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Alopecia areata (AA) is a common autoimmune disease resulting from damage of the hair follicle by T cells. The immune pathways required for autoreactive T cell activation in AA are not defined limiting clinical development of rational targeted therapies (1). Genome-wide association studies (GWAS) (2) implicated ligands for the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we show that cytotoxic [CD8.sup.+][NKG2D.sup.+] T cells are both necessary and sufficient for the induction of AA in mouse models of disease. Global transcriptional profiling of mouse and human AA skin revealed gene expression signatures indicative of cytotoxic T cell infiltration, an interferon-γ (IFN-γ) response and upregulation of several γ-chain (γc) cytokines known to promote the activation and survival of IFN-γ-producing [CD8.sup.+][NKG2D.sup.+] effector T cells. Therapeutically, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2) or interleukin-15 receptor β (IL-15Rb) prevented disease development, reducing the accumulation of [CD8.sup.+][NKG2D.sup.+] T cells in the skin and the dermal IFN response in a mouse model of AA. Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-γ and [γ.sub.c] cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease. Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near-complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA., Alopecia areata is a T cell-mediated autoimmune disease characterized phenotypically by hair loss and, histologically, by infiltrating T cells surrounding the hair follicle bulb (reviewed in ref. 1). Previous studies [...]

ABSTRACT Psoriasis affects approximately 2 percent of the population. Approximately 30-45 percent of those affected first experience symptoms during childhood or adolescence. Although biologics have proven to be a relatively [...]

Background: Limited options are available for the treatment of brittle nail syndrome., Objective: To assess the efficacy and safety of topical cyclosporine emulsion (CsAE) versus emulsion (vehicle) alone in the treatment of brittle nail syndrome., Results: Twenty-four patients were randomized to topical CsAE emulsion or emulsion (vehicle) for 24 weeks. Four fingernails of each patient were included; the 2 most severe brittle nails and the second most normal nail were treated with the same medication. The fourth nail, the most normal nail, remained untreated and was used to assess nail growth. The prespecified primary endpoint was change from baseline in Physician Global Assessment (PGA) score (0 to 5 scale) at each follow-up visit. Safety evaluations were conducted at each visit., Results: In the intent-to-treat population (n=12 for each treatment arm), the PGA score for treated nails improved from baseline (CsAE, 0.7 to 1.4; emulsion, 0.7 to 1.5; P<0.05 for each), with no significant between-group differences. Untreated nails did not improve in overall appearance (0.0 to 0.3 grade; P>0.05). Statistically and clinically significant improvement from baseline was reported for nail length/appearance in both CsAE and vehicle groups., Limitations: Sample size was relatively small. The difference in PGA between treated and untreated nails was not analyzed. Baseline disease severity may have been too mild, limiting detection of efficacy., Conclusions: Both CsAE and emulsion vehicle applied topically appeared to improve signs and symptoms of brittle nail syndrome and were well tolerated. These findings warrant corroboration in a larger population and inclusion of comparison with an inactive control and a higher concentration of CsAE, the former which may help in distinguishing the efficacy of vehicle emulsion from CsAE.

Brittle nail syndrome refers to nails that exhibit surface roughness, raggedness, and peeling. It is a common problem, with a higher prevalence among elderly patients. The goal of this study was to determine if tazarotene cream 0.1% ameliorates the signs and symptoms of brittle nails. In this open-label, single-center trial, participants applied tazarotene cream to the nails twice daily for 24 weeks. Signs and symptoms were rated by the investigators and by the participants during treatment and 12 weeks after discontinuation. Twenty participants were enrolled in the study; 1 participant withdrew prior to the 4-week followup visit. Of the 18 participants available for analysis (1 participant was excluded because baseline photographs were not available) for the primary end point of improvement in the physician global improvement assessment (PGIA), all 18 participants achieved improvement of the target nails at week 12 as well as 16 participants (88.9%) at week 24. All 18 participants had improvement in the PGIA score 12 weeks posttreatment at week 36. The physician global assessment (PGA) improved for 14 of 19 participants (73.7%) at both weeks 12 and 24; at week 24, 4 of 19 participants had achieved a PGA score of none. At week 36, 17 of 19 participants (89.5%) agreed that their nails had improved overall. Only 1 participant (5.3%) reported mild local irritation. This study demonstrated that tazarotene improves some of the changes noted in conjunction with brittle nail syndrome with minimal to no irritation.

Chemotherapeutic agents are known to cause a myriad of cutaneous side effects that the dermatologist is often called upon to identify and treat. The taxoid drug paclitaxel is commonly used in oncology. To date, there have been few adverse dermatologic effects reported secondary to paclitaxel use. This is in contrast to the related drug docetaxel. We report a case in which paclitaxel caused onycholysis and nail loss in a patient being treated for lung cancer. To our knowledge, this finding has not previously been reported in the American dermatologic literature, though it has been reported in association with docetaxel use. It is important for clinicians to recognize that onycholysis can be associated with paclitaxel. Prompt recognition may prevent the unnecessary use of antibiotics or antifungal medications. Discontinuation of paclitaxel chemotherapy generally is not required, and regrowth of nails can be expected following completion of therapy.