Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort.

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (+/- s.d.) period of 45.7 +/- 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17 +/- 64 and 1.64 +/- 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE.

Inactive systemic lupus erythematosus id associated with a normal stimulated Th(1)/Th(2) cytokine secretory pattern.

OBJECTIVES: To determine the Th(1)/Th(2)balance in systemic lupus erythematosus (SLE) patients with inactive disease. METHODS: A comprehensive analysis of peak secretion, overall cytokine production and secretory pattern of Th(1)and Th(2)cytokines from stimulated PBMC of 10 SLE patients with inactive disease and 10 age- and sex-matched controls. RESULTS: No significant differences were found in the peak and total secretion of all cytokines, as well as in the Th(1)and Th(2)secretory patterns and proliferative response between the two groups. CONCLUSION: Th(1)and Th(2) balance in inactive SLE is normal.

Headache in systemic lupus erythematosus and its relation to other disease manifestations.

OBJECTIVE: To investigate headache in systemic lupus erythematosus (SLE) and its relation to other disease manifestations. METHODS: Clinical and laboratory variables of 148 SLE patients were prospectively recorded in a computed data base. RESULTS: The patients were divided into two groups. Group A consisted of patients who reported moderate to severe headache on at least two consecutive encounters, and Group B consisted of the remainder of the patients, with mild or no headache. The two groups did not significantly differ in age or in sex distribution. Patients in Group A suffered from more severe joint pain and inflammation, muscle pain, photosensitivity, mouth ulcers, fever and fatigue. They also had higher disease activity scores, and a higher number showed central nervous involvement. There were no significant differences between the two groups in any of the laboratory variables examined, nor in the proportion of patients with renal involvement. The prevalence of non-thromboembolic central nervous system (CNS) manifestations was 7.2%. The sensitivity of headache for the diagnosis of non-thromboembolic CNS manifestations was 90.9%, and the specificity was 29.2%. On logistic regression analysis, the total arthritis score, muscle pain, fatigue and photosensitivity were each found to be significantly independently related to headache. CONCLUSIONS: Headache is common in SLE, and in the majority of patients is related to musculoskeletal and constitutional disease manifestations.

Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients.

Expression of the p21 ras protooncogene is reported to be increased in animal models and in patients with SLE. However, the expression of p21ras regulatory elements has not been determined. We determined the expression of p21ras, and its regulatory elements p120-ras-GAP and hSOS, in PBMC of 10 patients with inactive SLE (mean SLEDAI score 1.8+/-0.53) and 10 age- and sex-matched healthy controls. No difference was found between the two groups in the levels of p21 ras (3760+/-513 and 3367+/-335, P=0.25) and ras-GAP (1048+/-261 and 1534+/-247, P=0.11) in patients and controls, respectively. In contrast, levels of hSOS were significantly decreased in patients as compared to controls: 955+/-218 and 2306+/-327, P = 0.002, respectively. The mitogen-induced proliferative response was comparable in the two groups: SI 20.8+/-4.2 and 15.03+/-4.9, P=0.135, in patients and controls, respectively. Taken together, our data demonstrate that nonactive SLE patients are characterized by reduced hSOS expression and underscore the need for a comprehensive evaluation of p21ras pathway in these patients.

Treatment of staphylococcal septic arthritis in rabbits by systemic antibiotics and intra-articular corticosteroids.

OBJECTIVE: To assess the effect of intra-articular corticosteroids added to systemic antibiotics in experimental septic arthritis. METHODS: Rabbits were injected intra-articularly by Staphylococcus epidermidis. Rabbits received no additional treatment and served as control (group 1), were treated with systemic antibiotics (group 2), or treated with systemic antibiotics and intra-articular corticosteroids (group 3). After 15 days animals were killed and joint histopathological-histochemical parameters were assessed. RESULTS: All rabbits survived the experiment. The treated groups (2-3) had lower histological-histochemical scores in comparison with the untreated group (1). Group 3 had significantly lower scores in joint sections in comparison with group 2: (mean (SD) 6.5 (1.4) v 4.0 (1.0), p = 0.001 and 7.4 (2.6) v 4.2 (2.2), p = 0.01), because of lower damage expressed in clustering of chondrocytes, pannus formation, proteoglycan depletion, and synovitis. CONCLUSION: Addition of local corticosteroids to systemic antibiotics in septic arthritis seems to be harmless, and improves joint histological-histochemical parameters in this experimental setting.

Seasonal variations in manifestations and activity of systemic lupus erythematosus.

The purpose of the present study was to investigate a possible seasonal pattern in various clinical and laboratory manifestations in a group of systemic lupus erythamatosus (SLE) patients. One hundred and five SLE patients were followed up during a 4 yr period. Data on each of the clinical and laboratory variables examined, as well as the results of the disease activity index (SLEDAI), were plotted against the month during which they were obtained. Photosensitivity was the only variable to show a seasonal pattern, having higher scores during the summer months (1.04 +/- 0.16 in July vs 0.58 +/- 0.12 in December). We were unable to show seasonal patterns in any of the other variables examined. As a group, SLE patients do not show any significant seasonal pattern in disease manifestations and activity, except for photosensitivity. However, such a pattern may exist for the individual patient.

A study of the clinical differences between women and men with hyperprolactinemia.

A group of 64 women and 14 men with hyperprolactinemia were followed up in an endocrine service center for a mean of 43 months. The various parameters in each sex were compared. The mean age at first visit was 49 years in the men and 36 years in the women (p < 0.001). The peak prolactin index levels were 13.7 in the men and 5.5 in the women (p < 0.002). Macroprolactinomas were significantly more prevalent in the men (p < 0.002). The women complained significantly more about headache (p < 0.02), malaise (p < 0.02), restlessness (p < 0.03) and fatigue (p < 0.04). These symptoms had no correlation with the prolactin level. Thus, in the men the clinical manifestations of hyperprolactinemia came to attention at an older age and had a connection with a higher prevalence of macroprolactinoma. The possible mechanisms are discussed. Vague complaints, reported more often by the women, do not seem to correlate with the prolactin level.

Experimental septic arthritis in rabbits treated by a combination of antibiotic and steroid drugs.

OBJECTIVES: Intraarticular steroid injection is traditionally contraindicated during acute septic arthritis. However, there is abundant evidence which proves that the damage to the joint is not only due to the direct effect of bacteria, but also to the local protective mechanisms evoked by the organism. There is, therefore, theoretical justification for a combined therapy of systemic antibiotics and intraarticular corticostertoids in septic arthritis. METHODS: Experimental arthritis was induced by the intraarticular injection of Staphylococcus epidermidis in rabbits. The experimental scheme included three groups of animals: animals that were infected but not treated (group 1); animals treated with systemic antibiotics (group 2); and animals treated with systemic antibiotics and intraarticular steroids (group 3). Nine days later the animals were sacrificed and joint histopathological-histochemical indices were calculated. RESULTS: Animals from groups 2 and 3 had a smaller pannus, reduced proteoglycan loss, no loss of cartilage height and diminished synovial inflammation in comparison to the animals from group 1. The animals from groups 2 and 3 were identical in terms of cartilage cellularity, surface erosion, chondrocyte cloning, pannus formation and proteoglycan loss. Synovial inflammation appeared to be less pronounced in group 3 animals when compared to animals of group 2. CONCLUSION: Concomitant antibiotic-steroid treatment of septic arthritis seems to be harmless in this experimental setting.

Lymphadenopathy in systemic lupus erythematosus. Prevalence and relation to disease manifestations.

Lymphadenopathy (LAP) is a frequent sign in systemic lupus erythematosus (SLE). Yet, data concerning its relation to the various disease manifestations are scarce or absent. LAP was present in 23/90 (26%) SLE patients. Patients with LAP had significantly more constitutional symptoms of fatigue, fever and weight loss, more cutaneous symptoms and signs, a higher rate of hepatomegaly and splenomegaly, increased anti-dsDNA antibodies and decreased complement levels. Disease activity index was higher among patients with LAP, as was the intake of steroids and antimalaria medications. There was no difference in renal or central nervous system (CNS) involvement between patients with LAP and those without LAP.

Expression of rheumatoid arthritis in two ethnic Jewish Israeli groups.

OBJECTIVE: To investigate the expression of rheumatoid arthritis (RA) in Jewish Israeli patients according to ethnic origin. METHODS: RA patients who were seen in a primary public rheumatology clinic were divided into two groups according to ethnic origin (Sepharadic or Askenazi) and subjected to a cross sectional study. The two groups were compared for history, physical status, and radiographic and laboratory variables. The entire study population was again divided into two groups according to formal educational level, and these were also compared for the same variables as above. RESULTS: The patients of Sepharadic origin had significantly more pathological recordings of pain and fatigue, and greater Ritchie scores than those of Askenazi origin. The Sepharadic group patients were younger, had a lower educational level, and were predominantly female. The more educated group recorded significantly less pathological pain and fatigue, and had smaller Ritchie scores. Functional capacity and global disease severity, assessed by physician and patient, were also reduced in the more educated group. On multiple regression analysis, ethnic origin was found to be independently related to functional class. Education was found to be independently related to the Ritchie score. CONCLUSIONS: Disease manifestations in Jewish RA patients of Sepharadic origin are more serious compared with those in patients of Askenazi origin. In addition, low educational level is related to more severe disease manifestations in Israeli RA patients.

Fatigue in systemic lupus erythematosus. Prevalence and relation to disease expression.

Significant fatigue was observed in 63/83 (76%) SLE patients. Patients with fatigue had significantly lower lymphocyte counts (1090 +/- 60 vs 1675 +/- 205 cells/mm3 P = 0.003), and higher ratings for headache, nervousness and musculoskeletal symptoms and signs. These disease parameters also correlate significantly with the magnitude of fatigue. Fatigue correlated with disease activity index (r = 0.49 P < 0.001).

Expression of systemic lupus erythematosus in various ethnic Jewish Israeli groups.

OBJECTIVES: To assess the expression of systemic lupus erythematosus (SLE) in Jewish Israeli patients according to ethnic origin. METHODS: Eighty four patients with SLE were divided into groups according to origin and compared for history, physical examination, and laboratory variables. RESULTS: Patients of Sephardic origin had more serious disease manifestations than Ashkenazi patients in 60 of the 76 variables examined. They had significantly worse muscle pain, alopecia, and cutaneous vasculitis, higher antibodies to DNA and erythrocyte sedimentation rate, and significantly lower complement and leucocytes. Sephardic patients were divided into subgroups according to country: Mediterranean area, Iran-Iraq-India, and Yemen. All three subgroups had more serious disease manifestations than the Ashkenazi group, and the Yemenite patients had the most serious manifestations among the Sephardic subgroups. The Sephardic patients had a significantly lower education level, but only origin, and not education level or age, was significantly related to disease manifestations on multivariate analysis. CONCLUSION: More serious manifestations of SLE are found among Jewish patients of Sephardic origin, but these are not related to level of education or age.

Toward improved empiric management of moderate to severe urinary tract infections.

BACKGROUND: Guidelines to show whether a patient hospitalized because of a urinary tract infection (UTI) has a severe infection, and whether he or she is at high risk for harboring a multiresistant pathogen, are scant. The aims of the present study were to find (1) clinical and laboratory variables known within 24 hours of admission that, combined in a logistic model, will point to a high or low probability of bacteremia and (2) variables that can be used to define patients at high risk for the subsequent isolation of a multiresistant uropathogen. METHODS: In a set of patients consecutively admitted to a department of medicine because of UTI, we compared bacteremic vs nonbacteremic patients, and patients with a multiresistant uropathogen vs others, on logistic regression analysis. The logistic models derived were validated in a second set of patients with UTI. RESULTS: Among 247 patients with UTI (median age, 75 years), 80 of them with bacteremia, five factors were significantly and independently associated with bacteremia: serum creatinine level, leukocyte count, temperature, diabetes mellitus, and low serum albumin level. A logistic model incorporating those factors was used to divide the patients into three groups with increasing prevalence of bacteremia (6%, 39%, and 69%) and of death (3%, 6%, and 20%). Three factors were predictive of the subsequent isolation of a resistant uropathogen: use of antibiotics before admission, advanced age, and male gender. The combination of those factors was used to divide patients into two groups, with resistance to cefuroxime of 9% vs 28%, to gentamicin of 7% vs 20%, and to sulfamethoxazole-trimethoprim of 30% vs 50%. In a second set of 144 patients with UTI, the percentages of bacteremia in the three groups were 5%, 16%, and 55%, and those of death, 2%, 6%, and 17%. When divided by the second model, the resistance to cefuroxime in the two groups was 16% vs 30%; to gentamicin, 16% vs 28%; and to sulfamethoxazole-trimethoprim, 28% vs 59%. CONCLUSIONS: If prospectively validated in other settings, the models can be used to define groups of patients with UTI at low and high risk for bacteremia, and to help in the choice of empiric antibiotic treatment.

Patterns of multiple resistance to antibiotics in gram-negative bacteria demonstrated by factor analysis.

Principal component analysis was used to demonstrate the main associations between patterns of resistance to antibiotic drugs in 670 gram-negative bacteria consecutively isolated from blood cultures over a period of two years. Six factors were derived, which accounted for 84% of the total variance of the original matrix. Each factor represented an association between resistance to certain antibiotics as follows: factor 1: aztreonam, third generation cephalosporins and aminoglycosides; factor 2: first and second generation cephalosporins; factor 3: tetracycline and chloramphenicol; factor 4: ampicillin and ureidopenicillins; factor 5: trimethoprim/sulfamethoxazole; factor 6: fluoroquinolones. On two-way analysis of variance the difference in the factor scores was significant between bacteria for all factors except factor 5. The difference in factor scores between community and hospital acquired strains was significant only for factors 1, 2 and 6. Only the score of factor 6 showed a clear trend to increase with time during the two-year study period. Patients who were treated with antibiotics prior to bacteremia had higher scores for all factors, the difference being most marked in patients treated with fluoroquinolones. Factor analysis can be used to describe phenotypic associations between resistance to antibiotics, and the factor score used to compare groups of isolates and to demonstrate temporal and other trends.

Disease patterns of patients with systemic lupus erythematosus as shown by application of factor analysis.

Clinical and laboratory test data of 77 patients with systemic lupus erythematosus (SLE) were evaluated by factor analysis. Six factors representing disease patterns were extracted: cutaneous symptoms of alopecia, malar rash, rash and photosensitivity; renal involvement; the anticoagulant syndrome of phlebitis and partial thromboplastic time inversely related to platelet count; lymphopenia; viral or fibromyalgia symptoms of headache, nervousness, joint and muscle pain; and serology of anti-DNA antibodies and complement inversely related. Application of factor analysis reveals various clinical presentations of SLE.

Rash in systemic lupus erythematosus: prevalence and relation to cutaneous and non-cutaneous disease manifestations.

Rash is a common cutaneous sign in patients with systemic lupus erythematosus (SLE) but no data regarding its prevalence or relation to disease manifestations are known, possibly due to the fact that it is a common but non-specific sign. Rash was present in 48/81 (59%) patients with SLE. Patients with rash had more cutaneous symptoms and signs, lymphadenopathy, increased levels of antibodies to double stranded DNA and decreased complement levels. They were also receiving a higher dose of prednisone. There was no difference between patients with and without rash with respect to renal or central nervous system disease. Rash did not correlate with the disease activity index and clinical parameters of disease exacerbation.

Bacteremia in febrile patients. A clinical model for diagnosis.

Among 244 patients aged 18 to 98 years who were consecutively hospitalized in a department of internal medicine because of a febrile disease, 52 (21%) were bacteremic. On a logistic regression analysis, five variables known within 24 hours of admission were found to be associated both significantly and independently with bacteremia: low serum albumin level, low premorbid performance status, chills, renal failure, and an assumptive diagnosis of urinary tract infection on admission. The logistic model was used to divide patients into three groups. In group 1, the percentage of bacteremic patients was 5%, in group 2, 40%, and in group 3, 83%. The percentage of deaths in the three groups was 0%, 23%, and 50%, respectively. The model was validated in a second group of 257 patients. The percentage of bacteremia was 1% in group 1, 23% in group 2, and 65% in group 3. The death rate in three groups was 3%, 4%, and 35%, respectively. The accuracy of the attending physician in diagnosing bacteremia within 24 hours of hospitalization was compared with that of the model. Use of the model could have improved the diagnostic accuracy in 5% of the patients in group 1 and in 18% of patients in group 3.