Frontal fibrosing alopecia shows robust T helper 1 and Janus kinase 3 skewing.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia with unclear pathogenesis and a progressive course. The disease has a major impact on patients' quality of life and there is a lack of effective treatment to halt disease progression. METHODS: We profiled lesional and nonlesional scalp biopsies collected in 2017 from patients with FFA (n = 12) compared with scalp biopsies from patients with alopecia areata (AA) (n = 8) and controls (n = 8) to evaluate gene and protein expression, including the primary outcome (CXCL9). We determined significant differences between biomarkers using a two-sided Student's t-test adjusting P-values by false discovery rate. RESULTS: Significant increases were seen in CD8+ cytotoxic T cells, CD11c+ dendritic cells, CD103+ and CD69+ tissue-resident memory T cells in FFA and AA vs. control scalp (P < 0·05), with corresponding significantly upregulated granzyme B mRNA, particularly in FFA (P < 0·01). In AA, cellular infiltrates were primarily concentrated at the bulb, while in FFA these were mainly localized at the bulge. FFA demonstrated significant upregulation of T helper 1/intereferon (IFN) (IFN-γ, CXCL9/CXCL10), the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway (STAT1, JAK3) and fibrosis-related products (vimentin, fibronectin; P < 0·05), with no concomitant downregulation of hair keratins and the T-regulatory marker, forkhead box P3, which were decreased in AA. The stem cell markers CD200 and K15 demonstrated significantly reduced expression only in FFA (P < 0·05). CONCLUSIONS: These data suggest that follicular damage and loss of stem cells in FFA may be mediated through immune attack in the bulge region, with secondary fibrosis and reduced but still detectable stem cells. JAK/STAT-targeting treatments may be able to prevent permanent follicular destruction and fibrosis in early disease stages.

Association between bullous pemphigoid and neurologic diseases: a case-control study.

INTRODUCTION: In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. MATERIAL AND METHODS: This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. RESULTS: The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. CONCLUSIONS: Patients with bullous pemphigoid have a higher frequency of neurologic conditions.