Juvenile xanthogranuloma: forms of systemic disease and their clinical implications

Juvenile xanthogranuloma (JXG) with systemic (extracutaneous) involvement is a rare histiocytic disorder in which significant morbidity and occasional deaths may occur. The objective of this study was to characterize the spectrum of anatomic involvement, associated clinical problems, and management considerations in children with systemic JXG.

Two current cases and literature reports of 34 children with various forms of systemic AG were analyzed with respect to age, clinical presentation, site(s) of involvement, therapy, and outcome.

The median age of the 36 patients was 0.3 years (range, birth to 12 years). Symptoms were usually referable to bulky or infiltrative disease. Twenty patients had disease in two or more sites. Cutaneous lesions were present in fewer than half the patients. The most frequent extracutaneous sites of disease were the subcutaneous soft tissue (12); central nervous system (8); liver/spleen (8); lung (6); eye/orbit, oropharynx, and muscle (4 each); with three or fewer instances of disease in each of several other sites. Most patients were treated with excision or had spontaneous regression (some with organ involvement). However, 12 patients received treatment that included radiation or systemic chemotherapy. Survivors, some with long-term disabilities, included young children who had received radiation therapy to the brain, eye, skin, or heart. Two patients died of disease.

Systemic AG may involve varying numbers and combinations of extracutaneous sites. The extent of disease should be determined in patients with AG who are suspected to have systemic involvement. In contrast to the cutaneous form, systemic AG may be associated with significant complications requiring aggressive medical care. When feasible, surgical excision of lesions may be curative. Optimal treatment for symptomatic, unresectable disease is currently undefined but should be selected to minimize toxic effects in these children who are typically younger than 1 year old at presentation.