佐藤 健夫

AIM: This study aimed to evaluate the predictive value of serum humoral factors in determining the therapeutic responses to biologic DMARDs (bDMARDs), especially TNF inhibitors (TNFis), in patients with RA. METHODS: A cohort of 52 patients with RA who were treated with bDMARDs, including TNFis, abatacept, and tocilizumab, was analyzed. Serum samples were collected at baseline (t1), 5 ± 1 (t2), and 14 ± 2 weeks (t3) after treatment. A bead-based immunoassay was used to quantify serum cytokines/chemokines. Treatment response was determined 1 year after initiation. RESULTS: Distinct patterns of IL-6 behaviors were observed among different bDMARDs. Patients exhibiting IL-6 rebound at 14 weeks were more likely to be non-responders to TNFi after 1 year, and this rebound appeared to be associated with increases in IFN-γ and IL-12 levels. IFN-β was more detectable than IFN-α2 in RA. Additionally, patients with measurable IFN-β at baseline tended to be TNFi responders. CONCLUSION: Monitoring serum humoral factors may offer valuable insights into the likelihood of therapeutic success of TNFi in patients with RA. IL-6 rebound at 14 weeks might serve as an early indicator of non-responsiveness to TNFi. These findings highlight the potential of personalized treatment strategies for RA based on serum humoral factor profiling. Larger prospective studies are needed to validate these results and elucidate the underlying mechanisms.

A 53-year-old woman with a 6-year history of rheumatoid arthritis (RA) presented with pharyngeal pain, fever, and altered mental status. The patient had been treated with methotrexate (MTX) 12 mg/week, baricitinib 4 mg/day, and tacrolimus 2 mg/day. Magnetic resonance imaging of the brain revealed diffuse high-intensity lesions in the cerebral white matter, basal ganglia, brainstem, and right cerebellar hemisphere. She was diagnosed with Epstein-Barr virus (EBV) encephalitis due to elevated levels of EBV-DNA in the cerebrospinal fluid and serum. Although MTX-associated lymphoproliferative disorders are well-known complications in patients with RA, EBV encephalitis requires careful attention for such patients undergoing treatment with multiple potent immunosuppressants.

AIM: The use of an immunosuppressant is recommended as a treatment for remission induction in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the immunosuppressant is sometimes discontinued due to an adverse event. We sought to identify the cause and risk factors for immunosuppressant discontinuation in patients with AAV receiving remission induction treatment. METHODS: We retrospectively analyzed the cases of AAV patients treated in 2005-2016 with immunosuppressants to induce remission. We defined "discontinuation" as stopping, switching, or delaying immunosuppressant administration due to adverse events. We performed a multivariate analysis to identify risk factors for immunosuppressant discontinuation. RESULTS: We identified 50 patients treated with an immunosuppressant for remission induction: cyclophosphamide was used in 45 patients (90%), methotrexate in 4 (8%), and cyclosporine A in 1 patient (2%). Among them, 26 patients (52%) underwent discontinuation of the immunosuppressant. Infection and myelosuppression were the major causes of discontinuation. Multivariate Cox proportional hazards regression analysis revealed that a cumulative dose of prednisolone ≥ 2000 mg (hazard ratio [HR] =2.18, 95% confidence interval [CI] =1.37-3.70, P < .001), performance status of 3-4 (HR = 1.80, 95% CI = 1.07-3.03, P = .027), and oral cyclophosphamide (HR = 1.81, 95% CI = 1.11-2.97, P = .018) were independent risk factors correlated with immunosuppressant discontinuation. CONCLUSION: Physicians should be aware of risk factors predicting immunosuppressant discontinuation when treating AAV patients with an immunosuppressant.

Voice disorder is occasionally associated with systemic autoimmune diseases. Bamboo nodes of the vocal fold have a characteristic bamboo-shaped appearance and strongly indicate the presence of an underlying autoimmune disorder. Both mechanical and immunologic mechanisms are assumed to be involved in the pathogenesis of vocal disorder. We present a 27-year-old woman with hoarseness, sore throat, and a unilateral bamboo node of the vocal fold. Serum anti-SS-A and -SS-B antibodies were positive, but she had no systemic signs or symptoms suggestive of Sjögren's syndrome. Oral systemic glucocorticoid treatment was not effective, but surgical resection improved her hoarseness. Histopathologic findings of the resected vocal node revealed fibrosis with hyaline degeneration. Thereafter, she had no recurrence of hoarseness for 2 years. Bamboo nodes of the vocal fold may occur without definitive autoimmune diseases, although immunologic abnormalities such as autoantibody-positivity may occur.

症例は60歳，女性．半年以上診断が確定しなかった発熱の経過中に失行，構音障害，幻覚などの多彩な中枢神経症状が加わり，増悪した．血管内リンパ腫を疑い，骨髄生検と肝生検をはじめとする検査を施行したが診断は確定しなかった．皮疹は認められなかったが，ランダム皮膚生検によって血管内リンパ腫が確定し，化学療法が奏功した．<br>

We described clinicopathological features of eight patients (six females and two males) with isolated polyarteritis nodosa (PN). The age range of the patients was from 22 to 85 years. Six patients presented with fever, skin involvement and/or peripheral neuropathy related to the vasculitis. One patient presented with appendicitis, and the other patient presented with ovarian cyst. Biopsy specimens were obtained from 5 patients with skin and/or peripheral nerve involvement, and surgically resected specimens were obtained from one patient with appendicitis and from one patient with ovarian cyst. Fibrinoid necrosis of small to medium sized arteries was observed in all specimens. After resection, a patient with necrotizing vasculitis of the vermis and a patient with necrotizing vasculitis of the genital tract have not developed systemic vasculitis during the follow-up years. Four patients with peripheral nerve involvement responded well to high dose prednisolone therapy, however, two patients with PN confined to the skin (cutaneous PN) had frequent relapses, indicating that cutaneous PN has not necessarily a benign course.

症例は気管支喘息とアレルギー性鼻炎の既往がある92歳男性.経過中にメチシリン耐性ブドウ球菌・多剤耐性腸球菌による敗血症を繰り返したため抗生剤を投与した.抗生剤投与中に皮疹・肝障害・末梢血液中好酸球数増加が出現し, その経過に一致して心不全による呼吸困難感および胸水貯留, 心電図異常, び漫性心筋収縮能低下が出現した.抗生剤中止とステロイド剤投与により, 皮疹・肝障害・末梢血液中好酸球増多は改善, それに伴い心不全も軽快した.治療経過より好酸球増多は塩酸バンコマイシンもしくはテイコプラニンによる薬剤性を疑った.薬剤性好酸球増多症による心筋障害は稀であるが, 生命予後を左右する重大な合併症の一つである.本例は抗生剤投与中止とステロイド剤投与により治療し得た.

皮膚筋炎に特徴的な皮疹を呈するが筋症状を欠くamyopathic dermatomyositis(ADM)の56歳女性例を報告した.経過中,肺実質病変と縦隔気腫を伴った.肺病変と皮膚病変はステロイド・シクロスポリン併用に反応性が乏しく,サイクロホスファミドパルスを加えることで改善が得られた.これ迄に経験したADMの3例は,いずれも肺実質病変,縦隔気腫,皮膚血管病変を合併していた.又,3例とも皮膚粘膜に潰瘍病変や網状皮斑等の所見があることから,縦隔気腫の成因として,気道粘膜の血管病変により組織の壊死が生じ,そこから空気が漏れ出るという機序が想定された