Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions.

Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. As a group, they are relatively difficult to diagnose and distinguish both clinically as well as histologically. Many of these disorders have significant associations with systemic diseases that impact the patient's overall prognosis. In this update, we offer a discussion of emerging concepts and controversies in this field, as presented through evidence-based answers to seven important clinical questions regarding palisading and epithelioid granulomata. These questions offer an opportunity to review ten non-infectious granulomatous conditions that have implications for systemic disease: granuloma annulare, annular elastolytic giant cell granuloma, necrobiosis lipoidica, methotrexate-induced accelerated rheumatoid nodulosis, necrobiotic xanthogranuloma, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, palisaded neutrophilic granulomatous dermatitis, sarcoidosis, and metastatic Crohn disease. Recent clinical, epidemiologic, and laboratory studies have shed some light on these diseases, the association of these conditions with systemic disorders, and their overall prognoses.