Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results

Background. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods. Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%, p = 0.032 ) and recessive model (14.1% vs. 4.9%, p = 0.017 , OR = 3.2 (1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%, p = 0.009 , OR = 11 (1.3-89.2)) and recessive models (100% vs. 69.3%, p = 0.032 ), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%, p = 0.005 , OR = 10.1 (1.3-76.6) and 82.8% vs. 68.6, p = 0.041 , OR = 2.2 (1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1, p = 0.045 ) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3, p = 0.002 ) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2, p = 0.031 ) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.

Tocilizumab Effect on Lipid Profile in Correlation to Cardiovascular Events: A Retrospective Cohort Study

Objective. To study the effect of tocilizumab initiation on the lipid profile, in correlation to a composite of any cardiovascular events. Methods. A retrospective cohort study, using data from the King Faisal Specialist Hospital & Research Centre database, from January 2014 to December 2019. Patients with rheumatoid arthritis or juvenile idiopathic arthritis who were ≥18 years old, initiated either on tocilizumab or other biologic treatment (anti-TNFs or Rituximab), were included, with a follow-up interval duration at a minimum of 6–12 months up to 3-5 years. Any patient with established cardiovascular disease or aged <18 were excluded. Results. Only one cardiovascular mortality was reported in the tocilizumab group. Fifty percent of patients reached high cholesterol levels ≥ 5.2 mmol / L and LDL ≥ 3.37 mmol / L in the tocilizumab group at 36 months in a shorter time period compared to controls (60 months), P 0.001. There were no significant differences between groups for statin use (27% vs. 28%) However, there was a significantly higher mean dose of atorvastatin in the tocilizumab group compared to controls (20.6 mg vs. 16.6 mg, P 0.03). Conclusion. There was a lack of evidence of increased cardiovascular risk in correlation to hyperlipidemia secondary to tocilizumab treatment.

Cutaneous Manifestations of “Lupus”: Systemic Lupus Erythematosus and Beyond

Lupus, Latin for “wolf,” is a term used to describe many dermatologic conditions, some of which are related to underlying systemic lupus erythematosus, while others are distinct disease processes. Cutaneous lupus erythematosus includes a wide array of visible skin manifestations and can progress to systemic lupus erythematosus in some cases. Cutaneous lupus can be subdivided into three main categories: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus. Physical exam, laboratory studies, and histopathology enable differentiation of cutaneous lupus subtypes. This differentiation is paramount as the subtype of cutaneous lupus informs upon treatment, disease monitoring, and prognostication. This review outlines the different cutaneous manifestations of lupus erythematosus and provides an update on both topical and systemic treatment options for these patients. Other conditions that utilize the term “lupus” but are not cutaneous lupus erythematosus are also discussed.

Update in the Management of ANCA-Associated Vasculitis: Recent Developments and Future Perspectives

Significant progress has been made in the treatment of ANCA-associated vasculitides (AAV), notably in granulomatosis with polyangiitis and microscopic polyangiitis. Over the past few years, many innovative studies have changed the way we now induce and maintain remission in AAV; achieving remission while limiting treatment toxicity is the key. This article provides an in-depth, up-to-date summary of recent trials and suggests treatment algorithms for induction and maintenance of remission based on the latest guidelines. Future possible therapies in AAV will also be discussed.

Clinical Outcomes of Myocarditis after Moderate-Dose Steroid Therapy in Systemic Sclerosis: A Pilot Study

Background. Myocarditis is reported in systemic sclerosis (SSc); however, treatment options and outcomes are limited. Our objective was to define cardiac outcomes after moderate-dose steroid therapy in SSc patients with myocarditis. Method. An open-label study was conducted among SSc patients with myocarditis—as defined by cardiovascular magnetic resonance (CMR), disease onset <5 years, and a NYHA functional class ≥II. All enrolled patients received prednisolone (30 mg/d) which would be tapered off by week 24, and CMR was followed up at the end of treatment. Results. A total of 20 SSc patients were enrolled which 12 patients completed the study. At week 24, 8 of the 12 cases experienced improvement of myocarditis. Compared to those with no improvement, these 8 patients had significantly longer disease duration ( p = 0.03 ), higher heart rate at baseline ( p = 0.049 ) and week 24 ( p = 0.04 ), lower left ventricular (LV) and right ventricular (RV) stroke volume at baseline ( p = 0.002 and p = 0.01 ) and week 24 ( p = 0.01 and p = 0.02 ), and lower LV and RV cardiac output at week 24 ( p = 0.01 and p = 0.01 ). Four cases died during follow-up (3 due to cardiac complications, 1 due to renal crisis). The two who died from heart failure had very high NT-prohormone-brain natriuretic peptide (NT-proBNP) and impaired LV ejection fraction (LVEF), and the one who died from arrhythmia had very high sensitivity of cardiac Troponin-T (hs-cTnT). Conclusions. Moderate-dose steroid therapy may improve myocarditis in SSc. A proportion of patients died due to cardiac complications during treatment, particularly those with high hs-cTnT, high NT-proBNP, and impaired LVEF. This trial is registered with NCT03607071.

Intracytoplasmic Expression of IL-6 and IL-17A in Circulating CD4+ T Cells Are Strongly Associated with and Predict Disease Activity in Rheumatoid Arthritis: A Case-Control Study in Ghana

Background. T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. However, their role in RA within hitherto rare Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4+ T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity. Methods. This case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for flow cytometric analysis. Results. IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4, and IL-17/IL-10 expressions were significantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs. 0.82 (0.34-1.10) vs. 1.56 (1.39-1.68), p<0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), p<0.0001), and IL-17A/IL-10 (0.00 (0.00-0.39) vs. 0.15 (0.09-0.26) vs. 0.88 (0.41-1.47), p<0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (β=0.681, r2=0.527, p<0.0001), IL-17A (β=0.770, r2=0.593, p<0.0001), and IL-17A/IL-10 (β=0.677, r2=0.452, p<0.0001) expressions were significantly directly associated with DAS28 scores. IL-6 (cutoff=1.32, sensitivity=100.0%, specificity=100.0%, accuracy=100.0%, and AUC=1.000) and IL-17A (cutoff=0.58, sensitivity=100.0%, specificity=100.0%, accuracy=100.0%, and AUC=1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores. Conclusion. Th1- and Th17-related cytokines predominate in the pathophysiology of RA, with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context.

Direct Healthcare Costs Associated with Oligoarticular Juvenile Idiopathic Arthritis at a Single Center

Oligoarticular juvenile idiopathic arthritis (JIA) is a common disease in pediatric rheumatology. The management of oligoarticular JIA can result in a considerable economic burden. This study is a four-year, retrospective cost identification analysis performed to determine the annual direct cost of care for patients with oligoarticular JIA and possible predictive clinical factors. Direct healthcare costs were defined as those associated with office visits, laboratory studies, hospital admissions, joint injections, medications, infusions, radiology tests, and emergency room visits. Disease characteristics and patient information included ANA status, gender, age at diagnosis, duration from diagnosis to initial visit during the study period, and whether uveitis had been diagnosed. We identified 97 patients with oligoarticular JIA eligible for the study. The median age of diagnosis was 4.3 years. Positive ANA were noted in 75% of patients. 34% of patients received at least one intra-articular steroid injection. 32% of patients were prescribed a biologic during the study period, predominantly with other medications, while 23% of patients received only NSAIDs. 20% of patients were prescribed oral steroids. The average total direct medical cost in this study per year for an oligoarticular JIA patient was $3929±6985. Medications accounted for 85% of annual direct medical costs. Clinic visits and laboratory testing accounted for 8% and 5%, respectively. Patient characteristics and demographics were tested for association with direct medical costs by the Wilcoxon rank sum test and Kruskal-Wallis test. Patients who were ANA positive had increased annual costs compared to patients who are ANA negative. ANA-positive patients were found to have statistically significant costs, particularly, in laboratory tests, procedural costs, radiology costs, and medication costs. The results reported here provide information when allocating healthcare resources and a better understanding of the economic impact oligoarticular JIA has on the United States healthcare system.

Clinical Presentations of Lumbar Disc Degeneration and Lumbosacral Nerve Lesions

Lumbar disc degeneration is defined as the wear and tear of lumbar intervertebral disc, and it is mainly occurring at L3-L4 and L4-S1 vertebrae. Lumbar disc degeneration may lead to disc bulging, osteophytes, loss of disc space, and compression and irritation of the adjacent nerve root. Clinical presentations associated with lumbar disc degeneration and lumbosacral nerve lesion are discogenic pain, radical pain, muscular weakness, and cutaneous. Discogenic pain is usually felt in the lumbar region, or sometimes, it may feel in the buttocks, down to the upper thighs, and it is typically presented with sudden forced flexion and/or rotational moment. Radical pain, muscular weakness, and sensory defects associated with lumbosacral nerve lesions are distributed on lower extremities, the buttock, lower abdomen, and groin region. A lumbosacral plexus lesion presents different symptoms in the territories of the lumbar and sacral nerves. Patients with lumbar plexus lesion clinically present with weakness of hip flexion, knee extension, thigh adduction, and sensory loss in the lower abdomen, inguinal region, and over the entire medial, lateral, and anterior surfaces of the thigh and the medial lower leg, while sacral plexus lesion presents clinical symptoms at nerve fibers destined for the sciatic nerve, common peroneal nerve, and pudendal nerve. Weakness of ankle inversion, plantar flexion, and foot drop are the main clinical manifestations of the sacral plexus lesion area. Numbness and decreased sensation are also present along the anterolateral calf and dorsum of the foot. On examination, foot eversion is usually stronger than foot dorsiflexion. The patients may also present with pain and difficulty of bowel movements, sexual dysfunction assessments, and loss of cutaneous sensation in the areas of the anal canal, anus, labia major, labia minor, clitoris, penis, and scrotum.

Evaluation Effects of Laser Therapy and Extracorporeal Shock Wave Therapy with Clinical Parameters and Magnetic Resonance Imaging for Treatment of Plantar Fasciitis in Patients with Spondyloarthritis: A Randomized Controlled Trial

Objective. Low-level laser therapy (LLLT) and extracorporeal shock wave therapy (ESWT) is applied in the conservative treatment of inflammatory plantar fasciitis, which is also a characteristic feature of spondyloarthritis (SpA) (Gill, 1997 and Roxas, 2005). We determined and compared the effectiveness of LLLT and ESWT using magnetic resonance imaging (MRI). Methods. This study is a prospective, randomized, comparative, single-blind clinical study. Voluntarily followed 40 patients with the diagnosis of SpA and having pain at the heels at least for 6 months. Patients were divided randomly into two treatment groups. One group undertook 14 sessions of infrared Ga-Al-As LLLT, and the other group undertook 3 sessions ESWT. Feet functions of the patients were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) and Roles and Maudsley Scoring; VAS was evaluated for foot pain and function. In clinical assessment, disease activity was carried out by applying the BASDAI, the functional assessment was evaluated through the BASFI, and the patient quality of life was evaluated through the ASQoL; enthesitis was scored according to MASES assessment, performed before and at 1 month after treatment. The thickness of the plantar fascia was measured with MRI before and 1 month after treatment. Results. Compared with the pretherapy, progress in the feet function by AOFAS and Roles-Maudsley scoring and decrease in VAS levels were statistically significant in both groups (p<0.001). Only the VAS exercise score was superior to LLLT (p<0.05). The thickness of the plantar fascia had decreased significantly on MRI in all two groups. Conclusion. The treatment of plantar fasciitis with LLLT and ESWT was more successful in pain improvement and functional outcomes with the dose, frequency, and duration used in our study.

Vaccinations Do Not Increase Arthritis Flares in Juvenile Idiopathic Arthritis: A Study of the Relationship between Routine Childhood Vaccinations on the Australian Immunisation Schedule and Arthritis Activity in Children with Juvenile Idiopathic Arthritis

Background. Juvenile idiopathic arthritis (JIA) is a collective term for a group of inflammatory conditions of uncertain origin, which causes chronic arthritis in one or more joints. The clinical course of JIA is characterised by episodes of increased activity, termed flares. Vaccinations have previously been proposed as a “trigger” for some flares, although evidence supporting this is scant. Objective. To explore whether routine childhood vaccinations are associated with an increased risk of flares of arthritis activity in children with JIA. Methods. Patients aged below 6 years with a diagnosis of JIA were recruited from the Rheumatology Clinical Database at the Royal Children’s Hospital, Melbourne, Australia, from 1 January 2010 to 30 April 2016. Patient immunisation status was cross-checked with the Australian Childhood Immunisation Register (ACIR). The self-controlled case series methodology (Rowhani-Rahbar et al., 2012) was applied to determine whether the risk of arthritis flares in the three months following immunisation was greater than the baseline risk for each patient. Results. 138 patients were included in the study. 32 arthritis flares occurred in the 90 days following immunisation. The risk of arthritis flares during the 90 days following immunisation was reduced compared with patients’ baseline risk (RR 0.59 (95% CI 0.39-0.89, p=0.012)). Conclusion. Routine childhood immunisations were not associated with arthritis flare onset in patients with JIA. The risk of arthritis flares in the 90 days following vaccination was lower than the baseline risk. In the context of COVID19, vaccination will not increase interaction with the healthcare system beyond the immunisation encounter.