Brett A. King

Killing Two Birds with One Stone: Oral Tofacitinib Reverses Alopecia Universalis in a Patient with Plaque Psoriasis

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Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy

IMPORTANCE Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available. OBSERVATIONS Recent advances in the understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation. CONCLUSIONS AND RELEVANCE The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.

Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata

BACKGROUND Alopecia areata (AA) is an autoimmune disease characterized by hair loss mediated by CD8+ T cells. There are no reliably effective therapies for AA. Based on recent developments in the understanding of the pathomechanism of AA, JAK inhibitors appear to be a therapeutic option; however, their efficacy for the treatment of AA has not been systematically examined. METHODS This was a 2-center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome. RESULTS Of 66 subjects treated, 32% experienced 50% or greater improvement in SALT score. AA and ophiasis subtypes were more responsive than AT and AU subtypes. Shorter duration of disease and histological peribulbar inflammation on pretreatment scalp biopsies were associated with improvement in SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse events were limited to grade I and II infections. An AA responsiveness to JAK/STAT inhibitors score was developed to segregate responders and nonresponders, and the previously developed AA disease activity index score tracked response to treatment. CONCLUSIONS At the dose and duration studied, tofacitinib is a safe and effective treatment for severe AA, though it does not result in a durable response. Transcriptome changes reveal unexpected molecular complexity within the disease. TRIAL REGISTRATION ClinicalTrials.gov NCT02197455 and NCT02312882. FUNDING This work was supported by the US Department of Veterans Affairs Office of Research and Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish Society of Medicine, the Fernström Foundation, the Locks of Love Foundation, the National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients.

Background: Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA. Objective: We sought to evaluate the safety and efficacy of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of patients over an extended period of time. Methods: This is a retrospective study of patients age 18 years or older with AA with at least 40% scalp hair loss treated with tofacitinib. The primary end point was the percent change in Severity of Alopecia Tool (SALT) score during treatment. Results: Ninety patients met inclusion criteria. Of 65 potential responders to therapy, defined as those with alopecia totalis or alopecia universalis with duration of current episode of disease of 10 years or less or alopecia areata, 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in SALT score over 4 to 18 months of treatment. Patients with AA experienced a higher percent change in SALT score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events. Limitations: The retrospective nature of the data, the relatively small number of patients, and lack of a control group are limitations. Conclusion: Tofacitinib should be considered for the treatment of severe AA, alopecia totalis, and alopecia universalis; tofacitinib dose response will be better defined by randomized controlled trials.

Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection

BACKGROUND Hand-foot-and-mouth disease (HFMD) is an acute viral illness commonly caused by coxsackievirus (CV)-A16 and enterovirus 71 infections. Recently, atypical HFMD has been reported in association with CV-A6, an uncommon enterovirus strain. OBJECTIVE We sought to describe the clinical features of atypical HFMD associated with CV-A6 infection and its diagnostic laboratory evaluation. METHODS Patients presenting to our institution with history and examination suggestive of atypical HFMD from January 2012 to July 2012 were identified. Morphology and distribution of mucocutaneous lesions were recorded. Enterovirus infection was assessed by reverse transcriptase polymerase chain reaction of biologic specimens. Enterovirus type was determined by viral capsid protein 1 gene sequencing. RESULTS Two adults and 3 children with atypical HFMD were identified. Four of 5 patients exhibited widespread cutaneous lesions. In 2 patients with a history of atopic dermatitis, accentuation in areas of dermatitis was noted. Associated systemic symptoms prompted 4 of 5 patients to seek emergency care, and both adults were hospitalized for diagnostic evaluation. Infection with CV-A6 was confirmed in all patients. LIMITATIONS This study is a case series from a single institution. CONCLUSION Consideration of the expanded range of cutaneous findings in atypical HFMD caused by CV-A6 infection may assist clinicians in diagnosis and management.

JAK inhibitors in dermatology: The promise of a new drug class

&NA; New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK‐STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK‐STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

Tofacitinib for the treatment of alopecia areata and variants in adolescents

Background: There are no reliably effective therapies for alopecia areata (AA). Objective: We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a series of adolescent patients with AA. Methods: We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems. Results: Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%‐100%) at an average of 6.5 months of treatment. Adverse events were mild. Limitations: Limitations include the retrospective nature of the data, small sample size, and lack of a control group. Conclusion: Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials.

Capillary Malformation—Arteriovenous Malformation Syndrome: Review of the Literature, Proposed Diagnostic Criteria, and Recommendations for Management

Capillary malformation–arteriovenous malformation syndrome is an autosomal dominant disorder caused by mutations in the RASA1 gene and characterized by multiple small, round to oval capillary malformations with or without arteriovenous malformations. Ateriovenous malformations occur in up to one‐third of patients and may involve the brain and spine. Although making the diagnosis is straightforward in some patients, there are other patients for whom diagnostic criteria may be helpful in their evaluation. Here we review the literature regarding capillary malformation−arteriovenous malformation syndrome, propose diagnostic criteria, and discuss the care of patients with this condition.

Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure

Background: Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. Objective: To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo. Method: This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. Results: Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low‐dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration. Limitations: Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group. Conclusion: Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low‐level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.

Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome

To the editor: Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by (1) persistent peripheral eosinophilia, (2) target organ pathology mediated by infiltrating eosinophils, and (3) the absence of known infectious or allergic causes of hypereosinophilia.[1][1],[2][