Diana Tasher

PFAPA syndrome: new clinical aspects disclosed

Background: The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data on the natural history of this syndrome. Objective: To describe the presentation, clinical course, doctors’ awareness, therapeutic response and long-term follow-up of children with PFAPA syndrome. Methods: Children with PFAPA syndrome referred over a 5-year period (from January 1999 to January 2004) were enrolled in the study. Data were gathered from medical records, parents’ interviews, physical examination and telephone calls. Results: 54 patients with PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain (65%) and a lower rate of aphthous stomatitis (39%) than those in previous reports. Four different patterns of disease evolution were identified, including the relatively common (n = 14, 26%) and newly described course of alternating remissions and relapses. The remissions lasted 8.5 months on average (range 4–36 months). Diagnosis was established by primary paediatricians in 30 of 54 (56%) patients. However, a substantial delay in diagnosis was apparent (mean 15 months). Episodes were curtailed by a much lower dose of prednisone or equivalent corticosteroid (mean 0.6 mg/kg/day, range 0.15–1.5 mg/kg/day) than reported previously. Tonsillectomy was successful in the prevention of recurrence of further episodes in all six patients who underwent the procedure. Conclusions: We describe several new characteristics of PFAPA syndrome in children, contributing to our knowledge of this relatively unrecognised but troublesome syndrome. Early diagnosis and appropriate treatment can markedly improve the quality of life of both patients and families.

Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes

Aim: To review our experience with colchicine for the prophylaxis of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis).

Natural history of food allergy in infants and children in Israel

BACKGROUND Knowledge about the natural history of food allergy, especially sesame, is scarce. OBJECTIVE To follow the natural history of food allergies in Israel, particularly of sesame allergy. METHODS The survey was conducted based on clinical records and a detailed questionnaire of children diagnosed as having food allergy. RESULTS We found 234 children with suspected food allergy. Testing detected 283 allergies in 180 patients (77%) with confirmed diagnosis. The most common allergies were to cows milk (n = 125), eggs (n = 71), sesame (n = 30), and soy (n = 23). Of those with milk allergy, 69% were IgE mediated (group 1) and 31% were non-IgE mediated (group 2). Group 1 was more likely to have an atopic background than was group 2 (P = .003), whereas group 2 was more likely to have resolution of the allergy (35 of 39 [90%] in group 2 compared with only 32 of 86 [37%] in group 1, P < .001). Allergy to soy was found in 23 children, of whom 87% manifested with gastrointestinal symptoms and 21 (91%) were also allergic to cows milk. In 19 children (83%), the allergy resolved. Thirty children had allergy to sesame, and 73% of them had an atopic background. The allergy resolved in only 9 of these patients (30%) at a mean age of 2.8 years. CONCLUSIONS The distribution of food allergens in Israel differs from that in other countries. Non-IgE-mediated food allergy and particularly milk and soy allergy were likely to resolve completely with time. Sesame allergy was 1 of the most frequent in this cohort, was usually IgE mediated, and tended to resolve in only a few patients.

Invasive Bacterial Infections in Relation to Influenza Outbreaks, 2006–2010

BACKGROUND We aimed to define the excess morbidity associated with bloodstream infections (BSIs), imposed by pandemic H1N1 influenza during 2009-2010 (pH1N1/2009-2010) and seasonal influenza. METHODS Eight hospitals, accounting for 33% of hospitalizations in Israel, provided data on BSI during 2006-2010. The age-specific incidence of BSI due to Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes was determined. BSI incidence rate ratios (IRRs) during seasonal and pH1N1 influenza seasons were assessed. RESULTS Regular influenza seasons were characterized by increased rates of S. pneumoniae BSI but with no increase in S. aureus and S. pyogenes BSI rates. The pH1N1/2009-2010 influenza outbreak was characterized by (1) higher rates of S. pneumoniae bacteremia among children but not among adults (IRRs for S. pneumoniae BSI among children aged 0-4 years during the summer and winter of 2009-2010 were 14.8 [95% confidence interval {CI}, 5-43.7] and 6.5 [95% CI, 3.6-11.8], compared with 2006-2009 summers and influenza-active winter weeks, respectively [P < .0001]), higher rates of S. aureus BSI in all age groups (IRRs during the summer and winter of 2009-2010 were 1.6 [95% CI, 1.4-1.9] and 1.5 [95% CI, 1.2-1.7], compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]), higher rates of S. pyogenes BSI during 2009-2010 influenza season (IRR 2.7 [95% CI, 1.6-4.6] and 3.3 [95% CI, 1.9-5.8] during the summer and winter of 2009-2010, compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]). CONCLUSIONS pH1N1 influenza seasons were characterized by marked increases in invasive S. aureus and S. pyogenes infections among children and adults, with the highest increase in S. pneumoniae BSI among children.

Novel mutations in RAG1/2 and ADA genes in Israeli patients presenting with T-B- SCID or Omenn syndrome

The relative frequency of the different forms of SCID may vary in different countries. The most frequent form in Israel is the autosomal-recessive T-B- SCID or Omenn syndrome while X-linked SCID is rare. We report our immunological and genetic analyses in multicentre study of patients presenting with either T-B- SCID or Omenn syndrome. Among 16 patients, we identified 7 novel mutations in 6 patients. In the RAG1 gene we detected two novel mutations: L454Q and 469 fs-4bpdel. In the RAG 2 gene: 3 novel mutations: D65Y, G157V, and E480X. One T-B- SCID patient was found to be a compound heterozygote for new mutations in the ADA gene: W264X and R235W. Prenatal diagnosis was performed in 8 families while others refused due to religious reasons. Identification of the new mutations expands our knowledge regarding the unique features of SCID phenotype in Israel and may help the families seeking for genetic counseling.

Laboratory Challenges in Response to Silent Introduction and Sustained Transmission of Wild Poliovirus Type 1 in Israel During 2013

Wild poliovirus type 1 (WPV1) introduction into southern Israel in early 2013 was detected by routine environmental surveillance. The virus was identified genetically as related to the South Asian (SOAS) R3A lineage endemic to Pakistan in 2012. Intensified, high-throughput environmental surveillance using advanced molecular methods played a critical role in documenting and locating sustained transmission throughout 2013 and early 2014 in the absence of any acute flaccid paralysis. It guided the public health responses, including stool-based surveillance and serosurveys, to determine the point prevalence in silent excretors and measured the effect of vaccination campaigns with inactivated polio vaccine and bivalent oral polio vaccine on stopping transmission.

The genetic basis of severe combined immunodeficiency and its variants

Severe combined immunodeficiency (SCID) syndromes are characterized by a block in T lymphocyte differentiation that is variably associated with abnormal development of other lymphocyte lineages (B and/or natural killer [NK] cells), leading to death early in life unless treated urgently by hematopoietic stem cell transplant. SCID comprises genotypically and phenotypically heterogeneous conditions, of which the genetic basis for approximately 85% of the underlying immunologic defects have been recently elucidated. A major obstacle in deciphering the pathogenesis of SCID syndromes is that different mutations in a single gene may give rise to distinct clinical conditions and that a similar clinical phenotype can result from mutations in different genes. Mutation analysis is now an important component of the complete evaluation of a patient with SCID since it has a dramatic impact on many aspects of this potentially life-threatening disease such as genetic counseling, prenatal diagnosis, modalities of treatment, and, eventually, prognosis. Dr Robert Good, one of the founders of modern immunology, described the SCID syndrome as “experiments of nature.” By understanding the cellular and genetic basis of these immunodeficiency diseases and, eventually, normal immunity, we optimize the “bedside to research laboratory and back again” approach to medicine.

Hypertonic Saline and Acute Wheezing in Preschool Children

BACKGROUND: Most acute wheezing episodes in preschool children are associated with rhinovirus. Rhinovirus decreases extracellular adenosine triphosphate levels, leading to airway surface liquid dehydration. This, along with submucosal edema, mucus plaques, and inflammation, causes failure of mucus clearance. These preschool children do not respond well to available treatments, even oral steroids. This calls for pro–mucus clearance and prohydration treatments such as hypertonic saline in wheezing preschool children. METHODS: Randomized, controlled, double-blind study. Forty-one children (mean age 31.9 ± 17.4 months, range 1–6 years) presented with wheezing to the emergency department were randomized after 1 albuterol inhalation to receive either 4 mL of hypertonic saline 5% (HS) (n = 16) or 4 mL of normal saline (NS) (n = 25), both with 0.5 mL albuterol, twice every 20 minutes in the emergency department and 4 times a day thereafter if hospitalized. The primary outcome measured was length of stay (LOS) and the secondary outcomes were admission rate (AR) and clinical severity score. RESULTS: The LOS was significantly shorter in the HS than in the NS group: median 2 days (range 0–6) versus 3 days (range 0–5) days (P = .027). The AR was significantly lower in the HS than the NS group: 62.2% versus 92%. Clinical severity score improved significantly in both groups but did not reach significance between them. CONCLUSIONS: Using HS inhalations significantly shortens LOS and lowers AR in preschool children presenting with an acute wheezing episode to the emergency department.

Herpes zoster in a partially vaccinated pediatric population in central Israel.

Background: This study was performed during an era of partial vaccination with varicella vaccine in Israel to characterize ambulatory pediatric herpes zoster (HZ) cases in a population with partial varicella vaccination coverage. Methods: Data were collected from computerized databases of a population of 114,000 children. Records of children aged 0–18 years, diagnosed with HZ during 2006 to 2008 were reviewed by pediatric infectious diseases experts. Telephone interviews were done with a sample of the parents to get further clinical details. Results: Of 692 medical records reviewed, 450 cases were approved for analysis, and 77 interviews were conducted. Incidence of HZ was 130 of 100,000 person life-years. Peak incidence was detected in children aged 9–11 years (222/100,000 person life-years). Pain and fever accompanied 52% and 13% of episodes, respectively. Higher risk for HZ was found in children who had varicella during their first year of life (relative risk and 95% confidence interval: 13.5[9.6–18.8]; P < 0.001), and in children who had varicella during the second year of life (relative risk = 2 [1.5–2.6]; P < 0.001). Vaccination was found to be protective against HZ (relative risk = 0.42 [0.33–0.55]; P < 0.001). Conclusions: The epidemiology of HZ seems to be changing in a population with partial varicella vaccination rate. Our results may suggest that children who contracted chicken pox in their first year of life may benefit from varicella vaccination.

Neonatal herpes simplex virus infections in Israel.

Background: The incidence and the clinical characteristics of neonatal herpes simplex virus (NHSV) infection in Israel are unknown. Methods: We reviewed the medical records of NHSV cases who were born between January 2001 and December 2007 in 5 medical centers located in central Israel. Cases were identified using International Classification of Diseases, 9th revision codes. In addition, parents of survivors were interviewed by telephone. Results: In the 8-year study period, 22 cases of NHSV were identified (an incidence rate of 8.4 per 100,000 live births). Most patients (77.2%, 17 cases) manifested as skin, eye and/or mouth infection, 13.6% (3 cases) as localized central nervous system disease and 9.1% (2 cases) as disseminated disease. Most (76.4%) herpes viruses typed in our series were HSV-1. None of the mothers had documented intrapartum visible genital HSV lesions or a previous history of genital herpes. Ritual circumcision was the source of HSV-1 transmission in 7 infants (31.8% of cases). Conclusions: The incidence of NHSV infection in Israel was found to be similar to the lower part of the scale reported in the United States, however higher than the incidence reported in Canada or in Europe. Similar to more recent reports, our series demonstrates the shift toward the predominance of HSV-1 in NHSV infection. In addition, none of the mothers in our series had a previous history of genital herpes. This study emphasizes the need for awareness of HSV infection in Israeli neonates.