長嶋 孝夫

We herein report two patients with connective tissue disease who developed primary peritoneal cancer (PPC). Serum Krebs von den Lungen-6 (KL-6) levels increased when PPC was diagnosed, and these levels were correlated with the treatment and worsening of PPC in both cases. In one patient with systemic sclerosis, serum KL-6 levels increased despite stable interstitial lung disease (ILD), leading to a diagnosis of PPC. In the other patient with dermatomyositis and no ILD, PPC was diagnosed with elevated KL-6 levels four months post-treatment, without ILD development. Clinicians should be reminded that KL-6 is a tumor marker in various cancers.

A 60-year-old woman with a history of malignant lymphoma was referred to us with fever, sore throat, right-sided neck pain, and swelling while she was currently undergoing chemotherapy. Imaging studies, including computed tomography and ultrasonography of the neck, revealed significant perivascular wall thickening of the right carotid artery, which was suggestive of giant cell arteritis. However, fever, neck pain, and swelling resolved spontaneously and rapidly. Transient perivascular inflammation of the carotid artery (TIPIC) syndrome was most likely. However, these symptoms developed shortly after the administration of granulocyte colony-stimulating factor (G-CSF). Accordingly, the patient was diagnosed with G-CSF-induced aortitis mimicking TIPIC syndrome.

Cutaneous arteritis (CA) is a rare cutaneous manifestation of Crohn's disease. A 50-year-old woman with a 15-year history of CA was admitted to our hospital with a fever, abdominal pain, and hematochezia. Based on these symptoms and increased C-reactive protein levels, systemic vasculitis was considered. However, emergency colonoscopy revealed multiple longitudinal ulcers throughout the colon, thus suggesting Crohn's disease. Prednisolone (60 mg/day) was administered intravenously. A histopathological examination of the biopsied colonic mucosa revealed epithelioid granulomas, which confirmed the diagnosis of Crohn's disease. Because the systemic evolution of CA is rare, other comorbidities should be considered when patients with CA experience systemic manifestations.

A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

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 25-year-old man presented with a fever and right upper quadrant abdominal pain. Computed tomography (CT) of the abdomen revealed diffuse perihepatic capsular enhancement, suggesting perihepatitis. Although the patient was a man, Fitz-Hugh-Curtis syndrome was suspected based on the CT findings. Treatment with several antibiotics was ineffective. Urinary tract infection was ruled out due to negative urinary bacterial screening and careful history taking. He was finally diagnosed with systemic lupus erythematous (malar rash, pleuritis, positive antinuclear antibody, and positive anti-ds-DNA antibody). Perihepatitis resolved quickly with high-dose prednisolone. Perihepatitis may be the first manifestation of SLE.

A teenage girl with systemic lupus erythematosus (SLE) was admitted with fever, dry cough, and dyspnea on exertion. Chest computed tomography revealed bilateral diffuse infiltration and swelling of the mediastinal lymph nodes. The bronchoalveolar lavage (BAL) fluid was light red, suggesting diffuse alveolar hemorrhage (DAH). Therefore, glucocorticoid pulse therapy was initiated. However, blood and BAL fluid cultures showed the growth of Cryptococcus neoformans. The patient was diagnosed with disseminated cryptococcosis. The patient was treated with liposomal amphotericin B and flucytosine; the prednisolone dose was rapidly tapered. Infections should be thoroughly ruled out in patients with SLE and DAH.

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.

A 68-year-old woman presenting with rheumatoid arthritis was admitted due to pancytopenia caused by methotrexate. Pneumocystis jirovecii pneumonia was diagnosed based on the abnormal shadows observed on chest computed tomography, the presence of serum β-D-glucan, and positive P. jirovecii-DNA results in a sputum analysis. Subsequently, after treatment with leucovorin and trimethoprim-sulfamethoxazole, lung consolidation was found to be aggravated, along with a rapidly increasing leukocyte count. In addition, cytomegalovirus colitis was diagnosed. Both conditions were associated with immune reconstitution inflammatory syndrome caused by recovery from leukopenia. The patient was successfully treated with intravenous methylprednisolone pulse therapy and ganciclovir.

A 56-year-old woman presented with dermatomyositis positive for anti-melanoma differentiation-associated gene 5 antibody. No interstitial lung disease was detected. Despite treatment with methylprednisolone pulse therapy and cyclosporine, dysphagia developed. Furthermore, the presence of thrombocytopenia, elevated lactate dehydrogenase levels, and an undetectable haptoglobin level suggested the possibility of thrombotic microangiopathy (TMA). Disturbed consciousness developed shortly after TMA onset, and brain magnetic resonance imaging revealed hyperintensity lesions in the bilateral basal ganglia, thalami, and brainstem. The patient was diagnosed with atypical posterior leukoencephalopathy syndrome before dying of heart failure later that day. In conclusion, early TMA recognition and prompt intensive treatment are critical in such cases.

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.

A 72-year-old woman was admitted to our hospital with bilateral pleural effusions. She had a 31-year history of systemic lupus erythematosus and had been treated with prednisolone and azathioprine. Pleural fluid culture revealed Salmonella enterica subsp. arizonae infection. This pathogen rarely infects humans but is commonly found in the gut flora of reptiles, especially snakes. Our patient had not come in contact with reptiles. Despite antibiotic therapies and negative pleural cultures, the pleural effusion persisted. Colon cancer was detected concomitantly, and she finally died. The autopsy revealed that the pleuritis was due to underlying diffuse large B cell lymphoma.

Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE).Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed.Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg (n = 6), 300 mg (n = 5), or 1000 mg (n = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature.Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.

A 70-year-old man with systemic lupus erythematosus (SLE) presented with simultaneous right oculomotor nerve palsy and right facial nerve palsy. Brain magnetic resonance imaging and cerebrospinal fluid analysis revealed no abnormality. Coexistent Sjögren's syndrome was diagnosed on the basis of anti-SS-A antibody positivity, salivary gland scintigraphy, and histological findings on minor salivary gland biopsy. As there was no obvious cause of multiple cranial neuropathies, we supposed that the palsies were induced by either of the underlying diseases. The patient was treated with a high-dose of prednisolone and intravenous cyclophosphamide, and both palsies recovered almost completely within two weeks.

<p>  【症例】43歳，女性．【主訴】関節痛，皮疹，飛蚊症【現病歴】10年前に掌蹠膿疱症と診断．時折前胸部痛を自覚していた．2年前に左胸鎖関節の疼痛を認め，膝と足関節の関節炎を伴うようになり，かかりつけの整形外科でプレドニゾロン（PSL）10mg/日で加療．6ヶ月前に肝胆道系酵素の増多を認め，NASHと診断されPSLを1 mgまで漸減．霧視と飛蚊症を認め，かかりつけの眼科で肉芽種性ぶどう膜炎と診断．関節痛の増悪もあり当科に紹介となった．肝臓腫大，鼻唇溝および後頸部に5 mm大の紅色の鱗屑を伴う結節，PIP関節の関節炎を認めた．AST 67U/L，ALT 66U/L，ALP 536U/L，γGT 446U/L，ACE 85.3 mU/ml，sIL2R 4,110 U/ml，CTおよびMRIで両側肺門リンパ節腫大と多発する腫瘤性変化を伴う肝腫大，皮膚生検で巨細胞を伴う類上皮肉芽腫を認め，肝病変を伴うサルコイドーシスと診断した．掌蹠膿疱症と胸骨，鎖骨の骨炎と骨化あり，SAPHO症候群も併存していると判断．肝サルコイドーシスに対しPSL 30mg/日に増量し，肝胆道系酵素と皮膚病変と関節炎の改善を認めた．【考察】10年来の関節症状はSAPHO症候群で，更に肝サルコイドーシスを合併したものと判断した．乾癬にサルコイドーシスを合併するのは1.5％と報告されているが，SAPHO症候群での合併は報告がない．両疾患にP.acnesが発症に関与している点を踏まえ病態を検討する．</p>

【症例】27歳の女性【主訴】嗄声と咽頭痛【現病歴】約1年前から嗄声と咽頭痛とを自覚していた．耳鼻咽喉科を受診し，喉頭ファイバースコピーで竹節状声帯を指摘された．血液検査で抗核抗体が陽性であったため基礎疾患として膠原病が疑われ，プレドニゾロン30 mgを開始されたが改善を認めず，当科を紹介受診し，精査のため入院した．【入院後経過】入院時の検査で抗核抗体1280倍，リウマトイド因子，抗SS-A抗体および抗SS-B抗体が陽性であり，Sjogren症候群が疑われた．ガムテストおよびシルマーテストは陰性，口唇腺生検では軽度のリンパ球浸潤を認め，診断基準は満たさなかったが，プレドニゾロン投与により唾液腺炎が改善した可能性を考え，臨床的にSjogren症候群を疑った．【考察】竹節状声帯は1993年に本邦から寶迫らが全身性エリテマトーデス（SLE）患者に認められた特異な喉頭所見として初めて報告した．SLEなどの自己免疫性疾患に合併する病変として複数の報告があるが，病態は不明で確立された治療法はない．自己免疫性疾患に伴う特徴的な声帯病変である竹節状声帯では，嗄声が唯一の初発症状のこともあり，原因として自己免疫性疾患の存在を念頭に置くことが重要であると考える．【結語】Sjogren症候群が疑われた竹節状声帯の一例を経験したので，文献的考察を含めて報告する．

A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin O levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However,