Israel Medical Association Journal

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

Background: Pyogenic flexor tenosynovitis (PFT) is a common and severe hand infection. Patients who present early can be treated with intravenous antibiotics.

Objectives: To determine whether PFT caused by animal bites and treated with antibiotics leads to a different outcome than other disease etiologies due to the extensive soft tissue insult and different bacterial flora.

Methods: We conducted a retrospective cohort study of 43 consecutive patients who presented with PFT between 2013 and 2020. The 10 patients who presented with PFT following an animal bite were compared to those who presented with PFT caused by any other etiology.

Results: Patients who were bitten pursued medical attention sooner: 1.9 ± 1.4 days compared with 5.3 ± 4.7 days (P = 0.001). Despite the quicker presentation, patients from the study group received similar antibiotic types and duration as controls. All patients were initially treated with intravenous antibiotics under surveillance of a hand surgeon. One patient (10%) from the study group and four controls (12%) were treated surgically (P = 1). Average follow-up was 17 ± 16 days. At the end of follow-up, one (10%) patient from the study group and three (9%) controls sustained mild range of motion limitation and one (3%) patient from the control group had moderate limitations (P = 0.855).

Conclusions: Intravenous antibiotic treatment, combined with an intensive hand surgeon follow-up, is a viable option for the treatment of PFT caused by animal bites.

A 70-year-old male arrived at the emergency department (ED) with symptoms of fever, shivering, and sweating for 3 days. A dry cough started a week before admission. There were no other referring symptoms. The patient, a farmer by occupation, denied any animal bite or exposure, travel abroad, consumption of uncooked meat, or drink of unpasteurized milk products. In the ED, his vital signs showed hypotension with blood pressure of 70/40 mmHg, pyrexia of 39.4°C, and tachycardia of 100 beats per minute. On physical examination, the patient shivered. On auscultation, fast heart sounds were heard.

Background: Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared.

Objectives: To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy.

Methods: Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist.

Results: Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance.

Conclusions: Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.

Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.

Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.

Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere.

Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.

Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Objectives: To present two cases of subtrochanteric fractures related to bisphosphonate treatment and review of the current literature.

Conclusions: Despite the overall beneficial effect of bisphosphonates, further research is required to prevent this significant complication. 

Background: Hypovitaminosis D is common worldwide, even in sunny regions.

Objectives: To assess the prevalence and determinants of vitamin D deficiency in toddlers.

Methods: A cross-sectional prospective study was conducted in healthy Jewish children aged 1.5–6 years at five primary care pediatric clinics in the Jerusalem area during the period October 2009 to November 2010. Parents were interviewed regarding personal and demographic data and sun exposure. Blood samples were obtained for serum 25-hydroxyvitamin D [25-OHD] level. Vitamin D deficiency and insufficiency were defined as 25-OHD < 20 ng/ml and < 30 ng/ml, respectively.

Results: Of 247 children studied, 188 (76%) were ultra-Orthodox and 59 (24%) were Orthodox, traditional or secular. Mean (± SD) 25-OHD level was 25.7 ± 10 ng/ml. Only 73 children (29.6%) had sufficient 25-OHD levels, 104 (42.1%) had insufficiency, and 70 (28.3%) had 25-OHD deficiency. The difference between ultra-Orthodox and others was insignificant (25 ± 10 vs. 27.8 ± 10.5 ng/ml respectively, P = 0.062). Children aged 1.5–3 years had higher 25-OHD levels than those aged 3–6 years (28.6 ± 10.7 and 24 ± 9.2 ng/ml respectively, P < 0.001). Vitamin D deficiency was more common in winter (53%) and autumn (36%) than in summer (19%) and spring (16%). Toddlers attending long-day kindergartens had higher 25-OHD level than those staying at home or at short-day kindergartens (28.8 ± 11.5 and 24.7 ± 9.6 ng/ml respectively, P < 0.05).

Conclusions: A high prevalence of vitamin D deficiency was found in toddlers in our study, mainly in older children and in the winter and autumn. We recommend routine supplementation of vitamin D for children beyond the agear.

Background: Open neural tube defects are among the most common severely disabling birth defects. Secondary prevention by early diagnosis during pregnancy and abortion of affected fetuses lead to a marked reduction of NTD[1] incidence at birth. For primary prevention of these defects, in August 2000 the Israel Ministry of Health issued guidelines recommending a daily 0.4 mg folic acid supplement for all women in their childbearing years with special emphasis on the 3 months preceding conception and the first trimester of pregnancy.

Objectives: To compare the epidemiologic characteristics of NTD in Israel before and after the guidelines for folic acid supplementation.

Methods: A national registry of NTD was begun in 1999. Since the Ministry of Health published the recommendation for folic acid supplementation in mid-2000, the years 1999–2000 represent the status prior to the recommendation and the years 2002–2004 the status after.

Results: A marked decline in the rate of spina bifida was observed in the last 3 years (from 4.9 to 2.7 per 10,000 live births among Jews and 9.5 to 6.2 among Arabs and Druze). There was no apparent reduction for anencephaly.

Conclusions: Following the Ministry of Health guidelines on folic acid supplementation for women in the reproductive age, a marked reduction in the rates of NTD was observed. In light of this apparent success, continuous efforts should be made to increase the percentage of women taking the supplementation and, especially, to introduce folic acid fortification.

Background: Prone sleeping has been recognized as a risk factor for sudden infant death syndrome. Ten years ago, non-prone sleeping was recommended in many countries around the world including Israel. The rate of infants sleeping prone and the rate of parents' adherence with the recommendations have not been studied.

Objectives: To study infants' sleep position and parents’ adherence to recommendations, and to identify risk factors for prone sleeping following the campaign to prevent prone sleeping in the Israeli population.

Methods: We conducted a longitudinal telephone survey with the parents of 608 randomly selected 2 month old infants, repeated at 4 and 6 months.

Results: Non-prone sleeping decreased from 75% to 67% and 63% at 2, 4 and 6 months respectively. There was a significant relationship between prone positioning and the use of a home apnea monitor at 2 months (P = 0.038, odds ratio 1.37, 95% confidence interval 0.94–2.15). Other risk factors for prone sleeping were the level of religious practice, with ultra-Orthodox Jews having the highest prevalence (2 months: OR[1] 2.78, 95% CI[2] 1.75–4.55) and higher parity – especially in families with more than five children (P = 0.041).

Conclusions: The prone sleeping position is relatively high in Israel. Groups at high risk were closely associated with the level of religiousness and parity. Efforts to promote supine sleeping should be directed towards identifiable groups.

Background: The infant mortality rate is a health status indicator.

Objectives: To analyze the differences in infant mortality rates between Jews and Arabs in Israel between 1975 and 2000.

Methods: Data were used from the Central Bureau of Statistics and the Department of Mother, Child and Adolescent Health in the Ministry of Health.

Results: The IMR[1] in 2000 was 8.6 per 1,000 live births in the Israeli Arab population as compared to 4.0 in the Jewish population. Between 1970 and 2000 the IMR decreased by 78% among Moslems, 82% among Druze, and 88% among Christians, as compared to 79% in the Jewish population. In 2000, in the Arab population, 40% of all infant deaths were caused by congenital malformations and 29% by prematurity, compared to 23% and 53%, respectively, in the Jewish population. Between 1970 and 2000 the rate of congenital malformations declined in both the Arab and Jewish populations. In the 1970s the rate was 1.4 times higher in the Arab community than in the Jewish community, and in 2000 it was 3.7 times higher.

Conclusion: As in the Jewish population, the IMR in the Arab community has decreased over the years, although it is still much higher than that in the Jewish community. Much remains to be done to reduce the incidence of congenital malformations among Arabs, since this is the main cause of the high IMR in this population.