A 47-year-old Caucasian woman was admitted to our Rheumatology Unit, complaining a 6-month history of progressive appearance of tender ill-defined hard swellings on the right leg and the abdominal wall with severe erythema in overlying skin, associated with intermittent fever up to 39 C, not relieved by antipyretics and antibiotics.
The patient had fever up to 39 C, multiple tender erythematous swellings on abdomen wall and right leg, and several palpable lymphadenopathies on abdomen, neck, and right groin during admission to our Unit. She denied drug abuse, recent travel, or use of nonsteroidal anti-inflammatory drugs. Complete blood count revealed microcytic hypochromic anemia with hemoglobin 9.8 gm/dL, mean corpuscular volume 69 fl, and leucopenia with neutropenia (WBCs 1.3 x 103/L; N 48.3%, L 43.8%, M 3.8%, E 0.4%, B 2.2%).
Thrombocytopenia (up to 67 000/microL) had been briefly observed during the recovery period. There was an increase in alanine transaminase (ALT) 104 IU/L (normal range, 2-40) and aspartate aminotransferase (AST) 91 IU/L (normal range, 2-40), with an AST/ALT ratio < 1 and an increase of gamma GT 67 IU/L (normal range, 7-38). A slightly high serum lipid profile (triglycerides, total cholesterol, and low-density lipoprotein) was observed. Erythrocyte sedimentation rate (ESR) was 17 mm/h, C reactive protein (CPR) was 0.05 mg/dL. Normal immunoglobulin assay except high levels of IgM 443 mg/dL (n. 40-230) and of IgE 857 mg/dL (n. 2-200) was noticed. Complement 3, complement 4, cryoglobulin levels, serum lipase, serum amylase, alpha-1 antitrypsin, procalcitonin, haptoglobin, creatine phosphokinase, creatinine, azotemia, serum glucose concentration, bilirubin and bilirubin fraction, serum corrected calcium, and alkaline phosphatase were within normal range. Antithrombin was mildly elevated, 165% (normal range, 70-130). Severe hypofibrinogenemia 40 mg/dL (normal range, 200-450) with high levels of D-dimer 23 701 microg/mL (normal range, 0-500) were detected. The 24-hour urinary sample showed moderate proteinuria (1.6 gm/24 h). An increase of lactate dehydrogenase (LDH) 500 IU/L (n. 40-250) and beta-2 microglobulin 7.34 microg/mL (normal range, 0.8-2.7) was revealed. Partial thromboplastin time (PTT) was shorter. Prothrombin time and iron profile were normal. Albumin level was 3.2 gm/dL. A hypergammaglobulinemia (23.78%) was noted by protein electrophoresis. Serum and urine immunofixation were negative for free light chains. TORCH screening, tuberculosis screening, Coxsackie IgM, Brucella IgG and IgM, Borrelia IgG and IgM, and Parvovirus B19 were negative. The antinuclear antibodies, lupus anticoagulant screening, antineutrophil cytoplasmic antibodies, cryoglobulin, and antiphospholipid antibodies were negative. Viral hepatitis, autoimmune hepatitis, metabolic factors and in-born or hereditary disorders (Wilson disease, lypodystrophy), drug and toxins associated to high liver enzymes and excessive alcohol consumption, obesity, and diabetes mellitus were excluded.
A mild hepatosplenomegaly with widespread lymphadenopathy and left pleural effusion were detected using sonography and confirmed by neck, chest, and abdomen computed tomographic scan. The echocardiography detected a small pericardial effusion, with normal eject fraction and preserved systolic function. The endocrine and genital organs and the breast showed no clinical abnormalities.
Surgical skin sample showed lobular panniculitis with a lymph-histiocytic and neutrophilic infiltrates with necrosis of adipocytes, as seen in PWCD.
Bone marrow biopsy displayed a discrete hypercellular bone marrow with an increase of megakaryocytic proliferation and low grade of dysmorphia of myeloid cells. A widespread boost of stromal fibers was noticed at silver impregnation. The marrow changes were reactive and did not reflect a myelodysplastic syndrome.
Axillary lymph-node biopsy confirmed a reactive lymphadenopathy. The hematological specialist excluded hematological malignancies.
The liver biopsy evidenced a macro-vesicular steatosis with hepatocytes ballooning, as in NAFLD. Spotty necrosis, scattered mixed neutrophilic-lymphocytic inflammation, Mallory hyaline, and perisinusoidal fibrosis were absent.
On admission, levofloxacin (750 mg daily) and minocycline (200 mg daily) were empirically started and discontinued after 8 days for negative blood cultures. Mycophenolate mofetil (MMF) (2 gm daily) and prednisone (1 mg/kg daily, tapered to 5 mg daily in 3 months) were started. At 1-month follow-up, the improvement of skin lesion, the remission of fever, and complete normalization of blood count, proteinuria, and liver enzymes were recorded. A complete remission state, with just slightly hyper-pigmentated skin scares, was recorded at sixth month follow-up.
Of note, considering the prompt remission of proteinuria after prednisone and mycophenolate mofetil treatment, the kidney biopsy was not more performed.