Anemia and splenomegaly: what lies behind?

Dr Migone De Amicis and Dr FattizzoWe report the case of a 32-year-old man admitted to ourInternal Medicine Department for severe anemia andsplenomegaly. Four months before hospital admission, thepatient was admitted to the Emergency Department (ED) ofthe city where he lived, for a flu-like syndrome charac-terized by fever, diarrhea, profuse sweating and severebone pain in his ankles, knees and lumbosacral region. Thelaboratory tests excluded an infectious disease, but showeda severe unexplained microcytic anemia (Hb 5.2 g/dL,MCV 59 fL). The patient was known as beta-thalassemiacarrier, he denied health problems nor blood transfusion inthe past. He was discharged with diagnosis of ‘‘unex-plained anemia in beta thalassemia carrier,’’ and referred tothe Thalassemia Center of his city. The hematologicalwork-up was negative, and he was put on a regularhematological follow-up and a weekly blood transfusionregimen. In the next 3 months, he progressively developedsplenomegaly and motor ability impairment. Physical ex-amination revealed only diffuse cutaneous pallor and amild splenomegaly, confirmed at the abdomen US (spleenbipolar diameter 145 mm). Blood tests, although posttransfusion, documented persistent moderate microcyticanemia (Hb 8.7 g/dL, MCV 69 fL), undetectable hap-toglobin, increased serum ferritin (722 ng/mL) and ery-thropoietin value (414 U/L, n.v. 3.7–31.5). Betathalassemia trait was confirmed by increased HbA2 level(3.3 %) and normal fetal hemoglobin (0.9 %) at the he-moglobin HPLC test. Infections were excluded by commonserologic tests. A whole-body CT scan confirmed thesplenomegaly, and revealed a systemic lymphadenopathy(maximum diameter 25 mm in the neck, abdomen andinguinal regions) and widespread lytic bone lesions(homerus, femur, iliac wings, costal and sacral region, andall the dorsal vertebra), also confirmed by the scintigraphystudy. In the hypothesis of primary bone marrow (BM)disease, a marrow examination was performed. The aspi-rate demonstrated only a trilinear hypoplasia, while the BMhistology revealed the presence of numerous histiocyticlike aggregates. Erdheim–Chester disease was first hy-pothesized, but it was excluded since BRAF gene analysisdid not reveal any mutations [1, 2]. Thereafter, the patientwas discharged as affected by an ‘‘autoimmune diseasewith bone involvement,’’ and he continued to be regularlytransfused. The patient’s general condition progressivelyworsened, and he was therefore referred to our hospital.At admission, the patient complained of a draggingsensation in the abdomen, as a consequence of a massivesplenomegaly. On general physical examination, there wasmarked pallor and bilateral cervical lymphadenopathy(maximum diameter 20 mm). The heart and the lungs were