Massive clonal expansion of polycytotoxic skin and blood CD8+ T cells in patients with toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8+ T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Deep T cell receptor (TCR) repertoire sequencing identified massive expansion of unique CDR3 clonotypes in blister cells. The same clones were highly expanded in patient's blood, and the degree of their expansion showed significant correlation with disease severity. By transducing α and ß chains of the expanded clonotypes into a TCR-defective cell line, we confirmed that those cells were drug specific. Collectively, these results suggest that the relative clonal expansion and phenotype of skin-recruited CTLs condition the clinical presentation of cutaneous adverse drug reactions.

Baseline Characteristics of a National French E-Cohort of Hidradenitis Suppurativa in ComPaRe and Comparison with Other Large Hidradenitis Suppurativa Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition substantially impacting patients' quality of life; the pathogenesis remains unclear, and treatment is complex and not yet standardized. Observational data are increasingly being used to evaluate therapeutics in "real-life" interventions, and the development of e-cohorts is offering new tools for epidemiological studies at the population level. OBJECTIVE: The aim of this study was to describe the clinical characteristics and treatment history of HS participants in the Community of Patients for Research (ComPaRe) cohort and to compare these to other cohorts. METHODS: We performed a cross-sectional study of the baseline data of HS participants in ComPaRe, an e-cohort of patients with chronic diseases. Data were collected using patient-reported questionnaires about clinical-dem-ographic aspects, quality of life, and treatment history. RESULTS: A total of 396 participants (339 females, 57 males) were included (mean age 38 years); 83 (21%) had a family history of HS, 227 (57.3%) were current smokers, and 241 (60.9%) were overweight or obese. Most of the participants declared a Hurley stage II (n = 263, 66.4%) or III (n = 76, 20.3%). The breast was more frequently affected in women than men (37.5 vs. 5.3%, p < 0.0001), whereas the dorsal region was more frequently affected in men (39.5 vs. 10.9%, p < 0.0001). Increased disease stage was associated with obesity (25.9 vs. 33.8 vs. 51.3%, p = 0.02) and some HS localizations (genital [p < 0.005], pubis [p < 0.007], gluteal fold [p = 0.02], and groin [p < 0.0001]). The most frequently prescribed treatments were oral antibiotics (n = 362, 91.4%), especially amoxicillin-clavulanic acid and cyclins. Less than 10% of participants received biologics. Most of these results were consistent with previously published cohorts. CONCLUSION: Recruitment of participants by such a web platform can be a faster way to get relevant scientific data for a wide variety of patients that could be used for epidemiological studies and to evaluate therapeutics in "real-life" interventions.

Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients.

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.

Which Factors Determine Affected Sites in Hidradenitis Suppurativa?

BACKGROUND: The factors that determine whether an area of the body will be affected by hidradenitis suppurativa (HS) are unknown. METHODS: To address these factors, we performed multivariate regression analyses in a cohort of 1,138 patients. RESULTS: We found that the body sites affected occurred in specific combinations that were influenced by sex and body mass index. We also revealed unexpected correlations between some sites and other comorbidities such as inflammatory diseases, acne conglobata, or dissecting folliculitis of the scalp. CONCLUSION: Such correlations are crucial to unravel a disease as variable as HS and identify pathophysiological mechanisms to enable the provision of personalized management.

Are there distinct clinical and pathological features distinguishing idiopathic from drug-induced subacute cutaneous lupus erythematosus? A European retrospective multicenter study.

BACKGROUND: Clinical and pathologic criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial. OBJECTIVE: The aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathologic investigation. METHODS: Eleven European university dermatology units collected all diagnosed cases from January 2000 to December 2016. Board-certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student t test, exact test of goodness-of-fit, Fisher's exact test, and the Cochran-Mantel-Haenszel test for repeated measures. RESULTS: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and reported more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed a significant association of mucin deposition (P = .000083), direct immunofluorescence positivity for granular immunoglobulin M, and C3 deposits on the basement membrane zone (P = .0041) for I-SCLE and of leukocytoclastic vasculitis (P = .0018) for DI-SCLE. LIMITATIONS: This is a retrospective study. CONCLUSION: An integrated clinical and immunopathologic evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, and leukocytoclastic vasculitis is found in DI-SCLE.