Current Rheumatology Reviews - Volume 19, Issue 1, 2023

Background: Few studies have described lymphocytic interstitial pneumonia (LIP) in Sjögren's syndrome (SS). We aimed to analyze the clinical, therapeutic, and outcome of patients with SS and LIP. Methods: We searched for articles in PubMed/MEDLINE, LILACS, SciELO, and Cochrane from 1966 to 2020, in English, Spanish, French, Chinese, and Japanese literature had an English summary about LIP and SS. The keywords were "Sjögren syndrome" and "Lymphocytic interstitial pneumonia." Additionally, we report a patient with SS and LIP. Results: 27 patients with SS and LIP were found. The age range ranged from 14 to 73 years old, with only 3 male patients, with a predominance of LIP cases in patients with primary SS (22/27). In the following case, the LIP preceded SS by 2 years; in the other 26 patients, SS preceded it. The majority presented dyspnea, mainly on exertion, followed by a dry cough. Lung biopsy was performed in 10 studies. Therapy varied from the use of clinical observation, corticosteroids alone, or associated with immunosuppressants. Most studies have shown improvement or stabilization of the pulmonary condition after therapy (13/16 studies). Conclusion: This article reviews cases of lymphocytic interstitial pneumonia associated with Sjögren syndrome and shows a good outcome with adequate treatment. It emphasizes that early LIP diagnosis in patients with Sjogren Syndrome may be determined using lung computed tomography.

Rheumatologists encounter patients with psychiatric illnesses daily in their practice; however, formal training in rheumatology does not sufficiently equip rheumatologists with guidance for managing common psychiatric illnesses. This study reviews common clinical situations involving psychiatric symptoms, their relationship with rheumatologic conditions, and their effects on clinical presentation and management. We illustrate key principles in a case-based format and reflect on the management of psychiatric components. Based on these discussions and a brief review of the epidemiology of psychiatric illnesses, we emphasize the prevalence and significance of these problems in daily practice.

Fibromyalgia has previously been categorized as primary, secondary, and juvenile fibromyalgia. However, these definitions do not adequately explain the etiopathology of disease, nor do they help direct new specific therapies. Herein, we review the previously known categorizations of fibromyalgia. Based on common patient characteristics and previously studied pathophysiologies, we propose new subcategorizations of fibromyalgia that we have self-narrated, including hormonal fibromyalgia, neuroendocrine fibromyalgia, psychologic fibromyalgia, inflammatory fibromyalgia, and lastly neuropathic fibromyalgia. To verify, add to, and fully describe these selfnarrated categories of fibromyalgia that we have proposed, future research needs to be done.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the synovial joints, causing swelling and joint damage. RA has become a major public health concern, harming more than 1500 people per lakh of the world's population. This inflammatory disorder is more common in females in comparison to males (3:1). In the present work, a scientometric analysis of published articles on RA during the last five years [1st January 2016 to 2021] on 19/08/2021 in the Scopus database is performed and investigates the contribution of India. In this study, the top most productive countries and the contribution of India in this field were analyzed. The different journals, funding agencies, and productive authors from India who contributed to this field are also recognized. The average citation impact is 10 citations per paper. A total of 61% share was found for the International collaboration in India’s publication on rheumatoid arthritis. In India's output on rheumatoid arthritis, medicine produced the largest percentage of paper (60 percent). The top 15 journals publishing the maximum number of Indian papers contribute 1% share of global rheumatoid arthritis research (The highest number of papers (95 papers) published by the Indian Journal of Rheumatology). During the period 2016-2021, the top 10 highly cited papers got a total of 7045 citations, averaging 705 citations per publication. India was found to have a 5% (1974 publications) share of global output (42312 publications). In conclusion, there is a small number of researches on rheumatoid arthritis in a country, which holds the 2nd position in population across the world. There is a need for more research on rheumatoid arthritis in India.

Osteoporosis is an important public health concern, with secondary fragility fractures carrying a poor prognosis. The role of a Fracture Liaison Service (FLS) is to identify fragility fracture patients via investigation and risk assessment. This serves to address the osteoporosis treatment care gap that exists where the majority of patients with a new fragility fracture over 50-years-old fail to receive a bone mass density (BMD) scan and osteoporosis treatment, ultimately receiving inadequate care. Osteoporosis medication is effective in reducing secondary fragility fractures. However, treatment adherence poses a problem. The FLS serves to prevent more serious secondary fragility fractures such as hip fractures. This minimises operative costs and the cost of postoperative care and results in fewer secondary care and care home admissions, increasing healthcare savings. Implementation of the FLS is effective in increasing investigation, treatment initiation, and adherence, with a corresponding decrease in refracture rate and mortality. This paper aims to evaluate the previous osteoporosis treatment care gap, the effectiveness of osteoporosis medications currently available, and finally, the cost and clinical effectiveness of the FLS serving as a secondary prevention tool.

Systemic inflammatory diseases could produce neurologic complications, and they are frequently incorporated in the differential diagnosis of neurological symptoms. There are wellestablished criteria to meet the diagnosis of neurologic manifestations of these systemic diseases. Methods: However, the range of clinical presentations varies in each condition, and the prevalence of these complications differs between studies. Hence, in many cases, an etiological relationship is not clearly defined. Results and Conclusion: For these reasons, it is challenging to make an accurate diagnosis. We analyzed the spectrum of neurological manifestations in a cohort of patients with systemic lupus erythematosus, rheumatoid arthritis, Behçet disease and sarcoidosis in order to improve our current knowledge of these complications.

Background: Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population. Methods: Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes. Results: No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma. Conclusion: Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Background/Aims: Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis difficult. Host genetic factors, such as the Human Leukocyte Antigens (HLA) polymorphisms were associated with HCV infection, however, there are no studies that discriminate between HCVrelated RM and DCTD-related RM. This study focused on verifying associations between HLADRB1 and RM in patients with chronic hepatitis C, aiming to distinguish between DCTD-related RM and HCV-related RM. Methods: The participants were 152 individuals, of both sexes, aged between 18 and 80 years, and affected by chronic hepatitis C. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (Polymerase Chain Reactionsequence Specific Oligonucleotides). Results: A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. DRB1*08 allele seems to confer protection against RM in chronic hepatitis C. There is no susceptibility association between HLA-DRB1 alleles and RM. Conclusion: The absence of association between HLA-DRB1 and the rheumatologic manifestations studied suggests that the pathophysiological pathways of DCTD-related RM and HCV-related RM are distinct.

Background: This study aimed to evaluate the serum level of human leukocyte antigen G [HLA-G] in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls; moreover, it attempted to assess its relationship with SLE and RA disease activity indices. Methods: This descriptive study was conducted on 31 SLE patients (17 cases with a recent diagnosis and 14 cases with a previous diagnosis), 21 RA patients (7 cases with a recent diagnosis and 14 cases with a previous diagnosis), and 18 healthy controls who visited Ghaem Hospital affiliated to Mashhad University of Medical Sciences, Mahhad, Iran. SLE and RA activity indices were measured and recorded. Furthemore, soluble isoforms, including shed HLA-G1 and HLA-G5, were measured in serum samples via the ELISA method. Results: A comparison of the five groups showed no significant differences in the serum level of sHLA-G. However, sHLA-G serum level was significantly higher in SLE and RA patients compared to healthy controls (P<0.05). sHLA-G level showed no correlation with disease duration and activity in SLE and RA patients (P>0.05). However, a strong positive correlation was observed between the serum level of sHLA-G and 24-h urine protein in the previously diagnosed SLE group (r=0.83, P=0.01). Conclusion: It seems that the serum level of sHLA-G is higher in RA and SLE patients compared to healthy controls. Furthermore, a strong correlation was found between sHLA-G serum levels and 24-h urine protein in cases with a previous diagnosis of SLE.

Objective: To determine the frequency and assess the risk of cardiovascular disease in patients suffering from gout. Background: Gout is a sign of disturbed metabolism, which is associated with cardiovascular diseases (CVD). Soaring mortality is associated with a lot of risk factors and comorbid conditions, which have to be dealt with the help of scientists and practitioners. Methods: The following retrospective study included 218 patients suffering from gout according to the criteria of S.L. Wallace. The risk of major coronary events was calculated via the SCORE scale. Results: Arterial hypertension and BMI > 25 kg / m2 (90.8%) have prevailed among the respondents. Increased level of total cholesterol (TC) was detected in 63.8% cases, decreased level of highdensity lipoproteins - in 71.6%, and hypertriglyceridemia - in 60.5% relevantly. 175 patients (80.3%) had high cardiovascular risk (estimated more than 5%). 43 (19.7%) of them had a low and medium risk of developing fatal CVD (1-4%). The high share of patients suffering from gout was endangered with cardiovascular pathology. Conclusion: The most frequently matched risk factors among patients suffering from gout are an increase in BMI> 25 kg/m2 (90.8%) and dyslipidemia.

Background: Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity. Methods: We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR). Results: Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients. Conclusion: FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity.

Background: The negative effects of rheumatoid arthritis (RA) are multi-dimensional. Foot deformities lead to disability, pain, and impaired quality of life. Objective: Identifying the difficulties in functioning rheumatoid foot and assessing the quality of life in this aspect. Materials and Methods: The material included 50 patients of Rheumatology Policlinic of the Central Clinical Hospital of Interior Affairs in Warsaw and a matched control group of 50 individuals without RA. The degree of foot joint damage was assessed using the Manchester scale, lower limb movement and quality of life using the American Orthopedic Foot and Ankle Society Score and HAQ. Results: The duration of symptoms was 16.0 ± 8.9 years. High activity of RA measured by the DAS was observed in 20% of patients, moderate in 26%, and low in 54%. The most common foot deformities were: hammer toes (82%), longitudinal flat feet (74%), and hyperkeratosis (56%). The least frequent were: stiff toe (38%) and overlapping fingers (28%). In the RA group, the outcomes of the FAOS questionnaire were statistically significantly worse than in the control group in all categories (p<0.001). The worst-rated domain was the sport and recreation subscale (median 55.0), the best daily activity (median 86.8). The strongest relationship was demonstrated between the FAOS and HAQ indices. Spearman's HAQ correlation coefficient with the ADL subscale was r=-0.85, p<0.001; with the QOL, sport/recreation and pain subscales moderate, it was r=-0.72; r= 0.71, p <0.001. Conclusion: Lower limb movement function and quality of life are worse in RA patients; pain accompanies climbing and descending stairs; running and jumping require effort.

Objective: The current study aimed to evaluate the effect of raloxifene on the disease activity of postmenopausal patients with rheumatoid arthritis (RA) and the prevention of glucocorticoid- induced osteoporosis. Methods: This double-blind, randomized clinical trial was conducted at the Rheumatic Diseases Research Center affiliated with Mashhad University of Medical Sciences from 2015 to 2016. Postmenopausal women with RA were randomly treated with raloxifene or placebo after discontinuation of alendronate. Disease activity was evaluated using DAS28ESR, HAQ, and VAS before and every two months after the intervention. In addition, bone mineral densitometry was performed for patients before and 14 months after the intervention. The disease activity and densitometric criteria were compared between the two groups at a significant level of p <0.05. Results: A total of 17 patients were allocated to each group. The two groups were similar at baseline in underlying disease, age, duration of RA, duration of alendronate use, laboratory findings, and rheumatoid arthritis drugs. Moreover, the mean scores of DAS28ESR, HAQ, and VAS during visits were not significantly different between the intervention and control groups (p >0.05). Conclusion: The current study results could not prove any clinical benefits of adding raloxifene to standard therapies for patients with rheumatoid arthritis in improving their disease activity compared to placebo. Clinical Trial Registration Number: Trial registration number is NCT02982083

Abstract: Background: Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis characterized by necrosis, granulomatous inflammation, and vasculitis. It is characterized by the triad of the upper and lower respiratory system, lung, and kidney disease. Although it is usually a multisystemic disease, limited forms have also been described, and otolaryngological involvement is the first manifestation in up to 80-95% of the cases. Case Presentation: In this report, we describe the case of an ANCA negative patient with a limited form of GPA that presented a necrotic lesion confined to the right tonsil compatible with granulomatosis with polyangiitis, which later presented positive ANCA antibodies. Oral lesions may be the initial manifestation of GPA, and systemic involvement can be presented within weeks or months. Although the oral manifestations have been well described, the initial presentation with oral lesions is very rare, and presentation with oropharyngeal manifestation is even rarer. This disease is generally characterized by anti-neutrophil cytoplasmic antibodies (ANCA); however, there are rare cases with negative ANCA. Conclusion: The diagnosis was established based on the clinical presentation and the histopathological findings of the characteristic inflammatory pattern.

Background: Pulmonary manifestations and lung impairment are rarely associated with the Adult Still's Disease and are reported in less than 5%. Case Presentation: The present clinical case describes the Adult Still's Disease with pulmonary involvement in a 45- year-old male. The main clinical manifestations included continuous fever, failure to respond to antibiotic therapy, skin rashes, musculoskeletal syndrome and pharyngitis. Additionally, bronchopulmonary lymphadenopathy, interstitial changes and dense foci with clear contours were detected in the lungs. Laboratory abnormalities included neutrophilic leukocytosis, increased ALT, AST, and elevated serum inflammatory marker levels. A cyclical course characterised the disease with strictly defined time intervals between flare-ups and remissions. After the prescription of methylprednisolone with the subsequent addition of methotrexate, complete regression of clinical symptoms, normalization of laboratory tests, and partial regression of computed tomography findings in the lungs were observed. Conclusion: Despite the low incidence, pulmonary involvement is an unfavorable manifestation of Adult Still's Disease. An individual feature of this case report was the asymptomatic lung involvement manifested only by changes revealed through computed tomography. For a long time, flareups of the disease were considered bacterial infections of unclear nature requiring systemic antibiotics.

Background: IgA vasculitis is the most common form of systemic vasculitis in children but can occur in adults. Inciting antigens include infections, drugs, foods, insect bites, and immunizations. Antibiotics and tumor necrosis factor (TNF) alpha inhibitors are the most common class of drugs that cause IgA vasculitis. Although sotalol and rivaroxaban have been documented to cause leukocytoclastic vasculitis, we have never come across any literature attributing IgA vasculitis to either drug. Additionally, Rocky Mountain spotted fever has not been associated with IgA vasculitis despite being described in cutaneous and systemic vasculitis cases. Here, we present a case of IgA vasculitis triggered by sotalol with challenging differentials, including a recent infection with Rocky Mountain spotted fever, malignancy, and rivaroxaban as possible triggers. Case Presentation: 68 yr old male with a history of lung cancer treated with resection and chemotherapy 5 years ago is currently in remission, and recently was started on sotalol and rivaroxaban for new-onset paroxysmal atrial fibrillation. He presented with diffuse petechial/purpural rash on the lower limbs, multiple joint pain, severe abdominal pain and rectal bleeds, hemoptysis, and renal dysfunction. IgG titers for RMSF were high. Punch biopsy of skin and renal biopsy were consistent with IgA vasculitis. Sotalol and rivaroxaban were stopped. The patient was treated with oral prednisone, and his condition relatively improved. Conclusion: Ig A vasculitis is mostly a self-limiting disease, but adults tend to have a severe course. It is important to diagnose early and identify a trigger. Removing the offending agent or treating the underlying infection is an important aspect of management.