California has agreed to settle a lawsuit and pay $300,000 to an organization of Christian physicians and dentists who challenged a new provision in the state’s aid-in-dying law they said would violate their religious beliefs.

A federal judge ruled May 17 that doctors who oppose assisted suicide will not be required to document a terminally ill patient’s request for life-ending medication and refer to another doctor for the medication.

The Christian clinicians objected to the documentation requirement because it counted as one of the two oral requests required for a qualified patient to obtain aid-in-dying drugs under the law, according to their claim filed last February.

“This is a significant victory for religious and conscientious physicians in California. The government can’t force any health care professional to act against his faith or medical ethics,” said Alliance Defending Freedom senior counsel Kevin Theriot, who represented the plaintiffs, a Christian hospice physician and the Christian Medical & Dental Associations.

The litigation is one of a number of lawsuits recently filed by doctors in California and around the country regarding rights to free speech and religious expression.

Physicians and advocates including an anti-vaccine group filed two lawsuits claiming another California law violated their free speech rights. Under that law – temporarily halted while the lawsuits proceed – doctors could face medical board sanctions for communicating COVID-related misinformation to patients.

In Arkansas, two physicians joined a lawsuit challenging the state’s law that would prohibit clinicians from referring or providing transgender care. And physicians in April sued Idaho’s attorney general over free speech and other constitutional rights after a legal opinion suggested they could not refer patients for out-of-state abortions.

The provision in California’s aid-in-dying law was unconstitutional because “it violates objectors’ freedom of speech by requiring them to take part in implementing the law,” despite their objections to assisted suicide, U.S. District Judge Fernando Aenlle-Rocha of Los Angeles, an appointee of former President Donald Trump, ruled last September. He halted enforcement of the provision while the lawsuit proceeded.

Judge Aenlle-Rocha cited the Supreme Court’s 2018 ruling that said California violated the free-speech rights of anti-abortion clinics called “crisis pregnancy centers” by requiring them to notify their patients that the state makes abortions available to low-income women at little or no cost, the San Francisco Chronicle reported.
 

What led to the aid-in-dying lawsuit

The lawsuit was filed after an amendment to the 2015 California End of Life Option Act which took effect in January.

Under the 2015 law, which legalized physician-assisted suicide in the state, physicians could voluntarily participate in a patient’s aid-in-dying requests and refuse for “reasons of conscience, morality, or ethics.”

The 2015 law also provided legal immunity to individual physicians who refused to engage in activities such as providing information about the law or referring an individual to a clinician who prescribes aid-in-dying medication, according to the legislation.

The new law allowed state officials to impose criminal or civil penalties, including professional discipline or a licensing sanction, on a California-licensed physician who refused or failed to document a request, refer a patient, or assist a patient in any way with ending his life.

Under the settlement, state officials agreed to not enforce the documentation and referral requirements against objecting physicians, in addition to the paying the plaintiffs $300,000 for attorney’s fees.

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

California has agreed to settle a lawsuit and pay $300,000 to an organization of Christian physicians and dentists who challenged a new provision in the state’s aid-in-dying law they said would violate their religious beliefs.

A federal judge ruled May 17 that doctors who oppose assisted suicide will not be required to document a terminally ill patient’s request for life-ending medication and refer to another doctor for the medication.

The Christian clinicians objected to the documentation requirement because it counted as one of the two oral requests required for a qualified patient to obtain aid-in-dying drugs under the law, according to their claim filed last February.

“This is a significant victory for religious and conscientious physicians in California. The government can’t force any health care professional to act against his faith or medical ethics,” said Alliance Defending Freedom senior counsel Kevin Theriot, who represented the plaintiffs, a Christian hospice physician and the Christian Medical & Dental Associations.

The litigation is one of a number of lawsuits recently filed by doctors in California and around the country regarding rights to free speech and religious expression.

Physicians and advocates including an anti-vaccine group filed two lawsuits claiming another California law violated their free speech rights. Under that law – temporarily halted while the lawsuits proceed – doctors could face medical board sanctions for communicating COVID-related misinformation to patients.

In Arkansas, two physicians joined a lawsuit challenging the state’s law that would prohibit clinicians from referring or providing transgender care. And physicians in April sued Idaho’s attorney general over free speech and other constitutional rights after a legal opinion suggested they could not refer patients for out-of-state abortions.

The provision in California’s aid-in-dying law was unconstitutional because “it violates objectors’ freedom of speech by requiring them to take part in implementing the law,” despite their objections to assisted suicide, U.S. District Judge Fernando Aenlle-Rocha of Los Angeles, an appointee of former President Donald Trump, ruled last September. He halted enforcement of the provision while the lawsuit proceeded.

Judge Aenlle-Rocha cited the Supreme Court’s 2018 ruling that said California violated the free-speech rights of anti-abortion clinics called “crisis pregnancy centers” by requiring them to notify their patients that the state makes abortions available to low-income women at little or no cost, the San Francisco Chronicle reported.
 

What led to the aid-in-dying lawsuit

The lawsuit was filed after an amendment to the 2015 California End of Life Option Act which took effect in January.

Under the 2015 law, which legalized physician-assisted suicide in the state, physicians could voluntarily participate in a patient’s aid-in-dying requests and refuse for “reasons of conscience, morality, or ethics.”

The 2015 law also provided legal immunity to individual physicians who refused to engage in activities such as providing information about the law or referring an individual to a clinician who prescribes aid-in-dying medication, according to the legislation.

The new law allowed state officials to impose criminal or civil penalties, including professional discipline or a licensing sanction, on a California-licensed physician who refused or failed to document a request, refer a patient, or assist a patient in any way with ending his life.

Under the settlement, state officials agreed to not enforce the documentation and referral requirements against objecting physicians, in addition to the paying the plaintiffs $300,000 for attorney’s fees.

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

California has agreed to settle a lawsuit and pay $300,000 to an organization of Christian physicians and dentists who challenged a new provision in the state’s aid-in-dying law they said would violate their religious beliefs.

A federal judge ruled May 17 that doctors who oppose assisted suicide will not be required to document a terminally ill patient’s request for life-ending medication and refer to another doctor for the medication.

The Christian clinicians objected to the documentation requirement because it counted as one of the two oral requests required for a qualified patient to obtain aid-in-dying drugs under the law, according to their claim filed last February.

“This is a significant victory for religious and conscientious physicians in California. The government can’t force any health care professional to act against his faith or medical ethics,” said Alliance Defending Freedom senior counsel Kevin Theriot, who represented the plaintiffs, a Christian hospice physician and the Christian Medical & Dental Associations.

The litigation is one of a number of lawsuits recently filed by doctors in California and around the country regarding rights to free speech and religious expression.

Physicians and advocates including an anti-vaccine group filed two lawsuits claiming another California law violated their free speech rights. Under that law – temporarily halted while the lawsuits proceed – doctors could face medical board sanctions for communicating COVID-related misinformation to patients.

In Arkansas, two physicians joined a lawsuit challenging the state’s law that would prohibit clinicians from referring or providing transgender care. And physicians in April sued Idaho’s attorney general over free speech and other constitutional rights after a legal opinion suggested they could not refer patients for out-of-state abortions.

The provision in California’s aid-in-dying law was unconstitutional because “it violates objectors’ freedom of speech by requiring them to take part in implementing the law,” despite their objections to assisted suicide, U.S. District Judge Fernando Aenlle-Rocha of Los Angeles, an appointee of former President Donald Trump, ruled last September. He halted enforcement of the provision while the lawsuit proceeded.

Judge Aenlle-Rocha cited the Supreme Court’s 2018 ruling that said California violated the free-speech rights of anti-abortion clinics called “crisis pregnancy centers” by requiring them to notify their patients that the state makes abortions available to low-income women at little or no cost, the San Francisco Chronicle reported.
 

What led to the aid-in-dying lawsuit

The lawsuit was filed after an amendment to the 2015 California End of Life Option Act which took effect in January.

Under the 2015 law, which legalized physician-assisted suicide in the state, physicians could voluntarily participate in a patient’s aid-in-dying requests and refuse for “reasons of conscience, morality, or ethics.”

The 2015 law also provided legal immunity to individual physicians who refused to engage in activities such as providing information about the law or referring an individual to a clinician who prescribes aid-in-dying medication, according to the legislation.

The new law allowed state officials to impose criminal or civil penalties, including professional discipline or a licensing sanction, on a California-licensed physician who refused or failed to document a request, refer a patient, or assist a patient in any way with ending his life.

Under the settlement, state officials agreed to not enforce the documentation and referral requirements against objecting physicians, in addition to the paying the plaintiffs $300,000 for attorney’s fees.

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

Chicago – In the second-line setting of head and neck cancer, metronomic triple therapy outperformed clinician choice chemotherapy in both progression-free survival (PFS) and overall survival (OS), according to results from a new phase III clinical trial.

The study was conducted in India in a population that had not previously been treated with immunotherapy, but the results are likely applicable even when patients have been exposed to these agents, according to Rushabh Kothari, MD, DM, who presented the study (Abstract LBA6004), at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although immunotherapy is considered the first-line therapy for the disease, it is often unavailable in low- and middle-income countries: In India, about 3% of head and neck cancer patients receive it, Dr. Kothari said during his presentation.

The study offered improved outcomes and greater tolerability in this population, according to Dr. Kothari. “Metronome chemotherapy led to an improvement [in both OS and PFS] of around 2 months compared to physician’s choice of treatment in this difficult-to-treat population, and metronomic chemotherapy had multiple advantages [over other chemotherapies]. It is an oral treatment, there is an ease of administration, and it is very cost effective. It also lowers adverse events as we saw in the data,” said Dr. Kothari, a medical oncologist at Narayana Multispeciality Hospital in India, in an interview.

The improvement is meaningful given the dire circumstances these patients find themselves in, according to Dr. Kothari: “When you see a second-line relapsed metastatic head and neck cancer, their overall survival is dismal: It is less than 7 months with most of the available agents,” he said in the interview.

Metronomic chemotherapy is continuous, low-dose chemotherapy that includes an anti-angiogenic effect, according to Dr. Kothari. In the current study, the researchers employed a triple metronomic chemotherapy (TMC) that included methotrexate (9 mg/m² weekly), erlotinib (150 mg daily), and celecoxib (200 mg twice daily), which was compared to any of eight single-agent physician choice agents, all of which were consistent with National Comprehensive Care Network (NCCN) guidelines (NCCN-PC group).
 

Study methods and results

The study included 55 patients in the TMC arm and 59 in the NCCN-PC arm. Currently, 13 patients in the TMC arm and 6 in the NCCN-PC are still being treated.

More than 94.5% of the TMC arm and 91.5% of the NCCN-PC arm had previously received platinum-based therapy, and 49.1% and 47.5%, respectively, had received taxane.

The median OS was 181 days in the TMC group, versus 123 days in the NCCN-PC group (hazard ratio, 0.5076; 95% confidence interval, 0.325-0.792). The median PFS was 120 days and 70 days, respectively (HR, 0.4941; 95% CI, 0.312-0.738).

Adverse events were less frequent in TMC, including anemia (grade 3-5, 3.7% versus 14.8%; P = .038), neutropenia (0% versus 13.0%; P =.006), thrombocytopenia (0% versus 9.3%; P = .028), serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase (SGOT/SGPT) rise (0% versus 9.3%; P = .028), creatinine rise (0% versus 9.3%; P = .028), and diarrhea (1.9% versus 13.0%; P = .006).

“When you give lower doses continuously, the compliance is very good. When tolerance is good and compliance is good, that is the ideal regimen, which patients want,” said Dr. Kothari in the interview.

Dr. Kothari pointed out that the study included primarily patients with oral cavity cancers, including 89.1% of the TMC group and 83.1% of the NCCN-PC group. Oropharyngeal cancers are more common in high-income countries, but his own clinical experience suggests that the combination also performs well in that group, he said.

During a discussion part of the session, Ezra Cohen, MD, said that when pembrolizumab was moved from second-line to first-line therapy, it left an unmet need in second-line recurrent or metastatic disease.

He welcomed the new results.

“[The study shows] a much better toxicity profile with the triple metronomic therapy. In other words, we can deliver these reagents at the doses prescribed, with a toxicity profile I would say that is not only manageable, but that is in fact favorable. In addition to that, in a limited size phase III study, we see an improvement in the primary endpoint here of overall survival. So in a patient population that may not necessarily have access to anti-PD1 antibodies, we can offer a lower cost triple regimen that does appear to improve survival over standard regimens,” said Dr. Cohen, who is chief medical officer of Tempus.

Dr. Kothari has received honoraria from Alkem Laboratories, AstraZeneca, Bard Peripheral Vascular, Bristol Myers Squibb Foundation, Celon Pharma, Cipla, Emcure, Fresenius Kabi, Glenmark, Merck, Novartis, Pfizer, Roche, and Zydus Pharmaceuticals. He has consulted for or advised MSD. He has received research funding through his institution from Axis Clinicals, Lambda Therapeutic Research, Reliance Life Sciences, and Zydus Pharmaceuticals.

Dr. Cohen is an employee of Tempus and has held leadership positions at Akamis Bio, Kinnate Biopharma, Kura Oncology, and Pangaea Biotech. He has stock or other ownership interests in Kinnate Biopharma and Primmune Therapeutics. He has consulted for or advised Adagene, Astellas Pharma, Cidara, Eisai, Genmab, Gilboa Therapeutics, ITeos Therapeutics, Lilly, Merck, MSD, Nectin Tx, Novartis, Nykode Therapeutics, Pangea, PCI Biotech, Replimune, Roche, SOTERIA Precision Medicine, and Viracta Therapeutics.
 

Chicago – In the second-line setting of head and neck cancer, metronomic triple therapy outperformed clinician choice chemotherapy in both progression-free survival (PFS) and overall survival (OS), according to results from a new phase III clinical trial.

The study was conducted in India in a population that had not previously been treated with immunotherapy, but the results are likely applicable even when patients have been exposed to these agents, according to Rushabh Kothari, MD, DM, who presented the study (Abstract LBA6004), at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although immunotherapy is considered the first-line therapy for the disease, it is often unavailable in low- and middle-income countries: In India, about 3% of head and neck cancer patients receive it, Dr. Kothari said during his presentation.

The study offered improved outcomes and greater tolerability in this population, according to Dr. Kothari. “Metronome chemotherapy led to an improvement [in both OS and PFS] of around 2 months compared to physician’s choice of treatment in this difficult-to-treat population, and metronomic chemotherapy had multiple advantages [over other chemotherapies]. It is an oral treatment, there is an ease of administration, and it is very cost effective. It also lowers adverse events as we saw in the data,” said Dr. Kothari, a medical oncologist at Narayana Multispeciality Hospital in India, in an interview.

The improvement is meaningful given the dire circumstances these patients find themselves in, according to Dr. Kothari: “When you see a second-line relapsed metastatic head and neck cancer, their overall survival is dismal: It is less than 7 months with most of the available agents,” he said in the interview.

Metronomic chemotherapy is continuous, low-dose chemotherapy that includes an anti-angiogenic effect, according to Dr. Kothari. In the current study, the researchers employed a triple metronomic chemotherapy (TMC) that included methotrexate (9 mg/m² weekly), erlotinib (150 mg daily), and celecoxib (200 mg twice daily), which was compared to any of eight single-agent physician choice agents, all of which were consistent with National Comprehensive Care Network (NCCN) guidelines (NCCN-PC group).
 

Study methods and results

The study included 55 patients in the TMC arm and 59 in the NCCN-PC arm. Currently, 13 patients in the TMC arm and 6 in the NCCN-PC are still being treated.

More than 94.5% of the TMC arm and 91.5% of the NCCN-PC arm had previously received platinum-based therapy, and 49.1% and 47.5%, respectively, had received taxane.

The median OS was 181 days in the TMC group, versus 123 days in the NCCN-PC group (hazard ratio, 0.5076; 95% confidence interval, 0.325-0.792). The median PFS was 120 days and 70 days, respectively (HR, 0.4941; 95% CI, 0.312-0.738).

Adverse events were less frequent in TMC, including anemia (grade 3-5, 3.7% versus 14.8%; P = .038), neutropenia (0% versus 13.0%; P =.006), thrombocytopenia (0% versus 9.3%; P = .028), serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase (SGOT/SGPT) rise (0% versus 9.3%; P = .028), creatinine rise (0% versus 9.3%; P = .028), and diarrhea (1.9% versus 13.0%; P = .006).

“When you give lower doses continuously, the compliance is very good. When tolerance is good and compliance is good, that is the ideal regimen, which patients want,” said Dr. Kothari in the interview.

Dr. Kothari pointed out that the study included primarily patients with oral cavity cancers, including 89.1% of the TMC group and 83.1% of the NCCN-PC group. Oropharyngeal cancers are more common in high-income countries, but his own clinical experience suggests that the combination also performs well in that group, he said.

During a discussion part of the session, Ezra Cohen, MD, said that when pembrolizumab was moved from second-line to first-line therapy, it left an unmet need in second-line recurrent or metastatic disease.

He welcomed the new results.

“[The study shows] a much better toxicity profile with the triple metronomic therapy. In other words, we can deliver these reagents at the doses prescribed, with a toxicity profile I would say that is not only manageable, but that is in fact favorable. In addition to that, in a limited size phase III study, we see an improvement in the primary endpoint here of overall survival. So in a patient population that may not necessarily have access to anti-PD1 antibodies, we can offer a lower cost triple regimen that does appear to improve survival over standard regimens,” said Dr. Cohen, who is chief medical officer of Tempus.

Dr. Kothari has received honoraria from Alkem Laboratories, AstraZeneca, Bard Peripheral Vascular, Bristol Myers Squibb Foundation, Celon Pharma, Cipla, Emcure, Fresenius Kabi, Glenmark, Merck, Novartis, Pfizer, Roche, and Zydus Pharmaceuticals. He has consulted for or advised MSD. He has received research funding through his institution from Axis Clinicals, Lambda Therapeutic Research, Reliance Life Sciences, and Zydus Pharmaceuticals.

Dr. Cohen is an employee of Tempus and has held leadership positions at Akamis Bio, Kinnate Biopharma, Kura Oncology, and Pangaea Biotech. He has stock or other ownership interests in Kinnate Biopharma and Primmune Therapeutics. He has consulted for or advised Adagene, Astellas Pharma, Cidara, Eisai, Genmab, Gilboa Therapeutics, ITeos Therapeutics, Lilly, Merck, MSD, Nectin Tx, Novartis, Nykode Therapeutics, Pangea, PCI Biotech, Replimune, Roche, SOTERIA Precision Medicine, and Viracta Therapeutics.
 

Chicago – In the second-line setting of head and neck cancer, metronomic triple therapy outperformed clinician choice chemotherapy in both progression-free survival (PFS) and overall survival (OS), according to results from a new phase III clinical trial.

The study was conducted in India in a population that had not previously been treated with immunotherapy, but the results are likely applicable even when patients have been exposed to these agents, according to Rushabh Kothari, MD, DM, who presented the study (Abstract LBA6004), at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although immunotherapy is considered the first-line therapy for the disease, it is often unavailable in low- and middle-income countries: In India, about 3% of head and neck cancer patients receive it, Dr. Kothari said during his presentation.

The study offered improved outcomes and greater tolerability in this population, according to Dr. Kothari. “Metronome chemotherapy led to an improvement [in both OS and PFS] of around 2 months compared to physician’s choice of treatment in this difficult-to-treat population, and metronomic chemotherapy had multiple advantages [over other chemotherapies]. It is an oral treatment, there is an ease of administration, and it is very cost effective. It also lowers adverse events as we saw in the data,” said Dr. Kothari, a medical oncologist at Narayana Multispeciality Hospital in India, in an interview.

The improvement is meaningful given the dire circumstances these patients find themselves in, according to Dr. Kothari: “When you see a second-line relapsed metastatic head and neck cancer, their overall survival is dismal: It is less than 7 months with most of the available agents,” he said in the interview.

Metronomic chemotherapy is continuous, low-dose chemotherapy that includes an anti-angiogenic effect, according to Dr. Kothari. In the current study, the researchers employed a triple metronomic chemotherapy (TMC) that included methotrexate (9 mg/m² weekly), erlotinib (150 mg daily), and celecoxib (200 mg twice daily), which was compared to any of eight single-agent physician choice agents, all of which were consistent with National Comprehensive Care Network (NCCN) guidelines (NCCN-PC group).
 

Study methods and results

The study included 55 patients in the TMC arm and 59 in the NCCN-PC arm. Currently, 13 patients in the TMC arm and 6 in the NCCN-PC are still being treated.

More than 94.5% of the TMC arm and 91.5% of the NCCN-PC arm had previously received platinum-based therapy, and 49.1% and 47.5%, respectively, had received taxane.

The median OS was 181 days in the TMC group, versus 123 days in the NCCN-PC group (hazard ratio, 0.5076; 95% confidence interval, 0.325-0.792). The median PFS was 120 days and 70 days, respectively (HR, 0.4941; 95% CI, 0.312-0.738).

Adverse events were less frequent in TMC, including anemia (grade 3-5, 3.7% versus 14.8%; P = .038), neutropenia (0% versus 13.0%; P =.006), thrombocytopenia (0% versus 9.3%; P = .028), serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase (SGOT/SGPT) rise (0% versus 9.3%; P = .028), creatinine rise (0% versus 9.3%; P = .028), and diarrhea (1.9% versus 13.0%; P = .006).

“When you give lower doses continuously, the compliance is very good. When tolerance is good and compliance is good, that is the ideal regimen, which patients want,” said Dr. Kothari in the interview.

Dr. Kothari pointed out that the study included primarily patients with oral cavity cancers, including 89.1% of the TMC group and 83.1% of the NCCN-PC group. Oropharyngeal cancers are more common in high-income countries, but his own clinical experience suggests that the combination also performs well in that group, he said.

During a discussion part of the session, Ezra Cohen, MD, said that when pembrolizumab was moved from second-line to first-line therapy, it left an unmet need in second-line recurrent or metastatic disease.

He welcomed the new results.

“[The study shows] a much better toxicity profile with the triple metronomic therapy. In other words, we can deliver these reagents at the doses prescribed, with a toxicity profile I would say that is not only manageable, but that is in fact favorable. In addition to that, in a limited size phase III study, we see an improvement in the primary endpoint here of overall survival. So in a patient population that may not necessarily have access to anti-PD1 antibodies, we can offer a lower cost triple regimen that does appear to improve survival over standard regimens,” said Dr. Cohen, who is chief medical officer of Tempus.

Dr. Kothari has received honoraria from Alkem Laboratories, AstraZeneca, Bard Peripheral Vascular, Bristol Myers Squibb Foundation, Celon Pharma, Cipla, Emcure, Fresenius Kabi, Glenmark, Merck, Novartis, Pfizer, Roche, and Zydus Pharmaceuticals. He has consulted for or advised MSD. He has received research funding through his institution from Axis Clinicals, Lambda Therapeutic Research, Reliance Life Sciences, and Zydus Pharmaceuticals.

Dr. Cohen is an employee of Tempus and has held leadership positions at Akamis Bio, Kinnate Biopharma, Kura Oncology, and Pangaea Biotech. He has stock or other ownership interests in Kinnate Biopharma and Primmune Therapeutics. He has consulted for or advised Adagene, Astellas Pharma, Cidara, Eisai, Genmab, Gilboa Therapeutics, ITeos Therapeutics, Lilly, Merck, MSD, Nectin Tx, Novartis, Nykode Therapeutics, Pangea, PCI Biotech, Replimune, Roche, SOTERIA Precision Medicine, and Viracta Therapeutics.
 

MILAN – Most people with recent-onset chronic back pain who are referred to a rheumatologist and then diagnosed with definite axial spondyloarthritis (axSpA) maintain that diagnosis over the next 2 years, but for those with residual diagnostic uncertainty for axSpA, particular characteristics may help to identify those who will or will not go on to receive a definite diagnosis, according to presentations given at the annual European Congress of Rheumatology.

Although a rheumatologist’s early axSpA diagnosis is reliable, new research also presented at the meeting reveals that the axSpA clinical phenotype presentation has great heterogeneity around the world, adding to the challenge.

These findings also dovetail with the consensus of an expert panel from the Assessment of SpondyloArthritis international Society (ASAS) that determined early axSpA should be defined by a duration of axial symptoms of less than 2 years, a move that should make research studies of early disease more consistent.
 

Diagnosis at first sight

To help in overcoming the long diagnostic delay typically encountered by patients with axSpA, researchers involved in the longitudinal Spondyloarthritis Caught Early (SPACE) cohort have sought to measure the prevalence of axSpA and the reliability of an early diagnosis in patients with chronic back pain (CBP). SPACE researcher Mary Lucy Marques, MD, a rheumatologist at Coimbra (Portugal) Hospital and University Center, and PhD student at Leiden (the Netherlands) University Medical Center, presented the main results of the study, which included patients younger than 45 years with CBP of unknown origin lasting 3 months to 2 years.

Patients referred to rheumatologists were judged at each visit for the presence or absence of axSpA, and the baseline judgment was reviewed after 2 years to assess its reliability. Baseline diagnostic judgments remained rather stable, and definite axSpA was present in one-third of the patients referred to the rheumatologist (175 out of 555 patients; 32%). After 2 years, the number of patients with definite axSpA diagnosis changed to 165, due to 5% of the definite diagnoses being refuted and 8% gaining a definite axSpA diagnosis. Among the features related to axSpA, the presence (or absence) of imaging-detected sacroiliitis at baseline was the best discriminator for a definite diagnosis at 2 years.

In commenting on these findings, Alexandre Sepriano, MD, PhD, assistant professor of rheumatology, NOVA Medical School, Lisbon, Portugal, who was not involved in the study, said: “These data show that the key is likely the referral of the ‘right patients’ to tertiary care centers. The [ASAS] has developed referral criteria that can be used for this purpose. According to these, patients with chronic low back pain starting before 45 years of age should be referred to a rheumatologist if at least one additional SpA feature is present.

“It should be acknowledged that axSpA is not a disease of males only. In fact, there is a 1:1 ratio between males and females in the full spectrum of the disease. Also, although imaging findings are important, not all patients will have these. Similarly, not all patients with imaging abnormalities will have the disease, and their sole presence without other SpA features does not suffice for diagnosis.”
 

Repeated assessment: Is it worth it?

Despite the positive findings described above, residual diagnostic uncertainty remained for 15% of patients, representing an obstacle to initiating an appropriate treatment. Therefore, it is important to understand whether and how the repeated assessment of axSpA features is of value for a definite diagnosis.

This last question was addressed in a second abstract also presented by Dr. Marques that focused on the yield of repeated assessment in CBP patients with suspected axSpA from the SPACE cohort. The main outcome of the study was the clinical diagnosis of definite axSpA at 2 years. Compared with baseline, at the 2-year evaluation 32 patients changed their diagnosis and were classified as definite axSpA: Sixteen were previously described as uncertain axSpA at baseline, 11 as uncertain no axSpA, and 5 as definite no axSpA.

On average, three axSpA features were present at baseline with one or two adjunctive features found throughout the study that led to the final diagnosis of definite axSpA. These adjunctive features were most commonly response to NSAIDs and sacroiliitis on MRI. Dr. Marques and colleagues concluded that the yield of repeated assessment in this setting was modest for a new diagnosis of definite axSpA. “Usefulness of repeating MRI in terms of diagnostic yield is low but can be considered in HLA-B27+ patients, especially if male,” Dr. Marques said, commenting on the analysis of SpA features in patients who changed their diagnosis to definite axSpA at 2 years.

“The early diagnosis of axial spondyloarthritis remains a challenge,” Dr. Sepriano said in commenting on the second SPACE study. “Probably one of the main reasons is the yet suboptimal awareness of the [full spectrum] of the disease in a primary care setting, in which most patients will first show up to get medical care. It is now well-known that patients do not always have changes in pelvic radiographs and that waiting for these to make a diagnosis of [radiographic] axSpA results in further delay and in missing many patients who will never develop these changes.

“Still, recognizing the clinical picture of early axSpA and differentiating it from other more common causes of chronic back pain (e.g., degenerative spinal disease) can sometimes be difficult. Continuous efforts in raising awareness and in education will likely result in further reducing the diagnostic delay gap and, as such, improve the prognosis of this often-debilitating rheumatic inflammatory disease.”

One epidemiologic size does not fit all

According to data from the International Map of Axial Spondyloarthritis (IMAS), axSpA clinical phenotype presentation shows great heterogeneity around the world. Marco Garrido-Cumbrera, PhD, of the University of Seville in Spain, presented the results of an analysis of an IMAS online survey (2017-2022).

The study, supported by Novartis, aimed at exploring differences in axSpA clinical phenotype presentation in a large sample of unselected patients: a total of 5,557 individuals from 27 countries across five regions. The results showed statistically significant differences among countries in almost all the analyzed characteristics, from age at onset of symptoms (the highest in Latin America) to HLA-B27 positivity frequency (lowest in Latin America and highest in Asia).

Differences also emerged in the presence of a positive family history of the disease (most common in Europe) and of physical and mental comorbidities (common in Africa). The authors also reported treatment data showing that most of the patients had used NSAIDs, and almost half of the patients had ever taken biologic disease-modifying antirheumatic drugs. Data also showed a mean delay in diagnosis of 7 years, with the longest values observed in South Africa and the lowest in Asia.
 

A consensus definition of early AxSpA

Early axSpA for the first time has been defined based on ASAS expert consensus, and the definition was presented at the meeting by Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid. An international working group came to a definition based on the symptom duration and taking solely axial symptoms into account. At the end of a five-step process, the group successfully developed the first consensus definition of early axSpA: “patients with diagnosis of axSpA with axial symptoms duration of ≤ 2 years.” Also to be noted are axial symptoms as assessed by a rheumatologist, which should include spinal/buttock pain or morning stiffness.

As reported by the authors, this ASAS definition is based on expert consensus, with the limitation of a lack of scientific evidence to support it, especially with regard to the specific duration of symptoms from the time of disease onset. Nonetheless, ASAS recommends the use of this definition in studies referring to early axSpA.

Dr. Marques reports no relevant financial relationships. Dr. Navarro-Compán reports serving on the speakers bureau for AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; consulting for AbbVie, Eli Lilly, Galapagos, MoonLake, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; and receiving grant/research support from AbbVie and Novartis. Dr. Garrido-Cumbrera reports receiving grant or research support from Novartis.
 

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

MILAN – Most people with recent-onset chronic back pain who are referred to a rheumatologist and then diagnosed with definite axial spondyloarthritis (axSpA) maintain that diagnosis over the next 2 years, but for those with residual diagnostic uncertainty for axSpA, particular characteristics may help to identify those who will or will not go on to receive a definite diagnosis, according to presentations given at the annual European Congress of Rheumatology.

Although a rheumatologist’s early axSpA diagnosis is reliable, new research also presented at the meeting reveals that the axSpA clinical phenotype presentation has great heterogeneity around the world, adding to the challenge.

These findings also dovetail with the consensus of an expert panel from the Assessment of SpondyloArthritis international Society (ASAS) that determined early axSpA should be defined by a duration of axial symptoms of less than 2 years, a move that should make research studies of early disease more consistent.
 

Diagnosis at first sight

To help in overcoming the long diagnostic delay typically encountered by patients with axSpA, researchers involved in the longitudinal Spondyloarthritis Caught Early (SPACE) cohort have sought to measure the prevalence of axSpA and the reliability of an early diagnosis in patients with chronic back pain (CBP). SPACE researcher Mary Lucy Marques, MD, a rheumatologist at Coimbra (Portugal) Hospital and University Center, and PhD student at Leiden (the Netherlands) University Medical Center, presented the main results of the study, which included patients younger than 45 years with CBP of unknown origin lasting 3 months to 2 years.

Patients referred to rheumatologists were judged at each visit for the presence or absence of axSpA, and the baseline judgment was reviewed after 2 years to assess its reliability. Baseline diagnostic judgments remained rather stable, and definite axSpA was present in one-third of the patients referred to the rheumatologist (175 out of 555 patients; 32%). After 2 years, the number of patients with definite axSpA diagnosis changed to 165, due to 5% of the definite diagnoses being refuted and 8% gaining a definite axSpA diagnosis. Among the features related to axSpA, the presence (or absence) of imaging-detected sacroiliitis at baseline was the best discriminator for a definite diagnosis at 2 years.

In commenting on these findings, Alexandre Sepriano, MD, PhD, assistant professor of rheumatology, NOVA Medical School, Lisbon, Portugal, who was not involved in the study, said: “These data show that the key is likely the referral of the ‘right patients’ to tertiary care centers. The [ASAS] has developed referral criteria that can be used for this purpose. According to these, patients with chronic low back pain starting before 45 years of age should be referred to a rheumatologist if at least one additional SpA feature is present.

“It should be acknowledged that axSpA is not a disease of males only. In fact, there is a 1:1 ratio between males and females in the full spectrum of the disease. Also, although imaging findings are important, not all patients will have these. Similarly, not all patients with imaging abnormalities will have the disease, and their sole presence without other SpA features does not suffice for diagnosis.”
 

Repeated assessment: Is it worth it?

Despite the positive findings described above, residual diagnostic uncertainty remained for 15% of patients, representing an obstacle to initiating an appropriate treatment. Therefore, it is important to understand whether and how the repeated assessment of axSpA features is of value for a definite diagnosis.

This last question was addressed in a second abstract also presented by Dr. Marques that focused on the yield of repeated assessment in CBP patients with suspected axSpA from the SPACE cohort. The main outcome of the study was the clinical diagnosis of definite axSpA at 2 years. Compared with baseline, at the 2-year evaluation 32 patients changed their diagnosis and were classified as definite axSpA: Sixteen were previously described as uncertain axSpA at baseline, 11 as uncertain no axSpA, and 5 as definite no axSpA.

On average, three axSpA features were present at baseline with one or two adjunctive features found throughout the study that led to the final diagnosis of definite axSpA. These adjunctive features were most commonly response to NSAIDs and sacroiliitis on MRI. Dr. Marques and colleagues concluded that the yield of repeated assessment in this setting was modest for a new diagnosis of definite axSpA. “Usefulness of repeating MRI in terms of diagnostic yield is low but can be considered in HLA-B27+ patients, especially if male,” Dr. Marques said, commenting on the analysis of SpA features in patients who changed their diagnosis to definite axSpA at 2 years.

“The early diagnosis of axial spondyloarthritis remains a challenge,” Dr. Sepriano said in commenting on the second SPACE study. “Probably one of the main reasons is the yet suboptimal awareness of the [full spectrum] of the disease in a primary care setting, in which most patients will first show up to get medical care. It is now well-known that patients do not always have changes in pelvic radiographs and that waiting for these to make a diagnosis of [radiographic] axSpA results in further delay and in missing many patients who will never develop these changes.

“Still, recognizing the clinical picture of early axSpA and differentiating it from other more common causes of chronic back pain (e.g., degenerative spinal disease) can sometimes be difficult. Continuous efforts in raising awareness and in education will likely result in further reducing the diagnostic delay gap and, as such, improve the prognosis of this often-debilitating rheumatic inflammatory disease.”

One epidemiologic size does not fit all

According to data from the International Map of Axial Spondyloarthritis (IMAS), axSpA clinical phenotype presentation shows great heterogeneity around the world. Marco Garrido-Cumbrera, PhD, of the University of Seville in Spain, presented the results of an analysis of an IMAS online survey (2017-2022).

The study, supported by Novartis, aimed at exploring differences in axSpA clinical phenotype presentation in a large sample of unselected patients: a total of 5,557 individuals from 27 countries across five regions. The results showed statistically significant differences among countries in almost all the analyzed characteristics, from age at onset of symptoms (the highest in Latin America) to HLA-B27 positivity frequency (lowest in Latin America and highest in Asia).

Differences also emerged in the presence of a positive family history of the disease (most common in Europe) and of physical and mental comorbidities (common in Africa). The authors also reported treatment data showing that most of the patients had used NSAIDs, and almost half of the patients had ever taken biologic disease-modifying antirheumatic drugs. Data also showed a mean delay in diagnosis of 7 years, with the longest values observed in South Africa and the lowest in Asia.
 

A consensus definition of early AxSpA

Early axSpA for the first time has been defined based on ASAS expert consensus, and the definition was presented at the meeting by Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid. An international working group came to a definition based on the symptom duration and taking solely axial symptoms into account. At the end of a five-step process, the group successfully developed the first consensus definition of early axSpA: “patients with diagnosis of axSpA with axial symptoms duration of ≤ 2 years.” Also to be noted are axial symptoms as assessed by a rheumatologist, which should include spinal/buttock pain or morning stiffness.

As reported by the authors, this ASAS definition is based on expert consensus, with the limitation of a lack of scientific evidence to support it, especially with regard to the specific duration of symptoms from the time of disease onset. Nonetheless, ASAS recommends the use of this definition in studies referring to early axSpA.

Dr. Marques reports no relevant financial relationships. Dr. Navarro-Compán reports serving on the speakers bureau for AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; consulting for AbbVie, Eli Lilly, Galapagos, MoonLake, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; and receiving grant/research support from AbbVie and Novartis. Dr. Garrido-Cumbrera reports receiving grant or research support from Novartis.
 

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

MILAN – Most people with recent-onset chronic back pain who are referred to a rheumatologist and then diagnosed with definite axial spondyloarthritis (axSpA) maintain that diagnosis over the next 2 years, but for those with residual diagnostic uncertainty for axSpA, particular characteristics may help to identify those who will or will not go on to receive a definite diagnosis, according to presentations given at the annual European Congress of Rheumatology.

Although a rheumatologist’s early axSpA diagnosis is reliable, new research also presented at the meeting reveals that the axSpA clinical phenotype presentation has great heterogeneity around the world, adding to the challenge.

These findings also dovetail with the consensus of an expert panel from the Assessment of SpondyloArthritis international Society (ASAS) that determined early axSpA should be defined by a duration of axial symptoms of less than 2 years, a move that should make research studies of early disease more consistent.
 

Diagnosis at first sight

To help in overcoming the long diagnostic delay typically encountered by patients with axSpA, researchers involved in the longitudinal Spondyloarthritis Caught Early (SPACE) cohort have sought to measure the prevalence of axSpA and the reliability of an early diagnosis in patients with chronic back pain (CBP). SPACE researcher Mary Lucy Marques, MD, a rheumatologist at Coimbra (Portugal) Hospital and University Center, and PhD student at Leiden (the Netherlands) University Medical Center, presented the main results of the study, which included patients younger than 45 years with CBP of unknown origin lasting 3 months to 2 years.

Patients referred to rheumatologists were judged at each visit for the presence or absence of axSpA, and the baseline judgment was reviewed after 2 years to assess its reliability. Baseline diagnostic judgments remained rather stable, and definite axSpA was present in one-third of the patients referred to the rheumatologist (175 out of 555 patients; 32%). After 2 years, the number of patients with definite axSpA diagnosis changed to 165, due to 5% of the definite diagnoses being refuted and 8% gaining a definite axSpA diagnosis. Among the features related to axSpA, the presence (or absence) of imaging-detected sacroiliitis at baseline was the best discriminator for a definite diagnosis at 2 years.

In commenting on these findings, Alexandre Sepriano, MD, PhD, assistant professor of rheumatology, NOVA Medical School, Lisbon, Portugal, who was not involved in the study, said: “These data show that the key is likely the referral of the ‘right patients’ to tertiary care centers. The [ASAS] has developed referral criteria that can be used for this purpose. According to these, patients with chronic low back pain starting before 45 years of age should be referred to a rheumatologist if at least one additional SpA feature is present.

“It should be acknowledged that axSpA is not a disease of males only. In fact, there is a 1:1 ratio between males and females in the full spectrum of the disease. Also, although imaging findings are important, not all patients will have these. Similarly, not all patients with imaging abnormalities will have the disease, and their sole presence without other SpA features does not suffice for diagnosis.”
 

Repeated assessment: Is it worth it?

Despite the positive findings described above, residual diagnostic uncertainty remained for 15% of patients, representing an obstacle to initiating an appropriate treatment. Therefore, it is important to understand whether and how the repeated assessment of axSpA features is of value for a definite diagnosis.

This last question was addressed in a second abstract also presented by Dr. Marques that focused on the yield of repeated assessment in CBP patients with suspected axSpA from the SPACE cohort. The main outcome of the study was the clinical diagnosis of definite axSpA at 2 years. Compared with baseline, at the 2-year evaluation 32 patients changed their diagnosis and were classified as definite axSpA: Sixteen were previously described as uncertain axSpA at baseline, 11 as uncertain no axSpA, and 5 as definite no axSpA.

On average, three axSpA features were present at baseline with one or two adjunctive features found throughout the study that led to the final diagnosis of definite axSpA. These adjunctive features were most commonly response to NSAIDs and sacroiliitis on MRI. Dr. Marques and colleagues concluded that the yield of repeated assessment in this setting was modest for a new diagnosis of definite axSpA. “Usefulness of repeating MRI in terms of diagnostic yield is low but can be considered in HLA-B27+ patients, especially if male,” Dr. Marques said, commenting on the analysis of SpA features in patients who changed their diagnosis to definite axSpA at 2 years.

“The early diagnosis of axial spondyloarthritis remains a challenge,” Dr. Sepriano said in commenting on the second SPACE study. “Probably one of the main reasons is the yet suboptimal awareness of the [full spectrum] of the disease in a primary care setting, in which most patients will first show up to get medical care. It is now well-known that patients do not always have changes in pelvic radiographs and that waiting for these to make a diagnosis of [radiographic] axSpA results in further delay and in missing many patients who will never develop these changes.

“Still, recognizing the clinical picture of early axSpA and differentiating it from other more common causes of chronic back pain (e.g., degenerative spinal disease) can sometimes be difficult. Continuous efforts in raising awareness and in education will likely result in further reducing the diagnostic delay gap and, as such, improve the prognosis of this often-debilitating rheumatic inflammatory disease.”

One epidemiologic size does not fit all

According to data from the International Map of Axial Spondyloarthritis (IMAS), axSpA clinical phenotype presentation shows great heterogeneity around the world. Marco Garrido-Cumbrera, PhD, of the University of Seville in Spain, presented the results of an analysis of an IMAS online survey (2017-2022).

The study, supported by Novartis, aimed at exploring differences in axSpA clinical phenotype presentation in a large sample of unselected patients: a total of 5,557 individuals from 27 countries across five regions. The results showed statistically significant differences among countries in almost all the analyzed characteristics, from age at onset of symptoms (the highest in Latin America) to HLA-B27 positivity frequency (lowest in Latin America and highest in Asia).

Differences also emerged in the presence of a positive family history of the disease (most common in Europe) and of physical and mental comorbidities (common in Africa). The authors also reported treatment data showing that most of the patients had used NSAIDs, and almost half of the patients had ever taken biologic disease-modifying antirheumatic drugs. Data also showed a mean delay in diagnosis of 7 years, with the longest values observed in South Africa and the lowest in Asia.
 

A consensus definition of early AxSpA

Early axSpA for the first time has been defined based on ASAS expert consensus, and the definition was presented at the meeting by Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid. An international working group came to a definition based on the symptom duration and taking solely axial symptoms into account. At the end of a five-step process, the group successfully developed the first consensus definition of early axSpA: “patients with diagnosis of axSpA with axial symptoms duration of ≤ 2 years.” Also to be noted are axial symptoms as assessed by a rheumatologist, which should include spinal/buttock pain or morning stiffness.

As reported by the authors, this ASAS definition is based on expert consensus, with the limitation of a lack of scientific evidence to support it, especially with regard to the specific duration of symptoms from the time of disease onset. Nonetheless, ASAS recommends the use of this definition in studies referring to early axSpA.

Dr. Marques reports no relevant financial relationships. Dr. Navarro-Compán reports serving on the speakers bureau for AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; consulting for AbbVie, Eli Lilly, Galapagos, MoonLake, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; and receiving grant/research support from AbbVie and Novartis. Dr. Garrido-Cumbrera reports receiving grant or research support from Novartis.
 

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

MILAN – Serum uric acid of less than 6 mg/dL was achieved and maintained for a substantial period of time with a once-monthly infusion of SEL-212 in patients with refractory gout, according to results of the two phase 3 DISSOLVE I and II trials.

Both trials met their primary endpoints. In DISSOLVE I – the U.S. study – 56% of patients on SEL-212 at 0.15 mg/kg (high dose) achieved a response, defined as achievement and maintenance of a reduction in serum urate to less than 6 mg/dL for at least 80% of the time during month 6 of treatment. In DISSOLVE II – the global study – 46% of patients on SEL-212 on the 0.15-mg/kg dose achieved response.

In participants aged 50 years or older, there was a statistically significant higher response rate at the high dose of SEL-212 in both DISSOLVE I and II of 65% and 47%, respectively, compared with placebo.

Herbert S.B. Baraf, MD, clinical professor of medicine at George Washington University, Washington, and principal investigator of the DISSOLVE program, presented results of the two phase 3 trials during a late-breaking session at the annual European Congress of Rheumatology.

Arthritis Foundation

“The top-line data from the two SEL-212 phase 3 studies are encouraging. They show that induction of immunotolerance with an infusion of a rapamycin-containing nanoparticle (SEL-110), followed immediately by an infusion of pegadricase, a potent but immunogenic uricase, allows for a strong and sustained uric acid–lowering effect without the development of anti-drug antibodies,” Dr. Baraf said in an interview.

SEL-212 is a monthly two-part infusion therapy – a combination of Selecta Biosciences’s ImmTOR immune tolerance platform, and a therapeutic uricase enzyme (pegadricase), designed to treat refractory gout. SEL-110 (ImmTOR) is an immune-tolerizing, nanoencapsulated rapamycin administered 30 minutes before pegadricase and inhibits anti-pegadricase antibodies. SEL-37 is a pegylated uricase (pegadricase) that converts uric acid to excretable allantoin.

SEL-212 was originally developed by Selecta. Swedish Orphan Biovitrum (Sobi) licensed SEL-212 from Selecta in June 2020 and is responsible for development, regulatory, and commercial activities in all markets outside of China. Selecta is responsible for ImmTOR manufacturing. The phase 3 program for SEL-212 was run by Selecta and funded by Sobi.

It is understood that a biologic license application will be submitted to the Food and Drug Administration, most likely next year, and if approved, “the SEL-212 two-component infusion treatment would provide a monthly alternative to twice-monthly pegloticase, for patients with refractory gout,” Dr. Baraf added.
 

Details of the trials

The two DISSOLVE studies replicate double-blind, placebo-controlled trials in patients with chronic refractory gout. DISSOLVE I was carried out in 112 patients across 29 sites in the United States, and DISSOLVE II tested the two-part treatment in 153 patients across 37 sites in the United States, Russia, Ukraine, Georgia, and Serbia.

Both studies randomized patients 1:1:1 to a high dose (SEL-110 of 0.15 mg/kg plus SEL-037 of 0.2 mg/kg), low dose (SEL-110 of 0.1 mg/kg plus SEL-037 of 0.2 mg/kg), or placebo (saline) infused every 28 days for 6 months. Prophylaxis against infusion reactions and gout flares were given to all participants.

Adult patients had a 10- to 14-year history of symptomatic gout, with three or more flares over the 18 months prior to screening, or one or more tophus, or a diagnosis of gouty arthritis. They were also required to have chronic refractory gout with a failure to normalize serum uric acid with any xanthine oxidase inhibitor (for example, allopurinol) and to have not been previously exposed to uricase-based therapy. Serum uric acid had to be at least 7 mg/dL. Participants were balanced for age, body mass index, and sex across treatment groups. Gout severity was greater in DISSOLVE II, Dr. Baraf reported.

Both studies treated patients for 6 months, but DISSOLVE 1 continued with a 6-month, blinded safety extension. The primary endpoint in both studies was serum urate control during month 6, and secondary endpoints included tender and swollen joint counts, tophus burden, patient-reported outcomes of activity limitation, quality of life, and gout flare incidence.

In DISSOLVE I, patients on SEL-212 had a statistically significant higher response rate during month 6 of 56% with the high dose (P < .0001) and 48% with the low dose (P < .0001), compared with 4% of patients randomized to receive placebo. In DISSOLVE II, participants on SEL-212 had a statistically significant higher response rate during month 6 of 46% with the high dose (P = .0002) and 40% with the low dose (P = .0008), compared with 11% of patients randomized to receive placebo.

“We also saw significant reductions in serum uric acid for all treatment groups, compared with placebo,” Dr. Baraf reported. Mean percentage change was –62.3% and –58.3% in the high- and low-dose groups, respectively, in DISSOLVE I, and –58.1% and –52.2% in DISSOLVE II, respectively.

SEL-212 had a favorable safety profile with adverse events as expected across both doses, including mild to moderate stomatitis (3.4% in the low-dose group and 9.2% in the high-dose group versus 0% in the placebo group), and a greater number of infusion reactions at 24 hours and 1 hour after drug administration in both treatment groups versus placebo. Six patients had treatment-related serious adverse events, including two cases of anaphylaxis and one gout flare in both the high- and low-dose treatment groups. The 6-month extension period in the DISSOLVE I trial showed that the majority (75%) of patients who completed 6 months of SEL-212 treatment as a responder continued to be successfully treated through 12 months with no infusion reactions or safety signals.

“I expect more data will be forthcoming on the important clinical secondary endpoints targeted by SEL-212 therapy,” Dr. Baraf noted.
 

Need control arm taking allopurinol?

Roy Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas, commented on the study methods after the presentation. “The major problem with this study is that they say the patients had had insufficient response to allopurinol, and my guess is most had received 100-200 mg of allopurinol but were not titrated up to the maximum tolerated dose,” he said, adding: “they should have had a control arm of patients on allopurinol and titrated to the maximum tolerated dose. So, I don’t know what this is really telling us with respect to allopurinol, which is a relatively cheap drug.”

Dr. Baraf reported consulting with Horizon, Sobi, and Selecta; serving on Horizon’s speakers bureau, and receiving grant/research support from Horizon and Sobi. Dr. Fleischmann reported no financial relationship of relevance to this study.

MILAN – Serum uric acid of less than 6 mg/dL was achieved and maintained for a substantial period of time with a once-monthly infusion of SEL-212 in patients with refractory gout, according to results of the two phase 3 DISSOLVE I and II trials.

Both trials met their primary endpoints. In DISSOLVE I – the U.S. study – 56% of patients on SEL-212 at 0.15 mg/kg (high dose) achieved a response, defined as achievement and maintenance of a reduction in serum urate to less than 6 mg/dL for at least 80% of the time during month 6 of treatment. In DISSOLVE II – the global study – 46% of patients on SEL-212 on the 0.15-mg/kg dose achieved response.

In participants aged 50 years or older, there was a statistically significant higher response rate at the high dose of SEL-212 in both DISSOLVE I and II of 65% and 47%, respectively, compared with placebo.

Herbert S.B. Baraf, MD, clinical professor of medicine at George Washington University, Washington, and principal investigator of the DISSOLVE program, presented results of the two phase 3 trials during a late-breaking session at the annual European Congress of Rheumatology.

Arthritis Foundation

“The top-line data from the two SEL-212 phase 3 studies are encouraging. They show that induction of immunotolerance with an infusion of a rapamycin-containing nanoparticle (SEL-110), followed immediately by an infusion of pegadricase, a potent but immunogenic uricase, allows for a strong and sustained uric acid–lowering effect without the development of anti-drug antibodies,” Dr. Baraf said in an interview.

SEL-212 is a monthly two-part infusion therapy – a combination of Selecta Biosciences’s ImmTOR immune tolerance platform, and a therapeutic uricase enzyme (pegadricase), designed to treat refractory gout. SEL-110 (ImmTOR) is an immune-tolerizing, nanoencapsulated rapamycin administered 30 minutes before pegadricase and inhibits anti-pegadricase antibodies. SEL-37 is a pegylated uricase (pegadricase) that converts uric acid to excretable allantoin.

SEL-212 was originally developed by Selecta. Swedish Orphan Biovitrum (Sobi) licensed SEL-212 from Selecta in June 2020 and is responsible for development, regulatory, and commercial activities in all markets outside of China. Selecta is responsible for ImmTOR manufacturing. The phase 3 program for SEL-212 was run by Selecta and funded by Sobi.

It is understood that a biologic license application will be submitted to the Food and Drug Administration, most likely next year, and if approved, “the SEL-212 two-component infusion treatment would provide a monthly alternative to twice-monthly pegloticase, for patients with refractory gout,” Dr. Baraf added.
 

Details of the trials

The two DISSOLVE studies replicate double-blind, placebo-controlled trials in patients with chronic refractory gout. DISSOLVE I was carried out in 112 patients across 29 sites in the United States, and DISSOLVE II tested the two-part treatment in 153 patients across 37 sites in the United States, Russia, Ukraine, Georgia, and Serbia.

Both studies randomized patients 1:1:1 to a high dose (SEL-110 of 0.15 mg/kg plus SEL-037 of 0.2 mg/kg), low dose (SEL-110 of 0.1 mg/kg plus SEL-037 of 0.2 mg/kg), or placebo (saline) infused every 28 days for 6 months. Prophylaxis against infusion reactions and gout flares were given to all participants.

Adult patients had a 10- to 14-year history of symptomatic gout, with three or more flares over the 18 months prior to screening, or one or more tophus, or a diagnosis of gouty arthritis. They were also required to have chronic refractory gout with a failure to normalize serum uric acid with any xanthine oxidase inhibitor (for example, allopurinol) and to have not been previously exposed to uricase-based therapy. Serum uric acid had to be at least 7 mg/dL. Participants were balanced for age, body mass index, and sex across treatment groups. Gout severity was greater in DISSOLVE II, Dr. Baraf reported.

Both studies treated patients for 6 months, but DISSOLVE 1 continued with a 6-month, blinded safety extension. The primary endpoint in both studies was serum urate control during month 6, and secondary endpoints included tender and swollen joint counts, tophus burden, patient-reported outcomes of activity limitation, quality of life, and gout flare incidence.

In DISSOLVE I, patients on SEL-212 had a statistically significant higher response rate during month 6 of 56% with the high dose (P < .0001) and 48% with the low dose (P < .0001), compared with 4% of patients randomized to receive placebo. In DISSOLVE II, participants on SEL-212 had a statistically significant higher response rate during month 6 of 46% with the high dose (P = .0002) and 40% with the low dose (P = .0008), compared with 11% of patients randomized to receive placebo.

“We also saw significant reductions in serum uric acid for all treatment groups, compared with placebo,” Dr. Baraf reported. Mean percentage change was –62.3% and –58.3% in the high- and low-dose groups, respectively, in DISSOLVE I, and –58.1% and –52.2% in DISSOLVE II, respectively.

SEL-212 had a favorable safety profile with adverse events as expected across both doses, including mild to moderate stomatitis (3.4% in the low-dose group and 9.2% in the high-dose group versus 0% in the placebo group), and a greater number of infusion reactions at 24 hours and 1 hour after drug administration in both treatment groups versus placebo. Six patients had treatment-related serious adverse events, including two cases of anaphylaxis and one gout flare in both the high- and low-dose treatment groups. The 6-month extension period in the DISSOLVE I trial showed that the majority (75%) of patients who completed 6 months of SEL-212 treatment as a responder continued to be successfully treated through 12 months with no infusion reactions or safety signals.

“I expect more data will be forthcoming on the important clinical secondary endpoints targeted by SEL-212 therapy,” Dr. Baraf noted.
 

Need control arm taking allopurinol?

Roy Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas, commented on the study methods after the presentation. “The major problem with this study is that they say the patients had had insufficient response to allopurinol, and my guess is most had received 100-200 mg of allopurinol but were not titrated up to the maximum tolerated dose,” he said, adding: “they should have had a control arm of patients on allopurinol and titrated to the maximum tolerated dose. So, I don’t know what this is really telling us with respect to allopurinol, which is a relatively cheap drug.”

Dr. Baraf reported consulting with Horizon, Sobi, and Selecta; serving on Horizon’s speakers bureau, and receiving grant/research support from Horizon and Sobi. Dr. Fleischmann reported no financial relationship of relevance to this study.

MILAN – Serum uric acid of less than 6 mg/dL was achieved and maintained for a substantial period of time with a once-monthly infusion of SEL-212 in patients with refractory gout, according to results of the two phase 3 DISSOLVE I and II trials.

Both trials met their primary endpoints. In DISSOLVE I – the U.S. study – 56% of patients on SEL-212 at 0.15 mg/kg (high dose) achieved a response, defined as achievement and maintenance of a reduction in serum urate to less than 6 mg/dL for at least 80% of the time during month 6 of treatment. In DISSOLVE II – the global study – 46% of patients on SEL-212 on the 0.15-mg/kg dose achieved response.

In participants aged 50 years or older, there was a statistically significant higher response rate at the high dose of SEL-212 in both DISSOLVE I and II of 65% and 47%, respectively, compared with placebo.

Herbert S.B. Baraf, MD, clinical professor of medicine at George Washington University, Washington, and principal investigator of the DISSOLVE program, presented results of the two phase 3 trials during a late-breaking session at the annual European Congress of Rheumatology.

Arthritis Foundation

“The top-line data from the two SEL-212 phase 3 studies are encouraging. They show that induction of immunotolerance with an infusion of a rapamycin-containing nanoparticle (SEL-110), followed immediately by an infusion of pegadricase, a potent but immunogenic uricase, allows for a strong and sustained uric acid–lowering effect without the development of anti-drug antibodies,” Dr. Baraf said in an interview.

SEL-212 is a monthly two-part infusion therapy – a combination of Selecta Biosciences’s ImmTOR immune tolerance platform, and a therapeutic uricase enzyme (pegadricase), designed to treat refractory gout. SEL-110 (ImmTOR) is an immune-tolerizing, nanoencapsulated rapamycin administered 30 minutes before pegadricase and inhibits anti-pegadricase antibodies. SEL-37 is a pegylated uricase (pegadricase) that converts uric acid to excretable allantoin.

SEL-212 was originally developed by Selecta. Swedish Orphan Biovitrum (Sobi) licensed SEL-212 from Selecta in June 2020 and is responsible for development, regulatory, and commercial activities in all markets outside of China. Selecta is responsible for ImmTOR manufacturing. The phase 3 program for SEL-212 was run by Selecta and funded by Sobi.

It is understood that a biologic license application will be submitted to the Food and Drug Administration, most likely next year, and if approved, “the SEL-212 two-component infusion treatment would provide a monthly alternative to twice-monthly pegloticase, for patients with refractory gout,” Dr. Baraf added.
 

Details of the trials

The two DISSOLVE studies replicate double-blind, placebo-controlled trials in patients with chronic refractory gout. DISSOLVE I was carried out in 112 patients across 29 sites in the United States, and DISSOLVE II tested the two-part treatment in 153 patients across 37 sites in the United States, Russia, Ukraine, Georgia, and Serbia.

Both studies randomized patients 1:1:1 to a high dose (SEL-110 of 0.15 mg/kg plus SEL-037 of 0.2 mg/kg), low dose (SEL-110 of 0.1 mg/kg plus SEL-037 of 0.2 mg/kg), or placebo (saline) infused every 28 days for 6 months. Prophylaxis against infusion reactions and gout flares were given to all participants.

Adult patients had a 10- to 14-year history of symptomatic gout, with three or more flares over the 18 months prior to screening, or one or more tophus, or a diagnosis of gouty arthritis. They were also required to have chronic refractory gout with a failure to normalize serum uric acid with any xanthine oxidase inhibitor (for example, allopurinol) and to have not been previously exposed to uricase-based therapy. Serum uric acid had to be at least 7 mg/dL. Participants were balanced for age, body mass index, and sex across treatment groups. Gout severity was greater in DISSOLVE II, Dr. Baraf reported.

Both studies treated patients for 6 months, but DISSOLVE 1 continued with a 6-month, blinded safety extension. The primary endpoint in both studies was serum urate control during month 6, and secondary endpoints included tender and swollen joint counts, tophus burden, patient-reported outcomes of activity limitation, quality of life, and gout flare incidence.

In DISSOLVE I, patients on SEL-212 had a statistically significant higher response rate during month 6 of 56% with the high dose (P < .0001) and 48% with the low dose (P < .0001), compared with 4% of patients randomized to receive placebo. In DISSOLVE II, participants on SEL-212 had a statistically significant higher response rate during month 6 of 46% with the high dose (P = .0002) and 40% with the low dose (P = .0008), compared with 11% of patients randomized to receive placebo.

“We also saw significant reductions in serum uric acid for all treatment groups, compared with placebo,” Dr. Baraf reported. Mean percentage change was –62.3% and –58.3% in the high- and low-dose groups, respectively, in DISSOLVE I, and –58.1% and –52.2% in DISSOLVE II, respectively.

SEL-212 had a favorable safety profile with adverse events as expected across both doses, including mild to moderate stomatitis (3.4% in the low-dose group and 9.2% in the high-dose group versus 0% in the placebo group), and a greater number of infusion reactions at 24 hours and 1 hour after drug administration in both treatment groups versus placebo. Six patients had treatment-related serious adverse events, including two cases of anaphylaxis and one gout flare in both the high- and low-dose treatment groups. The 6-month extension period in the DISSOLVE I trial showed that the majority (75%) of patients who completed 6 months of SEL-212 treatment as a responder continued to be successfully treated through 12 months with no infusion reactions or safety signals.

“I expect more data will be forthcoming on the important clinical secondary endpoints targeted by SEL-212 therapy,” Dr. Baraf noted.
 

Need control arm taking allopurinol?

Roy Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center and codirector of the Metroplex Clinical Research Center, both in Dallas, commented on the study methods after the presentation. “The major problem with this study is that they say the patients had had insufficient response to allopurinol, and my guess is most had received 100-200 mg of allopurinol but were not titrated up to the maximum tolerated dose,” he said, adding: “they should have had a control arm of patients on allopurinol and titrated to the maximum tolerated dose. So, I don’t know what this is really telling us with respect to allopurinol, which is a relatively cheap drug.”

Dr. Baraf reported consulting with Horizon, Sobi, and Selecta; serving on Horizon’s speakers bureau, and receiving grant/research support from Horizon and Sobi. Dr. Fleischmann reported no financial relationship of relevance to this study.

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

Aurora, Colo. – The access to and quality of multiple sclerosis (MS) care varies substantially depending on a patient’s race, ethnicity, gender, and geography, according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”

The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
 

A ‘widespread and significant problem’

“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”

The pervasive impact of MS

Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).

Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.

“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
 

Access to care varied by race

Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.

A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.

White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
 

Other barriers to MS care

Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.

Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.

“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”

Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).

Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.

“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”

The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.

The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
 

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

SAN FRANCISCO – Music therapy improves negative symptoms of schizophrenia, such as lack of motivation, reclusiveness, and isolation, a new review of the literature suggests.

Although the study had conflicting results regarding the effects of music therapy on positive symptoms of schizophrenia, such as hallucinations, delusions, and disordered thoughts, it consistently shows that music therapy improves negative symptoms, poster presenter Amy Agrawal, MD, VA Boston Healthcare System and instructor of psychiatry at Harvard Medical School, Boston, said in an interview.

Pauline Anderson

Current antipsychotic drugs aren’t very effective in addressing negative symptoms of schizophrenia, and many patients are noncompliant with these drug regimens because of side effects.

“We need to target the negative symptoms of schizophrenia better,” said Dr. Agrawal. “The antipsychotic medications we have are not enough, so why don’t we start incorporating music therapy groups into the inpatient psychiatry setting as a standard of care?”

The findings were presented at the annual meeting of the American Psychiatric Association.

Dr. Agrawal has long been interested in music. As a child, she was a member of a state choir, but she hadn’t sung for years. After receiving several medals for her clarinet playing during her youth, she stopped playing while in medical school.
 

Instant boost

During the pandemic, though, she turned back to music and started singing regularly. “I noticed an instant boost in my mood and wondered why I stopped making music for so long, as it made me feel so much happier and calmer.”

She also noticed how music affected her sister, who has paranoid schizophrenia. She described an incident in which her sibling became so loud and paranoid at a restaurant that Dr. Agrawal thought they would be asked to leave.

Then her sister started singing a song she’d sung during a beauty contest years before. “With the music, she calmed right down; she was smiling; she was happy,” said Dr. Agrawal.

That incident made Dr. Agrawal feel, “I had my sister back.” She decided to bring music therapy to her inpatient psychiatry unit and soon noted the benefits for individual patients.

For this new study, Dr. Agrawal and her mentor carried out a literature search. “I was surprised at how many articles popped up, because the field of psychiatry can be very heavily medication based, but people are now getting very interested in this topic,” said Dr. Agrawal.

The review included seven articles, most of which were published within the past 3 years. Some articles specified that the therapy was conducted on an inpatient psychiatric unit, but others didn’t indicate the setting. Studies also didn’t specify whether the therapy was delivered by a trained music therapist.

There was an overall lack of clear measures, graphs, or statistics quantifying the benefits of music therapy on schizophrenia, noted Dr. Agrawal. “But from general statements in the articles, music therapy helped treat sleep disturbances and improved negative symptoms.”
 

Gets patients socializing

The music, she said, led patients to start socializing, talking about their emotions, and opening up to their clinicians about their mental health symptoms. “Some patients just did not engage at all, and then when the music came on, they would actively participate with the clinician.”

Dancing to music also tended to motivate patients to participate in their treatment, she added. Different forms of movement, such as rhythmic movements and creative exercises, can be added during music therapy.

In addition to improving negative schizophrenia symptoms, music therapy helps with sleep disturbances, depression, and regulating emotional behavior, the research shows. “When patients were agitated or upset, certain music would help them regulate their own affect,” said Dr. Agrawal.

However, it’s not clear from these studies what type of music – classical, rock, country, etc. – was most effective for people.

One article discussed the positive impact of music on patients with schizophrenia while at work. “They seem to have improved work performance,” Dr. Agrawal said.

The length of exposure to music therapy did not seem to make a difference in terms of whether the therapy had a positive effect, she added.
 

Key research wave

A “key next wave” of research should be to determine whether music therapy decreases the hospital readmission rate, said Dr. Agrawal.

There are several barriers to implementing music therapy programs in hospitals, including cost, the availability of trained therapists, and time constraints, she said.

“Regardless of the barriers, hospital administrators and psychiatrists need to know about this research so they will invest more efforts in recruiting music therapists and incorporating music group therapy into standard clinical practice for psychiatric patients so there are better clinical outcomes.”

Commenting on the research, Michelle B. Riba, MD, professor, department of psychiatry, University of Michigan, Ann Arbor, said the study adds to the literature “and helps us think about adjunctive treatments in a very difficult population.”

University of Michigan

Difficult topic to study

Although she found the review “very limited,” she recognizes the difficulty of studying music therapy on in-patient psychiatry units.

“Patients are there for short stays, most are getting other treatments, and it’s hard to segment people into negative vs. positive. Also, the ages and genders are different, and their previous treatments are different.”

While it’s sometimes difficult to conduct major research on a topic, “that doesn’t mean we can’t help people,” said Dr. Riba.

She noted that music therapy is beneficial not only for patients with schizophrenia but also is “soothing and relaxing” for those with other conditions. She runs a psychiatric oncology program at her institution’s cancer center, which offers music therapy along with art therapy.

Kevin M. Malone, MD, of University College Dublin, also has firsthand experience with music therapy. “We had a terrific music therapist as part of our clinical psychosis team,” he said in an interview.

University College Dublin

A version of this article was first published on Medscape.com.

SAN FRANCISCO – Music therapy improves negative symptoms of schizophrenia, such as lack of motivation, reclusiveness, and isolation, a new review of the literature suggests.

Although the study had conflicting results regarding the effects of music therapy on positive symptoms of schizophrenia, such as hallucinations, delusions, and disordered thoughts, it consistently shows that music therapy improves negative symptoms, poster presenter Amy Agrawal, MD, VA Boston Healthcare System and instructor of psychiatry at Harvard Medical School, Boston, said in an interview.

Pauline Anderson

Current antipsychotic drugs aren’t very effective in addressing negative symptoms of schizophrenia, and many patients are noncompliant with these drug regimens because of side effects.

“We need to target the negative symptoms of schizophrenia better,” said Dr. Agrawal. “The antipsychotic medications we have are not enough, so why don’t we start incorporating music therapy groups into the inpatient psychiatry setting as a standard of care?”

The findings were presented at the annual meeting of the American Psychiatric Association.

Dr. Agrawal has long been interested in music. As a child, she was a member of a state choir, but she hadn’t sung for years. After receiving several medals for her clarinet playing during her youth, she stopped playing while in medical school.
 

Instant boost

During the pandemic, though, she turned back to music and started singing regularly. “I noticed an instant boost in my mood and wondered why I stopped making music for so long, as it made me feel so much happier and calmer.”

She also noticed how music affected her sister, who has paranoid schizophrenia. She described an incident in which her sibling became so loud and paranoid at a restaurant that Dr. Agrawal thought they would be asked to leave.

Then her sister started singing a song she’d sung during a beauty contest years before. “With the music, she calmed right down; she was smiling; she was happy,” said Dr. Agrawal.

That incident made Dr. Agrawal feel, “I had my sister back.” She decided to bring music therapy to her inpatient psychiatry unit and soon noted the benefits for individual patients.

For this new study, Dr. Agrawal and her mentor carried out a literature search. “I was surprised at how many articles popped up, because the field of psychiatry can be very heavily medication based, but people are now getting very interested in this topic,” said Dr. Agrawal.

The review included seven articles, most of which were published within the past 3 years. Some articles specified that the therapy was conducted on an inpatient psychiatric unit, but others didn’t indicate the setting. Studies also didn’t specify whether the therapy was delivered by a trained music therapist.

There was an overall lack of clear measures, graphs, or statistics quantifying the benefits of music therapy on schizophrenia, noted Dr. Agrawal. “But from general statements in the articles, music therapy helped treat sleep disturbances and improved negative symptoms.”
 

Gets patients socializing

The music, she said, led patients to start socializing, talking about their emotions, and opening up to their clinicians about their mental health symptoms. “Some patients just did not engage at all, and then when the music came on, they would actively participate with the clinician.”

Dancing to music also tended to motivate patients to participate in their treatment, she added. Different forms of movement, such as rhythmic movements and creative exercises, can be added during music therapy.

In addition to improving negative schizophrenia symptoms, music therapy helps with sleep disturbances, depression, and regulating emotional behavior, the research shows. “When patients were agitated or upset, certain music would help them regulate their own affect,” said Dr. Agrawal.

However, it’s not clear from these studies what type of music – classical, rock, country, etc. – was most effective for people.

One article discussed the positive impact of music on patients with schizophrenia while at work. “They seem to have improved work performance,” Dr. Agrawal said.

The length of exposure to music therapy did not seem to make a difference in terms of whether the therapy had a positive effect, she added.
 

Key research wave

A “key next wave” of research should be to determine whether music therapy decreases the hospital readmission rate, said Dr. Agrawal.

There are several barriers to implementing music therapy programs in hospitals, including cost, the availability of trained therapists, and time constraints, she said.

“Regardless of the barriers, hospital administrators and psychiatrists need to know about this research so they will invest more efforts in recruiting music therapists and incorporating music group therapy into standard clinical practice for psychiatric patients so there are better clinical outcomes.”

Commenting on the research, Michelle B. Riba, MD, professor, department of psychiatry, University of Michigan, Ann Arbor, said the study adds to the literature “and helps us think about adjunctive treatments in a very difficult population.”

University of Michigan

Difficult topic to study

Although she found the review “very limited,” she recognizes the difficulty of studying music therapy on in-patient psychiatry units.

“Patients are there for short stays, most are getting other treatments, and it’s hard to segment people into negative vs. positive. Also, the ages and genders are different, and their previous treatments are different.”

While it’s sometimes difficult to conduct major research on a topic, “that doesn’t mean we can’t help people,” said Dr. Riba.

She noted that music therapy is beneficial not only for patients with schizophrenia but also is “soothing and relaxing” for those with other conditions. She runs a psychiatric oncology program at her institution’s cancer center, which offers music therapy along with art therapy.

Kevin M. Malone, MD, of University College Dublin, also has firsthand experience with music therapy. “We had a terrific music therapist as part of our clinical psychosis team,” he said in an interview.

University College Dublin

A version of this article was first published on Medscape.com.

SAN FRANCISCO – Music therapy improves negative symptoms of schizophrenia, such as lack of motivation, reclusiveness, and isolation, a new review of the literature suggests.

Although the study had conflicting results regarding the effects of music therapy on positive symptoms of schizophrenia, such as hallucinations, delusions, and disordered thoughts, it consistently shows that music therapy improves negative symptoms, poster presenter Amy Agrawal, MD, VA Boston Healthcare System and instructor of psychiatry at Harvard Medical School, Boston, said in an interview.

Pauline Anderson

Current antipsychotic drugs aren’t very effective in addressing negative symptoms of schizophrenia, and many patients are noncompliant with these drug regimens because of side effects.

“We need to target the negative symptoms of schizophrenia better,” said Dr. Agrawal. “The antipsychotic medications we have are not enough, so why don’t we start incorporating music therapy groups into the inpatient psychiatry setting as a standard of care?”

The findings were presented at the annual meeting of the American Psychiatric Association.

Dr. Agrawal has long been interested in music. As a child, she was a member of a state choir, but she hadn’t sung for years. After receiving several medals for her clarinet playing during her youth, she stopped playing while in medical school.
 

Instant boost

During the pandemic, though, she turned back to music and started singing regularly. “I noticed an instant boost in my mood and wondered why I stopped making music for so long, as it made me feel so much happier and calmer.”

She also noticed how music affected her sister, who has paranoid schizophrenia. She described an incident in which her sibling became so loud and paranoid at a restaurant that Dr. Agrawal thought they would be asked to leave.

Then her sister started singing a song she’d sung during a beauty contest years before. “With the music, she calmed right down; she was smiling; she was happy,” said Dr. Agrawal.

That incident made Dr. Agrawal feel, “I had my sister back.” She decided to bring music therapy to her inpatient psychiatry unit and soon noted the benefits for individual patients.

For this new study, Dr. Agrawal and her mentor carried out a literature search. “I was surprised at how many articles popped up, because the field of psychiatry can be very heavily medication based, but people are now getting very interested in this topic,” said Dr. Agrawal.

The review included seven articles, most of which were published within the past 3 years. Some articles specified that the therapy was conducted on an inpatient psychiatric unit, but others didn’t indicate the setting. Studies also didn’t specify whether the therapy was delivered by a trained music therapist.

There was an overall lack of clear measures, graphs, or statistics quantifying the benefits of music therapy on schizophrenia, noted Dr. Agrawal. “But from general statements in the articles, music therapy helped treat sleep disturbances and improved negative symptoms.”
 

Gets patients socializing

The music, she said, led patients to start socializing, talking about their emotions, and opening up to their clinicians about their mental health symptoms. “Some patients just did not engage at all, and then when the music came on, they would actively participate with the clinician.”

Dancing to music also tended to motivate patients to participate in their treatment, she added. Different forms of movement, such as rhythmic movements and creative exercises, can be added during music therapy.

In addition to improving negative schizophrenia symptoms, music therapy helps with sleep disturbances, depression, and regulating emotional behavior, the research shows. “When patients were agitated or upset, certain music would help them regulate their own affect,” said Dr. Agrawal.

However, it’s not clear from these studies what type of music – classical, rock, country, etc. – was most effective for people.

One article discussed the positive impact of music on patients with schizophrenia while at work. “They seem to have improved work performance,” Dr. Agrawal said.

The length of exposure to music therapy did not seem to make a difference in terms of whether the therapy had a positive effect, she added.
 

Key research wave

A “key next wave” of research should be to determine whether music therapy decreases the hospital readmission rate, said Dr. Agrawal.

There are several barriers to implementing music therapy programs in hospitals, including cost, the availability of trained therapists, and time constraints, she said.

“Regardless of the barriers, hospital administrators and psychiatrists need to know about this research so they will invest more efforts in recruiting music therapists and incorporating music group therapy into standard clinical practice for psychiatric patients so there are better clinical outcomes.”

Commenting on the research, Michelle B. Riba, MD, professor, department of psychiatry, University of Michigan, Ann Arbor, said the study adds to the literature “and helps us think about adjunctive treatments in a very difficult population.”

University of Michigan

Difficult topic to study

Although she found the review “very limited,” she recognizes the difficulty of studying music therapy on in-patient psychiatry units.

“Patients are there for short stays, most are getting other treatments, and it’s hard to segment people into negative vs. positive. Also, the ages and genders are different, and their previous treatments are different.”

While it’s sometimes difficult to conduct major research on a topic, “that doesn’t mean we can’t help people,” said Dr. Riba.

She noted that music therapy is beneficial not only for patients with schizophrenia but also is “soothing and relaxing” for those with other conditions. She runs a psychiatric oncology program at her institution’s cancer center, which offers music therapy along with art therapy.

Kevin M. Malone, MD, of University College Dublin, also has firsthand experience with music therapy. “We had a terrific music therapist as part of our clinical psychosis team,” he said in an interview.

University College Dublin

A version of this article was first published on Medscape.com.

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare. Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, though it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE, particularly in those with skin of color, as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4 Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphosopholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8

• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have far-reaching effects, negatively impacting quality of life and even mortality.

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare. Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, though it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE, particularly in those with skin of color, as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4 Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphosopholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8

• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have far-reaching effects, negatively impacting quality of life and even mortality.

THE COMPARISON

A A 23-year-old White woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose and eyelids but spares the nasolabial folds.

B A Black woman with malar erythema and hyperpigmentation from acute cutaneous lupus erythematosus. The nasolabial folds are spared.

C A 19-year-old Latina woman with malar erythema from acute cutaneous lupus erythematosus. The erythema also can be seen on the nose, chin, and eyelids but spares the nasolabial folds. Cutaneous erosions are present on the right cheek as part of the lupus flare. Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that affects the kidneys, lungs, brain, and heart, though it is not limited to these organs. Dermatologists and primary care physicians play a critical role in the early identification of SLE, particularly in those with skin of color, as the standardized mortality rate is 2.6-fold higher in patients with SLE compared to the general population.¹ The clinical manifestations of SLE vary.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

A meta-analysis of data from the Centers for Disease Control and Prevention National Lupus Registry network including 5417 patients revealed a prevalence of 72.8 cases per 100,000 person-years.² The prevalence was higher in females than males and highest among females identifying as Black. White and Asian/Pacific Islander females had the lowest prevalence. The American Indian (indigenous)/Alaska Native–identifying population had the highest race-specific SLE estimates among both females and males compared to other racial/ethnic groups.²

Key clinical features in people with darker skin tones

The diagnosis of SLE is based on clinical and immunologic criteria from the European League Against Rheumatism/American College of Rheumatology.^3,4 An antinuclear antibody titer of 1:80 or higher at least once is required for the diagnosis of SLE, as long as there is not another more likely diagnosis. If it is present, 22 additive weighted classification criteria are considered; each criterion is assigned points, ranging from 2 to 10. Patients with at least 1 clinical criterion and 10 or more points are classified as having SLE. If more than 1 of the criteria are met in a domain, then the one with the highest numerical value is counted.^3,4 Aringer et al^3,4 outline the criteria and numerical points to make the diagnosis of SLE. The mucocutaneous component of the SLE diagnostic criteria^3,4 includes nonscarring alopecia, oral ulcers, subacute cutaneous or discoid lupus erythematosus,⁵ and acute cutaneous lupus erythematosus, with acute cutaneous lupus erythematosus being the highest-weighted criterion in that domain. The other clinical domains are constitutional, hematologic, neuropsychiatric, serosal, musculoskeletal, renal, antiphosopholipid antibodies, complement proteins, and SLE-specific antibodies.^3,4

The malar (“butterfly”) rash of SLE characteristically includes erythema that spares the nasolabial folds but affects the nasal bridge and cheeks.⁶ The rash occasionally may be pruritic and painful, lasting days to weeks. Photosensitivity occurs, resulting in rashes or even an overall worsening of SLE symptoms. In those with darker skin tones, erythema may appear violaceous or may not be as readily appreciated.⁶

Worth noting

• Patients with skin of color are at an increased risk for postinflammatory hypopigmentation and hyperpigmentation (pigment alteration), hypertrophic scars, and keloids.^7,8

• The mortality rate for those with SLE is high despite early recognition and treatment when compared to the general population.^1,9

Health disparity highlight

Those at greatest risk for death from SLE in the United States are those of African descent, Hispanic individuals, men, and those with low socioeconomic status,⁹ which likely is primarily driven by social determinants of health instead of genetic patterns. Income level, educational attainment, insurance status, and environmental factors¹⁰ have far-reaching effects, negatively impacting quality of life and even mortality.

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵