Pyoderma Gangrenosum: Review and Recent Treatment Recommendations

Pyoderma gangrenosum (PG) is a neutrophilic skin disease which often has delayed diagnosis due to a vague clinical picture and symptoms.¹ It is typically characterized by large, deep ulcerations of the lower leg(s) with abnormal blue/violet/green coloration and undermined margins.^1-4 PG is typically associated with sporadic areas of gangrene; however, newer research shows PG ulcers are nonetheless typically sterile. It is not uncommon, though, to see periodic secondary superficial colonization.^1,2 The pathophysiology of PG is not entirely clear; however, hypotheses suggest that it arises from an autoimmune cycle between the innate and the adaptive immune responses.^5,6 

The innate immune system is the body’s first line of defense and is often referred to as the “nonspecific response.” It activates within 0-4 hours and is associated with mononuclear cells and granulocytes.⁶ The adaptive immune system has a slower response and is more specific. It is composed of 2 components; the humoral response, which utilizes B cells, and the cellular response, which utilizes T-helper cells or cytotoxic T cells.⁶ The innate system activates the adaptive system to create specific antibodies, which then causes a cascade of macrophage activation within the innate system. This feedback cycle enhances the innate system over a person’s lifetime.⁶ This cycle also contributes to why PG often presents in patients with other systemic inflammatory diseases, such as inflammatory bowel disease (IBS), hematologic disorders, or rheumatologic diseases. PG may also manifest following trauma or surgery.² Rare and severe cases may present with pulmonary involvement, further convoluting diagnosis and presentation.³

More on PG’s Presentation and Pertinent Findings

There are 7 subcategories of PG: ulcerative, bullous, pustular, vegetative, peristomal, postoperative, and the rarest variant, malignant pyoderma.^5,7 Ulcerative PG, which most commonly affects the legs, is a chronic and progressive disease that starts with small pustules or blisters which progressively widen, eventually burst, and create deep ulcers. PG may appear as venous insufficiency wounds, arterial wounds with necrosis, or a multitude of other lower extremity wounds. Skin biopsy may show neutrophilic infiltrate but otherwise lack PG-specific findings. PG may also show findings of subdermal neutrophilic infiltrate with surrounding necrosis, with or without vasculitis.³ An autoimmune rheumatic workup may also prove unremarkable in patients with PG.³ All these variables contribute to a delayed diagnosis of PG in many patients. One of the most important clinical signs of PG is an exacerbation following debridement or other trauma known as pathergy.^1,5

Notes on Diagnosis and Treatment

PG diagnosis is difficult and requires a multimodal approach.⁵ There are 3 different diagnostic scoring criteria available: the Su Criteria, the PARACELSUS score, and the Delphi Criteria.⁸ Clinically, a diagnosis should be made via clinical picture, biopsy with pathology, systemic disease evaluation, and an in-depth history of the wound. A pathology report should be obtained for both diagnostic criteria and for ruling out malignancy. Histological findings could include any of the following: neutrophilic infiltrate to the dermis, mixed inflammation markers, and lymphocytic vasculitis.^8,9 If vasculitis is present, it is important to rule out infection.⁹ Response to debridement or biopsy can also be used as an indicator for diagnosis.^5,9 

There is no set standard for treatment of PG.^2,5 The overall goal of treatment must include halting the inflammatory cycle.⁵ Managing mild cases of PG usually includes local corticosteroid, calcineurin inhibitors, topical  agents (tacrolimus, clobetasol, calcineurin inhibitors, or intralesional steroids.^2,5 Severe cases may necessitate complete excision with either full- or split-thickness skin graft application in addition to pharmacological suppression treatment.^4,5 However, if possible, one should avoid surgical treatment as it could cause pathergy. Pharmacologic therapy should begin with a systemic steroid or other fast-acting immunosuppressive agent.⁵ Occasionally, patients can progress to chronic, noninflammatory PG, especially after successful immunosuppressive therapy.⁴ Prednisone is the decades-long drug of choice; however, newer studies show that long-term efficacy may not be as high as previously thought.⁵ Dapsone and minocycline are antibiotics that have a high anti-inflammatory effect, and studies show as high as a 96.9% positive response rate with their use.⁷ Tumor necrosis factor (TNFα) therapy also has significant data showing effectiveness for treating PG.⁵

Local wound care should focus on nontraumatic methods, with nonadherent dressings in a moist environment.⁵ And, as previously mentioned, surgical intervention should be held until there is systemic immunosuppressive control and only performed under limited circumstances, due to the high risk for pathergy.^4,5 Autolytic debridement has less risk of pathergy than sharp, however.⁵ The role of negative pressure wound therapy (NPWT) is debated as some studies say there is a higher risk of pathergy, and other studies show it is an effective therapy with more improvement in healing time as well as patient satisfaction.⁵ 

Concluding Thoughts

Overall, PG treatment is complex and should involve multiple specialists. The importance of podiatrists in the initial diagnosis and workup of this disease cannot be overstated. Many patients will present with chronic, long-lasting wounds unresponsive to previous treatments. PG should be near the top of one’s differential diagnoses when seeing chronic leg wounds with a patchy appearance and ill-defined borders. With positive biopsy results, dermatologists, immunologists, or plastic surgeons may also be beneficial on the treatment team. Skin biopsies should include the wound and the border at an early stage to evaluate for PG and rule out malignancy that may warrant oncology referral. Thus, podiatrists are uniquely positioned to execute the necessary steps for early detection and multidisciplinary management of PG.  

Dr. Somma is Chief Resident at Phoenixville Hospital in Phoenixville, PA .

References
1.    Yamamoto T, Yamasaki K, Yamanaka K, et al. Clinical guidance of pyoderma gangrenosum 2022 [published online ahead of print, 2023 Jun 13]. 
J Dermatol. 2023;10.1111/1346-8138.16845. 
2.    Dey S, Sanghavi N, Wasserman A, Kar K. Treatment of pyoderma gangrenosum with mycophenolate and hyperbaric oxygen therapy: A case report and literature review. Cureus. 2023;15(4):e38159. 
3.    Vu MLD, Lin FE, Ashcroft CR, Van Der Veer SJ, Hall JR. A diagnostic dilemma: Atypical systemic pyoderma gangrenosum. Cureus. 2023;15(5):e38763. 
4.    Haag CK, Bacik L, Latour E, Morse DC, Fett NM, Ortega-Loayza AG. Perioperative management of pyoderma gangrenosum. J Am Acad Dermatol. 2020;83(2):369-374. doi:10.1016/j.jaad.2020.01.002
5.    Łyko M, Ryguła A, Kowalski M, Karska J, Jankowska-Konsur A. The pathophysiology and treatment of pyoderma gangrenosum-current options and new perspectives. Int J Mol Sci. 2024;25(4):2440. doi:10.3390/ijms25042440 https://pmc.ncbi.nlm.nih.gov/articles/PMC10889749/
6.    Innate and adaptive immunity. Innate and Adaptive Immunity - Creative Diagnostics. Accessed December 12, 2025. https://www.creative-diagnostics.com/innate-and-adaptive-immunity.htm. 
7.     Din RS, Tsiaras WG, Li DG, Mostaghimi A. Efficacy of systemic dapsone treatment for pyoderma gangrenosum: A retrospective review. J Drugs Dermatol. 2018;17(10):1058-1060.
8.    Haag C, Hansen T, Hajar T, et al. Comparison of three diagnostic frameworks for pyoderma gangrenosum. J Invest Dermatol. 2021;141(1):59-63. 
9.    George C, Deroide F, Rustin M. Pyoderma gangrenosum - a guide to diagnosis and management. Clin Med (Lond). 2019;19(3):224-228. doi:10.7861/clinmedicine.19-3-224