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A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections

DOI: 10.1155/2012/196417

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We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency disorders (CVIDs). Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu), which is found also in healthy controls. 1. Introduction Acute idiopathic thrombocytopenic purpura (ITP) is a well-known clinical entity in children. Generally, in children the disease is self-limiting and easily distinguished from a hematological malignancy, even without investigating the bone marrow [1]. However, the case becomes more complicated when the ITP becomes chronic and accompanying profound lymphadenopathy develops. We describe the diagnostic dilemma in a girl with these problems, who with time also developed recurrent respiratory infections, suffered from a prolonged episode of intractable diarrhea, a severe episode of varicella zoster infection and autoimmune hemolytic anemia. 2. Patient The girl, now 9 years of age, is the second child of healthy nonconsanguineous Caucasian parents. She was born after an uncomplicated pregnancy and delivery and showed normal growth and development. Her family history reveals allergy on the paternal side and autoimmune disease and malignancies on the maternal side. At the age of 14 months, she developed ITP and showed a partial slow recovery after 3 days of high-dose intravenous immunoglobulins (IVIGs) followed by prednisolone. One year later, she suffered a relapse during a mild parainfluenza type 3 infection and treatment with 3 days of high-dose IVIG was started again. A few days after receiving this second course of high-dose IVIG she developed cervical, axillary and inguinal lymphadenopathy and enlarged tonsils: this lymphadenopathy never resolved. There was no hepatomegaly, splenomegaly, or mediastinal or abdominal lymph node enlargement at that time. Blood tests showed a mild normocytic anemia (Hb 6.4?mmol/L, MCV 77?fL) and granulocytopenia (0.7–1.0 × 109/L) and large unstained cells in the hematology analyzer ( ; 0.4 × 109/L). A bone marrow aspirate and biopsy showed some atypical lymphocytes and specific maturational disturbances, but no malignancy. Bone marrow immunophenotyping was normal. FAS-mediated apoptosis of T-lymphoblasts was normal (two separate tests in two different laboratories). She


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