Primary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis. Interleukin‐18 (IL‐18), for which the gene was recently cloned, is a novel T helper 1 cytokine, which augments interferon‐gamma production. We designed this study to clarify the role of IL‐18 in primary biliary cirrhosis and to examine whether serum IL‐18 level can be a prognostic indicator for the disease. Serum IL‐18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty‐two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus‐related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL‐18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus‐related liver cirrhosis and obstructive jaundice (P < 0·05). The IL‐18 levels in primary biliary cirrhosis increased according to the disease progression, and fell promptly after living‐related liver transplantation. Moreover, serum IL‐18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL‐18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin‐18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.

Objectives The 2019 ACR/EULAR classification criteria for IgG4-related disease (IgG4-RD) have exclusion criteria including positive disease-specific autoantibodies, and these have been documented to have a high specificity. This study aimed to further validate these criteria as well as identify characteristics of patients showing false-negative results. Methods We retrospectively analysed 162 IgG4-RD patients and 130 mimickers. The sensitivity, specificity and fulfilment rates for each criterion were calculated, and intergroup comparisons were performed to characterize the false-negative cases. Results Both the IgG4-RD patients and mimickers were aged ≥65 years with male predominance. The final diagnoses of mimickers were mainly malignancy, vasculitis, sarcoidosis and aneurysm. The classification criteria had a sensitivity of 72.8% and specificity of 100%. Of the 44 false-negative cases, one did not fulfil the entry criteria, 20 fulfilled one exclusion criterion and 27 did not achieve sufficient inclusion criteria scores. The false-negative cases had fewer affected organs, lower serum IgG4 levels, and were less likely to have received biopsies than the true-positive cases. Notably, positive disease-specific autoantibodies were the most common exclusion criterion fulfilled in 18 patients, only two of whom were diagnosed with a specific autoimmune disease complicated by IgG4-RD. In addition, compared with the true-positive cases, the 18 had comparable serum IgG4 levels, number of affected organs, and histopathology and immunostaining scores despite higher serum IgG and CRP levels. Conclusions The ACR/EULAR classification criteria for IgG4-RD have an excellent diagnostic specificity in daily clinical practice. Positive disease-specific autoantibodies may have limited clinical significance for the diagnosis of IgG4-RD.

Seronegative rheumatoid arthritis (RA) is less likely to have extra-articular manifestations than seropositive RA. An 80-year-old man with polyarthritis was diagnosed with seronegative RA in which rheumatoid factors and anti-cyclic citrullinated peptides were not detected. He had multiple pulmonary nodules that diminished in size following treatment for RA, leading to the diagnosis of pulmonary rheumatoid nodules. During his treatment course, he developed scleritis, which could have resulted in blindness. As oral steroids did not improve his condition, topical steroid injections were administered, and his symptoms gradually improved. Here, we present a case of seronegative RA with an unusual combination of extra-articular manifestations: rheumatoid pulmonary nodules and scleritis.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase-or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauciimmune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.

Mixed connective tissue disease (MCTD), a multisystem autoimmune disease that was first proposed in 1972, has overlapping features with other autoimmune diseases. In recent studies, mixed connective tissue disease has been reported to change into other connective tissue diseases (CTD; such as systemic lupus erythematosus [SLE], polymyositis, and systemic sclerosis [SSc]) in the long term. We report the case of a 58-year-old Japanese man diagnosed with mixed connective tissue disease 15 years ago. During his clinical course, he developed discoid lupus erythematosus, pancytopenia, a low complement titer, proteinuria, and hematuria. He also turned positive for the anti-double-stranded deoxyribonucleic acid (dsDNA) antibody. A kidney biopsy revealed lupus nephritis (LN) class IV. Therefore, we considered this to be a shift from mixed connective tissue disease to systemic lupus erythematosus. We changed his treatment to lupus nephritis, after which he remained in remission. Our case suggests that mixed connective tissue disease may shift to other connective tissue diseases over a long period; therefore, it is necessary to identify whether patients with mixed connective tissue disease fulfill the diagnostic criteria for other connective tissue diseases when new manifestations appear.