Cutaneous eruptions from ibrutinib resembling epidermal growth factor receptor inhibitor-induced dermatologic adverse events.

BACKGROUND: Ibrutinib is an oral inhibitor of Bruton tyrosine kinase that is approved by the United States Food and Drug Administration for several lymphoproliferative disorders and chronic graft-versus-host disease. OBJECTIVE: To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor (EGFR) inhibitor-induced dermatologic adverse events. METHODS: Single-center retrospective cohort of patients referred to the Skin Toxicities Program for treatment of cutaneous eruptions while taking ibrutinib. RESULTS: Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae, or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. Most patients were able to continue ibrutinib therapy with focused treatment of their cutaneous toxicities. LIMITATIONS: This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. CONCLUSIONS: With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Risk Factors for the Development of Bullous Pemphigoid in US Patients Receiving Immune Checkpoint Inhibitors.

Importance: De novo bullous pemphigoid (BP) is a rare immune-mediated adverse event from immune checkpoint inhibitors (ICIs) that can necessitate permanent discontinuation of the anticancer therapy, but the risk factors for developing this toxic effect are unknown. Objective: To compare potential risk factors for BP in patients treated with ICIs who did and did not develop BP. Design, Setting, and Participants: This cohort and nested propensity score-matched case-control study was conducted at the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital. All patients at these facilities with de novo BP after ICI treatment were compared with all patients on the cancer registry who were treated with ICIs between October 1, 2014, and December 31, 2020. Patients with incomplete or blinded data regarding the ICI agent or total cycles were excluded. Exposures: In the cohort, assessed potential risk factors included age at ICI introduction, sex, ICI molecular target, and cancer type, which were then used as matching variables. In the propensity score-matched case-control analysis, risk factors assessed included sex, race and ethnicity, cancer stage, metastasis sites, idiopathic BP comorbidities, pre-ICI vaccination, radiation history, body mass index, and derived neutrophil-to-lymphocyte ratio. Main Outcomes and Measures: Diagnosis of BP at any point after ICI treatment, confirmed by direct immunofluorescence, indirect immunofluorescence, autoantibody serologies, or diagnostic consensus among study board-certified dermatologists. Odds ratios (ORs) and 95% CIs were calculated for all risk factors. In the secondary analysis, best overall responses to ICIs between cases and controls were compared by Fisher exact test. Results: Among 5636 patients treated with ICIs at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital during the study period, 35 (0.6%; median [IQR] age, 72.8 [13.4] years; 71.4% [25] male patients) developed BP. In a multivariate logistic regression model that assessed 2955 patients with complete data in the cancer registry, age 70 years or older (OR, 2.32; 95% CI, 1.19-4.59; P = .01), having melanoma (OR, 3.21; 95% CI, 1.51-6.58; P < .003), and having nonmelanoma skin cancer (OR, 8.32; 95% CI, 2.81-21.13; P < .001) were significantly associated with developing BP. In the nested 1:2 case-control comparison of all 35 cases to 70 propensity score-matched controls, a complete or partial response on initial restaging imaging was a risk factor for BP development (OR, 3.37; 95% CI, 1.35-9.30; P = .01). Bullous pemphigoid cases also more frequently exhibited overall tumor response to ICIs than matched controls (29 of 35 [82.9%] vs 43 of 70 [61.4%]; P = .03). Conclusions and Relevance: In this cohort study, age 70 years or older and skin cancer were associated with increased risk of developing ICI-associated BP. Given the association of BP with improved initial and best overall tumor responses, early identification and toxic effect-directed treatment should be prioritized, especially in individuals at risk for developing de novo BP.

Crowdfunding for Gender-Affirming Mastectomy: Balancing Fundraising With Loss of Privacy.

INTRODUCTION: Limitations in insurance coverage may cause patients to turn to crowdfunding to raise money for gender-affirming procedures. In this study, we analyze the impact of Medicaid insurance coverage on gender-affirming mastectomy campaigns posted on GoFundMe.com. METHODS: Between March 1 and 12, 2021, we accessed GoFundMe.com to analyze available campaigns requesting monetary contributions for gender-affirming mastectomy. Campaigns were identified using the search term "top surgery" followed by the state's name. Duplicate campaigns, campaigns whose primary goal was not gender-affirming mastectomy, and ongoing campaigns were excluded. Campaigns were then categorized according to their state's coverage of gender-affirming surgery: explicit exclusion (EE), explicit inclusion (EI), or no explicit statement of gender-affirming care. We collected data on the number of donors and shares, the fundraising goal, and the total amount raised for each campaign. Common themes within campaign narratives were identified and assessed by each reviewer. Finally, we collected data on the photographs posted by campaign creators. RESULTS: Our search yielded 790 campaigns, with an overall mean of 58 ± 99 donors and 212 ± 288 shares. The mean fundraising goal and amount raised among all campaigns were $6811 ± $5027 and $2579 ± $3072, respectively. Fundraising goals were most likely to be met in an EI state than an EE state (26.3% vs 8.1%; P < 0.001). The mean amount sought was highest in EE states and lowest in EI states, whereas the mean amount raised was lowest in EE states and highest in EI states. Of the campaigns, 97.1% mentioned personal or situational characteristics in the narrative section; 16.2% of all campaigns expressed negative feelings about posting on GoFundMe.com to raise money for their surgeries. CONCLUSION: Disparities in health care coverage of gender-affirming surgeries were seen between state categories, with a decreased need for crowdfunding in states explicitly including coverage of gender-affirming surgery. Many transgender patients used crowdfunding to pay for transition-related health care costs, relying on the kindness of strangers and their social network at the expense of their personal privacy. Expansion of legislative coverage of gender-affirming surgeries may alleviate some of this financial burden and reduce transgender patients' reliance on crowdfunding campaigns.

Geographic disparities in access to scalp cooling for the prevention of chemotherapy-induced alopecia in the United States.

BACKGROUND: Chemotherapy-induced alopecia is psychologically challenging for patients undergoing cancer treatment, and scalp cooling has been shown to prevent or decrease the hair loss. OBJECTIVE: To evaluate whether access to scalp cooling varies by geographic area in the United States. METHODS: Cancer treatment centers offering scalp cooling were identified using data from the Rapunzel Project. Medicare claims data were queried to evaluate the number of chemotherapy infusions occurring in each zip code in the United States. Geographic distribution of chemotherapy infusions and scalp cooling centers was determined using ArcGIS software. The average distance from the geographic center of all 5-digit zip codes in which chemotherapy infusions occur to the nearest scalp cooling center was calculated in miles. RESULTS: There are 366 chemotherapy infusion centers in the United States that offer scalp cooling. Overall, 43.9% of Medicare-billed chemotherapy infusions in the United States occur in zip codes less than 12.5 miles from a scalp cooling center, 24.8% occur between 12.5 and 49.9 miles away, and 31.3% occur more than 50 miles away. LIMITATIONS: Our results are only generalizable to patients seen at Medicare-accepting institutions in the United States. CONCLUSIONS: Geographic disparities affect which patients can access scalp cooling therapy, and implementation in suburban and rural areas would increase access for patients who wish to preserve their hair while undergoing chemotherapy.

A Call for Gender Identity Data Collection in iPLEDGE and Increasing the Number of Isotretinoin Prescribers Among Transgender Health Providers.

Acne is a common adverse event among trans-masculine people using testosterone as masculinizing hormone therapy. Isotretinoin is the most effective medication for severe recalcitrant acne and, as such, trans-masculine people with severe acne would likely benefit from treatment with this therapy. Incorporation of gender identity-based questions in iPLEDGE registration documentation will increase information about gender-diverse patients taking isotretinoin in the United States and allow better understanding of teratogenicity risks among these patients. An increase in the number of transgender health providers registered as isotretinoin prescribers in iPLEDGE would increase access to this effective medicine and may improve outcomes in these patients.

Skin cancer and skin cancer risk behaviors among sexual and gender minority populations: A systematic review.

BACKGROUND: Individuals of sexual and gender minorities may have different lifetime risk of skin cancer and ultraviolet radiation exposure than heterosexual persons. OBJECTIVE: To systematically review the prevalence of skin cancer and behaviors that increase risk of skin cancer among sexual and gender minority populations. METHODS: We performed a systematic literature review in PubMed/MEDLINE, Embase, Cochrane, and Web of Science, searching for articles through October 18, 2019, that investigated risk of skin cancer and behaviors among sexual and gender minority populations. RESULTS: Sexual minority men have a higher lifetime risk of any skin cancer (odds ratio range: 1.3-2.1) and indoor tanning bed use (odds ratio range: 2.8-5.9) compared with heterosexual men, whereas sexual minority women may use indoor tanning beds less frequently than heterosexual women and do not have an elevated risk of lifetime history of skin cancer. Gender-nonconforming individuals have higher lifetime prevalence of any skin cancer compared with cisgender men. LIMITATIONS: Most variables rely on self-reporting in their original studies. CONCLUSIONS: Sexual minority men disproportionately engage in use of indoor tanning beds, which may result in increased lifetime risk of skin cancer. Recognition of this risk is important for providing appropriate screening for patients in this population.

Association Between Sexual Orientation and Lifetime Prevalence of Skin Cancer in the United States.

Importance: Sexual minority men have reported higher rates of both indoor tanning and skin cancer than heterosexual men, and sexual minority women have reported lower or equal rates of both indoor tanning and skin cancer compared with heterosexual women. Bisexual men, in particular, have reported higher rates of indoor tanning bed use than heterosexual men; however, no study has investigated skin cancer prevalence among gay, lesbian, and bisexual individuals as separate groups. Objective: To evaluate the association between sexual orientation and lifetime prevalence of skin cancer. Design, Setting, and Participants: This cross-sectional study analyzed data from the 2014-2018 Behavioral Risk Factor Surveillance System (BRFSS) surveys of a noninstitutionalized population in the United States that included 877 650 adult participants who self-identified as being heterosexual, gay, lesbian, or bisexual. Main Outcomes and Measures: Self-reported lifetime history of skin cancer. Results: The study included 877 650 participants, including 364 833 heterosexual men (mean age, 47.7; 95% CI, 47.5-47.8), 7823 gay men (mean age, 42.7; 95% CI, 41.8-43.6), 5277 bisexual men (mean age, 39.4; 95% CI, 38.4-40.5), 484 341 heterosexual women (mean age, 49.7; 95% CI, 49.6-49.8), 5609 lesbian women (mean age, 41.8; 95% CI, 40.6-43.0), and 9767 bisexual women (mean age, 32.8; 95% CI, 32.3-33.3). The adjusted odds ratios (AORs) of skin cancer prevalence were significantly higher among both gay (AOR, 1.25; 95% CI, 1.03-1.50; P = .02) and bisexual men (AOR, 1.46; 95% CI, 1.01-2.10; P = .04) compared with heterosexual men. The AORs of skin cancer were statistically significantly lower among bisexual women (AOR, 0.75; 95% CI, 0.60-0.95; P = .02) but not among gay or lesbian women (AOR, 1.01; 95% CI, 0.77-1.33; P = .95) compared with the AORs of skin cancer among heterosexual women. Conclusions and Relevance: In this study, gay and bisexual men had an increased self-reported lifetime prevalence of skin cancer compared with the prevalence among heterosexual men. Patient education and community outreach initiatives focused on reducing skin cancer risk behaviors among gay and bisexual men may help reduce the lifetime development of skin cancer in this population. Continued implementation of the Behavioral Risk Factor Surveillance System's sexual orientation and gender identity module is imperative to improve understanding of the health and well-being of sexual minority populations.

Association of poor mental health and skin cancer development: a cross-sectional study of adults in the United States.

The relationship between mental health and skin cancer is poorly characterized. This cross-sectional study used 2016 Behavioral Risk Factor Surveillance System data to evaluate the association between mental health problems and skin cancer development. Multivariate logistic regression analyses were performed to calculate adjusted odds ratio (aOR) for skin cancer development by mental health problems, adjusting for potentially confounding demographic and lifestyle factors. Odds of skin cancer were significantly higher in those with mental health problems problems [aOR 1.24, 95% confidence interval (CI) 1.17-1.31, P < 0.001]; this finding remained in sensitivity analysis adjusting for sunburn history (aOR 1.34, 95% CI 1.09-1.63, P = 0.004). Our findings reveal an association between poor mental health and increased skin cancer prevalence. The direction of this association is unclear. Distress of a skin cancer diagnosis may promote mental health problems, while, conversely, mental health problems may biologically potentiate skin cancer or be associated with risk factors like indoor tanning. Nevertheless, we demonstrate an elevated prevalence of mental health problems in patients with skin cancer.

Psychiatric Adverse Events in Patients Taking Isotretinoin as Reported in a Food and Drug Administration Database From 1997 to 2017.

IMPORTANCE: Isotretinoin is a highly effective medication for severe acne. Although no causal link between isotretinoin and psychiatric adverse effects has been established, widespread media reporting of depression and suicidality with use of isotretinoin have raised concerns in both patients and clinicians and generated numerous cases of costly litigation. OBJECTIVE: To evaluate reports of psychiatric adverse events associated with isotretinoin use submitted to the US Food and Drug Administration from January 1, 1997, through December 31, 2017. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study evaluated reports of psychiatric adverse events with isotretinoin as the primary suspect drug in the US Food and Drug Administration's Adverse Event Reporting System from 1997 through 2017. Publicly available data on number of patients enrolled in the iPLEDGE program were used to calculate rates of completed suicide per 100 000 patients enrolled in iPLEDGE in 2009 and 2010. All data were analyzed between July 1, 2018, and January 31, 2019. MAIN OUTCOMES AND MEASURES: The main outcomes were frequency and type of psychiatric adverse events in patients taking isotretinoin. Secondary analyses were stratification by age and sex and evaluation of completed suicide rates. RESULTS: Between 1997 and 2017, 17 829 psychiatric adverse events with isotretinoin use were reported to the US Food and Drug Administration, with depressive disorders, emotional lability, and anxiety disorders reported most frequently. Of these events, 8936 (50.1%) were reported among men and 8362 (46.9%) among women; the sex of the individual was not reported for 531 events (3.0%). Of the 13 553 reports that included patient age, the mean (SD) age was 22.1 (8.6) years. More than half (52.5%) of all events occurred in 10- to 19-year-old individuals. Whereas depression and anxiety were reported equally between sexes, eating disorders were more common in females (58 of 85 [68.2%]), while attention-deficit/hyperactivity disorder (55 of 83 events [66.3%]) and completed suicides (290 of 368 [78.8%]) were more common in males. The rates of completed suicide were 8.4 and 5.6 suicides per 100 000 patients enrolled in iPLEDGE in 2009 and 2010, respectively. CONCLUSIONS AND RELEVANCE: Although depressive disorders and suicidality were frequently reported with isotretinoin use, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large. These data suggest that the rate of completed suicide in patients taking isotretinoin may be lower than that of the general US population. Many psychiatric adverse events unrelated to depression and suicidality were also reported, but it is unclear if they were a result of isotretinoin therapy. Although no causal link between isotretinoin and psychiatric risk has been established, patients taking the drug appear vulnerable to psychiatric concerns. Mandated monthly iPLEDGE visits may provide an opportunity to screen patients for psychiatric conditions and improve outcomes.

US Food and Drug Administration Reports of Pregnancy and Pregnancy-Related Adverse Events Associated With Isotretinoin.

IMPORTANCE: iPLEDGE is a rigorous program initiated in 2006 to reduce fetal exposure to isotretinoin, a disease-modifying medication for acne that carries a risk of teratogenesis. Despite the imposition of iPLEDGE requirements on patients and clinicians, the scope of isotretinoin-related adverse events is unknown. OBJECTIVE: To determine the frequency and rate of pregnancy and pregnancy-related adverse events among women taking isotretinoin reported to the US Food and Drug Administration (FDA). DESIGN, SETTING, AND PARTICIPANTS: Pregnancy reports from the FDA Adverse Event Reporting System, a public database of medication adverse event reports filed by prescribers, consumers, and manufacturers, were used to perform a retrospective analysis of pregnancy-related adverse events associated with isotretinoin from January 1, 1997, to December 31, 2017. Each individual reporting any pregnancy-related adverse event signified 1 pregnancy. Abortions, pregnancies that occurred while contraception was used, and fetal defects were counted as subgroups of total pregnancy events. MAIN OUTCOMES AND MEASURES: The frequency of pregnancy and of pregnancy-related events (abortions, pregnancies that occurred while using contraception, and fetal defects) were stratified by year that the FDA was notified of the event and by age. The rates of adverse events were calculated using isotretinoin prescribing data. RESULTS: There was a total of 6740 pregnancies among women taking isotretinoin reported to the FDA from 1997 to 2017, peaking in 2006 (768 pregnancies) before settling into a range of 218 to 310 annual reports of pregnancy after 2011. The mean (SD) age of the women was 24.6 (7.1) years. The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115 925) and 0.65% (768 of 117 784), with a peak in 2006. Although pregnancies, abortions, and fetal defects among women taking isotretinoin have decreased since the initiation of iPLEDGE in 2006, all 3 persist. CONCLUSIONS AND RELEVANCE: The number of reports of pregnancies, abortions, and fetal defects among women taking isotretinoin has decreased since peaking around the initiation of iPLEDGE in 2006. Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time. Despite the decrease, persistent reporting of pregnancy-related events in the last decade warrants investigation into the efficacy of iPLEDGE and exploration of new approaches for lowering fetal exposure to isotretinoin.