Letterer–Siwe disease, (LSD) or Abt-Letterer-Siwe disease, is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH) and is the most severe form, involving multiple organ systems such as the skin, bone marrow, spleen, liver, and lung.

[1][2] LCH and all its subtypes are characterized by monoclonal migration and proliferation of specific dendritic cells.

[2] Designating the four subtypes of LCH as separate entities are mostly of historical significance, because they are varied manifestations of the same underlying disease process, and patients also often exhibit symptoms from more than one of the four syndromes.

Histiocytes, a type of white blood cell, are part of the body's immune system.

When produced in excess, like in LCH and LSD, they attack the body's systems and cause the physical manifestations that are seen in these patients.

[3] Diagnosing Letterer-Siwe disease requires a complete work-up and examination because its symptoms are often non-specific and appear like other benign conditions.

[citation needed] In order to evaluate the degree of organ involvement in these patients, physicians may conduct a variety of diagnostic tests, such as [5] In addition, a work-up for congenital and acquired immunodeficiency syndromes should be completed.

[2] LSD may easily be missed for other conditions causing anemia, thrombocytopenia, and hepatosplenomegaly, but should be considered especially if the patient's disease course has been refractory to antibiotics.

Poor prognostic indicators include disseminated disease, age < 2 years, and the development of thrombocytopenia.