gms | German Medical Science

History: A 58-year-old male was referred to our department with suspected systemic sclerosis. The patient’s medical history consisted of ulcerative reflux disease and an incidentaloma of the adrenal gland, both diagnosed recently. The patient was an active smoker (50 py). He worked as a mason. There was no family history of autoimmune diseases.

Cardinal symptom by manifestation of disease: At admission he complained about persistent arthralgia of metacarpal, elbow, shoulder and knee joints lasting for nearly two years. Moreover, he reported about Raynaud’s phenomenon and weight loss of 20 kg within 2 years. He further noticed increased skin thickening of the upper extremities and trunk. Dyspnea was denied. The physical examination showed no abnormalities except for a diffuse skin fibrosis (mRSS 30/51).

Diagnostics: Blood tests showed an increased CRP concentration (50 mg/l), hypochromic normocytic anemia (11.3 g/dl), and thrombocytosis (423 ng/l). The troponin T concentration was increased (160 ng/l). Creatinine and blood urea nitrogen concentrations were normal. LDH was also normal. The ANA titer was increased (1:5120), and Scl-70-, histon- and NOR90-autoantibodies were positive. Moreover, a marked increase of MPO-ANCA was detected (101 U/ml). Urinalysis showed a microhematuria (288/µl) with moderate albuminuria (54 mg/g creatinine) and proteinuria (230 mg/g creatinine). A renal biopsy showed an IgA nephropathy with focal segmental glomerulosclerosis, tubular atrophy, and interstitial fibrosis (Oxford classification: M0 E0 S1 T1). A CT scan revealed diffuse bipulmonary ground-glass opacities suggestive of interstitial lung disease (ILD). The body plethysmography showed an isolated decrease in the diffusing capacity for carbon monoxide (DLCO) in the presence of a normal forced vital capacity. Normal findings were shown in BAL, ECG, and echocardiography.

Therapy: The therapy decision had to take the patient’s disease constellation with overlapping disease features into account. ANCA – the hallmark biomarker of ANCA-associated vasculitis (AAV) – are also detected in up to 20% of systemic sclerosis (SSc) patients. In SSc, ANCA are associated with serological markers of inflammation (ESR, CRP), myocardial involvement (high-sensitivity cardiac troponin T), and interstitial lung disease (ILD). Myeloperoxidase (MPO)-specific ANCA are more frequently detected than proteinase 3 (PR3)-specific ANCA in SSc [1], [2]. Biopsy-proven small vessel vasculitis and/or clinical surrogate features of vasculitis such as mononeuritis multiplex are less common in patients with SSc/AAV overlap [3], [4], [5]. Notably, ILD is far more frequent in SSc patients overlapping with biopsy-proven AAV (80–90%) than would be expected in either disease alone. Thus, ILD can be regarded as a generic feature of SSc/AAV overlap [3]. While respective data for ILD in SSc/AAV overlap are yet missing, it has been shown that ILD confers an increased risk for diffuse alveolar hemorrhage, immunosuppression-related infections, and poor outcome in MPO-AAV [6]. Intriguingly, ANCA can also be detected in up to 20% of IgA nephropathy (IgAN) cases and are associated with worse renal function and a higher prevalence of pulmonary involvement [7], [8]. Taken these considerations into account and based on the clinical presentation and findings, a diffuse cutaneous SSc overlapping with features of MPO-AAV and IgAN was diagnosed. To our knowledge, this is the first report on a patient with a SSc/MPO-AAV/IgAN overlap. The therapy decision had to consider severe skin involvement in combination with ILD, possible cardiac involvement and IgA nephropathy in our patient and increased mortality and worse prognosis of patients with overlapping features of SSc, AAV, and IgAN [1], [2], [3], [4], [5], [7], [8]. Thus, induction therapy was started combining rituximab and pulse cyclophosphamide analogous to the RITUXVAS scheme in AAV [9].

Further course: Pulse cyclophosphamide therapy was continued due to persistent disease activity. Subsequently, symptoms improved, CRP concentration became normal, and MPO-ANCA decreased in the following 6 months. Moreover, urine analysis showed a marked reduction in microhematuria and proteinuria.

Disclorures: None declared.