Infliximab-induced Remission of Postoperative Pyoderma Gangrenosum: A Case Report and Literature Review

Abstract

Background:

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, rapidly progressive cutaneous ulcers. Postoperative PG (PPG) represents a distinct variant that develops at surgical or traumatic sites due to the pathergy phenomenon. Early diagnosis is often challenging, as it requires the exclusion of other causes such as infection, and misdiagnosis may lead to inappropriate surgical interventions and treatment delays.

Methods:

We report the case of a 69-year-old man who developed extensive ulcerative lesions at both surgical sites following bilateral high ligation of the great saphenous veins for chronic venous insufficiency. Despite multiple surgical debridements and broad-spectrum antibiotics, the lesions continued to worsen. A diagnosis of PPG was made, and systemic corticosteroid therapy was initiated, resulting in partial improvement.

Results:

Infliximab was prescribed, leading to complete healing, and all immunosuppressive agents were discontinued, with the patient remaining in remission. This case highlights the importance of recognizing PPG in postsurgical ulcers that fail to respond to conventional therapy and demonstrated the efficacy of infliximab. A review of the literature on clinical outcomes and treatment regimens involving infliximab is also provided.

Conclusions:

Our case supports tumor necrosis factor-α inhibitors as effective steroid-sparing treatment for severe or refractory PPG.

Takeaways

Question: Does early treatment with infliximab enhance wound healing in patients with postoperative pyoderma gangrenosum (PPG)?

Findings: We report a postoperative ulcer that rapidly progressed despite antibiotics and repeated debridement. Once PPG was diagnosed, corticosteroids with early infliximab led to rapid pain relief, complete closure and sustained remission, in line with outcomes reported in prior case reports.

Meaning: Clinicians should be aware of clinical worsening in postoperative wounds. Successful management of PPG relies on early suspicion, avoidance of debridement, and rapid initiation of immunosuppression to prevent pathergy and optimize wound healing.

INTRODUCTION

Pyoderma gangrenosum (PG) is a chronic inflammatory disorder characterized by painful, progressive, necrotizing skin ulcers that can affect individuals of all ages. Although its exact pathogenesis remains unclear, dysregulated neutrophilic activity is thought to play a central role. PG often demonstrates pathergy, with lesions appearing or worsening at sites of minor trauma, providing a diagnostic clue. Confirmation typically requires a skin biopsy to exclude infection. Postoperative PG (PPG) has been reported across various surgical specialties, including orthopedic, cardiothoracic, general, plastic, and gynecologic surgery. It presents as rapidly progressive ulceration at surgical sites and is often misdiagnosed as infection or necrotizing fasciitis, leading to surgical debridement that may worsen the condition. Therefore, early recognition and prompt initiation of therapy are essential. Although standardized treatment guidelines are lacking, immunosuppressive therapy has demonstrated favorable outcomes. We report a case of PPG following vascular surgery for chronic venous insufficiency that responded successfully to infliximab.

CASE PRESENTATION

A 69-year-old man was referred for evaluation of progressive, painful ulcers following bilateral high ligation of the great saphenous veins with venous stripping (Fig. 1A). He was otherwise healthy, was a nonsmoker, and had a history of dyslipidemia and chronic venous insufficiency. He underwent bilateral high ligation and great saphenous vein stripping with stab avulsion, with no immediate postoperative complications reported. On postoperative day (POD) 5, he developed painful erythema patches on both groin surgical sites, accompanied by fever, for which oral amoxicillin-clavulanic acid was prescribed. Two days later, he was admitted with wound dehiscence and underwent incision and drainage; Gram staining of wound exudate was negative. In the absence of clinical improvement, antibiotics were escalated to intravenous meropenem and vancomycin.

Fig. 1.

Clinical photographs of the skin lesions before and after treatment. A, Deep ulcerations at the bilateral groin surgical sites with violaceous undermined borders, surrounding erythema, scattered black discoloration, and purulent wound bases. B and C, Clinical improvement after infliximab treatment (B, right groin; C, left groin).

On POD 8, he was transferred to our hospital with a provisional diagnosis of necrotizing fasciitis and underwent surgical debridement. A new ulcer appeared on his left shin the following day (Fig. 2). On POD 11, repeat debridement was performed, and intravenous colistin was initiated. The wound was managed by negative pressure wound therapy. Despite the use of broad-spectrum antibiotics, the ulcers rapidly expanded, causing extensive tissue necrosis and persistent fever. The patient subsequently developed sepsis with pulmonary edema and required intubation. A dermatology consultation was obtained on POD 14. Examination revealed two 13 × 15 cm purulent ulcers on both groins, with undermined borders, surrounded by bluish purple erythema, and covered with yellow-to-black necrotic tissue (Fig. 1A). Pain was severe (10 out of 10 on the numeric pain rating scale). Laboratory findings revealed anemia, leukocytosis with neutrophilia, and elevated levels of creatinine and direct bilirubin. A comprehensive infectious workup, including blood, urine, wound, and tissue cultures, was negative. Chest radiography was unremarkable. PPG was suspected, and intravenous dexamethasone 15 mg/d was initiated promptly. Incisional biopsy from the right groin showed epidermal ulceration with dense neutrophilic infiltration extending into the deep subcutaneous fat, consistent with PPG (Fig. 3). Special stains (Grocott methenamine silver, periodic acid-Schiff, Fite, acid-fast bacillus, and Brown and Brenn) and bacterial and fungal cultures were negative. Wounds were gently debrided only as necessary and covered with an alginate dressing to avoid pathergy. Screening for autoimmune disorders, inflammatory bowel disease, and solid and hematologic malignancies was negative.

Fig. 2.

A photograph of ulcers with erythematous to violaceous edges at surgical wound (right shin).

Fig. 3.

Histopathological findings of the skin lesion. A and B, Histopathology showed epidermal ulceration with diffuse inflammatory cell infiltration involving the dermis and subcutaneous tissue, including perifollicular infiltration (hematoxylin and eosin stain; A, ×40; B, ×400).

The patient had significant improvement in pain, fever, and leukocytosis. He was successfully extubated but developed steroid-induced hyperglycemia, prompting modification of therapy to oral prednisolone (60 mg/d) combined with cyclosporine (150 mg/d). After 42 days of corticosteroid therapy and slight improvement in the ulcer, the wound was still characterized by persistent heavy exudate and refractory pain and remained almost the same size; therefore, infliximab (5 mg/kg) was administered at baseline and repeated at weeks 2 and 6. Three weeks following the final infusion, the ulcers showed near-complete epithelialization with healthy granulation tissue and early scar formation (Fig. 1B and C). Cyclosporine was tapered over a period of 5 months, and prednisolone was gradually discontinued over 14 months (Fig. 4). The patient remained in complete remission without recurrence throughout the 14-month follow-up period.

Fig. 4.

Medication timeline.

DISCUSSION

Pyoderma gangrenosum (PG) is an uncommon, neutrophilic inflammatory disorder characterized by painful, erythematous to violaceous ulcerative plaques with undermined borders and pathergy, where lesions expand rapidly after minor trauma. PPG represents a pathergic response developing at surgical incision sites. It usually occurs within 2 weeks postoperatively,¹ with a mean onset of seven days,² and patients often present with fever, malaise, leukocytosis, and elevated inflammatory markers. Delayed diagnosis, averaging 15 days postoperatively, reflects the difficulty in distinguishing PPG from wound infection.² Although the chest and abdomen are commonly affected, lower extremities can also be involved, as in our patient. Rarely, lesions can occur in the anogenital region, where necrotizing fasciitis must be excluded. Early recognition is crucial to prevent unnecessary aggressive debridement, which can exacerbate the disease and hinder the timely initiation of immunosuppressive therapy.

Histopathology of PPG typically shows dense dermal neutrophil infiltration, similar to classic PG, and biopsy primarily serves to exclude alternative diagnoses. Our patient presented with wound dehiscence, severe pain, nonhealing ulcers developing within seven days postoperatively, violaceous undermined borders, rapid progression, poor response to antibiotics, worsening after debridement, and negative cultures, all consistent with prior PPG reports.² PG is often associated with systemic conditions, including inflammatory bowel disease, arthritis, and hematologic malignancies,^2,3 whereas PPG is less frequently linked to systemic disease.¹ However, screening for underlying conditions remains essential for optimal management. Hematologic dyscrasias have been reported as the most common systemic association in PPG.

Although early treatment is essential, standardized protocols for PPG are lacking. Management strategies are often adapted from PG guidelines,⁴ with goals to suppress inflammation, promote healing, control pain, and manage comorbidities. Systemic corticosteroids remain the first-line therapy,^5,6 typically administered as prednisone (1–2 mg/kg/d) or methylprednisolone (1 mg/kg/d),^7–9 inhibiting proinflammatory gene expression (eg, interleukin [IL]-1α, IL-1β), cytokine synthesis, and neutrophil migration. Most patients respond within 1–2 weeks, with halted lesion progression and pain relief.¹⁰ However, prolonged corticosteroid therapy with gradual tapering is often required, increasing the risk of adverse effects, including infection, insulin resistance, and hypertension. Steroid-sparing agents should be introduced during the tapering process. Cyclosporine is commonly used as a first-line adjunct, whereas azathioprine and methotrexate are alternative options with careful monitoring for bone marrow suppression. Healing is often slow, and delayed repair can substantially affect patient well-being, as observed in our case.

In refractory or severe cases, tumor necrosis factor (TNF)-α inhibitors—including infliximab, adalimumab, and etanercept—have shown efficacy^11–13 by neutralizing TNF-α and preventing recruitment of inflammatory cells to the skin.^11,12,14 Anti-TNF therapy has mainly been reported in patients with PG and underlying inflammatory bowel disease. Infliximab, the most commonly used induction agent, often achieves significant improvement, sustained wound healing, or complete remission without the need for additional therapy.¹³ Although no head-to-head studies confirm its superiority, the rapid onset associated with the infusion formulation may contribute to its favorable outcomes.

Through a literature review, we identified 19 instances of PPG in which infliximab was administered^12,15–29 (See table, Supplemental Digital Content 1, which displays the infliximab treatment of postoperative PG, https://links.lww.com/PRSGO/F111.) In our literature review, each article was reviewed independently by 2 reviewers (P.P. and N.P.), both at the title/abstract and full-text levels. Disagreements between the 2 reviewers regarding the studies’ eligibility were resolved via discussion with a third reviewer (P.R.). We included any case report, case series, or retrospective study describing PPG and/or infliximab in PubMed/MEDLINE and Google Scholar. We excluded studies with duplicate data from case reports and those with no English version available. Fifteen (79%) patients achieved a complete response, with approximately 60% remaining recurrence-free. Infliximab failed in one patient, who subsequently responded to adalimumab, supporting the feasibility of class switching. The most common regimen was 5 mg/kg on weeks 0, 2, and 6, followed by maintenance every 6–8 weeks. Adverse events were rare; however, 2 patients developed allergic reactions or severe serum sickness, necessitating discontinuation. Infliximab has also been used prophylactically to prevent pathergy in patients undergoing subsequent surgery, successfully preventing disease flare-ups.³⁰

Seven weeks postdiagnosis, the patient was initiated on infliximab therapy, as the condition remained refractory to conventional management with systemic corticosteroids and cyclosporine A. Although the initial dual-immunosuppressive regimen achieved clinical stabilization, it failed to induce complete wound closure. Following the introduction of the TNF-α inhibitor under rigorous clinical surveillance, the bilateral ulcerations demonstrated a marked reduction in maximal longitudinal dimensions, contracting from 13 and 15 cm to 3 and 3.5 cm, respectively. Complete clinical remission was ultimately achieved 18 weeks after the first infliximab administration.

A review of the literature highlights a comparable case by Imaizumi et al,¹⁶ in which infliximab was initiated within a nearly identical timeframe (48 d postdiagnosis). Notably, although their patient required 24 weeks to achieve complete remission, our patient reached full clinical resolution significantly faster, within 18 weeks. This accelerated recovery may be attributable to the synergistic effect of the dual-agent immunosuppressive regimen utilized in our case, whereas the patient described by Imaizumi et al received only corticosteroid monotherapy before biological intervention.

Furthermore, the healing velocity in our case aligns with broader literature suggesting that both timing and treatment intensity are critical. The most rapid clinical remission reported (7 wk) occurred in a patient who received infliximab exceptionally early (day 15)²⁷ in combination with a triple-therapy regimen (systemic corticosteroids and methotrexate). Collectively, these observations suggest that the early administration of infliximab, particularly when integrated with potent systemic immunosuppressive agents, significantly reduces the duration required for complete wound healing.

Although this report demonstrates the successful application of infliximab for the treatment of PPG, several significant limitations must be acknowledged. As a single case report, this article lacks generalizability. The clinical successes described here and within the included literature review may be subject to publication bias, as cases with favorable outcomes are more likely to be reported than those involving therapeutic failure or adverse events.

Our patient had no contraindications to infliximab, such as congestive heart failure, multiple sclerosis, or tuberculosis. Infliximab was initiated to prevent disease flares during steroid tapering, resulting in rapid ulcer improvement. Following the favorable response, we discussed with the patient the potential benefit of prophylactic infliximab if future aggressive surgery is required. Our experience, consistent with the current literature, suggests that early initiation of infliximab may improve response rates and facilitate faster wound healing in PPG.

CONCLUSIONS

Early recognition of PPG is crucial to prevent pathergy and unnecessary surgery. Prompt initiation of TNF-α inhibitors—particularly infliximab—can effectively control inflammation, promote wound healing, and improve patient outcomes, especially in cases of severe or refractory disease.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.

PATIENT CONSENT

Informed consent was obtained from the parents for the publication of the case report and clinical images.