RARE DISEASE
Pyoderma gangrenosum
Pyoderma gangrenosum
Pyoderma gangrenosum
Drug discovery
6
drugs
With orphan designations
Overview
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly progressive, painful ulcerations with violaceous undermined borders. It manifests through dysregulated innate immunity, often associated with systemic conditions (e.g., inflammatory bowel disease, arthritis) in 30-50% of cases [1][4][6]. Diagnosis remains clinical after excluding infectious/vascular causes [15][16], with treatment focusing on immunosuppression and advanced wound care [3][6][8].
Therapies
Mild: High-potency topical steroids (clobetasol), tacrolimus, antimicrobial dressings [3][6][18]
Moderate-severe: Systemic corticosteroids, cyclosporine, TNF-α inhibitors (infliximab/adalimumab) [3][8][13]
Adjuvant care: Pain management, avoidance of trauma/pathergy, staged surgical repair post-remission [1][6][18]
Categories: rare skin diseases, rare systemic and rheumatological diseases
Research Papers
1,398 drug discovery papers about Pyoderma gangrenosum, with 2 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,398 drug discovery papers about Pyoderma gangrenosum, with 2 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-16 | NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil activation in pyoderma gangrenosum across human and murine models.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, nonhealing cutaneous ulcers. Although dysregulated innate immunity and neutrophil activation are implicated in its pathogenesis, the underlying molecular mechanisms remain poorly defined. This study aimed to identify conserved pathogenic mechanisms by integrating analyses of human PG lesions and a brequinar-induced PG-like murine model and to assess therapeutic relevance. Skin biopsy specimens from patients with PG and publicly available RNA-sequencing data were analyzed alongside the murine model using histological and transcriptomic approaches. Cross-species transcriptomic integration identified shared inflammatory pathways between human and murine PG. Human PG lesions showed increased neutrophil infiltration, neutrophil extracellular trap formation, and a dominant type 1 inflammatory profile, all of which were recapitulated in the brequinar-induced mouse model, together with impaired wound healing. Transcriptomic analyses revealed enhanced oxidative stress responses and activation of the NLRP3/caspase-1 inflammasome pathway as a conserved pathogenic axis. In the murine model, both prednisolone and avacopan suppressed inflammatory cytokine expression and neutrophil activation; however, only avacopan significantly improved wound healing. Collectively, these findings suggest that NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil extracellular trap formation and may represent a PG-associated inflammatory pathway.
2026-08-15 | Preliminary exploration of effects of the JAK inhibitor tofacitinib on pyoderma gangrenosum: In vitro inhibition of NETs and Th17 differentiation.
Pyoderma gangrenosum (PG), a refractory inflammatory disorder, remains a condition with incompletely understood pathogenesis. Currently, no FDA-approved treatments are available. Janus kinase (JAK) inhibitors have been reported sporadically in case studies as effective treatments for PG. To characterize the cellular and molecular landscape associated with JAK/STAT (signal transducer and activator of transcription) pathway overactivation in PG lesions, and investigate the potential effects of tofacitinib on PG. Single-cell RNA sequencing (scRNA-seq) and multiplex immunohistochemistry (mIHC) were employed to characterize the cellular and molecular landscape of JAK/STAT pathway overactivation in PG. In vitro experiments (immunostaining, qPCR, western blot, flow cytometry) were performed to further validate the potential effects of tofacitinib on PG. We identified significant overactivation of the JAK/STAT pathway in PG lesions-particularly in advanced stages-which, in terms of immune inflammation, is primarily driven by myeloid cells and T cells. This activation was associated with enhanced neutrophil extracellular trap (NET) formation in myeloid cells and aberrant differentiation/plasticity of Th17 and Th17.1 (IL-17/IFN-γ double-producing) cells. In vitro cell experiments further demonstrated that the JAK inhibitor tofacitinib suppresses STAT phosphorylation in myeloid and T cells, myeloid NETosis, and IL-17A production. Our study investigated immunological profiling of PG lesions via scRNA-seq and mIHC, along with in vitro validation. These findings delineate a multi-axis cellular and molecular landscape of PG linked to aberrant JAK/STAT signaling, and provide preliminary in vitro evidence supporting potential inhibitory effects of tofacitinib on key pathological processes of PG.
2026-08-12 | Case Report: IVIG as a bridging strategy in high-risk antiphospholipid syndrome with infected cutaneous ulceration and thrombocytopenia.
Severe cutaneous ulceration in antiphospholipid syndrome (APS) with concurrent infection and thrombocytopenia presents a therapeutic dilemma: standard immunosuppression risks worsening infection, while anticoagulation risks hemorrhage. We present a high-risk case successfully managed using intravenous immunoglobulin (IVIG) as a bridging immunomodulatory strategy. A 73-year-old man with triple-positive APS and immune thrombocytopenic purpura (ITP) developed rapidly progressive leg ulcers with clinical features consistent with pyoderma gangrenosum-like disease, complicated by active MRSA and Pseudomonas aeruginosa infection and severe thrombocytopenia (12 × 109/L). Standard therapies were contraindicated: corticosteroids risked worsening infection; anticoagulation risked hemorrhage. The patient received IVIG (0.4 g/kg per dose, every 3 weeks) as primary immunomodulation, concurrent targeted antimicrobial therapy, temporary anticoagulation interruption, and discontinuation of baseline mycophenolate mofetil. Following platelet recovery above 70 × 109/L, therapeutic anticoagulation was resumed with enoxaparin (80 mg subcutaneously twice daily) and aspirin (75 mg daily). Over five months, progressive re-epithelialization culminated in complete healing with platelet recovery. This case supports the feasibility of IVIG as a bridging immunomodulatory strategy in high-risk APS cutaneous disease where standard therapies are contraindicated by concurrent infection and thrombocytopenia. The sequential management approach successfully resolved a clinically challenging scenario. This case illustrates how risk-adapted immunomodulation may enable safe management of complex APS manifestations.
2026-08-03 | Dual-Site Postsurgical Pyoderma Gangrenosum of the Breast and Back With Delayed Diagnosis: A Case Report
Objective: Unusual clinical course Background:Postsurgical pyoderma gangrenosum is a rare neutrophilic dermatosis that can mimic infection, wound dehiscence, malignancy, foreign-body reaction, or impaired surgical healing.Diagnostic delay is common and may lead to repeated debridement, which can worsen ulceration through pathergy.This case highlights the diagnostic challenge of multifocal postsurgical pyoderma gangrenosum involving anatomically distinct sites after procedures initially performed for presumed benign lesions. Case Report:A 70-year-old woman with celiac disease and prior left breast cancer treated with lumpectomy, chemotherapy, radiation, and implant reconstruction developed nonhealing ulcers of the left superior breast and left lower back after surgical treatment of benign lesions.Initial evaluation favored retained cyst lining, foreign-body reaction, infection, impaired wound healing, and possible implant-related complications.Despite advanced wound therapies, antimicrobials, and biologic wound products, both lesions progressively enlarged.Biopsies demonstrated abscess formation, multinucleated giant cells, and sinus tract formation without malignancy.Wound cultures and pulmonary findings complicated the diagnostic course, but neither targeted antimicrobial nor prolonged antifungal therapy produced sustained improvement.The diagnosis was clinically supported by worsening after procedural intervention, exclusion of malignancy and persistent infection, multifocal involvement, and rapid response after initiation of topical and intralesional corticosteroid therapy. Conclusions:This case supports considering postsurgical pyoderma gangrenosum in refractory postsurgical wounds that worsen despite local wound-directed interventions, particularly when lesions involve multiple anatomically distinct surgical sites.The complete resolution of both lesions after topical and intralesional corticosteroid therapy further supports the importance of recognizing an inflammatory, pathergy-driven process once infection, malignancy, and other local causes have been reasonably excluded.Earlier recognition may help avoid repeated procedural trauma, unnecessary treatment escalation, and prolonged morbidity.
2026-08-03 | Postoperative Pyoderma Gangrenosum Following Varicose Vein Surgery: Recognizing a Rare Surgical Mimic Before Extensive Tissue Loss.
Postoperative pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that frequently masquerades as a surgical site infection. Because its clinical presentation closely resembles postoperative cellulitis or even necrotizing soft tissue infection, diagnosis is often delayed. Misdiagnosis may result in unnecessary antibiotic escalation, repeated surgical interventions, and progressive tissue destruction due to pathergy. This case highlights the importance of early recognition of PG and serves as a reminder for surgeons to consider this uncommon diagnosis when postoperative wounds fail to respond to conventional treatment. A 75-year-old woman underwent elective open varicose vein surgery (ligation of neocrosse veins and phlebectomies) for recurrent symptomatic varicose veins of the left lower limb. One week postoperatively, she developed a painful erythematous wound that was initially diagnosed as a surgical site infection. Despite drainage, repeated wound care, and escalation from oral to broad-spectrum intravenous antibiotic therapy, the lesion rapidly progressed into an extensive necrotic ulcer. Repeated wound cultures and blood cultures remained sterile, while computed tomography scans demonstrated inflammatory changes without evidence of a drainable collection or necrotizing soft tissue infection. Following dermatological consultation, postoperative PG was suspected and confirmed by skin biopsy. High-dose systemic corticosteroid therapy was initiated, resulting in rapid clinical improvement, cessation of ulcer progression, and subsequent wound healing. This case illustrates the diagnostic challenge of postoperative PG and emphasizes several clinical features that should prompt reconsideration of a presumed surgical site infection, including disproportionate pain, rapidly progressive ulceration, sterile cultures, failure of appropriate antimicrobial therapy, and inconclusive imaging findings. Early recognition is essential, as surgical manipulation may exacerbate disease progression through pathergy. Postoperative PG should be considered in any patient presenting with a rapidly progressive postoperative wound that fails to improve despite appropriate antimicrobial treatment. Increased awareness among surgeons may facilitate earlier diagnosis, prevent unnecessary surgical procedures, and reduce the risk of extensive tissue loss.
2026-08-16 | NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil activation in pyoderma gangrenosum across human and murine models.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, nonhealing cutaneous ulcers. Although dysregulated innate immunity and neutrophil activation are implicated in its pathogenesis, the underlying molecular mechanisms remain poorly defined. This study aimed to identify conserved pathogenic mechanisms by integrating analyses of human PG lesions and a brequinar-induced PG-like murine model and to assess therapeutic relevance. Skin biopsy specimens from patients with PG and publicly available RNA-sequencing data were analyzed alongside the murine model using histological and transcriptomic approaches. Cross-species transcriptomic integration identified shared inflammatory pathways between human and murine PG. Human PG lesions showed increased neutrophil infiltration, neutrophil extracellular trap formation, and a dominant type 1 inflammatory profile, all of which were recapitulated in the brequinar-induced mouse model, together with impaired wound healing. Transcriptomic analyses revealed enhanced oxidative stress responses and activation of the NLRP3/caspase-1 inflammasome pathway as a conserved pathogenic axis. In the murine model, both prednisolone and avacopan suppressed inflammatory cytokine expression and neutrophil activation; however, only avacopan significantly improved wound healing. Collectively, these findings suggest that NLRP3 inflammasome activation is associated with type 1 inflammation and neutrophil extracellular trap formation and may represent a PG-associated inflammatory pathway.
2026-08-15 | Preliminary exploration of effects of the JAK inhibitor tofacitinib on pyoderma gangrenosum: In vitro inhibition of NETs and Th17 differentiation.
Pyoderma gangrenosum (PG), a refractory inflammatory disorder, remains a condition with incompletely understood pathogenesis. Currently, no FDA-approved treatments are available. Janus kinase (JAK) inhibitors have been reported sporadically in case studies as effective treatments for PG. To characterize the cellular and molecular landscape associated with JAK/STAT (signal transducer and activator of transcription) pathway overactivation in PG lesions, and investigate the potential effects of tofacitinib on PG. Single-cell RNA sequencing (scRNA-seq) and multiplex immunohistochemistry (mIHC) were employed to characterize the cellular and molecular landscape of JAK/STAT pathway overactivation in PG. In vitro experiments (immunostaining, qPCR, western blot, flow cytometry) were performed to further validate the potential effects of tofacitinib on PG. We identified significant overactivation of the JAK/STAT pathway in PG lesions-particularly in advanced stages-which, in terms of immune inflammation, is primarily driven by myeloid cells and T cells. This activation was associated with enhanced neutrophil extracellular trap (NET) formation in myeloid cells and aberrant differentiation/plasticity of Th17 and Th17.1 (IL-17/IFN-γ double-producing) cells. In vitro cell experiments further demonstrated that the JAK inhibitor tofacitinib suppresses STAT phosphorylation in myeloid and T cells, myeloid NETosis, and IL-17A production. Our study investigated immunological profiling of PG lesions via scRNA-seq and mIHC, along with in vitro validation. These findings delineate a multi-axis cellular and molecular landscape of PG linked to aberrant JAK/STAT signaling, and provide preliminary in vitro evidence supporting potential inhibitory effects of tofacitinib on key pathological processes of PG.
2026-08-12 | Case Report: IVIG as a bridging strategy in high-risk antiphospholipid syndrome with infected cutaneous ulceration and thrombocytopenia.
Severe cutaneous ulceration in antiphospholipid syndrome (APS) with concurrent infection and thrombocytopenia presents a therapeutic dilemma: standard immunosuppression risks worsening infection, while anticoagulation risks hemorrhage. We present a high-risk case successfully managed using intravenous immunoglobulin (IVIG) as a bridging immunomodulatory strategy. A 73-year-old man with triple-positive APS and immune thrombocytopenic purpura (ITP) developed rapidly progressive leg ulcers with clinical features consistent with pyoderma gangrenosum-like disease, complicated by active MRSA and Pseudomonas aeruginosa infection and severe thrombocytopenia (12 × 109/L). Standard therapies were contraindicated: corticosteroids risked worsening infection; anticoagulation risked hemorrhage. The patient received IVIG (0.4 g/kg per dose, every 3 weeks) as primary immunomodulation, concurrent targeted antimicrobial therapy, temporary anticoagulation interruption, and discontinuation of baseline mycophenolate mofetil. Following platelet recovery above 70 × 109/L, therapeutic anticoagulation was resumed with enoxaparin (80 mg subcutaneously twice daily) and aspirin (75 mg daily). Over five months, progressive re-epithelialization culminated in complete healing with platelet recovery. This case supports the feasibility of IVIG as a bridging immunomodulatory strategy in high-risk APS cutaneous disease where standard therapies are contraindicated by concurrent infection and thrombocytopenia. The sequential management approach successfully resolved a clinically challenging scenario. This case illustrates how risk-adapted immunomodulation may enable safe management of complex APS manifestations.
2026-08-03 | Dual-Site Postsurgical Pyoderma Gangrenosum of the Breast and Back With Delayed Diagnosis: A Case Report
Objective: Unusual clinical course Background:Postsurgical pyoderma gangrenosum is a rare neutrophilic dermatosis that can mimic infection, wound dehiscence, malignancy, foreign-body reaction, or impaired surgical healing.Diagnostic delay is common and may lead to repeated debridement, which can worsen ulceration through pathergy.This case highlights the diagnostic challenge of multifocal postsurgical pyoderma gangrenosum involving anatomically distinct sites after procedures initially performed for presumed benign lesions. Case Report:A 70-year-old woman with celiac disease and prior left breast cancer treated with lumpectomy, chemotherapy, radiation, and implant reconstruction developed nonhealing ulcers of the left superior breast and left lower back after surgical treatment of benign lesions.Initial evaluation favored retained cyst lining, foreign-body reaction, infection, impaired wound healing, and possible implant-related complications.Despite advanced wound therapies, antimicrobials, and biologic wound products, both lesions progressively enlarged.Biopsies demonstrated abscess formation, multinucleated giant cells, and sinus tract formation without malignancy.Wound cultures and pulmonary findings complicated the diagnostic course, but neither targeted antimicrobial nor prolonged antifungal therapy produced sustained improvement.The diagnosis was clinically supported by worsening after procedural intervention, exclusion of malignancy and persistent infection, multifocal involvement, and rapid response after initiation of topical and intralesional corticosteroid therapy. Conclusions:This case supports considering postsurgical pyoderma gangrenosum in refractory postsurgical wounds that worsen despite local wound-directed interventions, particularly when lesions involve multiple anatomically distinct surgical sites.The complete resolution of both lesions after topical and intralesional corticosteroid therapy further supports the importance of recognizing an inflammatory, pathergy-driven process once infection, malignancy, and other local causes have been reasonably excluded.Earlier recognition may help avoid repeated procedural trauma, unnecessary treatment escalation, and prolonged morbidity.
2026-08-03 | Postoperative Pyoderma Gangrenosum Following Varicose Vein Surgery: Recognizing a Rare Surgical Mimic Before Extensive Tissue Loss.
Postoperative pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that frequently masquerades as a surgical site infection. Because its clinical presentation closely resembles postoperative cellulitis or even necrotizing soft tissue infection, diagnosis is often delayed. Misdiagnosis may result in unnecessary antibiotic escalation, repeated surgical interventions, and progressive tissue destruction due to pathergy. This case highlights the importance of early recognition of PG and serves as a reminder for surgeons to consider this uncommon diagnosis when postoperative wounds fail to respond to conventional treatment. A 75-year-old woman underwent elective open varicose vein surgery (ligation of neocrosse veins and phlebectomies) for recurrent symptomatic varicose veins of the left lower limb. One week postoperatively, she developed a painful erythematous wound that was initially diagnosed as a surgical site infection. Despite drainage, repeated wound care, and escalation from oral to broad-spectrum intravenous antibiotic therapy, the lesion rapidly progressed into an extensive necrotic ulcer. Repeated wound cultures and blood cultures remained sterile, while computed tomography scans demonstrated inflammatory changes without evidence of a drainable collection or necrotizing soft tissue infection. Following dermatological consultation, postoperative PG was suspected and confirmed by skin biopsy. High-dose systemic corticosteroid therapy was initiated, resulting in rapid clinical improvement, cessation of ulcer progression, and subsequent wound healing. This case illustrates the diagnostic challenge of postoperative PG and emphasizes several clinical features that should prompt reconsideration of a presumed surgical site infection, including disproportionate pain, rapidly progressive ulceration, sterile cultures, failure of appropriate antimicrobial therapy, and inconclusive imaging findings. Early recognition is essential, as surgical manipulation may exacerbate disease progression through pathergy. Postoperative PG should be considered in any patient presenting with a rapidly progressive postoperative wound that fails to improve despite appropriate antimicrobial treatment. Increased awareness among surgeons may facilitate earlier diagnosis, prevent unnecessary surgical procedures, and reduce the risk of extensive tissue loss.
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Drug Discovery Landscape
6 orphan drug designations for Pyoderma gangrenosum.
6 orphan drug designations for Pyoderma gangrenosum.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
infliximab | antibodies | FDA | 2025-11-09 | — | ODDIFACT SAS |
spesolimab-sbzo | antibodies | FDA | 2025-04-16 | — | LEO Pharma Inc. |
Vilobelimab | antibodies | EMA | 2022-07-18 | — | InflaRx GmbH |
Vilobelimab | antibodies | FDA | 2022-06-27 | — | InflaRx N.V. |
Telacebec | — | FDA | 2021-01-13 | — | The Global Alliance for TB Drug Development, Inc. |
gevokizumab | antibodies | FDA | 2014-02-21 | — | XOMA (US) LLC |
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