Current Rheumatology Reviews - Volume 16, Issue 2, 2020

Background: Sudden sensorineural hearing loss (SSNHL) is defined as a sudden loss of hearing, usually unilateral, of more than 30 dB in 3 contiguous frequencies of the tonal audiometry. SSNHL estimates an incidence ranging from 5 to 20 per 100.000 people per year. In approximately 75% of cases, a cause cannot be identified. However, it could be a clinical manifestation of Systemic lupus erythematosus (SLE) and Antiphospholipid Syndrome (APS). Objective: This review will focus on the clinical presentation, diagnosis, and management of the SLE and APS associated SSNHL. Methods: We searched in PubMed, Scopus, Lilacs, and Cochrane reviewing reports of Sudden sensorineural hearing loss in SLE and/or APS. Articles written in English and Spanish, and were available in full text, were included. Results: In patients with SLE, bilateral involvement was frequent. Antiphospholipid antibodies were positive in the majority of the patients. Corticosteroids were the mainstay of the treatment. The auditory prognosis was poor with total hearing loss recovery reached in only 22% of patients. On the other hand, most of the patients with SSNHL and APS were males and presented associated symptoms such as vertigo, tinnitus and/or headache, 75% had bilateral disease. Lupus anticoagulant and aCL were found in equal proportions, all patients were anticoagulated, and aspirin was associated in 25% of the cases. Complete resolution or improvement of symptoms was observed in 25% of the patients. Conclusion: Sudden sensorineural hearing loss, can be a clinical feature of SLE and APS. Treating physicians should be aware of this devastating complication, especially when bilateral involvement occurs.

Background: Anorexia nervosa is a serious health condition characterized by a significant low body weight and alteration in body composition components. Aim: In the current paper, we aim to summarize the available literature concerning changes in body fat, lean, and bone masses, during anorexia nervosa and after complete weight restoration. Methods: Data were summarized using a narrative approach based on clinical expertise in the interpretation of the available evidence base in the literature. Results: The available data revealed three main findings. Firstly, anorexia nervosa causes a significant reduction in body fat mass, however it is completely restored after short-term weight normalization but with a central adiposity phenotype that does not seem to negatively influence treatment outcomes and appears to normalize after 1 year of normal weight maintenance. Secondly, anorexia nervosa causes a significant reduction in bone mineral density, but weight restoration is associated first (≈12 months) with stabilization of bone mineral density, followed by improvements (after ≈16 months); and finally, with complete normalization (after ≈30 months) after normal-weight maintenance. Thirdly, during anorexia nervosa loss of lean and skeletal body mass occurring in particular from the extremities rather than the central regions has been consistently reported, especially in patients with a Body Mass Index (BMI) ≤ 16.5 Kg/m2 however short-term weight restoration is associated with complete normalization. Conclusion: Anorexia nervosa adversely affects body composition, however this medical complication seems to be reversible through the main treatment strategy of body weight restoration followed by normal weight maintenance, and this should be openly discussed with patients.

The close association between osteoarthritis (OA) and obesity is well established. Mechanisms linking obesity and OA involve multifactorial phenomena such as systemic factors (i.e. adipokines and pro-inflammatory cytokines), hormonal disturbances (hyperinsulinemia) and muscule changes (i.e. sarcopenia and lower muscular tone). The concomitant increasing prevalence of the two diseases have major health, social and economic consequences. However, to date no specific recommendation for the medical management of obese patients with OA have been published. Current recommendations only specify that obese patients must lose weight and practice regular physical activity in addition to the usual care. Weight loss improves not only OA symptoms but also metabolic abnormalities and cardiovascular risk factors commonly altered in subjects with obesity. OA symptoms’ improvement has been shown to become clinically relevant from a weight loss > 5% of the body weight. In case of morbid obesity, bariatric surgery may be the only alternative for pain relief. After bariatric surgery, an appropriate calcium and vitamin D intake is recommended, since it has been shown that bariatric surgery was associated with a reduction in the bone mineral density and increased risk of fractures. An exercise program is essential for preserving healthy muscles during weight loss. Non-steroidal anti-inflammatory drugs and corticosteroids must be avoided, especially in obese patients with metabolic syndrome. In such patients symptomatic slow acting drugs for OA (i.e. glucosamine, chondroitin) and some anti-oxidant drugs (i.e. curcumin, ginger extracts, copper) may be helpful thanks to their excellent benefit/risk ratio and their mode of action which may have a positive impact on both OA and obesity-related metabolic disorders. Recent research focuses on the development of molecules aimed for promoting the production of heme oxygenase (HO-1). HO-1 decreases the production of oxygen free radicals and protects tissues from oxidative stress in the insulin resistance syndrome. Intra-articular (IA) injections of hyaluronic acid and corticosteroid have few adverse events. However, physicians must inform patients that IA treatments have a lower success rate in obese patients than in those with normal body mass index. Spa therapy contributes to relief pain, favour weight-loss and reduces metabolic abnormalities with a favourable risk/benefit balance.

Objectives: Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. Methods: Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. Results: Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). Conclusion: Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

Background: Diclofenac and curcumin is anticipated to have synergistic action. Hence, topical route of administration can be used in minimizing the issues with oral administration of both drugs. Objective: This research aims at formulation of controlled release dosage form containing curcumin microspheres and diclofenac diethylamine and then incorporating it into gel formulation for treatment of inflammation associated with rheumatoid arthritis. Methods: Curcumin microspheres were prepared, optimized and assayed. Gel containing microspheres was formulated and evaluated for physicochemical parameters like spreadability and viscosity. In vitro and ex vivo diffusion studies were carried out followed by evaluation of efficacy. Efficacy of the developed formulation was evaluated for anti-inflammatory activity. Results: Particle size, Zeta potential, pH, spreadability and viscosity of optimized Batch F1 was found to be in range 0.5 μm - 5 μm,-27.9 mV, 6.2, 105 g cm/s and 7500 cps respectively. In vitro diffusion of developed gel of diclofenac diethylamine and curcumin was found to be 92.16 ± 0.0040 % in 3 h and 92.54 ± 0.0036 % in 12 h as compared to 79.57 ± 0.004 % diffusion in 2 h for marketed gel, thus showing controlled delivery of curcumin. Conclusion: Decreased inflammation in formulation treated group by 72.53% and 50.75% in marketed treated group was seen. Thus the formulation developed showed prolonged activity as well as better anti-inflammatory activity.

Background: Behcet's disease is a potentially life threatening autoimmune disease with recurrent ulcers and unknown pathogenesis. Gender and human leukocyte antigen-B51 seem to have an effective role in the clinical features of the disease. Objective: The aim of this study is to evaluate the frequency of HLA-B5, 7, 8, 27 and 51 in behçet's disease in southwestern Iranian patients who visited the rheumatology clinic and to find the association between these HLA types and the disease. Methods: 63 patients with behcet's disease participated in this study and peripheral blood samples were collected from them. The expression of each HLA antigen was evaluated by standard lymphocytotoxicity technique. Results: Compared to other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 25% and 21% of patients were positive for HLA-B5 and HLA-B51, respectively. Conclusions: HLA-B5 and HLA-B51 are dominant positive HLA antigens among behcet's disease patients in the southwest of Iran; however, we cannot conclude that these antigens are valuable diagnostic or prognostic biomarkers due to our study limitations. We suggest studying the association between HLA-B antigens and inflammation severity in patients to determine the possible prognostic value of HLA-B antigens in Iranian population in the southwest and this region needs more studies in HLA subject among BD patients because of the frequency of BD to evaluate the value of HLA typing in BD prognosis.

Background: The relationship between SLE and traditional risk factors for cardiovascular events was evaluated. Methods: The data regarding sixty patients with SLE and 30 healthy controls (age and sex matched) were gathered using SLEDAI forms. Venous blood (10mL) from all the participants was examined for hs-CRP, homocysteine, VCAM1, CBC, anti-DNA antibody, C3, C4, low-density lipoprotein (LDL), cholesterol, FBS and triglyceride. The IMT of carotid arteries was determined bilaterally by ultrasound. Other measurements included insulin levels via Elisa (Linco/Millipore Corp) and the HOMA-IR index for insulin resistance. Results: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively. The average IMT in the test group was directly related to serum levels of VCAM1 (p<0.001), homocysteine (p<0.001), cholesterol (p<0.009), LDL (p<0.001), TG (p<0.001), and FPG (p=0.004). The association between other risk factors, insulin resistance, carotid IMT and SLEDAI, was nonexistent. Mean insulin and insulin resistance levels in all the participants were 0.43±2.06 μU/mL and 0.09±0.44, respectively. There was no significant difference between the test and control groups regarding serum insulin and insulin resistance levels (p=0.42 and p=0.9, respectively). None of the risk factors, such as hsCRP, VCAM1, or homocysteine, were shown to be related to insulin resistance (p=0.6, p=0.6, p=0.09, respectively). Conclusion: Our findings did not show an increase in the prevalence of atherosclerosis in patients with SLE. There was no association between IMT and insulin resistance. However, the former was associated with FPG, total cholesterol, LDL, TG, homocystein and VCAM1.

Background: Osteoarthritis (OA) is a painful social problem, which breaks down the articular cartilage, causes the failure of synovial joints and subchondral bone sclerosis. OA etiology is not completely understood, but joint trauma, infection, obesity, and diseases are the most important risk factors for OA developing. Recent studies suggested inflammatory factors and genetic components can be involved in the pathogenesis of OA. Experimental evidences suggest a linkage between Human Leukocyte Antigen (HLA) genetic diversity and OA. But a few studies have been conducted in this subject. Objective: To investigate the association between HLA-DRB1*0101 and OA in Iranian patients. Methods: Thirty patients with knee osteoarthritis and 30 healthy people as the control group were included in the study. Sex, weight, age, Body mass index (BMI) and height of all participants were recorded. HLA-DRB1*0101 was typed by PCR using the sequence-specific primer. Results: Our results showed 80% of knee osteoarthritis patients were positively HLA-DRB1*0101 (n=24), while only 26.7% of controls were positive (n=8) (P= 0.015). Conclusion: These findings proposed that there is a significant association between HLADRB1* 0101 and susceptibility to knee osteoarthritis.

Purpose: Systemic Lupus Erythematosus (SLE) in males is rare. Clinical and biological features, as well as, the outcome may differ comparatively to female patients. The purpose of our study is to define these clinical and biological features in Tunisian male patients presenting SLE. Methods: A mono-centric, retrospective and descriptive study of 96 patients followed for SLE out of which 21 are males. A comparative study was then performed between male and female patients groups. Results: Sex-ratio female/male was 3.6/1, the average age at diagnosis of SLE was 37.8±14 years. The most frequently noted clinical manifestations were: skin involvement (81%), renal involvement (71.4%) and joint damage (66.7). We observed a significant difference in clinical features between male and female patients (21 males and 76 females): renal failure (52% vs. 71.4%), serositis (23.8% vs. 2.7%), peripheral neuropathy (19% vs. 4%) and lung interstitial disease (14.3% vs. 1.3%). No significant difference was found in the positivity of serum antibodies between the two groups. Fifteen male patients (71.4%) had a SLEDAI score greater than or equal to 11, referring to high/very high disease activity. Out of the 32 patients who developed infectious complications during the course of the disease, 11 were male (52.4% of males). Concerning the male group, complete remission was observed in 10 patients (47.6%), while 10 others presented persistent sequella. We observed one death in the male group secondary to infective acute respiratory failure. Conclusion: SLE in male patients is rare and associated with poor prognosis. Disparity was observed in clinical and biological features as well as outcome in the different studies. In our study, we concluded that male lupus is more severe.

Introduction: Rheumatoid arthritis (RA) is biologically marked by a positive serum rate of rheumatoid factor (RA) and/or anti-citrullinated protein antibodies (ACPA). Nevertheless, 20% of RA cases remain seronegative. Objective: The main purpose of this study, is to bring out the clinical, biological, imaging, therapeutic, and evolutionary distinctions between seropositive RA and seronegative one. Methods: This is an observational cross-sectional study that involves patients with RA admitted in the rheumatology department, from the period between January 2012 and January 2018. RA seronegativity is described as the absence of both RF and ACPA, while seropositivity is recognized by the presence of at least one of the two antibodies. Results: 294 patients were included, of which 90% were seropositive and 10% seronegative. Therefore, RA in this study is seropositive most often. The bivariate analysis underscored plenty of differences, statistically notable, according to the RA immune status. In fact, patients with seropositive RA had more synovitis (p=0.049), more deformities (p=0.01), and more bone destruction on radiographs (p=0.04). Furthermore, RA in this Moroccan study was quite severe (p=0.006) and got more complicated by systemic manifestations (p=0.02). Whereas, no distinction was brought up between the two groups, concerning the use of biotherapy. As for the multivariate study, seropositive RA in these patients, had greater severity (p=0.009, OR=4.53) and was more deforming (p=0.03 OR=2.45). Conclusion: RA in our Moroccan context is dominated by the seropositive form. This seropositivity is often coupled with clinical severity and joint destruction, resulting in more deformities.

Background: Systemic sclerosis (SSc) is a systematic and rare autoimmune disease that affects many organs. N-acetylcysteine (NAC), thiol-containing compound, can act both as the precursor of reduced glutathione and direct scavenger of reactive oxygen species. Objective: We assessed the clinical effect of NAC on the pulmonary function test of patients with diffuse scleroderma. Methods: This study is a randomized double-blind clinical trial that was done on 25 patients with diffuse SSc without lung involvement on primary chest high-resolution computed tomography. Placebo was administered for 13 patients and 1200 milligram NAC for 12 patients. Body plethysmography parameters were assessed at the beginning of the study and after 24 weeks. Results: Patients in the two groups were matched in the basic demographic data like age, duration of disease, and modified Rodnan skin score. The analysis showed no significant differences in parameters of plethysmography between the two groups. After importing the data of 2 patients in the placebo-treated group, who developed interstitial lung disease, DLCO in the placebo-treated group was 90.69 ± 21.29 milliliter at the end of the study, which significantly decreased compared with the beginning of the study (102.30 ± 13.83 ml). Also, changes of DLCO between the two groups were significantly different. Conclusion: In this trial, the sensitivity of DLCO as the first marker in the evaluation of pulmonary function in patients with SSc was confirmed. On the other hand, NAC had no effect versus placebo in a period of 24 weeks.

Objective: Osteoarthritis is a degenerative disease of the joints. Non-steroidal antiinflammatory drugs (NSAIDs) are being used for the treatment of osteoarthritis. However, their use is limited due to complications, such as gastrointestinal bleeding. Therefore, it is necessary to find alternative treatments for osteoarthritis. Recently, nanomicelle curcumin has been developed to increase the oral bioavailability of curcumin. The aim of this study was to evaluate the effect of nano curcumin on the alleviation of the symptoms of knee osteoarthritis patients. Methods: In this randomized, double-blind controlled trial, the intervention group was administered 40 mg of nanocurcumin capsule every 12 hours over a period of six weeks, and the control group received the placebo (similar components of nanomicelle curcumin capsules yet without curcumin). In the final analysis, 36 patients in the nanocurcumin group and 35 patients in the placebo group were enrolled. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was filled for patients in their first visit and at the end of six weeks. Differences were statistically significant at P-value < 0.05. Results: There were no significant differences between the two groups regarding gender, age, Kellgren score, and the duration of the disease before the intervention. A significant decrease was observed in the overall score, along with the scores of pain, stiffness and physical activity subscales of the WOMAC questionnaire in patients of the nano curcumin group compared with the placebo group. Conclusion: Nanocurcumin significantly improves the symptoms of osteoarthritis patients.

Background: Giant Cell Arteritis (GCA), is the most common primary vasculitis. It affects large vessels such as the aorta and its branches. According to Chapel Hill Consensus, GCA is one of the larger vessel vasculitis. The underlying mechanism involves inflammation of the large arteries. The most frequent presentation consists of headache, polymyalgia, and jaw claudication. GCA can put the visual prognosis at risk, and rapid diagnosis is compulsory. Cotton wool spots, due to focal inner retinal ischemia, are an early diagnostic ophthalmological sign. The most frequent presentation is a rapid, partial or complete blindness. However, atypical presentations, such as uveitis, especially in the anterior chamber, can delay diagnosis. Case Report: We report a 75-year-old woman with GCA who initially presented with anterior uveitis and without any other clinical sign. At the beginning, there was the only ophthalmic sign and systemic inflammation, the all exhaustive work-up including positron emission tomography (PET) scan was negative. The biology was fully normal without auto-immune profile (Angiotensin converting enzyme level, Interferon Gamma Release Assay, Syphilis serology, antinuclear antibody titer, Rheumatoid factor, CCP antibodies, and chest x-ray were normal. HLA B27 was negative). In the following weeks, she subsequently developed large vessel vasculitis with headache and more typical sign. She developed cotton wool spots linked to retinal arteriolar hypoperfusion. Anterior uveitis has been reported rarely in GCA and moreover, it is very uncommon at the early stages of GCA. Our case stresses that uveitis onset can precede large vessels vasculitis and typical symptoms of GCA. PET-scan is a useful tool for atypical GCA, but its sensitivity is not perfect, and its repetition can be helpful in selected cases such as that of this patient.