Filipe Martins de Mello

Gout in the spine

Axial gout can affect all segments of the spine. It is manifested as back pain, as pain associated with neurological symptoms, and as neurological impairment without pain in 17.9%, 75.8% and 4.2% of cases, respectively. These manifestations were the first presentation of gout in many patients. Although x-rays as well as computed tomography and especially magnetic resonance scans can be very suggestive, histopathological, cytological and crystal analyses are the diagnostic gold standard. In most cases involving neurological manifestations, the patient underwent surgery, leading to satisfactory results. There are, however, some reports of full recovery following the usual clinical treatment for gout, suggesting that such treatment may be the initial option for those subjects with a history of gout and radiological findings of axial involvement.

Axial gout is frequently associated with the presence of current tophi, although not with spinal symptoms.

Study Design. Prospective cross-sectional study. Objective. To analyze the association of tomographically identified axial gouty lesions with clinical and laboratory characteristics. Summary of Background Data. Axial gout might be more common than previously thought. The true relationship of these lesions to symptoms or other gout-associated features is poorly understood. Methods. Forty-two patients with gout underwent thoracic and lumbar spine computed tomographic (CT) scans. CT scans were read by an experienced radiologist blinded to the features of the patients. Axial gout was defined as the presence of bony erosions, facet joints, or disc calcification and tophi in the axial skeleton. Epidemiological and clinical data were collected from medical records. At study entry, patients were evaluated for axial symptoms (back pain or neurological complaints) and subcutaneous tophi. The Fisher exact test and the Student t test were performed for statistical analyses of data. Results. Twelve (29%) of the 42 patients had CT evidence of axial gout. Axial tophi were identified in 5 patients (12%), interapophyseal joints erosions or calcifications in 7 patients (17%), and discal abnormalities in 9 patients (21%). Lumbar spine involvement was a universal finding. Five patients (42%) had thoracic spine involvement and 2 patients (18%) had sacroiliac lesions. No association was found between symptoms and axial gout (P = 0.62). Duration of gout, mechanism of disease (overproduction vs. underexcretion), and metabolic comorbidities were not related to axial involvement. A higher prevalence of axial gout was found between patients with current peripheral tophi (67% vs. 30%; P = 0.03); however, no association was found in patients with a past history of tophi (P = 0.72). Conclusion. Our study demonstrated a high prevalence of axial gout not associated with spine symptoms. This finding introduces a differential diagnosis in axial lesions in patients with gout. In addition, the unique association with a current but not previous history of peripheral tophi suggests that gout treatment might be effective in preventing or solving gout axial lesions. Level of Evidence: 3

Gota axialGout in the spine

Axial gout can affect all segments of the spine. It is manifested as back pain, as pain associated with neurological symptoms, and as neurological impairment without pain in 17.9%, 75.8% and 4.2% of cases, respectively. These manifestations were the first presentation of gout in many patients. Although x-rays as well as computed tomography and especially magnetic resonance scans can be very suggestive, histopathological, cytological and crystal analyses are the diagnostic gold standard. In most cases involving neurological manifestations, the patient underwent surgery, leading to satisfactory results. There are, however, some reports of full recovery following the usual clinical treatment for gout, suggesting that such treatment may be the initial option for those subjects with a history of gout and radiological findings of axial involvement

Ausência de associação entre os polimorfismos do gene interleucina-18 e artrite reumatoide

OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Lack of association between interleukin-18 polymorphisms and rheumatoid arthritis.

OBJECTIVE To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility

OBJECTIVE This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

FRI0386 Increased prevalence of metabolic syndrome is associated to nephrolithiasis but not to the presence of tophus in GOUT patients

Background Metabolic syndrome (MS) has been frequently associated to gout and, in fact, hyperinsulinemia enhances proximal tubular sodium reabsorption, leading to decreased renal uric acid excretion and hyperuricemia.No data regarding the prevalence of MS in gout subsets according to gout-associated clinical characteristics has been published to date. Objectives To determine the prevalence of MS in a large cohort of patients with gout followed at a single tertiary center, searching for related risk factors including metabolic profile, nephrolithiasis, reduced urate excretion and the presence of tophus. Methods This was a cross-sectional study of 158 patients with gout diagnosed according to the ACR criteria. MS was definedaccording to the National Cholesterol Education Program ATP III (NCEP-ATP III) and the International Diabetes Federation (IDF) criteria.Demographic, anthropometric (body mass index - BMI) and clinical data were collected. Fasting serum levels of uric acid, glucose, triglycerides and cholesterol fractions were analyzed by usual laboratory tests.Nephrolithiasis was demonstrated by routine ultrasonography and urate underexcretion was defined as a uric acid clearance lower than 7.5 ml/min. Fisher’s exact, chi-square, student’s T and Spearman’s test were used for statistical analysis and P≤0.05 was considered significant. Results Mean age of patients was 62.7±12.2 yrs (33 – 90 yrs), and 90.5% were males. Mean BMI was 29.13±5.70 kg/m2 (19.0 – 55.1 kg/m2). Hypertension was observed in 84.5% of patients, current alcohol consumption in 22.8%, coronary artery disease in 21% and diabetes mellitus in 19%. Mean serum uric acid, fasting glucose, triglycerides, LDL, HDL levels were 6.84 mg/dL, 107.2 mg/dL, 198.7 mg/dL, 116.7 mg/dL, 47.2 mg/dL respectively. Of note, 31% had nephrolithiasis and 52.5% had tophi. Estimated creatinine clearance was 73.15±29.35 ml/min and 86.1% patients manifested urate underexcretion.Remarkably, more than 70% of gout patients had MS (73% and 71% according to NCEP ATPIII and IDF criteria respectively). This increased prevalence of MS was alike in patients with tophaceous and non tophaceous gout, and regardless of uric acid excretionstatus (p>0,05). In contrast, the prevalence of MS was significantly higher in patients with nephrolithiasis compared to those without this complication (84.7% vs. 65.2%; p=0.026). Conclusions The elevated prevalence of MS in Brazilian gout patients (almost ¾) is higher than previously reported overall rates of MS in gout worldwide (62.8%) and in control populations (25.4%), suggesting possible interference of, dietary, geographical and/or genetic background. Our demonstration, for the first time, of increasedMS prevalence in gout unrelated to the occurrence of tophus, but associated to nephrolithiasis may suggest shared underlying physiopathologic mechanisms, such as the effect of hyperinsulinemia on the kidneys.Further studies are urged to clarify this relationship and therefore allow improvement of multiprofessional management of gout patients, in order to reduce long-term complications and prevent associated comorbidities. Disclosure of Interest None Declared

SAT0369 Spinal Lesions due to Tophaceous Gout – a Differential Diagnosis not Related to Symptoms

Background Axial gout was first described in 1950, and, since then, only a few anecdotal cases with severe neurological manifestations and adverse outcomes have been reported. Although traditionally considered to be rare, some evidences suggest that axial lesions due to gout might be more common than previously thought. The true relationship of these lesions to symptoms or other gout-associated features is poorly understood. Objectives We, therefore, aimed to describe the frequency of axial skeleton lesions in gout patients and to analyze the possible association of tomographically-identified axial gouty lesions and patients’ clinical or physiopathological characteristics. Methods Forty-two patients with gout diagnosed according to the 1977 ACR criteria underwent thoracic and lumbar spine computerized tomographic (CT) scans. CT scans were read by an experienced radiologist who was blinded to the clinical features of the patients. Axial gout was defined when specific gout features such as bony erosions, facet joints or disc calcification and tophi were present in the axial skeleton. Patients were included and underwent the scans in a prospective fashion, and a cross-sectional analysis of data was performed. Epidemiologic and clinical data were collected from chart reviews. All patients were questioned about axial symptoms (back pain or neurological complaints) and examined clinically, in the inclusion visit, for subcutaneous tophi. Urate hypoexcretion was defined as a urate clearance of less than 7.5 ml/min. Hyperuricemia was defined as a serum uric acid higher than 7.0 mg/dL for men or higher than 6.0 mg/dL for women. Chi-square, Fisher’s exact test and Student’s T test were performed for statistical analyses of association between variables. Results Patients were mainly male (93%). Mean age was 62.7 ± 11.1 years. Twelve (29%) of the 42 patients had CT evidence of axial gout, with axial tophi being identified in 5 (12%) subjects, interapophyseal joints erosions or calcifications in 7 (17%) and discal abnormalities (erosions or calcifications) in 9 (21%) subjects. Lumbar spine was always affected. Five (42%) had thoracic spine involvement and 2 (18%) had sacroiliac lesions as well. Despite the high prevalence of back pain and/or neurological manifestations (48% of the total population), no association was found between axial symptoms and axial gout (p=0,62). Duration of gout, mechanism of disease (hyperproduction vs. hypoexcretion) and metabolic commorbidities were also not related to the presence of axial involvement. Interestingly, a higher prevalence of axial gout was found between patients with current peripheral tophi (67% v. 30%; p=0,03), however no association was found with a past history of tophi that had already vanished due to therapy (p=0,72). Conclusions Our study found out a striking 29% prevalence of spine lesions in gout patients. When dealing with axial lesions in these patients, a suitable differential diagnosis that should be remembered is axial gout itself, even in the absence of symptoms, since it might be more common than previously thought and no association with axial symptoms has been reported. The fact that axial lesions were associated to currently existing peripheral tophi but not to a previous history of tophi points out to the fact that gout treatment might be effective in preventing or solving axial lesions. Disclosure of Interest None Declared