Body site distribution of pediatric-onset morphea and association with extracutaneous manifestations.

BACKGROUND: The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. OBJECTIVE: To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. METHODS: A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. RESULTS: A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). LIMITATIONS: Retrospective nature and the inclusion of only patients with clinical photographs. CONCLUSION: The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride.

IMPORTANCE: Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure. OBJECTIVE: Our chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5α-RI exposure served as a comparison control group for those with longer exposure. DESIGN: We used a single-group study design and classification tree analysis (CTA) to model PED (lasting ≥90 days after stopping 5α-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction. SETTING: Our data source was the electronic medical record data repository for Northwestern Medicine. SUBJECTS: The analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16-42 years old and exposed to finasteride ≤1.25 mg/day. MAIN OUTCOME AND MEASURES: Our main outcome measure was diagnosis of PED beginning after first 5α-RI exposure, continuing for at least 90 days after stopping 5α-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE5I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH). RESULTS: Among men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5α-RI, interquartile range (IQR) 631.5-2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5α-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p < 0.002). Among men 16-42 years old and exposed to finasteride ≤1.25 mg/day, 34 of 4,284 (0.8%) developed PED (persistence median 1,534 days, IQR 651-2,351 days); the multivariable model predicting PED had one variable: duration of 5α-RI exposure. Of 103 young men with new ED, 34 (33%) had new PED. Young men with >205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure. CONCLUSION AND RELEVANCE: Risk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.

Evidence for the association of Hashimoto's thyroiditis with psoriasis: a cross-sectional retrospective study.

BACKGROUND: Current information indicates that psoriasis is a metabolic disorder with systemic manifestations. Reports have revealed an association between psoriasis and several chronic autoimmune disorders. For one of these disorders, Hashimoto's thyroiditis (HT), there are scarce, and relatively unconfirmed, reports of an association with psoriasis. We sought to determine if such an association is detectable in a large medical record data repository. METHODS: We searched one institution's electronic medical record data repository from January 2010 to December 2013. Patients were identified by ICD-9 codes (psoriasis: 696.0; 696.1, HT: 245.2). Only data from patients with laboratory-confirmed HT (anti-thyroid peroxidase [anti-TPO] antibodies; thyroglobulin antibodies; serum thyroid-stimulating hormone; and free T3) were eligible for inclusion. Logistic regression analysis was used to obtain an odds ratio (OR) to establish an association between psoriasis and HT. Stratified analyses were performed to test for confounding variable and effect modification. RESULTS: Medical records for 856,615 individuals with documented encounters between January 1, 2010, and December 31, 2013, were detected. A total of 9654 had a diagnosis of psoriasis, and 1745 had a diagnosis of HT. Of these, 41 subjects were diagnosed with both conditions. A significant association existed for psoriasis and HT, even after adjusting for confounding variables that included gender, age, psoriatic arthropathy, and the use of systemic anti-psoriatic agents (OR = 2.49; 95% CI 1.79-3.48; P < 0.0001). CONCLUSIONS: This association has broad clinical impact and deserves further attention with regard to patient care, clinical research, and developmental therapeutics.

Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study.

INTRODUCTION: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. METHODS: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. RESULTS: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01-3.82); BCC and ARBs (OR 2.86; 95% CI 2.13-3.83), ACEIs (OR 2.23; 95% CI 1.78-2.81) and TZs (OR 2.11; 95% CI 1.60-2.79); SCC and ARBs (OR 2.22; 95% CI 1.37-3.61), ACEIs (OR 1.94; 95% CI 1.37-2.76), and TZs (OR 4.11; 95% CI 2.66-6.35). CONCLUSIONS: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis.

IMPORTANCE: Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting. OBJECTIVE: To assess safety reporting for clinical trial reports of finasteride for AGA. DATA SOURCES: MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center. STUDY SELECTION: Published clinical trial reports for finasteride treatment of AGA. DATA EXTRACTION AND SYNTHESIS: For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials. MAIN OUTCOMES AND MEASURES: Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias. RESULTS: Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer's full prescribing information and 33% took finasteride for more than 1 year. CONCLUSIONS AND RELEVANCE: Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.