RESUMEN
BACKGROUND AND OBJECTIVE: Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus. METHODS: We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg-/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort. RESULTS: Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg-/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3-8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg-/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users. CONCLUSIONS: In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg-/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg-/HBcAb+ patients is probably safe.
Asunto(s)
Antirreumáticos/farmacología , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Hígado/enzimología , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Antirreumáticos/uso terapéutico , Artritis Psoriásica/virología , Artritis Reumatoide/virología , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Terapia de Inmunosupresión , Incidencia , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Espondilitis Anquilosante/virología , Activación Viral/efectos de los fármacos , Adulto JovenRESUMEN
Introduction Mercury poisoning causes hearing loss in humans and animals. Acute and long-term exposures produce irreversible peripheral and central auditory system damage, and mercury in its various forms of presentation in the environment is ototoxic. Objective We investigated the otoacoustic emissions responses in a riverside population exposed to environmental mercury by analyzing the inhibitory effect of the medial olivocochlear system (MOCS) on transient otoacoustic emissions (TEOAE). Methods The purpose of the research was to evaluate the entire community independently of variables of sex and age. All of the participants were born and lived in a riverside community. After otolaryngologic evaluation, participants were received tympanometry, evaluation of contralateral acoustic reflexes, pure tone audiometry, and recording of TEOAEs with nonlinear click stimulation. Hair samples were collect to measure mercury levels. Results There was no significant correlation between the inhibitory effect of the MOCS, age, and the level of mercury in the hair. Conclusions The pathophysiological effects of chronic exposure may be subtle and nonspecific and can have a long period of latency; therefore, it will be important to monitor the effects of mercury exposure in the central auditory system of the Amazon population over time. Longitudinal studies should be performed to determine whether the inhibitory effect of the MOCS on otoacoustic emissions can be an evaluation method and diagnostic tool in populations exposed to mercury. .
Asunto(s)
Humanos , Espondiloartritis/epidemiología , África del Sur del Sahara/epidemiología , Artritis Psoriásica/epidemiología , Artritis Psoriásica/genética , Artritis Psoriásica/virología , Artritis Reactiva/epidemiología , Artritis Reactiva/genética , Artritis Reactiva/virología , Predisposición Genética a la Enfermedad , Infecciones por VIH/complicaciones , /genética , Espondiloartritis/diagnóstico , Espondiloartritis/genética , Espondiloartritis/virología , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/virologíaRESUMEN
Spondyloarthritis (SpA) is generally uncommon in sub-Saharan Africa, in part because of the rarity of HLA-B27 in this region. However, the relationship between HLA-B27 and SpA, particularly ankylosing spondylitis (AS), is complex. Despite the HLA-B 27:05 risk allele occurring in some West African populations, associated AS is not seen. In fact, most patients with AS are HLA-B27-negative, although there is emerging evidence that another class I HLA molecule, HLA-B 14:03, is associated with AS in black Africans. The Assessment of SpondyloArthritis International Society criteria for detecting early axial disease are of limited value in sub-Saharan Africa, because of both the rarity of HLA-B27 and very limited access to magnetic resonance imaging. Reactive arthritis (ReA), psoriatic arthritis, and undifferentiated SpA are seen mainly in the context of HIV infection, although the exact effect of the virus in the pathogenesis of arthritis is unclear. In Zambia, ReA is associated with the HLA-B*57:03 allele, which is paradoxically also associated with slow progression of HIV infection. HIV-associated ReA has a more protracted and aggressive course than standard ReA. Enthesitis-related arthritis is more common in children infected with HIV by vertical mother-to child transmission. Use of TNF inhibitors for axial disease is problematic, mainly because of cost, but also because of potential safety problems, especially reactivation of tuberculosis.
Asunto(s)
Espondiloartritis/epidemiología , África del Sur del Sahara/epidemiología , Artritis Psoriásica/epidemiología , Artritis Psoriásica/genética , Artritis Psoriásica/virología , Artritis Reactiva/epidemiología , Artritis Reactiva/genética , Artritis Reactiva/virología , Predisposición Genética a la Enfermedad , Infecciones por VIH/complicaciones , Antígeno HLA-B27/genética , Humanos , Prohibitinas , Espondiloartritis/diagnóstico , Espondiloartritis/genética , Espondiloartritis/virología , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/virologíaRESUMEN
Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNFα agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNFα treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNFα treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNFα treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNFα therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to anti-viral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNFα, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.
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Artritis Reumatoide/virología , Virus de la Hepatitis B/metabolismo , Hepatitis B/virología , Espondilitis Anquilosante/virología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Secuencias de Aminoácidos , Antivirales/farmacología , Artritis Reumatoide/complicaciones , ADN Polimerasa Dirigida por ADN/metabolismo , Femenino , Hepatitis B/complicaciones , Humanos , Lamivudine/farmacología , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Espondilitis Anquilosante/complicaciones , Activación ViralRESUMEN
OBJECTIVE: The risk of non-Hodgkin lymphoma is increased in rheumatoid arthritis (RA) but not in ankylosing spondylitis (AS). In RA, the degree of inflammation is closely associated with the lymphoma risk. Whether immunosuppressants such as methotrexate and TNFα antagonists affect the lymphoma risk in RA is unclear. The Epstein-Barr virus (EBV) may contribute to the pathogenesis of RA and may be involved in the development of lymphoma in patients taking methotrexate and/or TNFα antagonists, although these points remain debated. EBV load monitoring during immunosuppressive treatment may predict the occurrence of EBV-related lymphoma. Here, our objective was to prospectively measure the EBV load in patients receiving TNFα antagonists for RA or AS. METHODS: We prospectively studied patients with RA or AS before and after TNFα antagonist therapy initiation. The EBV load was measured in blood samples using the EBV R-gene Quantification Kit. Disease activity at the time of blood sampling was evaluated by determining the Disease Activity Score 28 (DAS28) in RA patients and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: We included 46 patients with RA (82.6% women; mean age, 52.7 ± 11.3 years) and 27 with AS (men, 81.5%; mean age, 45.1 ± 12.7 years). In the RA group, the EBV load was measured at baseline and 9.72 ± 5.7 months later. The baseline EBV load was undetectable in 33 (70.2%) patients; mean EBV load in the 13 remaining patients was 9389 copies/ml (3.47 log10 ± 0.45). Baseline EBV load did not correlate with disease activity (DAS28). At the follow-up assay, the EBV load became positive in five patients and increased significantly in one patient (four patients on etanercept, one on adalimumab, and one on infliximab); it became negative in six patients (five on adalimumab and one on etanercept) and showed non-significant changes in six patients. Mean EBV load in patients positive at follow-up was 3.63 ± 0.52 log10 copies/ml. Mean DAS28 was 4.78 ± 1.1 at baseline and 2.94 ± 1.24 at follow-up. At follow-up, a good EULAR response was noted in 33 (71.7%) patients and a moderate EULAR response in seven (15.2%) patients. In the AS group, the baseline EBV load measurement occurred after 12.9 ± 10.6 months. Baseline EBV load was undetectable in 25 (92.6%) patients; mean load in the remaining two patients was 4.15 ± 0.46 log10 copies/ml. At follow-up, the EBV load became positive in two patients (one on adalimumab and one on infliximab) and became negative in one patient (on adalimumab). Mean load in positive patients was 3.33 ± 0.24 log10 copies/ml. Mean BASDAI was 55.1 ± 16.2 at baseline and 17.88 ± 18.62 at follow-up. A positive EBV load was significantly more common in the RA group than in the AS group (P = 0.039). EBV load changes did not differ significantly between the RA and AS groups or across TNFα antagonists. No cases of lymphoma were recorded. CONCLUSION: Introducing TNFα antagonist therapy does not affect the EBV load in patients with RA or AS. EBV load monitoring is probably unnecessary in patients given TNFα antagonists for RA or AS.
Asunto(s)
Antirreumáticos/farmacología , Artritis Reumatoide/virología , Espondilitis Anquilosante/virología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Carga Viral/efectos de los fármacos , Adalimumab , Adulto , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Antirreumáticos/uso terapéutico , Etanercept , Femenino , Herpesvirus Humano 4 , Humanos , Inmunoglobulina G/farmacología , Inmunoglobulina G/uso terapéutico , Infliximab , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
The aim of this study was to determine whether FCRL5 genes in concert with human leukocyte antigen-B27 (HLA-B27) genotypes are associated with susceptibility to ankylosing spondylitis (AS) in Chinese population. One hundred and sixty-nine HLA-B27-positive AS patients (107 males and 62 females) and 184 HLA-B27-positive matched controls (112 males and 72 females) were analyzed from Han Chinese populations by case-control design, and their samples were genotyped using a panel of two single-nucleotide polymorphism (SNP) markers (rs6427384, rs12036228) within the FCRL5 gene by ligase detection reactions (LDRs) and the HLA-B27 subtypes were determined by polymerase chain reaction (PCR) using sequence-specific primer (SSP) methods. Our results show that in addition to B27, the SNPs rs6427384 and rs12036228 were associated with AS, and the C-T haplotype was higher in cases with AS than in the control population [74.8% vs 63.6%, Fisher's P = 0.003, odds ratio (OR) = 1.660,95% confidence interval (CI) = 1.184-- 2.326]. Our results suggest that, in addition to HLA-B27, a novel polymorphism within the FCRL5 gene confers susceptibility to AS in Han Chinese population.
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Antígeno HLA-B27/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Superficie Celular/genética , Espondilitis Anquilosante/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , China , Femenino , Antígeno HLA-B27/clasificación , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Receptores Fc , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/virologíaAsunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Virus de la Hepatitis B , Hepatitis B/tratamiento farmacológico , Espondilitis Anquilosante/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales de Origen Murino , Femenino , Hepatitis B/inmunología , Humanos , Rituximab , Espondilitis Anquilosante/virologíaRESUMEN
OBJECTIVE: The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of >200 mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients suggests that treatment with anti-TNF-alpha therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.
Asunto(s)
Antirreumáticos/uso terapéutico , Seropositividad para VIH/complicaciones , Enfermedades Reumáticas/virología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Fármacos Anti-VIH/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Terapia Antirretroviral Altamente Activa , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/virología , Artritis Reactiva/tratamiento farmacológico , Artritis Reactiva/virología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/virología , Recuento de Linfocito CD4 , Etanercept , Femenino , Estudios de Seguimiento , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/inmunología , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/inmunología , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/virología , Resultado del Tratamiento , Carga ViralRESUMEN
Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales Humanizados , Artritis Psoriásica/inmunología , Artritis Psoriásica/patología , Artritis Psoriásica/virología , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/inmunología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/patología , Humanos , Infliximab , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/patología , Espondilitis Anquilosante/virología , Activación Viral/efectos de los fármacos , Activación Viral/inmunologíaAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Apoptosis , Artritis Psoriásica/patología , Artritis Psoriásica/virología , Progresión de la Enfermedad , Hepacivirus/efectos de los fármacos , Hepacivirus/inmunología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/virología , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Espondilitis Anquilosante/patología , Espondilitis Anquilosante/virología , Activación Viral/efectos de los fármacos , Activación Viral/inmunologíaRESUMEN
Anti-TNFalpha therapy for rheumatic diseases appears to be safe in patients with chronic hepatitis C. However, the administration of anti-TNFalpha agents without initiation of prophylactic antiviral therapy (lamivudine 100 mg/day) in patients with chronic HBV infection results in exacerbation of liver disease. In this report, we describe our experience of long-term anti-TNFalpha therapy for ankylosing spondylitis in two inactive HBsAg carriers without preemptive antiviral treatment.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/virología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Etanercept , Hepatitis B Crónica/complicaciones , Humanos , Infliximab , Pruebas de Función Hepática , Masculino , Inducción de RemisiónRESUMEN
The possible role of infectious microorganisms in the disease process of both arthritis and autoimmunity continue to attract both basic and clinical researchers. However, proving a causal role for these suspects is a very difficult and complicated task. This article provides an update on various mechanisms in which microbes may play roles as inciting or perpetuating factors in the pathogenesis of connective tissue disease. It also focuses on current theories that specific microorganisms may play a role in rheumatoid arthritis and ankylosing spondylitis.