Current Rheumatology Reviews - Volume 16, Issue 4, 2020

Granulomatosis with polyangiitis (GPA) is a rare and systemic autoimmune disease, causing necrotizing vasculitis of small arteries and veins. The majority of diagnosed patients with GPA have circulating anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3). Here, we have reviewed the last findings and uncertainties regarding the treatment of GPA. Between the available treatments, in addition to corticosteroids, cyclophosphamide (CYP) is effective for remission-induction, while it is associated with some serious side effects, such as infertility and increased risk of malignancies. On the other side, rituximab (RTX) seems a safer alternative option and as effective as CYP. It could be used as both remission-induction and maintenance therapy in GPA patients, especially in women of childbearing age. Pregnant patients, who must not be exposed to the CYP and RTX could be well-managed with intravenous immunoglobulin (IVIg). Co-trimoxazole, which is widely used to treat certain bacterial infections or as prophylaxis in immunosuppressed patients, could be effective in preventing disease relapse. In the meantime, 15- deoxyspergualin, plasma exchange are other therapeutic options with a low level of evidence. Regarding potential treatments, ofatumumab, ocrelizumab, belimumab, atacicept, tabalumab, abatacept (CTLA4-Ig), and Janus kinase inhibitors seem to be effective. Renal involvement, older age, the presence of baseline organ damage, delayed-diagnosis of disease, rising in creatinine level, and higher neutrophil/lymphocyte ratio is associated with poor outcomes. Optimum doses of medications, prediction of treatment response and disease relapse, explaining lack of response in some patients, treating children with GPA, and management of GPA during the pregnancy are controversial issues, which need further studies.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies.

Background: Small fiber neuropathy and fibromyalgia are two conditions that share overlapping features. Although various treatments are available for use in fibromyalgia, the response often remains unsatisfactory. Prior studies have shown that in small fiber neuropathy of autoimmune etiology, intravenous immunoglobulin (IVIg) holds promise as an effective treatment. Methods: Herein we report the use of IVIg in 7 patients who have both fibromyalgia and small fiber neuropathy. Skin punch biopsy evaluating the nerve fiber density was performed prior to diagnosis and after 6 months of IVIg therapy in each individual. Patients’ symptoms were obtained via a fibromyalgia questionnaire pre- and post-treatment. Results and Conclusion: At the end of 6 months therapy, overall patients reported fewer fibromyalgia symptoms and skin biopsy demonstrated improvements as well. This retrospective pilot study suggests IVIg is a viable potential therapy in a subset of fibromyalgia patients who have small fiber neuropathy.

Objective: To describe the clinical features in patients with Behcet’s disease suffering from uveitis in Egypt and to compare the findings between both genders. Methods: 453 subjects fulfilling the 1990 Classification criteria for Behcet’s disease and with uveitis in at least one eye. Follow-up was done for two years. Results: Oral ulcers and recurrent iridocyclitis occurred in all patients during their disease course. The prevalence of genital ulcers, erythema nodosum, and joint involvement were similar between both sexes. The prevalence of all ocular findings was higher in females except for retinal hemorrhages. The incidence of secondary cataract and glaucoma in addition to vitreous opacities was similar between both sexes. 13.7% of patients had GIT manifestations. Vascular complications were present in 128 (28.2%) patients. Aseptic meningitis and hemiplegia were only found in males. 1.7% of males and 3.2% of females suffered from brainstem involvement. Superior sagittal sinus thrombosis was present in females only. Acute phase reactants (ESR & CRP) were significantly higher in females (p<0.0001). Conclusion: The disease characteristics of BD patients with uveitis in Egypt might be different from the BD patients of other countries. The markers of inflammation were higher in females compared to males. The ocular manifestations were more common in females.

Introduction: Methotrexate (MTX) is a highly effective therapy for patients with rheumatoid arthritis (RA). However, it has been associated with a range of liver related adverse events. The aim of our study was to evaluate the prevalence rate of liver fibrosis in RA patients and to assess the correlation of cumulative MTX dose with hepatic fibrosis in our context. Materials and Methods: This is a cross-sectional study, whose goal is to describe and analyze the factors correlated with the liver fibrosis in RA patients treated with methotrexate especially the cumulative dose of MTX, along the period lying between January 2012 and March 2019. The study was carried out in the Rheumatology Department of the University Hospital Hassan II of Fez. The patients have met the assessment of the ACR 2010 criteria. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis. A value of p <0.05 has been used to identify factors associated with liver fibrosis. Results: A total of 319 patients with RA were recruited who were on MTX treatment. There were 276 female and 43 male patients (female: male ratio of 6.3). The average age was 53 years + /-12.4 years. The average duration of symptoms was 10.68 +/-6.9 years. RA was seropositive for the rheumatoid factor or the anti-ccp in 90.3 %. Six patients (2%) had developed liver fibrosis while on MTX therapy. In the bivariate analysis, the liver fibrosis is significantly related to the hepatic cytolysis (p<0.001) and to the combination of MTX with other DMARDs (p<0.05). However, the multiple logistic regression analysis did not find any significant association between the groups. Conclusion: In our context, the prevalence rate of hepatic fibrosis in patients with rheumatoid arthritis under methotrexate is low. It is seen much more in patients treated with methotrexate in combination with other disease-modifying anti-rheumatic drugs (DMARDs). These results require confirmation in a larger number of patients.

Background: Familial Mediterranean fever (FMF) is an autoinflammatory disease with potentially devastating effects on the kidney, and the chronic subclinical inflammation may also be deleterious. Further, proteinuria has been associated with chronic inflammatory states. Objective: We aimed to probe whether red cell distribution width (RDW) can be used as a reliable indicator of subclinical disease in FMF patients. Methods: Ninety-nine children with FMF, according to the new pediatric FMF criteria, were included in the present study. All were attack-free at the time of the study. They were compared with 44 healthy age-matched controls. For all patients and controls, the following tests were done: Complete blood count (in the form of red cell count, leukocyte count, platelet count, hemoglobin, RDW and MCV), CRP, ESR, creatinine and an estimated glomerular filtration rate (e-GFR). For patients, serum and urine albumin and albumin/creatinine ratio were also determined. Group 1 consisted of 61 patients, who were not suffering from microalbuminuria, and Group 2 consisted of 38 patients who had confirmed albuminuria. Results: RDW and ESR were significantly higher in patients with FMF without microalbuminuria than in controls, while MCV was smaller in controls (p<0.05). Conclusion: RDW can be used as an indicator of subclinical inflammation in children with FMF. The tests are easy to perform and cheaper than more sophisticated tests. Microalbuminuria may be silent and occur on the background of normal levels of acute-phase reactants. All cases must be routinely checked for microalbuminuria.

Objective: To study the clinical and laboratory features of Antiphospholipid Syndrome (APS) in a cohort of Egyptian patients and compare between primary and secondary type on the basis of clinical and immunological pattern. Patients and Methods: We reviewed the medical records of 148 antiphospholipid syndrome patients following in Rheumatology and Rehabilitation department, Cairo University. Clinical and immunological data were recorded; subsequently, our patients were compared based on the type of APS, patient's age and sex. Results: The cohort consisted of 148 patients, 135 females (91.2%) and 13 males (8.8%). The mean age at onset was 23.6 ±7.66 years. 28.4% of patients had primary while, 71.6% of patients had secondary APS. Patients with secondary APS presented more frequently with the following manifestations compared to patients with primary APS: systemic manifestations (56.6% versus 4.8%, P-value: 0.00), venous thrombosis (41.5% versus 19%, P-value: 0.009), cutaneous vasculitis (19.8% versus 4.8%, P-value: 0.023), thrombocytopenia (37.7% versus 11.9%, P-value: 0.002) and hemolytic anemia (28.3% versus 4.8%, P-value: 0.002). On the other hand, total obstetric manifestations were more common in primary APS (92.5% versus 75%, P-value: 0.007). Juvenile onset APS presented more frequently with systemic (68.8%, p-value: 0.02), neurological (62.5%, p-value: 0.01) and renal manifestations (31.3%, p-value: 0.005). No statistically significant difference was found between males and females in our cohort. Conclusion: APS has broad spectrum manifestations, which may vary according to the patient’s age at disease onset and association with other diseases. Further more, different ethnicities may show different presentations.

Background: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease leading to functional limitations and subsequently impaired quality of life (QoL). Despite the fact that QoL was recognized as a significant perception, it was excluded from the core domains (defined by the Assessment of Spondyloarthritis International Society), because of ambiguity of measurement choice. Aim: To assess QoL in patients with AS using a generic; Short Form-36 (SF-36) and a diseasespecific; Ankylosing Spondylitis quality of life (ASQoL) instruments and to explore its relationship to the clinical characteristics, disease activity, functional status, and radiographic severity. Methods: A total of 47 AS patients who fulfilled modified New York criteria were included. Disease activity, functional status, spinal mobility, and radiographic severity were assessed by Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI) and Bath AS Radiology Index (BASRI) respectively. SF-36 and ASQoL instruments evaluated Qol. Results: Physical health was more affected especially in patients with peripheral arthritis by SF-36 (p=0.008) and ASQoL (p=0.022) scores. Both SF-36 total and ASQoL scores correlated significantly with BASDAI (r = -0.329, p = 0.024 and r = 0.420, p = 0.003), BASFI (r = -0.399, p = 0.005 and r = 0.513, p=0.001) and BASMI (r = -0.382, p = 0.008 and r = 0.482, p= 0.001) respectively. Conclusion: QoL was impaired in AS patients with highest impact on physical health especially in association with peripheral arthritis. SF-36 and ASQol have a comparable achievement in the evaluation of QoL in AS patients and both physical function and spinal mobility were identified as predictors of poor QoL.

Objective: Evidence for treating chikungunya arthritis early in the course of illness is scarce. This study assesses the efficacy of Methotrexate in early Chikungunya arthritis. Methods: It is a randomized controlled open-label assessor-blinded trial with a crossover design. Sixty patients with persistent post chikungunya arthritis with at least 3 or more tender or swollen joints (28 joint count) were recruited. MTX arm was given oral Methotrexate and NSAID arm was given NSAIDs (Naproxen 1 gm/day or Etoricoxib 120 mg/day). Patients were followed at 1, 2, 4 and 6 months. After 2 months patients in NSAID arm who have not achieved remission were given MTX. The primary endpoint was remission (no tender or swollen joints by 28 joint count) at 6 months. Secondary endpoints were change in CDAI, Indian HAQ, total steroid use, total NSAID use, and serious adverse effects. Intention to treat analysis was used. Results: TJC, SJC, CDAI and HAQ were matched between two at baseline. Remission was achieved by 28 patients (93%, CI- 78%-98%) in the NSAID arm and 26 patients (86%, CI-70%- 94%) in MTX arm (p=0.18). There was no significant difference in steroid need, change in HAQ, CDAI, TJC or SJC. Those who have not achieved remission had higher disease activity at baseline. Conclusion: A protocol-based approach with steroid and NSAIDs helped to achieve remission in most patients with early subacute phase of post-Chikungunya arthritis and the effect was comparable to that of early initiation of methotrexate.

Objective: Knee osteoarthritis (KOA) is defined as a chronic degenerative joint disease. Obesity is a significant risk factor for KOA. Omentin is an adipose tissue-induced adipokine. The aim of the present study was to investigate the correlation between obesity and serum omentin levels in patients with KOA. Methods: This study included 60 patients with KOA, 34 obese individuals (O-KOA) and 26 nonobese individuals (NO-KOA) and 40 controls, 17 obese individuals (OC) and 23 nonobese individuals (NOC) matched in terms of age, sex, and body mass index (BMI) who were recruited from the same polyclinic. Blood samples and knee radiographs were obtained from all the subjects, and clinical features, BMI, and laboratory parameters were recorded. The Kellgren–Lawrence (KL) grade and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index were used to classify the radiographic and clinical findings, respectively. Serum omentin levels were determined using an ELISA. Results: Serum omentin levels in patients were significantly lower than those in the controls (p < 0.05). When the BMI values and KL scores were considered, serum omentin levels significantly decreased in severe O-KOA versus in mild-to-moderate O-KOA. There was no statistically significant decrease in severe NO-KOA versus mild-to-moderate NO-KOA. There was a significant negative correlation between the serum omentin level and BMI and WOMAC index. All findings were supported by a receiver operating characteristic curve analysis. Conclusion: Serum omentin levels were inversely related to obesity and the severity of KOA. The data indicate that omentin may be a new biomarker of KOA to our knowledge and may aid the diagnosis of early-stage O-KOA, if our findings are supported by further studies involving much more samples.

Background: Liver involvement is not considered a typical extra-articular manifestation and has rarely been studied in rheumatoid arthritis (RA). We aimed to identify the prevalence and aetiologies of liver disease in RA patients. Methods: A cross-sectional study included 150 patients with RA enrolled over 5 years (2010- 2015). The clinical and paraclinical features of RA were analyzed. The clinical and biological characteristics of liver impairment and its aetiologies were collected. Results: One hundred and fifty RA patients (124 women) with a mean age of 57.09 years and a mean RA duration of 7.52 years were included. Liver involvement was diagnosed in 66 patients (44%). The liver disease was asymptomatic in 94% of the cases, revealed by increased gammaglutamyl transferase levels in 74% of the patients. The aetiologies of liver involvement were hepatotoxicity of medications in 38 cases (57%), hepatitis B and C in 14 patients (21%), fatty liver disease in 10 cases (15%), autoimmune liver disease in 2 patients (3%), hydatid cyst in 1 case (2%), and liver angiomas in 1 case (2%). Non-steroidal anti-inflammatory drugs and methotrexate were the drugs most often involved in the genesis of hepatotoxicity (21% and 20% of the cases, respectively). Conclusion: Liver involvement occurred in 44% of RA patients. Aetiologies were mainly hepatotoxicity and viral hepatitis B and C. Patients with RA should be systematically screened for liver disease, which is rarely symptomatic.

Background: Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect virtually any organ. Löfgren syndrome, characterized by erythema nodosum, hilar lymphadenopathy, fever and polyarthritis, represents only 20-30% of the cases of sarcoidosis. Only 2- 10% of the cases feature hypercalcemia. Case: The case of a 42-year-old Hispanic woman with a history of erythema nodosum and three weeks of nausea, emesis, constipation, asthenia, adynamia, polydipsia, and somnolence, concomitant with hypercalcemia, but normal parathyroid hormone (PTH) and 25-hydroxyvitamin D has been presented. The initial diagnostic approach was based upon the suspicion of multiple myeloma or bone metastases; however, further findings of bilateral hilar lymphadenopathy, elevated serum angiotensin-converting enzyme (ACE) and a right inguinal lymphadenomegaly suggested an alternate diagnosis. Biopsy of the latter supported sarcoidosis as the diagnosis. She was successfully treated in the hospital with zoledronic acid and as an outpatient with immunosuppressive therapy. Persistence of a previously undisclosed symptom of oligomenorrhea led to the detection of hyperprolactinemia secondary to hypophyseal infiltration, refractory to immunosuppressive therapy but with an adequate response to cabergoline. Conclusion: This case strays from Löfgren Syndrome’s expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adherence to the CARE guidelines of 2013 to include information in it.

Background: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder which is often misdiagnosed. We report here a case of SPS with a long diagnosis delay. Case: A 36-year-old man presented with an 11-year history of progressive stiffness and painful spasms of his both legs, with recent worsening of his condition over the last year resulting in a considerable difficulty of standing up and walking. As the patient developed phobic symptoms, he was considered as having a psychiatric illness and treated with antianxiety and antidepressant drugs. As no real improvement was observed, the patient was referred to internal medicine. Neurological examination showed paraspinal, abdominal and lower limbs muscle contraction with lumbar rigidity. These symptoms were associated to adrenergic symptoms: profuse sweating, tachycardia and high bloodpressure. Initial routine investigations revealed high blood glucose level. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles showed continuous motor unit activity in agonist and antagonist muscle. Electroencephalography and brain magnetic resonance imaging were normal. Immunologic tests according to radio immune assay technique revealed high level of serum anti-glutamic acid decarboxylase (anti-GAD65) antibodies. Diagnosis of autoimmune SPS was retained based on clinical, electrophysiological, and immunological findings. Pregabalin at the dose of 150 mg, three times a day was prescribed with satisfying response. Conclusion: SPS is supported by an autoimmune pathogenesis and anti-GAD antibodies seems to be very helpful when SPS is clinically suspected. Treatment of SPS is a challenge, given the scarcity of the syndrome and the absence of established recommendations.