Abstract
Pyoderma gangrenosum (PG) is a recurrent, painful, necrotizing ulcerative neutrophilic dermatosis. Facial PG (FPG) is a rare subtype of PG that is often misdiagnosed. A 20-year-old male with FPG showed improvement after treatment with a combination of prednisone and upadacitinib. Early diagnosis is crucial to avoid misdiagnosis.
1 Introduction
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that causes pustules and ulcerations (1). Its diagnosis and appropriate management are often delayed because of its rarity and the presence of numerous clinical variants. Although corticosteroids remain the primary first-line treatment for severe forms of PG, the use of Janus kinase inhibitors (JAKis) is promising (2, 3). To date, 31 cases of PG treated with JAKi have been reported and are presented in Table 1 (4–24). In this case report, the authors describe a 20-year-old man with long-standing, non-healing, and painful facial ulcers that were not responsive to multiple antibiotics and serial wound debridement. Treatment with Upadacitinib hydrate and a tapering course of oral prednisolone was initiated. However, FPG is a rare dermatological pathology lacking characteristic distinguishing features, making treatment challenging (25).
Table 1
| No. | Authors | Age | Sex | Location | Comorbidity | Culprit condition | JAK inhibitory | Concomitant | Final outcome |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Shanmugam et al. (4) 2013 | 63 | M | Bilateral foot and ankle | Polycythemia vera, DVT, h/o colon cancer, Raynaud’s phe nomenon, Gottron’s papules | Wound debridement | Ruxolitinib | MTX (withdrawn) | Improved |
| 2 | Nasifoglu et al. (5) (2018) | 64 | F | Both legs | Polycythemia vera, myelofibrosis | ND | Ruxolitinib | ND | Healed |
| 3 | Kochar et al. (6) (2019) | 49 | F | Lower extremity | CD s/p colectomy | ND | Tofacitinib | ND | Healed |
| 4 | Kochar et al. (6) (2019) | 24 | M | Peristomal/around the stoma | Pouchectomy due to stricturing and fistulizing CD of the pouch | End ileostomy | Tofacitinib | Vedolizumab | Healed |
| 5 | Kochar et al. (6) (2019) | 34 | M | Lower extremities | Proctectomy and colostomy for perianal CD | ND | Tofacitinib | ND | Improved |
| 6 | Gregory et al. (7) (2019) | ND | F | Legs and around the stoma | UC | Abdominal colectomy with end ileostomy and Hartman pouch | Tofacitinib | Infliximab | Improved |
| 7 | Choi et al. (8) (2020) | 64 | M | Face, scalp, trunk, arms, legs and groin | Cocaine use, atrial fibrillation | ND | Tofacitinib | Prednisone (taper), rivaroxaban (for atrial fibrillation) | Partial resolution |
| 8 | Sedano and Jairath (9) (2021) | 80 | F | Right hip | UC, and AA | ND | Tofacitinib | ND | Improved |
| 9 | Orfaly et al. (10) (2021) | 41 | F | Legs | Mixed connective tissue disorder, unspecified IBD | ND | Tofacitinib | IVIG, systemic corti costeroids (for mixed connective tissue disorder) | Partial resolution |
| 10 | Orfaly et al. (10) (2021) | 58 | F | Legs | RA | ND | Tofacitinib | HCQ and systemic corticosteroids (for RA) | Complete resolution |
| 11 | Orfaly et al. (10) (2021) | 55 | F | Legs | Psoriasis, psoriatic arthritis | ND | Tofacitinib | IVIG | Complete resolution |
| 12 | Orfaly et al. (10) (2021) | 70 | M | Legs | UC | ND | Tofacitinib | Prednisone (taper), dapsone | Partial resolution |
| 13 | Salmón Olav arría et al. (11) (2021) | 69 | F | Left knee and ankle | UC | ND | Tofacitinib | ND | Complete resolution |
| 14 | Scheinberg et al. (12) (2021) | 71 | F | Scalp | IgA multiple myeloma | Herpes zoster | Baricitinib | ND | Improved |
| 15 | Scheinberg et al. (12) (2021) | 59 | F | Leg | RA | ND | Baricitinib | ND | Healed |
| 16 | Kooybaran et al. (13) (2022) | 50 | F | Both legs | RA | ND | Upadacitinib | ND | Improved |
| 17 | Castro (14) (2023) | 73 | M | Left axilla | Metabolic syndrome and pasthistory of inactive familial Mediterranean fever | ND | Baricitinib | ND | Remission |
| 18 | Castro (14) (2023) | 89 | F | Legs and foot | ND | ND | Tofacitinib | ND | Healed and relapse-free |
| 19 | Van Eycken et al. (15) (2023) | 65 | F | Abdom | HLAB27 negative spondylarthritis (SpA) | Abdominal surgery scar | Upadacitinib | ND | Improved |
| 20 | Dos Santos et al. (16) (2023) | 45 | F | Legs | RA, SARS CoV-2 infection | ND | Upadacitinib | ND | Complete resolution |
| 21 | Wang et al. (17) (2024) | 44 | F | Left inguinal area | ND | ND | Baricitinib | ND | Healed |
| 22 | Sathyanarayana et al. (18) (2024) | 70 | F | Lower-limb | ND | ND | Tofacitinib | ND | Improved |
| 23 | Sathyanarayana et al. (18) (2024) | 43 | M | Bilateral lower-limb | ND | ND | Tofacitinib | ND | Improved |
| 24 | Sathyanarayana et al. (18) (2024) | 52 | F | Bilateral lower-limb | RA | ND | Tofacitinib | MTX (20 mg/week) | Improved |
| 25 | Mendolaro et al. (19) (2024) | 59 | F | Upper and lower limbs | CD | Colectomy and end ileostomy | Upadacitinib | ND | Improved |
| 26 | Köken Avşar et al. (20) (2024) | 41 | F | Right anterior leg | Enteropathic arthritis | ND | Tofacitinib | ND | Remission |
| 27 | Park et al. (21) (2024) | 62 | F | Lower limb | UC | ND | Upadacitinib | ND | Improved |
| 28 | Grisé et al. (22) (2024) | 82 | F | Lower extremities | Squamous cell carcinoma | Wide local excision | Baricitinib | ND | Improved |
| 29 | He and Tian (23) (2025) | 36 | F | Lower limbs | UC | ND | Upadacitinib | Schizophrenia | Healed |
| 30 | Estrella and Verallo-Rowell (24) (2025) | 54 | F | Right lateral ankle | UC | ND | Abrocitinib | ND | Improved |
| 31 | Gaig et al. (this case) | 20 | M | Face | ND | Local excision | Upadacitinib | Prednisolone | Improved |
Treatment of pyoderma gangrenosum with Janus kinase inhibitor.
M, male; F, female; Janus kinase, JAK; ND, not described; CD, Crohn’s disease; RA, Rheumatoid arthritis; UC, ulcerative colitis; AA, alopecia areata; IVIG, Intravenous immunoglobulins; HCQ, Hydroxychloroquine; RXT, Ruxolitinib; MTX, Methotrexate; DVT, deep vein thrombosis.
2 Case report
We report the case of a 20-year-old man who presented with a 4-month history of painful facial skin ulcers on 18 March 2025 (Figures 1A,B). The lesion appeared after excision of facial cysts. The patient had a history of eczema and acne, with no family history of similar conditions and psychosocial issues. On 10 March 2025, a biopsy suggested an infectious granuloma; however, negative acid-fast and periodic acid–Schiff stains were negative (Figure 1I). During previous evaluations of the ulcers, next-generation sequencing suggested the presence of Streptococcus pneumoniae and Klebsiella pneumoniae; however, antimicrobial therapy was ineffective. A second biopsy was conducted on 27 March 2025. Histopathological analysis of a skin-biopsy specimen obtained from the lesion border revealed a diffuse mixed inflammatory cell infiltrate. Cultures and polymerase chain reaction tests for deep mycosis and mycobacterial infections were negative. No acid-fast bacilli, fungi, or bacteria were identified using acid-fast or periodic acid—Schiff stains. Test results for herpes simplex virus 1, herpes simplex virus 2, interferon-gamma release assays, syphilis, human immunodeficiency virus, and hepatitis B DNA all showed no abnormalities. Additionally, tests for rheumatologic conditions and immunodeficiency were negative. At the current presentation, physical examination revealed a skin ulcer with a violaceous border on the right lower portion of the face (Figures 1C–E). We made the diagnosis of facial pyoderma gangrenosum (FPG). The patient was treated with oral prednisolone (0.5 mg/kg, six tablets) monotherapy once daily for 2 weeks. However, as the ulcer enlarged, treatment was escalated to combination therapy with Upadacitinib (15 mg once daily) for 8 weeks. Treatment with Upadacitinib hydrate and a tapering course of oral prednisolone was initiated. The patient took six tablets of prednisone orally daily for 2 weeks, took four tablets for 2 weeks, and reduced the dosage by one tablet per week until the medication was discontinued. By 3 April 2025, the majority of the ulcers on the left mandible and the left neck had healed. The skin lesion started to subside 1 month after the start of treatment. Our case responded well to Upadacitinib without adverse events. After 4 months, the patient reported complete resolution of the lesions (Figures 1F–H). At present, the patient is still under our follow-up schedule.
Figure 1
3 Discussion
PG is a debilitating skin disease marked by idiopathic neutrophil infiltration that causes the destruction of tissue and ulceration (24). Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG involves dysregulation of both innate and adaptive immunity (1), leading to a neutrophil-rich autoinflammatory process with the elevation of multiple cytokines (15, 26). Some of these cytokines act through the JAK/STAT pathway (3). The importance of the JAK/STAT pathway in PG has also been demonstrated through immunohistochemistry in skin biopsy specimens (27). The predisposition of PG is not well understood. Drug induction and the postoperative period are two potential triggers. In our case, the cause of FPG is due to the excision of left-sided facial cysts.
FPG is a rare subtype of PG (25). PG needs to be differentiated from infections, such as mycobacterial cellulitis, syphilitic granulomatous ulcers, and scrofuloderma; lupus vulgaris; malignancies; and vasculitis (2). It is often associated with various other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis (28). It may be associated with systemic inflammatory conditions, including inflammatory bowel disease (IBD), rheumatoid arthritis, or vasculitis, as well as leukemia or hepatitis. It may also be present in the setting of autoinflammatory syndromes, such as pyogenic arthritis, PG, and acne; PG, acne, and suppurative hidradenitis; and pyogenic arthritis, PG, acne, and suppurative hidradenitis, and in a small proportion of synovitis, acne, pustulosis, hyperostosis, and osteitis cases (28).
Diagnosing PG is challenging since there are no pathognomonic laboratory parameters or histopathological features (13). In 2018, a new Delphi consensus was published on the diagnostic criteria for PG, stating that diagnosis could be made by using one major and several minor criteria. The major criterion was neutrophilic infiltration at the ulcer edge on biopsy. The eight minor criteria are 1) the exclusion of infection; 2) a positive pathergy test; 3) a history of IBD or inflammatory arthritis; 4) the evolution of pustules, papules, or vesicles into ulcers within four days; 5) erythema, undermined borders, and tenderness around ulcers; 6) multiple ulcers with at least one location on the extensor surface of the lower leg; 7) cribriform or “wrinkled paper” scars at the site of healed ulcers; and 8) a reduction in ulcer size within one month after treatment with immunosuppressive drugs (29).
Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) followed by the addition of more slow-acting immunosuppressive drugs with superior adverse event profiles, including biologics, intravenous immunoglobulin (30), and JAK inhibitors (3, 28, 31). Our case and analysis of the previously published cases demonstrate JAKi as an effective treatment option for PG (3) (Table 1). Tofacitinib (a non-selective JAK inhibitor), ruxolitinib (JAK-1/2 inhibitor), and Upadacitinib (JAK-1 inhibitor) have been reported to be successful in treating PG in a handful of reported cases (10). Patients responded in a relatively brief period of time with few reported adverse events (22).
Patients documented to be treated with JAKis (Table 1) had a mean age of 55.2 years (range: 20–89 years) and consisted of 25.8% males and 74.2% females (Table 1). PG presented as ulcerations on the lower extremities in approximately 74% (23/31) of cases. Treatments were categorized as JAKi treatment combined with concomitant medications (11/31, 35.5%) or JAKi monotherapy without concomitant medications (20/31, 64.5%). Among JAKis, the most commonly used was tofacitinib (8/20, 40.0%), followed by baricitinib (5/20, 25%) and upadacitinib (5/20, 25%). Among JAKis used with concomitant medication, tofacitinib (8/11, 72.7%) was the most common, followed by upadacitinib (2/11, 18.2%) and ruxolitinib (1/11, 9.1%). The most common concomitant medication used was systemic corticosteroids (6/11, 54.5%).
4 Conclusion
While the management of PG is challenging because of the lack of standardized evidence-based treatments, notable advancements are being made in its identification and management. In our case, PG initially stabilized and subsequently decreased in severity under treatment with a JAKi and a tapering course of oral prednisolone.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
Ethics statement
The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
Author contributions
GG: Funding acquisition, Writing – original draft. LZ: Writing – review & editing. MH: Writing – review & editing. FS: Writing – review & editing. JC: Conceptualization, Validation, Writing – review & editing. JD: Writing – review & editing, Conceptualization, Validation.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the Natural Science Foundation of Wuhan (2025020701020244) and the Outstanding Doctor Fund Project of Wuhan No. 1 Hospital (2024D013).
Acknowledgments
The authors acknowledge the contributions of all the scientists in this area and apologize for failing to cite any study due to constraints of space.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
facial ulcers, pyoderma gangrenosum, Janus kinase inhibitor, Upadacitinib, neutrophilic dermatosis
Citation
Ge G, Zhan L, Huang M, Su F, Chen J and Dong J (2025) Case Report: Treatment of facial pyoderma gangrenosum with Upadacitinib. Front. Med. 12:1665013. doi: 10.3389/fmed.2025.1665013
Received
14 July 2025
Accepted
11 September 2025
Published
25 September 2025
Volume
12 - 2025
Edited by
Giusto Trevisan, University of Trieste, Italy
Reviewed by
Silvana Trincone, Maurizio Bufalini Hospital, Italy
Massimo Lucchi, Centro Studi Malattie Vascolari JF MERLEN, Italy
Updates
Copyright
© 2025 Ge, Zhan, Huang, Su, Chen and Dong.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jinbo Chen, chen999jb@163.com; Jing Dong, qianlicao1982@163.com
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.