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Langerhans cell histiocytosis in Infant/Neonate
See also in: Anogenital
Other Resources UpToDate PubMed

Langerhans cell histiocytosis in Infant/Neonate

See also in: Anogenital
Contributors: Vivian Wong MD, PhD, Elyse M. Love MD, Belinda Tan MD, PhD, Susan Burgin MD
Other Resources UpToDate PubMed


Langerhans cell histiocytosis (LCH) is a clinically heterogeneous group of rare idiopathic disorders in which dendritic histiocytes accumulate in one or many organs. LCH is a subgroup of "L group" histiocytosis that includes Erdheim-Chester disease (ECD), indeterminate cell histiocytosis, and mixed LCH / ECD.

LCH is a rare condition, occurring most commonly in White male children aged 1-4 years, but it may present from birth to adulthood. Studies in the United States have shown an increased incidence among individuals of Hispanic descent and a decreased incidence among Black children. The 3-year survival rate is approximately 80%, with age younger than 2 years, multiorgan involvement, and organ dysfunction portending a worse prognosis.

While 4 clinical variants were previously designated (Letterer-Siwe disease, Hand-Schüller-Christian syndrome, self-healing reticulohistiocytosis of Hashimoto-Pritzker [congenital self-healing histiocytosis], and eosinophilic granuloma), these categories have been largely abandoned in recent years due to significant overlap between the clinical entities and lack of prognostic relevance. Currently, patients are classified based on the number of organ systems involved (ie, single-system or multisystem LCH).

LCH can affect any organ of the body, with bones, skin, oral mucosa, genital mucosa, nail, bone marrow, lungs, liver, spleen, gastrointestinal tract, lymph nodes, and the central nervous system being the most common sites of involvement. The skin is affected in approximately 33% of LCH cases. The spleen, bone marrow, and liver are considered high-risk organs. Involvement of one or more of these organs is associated with a higher risk of dying from the disease. Although the lung was previously considered a high-risk organ, it is now known to be a rare cause of death. Most patients with lung involvement have a history of tobacco smoking. Skull bone lesions are considered to be a risk factor for central nervous system involvement. These patients may have a higher risk of developing diabetes insipidus and/or neurodegenerative complications.

LCH may recur after resolution and has an unpredictable course. LCH has further been associated with the development of leukemias and lymphomas. Additionally, disease sequelae, including endocrine (diabetes insipidus, growth delay), skeletal (scoliosis, abnormal dental development, hearing dysfunction), neuropsychological (cerebellar ataxia, learning disabilities), pulmonary, and hepatic (sclerosing cholangitis, cirrhosis) involvement can present up to decades after diagnosis.

Infant Considerations:
LCH often presents in the first year of life as a rash in the diaper area. Other findings may include lymphadenopathy, diffuse lung involvement, osteolytic involvement of the mastoid presenting with a picture of otitis media, and gastrointestinal involvement. Failure to thrive may be due to malabsorption. There is wide variation in the clinical spectrum. The congenital form presents with papules, nodules, or ulcers at birth; nodules may be solitary or few.

Adult Considerations:
LCH is even rarer in adults than children. The skin, bone, and lungs are most frequently involved. Systemic and progressive forms are rare.


C96.5 – Multifocal and unisystemic Langerhans-cell histiocytosis
C96.6 – Unifocal Langerhans-cell histiocytosis

65399007 – Langerhans cell histiocytosis

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Differential Diagnosis & Pitfalls

The differential is broad depending on the constellation of organ involvement.
  • Erdheim-Chester disease
  • Sinus histiocytosis with massive lymphadenopathy
  • Juvenile xanthogranuloma or adult xanthogranuloma
  • Necrobiotic xanthogranuloma
  • Multiple myeloma
  • Lymphoma
  • Vasculitis
  • Osteomyelitis
  • Primary tumors
  • Interstitial lung disease
  • Sarcoidosis
For cutaneous involvement, also consider in pediatric patients:
  • Seborrheic dermatitis usually lacks distinct papules. The presence of eroded, ulcerated, or purpuric lesions in a child thought to have seborrheic dermatitis should prompt a biopsy to rule out LCH.
  • Psoriasis – Also erythematous and scaly, but not papular or accompanied by systemic symptoms, and usually there is a family history of psoriasis.
  • Benign cephalic histiocytosis – Occurs between 2 months and 2 years; on the face and other portions of the head. It is caused by a non-Langerhans cell histiocytosis. Lesions regress spontaneously.
  • Scabies may resemble LCH clinically and histologically. Inquire about potentially affected family members.
  • Atopic dermatitis is much more pruritic and rapidly responds to topical steroids.
  • Diaper irritant contact dermatitis is localized to the diaper area and responds to gentle skin care and topical steroids.
  • Impetigo
  • Tinea cruris
  • Candidiasis
  • Herpes simplex virus
  • Varicella
  • Cytomegalovirus infection
  • Congenital candidiasis
  • Early congenital syphilis
  • Lichen aureus (see Capillaritis)
  • Erythema toxicum neonatorum
  • Transient neonatal pustular melanosis
  • Congenital Leukemia cutis
  • Neonatal erythropoiesis
  • Disseminated neonatal hemangiomatosis
  • Acropustulosis of infancy
  • Metastatic cutaneous melanoma
  • Incontinentia pigmenti
  • Hereditary Epidermolysis bullosa simplex

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Last Reviewed:06/13/2018
Last Updated:09/13/2022
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Langerhans cell histiocytosis in Infant/Neonate
See also in: Anogenital
A medical illustration showing key findings of Langerhans cell histiocytosis (Adult-Onset With Lung Involvement) : Chest pain, Fever, Pneumothorax, Dyspnea, Cigarette smoker
Clinical image of Langerhans cell histiocytosis - imageId=280377. Click to open in gallery.  caption: 'A close-up of showers of erythematous and purpuric macules and papules.'
A close-up of showers of erythematous and purpuric macules and papules.
Copyright © 2024 VisualDx®. All rights reserved.