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).
Histiocytosis (Histiocytosis X)
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
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
Synonyms Class I histiocytosis,
nonlipid reticuloendotheliosis, eosinophilic granulomatosis.
LCH has four overlapping forms:
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
4. Hashimoto–Pritzker disease: congenital self-healing
Age Any age, common 1 to 3 years.
Incidence Rare, 5/million
Genetics Familial case reports.
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.
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.
Type Papules, plaques, vesicles,
scale, petechiae, purpura, ulceration, necrosis.
Color Pink, flesh-colored.
Distribution Flexural areas: neck,
axillae (Fig. 19-1), and perineum > trunk (Fig. 19-2).
Histiocytosis X Erythematous
plaques with ulceration and maceration in the axilla of an infant.
Langerhans cell histiocytosis Erythematous
papules and a crusted, purpuric plaque on the abdomen of an infant.
Fever Lymphadenopathy (LAD). Ill
Pulmonary Infiltrate disease of
the lung bases and midzones, pneumothorax.
Bone Osteolytic lesions: calvarium,
sphenoid bone, sella turcica, mandible, long bones of upper extremities
Other Otitis media, diabetes/exophthalmus/ bony
lesions in Hand–Schüller–Christian variant.
The differential diagnosis of LCH includes seborrhea, candidiasis,
Darier disease, leukemia, lymphoma, multiple myeloma, urticaria
pigmentosa (UP), mycosis fungoides (MF), and non-LCH.
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+,
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.
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
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.
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.
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.