INTRODUCTION

Pyoderma gangrenosum (PG) is a rare and disabling inflammatory skin disorder that presents with painful and rapidly progressing skin ulcers. The pathogenesis of PG is not completely understood and has been associated with inflammatory bowel disease (IBD) in 41% of cases and inflammatory arthritis in 20% of cases. The condition was initially termed “phagédénisme géométrique” by Brocq in 1908 and later renamed PG by Brunsting in 1930.1,2 However, parastomal pyoderma gangrenosum (PPG) was first identified in the 1980s after proctocolectomy and ileostomy for ulcerative colitis (UC) and has an incidence of 0.6% among patients with ileostomy and IBD.3 Drug-induced PG is a rare dermatological condition that usually evolves into deep ulcers over a period of days to weeks.4

CASE REPORT

A 29-year-old man with a medical history of UC and sacroiliitis (HLA-B27) associated with polyarthritis presented to the hospital with abdominal pain and increased bloody diarrhea. He started experiencing bloody diarrhea 5–10 times a day a week before admission, prompting the patient to visit his gastroenterologist. Combination therapy with both oral and rectal mesalamine was prescribed, but the bloody diarrhea continued to progress. In terms of his IBD, he diagnosed with UC-pancolitis in 2014. He had a good response to sulfasalazine and infliximab. However, infliximab was discontinued due to muscle aches. He had another flare in 2018 of UC with pancolitis and was started on adalimumab with clinical remission. The patient was switched to ustekinumab due to financial issues. However, in 2021, he began to have arthropathy and sacroiliitis. He was diagnosed with sacrolitis (HLA-B27) and was switched to tofacitinib. In the emergency department, the patient was in acute distress and hemodynamically unstable. The patient's hospital course was further complicated by a toxic megacolon, necessitating an emergent total colectomy with an end ileostomy. After a prolonged stay in the intensive care unit, the patient was eventually discharged with tapering steroids only and scheduled for a follow-up visit.

Since discharge, the patient has been having weekly follow-up with the surgical service, and on the sixth week post discharge, he noticed a painful ulcerating lesion at the site of the ileostomy, which progressed to a larger wound over time (Figure 1). During the examination by the dermatologist, a tender 6 × 5 cm granulating ulcer with central ulceration and surrounding erythema, an undermining border, and a yellow exudate, consistent with PPG was noted. On reviewing the patient's medication list, it was discovered that the patient initiated treatment with secukinumab for worsening axial arthralgia by his rheumatologist in the fourth week post discharge. Dermatology deferred biopsy due to high clinical suspicion of PPG, and secukinumab was considered a potential culprit for the worsening skin findings, leading to its discontinuation. The patient was started on oral cyclosporine 250 mg, prednisone 60 mg, and clobetasol ointment. However, despite 3 months of adherence to the prescribed medications, the wound continued to grow. He had an endoscopy with normal findings (Figure 2). The medical team considered reintroducing anti-tumor necrosis factor biologics. However, due to the reactions to infliximab in the past, the decision was to hold. The surgical team decided to proceed with relocating the ileostomy while forming an ileal pouch-anal anastomosis. Approximately a month after the surgery, the patient began developing numerous erythematous, tender pustules on the chest, back, and posterior shoulders (Figure 3). Some of these pustules had an overlying yellow crust, whereas others exhibited active drainage that emerged after discontinuing immunosuppression for surgery. This was followed by a PPG flare. After restarting medical interventions, the patient's condition demonstrated improvement during follow-up visits.

Figure 1.:

Picture (A) represents the wound when it was first noticed. Picture (B) represents the wound after a follow-up. The lesion continued to progress despite being on optimal therapy for parastomal pyoderma gangrenosum. Picture (C) represents the lesion before the resiting of ileostomy.

Figure 2.:

No signs of erythema or ulcer in this endoscopy.

Figure 3.:

Picture (C) represents the lesion after the surgery; he was advised to continue taking immunotherapy and to follow up closely. Pictures (A, B) represent the new lesions that developed after the surgery.

DISCUSSION

Paradoxical reactions have been reported, where the use of certain drugs intended to alleviate conditions such as IBD or psoriasis results in the emergence or exacerbation of PG. Anti-tumor necrosis factor alpha (anti-tumor necrosis factor-α) agents, including infliximab, have been commonly associated with paradoxical reactions leading to PG.5 Currently, there are 3 biological agents used to target the interleukin-17A (IL-17A) pathway: secukinumab, brodalumab, and ixekizumab. Secukinumab is a recombinant, human IgG1 monoclonal antibody that binds to the protein IL-17A, a cytokine involved in the release of proinflammatory mediators. Secukinumab is approved for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. Adverse effects include severe infections and exacerbation of Crohn's disease.6 Secukinumab has been associated with PG induction in some case reports.7 An article from 2019 studied the relationship between IL-17 drugs and flare-ups of IBD, and it showed a total of 12 new IBD cases, translating to an incidence rate of 2.4 cases per 1,000 patients.8 Published cases further illustrate the complex dynamics, with one noting the development of PG after switching from adalimumab to secukinumab and another highlighting the successful treatment of PG with secukinumab.9,10

Consequently, healthcare practitioners are advised to contemplate alternative immune-modulating strategies for patients with IBD, especially in the context of ankylosing spondylitis or psoriasis.11 IBD is the most frequently diagnosed underlying systemic disease for PPG. In a study, 17 patients had the diagnosis of PPG and were started on treatment corticosteroid and appropriate stoma, resulting in an overall response rate of 73.3%.12 This case presents a unique secukinumab-induced refractory PPG in a patient with biologic-refractory UC. The initiation of secukinumab, intended to address worsening axial arthralgia, resulted in the emergence of PPG at the site of the ileostomy. What makes this report unique is the specific manifestation of refractory PPG in the context of secukinumab. Despite discontinuation of the drug and subsequent treatment with cyclosporine, prednisone, and clobetasol ointment, the wound continued to progress. The subsequent relocation of the ileostomy with improvement to the PPG but the development of PG on the chest, back, and posterior shoulders further add complexity to the case.

The discussion section emphasizes the evolving landscape of paradoxical reactions associated with biological treatments. The link between secukinumab and PG is based on limited case reports.7,10 Although our understanding is incomplete, recognizing this connection is crucial, especially for patients with an autoimmune history. IL-17 therapy initiation demands careful screening due to potential PG and IBD.

DISCLOSURES

Author contributions: A. Zaher: manuscript drafting, chart review and data abstraction, manuscript revision. M. Castillo: manuscript drafting, manuscript revision, is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

REFERENCES 1. Brocq L, Simon CL. Contribution à l'étude du phagédénisme. Bull Soc Méd Hop Paris. 1908:290–307. 2. Brunsting LA, Goeckerman WH, O'Leary PA. Pyoderma (echthyma) gangrenosum. Arch Derm Syphilol. 1930;22(4):655. 3. Mancini GJ, Floyd L, Solla JA. Parastomal pyoderma gangrenosum: A case report and literature review. Am Surg. 2002;68(9):824–6. 4. Wang JY, French LE, Shear NH, Amiri A, Alavi A. Drug-induced pyoderma gangrenosum: A review. Am J Clin Dermatol. 2018;19(1):67–77. 5. Puig L. Paradoxical Reactions: Anti-Tumor Necrosis Factor Alpha Agents, Ustekinumab, Secukinumab, Ixekizumab, and Others. Curr Probl Dermatol. 2018;53:49–63. 6. Garieri P Pyoderma Gangrenosum and Inflammatory Bowel Disease: A Combined Medical (https://www.europeanreview.org/wp/wp-content/uploads/5191-5199.pdf) (2022). Accessed August 13, 2023. 7. Wollina U, Schönlebe J, Fürll C. Pyoderma gangrenosum induced by secukinumab: A late paradoxical drug reaction. Dermatol Ther. 2020;33(1):e13161. 8. Yamada A, Wang J, Komaki Y, Komaki F, Micic D, Sakuraba A. Systematic review with meta-analysis: Risk of new onset IBD with the use of anti-interleukin-17 agents. Aliment Pharmacol Ther. 2019;50(4):373–85. 9. Jin K, Matsuzaki Y, Akasaka E, Nakano H, Sawamura D. Pyoderma gangrenosum triggered by switching from adalimumab to secukinumab. J Dermatol. 2019;46(3):e108–e109. 10. McPhie ML, Kirchhof MG. Pyoderma gangrenosum treated with secukinumab: A case report. SAGE Open Med Case Rep. 2020;8:2050313X20940430. 11. Fries W, Belvedere A, Cappello M, Orlando A, Trifirò G. Inflammatory bowel disease onset during secukinumab treatment: Real concern or just an expression of dysregulated immune response? Clin Drug Investig. 2019;39(8):799–803. 12. Funayama Y, Kumagai E, Takahashi K, Fukushima K, Sasaki I. Early diagnosis and early corticosteroid administration improves healing of peristomal pyoderma gangrenosum in inflammatory bowel disease. Dis Colon Rectum. 2009;52(2):311–4.