Oral Tofacitinib in Treatment of Cutaneous Sarcoidosis

Dear Editor, Sarcoidosis is a multisystem granulomatous disorder, that is popularly known as the “great mimicker” due to the varied skin manifestations. In about one-third of cases of sarcoidosis, skin lesions are the first manifestation of a systemic illness. Presently, there are no Food and Drug Administration(FDA)-approved treatments for cutaneous sarcoidosis, with steroids being the mainstay. A 34-year-old male presented with multiple asymptomatic skin eruptions on the face of three months duration. The lesions started as tiny swellings on the forehead, which rapidly progressed over a month to involve the face and neck. He was managed as a case of acne and folliculitis with oral retinoids and antibiotics by multiple practitioners with no relief of symptoms. He did not complain of any systemic symptoms in the form of joint pains, cough, chest pain, breathlessness, allergies, or evening rise of temperature. Dermatological examination showed multiple grouped non pruritic, non-tender, shiny skin-colored papules of varying sizes on the forehead, nose, and both cheeks [Figure 1a]. Dermoscopy showed multiple arborizing vessels with few white scales. Histopathology revealed orthokeratotic epidermis with focal hypergranulosis and follicular plugging. Reticular dermis showed well-formed epithelioid granulomas with few surrounding lymphocytes (naked granulomas) [Figure 2a] with multiple Langhans type of giant cells with interspersed asteroid bodies [Figure 2b].Figure 1: (a): multiple tiny grouped non pruritic, non-tender shiny skin- colored papules located on the forehead and nose. (b): Skin-colored papules showing near complete resolution in 12 weeks on the forehead and noseFigure 2: (a): Histopathology (H and E, 40x) showing orthokeratotic epidermis with focal hypergranulosis and follicular plugging. Reticular dermis showing well-formed epithelioid granulomas (black arrow) with few surrounding lymphocytes (naked granulomas). (b): Histopathology (H and E, 1000x) revealed intracytoplasmic eosinophilic star shaped structures called asteroid bodies (black arrow)Based on the above findings, a pulmonary evaluation, complete blood count, hepatic, renal functions, and blood sugar levels were performed and all the investigations were within normal limits. Serum angiotensin-converting enzyme level was 75IU/L. Mantoux test was negative. Based on the above clinical, histopathological, and radiological findings, a diagnosis of cutaneous sarcoidosis was made. The patient was admitted and started on oral predisolone (1 mg/kg/day) in tapering doses. Patient showed minimal clearance of lesions after 8 weeks of treatment. Exacerbation occurred in the form of fresh lesions on tapering the dose below 20 mg/ day. Due to the unsatisfactory results patient was tapered off from prednisolone and was started on tablet tofacitinib 5 mg twice a day. The lesions started shrinking in size 6 weeks post initiation of therapy with near complete resolution in 12 weeks [Figure 1b]. The dosage of tofacitinib was reduced to once daily with satisfactory response and no recurrence of fresh lesions. It has been noticed that upregulation of Janus Kinase – Signal Transducer and Activator of Transcription(JAK-STAT) dependent cytokine signaling, including interferon gamma (INF-γ) activity, is involved in the pathogenesis of sarcoidosis. Tofacitinib is a selective inhibitor of JAK 1/3 enzymes, thereby disrupting the JAK-STAT pathway, preventing the activation of STAT proteins and production of inflammatory cytokines like IFN-γ and IL-6. This leads to a reduction in inflammation and granuloma formation. This explains the rationale for the use of JAK inhibitors in the treatment of sarcoidosis.[1] The common side effects of JAK inhibitors are upper respiratory tract infection, nasopharyngitis, diarrhea, nausea, headache, etc., Recently, JAK inhibitors have shown promising results in the treatment of internal organ sarcoidosis.[2] However, the efficacy of treatment in cutaneous sarcoidosis is still not extensively studied and requires further controlled trials. To date, 11 case reports, comprising a total of 21 patients with cutaneous and internal organ sarcoidosis have demonstrated benefit from JAK inhibitors, with nine studies showing excellent treatment response and lower relapse rates with tofacitinib.[3] Isolated case reports demonstrating the efficacy of oral tofacitinib has been reported in the western population [Table 1] but the same is absent for the Indian population. There is significant unmet medical need in the novel treatment strategies of cutaneous sarcoidosis. The response of our patient’s resistant cutaneous lesions to tofacitinib is consistent with its efficacy previously reported in the western population.Table 1: Summary of case reports of JAK inhibitors (tofacitinib) treatment in sarcoidosisTo summarise, JAK inhibitors seem to hold a promising future for treatment of cutaneous sarcoidosis as a safe and effective treatment modality. This report aims to highlight the importance of JAK inhibitors in the treatment of cutaneous sarcoidosis to achieve good resolution and less relapse rates. 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 initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.