LONG-TERM RESULTS OF TREATMENT WITH DIRECT ACTING ANTIVIRALS, CORTICOSTEROIDS, PLASMAPHERESIS AND RITUXIMAB IN A PATIENT WITH CRYOGLOBULINEMIC VASCULITIS AND HCV INFECTION

Introduction:

Several glomerular diseases have been associated with HCV infection including mixed cryoglobulinemia syndrome (MCS) which is a systemic vasculitis. In its severe form, therapy should be started immediately. There are still questions concerning the optimum immunosuppressive regimen, the timing of administration of drugs, and the long-term efficacy of newer anti-viral drugs especially in patients with renal involvement.

Methods:

A 51-year-old female patient presented with weakness, leg edema, palpable purpura in lower legs, anemia, impaired renal function, and reduced urine output. One month earlier she was diagnosed with mild ulcerative colitis and was put on mesalazine.

At initial presentation, the patient was found with significant pericardial effusion and reduced ejection fraction, peripheral neuropathy, pulmonary fibrosis and ground glass opacities.

Urine sediment was active and 24h urine protein was 3.1 g.

Immunological work-up for ANCA-vasculitis or SLE was negative, but she was found hypocomplementemic, hypoglobulinemic with positive rheumatoid factor (RF). Immunofixation of serum and urine revealed monoclonic IgMκ. Cryoglobulins of type II (monoclonal IgM and polyclonal IgG) were positive with high burden (cryocrit 25%). Further evaluation revealed that she was HCV positive with high viral load (4.98X106 IU/ml), genotype 4, with liver fibrosis grade 3 albeit with normal liver function tests.

Renal biopsy showed glomerulonephritis with membranoproliferative-pattern and endocapillary hyaline thrombi with hypermicroscopic features suggestive of cryoglobulins. Immunofluorescence showed positivity for IgG/IgM/ C3/ C1q and both light chains κ and λ.

The work-up for non-Hodgkin lymphoma or lymphoproliferative disease was negative.

Results:

The clinical manifestations suggested a severe form of mixed cryoglobulinemia syndrome. Immunosuppressive therapy was started immediately with high-dose methylprednisolone (1 g X 3 days and then tapered over a period of 6 months). Concurrently, the patient underwent multiple haemodialysis treatments. Due to the severity of the disease, she also underwent 6 plasmapheresis treatments every other day. She was taken off dialysis one month after diagnosis and she generally showed an impressive clinical improvement but cryoglobulins remained positive (albeit in a lower level) as well as monoclonal protein and RF. She received rituximab (375 mg/m2 X 4 weeks) which was well tolerated and concurrently started direct acting antivirals (DAAs) (elbasvir+grazoprevir) (with some delay from the diagnosis due to logistic reasons). After that, kidney function improved furthermore and cryoglobulins, monoclonal protein and RF became negative, 5 months after diagnosis. HCV was not detected 5 months after anti-viral treatment. 

During the follow-up of 33 months, there were no serious adverse events recorded, no recurrence of the disease and all manifestations of MCD subsided. Kidney function is currently normal, and HCV is undetectable.

Conclusions:

A combined treatment consisting of immunosuppressive therapy and DAAs seems to offer a sustained long-term clinical response even in patients with severe MCS.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.