Comment on “Non-hepatitis virus-associated mixed essential cryoglobulinemia”

Abstract

To the Editor: We read with interest the instructive case of non-hepatitis virus-associated mixed essential cryoglobulinemia reported by Annear et al.1 The search for a situation underlying, accompanying, or preceding a glomerulonephritis can often be intriguing or puzzling, especially when it is regarding a latent, quiescent, or multiphasic viral infection presenting with a nonspecific clinical syndrome, such as in the presented case. Are serological tests alone adequate for the diagnosis of an acute infection and the connection of a glomerulonephritis to the corresponding infection? There are infections, such as parvovirus infections, wherein even the immunoglobulin M levels are maintained high for several months after the acute infection.2, 3 This finding restricts their diagnostic value and, therefore, one should be cautious in their interpretation for the diagnosis of the acute phase of infections. In this particular case, the diagnosis of acute parvovirus infection was made on the basis of the positive serological test. In such cases, the use of polymerase chain reaction test for the detection of viral nucleic acid, although lacks validation for many infections, can provide more solid answers regarding the diagnosis of an acute infection. Although one cannot rule out the possibility that parvovirus infection might have triggered the production of cryoglobulins, the presumed association of the cryoglobulinemic glomerulonephritis with parvovirus B19 infection needs a more careful dissection, as long as no etiological connection between the two entities has been documented in this case; moreover, unlike hepatitis C virus-related cryoglobulinemia, cryoglobulin was not found to be directed against parvovirus. From a clinical standpoint, this is not surprising, as long as it is known that chronic rather than acute infections usually lead to clinically significant cryoglobulinemia. Furthermore, it was shown earlier that specific immunoglobulin G antibodies to parvovirus B19 are found in the majority of essential mixed cryoglobulinemia cases, and that parvovirus infection is rather not implicated in the pathogenesis of mixed cryoglobulinemia.4 After all, the clinical syndrome in this case could be rather attributed to cryoglobulinemia itself. In this context, we believe that the title, as well as several points within the paper trying to associate the glomerulonephritis with a presumed acute parvovirus infection, might cause confusion to the reader. In situ hybridization in the renal tissue could provide more solid evidence regarding the probable causal relation between the infection and cryoglobulinemic glomerulonephritis.