Should asymptomatic bacteriuria be treated in lupus nephritis?

INTRODUCTION: The risk of infection in systemic lupus erythematosus (SLE) is associated with factors related to disease activity and immunosuppressive treatment. Recently, the persistence of asymptomatic bacteriuria (ASB) has been proposed as an environmental trigger for SLE and its flares, raising the question whether it should be treated systematically to reduce the risk of infection. To our knowledge, there is limited evidence on the screening and treatment of ASB in SLE. OBJECTIVE: The objective is to analyze the occurrence of infection and flare in patients with lupus nephritis with and without ASB. METHODS: A cross-sectional study of a cohort of patients with lupus nephritis during induction therapy with high-dose cyclophosphamide regimen was carried out between January 2018 and 2020, with a total of 37 patients investigated. Urine and blood samples from the two groups (with ASB and without ASB) where taken before the administration of cyclophosphamide. RESULTS: From the sampled 37 patients, 19 (51.4%) had ASB and 18 (48.6%) without ASB; both groups were well balanced in their demographics and clinical characteristics. No statistically significant association was found between the presence of ASB and the systemic lupus erythematosus disease activity index score (p = 0.604), and neither with the 24-h urine protein and leukocyte count (p > 0.177). Urinary tract infection occurred in 5.3% (1) of the patients with ASB, while 5.6% (1) of the patients in the group without ASB presented the infection, and the RR was 0.944 (0.06, 16.33) 95% CI; in addition, no statistically significant association was found between the presence of ASB and the occurrence of infection (p = 1,000). CONCLUSION: Our study did not find a statistically significant association of ASB with the occurrence of infection or disease activity. Further studies need it to clarify this, since treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance.

Copy Number Variation and Frequency of rs179008 in TLR7 Gene Associated with Systemic Lupus Erythematosus in Two Mexican Populations.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.

Recommendations of the Mexican College of Rheumatology for the management of psoriatic arthritis.

Psoriatic arthritis is a chronic systemic inflammatory disease that affects the skin, musculoskeletal structures and other organs and systems compromising functionality, quality of life and reducing the life expectancy of patients. It is a complex disease that requires specialist and timely care and management. The alternatives for treating the manifestations of psoriatic arthritis have increased and the effect of the different agents on specific manifestations has been clarified in recent studies. Therefore, we should incorporate the available evidence to build a strategy for the treatment of these patients. The Mexican College of Rheumatology selected a committee to evaluate these different alternatives and make recommendations. METHODS: The study group included 16 rheumatologists and 3 certified dermatologists, selected from different health institutions and regions of the country. An executive committee was formed to coordinate the meetings and a committee of experts selected the literature search criteria, prepared the research questions, rated the quality of the evidence, and produced the recommendations in the different disease domains based on the GRADE methodology. RESULTS: 24 updated recommendations were generated for the treatment of patients with psoriatic arthritis. The recommendations establish the role of the drugs currently available in our country. The importance of adequate disease control is emphasized, individualizing the level of involvement of each patient in each of the six domains potentially affected by the disease. In addition, the sequence in the choice of treatments available for each domain is established, based on their efficacy, safety profile and accessibility. CONCLUSIONS: With this consensus document, it will be possible to improve the care of patients with psoriatic arthritis. The recommendations were generated based on the best available information and in consideration of the Mexican health system.

Recommendations of the Mexican College of Rheumatology for the management of psoriatic arthritis. / Recomendaciones del Colegio Mexicano de Reumatología para el manejo de la artritis psoriásica.

Psoriatic arthritis is a chronic systemic inflammatory disease that affects the skin, musculoskeletal structures and other organs and systems compromising functionality, quality of life and reducing the life expectancy of patients. It is a complex disease that requires specialist and timely care and management. The alternatives for treating the manifestations of psoriatic arthritis have increased and the effect of the different agents on specific manifestations has been clarified in recent studies. Therefore, we should incorporate the available evidence to build a strategy for the treatment of these patients. The Mexican College of Rheumatology selected a committee to evaluate these different alternatives and make recommendations. METHODS: The study group included 16 rheumatologists and 3 certified dermatologists, selected from different health institutions and regions of the country. An executive committee was formed to coordinate the meetings and a committee of experts selected the literature search criteria, prepared the research questions, rated the quality of the evidence, and produced the recommendations in the different disease domains based on the GRADE methodology. RESULTS: 24 updated recommendations were generated for the treatment of patients with psoriatic arthritis. The recommendations establish the role of the drugs currently available in our country. The importance of adequate disease control is emphasized, individualizing the level of involvement of each patient in each of the six domains potentially affected by the disease. In addition, the sequence in the choice of treatments available for each domain is established, based on their efficacy, safety profile and accessibility. CONCLUSIONS: With this consensus document, it will be possible to improve the care of patients with psoriatic arthritis. The recommendations were generated based on the best available information and in consideration of the Mexican health system.

Acute myocardial infarction, as a rare manifestation in granulomatosis with polyangiitis.

La granulomatosis con poliangeítis es una vasculitis de pequeños vasos asociada a la presencia de anticuerpos anticitoplasma de neutrófilos, con manifestaciones cardíacas que son poco frecuentes, como pericarditis, miocarditis, arteritis coronaria y enfermedad valvular. Reportamos el caso de un paciente de 49 años con reciente diagnóstico de granulomatosis con poliangeítis, quien presentó infarto agudo del miocardio. Se consideró la actividad de la enfermedad como causa del infarto. Las manifestaciones clínicas cardiovasculares en la granulomatosis con poliangeítis son relevantes por ser marcadores de mal pronóstico.Granulomatosis with polyangiitis is a small vessel vasculitis associated to anti-neutrophil cytoplasmic antibodies, in which the cardiac manifestations are not common, as pericarditis, cardiomyopathy, coronary artery disease and vascular disease. We report a clinical case of a 49-year-old man with a recent diagnosis of granulomatosis with polyangiitis, he presented myocardial infarction. Disease activity was considered the cause of myocardial infarction. Cardiovascular clinical manifestations in granulomatosis with polyangiitis are relevant because are markers of poor prognosis.

Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis.

BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA.

IL-17A haplotype confers susceptibility to systemic lupus erythematosus but not to rheumatoid arthritis in Mexican patients.

AIM: Recent studies highlight the importance of the interleukin (IL)-17A cytokine in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). There are also reports of associations between some single nucleotide polymorphisms (SNPs) in IL-17A and RA but not SLE. Notably, these findings have not been replicated in all studied populations. The aim of this study was to investigate whether the IL-17A -737 T/C (rs8193036), -444A/G (rs3819024), -197G/A (rs2275913), and -121G/A (rs8193037) SNPs conferred susceptibility to SLE (or lupus nephritis) or to RA in a Mexican population. METHODS: The study included 1367 Mexican subjects, 501 with RA, 367 with SLE, and 499 healthy controls. IL-17A was genotyped using a TaqMan 5' allelic discrimination assay. RESULTS: Our results showed that the IL-17A -737 T/C, -444A/G, -197G/A, and -121G/A SNPs had similar genotype and allele frequencies in patients with SLE (or lupus nephritis) or RA and in controls. However, an IL-17A haplotype (TAGA) showed an association with SLE susceptibility (odds ratio 2.43, P = 0.004) but not with RA susceptibility. CONCLUSIONS: These results confirm that the IL-17A -737T/C, -444A/G, -197G/A, and -121G/A SNPs are not risk factors for RA, but the IL-17A TAGA haplotype is a risk factor for SLE. This is the first report to document an association between IL-17A and SLE susceptibility in adults.