|Year : 2021 | Volume
| Issue : 1 | Page : 57-58
Use of brodalumab for the treatment of pyoderma gangrenosum: A case report
Chang- Ming Huang, Tsen- Fang Tsai
Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
|Date of Submission||18-May-2020|
|Date of Decision||10-Aug-2020|
|Date of Acceptance||11-Aug-2020|
|Date of Web Publication||24-Mar-2021|
Dr. Tsen- Fang Tsai
Department of Dermatology, National Taiwan University Hospital, No. 7, Chung Shan S. Rd., Taipei 10048
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Huang CM, Tsai TF. Use of brodalumab for the treatment of pyoderma gangrenosum: A case report. Dermatol Sin 2021;39:57-8
Pyoderma gangrenosum (PG) is a rare inflammatory disorder currently classified as a neutrophilic dermatosis. It classically presents as chronic and recurrent painful nodules, plaques, or pustules that enlarge to form ulcers with undermined, violaceous borders. PG can be idiopathic, but up to 75% PG is associated with the underlying diseases such as inflammatory bowel disease, inflammatory arthritis, and hematological disorders.
We report the case of a 57-year-old female diagnosed with dermatomyositis, Sjogren's syndrome, and hyperthyroidism. Initially, she developed an asymptomatic, pea-sized, subcutaneous nodule on the left buttock in 2011. One week later, she received excision at another hospital. The 4-cm suture wound healed poorly with persistent discharge. Hidradenitis suppurativa (HS) was impressed. She received excision and primary closure again with a 12-cm suture wound 3 months later. Pathology reported suppurative inflammation, draining sinus formation, and extensive scarring. However, the excisional wound enlarged to an ulcer with an undermined violaceous border, which was regarded as a pathergy reaction. The painful ulcer persisted for 2 months before she visited our clinic in January 2012 [Figure 1]a. We did not notice the typical features of HS at the moment, such as comedones and multiple interconnected sinus tracts without normal skin in between. She was thus diagnosed with PG according to the clinical presentation. She received cyclosporine up to 250 mg/day, prednisolone 15–20 mg every other day, intralesional triamcinolone injection, and topical tacrolimus occlusion treatment. The lesion on the left buttock finally resolved in September 2013, with a residual cribriform scar [Figure 1]b. Overall, the pathological finding of neutrophilic infiltrate, pathergy, papules that ulcerated rapidly, typical morphology of the ulceration, and cribriform scar supported the diagnosis of PG.
|Figure 1: (a) Initial presentation at the outpatient clinic with a poor-healing linear ulcer with a violaceous, undermined border on the left buttock. (b) The left buttock pyoderma gangrenosum resolved with a residual cribriform scar.|
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Recurrent PG on the right buttock was noted in December 2018, which did not improve after cyclosporine up to 150 mg/day, colchicine 0.25 mg/day, prednisolone 10–20 mg/day, methotrexate 10 mg/week, and hydroxychloroquine 100 mg/day treatment. Furthermore, she suffered from adverse events including Cushing's syndrome, hypertension, hyperglycemia, and hypertrichosis. Thus, weekly secukinumab was added since April 2019 for seven doses (150 mg weekly from April 4 to May 15, and 300 mg on May 22). However, another PG lesion developed on her right buttock during secukinumab treatment. Brodalumab was then administered (210 mg weekly from June 3 to June 17 and brodalumab 210 mg biweekly since July 1). Both the PG lesions on the bilateral buttocks healed on week 11 [Figure 2]. She received brodalumab 210 mg biweekly until the end of October 2019. Meanwhile, we gradually tapered cyclosporine from 100 to 25 mg/day. Although the wound on the right buttock recurred, it remained small and stationary. Unfortunately, sudden-onset right putaminal hemorrhage happened in the early November 2019. Although there was no evidence of association, brodalumab was discontinued. Cyclosporine was increased to 250 mg/day due to the disease recurrence.
|Figure 2: Detailed treatment course of the biologics and clinical response. The biologics were used in addition to cyclosporine up to 150 mg/day, colchicine 0.25 mg/day, prednisolone 10–20 mg/day, methotrexate 10 mg/week, and hydroxychloroquine 100 mg/day.|
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| Discussion|| |
We presented a case of PG initially diagnosed with HS, which was treated with biologics targeting interleukin (IL)-17. PG and HS could share a common feature of inflammatory nodules initially., The association between PG and HS may be underreported previously. We could regard the overall history of our patient as PG with possible coexisting HS.
The pathophysiology of PG was considered to be multifactorial, including neutrophil dysfunction, immune dysregulation, and genetic influence. Early studies emphasized the role of defects in neutrophil chemotaxis in the pathogenesis of PG. Newer research focused on immune dysregulation that leads to abnormal neutrophil aggregation. T-cells recruit neutrophils through the production of chemokines, including IL-1β, IL-8, IL-17, and tumor necrosis factor-α. Increased IL-17 level was noted in PG skin.
There is a lack of consensus on the treatment of PG. Systemic corticosteroids, mycophenolate mofetil, infliximab, minocycline, and cyclosporine are common treatments for PG. Our patient received multiple treatments, including prednisolone, cyclosporine, secukinumab, followed by brodalumab. Secukinumab was chosen due to financial consideration. Both secukinumab and brodalumab demonstrated treatment effects, and the latter showed better treatment efficacy.
Secukinumab is a human IgG1 κ monoclonal antibody that binds to the IL-17A ligand, leading to blockade of IL-17A and IL-17A/F heterodimer. Brodalumab is a human IgG2 monoclonal antibody that binds to human IL-17 receptor A and blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F heterodimer. Theoretically, IL-17 blockades play a role in the treatment of PG because of their ability to block IL-17-dependent neutrophil migration. A recent study suggested that IL-17E promotes the recruitment of neutrophils through the activation of macrophages in a p38-dependent mechanism. Besides, IL-17E is upregulated in PG. Comparing the two biologics, IL-17E is blocked by brodalumab but not by secukinumab. This may explain the better treatment efficacy of brodalumab than secukinumab in our patient.
The efficacy of IL-17 antagonists in PG has rarely been reported. A 52-year-old female with refractory PG on bilateral hands showed a partial response to secukinumab. However, paradoxical drug reaction triggering PG was also reported in psoriasis or psoriatic arthritis patients treated with secukinumab or brodalumab.,
In short, we presented a case of refractory PG treated first with secukinumab and then brodalumab. To our knowledge, this is the first report of brodalumab in treating PG. Brodalumab may be a treatment option for PG patients who are refractory to traditional immunosuppressants or secukinumab.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
Prof. Tsen-Fang Tsai, a consultant editor of Dermatologica Sinica, had no role in the peer review process of or decision to publish this article.
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[Figure 1], [Figure 2]