Extra‐articular involvement of rheumatoid arthritis in three seropositive patients in the absence of initial joint involvement

Abstract

Introduction: Extra-articular involvement (EAI) in rheumatoid arthritis (RA) is rare, severe and usually presents after years of joint involvement. Onset of RA as lung involvement has been published. We describe a series of three patients with strongly positive anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) positive in the absence of joint symptoms, but with significant EAI. Methods: This is a descriptive case series of three patients evaluated in an academic medical center rheumatology clinic.Results: A 50-year-old female presented with severe recurrent scleritis in the background of strongly positive ACPA, but no joint involvement. Her ocular disease responded well to rituximab. Four years later, she developed peripheral inflammatory arthritis consistent with RA. A 74-year-old male presented after developing recurrent steroid-dependent serositis (pleuro-pericarditis) and interstitial lung disease (ILD). Serology was notable for strongly positive ACPA, but no joint involvement. Serositis responded well to adalimumab. Two years after initial symptoms, he developed peripheral joint involvement after holding adalimumab. A 56-year-old female presented with an isolated, biopsyproven subcutaneous rheumatoid nodule. Subsequently, she developed pancytopenia and fatigue. She tested strongly positive for ACPA and RF. Bone marrow biopsy was negative for malignancy and she had no evidence of infection. She responded to steroids and hydroxychloroquine and had not developed joint involvement after 2 years of follow-up. Conclusion:EAI as an onset of RA is a complex and not easily recognized entity if typical joints involvement is not yet present. Early diagnosis may help guide specific therapy and prevent sequelae and co-morbidities.

Pericarditis With Cardiac Tamponade Mimicking Yellow Nail Syndrome in a Patient With Rheumatoid Arthritis and a Paucity of Joint Symptoms

“…Furthermore, multiple extra-articular symptoms of rheumatoid arthritis can render the diagnosis of pericarditis challenging; therefore, it is necessary to carefully distinguish between various diseases with a similar presentation, such as yellow nail syndrome and pericarditis [5,16]. In our case, the patient had chronic sinusitis and bronchitis related to rheumatoid arthritis.…”

“…For the effective diagnosis of rheumatoid pericarditis, close follow-up and a high index of suspicion are essential in patients with multiple complications of rheumatoid arthritis. Additionally, a methodical and stepwise approach is required to rule out the differentials [16]. Many non-fatal complications of rheumatoid arthritis can progress chronically [5].…”

Recurrent ACPA-positive pericarditis, would it be a pre-clinical manifestation of RA?

“…Chirila et al reported three cases of extra-articular manifestations of RA in the presence of ACPA, initially without arthritis. These were a case of scleritis, a case of pleuropericarditis associated with diffuse interstitial lung disease (DIL), and a third case of histologically confirmed subcutaneous rheumatoid nodule [2]. The first and second cases presented with joint signs after four and two years, respectively.…”

Anti-citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Prospects

“…The citrulline-specific immune response can produce long-lived plasma cells and a stable titer of ACPAs, while the RF response can produce short-lived plasma cells and fluctuating levels of RF ( 52 ) ( Table 1 ). In addition, patients with strongly positive ACPAs and RF positivity in the absence of joint symptoms may have significant extra-articular involvement, including recurrent scleritis, pleuropericarditis, or interstitial lung disease ( 53 ). Moreover, high levels of ACPAs are associated with greater susceptibility to ocular diseases ( 54 ).…”