Treatment algorithm for adults with multifocal or multisystem LCH. Systemic therapy is indicated for patients with single-system unifocal disease involving critical organs or specific sites (nervous system, liver, spleen, etc). *Brain (esp. neurodegenerative LCH), liver (esp. sclerosing cholangitis). Liver transplant consult for sclerosing cholangitis. ^#Systemic therapy may be indicated in patients with symptomatic disease and unable to quit smoking. Lung transplantation referral should be undertaken if not eligible for or refractory to systemic treatments. 6-MP, 6-mercaptopurine; IMiDs, immunomodulators (thalidomide, lenalidomide); MTX, methotrexate; PD, progressive disease.