Yana Zdravkova

Systemic lupus erythematosus is a chronic autoimmune disorder affecting predominantly young women. Cardiac involvement in systemic lupus erythematosus is common and the typical manifestations are pericarditis, myocarditis, valvular disease, coronary artery disease, cardiac arrhythmias, and congestive heart failure. Clinical lupus myocarditis typically occurs early during lupus, in the context of high disease activity. It may present as an acute illness or have a chronic course with the development of cardiomyopathy. We present a clinical case of young patient who developed a severe dilated cardiomyopathy as a fi rst manifestation of systemic lupus erythematosus.

Objectives: This study aimed to analyze a group of patients with severe and refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) managed with rituximab and to report on treatment outcomes. Patients and methods: A total of 78 patients (41 females, 37 males; mean age: 50.1±13.4 years; range, 18 to 76 years) with AAV on rituximab treatment were included in the single-center, retrospective study conducted between 2009 and 2018. The diagnosis was established based on the 1990 classification criteria of the American College of Rheumatology and the definitions of vasculitis of Chapel Hill Consensus Conference. Laboratory and immunological tests were conducted. Disease activity was determined through the Birmingham Vasculitis Activity Score. Results: Rituximab was preferred over cyclophosphamide in 37 patients and used as a second-line therapy after cyclophosphamide in 41 cases. Rituximab treatment showed favorable outcomes with regard to serum creatinine levels, proteinuria, and hematuria, as well as in cases of isolated lung involvement. Nearly half of patients with pulmonary renal syndrome also improved, with 22.2% achieving remission. ANCAs were positive in 85.9% of patients at the onset of rituximab treatment and became negative in 82% of the positive cases. Adverse events were rare and included infusion reactions (one case of reactivation of a herpes zoster infection and one case of allergic reaction). Conclusion: Rituximab is an efficient and safe therapeutic option in patients with AAV who are difficult to treat, have insufficient response, or have not tolerated other treatments.

Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

Systemic vasculitides are a heterogenic group of disorders characterized by destructive inflammation and fibrinoid necrosis of the vascular wall, vessel occlusion and tissue ischemia. Vasculitides presenting with necrosis are included in neither of the contemporary classifications, even though this type of vascular pathology is the one with the most dramatic manifestations in rheumatology. There have been no analyses of the nosological association, clinical features and therapeutic management of the vasculitides with necrosis in the pertinent literature. The aim of the present study was to analyze vasculitides in the Bulgarian population in terms of their nosological association; to examine the portion that ANCA-associated vasculitides represent out of all vasculitic syndromes on the one hand, and to make an analysis of the vasculitides with necrosis according to their nosological association on the other. In the present study, we included 388 patients with vasculitis, 251 of whom were female and 137 male. We conducted a prospective and retrospective analysis which covered the patients with vasculitis who were admitted to the Clinic of Rheumatology over the period 2009-2018. ANCA-associated vasculitides were the most often diagnosed vasculitides in the Clinic of Rheumatology. Vasculitic manifestations over the course of connective tissue diseases (most often systemic lupus erythematosus and systemic sclerosis) were the second most common group. Life-threatening cases of vasculitis with necrosis were mainly the result of flares of different connective tissue diseases. The major necrotizing vasculitides (Wegener’s granulomatosis and microscopic polyangiitis) were responsible for 12.6% of the cases of vasculitis with necrosis. In order to establish the correct diagnosis and start the suitable treatment, it is of vital importance to recognize the different vasculitic syndromes and their wide differential diagnosis. Most of them respond well to the currently available therapeutic options, especially if the correct diagnosis has been established early.