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Migraine: Triptan responders are more likely to respond to erenumab
Key clinical point: Patients with migraine who showed a favorable response to at least one triptan had a higher likelihood to respond to erenumab treatment than those not responding to triptans.
Major finding: Triptan responders had higher odds for responding to erenumab treatment than the triptan nonresponders (odds ratio, 3.64; P = .014).
Study details: Findings are from an ancillary study from a real-life observational study involving 140 patients with migraine treated with erenumab for at least 6 months.
Disclosures: The publication fee was unconditionally granted by Novartis Farma S.r.l. The lead author along with some other authors declared no competing interests. Some authors declared financial and nonfinancial relationships with various pharmaceutical sources such as Eli Lilly, Novartis, Allergan, Teva, Abbott, Innovet Italia Srl, Epitech Group, and Lusofarmaco.
Source:Frattale I et al. J Headache Pain. 2021 Jan 6. doi: 10.1186/s10194-020-01213-3.
Key clinical point: Patients with migraine who showed a favorable response to at least one triptan had a higher likelihood to respond to erenumab treatment than those not responding to triptans.
Major finding: Triptan responders had higher odds for responding to erenumab treatment than the triptan nonresponders (odds ratio, 3.64; P = .014).
Study details: Findings are from an ancillary study from a real-life observational study involving 140 patients with migraine treated with erenumab for at least 6 months.
Disclosures: The publication fee was unconditionally granted by Novartis Farma S.r.l. The lead author along with some other authors declared no competing interests. Some authors declared financial and nonfinancial relationships with various pharmaceutical sources such as Eli Lilly, Novartis, Allergan, Teva, Abbott, Innovet Italia Srl, Epitech Group, and Lusofarmaco.
Source:Frattale I et al. J Headache Pain. 2021 Jan 6. doi: 10.1186/s10194-020-01213-3.
Key clinical point: Patients with migraine who showed a favorable response to at least one triptan had a higher likelihood to respond to erenumab treatment than those not responding to triptans.
Major finding: Triptan responders had higher odds for responding to erenumab treatment than the triptan nonresponders (odds ratio, 3.64; P = .014).
Study details: Findings are from an ancillary study from a real-life observational study involving 140 patients with migraine treated with erenumab for at least 6 months.
Disclosures: The publication fee was unconditionally granted by Novartis Farma S.r.l. The lead author along with some other authors declared no competing interests. Some authors declared financial and nonfinancial relationships with various pharmaceutical sources such as Eli Lilly, Novartis, Allergan, Teva, Abbott, Innovet Italia Srl, Epitech Group, and Lusofarmaco.
Source:Frattale I et al. J Headache Pain. 2021 Jan 6. doi: 10.1186/s10194-020-01213-3.
How does an emotionally drained workforce move on post pandemic?
Psychiatric community is facing ‘triple challenges’ tied to COVID
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
Psychiatric community is facing ‘triple challenges’ tied to COVID
Psychiatric community is facing ‘triple challenges’ tied to COVID
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
FROM NPA 2021
Quick byte: Curing diabetes
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Make the Diagnosis - March 2021
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
Because of the lack of improvement with topical corticosteroids, a skin biopsy was performed from a lesion on the lower back which showed an epidermis with compact hyperkeratosis and a thickened granular layer. Within the dermis, there was a lichenoid infiltrate of lymphocytes with a prominent interface change and rare dyskeratotic keratinocytes consistent with lichen planus.
Lichen planus is an inflammatory condition of the skin seen mainly in the adult population and is rare in children. This condition affects 0.5%-1% of the population, with maybe a higher prevalence in woman with no racial predilection in the adult or pediatric population. Most patients diagnosed are described to be over 40 years of age, but in children, the mean age for presentation is reported between the ages of 7 and 11.8 years.1 Interestingly, most of the published larger studies of lichen planus in children originate from India. In a U.K. study, about 80% of the cases reported were from children of Indian descent, as is our patient; so it is possible that lichen planus may be more prevalent in India.1 In a study based in the United States, cases were more prevalent in African American children.2
The exact cause of this condition is not known but studies have suggested that activated T cells, particularly CD8+, attack and cause apoptosis of the basal keratinocytes.3 There appears to be an up-regulation of Th1 cytokines such as interferon‐gamma, tumor necrosis factor–alpha, interleukin‐1 alpha, IL‐6, and IL‐8, as well as other apoptosis-related molecules.3
Lichen planus has been associated with other systemic conditions especially liver disease (chronic active hepatitis C and primary biliary cirrhosis). Children and adults may also have coexistence of other autoimmune diseases such as autoimmune polyendocrinopathy, myasthenia gravis, autoimmune thyroid disease, vitiligo, and thymoma. Some reports have also found a higher prevalence of atopic dermatitis in children with lichen planus.4
The lesions are typically described as the four “Ps” for pruritic, polygonal, purpuric flat-topped papules, and plaques. The papules of lichen planus have characteristically dry fine white streaks known as Wickham’s striae. The lesions can occur anywhere on the body, but they tend to occur more commonly on the flexures of the forearms, the wrists, ankles, shins, knees, and the torso. The face is rarely affected. In some patients oral, scalp (lichen planopilaris), nails, and rarely conjunctival, genital, and esophageal involvement can occur.2
In histopathology, the lesions are characterized by a wedge-shaped hypergranulosis, marked hyperkeratosis, and irregular sawtooth-like acanthosis of rete ridges on the epidermis. The dermal-epidermal junction typically shows an interstitial dermatitis. Civatte bodies may also be seen. On direct immunofluorescence, IgM-staining of the cytoid bodies in the dermal papilla or peribasilar areas are suggestive of lichen planus.1
The differential diagnosis of lichen planus includes severe lichenified atopic dermatitis, drug-induced lichen planus, graft-versus-host disease, psoriasis, pityriasis rosea, subacute cutaneous lupus, discoid lupus, secondary syphilis, and lichen simplex chronicus. Interestingly, our patient presented with lesions that were not pruritic and more generalized. Compared with eczema, were flexures are commonly affected, our patient’s lesions were localized to the ankles, wrists, extensor knees, and elbows, and no pruritus was reported. Lichenification of skin lesions occurs as a response to chronic scratching as it occurs in atopic dermatitis and lichen simplex chronicus, was considered in our patient, but the lack of pruritus and the more acute presentation made it unlikely.
Lichen planus is considered a self-limiting disease, so treatment is focused on the control of pruritus and to accelerate resolution. The first-line therapy for classic cutaneous lichen planus is the use of potent or superpotent topical corticosteroids for localized disease on the body and extremities and mild to mid-potency for intertriginous areas and the face. Clinical response should be assessed after 2-3 weeks of treatment. For patients with more generalized or recalcitrant disease like our patient, other treatment modalities like phototherapy (narrow-band UVB), a 4- to 6-week course of oral glucocorticoids, or acitretin may be considered. Our patient recently started narrow-band UVB. Other medications that have been reported beneficial for more severe cases include methotrexate, cyclosporine, griseofulvin, hydroxychloroquine, metronidazole, dapsone, and mycophenolate. Recent studies in the adult population have shown apremilast, a phosphodiesterase inhibitor, to be a promising medication for patients with cutaneous lichen planus, though this medication has not been approved yet for use in the pediatric population.5
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Payette MJ et al. Clin Dermatol. 2015 Nov-Dec;33(6):631-43.
2. Walton KE et al. Pediatr Dermatol. 2010;27:34-8.
3. Lehman JS et al. Int J Dermatol. 2009 Jul;48(7):682-94.
4. Laughter D et al. J Am Acad Dermatol. 2000;43:649-55.
5. Paul J et al. J Am Acad Dermatol. 2013 Feb;68(2):255-61.
There was no prior personal or family history of atopic dermatitis or psoriasis. He has no other medical conditions and is not taking any medications.
He denied any joint pain, sun sensitivity, mouth sores, or other symptoms. After the initial consultation he was treated with fluocinonide 0.05% ointment for 2 weeks with slight improvement on the lesions.
On physical exam he presented with hyperpigmented and violaceous lichenified papules and plaques on the extremities and the torso. (photos 1 and 2). He also had hyperpigmented violaceous macules on the eyelids and around the mouth (photos 1 and 2).
Influenza-related maternal morbidity has more than doubled over 15 years
Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.
, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.
“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.
The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.
The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.
Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:
- 0.02% with shock/sepsis.
- 0.01% needing mechanical ventilation.
- 0.04% with acute respiratory distress syndrome.
The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.
When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).
During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.
From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.
The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).
Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.
“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”
Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”
He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.
Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.
“What surprised me was the big difference in how severe maternal morbidity rates increased over time in the influenza group compared to the group without influenza,” Dr. Louis-Jacques, who moderated the session, said in an interview. She agreed with Dr. Wen that the findings underscore the benefits of immunization.
“The study means we should reinforce to mothers how important the vaccine is. It’s critical,” Dr. Louis-Jacques said. “We should encourage mothers to get it and focus on educating women, trying to understand and allay [any concerns about the vaccine] and reinforce the importance of flu vaccination to decrease the likelihood of these mothers getting pretty sick during pregnancy.”
Dr. Wen and Dr. Louis-Jacques had no disclosures.
Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.
, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.
“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.
The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.
The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.
Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:
- 0.02% with shock/sepsis.
- 0.01% needing mechanical ventilation.
- 0.04% with acute respiratory distress syndrome.
The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.
When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).
During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.
From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.
The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).
Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.
“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”
Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”
He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.
Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.
“What surprised me was the big difference in how severe maternal morbidity rates increased over time in the influenza group compared to the group without influenza,” Dr. Louis-Jacques, who moderated the session, said in an interview. She agreed with Dr. Wen that the findings underscore the benefits of immunization.
“The study means we should reinforce to mothers how important the vaccine is. It’s critical,” Dr. Louis-Jacques said. “We should encourage mothers to get it and focus on educating women, trying to understand and allay [any concerns about the vaccine] and reinforce the importance of flu vaccination to decrease the likelihood of these mothers getting pretty sick during pregnancy.”
Dr. Wen and Dr. Louis-Jacques had no disclosures.
Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.
, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.
Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.
“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.
The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.
The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.
Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:
- 0.02% with shock/sepsis.
- 0.01% needing mechanical ventilation.
- 0.04% with acute respiratory distress syndrome.
The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.
When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).
During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.
From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.
The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).
Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.
“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”
Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”
He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.
Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.
“What surprised me was the big difference in how severe maternal morbidity rates increased over time in the influenza group compared to the group without influenza,” Dr. Louis-Jacques, who moderated the session, said in an interview. She agreed with Dr. Wen that the findings underscore the benefits of immunization.
“The study means we should reinforce to mothers how important the vaccine is. It’s critical,” Dr. Louis-Jacques said. “We should encourage mothers to get it and focus on educating women, trying to understand and allay [any concerns about the vaccine] and reinforce the importance of flu vaccination to decrease the likelihood of these mothers getting pretty sick during pregnancy.”
Dr. Wen and Dr. Louis-Jacques had no disclosures.
FROM THE PREGNANCY MEETING
Vibrio vulnificus: Review of Mild to Life-threatening Skin Infections
Vibrio vulnificus is a member of the Vibrio genus. Most Vibrio species are nonpathogenic in humans; however, V vulnificus is one of the pathogenic strains.1 In Latin, the term vulnificus means “wounding,” and V vulnificus can cause life-threatening infections in patients. The mortality rate of V vulnificus infections is approximately 33% in the United States.2Vibrio vulnificus is a gram-negative bacterium that was first isolated by the Centers for Disease Control and Prevention in 1964 and was given its current name in 1979.3-6 It has been found in numerous organisms, including oysters, crabs, clams, shrimp, mussels, mullets, and sea bass.4 The vast majority of infections in the United States are due to oyster exposure and consumption.2,7Vibrio vulnificus is responsible for more than 95% of seafood-related deaths in the United States and has the highest mortality rate of all food-borne illness in the United States.2,5 It also has the highest per-case economic impact of all food-related diseases in the United States.1
What distinguishes a pathogenic vs nonpathogenic Vibrio isolate remains unknown; Vibrio species rapidly undergo horizontal gene transfer, making DNA isolation difficult.1 Some characteristics of V vulnificus that may confer virulence are the capsular polysaccharide, lipopolysaccharide, binding proteins, and tissue-degrading enzymes.1,5 First, encapsulated strains are more virulent and invasive than unencapsulated strains.1 The mucopolysaccharide capsule protects the bacterium from the immune system, allowing it to evade immune surveillance, cause more severe infection, and invade into the subcutaneous tissue.3,5 Second, production of sialic acid–like molecules alter the lipopolysaccharide, allowing for motility and biofilm formation.1 This allows the bacterium to survive in marine waters and within the bloodstream, the latter leading to sepsis in humans. Third, production of N-acetylglucosamine–binding protein A allows for adhesion to chitin. Shellfish consume chitin, and chitin accumulates in shellfish. N-acetylglucosamine–binding protein A also binds mucin; this may be how V vulnificus binds to mucin in the gastrointestinal tract in humans, causing gastroenteritis.1 Binding to the human mucosae also may allow the bacteria to gain access to the blood supply, leading to septicemia.4 Finally, tissue-degrading enzymes such as proteases are responsible for necrotizing wound infections associated with V vulnificus, as the enzymes allow for invasion into the skin and subcutaneous tissues. Proteases also increase vascular permeability and lead to edema.3 Hence, these virulence factors may provide V vulnificus the pathogenicity to cause infection in humans.
Three biotypes of V vulnificus have been discovered. Biotype 1 is the most common and is found worldwide in brackish water.8 It can cause the entire spectrum of illnesses, and it has a case fatality rate of 50% in humans. Biotype 1 is presumably responsible for all infections in the United States. Biotype 2 is found in the Far East and Western Europe; it inhabits a unique niche—saltwater used for eel farming. It typically causes infection in eels, but rarely it can cause wound infections in humans. Biotype 3 is found in freshwater fish farming in Israel, and it is a hybrid of biotypes 1 and 2.It can cause severe soft tissue infections in humans, sometimes requiring amputation.8
Epidemiology
Vibrio vulnificus is a motile, gram-negative, halophilic, aquatic bacterium.1,4,5,8,9 It is part of the normal estuarine microbiome and typically is found in warm coastal waters.1,5,10 The ideal conditions for growth and survival of V vulnificus are water temperatures at 18 °C (64.4 °F) and water salinities between 15 to 25 parts per thousand.2,8,9 These conditions are found in tropical and subtropical regions.2Vibrio vulnificus is found all over the world, including Denmark, Italy, Japan, Australia, Brazil, and the United States,2 where most infections come from oyster exposure and consumption in the Gulf of Mexico.2,8,11 The incidence of infection in the United States is highest between April and October.8,11
Some populations are at a higher risk of infection. Risk factors include male sex, liver cirrhosis, hemochromatosis, end-stage renal disease, immunosuppression, and diabetes mellitus.1,8,11 Healthy patients with no risk factors account for less than 5% of US V vulnificus infections.8
Male Predilection
Men are 6 times more likely to be affected by V vulnificus than women.Some hypotheses for this discrepancy are that estrogen is protective againstV vulnificus and that women may be less likely to engage in risky water activities and seafood handling.5 Additionally, older males (aged >60 years) are most often affected,1,8 likely due to the association between increasing age with number of comorbidities, such as diabetes mellitus, heart disease, and chronic disease.8
Iron Levels
Iron appears to play an important role in V vulnificus infection. Iron is essential for bacterial growth, and the ability to obtain iron from a host increases the organism’s pathogenicity.3Vibrio vulnificus rapidly grows when transferrin saturation exceeds 70%.8 Additionally, iron overload decreases the inoculum needed to cause sepsis in animal studies, which could play a role in human pathogenesis.4 Iron levels are elevated in patients with hemochromatosis due to increased iron absorption, cirrhosis and chronic liver disease due to impaired iron metabolism, and end-stage renal disease, especially in patients receiving parenteral iron.8
Immunosuppression
Patients who are immunocompromised and those with chronic liver disease are at an increased risk of infection because of neutrophils having decreased phagocytic activity.4
Diabetes Mellitus
Patients with diabetes mellitus may have peripheral neuropathy and may be unaware of pre-existing wounds that serve as entry points for V vulnificus.12
Etiology
Vibrio vulnificus infects humans via seafood consumption and handling as well as exposure to contaminated water.2,5 With respect to seafood consumption, raw shellfish are the primary type of seafood that harbor high levels of V vulnificus.5 Oysters are the most common etiology, but consumption of crabs, clams, and shrimp also can lead to infection.5,7Vibrio vulnificus contamination does not change the appearance, taste, or odor of shellfish, making it hard to detect.8 An inoculate of 1 million bacteria typically is necessary for infection after consumption.5 Contaminated seawater is another primary cause of V vulnificus infection. When open wounds are exposed to seawater harboring the bacteria, wound infections can arise.7 Infections can be acquired when swimming, fishing, or participating in water sports. Wound infections also occur while handling contaminated seafood, such as oyster shucking.5 There is a short incubation period for V vulnificus infections; the onset of symptoms and clinical outcome typically occur within 24 hours.5
Clinical Presentation
Vibrio vulnificus infections can have numerous clinical presentations, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis.1,8 There also is a spectrum of clinical outcomes; for instance, gastroenteritis typically is self-limited, whereas necrotizing fasciitis or sepsis can be fatal.2
Gastroenteritis
Vibrio vulnificus gastroenteritis is due to ingestion of contaminated shellfish.2,9 Symptoms typically are mild to moderate and include nausea, vomiting, diarrhea, fever, chills, abdominal pain, and cramping.2,4,8 Cases likely are underreported in the United States because gastroenteritis is self-limited, and many patients do not seek treatment.2,11
Wound Infections
Wound infections with V vulnificus have a cutaneous port of entry. Exposure to contaminated seawater or seafood can inoculate an open wound, leading to infection.7,8 Wound infections usually stem from 1 of 2 routes: (1) a pre-existing open wound gets infected while the patient is swimming in contaminated water, or (2) a traumatic injury occurs while the patient is handling contaminated shellfish, knives, or fishhooks. Many shellfish, such as oysters, have sharp points on their shells that can lacerate the skin.8 A wound on the hand can be contaminated by V vulnificus while handling contaminated seafood (eg, oyster shucking).13 Minor abrasions should not be dismissed; in fact, a small puncture or skin break often acts as the port of entry.9,11 Wound infections tend to arise within 7 days of exposure, though they can manifest up to 12 days after exposure.8 Wound infections can present as cellulitis, bullae, or ecchymoses.7 Lesions are exquisitely tender, and the skin is erythematous with marked surrounding soft tissue edema.3,4,8 Cellulitis typically arises first, with hemorrhagic bullae rapidly following.14 Lesions are limited to the affected extremity or area of inoculation.8 Systemic symptoms are rare, but fever and chills may accompany the infection.8,14 Unfortunately, lesions can become necrotic and progress rapidly to necrotizing fasciitis if left untreated.4,7,11 In these cases, secondary sepsis can occur.8
Necrotizing Fasciitis
Wound infections caused by V vulnificus can progress to necrotizing skin and soft tissue infections, such as necrotizing fasciitis and gangrene.5 Necrotizing fasciitis accounts for approximately one-third of V vulnificus infections.9 It usually stems from an open wound that is inoculated by contact with contaminated seafood or seawater.2,9 The wound infection begins as cellulitis with extreme tenderness, erythematous skin, and marked soft tissue edema, then rapidly progresses, becoming necrotic. These necrotic lesions present as black and purple eschars as the skin, blood supply, and subcutaneous tissues are infiltrated by the bacteria and destroyed. Lesions may have blistering or exudation. Many patients have accompanying systemic symptoms, including fever, chills, abdominal pain, diarrhea, hypotension, and sepsis.11,14 However, some patients may not present with systemic symptoms, so it is important to maintain a high index of suspicion even in the absence of these symptoms. The infection typically is limited to the affected extremity; necrotizing infections can lead to amputation and even death, depending on the extent of destruction and spread of the bacteria.11,13 The infection may spread beyond the inoculated extremity if the bacteria gains access to the bloodstream.8,9 In these cases, fulminant purpura or secondary septicemia can occur.8,15 Fatalityrates in the United States for necrotizing V vulnificus infections approach 30%.2 Necrotizing fasciitis accounts for approximately 8% of deaths associated with the pathogen in the United States.9
Interestingly, one reported case of necrotizing fasciitis associated with V vulnificus infection was triggered by acupuncture.16 The patient worked in a fish hatchery, where he was exposed to V vulnificus, and subsequent acupuncture led to the inoculation of bacteria into his bloodstream. This case raises the important point that we typically sequence the pathogenesis of V vulnificus infection as a patient having an open wound that is subsequently exposed to contaminated water; however, it also can follow the reverse sequence. Thus, proper cleansing of the skin after swimming in brackish water or handling shellfish is important to prevent V vulnificus infection.16 Additionally, dermatologists should be sure to cleanse patients’ skin thoroughly before performing procedures that could cause breaks in the skin.
Septicemia
Primary septicemia is the most common presentation of V vulnificus infection.2,8 Septicemia accounts for approximately 58% of V vulnificus infections in the United States.9 Infection typically occurs after ingestion of contaminated oysters, with subsequent absorption into the bloodstream through the ileum or cecum.2,8,9 Patients with chronic liver disease are 80 times more likely to develop primary sepsis than healthy individuals.8 Patients typically present with sudden-onset fever and chills, vomiting, diarrhea, and pain in the abdomen and/or extremities within hours to days of ingestion.4,8,9 The median time from ingestion to symptom onset is 18 hours.4,16 However, symptoms can be delayed up to 14 days.2 Progression is rapid; secondary lesions such as bullae, ecchymoses, cellulitis, purpura, macular or maculopapular eruptions, pustules, vasculitis, urticaria, and erythema multiforme–like lesions appear on the extremities within 24 hours of symptom onset. 2,3,4,8,17 Hemorrhagic bullae are the most common cutaneous manifestation of sepsis.4 Lesions are extremely tender to palpation.3 Cutaneous lesions can progress to necrotic ulcers, necrotizing fasciitis, gangrene, necrotizing vasculitis, or myonecrosis.4,8 Evidence of petechiae may indicate progression to disseminated intravascular coagulation (DIC). Elevated D-dimer and fibrin split products also may indicate DIC, and elevated creatine kinase may signify rhabdomyolysis.3 Unfortunately, septicemia has the worst outcomes of all V vulnificus presentations, with morality rates greater than 50% in the United States.1,2,4Vibrio vulnificus septicemia has a similar case-fatality rate to pathogens such as anthrax, Ebola virus disease, and the bubonic plague.5 Septicemia accounts for approximately 80% of the deaths associated with V vulnificus in the United States.8,9
Septicemia due to V vulnificus progresses to septic shock in two-thirds of cases.8 Septic shock presents with hypotension, mental status changes, and thrombocytopenia.2,8,17 Patients can become tachycardic, tachypneic, and hypoxic. Intubation may be required for resuscitation. In cases of septic shock secondary to V vulnificus infection, mortality rates reach 92%.3 Hypotension with a systolic blood pressure less than 90 mm Hg is a poor prognostic factor; patients presenting with hypotension secondary to V vulnificus infection have a fatality rate approaching 75% within 12 hours.2
Atypical Presentations
Rare atypical presentations of V vulnificus infection that have been reported in the literature include meningitis, corneal ulcers, epiglottitis, tonsillitis, spontaneous bacterial peritonitis, pneumonia, endometritis, septic arthritis, osteomyelitis, rhabdomyolysis endophthalmitis, and keratitis.2,4,6,13,18,19
Diagnosis
When diagnosing V vulnificus, providers need to obtain a thorough patient history, including any history of consumption or handling of raw seafood and recent water activities. Providers practicing in tropical climates or in warm summer months should keep V vulnificus in mind, as it is the ideal climate for the pathogen.9 Vital signs can range from unremarkable to fever, hypotension, tachycardia, and/or hypoxia. Skin examination may show exquisitely tender, erythematous skin with marked soft tissue edema, hemorrhagic bullae, ecchymoses, and/or necrosis. As physical examination findings can be nonspecific, wound cultures, blood cultures, and skin biopsies should be taken.
A wound culture and blood culture should be taken immediately if V vulnificus is suspected.8,11 A wound culture using discharge or fluid from necrotic or bullous lesions should be analyzed via gram stain.8,9 Gram stains of V vulnificus show short, slim, curved gram-negative rods under light microscopy.9,20 Special stains also can be done on cultures; V vulnificus is an oxidase-positive, lactose-positive, lysine-positive, salicin-positive, and arginine-negative organism. This knowledge can help differentiate V vulnificus from other gram-negative rods.13 Blood cultures will be positive in approximately 97% of patients with primary septicemia and 30% of patients with septicemia secondary to V vulnificus wound infections.3,9
Histologically, perilesional skin biopsies show epidermal necrosis with dermal and subcutaneous inflammation.12,17 There typically is an inflammatory infiltrate with neutrophilic abscesses and extensive tissue destruction in the subcutaneous tissue extending into the deep dermis.12,17 The superficial dermis is edematous but can lack the inflammatory infiltrate found in the subcutaneous tissue.17 Subepidermal bullae can form with numerous organisms within the fluid of the bullae. There also may be evidence of leukocytoclastic vasculitis with accompanying vessel wall necrosis. Fibrin clot formation and extravasated red blood cells may be visualized with few inflammatory cells but numerous organisms around the involved vessels.17
Management
Early diagnosis and treatment are vital.5,17 Cultures should be taken before aggressive treatment is started.3 Treatment is multifaceted; it requires antibiotics and wound care, except in cases of self-limited gastroenteritis.2,11 Aggressive debridement, fasciotomy, amputation, and supportive measures also may be necessary depending on the patient’s presentation.2,3,8,9 Establishing 2 peripheral intravenous lines is important in case rapid resuscitation becomes necessary.
Antibiotics
Primary cellulitis wound infections should be treated with doxycycline or a quinolone. If untreated, the wound can rapidly progress to necrotizing fasciitis.11 For necrotizing fasciitis and septicemia, broader-spectrum antibiotics are needed. For adults, ceftazidime plus doxycycline is the mainstay of antibiotic treatment for V vulnificus.2,9,11 For children, trimethoprim-sulfamethoxazole plus an aminoglycoside is preferred (Table).2,11
Antibiotic treatment has become more difficult as resistance arises. Antibiotic resistance likely is due to extensive antibiotic use in health care along with the agriculture and aquaculture industries using prophylactic and therapeutic antibiotics that wash into or are directly added to marine waters, where V vulnificus resides. Thus, antibiotic treatment should be tailored to the resistance profile of V vulnificus in various regions; for example, ceftazidime has an intermediate resistance profile in the United States, so cefotaxime and ceftriaxone may be better options.2
Wound Care
Wound infections must be extensively irrigated.9,21 For mild wound infections, proper wound care and oral antibiotics are appropriate (Table).21 Mild wounds should be irrigated thoroughly and followed by wound coverage to prevent progression, secondary infection, and necrosis. The dressing of choice will depend on the presenting lesion and provider preference; nonadherent, occlusive, or wet-to-dry dressings often are the best choices.22 Nonadherent dressings, such as petrolatum-covered gauze, do not pull off the newly formed epithelium when removed, making them beneficial to the skin’s healing process. Another option is occlusive dressings, which maintain a moist environment to hasten healing. They also enhance the autodigestion of necrotic tissue, which can be beneficial for necrotizing V vulnificus infections. Wet-to-dry dressings also may be used; these typically are comprised of gauze soaked with water, an astringent, and an antimicrobial or antiseptic solution. These dressings help to treat acute inflammation and also remove any exudate from the wound.22
Soft tissue and necrotizing infections require debridement.2,8 Early debridement decreases mortality rates.2,8,9 Necrotizing fasciitis often requires serial debridement to clear all the dead tissue and reduce the bacterial burden.8,9 Debridement prevents contiguous spread and metastatic seeding of the bacteria; it is important to prevent spread to the blood vessels, as vasculitis can necrose vessels, preventing antibiotics from reaching the dead tissue.17 Providers also should monitor for compartment syndrome, which should be treated with fasciotomy to decrease mortality.9,23 Many physicians leave V vulnificus–infected wounds open in order to heal by secondary intention.9 Hyperbaric oxygen therapy may be helpful as an adjunct to aggressive antimicrobial treatment for wound healing.8
Supportive Measures
Supportive care for dehydration, sepsis, DIC, and septic shock may be necessary, depending on the patient’s course. Treatment for severe V vulnificus infection includes intravenous fluids, crystalloids, oxygen, and/or intubation. Furthermore, if DIC develops, fresh frozen plasma, cryoprecipitate, a packed red blood cell transfusion, and/or anticoagulation may be required for resuscitation.3
Timing
Time to treatment and fatality rate are directly proportional in V vulnificus infection; the greater the delay in treatment, the higher the fatality rate.2 A 24-hour delay in antibiotic treatment is associated with a 33% case-fatality rate, and a 72-hour delay is associated with a 100% case-fatality rate.9 Even with early, appropriate treatment, mortality rates remain high.4
Prevention
Prevention of V vulnificus infections is an important consideration, especially for patients with chronic liver disease, immunosuppression, and hemochromatosis. Public education about the risks of eating raw shellfish is important.4 Oysters need to be treated properly to prevent growth and survival of V vulnificus.2 The most reliable method for destroying the bacteria is cooking shellfish.8,13 Only 15% of high-risk patients in the United States are aware of the risks associated with raw oyster consumption.3 High-risk patients should avoid eating raw oysters and shellfish and should cook seafood thoroughly before consumption.2,8 They also should wear protective clothing (ie, gloves) and eye protection when handling seafood and protective footwear (ie, wading shoes) while in seawater.2,8,13 It also is important to avoid contact with brackish water if one has any open wounds and to cleanse properly after exposure to brackish water or shellfish.2,8,16 Because severe V vulnificus infections can lead to death, prevention should be strongly encouraged by providers.2
Conclusion
Vibrio vulnificus infection typically occurs due to consumption of contaminated seafood or exposure to contaminated seawater. It most frequently affects older male patients with chronic liver disease, immunosuppression, hemochromatosis, or diabetes mellitus. Vibrio vulnificus can cause a vast spectrum of diseases, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis. Septicemia is the most common presentation of V vulnificus infection and accounts for the most fatalities from the bacteria. Septicemia often presents with fever, chills, vomiting, diarrhea, and hemorrhagic bullae. Vibrio vulnificus also commonly causes necrotizing fasciitis, which initially presents as cellulitis and rapidly progresses to hemorrhagic bullae or necrosis with accompanying systemic symptoms. Prompt diagnosis and treatment are vital to prevent mortality.
Interestingly, regions impacted by V vulnificus are expanding because of global warming.5,7Vibrio vulnificus thrives in warm waters, and increasing water temperatures are enhancing V vulnificus growth and survival.1,9 As global warming continues, the incidence of V vulnificus infections may rise. In fact, the number of infections increased by 78% between 1996 and 2006 in the United States.5 This rise likely was due to a combination of factors, including an aging population with more comorbidities, improvements in diagnosis, and climate change. Thus, as the number of V vulnificus infections rises, so too must providers’ suspicion for the pathogen.
- Phillips KE, Satchell KJF. Vibrio vulnificus: from oyster colonist to human pathogen [published online January 5, 2017]. PLOS Pathog. doi:10.1371/journal.ppat.1006053
- Heng SP, Letchumanan V, Deng CY, et al. Vibrio vulnificus: an environmental and clinical burden. Front Microbiol. 2017;8:997.
- Kumamoto KS, Vukich DJ. Clinical infections of Vibrio vulnificus: a case report and review of the literature. J Emerg Med. 1998;16:61-66.
- Borenstein M, Kerdel F. Infections with Vibrio vulnificus. Dermatol Clin. 2003;21:245-248.
- Baker-Austin C, Oliver JD. Vibrio vulnificus: new insights into a deadly opportunistic pathogen. Environ Microbiol. 2018;20:423-430.
- Kim SJ, Kim BC, Kim DC, et al. A fatal case of Vibrio vulnificus meningoencephalitis. Clin Microbiol Infect. 2003;9:568-571.
- Jones MK, Oliver JD. Vibrio vulnificus: disease and pathogenesis. Infect Immun. 2009;77:1723-1733.
- Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus infection: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis. 2011;15:E157-E166.
- Diaz JH. Skin and soft tissue infections following marine injuries and exposures in travelers. J Travel Med. 2014;21:207-213.
- Kikawa K, Yamasaki K, Sukiura T, et al. A successfully treated case of Vibrio vulnificus septicemia with shock. Jpn J Med. 1990;29:313-319.
- Perkins AP, Trimmier M. Recreational waterborne illnesses: recognition, treatment, and prevention. Am Fam Physician. 2017;95:554-560.
- Patel VJ, Gardner E, Burton CS. Vibrio vulnificus septicemia and leg ulcer. J Am Acad Dermatol. 2002;46(5 suppl):S144-S145.
- Ulusarac O, Carter E. Varied clinical presentations of Vibrio vulnificus infections: a report of four unusual cases and review of the literature. South Med J. 2004;97:613-618.
- Bross MH, Soch K, Morales R, et al. Vibrio vulnificus infection: diagnosis and treatment. Am Fam Physician. 2007;76:539-544.
- Hori M, Nakayama A, Kitagawa D, et al. A case of Vibrio vulnificus infection complicated with fulminant purpura: gene and biotype analysis of the pathogen [published online May 19, 2017]. JMM Case Rep. doi:10.1099/jmmcr.0.005096
- Kotton Y, Soboh S, Bisharat N. Vibrio vulnificus necrotizing fasciitis associated with acupuncture. Infect Dis Rep. 2015;7:5901.
- Hoffman TJ, Nelson B, Darouiche R, et al. Vibrio vulnificus septicemia. Arch Intern Med. 1988;148:1825-1827.
- Alsaad AA, Sotello D, Kruse BT, et al. Vibrio vulnificus tonsillitis after swimming in the Gulf of Mexico [published online June 28, 2017]. BMJ Case Rep. doi:10.1136/bcr-2017-221161
- Tison DL, Kelly MT. Vibrio vulnificus endometritis. J Clin Microbiol. 1984;20:185-186.
- Beatty NL, Marquez J, Mohajer MA. Skin manifestations of primary Vibrio vulnificus septicemia. Am J Trop Med Hyg. 2017;97:1-2.
- Foote A, Henderson R, Lindberg A, et al. The Australian mid-west coastal marine wound infections study. Aust Fam Physician. 2017;46:923-927.
- Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Elsevier; 2019.
- Kim CS, Bae EH, Ma SK, et al. Severe septicemia, necrotizing fasciitis, and peritonitis due to Vibrio vulnificus in a patient undergoing continuous ambulatory peritoneal dialysis: a case report. BMC Infect Dis. 2015;15:422.
Vibrio vulnificus is a member of the Vibrio genus. Most Vibrio species are nonpathogenic in humans; however, V vulnificus is one of the pathogenic strains.1 In Latin, the term vulnificus means “wounding,” and V vulnificus can cause life-threatening infections in patients. The mortality rate of V vulnificus infections is approximately 33% in the United States.2Vibrio vulnificus is a gram-negative bacterium that was first isolated by the Centers for Disease Control and Prevention in 1964 and was given its current name in 1979.3-6 It has been found in numerous organisms, including oysters, crabs, clams, shrimp, mussels, mullets, and sea bass.4 The vast majority of infections in the United States are due to oyster exposure and consumption.2,7Vibrio vulnificus is responsible for more than 95% of seafood-related deaths in the United States and has the highest mortality rate of all food-borne illness in the United States.2,5 It also has the highest per-case economic impact of all food-related diseases in the United States.1
What distinguishes a pathogenic vs nonpathogenic Vibrio isolate remains unknown; Vibrio species rapidly undergo horizontal gene transfer, making DNA isolation difficult.1 Some characteristics of V vulnificus that may confer virulence are the capsular polysaccharide, lipopolysaccharide, binding proteins, and tissue-degrading enzymes.1,5 First, encapsulated strains are more virulent and invasive than unencapsulated strains.1 The mucopolysaccharide capsule protects the bacterium from the immune system, allowing it to evade immune surveillance, cause more severe infection, and invade into the subcutaneous tissue.3,5 Second, production of sialic acid–like molecules alter the lipopolysaccharide, allowing for motility and biofilm formation.1 This allows the bacterium to survive in marine waters and within the bloodstream, the latter leading to sepsis in humans. Third, production of N-acetylglucosamine–binding protein A allows for adhesion to chitin. Shellfish consume chitin, and chitin accumulates in shellfish. N-acetylglucosamine–binding protein A also binds mucin; this may be how V vulnificus binds to mucin in the gastrointestinal tract in humans, causing gastroenteritis.1 Binding to the human mucosae also may allow the bacteria to gain access to the blood supply, leading to septicemia.4 Finally, tissue-degrading enzymes such as proteases are responsible for necrotizing wound infections associated with V vulnificus, as the enzymes allow for invasion into the skin and subcutaneous tissues. Proteases also increase vascular permeability and lead to edema.3 Hence, these virulence factors may provide V vulnificus the pathogenicity to cause infection in humans.
Three biotypes of V vulnificus have been discovered. Biotype 1 is the most common and is found worldwide in brackish water.8 It can cause the entire spectrum of illnesses, and it has a case fatality rate of 50% in humans. Biotype 1 is presumably responsible for all infections in the United States. Biotype 2 is found in the Far East and Western Europe; it inhabits a unique niche—saltwater used for eel farming. It typically causes infection in eels, but rarely it can cause wound infections in humans. Biotype 3 is found in freshwater fish farming in Israel, and it is a hybrid of biotypes 1 and 2.It can cause severe soft tissue infections in humans, sometimes requiring amputation.8
Epidemiology
Vibrio vulnificus is a motile, gram-negative, halophilic, aquatic bacterium.1,4,5,8,9 It is part of the normal estuarine microbiome and typically is found in warm coastal waters.1,5,10 The ideal conditions for growth and survival of V vulnificus are water temperatures at 18 °C (64.4 °F) and water salinities between 15 to 25 parts per thousand.2,8,9 These conditions are found in tropical and subtropical regions.2Vibrio vulnificus is found all over the world, including Denmark, Italy, Japan, Australia, Brazil, and the United States,2 where most infections come from oyster exposure and consumption in the Gulf of Mexico.2,8,11 The incidence of infection in the United States is highest between April and October.8,11
Some populations are at a higher risk of infection. Risk factors include male sex, liver cirrhosis, hemochromatosis, end-stage renal disease, immunosuppression, and diabetes mellitus.1,8,11 Healthy patients with no risk factors account for less than 5% of US V vulnificus infections.8
Male Predilection
Men are 6 times more likely to be affected by V vulnificus than women.Some hypotheses for this discrepancy are that estrogen is protective againstV vulnificus and that women may be less likely to engage in risky water activities and seafood handling.5 Additionally, older males (aged >60 years) are most often affected,1,8 likely due to the association between increasing age with number of comorbidities, such as diabetes mellitus, heart disease, and chronic disease.8
Iron Levels
Iron appears to play an important role in V vulnificus infection. Iron is essential for bacterial growth, and the ability to obtain iron from a host increases the organism’s pathogenicity.3Vibrio vulnificus rapidly grows when transferrin saturation exceeds 70%.8 Additionally, iron overload decreases the inoculum needed to cause sepsis in animal studies, which could play a role in human pathogenesis.4 Iron levels are elevated in patients with hemochromatosis due to increased iron absorption, cirrhosis and chronic liver disease due to impaired iron metabolism, and end-stage renal disease, especially in patients receiving parenteral iron.8
Immunosuppression
Patients who are immunocompromised and those with chronic liver disease are at an increased risk of infection because of neutrophils having decreased phagocytic activity.4
Diabetes Mellitus
Patients with diabetes mellitus may have peripheral neuropathy and may be unaware of pre-existing wounds that serve as entry points for V vulnificus.12
Etiology
Vibrio vulnificus infects humans via seafood consumption and handling as well as exposure to contaminated water.2,5 With respect to seafood consumption, raw shellfish are the primary type of seafood that harbor high levels of V vulnificus.5 Oysters are the most common etiology, but consumption of crabs, clams, and shrimp also can lead to infection.5,7Vibrio vulnificus contamination does not change the appearance, taste, or odor of shellfish, making it hard to detect.8 An inoculate of 1 million bacteria typically is necessary for infection after consumption.5 Contaminated seawater is another primary cause of V vulnificus infection. When open wounds are exposed to seawater harboring the bacteria, wound infections can arise.7 Infections can be acquired when swimming, fishing, or participating in water sports. Wound infections also occur while handling contaminated seafood, such as oyster shucking.5 There is a short incubation period for V vulnificus infections; the onset of symptoms and clinical outcome typically occur within 24 hours.5
Clinical Presentation
Vibrio vulnificus infections can have numerous clinical presentations, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis.1,8 There also is a spectrum of clinical outcomes; for instance, gastroenteritis typically is self-limited, whereas necrotizing fasciitis or sepsis can be fatal.2
Gastroenteritis
Vibrio vulnificus gastroenteritis is due to ingestion of contaminated shellfish.2,9 Symptoms typically are mild to moderate and include nausea, vomiting, diarrhea, fever, chills, abdominal pain, and cramping.2,4,8 Cases likely are underreported in the United States because gastroenteritis is self-limited, and many patients do not seek treatment.2,11
Wound Infections
Wound infections with V vulnificus have a cutaneous port of entry. Exposure to contaminated seawater or seafood can inoculate an open wound, leading to infection.7,8 Wound infections usually stem from 1 of 2 routes: (1) a pre-existing open wound gets infected while the patient is swimming in contaminated water, or (2) a traumatic injury occurs while the patient is handling contaminated shellfish, knives, or fishhooks. Many shellfish, such as oysters, have sharp points on their shells that can lacerate the skin.8 A wound on the hand can be contaminated by V vulnificus while handling contaminated seafood (eg, oyster shucking).13 Minor abrasions should not be dismissed; in fact, a small puncture or skin break often acts as the port of entry.9,11 Wound infections tend to arise within 7 days of exposure, though they can manifest up to 12 days after exposure.8 Wound infections can present as cellulitis, bullae, or ecchymoses.7 Lesions are exquisitely tender, and the skin is erythematous with marked surrounding soft tissue edema.3,4,8 Cellulitis typically arises first, with hemorrhagic bullae rapidly following.14 Lesions are limited to the affected extremity or area of inoculation.8 Systemic symptoms are rare, but fever and chills may accompany the infection.8,14 Unfortunately, lesions can become necrotic and progress rapidly to necrotizing fasciitis if left untreated.4,7,11 In these cases, secondary sepsis can occur.8
Necrotizing Fasciitis
Wound infections caused by V vulnificus can progress to necrotizing skin and soft tissue infections, such as necrotizing fasciitis and gangrene.5 Necrotizing fasciitis accounts for approximately one-third of V vulnificus infections.9 It usually stems from an open wound that is inoculated by contact with contaminated seafood or seawater.2,9 The wound infection begins as cellulitis with extreme tenderness, erythematous skin, and marked soft tissue edema, then rapidly progresses, becoming necrotic. These necrotic lesions present as black and purple eschars as the skin, blood supply, and subcutaneous tissues are infiltrated by the bacteria and destroyed. Lesions may have blistering or exudation. Many patients have accompanying systemic symptoms, including fever, chills, abdominal pain, diarrhea, hypotension, and sepsis.11,14 However, some patients may not present with systemic symptoms, so it is important to maintain a high index of suspicion even in the absence of these symptoms. The infection typically is limited to the affected extremity; necrotizing infections can lead to amputation and even death, depending on the extent of destruction and spread of the bacteria.11,13 The infection may spread beyond the inoculated extremity if the bacteria gains access to the bloodstream.8,9 In these cases, fulminant purpura or secondary septicemia can occur.8,15 Fatalityrates in the United States for necrotizing V vulnificus infections approach 30%.2 Necrotizing fasciitis accounts for approximately 8% of deaths associated with the pathogen in the United States.9
Interestingly, one reported case of necrotizing fasciitis associated with V vulnificus infection was triggered by acupuncture.16 The patient worked in a fish hatchery, where he was exposed to V vulnificus, and subsequent acupuncture led to the inoculation of bacteria into his bloodstream. This case raises the important point that we typically sequence the pathogenesis of V vulnificus infection as a patient having an open wound that is subsequently exposed to contaminated water; however, it also can follow the reverse sequence. Thus, proper cleansing of the skin after swimming in brackish water or handling shellfish is important to prevent V vulnificus infection.16 Additionally, dermatologists should be sure to cleanse patients’ skin thoroughly before performing procedures that could cause breaks in the skin.
Septicemia
Primary septicemia is the most common presentation of V vulnificus infection.2,8 Septicemia accounts for approximately 58% of V vulnificus infections in the United States.9 Infection typically occurs after ingestion of contaminated oysters, with subsequent absorption into the bloodstream through the ileum or cecum.2,8,9 Patients with chronic liver disease are 80 times more likely to develop primary sepsis than healthy individuals.8 Patients typically present with sudden-onset fever and chills, vomiting, diarrhea, and pain in the abdomen and/or extremities within hours to days of ingestion.4,8,9 The median time from ingestion to symptom onset is 18 hours.4,16 However, symptoms can be delayed up to 14 days.2 Progression is rapid; secondary lesions such as bullae, ecchymoses, cellulitis, purpura, macular or maculopapular eruptions, pustules, vasculitis, urticaria, and erythema multiforme–like lesions appear on the extremities within 24 hours of symptom onset. 2,3,4,8,17 Hemorrhagic bullae are the most common cutaneous manifestation of sepsis.4 Lesions are extremely tender to palpation.3 Cutaneous lesions can progress to necrotic ulcers, necrotizing fasciitis, gangrene, necrotizing vasculitis, or myonecrosis.4,8 Evidence of petechiae may indicate progression to disseminated intravascular coagulation (DIC). Elevated D-dimer and fibrin split products also may indicate DIC, and elevated creatine kinase may signify rhabdomyolysis.3 Unfortunately, septicemia has the worst outcomes of all V vulnificus presentations, with morality rates greater than 50% in the United States.1,2,4Vibrio vulnificus septicemia has a similar case-fatality rate to pathogens such as anthrax, Ebola virus disease, and the bubonic plague.5 Septicemia accounts for approximately 80% of the deaths associated with V vulnificus in the United States.8,9
Septicemia due to V vulnificus progresses to septic shock in two-thirds of cases.8 Septic shock presents with hypotension, mental status changes, and thrombocytopenia.2,8,17 Patients can become tachycardic, tachypneic, and hypoxic. Intubation may be required for resuscitation. In cases of septic shock secondary to V vulnificus infection, mortality rates reach 92%.3 Hypotension with a systolic blood pressure less than 90 mm Hg is a poor prognostic factor; patients presenting with hypotension secondary to V vulnificus infection have a fatality rate approaching 75% within 12 hours.2
Atypical Presentations
Rare atypical presentations of V vulnificus infection that have been reported in the literature include meningitis, corneal ulcers, epiglottitis, tonsillitis, spontaneous bacterial peritonitis, pneumonia, endometritis, septic arthritis, osteomyelitis, rhabdomyolysis endophthalmitis, and keratitis.2,4,6,13,18,19
Diagnosis
When diagnosing V vulnificus, providers need to obtain a thorough patient history, including any history of consumption or handling of raw seafood and recent water activities. Providers practicing in tropical climates or in warm summer months should keep V vulnificus in mind, as it is the ideal climate for the pathogen.9 Vital signs can range from unremarkable to fever, hypotension, tachycardia, and/or hypoxia. Skin examination may show exquisitely tender, erythematous skin with marked soft tissue edema, hemorrhagic bullae, ecchymoses, and/or necrosis. As physical examination findings can be nonspecific, wound cultures, blood cultures, and skin biopsies should be taken.
A wound culture and blood culture should be taken immediately if V vulnificus is suspected.8,11 A wound culture using discharge or fluid from necrotic or bullous lesions should be analyzed via gram stain.8,9 Gram stains of V vulnificus show short, slim, curved gram-negative rods under light microscopy.9,20 Special stains also can be done on cultures; V vulnificus is an oxidase-positive, lactose-positive, lysine-positive, salicin-positive, and arginine-negative organism. This knowledge can help differentiate V vulnificus from other gram-negative rods.13 Blood cultures will be positive in approximately 97% of patients with primary septicemia and 30% of patients with septicemia secondary to V vulnificus wound infections.3,9
Histologically, perilesional skin biopsies show epidermal necrosis with dermal and subcutaneous inflammation.12,17 There typically is an inflammatory infiltrate with neutrophilic abscesses and extensive tissue destruction in the subcutaneous tissue extending into the deep dermis.12,17 The superficial dermis is edematous but can lack the inflammatory infiltrate found in the subcutaneous tissue.17 Subepidermal bullae can form with numerous organisms within the fluid of the bullae. There also may be evidence of leukocytoclastic vasculitis with accompanying vessel wall necrosis. Fibrin clot formation and extravasated red blood cells may be visualized with few inflammatory cells but numerous organisms around the involved vessels.17
Management
Early diagnosis and treatment are vital.5,17 Cultures should be taken before aggressive treatment is started.3 Treatment is multifaceted; it requires antibiotics and wound care, except in cases of self-limited gastroenteritis.2,11 Aggressive debridement, fasciotomy, amputation, and supportive measures also may be necessary depending on the patient’s presentation.2,3,8,9 Establishing 2 peripheral intravenous lines is important in case rapid resuscitation becomes necessary.
Antibiotics
Primary cellulitis wound infections should be treated with doxycycline or a quinolone. If untreated, the wound can rapidly progress to necrotizing fasciitis.11 For necrotizing fasciitis and septicemia, broader-spectrum antibiotics are needed. For adults, ceftazidime plus doxycycline is the mainstay of antibiotic treatment for V vulnificus.2,9,11 For children, trimethoprim-sulfamethoxazole plus an aminoglycoside is preferred (Table).2,11
Antibiotic treatment has become more difficult as resistance arises. Antibiotic resistance likely is due to extensive antibiotic use in health care along with the agriculture and aquaculture industries using prophylactic and therapeutic antibiotics that wash into or are directly added to marine waters, where V vulnificus resides. Thus, antibiotic treatment should be tailored to the resistance profile of V vulnificus in various regions; for example, ceftazidime has an intermediate resistance profile in the United States, so cefotaxime and ceftriaxone may be better options.2
Wound Care
Wound infections must be extensively irrigated.9,21 For mild wound infections, proper wound care and oral antibiotics are appropriate (Table).21 Mild wounds should be irrigated thoroughly and followed by wound coverage to prevent progression, secondary infection, and necrosis. The dressing of choice will depend on the presenting lesion and provider preference; nonadherent, occlusive, or wet-to-dry dressings often are the best choices.22 Nonadherent dressings, such as petrolatum-covered gauze, do not pull off the newly formed epithelium when removed, making them beneficial to the skin’s healing process. Another option is occlusive dressings, which maintain a moist environment to hasten healing. They also enhance the autodigestion of necrotic tissue, which can be beneficial for necrotizing V vulnificus infections. Wet-to-dry dressings also may be used; these typically are comprised of gauze soaked with water, an astringent, and an antimicrobial or antiseptic solution. These dressings help to treat acute inflammation and also remove any exudate from the wound.22
Soft tissue and necrotizing infections require debridement.2,8 Early debridement decreases mortality rates.2,8,9 Necrotizing fasciitis often requires serial debridement to clear all the dead tissue and reduce the bacterial burden.8,9 Debridement prevents contiguous spread and metastatic seeding of the bacteria; it is important to prevent spread to the blood vessels, as vasculitis can necrose vessels, preventing antibiotics from reaching the dead tissue.17 Providers also should monitor for compartment syndrome, which should be treated with fasciotomy to decrease mortality.9,23 Many physicians leave V vulnificus–infected wounds open in order to heal by secondary intention.9 Hyperbaric oxygen therapy may be helpful as an adjunct to aggressive antimicrobial treatment for wound healing.8
Supportive Measures
Supportive care for dehydration, sepsis, DIC, and septic shock may be necessary, depending on the patient’s course. Treatment for severe V vulnificus infection includes intravenous fluids, crystalloids, oxygen, and/or intubation. Furthermore, if DIC develops, fresh frozen plasma, cryoprecipitate, a packed red blood cell transfusion, and/or anticoagulation may be required for resuscitation.3
Timing
Time to treatment and fatality rate are directly proportional in V vulnificus infection; the greater the delay in treatment, the higher the fatality rate.2 A 24-hour delay in antibiotic treatment is associated with a 33% case-fatality rate, and a 72-hour delay is associated with a 100% case-fatality rate.9 Even with early, appropriate treatment, mortality rates remain high.4
Prevention
Prevention of V vulnificus infections is an important consideration, especially for patients with chronic liver disease, immunosuppression, and hemochromatosis. Public education about the risks of eating raw shellfish is important.4 Oysters need to be treated properly to prevent growth and survival of V vulnificus.2 The most reliable method for destroying the bacteria is cooking shellfish.8,13 Only 15% of high-risk patients in the United States are aware of the risks associated with raw oyster consumption.3 High-risk patients should avoid eating raw oysters and shellfish and should cook seafood thoroughly before consumption.2,8 They also should wear protective clothing (ie, gloves) and eye protection when handling seafood and protective footwear (ie, wading shoes) while in seawater.2,8,13 It also is important to avoid contact with brackish water if one has any open wounds and to cleanse properly after exposure to brackish water or shellfish.2,8,16 Because severe V vulnificus infections can lead to death, prevention should be strongly encouraged by providers.2
Conclusion
Vibrio vulnificus infection typically occurs due to consumption of contaminated seafood or exposure to contaminated seawater. It most frequently affects older male patients with chronic liver disease, immunosuppression, hemochromatosis, or diabetes mellitus. Vibrio vulnificus can cause a vast spectrum of diseases, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis. Septicemia is the most common presentation of V vulnificus infection and accounts for the most fatalities from the bacteria. Septicemia often presents with fever, chills, vomiting, diarrhea, and hemorrhagic bullae. Vibrio vulnificus also commonly causes necrotizing fasciitis, which initially presents as cellulitis and rapidly progresses to hemorrhagic bullae or necrosis with accompanying systemic symptoms. Prompt diagnosis and treatment are vital to prevent mortality.
Interestingly, regions impacted by V vulnificus are expanding because of global warming.5,7Vibrio vulnificus thrives in warm waters, and increasing water temperatures are enhancing V vulnificus growth and survival.1,9 As global warming continues, the incidence of V vulnificus infections may rise. In fact, the number of infections increased by 78% between 1996 and 2006 in the United States.5 This rise likely was due to a combination of factors, including an aging population with more comorbidities, improvements in diagnosis, and climate change. Thus, as the number of V vulnificus infections rises, so too must providers’ suspicion for the pathogen.
Vibrio vulnificus is a member of the Vibrio genus. Most Vibrio species are nonpathogenic in humans; however, V vulnificus is one of the pathogenic strains.1 In Latin, the term vulnificus means “wounding,” and V vulnificus can cause life-threatening infections in patients. The mortality rate of V vulnificus infections is approximately 33% in the United States.2Vibrio vulnificus is a gram-negative bacterium that was first isolated by the Centers for Disease Control and Prevention in 1964 and was given its current name in 1979.3-6 It has been found in numerous organisms, including oysters, crabs, clams, shrimp, mussels, mullets, and sea bass.4 The vast majority of infections in the United States are due to oyster exposure and consumption.2,7Vibrio vulnificus is responsible for more than 95% of seafood-related deaths in the United States and has the highest mortality rate of all food-borne illness in the United States.2,5 It also has the highest per-case economic impact of all food-related diseases in the United States.1
What distinguishes a pathogenic vs nonpathogenic Vibrio isolate remains unknown; Vibrio species rapidly undergo horizontal gene transfer, making DNA isolation difficult.1 Some characteristics of V vulnificus that may confer virulence are the capsular polysaccharide, lipopolysaccharide, binding proteins, and tissue-degrading enzymes.1,5 First, encapsulated strains are more virulent and invasive than unencapsulated strains.1 The mucopolysaccharide capsule protects the bacterium from the immune system, allowing it to evade immune surveillance, cause more severe infection, and invade into the subcutaneous tissue.3,5 Second, production of sialic acid–like molecules alter the lipopolysaccharide, allowing for motility and biofilm formation.1 This allows the bacterium to survive in marine waters and within the bloodstream, the latter leading to sepsis in humans. Third, production of N-acetylglucosamine–binding protein A allows for adhesion to chitin. Shellfish consume chitin, and chitin accumulates in shellfish. N-acetylglucosamine–binding protein A also binds mucin; this may be how V vulnificus binds to mucin in the gastrointestinal tract in humans, causing gastroenteritis.1 Binding to the human mucosae also may allow the bacteria to gain access to the blood supply, leading to septicemia.4 Finally, tissue-degrading enzymes such as proteases are responsible for necrotizing wound infections associated with V vulnificus, as the enzymes allow for invasion into the skin and subcutaneous tissues. Proteases also increase vascular permeability and lead to edema.3 Hence, these virulence factors may provide V vulnificus the pathogenicity to cause infection in humans.
Three biotypes of V vulnificus have been discovered. Biotype 1 is the most common and is found worldwide in brackish water.8 It can cause the entire spectrum of illnesses, and it has a case fatality rate of 50% in humans. Biotype 1 is presumably responsible for all infections in the United States. Biotype 2 is found in the Far East and Western Europe; it inhabits a unique niche—saltwater used for eel farming. It typically causes infection in eels, but rarely it can cause wound infections in humans. Biotype 3 is found in freshwater fish farming in Israel, and it is a hybrid of biotypes 1 and 2.It can cause severe soft tissue infections in humans, sometimes requiring amputation.8
Epidemiology
Vibrio vulnificus is a motile, gram-negative, halophilic, aquatic bacterium.1,4,5,8,9 It is part of the normal estuarine microbiome and typically is found in warm coastal waters.1,5,10 The ideal conditions for growth and survival of V vulnificus are water temperatures at 18 °C (64.4 °F) and water salinities between 15 to 25 parts per thousand.2,8,9 These conditions are found in tropical and subtropical regions.2Vibrio vulnificus is found all over the world, including Denmark, Italy, Japan, Australia, Brazil, and the United States,2 where most infections come from oyster exposure and consumption in the Gulf of Mexico.2,8,11 The incidence of infection in the United States is highest between April and October.8,11
Some populations are at a higher risk of infection. Risk factors include male sex, liver cirrhosis, hemochromatosis, end-stage renal disease, immunosuppression, and diabetes mellitus.1,8,11 Healthy patients with no risk factors account for less than 5% of US V vulnificus infections.8
Male Predilection
Men are 6 times more likely to be affected by V vulnificus than women.Some hypotheses for this discrepancy are that estrogen is protective againstV vulnificus and that women may be less likely to engage in risky water activities and seafood handling.5 Additionally, older males (aged >60 years) are most often affected,1,8 likely due to the association between increasing age with number of comorbidities, such as diabetes mellitus, heart disease, and chronic disease.8
Iron Levels
Iron appears to play an important role in V vulnificus infection. Iron is essential for bacterial growth, and the ability to obtain iron from a host increases the organism’s pathogenicity.3Vibrio vulnificus rapidly grows when transferrin saturation exceeds 70%.8 Additionally, iron overload decreases the inoculum needed to cause sepsis in animal studies, which could play a role in human pathogenesis.4 Iron levels are elevated in patients with hemochromatosis due to increased iron absorption, cirrhosis and chronic liver disease due to impaired iron metabolism, and end-stage renal disease, especially in patients receiving parenteral iron.8
Immunosuppression
Patients who are immunocompromised and those with chronic liver disease are at an increased risk of infection because of neutrophils having decreased phagocytic activity.4
Diabetes Mellitus
Patients with diabetes mellitus may have peripheral neuropathy and may be unaware of pre-existing wounds that serve as entry points for V vulnificus.12
Etiology
Vibrio vulnificus infects humans via seafood consumption and handling as well as exposure to contaminated water.2,5 With respect to seafood consumption, raw shellfish are the primary type of seafood that harbor high levels of V vulnificus.5 Oysters are the most common etiology, but consumption of crabs, clams, and shrimp also can lead to infection.5,7Vibrio vulnificus contamination does not change the appearance, taste, or odor of shellfish, making it hard to detect.8 An inoculate of 1 million bacteria typically is necessary for infection after consumption.5 Contaminated seawater is another primary cause of V vulnificus infection. When open wounds are exposed to seawater harboring the bacteria, wound infections can arise.7 Infections can be acquired when swimming, fishing, or participating in water sports. Wound infections also occur while handling contaminated seafood, such as oyster shucking.5 There is a short incubation period for V vulnificus infections; the onset of symptoms and clinical outcome typically occur within 24 hours.5
Clinical Presentation
Vibrio vulnificus infections can have numerous clinical presentations, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis.1,8 There also is a spectrum of clinical outcomes; for instance, gastroenteritis typically is self-limited, whereas necrotizing fasciitis or sepsis can be fatal.2
Gastroenteritis
Vibrio vulnificus gastroenteritis is due to ingestion of contaminated shellfish.2,9 Symptoms typically are mild to moderate and include nausea, vomiting, diarrhea, fever, chills, abdominal pain, and cramping.2,4,8 Cases likely are underreported in the United States because gastroenteritis is self-limited, and many patients do not seek treatment.2,11
Wound Infections
Wound infections with V vulnificus have a cutaneous port of entry. Exposure to contaminated seawater or seafood can inoculate an open wound, leading to infection.7,8 Wound infections usually stem from 1 of 2 routes: (1) a pre-existing open wound gets infected while the patient is swimming in contaminated water, or (2) a traumatic injury occurs while the patient is handling contaminated shellfish, knives, or fishhooks. Many shellfish, such as oysters, have sharp points on their shells that can lacerate the skin.8 A wound on the hand can be contaminated by V vulnificus while handling contaminated seafood (eg, oyster shucking).13 Minor abrasions should not be dismissed; in fact, a small puncture or skin break often acts as the port of entry.9,11 Wound infections tend to arise within 7 days of exposure, though they can manifest up to 12 days after exposure.8 Wound infections can present as cellulitis, bullae, or ecchymoses.7 Lesions are exquisitely tender, and the skin is erythematous with marked surrounding soft tissue edema.3,4,8 Cellulitis typically arises first, with hemorrhagic bullae rapidly following.14 Lesions are limited to the affected extremity or area of inoculation.8 Systemic symptoms are rare, but fever and chills may accompany the infection.8,14 Unfortunately, lesions can become necrotic and progress rapidly to necrotizing fasciitis if left untreated.4,7,11 In these cases, secondary sepsis can occur.8
Necrotizing Fasciitis
Wound infections caused by V vulnificus can progress to necrotizing skin and soft tissue infections, such as necrotizing fasciitis and gangrene.5 Necrotizing fasciitis accounts for approximately one-third of V vulnificus infections.9 It usually stems from an open wound that is inoculated by contact with contaminated seafood or seawater.2,9 The wound infection begins as cellulitis with extreme tenderness, erythematous skin, and marked soft tissue edema, then rapidly progresses, becoming necrotic. These necrotic lesions present as black and purple eschars as the skin, blood supply, and subcutaneous tissues are infiltrated by the bacteria and destroyed. Lesions may have blistering or exudation. Many patients have accompanying systemic symptoms, including fever, chills, abdominal pain, diarrhea, hypotension, and sepsis.11,14 However, some patients may not present with systemic symptoms, so it is important to maintain a high index of suspicion even in the absence of these symptoms. The infection typically is limited to the affected extremity; necrotizing infections can lead to amputation and even death, depending on the extent of destruction and spread of the bacteria.11,13 The infection may spread beyond the inoculated extremity if the bacteria gains access to the bloodstream.8,9 In these cases, fulminant purpura or secondary septicemia can occur.8,15 Fatalityrates in the United States for necrotizing V vulnificus infections approach 30%.2 Necrotizing fasciitis accounts for approximately 8% of deaths associated with the pathogen in the United States.9
Interestingly, one reported case of necrotizing fasciitis associated with V vulnificus infection was triggered by acupuncture.16 The patient worked in a fish hatchery, where he was exposed to V vulnificus, and subsequent acupuncture led to the inoculation of bacteria into his bloodstream. This case raises the important point that we typically sequence the pathogenesis of V vulnificus infection as a patient having an open wound that is subsequently exposed to contaminated water; however, it also can follow the reverse sequence. Thus, proper cleansing of the skin after swimming in brackish water or handling shellfish is important to prevent V vulnificus infection.16 Additionally, dermatologists should be sure to cleanse patients’ skin thoroughly before performing procedures that could cause breaks in the skin.
Septicemia
Primary septicemia is the most common presentation of V vulnificus infection.2,8 Septicemia accounts for approximately 58% of V vulnificus infections in the United States.9 Infection typically occurs after ingestion of contaminated oysters, with subsequent absorption into the bloodstream through the ileum or cecum.2,8,9 Patients with chronic liver disease are 80 times more likely to develop primary sepsis than healthy individuals.8 Patients typically present with sudden-onset fever and chills, vomiting, diarrhea, and pain in the abdomen and/or extremities within hours to days of ingestion.4,8,9 The median time from ingestion to symptom onset is 18 hours.4,16 However, symptoms can be delayed up to 14 days.2 Progression is rapid; secondary lesions such as bullae, ecchymoses, cellulitis, purpura, macular or maculopapular eruptions, pustules, vasculitis, urticaria, and erythema multiforme–like lesions appear on the extremities within 24 hours of symptom onset. 2,3,4,8,17 Hemorrhagic bullae are the most common cutaneous manifestation of sepsis.4 Lesions are extremely tender to palpation.3 Cutaneous lesions can progress to necrotic ulcers, necrotizing fasciitis, gangrene, necrotizing vasculitis, or myonecrosis.4,8 Evidence of petechiae may indicate progression to disseminated intravascular coagulation (DIC). Elevated D-dimer and fibrin split products also may indicate DIC, and elevated creatine kinase may signify rhabdomyolysis.3 Unfortunately, septicemia has the worst outcomes of all V vulnificus presentations, with morality rates greater than 50% in the United States.1,2,4Vibrio vulnificus septicemia has a similar case-fatality rate to pathogens such as anthrax, Ebola virus disease, and the bubonic plague.5 Septicemia accounts for approximately 80% of the deaths associated with V vulnificus in the United States.8,9
Septicemia due to V vulnificus progresses to septic shock in two-thirds of cases.8 Septic shock presents with hypotension, mental status changes, and thrombocytopenia.2,8,17 Patients can become tachycardic, tachypneic, and hypoxic. Intubation may be required for resuscitation. In cases of septic shock secondary to V vulnificus infection, mortality rates reach 92%.3 Hypotension with a systolic blood pressure less than 90 mm Hg is a poor prognostic factor; patients presenting with hypotension secondary to V vulnificus infection have a fatality rate approaching 75% within 12 hours.2
Atypical Presentations
Rare atypical presentations of V vulnificus infection that have been reported in the literature include meningitis, corneal ulcers, epiglottitis, tonsillitis, spontaneous bacterial peritonitis, pneumonia, endometritis, septic arthritis, osteomyelitis, rhabdomyolysis endophthalmitis, and keratitis.2,4,6,13,18,19
Diagnosis
When diagnosing V vulnificus, providers need to obtain a thorough patient history, including any history of consumption or handling of raw seafood and recent water activities. Providers practicing in tropical climates or in warm summer months should keep V vulnificus in mind, as it is the ideal climate for the pathogen.9 Vital signs can range from unremarkable to fever, hypotension, tachycardia, and/or hypoxia. Skin examination may show exquisitely tender, erythematous skin with marked soft tissue edema, hemorrhagic bullae, ecchymoses, and/or necrosis. As physical examination findings can be nonspecific, wound cultures, blood cultures, and skin biopsies should be taken.
A wound culture and blood culture should be taken immediately if V vulnificus is suspected.8,11 A wound culture using discharge or fluid from necrotic or bullous lesions should be analyzed via gram stain.8,9 Gram stains of V vulnificus show short, slim, curved gram-negative rods under light microscopy.9,20 Special stains also can be done on cultures; V vulnificus is an oxidase-positive, lactose-positive, lysine-positive, salicin-positive, and arginine-negative organism. This knowledge can help differentiate V vulnificus from other gram-negative rods.13 Blood cultures will be positive in approximately 97% of patients with primary septicemia and 30% of patients with septicemia secondary to V vulnificus wound infections.3,9
Histologically, perilesional skin biopsies show epidermal necrosis with dermal and subcutaneous inflammation.12,17 There typically is an inflammatory infiltrate with neutrophilic abscesses and extensive tissue destruction in the subcutaneous tissue extending into the deep dermis.12,17 The superficial dermis is edematous but can lack the inflammatory infiltrate found in the subcutaneous tissue.17 Subepidermal bullae can form with numerous organisms within the fluid of the bullae. There also may be evidence of leukocytoclastic vasculitis with accompanying vessel wall necrosis. Fibrin clot formation and extravasated red blood cells may be visualized with few inflammatory cells but numerous organisms around the involved vessels.17
Management
Early diagnosis and treatment are vital.5,17 Cultures should be taken before aggressive treatment is started.3 Treatment is multifaceted; it requires antibiotics and wound care, except in cases of self-limited gastroenteritis.2,11 Aggressive debridement, fasciotomy, amputation, and supportive measures also may be necessary depending on the patient’s presentation.2,3,8,9 Establishing 2 peripheral intravenous lines is important in case rapid resuscitation becomes necessary.
Antibiotics
Primary cellulitis wound infections should be treated with doxycycline or a quinolone. If untreated, the wound can rapidly progress to necrotizing fasciitis.11 For necrotizing fasciitis and septicemia, broader-spectrum antibiotics are needed. For adults, ceftazidime plus doxycycline is the mainstay of antibiotic treatment for V vulnificus.2,9,11 For children, trimethoprim-sulfamethoxazole plus an aminoglycoside is preferred (Table).2,11
Antibiotic treatment has become more difficult as resistance arises. Antibiotic resistance likely is due to extensive antibiotic use in health care along with the agriculture and aquaculture industries using prophylactic and therapeutic antibiotics that wash into or are directly added to marine waters, where V vulnificus resides. Thus, antibiotic treatment should be tailored to the resistance profile of V vulnificus in various regions; for example, ceftazidime has an intermediate resistance profile in the United States, so cefotaxime and ceftriaxone may be better options.2
Wound Care
Wound infections must be extensively irrigated.9,21 For mild wound infections, proper wound care and oral antibiotics are appropriate (Table).21 Mild wounds should be irrigated thoroughly and followed by wound coverage to prevent progression, secondary infection, and necrosis. The dressing of choice will depend on the presenting lesion and provider preference; nonadherent, occlusive, or wet-to-dry dressings often are the best choices.22 Nonadherent dressings, such as petrolatum-covered gauze, do not pull off the newly formed epithelium when removed, making them beneficial to the skin’s healing process. Another option is occlusive dressings, which maintain a moist environment to hasten healing. They also enhance the autodigestion of necrotic tissue, which can be beneficial for necrotizing V vulnificus infections. Wet-to-dry dressings also may be used; these typically are comprised of gauze soaked with water, an astringent, and an antimicrobial or antiseptic solution. These dressings help to treat acute inflammation and also remove any exudate from the wound.22
Soft tissue and necrotizing infections require debridement.2,8 Early debridement decreases mortality rates.2,8,9 Necrotizing fasciitis often requires serial debridement to clear all the dead tissue and reduce the bacterial burden.8,9 Debridement prevents contiguous spread and metastatic seeding of the bacteria; it is important to prevent spread to the blood vessels, as vasculitis can necrose vessels, preventing antibiotics from reaching the dead tissue.17 Providers also should monitor for compartment syndrome, which should be treated with fasciotomy to decrease mortality.9,23 Many physicians leave V vulnificus–infected wounds open in order to heal by secondary intention.9 Hyperbaric oxygen therapy may be helpful as an adjunct to aggressive antimicrobial treatment for wound healing.8
Supportive Measures
Supportive care for dehydration, sepsis, DIC, and septic shock may be necessary, depending on the patient’s course. Treatment for severe V vulnificus infection includes intravenous fluids, crystalloids, oxygen, and/or intubation. Furthermore, if DIC develops, fresh frozen plasma, cryoprecipitate, a packed red blood cell transfusion, and/or anticoagulation may be required for resuscitation.3
Timing
Time to treatment and fatality rate are directly proportional in V vulnificus infection; the greater the delay in treatment, the higher the fatality rate.2 A 24-hour delay in antibiotic treatment is associated with a 33% case-fatality rate, and a 72-hour delay is associated with a 100% case-fatality rate.9 Even with early, appropriate treatment, mortality rates remain high.4
Prevention
Prevention of V vulnificus infections is an important consideration, especially for patients with chronic liver disease, immunosuppression, and hemochromatosis. Public education about the risks of eating raw shellfish is important.4 Oysters need to be treated properly to prevent growth and survival of V vulnificus.2 The most reliable method for destroying the bacteria is cooking shellfish.8,13 Only 15% of high-risk patients in the United States are aware of the risks associated with raw oyster consumption.3 High-risk patients should avoid eating raw oysters and shellfish and should cook seafood thoroughly before consumption.2,8 They also should wear protective clothing (ie, gloves) and eye protection when handling seafood and protective footwear (ie, wading shoes) while in seawater.2,8,13 It also is important to avoid contact with brackish water if one has any open wounds and to cleanse properly after exposure to brackish water or shellfish.2,8,16 Because severe V vulnificus infections can lead to death, prevention should be strongly encouraged by providers.2
Conclusion
Vibrio vulnificus infection typically occurs due to consumption of contaminated seafood or exposure to contaminated seawater. It most frequently affects older male patients with chronic liver disease, immunosuppression, hemochromatosis, or diabetes mellitus. Vibrio vulnificus can cause a vast spectrum of diseases, including gastroenteritis, wound infections, necrotizing fasciitis, and sepsis. Septicemia is the most common presentation of V vulnificus infection and accounts for the most fatalities from the bacteria. Septicemia often presents with fever, chills, vomiting, diarrhea, and hemorrhagic bullae. Vibrio vulnificus also commonly causes necrotizing fasciitis, which initially presents as cellulitis and rapidly progresses to hemorrhagic bullae or necrosis with accompanying systemic symptoms. Prompt diagnosis and treatment are vital to prevent mortality.
Interestingly, regions impacted by V vulnificus are expanding because of global warming.5,7Vibrio vulnificus thrives in warm waters, and increasing water temperatures are enhancing V vulnificus growth and survival.1,9 As global warming continues, the incidence of V vulnificus infections may rise. In fact, the number of infections increased by 78% between 1996 and 2006 in the United States.5 This rise likely was due to a combination of factors, including an aging population with more comorbidities, improvements in diagnosis, and climate change. Thus, as the number of V vulnificus infections rises, so too must providers’ suspicion for the pathogen.
- Phillips KE, Satchell KJF. Vibrio vulnificus: from oyster colonist to human pathogen [published online January 5, 2017]. PLOS Pathog. doi:10.1371/journal.ppat.1006053
- Heng SP, Letchumanan V, Deng CY, et al. Vibrio vulnificus: an environmental and clinical burden. Front Microbiol. 2017;8:997.
- Kumamoto KS, Vukich DJ. Clinical infections of Vibrio vulnificus: a case report and review of the literature. J Emerg Med. 1998;16:61-66.
- Borenstein M, Kerdel F. Infections with Vibrio vulnificus. Dermatol Clin. 2003;21:245-248.
- Baker-Austin C, Oliver JD. Vibrio vulnificus: new insights into a deadly opportunistic pathogen. Environ Microbiol. 2018;20:423-430.
- Kim SJ, Kim BC, Kim DC, et al. A fatal case of Vibrio vulnificus meningoencephalitis. Clin Microbiol Infect. 2003;9:568-571.
- Jones MK, Oliver JD. Vibrio vulnificus: disease and pathogenesis. Infect Immun. 2009;77:1723-1733.
- Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus infection: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis. 2011;15:E157-E166.
- Diaz JH. Skin and soft tissue infections following marine injuries and exposures in travelers. J Travel Med. 2014;21:207-213.
- Kikawa K, Yamasaki K, Sukiura T, et al. A successfully treated case of Vibrio vulnificus septicemia with shock. Jpn J Med. 1990;29:313-319.
- Perkins AP, Trimmier M. Recreational waterborne illnesses: recognition, treatment, and prevention. Am Fam Physician. 2017;95:554-560.
- Patel VJ, Gardner E, Burton CS. Vibrio vulnificus septicemia and leg ulcer. J Am Acad Dermatol. 2002;46(5 suppl):S144-S145.
- Ulusarac O, Carter E. Varied clinical presentations of Vibrio vulnificus infections: a report of four unusual cases and review of the literature. South Med J. 2004;97:613-618.
- Bross MH, Soch K, Morales R, et al. Vibrio vulnificus infection: diagnosis and treatment. Am Fam Physician. 2007;76:539-544.
- Hori M, Nakayama A, Kitagawa D, et al. A case of Vibrio vulnificus infection complicated with fulminant purpura: gene and biotype analysis of the pathogen [published online May 19, 2017]. JMM Case Rep. doi:10.1099/jmmcr.0.005096
- Kotton Y, Soboh S, Bisharat N. Vibrio vulnificus necrotizing fasciitis associated with acupuncture. Infect Dis Rep. 2015;7:5901.
- Hoffman TJ, Nelson B, Darouiche R, et al. Vibrio vulnificus septicemia. Arch Intern Med. 1988;148:1825-1827.
- Alsaad AA, Sotello D, Kruse BT, et al. Vibrio vulnificus tonsillitis after swimming in the Gulf of Mexico [published online June 28, 2017]. BMJ Case Rep. doi:10.1136/bcr-2017-221161
- Tison DL, Kelly MT. Vibrio vulnificus endometritis. J Clin Microbiol. 1984;20:185-186.
- Beatty NL, Marquez J, Mohajer MA. Skin manifestations of primary Vibrio vulnificus septicemia. Am J Trop Med Hyg. 2017;97:1-2.
- Foote A, Henderson R, Lindberg A, et al. The Australian mid-west coastal marine wound infections study. Aust Fam Physician. 2017;46:923-927.
- Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Elsevier; 2019.
- Kim CS, Bae EH, Ma SK, et al. Severe septicemia, necrotizing fasciitis, and peritonitis due to Vibrio vulnificus in a patient undergoing continuous ambulatory peritoneal dialysis: a case report. BMC Infect Dis. 2015;15:422.
- Phillips KE, Satchell KJF. Vibrio vulnificus: from oyster colonist to human pathogen [published online January 5, 2017]. PLOS Pathog. doi:10.1371/journal.ppat.1006053
- Heng SP, Letchumanan V, Deng CY, et al. Vibrio vulnificus: an environmental and clinical burden. Front Microbiol. 2017;8:997.
- Kumamoto KS, Vukich DJ. Clinical infections of Vibrio vulnificus: a case report and review of the literature. J Emerg Med. 1998;16:61-66.
- Borenstein M, Kerdel F. Infections with Vibrio vulnificus. Dermatol Clin. 2003;21:245-248.
- Baker-Austin C, Oliver JD. Vibrio vulnificus: new insights into a deadly opportunistic pathogen. Environ Microbiol. 2018;20:423-430.
- Kim SJ, Kim BC, Kim DC, et al. A fatal case of Vibrio vulnificus meningoencephalitis. Clin Microbiol Infect. 2003;9:568-571.
- Jones MK, Oliver JD. Vibrio vulnificus: disease and pathogenesis. Infect Immun. 2009;77:1723-1733.
- Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus infection: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis. 2011;15:E157-E166.
- Diaz JH. Skin and soft tissue infections following marine injuries and exposures in travelers. J Travel Med. 2014;21:207-213.
- Kikawa K, Yamasaki K, Sukiura T, et al. A successfully treated case of Vibrio vulnificus septicemia with shock. Jpn J Med. 1990;29:313-319.
- Perkins AP, Trimmier M. Recreational waterborne illnesses: recognition, treatment, and prevention. Am Fam Physician. 2017;95:554-560.
- Patel VJ, Gardner E, Burton CS. Vibrio vulnificus septicemia and leg ulcer. J Am Acad Dermatol. 2002;46(5 suppl):S144-S145.
- Ulusarac O, Carter E. Varied clinical presentations of Vibrio vulnificus infections: a report of four unusual cases and review of the literature. South Med J. 2004;97:613-618.
- Bross MH, Soch K, Morales R, et al. Vibrio vulnificus infection: diagnosis and treatment. Am Fam Physician. 2007;76:539-544.
- Hori M, Nakayama A, Kitagawa D, et al. A case of Vibrio vulnificus infection complicated with fulminant purpura: gene and biotype analysis of the pathogen [published online May 19, 2017]. JMM Case Rep. doi:10.1099/jmmcr.0.005096
- Kotton Y, Soboh S, Bisharat N. Vibrio vulnificus necrotizing fasciitis associated with acupuncture. Infect Dis Rep. 2015;7:5901.
- Hoffman TJ, Nelson B, Darouiche R, et al. Vibrio vulnificus septicemia. Arch Intern Med. 1988;148:1825-1827.
- Alsaad AA, Sotello D, Kruse BT, et al. Vibrio vulnificus tonsillitis after swimming in the Gulf of Mexico [published online June 28, 2017]. BMJ Case Rep. doi:10.1136/bcr-2017-221161
- Tison DL, Kelly MT. Vibrio vulnificus endometritis. J Clin Microbiol. 1984;20:185-186.
- Beatty NL, Marquez J, Mohajer MA. Skin manifestations of primary Vibrio vulnificus septicemia. Am J Trop Med Hyg. 2017;97:1-2.
- Foote A, Henderson R, Lindberg A, et al. The Australian mid-west coastal marine wound infections study. Aust Fam Physician. 2017;46:923-927.
- Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Elsevier; 2019.
- Kim CS, Bae EH, Ma SK, et al. Severe septicemia, necrotizing fasciitis, and peritonitis due to Vibrio vulnificus in a patient undergoing continuous ambulatory peritoneal dialysis: a case report. BMC Infect Dis. 2015;15:422.
Practice Points
- Vibrio vulnificus infection should be high on the differential for patients who present with chronic liver disease and immunosuppression; a history of raw seafood consumption or exposure to brackish water; and bullae, cellulitis, necrotic lesions, or sepsis.
- Time to treatment is directly proportional to mortality rates in V vulnificus infections, and prompt treatment with antibiotics, wound care, debridement, and supportive measures is necessary to decrease mortality rates.
- The incidence of V vulnificus infection is rising in the United States, likely due to a combination of factors, including an aging population with multiple comorbidities, improvements in diagnosis, and climate change.
Improving Dermatologic Care for South Asian Patients: Understanding Religious and Cultural Practices
Traditional garments are particularly important in both Sikhism and Islam. Sikhs began wearing symbolic garments in the 16th century as markers of their identity during periods of religious persecution. Today, many Sikhs continue to maintain this tradition of wearing the Five Ks—kesh (uncut hair, often tied in a turban), kanga (wooden hair comb), kirpan (symbolic dagger), kachha (cotton underwear), and kara (steel bracelet).2 Similarly, Islamic traditions also provide guidance for clothing. Many Muslim women wear the hijab (headscarf), a garment that originated as protective headgear for nomadic desert cultures and has come to symbolize modest dress. Traditionally, the hijab is worn in the presence of all men who are not immediate relatives, although patients may make exceptions for medical care. Some Muslim men also may cover their heads with a skullcap and/or maintain long beards (occasionally dyed with henna pigment) as a way of keeping continuity with the tradition of the Prophet Muhammad and his companions.3
Certain styles of headwear can cause high tension on hair follicles and have been associated with traction alopecia.4 Persistent use of the same turban, hijab, or comb also may lead to seborrheic dermatitis or fungal scalp infections. Dermatologists should advise patients about these potential challenges and suggest modifications in accordance with the patient’s religious beliefs; for example, providers can suggest removing headwear at night, using prophylactic antifungal shampoos, and/or tying the hair in a ponytail or loosening the headgear to reduce traction.
Although Hinduism does not have a unifying garment or hair tradition in the vein of Sikhism or Islam, all 3 religions share a strong emphasis on bodily modesty, which may affect dermatologic examinations. Patients from all 3 religions may seek to expose as little skin as possible during a physical examination, and many patients may be uncomfortable with a physician of the opposite gender. Dermatologists may find the following practices to be helpful5:
• Talk through each aspect of the skin examination while it is being performed and expose the least amount of skin necessary during the process
• Offer the patient a chaperone or a same-gender provider, if possible
• Empower patients to assist in adjusting garments themselves to help the physician visualize all parts of the skin
Some Sikhs also may have specific concerns regarding cutting their hair. One aspect of kesh is that every hair is sacred, and thus, many Sikhs refrain from removing hair on any part of the body. As such, providers should carefully obtain the patient’s informed consent before performing any procedure or physical examination maneuvers (eg, hair pull test) that may result in loss of hair.2
Physicians of all disciplines can help address these challenges through increased outreach and cultural awareness; for example, dermatologists can create skin care pamphlets translated into various South Asian languages and distribute them at houses of worship or other community centers. This may help patients identify their skin needs and seek appropriate care. The onus must be on physicians to make these patients feel comfortable seeking care by creating nonjudgmental, culturally knowledgeable clinical environments. When asking about social history, the physician might consider asking an open-ended question such as, “What role does religion/spirituality play in your life?” They can then proceed to ask specific questions about practices that might affect the patient’s care.5
Given the current coronavirus disease 2019 pandemic, South Asian patients may be even further discouraged from seeking dermatologic care. By understanding religious traditions and taking steps to address biases, dermatologists can help mitigate health care disparities and provide culturally competent care to South Asian patients.
- Nadimpalli SB, Cleland CM, Hutchinson MK, et al. The association between discrimination and the health of Sikh Asian Indians. Health Psychol. 2016;35:351-355.
- The five Ks. BBC website. Updated September 29, 2009. Accessed February 4, 2021. https://www.bbc.co.uk/religion/religions/sikhism/customs/fiveks.shtml
- Islam. BBC website. Accessed February 2, 2021. https://www.bbc.co.uk/religion/religions/islam/
- James J, Saladi RN, Fox JL. Traction alopecia in Sikh male patients. J Am Board Fam Med. 2007;20:497-498.
- Hussain A. Recommendations for culturally competent dermatology care of Muslim patients. J Am Acad Dermatol. 2017;77:388-389.
Traditional garments are particularly important in both Sikhism and Islam. Sikhs began wearing symbolic garments in the 16th century as markers of their identity during periods of religious persecution. Today, many Sikhs continue to maintain this tradition of wearing the Five Ks—kesh (uncut hair, often tied in a turban), kanga (wooden hair comb), kirpan (symbolic dagger), kachha (cotton underwear), and kara (steel bracelet).2 Similarly, Islamic traditions also provide guidance for clothing. Many Muslim women wear the hijab (headscarf), a garment that originated as protective headgear for nomadic desert cultures and has come to symbolize modest dress. Traditionally, the hijab is worn in the presence of all men who are not immediate relatives, although patients may make exceptions for medical care. Some Muslim men also may cover their heads with a skullcap and/or maintain long beards (occasionally dyed with henna pigment) as a way of keeping continuity with the tradition of the Prophet Muhammad and his companions.3
Certain styles of headwear can cause high tension on hair follicles and have been associated with traction alopecia.4 Persistent use of the same turban, hijab, or comb also may lead to seborrheic dermatitis or fungal scalp infections. Dermatologists should advise patients about these potential challenges and suggest modifications in accordance with the patient’s religious beliefs; for example, providers can suggest removing headwear at night, using prophylactic antifungal shampoos, and/or tying the hair in a ponytail or loosening the headgear to reduce traction.
Although Hinduism does not have a unifying garment or hair tradition in the vein of Sikhism or Islam, all 3 religions share a strong emphasis on bodily modesty, which may affect dermatologic examinations. Patients from all 3 religions may seek to expose as little skin as possible during a physical examination, and many patients may be uncomfortable with a physician of the opposite gender. Dermatologists may find the following practices to be helpful5:
• Talk through each aspect of the skin examination while it is being performed and expose the least amount of skin necessary during the process
• Offer the patient a chaperone or a same-gender provider, if possible
• Empower patients to assist in adjusting garments themselves to help the physician visualize all parts of the skin
Some Sikhs also may have specific concerns regarding cutting their hair. One aspect of kesh is that every hair is sacred, and thus, many Sikhs refrain from removing hair on any part of the body. As such, providers should carefully obtain the patient’s informed consent before performing any procedure or physical examination maneuvers (eg, hair pull test) that may result in loss of hair.2
Physicians of all disciplines can help address these challenges through increased outreach and cultural awareness; for example, dermatologists can create skin care pamphlets translated into various South Asian languages and distribute them at houses of worship or other community centers. This may help patients identify their skin needs and seek appropriate care. The onus must be on physicians to make these patients feel comfortable seeking care by creating nonjudgmental, culturally knowledgeable clinical environments. When asking about social history, the physician might consider asking an open-ended question such as, “What role does religion/spirituality play in your life?” They can then proceed to ask specific questions about practices that might affect the patient’s care.5
Given the current coronavirus disease 2019 pandemic, South Asian patients may be even further discouraged from seeking dermatologic care. By understanding religious traditions and taking steps to address biases, dermatologists can help mitigate health care disparities and provide culturally competent care to South Asian patients.
Traditional garments are particularly important in both Sikhism and Islam. Sikhs began wearing symbolic garments in the 16th century as markers of their identity during periods of religious persecution. Today, many Sikhs continue to maintain this tradition of wearing the Five Ks—kesh (uncut hair, often tied in a turban), kanga (wooden hair comb), kirpan (symbolic dagger), kachha (cotton underwear), and kara (steel bracelet).2 Similarly, Islamic traditions also provide guidance for clothing. Many Muslim women wear the hijab (headscarf), a garment that originated as protective headgear for nomadic desert cultures and has come to symbolize modest dress. Traditionally, the hijab is worn in the presence of all men who are not immediate relatives, although patients may make exceptions for medical care. Some Muslim men also may cover their heads with a skullcap and/or maintain long beards (occasionally dyed with henna pigment) as a way of keeping continuity with the tradition of the Prophet Muhammad and his companions.3
Certain styles of headwear can cause high tension on hair follicles and have been associated with traction alopecia.4 Persistent use of the same turban, hijab, or comb also may lead to seborrheic dermatitis or fungal scalp infections. Dermatologists should advise patients about these potential challenges and suggest modifications in accordance with the patient’s religious beliefs; for example, providers can suggest removing headwear at night, using prophylactic antifungal shampoos, and/or tying the hair in a ponytail or loosening the headgear to reduce traction.
Although Hinduism does not have a unifying garment or hair tradition in the vein of Sikhism or Islam, all 3 religions share a strong emphasis on bodily modesty, which may affect dermatologic examinations. Patients from all 3 religions may seek to expose as little skin as possible during a physical examination, and many patients may be uncomfortable with a physician of the opposite gender. Dermatologists may find the following practices to be helpful5:
• Talk through each aspect of the skin examination while it is being performed and expose the least amount of skin necessary during the process
• Offer the patient a chaperone or a same-gender provider, if possible
• Empower patients to assist in adjusting garments themselves to help the physician visualize all parts of the skin
Some Sikhs also may have specific concerns regarding cutting their hair. One aspect of kesh is that every hair is sacred, and thus, many Sikhs refrain from removing hair on any part of the body. As such, providers should carefully obtain the patient’s informed consent before performing any procedure or physical examination maneuvers (eg, hair pull test) that may result in loss of hair.2
Physicians of all disciplines can help address these challenges through increased outreach and cultural awareness; for example, dermatologists can create skin care pamphlets translated into various South Asian languages and distribute them at houses of worship or other community centers. This may help patients identify their skin needs and seek appropriate care. The onus must be on physicians to make these patients feel comfortable seeking care by creating nonjudgmental, culturally knowledgeable clinical environments. When asking about social history, the physician might consider asking an open-ended question such as, “What role does religion/spirituality play in your life?” They can then proceed to ask specific questions about practices that might affect the patient’s care.5
Given the current coronavirus disease 2019 pandemic, South Asian patients may be even further discouraged from seeking dermatologic care. By understanding religious traditions and taking steps to address biases, dermatologists can help mitigate health care disparities and provide culturally competent care to South Asian patients.
- Nadimpalli SB, Cleland CM, Hutchinson MK, et al. The association between discrimination and the health of Sikh Asian Indians. Health Psychol. 2016;35:351-355.
- The five Ks. BBC website. Updated September 29, 2009. Accessed February 4, 2021. https://www.bbc.co.uk/religion/religions/sikhism/customs/fiveks.shtml
- Islam. BBC website. Accessed February 2, 2021. https://www.bbc.co.uk/religion/religions/islam/
- James J, Saladi RN, Fox JL. Traction alopecia in Sikh male patients. J Am Board Fam Med. 2007;20:497-498.
- Hussain A. Recommendations for culturally competent dermatology care of Muslim patients. J Am Acad Dermatol. 2017;77:388-389.
- Nadimpalli SB, Cleland CM, Hutchinson MK, et al. The association between discrimination and the health of Sikh Asian Indians. Health Psychol. 2016;35:351-355.
- The five Ks. BBC website. Updated September 29, 2009. Accessed February 4, 2021. https://www.bbc.co.uk/religion/religions/sikhism/customs/fiveks.shtml
- Islam. BBC website. Accessed February 2, 2021. https://www.bbc.co.uk/religion/religions/islam/
- James J, Saladi RN, Fox JL. Traction alopecia in Sikh male patients. J Am Board Fam Med. 2007;20:497-498.
- Hussain A. Recommendations for culturally competent dermatology care of Muslim patients. J Am Acad Dermatol. 2017;77:388-389.
Practice Points
- Providers should familiarize themselves with traditional garments of Sikhism and Islam, including head coverings and other symbolic items.
- Inform patients about health-conscious methods of wearing traditional headwear, such as removing certain headwear at night and tying hair in methods to avoid causing traction alopecia.
- Talk through each aspect of the skin examination while it is being performed and expose the least amount of skin necessary during the process. Offer the patient a chaperone or a same-gender provider, if possible.
- Empower patients to assist in adjusting garments themselves to help the physician visualize all parts of the skin.
Short sleep predicts incident dementia and all-cause mortality
More evidence has emerged linking sleep deficiency, dementia, and mortality.
“Sleep disturbance and insufficiency have been shown to be associated with both the development and progression of Alzheimer’s disease and with all-cause mortality,” wrote Rebecca S. Robbins, PhD, of Brigham and Women’s Hospital, Boston, and colleagues. However, research on this topic has yielded conflicting results, and “few studies have included a comprehensive set of sleep characteristics in a single examination of incident dementia and all-cause mortality.”
In a study published in Aging, the researchers identified 2,812 adults aged 65 years and older from the National Health and Aging Trends Study (NHATS), a nationally representative longitudinal study of Medicare beneficiaries aged 65 years and older in the United States.
Participants completed surveys about sleep disturbance and duration in 2013 (1,575 individuals) and in 2014 (1,237 individuals), and the researchers examined the relationship between sleep disturbance and deficiency and incident dementia and all-cause mortality over the next 5 years. The average age of the study participants was 76.9 years, 60% were women, and 72% were White.
Overall, approximately 60% of the participants reported never or rarely having problems with alertness, approximately half said that they rarely or never napped, and more than half said they fell asleep in 15 minutes or less. Approximately 70% rated their sleep quality as good or very good, and more than 90% said they rarely or never snored.
The researchers examined the relationships between sleep characteristics and the development of incident dementia over 5 years. In a fully adjusted Cox multivariate analysis, individuals who slept 5 hours or less per night had approximately twice the risk for incident dementia as those who slept longer (hazard ratio, 2.04); risk of dementia also was higher among those who took 30 minutes or longer to fall asleep (HR, 1.45).
In addition, the risk of all-cause mortality was significantly higher among individuals who reported difficulty maintaining alertness some days or most days/every day (HR, 1.49 and HR, 1.65, respectively), routinely napping some days or most days/every day (HR, 1.38 and HR, 1.73, respectively), poor or very poor sleep quality (HR, 1.75), and sleeping 5 hours or less each night (HR, 2.38).
The study findings were limited by several factors including a population representing only one-quarter of the NHATS cohort, which prevented nationally representative estimates, the availability of only 2 years of sleep data, and small sample size for certain response categories, the researchers noted.
However, “our study offers a contribution to the literature on sleep among aging populations in its assessment of incident dementia and all-cause mortality and a range of sleep characteristics among older adults,” they said. In particular, “short sleep duration was a strong predictor of both incident dementia and all-cause mortality, suggesting this may be a sleep characteristic that is important – over and above the other predictors – of adverse outcomes among older adults,” and future areas for research include the development of novel behavioral interventions to improve sleep in this population.
The study was supported in part by the National Institute for Occupational Safety and Health; the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the Brigham Research Institute Fund to Sustain Research Excellence. Lead author Dr. Robbins disclosed fees from Denihan Hospitality, Rituals Cosmetics, Dagmejan, Asystem, and SleepCycle. Several coauthors disclosed relationships with multiple pharmaceutical companies, and support from various philanthropic organizations.
More evidence has emerged linking sleep deficiency, dementia, and mortality.
“Sleep disturbance and insufficiency have been shown to be associated with both the development and progression of Alzheimer’s disease and with all-cause mortality,” wrote Rebecca S. Robbins, PhD, of Brigham and Women’s Hospital, Boston, and colleagues. However, research on this topic has yielded conflicting results, and “few studies have included a comprehensive set of sleep characteristics in a single examination of incident dementia and all-cause mortality.”
In a study published in Aging, the researchers identified 2,812 adults aged 65 years and older from the National Health and Aging Trends Study (NHATS), a nationally representative longitudinal study of Medicare beneficiaries aged 65 years and older in the United States.
Participants completed surveys about sleep disturbance and duration in 2013 (1,575 individuals) and in 2014 (1,237 individuals), and the researchers examined the relationship between sleep disturbance and deficiency and incident dementia and all-cause mortality over the next 5 years. The average age of the study participants was 76.9 years, 60% were women, and 72% were White.
Overall, approximately 60% of the participants reported never or rarely having problems with alertness, approximately half said that they rarely or never napped, and more than half said they fell asleep in 15 minutes or less. Approximately 70% rated their sleep quality as good or very good, and more than 90% said they rarely or never snored.
The researchers examined the relationships between sleep characteristics and the development of incident dementia over 5 years. In a fully adjusted Cox multivariate analysis, individuals who slept 5 hours or less per night had approximately twice the risk for incident dementia as those who slept longer (hazard ratio, 2.04); risk of dementia also was higher among those who took 30 minutes or longer to fall asleep (HR, 1.45).
In addition, the risk of all-cause mortality was significantly higher among individuals who reported difficulty maintaining alertness some days or most days/every day (HR, 1.49 and HR, 1.65, respectively), routinely napping some days or most days/every day (HR, 1.38 and HR, 1.73, respectively), poor or very poor sleep quality (HR, 1.75), and sleeping 5 hours or less each night (HR, 2.38).
The study findings were limited by several factors including a population representing only one-quarter of the NHATS cohort, which prevented nationally representative estimates, the availability of only 2 years of sleep data, and small sample size for certain response categories, the researchers noted.
However, “our study offers a contribution to the literature on sleep among aging populations in its assessment of incident dementia and all-cause mortality and a range of sleep characteristics among older adults,” they said. In particular, “short sleep duration was a strong predictor of both incident dementia and all-cause mortality, suggesting this may be a sleep characteristic that is important – over and above the other predictors – of adverse outcomes among older adults,” and future areas for research include the development of novel behavioral interventions to improve sleep in this population.
The study was supported in part by the National Institute for Occupational Safety and Health; the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the Brigham Research Institute Fund to Sustain Research Excellence. Lead author Dr. Robbins disclosed fees from Denihan Hospitality, Rituals Cosmetics, Dagmejan, Asystem, and SleepCycle. Several coauthors disclosed relationships with multiple pharmaceutical companies, and support from various philanthropic organizations.
More evidence has emerged linking sleep deficiency, dementia, and mortality.
“Sleep disturbance and insufficiency have been shown to be associated with both the development and progression of Alzheimer’s disease and with all-cause mortality,” wrote Rebecca S. Robbins, PhD, of Brigham and Women’s Hospital, Boston, and colleagues. However, research on this topic has yielded conflicting results, and “few studies have included a comprehensive set of sleep characteristics in a single examination of incident dementia and all-cause mortality.”
In a study published in Aging, the researchers identified 2,812 adults aged 65 years and older from the National Health and Aging Trends Study (NHATS), a nationally representative longitudinal study of Medicare beneficiaries aged 65 years and older in the United States.
Participants completed surveys about sleep disturbance and duration in 2013 (1,575 individuals) and in 2014 (1,237 individuals), and the researchers examined the relationship between sleep disturbance and deficiency and incident dementia and all-cause mortality over the next 5 years. The average age of the study participants was 76.9 years, 60% were women, and 72% were White.
Overall, approximately 60% of the participants reported never or rarely having problems with alertness, approximately half said that they rarely or never napped, and more than half said they fell asleep in 15 minutes or less. Approximately 70% rated their sleep quality as good or very good, and more than 90% said they rarely or never snored.
The researchers examined the relationships between sleep characteristics and the development of incident dementia over 5 years. In a fully adjusted Cox multivariate analysis, individuals who slept 5 hours or less per night had approximately twice the risk for incident dementia as those who slept longer (hazard ratio, 2.04); risk of dementia also was higher among those who took 30 minutes or longer to fall asleep (HR, 1.45).
In addition, the risk of all-cause mortality was significantly higher among individuals who reported difficulty maintaining alertness some days or most days/every day (HR, 1.49 and HR, 1.65, respectively), routinely napping some days or most days/every day (HR, 1.38 and HR, 1.73, respectively), poor or very poor sleep quality (HR, 1.75), and sleeping 5 hours or less each night (HR, 2.38).
The study findings were limited by several factors including a population representing only one-quarter of the NHATS cohort, which prevented nationally representative estimates, the availability of only 2 years of sleep data, and small sample size for certain response categories, the researchers noted.
However, “our study offers a contribution to the literature on sleep among aging populations in its assessment of incident dementia and all-cause mortality and a range of sleep characteristics among older adults,” they said. In particular, “short sleep duration was a strong predictor of both incident dementia and all-cause mortality, suggesting this may be a sleep characteristic that is important – over and above the other predictors – of adverse outcomes among older adults,” and future areas for research include the development of novel behavioral interventions to improve sleep in this population.
The study was supported in part by the National Institute for Occupational Safety and Health; the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the Brigham Research Institute Fund to Sustain Research Excellence. Lead author Dr. Robbins disclosed fees from Denihan Hospitality, Rituals Cosmetics, Dagmejan, Asystem, and SleepCycle. Several coauthors disclosed relationships with multiple pharmaceutical companies, and support from various philanthropic organizations.
FROM AGING
COMMENT & CONTROVERSY
9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)
HPV vaccine for older ObGyns?
I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?
Gus Barkett, DO
Muskegon, Michigan
Dr. Barbieri responds
I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.
EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?
ANDREW M. KAUNITZ, MD (AUGUST 2020)
Discordant results on screening mammography
In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.1 Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.
I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.
Lisa Gennari, MD
Cincinnati, Ohio
Reference
1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.
Dr. Kaunitz responds
I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.1 That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).
In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.
Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.
Reference
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.
Continue to: NEW HORMONAL MEDICAL TREATMENT...
NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS
ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)
New AUB medical treatment
I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?
Geoffrey J. Zann, MD, MBA
Boca Raton, Florida
Dr. Barbieri responds
Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.
In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.1,2
Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.1,2
I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.
References
- Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
- Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.
9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)
HPV vaccine for older ObGyns?
I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?
Gus Barkett, DO
Muskegon, Michigan
Dr. Barbieri responds
I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.
EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?
ANDREW M. KAUNITZ, MD (AUGUST 2020)
Discordant results on screening mammography
In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.1 Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.
I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.
Lisa Gennari, MD
Cincinnati, Ohio
Reference
1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.
Dr. Kaunitz responds
I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.1 That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).
In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.
Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.
Reference
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.
Continue to: NEW HORMONAL MEDICAL TREATMENT...
NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS
ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)
New AUB medical treatment
I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?
Geoffrey J. Zann, MD, MBA
Boca Raton, Florida
Dr. Barbieri responds
Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.
In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.1,2
Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.1,2
I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.
References
- Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
- Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.
9vHPV VACCINE: PREVENTION OF OROPHARYNGEAL CANCER
ROBERT L. BARBIERI, MD (EDITORIAL; NOVEMBER 2020)
HPV vaccine for older ObGyns?
I am 67 years old and recently retired. I breathed in the smoke from laser conizations, LEEPs (loop electrosurgical excision procedures), and cautery of condyloma for 35 years. Am I a good candidate for the HPV vaccine?
Gus Barkett, DO
Muskegon, Michigan
Dr. Barbieri responds
I thank Dr. Barkett for his important question. As you know, the US Food and Drug Administration has approved 9vHPV vaccination for people 27 to 45 years of age. I do not believe there are sufficient data to provide an evidence-based answer for physicians with occupational exposure to HPV who are more than 45 years of age. My recommendation would be to have a consult with an otolaryngologist expert in HPV-induced oral-pharyngeal cancer.
EXAMINING THE EVIDENCE: HOW EFFECTIVE IS SCREENING MAMMOGRAPHY FOR PREVENTING BREAST CANCER MORTALITY?
ANDREW M. KAUNITZ, MD (AUGUST 2020)
Discordant results on screening mammography
In regard to the discussion on screening mammography for preventing breast cancer mortality, I would like to call attention to a more recent study than the ones referenced in the article. The study by Duffy and colleagues was from Sweden and included almost 550,000 women.1 Results of the study showed a statistically significant reduction of 41% in 10-year mortality and a 25% reduction in the incidence of advanced-stage disease at the time of diagnosis in women who underwent routine screening mammograms. In Sweden, routine screening is defined as a mammogram every 18 months for women aged 40 to 54 years and every 24 months after that, up to age 69.
I do not know if we will ever come to a consensus on the utility of mammograms or how often they should be done, but I wanted to illustrate this counterpoint.
Lisa Gennari, MD
Cincinnati, Ohio
Reference
1. Duffy SW, Tabar L, Yen AM, et al. Mammography screening reduces rates of advanced and fatal breast cancers: results in 549,091 women. Cancer. 2020;126:2971-2979.
Dr. Kaunitz responds
I thank Dr. Gennari for her interest in the Examining the Evidence discussion that summarized the findings of an article from Australia published in late summer of last year.1 That article indicated that as screening mammograms became common in the state of Victoria over several decades, the incidence of advanced breast cancer doubled, mirroring findings from the United States, Holland, and Norway. During the same time period, breast cancer mortality declined substantially. The authors concluded that all of the decline in breast cancer mortality that they observed since 1994 could be attributed not to screening mammography but rather to the introduction and uptake of adjuvant therapy (tamoxifen and chemotherapy).
In contrast, in the article Dr. Gennari cites, also published last summer, the authors found that the widespread uptake of screening mammograms among women residing in 9 counties in Sweden was associated with a decline in the incidence of advanced breast cancer. I am not able to explain these discrepant findings. However, as the authors pointed out, they employed a new strategy: measuring the incidence of breast cancer that proved fatal one decade after diagnosis.
Differing findings and interpretations of data that address benefits and risks of screening mammography lead to differing recommendations from professional societies and confusion among clinicians and our patients. Although it can be challenging in the constraints of time allotted for well-woman visits, I try to engage in shared decision making with my patients regarding when to start/stop mammography as well as frequency of screening.
Reference
- Burton R, Stevenson C. Assessment of breast cancer mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the state of Victoria, Australia. JAMA Netw Open. 2020:3:e208249.
Continue to: NEW HORMONAL MEDICAL TREATMENT...
NEW HORMONAL MEDICAL TREATMENT IS AN IMPORTANT ADVANCE FOR AUB CAUSED BY UTERINE FIBROIDS
ROBERT L. BARBIERI, MD (EDITORIAL; AUGUST 2020)
New AUB medical treatment
I appreciate Dr. Barbieri’s concise and pertinent review of myomatous disease etiology and treatments. I have a question regarding therapy with Oriahnn (elagolix, estradiol, and norethindrone acetate capsules). Most myomatous-related bleeding occurs in premenopausal women. The elagolix suppresses luteinizing hormone and follicle stimulating hormone, and the norethindrone is added to protect the endometrium from the estradiol. Do the elagolix and norethindrone also provide contraception?
Geoffrey J. Zann, MD, MBA
Boca Raton, Florida
Dr. Barbieri responds
Dr. Zann raises an important clinical question that arises often in practice. The US Food and Drug Administration (FDA) has not approved Oriahnn as a contraceptive. The FDA prescribing information recommends: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing Oriahnn. Oriahnn may delay the ability to recognize the occurrence of a pregnancy because it alters menstrual bleeding. Perform pregnancy testing if pregnancy is suspected and discontinue Oriahnn if pregnancy is confirmed.
In Oriahnn, the elagolix dose is 300 mg twice daily. If a patient reliably takes 600 mg of elagolix daily, it is highly unlikely that she will ovulate. However, in practice, many patients miss doses of their medication, reducing the contraceptive effectiveness. For example, the combined estrogen-progestin contraceptive is highly effective at suppressing ovulation, but the Centers for Disease Control and Prevention (CDC) estimates that 9% of women taking an estrogen-progestin contraceptive will become pregnant each year.1,2
Oriahnn also contains norethindrone acetate at a dose of 0.5 mg daily. The FDA has approved norethindrone at a dose of 0.35 mg daily as a contraceptive. The CDC estimates that 9% of women prescribed a progestin-only pill will become pregnant each year with typical use.1,2
I counsel my patients that if they reliably take their prescribed Oriahnn medication as directed, they are unlikely to become pregnant, and a backup method of contraception will further help to reduce their risk of becoming pregnant.
References
- Centers for Disease Control and Prevention. US selected practice recommendations for contraceptive use, 2013. MMWR Morbid Mortal Weekly Rep. 2013;62(RR-5):1-59.
- Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397-404.
Goldenseal may interfere with metformin absorption, jeopardizing glucose control
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
FROM CLINICAL PHARMACOLOGY & THERAPEUTICS