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Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Vacunas contra la COVID-19 , COVID-19 , Lupus Eritematoso Sistémico , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Persona de Mediana Edad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inducido químicamente , Masculino , Enfermedades Reumáticas/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Glucocorticoides/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Vacunación/efectos adversos , Anciano , AdultoRESUMEN
Osteoclasts, derived from the monocyte/macrophage line of bone marrow hematopoietic stem cell progenitors, are the sole bone-resorbing cells of the body. Conventional osteoclast differentiation requires macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune disease and inflammatory arthritis characterized by bone destruction. Increased levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in the serum and joints, cause excessive bone destruction. We have recently reported that stimulation of human peripheral blood monocytes with TNF-α and IL-6 induces the differentiation of osteoclasts with bone resorption activity. This review presents the functional differences between representative osteoclasts, conventional RANKL-induced osteoclasts, and recently identified proinflammatory cytokine (TNF-α and IL-6)-induced osteoclasts in RA patients. We believe novel pathological osteoclasts associated with RA will be identified, and new therapeutic strategies will be developed to target these osteoclasts and prevent the progression of bone destruction.
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Artritis Reumatoide , Resorción Ósea , Humanos , Osteoclastos/patología , Osteoclastos/fisiología , Factor de Necrosis Tumoral alfa , Interleucina-6 , Resorción Ósea/etiología , Resorción Ósea/patología , CitocinasRESUMEN
We herein report a case of diffuse large B-cell lymphoma (DLBCL) involving multiple renal and bone infiltrations presenting with giant cell arteritis-like (GCA)-like manifestations. One month prior, the present patient had left-sided temporal headache, jaw claudication, and renal failure. The patient was diagnosed with DLBCL based on a renal biopsy. After rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus intrathecal methotrexate/cytarabine/prednisone and rituximab, high-dose methotrexate, and cytarabine (R-MA) chemotherapy, the patient's clinical manifestations improved, and complete remission was achieved. DLBCL rarely but occasionally presents with GCA-like manifestations or multiple renal and bone infiltrations, highlighting the need for prompt and aggressive combination chemotherapy.
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We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.
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Artritis Reumatoide , Enfermedades Autoinmunes , COVID-19 , Miositis , Síndrome de Sjögren , Enfermedades del Nervio Trigémino , Femenino , Humanos , Adulto , Síndrome de Sjögren/complicaciones , SARS-CoV-2 , Vacunas contra la COVID-19/efectos adversos , COVID-19/complicaciones , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Miositis/etiología , ARN Mensajero , VacunaciónRESUMEN
During the treatment of a patient on hemodialysis with severe coronavirus disease 2019 (COVID-19), the patient was weaned from extracorporeal membrane oxygenation, which was used to treat severe COVID-19 pneumonia. However, the patient's condition worsened after the peak infection phase of COVID-19 because of acute respiratory distress syndrome with suspected hemophagocytic lymphohistiocytosis (HLH). After a bone marrow biopsy confirmed the diagnosis, methylprednisolone pulse therapy, followed by combination therapy (including oral prednisolone and cyclosporine) was immediately administered, and the patient survived. Because HLH can occur a month or more after the onset of COVID-19, even if the viral load is reduced to the point of being undetectable by reverse transcriptase-polymerase chain reaction, it can be considered to correspond to the "post-acute COVID-19 syndrome," which has recently been proposed. Early intervention is necessary, because HLH can be fatal. Therefore, it is important to know that HLH can occur at any stage of COVID-19 and to pay attention to the patient's progress over time, including checking the HScore.
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COVID-19 , Linfohistiocitosis Hemofagocítica , Humanos , COVID-19/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Médula Ósea/patología , BazoRESUMEN
We herein report a 49-year-old Japanese man with relapsing polychondritis (RP) and aseptic meningoencephalitis. Four years ago, the patient was diagnosed with RP. Prednisolone (PSL) was started at 30 mg/day, and the symptoms promptly disappeared. However, cognitive impairment gradually appeared from six months before hospitalization. Methylprednisolone pulse therapy was immediately initiated, followed by administration of PSL at 1 mg/kg/day. Intravenous cyclophosphamide was combined with PSL. After treatment, the patient's cognitive impairment clearly improved. In conclusion, RP rarely causes aseptic meningoencephalitis, highlighting the need for prompt and aggressive immunosuppressive therapy.
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Meningoencefalitis , Policondritis Recurrente , Masculino , Humanos , Persona de Mediana Edad , Policondritis Recurrente/complicaciones , Policondritis Recurrente/diagnóstico , Policondritis Recurrente/tratamiento farmacológico , Meningoencefalitis/complicaciones , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Prednisolona/uso terapéutico , Ciclofosfamida/uso terapéutico , Terapia de Inmunosupresión/efectos adversosRESUMEN
Herein, we report the case of a 67-year-old man with severe coronavirus disease (COVID-19) pneumonia and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine breakthrough infection during immunosuppressive therapy for connective tissue disease-related interstitial lung disease (CTD-ILD). The patient received glucocorticoids combined with tacrolimus as maintenance therapy. His serum anti-SARS-CoV-2-immunoglobulin G (IgG) antibody levels were extremely low at the onset of COVID-19 pneumonia, even after the second dose of SARS-CoV-2 mRNA vaccine (BNT162b2). After treatment for COVID-19 pneumonia, the levels of anti-SARS-CoV-2-IgG antibodies increased. These results indicated a lack of the ability to produce neutralising antibodies from immune cells despite the booster vaccination. Therefore, we suggest that advanced-age patients with CTD-ILD receiving immunosuppressive therapy with polypharmacy require consistent personal protection, vaccination of close caregivers, increased awareness, and booster vaccination. Moreover, we recommend that tacrolimus should be withdrawn for a while after vaccination under controlled conditions.
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COVID-19 , Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Masculino , Humanos , Anciano , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162 , Infección Irruptiva , Tacrolimus/uso terapéutico , SARS-CoV-2 , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Terapia de Inmunosupresión , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.
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Artritis Reumatoide , Síndrome de Sjögren , Humanos , Femenino , Abatacept/efectos adversos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Estudios Prospectivos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Administración IntravenosaRESUMEN
Since December 2020, coronavirus disease 2019 (COVID-19) vaccines have been distributed in most countries to prevent the onset and aggravation of COVID-19. There is little information regarding the long-term safety of the vaccines. We report three cases and a literature review of new-onset adult-onset Still's disease (AOSD) that occurred following COVID-19 vaccination. Our cases include moderate to severe AOSD, and two were complicated with macrophage activation syndrome. Seventeen cases of new-onset or relapse of AOSD following COVID-19 vaccination, including 14 identified in the literature review and our 3 patients, were all treated successfully with glucocorticoid therapy, immunosuppressive drugs, or biologic agents.
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Vacunas contra la COVID-19 , COVID-19 , Enfermedad de Still del Adulto , Adulto , Humanos , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Inmunosupresores/efectos adversos , Enfermedad de Still del Adulto/etiología , Enfermedad de Still del Adulto/complicaciones , Vacunación/efectos adversosRESUMEN
We encountered a 57-year-old Japanese woman with encapsulating peritoneal sclerosis (EPS) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis. The patient was admitted to our hospital because of ascites retention. Administration of tocilizumab, an anti-interleukin-6 receptor antibody, for her RA reduced the refractory ascites remarkably; however, she developed sudden acute gastrointestinal bleeding and died a year later. On autopsy, sclerotic thickening of the peritoneum showed diffuse infiltration of podoplanin-positive fibroblast-like cells, and a diagnosis of EPS was made. EPS rarely occurs in SLE, and tocilizumab may be a new treatment candidate for EPS.
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Artritis Reumatoide , Lupus Eritematoso Sistémico , Fibrosis Peritoneal , Esclerodermia Sistémica , Femenino , Humanos , Persona de Mediana Edad , Fibrosis Peritoneal/etiología , Ascitis/complicaciones , Artritis Reumatoide/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Esclerodermia Sistémica/complicacionesRESUMEN
Introduction: Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively. Case Description: A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud's phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40. Conclusion: In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.
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OBJECTIVE: We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. METHODS: Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. RESULTS: Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1ß, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. CONCLUSION: Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.
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Artritis Reumatoide/inmunología , Resorción Ósea/inmunología , Interleucina-6/inmunología , Osteoclastos/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/metabolismo , Densidad Ósea , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/metabolismo , Estudios de Casos y Controles , Citocinas/efectos de los fármacos , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Humanos , Subunidad p40 de la Interleucina-12/efectos de los fármacos , Subunidad p40 de la Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12/metabolismo , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/farmacología , Masculino , Metaloproteinasa 3 de la Matriz/efectos de los fármacos , Metaloproteinasa 3 de la Matriz/inmunología , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Factores de Transcripción NFATC/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/inmunología , Ligando RANK/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Streptococcus pyogenes is a rare pathogen that causes endogenous endophthalmitis (EE). A healthy 58-year-old woman was diagnosed with EE secondary to septic arthritis caused by S. pyogenes. She underwent enucleation after hospitalization for 14 days with appropriate antibiotic cover. A literature search for outcomes of this condition revealed reports on only 10 eyes among 8 cases identified: 8 eyes (80%) developed poor visual outcome and 5 eyes (50%) underwent enucleation. There were no cases with immunocompromise. Our case report and literature review suggest the importance of awareness of the occurrence of S. pyogenes infection in immunocompetent hosts, and thus early diagnosis and aggressive treatment may be required to improve visual outcome.
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Artritis Infecciosa , Endoftalmitis , Infecciones Estreptocócicas , Streptococcus pyogenes , Antibacterianos/uso terapéutico , Artritis Infecciosa/complicaciones , Artritis Infecciosa/microbiología , Endoftalmitis/diagnóstico , Endoftalmitis/microbiología , Endoftalmitis/terapia , Enucleación del Ojo , Femenino , Humanos , Persona de Mediana Edad , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/terapiaRESUMEN
Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.
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Artritis Reumatoide/sangre , Proteína C-Reactiva/análisis , Enfermedades de las Arterias Carótidas/sangre , Articulaciones/diagnóstico por imagen , Componente Amiloide P Sérico/análisis , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Progresión de la Enfermedad , Femenino , Humanos , Articulaciones/patología , Masculino , Persona de Mediana EdadRESUMEN
AIM: Superb microvascular imaging (SMI), a novel ultrasonography, is based on the sensitivity of Doppler technology. This study evaluated power Doppler (PD) ultrasound signals in patients with rheumatic disease using SMI and conventional PD imaging (cPDI) and compared the correlations of these signals to clinical assessments. METHODS: Thirty-nine patients with rheumatic disease (27 rheumatoid arthritis [RA] and 12 non-RA) were enrolled. We investigated SMI and cPDI signals in 26 joints using an Aplio 300. Individual scores were summed to calculate total SMI and cPDI scores. RESULTS: Total SMI scores were significantly higher than total cPDI scores in patients with RA, but not in those with the non-RA disease. Total SMI score was associated with serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity score 28-CRP and health assessment questionnaire disability index scores, and SMI were more sensitive to detect active synovitis than cPDI in RA patients. Among the joint regions, the wrists and metacarpophalangeal joints were more sensitive to the detection of synovial inflammation using SMI in patients with RA. CONCLUSION: SMI was more sensitive in detecting synovial inflammation than cPDI in patients with RA. SMI could be a potentially useful imaging modality for accurately diagnosing and monitoring the disease activity of RA.
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Artritis Reumatoide/diagnóstico por imagen , Articulación Metacarpofalángica/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Ultrasonografía Doppler/normasRESUMEN
Osteoclasts are differentiated from precursors of the monocyte/macrophage lineage originated from bone marrow hematopoietic stem cells and are the sole bone-resorbing cells in the body. Osteoclast differentiation is thought to require M-CSF (macrophage colony-stimulating factor) and RANKL (receptor activator of nuclear factor kappa-B ligand) signaling. However, it has recently been proposed that under chronic inflammatory conditions, such as systemic autoimmune diseases (e.g., rheumatoid arthritis), an increase in inflammatory cytokine levels within joints induces pathological osteoclast differentiation, causing excessive bone resorption. In addition, the authors have reported that stimulating mouse bone marrow monocytes and human CD14+ monocytes with combination of TNFα and IL-6 can induce differentiation of osteoclast-like cells, which are cells with bone resorption activity. In the present article, we discuss the mechanism of osteoclast differentiation of RANKL-independent bone-resorbing cells, using both data from the aforementioned report as well as the latest findings. Understanding the mechanisms underlying RANKL-independent, cytokine-mediated osteoclast differentiation could facilitate the development of novel therapies for inflammatory joint diseases.
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Diferenciación Celular/genética , Inflamación/etiología , Inflamación/patología , Osteoclastos/citología , Osteoclastos/fisiología , Animales , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Resorción Ósea/etiología , Citocinas/fisiología , Descubrimiento de Drogas , Humanos , Mediadores de Inflamación/fisiología , Interleucina-6/fisiología , Factor Estimulante de Colonias de Macrófagos , Ratones , Terapia Molecular Dirigida , Osteoclastos/patología , Ligando RANK/fisiología , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
When patients with autoimmune diseases, such as rheumatoid arthritis (RA), are treated with potent immunosuppressive therapy, the risk of opportunistic diseases inevitably increases. If patients have the misfortune to suffer from both opportunistic and active autoimmune diseases, correct diagnosis could sometimes be difficult since both diseases have inflammatory nature. The choice of treatment is another challenge in that aggressive immunosuppressive therapy can fuel the opportunistic infection. Here we report a case of RA patient with new onset rheumatoid vasculitis that was diagnosed in the process of treatment of Pneumocystis jirovecii pneumonia.
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Artritis Reumatoide/complicaciones , Infecciones Oportunistas/complicaciones , Pneumocystis carinii , Neumonía por Pneumocystis/complicaciones , Vasculitis Reumatoide , Anciano , Diagnóstico Diferencial , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Vasculitis Reumatoide/diagnóstico , RiesgoRESUMEN
We report the case of a Japanese woman with amyloid light chain (AL) amyloidoma in the abdominal aortic retroperitoneum and mesentery. Irregular soft tissue mass lesions with calcification in the abdominal aortic retroperitoneum and mesentery were initially detected by computed tomography at another hospital. The lesions gradually compressed the duodenum, causing symptoms of bowel obstruction. The patient was clinically diagnosed with retroperitoneal fibrosis, and prednisolone was administered at a dose of 40 mg/day. However, the lesions did not change in size and her symptoms continued. She was transferred to our hospital and underwent mesenteric biopsy for histopathology using abdominal laparotomy. The histopathological and immunohistological findings of the mesenteric specimen demonstrated lambda light chain deposition. Accordingly, the patient was finally diagnosed with AL amyloidoma with no evidence of systemic amyloidosis. After laparotomy, her general condition worsened because of complications of pneumonia and deep vein thrombosis. She died suddenly from acute myocardial infarction. We have concluded that abdominal aortic retroperitoneal and mesenteric AL amyloidoma may have very poor prognoses in accordance with previous reports. In addition, the size and location of AL amyloidoma directly influence the prognosis. We suggest that early histopathology is important for improving prognosis.
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OBJECTIVE: Synovial fibroblasts (SFs) produce matrix-degrading enzymes that cause joint destruction in rheumatoid arthritis (RA). Epigenetic mechanisms play a pivotal role in autoimmune diseases. This study was undertaken to elucidate the epigenetic mechanism that regulates the transcription of matrix metalloproteinases (MMPs) in RASFs. METHODS: MMP gene expression and histone methylation profiles in the MMP promoters were examined in RASFs. The effect of WD repeat domain 5 (WDR5) silencing on histone methylation and MMP gene expression in RASFs was analyzed. MMP gene expression, surface expression of the interleukin-6 (IL-6) receptor, phosphorylation of STAT-3, and binding of STAT-3 in the MMP promoters were investigated in RASFs stimulated with IL-6. RESULTS: The MMP-1, MMP-3, MMP-9, and MMP-13 genes were actively transcribed in RASFs. Correspondingly, the level of histone H3 trimethylated at lysine 4 (H3K4me3) was elevated, whereas that of H3K27me3 was suppressed in the MMP promoters in RASFs. The decrease in H3K4me3 via WDR5 small interfering RNA reduced the levels of messenger RNA for MMP-1, MMP-3, MMP-9, and MMP-13 in RASFs. Interestingly, IL-6 signaling significantly increased the expression of MMP-1, MMP-3, and MMP-13, but not MMP-9, in RASFs. Although the IL-6 signaling pathway was similarly active in RASFs and osteoarthritis SFs, STAT-3 bound to the MMP-1, MMP-3, and MMP-13 promoters, but not the MMP-9 promoter, after IL-6 stimulation in RASFs. CONCLUSION: Our findings indicate that histone methylation and STAT-3 regulate spontaneous and IL-6-induced MMP gene activation in RASFs. The combination of chromatin structure and transcription factors may regulate distinct arthritogenic properties of RASFs.
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Artritis Reumatoide/genética , Fibroblastos/metabolismo , Regulación de la Expresión Génica/inmunología , Histonas/metabolismo , Interleucina-6/inmunología , Metaloproteinasas de la Matriz/genética , Factor de Transcripción STAT3/inmunología , Membrana Sinovial/citología , Artritis Reumatoide/inmunología , Western Blotting , Estudios de Casos y Controles , Inmunoprecipitación de Cromatina , Fibroblastos/inmunología , Citometría de Flujo , Código de Histonas , Humanos , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/inmunología , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/inmunología , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/inmunología , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Metaloproteinasas de la Matriz/inmunología , Metilación , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/inmunología , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Activación TranscripcionalRESUMEN
A 64-year-old man presented with a complaint of left exophthalmos. Whole-body F-FDG PET/CT showed increased uptake in the soft tissue masses in the orbits, peripancreas, and left renal hilum. C-methionine (MET) PET/CT of the head and neck showed increased uptake in the orbits, and the SUVmax of the left orbital lesion was 7.0. The patient was finally diagnosed as IgG4-related disease by the results of increased serum IgG4 and the biopsy of the orbital lesion. Although C-MET is generally considered as a tumor-specific tracer, fibrous tissues of IgG4-related disease may be visualized by C-MET PET/CT.