Chronic Graft-versus-Host Disease-Associated Muscle Cramps: Severity and Response to Immunomodulatory Therapies.

Muscle cramps in patients with chronic graft-versus-host disease (cGVHD) are common and associated with impaired quality of life and symptom burden. Muscle cramps are not currently captured in the 2014 National Institutes of Health (NIH) response criteria, and thus characterization and response to immunomodulatory therapies are lacking. The objective of this study was to characterize muscle cramp frequency, duration, and pain level in patients with steroid-refractory cGVHD undergoing extracorporeal photopheresis (ECP). A single-center cohort of patients who underwent ECP for the indication of steroid-refractory cGVHD with muscle cramps at treatment initiation were followed from April 2021 to April 2023. Of 22 patients receiving ECP for cGVHD during the study period, 9 (41%) had muscle cramps at ECP initiation (6 males [66%]; median age, 59 years; range, 25 to 66 years). Seven of these 9 patients (78%) had multiple organs involved, and 7 (78%) had severe disease by the NIH Global Severity scale. Over a median treatment duration of 28 weeks (range, 10 to 48 weeks), 8 patients (89%) had decreased frequency of muscle cramps from a median of 5 episodes per week (range, 3 per day to 2 per week) to a median of <1 episode per week (range, 1 per month to 3 per week). The pain and duration of muscle cramps were not changed meaningfully. The NIH Global Severity score remained unchanged in 6 patients (67%) and was improved in 3 patients (33%). Muscle cramping is a morbid feature of cGVHD that may be sensitive to change with standard immunomodulatory therapies. Muscle cramp frequency should be further validated as a response measure in cGVHD.

Sex differences in initial treatment for genital extramammary Paget disease in the United States: A systematic review.

BACKGROUND: Surgery is the standard treatment for genital extramammary Paget disease (gEMPD). OBJECTIVE: To determine if gEMPD treatments and outcomes differ by sex and US region. METHODS: A systematic review was performed of all English-language studies on initial gEMPD treatment in Medline via PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. At least 2 reviewers performed title and abstract review and data extraction. Surgical categories included total skinning procedures, partial skinning procedures, Mohs micrographic surgery (MMS), or unspecified surgery. Chi-squared tests of association were used for comparisons. RESULTS: A total of 60 studies comprising 302 (79.7%) female and 77 (20.3%) male patients met criteria. Women were most often initially recommended partial skinning procedures. In all, 74 (24.5%) women and 0 men underwent a total skinning procedure. Men were more likely to be offered MMS than women (40.3% vs 1.9%, P < .0001), despite men having a significantly greater extent of disease involving the perineum and perianal skin (21.1% vs 1.7%, P < .0001). Treatment recommendations varied by US region. LIMITATIONS: Only 20 states were represented. CONCLUSION: Women are more frequently offered total skinning procedures for gEMPD while men are more frequently offered MMS. MMS offers less recurrence and morbidity than total skinning procedures and should be recommended equally to both female and male patients with gEMPD.

Prevalence of asthma in patients with atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: It is well established that asthma is common in patients with atopic dermatitis (AD). OBJECTIVES: We performed a systematic review and meta-analysis to determine the prevalence of asthma and respiratory symptoms in individuals with AD as well as the association between AD and asthma. METHODS: At least 2 authors independently searched the medical databases PubMed, EMBASE, LILACS, and SCOPUS for all English-language studies with data on asthma prevalence among patients with AD or the association between AD and asthma. Pooled odds ratios with 95% confidence intervals (CIs) and pooled proportions were estimated with random-effects models. The Newcastle-Ottawa scale was used to assess study quality. RESULTS: The search yielded 39,503 articles. Of these, 213 studies were included in a quantitative analysis. The overall pooled prevalence of asthma was 25.7% (95% CI, 23.7-27.7) in patients with AD and 8.1% (95% CI, 7.0-9.4) among reference individuals. There was a significant association between AD and asthma when compared with reference individuals (odds ratio, 3.03; 95% CI, 2.64-3.47). LIMITATIONS: The definitions of AD and asthma differed across the included studies and varied from self-report to physician diagnosed. CONCLUSIONS: Asthma is a common comorbidity of AD. Physicians should be cognizant of this relationship and address asthma symptoms in their patients.

Association of bullous pemphigoid and comorbid health conditions: a case-control study.

BACKGROUND: Bullous pemphigoid is an autoimmune skin disease characterized by the formation of blisters between the epidermis and dermis. Comorbidities of pemphigoid have not been well-described. Identification of comorbidities associated with pemphigoid is important to decrease morbidity and mortality. OBJECTIVE: To identify the comorbid health conditions of bullous pemphigoid. METHODS: This was a case-control study of 91 cases of pemphigoid verified by clinical and laboratory diagnosis and 546 age- and sex-matched controls with complete follow-up at a large metropolitan quaternary care medical center. RESULTS: The average age of bullous pemphigoid patients was 76 years and 53% of patients were female. Forty-eight (53%) of the BP patients had a history of inpatient hospitalization, of which 22 (24.2%) were hospitalized for either previously undiagnosed BP or an exacerbation of BP. Bullous pemphigoid was significantly associated with hypertension [adjusted odds ratio (95% confidence interval)]: [2.03 (1.24-3.32)], diabetes mellitus [2.59 (1.60-4.19)], chronic kidney disease [2.29 (1.19-4.40)], end-stage renal disease [3.82 (1.48-9.85)], basal cell carcinoma of the skin [6.00 (1.94-18.6)], and obstructive sleep apnea [5.23 (2.45-11.19)]. 78% of BP patients used at least one systemic immunosuppressant. There was no significant association between treatments for pemphigoid and any of the comorbidities. CONCLUSIONS: Bullous pemphigoid patients need screening for comorbid health conditions even though treatment options do not seem to be associated with these comorbidities.

Risks for noncutaneous second primary malignancy in cutaneous malignant melanoma survivors: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program.

BACKGROUND: It is known that malignant melanoma (MM) survivors are at increased risk of future primary MM. However, the risk for noncutaneous second primary malignancies (SPMs) is not as well-understood. METHODS: An observational study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database was performed, assessing data from patients diagnosed with primary cutaneous MM to measure overall, as well as specific, tumor type and risk of SPM. RESULTS: Of the 132,438 patients recruited in the study population (mean age 55.5 years; 54% male), 23,794 SPMs were observed (O) (18% of patients at a mean age of 68.8 years), while 17,923 SPMs were expected (E) to occur (O : E 1.33, 95% CI 1.31-1.34). Excluding cutaneous MM occurring as a new primary malignancy, there was a significantly increased risk for SPMs among cutaneous MM survivors for each of the following tumor types: eye and orbit melanoma, tracheal, thyroid, salivary gland, retroperitoneum, small intestine, kidney, lymphoid and hematopoietic system, lymphoma overall, non-Hodgkin lymphoma, lymphocytic leukemia overall, chronic lymphocytic leukemia, male genital system (including prostate), and breast. Certain gender-specific trends for SPMs were also detected. CONCLUSIONS: Patients with primary cutaneous MM are at increased risk for primary noncutaneous MM as well as noncutaneous SPMs that include numerous tumor types. Enhanced oncologic surveillance for a variety of tumor types in melanoma survivors is warranted.

Placebo responses in randomized controlled trials for systemic therapy in atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) has a variable disease course and intermittent triggers, and responses to topical therapy vary, potentially affecting the magnitude of the placebo response in AD trials. OBJECTIVE: To determine the predictors of increased placebo response in randomized controlled trials of AD. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials for systemic therapy in AD published during 2007-2018. We searched the Cochrane Library, Medline, Embase, Global Resource for EczemA Trials (GREAT), Literature of the Latin American and Caribbean Health Sciences (LILACS), and Scopus. Two authors performed study selection and data extraction. Multivariable mixed models were constructed for Cohen D of Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), numeric rating scale (NRS)-itch and visual analog scale (VAS)-itch, and Dermatology Life Quality Index (DLQI). RESULTS: Overall, 64 trials were included. Use of concomitant topical therapy prescriptions, study duration ≥3 months, and fewer treatment arms were associated with an increased placebo response for EASI, NRS- and VAS-itch, and DLQI. For EASI, the placebo response was increased in studies with a higher proportion of male patients, mild-moderate mean baseline EASI scores, and no blinding. For NRS-itch, and VRS-itch, higher placebo responses were associated with higher proportions of male patients and moderate-severe mean itch scores at baseline. CONCLUSION: Placebo responses can be reduced in clinical trials of systemic therapy in AD by incorporating double- and triple-blinding, balancing the sex distribution of patients, disallowing concomitant use of prescription topical therapy, and having shorter study durations.

Epidemiology of alopecia areata, ophiasis, totalis, and universalis: A systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is a common autoimmune alopecia with heterogeneous severity and distribution. Previous studies found conflicting results about AA epidemiology. OBJECTIVE: To determine the prevalence, incidence, and predictors of AA, alopecia totalis, alopecia ophiasis, and alopecia universalis. METHODS: A systematic review of all published cohort and cross-sectional studies that analyzed AA and its subtypes. MEDLINE, Embase, LILACS, Scopus, Cochrane Library, and GREAT were searched. At least 2 reviewers performed study title/abstract review and data extraction. Random-effects meta-analysis was used because of significant heterogeneity (I2 = 99.97%). RESULTS: Ninety-four studies met the inclusion criteria. The pooled prevalence (95% confidence interval, N) of AA overall was 2.11% (1.82-2.42, N = 302,157,365), with differences of population-based (0.75% [0.49-1.06%], N = 301,173,403) and clinic-based (3.47% [3.01-3.96], N = 983,962) studies. The prevalences of alopecia totalis, ophiasis, and universalis were 0.08% (0.04-0.13, N = 1,088,149), 0.02% (0.00-0.06, N = 1,075,203), and 0.03% (0.01-0.06, N = 1,085,444), respectively. AA prevalence (95% confidence interval) increased over time (<2000: 1.02% [0.85-1.22]; 2000-2009: 1.76% [1.51-2.03]; >2009: 3.22% [2.59-3.92]; P < .0001) and differed by region. AA prevalence was significantly lower in adults (1.47% [1.18-1.80]) than children (1.92% [1.31-2.65]; P < .0001). CONCLUSIONS: AA affects 2% of the global population. AA prevalence is lower in adults than children, is increasing over time, and significantly differs by region.

Measurement properties of the Patient-Reported Outcomes Measurement Information System Itch Questionnaire item banks in adults with atopic dermatitis.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) was recently developed. OBJECTIVE: To validate PIQ short forms in adults with AD. METHODS: Self-administered questionnaires and skin examinations were performed in 239 adults with atopic dermatitis (AD) in a dermatology practice setting. RESULTS: PIQ items had good content validity. PIQ item bank T-scores strongly correlated with each other, moderately correlated with numeric and verbal rating scales for worst or average itch and with itch frequency, moderately to strongly correlated with patient-oriented eczema measure, and weakly to moderately correlated with the Eczema Area and Severity Index and Objective-Scoring AD (Spearman correlations, P < .0001). There were significant and stepwise increases of T-scores for all item banks with increasing patient-reported global severity (Wilcoxon rank sum test, P < .0001). However, there was limited ability to discriminate between the lowest or highest 2 levels of AD or itch severity. Item banks showed good internal consistency (Cronbach α, 0.91-0.95). No differential item functioning was identified by age, sex, race/ethnicity, or educational level. There were floor effects for total scores, particularly in almost clear/mild AD or itch. LIMITATIONS: Single-center study. CONCLUSIONS: PIQ item bank short forms showed good content and construct validity and are feasible for potential use in clinical trials and practice.

Association between hidradenitis suppurativa, depression, anxiety, and suicidality: A systematic review and meta-analysis.

BACKGROUND: Previous studies found conflicting results about whether hidradenitis suppurativa (HS) is associated with depression or anxiety. OBJECTIVES: To determine the relationship of HS with depression and anxiety. METHODS: A systematic review was performed of published observational studies in MEDLINE, PubMed, Embase, Global Resource for Eczema Trials (GREAT), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane, Scopus, and PsychInfo that analyzed depression or anxiety in HS. Two reviewers performed title/abstract review and data extraction. Meta-analysis was performed with random-effects weighting. RESULTS: Thirty-eight studies met inclusion criteria; 27 had sufficient data for meta-analysis. The prevalences of depression (26.5% vs 6.6%) and anxiety (18.1% vs 7.1%) were higher in persons with versus without HS. Patients with HS had higher odds of depression in 12 of 13 studies and pooled analysis (odds ratio, 2.54; 95% confidence interval, 2.15-3.01), and anxiety in 6 of 6 studies and pooled analysis (odds ratio, 2.00; 95% confidence interval, 1.66-2.42). Similar results were found in sensitivity analyses for different methods of HS diagnosis (physician diagnosed and chart review) and control groups (healthy and dermatologic control individuals). HS was associated with higher antidepressant and anxiolytic use and with suicidality, but not mean depression and anxiety scale scores. LIMITATIONS: Individual-level data were unavailable. CONCLUSIONS: Patients with HS have higher odds of depression, anxiety, and suicidality.

Hyperkalemia in women with acne exposed to oral spironolactone: A retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program.

PURPOSE: The necessity of serum potassium monitoring for healthy women who are prescribed spironolactone for acne has been debated. The aim of this study was to compare the incidence of hyperkalemia in women 18 to 45 years of age to that in women 46 to 65 years of age, when treated with oral spironolactone for acne. METHODS AND MATERIALS: Data for all women 18 to 65 years of age who were prescribed oral spironolactone by a dermatologist for acne between January 2006 and October 2016 were extracted for analysis. Retrospective data were included for women who exhibited baseline serum potassium within the normal limits and who had repeat serum potassium monitoring within 12 months after initiation of spironolactone. The rate of incident hyperkalemia was determined. RESULTS: Of 618 women who received spironolactone for acne, 133 had serum potassium monitoring both before and after spironolactone initiation. Nine were excluded due to confounding comorbidities. Of the remaining 124 women, the mean age at initiation of spironolactone was 32 years (range, 18-57 years); 112 women were in the 18 to 45 years age group, and 12 were in the 46 to 65 years age group. All women had serum potassium within normal limits at baseline. Women in the 46 to 65 years age group had a significantly higher rate of incident hyperkalemia after spironolactone initiation compared with women 18 to 45 years of age (2 of 12 women [16.7%] vs. 1 of 112 women [< 1%]; p = .0245). CONCLUSIONS: Although controversy surrounds the clinical utility of serum potassium monitoring in healthy women exposed to spironolactone for acne, based on the findings from this large patient population, monitoring of serum potassium is warranted for women over 45 years of age given an age-related greater risk of hyperkalemia.

Association of Psoriasis with Psychiatric Hospitalization in United States Children and Adults.

BACKGROUND: Psoriasis is associated with psychosocial distress. Little is known about the relationship between psoriasis and mental health (MH) emergencies. OBJECTIVE: To examine the associations of psoriasis and MH hospitalizations in the USA. METHODS: Data from the 2002-2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n = 87,053,155 children and adults). RESULTS: Hospitalization for MH disorders occurred more commonly in those with psoriasis compared to those without psoriasis (4.04 vs. 2.21%). In multivariable logistic regression models, psoriasis was associated with higher odds of admission for any MH disorder overall (adjusted odds ratio [95% confidence interval]: 2.32 [2.24-2.41]), as well as 9 of the 15 MH-specific disorders examined. Associated MH disorders included: anxiety, schizophrenia, personality disorder, depression, substance use disorders, history of MH disorder, alcohol-related disorders, adjustment disorders, and cognitive disorders. Children with versus those without psoriasis were also more likely to have a primary hospitalization for any MH disorder (2.82 [2.24-3.56]). Psoriasis inpatients were also more likely to have a primary hospitalization for any MH disorder compared to those with alopecia areata (1.99 [1.45-2.74]) or hidradenitis suppurativa (3.97 [3.49-4.52]). Psoriasis patients hospitalized with any MH disorder had higher mean [95% confidence interval] cost of inpatient care (USD 11,004 [10,846-11,241] vs. 9,547 [8,730-10,364]; p < 0.0001) compared to those without psoriasis, with USD 1,610,860 excess costs annually, with the majority of the costs coming from depression and mood disorders. CONCLUSIONS: Children and adults with psoriasis had increased hospitalization for multiple MH disorders, which were associated with a considerable financial burden.

A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis.

BACKGROUND: Previous studies found conflicting results about whether atopic dermatitis (AD) begins in adulthood. OBJECTIVE: To determine rates, predictors, and phenotypic differences of adult-onset AD. METHODS: A systematic review was performed with all published observational studies in Medline, Embase, GREAT (Global Resource of EczemA Trials), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library, and Scopus that analyzed the age of AD onset beyond 10 years of age. At least two reviewers performed study title, abstract review, and data extraction. Pooled meta-analysis of the proportion of adult-onset AD was performed by using random-effects weighting (I2 = 99.3%). RESULTS: Overall, 25 studies met inclusion criteria. Seventeen studies reported age of AD onset as after 16 years of age and had sufficient data for meta-analysis. The pooled proportion (95% confidence interval) of adult-onset AD was 26.1% (16.5%-37.2%). Similar results were found in sensitivity analyses by AD diagnostic method, study region, and sex. Phenotypic differences were observed across studies for adult-onset and child-onset AD, including higher rates of foot dermatitis and personal history of atopy but lower rates of flexural lesions and other signs and symptoms. LIMITATIONS: Characteristics of adult-onset versus child-onset AD were not commonly reported. CONCLUSION: AD is not only a disease of childhood; 1 in 4 adults with AD report adult-onset disease, which has distinct clinical characteristics as compared to child-onset AD.

Association between atopic dermatitis, depression, and suicidal ideation: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is associated with psychologic distress. However, previous studies found conflicting results about whether AD is associated with increased depression or suicidality. OBJECTIVES: To determine the complex relationship between AD and depression. METHODS: A systematic review of all published observational studies in the MEDLINE, PubMed, Embase, Global Resource for Eczema Trials (GREAT), Latin American and Caribbean Health Sciences (LILACS), the Cochrane Library, Scopus, and PsychInfo databases that analyzed depression in AD was performed. Two reviewers performed study title and/or abstract review and data abstraction. Pooled meta-analysis was performed by using random-effects weighting. RESULTS: Overall, 106 studies met the inclusion criteria; 36 had sufficient data for meta-analysis. The prevalence of any depression was higher in persons with versus without AD (20.1% vs 14.8%). Similar results were found in sensitivity analyses of studies assessing clinical depression, depressive symptoms, and adults; studies with healthy controls; and studies of low and high study quality. AD was associated with significantly higher depression scale scores, parental depression, antidepressant use, and suicidality. No publication bias was detected. LIMITATIONS: Individual-level data were not available. CONCLUSIONS: Patients with AD have higher odds of depression and suicidality.

Associations of Nickel Co-Reactions and Metal Polysensitization in Adults.

BACKGROUND: Allergic contact dermatitis to metals is a significant clinical and public health problem. Little is known about the determinants of polysensitization to metals. OBJECTIVE: The aim of the study was to determine the frequency and predictors of nickel co-reactions and metal polysensitization. METHODS: This is a retrospective chart review of 686 adults (age ≥ 18 years) who were patch tested from 2014 to 2017. RESULTS: Overall, 267 patients (38.9%) had 1 or more positive patch-test reactions to a metal allergen, most commonly nickel (17.4%), mercury (12.3%), and palladium (9.2%). Nickel reactions were inversely associated with age (logistic regression; adjusted odds ratio [95% confidence interval], 0.39 [0.29-0.78]). Among patients with positive reactions to nickel, 34.5%, 15.1%, and 5.0% had positive reactions to 1, 2, or 3 additional metals, respectively. The most common nickel co-reactors were palladium, mercury, and gold. Polysensitization to metals occurred in 11.8% of patients. Polysensitization to metal allergens was associated with female sex (6.67 [1.01-44.21]) and inversely associated with age (0.40 [0.18-0.88]). CONCLUSIONS: Nickel-sensitized patients have high rates of metal co-reactions. Polysensitization to metals is common in adults. These results may help guide future strategies for allergen avoidance.

Allergic contact dermatitis to personal care products and topical medications in adults with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is associated with skin-barrier disruption, immune dysregulation, and application of emollients and topical medications that might predispose a person toward developing allergic contact dermatitis. OBJECTIVE: To determine the predictors of allergic contact dermatitis and relevant allergens in AD. METHODS: A retrospective chart review was performed for 502 adults (age ≥18 years) who were patch tested to an expanded allergen series during 2014-2017. RESULTS: Overall, 108 (21.5%) had current AD and 109 (21.7%) had past AD. Patients with and without current AD had similar proportions of any positive (+, ++, or +++ 80 [74.1%] vs 254 [64.5%], respectively, chi-squared P = .06); strong-positive (++ and +++ 34 [31.5%] vs 102 [25.9%], respectively, P = .25); and irritant (56 [51.9%] vs 188 [47.7%], respectively, P = .45) patch-test reactions. AD patients had significantly higher rates of positive reactions to ingredients in their personal care products and topical medications, including fragrance mix II (P = .04), lanolin (P = .03), bacitracin (P = .04), cinnamal (P = .02), budesonide (P = .01), tixocortol (P = .02), and chlorhexidine (P = .001); relevance was established in >90% of these reactions. Polysensitization occurred more commonly in patients with AD than without (35 [32.4%] vs 75 [19.0%]; P = .01). LIMITATION: Study was performed at a single center. CONCLUSION: AD patients had more positive patch-test reactions to ingredients in their personal care products, topical steroids, and antibiotics.