HLA-B27 Testing Research Articles

A guideline on biomarkers in the diagnosis and evaluation in axial spondyloarthritis.

To develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA). A joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated. A total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients' values and willingness as well as the objective of testing in the local context. This guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

Converting an HLA-B27 flow assay from the BD FACSCanto to the BD FACSLyric.

HLA-B27 is a major histocompatibility complex (MHC) class I antigen which exhibits strong association (90%) with ankylosing spondylitis. HLA-B27 detection in patients by flow cytometry is a widely used clinical test, performed on many different flow cytometer models. We sought to develop and validate a test conversion protocol for the HLA-B27 test performed on the BD FACSCanto to BD's newer FACSLyric flow cytometers. The development and validation experiments were performed using anti-HLA-B27*FITC/CD3*PE antibody-stained whole blood patient specimens. The anti-HLA-B27*FITC logarithmic median fluorescence (LMF) results on the BD FACSCanto were converted to median fluorescence intensity (MFI) values on the BD FACSLyric. Clustering of the HLA-B27 positive and negative values, using a 3rd order polynomial equation, resulted in a conversion of the BD FACSCanto cutoff values, negative (<150 LMF) and positive (≥160 LMF), to negative (<4530 MFI) and positive (≥6950 MFI) on the BD FACSLyric. Accuracy was assessed by comparing the flow results obtained on the BD FACSCanto and BD FACSLyric to a molecular PCR based assay. Additional validation parameters (compensation verification, intra- and inter-assay precision, and instrument comparison) were performed per the recommendations outlined in the Clinical and Laboratory Standards Institute (CLSI) H62 guidelines for validation of flow cytometry assays.

A Treatise about Some Anomalous Laboratory Investigation Results Accompanying HLA-B27 Positive Higher Age Group Population

HLA-B27 test is generally positive in spondyloarthritis (SpA) and ankylosing spondylitis (AS). Several anomalous laboratory test results are frequently found in HLA-B27-positive patients. In this study, we intended to evaluate two groups of HLA-B27 positive patients- one group belonging to the 13-40 years age group and another group belonging to the 41-71 years age group. The rationale of this partition was based on the age when AS first emerged and the age when the disease was set up for quite a few years respectively. We anticipate alterations of several familiar laboratory test outcomes between these two groups. After our analysis, we found that in the upper age group, neutrophil percentage and CRP levels were significantly increased, while lymphocyte percentage was significantly decreased. ESR levels also decreased but were not statistically significant. There was practically no change in average PCR ct values, haemoglobin levels, total count of leucocytes, uric acid, creatinine, SGPT, or HbA1C levels between the two groups. The plausible explanations behind these changes are discussed.

How to translate genetic findings into clinical applications in spondyloarthritis?

Spondyloarthritis (SpA) is characterized by a strong genetic predisposition evidenced by the identification of up to 50 susceptibility loci, in addition to HLA-B27, the major genetic factor associated with the disease. These loci have not only deepened our understanding of disease pathogenesis but also offer the potential to improve disease management. Diagnostic delay is a major issue in SpA. HLA-B27 testing is widely used as diagnostic biomarker in SpA but its predictive value is limited. Several attempts have been made to develop more sophisticated polygenic risk score (PRS). However, these scores currently offer very little improvement as compared to HLA-B27 and are still difficult to implement in clinical routine. Genetics might also help to predict disease outcome including treatment response. Several genetic variants have been reported to be associated with radiographic damage or with poor response to TNF blockers, unfortunately with lack of coherence across studies. Large-scale studies should be conducted to obtain more robust findings. Genetic and genomic evidence in complex diseases can be further used to support the identification of new drug targets and to repurpose existing drugs. Although not fully driven by genetics, development of IL-17 blockers has been facilitated by the discovery of the association between IL23R variants and SpA. Development of recent approaches combining GWAS findings with functional genomics will help to prioritize new drug targets in the future. Although very promising, translational genetics in SpA remains challenging and will require a multidisciplinary approach that integrates genetics, genomics, immunology, and clinical research.

The history and evolution of HLA typing external proficiency testing schemes in UK NEQAS for H&I.

The UK National External Quality Assessment Service (NEQAS) provide an external proficiency testing (EPT) service for clinical laboratories. UK NEQAS for Histocompatibility and Immunogenetics (H&I) has been providing EPT schemes for over 45years and has grown during this time to provide 19 EPT schemes. Accurate human leucocyte antigen (HLA) typing is critical to support safe clinical services, including transplantation, therefore high quality, relevant EPT schemes are required as part of a laboratory's quality assurance. This article reviews the development of the HLA typing EPT schemes, from the first HLA phenotyping scheme in 1975, via the first HLA genotyping scheme in 1992, through to the introduction in 2017 of HLA third field assessment results from next-generation sequencing technology. In addition, the introduction of EPT schemes to cover HLA associated diseases and pharmacogenetic reactions, including HLA-B27, HLA*B*57:01 and HLA-DQ for coeliac disease are discussed. The accuracy of laboratory EPT results for HLA phenotyping are >96% (2018-2022), HLA genotyping >99% (2020-2022), HLA-B27 testing >99% (2018-2022) and B*57:01 testing >99% (2017-2022). However, for HLA genotyping for coeliac disease 22%-46% of laboratories made errors in 2020-2022. On investigation, the high rate of unsatisfactory performance was attributed to laboratories lacking specific knowledge to interpret HLA genotyping results and accurately report HLA types for coeliac disease. A misleading commercial kit insert was also identified. The assessment of scheme results has uncovered several issues which have been addressed with the intention of educating participants and improving clinical services. The UK NEQAS for H&I EPT schemes have evolved over the past four decades to reflect changes in HLA typing technology, laboratory clinical practice and to cover post-analytical interpretative elements of HLA typing.

Current health resources required for the management of ankylosing spondylitis in developing areas of China.

Current health resources required for the management of ankylosing spondylitis in developing areas of China.

Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study

ObjectiveTo analyse the influence of HLA-B27 in the phenotypical expression of peripheral spondyloarthritis (pSpA).MethodThis is an observational cross-sectional study using data from the Assessment of SpondyloArthritis international Society perSpA registry,...

A case of diffuse idiopathic hyperostosis of bone (DISH) in a patient on hemodialysis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory progressive disease resulting in ossification of the anterior longitudinal ligament of the spine and tendons. Herein, we describe a case of DISH in a patient on long-term hemodialysis. The patient was a 79-year-old man undergoing hemodialysis for chronic kidney disease due to diabetic nephropathy. He presented to the emergency department complaining of back pain after a slip and fall. Radiographs revealed bamboo spine-like findings, extending from the cervical to the lumbar spine. Computed tomography and magnetic resonance imaging revealed a compression fracture of thoracic vertebra 12, with abnormal ossification of the anterior longitudinal ligament. Inter-vertebral vertical osseous bridges were also observed at the cervical 7 and lumbar 2 vertebrae. There was no obvious spinal cord compression. Leukocytosis and C-reactive protein levels were not elevated and the human leukocyte type antigen HLA-B27 test was negative. Based on this finding, a diagnosis of DISH was made. In the absence of neurological findings, the patient was treated conservatively. Our findings show an overlap between the clinical features of DISH and those of hemodialysis patients, including older age, male sex, and diabetes.

Interpreting Rheumatology Laboratory Tests

Interpreting Rheumatology Laboratory Tests

P103 Mapping the clinical profile of ankylosing spondylitis patients prescribed etanercept in India (The ESMA Study)

Abstract Background/Aims Tumor necrosis factor (TNF) blocking therapies like etanercept (ETN) have revolutionized the management of ankylosing spondylitis (AS). Clinical trials suggest that Etanercept exhibits beneficial effects in terms of improving disease severity of AS patients. Etanercept has also been shown to have a good safety profile as compared to other TNF inhibitors in terms of risk of tuberculosis (TB) which seems to be an important aspect especially in India, considering the high prevalence of TB here. Despite having an established efficacy and safety profile, data regarding patient profile of AS patients who are prescribed etanercept is not clear. Methods This retrospective, multicentric, cross sectional, data collection form based observational study was planned to evaluate the patient profile of AS patients who are prescribed etanercept in India. Results Retrospective data of 423 AS patients was collected across 48 centers in India. Mean age of AS patients prescribed ETN was 53.26±8.60 years. 84.63% patients were males while the remaining 15.37% were females. To some extent, this can be attributed to the epidemiology of AS which is seen more commonly in males. Average height and weight of the patients were 68.30±7.11 kg and 166.75±3.98 cm respectively. Mean Body mass index (BMI) of the patient group was 24.59±2.66 kg/m2. 6.38% patients were obese while 21.27% patients were in the overweight category. Most of the patients had a medication history of taking some or other non-steroidal anti-inflammatory drug (NSAID) (95.98%). Other drugs which were previously consumed by the patients included sulfasalazine (74.47%), methotrexate (26.95%), steroids (13.95%). 11.11% of patients had a previous medication history of biologic medications including infliximab (6.86%), adalimumab (2.84%), secukinumab (0.95%) and golimumab (0.47%). Most common comorbid disorder reported in the patient group was hypertension (15.60%). Other comorbidities were diabetes mellitus (7.32%), inflammatory bowel disorder (4.3%) and psoriasis (1.65%). Erythrocyte sedimentation rate (ESR) was done in 29.74% of the patients with a mean value of 20.42 ±10.35 mm/hr. C-reactive protein (CRP) was done in 25.76% patients with a mean value of 10.82±4.27 mg/L was reported.HLA-B27 antigen testing was done only for 13.23% patients. Among patients who were subjected to HLA-B27 testing, 78.57% were HLA-B27 positive while the remaining 21.43% patients were HLA-B27 negative. 95.03% of the patients were prescribed ETN dose of 50mg/week through subcutaneous route while 4.97% of patients received ETN dose of 25mg twice weekly. Sulfasalazine was prescribed in 78.72% of these patients and was the most commonly co-prescribed drug along with ETN. Other commonly co-prescribed medications included NSAIDS (32.62%), methotrexate (28.37%) and steroids (5.67%). Conclusion Etanercept is commonly used in patients not responding to NSAIDS &amp; sulfasalazine. It is even used in patients who have been on biologics previously. Disclosure A.B. Jain: Corporate appointments; Medical Advisor to Intas Pharmaceuticals Ltd, India. S. Warudkar: Corporate appointments; Medical Advisor to Intas Pharmaceuticals Ltd, India. N. Dave: Corporate appointments; Medical Advisor to Intas Pharmaceuticals Ltd, India. A. Chaturvedi: Corporate appointments; Medical Advisor to Intas Pharmaceuticals Ltd, India.

Comparative Analysis of a Developed Probe-Based Real-Time PCR and PCR-SSP for HLA-B*27 Detection among Thai Blood Donors

The human leukocyte antigen (HLA) class I gene, the B locus, allele 27, HLA-B*27 is one of the most fascinating risk factors that is strongly associated with developing spondyloarthropathies (SpA). HLA-B27 testing has been routinely available in the diagnosis of those diseases. This study aimed to develop a fluorogenic real-time PCR and to compare it with PCR-SSP to detect the HLA-B*27 allele among Thai blood donors. A total of 391 DNA samples were obtained from Thai blood donors at Thammasat University Hospital and tested for HLA-B*27 allele detection. A new real-time PCR was developed and validated to identify this allele and subsequently compared with those results tested with PCR-SSP. The sensitivity of detection was performed using known HLA-B*27-positive and -negative samples with concentrations ranging from 0.001 to 100 ng/µL. Additionally, HLA-B27 subtyping was performed by DNA sequencing containing second and third exons of this gene among all the HLA-B*27-positive donors. The validity of real-time PCR using known DNA controls and the results obtained by PCR-SSP techniques were in 100% concordance. The method was sensitive even at low DNA concentrations (1 ng/µL). Of 391 donors, 24 (6.14%; 95% CI, 3.97 - 9.00) were found to have the HLA-B*27 allele, while the remaining 367 (93.86%; 95% CI, 91.00 - 96.03) did not have this allele. Donors presented HLA-B*27-positive, HLA-B*27:06, the most common allele, followed by HLA-B*27:04, -B*27:05, and -B*27:07. HLA-B*27 using fluorogenic real-time qualitative PCR was found to be superior compared with that of PCR-SSP. The method is rapid, accurate, reliable, and sensitive for detection. In addition, this method provides convenience in the early treatment of SpA patients and relieves their suffering.

A nationwide questionnaire survey on the prevalence of ankylosing spondylitis and non-radiographic axial spondyloarthritis in Japan.

This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400-3900) and 800 (530-1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.

Biomarkers in axial spondyloarthritis and low back pain: a comprehensive review.

The spectrum of axial spondyloarthritis (AxSpA) (including both non-radiographic and radiographic AxSpA), also known as ankylosing spondylitis AS, has achieved growing recognition. With the development of treatments not only effective in controlling disease activity but also in slowing radiographic progression, and given the cost and risk profiles of these novel treatments and the limitations of current clinical criteria, imaging and peripheral blood biomarkers (C-reactive protein, HLA-B27 testing), the need for better biomarkers has never been greater. The purpose of this review is to present up-to-date information on the biomarkers for the diagnosis for assessing disease diagnosis, activity, treatment response, and radiographic progression of AxSpA, and entails multiple search strings used to identify articles of interest published in PubMed and the Cochrane database up to May 1, 2021. We present the current status of research in serologic biomarkers such as cytokines, adipokines, matrix metalloproteinases, calprotectin, CD74, antibodies, bone turnover markers, and circulating protein fragments of cartilage and connective tissue degradation and other biomarkers. Despite a great deal of work, most serologicresults have been disappointing and to date none perform better than CRP. Recent promising preliminary data for some has been published, but require further confirmation. Transcriptomic biomarkers such as micro-RNAs and genetic biomarkers also show promise to assist in diagnosis and possibly for radiographic severity, including a recently developed panel of genetic risk markers used in a polygenic risk score instrument in AS diagnosis. These need further confirmation and application in AS as well as in nr-AxSpA.

Clinical and laboratory features of patients with undifferentiated spondyloarthritis and ankylosing spondylitis.

The terms Spondyloarthritis and spondyloarthropathy (Spa) are used to define a group of diseases with related clinical characteristics and genetics. To report the clinical and demographic characteristics of ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA) and to evaluate the frequency of cyclic citrullinated peptide antibody (anti-CCP) positivity. Two hundred patients with USpA or AS, 100 control patients with a diagnosis of rheumatoid arthritis (RA) and 100 healthy volunteers were included. For each patient, their detailed medical histories, physical examination, whole blood counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-CCP, routine biochemical tests, and HLA-B27 test results were evaluated. ASDAS and BASDAI scores and morning stiffness were used to evaluate the disease activity. The presenting symptom of 73 (73%) patients in the AS group and 58 (58%) patients in the USpA group was pain in axial joints. A family history of Spa was positive in 32 patients from both groups (32%). A positive HLA-B27 was found in 55% of the AS group and 25% of the USpA group (p < 0.01 for the difference between groups). The frequency of positive HLA-B27 was significantly higher in individuals with a family history of SpA (p = 0.022). A positive Anti-CCP was found in 56% of the RA group, a significantly higher frequency compared with other groups (p < 0.001). The frequency of positive Anti-CCP in patients in AS (9%) and USpA (6%) was significantly higher than in healthy controls (p < 0.001). The frequency of anti-CCP positivity was higher in SpA patients than in healthy controls.

1267Prevalence and HLA-B27 Positivity Rate among Patients with Ankylosing Spondylitis/Non-Radiographic Axial Spondyloarthritis in Japan

Abstract Background Ankylosing spondylitis (AS) causes severe chronic inflammation of the spine and sacroiliac joints, leading to severe physical dysfunctions. Non-radiographic axial spondyloarthritis (nr-ax SpA) is a newly categorized disease in SpA that shows SpA without definite radiographic findings in sacroiliac joint. Although human leukocyte antigen (HLA) positivity is related to these diseases, little is known about the prevalence of these diseases and HLA-B27 positivity in Japan. Methods A nationwide survey was conducted from January to December 2017. 2221/8456 facilities (26.3%) were selected randomly as a target sample, comprising all three departments: orthopedics, pediatrics, and rheumatology. We estimated the number of these patients by using response and extraction rate, and calculated the HLA-B27 positivity rate. Results We estimated the prevalence of AS and nr-ax SpA as 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. HLA-B27 test was performed in 60% of patients with AS, of which 55.5% being HLA-B27 positive; however, they were less likely to receive HLA-B27 test if their estimated age of onset was over 50 years. Conclusions The prevalence in AS and nr-ax SpA and their HLA-B27 positivity rate in Japan were lower compared to other countries. Further studies will be required to reveal the association between HLA-B27 and the clinical features. Key messages The prevalence of AS and nr-ax SpA in Japan are estimated to be 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively, and are lower than those in other countries. In addition, HLA-B27 positivity rate was lower.

Comparison of Next-Generation Sequencing-Based Human Leukocyte Antigen Typing with Clinical Flow Cytometry and Allele-Specific PCR Melting Assays for HLA-B27 Genotyping.

Due to the strong association between ankylosing spondylitis and Human Leukocyte Antigen (HLA)-B27, accurate identification of HLA-B27 is important in the diagnosis of patients with suspected spondyloarthritides. For this study, we compared a high-resolution HLA-B typing method to the clinical flow cytometry and allele-specific PCR melting assays to determine clinical benefits of high-resolution testing. Residual clinical samples submitted for HLA-B27 testing by flow cytometry were tested by single-locus HLA-B genotyping using next-generation sequencing (NGS), and PCR with melting curve analysis, currently used as a reflex test for indeterminate flow cytometry results. Fifty out of the 51 samples (98%) positive by flow cytometry confirmed as HLA-B27 positive by PCR melting assay and by NGS. The sample that did not confirm was genotyped as HLA-B*07:02. All the samples negative by flow cytometry were confirmed as HLA-B27 negative by both PCR melting assay and NGS. For the group that was indeterminate by flow cytometry, 84.5% (n = 49) typed as positive for HLA-B27, while 15.5% (n = 9) were negative for HLA-B27 but positive for HLA-B*07:02. NGS was the only method able to distinguish between pathogenic and nonpathogenic HLA-B27 variants, in contrast to the flow cytometry or the PCR melting assays. Single-locus NGS is superior to flow cytometry and PCR melting assay for the unambiguous identification of HLA-B27 variants, and uniquely able to distinguish between pathogenic and nonpathogenic B27 alleles. Due to its high accuracy, it may be a feasible superior alternative to flow cytometry and traditional molecular methods for clinical HLA-B27 testing.

HLA-B27 is associated with reduced disease activity in axial spondyloarthritis

HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject’s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p < 0.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.

IMAGING OF ANKYLOSING SPONDYLITIS

Ankylosing spondylitis is among HLA-B27-associated diseases. Four common diseases of the HLA-B27- associated group include ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and reactive arthritis. This group is characterized by ankylosis, new bone formation and is common in large joints. Ankylosing spondylitis often have bilaterally asymmetrical sacroiliac joint involvement. Diagnosis is based on clinical, HLA-B27 testing and imaging. Conventional radiography is the classic diagnostic criteria. Magnetic resonance has recently been included in the 2009 ASAS diagnostic criteria for early diagnosis.

Personal Experiences with Diagnostic Delay Among Axial Spondyloarthritis Patients: A Qualitative Study.

IntroductionOn average, patients with axial spondyloarthritis (axSpA) suffer from symptoms up to 13 or more years before diagnosis, contributing to psychological distress and healthcare burdenMethodsWe conducted six semi-structured focus groups with 26 axSpA patients (from 3 rheumatology practices located in the states of Massachusetts, Colorado, and Pensylvania, USA) exploring early disease and diagnostic experiences. Verbatim transcripts were coded using a start list with emerging thematic codes added. A qualitative thematic analysis was performedResultsMany participants described meandering and frustrating diagnostic journeys. Participants reported that intermittent axSpA symptoms and idiopathic pain contributed to physician confusion and delay in patients seeking care. Participants were sometimes perceived as somaticizing, drug-seeking, or “crazy.” Diagnostic delay led to frustration and mental suffering. Doctors “giving up” was considered profoundly negative. Stories of symptoms fell into five areas: (1) pain; (2) stiffness; (3) impact on sleep; (4) impact on daily activities; and (5) changes with weather. Self-advocacy and family advocacy were considered essential. Participants suggested wider use of HLA-B27 testing and development of a definitive diagnostic testConclusionMost participants described significant suffering prior to axSpA diagnosis which could have been avoided with earlier intervention. Further research on the early disease experiences of axSpA patients is needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00321-z.

AB0692 REACTIVE ARTHRITIS ASSOCIATED WITH COVID-19 INFECTION: A REVIEW

Background:The incidence of COVID-19 infection is increasing globally with high mortality rate. Cytokine release syndrome might contribute to extra-pulmonary manifestations such as acute kidney injury, venous thrombosis, neurological complications, hepatic and myocardial injury. Reactive arthritis is an emerging musculoskeletal (MSK) manifestation post COVID-19 infection. Reactive arthritis manifests as asymmetrical, oligoarthritis mainly involving peripheral or axial joints of lower extremities and associated with extra-articular manifestations.Objectives:review the clinical presentation and management outcomes of COVID-19 associated reactive arthritis.Methods:A literature research was conducted using PubMed and Google scholar for published abstracts, case reports, and studies from January 2020 to January 2021. We used search keywords” reactive arthritis”, “COVID-19 pneumonia”, “ SARS CoV2 infection”, and “Musculoskeletal”. Descriptive analysis was used due to small sample size.Results:COVID-19 associated reactive arthritis is rarely reported. In review of literature, 10 cases were identified and we included our case of hip arthritis and avascular necrosis post COVID-19 infection. The mean age of cases (n=11) was of 42.8 years and 54.5 % of patients were males. (Table 1) The median duration of reactive arthritis diagnosis from COVID-19 infection ranged from 1 to 8 weeks. The severity of COVID-19 infection varied from mild (n= 6) to severe disease (n=2) per description in each reported case. Majority of the patients had oligoarticular involvement (2 to 4 joints) 45.5%, followed by monoarticular 36.4%, and polyarticular (&gt; 4 joints) in 18%. Extra-articular manifestations were identified in 54.5% of patients including skin rash (erythematous itchy rash), urticarial rash, wrist tendinitis, Achilles enthesitis /tendonitis and balanitis. HLA-B27 testing was done in five patients and only one patient had a positive result. Plain radiographs were normal. Therapy provided of such cases were NSAIDS (n=4), steroids (oral, intra-articular) (n=1) or combination of steroids and NSAIDS (n=3) with favorable outcomes. The median reported follow up period ranged from 1.5 to 8 weeks.Table 1.Characteristics of the reported reactive arthritis cases post COVID-19 infectionClinical data of patients (n=11)Results (n=11)Age (mean) 42.8 Years oldSex %Female (n= 5 [45.5%])Male (n= 6 [54.5%])Severity of COVID-19 infectionMild (n=6 [54.5%])Moderate (n=3 [27.3%])Severe (n= 2 [18%])Prior history of rheumatologic disease(n=0)Time to onset of reactive arthritis (median)1 to 8 weeksNumber of joints involved at time of diagnosisMonoarticular (n= 4[36.4%])Oligoarticular (n= 5[45.5%])Polyarticular (n= 2[18%])Location of involved joints (upper vs. lower limbs)Upper joints (18%)Lower joints (54.5%)Both (27.3%)Enthesitis(n= 1[9%]) AchillesTendonitis(n= 2[18%]) (wrist / Achilles tendonitis)Extra-articular involvement (eyes, skin, GI, GU, others)- Skin rash (n=2 [18%]) (erythematous itchy rash, urticarial rash)- GU: balanitis (n=1 [9%])Inflammatory back pain(n=0)Avascular necrosis of bone(n= 1[9%])HLA-B27(n= 1[9%]), (n = 5 tested)Autoimmune workupNegativeTreatment of reactive arthritis:DMARDs (n=0)NSAIDs (n=4 [36.4%])Steroids (n=1 [9%])NSAIDs and steroids (n= 3[27.3%])Not provided (n=2), others (n=1)Outcomes of MSK symptomsImprovement (n=11 [100%])Follow up period (Median, weeks)1.5 to 8 weeksGastrointestinal (GI), genitourinary (GU), NSAIDs: non-steroidal anti-inflammatory drugConclusion:Reactive arthritis is a rare MSK manifestations post COVID-19 infection. HLA-B27 positive testing might indicate severe and delayed form of arthritis with risk of recurrence. Larger studies are required to delineate the potential risk factors and long-term management outcomes for reactive arthritis associated with COVID-19 infection.