Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

A lower frequency of inflammatory back pain in male patients with ankylosing spondylitis compared with female patients.

In routine rheumatology practice, we noticed that a significant number of male ankylosing spondylitis (AS) patients did not experience inflammatory back pain (IBP). Based on this observation, we aimed to investigate the prevalence of IBP in male AS patients and compare it to that in female patients. Patients with AS who fulfilled the modified New York criteria were subjected to a face-to-face interview with a standardized questionnaire that addressed the IBP components based on the Berlin criteria. The study also included 63 patients with chronic mechanical back pain (MBP). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured, and Bath Ankylosing Spondylitis Disease Activity, Function, and Metrology Indexes (BASDAI, BASFI, and BASMI) were evaluated in patients with AS. There were 181 patients with AS (124 males, mean age 41.2 years; 57 females, mean age 44.6 years) and 63 patients with MBP (28 males, mean age 47.2 years; 35 females, mean age 43.5 years). The prevalence of IBP was found to be 87.7% in female and 66.1% in male patients with AS (p = 0.002). The specificity of the criteria was determined to be high both in females (85.7%) and males (89.2%). Female patients with AS had higher BASDAI levels than males (p = 0.048), but no difference was found in BASFI, BASMI, or serum CRP levels between genders. A considerable proportion of male patients with AS did not experience IBP, although they had similar CRP levels compared with females.

Evaluation of middle ear and hearing status of ankylosing spondylitis patients with wideband tympanometry and pure tone audiometry tests.

OBJECTIVES: The aim of this study was to evaluate the middle and inner ear function and hearing status of Ankylosing spondylitis (AS) patients. METHODS: One hundred twenty-four ears of 62 patients with AS and 90 ears (control group) of 45 healthy subjects were included in the study. The hearing levels of the participants were assessed with pure tone and high-frequency audiometry at the octave frequency between 250 and 16,000 Hz. The absorbance rates and resonance frequencies of middle ear were measured with the wideband tympanometry (WBT) test. AS group was divided into subgroups based on the disease activity, duration of follow-up, medications used for AS, and the subgroups were compared according to hearing status and absorbance and resonance frequencies of middle ears. RESULTS: A statistically significant difference was found between the AS and control groups in terms of air and bone conduction thresholds at frequencies of 250, 500, 1000, 2000, and 4000 Hz and the mean PTA1, PTA2, and PTA3 values (p < 0.05). In contrast, no statistically significant difference was observed between two groups in terms of high-frequency thresholds (8000-16,000 Hz). Although the middle ear resonance frequency obtained from the WBT test was higher in the AS group compared to the control group, no significant difference was observed (p > 0.05). The severity of disease adversely affected the hearing threshold at 250, and 500 Hz for air conduction, at 500 Hz for bone conduction threshold, and at PTA1 (p < 0.05). The duration and severity of disease did not affect absorbance values of WBT (p > 0.05). CONCLUSION: To our knowledge, this is the first study to demonstrate the effects of AS patients on the middle ear function with WBT and to report middle ear absorbance values and resonance frequency changes in AS patients. The higher resonance frequency values found by WBT in AS patients may be due to the stiffness that develops as a result of middle ear involvement. According to pure tone and high-frequency audiometry findings, it has been seen that AS leads to SNHL especially at low frequencies.

Rituximab on lung, skin, and joint involvement in patients with systemic sclerosis: A case series study and review of the literature.

OBJECTIVES: To evaluate the effectiveness of rituximab (RTX) in systemic sclerosis (SSc) patients. METHODS: Data were collected from patient charts before and after RTX administration for 1 year of follow-up time. An updated review of the literature was also done. RESULTS: Of 8 patients enrolled (mean age: 62.4 years; mean disease duration: 16.7 years), 2 patients with pulmonary arterial hypertension (PAH) died after the first RTX cycle. The follow-up data of the remaining 6 patients were evaluated. There was a significant improvement in arthritis of Disease Activity Score of 28 joints - C-reactive protein and Clinical Disease Activity Index compared with baseline. The median change in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and carbon monoxide diffusing capacity between baseline and 12 months were similar. Lung involvement was detected in 5/6 of survivor patients, FVC was improved in 2/5, worsened in 1/5, and remained stable in 2/5 at the end of 1 year. Among the 5 diffuse cutaneous SSc patients, none of the patients' mRSS deteriorated by more than 5 points, while one patient's mRSS improved by greater than 5 points. CONCLUSION: This study suggests that RTX is effective for arthritis in patients with SSc. Also, the effectiveness of RTX in skin and lung involvement of SSc was predominantly toward stable disease or improvement. Despite the long disease duration, the presence of patients who showed improvement in skin and lung involvement after RTX treatment suggests the need to investigate predictors of RTX response.

Metabolic syndrome is associated with increased cardiovascular risk and disease damage in patients with Takayasu arteritis.

OBJECTIVE: Metabolic syndrome (MetS) is one of the preventable risk factors for cardiovascular disease (CVD). The aim of this study was to investigate the effect of MetS on CVD and cumulative organ damage in a multi-center, large cohort of patients with Takayasu arteritis (TAK). METHODS: This is a cross-sectional study involving 192 consecutive TAK patients from seven tertiary rheumatology centers in Turkey. Clinical data of TAK patients fulfilling the 1990 American College of Rheumatology classification criteria were collected from medical records. They were evaluated for risk factors of CVD, disease activity, damage, and MetS at their last visits. RESULTS: A total of 192 consecutive TAK patients were included in this study. One hundred and fifty-eight (82%) were female, the mean age was 43.3 ± 13 years, and mean disease duration was 13.5 ± 9.3 years. MetS was detected in 50 (26%) of the patients and CVD was detected in 28 (14.6%). The presence of MetS was detected as an independent risk factor for CVD (P < 0.001). In addition, the mean vasculitis damage index of the group with MetS was significantly higher than in the other patients (4.5 ± 3.3 vs 3.2 ± 2.2, respectively, P = 0.004). CONCLUSION: The presence of MetS in TAK is associated with increased CVD and disease damage. Awareness and management of MetS can improve disease prognosis in patients with TAK.

Pregnancy in Takayasu's arteritis has a high risk of hypertension-related fetomaternal complications: A retrospective study of a Turkish cohort.

BACKGROUND: This study aimed to examine fetomaternal outcomes in pregnant women in a large Turkish Takayasu arteritis (TAK) cohort and to evaluate the effects of pregnancy on the disease in those patients. METHODS: This is a cohort study involving 296 pregnancies of 112 TAK patients from 8 tertiary rheumatology centers in Turkey. Pregnancies were divided into 2 groups as pre-d (before disease onset) and post-d (after disease onset). In addition, post-d pregnancies were further divided into 2 subgroups according to fetomaternal complications (FMC) development status. Finally, patients were grouped into those with and without a history of pregnancy after disease onset. RESULTS: In post-d pregnancies, rates of worsening hypertension, new-onset hypertension, and preeclampsia were higher than in pre-d pregnancies (0.9% vs 16%, P < .001, 0.5% vs 5.3%, P = .012, and 0% vs 4%, P = .013, respectively). Patients with FMC were more likely to have renal artery involvement (65% vs 21%, P = .003). The patients who had post-d were younger, had longer disease duration, and had more relapses number than other patients (P < .001, P = .028, P = .016, respectively). Vasculitis Damage Index (VDI) results were similar in patients with or without post-d pregnancies. CONCLUSION: Pregnancies after disease onset were found to be associated with HT and preeclampsia/eclampsia. HT-related FMCs are increased in TAK, and patients with renal artery involvement are at higher risk. The number of relapses increases in patients who become pregnant after disease onset, but pregnancy was not an independent risk factor for relapse. Pregnancy after the onset of disease had no negative effect on VDI.

The prevalence of Sjögren's syndrome and sicca symptoms in patients with systemic sclerosis and alpha-smooth muscle actin expression in biopsy specimens from minor salivary glands

Background/aim: This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren's syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of α-smooth muscle actin (α­SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Materials and methods: Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American­European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of focal lymphocytic sialadenitis and glandular fibrosis, also assessing the expression of α­SMA. Results: This cross-sectional study included 102 patients with SSc [91 females (89%), mean age 52.5 ± 12 years]. In this cohort 76 (75%) patients had sicca symptoms and 36 (35.3%) patients fulfilled the AECG criteria for SjS; all with limited form. Having SjS found to be associated with older age and the presence of positive anti-SS-A antibodies. On histopathologic examinations, glandular fibrosis was observed in 67 (80%) and lymphocytic sialadenitis was detected in 38 (45%) patients; but only 7 samples were positive for α­SMA. Conclusion: This study suggested sicca symptoms were found to be very common among patients with SSc. Also secondary SjS was detected in nearly one-third of patients with SSc; especially in limited subtype. Anti SS-A positivity and older age were detected as predictors for SjS. Histopathologic evaluations showed significant glandular fibrosis but rare α-SMA staining in patients with SSc.

Pyomyositis and muscle abscess due to Salmonella enteritidis in a patient with Behçet's syndrome: a case report.

Salmonella infections usually present with gastrointestinal manifestations including enterocolitis especially in immunocompromised patients. Haematogenous dissemination and abscesses are very rare complications of Salmonella species. This case report documents a patient with Behçet's syndrome (BS) who has pyomyositis due to Salmonella species. A 43-year-old male patient with BS presented to the outpatient rheumatology clinic with bilateral acute-onset lower extremity pain. However, over a short time the pain gradually increased and was accompanied by fever. The magnetic resonance scans demonstrated pyomyositis and muscle abscess in the adductor and obturator muscles. The cultures showed Salmonella enteritidis infection. The patient was successfully treated with antibiotic therapy. This case is important since it is one of the first in the literature to report an adult patient with BS and Salmonella pyomyositis.

Prevalence, etiology and risk factors of anemia in patients with newly diagnosed cancer.

PURPOSE: To determine the prevalence of anemia, and to evaluate the etiology and risk factors of anemia in patients with newly diagnosed cancer. METHODS: In this cross-sectional study, 310 patients with newly diagnosed cancer who were referred to a university hospital in Turkey over a 6-month period and 218 age-matched healthy individuals as controls were evaluated in terms of anemia: complete blood count (CBC), ferritin, transferrin saturation (TS%), serum iron (SI), cobalamin (B12), and folate levels. Carcinoma of the breast (21.3%), lung (12.9%), and gastrointestinal tract (GIT) (35.8%) accounted for the majority of the patients, and 44.7% of the patients had metastatic disease. RESULTS: Anemia was observed in 49.7% of patients with cancer and in 11.9% of healthy controls (p < 0.001). SI and TS% were lower in patients with cancer than in the controls (p < 0.001); however, the median serum ferritin level, which is also an acute-phase reactant, was higher in the patient group than the healthy matched controls (42.2 ng/mL and 41 ng/mL, respectively, p < 0.001). Folate and B12 deficiencies were seen more frequently in the cancer group than in the controls [6.5% and 0.9% (p < 0.001); 39.3% and 18.9% (p < 0.05), respectively]. In the cancer group, anemia was seen more frequently in the metastatic subgroup than in the non-metastatic subgroup (59.7% and 55.3%, respectively, p < 0.05). The prevalence of anemia was similar in both groups of patients with and without primary GIT cancers, as well as in patients who did and did not undergo tumor surgery (p > 0.05). CONCLUSION: This study showed that, at the time a patient is diagnosed as having cancer, the patient already has a significant risk for anemia, nearly five times that of healthy people. Having metastatic disease, and having nutritional deficiencies as iron, B12, and folate were evaluated as possible risk factors for anemia in patients with newly diagnosed cancer, whereas cancer with GIT localization and previous history of tumor surgery were not.

Imaging is the major determinant in the assessment of disease activity in Takayasu's arteritis.

OBJECTIVES: There are no valid follow-up parameters in the assessment of disease activity in Takayasu's arteritis (TAK). We investigated the impact of vascular imaging in the assessment of disease activity. METHODS: Patients with TAK who fulfilled the ACR criteria were included. Physician global assessment (PGA), the criteria defined by Kerr et al. and the Indian Takayasu Clinical Activity Score (ITAS2010) were evaluated. Patients were followed up since 3-6 months B-mode/Doppler ultrasonography (US) and 6-12 monthly magnetic resonance imaging/angiography (MRI/MRA). Active disease according to vascular imaging (Rad-Active) was defined based on the presence of any of the 3 parameters: (1) new vessel involvement by any imaging technique; (2) an increase in vessel wall thickness on US compared to previous one; (3) the presence of mural contrast enhancement/oedema on MRI/ MRA. The agreement of Rad-Active with other disease activity indexes was studied. Furthermore, ITAS-A-Rad index was developed by combining the vascular imaging with ITAS-A. RESULTS: A total of 410 visits in 52 patients were evaluated. The agreement was found to be 76% (κ: 0.52) between Rad-Active and PGA; 83% (κ: 0.57) between Rad-Active and Kerr's criteria. Both the agreements of ITAS2010 and acute phase reactants with PGA (69%, κ:0.38 and 60%, κ:0.22, respectively) and also Kerr's criteria (78%, κ:0.49 and 42%, κ:0.05, respectively) were lower compared to those of Rad-Active. Mean ITAS-A-Rad scores were higher in visits with active disease according to PGA and Kerr's criteria. CONCLUSIONS: The results of this study suggest that the vascular imaging should be included in the assessment of disease activity in TAK.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1ß, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1ß, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1ß and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1ß function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

Infliximab-associated focal segmental glomerulosclerosis in a patient with ankylosing spondylitis.

The introduction of tumor necrosis factor-alpha (TNF-α)-targeting drugs has given new opportunities in the treatment of various inflammatory rheumatic diseases and has been the most important development in the treatment of spondyloarthritis (SpA). However, the increasing use and longer follow-up periods of treatment also pose risks of developing various adverse effects ranging from common ones including infections to uncommon renal complications. This report describes a case of infliximab-induced focal segmental glomerulosclerosis (FSGS) in a 40-year-old female patient with ankylosing spondylitis (AS) who presented with asymptomatic proteinuria and microscopic hematuria. To the best of our knowledge, this is the second reported case of FSGS attributed to infliximab (IFX). A review of the English literature was conducted for cases of possible IFX-associated renal disorders in patients with SpA and SpA spectrum diseases. In this respect, the reported renal pathologies were IgA nephropathy, crescentic glomerulonephritis, acute renal artery occlusion, acute tubulointerstitial nephritis (ATIN), FSGS, and membranous glomerulopathy. Furthermore, partial or complete resolution was reported after cessation of therapy. In conclusion, although renal complications of TNF inhibitors (TNFi) are uncommon, spot urine evaluation may be recommended in the follow-up of patients treated with TNFi.

Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors.

Objectives: We explored the interactions of osteoprotegerin (OPG) with biomarkers of bone turnover and cytokines, including soluble receptor activator for nuclear factor kappa beta ligand (sRANKL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), and Wnt inhibitors in osteoporosis, vasculopathy and fibrosis related to systemic sclerosis (SSc). Methods: The study included 46 SSc patients and 30 healthy controls. Skin thickness, pulmonary fibrosis and/or hypertension, digital ulcers, and calcinosis cutis of SSc patients were assessed. We determined bone mineral density (BMD), and OPG, sRANKL, TRAIL, secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), sclerostin in the serum of both patients and controls. Results: OPG, sclerostin, and sFRP-1 levels were similar between patients and controls (P > 0.05). Femoral neck and lumbar spine BMD and vitamin D levels were lower, and the OC, NTX, sRANKL, DKK1 and TRAIL levels were significantly higher, in patients than in controls (p < 0.05). In subgroup analysis, patients with higher modified Rodnan skin score (mRodnan) had higher DKK-1, sclerostin, and TRAIL levels (p < 0.05); those with diffuse SSc subtype had lower BMD values than those with limited SSc (p < 0.05). Skin and pulmonary fibrosis linked negatively with BMD measures. Conclusion: we showed that sRANKL levels were higher and correlated with bone turnover markers. It may be related to osteoporosis in SSc. The OPG level was unaltered in SSc patients. Higher TRAIL levels associated with skin thickness may indicate vascular dysfunction or injury. Higher DKK-1 and sclerostin levels may be related to a reactive increase in cells and be prominently linked to fibrosis in SSc.

The validity and reliability study of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT) 2.0 questionnaire for the Turkish society.

BACKGROUND/AIMS: To translate the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT) 2.0 questionnaire from English to Turkish and to validate it. MATERIALS AND METHODS: UCLA SCTC GIT 2.0 was translated into Turkish using the translation-retranslation method. The available Turkish GIT 2.0 and the Short Form 36 (SF-36) were administered to 97 Turkish-speaking patients with systemic sclerosis (Ssc). Internal consistency reliability and structural validity were assessed by analyzing the correlations between the UCLA SCTC GIT 2.0 and the SF-36 scales. Internal consistency was determined by calculating Cronbach's alpha. For evaluation of reliability, the questionnaire scale was repeatedly applied to a subgroup of patients with a 2-week interval, and the intraclass correlation coefficient (ICC) was calculated. The Spearman's correlation coefficients between the GIT and the SF-36 scores were calculated. RESULTS: A group of 97 patients with Ssc with a mean age of 55.37±11.35 years and a female predominance (87.6%) were included in the study. The Cronbach's alpha value for the UCLA SCTC GIT 2.0 scale was 0.894. ICC was 0.821 (p=0.000). The scale showed acceptable reliability, with the exception of the diarrhea subscale (alpha=0.356). There was a moderate correlation between the total GIT score and the Short Form 36 (SF-36) subscales. All of the items in the scale were included in the validity analysis owing to their reliability. CONCLUSION: The Turkish GIT 2.0 scale showed good internal consistency, high reliability, and an acceptable validity.

Gender does not make a difference in "composite psoriatic disease activity index (CPDAI)" in patients with psoriatic arthritis.

The aim of the study was to investigate the relationship of CPDAI with other follow-up parameters and to evaluate gender differences in measures in psoriatic arthritis (PsA) patients. This cross-sectional study included patients with PsA followed up at a rheumatology outpatient clinic. Disease activity was assessed using CPDAI, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analog Scale (VASglobal) and Disease Activity Score (DAS28). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The Psoriasis Area and Severity Index (PASI) was used to measure of severity of psoriasis. Bath Ankylosing Spondylitis Functional (BASFI) and Metrology Indexes (BASMI), Health Assessment Questionnaire (HAQ), AS Quality of Life (ASQoL) and Dermatology Life Quality Index (DLQI) were evaluated. There were 117 patients with PsA (78 female) who fulfilled the Classification Criteria for Psoriatic Arthritis. Their mean CPDAI score was 3.67 (± 2.46). The CPDAI was positively correlated with tender/swollen joint counts, dactylitis and enthesitis. There was strong positive correlation between CPDAI and BASDAI, DAS28 and VASglobal, but no correlation found between the CPDAI and ESR, CRP and BASMI. Mean CPDAI scores were similar in females and males. Female patients were found to have worse subjective scores including BASDAI, VASglobal, BASFI, HAQ and ASQoL than males (p < 0.05). However, objective disease parameters such as ESR, CRP, tender/swollen joint counts, DAS28 and BASMI were similar in both gender groups. This study confirmed that CPDAI, a compound scale to assess disease activity in PsA, was well correlated with other disease activity measurements. Although subjective disease scores were higher in female patients, CPDAI was not affected by gender.

Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease.

PURPOSE OF REVIEW: We review our current knowledge about the clinical features of patients with ankylosing spondylitis (AS) who possess HLA-B*27 versus those who lack this gene. RECENT FINDINGS: ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. A genetic study supports the existence of an HLA-B27-independent common link between gut inflammation and AS. It is unusual to observe familial occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, psoriasis, or IBD. Although there are many similarities among AS patients possessing HLA-B*27 versus those lacking this gene, the former group has a younger age of onset, a shorter delay in diagnosis, a better clinical response to tumor necrosis factor inhibitors, a greater familial occurrence, a greater risk for occurrence of acute anterior uveitis, and a lower risk for occurrence of psoriasis and IBD. ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. It is unusual to observe occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, IBD, or psoriasis. A recent genetic study supports the existence of an HLA-B*27-independent common link between gut inflammation and AS.