Clinical Manifestations Of Atopic Dermatitis Research Articles

Clinical manifestations of atopic dermatitis and diagnostically meaningful indicators monitoring of immune status parameters in children with a confirmed diagnosis of HIV infection at abackground of highly active antiretroviral therapy

Background. The influence of HAART on the clinical manifestations of atopic dermatitis in HIV-infected children in parallel with the assessment of its effectiveness in relation to the dynamics of diagnostically important indicator of immune status and viral load. Methods. During the period from 1998 to 2008 among children in the check-up at the Moscow Regional Center of AIDS with a confirmed diagnosis of HIV infection in the formation of a group of 26 children, who retrospectively analyzed the clinical and immunological characteristics. To study the dynamics of changes in clinical manifestations of atopic dermatitis on the background of HAART, analyzed the quantitative indicators of CD4 + T-lymphocytes and assessed the changes in viral load. Results. As of 01.01.2009 years in the Moscow region reported 224 children with HIV infection, of whom 111 are under HAART children. Of the children in the HAART, 26 children (29%) to destination therapy have pronounced symptoms of atopic dermatitis (AD). All children of the group was appointed by HAART in accordance with accepted standards. Laboratory indices and clinical manifestations of AD were recorded before HAART and after 9 months after initiation of therapy. According to the results of clinical observations in the survey group of patients in 20 children (77%) 9 months after the appointment of HAART AD symptoms disappeared completely, while 5 children (19%) noted a clear improvement. Only one HIV-infected child (4%) AD was recurrent in nature. Analysis of laboratory data showed that prior to the start of HAART, quantitative indicators of CD4 + T-lymphocytes in children from this group (n = 26) was 23,69 ±4,24 per cent of the total number of lymphocytes. As a result of HAART, the proportion of CD4 + T lymphocytes increased to 29,35±2,61%. When comparing the results of the quantification of HIV RNA in plasma observed decrease in the value decimal logarithm of viral load from 5,22 ±0,21 to 1,54 ±0,71. Conclusions. Highly active antiretroviral therapy of HIV-infected children leads to a cessation of manifestation of AD not giving in to conventional therapy. This effect is realized against the background of the normalization of the indicators of CD4 + T-lymphocytes and reduction in viral load to not defined level.

A study of the frequency and characteristics of minor clinical manifestations in children with atopic dermatitis

Purpose : We aimed to evaluate the frequency and characteristics of minor clinical manifestations of atopic dermatitis (AD) in Korean children to aid the diagnosis and treatment of AD. Methods : From April 2007 to December 2007, we enrolled 106 children (aged 1 month [infants] to 15 years) diagnosed with AD at the Pediatric Allergy Respiratory Center in Soonchunhyang University Hospital. Clinical manifestations were examined and laboratory findings (total and specific immunoglobulin E [IgE] levels and peripheral blood eosinophil count) were analyzed and compared. Results : Minor symptoms, in order of frequency, included xerosis (78.3%), aggravation due to environmental or emotional stress (43.4%), lichenification (35.8%), orbital darkening (34.0%), periauricular eczema (33.0%), and cutaneous infection (31.1%). Older children (2 years) showed more orbital darkening (P=0.01), horizontal crease (P=0.01), and lichenification (P=0.001) than infants. Patients with severe AD (scoring atopic dermatitis [SCORAD] score, 40) showed higher frequencies of xerosis (P= 0.04), cutaneous infection (P=0.03), ichthyosis (P=0.18), keratosis pilaris (P=0.02), pityriasis alba (P=0.07), recurrent conjunctivitis (P=0.02), orbital darkening (P=0.001), aggravation due to environmental or emotional stress (P=0.05), facial eczema (P=0.001), lichenification (P=0.001), and hand/foot eczema (P=0.04) than those with mild-to-moderate AD. Children with atopic eczema showed more facial eczema (P=0.01) and lichenification (P=0.04) than those with non-atopic eczema. Conclusion : The clinical manifestations of AD were similar to those established by Hanifin and Rajka. However, we need to develop our own diagnostic criteria for AD, because the frequencies shown by our subjects differed from those observed in other countries.

Topical Application of Cream-emulsified CD86 siRNA Ameliorates Allergic Skin Disease by Targeting Cutaneous Dendritic Cells

Induction of the co-stimulatory molecule CD86 on dendritic cells (DCs) in the peripheral tissues is a critical event in triggering antigen-specific immune responses. In this study, we propose a new small interfering RNA (siRNA)-based therapy using cream-emulsified CD86 siRNA, targeting DCs for murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Topical application of CD86 siRNA efficiently inhibited CH and markedly decreased the numbers of infiltrating CD86(+) or major histocompatibility complex (MHC) class II(+) cells in murine ear skin. The total number of cells, the percentage of hapten-carrying DCs, and their CD86 expression in the regional lymph nodes (RLNs) also significantly decreased. These results suggest that the silencing of CD86 in local DCs inhibits the recruitment and migration of DCs into the skin and RLNs, respectively, resulting in reduced antigen-specific local inflammation. The therapeutic efficacy of the CD86 siRNA was confirmed in AD-prone NC/Nga mice. Treatment produced marked amelioration in the clinical manifestations of AD and reduced the antigen-specific production of interleukin-4 (IL-4) and serum immunoglobulin E (IgE) and IgG1. Our results suggest that the targeting of cutaneous DCs by CD86 siRNA may be a promising strategy in the treatment of allergic skin disease.

The Role of Cow Milk Allergy in Increasing the Severity of Atopic Dermatitis

Previous studies have shown that up to 33% of children with atopic dermatitis have experienced food hypersensitivity and among different kinds of food allergens Cow Milk (CM) has almost always been one of the most common food allergens in children. The aim of this study is to evaluate the cow milk allergy (CMA) as an increasing factor of severity of atopic dermatitis. One hundred and nineteen children (between 1.5 months and 12 years of age) with atopic dermatitis in the sense of Hanifin and Rajka's criteria entered this study and the severity of atopic dermatitis was identified via the SCORAD index. In order to make the diagnosis of cow milk allergy, a careful history, and a familial history of allergy was taken and the results of skin prick test (SPT) with CM and 4 other food allergen extracts, Radioallergosorbent test (RAST) with CM allergens and a food challenge test with cow milk (fresh or dried) were used. Also a total serum IgE determination and an eosinophil count (with a stool exam) were accomplished. The clinical manifestations of atopic dermatitis in patients was started from their first day of life up to 10 years of age. The family history in 83% of the patients was positive. Positive skin prick test and RAST with CM allergens were positive in 37.9% and 29.3% of cases respectively and the response to challenge test with cow milk was positive in 35 out of 40 patients and in total 44.5% had CMA according to a positive history of cow milk allergy and a positive outcome of the IgE tests (SPT and/or RAST) or a positive challenge test with CM allergens. The results showed that the most common food allergens in patients with atopic dermatitis are certainly cow milk allergens (44.5%) whereas other food allergens are tomato (29.41%), egg (28.57%), nuts (9.24%) and wheat (3.36%) according to the skin prick test. The mean total serum IgE was 307.11 ± 6.56 IU/ml (range = 6–5000) in children with CMA and 81.04 ± 5.97 IU/ml (range = 1–5000) in children without CMA while the mean eosinophil count was 569.52 ± 3.02 count/ml (range = 67–8500) and 314.22 ± 2.94 count/ml (range = 5–5000) respectively. The mean severity of atopic dermatitis according to the SCORAD index was 60.76 in children with CMA and 44.29 in children without CMA. The severity of atopic dermatitis in patients with CMA was significantly higher than patients without CMA (p < 0.0001). Also the mean total serum IgE and mean eosionophil counts in children with CMA were significantly higher than in children without CMA (P < 0.01 and p < 0.0001, respectively). It shows the important role of CM allergen proteins in the induction and in increasing the severity of AD in children.

Frequency and clinical role of Staphylococcus aureus overinfection in atopic dermatitis in children.

The goal of this study was to evaluate the frequency and role of Staphylococcus aureus infection in patients with atopic dermatitis (AD). In 81 children, ages 2 months to 9 years, affected with moderate to severe AD, 308 samples from the cutaneous lesions were obtained and analyzed. S. aureus was isolated in 52 children (64.2%). Five of these were also colonized by Streptococcus pyogenes and one by Candida albicans. In 61 patients, total IgE serum level and specific IgE were tested to evaluate their allergic status: in 43 children a diagnosis of extrinsic AD was made, while 18 were affected by intrinsic AD. A higher presence of the bacterium was observed in allergic (71%) versus nonallergic children (49%). Our data demonstrate the importance of S. aureus in the clinical manifestation of AD and, in particular, its role in worsening the eczematous lesions of the face, neck, and perineum in children less than 1 year of age.

Epidemiology, clinical features, and immunology of the "intrinsic" (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis).

Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica) pollen allergen in atopic dogs.

Using both in vivo and in vitro tests, dogs with atopic dermatitis were examined for sensitization with Japanese cedar (Cryptomeria japonica, CJ) pollen allergen. Ten dogs with clinical manifestation of atopic dermatitis were shown to be sensitized to CJ pollen based on the results of intradermal skin test and serum antigen-specific IgE test. In vitro lymphocyte stimulation test showed blastogenic response after stimulation with crude antigen of CJ pollen in all of the 5 cases examined. The peripheral leukocytes showed increased histamine release after stimulation with crude antigen of CJ pollen in 2 cases examined. These data indicate that a proportion of dogs with atopic dermatitis is sensitized to CJ pollen in a cell-mediated manner and show immediate phase reaction of type I hypersensitivity.

Regulation of peripheral blood mononuclear cell responses to Dermatophagoides farinae by substance P in patients with atopic dermatitis.

Neuropeptides mediate stress-induced cutaneous inflammation such as atopic dermatitis. The effect of substance P on proliferation and cytokine mRNA expression of peripheral blood mononuclear cells in response to Dermatophagoides farinae (Der f) was studied in atopic dermatitis patients with positive RAST scores to Der f. Upon stimulation with Der f peripheral blood mononuclear cells from patients proliferated in a B7-dependent (CD80- and CD86-dependent) manner, while those from the patients with negative scores, nonatopic eczematous dermatitis patients or normal individuals, did not. Based on the reactivity of normal individuals, atopic dermatitis patients with a stimulation index greater than 1.8 were tentatively defined as high responders, who comprised two-thirds of the patients. Proliferation in high responders was associated with upregulation of IL-2 mRNA expression and induction of IL-5 mRNA expression. Substance p at 10(-10) to 10(-8) M promoted the Der f-induced proliferation when added at the start of culture and upregulated IL-10 MRNA expression while downregulating IL-5 mRNA expression. Our results suggest that substance P modifies immune responses of atopic T cells to Der f by promoting proliferation and altering cytokine profiles, and thus modulates the clinical manifestations of atopic dermatitis.

The significance of reactions to purified fractions of Dermatophagoides pteronyssinus and Dermatophagoides farinae in canine atopic dermatitis

The significance of reactions to crude extracts and purified fractions of the house dust mites Dermatophagoides pteronyssinus (Der p I and Der p II) and Dermatophagoides farinae (Der f I and Der f II) was evaluated in dogs with clinical manifestations of atopic dermatitis (AD). In 13 healthy control dogs and eight dogs with AD, immediate skin test reactivity was determined to serial dilutions of Der p I, Der p II, Der f I and Der f II. In addition, allergen-specific IgGd antibodies were determined by means of an enzyme-linked immunosorbent assay (ELISA) and Western blots. The results suggest that, in contrast to what occurs in humans and despite immediate skin test reactivity in some dogs, Der p I, Der p II, Der f I and Der f II are unlikely to be major allergens in dogs with AD. However, only serum of atopic dogs consistently binds a 90 kDa polypeptide of D. farinae, as shown by Western blot analysis.

Periauricular Eczematization in Childhood Atopic Dermatitis

We investigated the prevalence of periauricular eczematization (PAE) in children with atopic dermatitis (AD) in Korea, and evaluated the clinical significance of the lesion in terms of its treatment in relation to a possible pathogenetic role for Staphylococcus aureus. Tentatively, PAE was classified as infraauricular and postauricular fissuring, which were observed in 62 (57.9%) and 37 (34.6%) of 107 patients, respectively. Sixty eight patients (64.5%) had infraauricular or postauricular fissures, or both, and this prevalence was significantly (p < 0.01) higher than that in controls (1.3%). Staphylococcus aureus was cultured from oozing material from infraauricular fissures in 12 of 14 patients, and topical application of erythromycin cream to the ear lesions led to faster and more definite improvement. Our study shows that PAE is a characteristic clinical manifestation of AD, probably induced by S. aureus. Topical antibiotics are worth trying for effective management of this disorder.

Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial T H2 response to a T H1 response in situ: An immunocytochemical study

In the pathogenesis of atopic dermatitis (AD), IgE plays an important role; and TH2 cells, producing IL-4, have been ascribed a key role in allergic diseases such as AD. To investigate the role of TH subpopulations in the onset and continuation of AD, we performed atopy patch tests (APTs) with house dust mite allergen in patients with AD. Punch biopsy specimens were taken from the APT site, and sections were immunocytochemically double-stained for IL-4 and interferon-gamma together with different membrane markers. This provides a unique model for studying the kinetics of the TH0, TH1, and TH2 responses in situ. The results show that in lesional skin interferon-gamma-positive cells predominate over IL-4-positive cells. The interferon-gamma-positive cells are mainly CD3+ and, in particular, CD4+ cells; the remainder are CD8+, RFD-1+, and RFD-7+ cells. The IL-4-positive cells are exclusively CD4+ T cells; no eosinophils or mast cells were found to stain for IL-4. With regard to the TH cell response, a clear dichotomy of the eczematous response to allergen in skin was observed. In the initiation phase IL-4 production by TH2 and TH0 cells is predominant over interferon-gamma production by TH1 and TH0 cells. In the late and chronic phases the situation is reversed and interferon-gamma production by TH1 and TH0 cells predominates over IL-4 production by TH2 and TH0 cells. Understanding the relationship between the observed biphasic response and clinical manifestation of AD is important for the development of therapeutic strategies.

アトピー性皮膚炎患者の多元性の検討(1)

アトピー性皮膚炎患者100例に対し, ダニ抗原に対する血中特異IgE値を測定すると共に, 同じ抗原を用いたパッチテストを実施した。その結果, ダニ特異IgE(RAST)値が中間的な値を示すことは少なく, 大部分が高値か低値の群に属したため, 結局, 検討した患者はまず, ダニのパッチテスト陽性群と陰性群に, さらに特異IgEの高値群と低値群の4群に分けられた。さらに各群に属する患者の臨床所見を検討した結果, それぞれの群にある程度特徴的な皮膚病変が存在した。即ち, パッチテストのみ陽性で血中IgE低値の群では, 肘膝関節屈側に皮疹が限局し, 個疹は苔癬化を伴う丘疹様病変であることが多く, 逆にパッチテスト陰性で血中IgE高値の群では, 浮腫性あるいは紅斑性の皮疹を呈することが多く, 顔面の皮疹を伴うことが多かった。パッチテスト陽性かつIgEも高値の患者では顔面, 頚部, 肘膝屈側を含めて広範囲に皮膚病変を呈することが多く, その皮疹は前2群の性格を兼備したような病変, 即ち苔癬化を伴う浸潤性瀰漫性紅斑を典型とすることが多かった。一方で, 両者ともに陰性のアトピー性皮膚炎患者には特徴的な臨床傾向を見い出せなかった。

Atopic dermatitis: a defect of intracellular secondary messenger systems?

The clinical manifestations of atopic dermatitis comprise a complex mixture of pharmacological, physiological and immunological responses. Circumstantial evidence suggests that atopic disease may arise consequent upon the migration of bone marrow-derived cells into the target tissue of skin or respiratory mucosa. Mediator release from such cells has been shown to be abnormal in atopic dermatitis, and itch, the hallmark of the disease, may be the result of chronic inflammatory mediator release into the skin. Abnormal release of mediators has been shown to correlate with inadequate nucleotide control of cell function. In particular, elevated cyclic AMP-specific PDE activity causing cyclic AMP hyporesponsiveness has been found in peripheral blood mononuclear leucocytes in atopic dermatitis. Investigation of this pathway has led to the discovery of additional abnormalities of other secondary messenger systems, including abnormalities of protein kinase C activity and of inositol activation. The biochemical abnormalities may be a consequence of down-regulation of the second messenger systems because of chronic exposure to low levels of inflammatory mediators, but may themselves subsequently permit further mediator release. They may provide a biochemical mechanism for many of the immunological abnormalities seen in atopic dermatitis. In particular, they offer a biochemical explanation for the paradox of increased type 1-mediated immunity and diminished cell-mediated immunity commonly observed in this complex disease.

Natural history and clinical manifestations of atopic dermatitis.

Natural history and clinical manifestations of atopic dermatitis.