Autoimmune Lymphoproliferative Syndrome (ALPS)

Price V. Auto-immune lymphoproliferative disorder and other secondary immune thrombocytopenias in childhood. Pediatr Blood Cancer. 2013;60 Suppl 1:S12-4.

“Primary immune thrombocytopenia (ITP) in childhood, typically presents as an acute self-limiting illness. However, secondary ITP is often a chronic disorder due to an underlying disease. Combined cytopenias in childhood, that is, secondary ITP occurring with auto-immune hemolytic anemia and/or auto-immune neutropenia, are often associated with disorders characterized by immune dysregulation. Such disorders include systemic lupus erythematosus, auto-immune lymphoproliferative syndrome, and common variable immune deficiency. Evans syndrome describes the combination of ITP, autoimmune hemolytic anemia, and/or autoimmune neutropenia. However, it is now clear that some patients with Evans syndrome have an underlying immunodeficiency. This report focuses on combined auto-immune cytopenias and highlights the challenges in their diagnosis and management.”

Full-text for Emory users.

Iyengar SR, Ebb DH, Yuan Q, Shailam R, Bhan AK. Case records of the Massachusetts General Hospital. Case 27-2013. A 6.5-month-old boy with fever, rash, and cytopenias. N Engl J Med. 2013 Aug 29;369(9):853-63.

“Most established treatment algorithms for ALPS identify prednisone as first-line therapy. Therefore, we initiated the administration of intravenous glucocorticoids while the boy was an inpatient, and treatment with oral prednisone was maintained after discharge. However, the cytopenias did not improve. On the basis of ALPS treatment guidelines, [10] the administration of mycophenolate mofetil was then initiated, resulting in relatively prompt remission of the cytopenias. Blood levels of vitamin B12, a biomarker of the disease, also declined. Biomarkers in the blood include vitamin B12 (levels are elevated in patients with ALPS, possibly because of the lymphocytic production of haptocorrin, [17] a serum protein that binds B12) and interleukin-10 (thought to be secreted from double-negative T cells [18,19]).”

Full-text for Children’s and Emory users.

Teachey DT. New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome. Curr Opin Pediatr. 2012 Feb;24(1):1-8.

“A number of key observations have been made recently that better define the pathophysiology of ALPS, including the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mechanism of decreased Fas expression, and the description of multiple genetic hits in FAS in some families that may explain the variable penetrance of the disease. In addition, ALPS has been shown to be a more common condition, as patients diagnosed with other disorders, including Evans syndrome and common variable immune deficiency, have been found to have ALPS. Finally, the treatment of the disease has changed as splenectomy and rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease. On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients.”

Free full-text. 

Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011 Nov 24;118(22):5741-51.

“Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented.”

Full-text for Children’s and Emory users.

Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, Rieux-Laucat F, Siegel RM, Su HC, Teachey DT, Rao VK. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010 Oct 7;116(14):e35-40.

“Lymphadenopathy in children for which no infectious or malignant cause can be ascertained constitutes a challenging diagnostic dilemma. Autoimmune lymphoproliferative syndrome (ALPS) is a human genetic disorder of lymphocyte apoptosis resulting in an accumulation of lymphocytes and childhood onset chronic lymphadenopathy, splenomegaly, multilineage cytopenias, and an increased risk of B-cell lymphoma. In 1999, investigators at the National Institutes of Health (NIH) suggested criteria to establish the diagnosis of ALPS. Since then, with approximately 500 patients with ALPS studied worldwide, significant advances in our understanding of the disease have prompted the need for revisions to the existing diagnostic criteria and classification scheme. The rationale and recommendations outlined here stem from an international workshop held at NIH on September 21 and 22, 2009, attended by investigators from the United States, Europe, and Australia engaged in clinical and basic science research on ALPS and related disorders. It is hoped that harmonizing the diagnosis and classification of ALPS will foster collaborative research and better understanding of the pathogenesis of autoimmune cytopenias and B-cell lymphomas.”

Free full-text. 

More PubMed results on ALPS.

Here’s the OMIM entry on ALPS.

Created 11/02/12, updated 05/13/14. 

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