Langerhans Cell Histiocytosis Clinical Presentation

Updated: Mar 07, 2017
  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
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Presentation

History

The clinical presentation of Langerhans cell histiocytosis (LCH) depends on the extent of dissemination.

Unifocal bony LCH is characterized by the development of solitary osseous lesions at any site. Unifocal bony LCH is least common in the hands and the feet. These lesions are often asymptomatic and are detected incidentally during investigation for unrelated disorders.

Patients with multisystem disease may have a protean history depending on the location of osteolytic lesions and the degree of organ dysfunction. Patients with Hand-Schüller-Christian syndrome (which occurs in 25% of patients with multifocal LCH) often present with recurrent episodes of otitis media and mastoiditis or with polyuria and polydipsia.

Letterer-Siwe disease presents with symptoms suggestive of a systemic infection or malignancy, including a generalized skin eruption, anemia, and hepatosplenomegaly.

The congenital form of LCH manifests as skin lesions at birth or during the early postnatal period. Cutaneous nodules and ulceration have onset early in life. Rarely, patients with purpuric lesions present with a blueberry-muffin appearance. [22] Symptoms of organ involvement may also occur.

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Physical Examination

Signs of Langerhans cell histiocytosis (LCH) depend on the localization and the extent of the disease. The clinical spectrum is broad, and an individual case may differ markedly from the prototypes described.

Solitary cutaneous disease presents with noduloulcerative lesions in the oral, perineal, perivulvar, or retroauricular regions. [28] Rarely, solitary cerebral lesions may occur. In adults with LCH, the pulmonary system is the most frequently involved organ system, and solitary pulmonary lesions may be the only manifestation. Chronic cough, dyspnea, chest pain, and recurrent pneumothoraces are typical signs and symptoms of pulmonary disease. [29]

Because of its protean nature, LCH must be considered in more unusual presentations, including protein-losing enteropathy in infants and combined pulmonary-thyroid involvement in adults. [30, 31]

Chronic unifocal LCH

Chronic unifocal LCH (eosinophilic granuloma of bone) classically presents as a solitary calvarial lesion in young adults; other frequent sites of involvement include vertebra, rib, mandible, femur, ilium, and scapula.

Lesions are usually asymptomatic, but bone pain and a soft tissue mass may occur. When calvarial lesions extend into the nervous system, a variety of neurologic manifestations may be seen. Bony lesions may cause otitis media by destruction of the temporal and mastoid bones, proptosis secondary to orbital masses, loose teeth from infiltration of the mandibles, or pituitary dysfunction due to involvement of the sella turcica.

Spontaneous fractures can result from osteolytic lesions of the long bones; vertebral collapse with spinal cord compression has been described. Mono-ostotic lesions of LCH may also appear in less common sites, such as the scapula. [32]

Classic multifocal LCH (Hand-Schüller-Christian disease)

The classic multifocal form of LCH (Hand-Schüller-Christian disease) includes diabetes insipidus, exophthalmos, and bony defects, particularly of the cranium. Lesions may affect a variety of systems, including liver (20%), spleen (30%), and lymph nodes (50%). Pulmonary involvement may occur. Osteolytic lesions of the long bones can lead to spontaneous fractures.

One third of patients have mucocutaneous lesions, most frequently infiltrated nodules and ulcerated plaques, especially in the mouth, axillae, and anogenital region. Other cutaneous manifestations include extensive coalescing, scaling, or crusted papules.

Acute disseminated LCH

Patients with acute disseminated LCH (multiorgan involvement) present with fever, anemia, thrombocytopenia, pulmonary infiltrates, skin lesions, and enlargement of lymph nodes, spleen, and liver. Cutaneous abnormalities are present in almost 80% of patients, frequently as the first sign. The eruption may be extensive, involving the scalp, face, trunk, buttocks, and intertriginous areas. Lesions consist of closely set petechiae and yellow-brown papules topped with scale and crust. The papules may coalesce to form an erythematous, weeping or crusted eruption mimicking seborrheic dermatitis. Intertriginous lesions are often exudative, and secondary infection and ulceration may occur. Note the images below.

Letterer-Siwe disease. Bilateral inguinal erosive Letterer-Siwe disease. Bilateral inguinal erosive plaques and erythematous papules on the abdomen. Courtesy of Dr Neil S. Prose.
Abdominal area of an infant with multiple erythema Abdominal area of an infant with multiple erythematous papules covered by scale and/or crust.
Typical purpuric lesions in Langerhans cell histio Typical purpuric lesions in Langerhans cell histiocytosis (must be distinguished from seborrheic dermatitis).

Osteolytic lesions are not common in the disseminated form of LCH, but the mastoid can be affected, resulting in a clinical picture of otitis media, which may be the presenting complaint. Aural discharge, conductive hearing loss, and postauricular swelling have been described. [33]

As described above, patients with pulmonary involvement present with chest pain, hemoptysis, dyspnea, failure to thrive, cystic changes, and pneumothorax; if lung disease is extensive, oxygen diffusion and lung capacity may be reduced. [34, 35]

Neurologic involvement may produce seizures, vertigo, headache, ataxia, and cognitive defects.

Congenital self-healing histiocytosis

Congenital self-healing histiocytosis presents at birth or during the early neonatal period with firm, red-brown, painless papulonodules (1-10 mm in diameter) or vesicles and crusts scattered over the scalp, face, and, to a lesser extent, trunk and the extremities. Lesions may ulcerate. Lesions may be solitary. Lesions may be followed by residual hypopigmented or hyperpigmented macules.

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Causes

The etiology of Langerhans cell histiocytosis (LCH) remains unknown.

Langerhans cell proliferation may be induced by a viral infection, a defect in intercellular communication (T cell–macrophage interaction), and/or a cytokine-driven process mediated by tumor necrosis factor, IL-11, and leukemia inhibitory factor. [23, 24, 25] Specifically, human herpesvirus 6 (HHV-6) has been proposed to contribute to the initiation and/or modulation of persistent LCH. However, other studies have not shown a correlation between HHV-6 and LCH, and their reported associations may represent coincidental findings. [26, 27]

Cigarette smoking may play a role as a chronic irritant in the development of eosinophilic granuloma of the lung.

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Complications

Complications appear in 30-50% of patients with Langerhans cell histiocytosis (LCH). The most common complications are orthopedic disabilities, hearing impairment, diabetes insipidus, skin scarring, and neuropsychologic defects (eg, anxiety, depression, decreased intellect). [18, 36, 37]

Patients with multisystem disease, craniofacial involvement, long-standing disease, or reactivation may be at increased risk of developing diabetes insipidus. [38, 39] Regular neurological examinations and whole brain MRI are recommended to evaluate for CNS lesions of LCH and for evidence of neurodegeneration in patients with newly recognized diabetes insipidus. [40]

Less common sequelae include chronic pulmonary dysfunction, liver cirrhosis, secondary malignancies such as acute lymphoblastic leukemia or solid tumors, and growth retardation. [41]

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