Early introduction oral immunotherapy for IgE-mediated cow's milk allergy: A follow-up study confirms this approach as safe and appealing to parents.

INTRODUCTION: Early introduction oral immunotherapy (E-OIT) in the first year of life can be a safe treatment for infants with cow's milk allergy (CMA). Once the protocol is completed, doubts remain whether children achieve tolerance or remain desensitized. According to current guidelines, this is determined by an avoidance period followed by a re-exposure to the food allergen during an in-hospital oral food challenge (OFC). In real life, this approach can be complicated, time-consuming, and anxiety-provoking for parents. We assessed the long-term safety of E-OIT for CMA in a cohort of children who switched to an unrestricted diet without testing the achievement of tolerance at the end of the OIT protocol. MATERIALS AND METHODS: We performed a descriptive analysis of the clinical follow-up of a cohort of children diagnosed with IgE-mediated CMA and undergoing E-OIT protocol in their first year of life. In a previous publication, the same cohort of patients had been studied to assess the feasibility of E-OIT for CMA. In the present study, we reported the results of a telephone survey, carried out through a questionnaire to their families enquiring about milk consumption and other ongoing atopic conditions of children. RESULTS: After an average of 4 years from the start of E-OIT, 62/73 patients (85% of the historical cohort) participated in the survey. Among them, all 56 patients who had previously successfully completed the protocol reported an unrestricted cow's milk intake. Ninety-three percent of these children did not experience any further allergic reactions, while the remaining 7% described only mild and transitory reactions until the 6-month period after the end of the protocol. CONCLUSIONS: This study confirmed the long-term safety of E-OIT for CMA and challenged the paradigm of the need for allergen food withdrawal to discern between desensitization and tolerance. It could be a starting point for planning future trials on this issue.

Anaphylaxis in atypical cold urticaria: case report and review of literature.

BACKGROUND: Cold-induced urticaria is a kind of physical urticaria characterized by the appearance of wheals after exposure to cold. The atypical form is a rare sub-type characterized by appearance of hives even in areas not directly exposed to the cold and by a negative cold stimulation test. Its diagnosis is often challenging because of the lack of specific tests and it is usually based on the patient's clinical history. Hypotension due to generalized exposure to the cold is described both in the typical and the atypical forms. CASE PRESENTATION: We describe a 9-year-old boy who, at the beginning of the summer after the first swim in the sea, developed generalized urticaria, dyspnea, conjunctival hyperemia, blurred vision and loss of strength. The child was treated with intramuscular steroid and intravenous antihistamine, and the symptoms quickly resolved. Insect bite, contact with fish and drug ingestion were denied, and no unusual food had been eaten before the swim. A tentative diagnosis was made of either aquagenic urticaria or cold urticaria, but the specific tests were negative. Although the cause was unknown, prophylactic treatment with antihistamines was prescribed but in spite of this, wheals developed all over the body, after every swim in the sea. The child then came to our attention and relying on clinical history a diagnosis of atypical cold urticaria was made: development of hives even in areas not directly exposed to cold and a negative response to the cold stimulation test, are the characteristic features of this rare form of cold urticaria. CONCLUSION: Atypical cold urticaria should be suspected in all cases of anaphylaxis related to cold exposure (i.e. contact with water) with a negative cold stimulation test.

Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy.

BACKGROUND: The study describes the demographic features, culprit foods, clinical features and outcomes for children presenting with acute fish and/or shellfish food protein-induced enterocolitis syndrome (FPIES) in four Italian paediatric allergy centres. METHODS: A retrospective/prospective study was undertaken. All children diagnosed with fish or shellfish FPIES were enrolled. The diagnosis of FPIES was based on Sicherer's or Miceli Sopo clinical criteria. Skin prick tests (SPT) were performed in all patients, at the time of diagnosis and prior to OFC. RESULTS: Seventy children were enrolled. Mean age at first episode was 14 months (range 6-46 months); mean age at diagnosis was 34 months (range 6-164 months). Sole and cod were the fish most commonly implicated. Fifty-seven of 70 (81%) children had FPIES exclusively to fish, 37 of 57 (65%) children had single-fish FPIES, 20 of 57 (35%) multiple-fish FPIES, nine of 70 (13%) presented adverse reactions exclusively to shellfish, and four of 70 (6%) presented adverse reactions to both fish and shellfish. Only four (5.7%) children presented episodes of acute FPIES with different foods (2 to cow's milk, 1 to egg, 1 to beef); in all cases, onset was prior to that of fish or shellfish FPIES. Fifteen of 70 (21%) children tolerated fish other than the offending fish. Twenty-four of 70 (34%) children achieved tolerance (age range 24-102 months). CONCLUSIONS: The chief peculiarities of acute fish and shellfish FPIES, compared to more frequent cow's milk or soy FPIES, are (i) later age of onset, (ii) longer persistence and (iii) possibility of tolerating fish other than the offending fish. Adverse reactions with shellfish are possible.

Microbiota in healthy skin and in atopic eczema.

The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.

Autoimmunity in atopic dermatitis: biomarker or simply epiphenomenon?

The idea that a mechanism of autoimmunity could play a role in the pathogenesis of atopic dermatitis gained support from the observation that patients with atopic dermatitis display IgE reactivity to a variety of human protein antigens, several of which have been characterized at molecular level. A broad spectrum of at least 140 IgE-binding self-antigens associated with atopic dermatitis has been demonstrated; they might promote, perpetuate, or both, skin inflammation by binding IgE antibodies or activating specific T cells. Even if the presence of autoreactivity seems to be associated with the severity of the disease and may be used as a parameter reflecting chronic tissue damage, at the state of art the role of autoimmunity in atopic dermatitis is far from clear. Data from the literature show that the use of autoantibodies as biomarkers of atopic dermatitis are still limited by the evidence that the epiphenomenon of autoreactivity is detectable only in a percentage of patients and that the involved self-allergens often are not the same; further longitudinal case-control studies are needed to investigate and to clarify the pathogenethic role of autoimmunity in the course of atopic dermatitis.

Cow's milk allergy in children, from avoidance to tolerance.

Food allergy is the primary cause of anaphylaxis in paediatric age affecting roughly 4% of children and their families worldwide, and requiring changes in dietary habits. The prognosis for food allergy in children has traditionally been regarded as good for the most frequent allergens, however the prognosis for cow's milk allergy in the pediatric age is currently considered to be worse than previously believed. There is now enough evidence that measures of avoidance for children at risk did not have any preventive effect whatsoever, but they still came to be counterproductive by avoiding the physiological interaction between food allergens and gastrointestinal mucosal immune system. Programs of specific oral tolerance induction (SOTI) have obtained interesting results in the treatment of food allergy supporting the idea that antigen exposure through gastrointestinal section is important to allow the development of tolerance. Nevertheless this approach is not yet considered "ready" for community recommendations. In this paper we describe our experience in the field of SOTI in children with cow's milk allergy.

IgE-mediated food allergy in children.

Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Prognosis is good for the most frequent allergens with almost all children outgrowing their allergy. However, the long-term implications for disease burden are substantial for children with persistent allergies (eg, peanuts, tree nuts, fish, and shellfish) and for those with high concentrations of milk, egg, and wheat IgE. Antigen avoidance has been the time-honoured approach both for prevention and treatment. However, findings from studies done in the past 5 years show that early contact with food can induce tolerance and desensitisation to foods. We review the epidemiology, natural history, and management of food allergy, and discuss the areas of controversy and future directions in research and clinical practice.

Autoimmune chronic urticaria: transferability of autologous serum skin test.

At least 30 % of children with chronic urticaria have an autoimmune aetiology with a positive autologous serum skin test (ASST). ASST is cheap, easy to perform and has good sensibility and specificity in detecting autoantibodies. In case of concern about reliability of ASST because of antihistamine medications, test transferability seems to be feasible.

Under pressure.

Physical urticaria is a rare but challenging subset of chronic urticaria. Wheals of pressure urticaria are typically delayed in appearance. A pressure test can easily be done to confirm the diagnosis.

The dietary paradox in food allergy: yesterday's mistakes, today's evidence and lessons for tomorrow.

During the last decades the prevalence of food allergy has significantly increased among children and antigen avoidance still remains the standard care for the management of this condition. Most reactions are IgE-mediated with a high risk of anaphylaxis requiring emergency medications in case of inadvertent ingestion. Recent studies showed that continuous administration of the offending food, rather than an elimination diet, could promote the development and maintenance of oral tolerance. Indeed, intestinal transit of food proteins and their interaction with gut-associated lymphoid tissue (GALT) is the essential prerequisite for oral tolerance. On the contrary, low-dose cutaneous exposure to environmental foods in children with atopic dermatitis and altered skin barrier facilitates allergic sensitization. The timing and the amount of cutaneous and oral exposure determine whether a child will have allergy or tolerance. Furthermore, previous preventive strategies such as the elimination diet during pregnancy and breastfeeding, prolonged exclusive breastfeeding and delayed weaning to solid foods did not succeed in preventing the development of food allergy. On the other hand, there could be an early narrow window of immunological opportunity to expose children to allergenic foods and induce natural tolerance. Finally, the gradual exposure to the offending food through special protocols of specific oral tolerance induction (SOTI) may be a promising approach to a proactive treatment of food allergy.