Journal of Medical Case Reports

Journal of Medical Case Reports, 2012

Introduction: Cow's milk allergy is the most frequent food allergy in Europe and western countries and shows a wide spectrum of clinical features, including atopic dermatitis and gastrointestinal disease. To the best of our knowledge, this report is the first to describe Kawasaki disease-like clinical features and echocardiographic alterations which resolved after a cow's milk-free diet. Case presentation: We report a case of a 9-month-old Caucasian girl with atopic dermatitis who developed clinical features commonly present in Kawasaki disease (erythematous skin rash, non-exudative conjunctivitis, fissured lips and neck lymph nodes), together with mild echocardiographic alterations (perivascular brightness, pericardial effusion) in the absence of fever. These features resolved within 2 weeks after the beginning of a cow's milk-free diet. Conclusion: Kawasaki disease has recently been considered a possible risk factor for subsequent allergic disease secondary to immune dysfunction. This case report suggests that the immune-related alterations which are commonly present in allergic patients could be similar to the antigen-related immune response in Kawasaki disease and thus could lead to similar clinical features.

Pediatric Allergy and Immunology, 2011

The 'hygiene hypothesis' continues to be relevant in explaining the increased prevalence of allergic (1) and autoimmune (2) diseases worldwide. It is hypothesized that the reduction in endotoxin exposure and microbial infections early in life (2), as well as widespread vaccination (3) in urbanized countries, leads to decreased T-helper cell type 1 (Th1) activation and an immunological deviation towards a greater T-helper cell type 2 (Th2)-driven allergic phenotype. But there is mounting evidence that other mechanisms are involved, including antigenic competition and homeostasis (4), immunoregulation by regulatory T cells (5, 6) or stimulation of non-antigenic ligands, e.g. toll-like receptors (4). Factors that can modulate this immunologic balance are likely to be strongest during the early period of life (7). Kawasaki disease (KD) is a generalized vasculitis, with a predilection to coronary artery involvement, and primarily affecting young children. It is also the leading cause of childhood-acquired cardiac disease, in particular coronary artery lesions. The diagnosis of KD is made clinically. Its aetiology remains unclear although there is much ongoing research into its pathophysiology. A possible theory is that KD is triggered by a superantigen associated with microbial infection (8).

The Journal of Pediatrics, 1986

Journal of Pediatrics and Pediatric Medicine, 2020

Multisystem Inflammatory Syndrome in Children (MIS-C) is appearing in infants, children, and young adults in association with COVID-19 (coronavirus disease 2019) infections of SARS-CoV-2. Kawasaki Disease (KD) is one of the most common vasculitides of childhood. KD presents with similar symptoms to MIS-C especially in severe forms such as Kawasaki Disease Shock Syndrome (KDSS). The observed symptoms for MIS-C and KD are consistent with Mast Cell Activation Syndrome (MCAS) characterized by inflammatory molecules released from activated mast cells. Based on the associations of KD with multiple viral and bacterial pathogens, we put forward the hypothesis that KD and MIS-C result from antibody activation of mast cells by Fc receptorbound pathogen antibodies causing a hyperinflammatory response upon second pathogen exposure. Within this hypothesis, MIS-C may be atypical KD or a KD-like disease associated with SARS-CoV-2. We extend the mast cell hypothesis that increased histamine levels are inducing contraction of effector cells with impeded blood flow through cardiac capillaries. In some patients, pressure from impeded blood flow, within cardiac capillaries, may result in increased coronary artery blood pressure leading to aneurysms, a well-known complication in KD. Multisystem Inflammatory Syndrome in Children (MIS-C, previously designated as Pediatric Multisystem Inflammatory Syndrome-PMIS) is appearing in infants, children, and young adults in association with COVID-19 (coronavirus disease 2019) infections 1-11. Kawasaki Disease (KD, previously called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood 12. KD presents with similar symptoms to MIS-C especially in severe forms such as Kawasaki Disease Shock Syndrome (KDSS). The cause of KD is currently unknown; KD has features similar to those associated with a viral infection. The leading hypothesis is that a ubiquitous infectious agent can induce KD in a genetically susceptible patient 13. This hypothesis is supported by the presence of IgA plasma cells identified in inflamed tissues and coronary arteries of KD patients 14. Associations between KD and multiple pathogens have been reported, including adenovirus 15,16 , human bocavirus 17 , coronavirus 16 , human coronavirus 229E 18 , human coronavirus (HCoV-NH) NL63 19 , cytomegalovirus 20 , dengue 21,22 , enterovirus 16,23 , Epstein-Barr virus 24 , human herpesvirus 6 25 , human lymphotropic virus 26 , human rhinovirus 16 , influenza 27 , measles 28 , parvovirus B19 29,30 , parainfluenza virus type 2 31 , respiratory syncytial virus (RSV) 32 , rotavirus 33 , varicella zoster (chicken pox) 34,35 , torque teno virus 36 , Staphylococcus aureus 37 , and Streptococcus 24,38. Postinfluenza vaccination KD has also been

Clinical & Experimental Allergy, 1993

In this investigation 98 children (median age 24 months) with cows' milk allergy (CMA) were studied over a median period of 2 years to see whether acquisition of clinical tolerance to cows' milk was associated with the changes in levels of IgG and IgE anticows' milk antibodies, and skin test reactivity to a cows' milk extract. Two groups of CMA patients were examined. The first were IgE sensitized and responded rapidly to small volumes of cows' milk with urticaria, and/or exacerbations of eczema, and/or wheeze, and/or vomiting (rt = 69). The second, a late reacting group (« = 29) demonstrated coughing, diarrhoea, eczematoid rashes, and/or a combination of these which developed more than 20 hr after commencing normal volumes of cows' milk. Significant immunological changes were confined to the 69 IgE sensitized immediate-reactinggroup of patients. Of these, there were 15 children who achieved clinical tolerance to cows' milk and they showed a significant fall in the levels of skin test reactivity to cows' milk over the study period (f <0-01). In addition, these 15 children had lower serum IgE antibodies to cows' milk proteins both at the outset and the final follow-up compared with the 54 patients whose CMA persisted. No consistent change in the IgG antibody responses to cows' milk proteins was seen in either group of patients over the study period. The findings suggest patients with immediate type hypersensitivity to cows' milk proteins whose disease persists for more than 2 years have a more severe dysregulation of IgE synthesis to cows' milk proteins from the outset. The role of humoral immune mechanisms in the pathogenesis of late reacting CMA remains unclear.

Allergy, 1999

BMJ, 2013

CLINICAL REVIEW of sugar can cause bloating and diarrhoea), these are extremely rare in very young children. Except after a gastrointestinal infection, infants with gastrointestinal symptoms on exposure to cows' milk are more likely to have cows' milk allergy than lactose intolerance. This article focuses on immune mediated reactions to cows' milk in children and reviews the evidence on how to diagnose and manage the condition. What is cows' milk allergy? Cows' milk allergy is an immune mediated reaction to proteins within milk. 3 Milk contains casein and whey fractions, each of which have five protein components. Patients can be sensitised to one or more components within either group. Cows' milk allergies are classified according to the underlying mechanism, which affects the presentation, diagnosis, treatment, and prognosis. IgE mediated allergy is an immediate type (type 1) hypersensitivity reaction that occurs rapidly after exposure, usually within 20 minutes. One of the main causes of symptoms is histamine release, and the symptoms are highlighted in table 1. Non-IgE mediated allergy is a delayed type (type 4) hypersensitivity reaction that seems to be equally common but less well described than IgE mediated cows' milk allergy. Non-IgE mediated milk allergy can occasionally cause a severe form of allergic reaction with acute gastrointestinal symptoms that can mimic sepsis (food protein induced enterocolitis syndrome). However, the T cell mediated reactions are usually more delayed and are often chronic because of continued milk exposure during infancy. Typical symptoms are largely gastrointestinal or cutaneous (table 1). 4 The high frequency of such symptoms in infants without cows' milk allergy, combined with the lack of an immediate temporal relation with milk exposure or any clinical tests, can make non-IgE mediated allergy difficult to diagnose. How does it present? IgE mediated allergy usually manifests within minutes but no longer than two hours after ingestion of cows' milk protein. Symptoms include angio-oedema of the oropharynx, oral pruritus, urticaria, and rhinorrhoea. Although most reactions are mild, around 15% may be more severe with features of anaphylaxis such as stridor or wheeze. 5 Non-IgE mediated allergy presents with more non-specific symptoms that are often chronic because of regular consumption. The most common presentations are treatment Cows' milk allergy mainly affects young children and because it is often outgrown is less commonly seen in older children and adults. It is one of the most common childhood food allergies in the developed world, second to egg allergy, 1 affecting 2-7.5% of children under 1 year of age. 2 The mainstay of treatment is to remove cows' milk protein from the diet while ensuring the nutritional adequacy of any alternative. Cows' milk allergy can often be recognised and managed in primary care. Patients warranting a referral to specialist care include those with severe reactions, faltering growth, atopic comorbidities, multiple food allergies, complex symptoms, diagnostic uncertainty, and incomplete resolution after cows' milk protein has been excluded. Although there are non-immune reactions to cows' milk, such as primary lactose intolerance (when malabsorption

Journal of the American College of Nutrition, 2005

Cow's milk allergy (CMA) is a complex disorder. Numerous milk proteins have been implicated in allergic responses and most of these have been shown to contain multiple allergenic epitopes. There is considerable heterogeneity amongst allergic individuals for the particular proteins and epitopes to which they react, and to further complicate matters, allergic reactions to cow's milk are driven by more than one immunological mechanism. Finally, the incidence and dominant allergic mechanisms change with age, with IgE-mediated reactions common in infancy and non-IgE-mediated reactions dominating in adults. The complexity of CMA has lead to many public misconceptions about this disorder, including confusion with lactose intolerance and frequent self-misdiagnosis. Indeed, the prevalence of self-diagnosed CMA in the community is 10-fold higher than the clinically proven incidence, suggesting a sizable population is unnecessarily eschewing dairy products. Avoidance of dairy foods, whether for true or perceived CMA, carries with it nutritional consequences and the provision of appropriate nutritional advice is important. In this review, the epidemiology and natural course of CMA is discussed along with our current understanding of its triggers and immunological mechanisms. We examine current strategies for the primary and secondary prevention of allergic sensitization and the ongoing search for effective therapies to ultimately cure CMA. Key teaching points • Cow's milk allergy is an inflammatory response to milk proteins and is distinct from lactose intolerance. • CMA is more prevalent in infants (2-6%) than in adults (0.1-0.5%), and the dominant immunological mechanisms driving allergic reactions change with age. • The prevalence of self-diagnosed CMA in the community is substantially higher than the incidence reported in blinded and controlled challenge trials, suggesting that a proportion of the population is unnecessarily eschewing dairy products • Breast-feeding is the best preventative strategy, although it cannot eliminate the risk of allergic sensitization in infants. • Management of CMA involves avoidance of dairy during the duration of the disease, and the provision of appropriate nutritional advice is important to prevent nutritional deficiencies, particularly for parents of young children who have dairy withdrawn from their diet due to either diagnosed or perceived CMA. Abbreviations: CMA ϭ cow's milk allergy, CMI ϭ cow's milk intolerance, DBPCFC ϭ double-blind, placebo-controlled food challenge, eHF ϭ extensively-hydrolyzed formulas, GALT ϭ gut-associated lymphoid tissue, IgE ϭ immunoglobulin E, IL-10 ϭ interleukin-10, pHF ϭ partially-hydrolyzed formulas, RAST ϭ radioallergosorbant test, SPT ϭ skin prick test, TGF-␤ ϭ transforming growth factor-beta, Th1 ϭ T helper cell-type1, Th2 ϭ T helper cell-type 2, T reg ϭ regulatory T cell.

Clinical <html_ent glyph="@amp;" ascii="&amp;"/> Experimental Allergy, 2000

World Family Medicine Journal/Middle East Journal of Family Medicine