Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Androgenetic alopecia incidence in transgender and gender diverse populations: A retrospective comparative cohort study.

BACKGROUND: Androgenetic alopecia (AGA) is a significant challenge for many transgender and gender diverse (TGD) patients, but the rate of AGA among TGD patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients has not yet been studied on a large scale. OBJECTIVE: We examined the incidence of AGA among TGD patients receiving GAHT compared to cisgender patients. METHODS: Retrospective cohort study using electronic health records from 37,826 patients seen at Fenway Health between August 1, 2014, and August 1, 2020. Crude and adjusted incidence rate ratios (aIRR) for AGA were calculated using Poisson regression. RESULTS: TGD patients receiving masculinizing GAHT had aIRR 2.50, 95% CI 1.71-3.65 and 1.30, 95% CI 0.91-1.86 compared to cisgender women and cisgender men, respectively. The rate of AGA for TGD patients receiving feminizing GAHT was not significantly different compared to cisgender men but was significantly increased compared to cisgender women (aIRR 1.91, 95% CI 1.25-2.92). LIMITATIONS: Inability to determine causation and limited generalizability. CONCLUSION: TGD patients receiving masculinizing GAHT have 2.5 times the rate of AGA compared to cisgender women, whereas TGD patients on feminizing GAHT did not have a significantly increased rate of AGA compared to cisgender men.

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2-Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments.

OBJECTIVE: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. STUDY DESIGN: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. RESULTS: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is variable in quality and/or quantity. CONCLUSIONS: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1.

OBJECTIVE: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted. RESULTS: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is limited in quality. CONCLUSION: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge.

Drug utilization patterns and adherence in patients on systemic medications for the treatment of psoriasis: A retrospective, comparative cohort study.

BACKGROUND: Nonadherence to systemic treatments for psoriasis leads to treatment failure and increased health care utilization. OBJECTIVE: Examine drug utilization patterns and adherence of new users of systemic medications for psoriasis. METHODS: We conducted a retrospective, comparative cohort study using a large US health insurance claims database including psoriasis patients who were new users of acitretin, adalimumab, etanercept, methotrexate, or ustekinumab. Adherence was measured by using proportion of days covered dichotomized as adherent (≥0.80) or nonadherent (<0.80). Odds ratios (ORs) and 95% confidence intervals (CIs) comparing adherence to each exposure (acitretin, adalimumab, etanercept, or ustekinumab) to the referent (methotrexate) were estimated via logistic regression, with pairwise 1:1 propensity score matching to adjust for potential confounders. RESULTS: In total, 22,742 patients were new users of systemic medications. Among these patients, adherence to adalimumab (OR 2.24, 95% CI 2.05-2.45); etanercept (OR 1.77, 95% CI 1.63-1.92); and ustekinumab (OR 2.54, 95% CI 2.24-2.87) was greater and acitretin (OR 0.57, 95% CI 0.50-0.63) lower compared with methotrexate. LIMITATIONS: Unable to evaluate reasons for discontinuation. CONCLUSION: We report greater adherence to biologics than methotrexate in new users. Further research is needed to understand overall low adherence to systemic medications for psoriasis.

Isotretinoin for Acne in Transgender and Gender-Diverse Individuals Receiving Masculinizing Hormone Therapy.

Importance: Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Objective: To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Design, Setting, and Participants: This multicenter retrospective case series study was conducted at 4 medical centers: Mass General Brigham, University of Pennsylvania, Emory University, and Fenway Health. It included patients aged between 12 and 49 years who were receiving masculinizing gender-affirming hormonal therapy and prescribed isotretinoin for the management of acne between August 14, 2015, and September 20, 2023. Exposure: Isotretinoin therapy for the management of acne. Main Outcomes and Measures: The percentage of patients experiencing improvement or clearance of acne, as well as rates of acne recurrence. Adverse effects and reasons for treatment discontinuation were also evaluated. Results: Among 55 included patients, the mean (SD) age was 25.4 years; 4 (7.3%) were Asian, 2 (3.6%) were Black, 4 (7.2%) were Hispanic, 1 was (1.8%) multiracial, and 36 (65.5%) were White. The median isotretinoin course duration was 6 months (IQR, 4.0-8.0), with a median cumulative dose of 132.7 mg/kg (IQR, 66.4-168.5); the cumulative dose was less than 90 mg/kg for 16 patients (29.1%) and less than 120 mg/kg for 22 patients (40.0%). Isotretinoin was associated with improvement in 48 patients (87.3%) and clearance in 26 patients (47.3%). For the 33 patients treated with a cumulative dose of 120 mg/kg or more, these rates increased to 32 patients (97.0%) and 21 patients (63.6%), respectively. Among the 20 patients who achieved acne clearance and had any subsequent health care encounters, the risk of recurrence was 20.0% (n = 4). The most frequently reported adverse effects were dryness (n = 44; 80.0%), joint pain (n = 8; 14.5%), and eczema (n = 5; 9.1%). Laboratory abnormalities were uncommon. Reasons for premature treatment discontinuation included cost, pharmacy issues, adverse effects, logistical reasons (scheduling), and wound healing concerns for gender-affirming surgery. Conclusion and Relevance: In this case series study of individuals with acne who were receiving masculinizing gender-affirming hormonal therapy and underwent isotretinoin treatment, isotretinoin was often effective and well tolerated. However, premature treatment discontinuation was common and associated with poorer outcomes. Further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving masculinizing gender-affirming hormonal therapy.

Product of the Physician Global Assessment and body surface area: a simple static measure of psoriasis severity in a longitudinal cohort.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is considered the gold standard assessment tool for psoriasis severity, but PASI is limited by its complexity and insensitivity in people with mild psoriasis. OBJECTIVE: We sought to evaluate the product of a Physician Global Assessment (PGA) and Body Surface Area (BSA) (PGAxBSA) as an alternative to PASI. METHODS: Psoriasis severity was evaluated at 6-month intervals in participants of the Utah Psoriasis Initiative registry. Correlation coefficients were used to compare PGAxBSA with PASI and the Simplified PASI (SPASI). RESULTS: Between August 2008 and November 2010, 435 assessments were completed in 226 participants. The median PASI score was 3.2 (interquartile range 1.8-5.4) and the median BSA was 3.0% (interquartile range 1.0%-5.0%). PGAxBSA had higher correlations with PASI than SPASI (0.87 vs 0.76, P < .001). PGAxBSA also had higher correlations with a Global Patient Assessment of psoriasis severity (0.65) than both PASI (0.59, P < .001) and SPASI (0.51, P < .001). LIMITATIONS: The use of PGAxBSA for measuring severe psoriasis and response to therapy is unclear, because most participants had mild to moderate psoriasis and data were not collected at predefined intervals in relation to therapy initiation. Interrater reliability was not assessed. CONCLUSIONS: PGAxBSA is a simple and sensitive instrument for measuring psoriasis severity.

Beliefs and counseling practices among dermatologists regarding sexual and other adverse effects of finasteride.

Finasteride may cause low libido and erectile dysfunction and the product label of finasteride also includes post-marketing reactions of sexual dysfunction that continued after discontinuation of treatment, as well as male infertility and depression. The aim of this study was to evaluate the beliefs and counseling practices among dermatologists regarding adverse effects of finasteride. Anonymous paper surveys were personally distributed to 122 attendees at two annual major dermatology meetings. The participation rate was 82% with 47% women and 77% residents of the United States. 51% of respondents believed that finasteride could cause sexual side effects and 18% believed that it could cause persistent sexual side effects. Fewer than a quarter believed that finasteride could cause depression or lower sperm counts. When initiating finasteride, 69% of respondents counseled at least half of their patients about potential sexual side effects with 52% for persistent sexual side effects and 30% for depression. This study identifies the need for greater awareness of the potential adverse effects of finasteride and identifies opportunities for improvement in counseling practices that reflect finasteride's product labeling.

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy. OBJECTIVE: We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease. METHODS: We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of plaque psoriasis and psoriatic arthritis. Twenty of 820 identified studies with a total of 6810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios. RESULTS: Odds ratios for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% confidence interval [CI] 1.05-1.33) and 0.70 (95% CI 0.40-1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI 0.92-1.11). The odds ratio for malignancy was 1.48 (95% CI 0.71-3.09) and 1.26 (95% CI 0.39-4.15) when nonmelanoma skin cancer was excluded. LIMITATIONS: Short duration of follow-up and rarity of malignancies and serious infections are limitations. CONCLUSIONS: There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors.

Incidence and Factors Associated With Acne Among Transgender Patients Receiving Masculinizing Hormone Therapy.

Importance: Acne is a common condition among transgender patients receiving masculinizing hormone therapy (MHT), but the incident risk and predictors of developing acne in this population have not yet been studied on a large scale. Objective: To assess risk of acne among a large population of transgender patients receiving MHT and clinical risk factors for acne diagnosis. Design, Setting, and Participants: A retrospective cohort study that included 988 patients who started MHT between January 1, 2014, and December 31, 2017, with at least 1 year of follow-up was performed. Data analysis was conducted from September 1 to 15, 2019. Data were obtained using electronic health records from a community health center serving the sexual and gender minority community. The population included every patient who began receiving MHT during the study period who was aged 18 years or older at the time of MHT initiation and whose assigned sex at birth was female. Main Outcomes and Measures: The main outcome was acne defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for acne. Overall prevalence and incidence proportions over 2 years after initiation of MHT were calculated. Baseline demographic and clinical characteristics were collected at the time of MHT initiation. A series of univariate analyses for all factors was calculated to test for an association with acne diagnosis, followed by multivariate analyses to test for independent predictors. Results: For 988 patients (median age, 25.8 years; interquartile range, 20.8-28.2 years), there was an overall acne prevalence of 31.1% (n = 307). The 1-year post-MHT acne incidence proportion was 19.0% and the 2-year incidence proportion was 25.1%. A younger age at MHT initiation was associated with a higher likelihood of developing acne, with a median of 22.4 years (interquartile range, 19.7-25.6 years) among patients who developed acne vs 24.7 years (interquartile range, 21.3-29.4 years) among patients who did not (P = .002). Conclusions and Relevance: Acne is a common condition among transgender patients on MHT, with a prevalence increasing from 6.3% to 31.1% following MHT initiation. Patients aged 18 to 21 years appear to be the most likely to develop acne after MHT initiation.

Excess hair, hair removal methods, and barriers to care in gender minority patients: A survey study.

BACKGROUND: In gender minority patients, electrolysis and laser hair removal may be necessary to reduce facial and body hair in individuals seeking a more feminine appearance and/or modified gender expression. These procedures may also be required preoperatively for some gender-affirming surgeries. AIMS: To identify (a) the frequency of unwanted facial and body hair, (b) the use of various hair removal methods, and (c) associated barriers to care in gender minority patients. METHODS: An online-based patient survey was distributed via social media on Facebook® , YouTube® , and Instagram® in fall 2018. Respondents were at least 18 years old and self-identified as a gender minority. RESULTS: In total, 991 responses were recorded with a completion rate of 77%. Considering excess hair, 84% of transwomen on feminizing hormone therapy (FHT: estrogen and anti-androgen therapy), 100% of transwomen not on FHT, and 100% of nonbinary individuals on FHT reported excess facial/body hair. Laser hair removal (18%) and electrolysis (17%) had similar rates of use in this cohort and were more commonly reported for nonsurgical gender-affirming purposes than preoperative preparation. Cost was the most frequently cited barrier to care. CONCLUSION: As the majority of transwomen and nonbinary people on feminizing hormone therapy had persistent excess facial/body hair, routine use of gender-affirming hormones is not sufficient to fully eliminate unwanted hair. There remains a critical need to advocate for more comprehensive insurance coverage for laser hair removal and electrolysis in gender minority patients.

Health Insurance Coverage of Permanent Hair Removal in Transgender and Gender-Minority Patients.

Importance: Hair removal can be an essential component of the gender affirmation process for gender-minority (GM) patients whose outward appearance does not align with their gender identity. Objective: To examine the health insurance policies in the Affordable Care Act (ACA) marketplace and Medicaid policies for coverage of permanent hair removal for transgender and GM patients and to correlate the policies in each state with statewide protections of coverage for gender-affirming care. Design and Setting: Private health insurance policies available on the ACA marketplace and statewide Medicaid policies were examined in a cross-sectional study from September 1 to October 31, 2019, and January 17 to 30, 2020. Policies were assessed for coverage of permanent hair removal. Language concerning hair removal was found in each policy's medical or clinical coverage guidelines and separated into general categories. Main Outcomes and Measures: Logistic regression analyses were performed to compare Medicaid policies and ACA policies in states with and without transgender protections. Results: A total of 174 policies were analyzed, including 123 private insurance policies and 51 statewide Medicaid policies. Of these policies, 8 (4.6%) permitted the coverage of permanent hair removal without explicit restrictions. The remaining 166 policies (95.4%) broadly excluded or did not mention gender-affirming care; prohibited coverage of hair removal or did not mention it; or only permitted coverage of hair removal preoperatively for genital surgery. The ACA marketplace policies in states without transgender care protections were less likely to cover hair removal without restrictions than ACA policies in states with protections (2 of 85 policies [2.4%] in states without transgender care protections vs 5 of 38 policies [13.2%] in states with transgender care protections), and Medicaid policies were less likely to cover preoperative or nonsurgical hair removal compared with ACA policies (6 of 51 Medicaid policies [11.8%] vs 47 of 123 ACA policies [38.2%]). Conclusions and Relevance: Despite adoption of statewide restrictions on GM health care exclusions by several states, most Medicaid and ACA policies examined in this study did not cover permanent hair removal for transgender patients. Many GM patients seeking hair removal may be required to pay out-of-pocket costs, which could be a barrier for gender-affirming care.

A prospective clinical trial of open-label etanercept for the treatment of hidradenitis suppurativa.

BACKGROUND: Medical therapies for hidradenitis suppurativa (HS) are often ineffective. Tumor necrosis factor-alpha inhibitors may be a potential treatment for patients with moderate to severe HS. OBJECTIVES: We sought to evaluate the safety and efficacy of etanercept for patients with severe HS. METHODS: We conducted a phase II clinical trial of etanercept (50 mg/wk subcutaneously) in patients with moderate to severe HS. Efficacy was measured using a Physician Global Assessment and several secondary physician- and patient-reported outcome measures. Responders were classified as those achieving at least a 50% reduction on the Physician Global Assessment score at week 12 compared with baseline. RESULTS: Only 3 of the 15 patients who entered the study were classified as responders (response rate of 20%; 95% confidence interval: 4.3-48.1) based on the intention-to-treat analysis. Dermatology Life Quality Index scores improved slightly from a median of 19 to 15 (P = .02). Comparison of baseline with week-12 Physician Global Assessment scores, and secondary outcome measures of lesion counts and patient pain scores, failed to show statistically significant improvement. Etanercept was generally well tolerated; however, two patients discontinued the study as a result of skin infections at the site of hidradenitis lesions requiring oral antibiotics. LIMITATIONS: Lack of a control group and a small number of participants are limitations. CONCLUSIONS: Our study demonstrated minimal evidence of clinically significant efficacy of etanercept (50 mg/wk subcutaneously) in the treatment of hidradenitis. Future studies using higher doses of etanercept are indicated; however, patients need to be carefully monitored for infection and other adverse events. Randomized, controlled trials will be necessary to demonstrate the risk-to-benefit ratio of tumor necrosis factor-alpha inhibitors in the treatment of hidradenitis.

Is there truly a risk of lymphoma from biologic therapies?

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. Biologics are generally safe and well tolerated. However, there has been concern over the risk of lymphoma with use of these agents because of their immunosuppressive properties. This review summarizes the current evidence in regards to lymphoma risk with biologic therapy obtained from case reports and case series, observational studies, clinical trials, and meta-analyses. The majority of data for T-cell inhibitors comes from case reports and relatively small, short-term clinical trials. In addition to published case reports and case series, TNF-alpha inhibitors have also been studied extensively in large cohort studies and meta-analyses of clinical trials derived primarily from the rheumatoid arthritis population. Current data are neither sufficient to completely rule out an increased risk of lymphoma associated with biologics, nor to firmly establish a causal relationship between biologics and lymphoma. Short- to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be very safe with respect to lymphoma risk, especially with TNF-alpha inhibitors in which their potential risks appear to be well defined. Continued vigilance is warranted; however, in the appropriate patient, the risk-to-benefit profile of psoriasis treatment with respect to lymphoma risk appears highly favorable.

Risk of Serious Infection in Patients Receiving Systemic Medications for the Treatment of Psoriasis.

IMPORTANCE: There is a need for better understanding of the comparative safety of systemic medications used in the treatment of psoriasis. OBJECTIVE: To compare the risk of serious infection associated with biologic and nonbiologic systemic medications in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study was conducted using medical and outpatient pharmacy claims from 2 large US health insurance claims databases from January 1, 2003, through September 30, 2015. We included patients with a diagnosis of psoriasis who were new users of systemic medications for psoriasis. EXPOSURES: Prescription claims for acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab. MAIN OUTCOMES AND MEASURES: The primary outcome was serious infection, defined by inpatient discharge diagnosis International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Cox proportional hazards regression was used to compare rates of serious infection for each exposure (acitretin, adalimumab, apremilast, etanercept, infliximab, and ustekinumab) with the referent group (methotrexate). We used pairwise 1:1 propensity score (PS) matching to adjust for potential confounders, which were assessed during a 180-day baseline period prior to study drug initiation. Results from the 2 databases were pooled via fixed-effects analysis. RESULTS: The databases included 31 595 patients in the Optum Clinformatics Data Mart and 76 112 patients in Truven MarketScan who were new users of acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, and ustekinumab. Users of acitretin, apremilast, infliximab, and methotrexate were older and had higher baseline comorbidity scores than subcutaneous biologic users (adalimumab, etanercept, and ustekinumab). The pooled PS-matched analysis yielded a decreased rate of overall serious infection in users of apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with methotrexate. We did not find a different rate of overall serious infection among users of acitretin, adalimumab, and infliximab compared with methotrexate. Subanalysis by type of serious infection showed a significantly increased risk of cellulitis among users of acitretin compared with methotrexate (PS-adjusted HR, 1.76; 95% CI, 1.11-2.80). CONCLUSIONS AND RELEVANCE: Among patients with psoriasis treated with systemic medications in 2 large US claims databases, new users of apremilast, etanercept, and ustekinumab had a decreased rate of serious infection compared with methotrexate.