Natural history of Behçet's disease focusing on remission of oral ulcers.

OBJECTIVES: To describe the long-term clinical course of each manifestation of Behçet's disease (BD) and clarify factors involved in oral ulcer (OU) remission using clinical information of BD patients. METHODS: We retrospectively studied 155 BD patients visiting our hospital (1989-2020). We defined remission criteria for each manifestation and examined long-term clinical changes. Classification and regression trees and multivariable analyses were performed to investigate OU prognostic factors; hazard ratios were used to assign scores to prognostic factors deemed significant [OU prognosis score (OuP score)]. Risk stratification was examined by dividing the OuP scores into four stages. RESULTS: OUs appeared earliest, with the slowest decline in prevalence observed post-BD diagnosis. OU presence was the most common factor inhibiting complete remission. Young age at OU onset, never smoker, presence of genital ulcers, positive pathergy test, no usage of tumour necrosis factor inhibitors or of immunosuppressants, and long-term non-treatment or symptomatic treatment for OUs were poor OU prognostic factors. Based on multivariable analysis, the area under the curve of the OuP score to predict OU prognosis was 0.678. CONCLUSIONS: Remission criteria for each symptom clarified that OU had the greatest impact on complete BD remission. Faster OU remission was associated with earlier OU therapeutic intervention other than symptomatic treatment.

Is Kimura's disease associated with juvenile temporal arteritis? A case report and literature review of all juvenile temporal arteritis cases.

Both juvenile temporal arteritis (JTA) and Kimura's disease are eosinophilic inflammatory conditions but exhibit different clinical manifestations. Here, we describe a case involving a 40-year-old man who developed JTA secondary to Kimura's disease. Approximately 3 years before admission, masses appeared on both posterior auricles. A biopsy of the right posterior auricle mass led to a diagnosis of Kimura's disease. Approximately 4 months before admission, both masses increased in size, and almost simultaneously, the left temporal artery became distended. Histopathology of a biopsy of the left temporal artery revealed inflammatory findings with marked eosinophil infiltration and significant intimal hyperplasia with stenosis of the vascular lumen, indicating JTA. An analysis of the 48 reported cases of JTA, identified in a literature review, and the present case, revealed that Kimura's disease was detected in 6 cases, all of which involved Asians. In conclusion, this case and the literature review suggest that JTA can be accompanied by another eosinophilic inflammation-based disorder, Kimura's disease, particularly in Asians. This newly highlighted relationship between JTA and Kimura's disease could lead to a better understanding of JTA, which is an extremely rare disease.

Efficacies of atovaquone, pentamidine, and trimethoprim/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared. METHODS: Hospitalized patients with connective tissue diseases who started steroid therapy and PCP prophylaxis were enrolled. PCP prophylaxis regimens were oral TMP-SMX, aerosolized pentamidine, or oral atovaquone. Information was retrospectively collected from medical records about laboratory findings, duration of PCP prophylaxis, and reasons for terminating PCP prophylaxis. RESULTS: Ninety-six patients received PCP prophylaxis. All of them were initially treated with TMP-SMX, but this was replaced during the study period with pentamidine in 33 patients and with atovaquone in 7. Forty-one (43%) patients discontinued TMP-SMX because of adverse events, and 5 (15%) also discontinued pentamidine. None of the patients discontinued atovaquone. The most frequent causes of TMP-SMX and pentamidine cessation were cytopenia (N = 15) and asthma (N = 2). The rates of continuing treatment with TMP-SMX, pentamidine, and atovaquone at one year after starting PCP prophylaxis were 55.3%, 68.6%, and 100%, respectively (P = 0.01). None of the patients developed PCP. CONCLUSION: Although TMP-SMX for PCP prophylaxis had to be discontinued in 43% of patients with connective tissue diseases, pentamidine and atovaquone were well tolerated.

Emergence of Smoldering ANCA-associated Glomerulonephritis during the Clinical Course of Mixed Connective Tissue Disease and Sjögren's Syndrome.

A 67-year-old woman presented with hematuria and proteinuria 16 and 11 months ago, respectively. She had been followed up as mixed connective tissue disease and Sjögren's syndrome for over 19 years. Blood chemistry showed no elevated serum creatinine or C-reactive protein but did reveal myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) of 300 U/dL. A kidney biopsy showed pauci-immune focal necrotizing glomerulonephritis. She was treated with prednisolone and rituximab, resulting in normal urinalysis and decreased MPO-ANCA. The complication of ANCA-associated glomerulonephritis should not be overlooked when abnormal urinalysis findings appear in the course of connective tissue disease, irrespective of the presence of rapidly progressive glomerulonephritis.

Association of ETS1 polymorphism with granulomatosis with polyangiitis and proteinase 3-anti-neutrophil cytoplasmic antibody positive vasculitis in a Japanese population.

ETS proto-oncogene 1, transcription factor (ETS1) is involved in various immune responses. Genome-wide association studies on systemic lupus erythematosus in Chinese populations identified the association of ETS1 polymorphism in 3' untranslated region, rs1128334A, which was associated with lower ETS1 expression. In view of substantial sharing of susceptibility genes across multiple autoimmune diseases, we examined whether ETS1 is associated with a rare autoimmune rheumatic disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099 healthy controls by logistic regression analysis under the additive model. AAV patients were classified into 285 microscopic polyangiitis (MPA), 92 granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33 unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm. Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. When the patients were classified according to the EMEA classification, rs1128334A allele was significantly increased in GPA (P = 0.0060, P c = 0.030, odds ratio (OR), 1.54; 95% confidence interval (CI), 1.13-2.10). With respect to the ANCA specificity, significant association was observed in PR3-ANCA positive AAV (P = 0.0042, P c = 0.021, OR, 1.72; 95% CI, 1.19-2.49). In conclusion, ETS1 polymorphism was suggested to be associated with GPA and PR3-ANCA positive AAV in a Japanese population.

Refractory optic perineuritis due to granulomatosis with polyangiitis successfully treated with methotrexate and mycophenolate mofetil combination therapy.

Optic perineuritis is an uncommon inflammatory disorder of the optic sheath that causes visual loss or eye pain. There are few case reports of optic perineuritis associated with granulomatosis with polyangiitis. Herein we report the case of a 37-year-old male with granulomatosis with polyangiitis and who presented with headache, blurred vision in the right eye, diplopia, and numbness in the right forehead. Brain magnetic resonance images (MRI) findings revealed hypertrophic pachymeningitis and refractory optic perineuritis. These were manageable only by means of weekly methotrexate and mycophenolate mofetil combination therapy but not with methotrexate, mycophenolate mofetil, intravenous cyclophosphamide, rituximab, azathioprine, or cyclosporine individually.

Characteristics of patients with intestinal Behçet's disease requiring treatment with immunosuppressants or anti-TNFα antibody.

OBJECTIVES: To identify the specific characteristics of patients with refractory intestinal Behçet's disease (BD) who required more than glucocorticoid (GC) and/or 5-aminosalicylic acid (5-ASA) treatment. METHODS: A retrospective review of the patient records in a university hospital identified 34 patients with intestinal BD. The patients treated only with glucocorticoid and/or 5-ASA (n = 8) were compared with refractory cases which required additional immunosuppressants, anti-TNFα antibodies, or surgery (n = 12). RESULTS: In the refractory group, ulcers were found outside the ileocecal region more often, and more active intestinal bleeding or melena was observed, than in the GC/5ASA-controlled group (75% vs 0%, p = 0.001), (58% vs 0%, p = 0.015). The refractory group also showed higher positivity for HLA-B51 (45% vs 0%, p = 0.044), higher blood C-reactive protein (CRP) levels (14.7 ± 8.74 vs 3.93 ± 6.33 mg/dL, p = 0.046), and a higher white blood cell or WBC count (14750 ± 6760 vs 7210 ± 1830/µl, p = 0.025) at onset. The existence of either HLA-B51, melena, or elevated CRP of more than 4 mg/dL predicted the refractory form of BD with 100% sensitivity and 85.7% specificity. CONCLUSIONS: Refractory intestinal BD was distinguished from the non-refractory form by distinct clinical and laboratory findings. These findings will be useful in identifying patients who require intensive therapy (e.g., anti-TNFα antibodies) in addition to GC/5ASA.

Etanercept for the treatment of intractable hemophagocytic syndrome with systemic lupus erythematosus.

A 41-year-old woman presented with continuous fever, and her laboratory data suggested the recrudescence of systemic lupus erythematosus. She was treated with 60 mg/day prednisolone. With a dose reduction of prednisolone, high fever and pancytopenia were observed again. A bone marrow biopsy revealed hemophagocytosis. The effects of steroid pulse therapy, high-dose intravenous immunoglobulin, cyclosporine A, and methotrexate were insufficient. However, after four injections of etanercept (25 mg, twice a week) subcutaneously, her symptoms had completely resolved. In such cases, therapy with etanercept may be effective.

Induction of type B synoviocyte-like cells from plasmacytoid dendritic cells of the bone marrow in rheumatoid arthritis and osteoarthritis.

We examined the capacities of bone marrow (BM) plasmacytoid dendritic cells (pDC) to differentiate into type B synoviocyte-like cells. BM aspiration samples were obtained from 24 rheumatoid arthritis (RA) patients and 19 osteoarthritis (OA) patients during joint operations from the iliac crest. CD34+ cells and pDC purified from BM mononuclear cells were cultured with or without SCF, GM-CSF, and TNF-α for 2-4 weeks. RA BM pDC as well as OA BM pDC comparably differentiated into fibroblast-like cells (FLC), expressing cadherin-11 and producing MMP-1, especially in the presence of TNF-α. Of note, depletion of BDCA4+ pDC from RA BM CD34+ cells significantly diminished their capacities to differentiate into FLC, which were restored by addition of BDCA4+cells in a dose-response manner. These results indicate that pDC is one of the progenitors of type B synoviocytes, suggesting that BM pDC might be involved in the pathogenesis of RA and OA.

Churg-Strauss syndrome complicated by central retinal artery occlusion: case report and a review of the literature.

A 68-year-old man was admitted with rapid visual loss. Churg-Strauss syndrome (CSS) was diagnosed, based upon the symptoms of asthma, eosinophilia, interstitial pneumonitis, and positive myeloperoxidase-anti neutrophil cytoplasmic antibody (MPO-ANCA). Light reflexes were absent and vision was completely lost in both eyes. Bilateral central retinal artery occlusion (CRAO) was observed by fluorescence angiography. Steroid pulse along with an anticoagulant improved the visual acuity to light perception and hand motion. CSS-associated CRAO should be considered when acute visual loss occurs.