X-linked Lymphoproliferative Syndrome Clinical Presentation

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Mar 9, 2011
 

History

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

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.

Lymphoma

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.

Hypogammaglobulinemia

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.

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Physical

Infectious mononucleosis

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

Lymphoma

Findings related to the site of involvement

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Causes

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.

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Contributor Information and Disclosures
Author

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, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Coauthor(s)

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 Clinical Oncology, and American Society of Hematology

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.

Specialty Editor Board

Koyamangalath Krishnan, MD, FRCP, FACP  Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, 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, and Royal College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Troy H Guthrie, Jr, MD  Director of Cancer Institute, Baptist Medical Center

Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University

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

Disclosure: Nothing to disclose.

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