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At a glance

It is a childhood immunologic disorder characterized by pathologic proliferation of histiocytes caused by the Langerhans cells. It is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH). It causes approximately 10% of LCH disease and is the most severe form. It is characterized by skin lesions (scaly skin involving the scalp, ear canals, and abdomen), lymphadenopathy, osteolytic lesions, and hepatosplenomegaly. Other organs involved are the spleen, brain, lungs, and bones. The presence of diabetes insipidus (DI) must be considered. Presents nonmalignant growths that represent accumulation of histiocytes. It is associated with a poor prognosis (70% mortality).

Synonyms

Letterer-Siwe Syndrome; Abt-Letterer-Siwe Syndrome; Siwe Disease.

History

The name Letterer-Siwe Disease was coined by Abt and Denenholz in 1936 to a condition that was first described in detail by Erich Letterer in 1924 and later extended by Sture Siwe in 1933.

Incidence

Reported between 1:200,000 and 1:3,300,000 live births. Most cases are sporadic. The prevalence is estimated at 1:500,000. The disease occurs almost exclusively in children less than 3 years old.

Genetic inheritance

Evidence supporting both autosomal dominant and recessive inheritance in different families.

Pathophysiology

Letterer-Siwe disease (LSD) is one of the Langerhans cell histiocytoses (LCH). Physiologically, Langerhans cells detect non–self-antigens and present them to the cells of the immune system (T cells), thus allowing an appropriate immune response from the body. They are normally found in the epidermis of the skin, but in LSD they spread to bone and other tissues and become associated with eosinophils. Lesions arise in many organs including bone, skin, spleen, liver, lungs, lymph nodes, and brain. Granulomatous inflammatory lesions develop and may proliferate and become destructive. These lesions later become less cellular, necrotic, and fibrotic.

Diagnosis

The hallmark of LSD is the presence of pathologic Langerhans cells in involved tissues. Specific histochemical, immunologic, and protein markers have been identified (Birbeck granules or positive S-100 beta protein and CD Ia antigen). These biochemical findings in addition to multiorgan involvement help make the diagnosis.

Clinical aspects

Although LSD has been described in adult patients, it is predominantly a condition affecting children age 2 months to 3 years. Clinical features include fever, anemia, thrombocytopenia, and the manifestations of histiocyte proliferation, including skin disorders (seborrheic, eczematous, pustular or nodular lesions particularly on the scalp), lytic lesions of the bones, and splenogenic thrombocytopenia. The lungs can be involved (nonproductive cough, dyspnea, pleural effusion, interstitial pneumonitis, and spontaneous pneumothorax). The hypothalamic involvement often results in DI. Eye protrusion may be present. The clinical course is very variable, and spontaneous remissions have occurred. Prognosis is generally poor. Treatment may include use of glucocorticoids, chemotherapeutic agents, bone marrow transplantation, and desmopressin for ...

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