Effect of exposure to silica in inducing autoimmune hepatitis: an experimental animal-controlled study.

OBJECTIVE: The aim of this experimental study is to investigate the effect of subcutaneous and oral sodium silicate in inducing the autoimmune hepatitis. MATERIALS AND METHODS: Twelve Brown Norway rats were studied, six rats were challenged with Sodium Silicate and the rest were challenged with normal saline as a control group. At 14th week post-sodium silicate or normal saline exposure, the rats were sacrificed. Histopathological studies were conducted in six positive autoantibodies responding silicate group rats and then compared with an equal number of negative autoantibodies responding control rats. RESULTS: The liver findings from sodium silicate group of animals showed a histopathological reaction in 3/6 (50%) compared with 0/6 of the corresponding control saline group (p = 0.09). However, the absolute differences in the percentage between the two groups was 50%, the subcutaneous sodium silicate sub-group showed hepatic tissue response close to being statistically significant level (p = 0.05). CONCLUSIONS: After correlating the results with autoantibodies including serum antinuclear antibodies and anti ribo-nucleoprotein response of the same rats, it is concluded that sodium silicate play a role in inducing the autoimmune hepatitis in a genetically susceptible rat model.

Superior mesenteric artery syndrome and intra-abdominal compartment syndrome in systemic lupus erythematosus.

Gastrointestinal manifestations of systemic lupus erythematosus (SLE) are common, occurring in about 50% of cases. They are usually mild, in the form of mouth ulcers, nausea, heartburn and mild abdominal pain, but they can be severe in cases of gastrointestinal vasculitis. In this report we describe an unusual combination of SLE complications, namely superior mesenteric artery syndrome (SMAS) and reversible acute obstructive renal failure. This was attributed to raised intra-abdominal pressure and hence intra-abdominal compartment syndrome (IACS) following weight loss secondary to an acute presentation of SLE with gastrointestinal vasculitis.

Herpes Zoster Infections in SLE in a University Hospital in Saudi Arabia: Risk Factors and Outcomes.

Patients with SLE carry an increased risk of infection that account for 11-23% of all hospitalized patients and 50% of all SLE patients develop major infections during the course of their disease. Globally Herpes Zoster has been reported as the most frequent viral infection in SLE patients. We determined the clinical spectrum, disease sequelae and the risk factors associated with the development of Herpes Zoster in patients with SLE and their outcomes. Retrospective case control study of Herpes Zoster infections was done in SLE patients between 1982 and 2006. Cases were matched 1:2 to controls for age, race, sex and duration of follow up. Clinical features of the cases from the time of lupus diagnosis to the time of Zoster were compared to their respective controls over similar time periods. Thirty two SLE cases were compared to sixty four controls. Cases were more likely to have received cyclophosphamide (P = .0223) and intravenous methylprednisolone pulse therapy (P = .0026), MMF (P < .02), had leucopenia (P = .0407) and hemolytic anemia (P = .0344). More cases than controls had lupus nephritis, cerebritis, thrombocytopenia but the differences did not reach statistical significance. The mean oral prednisolone dose and proportion of patients receiving immunosuppressives including pulse methylprednisolone therapy, IV Cyclophosphamide and mycophenolate was significantly higher in patients with active SLE compared to patients with SLE in remission at the time of Herpes Zoster (P < .05). Disseminated Zoster developed in patients with active SLE (7/9) compared to patients with SLE in remission (0/23). None of the patients had postherpetic neuralgia or bacterial super infection. Immunosuppressive medications were discontinued at the time of diagnosis of Zoster in 19 of 32 patients and all patients received antiviral medications.There were no permanent neurologic deficits or deaths. We conclude that Herpes Zoster infections occur at increased frequency among patients with SLE and carry significant morbidity. Immunosuppressive therapy and severe manifestations of lupus may be risk factors for the development of Herpes Zoster although not necessarily at the time of disease flare or immunosuppressive therapy. Our study suggests that although Herpes Zoster occurs frequently in patients with SLE, it has a relatively benign course.

Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia.

The aim of this study was to examine the pregnancy outcomes in patients with systemic lupus erythematosus (SLE) and the effect of SLE flare and treatment on pregnancy outcomes. We performed a retrospective evaluation of all pregnancies occurring in patients with SLE during the 27-year period from 1980 to 2006. Of the 319 women with SLE planning pregnancy after SLE onset, 176 (55.2%) conceived resulting in 396 pregnancies. Live births were significantly lower in proportion (70.2% vs. 85.7%) and more likely to end in fetal deaths (29.7% vs. 14.2%) and preterm births (26.7% vs. 5.8 %) in pregnancies occurring after SLE onset than in pregnancies occurring before SLE onset (p < 0.0001). With respect to different disease manifestations, we found that fetal loss was significantly higher in patients with antiphospholipid (aPL) antibodies than without (p < 0.001). Preterm deliveries were significantly more frequent in patients with lupus nephritis, anti-Ro/SSA antibodies, hypertension, history of intravenous cyclophosphamide treatment and aPL than those without these features (p < 0.05). Neonates with intrauterine growth retardation (IUGR) neonates were more common in hypertensive and Raynaud's-positive pregnancies (p < 0.05). SLE flares occurred in 30.8% pregnancies. There was increased risk of fetal loss, preterm births and IUGR in pregnancies with SLE exacerbations than without (p < 0.05). Prednisolone was found to improve the rate of live births, although it was also a predictor of prematurity. The predictors of pregnancy loss were lupus nephritis (odds ratio (OR) 7.3), aPL (OR 3.9), and SLE flares in pregnancy (OR 1.9). There was higher risk of preterm deliveries in patients with lupus nephritis (OR 18.9), anti-Ro antibodies (OR 13.9), hypertension (OR 15.7) and SLE flares (OR 2.5). IUGR was found to be associated with hypertension (OR 37.7), Raynaud's (OR 12.3), and SLE flares (OR 4.2). In conclusion, pregnancies in SLE patients with active lupus nephritis, anti-Ro/SSA antibodies, aPL, hypertension, Raynaud's phenomenon, active disease at conception and SLE exacerbations are at a higher risk of adverse pregnancy outcomes. It is important to carefully plan pregnancy, and experienced rheumatologists and obstetricians should monitor SLE patients in pregnancy and postpartum.

Induction of autoimmunity in Brown Norway rats by oral and parenteral administration of sodium silicate.

Silica and silicate may disturb immune function such as autoimmunity and tumour immunity. The main objective of this study was to examine the relation between sodium silicate and induction of autoimmunity in genetically susceptible rats. In this study, thirty Brown Norway rats were randomised into four treatment groups, the first and second group receiving 3 mg of sodium silicate (NaSiO(4)) (equivalent to 2 mg silica) in 0.2 mL of normal saline either per oral or subcutaneously, and the third and fourth group (control) receiving 0.2 mL of normal saline (0.9%) through the same corresponding route. A significant number of rats (80%) (P < 0.05) which received sodium silicate by the subcutaneous route showed a high level of serum ANA compared with controls. In the oral, sodium silicate group showed high serum ANA in an insignificant number of rats. Other autoantibodies in both groups (anti-dsDNA, anti-Smith, anti-SSA, anti-SSB) showed gradual increased post exposure, but the numbers of rats with positive titres post exposure was statistically not significant. Silica exposure in rats appears to induce the development of autoimmunity. A longer duration post exposure to silicate seems to be associated with greater risks.

Clinical and immunological manifestations in 624 SLE patients in Saudi Arabia.

Our objective was to study the demographic, clinical, laboratory features, therapy, and outcome of systemic lupus erythematosus (SLE) patients. In this retrospective study, which covered a 27-year period (1980-2006), 624 SLE patients referring to King Khalid University hospital, Riyadh were included. There were 566 females and 58 males (9.8:1) with a mean age of 34.3 (range 8-71) years and mean age at disease onset of 25.3 years (range 0.08-67). The mean disease duration was 9.3 years (range 0.3-30). The most common disease manifestations were hematological abnormalities (82.7%), arthritis (80.4%), and mucocutaneous symptoms (64.3%). The prevalence of malar rash was 47.9%, discoid rash 17.6%, photosensitivity 30.6%, oral ulcers 39.1%, serositis 27.4%, nephritis 47.9%, and neuropsychiatric manifestations 27.6%. Lymphopenia (40.3%), anti-Ro (53.1%), anti-La (26.6%), anti-Sm (41.6%), anticardiolipin IgG (49.7%), and IgM (33.5%) antibodies were highly prevalent. Antinuclear antibodies were detected in 99.7% and anti-DNA in 80.1% patients. Low C3 and C4 were observed in 45.4% and 42.2%, respectively. Therapy included oral steroids (96.2%), IV cyclophosphamide (34.1%) and azathioprine (32.1%) along with other drugs. Long-term remission was achieved in 82.4%, disease was active in 2.6%, renal failure occurred in 4.3% requiring dialysis, 6.7% lost follow up and 4.0% patients died. Infections (48%) and active SLE (36%) were the common causes of death. The 5- and 10-year patient survival rate was 98% and 97%, respectively. This study suggests that, in our patients, SLE manifests with features similar to SLE patients from other Arab countries and Caucasia. In comparison to Caucasians, higher prevalence of anti-Ro antibodies is observed in our study, in some Middle-Eastern and Asian countries; this may likely be due to inter-ethnic variation owing to genetic differences. Our 5-year patient survival rate was similar to that of western countries, while 10-year survival rate was better than that of most places.

The relationship between chondrocalcinosis and osteoarthritis in Saudi Arabia.

The association between articular chondrocalcinosis and osteoarthritis was sought by studying 92 patients over the age of 60. Anteroposterior and lateral X-ray projections of knees, hands and wrists were studied for the presence of chondrocalcinosis and osteoarthritis. Of the 92 patients (60 males, 32 females), six had chondrocalcinosis of the knees; two of them also had it in the wrist. The six cases with chondrocalcinosis were compared to the 86 cases without, for the presence of osteoarthritis in the different compartments of the knees, intercarpal joints (IC) and metacarpophalangeal joints (MCP). We found an association between chondrocalcinosis and osteoarthritis of the lateral knee compartment (odd ratio (OR) 10.59, 95% CI 3.47-34.9), second MCP joint (OR 3.27 95% CI 1.44-8.93), third MCP joints (OR 6.92, 95% CI 1.99-25.54) and IC joint (OR 5.69, 95% CI 1.14-29.7). No association was found with overall knee OA, medial knee compartment OA or patellofemoral OA. In conclusion, chondrocalcinosis was associated with OA of the lateral knee compartment, second MCP, third MCP and IC joints.

Characteristics of rheumatoid arthritis relative to HLA-DR in Saudi Arabia.

OBJECTIVE: To determine the clinical characteristics of rheumatoid arthritis in Saudi Arabia in relation to human leukocyte antigen type. METHODS: A group of 91 rheumatoid arthritis patients, 72 females and 19 males were studied for the various clinical, laboratory and radiological parameters along with human leukocyte antigen-DR phenotypes. Since human leukocyte antigen-DR10 was most commonly associated with rheumatoid arthritis in our population, we compared those patients with human leukocyte antigen-DR10 to those without. RESULTS: The comparison yielded differences in the presence of rheumatoid nodules, erosions, corticosteroid treatment, joint involvement at presentation, hemoglobin levels, and white cell count. Only the last 3 parameters showed a statistical significance. CONCLUSION: Human leukocyte antigen type of Saudi patients with rheumatoid arthritis influenced the course of the disease but only to a limited extent.

Adult-Onset Still's disease in Saudi Arabia.

We present a series of 14 Saudi patients diagnosed to have adult-onset Still's disease (AOSD). The clinical and laboratory pattern of AOSD in our series is more or less similar to that in other reported series, apart from having lower cardiac and pulmonary involvement than western series. The disease course was relatively benign, with only half the cases showing recurrences, which were controlled by alterations in the dosage of corticosteroid and NSAIDs. A comparison with other series is given.

Lymphomatoid granulomatosis with long survival.

We present a case of lymphomatoid granulomatosis presenting in a 35-year-old Saudi lady with long survival. She responded to treatment with intermittent cyclophosphamide infusion in addition to corticosteroids. This is the first case of lymphomatoid granulomatosis to be reported in the Arab world. The prolonged survival and response to intermittent cyclophosphamide infusion is discussed.

Hyperuricemia in Saudi Arabia.

The objective of this prospective study was to determine the prevalence of hyperuricemia and gout in a sample of Saudi individuals and their relationship to certain risk factors, namely, obesity, serum glucose, triglycerides, cholesterol, age, and sex. A total of 487 Saudis (250 males and 237 females) from 14 primary care clinics were interviewed, examined, and investigated. The mean age for the males was 46.89 +/- 17.01 years (range 14-83) and for the females 45.08 +/- 13.67 years (range 21-80). Serum uric acid (SUA) values above 420 micromol/l for males and 360 micromol/l for females were considered to be high. Of the 487 individuals, 41 (8.42%; 20 males and 21 females) had hyperuricemia. The mean SUA was 308.41 +/- 90.64 micromol/l for males and 254.59 +/- 85.79 micromol/l for females. In females, uric acid levels correlated significantly with age, body mass index (BMI), serum creatinine, and the erythrocyte sedimentation rate (ESR), but not with serum cholesterol or triglycerides. In males, uric acid levels only correlated significantly with BMI and serum creatinine. No case of gout was found.