Cutaneous findings and treatments in deficiency of interleukin-36 receptor antagonist (DITRA): A review of the literature.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

Pyoderma gangrenosum and impact on quality of life: A narrative review.

Pyoderma gangrenosum (PG) is an autoinflammatory disorder typically characterized by progressive ulcers with dense neutrophilic infiltrates in the absence of infectious causes. The chronic nature of this disease significantly impacts the patients' quality of life (QoL). Yet there is currently a dearth of information in the literature regarding standardised treatment guidelines and the impact of PG on patients' QoL. We conducted a literature search on PubMed using the terms "pyoderma gangrenosum" AND "quality of life." We identified nine relevant articles that provide insight into which domains are affected and what treatment can improve QoL. The most common domains involved are physical, emotional, and psychological. Patients tend to feel depressed/anxious, isolated, and embarrassed secondary to PG manifestations. Comorbidities such as Crohn's disease, monoclonal gammopathy of dermatologic significance, and ulcerative colitis can worsen the impact on these patients' QoL. Pain is also a significant contributor to decreasing patients' QoL. Treatments such as topical steroids, adalimumab, and canakinumab may help improve QoL scores. We believe this information can help clinicians guide the care of patients with PG and highlight the need for more studies and clinical trials focusing on PG treatments' impact on QoL.

Generalized pustular psoriasis-like widespread eruption following COVID-19 infection in a patient with spondyloarthropathy on adalimumab.

Generalized pustular psoriasis (GPP) is a form of pustular psoriasis that is distinguished by recurring or persistent outbreaks of non-acral primary sterile pustules. These eruptions can occur with or without systemic inflammation. Various factors, such as medications, stress and viral infection, have been identified as potential triggers for GPP flares. While several cases have detailed GPP-like eruptions in the setting of coronavirus disease 2019 (COVID-19) infection, few have explored the interplay between infection and biologic use in the development of GPP. In this case, we detail the history and management of a 45-year-old male patient with a prior history of spondyloarthropathy managed on a tumour necrosis factor-α inhibitor and recent COVID-19 infection presenting with a new, spreading pustular rash.

VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a novel autoinflammatory, late-onset, disorder first identified in 2020. It is caused by mutations in the UBA1 gene. The most prominent clinical features reported by VEXAS patients are cutaneous and haematological, having characteristic skin features reported as the initial presenting findings of the disease. VEXAS is a severe and treatment-resistant condition with high morbidity and mortality rates. Here, we examine all case reports and case series of VEXAS syndrome through March 2023 focusing on those presenting cutaneous manifestations. We discuss these manifestations and their reported treatment strategies. In many cases, it might be first suspected and diagnosed by dermatologists, highlighting their vital role in initiating timely multidisciplinary care.

A focused review of visible light therapies for vitiligo.

BACKGROUND: Vitiligo can be challenging to treat and exhibit an unpredictable clinical course. Phototherapy in the form of visible light can achieve both repigmentation and depigmentation outcomes in vitiligo, with minimal associated adverse events. This review focuses on the mechanistic understandings and clinical outcomes of visible light-based treatments for vitiligo. METHODS: Articles were retrieved from PubMed starting from May 1965 until August 2023, yielding 496 unique articles. We conducted title, abstract, and full-text screening to identify articles describing the use of visible light (380-750 nm), either as part of combination therapy or as monotherapy, for repigmentation or depigmentation treatment in vitiligo. RESULTS: Twenty-seven articles met inclusion criteria, offering preclinical and clinical data regarding the utilization of helium-neon laser (red light) and blue light-emitting diodes (LEDs) as methods of repigmentation therapy in vitiligo. Preclinical and clinical data on the utilization of Q-switched ruby laser (694 nm) and frequency-doubled (FD) Nd:YAG laser (532 nm) for vitiligo depigmentation therapy were also identified. CONCLUSION: While limited by small studies and a lack of standardized administration of phototherapy, the evidence for visible light's effectiveness in managing vitiligo is encouraging. Red light therapy using He-Ne lasers and blue light therapy via LEDs can stimulate repigmentation in patients with vitiligo with minimal adverse events. Q-switched ruby and FD Nd:YAG lasers provide viable, visible light depigmentation options, either alone or with topical agents. With limited clinical data, larger studies are needed to validate the efficacy of visible light therapy in treating vitiligo and to better understand its long-term outcomes.

Phototherapy for vitiligo: Quality and readability of online health information.

BACKGROUND/PURPOSE: Vitiligo is a depigmenting disorder that affects up to 2% of the population. Due to the relatively high prevalence of this disease and its psychological impact on patients, decisions concerning treatment can be difficult. As patients increasingly seek health information online, the caliber of online health information (OHI) becomes crucial in patients' decisions regarding their care. We aimed to assess the quality and readability of OHI regarding phototherapy in the management of vitiligo. METHODS: Similar to previously published studies assessing OHI, we used 5 medical search terms as a proxy for online searches made by patients. Results for each search term were assessed using an enhanced DISCERN analysis, Health On the Net code of conduct (HONcode) accreditation guidelines, and several readability indices. The DISCERN analysis is a validated questionnaire used to assess the quality of OHI, while HONcode accreditation is a marker of site reliability. RESULTS: Of the 500 websites evaluated, 174 were HONcode-accredited (35%). Mean DISCERN scores for all websites were 58.9% and 51.7% for website reliability and treatment sections, respectively. Additionally, 0/130 websites analyzed for readability scored at the NIH-recommended sixth-grade reading level. CONCLUSION: These analyses shed light on the shortcomings of OHI regarding phototherapy treatment for vitiligo, which could exacerbate disparities for patients who are already at higher risk of worse health outcomes.

Generalized pustular psoriasis: Quality and readability of online health information.

Generalized pustular psoriasis (GPP) is a multisystem disease with potentially life-threatening adverse effects. As patients increasingly seek health information online, and as the landscape for GPP changes, the quality of online health information (OHI) becomes progressively more important. This paper is the first of its kind to examine the quality, comprehensiveness and readability of online health information for GPP. Similar to pre-existing studies evaluating OHI, this paper examines 5 key search terms for GPP- 3 medical and 2 laymen. For each search term, the results were evaluated based on HONcode accreditation, an enhanced DISCERN analysis and a number of readability indices. Of the 500 websites evaluated, 84 (16.8%) were HONcode-accredited. Mean DISCERN scores of all websites were 74.9% and 38.6% for website reliability and treatment sections, respectively, demonstrating key gaps in comprehensiveness and reliability of GPP-specific OHI. Additionally, only 4/100 websites (4%) analysed for readability were written at the NIH-recommended sixth-grade level. Academic websites were significantly more difficult to read than governmental websites. This further exacerbates the patient information gap, particularly for patients with low health literacy, who may already be at higher risk of not receiving timely medical care.

A narrative review of studies assessing the quality of life in patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a clinical entity distinct from psoriasis, associated with a poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients' quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: 'generalized pustular psoriasis' OR 'pustular psoriasis' AND 'quality of life'. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient's perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.

Relatlimab-nivolumab: A practical overview for dermatologists.

BACKGROUND: Relatlimab is a human anti-lymphocyte activation gene 3 protein antibody approved for the treatment of metastatic or unresectable melanoma in combination with nivolumab, an existing programmed cell death protein 1 inhibitor. OBJECTIVE: In this article, we review the clinical literature on the efficacy and therapeutic use of the immune checkpoint inhibitor relatlimab in combination with nivolumab for metastatic melanoma. METHODS: We provide an overview of the mechanism of action, clinical efficacy, and safety profile of relatlimab-nivolumab through a review of recent publications on this emerging therapeutic combination. Ongoing clinical trials studying the use of relatlimab and associated areas of active investigation are also highlighted. CONCLUSION: This review strives to inform practicing dermatologists on the use of relatlimab-nivolumab as an approved first-line dual checkpoint inhibitor for metastatic melanoma in appropriate clinical cases.

Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort.

BACKGROUND: Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS). OBJECTIVE: Identify clinical factors associated with development of skin neoplasms in LS. METHODS: Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020. Multivariable logistic regression was performed to evaluate clinical factors associated with skin neoplasia. RESULTS: Of 607 LS carriers, 9.2% had LS-associated skin neoplasia and 15.0% had non-LS-associated skin neoplasia; 58.2% (353/607) had documentation of prior dermatologic evaluation; 29.7% (38/128) with skin neoplasms lacked a history of visceral LS-associated malignancy. LS-associated skin neoplasms were significantly associated with male sex, age, race, MLH1 pathogenic germline variants, MSH2/EPCAM pathogenic germline variants, and personal history of non-LS skin neoplasms. Non-LS-associated skin neoplasms was significantly associated with age, number of first- and second-degree relatives with non-LS-associated skin neoplasms, and personal history of LS-associated skin neoplasms. LIMITATIONS: Single-institution observational study; demographic homogeneity. CONCLUSIONS: Skin neoplasms are common in individuals with LS. We identified clinical factors associated with LS- and non-LS-associated skin neoplasms. Regular dermatologic surveillance should be considered for all LS carriers.

Mental health burden of patients with activity-limiting skin conditions: a national analysis.

Cutaneous diseases are the fourth leading cause of nonfatal disease burden globally. In this study, we aimed to investigate the psychological symptom burden in patients with chronic activity-limiting cutaneous diseases. Our findings suggest that this patient population experience a wide range of interference with their daily lives and exhibit higher psychological burdens and lower quality of life. This study also identified that patients with activity-limiting skin conditions do not seem to seek more professional help or take more medications, which may suggest a potential gap in adequate mental health support and resources.

A review of ethnomedicinal uses of shea butter for dermatoses in Sub-Saharan Africa.

Indigenous therapies, or traditional medicines (TMs), constitute a highly accessible and continuously growing health system in many parts of the world, including Sub-Saharan Africa (SSA). Shea butter, a fat produced from the kernels of the shea tree, has historically been used as an indigenous therapy for dermatologic ailments in SSA. Characterizing traditional therapeutic applications for shea butter is important to inform the continued development of TM in SSA. We conducted a literature review aimed at identifying all available publications on the use of shea butter to treat dermatoses within SSA and evaluating patterns of use. We found 24 dermatologic uses across 30 references. The most common study design was descriptive cross-sectional analysis (46.7%), often relying on the use of in-depth interviews, focus groups, and surveys. Eight SSA countries were represented and there were disparities in availability of information across SSA with the eastern and southern regions less likely to be represented. The most frequently investigated conditions were scabies, wound healing, and umbilical cord care. Shea butter was most commonly used in combination with other ingredients to produce a medical treatment with the most frequent adjuvant being Elaeis guineensis, African oil palm. Broad use of TM to treat varied skin diseases throughout SSA warrants increased investigations into this field in order to further develop the capacity of TM as a source of healthcare.

Characterization of intravascular papillary endothelial hyperplasia: a multicentre cohort.

Intravascular papillary endothelial hyperplasia (IPEH) is an uncommon benign malformation of the skin and subcutaneous tissue. In this retrospective multicentre study, we aimed to investigate the clinical and pathological features of 261 patients with IPEH. IPEH is classified into three categories; in our study, the proportions were pure (50%), mixed (46%) and extravascular (4%). IPEH frequently stained positive for immunohistochemical markers such as CD31, CD34, smooth muscle actin and erythroblast transformation-specific-related gene. Clinicians' initial impression of the lesion often included ambiguous terms such as 'soft tissue mass'. There is an opportunity for increased awareness of this lesion and its consideration within a differential diagnosis.

Medical chart validation of inpatient diagnosis codes for transfusion-related acute lung injury 2013-2015.

INTRODUCTION: Transfusion-related acute lung injury (TRALI), an adverse event occurring during or within 6 hours of transfusion, is a leading cause of transfusion-associated fatalities reported to the US Food and Drug Administration. There is limited information on the validity of diagnosis codes for TRALI recorded in inpatient electronic medical records (EMRs). STUDY DESIGNS AND METHODS: We conducted a validation study to establish the positive predictive value (PPV) of TRALI International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes recorded within a large hospital system between 2013 and 2015. A physician with critical care expertise confirmed the TRALI diagnosis. As TRALI is likely underdiagnosed, we used the specific code (518.7), and codes for respiratory failure (518.82) in combination with transfusion reaction (999.80, 999.89, E934.7). RESULTS: Among almost four million inpatient stays, we identified 208 potential TRALI cases with ICD-9-CM codes and reviewed 195 medical records; 68 (35%) met clinical definitions for TRALI (26 [38%] definitive, 15 [22%] possible, 27 [40%] delayed). Overall, the PPV for all inpatient TRALI diagnoses was 35% (95% confidence interval (CI), 28-42). The PPV for the TRALI-specific code was 44% (95% CI, 35-54). CONCLUSION: We observed low PPVs (<50%) for TRALI ICD-9-CM diagnosis codes as validated by medical charts, which may relate to inconsistent code use, incomplete medical records, or other factors. Future studies using TRALI diagnosis codes in EMR databases may consider confirming diagnoses with medical records, assessing TRALI ICD, Tenth Revision, Clinical Modification codes, or exploring alternative ways for of accurately identifying TRALI in EMR databases. KEY POINTS: In 169 hospitals, we identified 208 potential TRALI cases, reviewed 195 charts, and confirmed 68 (35%) cases met TRALI clinical definitions. As many potential TRALI cases identified with diagnosis codes did not meet clinical definitions, medical record confirmation may be prudent.

The CROWN act and dermatology: Taking a stand against race-based hair discrimination.

Race-based hair discrimination continues to disadvantage people of color who have been sent home from school or dismissed from their jobs on the premise that certain hairstyles, such as dreadlocks and knots, do not meet standards of professionalism. The Create a Respectful and Open World for Natural Hair (CROWN) Act, which was recently passed by several states and the House of Representatives, prohibits such discrimination based on a person's hair texture or hairstyle associated with race. Dermatologists serve a vital role in advocating for the skin and hair needs of all patients, spanning from the personal or clinical encounters level to population-level policy legislation. The act represents a critical opportunity for dermatologists to coalesce and support this important piece of legislation that defends skin of color and the fundamental human right to nondiscrimination.

Characterizing Dermatology Interest Groups (DIGs) in US Medical Schools: A Nationwide Survey of Student Leaders.

BACKGROUND: Dermatology is among the least racially/ethnically diverse medical specialties in the US Dermatology Interest Groups (DIGs). DIGs may play a critical role in addressing these disparities by facilitating early exposure and mentorship, both associated with higher rates of medical students pursuing specific fields. OBJECTIVE: This study sought to characterize the activities, goals, and challenges of DIGs in medical schools nationwide. METHODS: A 15-question survey was distributed electronically to 92 DIG leaders enrolled in four-year accredited allopathic/osteopathic medical schools nationwide. Data collected included DIG leaders’ demographic information, medical training stage, DIG size/age, number/type of DIG activities hosted, presence of faculty/resident mentors, and goals/challenges. RESULTS: There were 48 total and 46 complete responses (52% response rate). Most DIG leaders were female (81%), white (63%), and from allopathic medical schools of roughly equal geographic distribution. Over three-quarters of DIGs had affiliated dermatology departments and residencies. Most had faculty advisors; few had resident mentors. Presence of an affiliated dermatology department was associated with statistically significant increase in mentoring opportunities (P=0.034), significantly increased odds of having dedicated faculty mentors (OR=6.10, 95%CI 1.11–33.56), and non-significantly increased odds of having dedicated resident mentors (OR=2.96, 95%CI 0.33–26.79). DIG leaders self-identified early dermatology exposure, aiding in the match, relationship-building, and community engagement as main objectives and mismatches in opportunities, time, funding, and interest as main challenges. CONCLUSIONS: DIGs provide valuable opportunities to medical students exploring the field and may play a role in reducing future dermatology workforce disparities. Dermatology departments, residencies, and medical schools should support their aims and reduce structural barriers to success. J Drugs Dermatol. 2021;20(7):767-770. doi:10.36849/JDD.5732.

Access as equity: Addressing the distribution of the pediatric dermatology workforce.

While overall shortages in the pediatric dermatologist workforce have been well-documented, recent evidence indicates a geographic maldistribution of providers, which can further exacerbate health disparities for children. Wide geographic gaps in access to pediatric care constitute a critical public health issue and impede upon a child's right to access care. In this review, we examine the issue of geographic maldistribution of pediatric dermatologists through the lens of health equity: describing the problem, exploring the enablers of and barriers to change, and offering potential solutions.

Expanding the palette of pediatric playthings: A call to action for pediatric dermatologists.

Children recognize race and skin color from a young age. Given the important role of play in the development of children's understanding of social norms and cultural values, it is essential to incorporate toys and other educational materials with diverse skin tones to teach children about race and skin color. Analyses of children's books and toys have shown a lack of diversity in representation of races and skin types. Pediatric dermatologists are uniquely positioned to foster conversations about skin tone and advocating for more diverse materials in classrooms and clinics. In this manuscript, we discuss best practices and resources for facilitating discussions on skin tone with children in the dermatology clinic.

Differences in Utilization of Nonvideo Telemedicine Visits for Dermatologic Concerns in Underserved Populations During the COVID-19 Pandemic.

Background: Usage of telemedicine for virtual dermatology care during the COVID-19 pandemic on a national scale is poorly characterized, particularly for nonvideo encounters. Objective: We sought to compare utilization of telephone and asynchronous virtual care for dermatologic concerns 3 months before (December 2019-February 2020) and during the pandemic (March-May 2020) across patient populations. Methods: A retrospective study was performed using a national claims database with >280 million patients within the COVID-19 Research Database to identify monthly telephone and asynchronous virtual visits by diagnosis, age, income, and patient race/ethnicity. Results: Although overall visits for dermatologic concerns decreased by 27.2% during the pandemic, telephone and asynchronous visits increased significantly. Patients most likely to use telephone visits during the pandemic were of older age (relative risk ratio [RRR] = 1.043, p < 0.001), African American race (RRR = 2.03, p < 0.001), and household income <$29,000 (RRR = 1.51, p < 0.001). Limitations: Racial and ethnic data were available for 39.04% of patients and income data for 38.1% of patients. Conclusions: Underserved populations including African Americans, elderly, and low-income patients were more likely to utilize telephone formats during the pandemic. Further studies are needed to determine the reasons for these observed differences and whether there is differential quality between nonvideo and video telemedicine encounters to ensure that all patients are given equal access to the highest quality of virtual care.

Demographic and medical school characteristics associated with urban versus rural dermatology practice: A national cross-sectional study.

There are significant disparities in access to dermatologists in rural areas relative to urban areas. We examined the associations between demographic and medical school characteristics and entry into dermatology practice in urban versus rural counties. All dermatologists who graduated from U.S. allopathic or osteopathic medical schools in the 2020 Centers for Medicare & Medicaid Services Physician Compare Database were assessed. Dermatology practice locations were coded as metropolitan or non-metropolitan according to the Rural-Urban Continuum Codes. Of 10,076 dermatologists, 543 (5.4%) practiced in non-metropolitan counties. Male gender (odds ratio [OR] 1.48, 95% CI 1.23-1.77), public medical school attendance (OR 1.94, 95% CI 1.61-2.34), DO degree (OR 1.84, 95% CI 1.32-2.51), medical school location in a non-metropolitan county (OR 5.41, 95% CI 3.66-7.84), and medical school rural track program (OR 1.57, 95% CI 1.07-2.26) were associated with higher odds of non-metropolitan dermatology practice. Our findings highlight that male gender, graduation from a non-metropolitan or public medical school, DO degree, and rural tracks are associated with higher likelihood of non-metropolitan dermatology practice. These results can inform efforts within the field of dermatology to strengthen the rural dermatologist workforce and suggest that rural educational experiences during medical school may increase recruitment of rural dermatologists.