable. In Italy and Spain, towns were locked down, and tens of thousands of people (mostly older adults) have died. It was truly heartbreaking to see people alone and at their weakest with no family members allowed to be by their side.
A glimmer of hope
Despite all of this, there were superheroes—the nurses, physicians, allied health professionals, first responders, store workers, restaurant workers, delivery personnel, and others who didn’t have the option of staying home, or who volunteered to help people in need. In moments like this, the actions of these individuals give us hope, reminding us that the human spirit is resilient, and that we will get through this.
A rotation in the emergency department during COVID-19
As a psychiatry resident, it is unlikely that my peers and I face the same risks as our colleagues in other medical specialities. But those of us who happened to be in medical rotations during this time have had the chance to experience this very closely. My personal experience, albeit a brief one, of working in an emergency department with suspected COVID-19 patients has been sobering. Watching nurses and physicians walk into a room wearing personal protective equipment, fearful inside but with a reassuring smile for a scared patient, definitely was one of the most compelling moments of my life. Living in a distant land, with my daughter, wife, parents, and extended family back home in Nepal, has made this even more challenging.
We will overcome this as we have overcome previous challenges in the past. There will be death and chaos, but we will prevail. The only thing is to ask ourselves: How do we want to continue living when this is over?
During these unprecedented times, venturing into the unknown of the coronavirus disease 2019 (COVID-19) pandemic, a feeling of impending doom prevails. Almost all of us have been restricted to our homes. Although the physical dimensions of what we call home may vary, the meaning of this restriction is fairly universal. No matter how our sociodemographics differ, with no guidance for this situation from anything even remotely comparable in the past, our lives have been transformed into a work in progress.
During this pandemic, I have observed a wide range of human emotions and behavior—many of them familiar and predictable, some abysmal, and some inspiring.
’Why should I care?’
On December 31, 2019, health officials in China informed the World Health Organization about a pneumonia-like presentation in a group of people in Wuhan. On January 7, 2020, a novel coronavirus was identified as the cause, and the first death was reported a few days later. In the following days and weeks the disease rapidly spread, as did the growing sense that this was not a typical virus.
While these events occurred, the rest of the world was in what I call a ”Why should I care?” mode. Most humans tend to suffer from this indifference. This has been observed repeatedly through the years, such as when the Ebola outbreak occurred in Africa in 2014-2016. It was only when cases started to develop in Europe and the United States that other countries started to pay attention. A similar phenomenon has been observed every time we’ve faced a global outbreak (avian influenza, Middle East respiratory syndrome, etc.).
When are we going to learn? It is time to realize that global borders are more porous than we think, and human interactions cannot be blocked by any wall. When a catastrophic event, outbreak, or disaster starts in any part of the world, it is naive to assume that we will not be affected. We will eventually be affected—the only question is how, when, and to what extent? We are always all in this together.
An abundance of ignorance and stupidity
Within a few weeks of the first reports from China, cases of COVID-19 were reported in South Korea, Italy, Spain, Germany, and many other countries. Slowly, COVID-19 reached the United States, which as of mid-April had the highest number of cases worldwide. When COVID-19 hit the United States, the response was that of shock and anger. How could this happen to us? Why is the government not doing anything?
Amidst this pandemonium, ignorance and stupidity of the highest degree were commonplace. This was not restricted to any particular country or region. Almost 2 months into the pandemic, the Ministry of Tourism in my home country of Nepal declared Nepal a ”coronavirus-free zone” and took measures to bring in tourists, focusing specifically on China, where COVID-19 had already killed hundreds. In India, some people were drinking cow urine in hopes of warding off the virus. In the United Sates, thousands of young people flocked to beaches for Spring Break, disregarding measures for social distancing. ”If I get corona, I get corona,” one young man said in an interview that went viral. Personally, I have encountered people who responded to this pandemic by saying the disease was ”cooties” or ”just a flu,” and dismissing it with ”If I die from this, I die.”
Continue to: Rising panic and fear
Rising panic and fear
For most people, seeing COVID-19 at their doorstep triggered a panic, and sent many into a frenzy of buying and hoarding. Once again, we proved that people everywhere are equally stupid, as toilet paper began to vanish from stores across the globe. And yet, this again was a moment when some people began to experience a false sense of immunity: ”I have enough food, money, and toilet paper to last me for 2 years. Why should I be worried?”
When the numbers of COVID-19 deaths in Europe were first reported, the fear became palpable. In Italy and Spain, towns were locked down, and tens of thousands of people (mostly older adults) have died. It was truly heartbreaking to see people alone and at their weakest with no family members allowed to be by their side.
A glimmer of hope
Despite all of this, there were superheroes—the nurses, physicians, allied health professionals, first responders, store workers, restaurant workers, delivery personnel, and others who didn’t have the option of staying home, or who volunteered to help people in need. In moments like this, the actions of these individuals give us hope, reminding us that the human spirit is resilient, and that we will get through this.
A rotation in the emergency department during COVID-19
As a psychiatry resident, it is unlikely that my peers and I face the same risks as our colleagues in other medical specialities. But those of us who happened to be in medical rotations during this time have had the chance to experience this very closely. My personal experience, albeit a brief one, of working in an emergency department with suspected COVID-19 patients has been sobering. Watching nurses and physicians walk into a room wearing personal protective equipment, fearful inside but with a reassuring smile for a scared patient, definitely was one of the most compelling moments of my life. Living in a distant land, with my daughter, wife, parents, and extended family back home in Nepal, has made this even more challenging.
We will overcome this as we have overcome previous challenges in the past. There will be death and chaos, but we will prevail. The only thing is to ask ourselves: How do we want to continue living when this is over?
Screening for adolescent substance use; Changing routines during COVID-19
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Screening for adolescent substance use
I want to congratulate Dr. Verma on her article “Opioid use disorder in adolescents: An overview” (Evidence-Based Reviews,
Because evidence suggests there are continued barriers, such as time constraints, in evaluating for adolescent SUD,1,2 I believe the Screen to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol and Drug (BSTAD) should be included.3,4 The S2BI and BSTAD are brief screeners that assess substance use, are validated for adolescent patients, can be completed online, and can assist in identifying DSM-5 criteria for SUD.
The S2BI has demonstrated high sensitivity and specificity for identifying SUD.3 The single screening assessment for “past-year use” is quick and can be administered in a variety of clinical settings. The S2BI begins by asking a patient about his/her frequency of tobacco, alcohol, and/or marijuana use in the past year. If the patient endorses past-year use of any of these substances, the S2BI prompts follow-up questions about the use of prescription medications, illicit drugs, inhalants, and herbal products. A patient’s frequency of use is strongly correlated with the likelihood of having a SUD. Adolescents who report using a substance “once or twice” in the past year are very unlikely to have a SUD. Patients who endorse “monthly” use are more likely to meet the criteria for a mild or moderate SUD, and those reporting “weekly or more” use are more likely to have a severe SUD.
The BSTAD is an electronic, validated, high-sensitivity, high-specificity instrument for identifying SUD.1 It asks a single frequency question about past-year use of tobacco, alcohol, and marijuana, which are the most commonly used substances among adolescents. Patients who report using any of these substances are then asked about additional substance use. Based on the patient’s self-report of past year use, the screen places him/her into 1 of 3 risk categories for SUD: no reported use, lower risk, and higher risk. Each risk level maps to suggested clinical actions that are summarized in the results section.
Kevin M. Simon, MD
Child & Adolescent Psychiatry Fellow
Boston Children’s Hospital
Clinical Fellow in Psychiatry
Harvard Medical School
Boston, Massachusetts
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
References
1. Palmer A, Karakus M, Mark T. Barriers faced by physicians in screening for substance use disorders among adolescents. Psychiatr Serv. 2019;70(5):409-412.
2. D’Souza-Li L, Harris SK. The future of screening, brief intervention and referral to treatment in adolescent primary care: research directions and dissemination challenges. Curr Opin Pediatr. 2016;28(4):434-440.
3. Levy S, Weiss R, Sherritt L, et al. An electronic screen for triaging adolescent substance use by risk levels. JAMA Pediatr. 2014;168(9):822-828.
4. Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. Pediatrics. 2014;133(5):819-826.
Continue to: The author responds
The author responds
I thank Dr. Simon for his words of encouragement. I agree that both the S2BI and BSTAD have high sensitivity and specificity and are easy to use for screening for the use of multiple substances. Once substance use is established, both tools recommend administering high-risk assessment with additional scales such as the CRAFFT. During the initial evaluation, many psychiatrists take their patient’s history of substance use in detail, including age of onset, frequency, amount used, severity, and the time of his/her last use, without using a screening instrument. My article focused on instruments that can determine whether there is need for a further detailed evaluation. I agree that the S2BI and BSTAD would assist psychiatrists or physicians in other specialties (eg, pediatrics, family medicine) who might not take a complete substance use history during their initial evaluations.
Shikha Verma, MD
Rogers Behavioral Health
Kenosha, Wisconsin
Assistant Professor
Department of Psychiatry and Behavioral Health
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
Continue to: Changes as a result of COVID-19
Changes as a result of COVID-19
I thank Dr. Nasrallah for his editorial “During a viral pandemic, anxiety is endemic: The psychiatric aspects of COVID-19” (From the Editor,
I appreciated the editorial because it got me thinking about how the pandemic has changed me and my family:
1. We are engaging more in social media.
2. I feel uncomfortable when I go to the grocery store.
3. I feel better when I don’t access the news about COVID-19.
4. My children need physical socialization with their friends (sports, games, other activities, etc.).
5. My children function better with a schedule, but we find it difficult to keep them on a good schedule. Our teenagers stay up late at night (because all of their friends do), and they sleep in late the next morning.
Here are some positive changes:
1. Creating a weekly family calendar on a dry-erase board, so the family can see what is going on during the week.
2. Creating responsibility for our older children (eg, washing their own clothes, cleaning their bathroom).
3. Eating most meals as a family and organizing meals better, too.
4. Playing games together.
5. Cleaning the house together.
6. Getting outside to walk the dog and appreciate nature more.
7. Exercising.
8. Utilizing positive social media.
9. Getting caught up on life.
Again, I thank Dr. Nasrallah for writing this editorial because it led me to self-reflect on this situation, and helped me feel normal.
Doug Dolenc
Westfield, Indiana
Disclosure: The author reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Love in the time of coronavirus
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Several months ago, I sat with a woman just a few days after the emergent Cesarean section delivery of her first child. She cried as she told me about her entire life—childhood trauma, a pattern of difficult relationships, several miscarriages, and now, finally, a baby—delivered under circumstances so scary, all she remembered was overwhelming fear. Now, she had returned to the hospital with severe postpartum depression, layered with struggles that are common during the first days with a newborn—little sleep, loss of autonomy, guilt, and loneliness. It was hard to listen to it all, but I encouraged her to express her pain, believing that burdens are lighter when shared.
Words often fail us in times of desperation. Much of my education has involved borrowing words, phrases, or ideas from my experienced attendings and mentors, applying them like a salve when I don’t know what else to say. Sitting with another person in silence is often powerful enough, but when something needs to be said, I fall back on these inherited ideas. One of the mantras I often use, and what I said to my patient that day, is about hope: “When you’re down in this depression, you feel hopeless, and you can’t see the hope. It doesn’t mean there isn’t hope; just that you can’t see it.” I’ve watched that idea take root in patients who—despite their own beliefs in the moment—do get better, thus proving the point. Another favorite phrase: “With any luck at all, tomorrow will be better than today.” When you talk to someone on the worst day of their life, what else is there to say?
Today, my conversation with that woman seems like an eternity ago. Public discourse has been overtaken by coronavirus disease 2019 (COVID-19)—the journalism, reflections on the journalism, medical advice, debate about the medical advice, and the innumerable ways in which this worldwide strife has created pain: celebrations and long-awaited plans cancelled, weddings and funerals put on hold, isolation, loneliness, death, and, of course, the fear of death. Those feelings and any other permutations are valid; another phrase, “It’s OK to feel what you are feeling,” carries weight for me these days. I work in a hospital, so I add to the list the breathless fears about what’s going to happen in our local environment. The chronic uncertainty was wearing us thin even before we had begun to do here in Ohio what was already being done elsewhere: working extra shifts, intubating new patients, praying we don’t get sick ourselves.
Our work during COVID-19
Amidst this, my colleagues and I continue our work as psychiatrists, sitting with humans experiencing complex grief (a man whose wife died alone in a nursing home, because of visitor restrictions), confusion (delirium resulting from respiratory failure), and even psychosis (inability to access stabilizing medications coupled with crippling paranoia). These remain just as real and debilitating in a pandemic as they do in other times. In addition to pre-existing mental illnesses, for some individuals, the shared anxiety will progress to clinically significant disorders that may last even longer than the effects of the virus. The resulting complex symptoms could affect everything from home lives to interpersonal relationships to our local and global economies. These are not minor issues. Although often triaged aside in a disaster, our collective mental health remains in some ways more central than ever.
Modern psychiatry would not often use the word “love,” but that’s what I am trying to do—show love to the people who need it the most right now (which is all of us, really). This love takes strange shapes, and sometimes new forms, but it’s just about all I have to give. Like everyone else, I don’t have concrete answers for the grief and fear and panic. But I’m content to share the burden of pain, believing that burdens are lighter when shared. And I have a few words that, however little comfort they offer in the moment, are eventually proven true: Just because you can’t see the hope doesn’t mean it isn’t there. It’s OK to feel what you are feeling. With any luck at all, tomorrow will be better than today.
Multigene panel testing for colorectal cancer
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Dear colleagues and friends,
I write to introduce to you the new Perspectives section of GI & Hepatology News.
A more appropriate description is perhaps old-new, because Perspectives is the continuation and legacy of AGA Perspectives, the content of which has been consolidated into GI & Hepatology News. Perspectives will continue to feature the point/counterpoint expert debates about an important GI topic, which has historically been immensely popular with readers. In this edition, experts from Mayo Clinic and Cleveland Clinic discuss the pros and cons of universal multigene panel testing for colorectal cancer. These debates never end with the publication itself, and I hope they will continue to stimulate further thought and discussion. As always, I welcome your comments and suggestions for future topics.
–Charles I. Kahi, MD, MS, AGAF, is professor of medicine at Indiana University School of Medicine, Indianapolis. He is also an Associate Editor for GI & Hepatology News.
For everyone
By N. Jewel Samadder, MD, MSC
Traditionally, health care structure has been directed predominantly toward treatment rather than prevention. Advances in genomic medicine offer the opportunity to deliver a more personalized, predictive, and preventive strategy toward colorectal cancer. Approximately 150,000 men and women are diagnosed with colorectal cancer (CRC) every year in the United States.1 An estimated 10%-15% of these cancers are likely attributable to hereditary (germline) causes.2 Several genes are associated with an increased risk of developing CRC, and those of key interest include those for Lynch syndrome, MLH1, MSH2, MSH6, PMS2, EPCAM; adenomatous polyposis conditions (APC), MUTYH, POLE, POLD1, NTHL1; hamartomatous polyposis syndromes PTEN, SMAD4, STK11, and other rare cancer predisposition states where colorectal cancer is part of the phenotype, CHEK2 and TP532.
A universal strategy for multigene panel testing in all patients with CRC is an option versus the current strategy of guideline-based testing using family history and tumor features. In addition, the identification of germline alterations has substantial clinical implications including targeted therapies and future cancer prevention in the patient and relatives. This article will focus on the benefits of universal strategy for germline genetic evaluation in all patients with colorectal cancer.
The role and utility of current guideline-based testing
Given the therapeutic and prevention implications, the National Comprehensive Cancer Network (along with other professional organizations) has guidance on when patients with CRC should undergo genetic evaluation.3 Currently, these guidelines advocate an approach based heavily on family cancer history or utilizing colorectal phenotype based on the number and histology of polyps or tumor-based molecular features. Although family history is important for the diagnosis of hereditary CRC, the ability to accurately capture extended family cancer history in routine practice, from multiple generations and for different cancer types can be a challenge. The largest drawback of all such approaches is the focus on Lynch syndrome or only a few of the cancer predisposition syndromes. Recent studies have reported a substantial number (7%-10%) of CRC patients will have mutations in non–Lynch syndrome–associated genes and over half of these would be missed by using standard criteria for genetic evaluation.
Role of tumor-based screening approaches
More recently, health care institutions have begun to widely adopt “universal” tumor screening using microsatellite instability and/or immunohistochemistry (IHC) showing deficient expression of the mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to identify patients with colorectal or endometrial cancers that are likely to have Lynch syndrome. However, the sensitivity and specificity of IHC for Lynch syndrome ranges between 60% and 75% and there is considerable interobserver variation by pathologists in their interpretation.
Thus, both clinical guidelines (largely focused around family history and patient phenotype) and tumor molecular features will fail to identify a significant number of patients with inherited cancer predisposition.
Cost and availability of genetic testing
In the past, cost and availability of genetic testing were an impediment to such care. This has rapidly changed in the last few years. With modern next-generation sequencing technology and an ever increasing number of testing laboratories, the cost of genetic testing has dropped to below $500 and multigene panels can now test for dozens of genes in parallel offering comprehensive testing of genetic predisposition across multiple cancer types. The popularity of direct-to-consumer health-related genetic testing (with the inclusion of certain BRCA variants on these panels) has also fueled the public interest in cancer genetic testing.
Cancer prevention for family members
In individuals with CRC and hereditary cancer predisposition, implications for family members are clinically meaningful and include increased colorectal and extracolonic surveillance, consideration of risk-reducing hysterectomy, salpingo-oophorectomy, and bilateral mastectomy for colorectal, uterine, ovarian, breast, and other cancer prevention depending on the germline mutation.2 The goal of these intensive surveillance strategies is to either prevent the occurrence of cancer altogether or detect cancer at an earlier stage when cure is likely. Identifying these high-risk groups can thus play a significant role in our goal to reduce the burden of cancer in society.
Precision targeted treatment and chemoprevention
The treatment implications for patients with CRC and pathogenic mutations in the Lynch syndrome MMR genes are the best characterized and include response to immune checkpoint inhibitor therapy.4 Mismatch repair deficiency is highly predictive of response to immunotherapy in metastatic CRCs and led to expedited approval of both pembrolizumab and nivolumab monotherapies with disease control rates of 69%-77% with durable response and combination therapy with nivolumab and ipilimumab with likely even greater benefit. Multiple clinical trials are examining the role of immune checkpoint inhibitor therapy for first-line palliative treatment of MSI-high CRC (ClinicalTrials.gov ID NCT02563002; NCT02997228), adjuvant therapy (ClinicalTrials.gov ID NCT02912559), and even as potential chemoprevention in those with Lynch syndrome (ClinicalTrials.gov ID NCT03631641).
Long-term cancer prevention using a chemopreventive approach has long been a desire in the hereditary cancer community.5 The most well-studied group to date has been Lynch syndrome, where a large randomized clinical trial showed the effect of high-dose aspirin in decreasing the incidence of colorectal and other Lynch-associated cancers by nearly 60%.6 Similar smaller (earlier-phase) studies in familial adenomatous polyposis have suggested targeted chemoprevention options for the regression of colorectal or duodenal polyposis with COX inhibitors, EGFR inhibitors, DFMO (NCT01483144), and IL-23 blockade (ClinicalTrials.gov ID NCT03649971) may all be possible.
Cancer programs have already started to introduce genomic profiling (germline and tumor somatic) into the frontline care of their patients to help guide precision therapy approaches that optimize disease control, minimize side effects, and reduce risk of long-term recurrence.
The future
The approach to genomic profiling of cancer patients is rapidly changing because of the lack of sensitivity for the identification of these hereditary cancer predisposition syndromes utilizing current approaches focused on family history, clinical phenotype, and tumor features. The wide availability of low-cost/affordable multigene panel testing has implications for cancer therapy selection and cancer prevention. This supports establishing a universal approach to multigene panel testing of all patients with CRC.
It will be important for physicians of many different specialties – including gastroenterology and oncology – to become more adept in this changing landscape of genomic medicine and to work closely with the genetic counseling resources available in their communities to provide the best care for these high-risk cancer patients.
References
1. Siegel RL et al. CA Cancer J Clin. 2017;67:177-93.
2. Kanth P et al. Am J Gastroenterol. 2017;112:1509-25.
3. Gupta S et al. J Natl Compr Canc Netw. 2019;17:1032-41.
4. Ribas A, Wolchok JD. Science. 2018;359:1350-5.
5. Ramamurthy C et al. Surg Oncol Clin N Am. 2017;26:729-50.
6. Burn J et al. Lancet 2011;378:2081-7.
Dr. Samadder is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Phoenix. He is a consultant for Janssen Research & Development and Cancer Prevention Pharmaceuticals.
Not for everyone
By Carol A. Burke, MD, AGAF, and Brandie Heald Leach, MS
Multigene panel testing (MGPT) takes advantage of next-generation sequencing (NGS) a non-Sanger-based DNA sequencing technology which has revolutionized genomic research and clinical care because it can be run quickly, is lower cost than Sanger sequencing, can sequence an entire genome or exome, or specific genes of interest. Currently, cancer gene panels (disease specific or pan-cancer) are commonly utilized.
Approximately 10% of colorectal cancers (CRCs) are heritable because of a germline pathogenic variant (PV), most commonly in Lynch syndrome genes. Identification of patients with hereditary CRC is important because they are at greatest CRC and extracolonic cancer risk, benefit from aggressive cancer surveillance. and when indicated may need prophylactic surgery of at-risk organs, require multidisciplinary care, and may have at-risk family members who need testing.
Red flags regarding family cancer history may allow clinical inference as to the cause of CRC and direct who is offered germline testing. These include young age of cancer (age less than 50), synchronous or metachronous cancers, multiple relatives with CRC or extracolonic cancers, and cumulative lifetime numbers of adenomas or hamartomas. While overt clinical manifestations can be specific for predicting the causative gene defect, such as Amsterdam criteria for Lynch syndrome or numerous adenomas at a young age in familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations. While family pedigrees with a phenotype that meets clinical criteria, such as Amsterdam II, can be very specific (although less sensitive) for predicting Lynch syndrome, or overt clinical manifestations such as 100 adenomatous polyps in an individual by the age of 40 is highly suggestive of familial adenomatous polyposis, overlap can occur between syndromes and single gene testing has its limitations.
The current standard of care for patients with CRC is germline testing after assessment of tumor mismatch repair (MMR) proficiency by microsatellite instability (MSI) testing and/or immunohistochemistry (IHC). Broadly, tumors that show high levels of MSI and or loss of expression of MMR proteins (not attributed to MLH1 promoter hypermethylation or double somatic mutations/loss of heterozygosity) are considered MMR deficient (MMRd) and suggestive of Lynch syndrome. MMRd directs treatment (immune check point inhibitors) and is a hallmark of Lynch syndrome as 95% of Lynch syndrome–related CRCs are MMRd.
The utility of MGPT in individuals with CRC can be inferred from two studies. In both, a 25-gene pan-cancer panel test was performed. In the first, 1,058 unselected individuals with CRC at a mean age of 56 were assessed regardless of MMR status; 9.9% were diagnosed with moderately (4.7%) or highly penetrant (5.2%) PV.1 In these individuals with CRC, 31% were diagnosed with Lynch syndrome and nearly all Lynch syndrome patients had MMRd tumors and met criteria for germline testing for Lynch syndrome; 22% of patients had other high-penetrance PV found, the majority lacking clinical features consistent with the PV. The second study,2 tested 450 patients with CRC diagnosed under the age of 50. Germline PV were detected in 16%. The majority of patients with an MMRd tumor were diagnosed with Lynch syndrome. Eight percent of patients with an MMR-proficient tumor had a PV detected. Nearly one-third did not meet clinical criteria for testing. Germline variants of uncertain significance (VUS) were noted in approximately 32% of patients in both studies. These data support the current standard of tumor assessment for MMRd, followed by Lynch syndrome germline testing as directed by IHC.
While MGPT for patients with CRC is feasible, the high rates of VUS, detection of moderate and low penetrance PV for which no clinical guidance exists, and dearth of evidence on penetrance and cancer risk attributable to incidentally found PV, need consideration. Prior to germline testing, patients and providers must understand potential testing outcomes, possible detection of incidental findings and VUS, and how each influence patient cancer risks and management. The commercial genetic testing companies accumulate information on VUS over time and reclassify the significance of the finding, but this process could take months to years. Providers ordering genetic testing must have a system to inform the patient when a VUS is reclassified.
Pre- and post-test genetic counseling, ideally by an individual with understanding of medical genetics, should be offered, including caveats, risks, benefits, and alternatives to germline testing, a plan for results disclosure, including to family members, and a plan for follow-up care. Patients with uninformative findings and VUS need to be followed as technology and research evolve. Patient preferences regarding genetic testing need to be considered. There still remains stigma and fear associated with genetic testing. Despite protections from the Genetic Information Non-Discrimination Act, many patients remain fearful of genetic discrimination. A genetic diagnosis comes with the burden that it reveals not only information about the patient’s risks, but potentially also his/her family members’ risks. These are valid patient concerns that need to be vetted and addressed.
Selection of correct testing strategy is important. A patient with a known PV in the family might benefit most from single-site analysis for the family mutation. For a patient with an affected relative who had negative genetic testing, additional genetic testing for that patients is unlikely to be beneficial. For a patient with no known PV in the family who meet genetic testing criteria, a cancer gene panel should be considered. However, guidance on which MGPT to order is lacking in professional guidelines and often left to the discretion of the provider and patient. Utilization of a “disease specific panel” (i.e., a panel of genes related to CRC risk) is useful for understanding the cause of the patient’s disease and guiding treatment, screening, and cascade testing while minimizing the number of VUS identified. Pan-cancer gene panels increase diagnostic yield, but include identification of PV in genes unrelated to phenotype or more poorly described risk and management recommendations and have a higher rate of VUS.
Finally, the cost of MGPT to the health care system needs to be considered. Despite dropping costs, the process of genetic counseling and testing remains expensive and will rise if and when testing is expanded to all patients with CRC.
MGPT is not for everyone.
References
1. Yurgelun MB et al. J Clin Oncol. 2017;35:1086-95.
2. Pearlman R et al. JAMA Oncol. 2017 Apr 01;3(4):464-71.
Dr. Burke is with the department of gastroenterology, hepatology, and nutrition, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic; Ms. Leach is with the Center for Personalized Genetic Healthcare, Sanford R. Weiss Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic. Dr. Burke has no conflicts of interest, Ms. Leach serves on the advisory board of Invitae.
Let’s learn from our experience
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief
COVID-19 has revealed the worst and best of our country. Some have used it to validate their racism (my Korean-born son keeps me apprised of the Asian prejudice he has experienced) and a few leaders have made policy decisions based on ideology and not science, with disastrous consequences. That said, no world threat since those 13 days in October 1962 has demonstrated so decisively our interconnectedness. The best of our country has been demonstrated by our frontline health care workers, grocery clerks, people who deliver our packages, and volunteers who help feed our fellow citizens.
We are witnessing consequences of long-term health disparities that America continues to condone. Current hotspots are clustered in cities with high population density where people (usually minorities) lack ready access to health care and live with barriers to preventive care (poor nutritional options and a lack of sufficient primary care). We have underfunded our public health system and allowed politicians to ignore science. When testing was not prioritized initially, we lost the ability to isolate and trace index cases. If we want to honor those people who have died, let’s learn from our experience and change our priorities.
Private practices and health systems alike are being financially devastated. We are seeing massive numbers of people furloughed or laid off, as practices see drastic revenue loss. The transition to virtual health (video visits, remote patient monitoring) has been breath-taking with real implications about future needs for bricks and mortar. These changes in care delivery will be sustained in the future. Practice acquisitions have stopped, planned private equity exits are on hold, and the job market for graduating fellows will be challenging for the next 2 years. Now is a time for our GI societies to come together and find solutions for these problems so that our specialty can remain viable.
John I. Allen, MD, MBA, AGAF
Editor in Chief