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X-linked Lymphoproliferative Syndrome Clinical Presentation

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Nov 26, 2015


The most common manifestations of X-linked lymphoproliferative syndrome (XLP) are hemophagocytic lymphohistiocytosis, fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia.

The frequency of symptoms at presentation are hemophagocytic lymphohistiocytosis (32%), fulminant infectious mononucleosis (8%), lymphoma (14%), dysgammaglobulinemia (22%), only family history of XLP (17%), and other manifestations (7%).[11]

Fatal infectious mononucleosis

Fatal infectious mononucleosis occurs in approximately 60% of patients.

The median age of onset is 3-5 years.

The median survival is 1-2 months.

Patients present with fever, malaise, fatigue, lymphadenopathy, and hepatosplenomegaly.

Most develop fulminant hepatitis with massive hepatic necrosis, hepatic encephalopathy, and death.


20-30% of patients with X-linked lymphoproliferative syndrome (XLP) develop malignant and nonmalignant lymphoproliferative disorders.

The median age of onset is 5 years for EBV-exposed and 8 years for non-EBV–exposed patients.

The lymphomas are typically high-grade B cell lymphomas. More than half are Burkitt lymphomas.

The lymphomas are usually extranodal, including sites such as the intestines, central nervous system, liver, or kidneys.

Patients may respond to initial therapy; however, many die from relapse or infectious complications.

Nonmalignant disorders such as Wegener granulomatosis, lymphomatoid granulomatosis, and necrotizing vasculitis also occur.


One third of patients with X-linked lymphoproliferative syndrome (XLP) 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

Miscellaneous findings

Other manifestations of X-linked lymphoproliferative syndrome (XLP) include occasional cases of aplastic anemia, lymphocytic vasculitis, red cell aplasia, and a hemophagocytic syndrome associated with the initial EBV infection. All of these occur in fewer than 10% of patients.



Hemophagocytic lymphohistiocytosis

See the list below:

  • Fever
  • Splenomegaly
  • Pallor
  • Ecchymosis

Infectious mononucleosis

See the list below:

  • Fever
  • Pallor
  • Pharyngitis
  • Hepatosplenomegaly
  • Lymphadenopathy
  • Jaundice
  • Ecchymosis


See the list below:

  • Findings related to the site of involvement


In the majority of cases, X-linked lymphoproliferative syndrome (XLP) is caused by an inherited defect in the SH2D1A gene. In some patients, X-linked lymphoproliferative syndrome (XLP) is related to an inherited defect in XIAP.

Contributor Information and Disclosures

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.


Doris Ponce, MD Fellow, Department of Hematology/Oncology, New York Medical College

Doris Ponce, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.


M Wayne Saville, MD Associate Professor of Clinical Medicine, University of California at San Diego; Director, Hematology and Oncology, Global Medical Affairs, Biogen Idec, Inc

M Wayne Saville, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and Sigma Xi

Disclosure: Nothing to disclose.

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