Prognostic implications of mixed monoclonal cryoglobulinemia in Sjogren'sdisease


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Abstract

Aim. To specify the risk of severe systemic manifestations and transformation into malignant lymphoma in Sjogren's disease (SD) patients with monoclonal mixed cryoglobulinemia (MMC).
Material and methods. A prospective study performed in 1985-1990 included 248 SD patients followed up after the initial detection of monoclonal immunoglobulins (Ig) with serum active rheumatoid
factor (RF). The patients' cryoglobulins (CG) were examined. The type of CG was determined by
electrophoresis in agarose gel combined with immunofixation and Immunoelectrophoresis with monospecific antisera to heavy and light Ig chains. Biopsies of the lower lip salivary glands and skin were
made in all the patients with MMC and 40 patients without CG. The biopsies were studied histologically, histochemically and immunomorphologically. Clinical symptoms and prognosis were studied in
all the patients observed in 1985-2000 after the initial diagnosis of MMC. In suspected lymphoma development, histological and immunophenotypical studies of lymph node, bone marrow biopsies, trephine biopsies were made as well as myelograms, Ga-67 scintigraphy, CTofthe thoracic and abdominal cavities. The total of clinical, morphological, immunophenotypical and cytogenetic characteristics
of lymphoma was estimated by REAL classification.
Results. CG at first examination was detected in 50 (20.2%) of 248 patients with SD. 20 (40%) of 50
patients were diagnosed to have MMC with monoclonal IgM% (19) and IgA (1) in the serum with RF
activity. Ten (50%) patients with MMC developed lymphoma after 10.9 ±3.3 years, on the average.
In the absence of CG lymphoma developed in 5.5% (p < 0.001). B-cell intoxication in patients with
diffuse lymphadenopathy, foci of lymphoid infiltration in the lungs, ulcers of the cms and such indices
as stab neutrophilic shift, monocytosis, hypoproteinemia with hypogammaglobulinemia, disappearance
of the RF, CG, low CIC level, immunodeficiency of monoclonal Ig and appearance of the protein BJ
in the urine are markers of developing large B-cell immunosecreting lymphomas. Highly aggressive
diffuse LCL resulted in death of 70% SD patients with MMC; 30% died of immunocomplex cryoglobulinemic vasculitis. 10-15-year survival of SD patients after detection of MMC was 50%, free of CG
- 97% (p < 0.001).
Conclusion. MMC is a definite serological marker of developing lymphoma and ulcerative-necrotic
vasculitis in SD. In detection of MMC in SD patients it is necessary to prescribe early pathogenetically
validated treatment before development of life threatening manifestations.

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