Langerhans cell histiocytosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 23 Oct 2024

Last updated: 31 Oct 2023

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by activating mutations of the mitogen-activated protein kinase pathway. There is clonal proliferation of pathogenic Langerhans cells in single or multiple organs.

Clinical presentation is heterogeneous and ranges from self-healing bone lesions to multisystem, life-threatening disease.

Tissue biopsy of lesional cells showing the presence of CD1a and langerin (CD207) is definitive for diagnosis in the correct clinical setting.

Single-system disease may resolve without treatment and require careful monitoring only.

Single-system disease involving risk organs and multisystem disease is treated with systemic chemotherapy.

Targeted therapy has the potential to improve outcomes in otherwise refractory cases.

Adverse prognostic factors include poor response to therapy and risk-organ involvement.

Definition

LCH is a rare disease characterized by the clonal proliferation of pathogenic Langerhans cells, leading to inflammation and tissue destruction.[1]

LCH affects both children and adults, with almost twice the incidence in the pediatric age group. The most commonly involved organs in children are the bone, skin, pituitary gland, liver, spleen, hematopoietic system, lungs, lymph nodes, and central nervous system.[2]

LCH was previously called histiocytosis X.[3]

History and exam

Key diagnostic factors

age <15 years
bone pain and/or swelling
skin rash
polyuria and polydipsia
growth or sexual maturation failure
vertebra plana
hepatosplenomegaly

Full details

Other diagnostic factors

cough, dyspnea
chest pain
orbital abnormalities
jaundice
ascites
cytopenias
fever
anorexia
weight loss
irritability
ear pain
ear discharge
hearing loss
perforated tympanic membrane
headache
neurologic signs
bloody diarrhea
oral mucosa lesions
lymphadenopathy
thyroid enlargement

Full details

Risk factors

smoking
family history of thyroid disease
perinatal infections

Full details

Diagnostic tests

1st tests to order

CBC
LFTs
serum albumin
renal function
serum electrolytes
serum calcium
inflammatory markers
endocrine evaluation (adults)
BRAF V600E mutation analysis
skeletal survey (children)
chest x-ray (children)
abdominal ultrasound (children)
fluorodeoxyglucose positron emission tomography (FDG-PET) (adults)
MRI head with contrast (adults)
tissue biopsy

Full details

Tests to consider

endocrine evaluation (children)
coagulation studies (children)
pulmonary function tests
echocardiogram
high-resolution CT chest
audiometry
bone marrow aspirate and biopsy
MRI head with contrast (children)
MRI spine
CT head

Full details

Treatment algorithm

ACUTE

single-system disease: bone involvement

single-system disease: skin involvement

single-system disease: isolated lymph node involvement

single-system disease: lung involvement

single-system disease: CNS involvement

single-system disease: neurodegenerative disease

multisystem disease

ONGOING

relapsed/refractory disease

Contributors

Authors

Gaurav Goyal, MD

Assistant Professor of Medicine

University of Alabama at Birmingham

Department of Medicine

Division of Hematology/Oncology

Birmingham

Disclosures

GG has been reimbursed for advisory board by Opna Bio LLC, and receives royalties from UpToDate.

Acknowledgements

Dr Gaurav Goyal would like to gratefully acknowledge Dr Oussama Abla and Professor Kimo Stine, previous contributors to this topic.

Disclosures

OA declares that he has no competing interests. KS declares that he serves on the Board of the Histiocytosis Association (a nonprofit organization), has provided advice for a legal firm reviewing a case of LCH, and receives honoraria for membership of advisory boards to Pfizer and Behring.

Peer reviewers

R. Maarten Egeler, MD, PhD

Director of Pediatric Immunology, Hematology, Oncology, Bone Marrow Transplantation, and Autoimmune Diseases

Leiden University Medical Center

Leiden

The Netherlands

Disclosures

RME has previously worked with Dr Abla on a review of LCH. RME is an author of several references cited in this topic.

Rima Jubran, MD, MPH

Assistant Professor of Pediatrics

Keck School of Medicine

University of Southern California

Children's Hospital Los Angeles

Los Angeles

Disclosures

RJ declares that she has no competing interests.

Differentials
- Seborrheic dermatitis
- Juvenile xanthogranuloma (JXG)
- Rosai-Dorfman disease (RDD)
More Differentials
Guidelines
- Clinical practice guidelines in oncology: histiocytic neoplasms
- International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults
More Guidelines
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Langerhans cell histiocytosis

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

single-system disease: bone involvement

single-system disease: skin involvement

single-system disease: isolated lymph node involvement

single-system disease: lung involvement

single-system disease: CNS involvement

single-system disease: neurodegenerative disease

multisystem disease

relapsed/refractory disease

Contributors

Authors

Gaurav Goyal, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

R. Maarten Egeler, MD, PhD

Disclosures

Rima Jubran, MD, MPH

Disclosures

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

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