Type I cryoglobulinemia in multiple myeloma, a rare entity: analysis of clinical and biological characteristics of seven cases and review of the literature

Abstract

The type I cryoglobulins (CGs) account for 10-15% of all cryoglobulins and are found in patients with hematological disorders. We here describe the largest series of seven cases of type I cryoglobulinemia associated with multiple myeloma (MM) and provide a detailed review of the literature associated with this disorder, with the aim of improving the future diagnosis and therapeutic management of this rare disease. Six of the cases in our series were men aged 28-69 years, and most of the subject patients had an immunoglobulin G (IgG) monoclonal component and stage I indolent MM that manifested as cryoglobulin-related symptoms. The patients were all karyotypically normal. Clinical manifestations in this group were: skin lesions (five cases, 71.4%), rheumatologic failure (four cases, 57.1%), neurological abnormalities (two cases, 28.6%), mixed cutaneous/rheumatologic/renal defects (one case, 14.3%) and one case in which the cryoglobulinemia was asymptomatic. Two patients experienced acute renal failure but underwent a full recovery following treatment for MM. We conclude from our analysis that treatment approaches for severe type I cryoglobulinemia should involve plasmapheresis at the onset to achieve a rapid control of the CG-related symptoms, and that specific MM treatments should be introduced also at an early stage to avoid cryoglobulinemia relapse. In this context, bortezomib and lenalidomide are potentially the most effective therapeutic agents.

How I treat monoclonal gammopathy of renal significance (MGRS)

“…Disease flares are common and more often triggered by activity and orthostatism than by cold exposure. 78,79,84 Clinical and pathological renal manifestations are close to that observed in type I cryoglobulinemia. However, IF studies show that glomerular deposits contain both the monoclonal IgM and polyclonal IgG along with complement components.…”

“…82,83 Type I cryoglobulinemia may be observed in patients who would otherwise be classified as monoclonal gammopathy of undetermined significance (MGUS) based on level of clonal burden, MM, Waldenström's macroglobulinemia (WM) or any other type of B-cell lymphoid disorder secreting an entire MIg. [82][83][84] Patients should carefully avoid cold exposure and take appropriate protective measures. As data regarding management of this rare condition are scarce, the following recommendations are only guided by the panel experience:…”

A case of acute renal failure of multiple myeloma due to monoclonal type I cryoglobulinemia with thrombotic microangiopathy

“…Moreover, it is well known that monoclonal IgM in Waldenström's macroglobulinemia per se causes thrombosis, even if cryoglobulin is negative [8]. However, CG in multiple myeloma due to monoclonal IgG is recognized to be uncommon and moreover ARF in CG of multiple myeloma is even rarer [4]. Thus, our case is extremely unusual, especially in regard to the type of cryoglobulin.…”

“…However, in terms of renal lesions in type I CG, few large-scale studies have been conducted [1,4]. Electron microscopic images of CG are characterized by fine fibers arranged in parallel and various forms, such as fingerprint and microtubule structures.…”

Cold Urticaria: A Rare Manifestation of Lymphoma

“…CU cryoglobulins could represent IgG anti-IgE autoantibodies that react with IgE attached to mast cells. Cold temperature may favor the interaction of IgG anti-IgE autoantibodies to IgE attached to mast cells, causing mediator release [7].…”