World Journal of Pediatrics

, Volume 15, Issue 6, pp 536–545 | Cite as

Childhood Langerhans cell histiocytosis: a disease with many faces

  • Alexander K. C. LeungEmail author
  • Joseph M. Lam
  • Kin Fon Leong
Review Article



Langerhans cell histiocytosis (LCH) is a group of diseases characterized by the proliferation and accumulation of Langerhans cells. Clinical presentations of LCH vary widely.

Data sources

A PubMed search was conducted using Clinical Queries with the key term “Langerhans cell histiocytosis”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. This paper is based on, but not limited to, the search results.


Generally, patients with LCH can be divided into two groups based on the extent of involvement at diagnosis, namely, single-system LCH and multisystem LCH. The involvement may be unifocal or multifocal. Patients with isolated bone lesions typically present between 5 and 15 years of age, whereas those with multisystem LCH tend to present before 5 years of age. The clinical spectrum is broad, ranging from an asymptomatic isolated skin or bone lesion to a life-threatening multisystem condition. Clinical manifestations include, among others, "punched out" lytic bone lesion, seborrheic dermatitis-like eruption, erythematous/reddish-brown crusted/scaly papules/maculopapules/plaques/patches, and eczematous lesions, diabetes insipidus, hepatosplenomegaly, cytopenias, lymphadenopathy, and an acute fulminant disseminated multisystem condition presenting with fever, skin rash, anemia, thrombocytopenia, lymphadenopathy, and hepatosplenomegaly. The diagnosis is clinicopathologic, based on typical clinical findings and histologic/immunohistochemical examination of a biopsy of lesional tissue. Positive CD1a, S100, and/or CD207 (Langerin) immunohistochemical staining of lesional cells is required for a definitive diagnosis. Watchful waiting is recommended for patients with skin-only LCH. Patients with symptomatic or refractory skin-only LCH may be treated with topical tacrolimus/corticosteroids, topical nitrogen mustard, oral methotrexate, or oral hydroxyurea. The current recommended first-line therapy for patients with multisystem LCH is 12 months therapy with prednisone and vinblastine. Mercaptopurine is added for patients with risk organ involvements.


Because of the broad spectrum of clinical manifestations and the extreme diversity of disease, LCH remains a diagnostic dilemma. Morphological identification of LCH cells and positive immunochemical staining with CD1a, S100, and/or CD207 (Langerin) of lesional cells are necessary for a definitive diagnosis.


Cytopenia Diabetes insipidus Eczematous lesions Hepatosplenomegaly Lymphadenopathy Seborrheic dermatitis-like eruption 


Author contributions

AKCL wrote the first draft of the manuscript, as well as a statement of whether an honorarium, grant, or other form of payment was given to anyone to produce the manuscript. JML and KFL contributed to drafting and revising the manuscript. All authors have seen and approved the final version submitted for publication and take full responsibility for the manuscript.


There is no honorarium, grant, or other form of payment given to any of the authors/coauthors.

Compliance with ethical standards

Ethical approval

Not applicable.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.


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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  1. 1.Department of PediatricsThe University of Calgary, and The Alberta Children’s HospitalCalgaryCanada
  2. 2.Department of PediatricsUniversity of British ColumbiaVancouverCanada
  3. 3.Department of Dermatology and Skin SciencesUniversity of British ColumbiaVancouverCanada
  4. 4.Pediatric InstituteKuala Lumpur General HospitalKuala LumpurMalaysia

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