Current Rheumatology Reviews - Volume 20, Issue 2, 2024

Among instrumental techniques, nailfold capillaroscopy plays a leading role in the assessment of Raynaud's phenomenon (RP) patients because it is the only method that provides opportunities for morphological assessment of capillaroscopic findings in the nailfold area, with proven diagnostic and prognostic significance in rheumatology. The discussion about updating the classification of RP in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. The presence of dilation of the “true” capillary diameters in primary RP could be observed. There are some cases of primary RP where the capillaroscopic pattern is completely normal and there are no dilated capillaries present, which could be related to the duration and severity of the symptoms. It is possible that longer duration and greater severity are associated with the appearance of capillary dilations, but more research is needed to confirm it. Rarely, pathological capillaroscpic features of microangiopathy could be observed in RP patients in whom clinical, laboratory and immunological findings are compatible with the diagnosis “primary RP”. These cases should be defined as “suspected secondary RP” and require closer follow-up for the assessment of symptom evolution. Abnormal “scleroderma” type capillaroscopic pattern has been established as a new classification criterion for systemic sclerosis (SSc) in 2013. Similar changes (“scleroderma-like” pattern) could be observed in other rheumatic diseases, i.e., undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, including without evidence of overlap with scleroderma. The appearance of such microvascular abnormalities at disease presentation is less well studied in diseases different from SSc. However, “scleroderma-like” microangiopathy has also been reported as an initial sign in some systemic rheumatic diseases, such as UCTD and systemic lupus erythematosus. Thus, interpretation of capillaroscopic findings is performed in overall context, including clinical findings and laboratory and immunological test results.

Acroparesthesia is a symptom characterized by a subjective sensation, such as numbness, tingling, prickling, and reduced sensation, affecting the extremities (fingers and toes). Despite its frequency, data regarding its diagnostic approach and management are scarce. The etiological diagnosis of acroparesthesia is sometimes challenging since it can be due to abnormality anywhere along the sensory pathway from the peripheral nervous system to the cerebral cortex. Acroparesthesia can reveal several diseases. It can be associated with rheumatic complaints such as arthritis or myalgia. Further cautions are required when paresthesia is acute (within days) in onset, rapidly progressive, severe, asymmetric, proximal, multifocal, or associated with predominant motor signs (limb weakness) or severe dysautonomia. Acroparesthesia may reveal Guillain-Barré syndrome or vasculitis, requiring rapid management. Acroparesthesia is a predominant symptom of polyneuropathy, typically distal and symmetric, often due to diabetes. However, it can occur in other diseases such as vitamin B12 deficiency, monoclonal gammopathy of undetermined significance, or Fabry’s disease. Mononeuropathy, mainly carpal tunnel syndrome, remains the most common cause of acroparesthesia. Ultrasonography contributes to the diagnosis of nerve entrapment neuropathy by showing nerve enlargement, hypoechogenic nerve, and intraneural vascularity. Besides, it can reveal its cause, such as space-occupying lesions, anatomical nerve variations, or anomalous muscle. Ultrasonography is also helpful for entrapment neuropathy treatment, such as ultrasound-guided steroid injection or carpal tunnel release. The management of acroparesthesia depends on its causes. This article aimed to review and summarize current knowledge on acroparesthesia and its causes. We also propose an algorithm for the management of acroparesthesia.

Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.

Knee Osteoarthritis (KOA) is a degenerative joint ailment characterized by cartilage loss, which can be seen using imaging modalities and converted into imaging features. The older population is the most affected by knee OA, which affects 16% of people worldwide who are 15 years of age and older. Due to cartilage tissue degradation, primary knee OA develops in older people. In contrast, joint overuse or trauma in younger people can cause secondary knee OA. Early identification of knee OA, according to research, may be a successful management tactic for the condition. Scoring scales and grading systems are important tools for the management of knee osteoarthritis as they allow clinicians to measure the progression of the disease's severity and provide suggestions on suitable treatment at identified stages. The comprehensive study reviews various subjective and objective knee evaluation scoring systems that effectively score and grade the KOA based on where defects or changes in articular cartilage occur. Recent studies reveal that AI-based approaches, such as that of DenseNet, integrating the concept of deep learning for scoring and grading the KOA, outperform various state-of-the-art methods in order to predict the KOA at an early stage.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that predominantly affects young males. AS is a condition in which the spine and sacroiliac joints become inflamed. More specifically, most AS patients experience spine malformations over time, resulting in functional incapability. The etiopathogenesis of AS is a complex combination of genetic predisposition and environmental factors. Extensive studies on AS have revealed the central role of genetics and immune reactions in its etiology. However, an utmost agreement has yet to be created. The available evidence suggests that both autoinflammation and T-cell-mediated autoimmune processes have significant roles in the disease process of AS. So far, B cells have obtained moderately little attention in AS pathogenesis, primarily because of the absence of disease-defining autoantibodies. However, against general dogma, evidence is mounting showing B cell involvement. Disruptions depict this in circulating B cell populations, the increased expression of immunoglobulin (Ig)G, IgA, and IgM, and B cell infiltration within the axial skeleton of AS patients. Meanwhile, compared to many other inflammatory autoimmune disorders, AS has no disease-specific autoantibodies that help disease diagnosis. This study has provided an overview of the B lymphocytes and antibodies' role in AS pathogenesis. It also introduces autoantibodies that can be the prognosis and diagnosis biomarkers of AS.

Objective: This study aimed to investigate spinal involvement in psoriatic arthritis (PsA) patients using clinical and radiographic methods. Methods: A cross-sectional clinical study was conducted on 50 PsA patients diagnosed according to the CASPAR criteria. Clinical examinations and functional assessments were performed. A radiographic assessment of the spine was performed. Results: Out of 50 PsA patients (mean age of 45.50 ± 9.90 years), (males and females constituted 27 (54.0%) and 23 (46.0%) respectively), 76% had radiological axial involvement; (26%) with inflammatory axial pain and (50%) without inflammatory axial pain (subclinical). Three axial radiographic patterns were detected including spondylitis without sacroiliitis (15.78%), spondylitis with sacroiliitis (78.94%), and sacroiliitis without spondylitis (5.26%). In axial PsA patients, males were more affected than females (χ²=11.679, p = 0.003), with older age (H = 15.817, p < 0.001) and higher body mass index (BMI) (F = 5.145, p = 0.010), increased psoriasis duration (H = 9.826, p = 0.007) and severity (=25.171, p < 0.001), and more spinal movement limitations than PsA patients without axial involvement (F = 26.568, p < 0.001). Cervical involvement was higher than lumbar involvement. Axial radiographic severity assessed by the PsA Spondylitis Radiology Index was associated with increased disability as assessed by the Health assessment questionnaire (rs = 0.533, p = 0.001) and decreased quality of life assessed by short form-36 score (rs = -0.321, p = 0.050). Conclusion: This study shows that a high percentage of PsA patients had axial involvement with a high percentage of them having asymptomatic radiological findings. The cervical spine is more frequently and severely affected than the lumbar spine. Axial PsA occurs in males more than females with characteristic older age and higher BMI, increased psoriasis duration, and more limitation of spinal mobility.

Background: Knee osteoarthritis (KOA) is currently treated by regenerative therapies that aim to inhibit arthritic degeneration. Extracorporeal shock wave therapy (ESWT) is one of the physical regenerative approaches used for KOA management. However, little is known regarding the impact of shock wave treatment on matrix metalloproteinase-3 (MMP-3), which is one of the enzymes mediating cartilage degradation. Objectives: To evaluate the effect of ESWT on MMP-3 levels and pain intensity in patients with KOA. Methods: Fourteen patients diagnosed with Kellgren Lawrence, grades 2 and 3 KOA were recruited for the study. ESWT piezo shockwave was applied once a week for six weeks. MMP-3 levels in the blood were measured pre-test, mid-test (three weeks after therapy) and post-test (one week after the last session) by enzyme-linked immunosorbent assay (ELISA). The perceived pain was recorded at each session by the Wong Becker Face Scale. Results: The median pre-test, mid-test and post-test MMP-3 levels were 19.92 ng/mL, 15.89 ng/mL and 18.82 ng/mL, respectively, and there were significant differences between the pre-test and mid-test, and the pre-test and post-test values (p < 0.05). The pain scores also decreased significantly over the period of intervention. Conclusion: MMP-3 levels decreased significantly in KOA patients after ESWT, and the decline was most obvious after 3 weeks of therapy. Therefore, EWST should be considered as a suitable treatment option for KOA.

Background: Rheumatoid arthritis (RA), an autoimmune joint inflammatory disease, presents a significant challenge due to its prevalence, particularly among women, affecting around 6% of individuals over the age of 65. Novel insights into disease mechanisms are crucial for improved diagnostic and therapeutic approaches. Objective: Long non-coding RNAs (lncRNAs) have emerged as potential contributors to the pathogenesis of various autoimmune diseases, including RA. This study aims to investigate the unique roles of four lncRNAs-NEAT1, GAS5, TMEVPG1, and GAPLINC-in the etiology of RA. Methods: Leveraging isolated serum samples from RA patients and healthy controls, we comprehensively evaluated the expression profiles of these lncRNAs. Results: Notably, our findings unveil a distinctive landscape of lncRNA expressions in RA. Among them, GAPLINC exhibited a significantly elevated average expression in the serum samples of RA patients, suggesting a potential biomarker candidate for disease stratification. Importantly, reduced expression of NEAT1 and GAS5 was observed in RA patients, highlighting their possible roles as diagnostic and prognostic markers. Conversely, TMEVPG1 displayed unaltered expression levels in RA samples. Conclusion: Our study introduces a novel dimension to RA research by identifying NEAT1, GAS5, and GAPLINC as promising serological biomarkers. These findings hold significant clinical implications, offering potential avenues for improved diagnosis, disease monitoring, and therapeutic interventions in RA.

Background: In rheumatoid arthritis (RA), insulin resistance (IR) is related to inflammatory markers, disease activity, and progression of atherosclerotic changes. Triglyceride-glucose (TyG) index is a relatively new indicator of IR. Aims: The present study aimed to investigate the relationship between TyG index, disease activity and subclinical atherosclerosis (SCA) in RA patients. Methods: The present case-control study included 100 RA patients and 50 age- and sex-matched healthy controls. All participants were subjected to careful history taking through clinical examination and standard laboratory assessment. The TyG index was calculated as TyG index = ln (Fasting triglyceride (mg/dL) × fasting glucose (mg/dL))/2. Carotid intima-media thickness (CIMT) measurement was done using B-mode ultrasound. Results: Patients had significantly higher TyG index as compared to controls. Patients with high disease activity had significantly higher frequency of extraarticular manifestations (39.6% versus 51.6%, p = 0.028), higher Larsen score (3.8 ± 1.3 versus 2.8 ± 1.2, p < 0.001), higher anti-cyclic citrullinated peptide (anti-CCP) levels (median (IQR): 243.1 (205.0-408.0) U/ml versus 99.0 (78.0-332.5), p < 0.001), higher TyG index (4.8 ± 0.22 versus 4.67 ± 0.24, p = 0.006), and higher CIMT (0.87 ± 0.22 versus 0.77 ± 0.17 mm, p = 0.018). Patients with SCA had higher BMI (34.6 ± 6.2 versus 30.5 ± 5.3 Kg/m², p < 0.001), higher Larsen score (3.7 ± 1.4 versus 3.1 ± 1.3, p = 0.028) and higher TyG index (4.89 ± 0.23 versus 4.64 ± 0.19, p < 0.001). Binary logistic regression analysis identified patients’ age (OR (95% CI): 0.94 (0.89-0.99), p = 0.018), Larsen score (OR (95% CI): 1.93 (1.32-2.82), p = <0.001), anti-CCP (OR (95%): 1.04 (1.02-1.07), p = 0.032), and TyG index (OR (95% CI): 22.67 (2.14-240.4), p = 0.01) as significant predictors of high disease activity in multivariate analysis. Conclusion: IR estimated by the TyG index is related to disease activity and SCA in RA patients.

Background: Behçet's disease (BD) has a growing prevalence in Silk Road countries. The aim of our cross-sectional study was to explore the clinical and molecular predictors of quality of life in BD patients. Materials and Methods: One hundred and fifty consecutive Iranian BD patients with an age range between 20-50 years were included. The Leeds Behçet's disease quality of life (BDQoL) in Persian form was fulfilled to evaluate the quality of life. Anthropometric measurements were carried out using the calibrated scales. Iranian Behcet's Disease Dynamic Activity Measure (IBDDAM), Behcet's disease current activity form (BDCAF), and Total Inflammatory Activity Index (TIAI) were used to assess BD activity. mRNA expression of toll-like receptors 2 and 4 (TLR2 and TLR4) and tumor-necrosis-factor-alpha (TNF-α) levels in serum were measured by real-time polymerase chain reaction (PCR) and ELISA, respectively. Multiple linear backward regression at P = 0.1 was used to study the potential predictors of quality of life. Results: TLR2 and BDCAF were shown to be the most important predictors of quality of life in BD patients by 22%. There were positive associations between them (β = 0.326, p = 0.013 for BDCAF; β = 0.366, p = 0.006 for TLR2) and BDQoL value. Conclusion: Higher TLR2 expression as a key protein in recognizing pathogens by innate immunity and BDCAF value as a comprehensive BD assessing scale contribute to poor quality of life among BD patients. Emphasizing therapeutically, approaches associated with lower TLR2 expression and BDCAF value can be considered in future studies.

Background: Transverse myelitis is considered one of the cardinal features of neuromyelitis optica spectrum disorder (NMOSD), an immune-mediated inflammatory condition of the CNS characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and spinal cord. We describe a case in which a diagnosis of NMOSD was established, associated with West Nile Virus (WNV) infection. Case Presentation: A healthy 18-year-old female presented with intractable hiccups and rapidly progressing paraparesis. MRI demonstrated T2 edema extending from the medulla to the conus, consistent with longitudinally extensive transverse myelitis. Serum and CSF Aquaporin-4 IgG (AQP4) were both positive with high titers. In conjunction with antiviral therapy, immunomodulatory treatment was initiated using pulse methylprednisolone, plasmapheresis and Rituximab. A month and a half after admission, the patient was fully ambulatory with no residual symptoms. On her rheumatology follow-up visit, West Nile Virus-specific IgM in CSF was found to be positive from the patient’s initial presentation. Conclusion: We propose that West Nile Virus may have been the autoimmune trigger to the patient’s development of NMOSD, highlighting the importance of evaluating viral triggers in autoimmune diseases.

Background: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast. Case Presentation: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion. Conclusion: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.

Background: Adult-onset Still’s disease (AOSD) is a challenging diagnosis because of the variability in clinical presentation and lack of gold-standard diagnostic investigations. Even after diagnosis, the treatment is challenging, especially when the disease is refractory to first-line therapy. Multiple pharmacotherapeutic options exist for refractory AOSD, but treatment failures still occur. Etanercept, a Tumor necrosis factor (TNF)-alpha inhibitor, is one of the options that has been rarely used for refractory AOSD, with various outcomes ranging from no response to complete remission. Case Presentation: In this case, we highlight how a previously healthy lady had refractory AOSD to glucocorticoids, methotrexate, and hydroxychloroquine combination therapy. There was no response to interleukin (IL)-1 therapy, which necessitated a switch to a combination of etanercept, low-dose methotrexate, and low-dose glucocorticoids with complete remission for a total of three- -year follow-up. Conclusion: The combination of methotrexate and Etanercept can maintain remission in patients with refractory AOSD.