Israel Medical Association Journal

Background: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE).

Objective: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs.

Methods: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit.

Results: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32–6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28–0.87, P = 0.016), depicting a medium-to-high disease activity among the former.

Conclusions: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.

Objectives: To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.

Methods: We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.

Results: No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels < 200 mg/L and those with SAA levels > 200 mg/L (P = 0.027). SAA levels > 200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels > 150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels < 200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).

Conclusions: Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.

Background: Most data on the incidence of rheumatic fever come from hospital records. We presumed that there may be cases of RF[1] that do not require hospitalization, especially in countries with high quality community health care. 

Objectives: To explore the incidence and characteristics of RF using community-based data. 

Methods: A retrospective descriptive study was conducted among the members (more than 450,000) of the Clalit Health Services, Central district, during 2000–2005. The electronic medical files of members up to 40 years old with a diagnosis of RF in hospital discharge letters or during community clinic visits were retrieved. Patients with a first episode of RF according to the modified Jones criteria were included.

Results: There were 44 patients with a first episode of RF. All patients were under the age of 29. The annual incidence among patients aged 0–30 years was 3.2:100,000; the highest incidence was among children aged 5–14 years (7.5:100,000), and in males the incidence was 2.26 times higher than in females. The incidence was higher among patients from large families, of non-Jewish ethnicity, and from rural areas. Twenty-five percent of the patients were both diagnosed and treated in an ambulatory care setting.

Conclusions: Although the incidence of RF in the western world and in Israel is low, the disease still occurs and mainly affects children. Any future estimates of disease incidence should take into account that RF is becoming an ambulatorily treated disease.  

Background: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT[1] in Israel is not known.

Objective: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection.

Methods: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR[2]. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records.

Results: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03).

Conclusions: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT. 

Background: Pseudomembranous colitis is a well-recognized cause of diarrhea in patients receiving antibiotics and has significant consequences in terms of morbidity, mortality and cost. Clostridium difficile infection is the single most important infectious cause of PMC[1]. PMC is frequently nosocomial, with an increased risk of spread among institutionalized patients, both in hospitals and nursing homes.

Objective: To investigate the demographic, clinical and laboratory characteristics of PMC patients in an Israeli elderly population.

Methods: We studied 72 hospitalized patients with endoscopically proven PMC. The medical records of all patients including clinical history and laboratory data were reviewed, such as: age, pre-hospitalization status (dependency or not, in the community as compared to the nursing home), background medical history, presenting symptoms, antibiotic history, physical examination on admission, hematologic and biochemical parameters, treatment, duration of hospitalization, complications, mortality and recurrence of disease.

Results: Of the 72 patients (34 males and 38 females, mean age 77 years) 47% were nursing home residents. Pre-hospitalization antibiotic treatment was given to 91.4% for infections of the upper respiratory tract (45%) and urinary tract (45%). The most common antibiotics were cephalosporin (64%), penicillins (42%) and quinolones (28%). Sixty-four percent of the patients were treated with more than one antibiotic, 26% of patients received anti-acid therapy and 36% had been fed with a nasogastric tube. On admission, leukocytosis was found in 79% of patients, >20,000/mm³ in half of them; 60% were anemic, 60% had elevated erythrocyte sedimentation rate, and 78% had hypoalbuminemia. Treatment consisted of metronidazole (41%) or a combination of metronidazole and vancomycin (56%). Overall, 31% of patients recovered without complications, 29% died within 30 days of hospitalization, and 24% were re-hospitalized due to recurrence of PMC.

Conclusion: The most common antibiotics implicated in PMC are cephalosporin, penicillins and quinolones. The disease is associated with high mortality and recurrence rates.

Background: Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition associated with inflammatory bowel disease. PG[1] occurs rarely in IBD[2] patients and there are insufficient data on the clinical manifestations of this disease with IBD.

Objective: To determine the incidence, clinical manifestations and treatment of PG in patients with IBD and the connection to IBD, its activity and extent.

Methods: All patients hospitalized with IBD at a university hospital during a 20 year period were evaluated for the occurrence of PG.

Results: Of 986 patients hospitalized for IBD 6 suffered from PG (0.6% incidence). Their average age was 37 with equal sex distribution and equal distribution of Crohn’s disease and ulcerative colitis. PG appeared 6.5 years on average after diagnosis of IBD in all patients. The development of PG correlated with significant clinical exacerbation of IBD, the majority having active colitis at the onset of the PG. Extra-intestinal manifestations of IBD occurred in half the patients (sacroiliitis, peripheral arthritis and erythema nodosum). Pathergy was not elicited in any patients. Four patients had multiple skin lesions, frequently on the lower extremities. Diagnosis was made by skin biopsy in four patients. There was little correlation between amelioration of IBD and the skin lesions. Treatment consisted of high dose steroids and immunomodulatory drugs (cyclosporine, azathioprine and dapsone) in conjunction with topical treatment.

Conclusions: PG is a rare extra-intestinal manifestation of IBD that coincides with the exacerbation of the intestinal disease but does not always respond to treatment of the bowel disease.

Background: Acute myocardial infarction is rare in people under the age of 30.

Objective: To determine the clinical features and outcome in young patients presenting with AMI.

Methods: All patients aged 30 years and younger hospitalized with AMI during a period of 8 years (1993–2000) were evaluated for clinical features and outcome.

Results: Of the 3,758 patients with AMI, 15 were 30 years old or younger (0.4%). The mean age was 28 (range 21–30 years) and all were male. Eight had normal coronary arteries on angiogram; seven had obstructive coronary artery disease. Patients with OCA[1] had more classical risk factors for coronary disease. A complete diagnostic work-up was abnormal in four patients with NCA[2]: thrombophilia in two patients, spasm due to alcohol withdrawal and hyperthyroidism in one patient each. All patients presented with typical new-onset chest pain. None had a previous history of angina. All patients with OCA received reperfusion therapy as compared to one patient with NCA. Peak creatine phosphokinase in NCA and OCA was 504 ± 547 and 1,328 ± 440 respectively (P < 0.01). All patients with NCA had good left ventricular function on follow-up echocardiography, compared to only three in the OCA group (P = 0.02). There was one death due to cardiogenic shock in a patient with OCA. Follow-up of 4 ± 2 years demonstrated recurrent acute coronary syndromes in four of seven patients with OCA versus none in the NCA patients (P = 0.02).

Conclusions: AMI is rare in very young patients, and more than half have NCA. A thrombophilic tendency or spasm should be considered. Young patients with NCA have an excellent prognosis.

Diffuse idiopathic skeletal hyperostosis is often incorporated into osteoarthritis. Although DISH[1] often coexists with OA, patients affected by this disorder differ from patients with primary OA in several aspects: prevalence in the general population, gender distribution, anatomic site of primary involvement, magnitude and distribution in the spine and the peripheral joints. DISH is a distinct clinical entity. Its recognition as such should stimulate clinicians and researchers to focus on its pathogenesis, treatment and prevention.

Background: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel cystinuria is especially common among Libyan Jews who suffer from non-type I disease.

Objectives: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.

Methods: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.

Results: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients’ urinary pH. Eleven of the unaffected Libyan Jewish controls were found heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584+3 del AAGT mutation was not found in any of the Libyan Jewish controls.

Conclusion: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
 

Background: Lithium has been a part of the psychiatric pharmacopoeia for more than half a century. Its efficacy is marred by a narrow therapeutic index and significant toxicity.

Objectives: To increase physicians’ awareness of the various manifestations of lithium intoxication.

Methods: We reviewed the clinical data of cases of lithium poisoning occurring in a municipal hospital during a 10 year period.

Results: Eight patient records were located. The mortality rate was 12.5%. All patients were women and the mean age was 66.4 years. The most common symptoms were neurological. One illustrative case is described in detail with lithium serum levels showing the usual two-phase decline.

Conclusions: Lithium poisoning can present in many forms. Increased physician awareness and the early use of effective treatment, mainly hemodialysis, will prevent mortality and protracted morbidity associated with this condition.