Patient Vignette
Part 1 - Presentation
An 11-year-old boy presented with recurrent deep skin ulcers, which first began at the age of three years. The ulcers were similar in appearance to pyoderma gangrenosum, an uncommon form of skin ulceration, seen in a variety of autoimmune disorders, such as inflammatory bowel disease, arthritis, vasculitis and systemic lupus erythematosus. The ulcers involved many body areas, including the scalp, trunk, arms and legs, extending deep into the underlying subcutaneous tissues. They typically were very painful, usually sterile, and required weeks to months to heal. The scars displayed an unusual atrophic appearance that resembled "cigarette paper". Over the years, the patient has – unsuccessfully – undergone repeated evaluations in an attempt to diagnose an underlying disorder.
He has been treated with various medications, commonly used to treat pyoderma gangrenosum, such as corticosteroids, TNFantagonists, cyclosporine, among others.
More recent skin ulcers have been complicated by both bacterial and fungal superinfections. Of note: the hospital course until that moment had been free of significant infections (both related to his skin manifestations, as well as in other places). During episodes of skin ulceration, he would develop highly elevated white blood cell counts, typically exceeding 50,000/mm3, with most of the cells being neutrophils ("leukemoid reactions"). On the basis of these characteristics, and the new infectious complications, additional laboratory testing was obtained.
The figure (sidebar) represents the results of the flow cytometric assay "Adhesion Markers", which is a component of the "Neutrophil Function Tests". The principle of the assay is the combined detection of the adhesion molecules CD11b and CD18 (members of the β2 integrin family) on the cell surface of neutrophils (and other white blood cells).
The assay showed a marked reduction of CD11b/CD18 (dual-parameter dotplot on the right), as compared to the healthy control (middle dotplot; isotype controls on the right). The assay was repeated following neutrophil activation using several stimuli, to determine up-regulation of CD11b/CD18. No up-regulation was observed.
