Helicobacter Pylori Infection in Sjögren's Syndrome: Co-incidence or Causality?

BACKGROUND AND AIM: Lymphoid cell infiltration and destruction of exocrine glands, specifically lacrimal and salivary glands are characteristics of Sjogren's syndrome (SS). An etiological role has been proposed for Helicobacter pylori (H. pylori), interacting in the clinical course and complications of SS (including gastric cancer and lymphoma). The aim of this study was to identify the probable correlation between H. pylori infection and Sjogren's syndrome (SS). METHODS: In this case-control study, ELISA method was used to determine serum level of IgA and IgM anti H. pylori antibody in 43 subjects with SS according to the international criteria and 95 healthy subjects as control. SPSS-17 was used to analyze data with t-test. P value <0.05 were considered significant. RESULTS: Serum level of IgM (34.9% vs. 10.5%, p-value= 0.001) and IgA (67.4% vs. 46.3% p value= 0.021) anti H. pylori antibody were significantly higher in SS patients compared to the control group. There was a positive correlation between age and H. pylori infection (r=0.2, Pvalue= 0.05). CONCLUSION: Patients with SS had a higher prevalence of H. pylori infection compared to the normal population. Eradication of H. pylori is recommended particularly in older patients with SS.

HTLV-1 seroprevalance in sarcoidosis. A clinical and laboratory study in northeast of Iran.

AIM: Sarcoidosis is an autoimmune multiorgan granulomatosis disease with unknown origin. Some environmental factors such as viruses may induce the disease in genetically susceptible individuals. Human T cell lymphotropic virus type 1 (HTLV-1) can dysregulate the human immune system and the role of this virus in the pathogenesis of autoimmune diseases has been investigated and documented, such as in uveitis. In this study, we have focused on the seroprevalence of HTLV-1 in sarcoidosis in comparison to the normal population in the northeast of Iran, an endemic area for HTLV-1. METHODS: This cross-sectional study enrolled 125 patients with established sarcoidosis to evaluate the frequency of HTLV-1 and compare it with the normal population of Mashhad, Iran. Participants' blood samples were analyzed for HTLV-1 antibody by an enzyme-linked immunosorbent assay kit. Positive results were confirmed by polymerase chain reaction method. Finally, data were analyzed using SPSS 11. RESULTS: Among sarcoidosis patients 106 (84.8%) patients had a history of acute course and 19 (15.2%) had chronic sarcoidosis. Four percent of the patients versus 2.12% of the Mashhad population were HTLV-1 positive with no statistical difference (P = 0.201). In age- and sex-matched selected controls, 3.6% were HTLV-1 positive again with no statistical difference by sarcoidosis group (P = 0.52). There was no statistical difference between arthritis, erythema nodusom, uveitis, constitutional symptoms, abnormal chest radiography (parahilar lymphadenopathy) and computed tomography scan findings, respiratory symptoms, sex, the course of the sarcoidosis in HTLV-1 positive and negative sarcoidosis patients. CONCLUSION: The frequency of HTLV-1 in 125 sarcoidosis patients was 4%. In comparison with prevalence of HTLV-1 in Mashhad, HTLV-1 seroprevalence did not show any significant difference.

Immunology-Rheumatology Approach to Sudden Sensorineural Hearing Loss.

BACKGROUND: Sensorineural hearing loss (SNHL) and vestibular dysfunction have been described in various autoimmune disorders and systemic vasculitides. A high prevalence of SNHL is reported to occur in established rheumatologic diseases; however, immunologic and rheumatologic disorders make up a small proportion of patients with sudden sensorineural hearing loss (SSNHL). OBJECTIVES: This prospective study was carried out in order to determine the prevalence of rheumatologic and immunologic disorders in patients with SSNHL in Northeast Iran. METHODS: Patients with a diagnosis of SSNHL referred to our University Hospital were enrolled in this prospective study conducted over a period of 3 years. Immunology-rheumatology evaluations were performed in all patients, including detailed history, physical exams and laboratory tests such as erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), rheumatoid factor (RF), anti neutrophil cytoplasmic antibody (PR3, c-ANCA), perinuclear anti neutrophil cytoplasmic antibody (p-ANCA), antiphospholipid antibody, anti-cyclic citrullinated peptide (ACCP), and complement proteins C3 and C4. RESULTS: Eighty-three patients with a mean age of 42.04±16.94 years were admitted into the study. The female-to-male ratio was 47% to 53%. ANA was positive in one patient, RF in six, p-ANCA in two, ACCP in one, and antiphospholipid antibody was positive in three patients with low titers. No diagnosis of rheumatologic diseases was detected, except for one patient who was diagnosed with primary Sjögren's syndrome. Fewer than 5% all cases had specific positive immunologic tests. CONCLUSION: The low frequency of immunology-rheumatology positive tests and disorders in our patients with SSNHL indicates that it is not reasonable to routinely perform all related tests for every patient. Instead, clinical evaluations should be used to decide whether or not to conduct these tests.

Relationship between cartilage oligomeric matrix protein (COMP) and rheumatoid arthritis severity.

BACKGROUND: Serum cartilage oligomeric matrix protein (COMP) is a non-collagen glycoprotein produced by the cartilage, synovium, tendon, and meniscus. Recent studies showed that COMP is a reliable factor for monitoring cartilage damage. OBJECTIVE: To determine the relationship between serum COMP concentration and the severity of rheumatoid arthritis (RA). METHODS: This cross-sectional study lasted from 2013 to 2015 at the Rheumatology Clinic of Ghaem Hospital, Mashhad, Iran. The study population consisted of eligible patients who presented to our clinic during the study period. Four groups (150 subjects) were included as early RA (50 patients), late RA (50 patients), grades II and III OA (osteoarthritis) (25 cases, 17 grade II and 8 grade III joint destruction), and healthy controls (25 individuals). These were included consecutively. Serum COMP level was assessed by sandwich ELISA technique. In addition, ESR, hs-CRP, serum RF, and anti-CCP were assayed. X-rays of the knees (in OA) and hands (in RA) were examined for the degree of joint damage/erosion using the Short Erosion Scale (SES) in RA and Kellgren-Lawrence grading in OA. Analysis of variance (ANOVA) to compare mean COMP level among the groups and ROC (Receiver Operating Characteristic) analysis to determine the diagnostic accuracy of COMP in diagnosis of late RA were used by SPSS software (ver. 20.0). RESULTS: Mean (±SD) serum COMP levels were 18 (±10.6) U/L in early RA, 19.3 (±9.6) U/L in late RA, 10.9 (±4.5) U/L in OA, and 4.2 (±3.8) in controls; p<0.001. Serum COMP level was higher in RA and OA groups when compared to control group. Mean (±SD) SES score was 13.5 (±7.5) in early RA and 16.4 (±9.7) in late RA (p=0.093). There was a significant positive correlation between COMP level and disease severity in early RA (r=0.677, p<0.001) as well as in late RA (r=0.753, p<0.001). Serum COMP level at a concentration of 15.25 U/L had a sensitivity of 68% and specificity of 70% to discriminate late RA from early RA (area under curve= 69% (95% CI: 58% to 79%; p=0.001). CONCLUSION: COMP had positive significant correlation with early and late RA severity. This serum biomarker can be a useful and easy tool for monitoring of RA patients either at early or late stages of the disease.

Serum alpha-actinin antibody status in systemic lupus erythematosus and its potential in the diagnosis of lupus nephritis.

BACKGROUND: In lupus nephritis (LN), deposition of pathogenic autoantibodies in the glomeruli is mediated via cross-reactivity with alpha-actinin. Association of serum alpha-actinin antibody (AαA) with LN has been shown in a few studies but the results are controversial. METHODS: Eighty patients into entered the study. The diagnosis of SLE was confirmed according to the American College of Rheumatology criteria and LN was diagnosed by proteinuria ≥ 500 mg/24 hour and kidney biopsy. Serum AαA was measured with ELISA method. Receiver operating characteristics curve (ROC) analysis was applied to determine an optimal cutoff value for AαA to discriminate patients with and without LN at the highest sensitivity and specificity. The association of AαA with LN was determined by logistic regression analysis with calculation of odds ratio (OR). RESULTS: Serum AαA was significantly lower in LN as compared with SLE patients without LN (P=0.001). Serum AαA at cutoff levels ≤ 59.5 pg/ml discriminated the two groups with sensitivity, specificity, positive predictive values of 60%. 90% and 85.7%, respectively. Serum AαA level ≤ 59.5 pg/ml was significantly associated with LN (OR=13.5, P=0.001) and the OR increased to 25.2 (P=0.003) after adjustment for age, sex, C3, C4, anti-ds-DNA, SLEDAI. CONCLUSION: This study indicates that serum AαA decreases in LN and serum level ≤ 59.5 pg/ml is SLE and is predictive of nephritis.

Serum Trace Element Concentrations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity.

Oral Glucosamine Effect on Blood Glucose and Insulin Levels in Patients With Non-Diabetic Osteoarthritis: A Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVES: This study aims to determine the effects of oral glucosamine on glucose metabolism and insulin resistance in non-diabetic patients with osteoarthritis in Northeastern Iran. PATIENTS AND METHODS: This placebo-controlled, randomized clinical trial included 40 non-diabetic patients with osteoarthritis (15 males, 25 females, mean age 63.8±7.64 years; range 49 to 80 years). Patients were randomly divided into two equal groups and treated with oral glucosamine sulfate 1500 mg a day or placebo for 90 days. Fasting blood sugar, glucose tolerance test with 75 grams glucose and serum insulin levels, and homeostatic model assessment-insulin resistance were evaluated initially and at the end of intervention. RESULTS: There were no significant differences between the groups in terms of blood sugar, glucose tolerance test, and insulin levels at the beginning and end of the study. In the oral glucosamine group, there were no significant changes in fasting blood sugar (94.1±7.14 mg/dL versus 93.5±9.45 mg/dL, p=0.15), glucose tolerance test (99.3±8.99 mg/dL versus 103.3±10.1 mg/dL, p=0.07), and homeostatic model assessment-insulin resistance (1.57±0.21 versus 1.48±0.21, p=0.13) after treatment. Also, placebo did not significantly affect serum glucose levels and insulin resistance. CONCLUSION: Oral glucosamine with routine dosage was safe in our non-diabetic patients with osteoarthritis and had no significant effect on glucose metabolism and insulin resistance.

Evaluation of the incidence of discoid lupus erythematosus in patients with systemic lupus erythematosus and its relationship to disease activity.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with wide clinical features ranging from cutaneous manifestations to systemic disease. Skin is one of the most commonly affected organs in SLE. OBJECTIVE: To determine whether there is any correlation between discoid lupus erythematosus (DLE) and the severity of SLE. METHODS: In a prospective cross-sectional study, 60 consecutive patients with newly diagnosed SLE were enrolled. Skin biopsy was performed to establish the diagnosis of DLE. Disease activity was determined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). A SLEDAI-2K score ≥ 10 was considered active and severe disease. RESULTS: Eleven SLE patients (9 females and 2 males) had DLE (18.3%) and 49 patients (46 females and 3 males) had SLE without DLE (81.7%). The mean age of patients with DLE was 30.18 ± 11.07 years and in patients without it was 28.4 ± 10.26 years (p  =  .6). Three of 11 patients with DLE (27.3%) and 14 of 49 patients without DLE (28.6%) had a SLEDAI-2K score ≥ 10 (p  =  1). CONCLUSION: The presence of DLE in our patients with SLE was not associated with less severe disease.

HLA-DRB1 frequency in patients with familial and sporadic rheumatoid arthritis in north east of Iran.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that has a strong correlation with HLA-DRB1. Family history is considered a known risk factor for RA. The aims of this study were to compare the frequency of HLA-DRB1 alleles between patients with sporadic and familial RA and also between healthy controls with RA patients (sporadic and familial) and clarify if familial RA is more severe than sporadic RA. This study included 129 consecutive patients with sporadic and 48 cases with familial (first-degree siblings) RA who visited a rheumatology unit. Demographic data, including extra-articular involvement, mean disease activity according to DAS28 (ESR) criteria, and main laboratory findings, were compared between patients with sporadic and familial RA. HLA-DRB1 typing was carried out using the PCR-SSP method, and the frequency of each allele was determined in all cases and compared with the results of HLA-DRB1 frequencies in 72 healthy controls who were previously reported by our group in northeast Iran. Patients with sporadic and familial RA were matched in age and sex, most of the cases in both groups were females. The mean age of patients was 45 years. Ocular involvement was the most frequent extra-articular manifestation of our patients. There was no significant difference between the two groups in visual analogue scale (VAS) index, number of inflamed or tender joints, extra-articular involvements, and main laboratory findings. HLA-DRB1* 01 (55 %), 04 (48 %), and 03 (43 %) alleles were the most frequent alleles in both sporadic and familial diseases. The frequency of HLA-DRB1*11 and HLA-DRB1*13 was significantly higher in normal participants compared with RA (p = 0.001). There was no significant difference in the HLA-DRB1 allele's frequency between sporadic and familial RA. Therefore, familial aggregation was not associated with RA severity.

Does searching for antineutrophil cytoplasmic antibodies help with the diagnosis of Adult-onset Still's disease?

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. It is a seronegative disease with multisystemic manifestations. One of the important laboratory findings in AOSD is negative results for rheumatoid factor and antinuclear antibody. Because there is no specific, pathognomonic test for AOSD, diagnosis is based on a set of clinical and laboratory criteria and exclusion of other diseases like infections, malignancies, and vasculitis. It is obvious that antineutrophil cytoplasmic antibodies (ANCAs) are specific for vasculitis; however, few studies detected some types of these antibodies in rheumatoid arthritis, juvenile chronic arthritis, and still's disease. The aim of this study was to investigate whether or not ANCAs exist in sera of patients with AOSD. Forty-one AOSD patients were enrolled in this prospective study; patients were diagnosed according to Yamaguchi criteria and exclusion of other diseases by at least 6-months follow-up. Sera from all patients were tested for p-ANCA and c-ANCA by indirect immunofluorescence assay. Confirmatory antigenic testing for proteinase 3 (PR3) and myeloperoxidase (MPO) ANCA subtypes then were performed on positive sera. Only one patient with AOSD in this study showed low titer of MPO-ANCA in her sera. In a 1-year follow-up, ANCA did not predict vasculitis in this patient. This study suggested that patients with AOSD are mostly seronegative for ANCAs too. Positive ANCA appears to be an epiphenomenon and has not any association with vasculitis in AOSD.

Bone densitometry in patients with osteomalacia: is it valuable?

Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton. The clinical features of osteomalacia include musculoskeletal vague pain and muscle weakness. In its mild and early stages, osteomalacia may be misdiagnosed with variety of musculoskeletal diseases including osteopenia and osteoporosis, and for early diagnosis high rate of suspicion of osteomalacia is necessary. Our purpose was to determine the amount of bone mineral density (BMD) in patients with osteomalacia and to evaluate the efficiency of bone densitometry in these patients. Diagnosis of our patients was based on history, physical, laboratory and radiological findings and in three patients with bone biopsy and histological approval. BMD (gm/cm(2)) at the lumbar vertebrae (L2-L4) and femoral neck were measured by dual X-ray absorptiometry in 20 patients with osteomalacia (16 females and 4 males, age range 20 to 60 years, mean 39 years) before treatment, comparing with 28 matched healthy individuals, and their T scores were evaluated according to WHO criteria for the diagnosis of osteopenia and osteoporosis. 14 patients with osteomalacia (70%) had BMD in amount of osteoporosis in the lumbar spine, and 12 patients with osteomalacia (60%) had BMD in amount of osteoporosis in their femoral neck. 50% of the patients had T≥ -3. We concluded that bone densitometry may detect osteoporosis in up to 70% of patients with osteomalacia. Middle aged individuals with significant osteoporosis should be evaluated for osteomalacia, beside other causes of secondary osteoporosis. Measurement of BMD in patients with osteomalacia is helpful for assessment of the severity of bone condition and following management.

A comparative study of the usefulness of color vision, photostress recovery time, and visual evoked potential tests in early detection of ocular toxicity from hydroxychloroquine.

Ocular toxicity from hydroxychloroquine (HCQ) is rare, but its potential permanence and severity makes it imperative to employ measures and screening protocols to minimize its occurrence. This study was performed to assess the usefulness of color vision, photo stress recovery time (PSRT), and visual evoked potentials (VEP) in early detection of ocular toxicity of HCQ, in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). 86 patients were included in the study and divided into three groups: (1) with history of HCQ use: interventional 1 (Int.1) without fundoscopic changes and Int.2 with fundoscopic changes; and (2) without history of HCQ use, as control. Visual field, color vision, PSRT and VEP results were recorded for all patients and the effect of age, disease duration, treatment duration and cumulative dose of HCQ on each test was assessed in each group. There was a significant relationship among PSRT and age, treatment duration, cumulative dose of HCQ and disease duration (P<0.001 for all). Color vision was normal in all the cases. P100 amplitude was not different between the three groups (P=0.846), but P100 latency was significantly different (P=0.025) and for Int.2 it was greater than the others. The percentage of abnormal visual fields for Int.2 was more than Int.1 and control groups (P=0.002 and P=0.005 respectively), but Int.1 and control groups were not significantly different (P>0.50). In the early stages of maculopathy, P100 latencies of VEP and PSRT are useful predictors of HCQ ocular toxicity. In patients without ocular symptoms and fundoscopic changes, the P100 latency of VEP predicts more precisely than the others.

Primary hypertrophic osteoarthropathy with myelofibrosis.

Primary hypertrophic osteoarthropathy or pachydermoperiostosis is a rare congenital disease characterized by clubbing of the fingers, periostitis of the distal long bones, and hypertrophic skin changes (pachydermia) including thick folds in the skin of the face, forehead, scalp and extremities, and also joint pain. Clinical manifestations of this disease generally appear among the young and middle-aged. In this article we report a case of a 43-year-old man with pachydermoperiostosis. His skin and joint manifestations were prominent. He had also anemia, and bone marrow biopsy showed myelofibrosis.

Extramedullary hematopoiesis with spinal cord compression in beta-thalassemia intermedia.

Spinal cord compression due to extramedullary hematopoiesis is a rare manifestation of thalassemia. We present a 28-year-old woman with beta-thalassemia intermedia and progressive paraparesis. She had a thoracic extradural extramedullary mass lesion on MRI. She improved after receiving multiple transfusions. Clinical awareness of this phenomenon with early treatment is essential for a successful outcome.