X-linked Lymphoproliferative Syndrome Clinical Presentation

Updated: Jan 24, 2022
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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The main clinical features of X-linked lymphoproliferative syndrome type 1 (XLP1) are hemophagocytic lymphohistiocytosis (HLH) , dysgammaglobulinemia, severe fulminant infectious mononucleosis and lymphoma. Less frequent manifestations of XLP1 are aplastic anemia, vasculitis, and lymphoid granulomatosis. [13]

Up to 50% of patients demonstrate a range of immune abnormalities, ranging from impaired vaccine responses to generalized hypo-gammaglobulinemia. These may be incidental findings during a diagnostic workup or lead to recurrent infections, particularly respiratory infections. [6]

One third of patients manifest hypogammaglobulinemia, typically by a median age of 8 years. Patients with isolated hypogammaglobulinemia have a less severe course than others with this disease. Life-threatening infections seem to be rare, especially if intravenous immunoglobulin (IVIG) is administered on a regular basis

Up to 35% of patients have no evidence of previous Epstein-Barr virus (EBV) infection; many of these patients are diagnosed based on family history.  In EBV-negative patients, XLP1 is associated with higher rates of dysgammaglobulinemia and lymphoma. However, EBV-negative boys with XLP1 can still develop HLH, although less frequently than those with EBV infection, and the trigger is unknown. [5]  


Males with XLP2 are more likely to develop HLH without EBV infection, usually have an enlarged spleen (splenomegaly). They may also have inflammation of the large intestine (colitis). [4, 13]




Physical Examination

Fulminant infectious mononucleosis/HLH associated with EBV

Affected individuals typically have lymphadenopathy and hepatosplenomegaly with extensive parenchymal damage including fulminant hepatitis, hepatic necrosis, and profound bone marrow failure. Involvement of other organs may include the spleen ("white pulp" necrosis), heart (mononuclear myocarditis), and kidney (mild interstitial nephritis). [13]


The lymphomas seen in XLP1 are typically high-grade B-cell lymphomas, non-Hodgkin type, often extranodal, particularly involving the intestine. Approximately 75% of lymphomas occur in the ileocecal region. Other sites include the central nervous system, liver, and kidney. [13]