Polyangiitis Overlap Syndrome with Granulomatosis and Systemic Sclerosis: Diagnostic Challenge

The association of vasculitis with other connective tissue diseases is significant. In the study by Guibert et al. [4], patients with SS and AAV had a higher relapse rate (non-renal, 25% vs. 7.7%, p = 0.037) and were more likely to experience a venous thrombotic event (31.2% vs. 10%, p = 0.021) compared to those with vasculitis alone.

Possible explanations for this association include exposure to common risk factors and reduced immune tolerance to ANCA antigens, which are present in up to 35% of SS patients (with bactericidal permeability-increasing protein [BPI] and cathepsin G being the main ones) despite this, only a minority will develop the disease [5,6]. BPI, a constituent of azurophilic granules in neutrophils with activity against various Gram-negative bacteria, is closely related to chronic respiratory tract infections. It is believed that the presence of interstitial lung disease in SS increases the risk of pulmonary infections and may play a role in inducing anti-BPI antibodies. BPI inhibits angiogenesis by inducing endothelial cell apoptosis, and anti-BPI antibodies could inhibit its antiproliferative effect on the vascular endothelium, thereby promoting angiogenesis, though its role is not yet fully understood, and in vitro studies are needed to confirm this.

Our case differs from others reported in the literature, as the most common scenario is that patients with SS develop vasculitis  [1,4-6]. In our patient, the clinical presentation began with vasculitis, and no renal involvement was found at that time, which aligns with the findings of Masiak et al  [7] where patients with vasculitis and autoimmune diseases had less renal involvement (45.0% vs. 70.9%, p = 0.001), although this overlap was not reported in that study. This case also underscores the need for a multidisciplinary approach with timely referral to a rheumatologist to prevent complications.