岡崎 仁昭

【目的】当科におけるSLE患者のループス腸炎合併例の臨床的検討を行った．【方法】2001年1月～2012年12月までに入院したSLE患者431例中，ループス腸炎と診断した16例（3.7%）（再発含め延べ22例）を対象とした．ループス腸炎の診断は，画像で腸管壁の肥厚を認め，副腎皮質ステロイドによる治療を要した症例とした．【結果】ループス腸炎発症時の年齢（35歳，18～66歳）（中央値，範囲），SLE発症からループス腸炎発症までの期間（5年，0～19年），臨床症状は腹痛が19/22例，下痢が17/22例，悪心・嘔吐が16/22例であった．白血球減少 0/22例；血小板減少 1/22例；貧血 2/22例；低補体血症 15/22例；抗ds-DNA抗体上昇 15/22例，抗SS-A抗体陽性 11/16例，抗RNP抗体陽性 5/16例，CRP（0.81 mg/dl，0.01～17.5 mg/dl），SLEDAI（8.5，0～23）であった．腸管浮腫の部位は小腸+大腸が最も多く17/22例．腹水 18/22例，水腎症 7/22例を認めた．治療は15/22例にステロイドパルス療法が併用され，免疫抑制薬の併用は3例であった．再発は5/16例に認めた．【結論】当科におけるループス腸炎の特徴は，抗SS-A抗体陽性例が多く，血球異常はほとんど認めず，治療経過は良好であった．

Objective Prednisolone has traditionally been tapered below 30 mg daily before patients are discharged from hospitals in Japan because of concerns regarding the development of infectious complications. We undertook this study to compare the incidence of infectious complications in patients taking more than 30 mg of prednisolone daily with those taking less than 30 mg. Patients and Methods The medical records of fifty-seven patients with systemic lupus erythematosus (SLE) were reviewed retrospectively, and divided into three groups based on the dose of glucocorticoids at the time of discharge: group A (n=13), newly-diagnosed SLE patients taking more than 30 mg of prednisolone daily; group B (n=22), newlydiagnosed SLE patients taking less than 30 mg; and group C (n=22), patients with an established diagnosis taking more than 30 mg daily for the treatment of an exacerbation of symptoms. The development of infectious complications within two months after discharge was identified from a review of the medical records to determine the effect of glucocorticoid dose at the time of discharge on the subsequent development of infectious complications. Results Two patients in group A and three in group C developed infectious complications within two months following discharge, while no patients in group B contracted an infection. These included herpes zoster in group A (n=2) and herpes zoster, urinary tract infection and Pneumocystis jirovecii pneumonia in group C (n=3, one each). However, the incidence of infectious complications comparing groups A and B, and groups A and C was not statistically significantly different( p>0.05). There was no correlation between the incidence of infection and the total dose of glucocorticoids given during admission.Conclusion Although this study was retrospective and involved only a small number of patients with SLE, there is no increased risk of developing infectious complications in pa-tients receiving more than 30 mg of prednisolone daily at the time of hospital discharge, compared to those taking less than 30 mg. Based on these results, prolonging hospitalization only to reduce the dose of prednisolone to less than 30 mg daily lacks justifiable grounds, even if it has been a tacit consensus in Japan.

2005年1月から6月までにアレルギーリウマチ科に入院した100症例を対象とし,入院時と入院1週間後に血中Dダイマー値を測定した。Dダイマーレベルが高値またはその変化が大きかった症例と,下肢深部静脈血栓症(DVT)を疑わせる症状を有する症例について下肢静脈超音波検査を行い,DVTの有無を検査した。その結果,100例中5例にDVTを認めた。うち3例は入院前からDVTを発症しており,2例は入院中に新たにDVTを発症した。DVTがみつかった5症例は全例臨床症状を伴っていたが,臨床症状を伴っていてもDダイマーレベルが上昇していない症例は,下肢静脈超音波検査にてDVTは見られなかった。Dダイマーレベルの変化と臨床症状が見られた症例に対して下肢静脈超音波検査を行うことにより,効率的にDVTを診断できるものと考えられた。

We describe an unusual presentation of a localized form of polyarteritis nodosa (PAN) manifested by fever of undetermined origin (FUO). Biopsies of the gastrocnemius muscle revealed necrotizing arteritis and initiation of prednisolone (PSL) brought rapid response. The PAN localized to muscle is rare furthermore, this disease presented as FUO is very rare. We want to increase awareness that muscle can be also a single-affected site as well as other well known sites such as appendix, gallbladder, uterus or testis, and skin. Since there is no single appellation for this disease, we would like to propose the term "muscular PAN.". © Springer-Verlag 2004.

Vasoactive intestinal peptide (VIP) has been suggested to play some roles in atopic dermatitis. Tissue of VIP levels has been reported to increase in chronic lichenified lesions of atopic dermatitis (AD). To analyze whether serum levels of VIP in AD patients are elevated compared with normal controls and correlated with the disease severity, we measured serum levels of VIP using enzyme-linked immunosorbent assay in 53 patients with AD and 21 healthy individuals. The results showed that serum levels of VIP in AD patients (345.8 +/- 71.5 mug/ml) were significantly higher than those in healthy individuals (307.1 +/- 42.6 mug/ml). However, a correlation was not found between serum VIP levels and disease severity, other markers including serum LDH levels, total serum IgE levels, and peripheral blood eosinophil counts in patients with AD. This indicates that VIP levels in AD patients were elevated not only in the skin but also in the serum, suggesting that increased serum VIP levels in the patients with AD might be involved in its pathogenesis. (C) 2003 Elsevier Science Ireland Ltd. and the Japanese Society of Investigative Dermatology. All rights reserved.

Vasoactive intestinal peptide (VIP) has been suggested to play some roles in atopic dermatitis. Tissue of VIP levels has been reported to increase in chronic lichenified lesions of atopic dermatitis (AD). To analyze whether serum levels of VIP in AD patients are elevated compared with normal controls and correlated with the disease severity, we measured serum levels of VIP using enzyme-linked immunosorbent assay in 53 patients with AD and 21 healthy individuals. The results showed that serum levels of VIP in AD patients (345.8 +/- 71.5 mug/ml) were significantly higher than those in healthy individuals (307.1 +/- 42.6 mug/ml). However, a correlation was not found between serum VIP levels and disease severity, other markers including serum LDH levels, total serum IgE levels, and peripheral blood eosinophil counts in patients with AD. This indicates that VIP levels in AD patients were elevated not only in the skin but also in the serum, suggesting that increased serum VIP levels in the patients with AD might be involved in its pathogenesis. (C) 2003 Elsevier Science Ireland Ltd. and the Japanese Society of Investigative Dermatology. All rights reserved.

Objective. To examine the effects of a novel immunosuppressant, FTY720, on hematolymphoid cells and the clinical course of MRL-1pr/1pr (MRL/1pr) mice genetically predisposed to systemic lupus erythernatosus (SLE). Methods. Apoptosis of hematolymphoid cells was determined in vitro by FACScan after staining with propidium iodide or merocyanine 540. From 4 months of age, 15 female MRL/1pr mice received oral administration of 2 mg/kg each of FTY720, methylprednisolone (mPSL), or vehicle, 3 times per week. Therapeutic efficacy was evaluated by levels of anti-dsDNA antibodies in serum and the survival rate. In parallel, T cell proliferation and secretion of interleukin 2 IL-2) induced by anti-CD3, phenotypes of the spleen, lymph node and bone marrow cells, as well as immunohistochemistry of the kidney, were examined in vitro. Results. FTY720 at 2 muM induced apoptosis in more than 70% of double negative (CD4-/CD8-) T cells from the spleen of MRL/1pr mice in vitro. Oral FTY720 was tolerated well with no apparent side effects. FTY720 treated and control mice gained weight at an identical pace through to 9 months of age. FTY720 significantly suppressed the production of anti-dsDNA antibodies (FTY720 vs control: 1739 +/- 898 U/ml vs 410 +/- 356 U/ml at 8 months of age; p < 0.05) and reduced the deposition of IgG in glomeruli compared to control animals. At 9 months of age, the survival rate in the FTY720 treated mice was 86.9% compared to 33.0% in controls (p < 0.01). FTY720 decreased the number of double negative T cells from the spleen and lymph nodes in vivo, and increased T cell proliferation and IL-2 secretion induced by anti-CD3 stimulation in vitro. Conclusion. FTY720 suppressed the development of autoimmunity and prolonged the lifespan of female MRL/1pr mice. Suppression of autoimmunity, at least in part, may have resulted from an apoptogenic potential of FTY720. Hence, it could be useful for primary or adjunctive therapy of human SLE.

Objective. To examine the effects of a novel immunosuppressant, FTY720, on hematolymphoid cells and the clinical course of MRL-1pr/1pr (MRL/1pr) mice genetically predisposed to systemic lupus erythernatosus (SLE). Methods. Apoptosis of hematolymphoid cells was determined in vitro by FACScan after staining with propidium iodide or merocyanine 540. From 4 months of age, 15 female MRL/1pr mice received oral administration of 2 mg/kg each of FTY720, methylprednisolone (mPSL), or vehicle, 3 times per week. Therapeutic efficacy was evaluated by levels of anti-dsDNA antibodies in serum and the survival rate. In parallel, T cell proliferation and secretion of interleukin 2 IL-2) induced by anti-CD3, phenotypes of the spleen, lymph node and bone marrow cells, as well as immunohistochemistry of the kidney, were examined in vitro. Results. FTY720 at 2 muM induced apoptosis in more than 70% of double negative (CD4-/CD8-) T cells from the spleen of MRL/1pr mice in vitro. Oral FTY720 was tolerated well with no apparent side effects. FTY720 treated and control mice gained weight at an identical pace through to 9 months of age. FTY720 significantly suppressed the production of anti-dsDNA antibodies (FTY720 vs control: 1739 +/- 898 U/ml vs 410 +/- 356 U/ml at 8 months of age; p < 0.05) and reduced the deposition of IgG in glomeruli compared to control animals. At 9 months of age, the survival rate in the FTY720 treated mice was 86.9% compared to 33.0% in controls (p < 0.01). FTY720 decreased the number of double negative T cells from the spleen and lymph nodes in vivo, and increased T cell proliferation and IL-2 secretion induced by anti-CD3 stimulation in vitro. Conclusion. FTY720 suppressed the development of autoimmunity and prolonged the lifespan of female MRL/1pr mice. Suppression of autoimmunity, at least in part, may have resulted from an apoptogenic potential of FTY720. Hence, it could be useful for primary or adjunctive therapy of human SLE.

Soluble human ST2 protein (IL1RL1-a) in the sera of patients with various autoimmune diseases was identified by a newly developed procedure using specific monoclonal antibodies. After immunoprecipitation and subsequent immunoblotting, a glycosylated protein of about 60 kDa was detected in the sera of SLE patients, but not in the sera of healthy controls. The experiments using gel filtration and SDS-PAG;E under a nonreducing condition indicated the existence of the ST2 multimer in serum. The mobility of the natural protein was slower than that of the recombinant human ST2 protein produced by COS7 cells in SDS-PAGE, suggesting a difference of glycosylation between humans and monkeys. The identification of the natural human ST2 protein should be important both to fundamental researches and the further clarification of the clinical implications of the ST2 protein. (C) 2001 Academic Press.

Objective. To investigate the mechanism of autoimmune phenomena, occasionally seen in patients with rheumatoid arthritis treated with bucillamine (BUC) and D-penicillamine (D-Pcn), by evaluating their effects on apoptosis of T cells induced by T cell receptor activation or dexamethasone. Methods. In vitro apoptosis was induced in a T cell hybridoma (SSP3.7) and a B cell line (WEHI 231) by activation of respective receptors or dexamethasone, in the presence or absence of BUC or D-Pen. lit vivo apoptosis was induced in BALB/c mice by staphylococcal enterotoxin B (SEB), with or without BUC or D-Pen, and thymocytes were examined for it by FACS. Results. Stimulation with anti-CD3 and dexamethasone induced apoptosis in 72% and 71% of SSP3.7 cells, respectively. However, only 16% of SSP3.7 cells became apoptotic by anti-CD3 when BUC was added to the culture media. By contrast, 80% of SSP3.7 cells became apoptotic when stimulated by dexamethasone, even in the presence of BUG. BUC did not affect apoptosis of WEHI 231 cells induced by anti-IgM. Although SA981 (a metabolite of BUG) inhibited apoptosis of SSP3.7 cells induced by anti-CD3, D-Pen did not. BUG, SA981, or D-Pen did not significantly influence the level of interleukin 2 secretion stimulated by anti-CD3. In contrast, both BUC and D-Pen inhibited apoptosis of V beta 8+ thymocytes induced in vivo by SEE superantigen. Neither BUC nor D-Pen significantly changed the number of CD4+CD8+ thymocytes in BALB/c mice injected with dexamethasone. Conclusion. BUC decreased, while D-Pen did not, the apoptosis of T cells stimulated by anti-CD3 in vitro, although they both inhibited the deletion of immature thymocytes reactive with SEE in vivo. This may explain autoimmune phenomena sometimes seen during the treatment of rheumatic patients with these drugs.

The frequency, clinical profile, treatment and outcome of subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) were assessed retrospectively, based on the case records of SLE of the Jichi Medical School Hospital over a 20 year period. Clinically defined SAH was found in 10 (3.9%) out of 258 SLE patients, which represented a frequency higher than previously assumed. Five patients had active SLE and lacked an apparent cause of SAH, other than SLE. A high mortality rate (5/5), no visible aneurysm on angiogram (3/4), and an onset during intractable SLE or after discontinued or no steroid therapy because of medical noncompliance (4/5) were characteristic of patients with active SLE, and thus an earlier successful suppression of SLE, if possible, might have plt vented their SAH. In contrast, in the 5 patients with inactive SLE, 2 out of 3 saccular aneurysms were succcessfuly clipped and small bleeding of one patient without aneurysms remitted spontaneously without the need for additional steroid therapy. When one death, which occurred outside of medical care, was excluded, the survival ratio of the hospitalized SAH patients with inactive SLE was significantly better than that with active SLE (3/4 versus 0/5, P = 0.0476). In conclusion, the relatively common occurence of SAH in SLE patients, and a significantly different clinical impact of SAH in respect to active and inactive SLE, were suggested from the results.

A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non- steroidal anti-inflammatory agents, oral prednisolone and low- dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastrointestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of γ- allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of β-and γ-allele. The presence of γ-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.