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Colchicine is a unique anti-inflammatory drug with respect to its limited clinical usefulness and its mode of action. Colchicine is mainly indicated for the treatment and prophylaxis of gout and familial Mediterranean fever. Its mode of action includes modulation of chemokine and prostanoid production and inhibition of neutrophil and endothelial cell adhesion molecules by which it interferes with the initiation and amplification of the joint inflammation. This paper discusses its adverse effects and indications.

Objective: To determine the urinary levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with systemic lupus erythematosus (SLE) and to assess their relationship with clinical and laboratory features and the degree of activity and damage associated with the disease., Methods: The study sample included 24 consecutive patients with SLE. 24-hour urine samples were collected for the determination of soluble VCAM-1 and ICAM-1 levels by ELISA. Disease activity was defined by the SLE Disease Active Index (SLEDAI) and disease outcome by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ ACR) damage index., Results: The urinary soluble VCAM-1 level was significantly higher in patients with SLE compared to normal controls (32.35+/-34.27 vs. 4.66+/-3.8 ng/mg creatinine, p = 0.0005) and statistically significantly correlated with disease activity (SLEDAI), a low serum C3 level, decreased creatinine clearance and albuminuria, as well as with disease damage (SLICC/ACR damage index). In contrast, the urinary soluble ICAM-1 level was not significantly higher in the patients' group compared with the controls (4.5+/-5.19 vs. 2.72+/-2.31 ng/mg creatinine, p=0.2), but was statistically significantly correlated with hematuria and albuminuria., Conclusion: Our data suggest that the urinary level of soluble VCAM-1 significantly correlates with overall disease activity and damage scores, but not with nephritis in SLE.

Objective: The pathergy reaction is a unique feature of Behçet's disease (BD) and, according to the International Study Group (ISG), is among the major criteria required for the diagnosis. Different positive pathergy reaction rates in BD have been reported worldwide. We evaluated the prevalence of the pathergy reaction in Israeli BD patients, and its relation to mucocutaneous and systemic manifestations of the disease., Methods: Forty-three patients were studied, all of whom fulfilled the ISG criteria for BD. The mucocutaneous and systemic disease manifestations were analyzed with respect to the presence of the pathergy reaction, and a systemic severity score for BD was calculated according to the potential morbidity and mortality associated with various clinical features., Results: Nineteen patients (44.2%) had a positive pathergy test. The pathergy-positive and pathergy-negative BD groups showed a similar male:female ratio, age at disease onset, and mean disease duration. They also exhibited similar HLA-B5 levels and a similar frequency of oral ulcerations in close family members. The mucocutaneous manifestations, systemic disease expression, and severity score were similar in patients with and without the pathergy reaction., Conclusion: The presence of a positive pathergy reaction, although common in Israeli BD patients, is not associated with an increased risk for specific mucocutaneous or systemic manifestations of the disease, and probably does not predict a more severe disease course.

Problem: To investigate if controlled ovarian hyperstimulation (COH) affects the expression of neutrophil adhesion molecules and if a correlation exists between neutrophil activation and serum sex-steroid levels., Method of Study: The pilot study was carried out in the in vitro fertilization (IVF) unit of our department, and required no modification of our routine IVF protocol. Four patients arriving for baseline hormonal profile on day 1 of the menstrual cycle before initiation of COH (control group) and 11 patients admitted for oocyte recovery (study group) were included. Venous blood was obtained from all patients and examined for hormonal profile and neutrophil activation. The latter was performed by staining for the surface adhesion molecules beta2 integrin and L-selectin. Positive cell count and mean fluorescence intensity were determined by flow cytometry., Results: While neutrophil L-selectin was significantly lower in the study group than in the control group, neutrophil beta2 integrin was nonsignificantly higher. Though no significant correlations were found between neutrophil adhesion molecules and patient age, serum estradiol level, and human chorionic gonadotropin level; neutrophil L-selectin was negatively correlated with serum progesterone levels., Conclusions: COH leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for promoting fertility and preventing complications of COH.

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.

There were 55 Israeli patients with Behcet's disease (BD) included in a study conducted to determine the correlation between HLA-B5 and clinical manifestations and severity of the disease. The systemic manifestations of BD were analyzed in relation to HLA typing, and a systemic severity score for BD was calculated according to potential morbidity and mortality associated with various clinical features. Of the 55 patients, 42 (76.4%) were sephardic Jews, 2 (3.6%) were ashkenazi Jews, and 11 (20.0%) were Israeli Arabs. There were 39 (70.9%) HLA-B5 positive patients; they had a significantly higher incidence of thrombophlebitis and a lower rate of erythema nodosum. The HLA-B5-positive patients were significantly older at disease onset, and their severity score tended to be higher, although not statistically significant.The results of our study imply that HLA-B5 in Israeli patients is associated with specific clinical features, especially more vascular disease, and may be associated with a more severe course of BD. This is of general interest because American and North European patients also have less HLA-B5 and less severe disease. (J Clin Rheumatol 1999;5:137-140).

Objective: To explore the main patterns of Behçet's disease (BD) expression, applying factor analysis., Methods: Sixty-eight BD patients were studied. The following disease manifestations were used for the factor analysis: genital ulcerations, typical skin lesions (erythema nodosum, folliculitis or papulo-pustular rash), uveitis, CNS involvement, joint disease, deep vein and superficial vein thrombosis, and gastrointestinal manifestations. The results were further analyzed according to sex, HLA typing, and childhood vs. adult-onset disease., Results: Five factors were derived, which accounted for 69% of the variance of the matrix. Factor 1 represented the association between folliculitis and genital ulceration. Factor 2 represented the association between papulo-pustular rash and gastrointestinal symptoms. Factor 3 represented the inverse association between superficial vein thrombosis and erythema nodosum. Factor 4 represented the correlation between deep vein thrombosis and neuro-Behçet. Factor 5 represented joint disease. No difference was found between males and females in relation to factors 1, 2 or 5, but factors 3 and 4 had higher scores in male patients (p = 0.1 and p = 0.07, respectively). Factor 3 was significantly higher in patients with HLA-B5, compared to HLA-B5-negative BD patients (p < 0.001). Factors 1 and 3 were higher in patients with adult onset of the disease (p = 0.07, and p = 0.003, respectively), while factor 2 was higher in patients with childhood-onset BD (p = 0.07)., Conclusions: The application of factor analysis revealed possible associations between distinct types of skin lesions, or venous thrombosis, and other disease manifestations of Behçet's syndrome, some of which were sex, age at onset, or HLA-related.

Objective: To evaluate the correlation between the age at onset of Behcet's disease (BD) and sex distribution, mode of disease appearance, and number of organs involved during the disease., Methods: BD was defined according to the International Study Group criteria. Data from medical files and from patient interviews were collected. Results were analyzed for children and adults, according to age at disease onset. A systemic involvement index was calculated as the sum of visceral organ systems involved., Results: Fifty-nine patients with BD were studied, 26 male and 33 female. The mean age at disease onset was 8.4 +/- 4.5 years in children and 29.8 +/- 7.9 years in adults. The age of onset was significantly lower in male versus female patients. BD presented in children almost entirely as recurrent aphthous stomatitis, while in adults, less than one-third of patients presented first with oral ulcers. The mean age at disease onset of patients who presented first with oral ulcers was significantly lower than the age of patients presenting first with non-oral aphthosis. The mean systemic involvement index was higher in adult onset than in juvenile onset disease. A significant linear correlation was found between age of disease onset and total number of visceral organ systems involved., Conclusion: BD was observed to occur earlier in males than in females. The first manifestation of BD in children is almost exclusively in the form of oral ulcers, while older patients have a large proportion of non-oral aphthosis as their first disease manifestation. Disease onset at an older age is positively correlated with increased disease spectrum.

Previous studies have shown that neutrophils in the circulation of patients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the beta 2-integrin CD11b/CD18. Since activation of neutrophils leads to altered expression of another adhesion molecule, L-selectin (LS), we examined neutrophils from patients with SLE for changes in the expression of CD11b/CD18 and LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean fluorescence 225 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU), respectively]. However, as previously reported, neutrophils from patients with more active disease (activity score > or = 3, UCH Middlesex activity score) expressed greater CD11b/CD18 than neutrophils from controls (319 +/- 40 RFU, P < 0.03, n = 9) or from patients with less active disease (193 +/- 10 RFU, P < 0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (100 nM) induced up-regulation of CD11b/CD18 in cells from both SLE patients and controls (205 +/- 12% vs 239 +/- 15% of basal, respectively), but neutrophils from the most active patients (score > or = 3) increased CD11b/CD18 expression less than controls (175 +/- 12% of basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P < 0.003, n = 20). Surprisingly, we observed no change in LS expression on neutrophils from SLE patients compared to controls (143 +/- 14 vs 141 +/- 16 RFU, respectively) even in patients with the highest activity indices (154 +/- 21 RFU). In contrast to CD11b/CD18, there was no correlation between LS expression and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the expression of LS similarly in both controls and SLE patients (67 +/- 3% vs 58 +/- 4% reduction, respectively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11b/CD18 expression do not correlate with LS expression on neutrophils from patients with active SLE.(ABSTRACT TRUNCATED AT 400 WORDS)

Objective: To determine the value of measurement of serum soluble tumor necrosis factor receptor (sTNFR), compared with established parameters such as anti-double-stranded DNA, in monitoring systemic lupus erythematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity., Methods: Fifty-three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort study. Serum levels of sTNFR were measured by a unique 2-sided capture enzyme-linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR., Results: The mean +/- SD concentrations of both the p55 (type I) and p75 (type II) soluble receptors were significantly higher in a group of 46 SLE patients than in controls: 1.89 +/- 0.89 ng/ml versus 0.77 +/- 0.19 ng/ml and 7.25 +/- 3.89 ng/ml versus 3.02 +/- 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects and these patients (as well as in 7 additional patients on whom sequential studies were performed) correlated with disease activity more than did the occurrence of serum anti-DNA antibodies (correlation coefficients with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respectively, and 0.51 for anti-DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor extent, reduced clearance due to impairment of renal function. Sera of the SLE patients had a marked inhibitory effect on the in vitro cytocidal activity of TNF, and this was shown to result entirely from their higher sTNFR receptor concentration., Conclusion: An increase in serum levels of sTNFR may become a useful marker for SLE activity since it shows a stronger correlation than do any other laboratory or clinical parameters employed presently in the daily clinical setting. At the concentrations attained in the serum of SLE patients, sTNFR effectively inhibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.

Two patients with life threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to corticosteroid and immunosuppressive therapy, were treated with high dose intravenous immunoglobulin (IVIG). Following IVIG therapy, lupus pneumonitis and encephalitis in the first patient, and lupus nephritis in the second patient, resolved. Continuous treatment with IVIG, every 4 weeks for up to 20 months induced a prolonged clinical and laboratory remission. Treatment with cytotoxic agents was stopped, and the dosage of corticosteroids lowered. Exacerbation of lupus nephritis occurred in the second patient after 10 months of IVIG therapy. We suggest that prolonged use of high dose IVIG may be a useful therapy for acute exacerbations of SLE and for inducing prolonged remissions.

Brain magnetic resonance imaging (MRI) was performed in 21 patients with systemic lupus erythematosus (SLE) with and without lupus anticoagulant (LAC), one lupus-like patient and 5 patients with primary antiphospholipid antibody syndrome. Thirteen patients had white matter focal brain lesions on MRI, 10 of whom had LAC (p = 0.03). We found no correlation between these lesions and neurologic manifestations, nor any clinical or serologic indices of activity of SLE. Our MRI lesions were similar to those described in multiple sclerosis and may indicate a similar pathologic process.

A 15-year-old girl with right-sided cerebral infarct in association with lupus anticoagulant is described. The literature on the primary antiphospholipid syndrome and its neurological complications is reviewed.

A 60-year-old woman with disseminated small cell carcinoma of the lung and hemophagocytosis by the metastatic cells in the bone marrow is presented. It is the first clinicopathologic report on phagocytosis of erythrocytes by lung tumor cells in concordance with a recently described evidence of a macrophage origin of small cell carcinoma of the lung.

A 20-year-old woman with C7 deficiency and fulminant meningococcemia that appeared after a blunt head trauma is described. This C7 deficiency was found in two of her siblings and should be suspected in patients presenting with neisserial infections.

Purpose: The purpose of this study was to assay serum cobalamin levels in patients with systemic lupus erythematosus (SLE) as there are few case reports on the association of pernicious anemia and SLE., Patients and Methods: Serum cobalamin levels were assayed in 43 female SLE patients by a radio-dilution assay using purified intrinsic factor., Results: Cobalamin levels were found to be significantly lower in the SLE group compared with a normal control group, eight of whom (18.6%) had serum cobalamin levels equal to or lower than 180 pg/mL (mean: 129.25 +/- 40.05 pg/mL). None of the SLE patients had been found to have pernicious anemia. The transcobalamin II level and unsaturated vitamin B12 binding capacity, but not the cobalamin level, were positively correlated with SLE activity., Conclusion: Our results may indicate a subtle cobalamin deficiency in SLE patients without pernicious anemia.

Nine patients with subacute cutaneous lupus erythematosus (SCLE) are described, all of whom had systemic involvement of the disease although usually milder than in systemic lupus erythematosus. None of the patients had renal disease or died of SCLE.