-
[show abstract]
[hide abstract]
ABSTRACT: This study demonstrates whether serum β2-microglobulin (β2-MG) level can be an indicator of the status of systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and development of hemophagocytic syndrome (HPS) complication. Serum β2-MG level was compared between the active and inactive statuses of SLE and AOSD in hospitalized patients. Active status was defined as a state for which a therapy was introduced. Serum β2-MG level was also compared between patients with and without HPS complication. HPS was diagnosed on the basis of clinical and pathological findings. Laboratory markers of HPS including peripheral blood cell counts and levels of serum lactate dehydrogenase (LDH), serum ferritin, plasma fibrin/fibrinogen degradation product (FDP), and plasma D-dimer were examined to determine their correlations with serum β2-MG level. Sixteen SLE and seven AOSD patients (all females, aged 39.0 ± 16.4) were included. The serum β2-MG level was high in the active status of underlying diseases and decreased significantly after the therapy (3.5 ± 1.4 vs. 2.1 ± 0.8 mg/L, p < 0.001). Among patients with active status, the β2-MG level was higher in patients with HPS (two with SLE and three with AOSD) than in patients without HPS (4.9 ± 1.8 vs. 3.3 ± 1.4 mg/L, p < 0.05). Serum β2-MG level significantly correlated with the levels of serum LDH (r s = 0.42, p < 0.05), plasma FDP (r s = 0.58, p < 0.05), and plasma D-dimer (r s = 0.77, p < 0.01). Serum β2-MG level would be a useful indicator of disease activity and development of HPS complication in patients with SLE and AOSD.
Clinical Rheumatology 03/2013; · 2.00 Impact Factor
-
Allergology International 06/2012; 61(3):503-5.
-
International Journal of Rheumatic Diseases 04/2012; 15(2):e31-3. · 0.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angioedema with eosinophilia (AE) is mostly reported in Japanese patients, and only as case reports. In this study, we aimed to determine how prevalent AE cases appear, the characteristic features and the course of AE, and to evaluate whether corticosteroid therapy for AE is necessary or not.
The patients whose blood samples showed an eosinophil count of ≥2,000/μL, among the samples tested for blood cell counts and differential counts between January 2006 and December 2010, in Japanese Red Cross Medical Center, were firstly included. Among these, patients with AE were extracted.
All of the 11 patients were Japanese young females. One patient with arthralgia showed radioisotope accumulation in the joints by bone scintigraphy. The peak peripheral blood eosinophil count was 7,839 ± 6,008 (2,130-23,170)/μL after visiting our hospital. An increase in white blood cell count was only due to an increase in eosinophil count. Serum C-reactive protein and IgE levels remained almost normal. Peripheral blood eosinophil count decreased steadily for 8 weeks, regardless of corticosteroid use. Edema in all of the patients and arthralgia in 6 patients improved within 12 weeks. As far as followed, none of the patients had a recurrence of AE.
AE developed in Japanese young females and likely showed a single course. In AE, the count of eosinophil of 104/μL was observed. Only eosinophil count increased among leukocyte series. Serum C-reactive protein and IgE levels remained almost normal. The eosinophil count in AE patients will return to the normal level within 8 weeks even without corticosteroid therapy.
Allergology International 02/2012; 61(2):259-63.
-
Nihon Naika Gakkai Zasshi 07/2011; 100(7):1956-8.
-
Arerugī = [Allergy] 01/2011; 60(1):1-8.
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate the cut off levels of serum KL-6 indicating patients with interstitial pneumonitis (IP) and patients with active IP associated with connective tissue diseases (CTDs).
CTD patients whose serum KL-6 level was measured were included. IP was diagnosed on the basis of medical records including XP/CT findings, and active IP was assumed in case that intervention for IP was newly added. The cut off levels were determined by receiver operating characteristic (ROC) curve analysis.
Among 240 (174 females) patients, 67 (42) had IP and 15 (9) had active IP. The ages of patients with and without IP, and with active IP and with inactive IP were 70.3±9.5 and 62.8±15.3, and 72.8±8.1 and 69.6±9.8, respectively. IP was significantly more prevalent in males and the elderly. The KL-6 levels were 990±90 and 301±12 U/mL in patients with and without IP, and 1,905±236 and 726±54 U/mL in those with active IP and with inactive IP, respectively. ROC curve analysis showed a cut off level of 509 U/mL for indicating IP, and that of 1,051-1,060 U/mL for indicating active IP.
A serum KL-6 level of higher than 500 U/mL is a marker of the presence of IP, and a level of higher than 1,000 U/mL is a marker of the presence of active IP associated with CTDs.
Internal Medicine 01/2011; 50(23):2889-92. · 0.94 Impact Factor
-
Rheumatology (Oxford, England) 05/2010; · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis.
The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-alpha, interleukin 6, interferon-gamma, ferritin, and beta2-microglobulin (beta2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered.
Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still's disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and beta2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; beta2m: 18.8 vs 5.4 mg/dl, p = 0.0058).
The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ss(2)m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.
The Journal of Rheumatology 03/2010; 37(5):967-73. · 3.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The present history is most important to pick out an allergen causative of his/her allergy. Skin tests or tests for serum are available for the detection of allergen-specific IgE. Skin tests include prick test and intradermal test. The former should be preceded the latter to avoid systemic allergic adverse reactions with the latter. Each test for blood or skin has both merits and demerits. Sensitivity of skin test is better than blood test. Skin patch test can detect delayed type allergy, additionally cross reacting antigens should be concerned. The immunologic mechanism of drug allergy has not yet been elucidated enough.
Nippon rinsho. Japanese journal of clinical medicine 11/2009; 67(11):2109-14.
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA.
The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it.
Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P = 0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of <60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 +/- 9.4 vs 10.1 +/- 8.1 mg/dl, P = 0.03) and a low albumin level (2.7 +/- 0.6 vs 3.3 +/- 0.5 g/dl, P = 0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 +/- 394 vs 1203 +/- 399/microl, P = 0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered.
Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.
Rheumatology (Oxford, England) 09/2009; 48(10):1265-8. · 4.24 Impact Factor
-
Osamu Kaminuma,
Fujiko Kitamura,
Shoichiro Miyatake,
Kazuko Yamaoka,
Hiroyuki Miyoshi, Shigeko Inokuma,
Hideki Tatsumi,
Soichi Nemoto,
Noriko Kitamura,
Akio Mori,
Takachika Hiroi
[show abstract]
[hide abstract]
ABSTRACT: Regardless of T(H)1/T(H)2 theory, CD4(+) T cells of patients with allergic asthma, a typical T(H)2 disease, and those of healthy subjects expressed equivalent levels of IFN-gamma, even though T(H)2 cytokines were significantly upregulated in asthmatic patients.
The mechanisms underlying distorted T(H)2 cell polarization in human T cells were elucidated.
Cytokine-producing activity and the expression of T(H)1/T(H)2-specific transcription factors in naïve, T(H)1/T(H)2, or both CD4(+) T cells derived from human peripheral and cord blood were comparatively analyzed. The mechanisms of the differential expression of T-box 21 transcription factor (T-bet) in the cells were assessed by determining the chromatin accessibility at the TBX21 gene. The functional roles of T-bet and other transcription factors in human T(H)1/T(H)2 differentiation were further investigated.
T(H)2 cells derived from naive CD4(+) T cells in peripheral blood but not in cord blood produced IFN-gamma. T-bet was expressed in peripheral, but not cord blood, resting naive T cells. Consistently, the accessibility at the proximal TBX21 gene promoter in peripheral naive T cells was higher than that in cord blood naive T cells. IFN-gamma-producing activity was induced in T(H)2-differentiated cord blood T cells by means of ectopic expression of T-bet. In addition, a reduction of T-bet in peripheral T cells suppressed IFN-gamma production. T-bet not only upregulated IFN-gamma but also downregulated IL-4 and IL-13 gene transcription, independently of the modification of T(H)1/T(H)2 balance.
The expression of T-bet at a naive stage is crucial for the development of IFN-gamma-producing T cells in human peripheral blood, even in T(H)2-related diseases.
The Journal of allergy and clinical immunology 05/2009; 123(4):813-23.e3. · 9.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan.
We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan. Multivariable logistic analysis was performed to identify the risk factors for newly developed and/or exacerbation of ILD.
Sixty-one (1.2%) of 5054 RA patients who received LEF were reported to have development and/or exacerbation of ILD as an adverse drug reaction to LEF, judged by the attending physicians. Multivariable logistic regression analysis identified pre-existing ILD [odds ratio (OR) 8.17; 95% CI 4.63, 14.4], cigarette smoking (3.12; 95% CI 1.73, 5.60), a low body weight (<40 kg vs >50 kg) (2.91; 95% CI 1.15, 7.37) and the use of a loading dose (3.97; 95% CI 1.22, 12.9) as independent risk factors for LEF-induced ILD.
Pre-existing ILD was the most important risk factor for LEF-induced ILD. We suggest that LEF should not be prescribed for RA patients complicated with ILD.
Rheumatology (Oxford, England) 04/2009; 48(9):1069-72. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate the background and clinical features of intrapulmonary hemorrhage in collagen-vascular diseases (CVD) patients.
The charts of collagen-vascular diseases patients who were hospitalized and had intrapulmonary hemorrhages between 1981 and 2006 were retrospectively examined for underlying diseases, clinical and laboratory features, and treatments and outcomes.
Of 4,017 patients, 11 females aged 52.1+/-12 had total of 17 episodes of diffuse or non-diffuse intrapulmonary hemorrhage. Fourteen episodes of diffuse alveolar hemorrhage (DAH) developed in 4 microscopic polyangiitis (MPA) patients having a high MPO-ANCA level, 4 systemic lupus erythematosus (SLE) patients having a high SLEDAI score, and 1 SLE/MPA patient having a high MPO-ANCA level. Among the 9 DAH patients, 2 had complicated Goodpasture syndrome, 3 had thrombotic thrombocytopenic purpura (TTP), and 1 had disseminated intravascular coagulation. In DAH the peripheral blood hemoglobin level decreased from 9.3+/-2.2 (n=13) to 6.8+/-1.5 g/dL (n=14, p<0.0001) at 0.5+/-0.7 g/dL/day, and the lymphocyte count decreased from 854+/-424 to 462+/-376 /microL. No patient died of DAH, including 1 who spontaneously remitted. The 3 episodes of non-DAH included 2 pulmonary aneurysm ruptures in 1 SLE patient, and 1 thromboembolism that developed in 1 SLE patient who had anti-phospholipid antibody; their SLEDAI scores were low and these remitted spontaneously.
Of intrapulmonary hemorrhage in CVD patients, DAH developed with active MPA or SLE, upon which Goodpasture syndrome or TTP was occasionally superimposed. With DAH, the magnitude of peripheral blood Hb level decrease was approximately 0.5 g/dL/day, and the lymphocyte count decreased. No patient died of DAH.
Internal Medicine 01/2009; 48(11):891-7. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n=9) and without (n=13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.
Modern Rheumatology 07/2008; 18(5):442-6. · 1.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 62-year-old man developed a fever, fatigue, anorexia and arthralgia. Central hypocorticoidism and central hypothyroidism were observed, and a low serum antidiuretic hormon level without symptoms of diabetes insipidus, as well. Images showed swelling of pituitary stalk, mediastinal and hilar lymphnodes and pancreas, pulmonary infiltrates and retroperitoneal mass. Serum CRP level was 20.6 mg/dL, and IgG4 level was 292 mg/dL. Lung biopsy revealed pseudotumor containing IgG4-positive plasmacytes, and obliterative vasculitis both in arterioles and venules. These features were similar to those of reported IgG4-related autoimmune disease. However, replacement steroid therapy for hypocorticoidism brought about almost complete recovery except that diabetes insipidus got apparent. This is the first report on the efficacy of only a small dose of steroid, and on features of pituitary stalk involvement and central hypocorcicoidism.
Internal Medicine 02/2008; 47(12):1139-42. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 60-year-old rheumatoid arthritis (RA) female with lung fibrosis was treated with leflunomide (LEF) for only 12 days, and responded well. Twenty-five days after the withdrawal of the drug, she had fever, dyspnea, and an elevated serum C-reactive protein level. Chest CT revealed ground-glass opacities (GGOs) and consolidations forming a mosaic pattern, in lung fields including the upper, anterior and central areas, and honeycomb patterns in the lung bases and backs. The level of plasma A771726, an active metabolite of LEF, was still as high as that usually noted under LEF therapy. After pulsed steroid and cholestyramine administration, A771726 was depleted and she recovered. The peripheral blood lymphocyte count that had been approximately 1,000/microL, decreased to 220/microL just at the onset of lung injury, and rapidly and steadily returned to the preinjury level preceding recovery from the injury. Serum albumin level decreased in association with lung injury, and gradually returned to the preinjury level. Special caution is necessary when prescribing leflunomide to elderly patients with preexisting interstitial lung disease, and remains necessary until at least 1 month after its withdrawal.
Modern Rheumatology 02/2008; 18(1):96-9. · 1.58 Impact Factor
-
Internal Medicine 02/2008; 47(19):1763-4. · 0.94 Impact Factor
-
Arerugī = [Allergy] 11/2007; 56(10):1240-7.
-
[show abstract]
[hide abstract]
ABSTRACT: Weekly pulsed low-dose methotrexate (MTX) is a standard regimen for rheumatoid arthritis (RA). Severe adverse reactions to MTX, such as pneumonia and cytopenia, sometimes occur; however, it is difficult to predict the development of these adverse reactions. In this article, we examine the serum concentrations of orally administered MTX of 69 Japanese patients with RA in the clinical setting. The maximum serum concentration (C (max)) after the first dose of the weekly administration and the time at which C (max) was obtained (T (max)) were analyzed. C (max) correlated with the administered dose before measurement. The average T (max) was 2.0 +/- 0.8 h, and none of the patients showed a T (max) of more than 4 h. In addition, we demonstrated that the weekly MTX dosage and the mean dosage of steroids were significantly higher in patients with adverse reactions than in those without them, and the C (max) after the first dose of the weekly administration particularly correlated with the incidence of adverse reactions (P < 0.001). In fact, the cut-off point of C (max) (0.16 micromol/l) was a sensitive predictor of the adverse reactions (sensitivity 81% and specificity 67%). We concluded that C (max) after the first dose of weekly administration is a useful parameter for predicting the development of adverse reactions to MTX.
Modern Rheumatology 01/2007; 17(4):311-6. · 1.58 Impact Factor
