Successful treatment of bullous pemphigoid with baricitinib: A case report

Abstract

Dear Editor, A 64-year-old Taiwanese male, nonsmoker, with a history of hypertension and type 2 diabetes mellitus has been regularly taking metformin for glycemic control. The patient was previously diagnosed with biopsy-proven bullous pemphigoid after experiencing multiple itchy erythema and blisters all over the whole body for 3 months. He was treated with prednisolone 10 mg three times daily and azathioprine 25 mg daily. Lesions showed improvement during the first 2-week follow-up. However, while the prednisolone dose was tapered down to 10 mg daily, the disease flared up again. He presented at our hospital with multiple tense bullae and erosions on erythematous pruritic wheals over the neck, trunk, and limbs without mucosal involvement [Figure 1]. Laboratory tests revealed eosinophilia and elevated levels of immunoglobulin E (IgE). There were no positive findings for potential infectious risk factors such as hepatitis B virus, hepatitis C virus, and Cytomegalovirus, as well as tumor markers. The score of Bullous Pemphigoid Disease Area Index (BPDAI) is 69 and the Visual Analog Scale (VAS) of pruritus is 9.Figure 1: Multiple tense bullae and erosions on erythematous pruritic wheals over the (a) neck, anterior chest, and (b) bilateral thighs.Initially, we treated the patient with intravenous methylprednisolone 4 mg/day, doxycycline 100 mg twice daily, systemic antihistamines, and topical steroids. However, we observed hyperglycemia, with poor-controlled blood sugar levels increasing up to 480 mg/dL. After discussing the options with the patient, we prescribed oral baricitinib 4 mg/day. Subsequently, we initiated the tapering of the systemic steroid in 2 days. At 1-week follow-up, the erythema on the body has disappeared and no new blisters have formed. The pruritus has also subsided, leaving only the wounds from the ruptured blisters [Figure 2]. No flare-up was noted after 8-week follow-up without any adverse event, and the BPDAI and VAS of pruritus have decreased to 0 points.Figure 2: (a and b) After 2 weeks of baricitinib treatment, the lesions showed resolution with residual erythema and scarring.Baricitinib is a first-generation Janus kinase (JAK) inhibitor. It works by targeting JAK1 and JAK2 proteins, which play a key role in regulating the immune response and inflammatory pathways.[1] To date, baricitinib has been found to be effective in treating rheumatoid arthritis, alopecia areata, and atopic dermatitis. Although the mechanism of JAK inhibitors in treating blood pressure (BP) is not yet established, several studies have shown its efficacy. Xiao et al. reported successful treatment of concurrent BP and plaque psoriasis with baricitinib in an 83-year-old man, who showed significant improvement and complete remission without adverse effects.[2] Fan and Wang have reported that seven cases of recalcitrant BP were successfully treated with tofacitinib and maintained complete remission during 9 months of follow-up.[3] In the pathogenesis of BP, mast cell degranulation and the release of various cytokines and chemokines are key factors in initiating the inflammatory cascade and leading to blister formation. Mast cell degranulation can be induced by various signaling molecules, including complement components and IgE BP180 antibodies.[4] Activated mast cells release mediators, including tumor necrosis factor-α, PAF, interleukin 1 (IL-1), IL-2, IL-5, and IL-6, which can attract and activate eosinophils and neutrophils along the basement membrane zone, which ultimately contributes to blister formation.[5] The JAK/signal transducer and activator of transcription (STAT) pathway is one of the most important signaling pathways for cytokines and growth factors. For example, IL-4 and IL-13 activate JAK1 and JAK3, which in turn activate the downstream signaling molecule STAT6, leads to the production of immunoglobulin G autoantibodies that target BP180 and BP230.[6] In addition, IL-5 can activate JAK1 and JAK2, leading to the downstream activation of STAT5, which is involved in the recruitment and activation of eosinophils.[7] As its significant role in the activation of a wide range of cytokines and chemokines, the JAK/STAT pathway has been identified as a potential target for therapeutic interventions. Traditional treatment for BP primarily involves topical and systemic corticosteroids, as well as immunosuppressants. Despite their effectiveness, these treatments are associated with notable adverse effects and potential risks, especially in elderly patients with multiple comorbidities. The potential side effects of systemic corticosteroids include an increased risk of infections, osteoporosis, adrenal insufficiency, glucose intolerance, and peptic ulcer disease. In contrast, JAK inhibitors are more targeted and result in fewer systemic side effects. However, while there is still debate over whether the use of JAK inhibitors increases the risk of venous thromboembolism and herpes zoster, these potential risks still warrant attention. In conclusion, the case we reviewed demonstrated successful treatment of BP with baricitinib. JAK inhibitors may provide a promising treatment option for BP without significant adverse effects, while the precise mechanisms remain unclear. Further investigative research is necessary to better understand the mechanisms by which JAK inhibitors act, their potential side effects, as well as the rate of recurrence in BP treatment. Ethical approval Reviewed and approved by the Institutional Review Board of Tri-Service General Hospital (TSGHIRB No.: B202315086). Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Date availability statement The datasets generated during and/or analyzed during the current study are publicly available. Financial support and sponsorship Nil. Conflicts of interest Prof. Wei-Ming Wang, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.