Autoimmune Lymphoproliferative Syndrome Clinical Presentation
- Author: Luke M Webb, MD; Chief Editor: Harumi Jyonouchi, MD more...
The initial presentation of autoimmune lymphoproliferative syndrome (ALPS) is often that of persistent lymphadenopathy or splenomegaly followed by an autoimmune disease such as idiopathic thrombocytopenic purpura (ITP) or hemolytic anemia in an otherwise healthy child. To meet the case definition of ALPS, a patient must have chronic, nonmalignant lymphadenopathy or splenomegaly that lasts for 6 months or longer.
Associated multilineage cytopenias due to autoantibodies or splenic sequestration can lead to petechiae, bleeding, pallor, icterus, fatigue, and recurrent infections; the latter are mostly due to neutropenia. A family history of similar disorders may be noted; these are usually inherited in an autosomal dominant fashion. A thorough review of a patient’s extended family for a history of adenopathy, cytopenias, splenectomies, or lymphoma can provide helpful information and clues in diagnosing ALPS.
Careful attention to the development of systemic B symptoms (eg, fever, drenching night sweats, pruritus, and weight loss) is important for cancer surveillance in those at high-risk for B cell lymphoma. Some of the patients also develop autoimmune diseases that affect other organs (eg, autoimmune hepatitis, glomerulonephritis, uveitis, and Guillain-Barre syndrome).
The lymphadenopathy and hepatosplenomegaly seen in patients with ALPS can often be remarkable, sometimes visibly distorting anatomic landmarks (see the image below).
In as many as 50% of children with ALPS, splenectomy is eventually performed, usually due to refractory cytopenias. Many of these patients are diagnosed long after splenectomy has been performed and therefore do not have associated splenomegaly at the time when ALPS is diagnosed.
Areas most commonly affected by lymphadenopathy include the neck and axillary regions, but careful assessment of epitrochlear, femoral, inguinal, and other lymph node chains is important in the assessment. Petechiae, pallor, icterus, and evidence of infections may be found in patients with characteristic cytopenias. Ongoing surveillance in these patients should include careful attention to the development of changes in lymph node size or the appearance of new focal or generalized lymphadenopathy and worsening splenomegaly.
Complications of ALPS include the development of lymphoma or other malignancy and the development of pneumococcal sepsis or other serious systemic infection (secondary to asplenia, autoimmune neutropenia, or both; see the image below).
Patients with genetic mutations that affect the intracellular domain of the Fas protein have a more severe clinical manifestation from early childhood and are found to have a 51-fold higher risk of Hodgkin lymphoma and a 14-fold increased risk of non-Hodgkin lymphoma. A report on the largest cohort of ALPS patients worldwide showed an approximate 6% incidence of lymphoma in patients with ALPS overall, with a median age at presentation of 17 years.
Lymphadenopathy in ALPS patients with lymphoma can be especially difficult to discern because persistent lymphadenopathy is common even as the patient progresses into adulthood. Like any sporadic lymphomas, however, ALPS-associated lymphomas are amenable to chemotherapy and should be managed accordingly. ALPS-associated lymphadenopathy and splenomegaly tend to become less prominent with age. In patients who have undergone splenectomy, asplenia-related sepsis is a significant lifelong cause of morbidity and mortality.
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