IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial.

Toll-like receptor-driven and interleukin-1 (IL-1) receptor-driven inflammation mediated by IL-1 receptor-associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600-1,600 mg and after 14 daily doses of ≥95% at 50-200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885 .

Langerhans Cell Histiocytosis Presenting With Clinical Features of Hidradenitis Suppurativa.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease of myeloid dendritic cells with a widely variable presentation of organ system involvement and severity. In this case report, we share the details of a rare case of cutaneous LCH resembling hidradenitis suppurativa (HS).

Associations between household income and disordered eating differ across sex and racial identity in a population-based sample of adults.

BACKGROUND: Most research on socioeconomic status (SES) and eating disorders (EDs) has focused on young White women. Consequently, little is known regarding how SES may relate to EDs/disordered eating in older adults, men, or people with different racial identities. We examined whether associations between SES and EDs/disordered eating differed across age, sex, and racial identity in a large, population-based sample spanning early-to-later adulthood. METHODS: Analyses included 2797 women and 2781 men ages 18-65 (Mage = 37.41, SD = 7.38) from the population-based Michigan State University Twin Registry. We first examined associations between SES and dimensional ED symptoms, binge eating (BE), and self-reported ED diagnoses across age and sex in the full sample. We then examined the impact of racial identity on associations by conducting within- and between-group analyses among Black and White participants. RESULTS: In the full sample, lower SES was associated with significantly greater odds of BE and lifetime EDs in men, but not women, across adulthood. The association between lower SES and greater BE risk was stronger for Black men than for White men, though significant in both groups. Conversely, Black women showed a positive association between SES and dimensional ED symptoms that significantly differed from effects for Black men and White women. CONCLUSIONS: Associations between socioeconomic disadvantage and EDs/disordered eating may be particularly robust for men in adulthood, especially men with a marginalized racial identity. Oppositely, Black women may encounter social pressures and minority stress in higher SES environments that could contribute to somewhat heightened ED risk. PUBLIC SIGNIFICANCE: Little is known regarding how associations between socioeconomic status (SES) and eating disorders (EDs) may differ across age/sex or racial identity. We found lower SES was associated with greater odds of a lifetime ED or binge eating in men only, with a particularly strong association between lower SES and binge eating for Black men. Results highlight the importance of examining how SES-ED associations may differ across other aspects of identity.

Diversity and Career Goals of Graduating Allopathic Medical Students Pursuing Careers in Dermatology.

Importance: Dermatology is one of the least diverse specialties, while patients from minority racial and ethnic groups and other underserved populations continue to face numerous dermatology-specific health and health care access disparities in the US. Objectives: To examine the demographic characteristics and intended career goals of graduating US allopathic medical students pursuing careers in dermatology compared with those pursuing other specialties and whether these differ by sex, race and ethnicity, and/or sexual orientation. Design, Setting, and Participants: This secondary analysis of a repeated cross-sectional study included 58 077 graduating allopathic medical students using data from the 2016 to 2019 Association of American Medical Colleges Graduation Questionnaires. Main Outcomes and Measures: The proportion of female students, students from racial and ethnic groups underrepresented in medicine (URM), and sexual minority (SM) students pursuing dermatology vs pursuing other specialties. The proportions and multivariable-adjusted odds of intended career goals between students pursuing dermatology and those pursuing other specialties and by sex, race and ethnicity, and sexual orientation among students pursuing dermatology. Results: A total of 58 077 graduating students were included, with 28 489 (49.0%) female students, 8447 (14.5%) URM students, and 3641 (6.3%) SM students. Female students pursuing dermatology were less likely than female students pursuing other specialties to identify as URM (96 of 829 [11.6%] vs 4760 of 27 660 [17.2%]; P < .001) or SM (16 [1.9%] vs 1564 [5.7%]; P < .001). In multivariable-adjusted analyses, students pursuing dermatology compared with other specialties had decreased odds of intending to care for underserved populations (247 of 1350 [18.3%] vs 19 142 of 56 343 [34.0%]; adjusted odd ratio [aOR], 0.40; 95% CI, 0.35-0.47; P < .001), practice in underserved areas (172 [12.7%] vs 14 570 [25.9%]; aOR, 0.40; 95% CI, 0.34-0.47; P < .001), and practice public health (230 [17.0%] vs 17 028 [30.2%]; aOR, 0.44; 95% CI, 0.38-0.51; P < .001) but increased odds of pursuing research (874 [64.7%] vs 29 121 [51.7%]; aOR, 1.76; 95% CI, 1.57-1.97; P < .001) in their careers. Among students pursuing dermatology, female, URM, and SM identities were independently associated with increased odds of caring for underserved populations (eg, URM: aOR, 4.05; 95% CI, 2.83-5.80) and practicing public health (eg, SM: aOR, 2.55; 95% CI, 1.51-4.31). URM students compared with non-URM students pursuing dermatology had increased odds of intending to practice in underserved areas (aOR, 3.93; 95% CI, 2.66-5.80), and SM students compared with heterosexual students pursuing dermatology had increased odds of intending to become medical school faculty (aOR, 1.60; 95% CI, 1.01-2.57), to pursue administrative roles (aOR, 1.60; 95% CI, 1.01-2.59), and to conduct research (aOR, 1.73; 95% CI, 1.01-2.98). Conclusions and Relevance: The findings of this cross-sectional study suggest that diversity gaps continue to exist in the dermatology workforce pipeline. Efforts are needed to increase racial and ethnic and sexual orientation diversity and interest in careers focused on underserved care and public health among students pursuing dermatology.

A cotwin control study of associations between financial hardship and binge eating phenotypes during COVID-19.

BACKGROUND: COVID-19 was associated with significant financial hardship and increased binge eating (BE). However, it is largely unknown whether financial stressors contributed to BE during the pandemic. We used a longitudinal, cotwin control design that controls for genetic/environmental confounds by comparing twins in the same family to examine whether financial hardship during COVID-19 was associated with BE. METHODS: Female twins (N = 158; Mage  = 22.13) from the Michigan State University Twin Registry rated financial stressors (e.g., inability to afford necessities) daily for 49 consecutive days during COVID-19. We first examined whether financial hardship was associated with BE phenotypes across the full sample. We then examined whether cotwins who differed on financial hardship also differed in BE. RESULTS: Participants who experienced greater mean financial hardship across the study had significantly greater dimensional BE symptoms, and participants who experienced greater financial hardship on a given day reported significantly more emotional eating that day. These results were replicated in cotwin control analyses. Twins who experienced more financial hardship than their cotwin across the study reported greater dimensional BE symptoms than their cotwin, and participants who experienced more financial hardship than their cotwin on a given day reported greater emotional eating that day. Results were identical when restricting analyses to monozygotic twins, suggesting associations were not due to genetic confounds. CONCLUSIONS: Results suggest that BE-related symptoms may be elevated in women who experienced financial hardship during COVID-19 independent of potential genetic/environmental confounds. However, additional research in larger samples is needed. PUBLIC SIGNIFICANCE: Little is known regarding how financial difficulties during the COVID-19 pandemic may have contributed to increased binge eating (BE). We found preliminary evidence that financial hardship during COVID-19 may be associated with greater rates of BE-related symptoms even when comparing twins from the same family. While additional research is needed, results suggest that people who experienced financial hardship during COVID-19 may be at increased risk for BE.

Cross-Cultural Comparisons in Implicit and Explicit Age Bias.

Most research documenting bias against older adults has been conducted in individualistic and industrialized cultures. In the current study, we examined cultural variation in attitudes toward older adults and subjective age in a large sample of 911,982 participants (Mage = 27.42, SD = 12.23; 67.6% women) from 68 different countries (Msize = 12,077; Mdnsize = 425.5). We hypothesized that age bias would be lower among those living in highly collectivistic countries. We found that living in collectivistic countries was associated with less implicit and explicit age bias, and greater feelings of warmth toward older adults compared with highly individualistic countries. Given the impact of age bias and prejudice on both the targets and perpetrators of bias, further research is needed to examine the causes of and interventions for bias against older adults.

Acute generalized exanthematous pustulosis and Stevens-Johnson syndrome overlap due to hydroxychloroquine: a case report.

BACKGROUND: Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. CASE PRESENTATION: A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme-like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient's rash ultimately resolved, as did her cutaneous pain and pruritus. CONCLUSIONS: Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.

Individual differences in personality predict the use and perceived effectiveness of essential oils.

Essential oil (EO) use is growing in popularity and ostensibly used for treating or preventing various ailments or conditions. Despite the increase in use, there is a paucity of research on psychosocial predictors of EO use and their perceived effectiveness. However, several psychosocial characteristics are associated with health-promoting behavior and a tendency to believe in homeopathic cures. In the current study, we examined a variety of individual differences in the use and perceived effectiveness of essential oils in a sample of 1,202 participants (Mage = 31.33, SD = 13.77; 61.7% women, 75.6% Caucasian). We found that receptivity to pseudo-profound fabricated statements and religiosity were the most consistent predictors of greater use of, perceived effectiveness of, and a willingness to spend more money on EOs.

Coccidioidomycosis.

A 23-year-old man presented with new-onset pruritic and painful urticarial lesions and targetoid erythematous plaques on both palms, the trunk, and the upper and lower extremities (Figure 1). Additionally, small pustules were discovered on the neck (Figure 2), and there with edematous erythematous vermillion lips with splaying onto the cutaneous lips without ulceration. The patient stated he had had a fever before the eruption, fatigue, chills, myalgias, and sore throat. A chest x-ray was obtained and showed bilateral infiltrates. Two 4-mm punch biopsies were performed on the left forearm and left side of the neck; a resulting section from the left forearm is shown in Figure 3.

The efficient, effective community hospital inpatient dermatology consult.

Hospital dermatology is often thought to be too cumbersome for the private practicing dermatologist to handle, leaving patients in our communities without needed care and our medical colleagues in the dark when it comes to diagnosing and/or managing skin disease in the hospitalized patient. This notion that "someone else will figure it out" undervalues our expertise as a specialty and threatens the appropriate health outcomes we knowingly understand patients deserve. In this manuscript, we intend to break down the hospital consult conceptually so as to make clear how simple it can be to help our physician colleagues and make an important impact upon patients at their most vulnerable time.

Flagellate shiitake mushroom dermatitis.

An 84-year-old woman presented with 5 days of a pruritic skin eruption that formed arciform and linear patterns. She was diagnosed with flagellate shiitake mushroom dermatitis related to shiitake mushroom consumption the day prior symptom onset.

Sex hormones and the genesis of autoimmunity.

BACKGROUND: The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation. OBSERVATIONS: English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of "lupus-prone" mice are readily available. CONCLUSIONS: Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae.