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Childhood Langerhans cell histiocytosis: a disease with many faces

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Abstract

Background

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.

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.

Conclusions

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.

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  1. Department of Pediatrics, The University of Calgary, and The Alberta Children’s Hospital, #200, 233, 16th Avenue NW, Calgary, AB, T2M 0H5, Canada

    Alexander K. C. Leung

  2. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Joseph M. Lam

  3. Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, BC, Canada

    Joseph M. Lam

  4. Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia

    Kin Fon Leong

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Leung, A.K.C., Lam, J.M. & Leong, K.F. Childhood Langerhans cell histiocytosis: a disease with many faces. World J Pediatr 15, 536–545 (2019). https://doi.org/10.1007/s12519-019-00304-9

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