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Case 161
Diagnosis
 
     
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Diagnosis: Cryoglobulinemic Glomerulonephritis

The biopsy was initially diagnosed as immune complexes mediated MPGN, but the presence of intracapillary hyaline material ("hyaline thrombi") (figures 5 and 6), vasculitis (figures 8 and 9) and a marked predominance of one of the two light chains, with kappa marking similar to IgM, and lambda and IgG weaker, they strongly suggested mixed cryoglobulinemia. Additional studies in the patient demonstrated cryoglobulins and a low-grade B lymphoma: Cryoglobulinemic GN, in the context of mixed type II cryoglobulinemia. It is very common to find hypocomplementemia in these cases, and as a finding that helps, the decrease in C4 is usually greater than in C3. Light chains can be expressed with the same intensity, since there are two immunoglobulins and one is polyclonal (type II), however, in some cases there is a clear predominance of one of the two, as in our case.

Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II cryoglobulinemia), or only of polyclonal Igs (mixed type III cryoglobulinemia). The manifestations of type I cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin's lymphoma. The treatment depends mainly on the cause of the cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I cryoglobulinemia. (Desbois AC, et al. Cryoglobulinemia: An update in 2019. Joint Bone Spine. 2019 Feb 4. [Epub ahead of print] [PunMed link]).

See the chapter: Amyloidosis... and Cryoglobulinemiaof our Tutorial.

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References

  • Desbois AC, Cacoub P, Saadoun D. Cryoglobulinemia: An update in 2019. Joint Bone Spine. 2019 Feb 4. doi: 10.1016/j.jbspin.2019.01.016. [Epub ahead of print] [PunMed link]
  • Chen YP, Cheng H, Rui HL, Dong HR. Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice. Chin Med J (Engl). 2019;132(14):1723-1732. [PubMed link]
  • Mazzaro C, Maso LD, Mauro E, Gattei V, Ghersetti M, Bulian P, Moratelli G, Grassi G, Zorat F, Pozzato G. Survival and Prognostic Factors in Mixed Cryoglobulinemia: Data from 246 Cases. Diseases. 2018 May 3;6(2). [PubMed link]
  • Milovanova SY, Lysenko Kozlovskaya LV, Milovanova LY, Mrykhin NN, Russkih AV, Muchin NA. HCV-associated mixed cryoglobulinemia and b-cell non-Hodgkin's lymphoma - pathogenetically related problems. Ter Arkh. 2018;90(6):112-120. [PubMed link]
  • Coliche V, Sarda MN, Laville M, Chapurlat R, Rheims S, Sève P, Théry-Casari C, Lega JC, Fouque D. Predictive factors of renal involvement in cryoglobulinaemia: a retrospective study of 153 patients. Clin Kidney J. 2018;12(3):365-372. [PubMed link]
  • Muchtar E, Magen H, Gertz MA. How I treat cryoglobulinemia. Blood. 2017;129(3):289-298. [PubMed link]
  • Zaidan M, Terrier B, Pozdzik A, Frouget T, Rioux-Leclercq N, Combe C, Lepreux S, Hummel A, Noël LH, Marie I, Legallicier B, François A, Huart A, Launay D, Kaplanski G, Bridoux F, Vanhille P, Makdassi R, Augusto JF, Rouvier P, Karras A, Jouanneau C, Verpont MC, Callard P, Carrat F, Hermine O, Léger JM, Mariette X, Senet P, Saadoun D, Ronco P, Brochériou I, Cacoub P, Plaisier E; CryoVas study group. Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN. J Am Soc Nephrol. 2016;27(4):1213-24. [PubMed link]

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