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The disorders of xanthohistiocytic proliferation involving histiocytes,
foam cells, and mixed inflammatory cells are divided into Langerhans
cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH).
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Langerhans Cell
Histiocytosis (Histiocytosis X)
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LCH is an idiopathic spectrum of disorders characterized by a
clonal proliferation of Langerhans cells. Clinically, LCH is characterized
by lytic bony lesions and cutaneous findings that range from soft
tissue swelling to eczema- and seborrheic dermatitis-like skin changes
and ulceration.
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Histiocytosis can be extremely difficult to diagnose. In infants
with diaper rash that will not heal, particularly if there are erosions
in the folds or petechiae/purpura, histiocytosis should
be considered.
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Synonyms Class I histiocytosis,
nonlipid reticuloendotheliosis, eosinophilic granulomatosis.
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LCH has four overlapping forms:
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1. Letterer–Siwe disease: aggressive LCH
with diffuse skin and organ infiltration and thrombocytopenia
2. Hand-Schüller-Christian disease: LCH with lytic skull
lesions, exophthalmos, and diabetes insipidus
3. Eosinophilic granuloma: single osteolytic bony lesion ± skin/soft
tissue lesion
4. Hashimoto–Pritzker disease: congenital self-healing
reticulohistiocytosis
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Age Any age, common 1 to 3 years.
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Incidence Rare, 5/million
children.
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Genetics Familial case reports.
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The proliferating Langerhans cell appears to be primarily responsible
for the clinical manifestation of LCH. The stimulus for the proliferation
may be a disturbance of intracellular lipid metabolism, a reactive
response to infection (?viral), a primary immunologic disorder of
the host, or an inherited neoplastic disorder.
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LCH has a broad clinical spectrum, but in the most aggressive
form (Letterer–Siwe disease), the infant appears systemically
ill with a generalized skin eruption (seborrhea, petechiae, and
purpura) followed by fever, anemia, thrombocytopenia, adenopathy,
hepatosplenomegaly, and/or skeletal lesions.
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Type Papules, plaques, vesicles,
scale, petechiae, purpura, ulceration, necrosis.
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Color Pink, flesh-colored.
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Distribution Flexural areas: neck,
axillae (Fig. 19-1), and perineum > trunk (Fig. 19-2).
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Fever Lymphadenopathy (LAD). Ill
appearance.
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Pulmonary Infiltrate disease of
the lung bases and midzones, pneumothorax.
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Liver Hepatosplenomegaly.
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Bone Osteolytic lesions: calvarium,
sphenoid bone, sella turcica, mandible, long bones of upper extremities
(UEs), vertebrae.
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Other Otitis media, diabetes/exophthalmus/ bony
lesions in Hand–Schüller–Christian variant.
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Differential
Diagnosis
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The differential diagnosis of LCH includes seborrhea, candidiasis,
Darier disease, leukemia, lymphoma, multiple myeloma, urticaria
pigmentosa (UP), mycosis fungoides (MF), and non-LCH.
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Laboratory Examinations
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Histopathology Proliferation of
Langerhans cells with distinct morphologic (pale eosinophilic cytoplasm,
a kidney-shaped nucleus), ultrastructural (Birbeck granules), and
immune-histochemical markers (CD1a+, ATPase+,
S-100+, langerin (CD207)+, α-d-mannosidase+,
peanut agglutinin+).
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Radiographic Findings Osteolytic
lesion in calvarium, femur, rib, sphenoid, sella turcica, mandible,
long bones of UEs. Chest: diffuse interstitial fibrosis in lung
bases and midzones, pneumothorax.
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The prognosis of LCH varies according to the extent of systemic
involvement. Patients with eosinophilic granuloma or Hashimoto–Pritzker
disease (congenital self-healing reticulohistiocytosis) have a relatively
benign course with excellent prognosis. Patients older than 2 years
at the time of diagnosis, without involvement of the hematopoietic
system, liver, lungs, or spleen, have 100% probability
of survival.
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Patients with systemic involvement have a higher mortality rate,
especially children diagnosed before age 2 years with liver, lungs,
spleen, or hematopoietic involvement. Even with aggressive treatment,
mortality ranges from 38% to 54%. Of note, patients
with leukemia (acute lymphoblastic leukemia or acute nonlymphoblastic
leukemia) or solid tumors may have an increased incidence of LCH
and vice versa.
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The management and treatment of LCH is dependent upon the severity
and extent of involvement. Mild skin-only LCH can be treated with
topical steroids, antibacterial agents, psoralen ultraviolet A (PUVA),
and topical nitrogen mustard. Localized bony lesions can be treated
with nonsteroidal anti-inflammatory drugs (NSAIDs), intralesional
steroids, curette with, or without, bony chip packing, or low-dose
(300–600 rads) irradiation.
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Multisystem LCH can be systemically treated with corticosteroids,
vinblastine, methotrexate, or epipodophyllotoxin (etoposide). Failure
to respond to treatment after 6 weeks of these drugs is a poor prognostic
indicator. Even in responsive patients, there is a high (58%)
rate of LCH reactivity. Reactive disease can be treated with etanercept,
cyclosporine, 2-chlorodeoxyadenosine, or imatinib mesylate. Finally,
in recalcitrant cases, bone marrow, stem cell liver or lung transplantation
may be necessary.