Supplementation with probiotics in the first 6 months of life did not protect against eczema and allergy in at-risk Asian infants: a 5-year follow-up.

BACKGROUND: Healthy gut microflora is essential for oral tolerance and immunity. A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature. OBJECTIVE: In this follow-up study, we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes. METHODS: We analyzed the charts and electronic databases of the PROMPT (Probiotics in Milk for the Prevention of Atopy Trial) study cohort. This cohort consisted of 253 infants at risk for allergy who were administered cow's milk supplemented with or without probiotics from the first day of life to the age of 6 months. The cohort was then followed up until the children were 5 years old and clinical outcomes were assessed. RESULTS: Of the 253 children recruited into the study, 220 (87%) completed the follow-up. At the age of 5 years, there were no significant differences between the groups in the proportion of children who had developed any asthma, allergic rhinitis, eczema, food allergy and sensitization to inhalant allergens. Similar growth rates were observed in both groups. CONCLUSIONS: The supplementation of probiotics in early childhood did not play a role in the prevention of allergic diseases. Clinical/Key Message: Early-life supplementation with probiotics did not change allergic outcomes at 5 years of age.

Anaphylaxis to cow's milk formula containing short-chain galacto-oligosaccharide.

BACKGROUND: On the basis of the proven prebiotic effects of oligosaccharides in cow's milk formula (CMF) in infants, CMFs are supplemented with oligosaccharides. OBJECTIVE: We present a series of 5 cases of cow's milk-tolerant but atopic patients with a history of respiratory allergies. All had anaphylaxis after the ingestion of CMF supplemented with short-chain galacto-oligosaccharide (scGOS). The allergen trigger was investigated. METHODS: Clinical histories were collated. Skin prick tests (SPTs) and basophil activation tests (BATs) were carried out with the eliciting CMF that triggered anaphylaxis, with or without supplemented prebiotics (scGOS) and with scGOS fractions containing oligosaccharides of different chain lengths. RESULTS: The median age of presentation was 6 years (range, 5-38 years). Anaphylaxis occurred within 30 minutes of the first known exposure to CMF supplemented with prebiotics in all patients. Only 1 patient was subjected to oral challenge, which resulted in an anaphylactic reaction. All patients demonstrated IgE sensitization through SPTs and BATs to scGOS and fractions of scGOS containing 3 sugar units or greater but not to cow's milk or long-chain fructo-oligosaccharide. Eight child control subjects tolerant to regular ingestion of scGOS-supplemented CMF and 1 adult volunteer were found to have negative results to scGOS through SPTs and BATs. In addition, in vitro BATs with donor basophils sensitized with sera from 2 of the 3 reported cases showed reactions to scGOS. The scGOS-induced basophil activation was inhibited in the presence of wortmannin, a phosphatidylinositol 3-kinase inhibitor. CONCLUSIONS: This study describes an unusual form of IgE-mediated anaphylaxis triggered by low-molecular-weight oligosaccharides in scGOS. The primary sensitizer for this phenomenon requires further investigation.

Etoricoxib: a safe alternative for NSAID intolerance in Asian patients.

BACKGROUND: NSAID intolerance is not uncommon. Etoricoxib, a cox-2 inhibitor NSAID, has been shown to be a safe alternative in these patients. This study aims to determine the rate of NSAID intolerant patients who are able to tolerate etoricoxib without adverse reactions. METHODS: This study analyzed charts and electronic databases of all patients referred to the allergy clinics of the National University Hospital and Gleneagles Hospital in Singapore from 2006-2011 for oral provocation tests to etoricoxib (cumulative dose of 120 mg), on the background of NSAID intolerance. Demographics, atopic comorbidities, history of chronic urticaria, inciting NSAID, onset and type of reaction, and provocation test outcomes were obtained. RESULTS: A total of 74 patients (mean age 37; range: 16-72 years) underwent provocation tests to etoricoxib. Of these, 59% were female. Majority were Chinese (69%), followed by Malay (12%), Caucasian (8%), Indian (5%) and various other races (6%). Forty-six percent of the study population had atopic comorbidities, and 4% had concomitant chronic urticaria. Eighty percent of patients had a history of intolerance to 1 NSAID, while the rest (20%) had intolerance to multiple NSAIDS. Forty-one percent of patients had concomitant acetaminophen intolerance. Some of the patients had multiple symptoms on presentation, the most common of which were periorbital and facial edema (90%), breathing difficulties (26%) and urticaria (25%), with the onset of reaction occurring mostly within 30 minutes to 1 hour. Etoricoxib was tolerated in 95% of the patients. Subjects who reacted to the challenge all had mild reactions which resolved with antihistamines. CONCLUSIONS: Etoricoxib is a safe alternative in NSAID intolerant patients. Nevertheless, it is advised that patients should undergo provocation tests to confirm tolerance.

Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/ß (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

Features of childhood atopic dermatitis.

Eczema or atopic dermatitis (AD) is the most common skin disease in children, and recent data derived from several studies showed that the prevalence of AD is still increasing in most Asian countries. The role of allergic reactions in AD is still a matter of debate. In some children allergy is not involved, while in others allergic reactions can trigger and maintain the skin lesions. Therefore, AD is now considered as a group of skin diseases with as a common feature the existence of a chronic skin inflammation. The underlying mechanisms of AD are not uniform, but differ from patient to patient, and also differ in one patient in time, suggesting the existence of different subtypes of AD, in a complex interplay. From different studies it is now suggested that at least 4 different players are involved in AD. These 4 players are: congenital skin barrier defects, allergy, autoimmunity (i.e. the production of autoantibodies against skin cells), and microbial agent colonization, especially colonization with bacteria, mainly Staphylococcus aureus. Much more needs to be discovered on the mechanisms of AD and other "players" might be discovered soon, as the current "4-player-model" cannot explain all features of AD. Treatment of AD might change in the near future. Today's cornerstones of treatment are still moisturizers (from a young age to prevent further skin barrier dysfunctions and allergic sensitization), local corticosteroids, and antiseptics, but new future therapeutic approaches become very likely.

Necrotising enterocolitis in a newborn infant treated with octreotide for chylous effusion: is octreotide safe?

Octreotide is a somatostatin analogue used for treating congenital chylothorax and congenital hyperinsulinism in infants. By increasing splanchnic arteriolar resistance and decreasing gastrointestinal blood flow, octreotide indirectly reduces lymphatic flow in chylous effusions.Splanchnic ischaemia following octreotide predisposes infants to necrotising enterocolitis (NEC). Although NEC occurrence in infants treated with octreotide for hyperinsulinaemic hypoglycaemia has been reported widely, its incidence in infants with chylothroax is low. We describe a case of congenital chylothorax in a preterm infant who had poor response to thoracentesis. Although octreotide initiation lead to resolution of chylothorax, he developed NEC. Cessation of octreotide and medical management resulted in rapid resolution of NEC. Since octreotide is generally used as the first-line treatment for chylous effusion, the risk of NEC should be considered, especially when the dosage is increased. Infants on octreotide should be closely observed for early signs and symptoms of NEC to avert surgical emergency.

Clinical phenotype and allergen sensitization in the first 2 years as predictors of atopic disorders at age 5 years.

INTRODUCTION: From a birth cohort of at-risk Asian infants, we prospectively investigated the role of early onset allergen sensitization and clinical phenotypes as risk factors for atopic disorders at the age of 5 years. METHODS AND MATERIALS: The study recruited 253 families with a history of allergic disease in a first degree relative from an antenatal clinic in Singapore. The children were followed prospectively to assess clinical outcomes and skin prick test was performed at 2 and 5 years of age. RESULTS: Allergen sensitization (food and/or house dust mites) alone at 2 years of age was not associated with increased risk of wheeze and eczema at 5 years. However, the clinical phenotype (eczema and wheeze) with or without the presence of concomitant allergen sensitization at 2 years increased this risk. For eczema, eczema alone at year 2 increased the risk of eczema at year 5 (adjOR = 7.1; 95 % CI: 1.8-27.8) and this was further increased by the presence of allergen sensitization (adjOR = 25.4; 95 % CI: 4.7-138.5) and the concomitant presence of both wheeze and allergen sensitization (adjOR = 64.9; 95 % CI: 4.7-900.0). For wheeze, wheeze alone at 2 years (adjOR = 4.5; 95 % CI: 1.4 -14.8), and wheeze with concomitant allergen sensitization and eczema (adjOR = 13.9; 95 % CI: 1.2-168.5) increased the risk of wheeze at 5 years. The exception was rhinitis, where allergen sensitization alone at 2 years (adjOR = 5.6; 95 % CI: 1.1-29.2) increased the risk of rhinitis at 5 years. Early onset of eczema at 2 years also increased the risk of rhinitis (adjOR = 6.8; 95 % CI: 2.0-23.1). CONCLUSION: In this Asian birth cohort, the clinical phenotype (eczema and wheeze) with or without concomitant allergen sensitization in the first 2 years of life were strong predictors of atopic disorders at 5 years.

Clinical characteristics and outcomes of patients undergoing drug provocation tests (DPTs).

INTRODUCTION: Patients who have an adverse drug reaction are frequently labelled drug allergic without undergoing proper evaluation and confirmatory testing. These drug allergy labels may be inaccurate, leading to unnecessary lifelong avoidance. The aim of this study was to review the patients that underwent drug provocation tests (DPTs) in our centre and examine the usefulness of DPTs in confirming or rejecting a diagnosis of drug hypersensitivity. MATERIALS AND METHODS: The study design was a retrospective chart review of all adult patients who underwent drug provocation in the allergy unit at the National University Hospital, Singapore, for single or multiple suspected drug allergies from the period January 2009 to June 2011. RESULTS: Eighty-seven patients underwent 123 DPTs (median age 41; interquartile range 28 to 50). Twenty-one patients underwent multiple DPTs. The most common culprit drugs reported were antibiotics (43.9%) of which beta-lactams were implicated in 75.9% of the cases. This was followed by non-steroidal anti-inflammatory drugs (NSAIDS) in 15.4%, paracetamol in 7.3% and both NSAIDs and paracetamol in 3.3%. Rash was the most commonly reported symptom (41.5%), followed by angioedema (32.5%), anaphylaxis (9.8%), and other symptoms including respiratory (2.4%), gastrointestinal (0.8%) and others (13.0%). The majority of DPTs were performed to antibiotics (43.9%), NSAIDs (19.5%) and paracetamol (6.5%). DPTs were negative in 93.5% of subjects and positive in 6.5%. Of the 8 positive DPTs, none had a serious reaction, with 5 patients requiring rescue therapy, which comprised solely of oral antihistamines. CONCLUSION: Suspected drug hypersensitivity is common but true drug allergy is rare. DPTs remain the gold standard and should be included as part of an investigative protocol. DPTs are a safe and valuable diagnostic tool in the hands of the experienced clinician.

Gianotti-Crosti syndrome: case report of a pruritic acral exanthema in a child.

Gianotti-Crosti syndrome (GCS) is a sporadic dermatosis affecting mainly children. It is characterized by multiple, confluent, monomorphic and pruritic pink to red-brown papules or papulovesicles, distributed symmetrically on the face, extensor surfaces of the extremities and buttocks, commonly sparing the trunk, palms and soles. This can be preceded by a viral infection, and may be accompanied by fever, hepatosplenomegaly, or lymphadenopathy. Personal and family history of atopy appears to be a risk factor in the subsequent development of GCS, thus frequently diagnosed as atopic dermatitis. We report a case of a 4-year-old boy from our institution with generalized, pruritic, papulovesicular rashes on the face and extremities for one month. He was diagnosed to have atopic dermatitis and treated as such, before presentation to our institution. As the signs and symptoms in GCS are similar to atopic dermatitis, we suggest that this diagnosis be considered when presented with a similar case.

House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old.

BACKGROUND: Identifying toddlers at increased risk of developing persistent wheeze provides an opportunity for risk-reducing interventions. House dust mite (HDM) allergen sensitization might identify this group of high-risk children. OBJECTIVE: We examined whether a positive skin prick test (SPT) to at least 1 of the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze at age 8 to 14 years old. METHODS: A cohort of 78 children, who had wheezing episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were enrolled. SPT results were obtained from the National University Hospital database. Four to 9 years later, the children, currently between 8 to 14 years old, were re-assessed for persistence of asthma symptoms and other atopic disorders via a telephone interview. A validated questionnaire on current wheezing and asthma, developed by the International Study of Asthma and Allergies in Childhood, was used. Fisher's exact test was used to evaluate the association between persistence of asthma and a positive SPT. RESULTS: Of the 78 children who participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative children had persistence of asthma symptoms. There is a significant association between a positive SPT during the preschool years, and persistence of asthma (p = 0.0314 [<0.05]). CONCLUSION: HDM sensitization at ages 2 to 5 years old in wheezing children predicts persistence of asthma after 4 to 9 years. This in turn may have benefits for management of asthma in this high-risk group.