LANGERHANS CELL HISTIOCYTOSIS IN CHILDREN
Langerhans cell histiocytosis (LCH) previously known as histiocytosis-X, eosinophilic granuloma, Hand-Schüller-Christian disease, or Letterer-Siwe disease is a disorder of the Langerhans cell, a bone marrow–derived dendritic cell that has a key role in antigen processing. Normal Langerhans cells located in the epidermis, lymph nodes, thymic epithelium, and bronchial mucosa process antigens and then migrate to lymphoid tissues, where they function as effector cells stimulating T-cell responses. Although the cause of the defect in LCH is unknown, it is a result of immunologic dysfunction. In LCH, the Langerhans cell loses its ability to present antigens.
LCH in children is rare, affecting
three to ﬁve children per million each year. LCH may present as a localized or
diffuse disorder. When localized, the presenting ﬁndings may include bone,
skin, or lymph node involvement. In infants, brown-purplish papules may be
evident, which are usually associated with a benign and self-healing course in
the ﬁrst year of life. However, multisystem disease may become evident later in
childhood. When skin-limited LCH is suspected, it should be conﬁrmed with
computed tomographic (CT) imaging of the chest and abdomen and bone marrow
biopsy to verify that there are no other abnormalities. Later in infancy,
skin-limited LCH presents as a red papular rash variably involving the neck,
axilla, abdomen, back, groin, and scalp.
The most common site of involvement
in childhood LCH is bone, typically presenting as a lytic skull lesion
identiﬁed in the evaluation of localized pain and erythema. Other bones that
may be involved include ribs, cervical vertebral bodies, humerus, and femur.
LCH lesions can extend from the bone and cause mass-effect presentations. For
example, skull base, maxillofacial bone, and sellar involvement may lead to
hearing loss, exophthalmos, cranial nerve palsies, and diabetes insipidus (DI).
On skull radiographs, extensive involvement of the skull may be observed with
irregularly shaped, lucent lesions “geographic
skull.” DI is the most common endocrine manifestation of LCH, and it may be the
initial presenting symptom complex (see Plate 1-27). These patients also have
varying degrees of anterior pituitary
insufﬁciency. In patients with pituitary dysfunction, thickening of the
pituitary stalk is usually evident.
LCH may present as isolated
lymphadenopathy, usually of the cervical or mediastinal lymph nodes.
Diffuse multisystem disease often
involves the liver and spleen. Patients with hepatic involvement may present
with signs and symptoms related to clotting factor deﬁciencies, increased
bilirubin, and low serum albumin. Cytopenias may result from the splenomegaly.
When the lungs are involved, LCH appears in a cystic and nodular pattern; the
ﬁrst sign of pulmonary involvement may be pneumothorax (see Plate 1-29).
LCH in the lung can cause diffuse
ﬁbrosis with symptoms of dyspnea. Bone marrow involvement is common in patients
with diffuse disease. Ataxia and cognitive dysfunction sometimes result from
LCH lesions involving the cerebellum or basal ganglia.
In the past, LCH was referred to as
Hand-Schüller-Christian disease if the triad of skull defects, DI, and
exophthalmos were prominent. Letterer-Siwe disease was the old term used
to describe the presentation of LCH with extensive multiorgan involvement
(e.g., skin, lungs, liver, spleen, lymph nodes, bone marrow, lymph nodes). Eosinophilic
granuloma was the term used to describe
localized lesion(s) conﬁned to bone.