Diagnostic Delay in Ankylosing Spondylitis: Related Factors and Prognostic Outcomes.

OBJECTIVES: This study aims to evaluate diagnostic delay, factors which are related to diagnostic delay, and the effect of diagnostic delay on prognostic outcomes in terms of spinal and hip mobility, functional status, disease activity, quality of life, cervical rotation, tragus to wall distance, and sacroiliitis severity in an Iranian population with ankylosing spondylitis (AS). PATIENTS AND METHODS: One hundred and sixty three patients (129 males, 34 females; mean age 37.74±9.88 years; range 18 to 65 years) with AS who met modified New York 1984 criteria were enrolled consecutively in a cross sectional survey. The main outcome variable (diagnostic delay) was defined as the interval between appearance of first symptoms and correct diagnosis of AS. Enthesitis, negative human leukocyte antigen B27 (HLA- B27), and educational level were among the factors of which their relationship to diagnostic delay were evaluated. The prognostic outcomes were measured using Bath ankylosing spondylitis functional index, Bath ankylosing spondylitis disease activity index, AS quality of life, Bath ankylosing spondylitis metrology index, chest expansion, and radiographic sacroiliitis severity. RESULTS: Diagnostic delay was mean 7.88±7.17 years. Diagnostic delay was longer in patients with enthesitis (8.80±7.27) compared to patients without enthesitis (6.04±6.66) (p=0.007) and in HLA-B27 negative patients (10.10±7.44) compared to HLA-B27 positive patients (7.14±6.96) (p=0.013). Educational level was negatively correlated with diagnostic delay (p=0.002, r= -0.24). Diagnostic delay was correlated with Bath ankylosing spondylitis functional index (p=0.003, r=0.23), Bath ankylosing spondylitis disease activity index (p=0.026, r=0.18), AS quality of life (p=0.008, r=0.21), Bath ankylosing spondylitis metrology index (p<0.001, r=0.41), chest expansion (p<0.001, r= - 0.38), and sacroiliitis grading (p=0.042, r=0.16). CONCLUSION: Negative HLA-B27, enthesitis, and low educational level are factors which affect diagnostic delay in AS. Individuals with enthesitis or low educational level should be evaluated accurately without causing delay in diagnosis since longer delay may lead to poorer prognostic outcomes.

Gender differences in Iranian patients with ankylosing spondylitis.

Inequalities in features and severity of ankylosing spondylitis (AS) have been noticed between men and women, suggesting a possible influence of gender on disease phenotypes. Comparing disease features and characterization of gender differences in clinical features and medications could help elucidate the potential influence of gender on the severity of AS in patients. This study aims to assess the influence of gender on disease patterns in Iranian patients with AS. Three hundred and twenty patients diagnosed with primary AS were assessed for demographic variables, clinical manifestations, HLA status, disease severity, functional capacities, quality of life, and treatment status. Sixty-seven women and 253 men were included corresponding to a male to female ratio of 3.78:1. Both groups were similar regarding ethnicity, positive family history, and juvenile onset AS. HLA-B27 was more frequent among males (78.3 vs. 55.2%; p < 0.001). There was a higher proportion of female patients with overall enthesitis (p < 0.05). Extra-articular manifestations and treatment modalities presented similar frequencies in both genders. No difference in gender-associated diagnostic delays was observed. Female disease was at least as severe as male disease, and in some aspects, females presented with more severe disease. Despite a relatively similar disease profile, we observed a higher rate of enthesitis among women. Together with the equally high rate of disease activity indices in both genders, these findings indicate an overall longer delay to diagnosis in our country. Early detection and specialized care would be of great practical importance.

Are clinical measures influenced by various ethnic origins in Iranian patients with ankylosing spondylitis?A pilot study.

BACKGROUND: Ankylosing spondylitis (AS) may manifest with heterogeneous patterns according to ethnic origins. The purpose of this study was to describe the influence of various Iranian ethnic origins on clinical measures in patients with AS. METHODS: 0ne hundred sixty-three AS patients diagnosed by modified New York 1984 criteria were enrolled consecutively. The patients were classified into Fars, Turk, Kord, Lor and other ethnic origins. Several clinical measures were described and compared between the ethnic origins. RESULTS: The highest and the lowest finger to floor distance was observed for Fars ethnicity (20.4±14.8) and other ethnicities (5.9±8.1), respectively (P=0.04). The frequency of severe decrease in cervical slope was significantly different between various ethnicities (P=0.025). The most and the least frequency of severe decrease in cervical slope was observed in Fars patients (61.3%) and other ethnicities (20%), respectively. The frequency of severe thoracic kyphosis was significantly dissimilar between various ethnicities (P=0.006). The most and the least frequency of severe increase in thoracic kyphosis was observed in Fars (68.8%) and Lor patients (25%), respectively. A significant relationship was seen only between other ethnicities and finger to floor distance, lateral lumbar flexion, chest expansion and BASDAI (P<0.05). CONCLUSION: Clinical expression variations in AS disease might be influenced by various Iranian ethnic origins. A larger sample size with other Iranian ethnicities (Baluch, Arab, etc) is required to clear the definite relationship between Iranian ethnicities and clinical expression.

Pure red cell aplasia as a presenting feature in systemic lupus erythematosus and association with thymoma, hypothyroidism and hypoparathyroidism: a case report and literature review.

This paper presents a 54-year-old female with lupus whom severe anaemia due to pure red cell aplasia (PRCA) was the first manifestation. There was seven years interval between PRCA onset and diagnosis of lupus. Thymectomy due to thymoma had been carried out six years before but anaemia sustained. Hypothyroidism and hypoparathyroidism were other associated diseases. Severe anaemia and the need for monthly blood infusions were resolved following treatment with Prednisolone, Hydroxychloroquine and Levothyroxine.

Evaluating the reliability of Persian version of ankylosing spondylitis quality of life (ASQoL) questionnaire and related clinical and demographic parameters in patients with ankylosing spondylitis.

Ankylosing spondylitis quality of life (ASQoL) is an instrument for assessing quality of life (QoL). The aims of this study were to assess the reliability of Persian version of ASQoL questionnaire and evaluation of QoL status and related factors in ankylosing spondylitis (AS). One hundred and sixty-three Iranian patients with AS who fulfilled modified New York criteria were enrolled. Patients were evaluated using questionnaires including demographic and clinical variables, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), fatigue, Bath AS Metrology Index, pain and ASQoL. Reliability and validity of Persian version of ASQoL were evaluated by test-re-test agreement, internal consistency and correlation with specific scales. Relationship of parameters with ASQoL was analyzed by multiple regression. Age, disease duration and ASQoL score (mean ± SD) were 37.74 ± 9.88, 14.49 ± 8.47 and 8.02 ± 5.28 years, respectively. Test-re-test reproducibility for ASQoL was good as assessed by intra-class correlation coefficient (ICC: 0.97, P < 0.001). Internal consistency was high (Cronbach's alpha: 0.91). Convergent validity was confirmed by correlation of ASQoL score with specific scales (BASFI, r = 0.74, BASDAI, r = 0.6, fatigue, r = 0.56, depression, r = 0.24, intermalleolar distance, r = -0.44 and educational level, r = -0.37). Persian version of ASQoL is a valid and reliable scale to assess QoL in AS. Function, fatigue, mood, hip mobility and education are the factors which should be noted to achieve the best QoL.

Clinical characteristics and medical management of Iranian patients with ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease with variable clinical expression. Ethnic, racial and geographical factors have been associated with disease occurrence and expression. We intended to describe the clinical characteristics and assess the disease severity and treatment status in Iranian AS patients. METHODS: A total of 320 AS patients were assessed for demographic variables, clinical manifestations, human leukocyte antigen (HLA) status, disease severity, functional capacities, quality of life and treatment status. RESULTS: A gender ratio of 3.8:1, an average age onset of 27 ± 7.3 and a mean diagnostic delay of 8 years were observed. Eleven percent had juvenile onset AS. Positive family history was higher than that observed in most other countries. Enthesitis was a very common finding involving more than two-thirds of our patients. Uveitis was the leading extra-articular manifestation. We found an HLA-B27 prevalence of 73% and four HLA-B27 subtypes. Disease activity was high and the functional status was poor as indicated by mean Bath AS Disease Activity, Functional and Metrology indices. Quality of life was considerably impaired in our patients. We found a low percentage of patients on biological medications and a relatively higher percentage on disease modifying anti-rheumatic drugs and corticosteroids. CONCLUSIONS: Our results demonstrate a broad characterization of Iranian AS patients providing a better understanding of this disease. A national multicenter registry would enable larger- scale prospective studies to be carried out further evaluating the disease burden on patients and society.

Effect of HLA-B*27 and its subtypes on clinical manifestations and severity of ankylosing spondylitis in Iranian patients.

The aim of this study was to assess the role of HLA-B*27 and it's subtypes in determining severity and clinical manifestations of ankylosing spondylitis (AS).A total of 163 AS patients were assessed for clinical manifestations and severity using structured questionnaires. HLA-B*27 screening and B*27 sub-typing were performed by PCR.One hundred twenty two patients (74.8%) were B*27 positive. The male to female ratio, peripheral arthritis, steroid use, intense dorsal kyphosis and decrease of cervical slope had a significantly higher frequency in B*27 positive patients compared to B*27 negative ones (p=0.01, 0.001, 0.01, 0.04 and 0.04, respectively). However, the age of diagnosis was significantly lower in B*27 positive patients (p=0.005). Trend in uveitis and some severity markers including: BASMI and ASQoL were toward higher values in B*27 positive group with no significant difference. After controlling confounding variables, significant relationship was found only between B*27 and BASMI (p=0.01). B*27 subtypes in patients were included B*2705: 48.4%, B*2702: 42.6%, B*2704: 5.7% and B*2707: 3.3%. No significant differences were seen for severity markers and clinical manifestations between subtypes; although trend toward lower values of severity markers, less intense dorsal kyphosis and less decrease of cervical slope were observed in B*2704 and B*2707 versus other polymorphisms.Clinical features and severity of AS is influenced by HLA-B*27. Trend toward higher severity markers in B*2705 and B*2702 versus other polymorphisms might be subject of interest for evaluation in other ethnicities with concentration to other novel susceptibility genes co-inherited in each B*27 subtype.

Depicting and comparing the time to normalize "erythrocyte sedimentation rate" following two combination therapies in rheumatoid arthritis patients: a randomized clinical trial.

BACKGROUND: Erythrocyte sedimentation rate (ESR) is one of the predictors of improvement in handling rheumatoid arthritis. This study was designed to define and compare the time of achieving normal ESR and also the percentage for the normalization of this marker at several points of time in two different combination therapies. METHODS: Fifty-two rheumatoid arthritis patients randomly received methotrexate, chloroquine, prednisolone (MCP) or azathioprine, chloroquine, prednisolone (ACP) and all were followed up for 34 weeks. Chloroquine and azathioprine were given, 150 mg/d and 2 mg/kg/d, respectively. Methotrexate was given, 0.2 mg/kg/week and simultaneously increased 2.5 mg monthly if no clinical response was seen. Prednisolone was started, 0.3 mg/kg/d and tapered after one week. ESR at baseline and during follow-up were checked. The data were collected and analyzed. This clinical trial was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: 2012110611383N1. RESULTS: The percentages of obtaining normal ESR after 2nd, 4th, 6th, 8th, 18th, 34th weeks of follow up were 42.4%, 53.9%, 57.7%, 65.4%, 88.5%, 96.2% in the MCP group and 47.9%, 65.3%, 74%, 78.3%, 82.7%, 87% in the ACP group. The mean time of obtaining normal ESR was 9.15 (95%CI, 5.58 to 12.73) weeks in MCP group and 9.04 (4.04 to 14.05) weeks in the ACP group (p>0.05). CONCLUSION: The results show that the time to achieve normal ESR and percentage of its normalization were almost the same in both treated groups.

Severe dental caries as the first presenting clinical feature in primary Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome is an autoimmune syndrome involving the exocrine glands specially the salivary and lacrimal glands leading to xerostomia and xerophtalmia. This paper presents a case with primary Sjögren's syndrome that severe dental caries were the first clinical manifestation. CASE PRESENTATION: A 42-year-old man was referred to the School of Dentistry, Tehran University of Medical Sciences due to unexplained severe dental decays. After systematic evaluation and consultation with the rheumatologist and the ophthalmologist, the diagnosis of primary Sjögren's syndrome was suggested and confirmed by serologic and histopathologic study. CONCLUSION: Primary Sjögren's syndrome should be considered in the differential diagnosis of patients with early severe dental caries.

Association between endoplasmic reticulum aminopeptidase-1 (ERAP-1) and susceptibility to ankylosing spondylitis in Iran.

Ankylosing spondylitis (AS) is an inflammatory arthritis, which affects mainly spine and sacroiliac joints. According to recent studies, ERAP1 is the second most common candidate gene for AS susceptibility after HLA-B27. The aim of this study was to determine the association of ERAP1 gene polymorphisms with AS in Iranian population.The study group comprised 387 Iranian AS patients and 316 healthy controls from Iran. Using Real Time PCR allelic discrimination method, we genotyped four SNPs (rs30187, rs469876, rs13167972 and rs27434) of ERAP1. We found that rs30187 and rs27434 were significantly associated with AS in Iranian population (P=6×10-5, P=7×10-3, respectively). The rs30187 T/T genotype was associated with AS compared with C/C genotype (P=1.5×10-5). The rs27434 G/G genotype was inversely associated with AS (P=5×10-3). Two specific haplotypes including: rs30187/ rs469876/ rs13167972/ rs27434 TAAA and CAGG were associated with increased and decreased risk of AS in Iranian population, respectively. These results indicated that ERAP1 SNPs and haplotypes were associated with AS in Iranian population.

Evaluation of the Iranian versions of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Patient Acceptable Symptom State (PASS) in patients with ankylosing spondylitis.

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) are widely used instruments in assessment of patients suffering from ankylosing spondylitis (AS). The Patient Acceptable Symptom State (PASS) is regarded as a target for patients' well-being. The aim of this study was to translate and adapt BASDAI, BASFI and PASS into the Iranian official language, Farsi, and evaluate their reliability and validity. Ninety patients with AS were included in this study. The questionnaires were translated into Farsi and back translated into English, modified until the final versions were approved with minor adaptations and the VAS was changed to numerical rating scales from 0 to 10. Forty-eight-hour test-retest agreement showed good reliability: interclass correlation coefficient (ICC) for BASDAI was 0.93 (CI at 95%, 0.90-0.95), for BASFI was 0.96 (CI at 95%, 0.94-0.97) and for PASS was 0.87 (CI at 95%, 0.79-0.92). Chronbach's alpha was 0.95, 0.96 and 0.87 for BASDAI, BASFI and PASS, respectively. BASDAI showed a significant correlation with patient global disease activity index, nocturnal back pain, total back pain, number of swollen joints, number of enthesites, morning stiffness, Bath Ankylosing Spondylitis Global Score (BAS-G), BASFI and BASMI. A significant correlation was also found between BASFI and occiput-to-wall distance, mentum-to-sternum distance, chest expansion, finger-to-floor distance, number of swollen joints, number of enthesites, nocturnal back pain, total back pain, BAS-G, BASDAI and BASMI. Patients who answered "no" to PASS (found their condition unsatisfactory) reported significantly increased pain scores, patient global disease activity scores, BAS-G, BASDAI and BASFI scores. The results showed that the Iranian versions of BASDAI, BASFI and PASS are adequately reliable and valid in patients with AS.

Urolithiasis in ankylosing spondylitis: Correlation with Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis metrology index (BASMI).

BACKGROUND: Increased incidence of renal stone has been reported in ankylosing spondylitis (AS), but unlike some well-known renal involvements, they have not been fully studied. The aim of this study was to investigate the association of AS with urolithiasis and also the relation between urinary stone and severity markers. METHODS: One hundred-sixty three AS patients were included in a cross-sectional study from Iranian AS association, Iran Rheumatology Center and Rheumatology Clinic of Shariati Hospital in Tehran. Prevalence of urolithiasis in AS patients was compared with results of a nationwide survey in Iran. Bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI) and bath ankylosing spondylitis metrology index (BASMI) were determined for assessment of disease severity. RESULTS: Urolithiasis was observed in 11.7% of AS patients versus 5.7% of normal population (p=0.001). After the elimination of corticosteroid effect, the prevalence of urolithiasis was still higher in AS patients than normal population but without maintaining significant difference. Significant higher values of BASFI, BASMI, BASDAI scores were observed in AS with urolithiasis than AS without urolithiasis. CONCLUSION: The results confirmed the association of AS with urolithiasis. However, this may be partly due to the effect of other factors such as corticosteroid. Moreover, urolithiais is accompanied with more severe diseases.