II. Epidemiology

  1. Rare Prevalence: 4 to 5 per 1 Million Children

III. Precautions

  1. Exercise caution in age <3 years presenting with atypical, refractory skin lesions (often misdiagnosed initially)

IV. Pathophysiology

  1. Rare group of disorders with proliferation of Langerhans Cells (White Blood Cell subtype)
    1. Originates in the Bone Marrow from progenitor cell proliferation of myleoid Dendritic Cells
  2. Lesions infiltrate bones (80% of cases, esp. skull), skin, lung and in some cases the Pituitary Gland
  3. Most often presents in childhood, especially infancy, with atypical skin lesions mistaken for other conditions (e.g. Eczema)
  4. Oncogenic mutation BRAF V600E found in 64% of cases

V. Symptoms

  1. Fever
  2. Sore Oral Mucosa
  3. Atypical rash (see below)

VI. Findings

  1. Classic Triad (10%)
    1. Lytic bone lesions (esp. Skull defects)
    2. Diabetes Insipidus
    3. Exophthalmos
  2. Multisystem findings in >87% of patients with skin lesions
    1. Acute disseminated multisystem disease is more common in age <3 years
    2. Growth retardation
    3. Developmental Delay
  3. Oral Changes
    1. Gum swelling and necrosis
    2. Extrusion of teeth
  4. Atypical skin lesions
    1. Seborrhea-like lesions
      1. Scaly red-brown Papules
    2. Eczema-like lesions
      1. Erythematous, scaly lesions on scalp, flexor folds
    3. Petechiae, Purpura or hemorrhagic crusts
    4. Other lesions
      1. Minute xanthomatous Nodules
      2. Raised yellow to brown lesions in neck and axilla
  5. Bone lesions (80% of cases)
    1. Skull is most often affected
  6. Hematologic
    1. Lymphadenopathy
    2. Hepatomegaly
    3. Splenomegaly
  7. Lung changes
    1. See Pulmonary Histiocytosis X

VII. Labs

  1. Complete Blood Count
    1. Hemoglobin or Hematocrit consistent with Anemia
    2. White Blood Cell Count consistent with Leukopenia
    3. Platelet Count consistent with Thrombocytopenia
  2. Chemistry panel and Serum osmolarity
    1. Diabetes Insipidus changes

VIII. Imaging

IX. Diagnosis

  1. Skin biopsy
  2. Bone Marrow Biopsy

X. Prognosis

  1. Multisystem disease
    1. More common in age <3 years
    2. Worse prognosis if involvement of liver, Bone Marrow or Spleen (five year survival 77%)
  2. Single organ involvement
    1. More common in age >3 years old
    2. Better prognosis with five year survival approaching 100%

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Ontology: Histiocytosis, Langerhans-Cell (C0019621)

Definition (MSH) A group of disorders resulting from the abnormal proliferation of and tissue infiltration by LANGERHANS CELLS which can be detected by their characteristic Birbeck granules (X bodies), or by monoclonal antibody staining for their surface CD1 ANTIGENS. Langerhans-cell granulomatosis can involve a single organ, or can be a systemic disorder.
Definition (NCI_NCI-GLOSS) A group of rare disorders in which too many Langerhans cells (a type of white blood cell) grow in certain tissues and organs including the bones, skin, and lungs, and damage them. Langerhans cell histiocytosis may also affect the pituitary gland (which makes hormones that control other glands and many body functions, especially growth). Langerhans cell histiocytosis is most common in children and young adults.
Definition (NCI) A neoplastic proliferation of Langerhans cells which contain Birbeck granules by ultrastructural examination. Three major overlapping syndromes are recognized: eosinophilic granuloma, Letterer-Siwe disease, and Hand-Schuller-Christian disease. The clinical course is generally related to the number of organs affected at presentation. (WHO, 2001)
Definition (NCI) A multifocal, unisystem form of Langerhans-cell histiocytosis. There is involvement of multiple sites in one organ system, most frequently the bone. Patients are usually young children presenting with multiple destructive bone lesions.
Definition (CSP) group of disorders of histiocyte proliferation which includes Letterer-Siwe disease; Hand-Schueller-Christian syndrome; and eosinophilic granuloma; Langerhans cells are components of the lesions.
Concepts Neoplastic Process (T191)
MSH D006646
ICD10 C96.6 , C96.5, C96.0
SnomedCT 190956004, 128809007, 39795003, 154583006, 154773005, 110450007, 234439008, 267510005, 269628007, 190960001, 128811003, 65399007, 190955000
English Granulomatosis, Langerhans-Cell, Histiocytosis X, Histiocytosis, Langerhans Cell, Histiocytosis, Langerhans-Cell, Histiocytosis-X, Langerhans-Cell Granulomatosis, Different progress histiocyto, Histiocytosis X , unspecified, LCH-Langerh cell histiocytosis, Langerhans histiocyt syndrome, Langerhans histiocytic syndrome, LANGERHANS CELL HISTIOCYTOSIS, LCH, LETTERER SIWE DIS, SCHUELLER CHRISTIAN DIS, Hand Schuller Christian disease, multifocal eosinophilic granuloma, multifocal eosinophilic granuloma (diagnosis), Langerhans cell histiocytosis, no ICD-O subtype, Langerhans cell histiocytosis (diagnosis), histiocytosis (histiocytosis X), histiocytosis X, Hand-Schuller-Christian diseas, Langerhans-Cell Histiocytosis, Schüller-Christian syndrome, Langerhans' cell histiocytosis, Langerhans' cell granulomatosis, Hand-Schueller-Christian disease, Langerhans-cell histiocytosis NOS, Letterer-Siwe disease, Histiocytosis, Langerhans-Cell [Disease/Finding], Disease, Hand-Schüller-Christian, Hand-Schüller-Christian Syndrome, Hand Schüller Christian Syndrome, Syndrome, Hand-Schüller-Christian, Disease, Hand-Schueller-Christian, Hand Schüller Christian Disease, Hand-Schueller-Christian Disease, Hand Schueller Christian Disease, Hand-Schüller-Christian Disease, hand-schueller-christian disease, langerhans cell histiocytosis, hand schuller christian disease, schuller christian syndrome, disease hand schuller christian, hand christian schuller disease, cell histiocytosis langerhans, histiocytosis-x, langerhans cell disease, langerhans cell granulomatosis, generalized histiocytosis, christian disease hand schuller, cell histiocytosis langerhan, langerhan's cell histiocytosis, christian diseases hand schuller, cells histiocytosis langerhans, histiocytosis x, cell granulomatosis langerhans, hand-schuller-christian disease, Multifocal and unisystemic Langerhans cell histiocytosis, Aleukemic Reticuloendothelioses, Systemic, Type 2 Histiocytosis, Reticuloendothelioses, Non-Lipid, Reticuloendotheliosis, Non-Lipid, Systemic Aleukemic Reticuloendothelioses, Non Lipid Reticuloendotheliosis, Non-Lipid Reticuloendothelioses, Reticuloendotheliosis, Systemic Aleukemic, Histiocytoses, Type 2, Non-Lipid Reticuloendotheliosis, Reticuloendothelioses, Systemic Aleukemic, Aleukemic Reticuloendotheliosis, Systemic, Type 2 Histiocytoses, Histiocytosis, Type 2, Systemic Aleukemic Reticuloendotheliosis, histiocytoses (histiocytosis x) langerhans (diagnosis), histiocytoses (histiocytosis x) langerhans, Langerhans Cell Histiocytoses, Langerhans Cell Histiocytosis, Cell Histiocytoses, Langerhans, Histiocytoses, Langerhans Cell, Cell Histiocytosis, Langerhans, Cell Granulomatoses, Langerhans, Langerhans Cell Granulomatoses, Granulomatosis, Langerhans Cell, Langerhans Cell Granulomatosis, Cell Granulomatosis, Langerhans, Granulomatoses, Langerhans Cell, Hand-Schuller-Christian syndr., Langerhans' cell histiocytosis (morphologic abnormality), Hand - Schuller - Christian disease, Langerhan's cell histiocytosis (disorder), Histiocytosis X, unspecified, Histiocytosis X (chronic), Histiocytosis X, unspecified (disorder), Langerhans cell histiocytosis, no International Classification of Diseases for Oncology subtype, Langerhans cell histiocytosis, no ICD-O subtype (morphologic abnormality), Langerhans cell histiocytosis, no International Classification of Diseases for Oncology subtype (morphologic abnormality), Hand-Schueller-Christian syndrome, Langerhans cell histiocytosis, polyostotic, Chronic differentiated progressive histiocytosis, Chronic disseminated histiocytosis X, Chronic histiocytosis X, Chronic idiopathic xanthomatosis, Generalized histiocytosis of bones, Hand-Schuller-Christian disease, Differentiated progressive histiocytosis, Histiocytosis X syndrome, LCH - Langerhan's cell histiocytosis, Langerhan's cell histiocytosis, Langerhans cell granulomatosis, Schuller-Christian syndrome, Langerhans cell histiocytosis, Generalised histiocytosis of bones, Hand-Schuller-Christian disease [obs], Hand-Schüller-Christian disease (disorder), Hand-Schüller-Christian disease, Histiocytosis X [obs], Histiocytosis X syndrome (disorder), Langerhans cell disease, Langerhans cell histiocytosis (disorder), Langerhans cell histiocytosis, multifocal (morphologic abnormality), Langerhans cell histiocytosis, multifocal, Langerhans cell histiocytosis, poly-ostotic, Hand-Schüller-Christian, Langerhans' cell; histiocytosis, Schüller-Christian, X; histiocytosis, chronic, X; histiocytosis, histiocytosis; Langerhans' cell, histiocytosis; X, chronic, histiocytosis; X, Histiocytosis X, NOS, Histiocytosis X , chronic, Histiocytosis X , unspecified (disorder), Langerhans cell histiocytosis (morphologic abnormality), Hand-Schuller-Christian Disease, Chronic Histiocytosis X, Disease, Schueller-Christian, Generalized Histiocytoses, Generalized Histiocytosis, Hand Schueller Christian Syndrome, Hand-Schueller-Christian Syndrome, Histiocytoses, Generalized, Histiocytosis, Generalized, Letterer Siwe Disease, Letterer-Siwe Disease, Schueller Christian Disease, Schueller-Christian Disease, Syndrome, Hand-Schueller-Christian, Disease, Letterer-Siwe
Spanish histiocitosis de células de Langerhans, no clasificada como subtipo en CIE-O, enfermedad de Hand - Schuller - Christian (trastorno), enfermedad de Hand-Schüller-Christian (trastorno), enfermedad de Hand-Schüller-Christian, Xantomatosis idiopática crónica, Enfermedad de Hand-Schueller-Christian, Histiocitosis de las células de Langerhans, Granulomatosis de las células de Langerhans, histiocitosis de células de Langerhans [dup] (anomalía morfológica), histiocitosis de células de Langerhans (trastorno), síndrome histiocítico de Langerhans, enfermedad de células de Langerhans, histiocitosis progresiva diferenciada, histiocitosis X, no especificada, histiocitosis X, no especificada (trastorno), enfermedad de Hand - Schuller - Christian, enfermedad de las células de Langerhans, granulomatosis de células de Langerhans, histiocitosis X (trastorno), histiocitosis X crónica, histiocitosis X diseminada crónica, histiocitosis X, histiocitosis de células de Langerhans (anomalía morfológica), histiocitosis de células de Langerhans, multifocal (anomalía morfológica), histiocitosis de células de Langerhans, multifocal, histiocitosis de células de Langerhans, poliosteósica, histiocitosis de células de Langerhans, histiocitosis generalizada de los huesos, histiocitosis progresiva diferenciada crónica, síndrome de histiocitosis X (trastorno), síndrome de histiocitosis X, xantomatosis idiopática crónica, histiocitosis de células de Langerhans, no clasificada como subtipo en CIE-O (anomalía morfológica), Granulomatosis de Células de Langerhans, Histiocitosis de Células de Langerhans, Histiocitosis X
Swedish Langerhanscellshistiocytos
Czech Handův-Schuellerův-Christianův syndrom, Lettererova-Siweova nemoc, histiocytóza z Langerhansových buněk, Histiocytóza z Langerhansových buněk, Chronická idiopatická xantomatóza, Hand-Schüller-Christianova choroba, Histiocytóza Langerhansových buněk ???
Finnish Langerhansinsoluhistiosytoosi
Italian Istiocitosi generalizzata, Istiocitosi X, Malattia di Letterer-Siwe, Granulomatosi a cellule di Langerhans, Sindrome di Hand-Schueller-Christian, Xantomatosi idiopatica cronica, Malattia di Hand-Schueller-Christian, Istiocitosi a cellule di Langerhans, Istiocitosi delle cellule di Langerhans
Croatian Not Translated[Histiocytosis, Langerhans-Cell]
Portuguese Granulomatose da célula Langerhan, Histiocitose de células de Langerhans, Xantomatose crónica idiopática, Doença de Hand-Schüller-Christian, Granulomatose de Células de Langerhans, Histiocitose de Células de Langerhans, Histiocitose X
French Granulomatose des cellules de Langerhans, Xanthomatose idiopathique chronique, Histiocytose X, Histiocytose langerhansienne, Histiocytose à cellules de Langerhans, Maladie de Hand-Schüller-Christian, Maladie de Letterer-Siwe, Granulomatose à cellules de Langerhans, Histiocytose des cellules de Langerhans
Dutch chronische idiopathische xanthomatosis, langerhanscelhistiocytose, Langerhans-cel granulomatose, Hand-Schueller-Christian ziekte, Langerhans-cellen; histiocytose, X; histiocytose, chronisch, X; histiocytose, histiocytose; Langerhans-cellen, histiocytose; X, chronisch, histiocytose; X, Histiocytose, Langerhanscel-, Histiocytose-X, Langerhanscelgranulomatose, Langerhanscelhistiocytose
German Hand-Schueller-Christian-Krankheit, Langerhans-Zell-Histiozytose, chronische idiopathische Xanthomatose, eosinophiles Knochengranulom, Histiozytose X, Histiozytose, Langerhans-Zell-, Langerhanszell-Granulomatose, Histiocytosis X
Japanese ランゲルハンスサイボウニクゲシュショウ, マンセイトクハツセイオウショクシュショウ, 慢性特発性黄色腫症, ランゲルハンスサイボウソシキキュウショウ, ハンドシューラークリスチャンビョウ, ハンド・シューラー・クリスチャン病, ハンド-シュラー-クリスチャン病, 組織球症-Langerhans細胞, 無白血病性細網内皮症, 感染性細網内皮症, 細網内皮症-感染性, 細網内皮症-全身性, 全身性細網内皮症, レッテラー-シーベ病, レットル-ジーベ病, Hand-Schueller-Christian症候群, 細網内皮症-無白血病性, ハンド-シュラー-クリスチャン症侯群, レッテラー細網症, レッテラー・シーベ病, 全身性組織球増殖症, 組織球症-全身性, 組織球症-非脂質性, 組織球増殖症-全身性, 非脂質性組織球症, Schueller-Christian病, 全身性組織球症, ハンド-シュレル-クリスチャン症侯群, リトラー-ジーベ病, Letterer-Siwe病, 無白血病性細網症, レットレル・ジーベ病, レテラー・ジーヴェ病, 非脂質性組織球増殖症, レテラー-ジーヴェ病, Langerhans細胞組織球症, ランゲルハンス細胞組織球症, ランゲルハンス細胞肉芽腫症, 原因不明性組織球増殖症, 組織球増殖症-原因不明性, 組織球症-ランゲルハンス細胞, 組織球症X, Langerhans細胞肉芽腫症, 原因不明性組織球増殖, 組織球増殖症X, 肉芽腫症-Langerhans細胞, 肉芽腫症-ランゲルハンス細胞
Polish Zespół Handa-Schullera-Christiana, Ziarniniakowatość Langerhansa, Histiocytoza z komórek Langerhansa, Histiocytoza X, Choroba Letterera-Siwego
Hungarian Chronicus idiopathiás xanthomatosis, Hand-Schüller-Christian-betegség, Langerhans sejtes granulomatosis, Langerhans-sejt histiocytosis
Norwegian Hand-Schüller-Christians sykdom, Histiocytosis X, Langerhans' celle histiocytose, Letterer-Siwes sykdom