#3644 Type II cryoglobulinemic vasculitis with renal involvement in a patient with lymphoplasmacytic lymphoma: a rare case report

Abstract Background and Aims Cryoglobulins (CGs) are immune complexes that precipitate at low temperatures, potentially leading to cryoglobulinemic vasculitis (CryoVas). CryoVas has been associated with lymphoproliferative disorders, infections, and autoimmune diseases. Lymphoplasmacytic lymphoma (LPL) is a rare B-cell lymphoma that primarily affects the bone marrow, with occasional involvement of the spleen and lymph nodes. LPL does not always produce monoclonal immunoglobulins and its progression is usually indolent. We present an unusual case of CryoVas with renal involvement in a patient with LPL, where no circulating monoclonal immunoglobulin was detected. Case description A 71-year-old woman diagnosed with systemic sclerosis (SSc), followed in rheumatology consultation since 2013, medicated with prednisolone 5 mg/day and mycophenolate mofetil 500 mg twice a day, myasthenia gravis treated with pyridostigmine three times a day, lymphoplasmacytic lymphoma under surveillance in hematology consultation, and bimalleolar cutaneous ulcers under dressing treatment for several months, presented to our hospital's emergency department with symptoms of dyspnea, orthopnea, and lower limb edema with a two-week evolution. She was hospitalized for further evaluation with suspected nephritic syndrome, presenting with anasarca, hypertension (BP 160/80 mmHg), and new-onset non-oliguric acute kidney injury KDIGO 1 (serum creatinine 1.5 mg/dL, previously 1 mg/dL), with urinalysis showing leukocytes (+++) and erythrocytes (+++), and urinary sediment evaluation revealing dysmorphic erythrocyturia. Renal ultrasound and transthoracic echocardiogram did not reveal any significant findings. Laboratory tests revealed mild normocytic normochromic anemia (8.6 g/dL), normal haptoglobin, peripheral blood smear without schistocytes, and negative Coombs test. Proteinuria of 3g/24 h and albuminuria of 2300 mg/24 h were present, with normal serum albumin level. There were elevated erythrocyte sedimentation rate and C-reactive protein, at 86 mm/1st hour and 39 g/dL, respectively. Serological tests were negative for Hepatitis B, Hepatitis C, and HIV. The immunological study revealed negative results for rheumatoid factor, anti-Ds DNA, ANCA, anti-glomerular basement membrane, with ANA titers of 1/640 with a speckled pattern, low C4 (<1 mg/dL), normal C3 levels, and the presence of positive cryoglobulins, which were later characterized as type 2 (immunoglobulins of IgA, IgG, and IgM types with polyclonal characteristics but including one monoclonal IgM/Kappa fraction with slight rheumatoid factor activity). Serum protein electrophoresis, serum immunofixation electrophoresis, urinary protein electrophoretic/immunofixation analysis were negative. Serum free light chain kappa and lambda were 1.64 mg/dL and 2.37 mg/L, respectively, with a FLC ratio of 1.45, which is normal. CT scan and PET showed no findings. Subsequently, she underwent a renal biopsy, which showed a membranoproliferative pattern on optical microscopy, with mesangial and endocapillary proliferation, without evidence of intraluminal thrombi. Immunofluorescence showed restriction of IgM chains ++ (mesangial and membranous) and kappa light chains ++ (mesangial and membranous). Electron microscopy revealed the presence of dense mesangial, subendothelial, and mesangiocapillary deposits, focal fusion of podocyte foot processes, and absence of organized structures. In the presence of glomerulonephritis secondary to type 2 CryoVas, with no evidence of progression of the hematological disease, and no infectious or immunological cause identified, it was decided to treat with rituximab 1g separated by 15 days along with the initiation of corticosteroid therapy with prednisolone at a dose of 0.5 mg/kg/day. Conclusion We present a rare case of type 2 CryoVas with negative rheumatoid factor and renal involvement in a patient with lymphoplasmacytic lymphoma, a condition that typically follows an indolent course. To the best of our knowledge, this is only the second such case reported in the literature.