SAMUEL KATSUYUKI SHINJO
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Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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article 4 Citação(ões) na Scopus Miopatia inflamatória induzida por adalimumab na artrite reumatóide(2012) SOUZA, Fernando Henrique Carlos de; BARROS, Thiago Bitar Morais; LEVY-NETO, Mauricio; SHINJO, Samuel KatsuyukiThe application of immunobiologics for the rheumatoid arthritis treatment may present as a rare complication the development of inflammatory myopathy. Until this moment, there have been described in literature only seven cases of inhibitors of tumor necrosis factor induced-myositis. In this paper, we report the case of the patient with 39 years-old with eight years of arthritis rheumatoid and that due to refractory to various immunosuppressive drugs, the adalimumab was introduced, and evolved to dermatomyositis status.- Antiphospholipid syndrome and dermatomyositis/polymyositis: a rare association(2012) SOUZA, Fernando Henrique Carlos de; LEVY-NETO, Mauricio; SHINJO, Samuel KatsuyukiThe association between antiphospholipid syndrome and idiopathic inflammatory myopathies has been rarely reported in the literature. In this paper we report two patients with antiphospholipid syndrome diagnosed with concomitant dermatomyositis or polymyositis. We also reviewed the literature on this overlapping of two systemic autoimmune entities.
- Dermatomiosite recém-diagnosticada em idosos como preditiva de malignidade(2012) SOUZA, Fernando Henrique Carlos de; SHINJO, Samuel KatsuyukiObjetivo: Os sintomas da dermatomiosite (DM) podem ser um indício da existência de um câncer oculto. Melhorar a detecção precoce é essencial, porém não há estudos avaliando em curto prazo os fatores preditivos para a doença. Método: Estudo retrospectivo, monocêntrico, incluindo pacientes com DM definida (pelo menos quatro dos cinco critérios de Bohane Peter, 1975), no período entre 1991 e 2011. A presença de malignidade foi limitada a um período de até 12 meses após o diagnóstico da doença. Resultados: Houve 12 casos de neoplasias em 139 pacientes (pele, trato gastrintestinal, próstata, tireoide, mama, pulmão e trato geniturinário). Os pacientes com neoplasia tiveram maior média de idade que os controles (56,8 ± 15,7vs. 40,3 ± 13,1 anos, respectivamente, P = 0,004; odds ratio 1,09; intervalo de confiança de 95%: 1,04–1,14). Não foram observadas diferenças estatísticas em relação a gênero, etnia, frequência de sintomas constitucionais, envolvimento de órgãos e sistemas e/ou alterações laboratoriais. Conclusão: Na DM recém-diagnosticada, a idade tardia ao diagnóstico foi um fator preditivo de malignidade.
conferenceObject Peripheral Neuropathy Due to Systemic Lupus Erythematosus (SLE) Itself: Incidence, Disease Risk Factors and Outcome(2012) FARGETTI, Simone; SHINJO, Samuel K.; PASOTO, Sandra G.; CALICH, Ana L.; BONFA, Eloisa; BORBA, Eduardo F.Background/Purpose: Peripheral neuropathy (PN) solely attributable to SLE itself is difficult to define since most of these patients are exposed to several other conditions that may cause this manifestation. The aim is to determine characteristics and outcome of PN attributed exclusively to SLE and its possible association with clinical/laboratorial features in a large cohort. Methods: SLE patients (ACR 1997) with PN were identified from our Lupus Outpatient Clinic computerized database of 1038 patients. Only patients with definitive PN proved by electroneuromyography were included. Exclusion criteria were conditions related to PN: diabetes mellitus, alcohol consumption, use of any drug related to neuropathy (thalidomide, statins, etc.), thyroid disease, infection, cancer, vitamin B12 deficiency, renal or hepatic failure, and other autoimmune disease (antiphospholipid syndrome, Sjogren’s syndrome, etc.). Medical records were extensively reviewed and included clinical/laboratorial data, treatment, and evolution. Each SLE patient with PN [n 22] was compared with 2 SLE patients without PN (controls) [n 44] that were age- and sex-matched and had similar disease duration. Results: PN exclusively attributed to SLE was identified in 22 patients (2.1%). The mean age (34.4 11.6 vs. 33.9 9.6 years, p 0.85) and disease duration (9.2 7.7 vs. 9.9 6.8 years, p 0.73) of PN were similar to controls. The interval between SLE onset and PN diagnosis was 4.9 5.7 years and the mean SLEDAI scores was higher in PN patients (5.4 7.6 vs. 1.8 2.9,p 0.001). The most common pattern on electroneuromyography was sensorimotor polyneuropathy of lower limbs (50%), followed by monon-europathy (26.9%), and polyradiculoneuropathy (15.3%). PN was associated to hematological involvement (72.7% vs. 43.2%,p 0.036), leukopenia (50% vs. 20.5%,p 0.022), lymphopenia (68.2% vs. 29.5%,p 0.004), cutaneous vasculitis (54.5% vs. 22.7%,p 0.014), and anti-Sm (50% vs. 15.9%,p 0.007). Multivariate analysis revealed that PN was related to anti-Sm (OR 5.36; 95%CI 1.37–20.99) and cutaneous vasculitis (OR 4.97; 95%CI 1.23–20.08). All SLE patients received corticosteroids, most of them associated with immunosuppressive drug (59% cyclophosphamide; 31.8% azathioprine). After immunosuppressive therapy, 63.6% improved of neurological symptoms and 31.8% remained stable. Conclusion: Our study suggested that PN attributed to SLE itself is rare in the absence of other conditions and seems to be strongly associated to anti-Sm antibodies and cutaneous vasculitis. A favorable outcome with immunosuppressive therapy is observed in most of SLE patients with this neurological manifestation.- Adult dermatomyositis: experience of a Brazilian tertiary care center(2012) SOUZA, Fernando Henrique Carlos de; BARROS, Thiago Bitar Moraes; LEVY-NETO, Mauricio; SHINJO, Samuel KatsuyukiObjective: To report the results of a retrospective cohort involving 139 patients with dermatomyositis, conducted from 1991 to 2011. Methods: All patients met at least four of the five Bohan and Peter criteria (1975). Results: The patients' mean age at disease onset was 41.7 +/- 14.1 years, and mean disease duration was 7.2 +/- 5.2 years. The sample comprised 90.2% white patients and 79.9% female patients. Constitutional symptoms occurred in less than half of the patients. Cutaneous and joint involvements occurred in 95.7% and 41.7% of the patients, respectively. Incipient pneumopathy, ground glass opacities and/or pulmonary fibrosis were present in 48.2% of the patients. All patients received prednisone (1 mg/kg/day) and 51.1% also received intravenous methylprednisolone (1 g/day for three days). Several immunosuppressants were used as corticosteroid sparing agents according to tolerance, side effects and/or refractoriness. Although disease relapse (clinical and/or laboratory) occurred in 53.2% of the patients, 76.3% were in disease remission at the end of the study. The rate of severe infection was 35.3%, and herpes zoster predominated. There were 15(10.8%) cases of cancer, 12 within one year after the diagnosis. There were 16 deaths (11.5%), and their major causes were sepsis/septic shock (27.5%), pneumopathy attributed to the disease (31.3%), neoplasms (31.3%), and cardiovascular events (12.5%). Conclusions: In this study, the clinical and laboratory data were similar to those of other population groups described in the literature, with minimal differences regarding the frequency and characteristics of the extramuscular manifestations.
- Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis(2012) SHINJO, Samuel Katsuyuki; SALLUM, Adriana Maluf Elias; SILVA, Clovis Artur; MARIE, Suely Kazue NagahashiOBJECTIVE: To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis. METHOD: In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter's criteria) and a control group consisting of four dystrophic and five Pompe's disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X). RESULTS: The mean ages at disease onset were 42.0 +/- 15.9 and 7.3 +/- 3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a significantly higher frequency of major histocompatibility complex I (96.4% vs. 50.0%, p<0.001) compared with major histocompatibility complex II expression (14.3% vs. 53.6%, p = 0.004) was observed in juvenile dermatomyositis. Fiber damage (p = 0.006) and increased connective tissue (p<0.001) were significantly higher in adult dermatomyositis compared with the presence of perifascicular atrophy (p<0.001). The results of the histochemical and histological data did not correlate with the demographic data or with the clinical and laboratory features. CONCLUSION: The overexpression of major histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.
- Overexpression of Ankyrin Repeat Domain Containing Protein 1 Gene (ANKRD1) in Dermatomyositis Muscle Biopsies Is Correlated to Hypoxia and Perifascicular Atrophy(2012) SHINJO, Samuel K.; OBA-SHINJO, Sueli M.; UNO, Miyuki; MARIE, Suely K. N.Background/Purpose: ANKRD1 codes for ankyrin repeat domain containing protein 1, which belongs to the muscle ankyrin repeat protein family involved in a mechano-signaling pathway that links myofibrillar stress response to muscle gene expression. In addition, ANKRD1 has an important role in transcriptional regulation, myofibrillar assembly, cardio-genesis, myogenesis and also possibly in angiogenesis. Microvasculopathy is considered as a cornerstone and early pathological change in dermatomyositis (DM), leading to hypoxia, capillary necrosis and muscle perifascicular atrophy. These alterations could upregulate genes involved in myogenesis and angiogenesis like ANKRD1. Therefore, we analyzed ANKRD1 expression in muscle biopsies of DM patients and correlated with other hypoxia parameters. Methods: RNA was extracted from frozen muscle biopsies samples of 30 untreated adult DM patients (Bohan and Peter’s criteria, 1975). As a control group, we analyzed 20 muscle biopsies with no histological change from untreated adult patients with non-inflammatory myopathy diseases. The gene coding for hypoxia-inducible factor 1, alpha subunit (HIF1A) was analyzed to estimate hypoxia degree. The ANKRD1 and HIF1A transcript expression levels were determined by quantitative real time PCR using Sybr Green method. Perifascicular atrophy was analyzed histologically by semi-quantitative method of HE stained biopsies. Expression and localization of ANKRD1 and HIF1a in muscle biopsies was accessed by immunohistochemistry. Results: Higher ANKRD1 and HIF1A expressions levels were observed in DM relative to control group (p<0.001 and p<0.001). In addition, the expression levels of both genes were correlated (r=0.703, P=0.001). We also observed a positive correlation of both genes to perifascicular atrophy (r=0.420, p=0.023 and r=0.404, p=0.030, respectively). However, ANKRD1 and HIF1A expression levels did not correlate to demographic, clinical and laboratory features (p>0.05). Immunohistochemistry showed that ANKRD1 and HIF1a were expressed mainly by atrophic muscle perifascicular cells. Conclusion: Our results demonstrated ANKRD1 is overexpressed, correlated to HIF1A in perifascicular atrophic fibers of DM muscle specimens. ANKRD1 involvement in myogenesis and angiogenesis mechanism will be further investigated.
- Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and polymyositis: Immunogenicity independent of therapy and no harmful effect in disease(2012) SHINJO, Samuel Katsuyuki; MORAES, Julio Cesar Bertacini de; LEVY-NETO, Mauricio; AIKAWA, Nadia Emi; RIBEIRO, Ana Cristina de Medeiros; SAAD, Carla Goncalves Schahin; PRECIOSO, Alexander; SILVA, Clovis Artur; BONFA, EloisaThe goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1 +/- 9.9 vs. 43.8 +/- 8.4 years, p = 0.607) and gender distribution (p = 1.00) were comparable between the patients and controls. After 21 days, seroconversion (p = 0.394), seroprotection (p = 0.08), GMT (p = 0.573) and the FI in the GMT (p = 0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p = 0.20) and aldolase levels (p = 0.98), the physicians' VAS (p = 1.00), the patients' VAS (p = 1.00) and the MMT-8 (p = 1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p = 0.969), GC >0.5 mg/kg/day (p = 0.395) and GC + immunosuppressors (p = 0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p > 0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.(c) 2012 Elsevier Ltd. All rights reserved.
article 3 Citação(ões) na Scopus Hepatite autoimune e dermatomiosite: uma rara associação(2012) SOUZA, Fernando Henrique Carlos de; BARROS, Thiago Bitar Moraes; MORAES, Mariana Teichner de; MISSUMI, Larissa Sayuri; LIMA, Fabiana Roberto; LEVY-NETO, Mauricio; SHINJO, Samuel KatsuyukiThe association between autoimmune hepatitis and idiopathic inflammatory myopathies has been rarely described in literature. To our knowledge, there are only five reports of autoimmune hepatitis, all coursing with polymyositis. In the present work, we describe a female patient at the age of 58 with cutaneous lesions (heliotrope), progressive proximal muscle weakness of four limbs and constitutional symptoms for 12 months, and worsened two months ago. She had also been episodes of jaundice for five months. During hospitalization, after intense clinical investigation, the diagnosis of dermatomyositis and autoimmune hepatitis were defined, and the patient had a good clinical and laboratory response to corticosteroids and immunosuppressive.conferenceObject Combined Glucosamine and Chondroitin Sulfate, Once of Three Times Daily, Provide Clinically Relevant Analgesia in Knee Osteoarthritis(2012) PROVENZA, Jose R.; SHINJO, Samuel K.; SILVA, Joyce M.; PERON, Carla R. G. S.; ROCHA, Francisco A. C.Background/Purpose: The analgesic efficacy of combined glucosamine and chondroitin sulfate (CS) in knee osteoarthritis (OA) remains controversial. Criticism to previous studies includes small sample size, short term evaluation and lack of intent-to-treat (ITT) analysis. Glucosamine sulfate (GS) or hydrochloride (GH) formulations and dosing schedule relevance are also not clearly defined. Methods: 1,120 subjects with radiographic knee OA (Kellgren/Lawrence grades 2–3) and moderate-severe knee pain flare after analgesic washout were randomized (1:1:1) at 16 centers in Brazil to receive GS 500mg/CS 400mg three times daily capsules (GI) or once daily sachet (GII), or GH 500mg/CS 400mg three times daily capsules (GIII) for a 16 week trial. Acetaminophen up to 3,750mg daily was a rescue medication. Primary outcome (ITT) was patient reported pain intensity in the affected knee and variation of Lequesne’s index (LI) at 16 weeks. Monthly secondary outcomes were mean changes from baseline in patient reported pain and LI, patient and physician global assessments of disease activity, acetaminophen consumption, and adherence. Sample size calculation considered a non-inferiority evaluation allowing a difference of less than 1.7 points in the LI and a decrease of pain less than 18mm in GI and GII, as compared to GIII. Safety evaluations were done at each monthly visit. Results: The ITT population comprised 302, 301, and 306 patients in GI, GII and GIII, respectively, and 911 patients for safety. Demographic data were equally comparable in all groups. The criterion for non-inferiority analysis of GI and GII in relation to GIII, based on confidence interval (95%), was met for pain intensity and LI. The mean of pain reduction (GI: -30.9±1.5; GII: -28.7±1.5; GIII: -29.7±1.5 mm) was significant for all groups at week 16 (P<0.001). Similarly, the mean of LI decrease was significant in all groups (GI: -3.8±0.2; GII: -3.7±0.2; GIII: -3.9±0.2) (P<0.001). Moreover, reduction of acetaminophen consumption (-5, -3, and -5 weekly tablets for GI, GII, and GIII, respectively) was also significant in all groups (P<0.005). Withdrawal rate was 18.2%, 19.3%, and 19.3% for GI, II, and III. Patients that did not complete the study were 77 (44.8%) for lack of adherence, 16 (9.3%) consent withdrawal, 11 (6.4%) adverse events, 8 (4.7%) lost to follow-up, and 17 (9.9%) for other causes. Conclusion: This is the largest study showing that GS/CS and GH/CS provide clinically meaningful and sustained analgesia in knee OA regardless of dose fractionation. GS/CS (capsule or sachet) and GH/CS formulations are equally effective and safe to treat symptomatic knee OA.