Lessons from the clinical course of IgE-mediated cow milk allergy in Israel.

Cow milk and milk products are the most common food products consumed in Israel; rates of allergy to cow milk exceed those of peanuts in infants and children. The aim of the present study was to evaluate retrospectively the clinical features and natural course of immunoglobulin (Ig) E-mediated cow milk allergy (CMA) in Israel. Data of children diagnosed with CMA from 1995 to 2003, were collected regarding age at first and most recent reactions, symptoms and signs, family history of atopy, other allergic diseases, emergency department visits, hospitalizations, and treatment. Patients with transient CMA were compared to those with persistent CMA (> or =3 yr old). The study group consisted of 105 patients, 43 with transient CMA (age range: 0.48-11 yr). The remaining 62 patients (age range: 3-16.5 yr) did not achieve tolerance to cow milk during the follow-up period. No differences were found between the groups in mean age and symptoms and signs at the first allergic reaction and family history of atopy. Patients with persistent CMA had a higher rate of asthma than patients with transient CMA (61.2% vs. 18.6%, p < 0.001). Fifty patients with persistent CMA had 137 subsequent allergic reactions after diagnosis, 25% of the reactions were due to oral milk challenge at the clinic and 75% due to accidental exposure, of which 13% required an emergency department visit and 8%, hospitalization. Only 19% of the reactions were treated with epinephrine injection. In conclusion, in our experience, less than half of the children diagnosed with IgE-mediated CMA during 9 yr, outgrew it. The patients with persistent CMA have a higher prevalence of asthma compared with the general population or to children with transient CMA. The high number of recurrent allergic reactions due to accidental exposure and the low rate of epinephrine usage in these patients point to a need for better education of patients and their families.

Eyelash length in children and adolescents with allergic diseases.

Long eyelashes may be congenital, acquired in association with certain systemic diseases, or drug induced. In the past, long eyelashes were considered an external sign found in children with allergic diseases. However, this claim has never been examined in a controlled study. We compared the eyelash lengths of allergic children and adolescents with perennial allergic rhinitis, with or without bronchial asthma and atopic dermatitis (n = 60) to those of age- and sex-matched nonallergic controls (n = 80). The eyelashes of the allergic patients were found to be significantly longer than those of the controls: 9.43 +/- 1.39 mm versus 8.45 +/- 1.30 mm (p < 0.001). Eyelash length did not differ between patients with allergic rhinitis only (n = 31; 9.65 +/- 1.43 mm) and patients with allergic rhinitis and other allergic diseases (n = 29; 9.19 +/- 1.31 mm) (p = 0.196). These results indicate that children and adolescents with allergic diseases have longer eyelashes compared to nonatopic controls and that long eyelashes may be a part of the phenotype of the allergic patient.

Chronic urticaria: association with thyroid autoimmunity.

BACKGROUND: Though autoimmune phenomena have been regularly associated with chronic urticaria in adults, data in children are sparse. AIM: To describe our experience with children and adolescents with chronic urticaria and autoimmunity. METHODS AND RESULTS: Of 187 patients referred for evaluation of chronic urticaria during a 7.5 year period, eight (4.3%), all females aged 7-17 years, had increased levels of antithyroid antibody, either antithyroid peroxidase antibody (n = 4, >75 IU/ml), antithyroglobulin antibody (n = 2, >150 IU/ml), or both (n = 2). The duration of urticaria was four months to seven years. Five patients were euthyroid, one of whom was found to have increased antithyroid antibody levels five years after onset of the urticaria. One patient was diagnosed with Hashimoto thyroiditis three years before the urticaria, and was receiving treatment with thyroxine. Two other hypothyroid patients were diagnosed during the initial work up for urticaria (thyroxine 9.2 pmol/l, thyroid stimulating hormone (TSH) 40.2 mIU/l) and five years after onset of the urticaria (thyroxine 14 pmol/l, TSH 10.3 mIU/l). Both were treated with thyroxine but neither had remission of the urticaria. Five patients had a low positive titre of antinuclear antibodies. CONCLUSION: Children with chronic urticaria should be screened periodically for thyroxine, TSH, and antithyroid antibodies, as thyroid autoimmunity and hypothyroidism may appear several years after onset of the urticaria.

Epidemiological trends of pediatric emergency referrals in Israel.

BACKGROUND: In the last decade pediatric emergency medicine in Israel advanced to a stage of independent emergency pediatric departments. At the same time, injuries and childhood, trauma--a global health problem--became the main cause of mortality and emergency referrals in children over the age of one year. OBJECTIVE: To determine the extent of pediatric referrals to emergency departments and the rate of pediatric trauma referrals in Israel. METHODS: The records from EDs of Israel's 24 public hospitals for a 6 year period (1994-99) were collected. The records based on computerized ED records were used to identify the basic demographics of pediatric ED referrals. Routine data for all pediatric patients were collected from pediatric and general EDs. This study is an analysis of the accumulated anonymous ED databases. RESULTS: Pediatric referrals to EDs accounted for 2,907,912 patients, 37% of them due to trauma. The mean hospitalization rate was 21%. No significant changes were observed during the 6 years in the rate of pediatric ED referrals and in the ED hospitalization rate of children. There is a constant trend of increase in trauma referrals of children. CONCLUSIONS: The ED is a major site for the delivery of healthcare to children in Israel. One of every four children in the community is referred every year to an ED, and more than one-third of those referrals are due to trauma.

Clinical information system based on the medical smart card.

BACKGROUND: Over the last 5 years Israel has implemented a nationwide health insurance plan covering the entire population of the country. We have developed a clinical information system based on electronic-chip health care medical smart cards. Health care cards are used in several European countries and chip smart cards have been successful in many sectors. Our project involves the community use of the MSC, thereby enabling health care professionals to skillfully employ card systems in the health care sector. This system can easily arrange electronic medical charts in clinics, facilitating the confidential sharing of personal health databases among health professionals. OBJECTIVES: To develop an MSC applicable for daily use in the community and hospital system. RESULTS AND CONCLUSIONS: The MSC project, currently underway in Israel and the USA, will aid in determining the costs, benefits and feasibility of the MSC. Successful implementation of the MSC in chosen clinics will promote a nationwide willingness to adopt this promising technology.

Familial Mediterranean fever: effects of genotype and ethnicity on inflammatory attacks and amyloidosis.

OBJECTIVE: The gene causing familial Mediterranean fever (FMF)-an autosomal recessive disease characterized by recurrent short episodes of fever associated most commonly with peritonitis, pleuritis, and arthritis-has recently been found and several mutations identified. The most severe complication of the disease is amyloidosis, which can lead to renal failure. The aim of this study was to investigate the role of genetic versus nongenetic factors on the phenotype as well as on the development of amyloidosis in FMF in a large and heterogeneous group of patients. METHODOLOGY: We studied 382 patients from 4 ethnic origins living in different environments: North African Jews, other Jews, Turks, Armenians living in the United States, and Armenians from Yerevan, Armenia. Information regarding amyloidosis was available for 371 patients. We examined the association between the mutation M694V and the development of amyloidosis, and we also compared the clinical characteristics of the inflammatory attacks in patients from different ethnic origins, while controlling for the type of mutation. RESULTS: A significant association was found between amyloidosis and the most common mutation in exon 10 of the FMF gene (MEFV), M694V (for M694V homozygotes, relative risk = 1.77; 95% CI = 1.16-2.71). Amyloidosis was present in 44 of 171 homozygous FMF patients (25.7%), in 22 of 143 compound heterozygous FMF patients (15.4%), and in 7 of 57 patients carrying other mutations (12.3%). In homozygotes for M694V who had not been treated with colchicine before 20 years of age, the risk of amyloidosis developing before this age was 61.0%. In our series, there were no cases of amyloidosis in 16 patients carrying the common mutation E148Q. We found that the type and severity of the FMF inflammatory symptoms were associated with both the genotype and the country of residence of the patient. CONCLUSIONS: In the light of the high frequency of amyloidosis in homozygotes for the mutation M694V, colchicine treatment should be given to this group irrespective of the severity of the inflammatory attacks to prevent the development of amyloidosis. Our findings also suggest that factors other than genotype, such as environment or genes other than MEFV, play a role in the determination of the severity of the inflammatory attacks in FMF. amyloidosis, specific mutation, phenotype-genotype correlation, ethnicity.

The prevalence of specific IgE antibodies to natural rubber latex in healthcare workers in Israel.

BACKGROUND: According to studies from different countries, the prevalence of natural rubber latex sensitization in healthcare workers ranges from 2.9 to 17%. OBJECTIVE: To estimate the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. METHODS: Three hundred healthcare workers, mostly from a major pediatric tertiary care facility, and 15 non-healthcare workers completed a questionnaire on signs and symptoms of NRL allergy and other respiratory and food allergies. NRL-specific IgE antibodies were assayed with the DPC AlaSTAT-ELISA method. RESULTS: Seventy of the 300 workers (23.3%) reported symptoms of NRL allergy: hand eczema and pruritus in 63, upper respiratory tract and ocular symptoms in 10, shortness of breath in 2, and generalized rash in 6. None had anaphylaxis due to latex exposure. There was a significant correlation of symptoms of NRL allergy with atopy and job category (nurses, laboratory technicians, nurse assistants and dental medicine workers), but not with gender, age, or years of employment. The in vitro tests for specific IgE antibodies against NRL were positive (> or = 0.70 IU/ml) in five workers (1.66%). CONCLUSIONS: This is the first study of the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. Our 1.66% sensitization rate is much lower than that reported for healthcare workers in other countries. This difference may be due to our inclusion of a study population with a relatively low exposure to latex gloves (pediatricians compared to surgeons). Further studies are needed in this and other high risk populations in Israel.

Seroprevalence of pertussis antibodies among adolescents in Israel.

BACKGROUND: There is an increasing number of reports of pertussis among older children and adults. The development and licensure of an acellular pertussis vaccine offer the possibility of adult vaccination against the disease. Information on immunity to pertussis in this age group is needed before any vaccination policy can be considered. OBJECTIVES: To study the seroepidemiology of pertussis antibodies in a random sample of adolescents. METHODS: Serum IgG antibodies to whole-cell lysate of Bordetella pertussis were measured by enzyme-linked immunosorbent assay in sera of 533 Israeli military recruits aged 17-18 years. Epidemiologic variables were collected by a questionnaire and analyzed for correlation with pertussis antibodies. RESULTS: Of the sera tested 58.6% were positive for pertussis IgG antibodies, while 35.4% were negative and 6% were borderline. The seropositivity rate was significantly higher among females and non-smokers than among males and smokers. Serum samples of subjects found negative to Bordetella pertussis on recruitment were tested again, using the same ELISA assay, 2-3 years later. Seroconversion during the 3 year military service was detected in 12.5% of 40 subjects. Using the pertussis toxin as the antigen in a subsample of 160 sera, the seroprevalence was lower than that detected by the whole-cell lysate on the same sera (45% vs. 58%). CONCLUSIONS: A significant part of the adolescent population in Israel has low titer of serum IgG antibodies to the multiple antigens of B. pertussis. The relatively low concentration of anti-pertussis antibodies, together with the serological evidence of exposure to the disease indicates that booster immunization with the acellular pertussis vaccine of military recruits should be considered after more information on the incidence of clinical cases of pertussis will be available.

Immunity to varicella zoster virus in young Israeli adults.

BACKGROUND: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only. OBJECTIVES: To determine the rate of immunity to VZV in young Israeli adults. METHODS: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens. RESULTS: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant. CONCLUSION: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

Herpes simplex-associated erythema multiforme (HAEM): a clinical therapeutic dilemma.

Erythema multiforme of the mouth is an acute vesiculo-ulcerative lesion, which presents a diagnostic and therapeutic challenge to the clinician. Herpes simplex is described as the most frequent cause of this disease. Controversy exists in the literature as to the definition of oral erythema multiforme and the role of systemic corticosteroids in its treatment. Recent treatment protocols advocate the use of systemic acyclovir, especially in cases triggered by the herpes simplex virus. Two cases of successful treatment of oral erythema multiforme with systemic corticosteroids after acyclovir treatment had failed are presented.

Cerebrospinal fluid leukocyte aggregation in meningitis.

OBJECTIVE: To evaluate whether the difference in aggregation of cerebrospinal fluid cells from patients with bacterial, viral, aseptic and partially treated meningitis can be used for diagnostic purposes. METHODS: Cerebrospinal fluid samples of 100 patients with meningitis (15 bacterial, 13 partially treated, 10 viral and 62 aseptic) were compared on the basis of the predefined leukocyte aggregation score (LAS). RESULTS: Mean LAS was 56% in the bacterial meningitis group (range, 15 to 90%), 5.8% in the partially treated meningitis group (range, 0 to 27%), 2% in the proven viral meningitis group (range, 0 to 5%) and 2% in the aseptic meningitis group (range, 0 to 15%). All patients with bacterial meningitis had a LAS of > 15%, whereas all those with viral or aseptic meningitis had a score of < 15%. Although most patients with partially treated meningitis had a low LAS, several had higher scores, which may indicate bacterial infection. There was no statistical correlation between number of cells, type of cells (mononuclear or polymorphonuclear) or cerebrospinal fluid protein and glucose concentration and degree of leukocyte aggregation for the different groups. CONCLUSION: Measurement of the LAS may contribute to the immediate differential diagnosis of bacterial or viral meningitis, especially in patients with very high pleocytosis, as sometimes seen in enteroviral meningitis. It may also serve as a guide for the likelihood of bacterial infection in cases of partially treated meningitis. Additional studies are needed to confirm these observations.

Congenital Wells syndrome.

We describe a girl with eosinophilic cellulitis (Wells syndrome) in whom the disease appeared immediately after birth with subcutaneous nodules on the scalp and trunk, followed by the characteristic skin swelling and erythema at the age of 6 months. The lesions disappeared after a few weeks, but recurred several times. The mother had consumed large quantities of medications during the pregnancy, including iron, vitamins, and "natural remedies." Based on time of onset, this may be regarded as a unique case of congenital Wells syndrome. Its relation to the medications taken by the mother remains speculative. Subcutaneous nodules may be the presenting sign of Wells syndrome in children.

Immune deficiency in glycogen storage disease type 1B.

Patients with glycogen storage disease type 1B present the clinical features of glycogen storage disease type 1A. In addition, they are susceptible to recurrent bacterial infection and have recurrent oral ulcers and occasionally Crohn's-like disease. There features are due to immune dysfunction caused by a combination of neutropenia and impaired phagocytic functions.

Myopia in neurofibromatosis type 1.

We studied the prevalence of myopia in 17-year-old Israeli military recruits with neurofibromatosis type 1 (NF1). Twenty-four percent of the youngsters with neurofibromatosis had myopia, compared to 19% of the controls; this difference was statistically significant (P < 0.03). The recruits with NF1 had a slightly lower IQ, fewer years of education, and lower height and weight than the controls. Thus, these factors, which have been reported to be associated with myopia, did not significantly influence the high prevalence of myopia in the neurofibromatosis subjects. A high prevalence of myopia seems to be an additional feature of NF1.