Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrichs original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present with similar but less severe symptoms and are caused by mutations of the same gene. Signs and symptoms
WAS occurs most often in males due to its X-linked recessive pattern of inheritance, affecting between 1 and 10 males per million. The first signs are usually petechiae and bruising, resulting from a low platelet count (i.e. thrombocytopenia). Spontaneous nose bleeds and bloody diarrhea are also common and eczema typically develops within the first month of life. Recurrent bacterial infections typically develop by three months of age. The majority of children with WAS develop at least one autoimmune disorder, and cancers (mainly lymphoma and leukemia) develop in up to a third of patients. Immunoglobulin M (IgM) levels are reduced, IgA and IgE are elevated, and IgG levels can be normal, reduced, or elevated. In addition to thrombocytopenia, WAS patients have abnormally small platelets (i.e. microthrombocytes) and ~30% also have elevated eosinophil  counts (i.e. eosinophilia). Pathophysiology
The microthrombocytes seen in WAS patients have only been observed in one other condition, ARPC1B deficiency. In both conditions the defective platelets are thought to be removed from circulation by the spleen and/or liver, leading to low platelet counts.
Study of eltrombopag, a thrombopoietic agent used to increase platelets in immune thrombocytopenic purpura (ITP), in WAS concluded that although it increased platelet numbers it failed to increase platelet activation in most patients. It has since been proposed the eltrombopag may be used to bridge to HCT in patients with severe thrombocytopenia to normalize platelet numbers without transfusions and decrease bleeding events. Anemia from bleeding may require iron supplementation or blood transfusion. Regular surveillance of blood counts is recommended. Infections and autoimmune disease
For patients with frequent infections, intravenous immunoglobulins (IVIG) or subcutaneous immunoglobulins can be regularly scheduled to boost the immune system. Adequacy of IVIG replacement can be assessed via periodic lab draws. WAS patients with immune system compromise may benefit from antibiotic prophylaxis, for example by taking trimethoprim-sulfamethoxazole to prevent Pneumocystis jirovecii-related pneumonia. Similarly, prophylactic antibiotic use may also be considered in patients with recurrent bacterial sinus or lung infections. When there are signs or symptoms of an infection, prompt and thorough evaluation is important including blood cultures to guide therapy (often IV antibiotics). Live vaccines (such as MMR or rotavirus) should be avoided during routine childhood vaccination. Inactivated vaccines may be given safely but may not provide protective levels of immunity. Eczema is generally treated with topical steroids, and if chronic skin infections exacerbate eczema an antibiotic may also be given. Autoimmune disease is managed with judicious use of appropriate immunosuppressants.Gene therapy
For severely affected males without an HLA-matched donor, studies of correcting Wiskott–Aldrich syndrome with gene therapy using a lentivirus are underway.