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Removal of Immunosuppression Unmasks a Case of Autoimmune Lymphoproliferative Syndrome (ALPS)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Mirinda A. Gillespie, MD, Sheila M. Bina, MD, Jennifer W. Leiding, MD
Rationale: ALPS is a disorder of lymphocyte homeostasis most commonly caused by defects in the FAS apoptotic pathway. Common features include lymphoproliferation, autoimmune cytopenias, and immunodeficiency. Variable penetrance leads to under-diagnosis.  We present a child with ALPS whose diagnosis was confounded by the use of immunomodulatory therapies. 

Methods: Retrospective chart review was performed.  

Results: This patient had multiple congenital anomalies concerning for CHARGE syndrome (esotropia, pre-auricular pits, coarctation of the aorta), recurrent mild infections, failure-to-thrive, and onset of severe thrombocytopenia at 1 year.  However, mutations in CHD7 and 22q11 were excluded. Thrombocytopenia was idiopathic and recalcitrant to corticosteroids, IVIG, rituximab and vincristine, but stabilized at 4 years following initiation of mycophenolate mofetil (MMF).  Evaluation at 6 years showed profound hypogammaglobulinemia (IgG 47mg/dl, IgA <7mg/dl, IgM 25mg/dl) and non-protective vaccine titers, 5 years post rituximab. Monthly replacement gammaglobulin was initiated. With IVIG, thrombocytopenia improved, and so MMF was weaned.  Within a few months, she developed massive splenomegaly (19cm), and large mediastinal lymphadenopathy. Evaluation for lymphoma was unrevealing. Laboratory assessment showed elevated vitamin B12 (1298pg/ml), elevated double negative T cells (98cells/ul), and elevated B220+ double negative T cells (79%), all consistent with ALPS. Genetic evaluation is pending. Once malignancy was excluded, MMF was re-started; lymphadenopathy and splenomegaly improved. 

Conclusions: Medications administered for symptomatic palliation can unintentionally mask aspects of the presentation and obscure recognition of ALPS. MMF is an effective immunosuppressive agent in treating ALPS related lymphoproliferation.