Atopic Manifestations Research Articles

Role of Inhalant and Food Allergens in Child Sensitization: A Prospective Study in 176 Children

Background: The origin of atopic disease is poly factorial and the development of atopic manifestations appears to be linked to interactions between genetic and environmental factors. Such data seem to focus attention on the rising prevalence rates of atopic dermatitis, a common debilitating skin codition in infants and young children. They also often have asthma and/or allergic rhinitis.

Atopic Manifestations: Dermatitis, Allergic Rhinitis and Asthma in Patients With Hypogammaglobulinemia.

Background:Most of the hypogammaglobulinemic patients have a clinical history in favor of allergic respiratory disease. Nevertheless, in these patients the importance and prevalence of atopic disorders have not been completely explained.Objectives:This study was aimed to evaluate atopic manifestations (dermatitis, allergic rhinitis and asthma) and pulmonary function in patients with hypogammaglobulinemia.Patients and Methods:We used the international study of asthma and allergies in childhood (ISAAC) questionnaire in forty-five patients diagnosed with hypogammaglobulinemia and spirometry was done in 41 patients older than 5 years.Results:Spirometry results were normal in 21 (51%), and showed obstructive in 15 (37%) and restrictive pattern in 5 (12%) of the 41 patients who were evaluated. By the end of the study, asthma was diagnosed in nine (20%) patients and other atopies (rhinitis and dermatitis) identified in 10 (22%), and four (9%), respectively.Conclusions:Atopic conditions should be investigated in the hypogammaglobulinemic patients and the prevalence in these patients may be higher than in normal population. Also, it is recommended to perform a pulmonary function test as a routine procedure in patients with hypogammaglobulinemia and atopy should be assessed in these patients.

Penile Cancer in a Man With Netherton Syndrome

Netherton syndrome (NS) is a rare autosomal recessive skin disease with severe skin inflammation and scaling, a specific hair shaft defect (trichorrhexis invaginata or bamboo hair), and severe atopic manifestations including atopic dermatitis and hay fever with high serum immunoglobulin E levels and hypereosinophilia. NS is caused by loss-of-function mutations in serine protease inhibitor of Kazal-type 5 (SPINK5) encoding lympho-epithelial Kazal-type-related inhibitor (LEKTI) expressed in the stratified epithelia. We report the first case of penile squamous cell carcinoma in a patient with NS.

Immune response against 2,4-dinitrofluorobenzene-induced atopic dermatitis-like clinical manifestation is suppressed by spermidine in NC/Nga mice.

Of the biogenic polyamines, spermidine is a natural constituent of living cells and organisms. Spermidine is associated with regulation of cell growth, proliferation and differentiation, and with the suppression of oxidation and inflammation. Atopic dermatitis (AD) is a chronic inflammatory skin disease that has a complex and multiple pathogenesis, which includes genetic abnormality, modified or abnormal immune response and the production of nitric oxide and reactive oxygen species. We investigated whether spermidine can relieve AD-like clinical manifestation induced by the continual application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. Spermidine at concentrations of 1 or 10 mg/kg reduced increasing ear swelling and attenuated oedema, haemorrhage and hyperkeratosis in AD-like skin lesions. Repetitive application of DNFB induced inflammatory cell infiltration to skin lesions, whereas intraperitoneal injection of spermidine inhibited DNFB-evoked infiltration of eosinophils, mast cells and T lymphocytes. Furthermore, spermidine suppressed mast cell degranulation and production of interferon-gamma by activated CD4(+) T cells in AD-like skin lesions. Spermidine may be a potential therapeutic agent for treatment of AD.

DOCK8 primary immunodeficiency syndrome

A 3-year-old boy presented to our dermatology department in July, 2013, with a history of moderate atopic dermatitis, food allergy to cow’s milk protein and hen’s egg, and a 4 week history of very extensive molluscum contagiosum. Initial treatment with topical cantharidin and imiquimod had been unsuccessful. The family had no history of immunodefi ciency. Investigations showed lymphopenia with abnormal T-cell subsets (CD4 lymphocyte count of 0·384 × 109 cells per L [normal range 0·5–2·4 × 109 cells per L], CD3 lymphocyte count of 0·462 × 109 cells per L [0·9–4·5 × 109 cells per L], and CD8 lymphocyte count of 0·074 × 109 cells per L [0·3–1·6 × 109 cells per L]), increased IgE (2567 kIU/L [ 3%). Pneumococcal antibody serotypes, except 23F, were detected at negligible concentrations, despite previous vaccination. Clinical examination showed extensive sheets of molluscum on the trunk, genital region, ears, and eyelids with occipital and submandibular lymphadenopathy (fi gure). Naso pharyn geal swabs detected adenovirus DNA. The molluscum did not improve with two intravenous infusions of cidofovir in July, 2013. Because the clinical manifestations and the initial immunology screen suggested DOCK8 immuno defi ciency syndrome we ordered Sanger sequencing that subsequently identifi ed two compound heterozygous mutations in the DOCK8 gene on chromosome 9q24. Mutations in DOCK8 underlie most cases of autosomal recessive hyper-IgE syndrome and are associated with reduced numbers of T cells, B cells, and natural killer cells, with impaired CD8 T-cell proliferation and activation. Aff ected individuals have increased susceptibility to viral, bacterial, and fungal infections and have atopic manifestations including atopic dermatitis and food allergies. In our patient, the unusual severity of the molluscum infection along with the mild atopic dermatitis and food allergy suggested the diagnosis of DOCK8 primary immunodefi ciency syndrome, prompting further work-up. Presentation is characterised by recurrent infections with staphylococcus, cutaneous herpes, or human papillomavirus, respiratory and gastrointestinal infections, and an increased risk of squamous-cell carcinomas. Development of substantial numbers of molluscum contagiosum should raise suspicions about this condition. Management of DOCK8 immunodefi ciency includes prophylactic antibiotic, antifungal, and antiviral therapy. In view of the high risk of early death from opportunistic infection or malignancy, we have transplanted fi ve patients with DOCK8 defi ciency, all of whom are alive and well and free of all symptoms. In January, 2014, our patient received an HLA-identical sibling donor bone marrow transplant. He developed grade 2 skin graft versus host disease which resolved by 1 year after the transplantation, with complete clearance of the molluscum lesions and good immune reconstitution with 100% donor chimerism.

Rhinitis in the first 18 months of life: exploring the role of respiratory viruses.

BackgroundRhinitis is common in early childhood, but allergic rhinitis is considered a later manifestation of the atopic march. This study aimed to evaluate rhinitis (allergic and non‐allergic) in the first 18 months of life, its link with other atopic manifestations and the role of respiratory viruses.MethodsSubjects (n = 1237) of the Singapore GUSTO birth cohort were followed up quarterly until 18 months of age with questionnaires to screen for rhinitis symptoms lasting at least 2 wk and with monthly calls to positive subjects to detect prolonged/recurrent rhinitis symptoms (total duration ≥4 wk). Anterior nasal swabbing for molecular‐based virus detection was conducted during these visits and near (within a month) rhinitis episodes. Skin prick testing to common environmental and food allergens was conducted at the 18 month visit.ResultsProlonged/recurrent rhinitis was significantly associated with history of parental atopy (mother: aOR = 2.17; father: aOR = 1.82) and atopic comorbidities of eczema (aOR = 2.53) and wheeze (aOR = 4.63) (p < 0.05), though not with allergen sensitization. Although the frequency of nasal respiratory virus detection during scheduled quarterly visits did not differ between prolonged/recurrent rhinitis and matched controls (p > 0.05), virus detection was higher in swabs obtained within a month following rhinitis episodes in prolonged/recurrent rhinitis subjects compared with scheduled visits (adjusted p = 0.04).ConclusionsBased on the duration of rhinitis symptoms, this study defined a subset of early childhood rhinitis which was associated with atopic predisposition and comorbidities. Persistent respiratory viral shedding may contribute to the symptomatology. Whether this entity is a precursor of subsequent childhood allergic rhinitis will require longer follow‐up.

Fatty Acid Transport Protein 1 Can Compensate for Fatty Acid Transport Protein 4 in the Developing Mouse Epidermis

SUMMARYFatty acid transport protein (FATP) 4 is one of a family of six FATPs that facilitate long- and very long-chain fatty acid uptake. Mice lacking FATP4 are born with tight, thick skin and a defective barrier; they die neonatally due to dehydration and restricted movements. Mutations in SLC27A4, the gene encoding FATP4, cause ichthyosis prematurity syndrome (IPS), characterized by premature birth, respiratory distress, and edematous skin with severe ichthyotic scaling. Symptoms of surviving patients become mild, though atopic manifestations are common. We previously showed that suprabasal keratinocyte expression of a Fatp4 transgene in Fatp4 mutant skin rescues the lethality and ameliorates the skin phenotype. Here we tested the hypothesis that FATP1, the closest FATP4 homolog, can compensate for the lack of FATP4 in our mouse model of IPS, as it might do postnatally in IPS patients. Transgenic expression of FATP1 in suprabasal keratinocytes rescued the phenotype of Fatp4 mutants, and FATP1 sorted to the same intracellular organelles as endogenous FATP4. Thus, FATP1 and FATP4 likely have overlapping substrate specificities, enzymatic activities, and biological functions. These results suggest that increasing expression of FATP1 in suprabasal keratinocytes could normalize the skin of IPS patients and perhaps prevent the atopic manifestations.

Effects of Lobophytum crassum extract(MC-1) on Various Immunological Factors Related to Pathogenesis of Atopic Dermatitis in Dermatophagoides Pteronyssinus Treated NC/Nga mice

ABSTRACT Objectives : The aim of this study was to confirm whether or not coral has a preventive effect on development of atopic dermatitis induced by house mite(dermatophagoides pteronyssinus) in NC/Nga mice.Methods : This study was undertaken by using a reliable Atopic dermatiti s mouse model demonstrating similar immune response. Lobophytum crassum was administered orally to NC/Nga mouse for 3 weeks. In order to verify the effectiveness of Lobophytum crassum in atopic dermatitis treatment, its role in immune factors were observed in NC/Nga mice.Results : ALT, AST, BUN and creatine levels were all within in the normal ranges in MC-1 200 and 400 (㎎/㎏) treated groups, indicating no induced toxicity. MC-1 200 and 400 (㎎/㎏) groups decreased of atopic dermatitis skin manifestation in NC/Nga mouse of MC-1 200 and 4 00 (㎎/㎏) groups compared to that of the control group and decreased the ratio of WBC and lymphocyte in blood.Also, MC-1 200 and 400 (㎎/㎏) groups significant decreased the ratio of CD4+, CD8+, CD11b+/Gr1+, B220/CD23 and CD4/CD25 immune cell ratio in ALN. Finally MC-1 2 00 and 400 (㎎/㎏) groups significantly increased the ratio of CD4+, CD8+, B220/CD23 and CD4/CD25 immun e cells in DLN.Conclusions : Theses results suggested that Lobophytum crassum has suppressi ve effects on aberrant and overactive immunological activities in dermatophagoides pterony ssinus-induced dermatitis mice of NC/Nga.Key words : Atopic dermatitis, Dermatophagoides pteronyssinus, Immune, Lob ophytum crassum(MC-1), NC/Nga

The role of the innate immune system in atopic dermatitis

The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasia.

Recently, patients with hypohidrotic/anhidrotic ectodermal dysplasia (H/AED) have been reported to have a higher prevalence of symptoms suggestive of atopic disorders than the general population. To better understand atopic diathesis in H/AED, 6 cases of clinically or genetically diagnosed H/AED were examined. The following criteria were evaluated with patient consent: sweating, blood test results, histopathology and filaggrin staining. Five of 6 H/AED cases displayed atopic dermatitis-like manifestations, and 3 of these 5 cases experienced periorbital lesions. H/AED patients tended to present with atopic dermatitis-like eruptions with characteristics potentially indicative of periorbital lesions. Atopic diathesis in H/AED appeared not to be associated with filaggrin. We could speculate that hypohidrosis or anhidrosis itself might impair skin barrier function and contribute to atopic diathesis.

A Case of IFAP Syndrome with Severe Atopic Dermatitis

Introduction. The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia. Case Report. A three-month-old Caucasian, male patient was observed with noncicatricial universal alopecia and persistent eczema from birth. He had dystrophic nails, spiky follicular hyperkeratosis, and photophobia which became apparent at the first year of life. Short stature and psychomotor developmental delay were also noticed. Histopathological examination of skin biopsy on left thigh showed epidermis with irregular acanthosis, lamellar orthokeratotic hyperkeratosis, and hair follicles fulfilled by parakeratotic hyperkeratosis. The chromosomal study showed a karyotype 46, XY. Total IgE was 374 IU/mL. One missense mutation c.1360G>C (p.Ala454Pro) in hemizygosity was detected on the MBTPS2 gene thus confirming the diagnosis of IFAP syndrome. Conclusions. We describe a boy with a typical clinical presentation of IFAP syndrome and severe atopic manifestations. A novel missense mutation c.1360G>C (p.Ala454Pro) in MBTPS2 gene was observed. The phenotypic expression of disease is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol and endoplasmic reticulum homeostasis. It can cause epithelial disturbance with failure in differentiation of epidermal structures and abnormal skin permeability barrier. However, no correlation phenotype/genotype could be established.

ALLERGY PREVENTION IN CHILDREN DURING THE INTRODUCTION OF COMPLEMENTARY FEEDING PRODUCTS

The article covers modern approaches to the prevention of allergic diseases in children. We discuss the most common food allergens in the early childhood, main mechanisms of food tolerance formation and opportunities of dietary preventive measures in a risk group of the allergy development. One of the important issues, in practical terms, is the question of time and peculiarities of the complementary feeding introduction in this category of children. The own experience of use of hypoallergenic complementary feeding products in children from the risk group and with mild manifestations of atopy is presented.

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET)

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET)

The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3-CD4+ aberrant T-cell phenotype.

The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network. All patients who met the recent criteria of hypereosinophilia (HE) or HES and who had a persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included. Clinical and laboratory data were retrospectively collected by chart review. CD3-CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range, 5–75 yr]). Half (48%) had a history of atopic manifestations. Clinical manifestations were dermatologic (81%), superficial adenopathy (62%), rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%), and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35 G/L (range, 0.01–28.3), with a clonal TCRγδ rearrangement in 76% of patients. The mean follow-up duration after HES diagnosis was 6.9 ± 5.1 years. All patients treated with oral corticosteroids (CS) (n = 18) obtained remission, but 16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years after diagnosis, and 3 deaths occurred during follow-up.In conclusion, clinical manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to skin, and can involve all tissue or organs affected in other types of HE. Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always effective in these patients, but CS-sparing treatments are frequently needed. The occurrence of T-cell lymphoma, although rare in our cohort, remains a major concern during follow-up.

A case of a combination of Crocker - Adamson follicular spinulosa, lichen acuminatus and Little - Lassueur syndrome

The article describes a clinical case of a combination of Crocker-Adamson follicular spinulosa, lichen acuminatus and Little-Lassueur syndrome in a young man aged 17. The patient had the onset of atopic manifestations at an early age (atopic dermatitis, rhinitis, conjunctivitis) along with disorders related to the process of keratosis. The article provides current data on the etiology, pathogenesis and treatment of these diseases.

IgE allergen component-based profiling and atopic manifestations in patients with Netherton syndrome

IgE allergen component-based profiling and atopic manifestations in patients with Netherton syndrome

Elaidic, vaccenic, and rumenic acid status during pregnancy: association with maternal plasmatic LC-PUFAs and atopic manifestations in infants.

Few studies have explored whether fetal exposure to trans fatty acids (TFAs) influences the inception of atopic diseases. The aim of this study was to investigate the relationship between the concentration of specific TFAs (elaidic, vaccenic, and rumenic acids) in maternal plasma and the risk of developing atopic manifestations in the first year of life. A subsample from a population-based pregnancy cohort of the INMA Project was analyzed. Maternal intake of fatty acids was assessed by a food-frequency questionnaire (75.5% of the cohort). TFAs and n-3 and n-6 long-chain polyunsaturated fatty acids were measured in samples of plasmatic phospholipids at 12 wk of pregnancy. Information regarding eczema and wheeze in offspring was obtained through questionnaires at ages 6 and 14 mo. Elaidic acid correlated negatively with n-3 long-chain polyunsaturated fatty acids (total, eicosapentaenoic acid, and docosahexaenoic acid), and rumenic acid positively with both n-3 and n-6 long-chain polyunsaturated fatty acids in maternal plasma. Neither of these two fatty acids was associated with the risk of atopic eczema or wheeze in offspring in the first year of life. However, a higher vaccenic acid level was found to be linked to a lower risk of atopic eczema. High vaccenic acid concentrations in maternal plasma may protect offspring against atopic eczema in infancy.

The transaldolase, a novel allergen of Fusarium proliferatum, demonstrates IgE cross-reactivity with its human analogue.

Fusarium species are among airborne fungi and recognized as causative agents of human atopic disorders. However, Fusarium allergens have not been well characterized and the lack of information limits clinical diagnosis and treatment of fungal allergy. The purpose of this study is to identify and characterize important allergens of F. proliferatum. IgE-reacting F. proliferatum components were identified by immunoblot using serum samples from patients of respiratory atopic diseases. Characterization of allergens and determination of IgE cross-reactivity were performed by cDNA cloning, then homologous expression and immunoblot inhibition studies. We identified nine different F. proliferatum components that can be recognized by IgE antibodies in 17 (28%) of the 60 atopic sera tested. Components with molecular masses of about 43, 37.5 and 36.5 kDa with IgE-binding frequencies of about 88, 47 and 53%, respectively, were considered as important allergens of F. proliferatum. The 37.5 kDa IgE-binding component was putatively considered as a transaldolase protein of F. proliferatum. The full-length cDNA of F. proliferatum transaldolase was subsequently cloned. It encodes an open reading frame of 312 amino acids and has sequence identifies of 73 and 61%, respectively, with Cladosporium and human transaldolases. The purified recombinant F. proliferatum transaldolase can inhibit the IgE-binding against the 37.5 kDa component of F. proliferatum and the transaldolase allergen from Cladosporium cladosporioides. More importantly, the recombinant F. proliferatum transaldolase can inhibit IgE-binding against human transaldolase in a concentration-dependent manner. Thus, a novel and important F. proliferatum transaldolase allergen was identified. In addition to IgE cross-reactivity between the Fusarium and the Cladosporium transaldolase allergens, IgE cross-reactivity between the Fusarium and the human transaldolases also exists and might contribute to atopic manifestations in the absence of exogenous allergen exposure.

PD36 ‐ Evaluation of intracellular cytokines IL‐2, IFNγ, IL‐4 and IL‐5 in children with atopic dermatitis and correlations with other immunological and epidemiological parameters

Atopic dermatitis is a chronic inflammatory disorder of the skin, charachterised by a TH2 skewed cytokine profile, usually elevated total serum IgE and can be co coexpressed with other atopic clinical manifestations. The atopic skin is prone to bacterial colonization and that has an effect on immunological parameters. Atopic Dermatitis has been correlated with IgG hypoglobulinaemia, low serum IgA and downregulation of the CD8 lymphocytes in peripheral blood.

Glutathione S transferase theta1 and mu1 gene polymorphisms and phenotypic expression of asthma in Egyptian children: a case–control study

BackgroundAsthma is the result of a complex interaction between environmental factors and genetic variants that confer susceptibility. The glutathione S-transferases (GSTT1 and GSTM1) are phase II enzymes thought to protect the airways from oxidative stress. Few and contradictory data are available on the association between asthma development and GSTT1 and GSTM1 polymorphisms in different ethnic groups. The current study aimed to investigate whether these polymorphisms are associated with asthma development in the Egyptian population.MethodsThe cross-sectional study was performed on 94 asthmatic children 6 -12 yrs and 90 matched healthy controls. Candidates were subjected to clinical evaluation and measurement of absolute blood eosinophilic count, total serum IgE, and GSTT1 and GSTM1 genotype by multiplex PCR technique.ResultsThe results for GSTT1 null genotype were 87.2% and 97.2% for asthmatic children and controls respectively and showed to be significantly more in controls (P =0.007, OR:0.683, CI: 0.034 -0.715). The results for GSTM1 null genotype were 50% and 61.1% for asthmatic children and controls respectively and showed to be nonsignificant (p = 0.130, OR: 1.000, CI: 0.54- 1.86). Also, no association was detected between GSTT1 and GSTM1 polymorphisms and atopic conditions or asthma severity.ConclusionThe significant detection of GSTT1 null genotype more in controls than in asthmatics with no association with other atopic manifestations or asthma severity and the lack of association detected between GSTM1 polymorphism in relation to asthma, atopy or asthma severity confirm the uncertain role of those genes in the development of asthma.