Yoshiro Horai

Rheumatoid arthritis (RA) is a systemic rheumatic disease. Its most prominent characteristic is synovitis, which manifests clinically as arthritis, resulting in joint damage. Interstitial lung disease (ILD) is an extraarticular manifestation of RA that hinders therapeutic goals, affects life prognosis, and can be worsened by the administration of disease-modifying antirheumatic drugs (DMARDs). Therefore, proper management of ILD, including consideration of risk factors such as the systemic disease activity of RA and autoantibodies, and early detection with high-resolution computed tomography are required at the introduction of DMARDs. Methotrexate, a class of DMARD used as the anchor drug for RA treatment, has been recognized as likely to worsen RA-ILD. However, there are currently reports suggesting that methotrexate may have beneficial effects on RA-ILD. Conversely, several studies have also shown exacerbations of ILD with the administration of biological DMARDs, which are thought of as tolerable for patients with RA-ILD. Rheumatologists should be wary of emergence or changes in the activity of ILD and arthritis during treatment of any kind with DMARDs. Further studies are warranted to clarify underlying ethnic factors, such as the possible effects of antimelanoma differentiation-associated gene 5 antibodies on RA-ILD.

Background/Objectives: Lymphoproliferative disorders (LPDs) are adverse effects of methotrexate (MTX) prescribed for rheumatoid arthritis (RA). Sjögren’s disease (SjD), for which the presence of anti-Ro/SS-A antibodies (Abs) is a diagnostic criterion, might accompany RA and be a risk factor for LPDs. We conducted a retrospective study to analyze the effects of SjD or anti-Ro/SS-A Ab positivity on the clinical course of patients with RA complicated by LPDs. Methods: We retrospectively analyzed 25 patients in our department who had RA complicated by LPDs, specifically collecting clinical information regarding the complications of SjD and positivity for anti-Ro/SS-A Abs. Results: In total, 25 patients with RA were included in this study, 3 of which were diagnosed with SjD by attending physicians based on sicca symptoms and positiveness of anti-Ro/SS-A antibodies. No significant differences in clinical characteristics except for SjD diagnosis given by attending physicians were found between the patients positive for anti-Ro/SS-A Abs and the patients negative for anti-Ro/SS-A Ab. The most common histologic LPD subtype was diffuse large B cell lymphoma, while mucosa-associated lymphoid tissue lymphoma, the histologic subtype often diagnosed as SjD-LPD, was found in only one patient, who was positive for anti-Ro/SS-A Abs without an SjD diagnosis. There were no significant differences in the intervals between the RA and LPD diagnoses and those of SjD and anti-Ro/SS-A Ab positivity. Conclusions: While the rate of anti-Ro/SS-A Ab positivity in the study population seemed to be higher than that in the general RA population, any potential effects of SjD on RA-LPD development were not ascertained in this study.

We herein report a patient with immunoglobulin (Ig)G4-related hypertrophic pachymeningitis (HP) with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) positivity without renal dysfunction at the time of the diagnosis who subsequently developed nephritis after an unplanned interruption of maintenance glucocorticoid therapy. A renal biopsy specimen obtained at the time of the development of renal dysfunction revealed the possibility of both ANCA-associated nephritis and IgG4-related tubulointerstitial nephritis, with no HP relapse. The present case highlights the need to monitor other organ complications, including renal damage, in patients with IgG4-related HP with MPO-ANCA positivity, even after achieving remission.

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Sjögren’s Disease (SjD) is an autoimmune disorder characterized by sicca symptoms arising from impaired salivary and lacrimal gland function and accompanying extraglandular involvement. SjD is recognized as an illness of female dominance for which the 2002 American–European Consensus Group Classification Criteria and the American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 classification criteria are utilized for inclusion in clinical trials, and treatment recommendations from countries belonging to the American College of Rheumatology or the European Alliance of Associations for Rheumatology are globally recognized. It is presumed that there are geographical differences among female sufferers, and unique diagnostic criteria and recommendations are used in clinical practice in Japan. In addition to the items included in the classification criteria, several methods to measure saliva secretion, serum biomarkers, and artificial intelligence tools have recently been reported to be useful for the assessment of SjD. While symptomatic therapies including tear drops, artificial saliva, and muscarinic agonists are still the mainstay for treating SjD, several kinds of molecular targeted drugs, such as biological drugs and Janus kinase inhibitors, that are expected to improve the prognosis of SjD have been tested in recent clinical trials.

We herein report three cases of microscopic polyangiitis (MPA). Two patients were administered avacopan in combination with glucocorticoid (GC), whereas one patient was treated with avacopan monotherapy; none of the patients were co-administered either rituximab or cyclophosphamide. The doses of GC were successfully reduced after the introduction of avacopan in the two patients, and the serum C-reactive protein levels decreased in the patient treated with avacopan monotherapy. Avacopan may therefore be effective either in combination with GC or as monotherapy, even for patients at a high risk of developing adverse effects when administered rituximab or cyclophosphamide.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a disease entity characterized by systemic vasculitis positive for ANCAs, which often leads to severe organ damage such as diffuse bronchoalveolar hemorrhage and rapidly progressive glomerulonephritis. It is known that the incidence and characteristics of AAV vary depending on region, and differences in the peak age of onset, the ratio of positive rates of MPO-ANCA to PR3-ANCA, and occurrence rates of GPA and MPA may have resulted in different approaches to clinical practice. It may also be necessary to modify therapeutic strategies according to ethnic factors. Avacopan is a therapeutic option recently recommended for the management of AAV; however, the rate of severe liver injuries associated with avacopan was reported to be relatively high in the Japanese population. In this review, we introduce current globally recognized knowledge on the diagnosis and treatment of AAV, including a comparison of patient characteristics and clinical practice between Europe and Japan obtained from the recent literature.

Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of the bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren’s syndrome (SS), another rheumatic disease caused by the lymphocytic infiltration of exocrine glands, with dry eye and dry mouth being the two most common symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker of SS, are positive in patients with RA at a certain rate. The coexistence of SS and/or positivity for anti-Ro/SS-A antibodies in patients with RA influences disease activity and the effectiveness of several classes of disease-modifying antirheumatic drugs (DMARDs). Furthermore, RA, SS, and certain DMARDs, including methotrexate, are associated with the onset of lymphoproliferative disorders (LPD). In contrast, several biological DMARDs, such as tocilizumab and rituximab, are plausible options without the risk of LPD relapse. Considering the results of the studies introduced in this article, RA with SS and/or positivity for anti-Ro/SS-A antibodies could be considered a phenotype different from isolated RA from the perspective of refractoriness to DMARD therapy and LPD risk. Hence, rheumatologists should observe caution when choosing DMARDs. Further studies are needed to establish the appropriate treatment for patients with RA, SS, and/or the presence of anti-Ro/SS-A antibodies.

It is our pleasure to present the Special Issue “Diagnosis and Treatment of Sjögren’s Syndrome” to the readers of the Journal of Clinical Medicine

Sjögren’s syndrome (SS) is a rheumatic disease characterized by sicca and extraglandular symptoms, such as interstitial lung disease and renal tubular acidosis. SS potentially affects the prognosis of patients, especially in cases of complicated extraglandular symptoms; however, only symptomatic therapies against xerophthalmia and xerostomia are currently included in the practice guidelines as recommended therapies for SS. Considering that SS is presumed to be a multifactorial entity caused by genetic and environmental factors, a multidisciplinary approach is necessary to clarify the whole picture of its pathogenesis and to develop disease-specific therapies for SS. This review discusses past achievements and future prospects for pursuing the pathophysiology and therapeutic targets for SS, especially from the perspectives of viral infections, toll-like receptors (TLRs), long-noncoding RNAs (lncRNAs), and related signals. Based on the emerging roles of viral infections, TLRs, long-noncoding RNAs and related signals, antiviral therapy, hydroxychloroquine, and vitamin D may lower the risk of or mitigate SS. Janus-kinase (JAK) inhibitors are also potential novel therapeutic options for several rheumatic diseases involving the JAK-signal transducer and activator of transcription pathways, which are yet to be ascertained in a randomized controlled study targeting SS.