Introduction
Pyoderma gangrenosum (PG) is a rare, non-infectious neutrophilic dermatosis characterized by rapidly progressive, painful ulcerations with undermined violaceous borders and purulent or hemorrhagic discharge [1]. It is most often associated with systemic diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), hematologic malignancies, and other autoimmune disorders [2–4]. Although uncommon, PG can also develop as a severe postoperative complication, with surgical trauma acting as a trigger through the pathergy phenomenon, whereby even minor injuries provoke exaggerated inflammatory responses [5, 6].
The estimated incidence of PG is approximately 0.63 per 100,000 person-years, with a median onset around 59 years of age [7]. A female predominance has been reported in some cohorts, with up to 76% of cases occurring in women [8]. Familial clustering and associations with immune dysregulation further suggest a genetic and immune logic predisposition. Importantly, up to 70% of PG cases are linked to an underlying systemic condition, underscoring the need for clinicians to investiate comorbidities when diagnosing and managing this entity [4, 8–10].
In the context of orthopaedic surgery, PG poses a unique diagnostic challenge. Following a joint replacement, its clinical presentation, including erythema, wound breakdown, purulent discharge, and elevated inflammatory markers, closely mimics early prosthetic joint infection (PJI). This overlap often results in delayed diagnosis, prolonged antibiotic use, and repeated debridements, which paradoxically worsen the lesions due to pathergy. Misdiagnosis can hove devastating consequences, including poor functional outcomes, limb loss and even death [11–14].
Given these challenges, timely recognition of PG after prosthetic implantation is crucial. This review synthesizes the available literature to provide an updated overview of the epidemiology, pathophysiology, clinical features, diagnosis, and management of PG in the setting of joint arthroplasty (JA). In particular, it aims to enhance orthopaedic surgeons’ awareness and knowledge of this rare but serious complication.
Epidemiology and clinical features
PG generally manifests on the lower extremities, particularly favouring the knee region. PG has been documented in many regions of the body, including the breast area, hand, knee, neck, and peristomal skin [9]. Inan et al. noted that approximately 70% of PG cases are associated with systemic conditions such as IBD, hematologic disorders, or RA, and that surgical or traumatic triggers precede disease onset in 25–50% of patients; clinically, PG is characterized by rapidly progressive, painful ulcers with undermined, violaceous borders, most commonly affecting the lower extremities [15]. Sterile cortical osteolysis has been noted close to PG ulcers as an additional extracutaneous feature of the condition [16]. Regions abundant in subcutaneous adipose tissue have a comparatively elevated risk; nevertheless, thorough research in this domain is lacking [17]. Surrounding skin is typically erythematous with infiltration and oedema, and ulcer edges are often violaceous and undermined [5].
Pathophysiology and risk factors
PG likely reflects neutrophil dysregulation and up-regulated pro-inflammatory cytokine signalling (for example, IL-8 and IL-1β); clinical responses to tumor necrosis factor-α (TNF-α) inhibitors also implicate TNF-α, though mechanisms remain incompletely defined [5, 18, 19]. In patients with IBD, PG is increasingly recognized as an autoinflammatory neutrophilic dermatosis linked to immune dysregulation [20]. Neutrophil dysfunction, aberrant chemotaxis, and excessive cytokine signalling, particularly involving IL-23/IL-17 and TNF-α pathways, mirror the inflammatory circuits active in ulcerative colitis and Crohn’s disease [21]. Dysregulated inflammasomes and anus kinase/signal transduction and activator of transcription (JAK/STAT) signalling further connect PG to IBD pathogenesis [22]. PG lesions often parallel intestinal disease activity but may also arise independently, underscoring the systemic nature of immune dysregulation in this patient group [23, 24].
A hallmark feature of PG is pathergy [18]. In support of this, Kim et al. found that all cases of postoperative PG in their 20-year Korean cohort had a preceding history of trauma, underscoring the clinical importance of pathergy in surgical settings [1]. After JA, surgical trauma combined with immune dysregulation and systemic inflammatory comorbidities can precipitate PG, which worsens with repeated surgical interventions due to the underlying hyperinflammatory nature of the disease [17, 25]. Blood diseases like leukemia, myelodysplastic syndromes, and monoclonal gammopathy are linked with PG, perhaps as a result of aberrant immune cell function [5, 6]. Chronic use of corticosteroids, biologics, or chemotherapy agents can change immune regulation, predisposing to PG in susceptible patients [18, 26].
Clinical presentation of PG after arthroplasty
After JA, PG most often mimics PJI, presenting with erythema, wound breakdown, and purulent drainage within 1–3 weeks postoperatively. The knee is the most frequently affected joint, followed by the hip, while cases involving the shoulder are rare and those after elbow or ankle arthroplasty have not been reported. Across approximately 17 published reports, lesions typically appeared within the acute postoperative period and were initially misdiagnosed as infection, leading to repeated debridements, implant exchanges, or antibiotic courses before biopsy confirmed PG. Most patients responded rapidly to systemic corticosteroids and adjunct immunosuppressive therapy, sometimes combined with flap reconstruction or VAC dressing. Outcomes are usually favourable when treatment is started early; however, delayed recognition is associated with prolonged hospitalization, limb loss, and, in isolated cases, fatal systemic complications. These findings underscore the importance of maintaining a high index of suspicion for PG in patients with atypical or worsening postoperative wounds unresponsive to antibiotics [12, 13, 27–41].
A summary of key case reports describing the clinical presentation, culture results, and treatment outcomes of PG following JA is presented in Table 1.
Table 1
Reported cases of post-arthroplasty PG: onset, diagnosis, and outcomes
| Author [ref.] | Age | Sex | Joint/procedure | Comorbidities/risk factors | Time to onset | Initial diagnosis | Final treatment | Clinical outcome |
|---|---|---|---|---|---|---|---|---|
| Attar et al. [27] | 80 | F | Bilateral TKA | DVT/PE (on warfarin), prior PG | Day 7 | Acute PJI | CS + bilateral flap reconstructions | Full wound healing, functional recovery |
| Wadia et al. [28] | 80 | F | Bilateral simultaneous TKA | Nonsignificant (previous gynaecologic surgery only) | Day 3–7 | PJI | High-dose systemic CS (prednisolone 60 mg daily); supportive wound care | Improved following correct diagnosis |
| Nakajima et al. [29] | 80 | F | TKA | Type 2 diabetes mellitus, positive rheumatoid factor | Day 5–7 (PG dx Day 17) | PJI/NF | Systemic CS (prednisolone 20 mg), cyclosporine 100 mg/day, LDMF reconstruction | Complete wound healing in 3 months; functional knee motion from 0–110°; ambulated with T-cane |
| Hill et al. [30] | 63 | F | UKA | Sjögren’s syndrome | Day 6 (wound breakdown) | PJI | High-dose systemic CS, VAC, hyperbaric oxygen, medial gastrocnemius flap with STSG | Progressive wound healing achieved; functional recovery |
| Yik et al. [31] | 56 | M | TKA | – | Day 6 (PG dx Day 15) | PJI | Systemic CS (oral prednisone 0.5 mg/kg), medial gastrocnemius flap with STSG | Wound healed successfully, no recurrence of PG |
| Loomis et al. [32] | 62 | M | Bilateral TKA | HTN, HLD, AF, obesity | Day 9 (diagnosed > POD 20) | PJI/NF | CS 1 mg/kg; Integra dermal substitute + full-thickness skin graft | Healed; ROM > 125°; unassisted ambulation; complete healing at 12 months |
| Shah et al. [12] | 65 | F | TKA | Overweight; HTN | Day 6 (PG dx Day 16) | PJI | CS, VAC, antibiotics, gastrocnemius flap | Died from septicaemia after flap |
| Jain et al. [33] | 63 | M | TKA + fasciocu-taneous flap | HTN; multiple prior knee arthroscopies | Day 6 (worsening after flap ~Day 46) | PJI | Prednisolone 40 mg daily + antibiotics + wound coverage with saphenous flap and STSG | Healed over 8 weeks |
| De Thomasson et al. [34] | 65 | F | THR | Past history of colon and pancreatic adenocarcinoma (no recurrence) | Day 8 | Acute PJI | High-dose oral prednisone (1 mg/kg) + minocycline | Rapid improvement; complete healing by 6 weeks; normal function and no recurrence at 2 years |
| Mizushima et al. [35] | 69 | M | THR | Myelodysplastic syndrome with pancytopenia | Day 7 | PJI | Systemic CS | Wound improved after steroid administration |
| Burnett et al. [36] | 76 | M | Revision THR | AF (warfarin) | Day 4–7 | SSI/necrosis due to hematoma | Multiple debridements + VAC (no systemic steroids) | Wound healed; asymptomatic at 7 years |
| Kühn et al. [37] | 58 | F | Revision THR | – | Day 8 | PJI | IV prednisolone infusion (600 → 200 mg/day) | Rapid improvement; wound healed |
| Armstrong et al. [38] | 69 | M | THR | Prior history of PG | Early | PJI | Minimal debridement + CS | Wound healed; prophylactic steroids suggested for future PG patients |
| She et al. [39] | 65 | M | THR for FNR | Prior PG (ankle ulcer, healed with prednisone); bilateral femoral head necrosis | No recurrence | – | Perioperative prophylactic steroids (hydrocortisone + prednisone), wound care, prednisone maintenance | Healed well, no recurrence, full hip function at 1 year |
| Antoni et al. [40] | 55 | F | HA for FNR in a patient with active PG | Active PG on treatment | Pre-existing PG before fracture | – | HA after 13 days after improvement with CS (40 → 20 mg), peri-op antibiotics, tissue-sparing closure | Complete wound healing without PG at surgical site; full ROM at 7 months |
| Laskaratou et al. [13] | 86 | F | HA for FNR | – | Day 3 (PG dx Day 13) | Infection → debridement + implant exchange | CS, VAC, wound closure | Died at 7 months (pancytopenia complications) |
| Domej et al. 2017 [41] | 75 | F | RSA | Non-Hodgkin lymphoma (in remission) | 7–14 | PJI | Multiple revisions, spacer, antibiotics → CS + VAC therapy | Wound healing, pain relief, improved shoulder function; stable prosthesis at 6 months |
[i] TKA – total knee arthroplasty, UKA – unicompartmental knee arthroplasty, THR – total hip replacement, HA – hemiarthroplasty, FNR – femoral neck fracture, RSA – reverse shoulder arthroplasty, PG – pyoderma gangrenosum, CS – corticosteroid, DVT – deep vein thrombosis, PE – pulmonary embolism, HTN – hypertension, HLD – hyperlipidaemia, AF – atrial fibrillation, PJI – prosthetic joint infection, NF – necrotizing fasciitis, VAC – vacuum-assisted closure, CRP – C-reactive protein, LDMF – latissimus dorsi myocutaneous flap, STSG – split thickness skin graft, PE – polyethylene exchange.
Diagnostic approach for PG
Clinical evaluation and recognition of characteristic lesions
The classic presentation of PG is a rapidly growing, painful wound that develops close to the site of surgery, with violaceous borders, undermined edges, and surrounding inflammatory skin [9, 17]. A history of trauma, raises clinical suspicion, particularly in patients with underlying IBD or RA [8]. Diagnosis relies on a high index of clinical suspicion, supported by negative cultures and variable histopathology [8, 42].
Differential diagnosis
After JA, clinicians must carefully differentiate PG from other conditions that can present with similar wound-related complications. Important differential diagnoses include SSIs, vasculitis, necrotizing fasciitis, autoimmune blistering diseases, cutaneous malignancies, and vascular insufficiency ulcers [8]. Drug reactions and traumatic wound dehiscence should also be considered. Accurate distinction is critical, in order to avoid unnecessary surgical intervention, which can exacerbate PG [8, 9].
Role of biopsy in the diagnosis
Histopathology of PG typically demonstrates neutrophilic infiltration, dermal oedema, tissue necrosis, and leukocytoclastic debris at the ulcer margins. However, these features are not pathognomonic, and the primary role of biopsy is to exclude alternative diagnoses such as infection, vasculitis, or malignancy. Biopsy becomes particularly valuable when wound cultures are negative and an ulcer continues to worsen despite appropriate antibiotic therapy, prompting clinicians to consider non-infectious aetiologies [8, 9].
Role of laboratory tests in the diagnosis of PG
Laboratory investigations in PG are largely non-specific and serve to support, rather than confirm, the clinical diagnosis. PG should be suspected when wound or blood cultures remain negative despite persistent inflammation and progressive ulceration [9]. Routine laboratory workup often includes autoimmune panels, such as antinuclear antibodies, rheumatoid factor, and other immunologic markers, which are useful for detecting associated systemic conditions [8, 17].
Importantly, patients with PG frequently exhibit neutrophilia and elevated acute-phase reactants (CRP and ESR). This inflammatory profile closely resembles that of bacterial infection and may persist even when cultures are sterile. As a result, standard inflammatory markers cannot reliably distinguish PG from PJI on, contributing to diagnostic uncertainty in the early postoperative period [43, 44].
Microbiological confusion in diagnosing PG
Unlike true infections, ulcers in PG are sterile, with cultures remaining negative despite extensive necrosis [25]. A careful interpretation of microbiological results, particularly the persistence of negative cultures despite clinical deterioration, combined with clinical suspicion, is essential for distinguishing PG from bacterial infection.
Management and treatment of PG after arthroplasty
Effective management of PG following a JA requires early recognition and prompt initiation of immunosuppressive therapy, while avoiding unnecessary surgical interventions that can worsen disease progression through pathergy.
Medical management
First-line drugs are corticosteroids (oral or intravenous). Steroid-sparing agents, including cyclosporine, mycophenolate mofetil, tacrolimus, azathioprine, and dapsone, are recommended for patients requiring prolonged immunosuppression or when corticosteroid toxicity is a concern [18, 26].
Adjunctive topical treatments, such as high-potency corticosteroids or calcineurin inhibitors, may help control localized inflammation around wound margins [5].
Biologic therapies have an increasingly important role, particularly in refractory postoperative PG or in patients with concomitant autoimmune disease. TNF-α inhibitors (e.g., infliximab, adalimumab) and interleukin inhibitors (e.g., ustekinumab) have demonstrated clinical efficacy in difficult-to-control or recurrent cases [18, 20]. Biologics may also be considered for patients who experience frequent relapses despite conventional agents [18].
Patient education remains essential. Individuals should be instructed on appropriate wound care and encouraged to promptly report new ulcerations, delayed wound healing, or early signs of recurrence, as timely intervention can prevent significant complications [25, 45].
Surgical management
Once inflammation is controlled, reconstructive procedures, including muscle flaps, skin grafts, and negative pressure wound therapy, may be used to optimize wound closure and protect prosthetic implants [30, 45].
Monitoring and long-term management
Once clinical improvement is achieved, immunosuppressive therapy should be tapered gradually to minimize the risk of relapse while avoiding complications from prolonged corticosteroid use [18]. Patients with underlying autoimmune diseases, require particularly close follow-up, as systemic inflammation can predispose them to recurrent episodes [5, 25].
Multidisciplinary care
A coordinated multidisciplinary approach is essential in managing postoperative PG. Collaboration among surgical, dermatologic, rheumatologic, and infectious disease teams enables timely diagnosis, appropriate immunosuppressive treatment, and avoidance of unnecessary procedures. This integrated care model improves wound healing, preserves prosthetic implants, and reduces the risk of recurrence and long-term morbidity [17, 25, 45].
Mortality and outcomes
While PG is associated with significant morbidity, mortality is uncommon yet clinically significant [12, 13]. The majority of patients recover with prompt and appropriate immunosuppressive therapy [8, 17]. Delayed diagnosis increases morbidity, with severe systemic disease, PG can progress to severe complications, including sepsis, prosthesis exposure, or functional loss [9, 11, 14, 17, 46].
Discussion
PG following JA surgeries is an uncommon but clinically important postoperative complication that poses significant diagnostic and therapeutic challenges. Its rarity, combined with clinical resemblance to PJIs, complicates timely recognition [9, 17]. Patients frequently present features that mimic bacterial infections and thus prompt unnecessary surgical debridement or antibiotic administration [12].
Arthroplasty-associated PG tends to be more aggressive, with deeper ulceration, increased risk of implant exposure, and prolonged morbidity [45, 47]. In contrast, non-arthroplasty PG, such as after fracture fixation, spinal procedures, or soft-tissue surgeries, typically remains more localized and carries a lower risk of implant-related complications, though it is equally prone to misdiagnosis [14, 48]. These differences underscore the importance of tailoring management strategies to the surgical context.
From an immunologic standpoint, postoperative PG appears to differ from classical PG. In the Mayo Clinic cohort by Tolkachjov et al. [17], associated systemic diseases such as IBD, RA, or hematologic disorders were significantly less common than the ~70% reported in classical PG. This suggests that postoperative PG may arise even in otherwise healthy individuals without baseline immune dysregulation, making preoperative risk stratification more challenging.
As summarized in Table 1, the majority of reported patients did not exhibit classical PG-associated systemic diseases. Only a small number showed potential systemic associations: Nakajima et al. [29] reported a patient with positive rheumatoid factor without a confirmed autoimmune diagnosis; Hill et al. [30] described a patient with Sjögren’s syndrome; and Mizushima et al. [35] presented a case involving myelodysplastic syndrome treated with granulocyte colony-stimulating factor, both relevant to immune dysregulation. The remaining cases involved common comorbidities not typically linked to PG pathogenesis. Taken together, these findings reinforce that post-arthroplasty PG represents a distinct postoperative phenotype in which traditional comorbidity profiles have limited predictive value.
In a dataset of over 2,200 cases, Łyko et al. reported wide variability in presentation and outcomes, highlighting the complexity of managing this condition across different settings [19]. Similarly, Guliyeva and Janis emphasized the role of plastic surgical intervention in advanced or misdiagnosed postsurgical PG cases, reinforcing the need for timely diagnosis and interdisciplinary care [45].
Moving forward, clinicians should maintain a high index of suspicion for PG in patients with poor wound healing after JA, especially those with autoimmune comorbidities and negative cultures [17, 49]. Future research must focus on standardizing diagnostic criteria, educating surgical teams on postoperative PG, and exploring new immunomodulatory therapies that can improve outcomes [18].
This review is limited by the nature of the available literature, which predominantly consists of case reports and small case series. The lack of large-scale prospective studies restricts the ability to establish standardized diagnostic or treatment guidelines. Reporting bias is also likely, as more severe or unusual cases are preferentially published, potentially overestimating complication rates. Moreover, heterogeneity in clinical presentation, diagnostic criteria, and therapeutic approaches across studies complicates direct comparisons and synthesis. Finally, the absence of long-term follow-up data in many reports limits understanding of recurrence rates, functional outcomes, and prosthesis survival in patients with post-arthroplasty PG.
Conclusions
Although rare, PG after JA is a serious and frequently unrecognized postoperative complication. Its close resemblance to periprosthetic joint infection often results in unnecessary debridement and prosthesis removal, leading to worse outcomes. It significantly influences patient recovery and surgical outcomes. The review emphasizes early diagnosis, exclusion of infection, and early treatment with immunosuppressive medication. A multidisciplinary approach is essential to ensure good outcomes and reducing complications. The review also highlights the necessity of heightened clinical awareness and diligent postoperative monitoring to prevent delays in diagnosis. Future studies should develop standardized diagnostic guidelines, and the effectiveness of newer biologic agents needs to be evaluated.
