Pyoderma gangrenosum (ORPHA:48104)
A rare inflammatory neutrophilic dermatosis characterized by painful cutaneous ulcerations with a violaceous and undermined border affecting the lower extremities; however, any hair-bearing area can be affected.
Epidemiology
The worldwide incidence of pyoderma gangrenosum (PG) is estimated to be between 3-10 cases per million people with an increased incidence in women. The exact prevalence of PG is unknown but has been estimated to be approximately 1 in 17,000 adults. It tends to affect middle-aged individuals (40-60 years).
Clinical description
Clinically, onset occurs with pustules, nodules, or ulcers on the lower extremity with a violaceous, undermined border. Ulcers are primarily sterile but may be complicated by secondary microbial colonization. They can rapidly progress and turn into very painful ulcers of variable depth and size. Other presentations are rarer and include peristomal, pustular, bullous, and vegetative/superficial granulomatous PG as well as extracutaneous manifestations (most commonly pulmonary). The clinical course is unpredictable; it can be mild or severe, chronic, or relapsing with significant morbidity; some patients might heal spontaneously.
Etiology
The etiology has not yet been clearly determined.
Diagnostic methods
Diagnosis of PG is based on clinical presentation, exclusion of other causes of ulceration, and can be supported by histopathology showing neutrophilic infiltrate (though this is not specific and may be evident only in acute cases). Tissue culture is often necessary to rule out superinfection. Diagnosis may be assisted with use of existing clinical frameworks, including PARACELSUS score, Delphi criteria, and Mayo Clinic criteria.
Differential diagnosis
PG can occur spontaneously or in association with other autoimmune conditions, including most commonly inflammatory bowel disease (IBD), rheumatologic conditions, hematologic disorders, or in association with autoinflammatory syndromes including PAPA (pyogenic arthritis, PG, and acne), PASH (PG, acne, and suppurative hidradenitis), PAPASH (pyogenic arthritis, acne, PG, and suppurative hidradenitis), PAC (PG, acne, and ulcerative colitis), PsAPASH (psoriatic arthritis, PG, acne and suppurative hidradenitis), PAMI (PSTPIP1-associated myeloid related proteinemia syndrome), and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis). The most common differential diagnoses in clinical practice are chronic venous ulcers, calciphylaxis, and factitial ulcers. Other entities include vasculitic/vasculopathic ulcers, metastatic Crohn's disease, hidradenitis suppurativa, other neutrophilic dermatoses (e.g., Sweet's Syndrome), infectious (e.g. Leishmaniasis, Buruli ulcer, Lues maligna), Marjolin and neoplastic ulcers.
Management and treatment
Treatment of PG remains challenging and there is currently no FDA-approved medication for its treatment. Prednisolone is approved in Europe by the EMA and adalimumab is approved in Japan by the Pharmaceutical and Medical Devices Agency. In addition to pharmacological interventions, wound and pain management are also necessary. Globally, the cornerstone of treatment remains systemic corticosteroids and cyclosporine, with a step-up to biologics as second line therapies in addition to wound care and pain management.
Prognosis
Despite recent advances in therapy, the prognosis of PG remains unpredictable. Recurrence rates have been reported in up to 30% of patients. Patients carry an increased mortality rate, three times higher than that of the general population, which may be due to associated conditions rather than PG itself though this remains to be elucidated.

                            Last update: 
                            June 2024


                            - Expert reviewer(s): 
                             Sarah BECKER  - Dr Alex ORTEGA-LOAYZA