Clinical Guidance

Autoimmune lymphoproliferative syndrome (ALPS) can be considered a prototypic disorder of defective lymphocyte homeostasis . The manifestations are lymphadenopathy, hepatosplenomegaly with or without hypersplenism, and autoimmune disease, mostly directed toward blood cells. In addition, the risk of lymphoma is increased.

Summary of Clinical Manifestations of ALPS

Lymphoproliferation of non-malignant lymphoid cells

• Lymphadenopathy

• Splenomegaly (± hypersplenism)

• Hepatomegaly

Autoimmunity

• Autoimmune hemolytic anemia

• Autoimmune thrombocytopenia

• Autoimmune neutropenia

• Glomerulonephritis

• Autoimmune hepatitis

• Guillain Barr syndrome

• Uveitis, iridocyclitis

• Other autoimmune disorders (in individual cases)

Neoplasia (including benign tumors)

Source: GeneReviews — "Autoimmune Lymphoproliferative Syndrome"

Differential Diagnosis

ALPS-like disorders. Pathogenic variants in genes inside (other than FAS, FASLG, and CASP10) and outside Fas/FasL pathway have been reported in association with clinical findings similar to ALPS. However, they either do not fulfill the current diagnostic criteria of ALPS or have other distinct phenotypes, and therefore are listed as ALPS-like disorders. These include:

Source: GeneReviews — "Autoimmune Lymphoproliferative Syndrome"

Clinical Guidance

Splenectomy to control autoimmune cytopenias and/or massive splenomagaly is discouraged because it typically does not lead to permanent remission of autoimmunity and may be associated with an increased risk for infections. The two recent cohort studies reveal clear-cut consequences of splenectomy. In the French cohort, nine (30%) of 30 affected individuals who underwent splenectomy suffered 17 cases of severe invasive bacterial infection with four deaths after splenectomy; in the NIH cohort, 27 (41%) of 66 affected individuals suffered one or more episodes of sepsis with seven deaths. Of note: Antimicrobial prophylaxis and appropriate vaccinations did not prevent the majority of episodes of sepsis, although poor adherence was a risk factor in the French cohort . The use of over-the-counter medications such as aspirin and other nonsteroidal anti-inflammatory drugs should be discussed with a physician as some of these medications can interfere with platelet function.

Source: GeneReviews — "Autoimmune Lymphoproliferative Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Autoimmune Lymphoproliferative Syndrome"