Snapshot A 1-year-old boy is brought to the emergency room for a new rash in the diaper area along with fever. On physical exam, along the inguinal folds, there are pink eroded papules on background of petechiae and purpura, as well as pink greasy discrete papules on the scalp and trunk. A radiograph of the cranium shows punched out lytic lesions. Introduction Overview Langerhan cell histiocytosis (LCH) describes a group of conditions caused by proliferation of dendritic (Langerhan) cells traditionally classified by 4 subtypes, but more recent classification is based on extent of dissemination Langerhan Cell Histiocytosis (LCH)Letterer-SiweHand-Schuller-ChristianHashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis)Eosinophilic GranulomaDemographics< 2 years of age2-6 years of ageNeonatal period7-12 years of agePulmonary involvement seen in ages 30-40 yearsInvolvementSkin, bone, and viscerapulmonary infiltrates, lymph nodules, liver, and spleenSkin, bone, and visceraliver, spleen, and lymph nodesSkin-limitedPrimarily bone > skinPulmonary involvementPrognosisPoor prognosis with disseminated diseaseChronic and progressiveRapid spontaneous resolution is likelyGood prognosis Epidemiology Incidence rare Demographics males > females Risk factor smoking pulmonary involvement ETIOLOGY Pathogenesis mechanism proliferation of Langerhan cells, which are immature and are unable to stimulate T-cells via antigen presentation thought to be reactive or neoplastic BRAF V600E mutation can be found in LCH Presentation Clinical Presentation of LCHLetterer-SiweHand-Schuller-ChristianHashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis)Eosinophilic GranulomaSymptomsAcutely disseminated lesions affecting the skin, bone, and internal organsFeverBone painTriad of diabetes insipidus, osteolytic bone lesions (cranium), and exophthalmosSkin lesions that crust and resolves spontaneouslySolitary indolent bone lesions (cranium most common) with spontaneous bone fracturesPhysical examPink papules, pustules, vesicles, petechiae, purpura, and erosions on the scalp, flexural surfaces, and trunkSecondary impetiginization commonSkin findings similar to Letterer-SiweMultipe red to brown papulonodules, some with erosionsTenderness at site of bone lesions Other symptoms recurrent ear infections dizziness headache limping (due to leg pain) failure to thrive developmental delay Imaging Bone radiograph views cranium or other skeletal survey findings punched out lytic lesions Chest radiograph findings may show pulmonary nodules or infiltrate Studies Serum studies liver function test to evaluate for liver involvement baseline complete blood count Urine studies to evaluate for diabetes insipidus Pulmonary function test to evaluate for pulmonary involvement Histology S100+, CD1a+, and Langerin+ proliferation of histiocytes with mixed inflammatory infiltrate Electron microscopy Birbeck granules or “tennis rackets Differential Multiple myeloma key distinguishing factors may also have “punched out” lytic bone lesions typically affects older adults, and protein electrophoresis of the serum (SPEP) will reveal monoclonal gammopathy Treatment Medical corticosteroids indications to slow autoimmune reaction chemotherapy indications for severe cases in children drugs cyclophosphamide, etoposide, methotrexate, and vinblastine radiation therapy indications bone lesions vasopressin indications diabetes insipidus bisphosphonates indication prevent bone destruction from bone lesion Surgical curettage or excision indications bone lesions Complications Bone fractures Hypercalcemia (from lytic bone lesions) Spontaneous pneumothorax Infections Hearing impairment Prognosis Worse with BRAF V600E mutation Worse if there is failure to respond to 6 weeks of treatment