Pain

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

TOPLINE:

In patients with fibromyalgia, cognitive behavior therapy (CBT) can reduce pain through its effect on pain-related catastrophizing, which involves intensified cognitive and emotional responses to things like intrusive thoughts, a new study suggests.

METHODOLOGY:

• The study included 98 female patients with fibromyalgia (FM), mean age about 42 years, who underwent a baseline neuroimaging assessment and were randomly assigned to CBT (where patients learned to identify negative thoughts and use cognitive restructuring to diminish pain-related distress) or a matched educational intervention (where patients learned about fibromyalgia and chronic pain); both groups had eight weekly individual 60- to 75-minute visits.
• The primary outcome was the pain interference subscale of the Brief Pain Inventory (BPI); secondary outcomes included the BPI pain severity subscale, the Fibromyalgia Impact Questionnaire–Revised (FIQR), and the Pain Catastrophizing Scale (PCS), which includes subscales of rumination, magnification, and helplessness.
• Researchers used functional magnetic resonance imaging (fMRI)-adapted task to investigate the neural circuitry supporting pain catastrophizing.

TAKEAWAY:

• After controlling for baseline values, BPI pain interference scores were significantly reduced, with a larger reduction in the CBT group, compared with the education group (P = .03), which was also the case for FIQR scores (P = .05) and pain catastrophizing (P = .04).
• There were larger reductions in pain-related symptomatology in the CBT group, but they did not reach statistical significance.
• Following CBT treatment, the study showed reduced connectivity between regions of the brain associated with self-awareness, pain, and emotional processing.

IN PRACTICE:

The results “highlight the important role of targeting pain catastrophizing with psychotherapy, particularly for patients reporting high levels of catastrophizing cognitions” write the authors, adding that altered network connectivity identified by the study “may emerge as a valuable biomarker of catastrophizing-related cognitive and affective processes.”

SOURCE:

The study was carried out by Jeungchan Lee, PhD, department of radiology, center for biomedical imaging, Massachusetts General Hospital, Boston, and the Discovery Center for Recovery from Chronic Pain, Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, and colleagues. It was published in Arthritis & Rheumatology.

LIMITATIONS:

Findings were limited to female participants. CBT for chronic pain includes different therapeutic modules, and the study can’t draw definitive conclusions regarding which CBT skills were most beneficial to patients in reducing catastrophizing. Baseline symptom severity was higher for the CBT group, which may complicate interpretation of the findings.

DISCLOSURES:

The study received support from the National Institutes of Health: National Center for Complementary and Integrative Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with fibromyalgia, cognitive behavior therapy (CBT) can reduce pain through its effect on pain-related catastrophizing, which involves intensified cognitive and emotional responses to things like intrusive thoughts, a new study suggests.

METHODOLOGY:

• The study included 98 female patients with fibromyalgia (FM), mean age about 42 years, who underwent a baseline neuroimaging assessment and were randomly assigned to CBT (where patients learned to identify negative thoughts and use cognitive restructuring to diminish pain-related distress) or a matched educational intervention (where patients learned about fibromyalgia and chronic pain); both groups had eight weekly individual 60- to 75-minute visits.
• The primary outcome was the pain interference subscale of the Brief Pain Inventory (BPI); secondary outcomes included the BPI pain severity subscale, the Fibromyalgia Impact Questionnaire–Revised (FIQR), and the Pain Catastrophizing Scale (PCS), which includes subscales of rumination, magnification, and helplessness.
• Researchers used functional magnetic resonance imaging (fMRI)-adapted task to investigate the neural circuitry supporting pain catastrophizing.

TAKEAWAY:

• After controlling for baseline values, BPI pain interference scores were significantly reduced, with a larger reduction in the CBT group, compared with the education group (P = .03), which was also the case for FIQR scores (P = .05) and pain catastrophizing (P = .04).
• There were larger reductions in pain-related symptomatology in the CBT group, but they did not reach statistical significance.
• Following CBT treatment, the study showed reduced connectivity between regions of the brain associated with self-awareness, pain, and emotional processing.

IN PRACTICE:

The results “highlight the important role of targeting pain catastrophizing with psychotherapy, particularly for patients reporting high levels of catastrophizing cognitions” write the authors, adding that altered network connectivity identified by the study “may emerge as a valuable biomarker of catastrophizing-related cognitive and affective processes.”

SOURCE:

The study was carried out by Jeungchan Lee, PhD, department of radiology, center for biomedical imaging, Massachusetts General Hospital, Boston, and the Discovery Center for Recovery from Chronic Pain, Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, and colleagues. It was published in Arthritis & Rheumatology.

LIMITATIONS:

Findings were limited to female participants. CBT for chronic pain includes different therapeutic modules, and the study can’t draw definitive conclusions regarding which CBT skills were most beneficial to patients in reducing catastrophizing. Baseline symptom severity was higher for the CBT group, which may complicate interpretation of the findings.

DISCLOSURES:

The study received support from the National Institutes of Health: National Center for Complementary and Integrative Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with fibromyalgia, cognitive behavior therapy (CBT) can reduce pain through its effect on pain-related catastrophizing, which involves intensified cognitive and emotional responses to things like intrusive thoughts, a new study suggests.

METHODOLOGY:

• The study included 98 female patients with fibromyalgia (FM), mean age about 42 years, who underwent a baseline neuroimaging assessment and were randomly assigned to CBT (where patients learned to identify negative thoughts and use cognitive restructuring to diminish pain-related distress) or a matched educational intervention (where patients learned about fibromyalgia and chronic pain); both groups had eight weekly individual 60- to 75-minute visits.
• The primary outcome was the pain interference subscale of the Brief Pain Inventory (BPI); secondary outcomes included the BPI pain severity subscale, the Fibromyalgia Impact Questionnaire–Revised (FIQR), and the Pain Catastrophizing Scale (PCS), which includes subscales of rumination, magnification, and helplessness.
• Researchers used functional magnetic resonance imaging (fMRI)-adapted task to investigate the neural circuitry supporting pain catastrophizing.

TAKEAWAY:

• After controlling for baseline values, BPI pain interference scores were significantly reduced, with a larger reduction in the CBT group, compared with the education group (P = .03), which was also the case for FIQR scores (P = .05) and pain catastrophizing (P = .04).
• There were larger reductions in pain-related symptomatology in the CBT group, but they did not reach statistical significance.
• Following CBT treatment, the study showed reduced connectivity between regions of the brain associated with self-awareness, pain, and emotional processing.

IN PRACTICE:

The results “highlight the important role of targeting pain catastrophizing with psychotherapy, particularly for patients reporting high levels of catastrophizing cognitions” write the authors, adding that altered network connectivity identified by the study “may emerge as a valuable biomarker of catastrophizing-related cognitive and affective processes.”

SOURCE:

The study was carried out by Jeungchan Lee, PhD, department of radiology, center for biomedical imaging, Massachusetts General Hospital, Boston, and the Discovery Center for Recovery from Chronic Pain, Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, and colleagues. It was published in Arthritis & Rheumatology.

LIMITATIONS:

Findings were limited to female participants. CBT for chronic pain includes different therapeutic modules, and the study can’t draw definitive conclusions regarding which CBT skills were most beneficial to patients in reducing catastrophizing. Baseline symptom severity was higher for the CBT group, which may complicate interpretation of the findings.

DISCLOSURES:

The study received support from the National Institutes of Health: National Center for Complementary and Integrative Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Center for Research Resources. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

A version of this article first appeared on Medscape.com.

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

A version of this article first appeared on Medscape.com.

Chronic cough took center stage at the European Respiratory Society Congress session titled “Conditions We Are Just Dealing With the Tip of the Iceberg in Primary Care: Frequently Mismanaged Conditions in Primary Health Care.”

“When it comes to chronic cough, general practitioners often feel lost,” Miguel Román Rodríguez, family doctor and an associate professor of family medicine at the University of the Balearic Islands, Palma, Mallorca, Spain, and one of the chairs of the session, said to this news organization.

“GPs are central in diagnosing conditions like chronic cough. We bring something that the specialists don’t bring: the knowledge of the context, of the family, the longitudinal history,” echoed the second chair of the session, Hilary Pinnock, family physician and professor of primary care respiratory medicine at the University of Edinburgh.
 

Understanding the multifaceted nature of chronic cough

Imran Satia, an assistant professor at McMaster University, Hamilton, Ont., guided attendees at the Milan, Italy, meeting through a comprehensive exploration of chronic cough. The first issue he addressed was the definition of the condition, emphasizing that it is defined by its duration, with chronic cough typically lasting for more than 8 weeks. Prof. Satia pointed out common associations of chronic cough, including asthma, nasal disease, and reflux disease.

Delving into epidemiology, he cited a meta-analysis indicating a global prevalence of approximately 10% in the adult population, with significant regional variability: from 18.1% in Australia to 2.3% in Africa. Notably, the Canadian Longitudinal Study on Aging found an overall prevalence of 16% at baseline. “The most common risk factor was smoke, but even in nonsmokers the prevalence reached 10%,” Prof. Satia added, highlighting that it increased with age and changed depending on location. “The most common associated comorbidities were heart failure and hypertension, but also conditions related to chronic pain, mood, and anxiety,” he explained.

Mental health was identified as a crucial factor in chronic cough, with psychological distress and depressive symptoms emerging as risk factors for developing chronic cough over the next 3 years, contributing to a 20% increased risk.
 

Effective management strategies

Prof. Satia proposed the use of algorithms to aid in the management of patients with chronic cough in primary care. He introduced a Canadian algorithm that offers specific recommendations for both primary and secondary care.

The algorithm’s primary care assessment, step 1, includes a comprehensive evaluation of the cough history (duration, severity, triggers, nature, location); cardiorespiratory, gastrointestinal, and nasal symptoms; and use of angiotensin-converting enzyme inhibitors and smoking status. Essential diagnostic tests, such as chest radiography (to check for structural disease), complete blood cell count, and spirometry (with or without bronchodilator reversibility), were emphasized. Urgent referral criteria encompassed symptoms like hemoptysis, weight loss, fever, or abnormal chest radiography findings.

“When checking for cough history, GPs should always consider factors like the presence of dry or productive cough, mental health, presence of chronic pain, stroke, and swallowing,” said Prof. Satia, stressing the importance of documenting the impact of chronic cough on quality of life, work life, social life, and family life. “This is something that doctors sometimes do not ask about. They may think that these are not major problems, but acknowledging their importance can help the patient,” he added.

Step 2 of the algorithm focuses on treatment options tailored to specific diagnoses, such as asthma or chronic obstructive pulmonary disease. Prof. Satia urged caution, emphasizing that treatment should only be initiated when evidence of these conditions is present. Additionally, he encouraged early consideration of cough hypersensitivity syndrome when patients exhibit coughing in response to low levels of mechanical stimulation.
 

Current treatments and future prospects

Prof. Satia presented an overview of existing treatments for chronic cough, outlining their respective advantages and disadvantages. For instance, speech therapy is a patient-led approach with no side effects but entails challenges related to access, costs, and patient motivation. On the other hand, low-dose morphine offers rapid relief but is associated with issues like nausea, stigma, and constipation.

Looking ahead, Prof. Satia shared the results of COUGH-1 and COUGH-2, pivotal phase 3 trials evaluating the oral, peripherally acting P2X3-receptor antagonist gefapixant. This drug, currently approved in Switzerland and Japan, demonstrated a significant reduction in cough frequency, compared with placebo, with rapid and sustained effects. “The estimated relative reduction for 45 mg was 18.45% in COUGH-1 (12 weeks) and 14.64% in COUGH-2 (24 weeks). Of note, cough reduction is very quick and sustained with gefapixant, but a 40% reduction is observed in the placebo arm,” commented Prof. Satia.

Experts unanimously stressed the importance for specialists and GPs of effective communication in managing chronic cough, involving both patients and their families.

“As GPs, we are crucial to manage the common problems, but we are also crucial to spot the needle in the haystack: this is extremely difficult and challenging, and we need support from our colleagues,” Dr. Pinnock concluded.

Prof. Satia reported funding from Merck MSD, AstraZeneca, and GSK; consulting fees from Merck MSD, Genentech, and Respiplus; and speaker fees from AstraZeneca, GSK, and Merck MSD.

A version of this article first appeared on Medscape.com.

Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or both medications together can effectively manage a child’s toothache as a stopgap until definitive treatment is available, according to a new guideline.

The guideline, published in the September issue of the Journal of the American Dental Association, does not recommend opioids for a toothache or after tooth extraction in this population.

Opioid prescriptions for children entail risk for hospitalization and death. Yet, some dentists continued to prescribe contraindicated opioids to young children after a Food and Drug Administration warning in 2017 about the use of tramadol and codeine in this population, the guideline notes.

Opioid prescribing to children also continued after the American Academy of Pediatric Dentistry in 2018 recommended acetaminophen and NSAIDs as first-line medications for pain management and said that the use of opioids should be “rare.”

Although the new guidance, which also covers pain management after tooth extraction, is geared toward general dentists, it could help emergency clinicians and primary care providers manage children’s pain when definitive treatment is not immediately available, the authors noted.

Definitive treatment could include pulpectomy, nonsurgical root canal, incision for drainage of an abscess, or tooth extraction.

If definitive care in 2-3 days is not possible, parents should let the health care team know, the guideline says.

“These pharmacologic strategies will alleviate dental pain temporarily until a referral for definitive dental treatment is in place,” the authors wrote.

The American Dental Association (ADA) endorsed the new guideline, which was developed by researchers with the ADA Science & Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania School of Dental Medicine in Philadelphia.

The guideline recommends ibuprofen and, for children older than 2 years, naproxen as NSAID options. The use of naproxen in children younger than 12 years for this purpose is off label, they noted.

The guideline suggests doses of acetaminophen and NSAIDs on the basis of age and weight that may differ from those on medication packaging.

“When acetaminophen or NSAIDs are administered as directed, the risk of harm to children from either medication is low,” the guideline states.

“While prescribing opioids to children has become less frequent overall, this guideline ensures that both dentists and parents have evidence-based recommendations to determine the most appropriate treatment for dental pain,” senior guideline author Paul Moore, DMD, PhD, MPH, professor emeritus at the University of Pittsburgh’s School of Dental Medicine, said in a news release from the ADA. “Parents and caregivers can take comfort that widely available medications that have no abuse potential, such as acetaminophen or ibuprofen, are safe and effective for helping their children find relief from short-term dental pain.”

A 2018 review by Dr. Moore and coauthors found that NSAIDs, with or without acetaminophen, were effective and minimized adverse events, relative to opioids, for acute dental pain across ages.

The new recommendations for children will “allow for better treatment of this kind of pain” and “will help prevent unnecessary prescribing of medications with abuse potential, including opioids,” Patrizia Cavazzoni, MD, director of the FDA Center for Drug Evaluation and Research, said in the news release.

The report stems from a 3-year, $1.5 million grant awarded by the FDA in 2020 to the University of Pittsburgh and the ADA Science & Research Institute to develop a clinical practice guideline for the management of acute pain in dentistry in children, adolescents, and adults. The recommendations for adolescents and adults are still in development.

The report was supported by an FDA grant, and the guideline authors received technical and methodologic support from the agency. Some authors disclosed ties to pharmaceutical companies.

A version of this article appeared on Medscape.com.

Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or both medications together can effectively manage a child’s toothache as a stopgap until definitive treatment is available, according to a new guideline.

The guideline, published in the September issue of the Journal of the American Dental Association, does not recommend opioids for a toothache or after tooth extraction in this population.

Opioid prescriptions for children entail risk for hospitalization and death. Yet, some dentists continued to prescribe contraindicated opioids to young children after a Food and Drug Administration warning in 2017 about the use of tramadol and codeine in this population, the guideline notes.

Opioid prescribing to children also continued after the American Academy of Pediatric Dentistry in 2018 recommended acetaminophen and NSAIDs as first-line medications for pain management and said that the use of opioids should be “rare.”

Although the new guidance, which also covers pain management after tooth extraction, is geared toward general dentists, it could help emergency clinicians and primary care providers manage children’s pain when definitive treatment is not immediately available, the authors noted.

Definitive treatment could include pulpectomy, nonsurgical root canal, incision for drainage of an abscess, or tooth extraction.

If definitive care in 2-3 days is not possible, parents should let the health care team know, the guideline says.

“These pharmacologic strategies will alleviate dental pain temporarily until a referral for definitive dental treatment is in place,” the authors wrote.

The American Dental Association (ADA) endorsed the new guideline, which was developed by researchers with the ADA Science & Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania School of Dental Medicine in Philadelphia.

The guideline recommends ibuprofen and, for children older than 2 years, naproxen as NSAID options. The use of naproxen in children younger than 12 years for this purpose is off label, they noted.

The guideline suggests doses of acetaminophen and NSAIDs on the basis of age and weight that may differ from those on medication packaging.

“When acetaminophen or NSAIDs are administered as directed, the risk of harm to children from either medication is low,” the guideline states.

“While prescribing opioids to children has become less frequent overall, this guideline ensures that both dentists and parents have evidence-based recommendations to determine the most appropriate treatment for dental pain,” senior guideline author Paul Moore, DMD, PhD, MPH, professor emeritus at the University of Pittsburgh’s School of Dental Medicine, said in a news release from the ADA. “Parents and caregivers can take comfort that widely available medications that have no abuse potential, such as acetaminophen or ibuprofen, are safe and effective for helping their children find relief from short-term dental pain.”

A 2018 review by Dr. Moore and coauthors found that NSAIDs, with or without acetaminophen, were effective and minimized adverse events, relative to opioids, for acute dental pain across ages.

The new recommendations for children will “allow for better treatment of this kind of pain” and “will help prevent unnecessary prescribing of medications with abuse potential, including opioids,” Patrizia Cavazzoni, MD, director of the FDA Center for Drug Evaluation and Research, said in the news release.

The report stems from a 3-year, $1.5 million grant awarded by the FDA in 2020 to the University of Pittsburgh and the ADA Science & Research Institute to develop a clinical practice guideline for the management of acute pain in dentistry in children, adolescents, and adults. The recommendations for adolescents and adults are still in development.

The report was supported by an FDA grant, and the guideline authors received technical and methodologic support from the agency. Some authors disclosed ties to pharmaceutical companies.

A version of this article appeared on Medscape.com.

Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or both medications together can effectively manage a child’s toothache as a stopgap until definitive treatment is available, according to a new guideline.

The guideline, published in the September issue of the Journal of the American Dental Association, does not recommend opioids for a toothache or after tooth extraction in this population.

Opioid prescriptions for children entail risk for hospitalization and death. Yet, some dentists continued to prescribe contraindicated opioids to young children after a Food and Drug Administration warning in 2017 about the use of tramadol and codeine in this population, the guideline notes.

Opioid prescribing to children also continued after the American Academy of Pediatric Dentistry in 2018 recommended acetaminophen and NSAIDs as first-line medications for pain management and said that the use of opioids should be “rare.”

Although the new guidance, which also covers pain management after tooth extraction, is geared toward general dentists, it could help emergency clinicians and primary care providers manage children’s pain when definitive treatment is not immediately available, the authors noted.

Definitive treatment could include pulpectomy, nonsurgical root canal, incision for drainage of an abscess, or tooth extraction.

If definitive care in 2-3 days is not possible, parents should let the health care team know, the guideline says.

“These pharmacologic strategies will alleviate dental pain temporarily until a referral for definitive dental treatment is in place,” the authors wrote.

The American Dental Association (ADA) endorsed the new guideline, which was developed by researchers with the ADA Science & Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania School of Dental Medicine in Philadelphia.

The guideline recommends ibuprofen and, for children older than 2 years, naproxen as NSAID options. The use of naproxen in children younger than 12 years for this purpose is off label, they noted.

The guideline suggests doses of acetaminophen and NSAIDs on the basis of age and weight that may differ from those on medication packaging.

“When acetaminophen or NSAIDs are administered as directed, the risk of harm to children from either medication is low,” the guideline states.

“While prescribing opioids to children has become less frequent overall, this guideline ensures that both dentists and parents have evidence-based recommendations to determine the most appropriate treatment for dental pain,” senior guideline author Paul Moore, DMD, PhD, MPH, professor emeritus at the University of Pittsburgh’s School of Dental Medicine, said in a news release from the ADA. “Parents and caregivers can take comfort that widely available medications that have no abuse potential, such as acetaminophen or ibuprofen, are safe and effective for helping their children find relief from short-term dental pain.”

A 2018 review by Dr. Moore and coauthors found that NSAIDs, with or without acetaminophen, were effective and minimized adverse events, relative to opioids, for acute dental pain across ages.

The new recommendations for children will “allow for better treatment of this kind of pain” and “will help prevent unnecessary prescribing of medications with abuse potential, including opioids,” Patrizia Cavazzoni, MD, director of the FDA Center for Drug Evaluation and Research, said in the news release.

The report stems from a 3-year, $1.5 million grant awarded by the FDA in 2020 to the University of Pittsburgh and the ADA Science & Research Institute to develop a clinical practice guideline for the management of acute pain in dentistry in children, adolescents, and adults. The recommendations for adolescents and adults are still in development.

The report was supported by an FDA grant, and the guideline authors received technical and methodologic support from the agency. Some authors disclosed ties to pharmaceutical companies.

A version of this article appeared on Medscape.com.

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

P ruritus is a characteristic and often debilitating clinical manifestation reported by about 50% of patients with polycythemia vera (PV). The exact pathophysiology of PV-associated pruritus is poorly understood. The itch sensation may arise from a central phenomenon without skin itch receptor involvement, as is seen in opioid-induced pruritus, or peripherally via unmyelinated C fibers. Various interventions have been used with mixed results for symptom management in this patient population.¹

Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and fluoxetine, have historically demonstrated some efficacy in treating PV-associated pruritus.² Alongside SSRIs, phlebotomy, antihistamines, phototherapy, interferon a, and myelosuppressive medications also comprise the various current treatment options. In addition to lacking efficacy, antihistamines can cause somnolence, constipation, and xerostomia.^3,4 Phlebotomy and cytoreductive therapy are often effective in controlling erythrocytosis but fail to alleviate the disabling pruritus.^1,5,6 More recently, suboptimal symptom alleviation has prompted the discovery of agents that target the mammalian target of rapamycin (mTOR) and Janus kinase 2 (Jak2) pathways.¹

Naltrexone is an opioid antagonist shown to suppress pruritus in various dermatologic pathologies involving histamine-independent pathways.^3,7,8 A systematic search strategy identified 34 studies on PV-associated pruritus, its pathophysiology and interventions, and naltrexone as a therapeutic agent. Only 1 study in the literature has described the use of naltrexone for uremic and cholestatic pruritus.⁹ We describe the successful use of naltrexone monotherapy for the treatment of pruritus in a patient with PV.

Case Presentation

A 40-year-old man with Jak2-positive PV treated with ruxolitinib presented to the outpatient Michael E. DeBakey Veterans Affairs Medical Center Supportive Care Clinic in Houston, Texas, for severe refractory pruritus. Wheals manifested in pruritic regions of the patient’s skin without gross excoriations or erythema. Pruritus reportedly began diffusely across the posterior torso. Through the rapid progression of an episode lasting 30 to 45 minutes, the lesions and pruritus would spread to the anterior torso, extend to the upper extremities bilaterally, and finally descend to the lower extremities bilaterally. A persistent sensation of heat or warmth on the patient’s skin was present, and periodically, this would culminate in a burning sensation comparable to “lying flat on one’s back directly on a hornet’s nest…[followed by] a million stings” that was inconsistent with erythromelalgia given the absence of erythema. The intensity of the pruritic episodes was subjectively also described as “enough to make [him] want to jump off the roof of a building…[causing] moments of deep, deep frustration…[and] the worst of all the symptoms one may encounter because of [PV].”

Pruritus was exacerbated by sweating, heat, contact with any liquids on the skin, and sunburns, which doubled the intensity. The patient reported minimal, temporary relief with cannabidiol and cold fabric or air on his skin. His current regimen and nonpharmacologic efforts provided no relief and included oatmeal baths, cornstarch after showers, and patting instead of rubbing the skin with topical products. Trials with nonprescription diphenhydramine, loratadine, and calamine and zinc were not successful. He had not pursued phototherapy due to time limitations and travel constraints. He had a history of phlebotomies and hydroxyurea use, which he preferred to avoid and discontinued 1 year before presentation.

Despite improving hematocrit (< 45% goal) and platelet counts with ruxolitinib, the patient reported worsening pruritus that significantly impaired quality of life. His sleep and social and physical activities were hindered, preventing him from working. The patient’s active medications also included low-dose aspirin, sertraline, hydroxyzine, triamcinolone acetonide, and pregabalin for sciatica. Given persistent symptoms despite multimodal therapy and lifestyle modifications, the patient was started on naltrexone 25 mg daily, which provided immediate relief of symptoms. He continues to have adequate symptom control 2 years after naltrexone initiation.

Literature Review

A systematic search strategy was developed with the assistance of a medical librarian in Medline Ovid, using both Medical Subject Heading (MeSH) terms and synonymous keywords. The strategy was then translated to Embase, Web of Science, and Cochrane to extract publications investigating PV, pruritus, and/or naltrexone therapy. All searches were conducted on July 18, 2022, and the results of the literature review were as follows: 2 results from Medline Ovid; 34 results from Embase (2 were duplicates of Medline Ovid results); 3 results from Web of Science (all of which were duplicates of Medline Ovid or Embase results); and 0 results from Cochrane (Figure).

Discussion

Although pruritus is a common and often excruciating manifestation of PV, its pathophysiology remains unclear. Some patients with decreasing or newly normal hematocrit and hemoglobin levels have paradoxically experienced an intensification of their pruritus, which introduces erythropoietin signaling pathways as a potential mechanism of the symptom.⁸ However, iron replacement therapy for patients with exacerbated pruritus after phlebotomies has not demonstrated consistent relief of pruritus.⁸ Normalization of platelet levels also has not been historically associated with improvement of pruritus.^8,9 It has been hypothesized that cells harboring Jak2 mutations at any stage of the hematopoietic pathway mature and accumulate to cause pruritus in PV.⁹ This theory has been foundational in the development of drugs with activity against cells expressing Jak2 mutations and interventions targeting histamine-releasing mast cells.^9-11

The effective use of naltrexone in our patient suggests that histamine may not be the most effective or sole therapeutic target against pruritus in PV. Naltrexone targets opioid receptors in all layers of the epidermis, affecting cell adhesion and keratinocyte production, and exhibits anti-inflammatory effects through interactions with nonopioid receptors, including Toll-like receptor 4.¹² The efficacy of oral naltrexone has been documented in patients with pruritus associated with immune checkpoint inhibitors, psoriasis, eczema, lichen simplex chronicus, prurigo nodularis, cholestasis, uremia, and multiple rheumatologic diseases.^{3,4,7-9,12-14} Opioid pathways also may be involved in peripheral and/or central processing of pruritus associated with PV.

Importantly, patients who are potential candidates for naltrexone therapy should be notified and advised of the risk of drug interactions with opioids, which could lead to symptoms of opioid withdrawal. Other common adverse effects of naltrexone include hepatotoxicity (especially in patients with a history of significant alcohol consumption), abdominal pain, nausea, arthralgias, myalgias, insomnia, headaches, fatigue, and anxiety.¹² Therefore, it is integral to screen patients for opioid dependence and determine their baseline liver function. Patients should be monitored following naltrexone initiation to determine whether the drug is an appropriate and effective intervention against PV-associated pruritus.

CONCLUSIONS

This case study demonstrates that naltrexone may be a safe, effective, nonsedating, and cost-efficient oral alternative for refractory PV-associated pruritus. Future directions involve consideration of case series or randomized clinical trials investigating the efficacy of naltrexone in treating PV-associated pruritus. Further research is also warranted to better understand the pathophysiology of this symptom of PV to enhance and potentially expand medical management for patients.

Acknowledgments

The authors thank Amy Sisson (The Texas Medical Center Library) for her guidance and support in the literature review methodology.

P ruritus is a characteristic and often debilitating clinical manifestation reported by about 50% of patients with polycythemia vera (PV). The exact pathophysiology of PV-associated pruritus is poorly understood. The itch sensation may arise from a central phenomenon without skin itch receptor involvement, as is seen in opioid-induced pruritus, or peripherally via unmyelinated C fibers. Various interventions have been used with mixed results for symptom management in this patient population.¹

Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and fluoxetine, have historically demonstrated some efficacy in treating PV-associated pruritus.² Alongside SSRIs, phlebotomy, antihistamines, phototherapy, interferon a, and myelosuppressive medications also comprise the various current treatment options. In addition to lacking efficacy, antihistamines can cause somnolence, constipation, and xerostomia.^3,4 Phlebotomy and cytoreductive therapy are often effective in controlling erythrocytosis but fail to alleviate the disabling pruritus.^1,5,6 More recently, suboptimal symptom alleviation has prompted the discovery of agents that target the mammalian target of rapamycin (mTOR) and Janus kinase 2 (Jak2) pathways.¹

Naltrexone is an opioid antagonist shown to suppress pruritus in various dermatologic pathologies involving histamine-independent pathways.^3,7,8 A systematic search strategy identified 34 studies on PV-associated pruritus, its pathophysiology and interventions, and naltrexone as a therapeutic agent. Only 1 study in the literature has described the use of naltrexone for uremic and cholestatic pruritus.⁹ We describe the successful use of naltrexone monotherapy for the treatment of pruritus in a patient with PV.

Case Presentation

A 40-year-old man with Jak2-positive PV treated with ruxolitinib presented to the outpatient Michael E. DeBakey Veterans Affairs Medical Center Supportive Care Clinic in Houston, Texas, for severe refractory pruritus. Wheals manifested in pruritic regions of the patient’s skin without gross excoriations or erythema. Pruritus reportedly began diffusely across the posterior torso. Through the rapid progression of an episode lasting 30 to 45 minutes, the lesions and pruritus would spread to the anterior torso, extend to the upper extremities bilaterally, and finally descend to the lower extremities bilaterally. A persistent sensation of heat or warmth on the patient’s skin was present, and periodically, this would culminate in a burning sensation comparable to “lying flat on one’s back directly on a hornet’s nest…[followed by] a million stings” that was inconsistent with erythromelalgia given the absence of erythema. The intensity of the pruritic episodes was subjectively also described as “enough to make [him] want to jump off the roof of a building…[causing] moments of deep, deep frustration…[and] the worst of all the symptoms one may encounter because of [PV].”

Pruritus was exacerbated by sweating, heat, contact with any liquids on the skin, and sunburns, which doubled the intensity. The patient reported minimal, temporary relief with cannabidiol and cold fabric or air on his skin. His current regimen and nonpharmacologic efforts provided no relief and included oatmeal baths, cornstarch after showers, and patting instead of rubbing the skin with topical products. Trials with nonprescription diphenhydramine, loratadine, and calamine and zinc were not successful. He had not pursued phototherapy due to time limitations and travel constraints. He had a history of phlebotomies and hydroxyurea use, which he preferred to avoid and discontinued 1 year before presentation.

Despite improving hematocrit (< 45% goal) and platelet counts with ruxolitinib, the patient reported worsening pruritus that significantly impaired quality of life. His sleep and social and physical activities were hindered, preventing him from working. The patient’s active medications also included low-dose aspirin, sertraline, hydroxyzine, triamcinolone acetonide, and pregabalin for sciatica. Given persistent symptoms despite multimodal therapy and lifestyle modifications, the patient was started on naltrexone 25 mg daily, which provided immediate relief of symptoms. He continues to have adequate symptom control 2 years after naltrexone initiation.

Literature Review

A systematic search strategy was developed with the assistance of a medical librarian in Medline Ovid, using both Medical Subject Heading (MeSH) terms and synonymous keywords. The strategy was then translated to Embase, Web of Science, and Cochrane to extract publications investigating PV, pruritus, and/or naltrexone therapy. All searches were conducted on July 18, 2022, and the results of the literature review were as follows: 2 results from Medline Ovid; 34 results from Embase (2 were duplicates of Medline Ovid results); 3 results from Web of Science (all of which were duplicates of Medline Ovid or Embase results); and 0 results from Cochrane (Figure).

Discussion

Although pruritus is a common and often excruciating manifestation of PV, its pathophysiology remains unclear. Some patients with decreasing or newly normal hematocrit and hemoglobin levels have paradoxically experienced an intensification of their pruritus, which introduces erythropoietin signaling pathways as a potential mechanism of the symptom.⁸ However, iron replacement therapy for patients with exacerbated pruritus after phlebotomies has not demonstrated consistent relief of pruritus.⁸ Normalization of platelet levels also has not been historically associated with improvement of pruritus.^8,9 It has been hypothesized that cells harboring Jak2 mutations at any stage of the hematopoietic pathway mature and accumulate to cause pruritus in PV.⁹ This theory has been foundational in the development of drugs with activity against cells expressing Jak2 mutations and interventions targeting histamine-releasing mast cells.^9-11

The effective use of naltrexone in our patient suggests that histamine may not be the most effective or sole therapeutic target against pruritus in PV. Naltrexone targets opioid receptors in all layers of the epidermis, affecting cell adhesion and keratinocyte production, and exhibits anti-inflammatory effects through interactions with nonopioid receptors, including Toll-like receptor 4.¹² The efficacy of oral naltrexone has been documented in patients with pruritus associated with immune checkpoint inhibitors, psoriasis, eczema, lichen simplex chronicus, prurigo nodularis, cholestasis, uremia, and multiple rheumatologic diseases.^{3,4,7-9,12-14} Opioid pathways also may be involved in peripheral and/or central processing of pruritus associated with PV.

Importantly, patients who are potential candidates for naltrexone therapy should be notified and advised of the risk of drug interactions with opioids, which could lead to symptoms of opioid withdrawal. Other common adverse effects of naltrexone include hepatotoxicity (especially in patients with a history of significant alcohol consumption), abdominal pain, nausea, arthralgias, myalgias, insomnia, headaches, fatigue, and anxiety.¹² Therefore, it is integral to screen patients for opioid dependence and determine their baseline liver function. Patients should be monitored following naltrexone initiation to determine whether the drug is an appropriate and effective intervention against PV-associated pruritus.

CONCLUSIONS

This case study demonstrates that naltrexone may be a safe, effective, nonsedating, and cost-efficient oral alternative for refractory PV-associated pruritus. Future directions involve consideration of case series or randomized clinical trials investigating the efficacy of naltrexone in treating PV-associated pruritus. Further research is also warranted to better understand the pathophysiology of this symptom of PV to enhance and potentially expand medical management for patients.

Acknowledgments

The authors thank Amy Sisson (The Texas Medical Center Library) for her guidance and support in the literature review methodology.

P ruritus is a characteristic and often debilitating clinical manifestation reported by about 50% of patients with polycythemia vera (PV). The exact pathophysiology of PV-associated pruritus is poorly understood. The itch sensation may arise from a central phenomenon without skin itch receptor involvement, as is seen in opioid-induced pruritus, or peripherally via unmyelinated C fibers. Various interventions have been used with mixed results for symptom management in this patient population.¹

Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and fluoxetine, have historically demonstrated some efficacy in treating PV-associated pruritus.² Alongside SSRIs, phlebotomy, antihistamines, phototherapy, interferon a, and myelosuppressive medications also comprise the various current treatment options. In addition to lacking efficacy, antihistamines can cause somnolence, constipation, and xerostomia.^3,4 Phlebotomy and cytoreductive therapy are often effective in controlling erythrocytosis but fail to alleviate the disabling pruritus.^1,5,6 More recently, suboptimal symptom alleviation has prompted the discovery of agents that target the mammalian target of rapamycin (mTOR) and Janus kinase 2 (Jak2) pathways.¹

Naltrexone is an opioid antagonist shown to suppress pruritus in various dermatologic pathologies involving histamine-independent pathways.^3,7,8 A systematic search strategy identified 34 studies on PV-associated pruritus, its pathophysiology and interventions, and naltrexone as a therapeutic agent. Only 1 study in the literature has described the use of naltrexone for uremic and cholestatic pruritus.⁹ We describe the successful use of naltrexone monotherapy for the treatment of pruritus in a patient with PV.

Case Presentation

A 40-year-old man with Jak2-positive PV treated with ruxolitinib presented to the outpatient Michael E. DeBakey Veterans Affairs Medical Center Supportive Care Clinic in Houston, Texas, for severe refractory pruritus. Wheals manifested in pruritic regions of the patient’s skin without gross excoriations or erythema. Pruritus reportedly began diffusely across the posterior torso. Through the rapid progression of an episode lasting 30 to 45 minutes, the lesions and pruritus would spread to the anterior torso, extend to the upper extremities bilaterally, and finally descend to the lower extremities bilaterally. A persistent sensation of heat or warmth on the patient’s skin was present, and periodically, this would culminate in a burning sensation comparable to “lying flat on one’s back directly on a hornet’s nest…[followed by] a million stings” that was inconsistent with erythromelalgia given the absence of erythema. The intensity of the pruritic episodes was subjectively also described as “enough to make [him] want to jump off the roof of a building…[causing] moments of deep, deep frustration…[and] the worst of all the symptoms one may encounter because of [PV].”

Pruritus was exacerbated by sweating, heat, contact with any liquids on the skin, and sunburns, which doubled the intensity. The patient reported minimal, temporary relief with cannabidiol and cold fabric or air on his skin. His current regimen and nonpharmacologic efforts provided no relief and included oatmeal baths, cornstarch after showers, and patting instead of rubbing the skin with topical products. Trials with nonprescription diphenhydramine, loratadine, and calamine and zinc were not successful. He had not pursued phototherapy due to time limitations and travel constraints. He had a history of phlebotomies and hydroxyurea use, which he preferred to avoid and discontinued 1 year before presentation.

Despite improving hematocrit (< 45% goal) and platelet counts with ruxolitinib, the patient reported worsening pruritus that significantly impaired quality of life. His sleep and social and physical activities were hindered, preventing him from working. The patient’s active medications also included low-dose aspirin, sertraline, hydroxyzine, triamcinolone acetonide, and pregabalin for sciatica. Given persistent symptoms despite multimodal therapy and lifestyle modifications, the patient was started on naltrexone 25 mg daily, which provided immediate relief of symptoms. He continues to have adequate symptom control 2 years after naltrexone initiation.

Literature Review

A systematic search strategy was developed with the assistance of a medical librarian in Medline Ovid, using both Medical Subject Heading (MeSH) terms and synonymous keywords. The strategy was then translated to Embase, Web of Science, and Cochrane to extract publications investigating PV, pruritus, and/or naltrexone therapy. All searches were conducted on July 18, 2022, and the results of the literature review were as follows: 2 results from Medline Ovid; 34 results from Embase (2 were duplicates of Medline Ovid results); 3 results from Web of Science (all of which were duplicates of Medline Ovid or Embase results); and 0 results from Cochrane (Figure).

Discussion

Although pruritus is a common and often excruciating manifestation of PV, its pathophysiology remains unclear. Some patients with decreasing or newly normal hematocrit and hemoglobin levels have paradoxically experienced an intensification of their pruritus, which introduces erythropoietin signaling pathways as a potential mechanism of the symptom.⁸ However, iron replacement therapy for patients with exacerbated pruritus after phlebotomies has not demonstrated consistent relief of pruritus.⁸ Normalization of platelet levels also has not been historically associated with improvement of pruritus.^8,9 It has been hypothesized that cells harboring Jak2 mutations at any stage of the hematopoietic pathway mature and accumulate to cause pruritus in PV.⁹ This theory has been foundational in the development of drugs with activity against cells expressing Jak2 mutations and interventions targeting histamine-releasing mast cells.^9-11

The effective use of naltrexone in our patient suggests that histamine may not be the most effective or sole therapeutic target against pruritus in PV. Naltrexone targets opioid receptors in all layers of the epidermis, affecting cell adhesion and keratinocyte production, and exhibits anti-inflammatory effects through interactions with nonopioid receptors, including Toll-like receptor 4.¹² The efficacy of oral naltrexone has been documented in patients with pruritus associated with immune checkpoint inhibitors, psoriasis, eczema, lichen simplex chronicus, prurigo nodularis, cholestasis, uremia, and multiple rheumatologic diseases.^{3,4,7-9,12-14} Opioid pathways also may be involved in peripheral and/or central processing of pruritus associated with PV.

Importantly, patients who are potential candidates for naltrexone therapy should be notified and advised of the risk of drug interactions with opioids, which could lead to symptoms of opioid withdrawal. Other common adverse effects of naltrexone include hepatotoxicity (especially in patients with a history of significant alcohol consumption), abdominal pain, nausea, arthralgias, myalgias, insomnia, headaches, fatigue, and anxiety.¹² Therefore, it is integral to screen patients for opioid dependence and determine their baseline liver function. Patients should be monitored following naltrexone initiation to determine whether the drug is an appropriate and effective intervention against PV-associated pruritus.

CONCLUSIONS

This case study demonstrates that naltrexone may be a safe, effective, nonsedating, and cost-efficient oral alternative for refractory PV-associated pruritus. Future directions involve consideration of case series or randomized clinical trials investigating the efficacy of naltrexone in treating PV-associated pruritus. Further research is also warranted to better understand the pathophysiology of this symptom of PV to enhance and potentially expand medical management for patients.

Acknowledgments

The authors thank Amy Sisson (The Texas Medical Center Library) for her guidance and support in the literature review methodology.

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Knowing whether a patient has radiographic or nonradiographic axial spondyloarthritis will not change management, experts say. What matters is recognizing that the patient has inflammatory back pain (IBP) and clinical features of spondyloarthritis and that the patient is referred to a rheumatologist as soon as possible.
 

Out with the old, in with the new

Axial spondyloarthritis is characterized by chronic inflammation of the sacroiliac (SI) joints, and spine. It’s a modern term that includes ankylosing spondylitis (AS) and that refers to opposite ends of a disease spectrum.

Nonradiographic axial spondyloarthritis (nr-axSpA) is so termed because there are no definitive visible changes on plain x-rays, although inflammatory changes may be seen on MRI.

Radiographic axial spondyloarthritis (r-axSpA) is the same as AS to some extent and is associated with clear signs of joint damage (that is, of past inflammation) on x-rays.

“Axial spondyloarthritis is one disease, and whether it is radiographic or nonradiographic makes zero difference in the management of the patient,” says Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at Oregon Health and Science University, Portland. The distinction came about in 2009 to facilitate scientific and clinical research, he explains, and to enable the use of tumor necrosis factor inhibitors, which were new at the time, for patients who could not be classified as having AS.

“We have known what ankylosing spondylitis is for a long time because we have been doing plain x-rays of the sacroiliac joints, and if we see classical changes of sacroiliitis, we have the diagnosis. However, MRI changed everything,” Dr. Deodhar says. Now it’s possible to see inflammatory changes in the SI joints and early joint damage, which was not possible to see on x-ray until many years later.
 

Reassuring for patients?

“Currently, we don’t really have different treatments,” Dr. Deodhar notes. Perhaps the only benefit is that it might be reassuring for patients to know that they have the nonradiographic form. Receiving a diagnosis of axial spondyloarthritis comes as quite a shock. It’s a diagnosis that is potentially going to affect them for the rest of their lives, and some patients worry that they’ll develop the classic “bamboo” spine of AS, he adds. So, being able to tell patients that they have nr-axSpA and that they are going to be treated early and aggressively may be somewhat comforting.

“It’s a continuum of a disease state, but a lot of people will stay at the nonradiographic stage,” points out Portland-based internist Beth Smith, DO, associate professor of medicine at OHSU.

“A good portion of individuals who may have an MRI that’s positive will either go into remission or just stay at that stage of the disease; they won’t necessarily progress to radiographic sacroiliitis,” she adds.
 

Spotting nr-axSpA in practice

Nr-axSpA can be tricky to spot in clinical practice, and its diagnosis in primary care largely relies on patients’ clinical presentation and identifying IBP. This is the key symptom. When someone younger than 45 years experiences back pain that is characterized by insidious and chronic onset and that improves with anti-inflammatory agents and activity but that worsens with rest and is worse at night, then imaging of the SI joints may be appropriate.

“You have to have that index of suspicion in order to even think about ordering the appropriate imaging test,” Dr. Smith says. IBP may be the big clue, but patients may also return on separate occasions with multiple associated complaints, such as plantar fasciitis, tennis elbow, or other conditions, such as psoriasis, she says.

Ordering HLA-B27 and C-reactive protein tests may be useful prior to conducting any imaging, Dr. Smith says, “and if imaging is ordered, make sure it is an x-ray of the sacroiliac joint, not the lumbar spine.”

Dr. Deodhar cautions: “A single anterior-posterior view of the pelvis is enough to look at the sacroiliac joint.” There is no need to order separate views of the right and left SI joints; doing so will provide no additional useful information and exposes the patient to unnecessary radiation.

Importantly, consider whether an x-ray of the lumbar spine is needed for a patient with chronic back pain, he says. “You should do an investigation that is going to make a difference to your management. If you take 100 patients with back pain, 95% of the time, it is going to be mechanical back pain. Why do an x-ray of the lumbar spine?” Dr. Deodhar asks rhetorically.

It should also be borne in mind that x-rays can be nonspecific, and several conditions may mimic sacroiliitis, such as osteitis condensans ilii in women who have given birth, osteoarthritis of the SI joints, and old infection of the SI joints.
 

MRIs need specialist interpretation

MRIs of the lumbar spine are overused to diagnose back pain, and while they might be sensitive to early inflammatory changes in SI joints, they require an expert eye for interpretation.

“MRI of the SI joints is to be used wisely in patients when there is enough clinical suspicion,” Dr. Deodhar advises. Even when an MRI is negative for sacroiliitis, patients could still have axial spondyloarthritis.

MRIs of the SI joints are needed, but not of the lumbar spine, he stresses. Views of the lumbar spine may show only signs of disk degeneration and perhaps osteoarthritis.

Moreover, Dr. Deodhar says, “MRI is so sensitive that we used to think that bone marrow edema is good enough for telling us there is sacroiliitis.” However, even people without IBP can have bone marrow edema; “exercise can show bone marrow edema,” he says.

So, “If there’s a suspicion of axial spondyloarthritis, the patient should be referred to a rheumatologist,” who will discuss the interpretation with highly specialized musculoskeletal radiologists.
 

Take-home messages

Whether it is nr-axSpA or r-axSpA, “the burden of disease for the patient is the same; treatment is the same,” says Dr. Deodhar. Patients should be referred to a rheumatologist as soon as possible if axial spondyloarthritis is suspected. A single x-ray of the pelvis should be performed to see the SI joints, but MRIs should be left to secondary care, he suggests.

Dr. Smith notes: “Having that index of suspicion of an inflammatory etiology for the back pain is essential.” It ensures that “patients can get early and appropriate treatment for a disease that’s very different from the mechanical back pain that we mostly see in primary care.”

Dr. Deodhar has received research grants or has acted as a consultant to multiple pharmaceutical companies, including AbbVie, Bristol-Myers Squibb, Celgene, Janssen, UCB, Novartis, Pfizer, and Eli Lilly. Dr. Smith reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More than 3 decades ago, John E. Sarno, MD, published Healing Back Pain, a popular book that garnered something of a cult following. Looking at his own practice, Dr. Sarno, a rehabilitation medicine specialist in New York, saw that most of his patients with chronic pain did not have evidence of acute injury or degenerative disk disease. Their persistent pain appeared to be independent of any structural damage to the spine. Dr. Sarno attributed the pain to what he called tension myoneural syndrome (TMS), or the body’s reaction to suppressed stress and emotional turmoil. Resolving that psychological conflict, Dr. Sarno believed, would lead to an improvement in pain.
 

Dr. Sarno’s theory has met skepticism from the mainstream community, but glowing testimonies from patients who say they benefited from his strategies fill the Internet. Dr. Sarno wrote several books on his ideas before his death in 2017. But he published only one peer-reviewed study, a 2003 review in the Archives of Physical Medicine and Rehabilitation coauthored by Ira Rashbaum, MD.

This news organization spoke recently with Dr. Rashbaum, a physiatrist and chief of tension myoneural syndrome at NYU Langone Health, New York, about TMS and how he manages patients with chronic pain. The interview has been edited for length and clarity.

What is your theory of back pain?

Dr. Rashbaum: My null hypothesis is that back pain is not due to psychological issues, so as to not be a biased doctor, I try to accept the null hypothesis or reject the null hypothesis. In most cases chronic back pain is not due to structural etiology. My sense is it’s a mind-body issue – the avoidance of feeling strong emotions like anger, rage, sadness, fear, shame, and guilt. Patients can embrace psychoeducational programs and if they don’t get better, we work with a psychotherapist or a licensed mental health counselor to help work through the patient’s feelings. That’s my experience over a number of years.

How do you determine if a patient has back pain from a mind-body issue or another cause?

Dr. Rashbaum: I do a very careful medical history, including a physical examination and review of any diagnostic studies they’ve undergone. In most situations, there’s not really a medical cause of the back pain. For instance, a lot of asymptomatic individuals have all sorts of horrible findings on medical imaging like CTs and MRIs, and the reverse is also true – many people with negative findings on imaging tests experience significant pain. My job as a diagnostician is to see how much of this is really a mind-body problem or something that stems from structural pathology.

How well do your patients react to being told that their back pain is, in a way, “in their head?”

Dr. Rashbaum: I have a skewed population. I’m sort of like a guru in mind-body back pain, so the people who come to me are already thinking along those lines. I ask: “What’s going on in your life?” Maybe there are job issues, marital issues, health issues, and I’d say that it’s certainly possible that stress can be causing this back pain.

Sometimes when I see a patient referred from another physician, I’m a bit hesitant to ask about what’s going on in their life. Even earlier today, I’d seen a patient with back pain and I had a sense that they were not really going to be open to a mind-body approach. So I said, do physical therapy.

What do you recommend primary care clinicians do with patients with back pain?

Dr. Rashbaum: You have to do a proper neurologic examination and musculoskeletal examination. It’s a tough situation because doctors in primary care have limited time to take care of patients. It’s difficult to have a deeper dive just to kind of see what’s going on in their life. But you can recommend useful agents like acetaminophen and muscle relaxants, which are sometimes okay.

What sorts of things do you tell patients to say to themselves when they’re experiencing pain? 

Dr. Rashbaum: If the pain is severe, I recommend they take medication – over-the-counter analgesics or a muscle relaxant, if they have them – and take a warm shower or bath. I prefer acetaminophen up to three times per day, if that’s okay with the patient’s primary care physician, over NSAIDs because most pain is noninflammatory in nature. Once the pain is more manageable, patients should journal about what’s going on in their lives and/or meditate, and try to feel any strong emotions, such as anger, sadness, or fear.

What do you say to clinicians who are dismissive of the notion that chronic pain may stem from emotional repression, and that addressing the latter can resolve the former – particularly those who point to a lack of peer-reviewed data for such a link?

Dr. Rashbaum: I would tell them they could be looking harder for that evidence. For example, in a patient page from JAMA from April 24, 2013, on low back pain, often the cause of back pain is unknown. There are data in spine surgical journals that patients with psychological issues do worse with spine surgery. And in 2016 JAMA published a study from Cherkin and colleagues, which found that, among adults with chronic low back pain, treatment with mindfulness-based stress reduction or cognitive behavioral therapy resulted in greater improvement in back pain and functional limitations at 26 weeks, compared with usual care.

My feeling is that these psychosocial interventions are easy to try, relatively inexpensive, noninvasive, and, in my experience, often can lead to marked improvements. I believe that, for the vast majority of people with chronic pain, it makes much more sense to start by addressing mind-body issues than turning to that approach as a last resort.

Dr. Rashbaum reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More than 3 decades ago, John E. Sarno, MD, published Healing Back Pain, a popular book that garnered something of a cult following. Looking at his own practice, Dr. Sarno, a rehabilitation medicine specialist in New York, saw that most of his patients with chronic pain did not have evidence of acute injury or degenerative disk disease. Their persistent pain appeared to be independent of any structural damage to the spine. Dr. Sarno attributed the pain to what he called tension myoneural syndrome (TMS), or the body’s reaction to suppressed stress and emotional turmoil. Resolving that psychological conflict, Dr. Sarno believed, would lead to an improvement in pain.
 

Dr. Sarno’s theory has met skepticism from the mainstream community, but glowing testimonies from patients who say they benefited from his strategies fill the Internet. Dr. Sarno wrote several books on his ideas before his death in 2017. But he published only one peer-reviewed study, a 2003 review in the Archives of Physical Medicine and Rehabilitation coauthored by Ira Rashbaum, MD.

This news organization spoke recently with Dr. Rashbaum, a physiatrist and chief of tension myoneural syndrome at NYU Langone Health, New York, about TMS and how he manages patients with chronic pain. The interview has been edited for length and clarity.

What is your theory of back pain?

Dr. Rashbaum: My null hypothesis is that back pain is not due to psychological issues, so as to not be a biased doctor, I try to accept the null hypothesis or reject the null hypothesis. In most cases chronic back pain is not due to structural etiology. My sense is it’s a mind-body issue – the avoidance of feeling strong emotions like anger, rage, sadness, fear, shame, and guilt. Patients can embrace psychoeducational programs and if they don’t get better, we work with a psychotherapist or a licensed mental health counselor to help work through the patient’s feelings. That’s my experience over a number of years.

How do you determine if a patient has back pain from a mind-body issue or another cause?

Dr. Rashbaum: I do a very careful medical history, including a physical examination and review of any diagnostic studies they’ve undergone. In most situations, there’s not really a medical cause of the back pain. For instance, a lot of asymptomatic individuals have all sorts of horrible findings on medical imaging like CTs and MRIs, and the reverse is also true – many people with negative findings on imaging tests experience significant pain. My job as a diagnostician is to see how much of this is really a mind-body problem or something that stems from structural pathology.

How well do your patients react to being told that their back pain is, in a way, “in their head?”

Dr. Rashbaum: I have a skewed population. I’m sort of like a guru in mind-body back pain, so the people who come to me are already thinking along those lines. I ask: “What’s going on in your life?” Maybe there are job issues, marital issues, health issues, and I’d say that it’s certainly possible that stress can be causing this back pain.

Sometimes when I see a patient referred from another physician, I’m a bit hesitant to ask about what’s going on in their life. Even earlier today, I’d seen a patient with back pain and I had a sense that they were not really going to be open to a mind-body approach. So I said, do physical therapy.

What do you recommend primary care clinicians do with patients with back pain?

Dr. Rashbaum: You have to do a proper neurologic examination and musculoskeletal examination. It’s a tough situation because doctors in primary care have limited time to take care of patients. It’s difficult to have a deeper dive just to kind of see what’s going on in their life. But you can recommend useful agents like acetaminophen and muscle relaxants, which are sometimes okay.

What sorts of things do you tell patients to say to themselves when they’re experiencing pain? 

Dr. Rashbaum: If the pain is severe, I recommend they take medication – over-the-counter analgesics or a muscle relaxant, if they have them – and take a warm shower or bath. I prefer acetaminophen up to three times per day, if that’s okay with the patient’s primary care physician, over NSAIDs because most pain is noninflammatory in nature. Once the pain is more manageable, patients should journal about what’s going on in their lives and/or meditate, and try to feel any strong emotions, such as anger, sadness, or fear.

What do you say to clinicians who are dismissive of the notion that chronic pain may stem from emotional repression, and that addressing the latter can resolve the former – particularly those who point to a lack of peer-reviewed data for such a link?

Dr. Rashbaum: I would tell them they could be looking harder for that evidence. For example, in a patient page from JAMA from April 24, 2013, on low back pain, often the cause of back pain is unknown. There are data in spine surgical journals that patients with psychological issues do worse with spine surgery. And in 2016 JAMA published a study from Cherkin and colleagues, which found that, among adults with chronic low back pain, treatment with mindfulness-based stress reduction or cognitive behavioral therapy resulted in greater improvement in back pain and functional limitations at 26 weeks, compared with usual care.

My feeling is that these psychosocial interventions are easy to try, relatively inexpensive, noninvasive, and, in my experience, often can lead to marked improvements. I believe that, for the vast majority of people with chronic pain, it makes much more sense to start by addressing mind-body issues than turning to that approach as a last resort.

Dr. Rashbaum reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More than 3 decades ago, John E. Sarno, MD, published Healing Back Pain, a popular book that garnered something of a cult following. Looking at his own practice, Dr. Sarno, a rehabilitation medicine specialist in New York, saw that most of his patients with chronic pain did not have evidence of acute injury or degenerative disk disease. Their persistent pain appeared to be independent of any structural damage to the spine. Dr. Sarno attributed the pain to what he called tension myoneural syndrome (TMS), or the body’s reaction to suppressed stress and emotional turmoil. Resolving that psychological conflict, Dr. Sarno believed, would lead to an improvement in pain.
 

Dr. Sarno’s theory has met skepticism from the mainstream community, but glowing testimonies from patients who say they benefited from his strategies fill the Internet. Dr. Sarno wrote several books on his ideas before his death in 2017. But he published only one peer-reviewed study, a 2003 review in the Archives of Physical Medicine and Rehabilitation coauthored by Ira Rashbaum, MD.

This news organization spoke recently with Dr. Rashbaum, a physiatrist and chief of tension myoneural syndrome at NYU Langone Health, New York, about TMS and how he manages patients with chronic pain. The interview has been edited for length and clarity.

What is your theory of back pain?

Dr. Rashbaum: My null hypothesis is that back pain is not due to psychological issues, so as to not be a biased doctor, I try to accept the null hypothesis or reject the null hypothesis. In most cases chronic back pain is not due to structural etiology. My sense is it’s a mind-body issue – the avoidance of feeling strong emotions like anger, rage, sadness, fear, shame, and guilt. Patients can embrace psychoeducational programs and if they don’t get better, we work with a psychotherapist or a licensed mental health counselor to help work through the patient’s feelings. That’s my experience over a number of years.

How do you determine if a patient has back pain from a mind-body issue or another cause?

Dr. Rashbaum: I do a very careful medical history, including a physical examination and review of any diagnostic studies they’ve undergone. In most situations, there’s not really a medical cause of the back pain. For instance, a lot of asymptomatic individuals have all sorts of horrible findings on medical imaging like CTs and MRIs, and the reverse is also true – many people with negative findings on imaging tests experience significant pain. My job as a diagnostician is to see how much of this is really a mind-body problem or something that stems from structural pathology.

How well do your patients react to being told that their back pain is, in a way, “in their head?”

Dr. Rashbaum: I have a skewed population. I’m sort of like a guru in mind-body back pain, so the people who come to me are already thinking along those lines. I ask: “What’s going on in your life?” Maybe there are job issues, marital issues, health issues, and I’d say that it’s certainly possible that stress can be causing this back pain.

Sometimes when I see a patient referred from another physician, I’m a bit hesitant to ask about what’s going on in their life. Even earlier today, I’d seen a patient with back pain and I had a sense that they were not really going to be open to a mind-body approach. So I said, do physical therapy.

What do you recommend primary care clinicians do with patients with back pain?

Dr. Rashbaum: You have to do a proper neurologic examination and musculoskeletal examination. It’s a tough situation because doctors in primary care have limited time to take care of patients. It’s difficult to have a deeper dive just to kind of see what’s going on in their life. But you can recommend useful agents like acetaminophen and muscle relaxants, which are sometimes okay.

What sorts of things do you tell patients to say to themselves when they’re experiencing pain? 

Dr. Rashbaum: If the pain is severe, I recommend they take medication – over-the-counter analgesics or a muscle relaxant, if they have them – and take a warm shower or bath. I prefer acetaminophen up to three times per day, if that’s okay with the patient’s primary care physician, over NSAIDs because most pain is noninflammatory in nature. Once the pain is more manageable, patients should journal about what’s going on in their lives and/or meditate, and try to feel any strong emotions, such as anger, sadness, or fear.

What do you say to clinicians who are dismissive of the notion that chronic pain may stem from emotional repression, and that addressing the latter can resolve the former – particularly those who point to a lack of peer-reviewed data for such a link?

Dr. Rashbaum: I would tell them they could be looking harder for that evidence. For example, in a patient page from JAMA from April 24, 2013, on low back pain, often the cause of back pain is unknown. There are data in spine surgical journals that patients with psychological issues do worse with spine surgery. And in 2016 JAMA published a study from Cherkin and colleagues, which found that, among adults with chronic low back pain, treatment with mindfulness-based stress reduction or cognitive behavioral therapy resulted in greater improvement in back pain and functional limitations at 26 weeks, compared with usual care.

My feeling is that these psychosocial interventions are easy to try, relatively inexpensive, noninvasive, and, in my experience, often can lead to marked improvements. I believe that, for the vast majority of people with chronic pain, it makes much more sense to start by addressing mind-body issues than turning to that approach as a last resort.

Dr. Rashbaum reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

A version of this article first appeared on Medscape.com.

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

A version of this article first appeared on Medscape.com.

Primary care practitioners have an important role to play in helping to diagnose people with axial spondyloarthritis (axSpA) much sooner than is currently being achieved, according to several experts who are championing the need for the earlier diagnosis of the condition.

AxSpA is an inflammatory condition of the spine and joints that often goes undiagnosed for many years. Worldwide, the average time to diagnosis was found to be up to 6 years in a recent systematic review. But patient advocacy groups in both the United Kingdom and United States say that the delay can be much longer, possibly up to 10 years or more.
 

Being aware is key

“We know people get significant pain and functional difficulties if it’s not picked up early, and that impacts on patients financially,” said Toby Wallace, MBChB, a general practitioner based at the Derwent Practice in Malton, North Yorkshire, England, and one of 12 Champions in Primary Care for the National Axial Spondyloarthritis Society in the United Kingdom.

Being aware of the condition is vital to improving the time to patients getting diagnosed and treated, Dr. Wallace said in an interview. The quicker patients can be identified and referred onward on to a specialist rheumatology colleague means the sooner they will receive the appropriate care.
 

Chronic back pain

One of the key symptoms of axSpA is back pain, said Dr. Wallace. Back pain is an “extremely common” symptom seen in primary care – an estimated 60% or more of adults will have a back problem in their lifetime – but with axSpA, “it’s more about it being a persistent pain that is not going away.”

Fellow NASS Primary Care Champion and advanced practice physiotherapist Sam Bhide, MSc, calls them the “frequent flyers.”

As a first-contact practitioner, much of her practice consists of seeing people presenting with back pain, many of whom may have already been seen by other professionals but diagnosed with mechanical back pain.

“These patients return due to lack of improvement in their ongoing back pain symptoms,” Ms. Bhide noted. But how do you know if it is axSpA causing the pain?

“Normally, we would look for people who have had back pain for more than 3 months, or that gradually progresses on and off over weeks, months, or years, and their symptoms ease but do not resolve completely,” she said.
 

Eased by exercise and medication

“Essentially we are looking for people with inflammatory back pain,” Ms. Bhide explains.

The pain is often eased with anti-inflammatory medication and with exercise, “which is why these people get missed because they are managing their symptoms with exercises and their anti-inflammatories,” she said.
 

Sleep disturbance and morning stiffness

Sleep disturbance and feeling stiff in the spine for at least 30 minutes upon waking in the morning are other big indicators that chronic back pain may be due to axSpA, Dr. Wallace said.

“Waking in the early hours of the morning with pain or stiffness and having to get up and move around is fairly usual.”

Signs and symptoms

• Age < 45 years.

• Chronic back pain (3+ months).
• Morning stiffness (> 30 minutes).
• Improvement with exercise, not rest.
• Responds to anti-inflammatory medications.
• Night awakenings due to pain.
• Alternating buttock pain.
• Enthesitis and tendonitis.
• Swollen fingers or toes (dactylitis).

Aged under 45 years

AxSpA typically occurs in younger people, but it can be diagnosed at a later age, said Raj Sengupta, MBBS, a consultant rheumatologist and clinical lead for axSpA at the Royal National Hospital for Rheumatic Diseases in Bath, England.

“In someone who’s under the age of 45, if they’ve had more than 3 months of back pain, then you should be thinking about axial spondyloarthritis already,” he said.

“The proviso is that in someone who’s older, actually asking them when their back pain started is relevant, because that person may have had symptoms that started at age 20, but for whatever reason, they didn’t seek help,” said Dr. Sengupta. “They could still have undiagnosed axial spondyloarthritis.”
 

Women can be affected as much as men

Importantly, it appears that women can be just as affected as men, particularly in the early stages of the disease, said Dr. Sengupta.

“In the old days, people just thought of it as a ‘men-only’ disease, but what we’ve learned is that the earlier stage of the disease, the prevalence is much more 50:50,” he said.

“The sad part is that over the years women have been really underdiagnosed because of this false message that has gone about, saying women can’t get it. So, sadly, you see greater delays in diagnosis in women because of that.”
 

Other symptoms and associated conditions

In people with early axSpA, “pain tends to be over the sacroiliac joints, which is over the buttocks, so it’s often confused with sciatica,” explains Dr. Sengupta. Alternating buttock pain is something to take note of, as is tendonitis and enthesitis. The latter is inflammation where the tendons or ligaments are inserted into bone, so it means that people may have problems such as Achilles heel, tennis elbow, or even musculoskeletal chest pain. Dactylitis – swollen fingers or toes – is another sign seen in some people with axSpA.

Associated conditions (including family history)

• Psoriasis.
• Inflammatory bowel disease.
• Eye inflammation (uveitis or iritis).

“Family history is also really important,” although not essential, Dr. Sengupta said. And not only if there is axSpA in the family, but also if there are other conditions such as psoriasis or inflammatory bowel disease. Another commonly associated condition is eye inflammation, which can be uveitis or iritis.
 

What about tests and tools?

Testing for HLA-B27 – which has a known association with axSpA – and measuring blood levels of C-reactive protein may be helpful, but “even if they are normal, that shouldn’t be reassuring you that this can’t be ankylosing spondylitis [in a patient with a] strong inflammatory back pain story.”

Ordering an MRI scan may be possible within primary care, depending on where you are in the world, but the results do need to be interpreted with expert eyes, Dr. Sengupta advises.

There are online tools available to help with the diagnosis of axSpA, Dr. Sengupta said, such as the Spondyloarthritis Diagnosis Evaluation Tool (SPADE). Efforts are also underway to create online systems that help to flag symptoms in general practice.
 

Tests and tools

• HLA-B27 association.
• Elevated C-reactive protein.
• Sacroiliitis on MRI.
• SPADE tool.

The bottom line is that many more patients could potentially be identified earlier in primary care by careful assessment of the clinical symptoms and asking about the family history and associated conditions.

At its simplest, if you see “someone under the age of 45, if they’ve had 3 months of back pain, and they keep on coming back to say, ‘My back’s really bad,’ think about axial spondyloarthritis,” said Dr. Sengupta.

A version of this article first appeared on Medscape.com.

The prevalence of gout is skyrocketing worldwide, and while drugs in the pipeline hold promise for improving the efficacy and safety of treatment, experts warn that “gout remains suboptimally managed.”

“For a really well-understood disease, gout is remarkably undertreated,” said Robert A. Terkeltaub, MD, professor of medicine emeritus at the University of California, San Diego. “This is amazing and depressing because allopurinol has been around for about 60 years or so.”

Randomized, controlled trials show that 80%-90% of patients with gout can be effectively treated to target with existing gout therapies. “Over a year or two, gout flares improve and patients do well,” Dr. Terkeltaub said.

By lowering excessive levels of serum urate, current therapies slow the formation of monosodium urate crystals that precipitate within joints and soft tissues, inducing a highly inflammatory local response with superimposed systemic inflammation. These therapies reduce the frequency of excruciatingly painful gout flares.

“Many patients with gout are not taking urate-lowering therapy at all,” Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital, also in Boston, said in an interview.

“Unfortunately, a common problem in gout is treatment inertia,” said Tuhina Neogi, MD, PhD, chief of rheumatology at Boston Medical Center.

On a global scale, only one-third of patients with gout are started on urate-lowering therapy, and more than 50% abandon treatment after 1 year. As a result, the effectiveness of urate-lowering therapies in reality is well below 50%, Dr. Terkeltaub said.

“I think gout has been taken less seriously than it should be for quite some time,” he explained in an interview. Gout’s impact on health and well-being is no trivial matter. A recent study showed that a diagnosis of gout was associated with an increased risk of anxiety and depression, and there is new evidence suggesting that gout flares are associated with an increased risk of cardiovascular events, including fatal myocardial infarction and stroke.

“We need drugs that are not just effective but also safe, and we need to incorporate real-world data into our assessment of treatment effectiveness, especially in the presence of comorbidities,” Dr. Terkeltaub said.

The prevalence of what used to be thought of as the “disease of kings” has increased 100% over the last 30 years, outstripping world population growth and life expectancy. In the United States, an estimated 5% of adults, or 12 million, have gout. Globally, the number affected exceeds 50 million.

The patient demographics associated with gout have also expanded. Once seen primarily in fleshy, middle-aged men of privilege, gout affects more women, more adults at either end of the age spectrum, and more people in Third World countries than ever before.
 

Management

In the United States, the optimal management of gout remains the subject of debate, with differences in expert opinion reflected in evidence-based clinical guidelines. “We know that the perception of gout is different between primary care physicians, patients, and rheumatologists,” Dr. Terkeltaub said.

The 2017 American College of Physicians guidelines for the management of gout recommend a treat-to-symptom approach to urate-lowering therapy. However, the 2020 American College of Rheumatology guidelines reinforce a standard treat-to-target strategy to a serum urate target of < 6.0 mg/dL.

In their report, the ACR guidelines’ authors stated that the use of urate-lowering therapy for gout has not increased in the last decade. Research shows that adherence to treatment for gout continues to be the lowest among seven common chronic medical conditions, including hypertension and seizure disorders, they said.

Some physicians don’t recommend urate-lowering medication to their patients with gout, and others don’t up-titrate it sufficiently to meet the recommended serum urate target, said Dr. Tedeschi. The latter “can require increasing the dose of allopurinol well beyond the 300 mg that often seems the landing point for many patients with gout,” she pointed out.

In fact, it can take up to 800 mg a day of allopurinol – less in patients with moderate to severe kidney disease – to reduce the symptom burden in gout. And it can take a year or longer of drug testing and titration to reach the optimal serum urate target. Paradoxically, gout flares usually get worse during this time.

“We need to reduce the time it takes to get the patient to the serum urate target, and simplify regimens with once-a-day dosing,” Dr. Terkeltaub said. “We also need greater precision so that we can get a home run, hitting the serum urate target the first or second visit, with minimal dose titration.”

Clinician education is important, but education alone is not enough, Dr. Neogi emphasized. “Just as clinicians treat-to-target in other conditions such as hypertension and diabetes, or titrate warfarin to maintain a certain level of anticoagulation, gout must be monitored and treatments adjusted accordingly,” she said.

Practice changes, such as partnering with nursing or pharmacy, may help facilitate in-clinic dose titration, “much like a warfarin clinic,” Dr. Neogi suggested.

That’s exactly what Dr. Terkeltaub has done. Overwhelmed by the number of gout consults, Dr. Terkeltaub and his team set up a pharmacist-managed, rheumatology-supervised clinic to care for gout patients remotely. The model has been very successful, he said. Nurses and clinical pharmacists educate the patients and manage their lab testing and prescriptions, all according to ACR guidelines.

The treatment of gout has become more complex, with a greater risk of drug complications and interactions, particularly in older patients with comorbid diabetes, chronic kidney disease, and heart disease. Many of the patients he sees are already on “10, 15, or 20 other medications,” Dr. Terkeltaub noted.

The steps involved in the titration of urate-lowering therapy also complicate the treatment of gout, making it impractical for many patients and impossible for others whose access to primary care is limited to one or two visits a year. The process of drug titration, with steadily increasing doses, can make patients anxious about the possibility of being overmedicated. Taking a drug every day, even when joints feel “normal,” can also increase the risk of nonadherence.

“In our conversations with patients with gout, it’s extremely important that we counsel them about the need to take urate-lowering therapy on an ongoing basis to reduce the risk of a gout flare,” said Dr. Tedeschi. “Patients need to have prescription refills available and know to contact the doctor before they run out, so that the chances of having a gout flare are reduced.”
 

Current drugs

Although urate-lowering drugs form the cornerstone of gout therapy, there are only three oral medications available in the United States currently, and all have significant limitations. “We need more drugs, basically,” Dr. Terkeltaub said.

• Allopurinol (Zyloprim, Aloprim), an inexpensive xanthine oxidase inhibitor (XOI), is still considered a first-line treatment, but is associated with allopurinol hypersensitivity syndrome. In select patients of Asian, African, and Arab descent, this adverse drug reaction can be life-threatening, and is associated with a mortality rate of 20%-25%.
• Febuxostat (Uloric), another XOI, is considered a second-line drug in the treatment of gout, but has carried a boxed warning from the Food and Drug Administration since 2019. It is associated with a significantly increased risk of cardiovascular death.
• Probenecid (Probalan), a uricosuric agent that increases renal uric acid excretion, is associated with an increased risk of drug interactions and kidney stones, and is rarely used.

Drugs in the pipeline

New drugs in the pipeline offer treatment options that are not only effective but also safe. “This will be important in clinical practice, especially for patients in whom existing medications are contraindicated or there is an increased risk of side effects,” Dr. Neogi said.

Most of these investigational drugs are uricosuric agents that increase the renal excretion of uric acid, reducing serum levels. “The pipeline of new drugs is rich,” Dr. Terkeltaub said. “These drugs are very selective and really work well and they appear to be safe.”

AR882, an inhibitor of selective uric acid transporter 1 (URAT1), is shaping up to be one of them. In July, results from a phase 2b study of AR882 were presented at the annual European Congress of Rheumatology in Milan. They showed that in the intent-to-treat population, 73% of patients had serum uric acid levels < 5 mg/dL and 55% had < 4 mg/dL by week 12 of therapy. In the per-protocol analysis, 82% had serum uric acid levels < 5 mg/dL and 63% < 4 mg/dL.

“These efficacy results are not typically what you see with a once-daily oral medication, so it is really exciting,” said Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, San Diego, who presented the results.

“More efficacious URAT1 inhibitors that are safe and have a reduced pill burden will be useful additions to current urate lowering options,” Dr. Neogi said.

The recent phase 3 DISSOLVE I and II trials of the investigational uricase-based infusion therapy SEL-212 in refractory gout have also demonstrated encouraging results, particularly in older patients. In DISSOLVE I, a response rate of 65% was observed in patients 50 years of age and older at least 80% of the time during month 6 of treatment. In DISSOLVE II, a response rate of 47% was reported in older patients.

SEL-212, which is made up of PEGylated uricase (pegadricase) coadministered with sirolimus (Rapamycin), will be submitted for U.S. regulatory approval in the first half of 2024.

In the management of gout flares, interleukin (IL)-1beta and inflammasome inhibitors, both of which target specific inflammatory pathways, could also provide attractive additions to urate-lowering therapies. Other agents commonly used in the treatment of flares, such as NSAIDs, steroids, and colchicine (Colcrys), are not as specific, and have side effects that often limit their usability, Dr. Neogi said.

In the meantime, new research indicates that an inflammasome inhibitor that has already been approved for use in diabetes may provide distinct benefits for the management of gout. An analysis of data from 15,067 adults with both gout and type 2 diabetes showed that when a sodium-glucose cotransporter 2 (SGLT-2) inhibitor was added to urate-lowering therapy, the symptoms of gout, including flares, were significantly reduced, resulting in fewer emergency department visits and hospitalizations.

“SGLT-2 inhibitors have anti-inflammatory activity that limits the progression of kidney failure, heart failure, and will also lower the serum uric acid,” said Dr. Terkeltaub. “That’s a major development.”

Dr. Neogi disclosed relationships with Novartis, Pfizer/Lilly, and Regeneron, Dr. Terkeltaub reported relationships with Dyve, Fortress, and Atom, and Dr. Tedeschi reported a relationship with Novartis.

This story was updated on August 14, 2023.

The prevalence of gout is skyrocketing worldwide, and while drugs in the pipeline hold promise for improving the efficacy and safety of treatment, experts warn that “gout remains suboptimally managed.”

“For a really well-understood disease, gout is remarkably undertreated,” said Robert A. Terkeltaub, MD, professor of medicine emeritus at the University of California, San Diego. “This is amazing and depressing because allopurinol has been around for about 60 years or so.”

Randomized, controlled trials show that 80%-90% of patients with gout can be effectively treated to target with existing gout therapies. “Over a year or two, gout flares improve and patients do well,” Dr. Terkeltaub said.

By lowering excessive levels of serum urate, current therapies slow the formation of monosodium urate crystals that precipitate within joints and soft tissues, inducing a highly inflammatory local response with superimposed systemic inflammation. These therapies reduce the frequency of excruciatingly painful gout flares.

“Many patients with gout are not taking urate-lowering therapy at all,” Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital, also in Boston, said in an interview.

“Unfortunately, a common problem in gout is treatment inertia,” said Tuhina Neogi, MD, PhD, chief of rheumatology at Boston Medical Center.

On a global scale, only one-third of patients with gout are started on urate-lowering therapy, and more than 50% abandon treatment after 1 year. As a result, the effectiveness of urate-lowering therapies in reality is well below 50%, Dr. Terkeltaub said.

“I think gout has been taken less seriously than it should be for quite some time,” he explained in an interview. Gout’s impact on health and well-being is no trivial matter. A recent study showed that a diagnosis of gout was associated with an increased risk of anxiety and depression, and there is new evidence suggesting that gout flares are associated with an increased risk of cardiovascular events, including fatal myocardial infarction and stroke.

“We need drugs that are not just effective but also safe, and we need to incorporate real-world data into our assessment of treatment effectiveness, especially in the presence of comorbidities,” Dr. Terkeltaub said.

The prevalence of what used to be thought of as the “disease of kings” has increased 100% over the last 30 years, outstripping world population growth and life expectancy. In the United States, an estimated 5% of adults, or 12 million, have gout. Globally, the number affected exceeds 50 million.

The patient demographics associated with gout have also expanded. Once seen primarily in fleshy, middle-aged men of privilege, gout affects more women, more adults at either end of the age spectrum, and more people in Third World countries than ever before.
 

Management

In the United States, the optimal management of gout remains the subject of debate, with differences in expert opinion reflected in evidence-based clinical guidelines. “We know that the perception of gout is different between primary care physicians, patients, and rheumatologists,” Dr. Terkeltaub said.

The 2017 American College of Physicians guidelines for the management of gout recommend a treat-to-symptom approach to urate-lowering therapy. However, the 2020 American College of Rheumatology guidelines reinforce a standard treat-to-target strategy to a serum urate target of < 6.0 mg/dL.

In their report, the ACR guidelines’ authors stated that the use of urate-lowering therapy for gout has not increased in the last decade. Research shows that adherence to treatment for gout continues to be the lowest among seven common chronic medical conditions, including hypertension and seizure disorders, they said.

Some physicians don’t recommend urate-lowering medication to their patients with gout, and others don’t up-titrate it sufficiently to meet the recommended serum urate target, said Dr. Tedeschi. The latter “can require increasing the dose of allopurinol well beyond the 300 mg that often seems the landing point for many patients with gout,” she pointed out.

In fact, it can take up to 800 mg a day of allopurinol – less in patients with moderate to severe kidney disease – to reduce the symptom burden in gout. And it can take a year or longer of drug testing and titration to reach the optimal serum urate target. Paradoxically, gout flares usually get worse during this time.

“We need to reduce the time it takes to get the patient to the serum urate target, and simplify regimens with once-a-day dosing,” Dr. Terkeltaub said. “We also need greater precision so that we can get a home run, hitting the serum urate target the first or second visit, with minimal dose titration.”

Clinician education is important, but education alone is not enough, Dr. Neogi emphasized. “Just as clinicians treat-to-target in other conditions such as hypertension and diabetes, or titrate warfarin to maintain a certain level of anticoagulation, gout must be monitored and treatments adjusted accordingly,” she said.

Practice changes, such as partnering with nursing or pharmacy, may help facilitate in-clinic dose titration, “much like a warfarin clinic,” Dr. Neogi suggested.

That’s exactly what Dr. Terkeltaub has done. Overwhelmed by the number of gout consults, Dr. Terkeltaub and his team set up a pharmacist-managed, rheumatology-supervised clinic to care for gout patients remotely. The model has been very successful, he said. Nurses and clinical pharmacists educate the patients and manage their lab testing and prescriptions, all according to ACR guidelines.

The treatment of gout has become more complex, with a greater risk of drug complications and interactions, particularly in older patients with comorbid diabetes, chronic kidney disease, and heart disease. Many of the patients he sees are already on “10, 15, or 20 other medications,” Dr. Terkeltaub noted.

The steps involved in the titration of urate-lowering therapy also complicate the treatment of gout, making it impractical for many patients and impossible for others whose access to primary care is limited to one or two visits a year. The process of drug titration, with steadily increasing doses, can make patients anxious about the possibility of being overmedicated. Taking a drug every day, even when joints feel “normal,” can also increase the risk of nonadherence.

“In our conversations with patients with gout, it’s extremely important that we counsel them about the need to take urate-lowering therapy on an ongoing basis to reduce the risk of a gout flare,” said Dr. Tedeschi. “Patients need to have prescription refills available and know to contact the doctor before they run out, so that the chances of having a gout flare are reduced.”
 

Current drugs

Although urate-lowering drugs form the cornerstone of gout therapy, there are only three oral medications available in the United States currently, and all have significant limitations. “We need more drugs, basically,” Dr. Terkeltaub said.

• Allopurinol (Zyloprim, Aloprim), an inexpensive xanthine oxidase inhibitor (XOI), is still considered a first-line treatment, but is associated with allopurinol hypersensitivity syndrome. In select patients of Asian, African, and Arab descent, this adverse drug reaction can be life-threatening, and is associated with a mortality rate of 20%-25%.
• Febuxostat (Uloric), another XOI, is considered a second-line drug in the treatment of gout, but has carried a boxed warning from the Food and Drug Administration since 2019. It is associated with a significantly increased risk of cardiovascular death.
• Probenecid (Probalan), a uricosuric agent that increases renal uric acid excretion, is associated with an increased risk of drug interactions and kidney stones, and is rarely used.

Drugs in the pipeline

New drugs in the pipeline offer treatment options that are not only effective but also safe. “This will be important in clinical practice, especially for patients in whom existing medications are contraindicated or there is an increased risk of side effects,” Dr. Neogi said.

Most of these investigational drugs are uricosuric agents that increase the renal excretion of uric acid, reducing serum levels. “The pipeline of new drugs is rich,” Dr. Terkeltaub said. “These drugs are very selective and really work well and they appear to be safe.”

AR882, an inhibitor of selective uric acid transporter 1 (URAT1), is shaping up to be one of them. In July, results from a phase 2b study of AR882 were presented at the annual European Congress of Rheumatology in Milan. They showed that in the intent-to-treat population, 73% of patients had serum uric acid levels < 5 mg/dL and 55% had < 4 mg/dL by week 12 of therapy. In the per-protocol analysis, 82% had serum uric acid levels < 5 mg/dL and 63% < 4 mg/dL.

“These efficacy results are not typically what you see with a once-daily oral medication, so it is really exciting,” said Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, San Diego, who presented the results.

“More efficacious URAT1 inhibitors that are safe and have a reduced pill burden will be useful additions to current urate lowering options,” Dr. Neogi said.

The recent phase 3 DISSOLVE I and II trials of the investigational uricase-based infusion therapy SEL-212 in refractory gout have also demonstrated encouraging results, particularly in older patients. In DISSOLVE I, a response rate of 65% was observed in patients 50 years of age and older at least 80% of the time during month 6 of treatment. In DISSOLVE II, a response rate of 47% was reported in older patients.

SEL-212, which is made up of PEGylated uricase (pegadricase) coadministered with sirolimus (Rapamycin), will be submitted for U.S. regulatory approval in the first half of 2024.

In the management of gout flares, interleukin (IL)-1beta and inflammasome inhibitors, both of which target specific inflammatory pathways, could also provide attractive additions to urate-lowering therapies. Other agents commonly used in the treatment of flares, such as NSAIDs, steroids, and colchicine (Colcrys), are not as specific, and have side effects that often limit their usability, Dr. Neogi said.

In the meantime, new research indicates that an inflammasome inhibitor that has already been approved for use in diabetes may provide distinct benefits for the management of gout. An analysis of data from 15,067 adults with both gout and type 2 diabetes showed that when a sodium-glucose cotransporter 2 (SGLT-2) inhibitor was added to urate-lowering therapy, the symptoms of gout, including flares, were significantly reduced, resulting in fewer emergency department visits and hospitalizations.

“SGLT-2 inhibitors have anti-inflammatory activity that limits the progression of kidney failure, heart failure, and will also lower the serum uric acid,” said Dr. Terkeltaub. “That’s a major development.”

Dr. Neogi disclosed relationships with Novartis, Pfizer/Lilly, and Regeneron, Dr. Terkeltaub reported relationships with Dyve, Fortress, and Atom, and Dr. Tedeschi reported a relationship with Novartis.

This story was updated on August 14, 2023.

The prevalence of gout is skyrocketing worldwide, and while drugs in the pipeline hold promise for improving the efficacy and safety of treatment, experts warn that “gout remains suboptimally managed.”

“For a really well-understood disease, gout is remarkably undertreated,” said Robert A. Terkeltaub, MD, professor of medicine emeritus at the University of California, San Diego. “This is amazing and depressing because allopurinol has been around for about 60 years or so.”

Randomized, controlled trials show that 80%-90% of patients with gout can be effectively treated to target with existing gout therapies. “Over a year or two, gout flares improve and patients do well,” Dr. Terkeltaub said.

By lowering excessive levels of serum urate, current therapies slow the formation of monosodium urate crystals that precipitate within joints and soft tissues, inducing a highly inflammatory local response with superimposed systemic inflammation. These therapies reduce the frequency of excruciatingly painful gout flares.

“Many patients with gout are not taking urate-lowering therapy at all,” Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and head of crystal-induced arthritis diseases at Brigham and Women’s Hospital, also in Boston, said in an interview.

“Unfortunately, a common problem in gout is treatment inertia,” said Tuhina Neogi, MD, PhD, chief of rheumatology at Boston Medical Center.

On a global scale, only one-third of patients with gout are started on urate-lowering therapy, and more than 50% abandon treatment after 1 year. As a result, the effectiveness of urate-lowering therapies in reality is well below 50%, Dr. Terkeltaub said.

“I think gout has been taken less seriously than it should be for quite some time,” he explained in an interview. Gout’s impact on health and well-being is no trivial matter. A recent study showed that a diagnosis of gout was associated with an increased risk of anxiety and depression, and there is new evidence suggesting that gout flares are associated with an increased risk of cardiovascular events, including fatal myocardial infarction and stroke.

“We need drugs that are not just effective but also safe, and we need to incorporate real-world data into our assessment of treatment effectiveness, especially in the presence of comorbidities,” Dr. Terkeltaub said.

The prevalence of what used to be thought of as the “disease of kings” has increased 100% over the last 30 years, outstripping world population growth and life expectancy. In the United States, an estimated 5% of adults, or 12 million, have gout. Globally, the number affected exceeds 50 million.

The patient demographics associated with gout have also expanded. Once seen primarily in fleshy, middle-aged men of privilege, gout affects more women, more adults at either end of the age spectrum, and more people in Third World countries than ever before.
 

Management

In the United States, the optimal management of gout remains the subject of debate, with differences in expert opinion reflected in evidence-based clinical guidelines. “We know that the perception of gout is different between primary care physicians, patients, and rheumatologists,” Dr. Terkeltaub said.

The 2017 American College of Physicians guidelines for the management of gout recommend a treat-to-symptom approach to urate-lowering therapy. However, the 2020 American College of Rheumatology guidelines reinforce a standard treat-to-target strategy to a serum urate target of < 6.0 mg/dL.

In their report, the ACR guidelines’ authors stated that the use of urate-lowering therapy for gout has not increased in the last decade. Research shows that adherence to treatment for gout continues to be the lowest among seven common chronic medical conditions, including hypertension and seizure disorders, they said.

Some physicians don’t recommend urate-lowering medication to their patients with gout, and others don’t up-titrate it sufficiently to meet the recommended serum urate target, said Dr. Tedeschi. The latter “can require increasing the dose of allopurinol well beyond the 300 mg that often seems the landing point for many patients with gout,” she pointed out.

In fact, it can take up to 800 mg a day of allopurinol – less in patients with moderate to severe kidney disease – to reduce the symptom burden in gout. And it can take a year or longer of drug testing and titration to reach the optimal serum urate target. Paradoxically, gout flares usually get worse during this time.

“We need to reduce the time it takes to get the patient to the serum urate target, and simplify regimens with once-a-day dosing,” Dr. Terkeltaub said. “We also need greater precision so that we can get a home run, hitting the serum urate target the first or second visit, with minimal dose titration.”

Clinician education is important, but education alone is not enough, Dr. Neogi emphasized. “Just as clinicians treat-to-target in other conditions such as hypertension and diabetes, or titrate warfarin to maintain a certain level of anticoagulation, gout must be monitored and treatments adjusted accordingly,” she said.

Practice changes, such as partnering with nursing or pharmacy, may help facilitate in-clinic dose titration, “much like a warfarin clinic,” Dr. Neogi suggested.

That’s exactly what Dr. Terkeltaub has done. Overwhelmed by the number of gout consults, Dr. Terkeltaub and his team set up a pharmacist-managed, rheumatology-supervised clinic to care for gout patients remotely. The model has been very successful, he said. Nurses and clinical pharmacists educate the patients and manage their lab testing and prescriptions, all according to ACR guidelines.

The treatment of gout has become more complex, with a greater risk of drug complications and interactions, particularly in older patients with comorbid diabetes, chronic kidney disease, and heart disease. Many of the patients he sees are already on “10, 15, or 20 other medications,” Dr. Terkeltaub noted.

The steps involved in the titration of urate-lowering therapy also complicate the treatment of gout, making it impractical for many patients and impossible for others whose access to primary care is limited to one or two visits a year. The process of drug titration, with steadily increasing doses, can make patients anxious about the possibility of being overmedicated. Taking a drug every day, even when joints feel “normal,” can also increase the risk of nonadherence.

“In our conversations with patients with gout, it’s extremely important that we counsel them about the need to take urate-lowering therapy on an ongoing basis to reduce the risk of a gout flare,” said Dr. Tedeschi. “Patients need to have prescription refills available and know to contact the doctor before they run out, so that the chances of having a gout flare are reduced.”
 

Current drugs

Although urate-lowering drugs form the cornerstone of gout therapy, there are only three oral medications available in the United States currently, and all have significant limitations. “We need more drugs, basically,” Dr. Terkeltaub said.

• Allopurinol (Zyloprim, Aloprim), an inexpensive xanthine oxidase inhibitor (XOI), is still considered a first-line treatment, but is associated with allopurinol hypersensitivity syndrome. In select patients of Asian, African, and Arab descent, this adverse drug reaction can be life-threatening, and is associated with a mortality rate of 20%-25%.
• Febuxostat (Uloric), another XOI, is considered a second-line drug in the treatment of gout, but has carried a boxed warning from the Food and Drug Administration since 2019. It is associated with a significantly increased risk of cardiovascular death.
• Probenecid (Probalan), a uricosuric agent that increases renal uric acid excretion, is associated with an increased risk of drug interactions and kidney stones, and is rarely used.

Drugs in the pipeline

New drugs in the pipeline offer treatment options that are not only effective but also safe. “This will be important in clinical practice, especially for patients in whom existing medications are contraindicated or there is an increased risk of side effects,” Dr. Neogi said.

Most of these investigational drugs are uricosuric agents that increase the renal excretion of uric acid, reducing serum levels. “The pipeline of new drugs is rich,” Dr. Terkeltaub said. “These drugs are very selective and really work well and they appear to be safe.”

AR882, an inhibitor of selective uric acid transporter 1 (URAT1), is shaping up to be one of them. In July, results from a phase 2b study of AR882 were presented at the annual European Congress of Rheumatology in Milan. They showed that in the intent-to-treat population, 73% of patients had serum uric acid levels < 5 mg/dL and 55% had < 4 mg/dL by week 12 of therapy. In the per-protocol analysis, 82% had serum uric acid levels < 5 mg/dL and 63% < 4 mg/dL.

“These efficacy results are not typically what you see with a once-daily oral medication, so it is really exciting,” said Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, San Diego, who presented the results.

“More efficacious URAT1 inhibitors that are safe and have a reduced pill burden will be useful additions to current urate lowering options,” Dr. Neogi said.

The recent phase 3 DISSOLVE I and II trials of the investigational uricase-based infusion therapy SEL-212 in refractory gout have also demonstrated encouraging results, particularly in older patients. In DISSOLVE I, a response rate of 65% was observed in patients 50 years of age and older at least 80% of the time during month 6 of treatment. In DISSOLVE II, a response rate of 47% was reported in older patients.

SEL-212, which is made up of PEGylated uricase (pegadricase) coadministered with sirolimus (Rapamycin), will be submitted for U.S. regulatory approval in the first half of 2024.

In the management of gout flares, interleukin (IL)-1beta and inflammasome inhibitors, both of which target specific inflammatory pathways, could also provide attractive additions to urate-lowering therapies. Other agents commonly used in the treatment of flares, such as NSAIDs, steroids, and colchicine (Colcrys), are not as specific, and have side effects that often limit their usability, Dr. Neogi said.

In the meantime, new research indicates that an inflammasome inhibitor that has already been approved for use in diabetes may provide distinct benefits for the management of gout. An analysis of data from 15,067 adults with both gout and type 2 diabetes showed that when a sodium-glucose cotransporter 2 (SGLT-2) inhibitor was added to urate-lowering therapy, the symptoms of gout, including flares, were significantly reduced, resulting in fewer emergency department visits and hospitalizations.

“SGLT-2 inhibitors have anti-inflammatory activity that limits the progression of kidney failure, heart failure, and will also lower the serum uric acid,” said Dr. Terkeltaub. “That’s a major development.”

Dr. Neogi disclosed relationships with Novartis, Pfizer/Lilly, and Regeneron, Dr. Terkeltaub reported relationships with Dyve, Fortress, and Atom, and Dr. Tedeschi reported a relationship with Novartis.

This story was updated on August 14, 2023.