Snapshot A 4-year-old boy is brought to his pediatrician by his mother who reports that he has had a fever, recurrent ear infections, and has been complaining of headaches and chronic pain in his left leg for several weeks. A radiograph is shown. Introduction Cancer-like group of syndromes related to proliferation of histiocytes (Langerhans cells) macrophage-like cells of the skin Thought to be autoimmune in origin Three major variants include Letterer-Siwe Disease acute aggressive and disseminated variant usually fatal in infants Hand-Schuller-Christian syndrome chronic progressive variant with onset prior to five years of age classic triad includes skull lesions diabetes insipidus exophthalmus Eosinophilic granuloma extraskeletal generally limited to lung best prognosis and sometimes regresses spontaneously Epidemiology affects roughly 1:200,000 individuals per year can occur in children or adults peak incidence occurs in children 5-10 years of age pulmonary histiocytosis is most common variant in adults peak incidence in 30-40 years of age Presentation Symptoms symptoms range depending on severity of disease and age of affected individual children abdominal pain dizziness ear infections/drainage orbital protrusion fever headache jaundice limping (due to leg pain) mental dysfunction rash seizures shortened height swollen lymph glands thirst vomiting adults bone pain chest pain cough fever malaise urinary frequency rash dyspnea thirst unintentional weight loss Physical exam tumors in weight-bearing bones may be identified i.e. legs and spine failure to thrive delayed puberty mental instability or delayed development hyperventilation Evaluation Radiography may show classic "punched out" lesions in skull not to be confused with multiple myeloma skeletal survey may show identify other bony lesions CXR may demonstrate pulmonary nodules Skin biopsy to look for presence of Langerhans cells CBC may show lymphocytosis Bronchoscopy usually with biopsy in adults to evaluate pulmonary histiocytosis PFTs may indicated respiratory dysfunction Differential Multiple myeloma, lymphomas Treatment Medical management corticosteroids indicated to slow autoimmune reaction cyclophosphamide, etoposide, methotrexate, and vinblastine may be indicated in severe cases in children radiation therapy may be indicated for bony lesions smoking cessation may reduce incidence and severity of pulmonary histiocytosis supportive care antibiotics for infection mechanical ventilation hormone replacement therapy physical therapy medicated shampoos Surgical intervention tumor resection may be indicated in large bony lesions especially in leg tumors Prognosis, Prevention, and Complications Prognosis depends on specific type and severity of disease 50% of pulmonary histiocytosis cases are fatal young children, especially infants, usually die of disease Prevention there are no known preventive measures for childhood disease smoking cessation can reduce risk of pulmonary histiocytosis Complications multiple organ involvement can lead to death, spontaneous pneumothorax,