Essential mixed cryoglobulinemia (type II: with monoclonal and polyclonal component) A 52-year old Greek female patient was admitted to our Department because of anemia, arthralgias, Raynaud's phenomenon and generalized dermatitis of lower extremities. Her past medical history was unremarkable except of hepatitis A at the age of 22. Arthralgias, involving the right ankle and both knees, Raynaud's phenomenon, fatigue and dyspnea on slight exertion presented two months before admission. A normocytic, normochromic anemia (Hb 11.2 g/dL, Ht 33.4%) had been found with normal biochemical profile and negative tests for the detection of rheumatic diseases (RF, ANA, ENA and anti-DNA). The administration of non-steroid anti-inflammatory medication had a strong analgesic effect in arthralgias. Dermatitis of both lower extremities was also added 15 days before admission. The physical examination revealed pallor, cervical and axillae microlymphadenopathy (max diameter of less than 1.5 cm), mild splenomegaly (2 cm below costal margin) and a generalized non-pruritic purpuric rash in both lower extremities (fig. 1). Her temperature was 37.3 °C, blood pressure was 155/80 mmHg and the pulse rate was 82/min. There was no hepatomegaly or abdominal sensitivity and the neurological examination was unremarkable. The patient's hematology was as follows: WBC 5.6x109/L (neutrophils 54%, lymphocytes 39%, monocytes 5% and eosinophils 2%), Hb 10.3 g/dL, Ht 32.8% and platelet count 192x109/L. The anemia was normochromic, normocytic and peripheral blood smears revealed micro-aggregates of red cell without any morphological disorder. The morphology of white cells and platelets was also normal. The reticulocyte count was 2% and the sedimentation rate was 68 mm/1st hour. The biochemical profile showed an increase of serum transaminases (SGOT 48 U/L, SGPT 52 U/L), alkaline phosphatase (380 U/L) and lactate dehydrogenase (540 U/L) with normal renal and thyroid function tests. Hypergammaglobulinemia (4.8 g/dL) with a monoclonal component was also present. The quantitative analysis of γ-globulins was as follows: IgG 3.1 g/dL, IgA 0.28 g/dL, and IgM 1.46 g/dL. Serum immunofixation revealed an IgMκ monoclonal component while there was no Bence-Jones paraprotein in the urine. The direct Coombs reaction was negative as well as the tests for HIV, HBV and HCV infection. Laboratory investigation for rheumatic diseases, including RA-test, ANA, anti-DNA and anti-ENA antibodies was negative. However the C3 and C4 components of the complement were decreased. The test for detection of cryoglobulins was positive. CT scan of the thorax, abdomen and pelvis only showed the splenomegaly. A bone marrow aspiration and biopsy showed focal aggregates of polyclonal lymphocytes and a slight increase of polyclonal plasma cells (fig. 2). Skin biopsy revealed a typical leukocytoclastic vasculitis characterized by perivascular infiltration with granulocytes and mononuclear cells, endothelial swelling and intravascular hyalin deposits. Deposits of IgM, IgG and C3 were also detected in the vessel walls. The administration of prednisone resulted in the disappearance of purpuric rash and arthralgias. Hemoglobin was increased to normal and the patient is now in excellent condition two months after initiation of treatment. |