CASE #1: Pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a rare, ulcerative, cutaneous condition that affects approximately three to 10 individuals per million population each year.1 Although the condition may affect individuals at any age, it most often occurs between the second and fifth decades of life. PG develops in women at a slightly higher proportion than in men and without racial predilection.

The etiology and pathogenesis of PG has remained unclear since it was first described in 1930.2 The condition was originally considered to be pathognomonic of inflammatory bowel disease but has since been described in association with a variety of other disorders. Considering the fact that approximately 50% of cases occur in association with systemic diseases known to have autoimmune pathogenesis, immunologic dysregulation is suspected to play a factor in the development of PG. Impaired neutrophil chemotaxis also appears to contribute to the development of PG, as is evident by the presence of massive neutrophil infiltrates within most lesions.

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Studies on some PG lesions have shown overexpression of interleukin-8 (IL-8), a potent leukocyte chemotactic agent.3 Skin trauma or injury may result in new ulcerations or exacerbation of existing ones in a phenomenon termed pathergy.4 The existence of pathergy suggests that the pathogenesis of PG involves an exaggerated, uncontrolled inflammatory response to nonspecific stimuli. PG is a common feature of a recently described autosomal-dominant genetic disorder known as “PAPA syndrome” (pyogenic sterile arthritis, pyoderma gangrenosum, and acne). The mutated gene is localized to chromosome 15q and results in neutrophilic infiltration, further asserting that immune dysregulation may be a common factor in the pathogenesis of PG. However, there is insufficient evidence to support the assertion that disturbances in immunoregulation play a role in all cases.

The initial presentation of PG is that of a painful superficial hemorrhagic pustule or deep-seated nodule. This later develops into an ulcer with irregular, raised, and dusky-red or violaceous borders with a boggy, purulent, and necrotic base. As the ulcer advances, the raised border becomes soggy and perforated such that the area drains pus when pressure is applied. The lesion is typically surrounded by an erythematous halo that spreads centrifugally from the advancing border of the ulcer into nearby skin. The base of the ulcer may be covered by hemorrhagic exudates or necrotic eschar or become studded with microabscesses. There is often a solitary lesion, but sometimes multiple isolated ulcers may be seen or clusters may develop and coalesce into multicentric ulcerations.

There are two primary variants of PG. The classic ulcerative form usually presents on the trunk and lower extremities whereas the superficial atypical variant occurs more frequently on the arms, hands, and face. Other clinical variants include bullous and pustular forms. PG most commonly involves the skin, but there have been rare cases of extracutaneous manifestations, of which culture-negative pulmonary infiltrates are the most common. Pain at the lesion site is the hallmark symptom of PG. Although systemic symptoms are most often absent, patients may appear toxic or become febrile during an acute onset.

Systemic diseases commonly associated with PG include inflammatory bowel disease (Crohn’s disease and ulcerative colitis), arthritis, rheumatologic disorders, hematologic diseases (myelogenous leukemia, hairy cell leukemia, myelofibrosis), HIV infection, sarcoidosis, and monoclonal gammopathy. Differential diagnosis for PG includes atypical mycobacteria infection, clostridial infection, deep fungal infection, antiphospholipid syndrome, stasis ulcers, insect bites, Wegener’s granulomatosis, leukocytoclastic vasculitis, and lymphoma. The diagnosis of PG is most often one of exclusion primarily based on clinical presentation and course. Exudates from the ulcer should be cultured to rule out bacteria, fungi, atypical mycobacteria, and virus infection. A biopsy is recommended in most cases to exclude infection, vasculitis, or malignancy.1 Given the possibility of pathergy, the decision to biopsy should be made with caution.

Histopathologic findings are usually nonspecific, revealing edema, dense neutrophilic infiltrates, and lymphocytic vasculitis with liquefaction necrosis of the overlying epidermis. As lesions progress, biopsy may reveal suppurative granulomatous dermatitis and prominent fibroplasia. Such nonspecific laboratory findings as elevated erythrocyte sedimentation rate and leukocytosis may be present. A detailed history may reveal such underlying conditions as mentioned earlier. Investigate further to confirm a suspected underlying disease, and treat accordingly.

While there is no uniformly effective therapy for PG, best results have been reported with the use of immunosuppressive and modulating agents.1 The treatment approach should be determined by extent and depth of lesion, presence or absence of associated diseases, and patient status and perceived tolerance to specific therapy. Therapeutic goals of treatment are reducing pain and inflammation and promoting wound healing. Mild singular lesions are treated locally with dressings, limb elevation, topical tacrolimus, intralesional triamcinolone, and/or cyclosporine injections. Common systemic treatments for more severe disease include corticosteroid, sulfasalazine, and cyclosporine. Treatment directed at underlying diseases, if present, can result in improvement of lesions. If surgical repair is unavoidable, care should be taken. Perioperative prophylaxis with systemic corticosteroid or cyclosporine may be indicated in such cases to avoid pathergy. This patient’s PG never resolved, despite repeated injections of intralesional Kenalog (triamcinolone). He was eventually lost to follow-up.