EXPERT ANALYSIS FROM SDEF LAS VEGAS DERMATOLOGY SEMINAR
LAS VEGAS (FRONTLINE MEDICAL NEWS) – Though pyoderma gangrenosum and other neutrophilic skin disorders are rare, clinicians should include them in their differential, especially for nonhealing surgical wounds or skin “infections.”
Since these painful areas of ulceration need corticosteroid treatment, not antibiotics, for resolution, accurate diagnosis is critical for healing, Dr. J. Mark Jackson said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.
In a review of pyoderma gangrenosum (PG) and its cousins at the meeting, Dr. Jackson noted that the etiology of PG is unknown, but disordered neutrophilic chemotaxis is thought to be a factor. The many different manifestations of this disease are now collectively called the “neutrophilic dermatoses,” he said.
“Pyoderma gangrenosum is a very important diagnosis to consider in the differential diagnosis for nonhealing ulcerations, as suspicion and early recognition of this debilitating condition can prevent long-term sequelae such as pain, scarring, and long-term immunosuppressive medications,” said Dr. Jackson of the department of dermatology at the University of Louisville (Ky.).
The diagnosis should be suspected in the setting of a painful cutaneous ulcer with necrolysis. The border is typically irregular, violaceous, and undermined, he said, adding that this classic undermined border is caused by the sheets of neutrophils that characterize the disease.
Noting that half of patients with PG have underlying associated conditions such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and hematologic malignancies, Dr. Jackson emphasized that systemic disease associated with PG should heighten suspicion. “Histopathologic findings may be consistent with but not diagnostic of PG,” and can include a sterile dermal neutrophilia, with or without mixed inflammation and a lymphocytic vasculitis.
“Where you biopsy is important,” he continued, emphasizing that the biopsy must capture the margin of ulceration, where the sheets of neutrophils characteristic of PG will be seen on pathology.
Therapy consists of corticosteroids, with or without an immunosuppressive agent, and cessation of treatments that may continue to provoke pathergy.
Other diseases should also be considered in the differential diagnosis, including dangerous infectious causes, such as atypical mycobacteria, deep fungal infections, and staphylococcal and streptococcal infections. Squamous cell carcinoma, lymphoma, and leukemia may also present with similar lesions, as may metastatic Crohn’s disease, Dr. Jackson said. Several vasculitic and vasculopathic inflammatory conditions can also have similar appearances, including Wegener’s granulomatosis and vasoocclusive disorders such as peripheral vascular disease and cryoglobulinemia.
Classically, PG presents as painful ulcerated areas, most often on the lower extremities, that have a typical undermined border, caused by the sheets of neutrophils that characterize PG, he pointed out. PG may be mistaken for venous stasis ulcers, pressure ulcers, and cellulitis, but it doesn’t improve with antibiotics and mechanical manipulation from exfoliative dressings – and debridement may worsen the condition.
For susceptible individuals, surgery may provoke a pathergic response and trigger PG at the site of the surgical wound, and dogged attempts at conventional wound care may cause continued pathergy and begin a vicious cycle, Dr. Jackson said.
Peristomal pyoderma gangrenosum is a disease subcategory that may be seen in patients whose inflammatory bowel disease has been surgically treated and who have a stoma. Patients will have ulcerating lesions around their stoma site that are often misdiagnosed and treated as infections. Some wound care therapies, such as debridement, may continue to provoke the pathergic response and worsen peristomal PG, he said.
Though associated disease is seen in up to 50% of individuals with PG, there’s no predictable timeline linking the development of PG with the course of the associated disorder. In classic PG, usually occurring on the legs, autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis or another inflammatory arthritis, and paraproteinemia may be seen. Atypical PG, occurring more commonly on the upper extremities and face, is associated with myelogenous leukemia and preleukemic states, Dr. Jackson said.
Pyoderma gangrenosum lesions improve with corticosteroid administration. Depending on disease severity and location, topical, intralesional, or systemic steroids may be used.
Adjunctive treatments for PG and other neutrophilic dermatoses can include antibiotics with anti-inflammatory properties, such as minocycline or doxycycline, dapsone, and metronidazole. Immunosuppressives such as cyclosporine, azathioprine, and mycophenolate mofetil may also help speed resolution. In some cases, skin grafts may be necessary.
PG patients with Crohn’s disease or rheumatoid arthritis who are prescribed tumor necrosis factor–alpha (TNF-alpha) inhibitors for their systemic disease may also see improvement in PG lesions, Dr. Jackson said.
Other rare categories of neutrophilic dermatoses include Sweet’s syndrome, an acute febrile neutrophilic dermatosis, and neutrophilic dermatosis of the dorsum of the hand.
Neutrophilic invasion can also occur in other organs. “These extracutaneous lesions are also ‘sterile’ neutrophilic abscesses, which are often misdiagnosed as infections,” Dr. Jackson said. The most common site of extracutaneous neutrophilic infiltration is the lungs, though any organ system may be affected.
Dr. Jackson disclosed that he has received research support, honoraria, consulting fees, and other support from Abbvie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.
The Skin Disease Education Foundation and this news organization are owned by the same parent company.
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