Clinical disease activity index applicability in lupus arthropathy: Unraveling underdiagnosed joint activity.

INTRODUCTION: Lupus arthropathy (LA) ranges from arthralgia and non-deforming arthritis to severe forms such as Jaccoud-type deformities and mutilating arthritis. Considering the evolving concept of LA, measuring arthritis activity in lupus patients may require a more practical and sensitive tool other than the classical composite scores. METHODS: In this cross-sectional study, we evaluated the articular pattern of a sample of SLE patients which were divided into those that scored in articular domain on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and those with activity arthritis using the Clinical Disease Activity Index (CDAI). After all, we analyzed the association between CDAI and arthritis by SLEDAI-2K as well as its association with the presence or not of Jaccoud-type arthropathy (JA). RESULTS: A total of 127 patients with SLE were evaluated. According to SLEDAI-2K, 17 (13.4%) patients have scored in its joint criteria and 32 patients (25.19%) were considered to have some articular activity by CDAI. A total of 16 patients (50%) who scored some activity on CDAI did not score in articular domain of SLEDAI-2K. Also, the presence of Jaccoud-type arthropathy was significantly associated with arthritis activity according to the CDAI score (p = .014) but not with SLEDAI-2K joint criteria (p = .524). CONCLUSION: The CDAI was not directly associated with the presence of arthritis by the joint criteria of SLEDAI-2K and the presence of JA was significantly associated with the CDAI but not with arthritis at SLEDAI-2K.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study

Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccouds arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position 1237 with psychosis and anemia (p 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição 1237 com psicose e anemia (p 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccouds arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.(AU)

O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.(AU)

Jaccoud's arthropathy in SLE: findings from a Latin American multiethnic population.

OBJECTIVE: To compare the clinical, laboratory and outcome features of SLE patients with and without Jaccoud's arthropathy (JA) from the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort. METHODS: 1480 patients with SLE [(34 centres, 9 Latin American countries with a recent diagnosis (≤2 years)] constitute the GLADEL cohort. JA was defined as reducible deformity of the metacarpophalangeal axis, without radiographic erosions at any time. Within this cohort, a nested case-control study was carried out. Control was matched for age, gender and centre in a 1:3 proportion. The variables included were: sociodemographic, clinical and immunological features, disease activity, damage and mortality. Comparisons were performed with Wilcoxon and χ2 tests for continuous and categorical variables, respectively. ORs and 95% CIs and Kaplan-Meier survival curve were estimated. RESULTS: Of 1480 patients, 17 (1.1%) JA patients were identified; 16 (94.1%) of them were women, mean age: 31.0 years (SD 12.0). Five (29.4%) patients presented JA at SLE diagnosis and 12 (70.6%) after. The median follow-up time and all disease features were comparable in both groups except for a higher frequency of pneumonitis in the patients with JA [4 (23.5) vs 1 (2.0); p=0.012; (OR: 15.4; 95% CI 1.6 to 149.6)]. The SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage Index and the Kaplan-Meier survival curve were similar in both groups. CONCLUSION: JA may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or in survival.

Artropatía de jaccoud en el lupus eritematoso sistémico. Revisión de la literatura a propósito de un caso / Jaccoud arthropathy in Systemic Lupus Erythematosus. Literature review on a case

El Lupus eritematoso sistémico es una colagenosis de etiología aún desconocida, que muestra una patogenia de carácter multifactorial, aunque con marcada referencia autoinmune; ocasiona afectación multisistémica y presenta un curso clínico variable. Es más frecuente en las mujeres que en los hombres en proporción 8:1 y en determinadas razas; su pico de incidencia se sitúa entre los 15 y 40 años de edad. La mayoría de los autores describen la afectación articular del lupus como una artritis no erosiva ni deformante y resulta muy infrecuente que afecte las articulaciones interfalángicas distales. Sin embargo, algunos pacientes pueden presentar erosiones y deformaciones articulares que logran hacerse permanentes, ocasionando una pérdida importante de la función articular. Se presenta el caso de una paciente con dicha complicación por la importancia que reviste su diagnóstico oportuno para evitar el deterioro articular irreversible.

Systemic lupus erythematosus is a collagenous of still unknown etiology, showing a multifactorial pathogenesis, although with marked autoimmune reference; It causes multisystemic involvement and presents a variable clinical course. It is more common in women than in males in proportion 8:1 and in certain races; Its peak incidence is between 15 and 40 years old. Most authors describe the joint involvement of Lupus as a non-erosive or deforming arthritis and is very rare to affect distal interphalangeal joints. However, some patients may have articular erosions and deformations that manage to become permanent, causing a significant loss of joint function. The case of a patient with this complication is presented because of the importance of its timely diagnosis in order to avoid irreversible articular deterioration.

Association of CXCL13 serum level and ultrasonographic findings of joints in patients with systemic lupus erythematosus and Jaccoud's arthropathy.

Objectives The objective of this paper is to perform an ultrasonography (US) analysis of hands and wrists in two groups of patients with systemic lupus erythematosus (SLE), with and without Jaccoud's arthropathy, matched by age and disease duration and to correlate them with levels of CXCL13 clinical features, laboratory tests and disease activity score. Methods Sixty-four patients with SLE were enrolled, 32 with and 32 without Jaccoud's arthropathy. Each patient underwent physical examination, laboratory tests (including CXCL13 by ELISA) and bilateral US. Synovial hypertrophy, tenosynovitis and erosions were evaluated according to a semiquantitative grading system with a 0-3 rating. US findings were correlated with serum levels of CXCL13, other serological parameters and disease activity index. Results Synovitis was found in 25/64 patients (39%) and tenosynovitis in 14/64 (22%). These findings were more frequent in SLE patients with Jaccoud's arthropathy, particularly tenosynovitis ( p = 0.002) and synovitis ( p = 0.01). Median serum level of CXCL13 was 20.16 pg/ml in the whole population (23.21 pg/ml in the Jaccoud's arthropathy group and 11.48 pg/ml in the group without). There was an association between the presence of disease activity and high level of CXCL13 ( p = 0.004). However, no association was found between high levels of CXCL13 and "arthritis" in SLEDAI, swollen joints on physical examination or synovitis on US. Conclusions US findings in joints of SLE patients with Jaccoud's arthropathy confirm that synovitis and tenosynovitis are common in these patients. In addition, serum level of CXCL13 is associated with disease activity in SLE but does not seem to be a biomarker for arthritis in these patients.

Characterization of chronic arthritis in a multicenter study of 852 childhood-onset systemic lupus erythematosus patients.

Chronic arthritis (CA) is an unusual condition in childhood-onset systemic lupus erythematosus (cSLE) and data in children is very limited. The aim of the study is to assess CA in a large population of cSLE patients, in a multicenter cross-sectional study including 852 cSLE patients followed in ten Pediatric Rheumatology referral services in state of São Paulo, Brazil. CA was observed in 32/852 (3.7 %) cSLE patients mostly in hands and ankles. Chronic monoarthritis was diagnosed in four cSLE patients, oligoarthritis in nine and polyarthritis in 19. In the latter group, six had rhupus syndrome. Two oligoarticular patients had Jaccoud's arthropathy. CA was an isolated manifestation observed at disease onset in 13/32 (41 %) cSLE patients, and juvenile idiopathic arthritis (JIA) was the first diagnosis in 18/32 (56 %). The comparison of last visit of patients with CA and without this manifestation revealed higher frequency of splenomegaly (28 vs. 11 %, p = 0.002). The median of SLICC/ACR-DI score [1(0-9) vs. 0(0-7), p = 0.003] was significantly higher in CA patients compared to patients without this manifestation, likewise the frequency of musculoskeletal damage (31 vs. 9 % p = 0.001). Frequencies of treatment with nonsteroidal anti-inflammatory drugs (75 vs. 26 %, p < 0.0001), hydroxychloroquine sulfate (87 vs. 59 %, p = 0.001) and methotrexate (47 vs. 22 %, p = 0.001) were significantly higher in CA patients. This large multicenter study allowed us to characterize CA as a rare and early manifestation of cSLE, frequently mimicking JIA at disease onset. It is predominantly polyarticular, involving more often hands and ankles and it is associated with significant musculoskeletal accrual damage.

Severe Jaccoud's arthropathy in systemic lupus erythematosus.

Jaccoud's arthropathy (JA) is a clinical situation nowadays present mostly in systemic lupus erythematosus (SLE). It is characterized by the presence of joint deformities such as "swan neck," ulnar deviation and "Z-thumb" resembling rheumatoid arthritis (RA) but that are passively correctable and without bone erosion on plain radiographs. From our cohort of SLE patients with JA, we selected a subgroup with a more severe form of this arthropathy and looked at their clinical and laboratory profile as well as studied the magnetic resonance imaging (MRI) findings or ultrasound (US) obtained from the hand with most evident deformities. Seven SLE patients with a severe form of JA were identified. All seven patients have "swan neck," ulnar deviation and "Z-thumb" deformities. Two out of seven had "mutilans-type JA" and four had fixed deformities in the metacarpophalangeal (MCP) joints. The MRI of the hand with more evident deformity clinically performed in six cases and US performed in one case showed mild synovitis in five and moderate synovitis in two patients, mild flexor tenosynovitis in six and severe tenosynovitis in one. Only two small bone erosions were observed in the second and third MCP joints of one patient with moderate synovitis. Severe JA compromises the functional capacity of the joints and imposes the risk of misdiagnosis of RA. With the improvement of the survival rate of SLE and the lack of specific prophylactic or therapeutical measures for JA, it is reasonable to assume that more and more cases of severe JA are going to be identified.