The relationship between Sjogren’s syndrome, systemic sclerosis and lymphoproliferative diseases

Despite the large number of studies devoted to the study of systemic sclerosis (SSc), the high risk of developing lymphomas in this disease, the relationship of their development with certain subtypes of SSc and specific SSc-associated autoantibodies is still debated in the literature.

Aim. To study demographic, clinical, laboratory and immunological characteristics of patients with a combination of primary Sjogren’s syndrome (pSS) and SSc and diagnosed lymphoproliferative diseases (LPDs); to characterize morphological/immunomorphological variants and course of non-Hodgkin’s lymphomas (NHL), developing in patients with these rheumatic diseases (RDs).

Materials and methods. In 1998–2018 at the Nasonova Research Institute of Rheumatology, 13 patients with clinical and laboratory manifestations of pSS (12) and SSc (13) were diagnosed with various lymphoproliferative diseases (LPDs). In 3 cases, an induced RD was observed: 1 case of a diffuse, rapidly progressive form of SSc, 2 cases of pSS in combination with a limited form of SSc after chemotherapy and radiation therapy of Hodgkin’s lymphoma (1), B-cell NHL (1) and CR of the breast (1) respectively. The first 2 cases were excluded from the analysis, since the development of lymphomas is not pathogenetically associated with RD.

Results. Of 11 patients with LPDs, 10 after a long course of RDs were diagnosed with NHL [MALT lymphoma of the parotid salivary glands – 7, disseminated MALT lymphoma – 2, disseminated MALT lymphoma with transformation into diffuse large B-cell lymphoma (DLBCL) – 1]. RDs debuted with Raynaud’s phenomenon (RP) in 64.5% and pSS manifestations in 45.5% of patients. Stomatological manifestations of pSS were characterized by recurrent parotitis in 36%, significant parotid gland enlargement with massive infiltration of labial salivary glands (focus score >4) in 100%, severe xerostomia in 70%, extraglandular manifestations and lymphadenopathy in 50% of patients. The course of the SSc was characterized by mild RP with various types of capillaroscopic changes and mild lung changes and non-significant progression during long-term follow-up (median – 22 years). The entire spectrum of SSс specific antibodies (anticentromere antibodies – 60%, antibodies to ribonucleoprotease III – 30%, Pm/Scl – 10%), excepting antibodies to topoisomerase I, as well as pSS specific autoantibodies (antiRo/La – 70%, RF (rheumatoid factor) – 90%), were detected in patients with a combination of these RDs.

Conclusion. pSS is often combined with a limited form of SSc regardless of the type of autoantibodies detected. The presence of pSS, rather than SSc, is a high-risk factor for the development of NHL in this group of patients. The patients with pSS and SSc are characterized by a steady progression of pSS with a slow and mild course of SSc throughout the observation period. The development of severe stomatological manifestations and high immunological activity of pSS contribute to the development of localized MALT lymphomas (70%) and disseminated MALT lymphomas (30%) with primary lesions of the salivary glands and transformation into DLBCL in case of their late diagnosis. The optimal method for preventing the development of NHL in this group of patients is the early diagnosis of pSS, the appointment of alkylating cytotoxic agents and/or anti-B-cell therapy in the early stages of pSS. Given the possibility of transformation of localized NHL into DLBCL, for early diagnosis, minimally invasive surgical biopsies of significantly enlarged parotid salivary glands should be performed before glucocorticoids are prescribed. Detection of positive B-cell clonality and lymphoepithelial lesions in the parotid salivary gland is considered a predictor of MALT lymphoma development during follow-up. Localized and disseminated MALT lymphomas in patients with pSS and SSc respond well to therapy, in contrast to MALT lymphomas transformed into DLBCL.