ALPS: The Rare Diamond among Lymphadenopathies

Introduction: Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare primary immunodeficiency belonging to the subgroup of immune dysregulation diseases. It’s a disorder of lymphocytic apoptosis’ mediators, with subsequent generalized chronic non-malignant and non-infectious lymphoproliferation, and expansion of an unusual population of T lymphocytes (double-negative T cells). Chronic lymphadenomegaly and/or splenomegaly and autoimmune cytopenias are common characteristics.

Clinical Case: Four-year-old male, without personal relevant background, observed in paediatric consultation, due to cervical lymphadenopathy detected by two years of age, exacerbated in infectious contexts and in the last six months. Splenomegaly noticed during an acute febrile episode. Without constitutional symptoms. Maternal family history: autoimmune haemolytic anaemia. At physical examination, he had elastic and mobile cervical bilateral adenopathy conglomerates and splenomegaly. Complementary diagnostic tests (in fasting and without disease): Cervical echography: multiple ganglionic formations probably of reactive nature. Abdominal ultrasonography: globous liver and splenomegaly, with multiple ganglionic formations adjacent to splenic thread and pancreas. Blood test: Haemoglobin 12,3 g/dL, Total leucocytes 6,4x10⁹/L, Platelets 144x10⁹/L (150-450), Peripheral blood smear “reactive lymphocytes and slight anisocytosis”, C-reactive protein 0,46 mg/dL, Cholesterol HDL 18 mg/dL (>45), Triglycerides 207 mg/dL (≤90), IgA 197 mg/dL, IgG 2150 mg/dL (350-1620), IgM 20 mg/dL (30 – 265).Considering the diagnosis of ALPS, he was sent to a Tertiary Hospital’s primary immunodeficiency consultation. The subsequent study reveals: B12 8124 pg/mL (295-1769); Immunophenotyping 10% lymphocytes α/βCD3+CD4-CD8-; Genetic study: Fas deficit heterozygosity for mutation c.817C>A (p.Q273K).

He completed two prednisolone cycles. Currently (7 years old), under sirolimus, with frank improvement in lymphadenopathy dimensions and hepatosplenomegaly.

Conclusion: This clinical case illustrates the importance of the high level of clinical suspicion regarding generalized chronic lymphadenopathies and/or splenomegaly. Despite ALPS’s non-malignant nature, the diagnosis may be quite challenging and requires long-term clinical surveillance, particularly because of the increased risk of malignancy.