A simple method to rapidly assess the tibial tuberosity-trochlear groove distance using computed tomography.

BACKGROUND: The tibial tuberosity-trochlear groove (TTTG) distance is used to assess patellofemoral instability (PFI) and the likelihood of the development of patellofemoral disorders. The current gold standard in the assessment of the TTTG is computed tomography (CT) or magnetic resonance imaging (MRI). The current image software used for viewing these CT images does not allow for easy assessment of the TTTG. AIMS: This study presents a simple method to measure the TTTG on any image software, utilizing easily available and affordable stationary. METHODS: Four consecutive patients with no known knee pathologies were selected from recent studies at our institution. Their TTTGs were measured using this study's method and validated using the standard, freely available image analysis software Fiji. Pre-defined anatomical landmarks were located and marked using adhesive pieces of paper. The TTTG was defined as the distance between parallel lines through the apex of the tibial tuberosity and trough of the trochlear groove, where each of these lines is perpendicular to the Dorsal Condylar Line. RESULTS: The TTTG measured using this study's method was found to be in agreement with the measurements made using Fiji software. CONCLUSIONS: This study demonstrates that the TTTG can be simply and quickly assessed using readily available and affordable stationery, without the need for expensive or complex secondary analysis software. This could allow for the assessment of PFI in the outpatient clinic whilst the patient is present, offering valuable assistance to the orthopaedic surgeon in clinical decision making.

High bone turnover and hyperparathyroidism after surgery for tumor-induced osteomalacia: A case series.

Tumor-induced osteomalacia (TIO) is an ultrarare disorder that is caused by renal phosphate wasting due to uncontrolled tumoral production of fibroblast growth factor 23 (FGF23) from phosphaturic mesenchymal tumors. Surgical removal of the tumor is curative. There is limited information on the biochemical changes in mineral metabolism and bone remodeling activity after surgery, but it is reported that surgery is followed by a hungry bone syndrome (HBS) with hypocalcemia and secondary hyperparathyroidism. We report the biochemical response to surgery in two patients, who presented with severe TIO, as manifested by proximal myopathy, multiple stress fractures, high FGF23, low serum phosphate, low maximum renal phosphate reabsorption threshold (TmP/GFR), and low 1,25-dihydroxy-vitamin D (1,25(OH)2D). Prior to surgery, both patients developed secondary hyperparathyroidism and one case had progressed to tertiary hyperparathyroidism. After surgery there was normalization of FGF23, TmP/GFR, and phosphate. High 1,25(OH)2D was recorded. One patient had hypocalcaemia and worsening secondary hyperparathyroidism consistent with HBS; the other patient did not have hypocalcemia but had worsening tertiary hyperparathyroidism that only resolved with cinacalcet. There was a marked increase in bone remodeling markers, both resorption and formation, consistent with a high bone turnover state. There was a different pattern of change in bone specific alkaline phosphatase, reflecting healing of osteomalacia. Biochemical monitoring in the post-surgical management of TIO is warranted for guiding adjustments in medical intervention, both short-term and long-term. Future use of burosumab prior to surgery for TIO may ameliorate the immediate post-surgery effects.

Prostate cancer detection with magnetic resonance imaging (MRI)/ cognitive fusion biopsy: Comparing standard and targeted prostate biopsy with final prostatectomy histology.

INTRODUCTION: The use of multiparametric magnetic resonance imaging (MRI) with targeted biopsies of the prostate improves the diagnosis of clinically significant prostate cancer. Recent studies have shown that targeted prostate biopsies also more accurately predict final histopathology after radical prostatectomy (RP). There are three broad techniques for performing MRI-targeted prostate biopsy: cognitive MRI/ultrasound (US) fusion, software MRI/US fusion, and in-bore MRI-guided. Current practices recommend that a standard systematic 12-core prostate biopsy be performed, as well as targeted biopsies in patients with positive MRI findings. This study aimed to evaluate the accuracy of histological grading of cognitive MRI/US fusion prostate biopsy by comparing the histology from the targeted biopsy specimens (TB), standard systematic specimens (SB), and the combination of both (CB) specimens with the final histological grade from subsequent prostatectomy. METHODS: A retrospective, single-center review of 115 patients who underwent standard systematic and cognitive MRI/US-targeted biopsy of the prostate before undergoing a RP between 2016 and 2019 was performed. MRI findings, biopsy, final histology International Society of Urological Pathology (ISUP) grades, and patient demographics were collected. Cochran's Q test and McNemar test were used to compare the differences in upgrading, downgrading, and concordance between each biopsy group. RESULTS: The concordance between SB, TB, and CB biopsy were 28.7%, 49.6%, and 50.4%, respectively. There was no significant difference in concordance between TB and CB. Patients were more likely to be downgraded on the final histology when comparing CB with TB alone (26.1% vs. 16.5%, p<0.05). In cases where an ISUP grade 1 cancer was diagnosed on TB (n=24), there was a 62.5% chance that the final histology would be upgraded. In the same sample, when combined with a SB, the risk of upgrading on final histology was reduced to 37.5%. CONCLUSIONS: Although grading concordance between TB and CB were similar, the concomitant use of a SB significantly reduced the rate of upgrading in the final RP histopathology. CB may result in better decision-making regarding treatment options and also have implications for intraoperative planning.

The Integration of Active Learning Teaching Strategies Into a Radiology Rotation for Medical Students Improves Radiological Interpretation Skills and Attitudes Toward Radiology.

PURPOSE: In recent years, there has been increased recognition of the benefits of teaching by active learning. However, there is a paucity of experimental studies utilizing active learning in undergraduate radiology rotations, which is traditionally a passive learning experience. We designed a new radiology rotation that integrated teaching by active learning. We prospectively examined the efficacy of this new rotation compared to our standard rotation in terms of students' radiological competency and attitudes toward radiology, as well as impact on departmental efficiency. METHODS: This was a prospective cohort study involving fourth year medical students completing a 1-week radiology rotation at our department between January and April 2018. One cohort completed a rotational model which incorporated active learning sessions (integrated cohort) while the remainder were taught using traditional passive learning methods (standard cohort). All participants completed a radiology examination before and after the rotation and were surveyed on their attitudes toward radiology. RESULTS: A total of 105 students enrolled in the study. The mean postrotation competency score obtained by the integrated cohort was significantly higher than that obtained by the standard cohort (82% vs 62%; P < 0.001). The integrated rotation freed up 7 hours of radiologists' time per week. While the students completing the integrated rotation had a more positive perception of radiology, they were no more likely to express a desire to pursue a career in radiology. CONCLUSIONS: The integration of active learning sessions into an undergraduate radiology rotation results in an improvement in students' postrotation radiological competency and attitudes toward radiology.

Performance characteristics and predictors of temporal artery ultrasound for the diagnosis of giant cell arteritis in routine clinical practice in a prospective cohort.

OBJECTIVES: The diagnosis of giant cell arteritis (GCA) is primarily a clinical one. Temporal artery (TA) ultrasound (US) has been proposed as a new diagnostic tool. We aimed to assess the performance characteristics of TA US in routine clinical practice. METHODS: All patients presenting with suspected GCA to our institution are recruited to a prospective registry. Patients who had both a TA US and biopsy (TAB) performed at the time of presentation were included in the current study. The performance characteristics of TA US was compared to physician diagnosis at six months following presentation. Predictive factors for a positive TA US were explored in univariate and multivariable logistic regression analyses. RESULTS: 162 patients were included, 123 (76%) with GCA. Mean (SD) duration of glucocorticoid therapy was 6.6 days (19.4) at the time of TA US. TA US had a sensitivity of 52.8% (95%CI 43.7, 61.9) and specificity of 71.8% (95%CI 54.9, 84.5) for the diagnosis of GCA. Glucocorticoid duration did not significantly impact the results. A sequential strategy of TA US followed by TAB in the case of a negative US had a sensitivity of 78.9% (95%CI 70.1, 85.5) and specificity of 71.8% (95%CI 54.9, 84.5), equivalent to a simultaneous testing strategy. The only factor independently predictive of a positive TA US was male sex (OR 5.53, 95% CI 2.72 to 11.22, p<0.001). CONCLUSIONS: TA US is potentially useful in the diagnosis of GCA; however, interpretation of its results requires knowledge of the performance characteristics in the target population.

Diagnostic Utility of Computed Tomographic Angiography in Giant-Cell Arteritis.

Background and Purpose- The diagnosis of giant-cell arteritis (GCA) is challenging. Superficial temporal artery biopsy and ultrasound are positive in only 50%. We evaluated computed tomographic angiography (CTA) of the head in GCA. Methods- This case-control study was performed using a prospective GCA registry. Cases presented with stroke symptoms, had a CTA, and were subsequently diagnosed with GCA. Age- and sex-matched controls presented with stroke symptoms, had a CTA, and were not diagnosed with GCA. CTAs were evaluated for the presence of superficial temporal artery abnormalities. Results- Fourteen cases met the inclusion criteria and were matched with 14 controls. Blurred vessel wall margins and perivascular enhancement was found in 10 cases (71.4%) and 2 controls (14.3%). CTA has an accuracy of 78.6%, sensitivity of 71.4%, and a specificity of 85.7% for GCA. Conclusions- CTA detects superficial temporal artery abnormalities in GCA. This may facilitate early diagnosis and prompt implementation of potentially sight-saving and stroke-preventing treatment.

Breast Arterial Calcification on screening mammography can predict significant Coronary Artery Disease in women.

INTRODUCTION: Breast Arterial Calcification (BAC) on digital mammography has been associated with an increased risk of Coronary Artery Disease (CAD). We aimed to investigate the association of BAC with findings on Coronary Computed Tomography Angiography (CCTA) within a cohort of women from the national breast screening program. METHODS: Symptomatic women (chest pain) aged between 50 and 65 who underwent a CCTA and who also had a screening mammography between 2014 and 2015 were recorded. BAC and CAD-RADS™: Coronary Artery Disease-Reporting and Data System were scored by separate blinded specialist radiologists. Cardiac risk factors were recorded. Patients' cardiac follow up (with Exercise Stress Test, Percutaneous Coronary Intervention or echocardiography) and cardio-protective medications were also documented. RESULTS: 219 eligible women underwent a CCTA. Of these, 104 patients also underwent digital mammography. Using standard linear regression BAC was identified as a significant predictor of CAD-RADs ≥3 disease. Using binomial logistic regression, BAC remained associated with CAD-RADs ≥3 (p=0.023). A significantly higher proportion of patients with BAC >1 were on cardio-protective medications (p=0.041) and had medications initiated or changed, or had further cardiac investigation (p=0.037 and p=0.019, respectively) than those with no BAC, after a mean follow-up of 20.6 (range 15-27) months. CONCLUSION: BAC diagnosed on 2 yearly screening mammography predicts CAD-RADs ≥3 disease in symptomatic patients.

Identifying Incomplete Atypical Femoral Fractures With Single-Energy Absorptiometry: Declining Prevalence.

BACKGROUND: Atypical femur fractures (AFFs) are associated with long-term bisphosphonate (BP) therapy. Early identification of AFF prior to their completion provides an opportunity to intervene, potentially reducing morbidity associated with these fractures. Single-energy X-ray absorptiometry (SE) is an imaging method recently shown to detect incomplete AFF (iAFF) prior to fracture completion. METHODS: Between May 2013 and September 2014, we assessed 173 patients who had been prescribed BP therapy for >5 years for iAFF using SE at their presentation for routine bone mineral density testing. We compared these findings with those of our previously published prospective study (n = 257) in which the femur was imaged for iAFF using dual-energy X-ray absorptiometry. In addition, we estimated the yearly prevalence of complete AFF among patients with subtrochanteric fracture at our institution from 2006 to 2014, and we evaluated prescribing trends for BP in Ireland from 2009 to 2014. RESULTS: No patients had iAFF using SE femur compared with a prevalence of 2.7% in the earlier study. Between 2006 and 2014, we observed a rise and decline in AFFs at our hospital and a similar national trend in BP prescribing. CONCLUSIONS: AFFs appear to be decreasing. New customized scan modes of dual-energy X-ray absorptiometry systems, which visualize the entire femur at high image quality and take measurements, have the potential to identify iAFF prior to fracture completion and to ascertain those at highest risk of AFF.

Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial.

BACKGROUND: Lowserum vitamin D levels are associated with susceptibility to, and severity of, multiple sclerosis. High dose vitamin D has been proposed as a potential immunomodulator in multiple sclerosis. OBJECTIVES: We performed a single centre, investigator-led, exploratory, double-blind, randomised, placebo controlled, trial of vitamin D3 in clinically isolated syndrome and healthy control participants to assess its immunological effects. Secondary end-points included clinical and magnetic resonance imaging outcomes and safety. METHODS: Clinically isolated syndrome patients and healthy control participants were randomised to: placebo, 5000 IU or 10,000 IU vitamin D3/day (Vigantol oil). Study duration was 24 weeks. RESULTS: The trial did not meet its primary end point, with no difference in the frequency of pro-inflammatory CD4+ T cells (interleukin (IL)-17+/interferon (IFN)-γ+) seen. A higher level of disease freedom (67% versus 50%) was seen in those with serum 1,25 (OH) vitamin D levels>100 nmol/l but this did not reach significance. High dose vitamin D3 was well tolerated with no safety signal. CONCLUSIONS: High dose vitamin D3 over 24 weeks was well tolerated but without immunological, magnetic resonance imaging or clinical evidence of benefit. The hypothesised therapeutic effects in clinically isolated syndrome or multiple sclerosis patients may require longer periods of administration or may only be seen in patients treated with vitamin D3 as an adjunct to established disease modifying therapies.

Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis.

BACKGROUND: The aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA). METHODS: Biological-treatment-naïve PsA patients with active disease including synovitis of a knee were enrolled in this single-centre, crossover study. Patients were randomised to receive intravenous abatacept 3 mg/kg of body weight or placebo infusion on day 1, 15 and 29; thereafter abatacept 10 mg/kg of body weight was administered every 28 days for 5 months. Clinical data were collected at each visit. Synovial biopsy of the involved knee was obtained at baseline and 2 and 6 months. MRI of the same knee and skin biopsy was performed prior to arthroscopy. RESULTS: Fifteen patients were recruited. Significant improvements in the joint-related measures were observed; 90% were European League Against Rheumatism criteria responders and 30% achieved psoriasis area severity index (PASI)50 at 6 months. Reduction in synovitis (P = 0.016) and vascularity (P = 0.039) macroscopic scores consistent with decrease in total MRI score (P = 0.016) were noticed. Abatacept decreased the immunohistological expression of FOXP3+ cells (P = 0.027), specifically the expression of CD4+FOXP3+ regulatory T cells (Tregs) (P = 0.008) in the synovium over 6 months. There was no significant clinical or immunohistological change in any of the skin measures. CONCLUSION: This is the first study assessing synovial and psoriatic skin immunpathological changes following abatacept treatment in PsA. Reduction in Treg expression in the synovium but not in the psoriatic lesion suggests abnormal Treg function in PsA with differential suppressive capacity in the synovium compared to the lesional skin. The results of this study demonstrate that abatacept 10 mg/kg of body weight might be an effective treatment option for joint disease in patients with PsA. TRIAL REGISTRATION: Irish Health Products Regulatory Authority. TRIAL REGISTRATION NUMBER: CT 900/489/1 - Abatacept (case number: 2077284, EudraCT Number: 2009-017525-19, Protocol number: 77777). Registered on 12 March 2010.

Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis.

OBJECTIVES: We aimed to 1) identify clinical and genetic associations of sacroiliitis (SI) in patients with psoriatic arthritis (PsA), and 2) describe the different radiographic patterns of SI in PsA and their clinical and genetic associations. METHODS: 283 PsA patients, fulfilling CASPAR criteria, underwent detailed skin and rheumatologic assessments. In addition, HLA-B*27 and B*080101 status was recorded, which have been shown as the key genetic markers of radiographic SI in PsA. Grade 2 Unilateral or bilateral radiographic changes of SI were required for inclusion and involvement was further defined as asymmetrical or symmetrical. RESULTS: 70 patients (25%) had radiographic SI; all either with a present or past history of backache. Regression analysis demonstrated a significant association of SI with peripheral joint erosions (p=0.043), PASI maximum (p=0.041), younger age of PsA onset (p=<0.001), presence of HLA-B*0801 (p=0.002) and only marginal significance with HLA-B*2705 (p=0.059). Asymmetrical SI was noted in 51 patients (73%). In striking contrast to those patients with symmetrical SI, patients with asymmetrical SI were more likely to be female (p=0.04), have a trend towards more severe nail disease (p=0.08) and peripheral joint erosions (p=0.08), more osteolysis (p=0.01), more HLA-B*0801 positivity (p=0.001) and much less HLA-B*270502 positivity (p=<0.001). CONCLUSIONS: PsA developing at a younger age, severe skin disease, peripheral joint erosions, and HLA-B*0801 are significantly associated with SI, and there was only a marginal trend towards significance for HLA-B*2705. HLA-B*27 positive Axial-PsA patients resemble AS, while HLA-B*0801 positive Axial-PsA patients have asymmetrical and/or unilateral SI, which are typical of PsA.

The Use of Twitter by Radiology Journals: An Analysis of Twitter Activity and Impact Factor.

PURPOSE: Medical journals use social media as a means to disseminate new research and interact with readers. The microblogging site Twitter is one such platform. The aim of this study was to analyze the recent use of Twitter by the leading radiology journals. METHODS: The top 50 journals by Impact Factor were included. Twitter profiles associated with these journals, or their corresponding societies, were identified. Whether each journal used other social media platforms was also recorded. Each Twitter profile was analyzed over a one-year period, with data collected via Twitonomy software. Klout scores of social media influence were calculated. Results were analyzed in SPSS using Student's t test, Fisher contingency tables, and Pearson correlations to identify any association between social media interaction and Impact Factors of journals. RESULTS: Fourteen journals (28%) had dedicated Twitter profiles. Of the 36 journals without dedicated Twitter profiles, 25 (50%) were associated with societies that had profiles, leaving 11 (22%) journals without a presence on Twitter. The mean Impact Factor of all journals was 3.1 ± 1.41 (range, 1.7-6.9). Journals with Twitter profiles had higher Impact Factors than those without (mean, 3.37 vs 2.14; P < .001). There was no statistically significant difference between the Impact Factors of the journals with dedicated Twitter profiles and those associated with affiliated societies (P = .47). Since joining Twitter, 7 of the 11 journals (64%) experienced increases in Impact Factor. A greater number of Twitter followers was correlated with higher journal Impact Factor (R2 = 0.581, P = .029). CONCLUSIONS: The investigators assessed the prevalence and activity of the leading radiology journals on Twitter. Radiology journals with Twitter profiles have higher Impact Factors than those without profiles, and the number of followers of a journal's Twitter profile is positively associated with Impact Factor.

The clothes maketh the sign.

UNLABELLED: Pattern recognition is a key tool that enables radiologists to evoke certain diagnoses based on a radiologic appearance. In Shakespeare's Hamlet, Polonius tells his son Laertes to dress well because "apparel oft proclaims the man"; this phrase is now expressed in modern parlance as "the clothes maketh the man". Similarly in radiology, appearances are everything, and in the case of radiologic signs, occasionally "the clothes maketh the sign". The radiologic signs described in this pictorial review resemble items of clothing, fabric types, headwear, or accessories and are found in the musculoskeletal, pulmonary, gastrointestinal, and genitourinary systems. These "clothing signs" serve as a useful visual trigger to help radiologists to identify particular disease entities. TEACHING POINTS: • Pattern recognition enables radiologists to evoke a diagnosis based on radiologic appearance. • The radiologic signs described in this review resemble clothing, fabric, or accessories. • These "clothing signs" serve as visual triggers that evoke particular disease entities.

Evaluation of the incidence of pulmonary embolus in the early postoperative period following cemented hemiarthroplasty.

PURPOSE: Little is known regarding the incidence of early postoperative pulmonary embolus (PE) following hip fracture surgery. Clinical suspicion of PE mandates therapeutic anticoagulation, adding a further insult to those of trauma and surgery in a physiologically frail population. The aim of the study was to evaluate for the presence of PEs by performing postoperative CT pulmonary angiography (CTPA) in patients who demonstrated intraoperative, or early postoperative cardiorespiratory lability following surgery with a cemented prosthesis for intracapsular hip fracture. METHODS: All patients undergoing cemented hemiarthroplasty for displaced intracapsular neck of femur fracture were recruited during a 6-month period, and signed consent obtained from the patient or their next of kin for CTPA in the event of any cardiorespiratory instability. Patient demographics, comorbidities were reviewed, and premorbid mobility status documented. RESULTS: 18 of the 66 patients in the study having cemented hemiarthropalsty demonstrated intra- or early postoperative lability, all had early postoperative CTPA scans. 6 of the 18 were noted to have PE. All had more than 1 risk factor for VTE on admission (excluding their injury). Patients diagnosed with PE had a higher ASA grade, and lower mobility scores than those who did not have a PE. CONCLUSIONS: Clinical suspicion alone is inadequate to diagnosis PE in patients undergoing cemented hip arthroplasty. Only 1 in 3 patients suspected of PE on account of intraoperative or immediate postoperative cardiorespiratory lability was found to have a PE based on CTPA. Early postoperative CTPA is helpful to prevent unnecessary anticoagulation for suspected PE.

Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry.

OBJECTIVES: To examine changes in hand BMD as measured by digital X-ray radiogrammetry (DXR-BMD) in early PsA compared with RA patients prior to and 3 and 12 months after introducing an antirheumatic treatment. Further, to identify predictors for hand bone loss at the time of disease presentation. METHODS: Recent-onset, active, treatment-naïve patients were recruited. Clinical assessment, hand X-rays and DXR were obtained at 0, 3 and 12 months. Mean DXR-BMD for both hands and changes in DXR-BMD (mg/cm(2)/month) were compared between the two groups. We compared baseline disease characteristics of patients with normal hand DXR-BMD with those with bone loss. Logistic regression analyses were performed to identify predictors of hand BMD loss. RESULTS: A total of 64 patients were included. Hand DXR-BMD decreased in RA throughout the study (P = 0.043). Changes in periarticular bone density over 12 months differed between PsA and RA (P = 0.001). Hand bone loss at 3 months was associated with elevated BMI [odds ratio (OR) = 3.59, P = 0.041] and heavier alcohol intake (OR = 1.13, P = 0.035). Diagnosis of RA (OR = 57.48, P = 0.008), heavier alcohol intake (OR = 1.27, P = 0.012) and higher swollen joint count (SJC28) (OR = 1.5, P = 0.036) were independent predictors for hand bone loss in the first year. CONCLUSION: Following treatment, we found ongoing hand bone loss in RA and unchanged periarticular bone density in PsA, supporting the hypothesis that different pathomechanisms are involved in hand bone remodelling in PsA. Presence of RA, heavier alcohol intake and higher SJC were identified as independent predictors for hand bone loss over 1 year.

Epidemiological study of soft-tissue sarcomas in Ireland.

Soft-tissue sarcomas (STS) account for 1% of adult and 7% of pediatric malignancies. Histopathology and classification of these rare tumors requires further refinements. The aim of this paper is to describe the current incidence and survival of STS from 1994 to 2012 in Ireland and compare these with comparably coded international published reports. This is a retrospective, population study based on the data from the National Cancer Registry of Ireland (NCRI). Incidence and relative survival rates for STS in Ireland were generated. Incidence of STS based on gender, age and anatomical location was examined. Annual mean incidence rate (European Age Standardized) in Ireland between 1994 and 2012 was 4.48 ± 0.15 per 100,000 person-years. The overall relative 5-year survival rate of STS for the period 1994-2011 in Ireland was 56%, which was similar to that reported in the U.K. but lower than in most of Europe and U.S.A. Survival rate fluctuated over the period examined, declining slightly in females but showing an increase in males. STS incidence trends in Ireland were comparable to international reports. Survival trends of STS were significantly different between Ireland and other European countries, requiring further study to understand causation.

Certain class I HLA alleles and haplotypes implicated in susceptibility play a role in determining specific features of the psoriatic arthritis phenotype.

OBJECTIVES: Psoriatic arthritis (PsA) susceptibility is associated with several different class I alleles, suggesting separate patterns of MHC effect. This exploratory study was based on the hypothesis that heterogeneity of the clinical phenotype of PsA might be explained by differing associations of clinical features with these susceptibility genes. METHODS: The clinical phenotype of 282 PsA patients in a cohort previously studied for associations with human leukocyte antigen (HLA)-B and HLA-C genotypes was first preliminarily assessed by univariate associations of susceptibility genes with specific clinical characteristics. To explore the potential genotypic effects of pairwise combinations of different HLA-B and C alleles/haplotypes, we created a series of allele/haplotype risk scores combining single alleles/haplotypes separately associated with being in the highest PsA severity propensity tertile based on the features studied by univariate analysis. RESULTS: In exploratory univariate analyses, B*27:05:02 was positively associated with enthesitis, dactylitis and symmetric sacroiliitis, whereas B*08:01:01-C*07:01:01and its component alleles were positively associated with joint fusion and deformities, asymmetrical sacroiliitis, and dactylitis. HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis. The highest propensity score for severe PsA was with B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01 and B*37:01:01-C*06:02:01, but not the B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01 haplotypes. In contrast, B*44 haplotypes were associated with presence of milder disease, and in univariate analysis with a decreased frequency of enthesitis, joint fusion, deformities and dactylitis. CONCLUSIONS: Different HLA susceptibility genes were associated with particular features that defined the PsA phenotype of a given patient. Additive interactions between different susceptibility HLA alleles defined the propensity for a more severe or milder musculoskeletal phenotype.