Assessment of IgE-mediated food allergies in children with atopic dermatitis

BackgroundAtopic dermatitis (AD) is an inflammatory disease of the skin, which is characterised by a chronic relapsing course.AimThe aim of the study was to assign the prevalence of clinically active food allergies among a group of children between 3 months and 7 years of age, with AD.MethodsEighty-eight children with AD were screened for specific IgE antibodies to food proteins. All patients with AD and specific IgE antibodies to food proteins were subjected to Oral Food Challenges (OFCs) with the relevant foods.ResultsFood-sensitised patients with moderate levels of sIgE had clinically active food allergy to milk (39.28%) and egg (42.34%) on the basis of positive OFCs. High IgE and eosinophilia had a prevalence of almost 80% and 25%, regardless of concomitant food sensitisation and disease severity.ConclusionsIn this study, clinically active food allergies were recognised in 26.13% of children with AD. Nevertheless, no association was confirmed between food sensitisation and AD severity. High IgE and peripheral eosinophilia have not been found more prevalent among children with severe AD nor among children with food sensitisation. Infants and younger children with AD should be screened for an underlying food allergy, regardless of disease severity.     

The role of food allergy in atopic dermatitis

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease affecting more than 10% of all children. Sensitization to foods triggers isolated skin symptoms in about 30% of children. These symptoms include immediate reactions within minutes after ingesting food without exacerbation of AD and early and late exacerbations of AD. It is important to identify clinically relevant sensitizations to foods using skin prick tests, a specific IgE blood test (ImmunoCAP; Phadia, Portage, MI, USA), and double-blind, placebo-controlled food challenges to initiate appropriate dietary interventions and avoid unnecessary dietary restrictions. Children with AD triggered by food allergens demonstrate a distinct immune response upon stimulation of their peripheral blood mononuclear cells with food allergen. A defective skin barrier and increased intestinal permeability appear to facilitate allergen sensitization. Appropriate skin care to maintain skin barrier function and dietary avoidance of highly allergenic foods during infancy may help to prevent allergen sensitization, thereby reducing the severity of AD and food allergies.     

IgE values and T-lymphocyte subsets in children with atopic eczema/dermatitis syndrome.

High levels of IgE and IgE-mediated reactions represent a typical finding in patients with atopic eczema/dermatitis syndrome (AEDS). However, 10-30% of patients usually do not show any increase of total blood IgE levels and any detectable specific IgE sensitization. We performed this study to evaluate the difference of T-lymphocyte subsets in AEDS patients with high or normal IgE values. We enrolled 21 children with AEDS who were at least two years of age (8 boys and 13 girls, aged 2-13 years) and 20 children as control cases with the same age and sex. These patients were classified as IgE-associated AEDS or not IgE-associated AEDS syndrome according to their IgE levels. We used monoclonal antibodies against CD3 (T cells), CD4 (T-helper cells), CD8 (T-cytotoxic cells), CD 19 (B cells), CD56 and CD16 (natural killer cells), CD3/HLA-DR (activated T cells), CD45Ra in CD4 (naive lymphocytes), CD25 (interleukin-2 receptor), CD57 in CD3 (suppressor/cytotoxic), and CD5 in CD20 (Becton Dickinson, Mountain View, CA). The severity of atopic dermatitis (AD) was determined according to the Scoring Atopic Dermatitis (SCORAD) index. Moreover, we checked the levels of peripheral blood eosinophils and of total and specific IgE for a panel of inhalant and food allergens. We found that the CD8+ level was significantly lower and the CD4/CD8 ratio was significantly higher than in healthy cases. Moreover, patients with not IgE associated AEDS (aAD) showed CD4+ levels significantly higher than IgE aAD patients and healthy controls. We found no difference of the SCORAD index in the two groups but there was an inverse relationship between this index and CD4/CD8 ratio. We did not find any correlation between IgE levels and the SCORAD index between eosinophils and SCORAD index or between age and IgE values. A decrease of CD8+ circulating T cells and an increase of the CD4/CD8 ratio are peculiar findings in AEDS patients with either high or normal IgE values.     

Sensitization in early age to food allergens in children with atopic dermatitis

BackgroundClinical and laboratory evidence increasingly supports the notion that food allergy plays a role in the pathogenesis of atopic dermatitis (AD). However, the prevalence of clinically significant food hypersensitivity among children with AD remains an unanswered question.ObjectiveTo prospectively determine the prevalence of IgE-mediated food hypersensitivity among patients referred to a dermatology department for evaluation of AD, and to analyze the clinical relevance of these sensitizations in AD.MethodsWe studied 44 infants of both sexes, aged less than 12 months old, who attended the dermatology department with symptoms of AD. Compliance with Hanifin-Rajka criteria was confirmed and the severity of AD was evaluated using the SCORAD index. IgE-mediated sensitization to cow's milk, alpha-lactalbumin, beta-lactoglobulin, casein, eggwhite, egg-albumin, ovomucoid and foods introduced into the diet was studied using the skin prick test (SPT) and measurement of specific serum IgE (sIgE) by CAP System fluorescein-enzyme immunoassay.Cow's milk, as well as suspected foods from the clinical history or those with a positive SPT and/or sIgE, were withdrawn from the diet to evaluate improvement in AD, and an open controlled challenge test was carried out.ResultsOf the 44 patients studied, sensitization to foods was detected in 27 (61%). No changes were observed in AD during the elimination diet or when the eliminated foods were subsequently reintroduced into the diet. The results of open controlled food challenges were positive in 12 patients (27 %).ConclusionsA high prevalence of food sensitization was found in infants with AD. The most frequent sensitization observed was to egg, although with little clinical relevance since this food had not been introduced into the diet.In the sample studied, the clinical relevance of the observed food hypersensitivities was confirmed in relation to AD. Further studies are required to confirm these results.     

Pneumocystis carinii pneumonia in a patient with hyper-IgE syndrome]

A 15-year-old girl with abnormal findings detected on a medical check-up chest x-ray film was admitted to our center. High-resolution computed tomography, performed upon hospitalization, demonstrated panlobular nodular darkening in left lung fields, and an expanding, blended, map-like darkening near the pleura. Since a Grocott stain-positive cyst was confirmed histopathologically by transbronchial lung biopsy, the patient was given a diagnosis of Pneumocystis carinii pneumonia. Drug therapy was initiated with sulfamethoxaxole trimethoprim (Baktar), and on the 58th day, chest CT confirmed that the darkening observed at admission had virtually disappeared. Underlying diseases, such as AIDS, malignant lymphoma and secondary immunodeficiency caused by immunosuppressive agents or adrenocorticosteroids, were excluded as the cause of P. carinii pneumonia based on clinical/laboratory findings. Under the suspicion of the possibility of primary immunodeficiency, various immunological competence tests were performed. However, no abnormal findings indicating cell-mediated immunity, humoral immunity, complement immune function, neutrophil phagocytic capacity, or bactericidal capacity were recognized. Since significant increase of serum IgE suggested hyper-IgE syndrome, IgE antibody specific to Staphylococcal enterotoxin A and B, and the exotoxins of Staphylococcus aureus were measured with positive results. Since all three diagnostic criteria for hyper-IgE syndrome (i.e., high serum IgE values, positive IgE antibody specific to Staphylococcal enterotoxin and recurrent infection) were fulfilled, hyper-IgE syndrome was diagnosed. This is a rare case of hyper-IgE syndrome as a result of P. carinii pneumonia.     

Immune dysregulation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic, inflammatory skin disease characterized by cutaneous hyperreactivity to environmentals triggers. Recent data suggest the presence of two different forms of AD: an extrinsic AD with elevated IgE involving 70-80% of the patients and an intrinsic AD with serum IgE not elevated and no specific IgE. Patients with extrinsic AD have elevated Th2- and decreased Thl-expressing cells in the peripheral blood, with elevated IL-4 and IL-13 expression, as well as IL-5. On the contrary, the intrinsic AD is linked with much lower levels of IL-4 and IL-13. Genetic factors are involved in the control of the disease and in the intrinsic AD the same chromosomal regions seem to be associated with psoriasis susceptibility. The AD is characterized by a complex of immunological alterations involving interactions between IgE-bearing antigen-presenting cells, T-cell activation, mast-cell degranulation, keratinocytes, eosinophils, and a combination of immediate and cellular immune responses. Inflammatory dendritic epidermal cells constitute a distinct dendritic cells population that is mainly found in AD and could induce the Th2/Thl isotopic switch contributing to AD chronic phase. Therapy is based on interventation in the pathophysiology of atopic eczema and elimination of exogenous provocation factors.     

Septic arthritis in a case of hyper-IgE syndrome

Hyper-IgE syndrome (HIES) is characterized by recurrent skin and pulmonary infections (mainly bacterial), eczematous dermatitis and elevated serum IgE levels. Associated abnormalities in some patients include coarse facial features, failure or delay of shedding of primary teeth, recurrent fractures, hyperextensible joints, and scoliosis. Laboratory abnormalities include elevated total serum IgE levels, typically ranging from 1000 to greater than 50,000IU/mL and variable eosinophilia. The diagnosis of HIES is based upon the presence of suggestive clinical and laboratory findings. A definitive laboratory test is not commercially available at present. Management of patients with HIES is focused on skin care, prevention of infection, prompt and complete treatment of infections that do develop, and control of pulmonary complications.     

Serum concentration of dehydroepiandrosterone sulfate and testosterone in women with severe atopic eczema/dermatitis syndrome.

BACKGROUND: Although a growing body of evidence indicates that androgens modulate immune response and certain alterations in sex hormone metabolism and balance are thought to predispose an individual to immune-mediated diseases, few studies have investigated the role of androgens in atopic eczema/dermatitis syndrome (AEDS). OBJECTIVE: We evaluated serum concentration of dehydroepiandrosterone sulfate (DHEA-S) and total testosterone in women with severe AEDS to characterize the hormonal milieu of such patients. METHODS: Serum concentrations of DHEA-S and total testosterone in 13 female patients with severe AEDS were compared with concentrations in weight- and age-matched healthy controls. Measurement was by electrical chemiluminescence immunoassay. RESULTS: There were no significant differences in serum concentrations of DHEA-S or testosterone between the 2 groups. We found no correlation between serum concentrations of DHEA-S and total immunoglobulin E. CONCLUSION:This small study suggests there may be no abnormalities in peripheral blood concentrations of DHEAS-S and total testosterone in women with severe AEDS.     

Immunoglobulins in tears and sera in patients with atopic dermatitis.

The aim of the study was to investigate the role of circulating (i.e., present in the serum) and locally produced (i.e., in the lamina propria of mucous membranes) immunoglobulins including IgE. The IgG, IgA, IgM immunoglobulins, and IgE (total and specific) were measured in patients' sera with atopic dermatitis (AD) (n = 93). As control subjects 83 healthy volunteers, matched for sex and age, were included. The IgG and IgM levels were within the normal range. Mean value of the total IgA (2.55 +/- 0.26 g/L, in controls 1.49 +/- 0.32 g/L) and IgE (609 IU/mL, in controls below 40 IU/mL) levels were significantly elevated (p < 0.05) in sera of AD patients. Based on the serum total IgE levels (above or below 40 IU/mL) the patients were divided into RAST-positive and RAST-negative types of allergy, respectively. RAST-positive AD (n = 79) showed hypersensitivity to inhalant and food allergens determined by the specific IgE test. The majority of RAST-positive AD cases (n = 68) presented only skin manifestations, while the rest of the patients (n = 11) had rhinoconjunctivitis as well. RAST-positive AD patients with rhinoconjunctivitis showed an increased IgE level in tears (above 10 IU/mL). The specific IgE test positivity in tears correlated with elevated serum total IgE levels and specific IgE positivity (r = 0.925). Total and allergen-specific IgE in the tears can be used to diagnose allergy in vitro. It is believed that the mucosal permeability is enhanced in the atopic inflammatory process, and this may facilitate the transmission of environmental allergens.     

Contact sensitization in children with atopic dermatitis

Background

Atopic dermatitis is a common illness in childhood. Children with atopic dermatitis are prone to develop cutaneous sensitization due to skin barrier dysfunction.

Efficacy of hyperbaric oxygenation in atopic dermatitis.

Ten patients (5 with atopic dermatitis and 5 with asthma-prurigo) aged 8-38 years, were treated with hyperbarie oxygenation, at the Institute of Maritime and Tropical Medicine. Daily one exposure was applied at 0.1 MPa pure oxygen, during 15 days. Parallelly to the clinical evaluation also G, M, E immunoglobulins and the level of C3 and C4 complement were determined. All patients given this treatment improved clinically. In 9 of them, the level of IgE immunoglobulin decreased. The complement levels also decreased.     

Severe obstructive sleep apnea syndrome in a toddler

We report the case of a 3-year-old boy who had experienced intense snoring, frequent awakenings, intense respiratory effort during sleep, and delayed growth starting at the age of 15 months. He underwent adenoidectomy at 18 months. Symptoms initially improved but reappeared 3 months after surgery. He underwent a second adenoidectomy, this time with tonsillectomy, but there was no significant clinical improvement. Polysomnography revealed severe sleep apnea-hypopnea with an apnea-hypopnea index of 45. Continuous positive airway pressure improved sleep quality, although some symptoms, mainly snoring, persisted. A third adenoidectomy was necessary to normalize his breathing pattern during sleep.     

Acute myocarditis with transient eosinophilia and serum hyper-IgE-emia in a patient with atopic dermatitis

A 14-year-old girl with acute myocarditis, transient eosinophilia, and hyper-IgE-emia associated with atopic dermatitis is described. The patient was admitted because of severe heart failure and shock, and severe atopic dermatitis was seen. Blood examinations showed moderate eosinophilia (1917/mm³) and hyper-IgE-emia (830 IU/ml). The response to treatment with dopamine was excellent, and the congestive heart failure was gradually ameliorated, followed by improvement in her atopic dermatitis. In addition, rapid improvement in eosinophilia and hyper-IgE-emia was observed. Histopathological examination of the right ventricular myocardium obtained by endomyocardial biopsy showed mild interstitial fibrosis and mild infiltrations of inflammatory cells, indicating myocarditis. We speculated that the transient eosinophilia and hyper-IgE-emia in the present case indicated that an allergen induced strong allergic reactions, including type 1 allergy, and caused both acute myocarditis and deterioration of the atopic dermatitis; specifically noteworthy is that the patient's disease rapidly improved without corticosteroid treatment. Received: April 6, 2001 / Accepted: September 7, 2001     

Delay of growth and development in children with bronchial asthma, atopic dermatitis and allergic rhinitis.

The elevated incidence of short stature (body height < (-)x - 2s), skeletal retardation and delayed puberty in children with bronchial asthma or atopic dermatitis is generally attributed to the severity of the disorder. However, a series of findings indicate a causal influence of the atopy and the existence of atopic skeletal retardation per se.The observation that children with atopic disorders, whether bronchial asthma, atopic dermatitis or allergic rhinitis, exhibit a rate of short stature that is twice to five times higher than normal indicates atopic and thus genetically determined influences. The elevated prevalence of short stature associated with allergic rhinitis is especially significant, as this disorder cannot be included among the severe chronic disorders. The fact that skeletal retardation is more prevalent in boys than in girls by a ratio of about 2:1 and that a significantly more marked retardation of bone maturation is found in atopic in comparisons with non-atopic asthmatics also lend support to this postulation. The clinical relevance of atopic growth retardation is also supported by the close interaction of pathophysiological basal mechanisms of bone metabolism and the atopy status. Thus the local growth factor prostaglandin E(2) (PGE(2)), which is important for bone metabolism, is also a messenger substance for the immediate and late allergic reaction. The platelet-activating factor (PAF), as one of the strongest mediators in the pathogenesis of allergic disorders, influences the PGE(2) synthesis in the osteoblasts. These relationships show that atopy-dependent imbalances in the complex system of local and systemic growth factors can certainly lead to disturbance of skeletal maturation which may delay growth and development in atopic children. In order to verify these assumptions it is necessary to research the interaction of local growth factors (particularly the roles of PGE(2), PAF and IGF I) in the skeletons of children of short stature suffering from atopic disorders.This should also include the possible effects on the overall hormonal factors influencing bone maturation. Atopy should be included in the differential diagnosis programme to clarify growth and development disturbances.     

Hemopoietic progenitor cells in atopic dermatitis skin lesions.

We have recently shown the expression of lymphoid early developmental markers, including CD104, Thy 1, CD1a, Pgp-1 and TdT, by the cells constituting atopic dermatitis skin infiltrates. To further characterize the cellular phenotypes we used an indirect immunoperoxidase assay to analyze sections from two atopic dermatitis lesion skin biopsies using the following as first step monoclonal antibodies (MAB): anti-CD34, CD2, CD5 and CD7. CD34+ mononuclear cells and endothelial cells were identified. A strong immunoreaction was observed for the T-lineage marker CD2 and CD5, but a poor reaction, if any, was seen for the CD7. Since CD34+ marrow and blood cells are currently believed to be the major source of the hemopoietic precursors, our data provide further substantial evidence supporting the hypothesis that the atopic dermatitis skin cell infiltrate represents an ongoing T-lineage in situ differentiation process regulated by the skin epithelial microenvironment. The observed defective expression of the CD7 antigen requires further investigation for its confirmation as a possible constant feature in atopic dermatitis.