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Indian J Dermatol
Indian J Dermatol
IJD
Indian J Dermatol
Indian Journal of Dermatology
0019-5154
1998-3611
Wolters Kluwer - Medknow India

IJD-69-343
10.4103/ijd.ijd_1109_23
Correspondences
Refractory Giant Perianal Pyoderma Gangrenosum Successfully Treated with Tofacitinib
Xiao Yu 1234
Liao Shuanglu 1234
Hu Danchen 5
Li Ruoyu 1234
Tu Ping 1234
Wang Xiaowen 1234
Zhong Shaomin 1234
1 From the Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China
2 Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
3 National Clinical Research Center for Skin and Immune Diseases, Beijing, China
4 NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China
5 Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China E-mail: zhongshaomin@sina.com
Jul-Aug 2024
19 8 2024
69 4 343344
12 2023
1 2024
Copyright: © 2024 Indian Journal of Dermatology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcDear Editor,

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. The most common subtype is the ulcerative variant featured by painful marginated ulceration with undermined borders.[1] To date, the treatment of PG is still in challenge. Common therapies include immunosuppressive drugs and biological agents, such as prednisone, cyclosporine and tumour necrosis factor (TNF) inhibitors.[2]

A 41-year-old man with a 6-year history of recurrent painful ulcerations on his buttocks presented to the dermatology clinic. Six years ago, he developed a painful ulcer in the anal region. Based on nonspecific histopathological and laboratory findings, the diagnosis of ulcerative PG was determined. No systemic disease was detected. The therapeutic intervention comprising methylprednisolone, cyclosporine and thalidomide cured his skin lesion. Four years ago, the patient experienced a relapse that was controlled by the combination of cyclosporine and thalidomide. Two years ago, a deep ulceration emerged around his anus with rapid deterioration. He received infliximab and secukinumab successively as conventional immunosuppressive medications did not work out. Neither biologic agent yielded satisfactory results. The sizable ulcer extended to involve the scrotum, concomitant with profuse haemorrhage and excruciating pain.

Physical examination revealed a deep perianal ulcer, approximately 15 cm × 10 cm, with violaceous borders [Figure 1a]. Before tofacitinib 10 mg per day was prescribed, complete blood cell counts, coagulation assessments, test for hepatitis B, liver and kidney function evaluations and T-SPOT.TB test were performed. Other than a previous hepatitis B infection, no other abnormalities were detected. A marked amelioration of his skin lesion was observed within 2 months. Simultaneously, the patient developed multiple scrotal warts, which regressed after cryotherapy and imiquimod therapy [Figure 1b]. After 1.5 years, the ulcer shrank to approximately 3 cm × 2 cm, accompanied by the formation of scar tissue [Figure 1c], but he had to constantly strain during defecation due to scar contracture. Over the next year, the patient took alternate doses of tofacitinib, alternating between 10 mg and 5 mg, and maintained stable skin lesions. In the current case, the patient underwent rigorous monitoring for potential adverse effects, with blood tests including complete blood cell counts, coagulation assessments, D-dimer levels and liver and kidney function evaluations conducted every 3 months throughout the first year. Subsequently, these tests were performed every 6 months. Additionally, the patient’s annual health check-ups consistently showed no indications of tumours, activation of hepatitis B virus or tuberculosis infection.

Figure 1 (a) Before treatment, physical examination showed a deep perianal ulcer, surrounded by violaceous borders and erythema. (b) Significantly improved ulcer after 2 months of tofacitinib treatment, with warts on the scrotum. (c) After 1.5-year treatment of tofacitinib, the ulcer shrank to approximately 3 cm × 2 cm, with atrophic scarring around it

PG is an autoinflammatory disease, of which pathophysiology is related to various inflammatory cytokines, aberrant neutrophil activity and genetic predisposition. Patients with PG often present with comorbid systemic diseases, such as inflammatory bowel disease, rheumatoid arthritis and haematological cancer.[1] As PG progresses rapidly, it requires fast-acting immunosuppressive drugs, such as cyclosporine or corticosteroids as the initial regimen.[1] However, only 47% of patients with cyclosporine or prednisolone treatment have ulcer healing, and about 30% of recovered patients have a recurrence.[3] Biologics exhibit an escalating employment in PG treatment. TNF antagonists and interleukin inhibitors demonstrate respective complete response rates of 67% and 57%.[4]

Tofacitinib is an oral, small-molecular Janus kinase (JAK) inhibitor targeting JAK1/3. It could impede the signalling pathways of IL-4, IL-15 and IL-6 through the suppression of JAK3-STAT5/6 and JAK1-STAT3/4, leading to the inhibition of neutrophil activation and subsequent inflammatory processes.[5] Although it carries multiple adverse effect warnings regarding serious infections, cancers and thrombosis, this patient showed none of them during long-time treatment with tofacitinib except scrotal warts.

This report presents a patient with recurrent and treatment-resistant PG who demonstrated substantial improvement after tofacitinib administration. Nonetheless, the patient still suffered from defecation disturbance caused by scar contracture after ulcer healing. Therefore, timely and effective treatment is pivotal in preventing irreversible sequelae in PG patients. Tofacitinib may serve as a preferred option for PG with long-term safety and rapid effect.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

We thank the patient for granting permission to publish this information.
==== Refs
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2 Maronese CA Pimentel MA Li MM Genovese G Ortega-Loayza AG Marzano AV Pyoderma gangrenosum: An updated literature review on established and emerging pharmacological treatments Am J Clin Dermatol 2022 23 615 34 35606650
3 Ormerod AD Thomas KS Craig FE Mitchell E Greenlaw N Norrie J Comparison of the two most commonly used treatments for pyoderma gangrenosum: Results of the STOP GAP randomised controlled trial BMJ 2015 350 h2958 26071094
4 Ben Abdallah H Fogh K Vestergaard C Bech R Pyoderma gangrenosum and interleukin inhibitors: A semi-systematic review Dermatology 2022 238 785 92 34710873
5 Futosi K Fodor S Mocsai A Neutrophil cell surface receptors and their intracellular signal transduction pathways Int Immunopharmacol 2013 17 638 50 23994464
