Letterer-Siwe Disease (LSD)

Childhood immunologic disorder characterized by pathologic proliferation of histiocytes caused by the Langerhans cells. Involves mainly the skin, bones, brain, lungs, spleen, and liver. The presence of diabetes insipidus must be considered. Presents nonmalignant growths that represent accumulation of histiocytes. Poor prognosis (70% mortality).

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

Reported between 1:200,000 and 1:3,300,000 live births. Most cases are sporadic.

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

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.

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.

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). Hypothalamic involvement resulting in diabetes insipidus (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 DI.

Blood examination: cell blood count, platelet count must be obtained. Determine whether DI is present; evaluate electrolytes. Evidence of long bone involvement should be sought. Consider perioperative glucocorticoid coverage. A chest x-ray film should be obtained. Coagulation profile and bleeding time must be available.

Correction of anemia and thrombocytopenia may be necessary. Be vigilant for presence of DI. Care should be taken when moving patients to prevent pathologic fractures where bony lesions are present. In the presence of lung involvement, the potential for pneumothorax, and/or pleural fusion, mechanical ventilation must be used judiciously.

Perioperative glucocorticoid coverage may be necessary. Consider side effects of chemotherapeutic agents.

Histiocytosis: Rare spectrum of disorders characterized by proliferation and accumulation of histiocyte in various lesions within the body. Lesions may include Langerhans cells, monocytes, and eosinophils. Most affected individuals have single or multiple bone lesions characterized by degenerative changes and osteolysis. Although the skull is most commonly affected, there may be involvement of the vertebrae and the long bones of the arms and legs. Some individuals present with DI. The exact cause of LCH cell histiocytosis is unknown. Langerhans cell histiocytosis has replaced the older, less specific term histiocytosis X. Histiocytosis X encompassed three entities known as eosinophilic granuloma, Hand-Schüller-Christian disease, and LSD, which are all characterized by the accumulation of histiocytes. The X denoted that the cause and development of the disorder were not understood.

Hashimoto-Pritzker Disease: Specific form of LCH occurring in newborns or young infants and characterized by the formation of papules, nodules, or vesicles eventually leading to ulcerations. The face, limbs, palms, and soles are most often affected. These skin lesions usually heal without treatment within a few weeks or months. These cases may also be referred to as congenital self-healing histiocytosis or pure cutaneous histiocytosis.

Hand-Schüller-Christian Disease: Old term used to describe multifocal LCH occurring in association with DI and exophthalmos. Multiple bony lesions most often affect the skull. In affected individuals with this form of LCH, bony lesions may affect the liver, spleen, and lymph nodes.

Rosai-Dorfman Disease: Characterized by histiocytosis affecting the sinuses and the lymph nodes, resulting in lymphadenopathy. Organs affected include the central nervous system, skin, and kidneys. The exact cause is unknown. The disorder may also be known as sinus histiocytosis with massive lymphadenopathy.

Mastocytosis: Characterized by the accumulation of mast cells in skin, bone marrow, and internal organs such as the liver, spleen, and lymph nodes. Also known as urticaria pigmentosa and characterized by small, brownish, flat or elevated lesions that may be surrounded by reddened, itchy skin. Hepatosplenomegaly, abdominal pain and diarrhea, and hypertension are present. The exact cause of mastocytosis is unknown.

Erdheim-Chester Disease (ECD): Multisystem disorder of adulthood characterized by the accumulation of histiocytes. It affects the long bones, skin, ophthalmic regions, lungs, brain, pituitary gland, and additional tissues and organs.