Background <p>Langerhans cell histiocytosis (LCH) is a rare disease caused by a disorder of dendritic cells. LCH mainly occurs in children and the damage of tissue is caused by proliferative dendritic cells which also provides important evidence for the diagnosis of this disease. In most LCH patients, only a single organ in the body is affected; however, multisystem involvement may occur, commonly affecting the bone marrow, liver, lungs, and central nervous system. In this report, we describe a case of multisystem LCH involving the skin, lungs, thyroid gland, liver, nails, and spleen.</p> Case introduction <p>A 20-year-old Han Chinese man was admitted into the liver disease department with complaints of anorexia, fatigue, and jaundice. Physical examination revealed extensive cutaneous lesions, nail lesions, macular sclera, and bilateral goiter. Lymphocytic thyroiditis was diagnosed based on fine-needle aspiration biopsy of the thyroid gland and corroborating clinical features—including the characteristic skin rash. Liver biopsy confirmed sclerosing cholangitis (SC). Response to treatment with Etoposide (VP-16), Prednisone acetate tablets, cyclophosphamide, and vinblastine was excellent. However, the erythrocyte sedimentation rate (ESR) was initially elevated above the normal reference range. With disease remission, the corresponding ESR levels decreased.</p> Conclusions <p>LCH in this case involved not only the skin and thyroid, but also the liver, lungs, nails and possibly the spleen. Currently there are no standard treatment options and treatment needs to be individualized. It is rare that LCH with sclerosing cholangitis is the first presentation, and we should be vigilant to whether other organs are involved. An elevated ESR may be a valuable indicator of disease activity in patients with Langerhans cell histiocytosis.</p>