Artigos - Dermatite Atópica
1. Simpson EL, Hanifin JM.
Atopic dermatitis.
J Am Acad Dermatol. 2005 Jul;53(1):115-28. No abstract available.
INTRODUCTION: AD is a chronic inflammatory skin disease that usually occurs in persons with a personal or family history of other atopic conditions, such as asthma and allergic rhinitis. The prevalence is high, especially in children, and it has risen considerably in recent decades, leading to considerable epidemiological study. The past 30 years have also seen an enormous outpouring of laboratory investigations, primarily in the immunological realm. New concepts of causation have proliferated, whereas many old ones have regressed. It is interesting to look back at ideas that seem illogical now to appreciate that the same affinity for new and fashionable trends continues today in our confused and frustrated pursuit of clarity. This is especially true in the immunological realm where nearly every assay gives results that differ from normal controls. As a result, long lists of “abnormalities” have been described, but many are uninterpretable and perhaps meaningless because they were not subjected to comparisons with other eczemas or with other atopic conditions. It is impossible and uncritical in a “synopsis” to reference every paper describing defects in AD, but we have tried to select those that seem most relevant for continued study.
2. Abramovits W.
Atopic dermatitis.
J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93.
Atopic dermatitis (AD) is commonly associated with immunoglobulin E (IgE) antibody-related mechanisms, which are the focus of this article. The vast majority of patients with AD exhibit hyperproduction of IgE, particularly during disease onset or flare. IgE-dependent late-phase reactions may influence the chronic inflammatory response in AD. Clearly, genetics plays a major role in determining who develops AD. However, the recent increase in AD prevalence suggests that a complex interaction between environmental factors and susceptibility genes results in clinical expression of the disorder. These immunologic "triggers" differ among individuals and include various foods, airborne allergens, irritants and contactants, hormones, stress, climate, and microorganisms. Although much about AD remains to be elucidated, our current understanding of its pathophysiology has provided clinicians with the ability to construct more rational therapeutic interventions, including multiple-agent regimens that provide both immediate relief and effective long-term management. Future advances will come from identification of the genes causing this disease and further elucidation of the immunoregulatory mechanisms involved in the pathogenesis of AD.
3. Williams HC.
Clinical practice. Atopic dermatitis.
N Engl J Med. 2005 Jun 2;352(22):2314-24. Review. No abstract available.
4. Pastar Z, Lipozencic J, Ljubojevic S.
Etiopathogenesis of atopic dermatitis--an overview.
Acta Dermatovenerol Croat. 2005;13(1):54-62.
Atopic eczema/dermatitis syndrome is a term that covers different subtypes of atopic dermatitis. The "intrinsic" type of atopic dermatitis is non-IgE-associated, and the "extrinsic" type is IgE-associated atopic eczema/dermatitis syndrome. In the etiopathogenesis of atopic dermatitis there are well known interactions among genetic, environmental, skin barrier, immune factors, and stress. Genetic factors determine the expression of atopic dermatitis as pure or mixed with concomitant respiratory or intestinal allergy, depending on genetic susceptibility. Immunologic abnormalities of type I and type IV reactions have been described in patients with atopic dermatitis. Immunologic triggers are aeroallergens, food allergens, microbial products, autoallergens and contact allergens. Immune reactions determine many features of atopic dermatitis. These immune reactions also include cell mediated or delayed hypersensitivity. The currently accepted model proposes a predominant Th2 cytokine milieu in the initiating stages of acute atopic dermatitis lesions, and a mixed Th1 and Th2 pattern in chronic lesions. A two-phase model includes Th2 initiation with attraction of macrophages and eosinophils, which in turn produce interleukin 12 that is the activator of Th1 type response. Atopic dermatitis skin contains an increased number of IgE-bearing Langerhans cells which bind allergens via the high-affinity IgE receptor (FcepsilonRI). Langerhans cells play an important role in cutaneous allergen presentation to Th2 cells via major histocompatibility molecules. Eosinophilia and IgE production are influenced by type 2 cytokines. Degranulation of eosinophils occurs in the dermis with the release of toxic proteins such as major basic protein and could account for much of the inflammation. Mast cells are increased in number and produce mediators other than histamine that induce pruritus and may have an effect on interferon gamma expression. Mast cells produce a number of proinflammatory cytokines. There is an elevated production of prostaglandin E2 by peripheral monocytes. Prostaglandin E2 has at least two potential roles in the initiation of atopic dermatitis. Firstly, it reduces interferon-gamma production by T helper cells, thereby favoring the initial, dominant Th2 immune response; and secondly, it directly enhances IgE production by B lymphocytes with an increased secretion of interleukin 4, interleukin 5 and interleukin 13. Many lesions of atopic dermatitis result from scratching, thus it is tempting to speculate that immune perturbations in genetically predisposed individuals provoke the release of local pruritogens and keratinocyte-derived cytokines, which then further exacerbate the previously described immune response.
5. Darsow U, Lubbe J, Taieb A, Seidenari S, Wollenberg A, Calza AM, Giusti F, Ring J; European Task Force on Atopic Dermatitis.
Position paper on diagnosis and treatment of atopic dermatitis.
J Eur Acad Dermatol Venereol. 2005 May;19(3):286-95.
The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti-inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti-inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti-inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have proved to be helpful.
6. Hoffjan S, Epplen JT.
The genetics of atopic dermatitis: recent findings and future options.
J Mol Med. 2005 May 18; [Epub ahead of print]
Atopic dermatitis (AD) is a chronic pruritic skin disease affecting up to 15% of children in industrialized countries. AD belongs to the group of allergic disorders that include food allergy, allergic rhinitis, and asthma. A multifactorial background for AD has been suggested, with genetic as well as environmental factors influencing disease development. Genome-wide screens for AD have been completed in four different populations to date. Interestingly, the susceptibility regions identified for AD show little overlap with asthma susceptibility regions, suggesting that, at least in part, separate genes might be involved in the pathogenesis of the different atopic disorders. Instead, some of the identified regions overlap with susceptibility regions for psoriasis, another chronic skin disease. Thus, genes expressed in the skin might play an important role in AD pathogenesis, in addition to genes influencing atopic diatheses. Although no veritable "AD gene" has been identified by positional cloning to date, examples from other complex genetic disorders such as asthma show that this goal is likely to be reached in the near future. Candidate gene studies, on the other hand, have identified 19 genes that were shown to be associated with AD in at least one study. The results of genome-wide screens as well as candidate gene studies are evaluated here in detail.
7. Allam JP, Bieber T, Novak N.
Recent highlights in the pathophysiology of atopic eczema.
Int Arch Allergy Immunol. 2005 Feb;136(2):191-7. Epub 2005 Feb 8. Review
Atopic eczema (AE) belongs to the group of atopic diseases that have become increasingly prevalent over the last decades. The pathophysiology of AE has long remained enigmatic, but much scientific effort has been invested in elucidating the genetic background and the immunological mechanisms underlying AE, leading to a better understanding of this complex disease and to new therapeutic strategies. This review provides an update on the scientific progress that has been achieved in clarifying the pathophysiological mechanisms of AE.
8. Ou LS, Leung DY.
Advances in atopic dermatitis.
Chang Gung Med J. 2005 Jan;28(1):1-8. Review.
Atopic dermatitis (AD) is a highly pruritic, chronic, and relapsing inflammatory skin disorder affecting 10-20% of children worldwide. During the past year there have been significant advances in our understanding of the cellular and immunologic mechanisms underlying AD as well as the immunologic triggers involved in its pathogenesis. The introduction of a new class of topical anti-inflammatory medications, topical calcineurin inhibitors, has significantly increased our treatment options and led to the rethinking of potential management approaches in AD.
9. Boguniewicz M.
Update on atopic dermatitis: insights into pathogenesis and new treatment paradigms.Allergy Asthma Proc. 2004 Sep-Oct;25(5):279-82. Review.
Atopic dermatitis (AD) is a common skin disorder whose prevalence has increased, similarly to other atopic diseases. The immunopathogenesis of AD is complex, although Staphylococcus aureus may play an important role in cutaneous inflammation, possibly resulting from a deficiency in antimicrobial peptide secretion in the skin. Although more than 50% of patients will go on to develop asthma and allergies, atopic dermatitis is often the start of the "atopic march." Studies with topical fluticasone provide a rationale for maintenance therapy, whereas studies with the topical nonsteroidal immunomodulator pimecrolimus in patients as young as 3 months of age suggest that early intervention may be an effective strategy in treating this chronic, relapsing skin disease.
10. Mittermann I, Aichberger KJ, Bunder R, Mothes N, Renz H, Valenta R.
Autoimmunity and atopic dermatitis.
Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):367-71. Review.
PURPOSE OF REVIEW: It has been demonstrated that a considerable percentage of patients suffering from atopic dermatitis mount IgE autoantibodies against a broad variety of human proteins. This review summarizes evidence for autoimmune mechanisms in atopic dermatitis and suggests novel pathomechanisms that may be involved in this disease. RECENT FINDINGS: It has been shown that patients suffering from atopic dermatitis exhibit IgE autoreactivity to human proteins. These autoantigens are expressed in a variety of cell and tissue types. Complementary DNAs coding for IgE autoantigens have been identified, cloned and characterized at the molecular level. Using purified recombinant IgE autoantigens, it has been shown in paradigmatic models that IgE autoimmunity may be a pathogenetic mechanism in atopic dermatitis. Moreover, it has been shown that the levels of IgE autoantibodies are associated with severity of disease. SUMMARY: Patients suffering from severe manifestations of atopy mount IgE autoantibodies against a variety of human proteins. The levels of IgE autoantibodies correspond with disease severity. Several mechanisms of IgE autoimmunity may contribute to the pathogenesis of atopic dermatitis.
11. Donnell AT, Tripathi A.
Atopic dermatitis.
Allergy Asthma Proc. 2004 Jul-Aug;25(4 Suppl 1):S42-3. Review. No abstract available.
12. Haagerup A, Bjerke T, Schiotz PO, Dahl R, Binderup HG, Tan Q, Kruse TA.
Atopic dermatitis -- a total genome-scan for susceptibility genes.
Acta Derm Venereol. 2004;84(5):346-52.
Atopic dermatitis is one of the most common chronic diseases of childhood and closely related to other clinical manifestations of allergy. The incidence is high and still increasing. The genetic contribution to disease development is substantial and complex. Only recently genetic research has begun to focus on this phenotype, and specific susceptibility genes remain to be found. To identify candidate regions holding genes for atopic dermatitis we performed a genome-scan in Danish affected sib-pair families containing sib-pairs matching a phenotype definition of both clinical atopic dermatitis and confirmed specific allergy. The scan was undertaken using 446 microsatellite markers and non-parametric linkage results were obtained from the MAPMAKER/SIBS computer program. We found evidence of linkage to three candidate regions in chromosomes 3p (MLS=2.14), 4p (MLS=2.00) and 18q (MLS=2.25), one of which has not been reported previously. Eight additional regions showed weaker but positive results.
13. Sturgill S, Bernard LA.
Atopic dermatitis update.
Curr Opin Pediatr. 2004 Aug;16(4):396-401. Review.
PURPOSE OF REVIEW: Atopic dermatitis, one of the most common chronic illnesses of childhood, is encountered routinely by all providers of health care to children. RECENT FINDINGS: In recent years there has been a dramatic rise in the prevalence of atopic dermatitis and therefore a rapid increase in the number of studies investigating various aspects of the disease. Consequently, hundreds of publications are released each year, and it is difficult to stay up to date on the latest advances. SUMMARY: This review will examine and summarize recent literature on the diagnosis, epidemiology, pathogenesis, treatment, and complications of atopic dermatitis.
14. Eichenfield LF.
Consensus guidelines in diagnosis and treatment of atopic dermatitis.
Allergy. 2004 Aug;59 Suppl 78:86-92.
Atopic dermatitis is a common condition of great health significance. Consensus-driven guidelines of care or specific practice parameters may be useful, as are treatment algorithms based upon disease severity. Development of consensus guidelines on diagnosis and treatment of atopic dermatitis are discussed, and disease-severity-based guidelines of care proposed.
15. Bardana EJ Jr.
Immunoglobulin E- (IgE) and non-IgE-mediated reactions in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS).
Allergy. 2004 Aug;59 Suppl 78:25-9. Review.
AEDS is a chronic, relapsing, highly pruritic inflammatory skin disease that commonly begins in childhood. Two forms of this disorder exist, i.e. an allergic (extrinsic) form and a nonallergic (intrinsic) form. There are clear genetic, humoral and cellular differences between the allergic and nonallergic forms of AEDS. The allergic variants express local IgE production in affected tissue and both allergic and nonallergic triggers play a major role in the expression of disease. The role of allergens is very important in the immunopathogenesis of AEDS. Nonimmunological triggers play a secondary modulatory role often hampering treatment effort and optimal response to therapeutic efforts.
16. Flohr C, Johansson SG, Wahlgren CF, Williams H.
How atopic is atopic dermatitis?
J Allergy Clin Immunol. 2004 Jul;114(1):150-8. Review.
BACKGROUND: The extent to which the phenotype of atopic dermatitis (AD) is truly atopic has been the subject of much debate. OBJECTIVE: We sought to systematically evaluate the evidence for the value of measurement of IgE antibodies in diagnosing AD and whether knowledge of IgE sensitization increases clinical diagnostic and predictive ability. METHODS: We searched Medline from its inception until September 2003. Only studies that measured atopy as either skin prick test positivity or IgE-antibody sensitization to environmental allergens were included within a descriptive analysis. Because the small number of studies of adequate quality did not allow a formal meta-analysis, we assigned strength of evidence according to predefined quality criteria and ranked studies accordingly. RESULTS: Inclusion of atopy as part of the diagnostic criteria for AD did not enhance the criteria's sensitivity and specificity in relation to the clinical phenotype of AD. The strength of association between atopy and AD varied significantly between hospital studies (47% to 75%; n=14 studies) and was stronger in hospital than in community populations (7.4% to 78%; n=13 studies). Whereas study quality did not have an effect on atopy prevalence in hospital populations, low atopy prevalences in community surveys were seen in less rigidly conducted studies. AD severity was positively associated with the number of positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that measured both. Only one study suggested that IgE-specific sensitization to hen's egg is associated with subsequent development of AD, and 2 studies found that allergen-specific IgE sensitization in patients with AD is a prognostic marker for allergic airway disease in later life. Atopy-associated AD might also have a worse long-term prognosis than AD that is not associated with atopy. CONCLUSION: Although atopy is clearly associated with AD, the role of IgE sensitization in AD needs further study. Current evidence suggests that up to two thirds of persons with AD are not atopic, which implies that continued use of the term atopic dermatitis is problematic. Longitudinal studies are needed to compare the treatment response and prognosis of IgE-associated and non-IgE-associated AD.
17. Hanifin JM, Cooper KD, Ho VC, Kang S, Krafchik BR, Margolis DJ, Schachner LA, Sidbury R, Whitmore SE, Sieck CK, Van Voorhees AS.
Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association "Administrative Regulations for Evidence-Based Clinical Practice Guidelines."
J Am Acad Dermatol 2004;50:391-404.
18. Leung DY, Bieber T.
Atopic dermatitis.
Lancet 2003;361:151-160. Review
Atopic dermatitis is a highly pruritic chronic inflammatory skin disorder affecting 10-20% of children worldwide. Symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. This disease results from an interaction between susceptibility genes, the host's environment, pharmacological abnormalities, skin barrier defects, and immunological factors. New management approaches have evolved from advances in our understanding of the pathobiology of this common skin disorder.
19. Galli E, Cicconi R, Rossi P, Casati A, Brunetti E, Mancino G.
Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches.Curr Mol Med. 2003 Mar;3(2):127-38. Review.
Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic.
20. Barnetson RS, Rogers M.
Childhood atopic eczema.
BMJ. 2002 Jun 8;324(7350):1376-9. Review. No abstract available.
21. Cookson WO, Moffatt MF.
The genetics of atopic dermatitis.
Curr Opin Allergy Clin Immunol 2002;2:383-387.
PURPOSE OF REVIEW: Atopic dermatitis is typified by itchy, inflamed skin. It is increasingly common in the developed world and is a major cause of morbidity in infants and young children. Most children with the disease have high levels of immunoglobulin E and many have concomitant asthma. The cause of the disease is unknown, but it is highly heritable. Identification of the genes and genetic variants underlying atopic dermatitis may lead to new treatments and better classification of children with the disease. RECENT FINDINGS: Preliminary genetic studies have identified genes or clusters of genes that are expressed in the outermost layer of the skin to be just as important as genes that may modify the atopic process. These genes may influence other diseases, including psoriasis. Genome screens in mouse models seem to indicate involvement of some of the equivalent chromosomal regions as for human disease. SUMMARY: The findings suggest that atopy in atopic dermatitis may be a secondary process, rather than the cause of the disease. The barrier function of the skin is seen not to be merely passive. Identification of the genes underlying atopic dermatitis is feasible and likely within a few years.
22. Leung DY, Soter NA.
Cellular and immunologic mechanisms in atopic dermatitis.
J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S1-S12. Review.
Atopic dermatitis is a chronic inflammatory skin disease that is frequently associated with respiratory allergies. Atopic dermatitis develops as a result of a complex interrelationship of environmental, immunologic, genetic, and pharmacologic factors. Efforts to understand the relative contributions of these factors have led to research seeking to identify the relevant effector cells and mediators involved in the pathogenesis of atopic dermatitis. These factors include the pattern of local cytokine release, the differentiation of helper T cells, multiple roles of IgE, skin-directed cell responses, infectious agents, and superantigens. This article reviews these cellular and immunologic mechanisms underlying atopic dermatitis and discusses how an understanding of their role in the inflammatory process may lead to improved treatments for atopic dermatitis.
23. Rystedt I.
Long term follow-up in atopic dermatitis.
Acta Derm Venereol Suppl (Stockh) 1985;114:117-120.
A long-term follow-up study (minimum 24 years) has been carried out on 955 individuals with a history of atopic dermatitis (AD), who in childhood had been in- or out-patients at the Department of Dermatology, Karolinska Hospital, Stockholm. 62% of the in-patients and 40% of the out-patients still had dermatitis at investigation. The most common site was the hands. Eczematous hand involvement in childhood had been of predominant importance for the occurrence of hand eczema in adult life. Both tabular and stepwise logistic regression analyses revealed that the prognostically unfavorable factors as regards healing were, in order of importance, severe (widespread) dermatitis in childhood, family history of AD, associated allergic rhinitis, and/or bronchial asthma (with allergic rhinitis as the dominant of these two factors), female sex and early age at onset. Fewer than 20% of the individuals with all these prognostic factors were healed at the time of investigation, whereas 85% of those with none of the factors were healed. Persistent dry/itchy skin in adulthood was also found to be associated with persistent or recurring AD to a significantly (p less than 0.001) higher degree than normal skin. As this factor cannot be used as a predictor in childhood, it was not included in the regression analyses.
Atopic dermatitis.
J Am Acad Dermatol. 2005 Jul;53(1):115-28. No abstract available.
INTRODUCTION: AD is a chronic inflammatory skin disease that usually occurs in persons with a personal or family history of other atopic conditions, such as asthma and allergic rhinitis. The prevalence is high, especially in children, and it has risen considerably in recent decades, leading to considerable epidemiological study. The past 30 years have also seen an enormous outpouring of laboratory investigations, primarily in the immunological realm. New concepts of causation have proliferated, whereas many old ones have regressed. It is interesting to look back at ideas that seem illogical now to appreciate that the same affinity for new and fashionable trends continues today in our confused and frustrated pursuit of clarity. This is especially true in the immunological realm where nearly every assay gives results that differ from normal controls. As a result, long lists of “abnormalities” have been described, but many are uninterpretable and perhaps meaningless because they were not subjected to comparisons with other eczemas or with other atopic conditions. It is impossible and uncritical in a “synopsis” to reference every paper describing defects in AD, but we have tried to select those that seem most relevant for continued study.
2. Abramovits W.
Atopic dermatitis.
J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93.
Atopic dermatitis (AD) is commonly associated with immunoglobulin E (IgE) antibody-related mechanisms, which are the focus of this article. The vast majority of patients with AD exhibit hyperproduction of IgE, particularly during disease onset or flare. IgE-dependent late-phase reactions may influence the chronic inflammatory response in AD. Clearly, genetics plays a major role in determining who develops AD. However, the recent increase in AD prevalence suggests that a complex interaction between environmental factors and susceptibility genes results in clinical expression of the disorder. These immunologic "triggers" differ among individuals and include various foods, airborne allergens, irritants and contactants, hormones, stress, climate, and microorganisms. Although much about AD remains to be elucidated, our current understanding of its pathophysiology has provided clinicians with the ability to construct more rational therapeutic interventions, including multiple-agent regimens that provide both immediate relief and effective long-term management. Future advances will come from identification of the genes causing this disease and further elucidation of the immunoregulatory mechanisms involved in the pathogenesis of AD.
3. Williams HC.
Clinical practice. Atopic dermatitis.
N Engl J Med. 2005 Jun 2;352(22):2314-24. Review. No abstract available.
4. Pastar Z, Lipozencic J, Ljubojevic S.
Etiopathogenesis of atopic dermatitis--an overview.
Acta Dermatovenerol Croat. 2005;13(1):54-62.
Atopic eczema/dermatitis syndrome is a term that covers different subtypes of atopic dermatitis. The "intrinsic" type of atopic dermatitis is non-IgE-associated, and the "extrinsic" type is IgE-associated atopic eczema/dermatitis syndrome. In the etiopathogenesis of atopic dermatitis there are well known interactions among genetic, environmental, skin barrier, immune factors, and stress. Genetic factors determine the expression of atopic dermatitis as pure or mixed with concomitant respiratory or intestinal allergy, depending on genetic susceptibility. Immunologic abnormalities of type I and type IV reactions have been described in patients with atopic dermatitis. Immunologic triggers are aeroallergens, food allergens, microbial products, autoallergens and contact allergens. Immune reactions determine many features of atopic dermatitis. These immune reactions also include cell mediated or delayed hypersensitivity. The currently accepted model proposes a predominant Th2 cytokine milieu in the initiating stages of acute atopic dermatitis lesions, and a mixed Th1 and Th2 pattern in chronic lesions. A two-phase model includes Th2 initiation with attraction of macrophages and eosinophils, which in turn produce interleukin 12 that is the activator of Th1 type response. Atopic dermatitis skin contains an increased number of IgE-bearing Langerhans cells which bind allergens via the high-affinity IgE receptor (FcepsilonRI). Langerhans cells play an important role in cutaneous allergen presentation to Th2 cells via major histocompatibility molecules. Eosinophilia and IgE production are influenced by type 2 cytokines. Degranulation of eosinophils occurs in the dermis with the release of toxic proteins such as major basic protein and could account for much of the inflammation. Mast cells are increased in number and produce mediators other than histamine that induce pruritus and may have an effect on interferon gamma expression. Mast cells produce a number of proinflammatory cytokines. There is an elevated production of prostaglandin E2 by peripheral monocytes. Prostaglandin E2 has at least two potential roles in the initiation of atopic dermatitis. Firstly, it reduces interferon-gamma production by T helper cells, thereby favoring the initial, dominant Th2 immune response; and secondly, it directly enhances IgE production by B lymphocytes with an increased secretion of interleukin 4, interleukin 5 and interleukin 13. Many lesions of atopic dermatitis result from scratching, thus it is tempting to speculate that immune perturbations in genetically predisposed individuals provoke the release of local pruritogens and keratinocyte-derived cytokines, which then further exacerbate the previously described immune response.
5. Darsow U, Lubbe J, Taieb A, Seidenari S, Wollenberg A, Calza AM, Giusti F, Ring J; European Task Force on Atopic Dermatitis.
Position paper on diagnosis and treatment of atopic dermatitis.
J Eur Acad Dermatol Venereol. 2005 May;19(3):286-95.
The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti-inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti-inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti-inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have proved to be helpful.
6. Hoffjan S, Epplen JT.
The genetics of atopic dermatitis: recent findings and future options.
J Mol Med. 2005 May 18; [Epub ahead of print]
Atopic dermatitis (AD) is a chronic pruritic skin disease affecting up to 15% of children in industrialized countries. AD belongs to the group of allergic disorders that include food allergy, allergic rhinitis, and asthma. A multifactorial background for AD has been suggested, with genetic as well as environmental factors influencing disease development. Genome-wide screens for AD have been completed in four different populations to date. Interestingly, the susceptibility regions identified for AD show little overlap with asthma susceptibility regions, suggesting that, at least in part, separate genes might be involved in the pathogenesis of the different atopic disorders. Instead, some of the identified regions overlap with susceptibility regions for psoriasis, another chronic skin disease. Thus, genes expressed in the skin might play an important role in AD pathogenesis, in addition to genes influencing atopic diatheses. Although no veritable "AD gene" has been identified by positional cloning to date, examples from other complex genetic disorders such as asthma show that this goal is likely to be reached in the near future. Candidate gene studies, on the other hand, have identified 19 genes that were shown to be associated with AD in at least one study. The results of genome-wide screens as well as candidate gene studies are evaluated here in detail.
7. Allam JP, Bieber T, Novak N.
Recent highlights in the pathophysiology of atopic eczema.
Int Arch Allergy Immunol. 2005 Feb;136(2):191-7. Epub 2005 Feb 8. Review
Atopic eczema (AE) belongs to the group of atopic diseases that have become increasingly prevalent over the last decades. The pathophysiology of AE has long remained enigmatic, but much scientific effort has been invested in elucidating the genetic background and the immunological mechanisms underlying AE, leading to a better understanding of this complex disease and to new therapeutic strategies. This review provides an update on the scientific progress that has been achieved in clarifying the pathophysiological mechanisms of AE.
8. Ou LS, Leung DY.
Advances in atopic dermatitis.
Chang Gung Med J. 2005 Jan;28(1):1-8. Review.
Atopic dermatitis (AD) is a highly pruritic, chronic, and relapsing inflammatory skin disorder affecting 10-20% of children worldwide. During the past year there have been significant advances in our understanding of the cellular and immunologic mechanisms underlying AD as well as the immunologic triggers involved in its pathogenesis. The introduction of a new class of topical anti-inflammatory medications, topical calcineurin inhibitors, has significantly increased our treatment options and led to the rethinking of potential management approaches in AD.
9. Boguniewicz M.
Update on atopic dermatitis: insights into pathogenesis and new treatment paradigms.Allergy Asthma Proc. 2004 Sep-Oct;25(5):279-82. Review.
Atopic dermatitis (AD) is a common skin disorder whose prevalence has increased, similarly to other atopic diseases. The immunopathogenesis of AD is complex, although Staphylococcus aureus may play an important role in cutaneous inflammation, possibly resulting from a deficiency in antimicrobial peptide secretion in the skin. Although more than 50% of patients will go on to develop asthma and allergies, atopic dermatitis is often the start of the "atopic march." Studies with topical fluticasone provide a rationale for maintenance therapy, whereas studies with the topical nonsteroidal immunomodulator pimecrolimus in patients as young as 3 months of age suggest that early intervention may be an effective strategy in treating this chronic, relapsing skin disease.
10. Mittermann I, Aichberger KJ, Bunder R, Mothes N, Renz H, Valenta R.
Autoimmunity and atopic dermatitis.
Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):367-71. Review.
PURPOSE OF REVIEW: It has been demonstrated that a considerable percentage of patients suffering from atopic dermatitis mount IgE autoantibodies against a broad variety of human proteins. This review summarizes evidence for autoimmune mechanisms in atopic dermatitis and suggests novel pathomechanisms that may be involved in this disease. RECENT FINDINGS: It has been shown that patients suffering from atopic dermatitis exhibit IgE autoreactivity to human proteins. These autoantigens are expressed in a variety of cell and tissue types. Complementary DNAs coding for IgE autoantigens have been identified, cloned and characterized at the molecular level. Using purified recombinant IgE autoantigens, it has been shown in paradigmatic models that IgE autoimmunity may be a pathogenetic mechanism in atopic dermatitis. Moreover, it has been shown that the levels of IgE autoantibodies are associated with severity of disease. SUMMARY: Patients suffering from severe manifestations of atopy mount IgE autoantibodies against a variety of human proteins. The levels of IgE autoantibodies correspond with disease severity. Several mechanisms of IgE autoimmunity may contribute to the pathogenesis of atopic dermatitis.
11. Donnell AT, Tripathi A.
Atopic dermatitis.
Allergy Asthma Proc. 2004 Jul-Aug;25(4 Suppl 1):S42-3. Review. No abstract available.
12. Haagerup A, Bjerke T, Schiotz PO, Dahl R, Binderup HG, Tan Q, Kruse TA.
Atopic dermatitis -- a total genome-scan for susceptibility genes.
Acta Derm Venereol. 2004;84(5):346-52.
Atopic dermatitis is one of the most common chronic diseases of childhood and closely related to other clinical manifestations of allergy. The incidence is high and still increasing. The genetic contribution to disease development is substantial and complex. Only recently genetic research has begun to focus on this phenotype, and specific susceptibility genes remain to be found. To identify candidate regions holding genes for atopic dermatitis we performed a genome-scan in Danish affected sib-pair families containing sib-pairs matching a phenotype definition of both clinical atopic dermatitis and confirmed specific allergy. The scan was undertaken using 446 microsatellite markers and non-parametric linkage results were obtained from the MAPMAKER/SIBS computer program. We found evidence of linkage to three candidate regions in chromosomes 3p (MLS=2.14), 4p (MLS=2.00) and 18q (MLS=2.25), one of which has not been reported previously. Eight additional regions showed weaker but positive results.
13. Sturgill S, Bernard LA.
Atopic dermatitis update.
Curr Opin Pediatr. 2004 Aug;16(4):396-401. Review.
PURPOSE OF REVIEW: Atopic dermatitis, one of the most common chronic illnesses of childhood, is encountered routinely by all providers of health care to children. RECENT FINDINGS: In recent years there has been a dramatic rise in the prevalence of atopic dermatitis and therefore a rapid increase in the number of studies investigating various aspects of the disease. Consequently, hundreds of publications are released each year, and it is difficult to stay up to date on the latest advances. SUMMARY: This review will examine and summarize recent literature on the diagnosis, epidemiology, pathogenesis, treatment, and complications of atopic dermatitis.
14. Eichenfield LF.
Consensus guidelines in diagnosis and treatment of atopic dermatitis.
Allergy. 2004 Aug;59 Suppl 78:86-92.
Atopic dermatitis is a common condition of great health significance. Consensus-driven guidelines of care or specific practice parameters may be useful, as are treatment algorithms based upon disease severity. Development of consensus guidelines on diagnosis and treatment of atopic dermatitis are discussed, and disease-severity-based guidelines of care proposed.
15. Bardana EJ Jr.
Immunoglobulin E- (IgE) and non-IgE-mediated reactions in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS).
Allergy. 2004 Aug;59 Suppl 78:25-9. Review.
AEDS is a chronic, relapsing, highly pruritic inflammatory skin disease that commonly begins in childhood. Two forms of this disorder exist, i.e. an allergic (extrinsic) form and a nonallergic (intrinsic) form. There are clear genetic, humoral and cellular differences between the allergic and nonallergic forms of AEDS. The allergic variants express local IgE production in affected tissue and both allergic and nonallergic triggers play a major role in the expression of disease. The role of allergens is very important in the immunopathogenesis of AEDS. Nonimmunological triggers play a secondary modulatory role often hampering treatment effort and optimal response to therapeutic efforts.
16. Flohr C, Johansson SG, Wahlgren CF, Williams H.
How atopic is atopic dermatitis?
J Allergy Clin Immunol. 2004 Jul;114(1):150-8. Review.
BACKGROUND: The extent to which the phenotype of atopic dermatitis (AD) is truly atopic has been the subject of much debate. OBJECTIVE: We sought to systematically evaluate the evidence for the value of measurement of IgE antibodies in diagnosing AD and whether knowledge of IgE sensitization increases clinical diagnostic and predictive ability. METHODS: We searched Medline from its inception until September 2003. Only studies that measured atopy as either skin prick test positivity or IgE-antibody sensitization to environmental allergens were included within a descriptive analysis. Because the small number of studies of adequate quality did not allow a formal meta-analysis, we assigned strength of evidence according to predefined quality criteria and ranked studies accordingly. RESULTS: Inclusion of atopy as part of the diagnostic criteria for AD did not enhance the criteria's sensitivity and specificity in relation to the clinical phenotype of AD. The strength of association between atopy and AD varied significantly between hospital studies (47% to 75%; n=14 studies) and was stronger in hospital than in community populations (7.4% to 78%; n=13 studies). Whereas study quality did not have an effect on atopy prevalence in hospital populations, low atopy prevalences in community surveys were seen in less rigidly conducted studies. AD severity was positively associated with the number of positive skin prick test responses or IgE-antibody levels in 7 of 8 studies that measured both. Only one study suggested that IgE-specific sensitization to hen's egg is associated with subsequent development of AD, and 2 studies found that allergen-specific IgE sensitization in patients with AD is a prognostic marker for allergic airway disease in later life. Atopy-associated AD might also have a worse long-term prognosis than AD that is not associated with atopy. CONCLUSION: Although atopy is clearly associated with AD, the role of IgE sensitization in AD needs further study. Current evidence suggests that up to two thirds of persons with AD are not atopic, which implies that continued use of the term atopic dermatitis is problematic. Longitudinal studies are needed to compare the treatment response and prognosis of IgE-associated and non-IgE-associated AD.
17. Hanifin JM, Cooper KD, Ho VC, Kang S, Krafchik BR, Margolis DJ, Schachner LA, Sidbury R, Whitmore SE, Sieck CK, Van Voorhees AS.
Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association "Administrative Regulations for Evidence-Based Clinical Practice Guidelines."
J Am Acad Dermatol 2004;50:391-404.
18. Leung DY, Bieber T.
Atopic dermatitis.
Lancet 2003;361:151-160. Review
Atopic dermatitis is a highly pruritic chronic inflammatory skin disorder affecting 10-20% of children worldwide. Symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. This disease results from an interaction between susceptibility genes, the host's environment, pharmacological abnormalities, skin barrier defects, and immunological factors. New management approaches have evolved from advances in our understanding of the pathobiology of this common skin disorder.
19. Galli E, Cicconi R, Rossi P, Casati A, Brunetti E, Mancino G.
Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches.Curr Mol Med. 2003 Mar;3(2):127-38. Review.
Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic.
20. Barnetson RS, Rogers M.
Childhood atopic eczema.
BMJ. 2002 Jun 8;324(7350):1376-9. Review. No abstract available.
21. Cookson WO, Moffatt MF.
The genetics of atopic dermatitis.
Curr Opin Allergy Clin Immunol 2002;2:383-387.
PURPOSE OF REVIEW: Atopic dermatitis is typified by itchy, inflamed skin. It is increasingly common in the developed world and is a major cause of morbidity in infants and young children. Most children with the disease have high levels of immunoglobulin E and many have concomitant asthma. The cause of the disease is unknown, but it is highly heritable. Identification of the genes and genetic variants underlying atopic dermatitis may lead to new treatments and better classification of children with the disease. RECENT FINDINGS: Preliminary genetic studies have identified genes or clusters of genes that are expressed in the outermost layer of the skin to be just as important as genes that may modify the atopic process. These genes may influence other diseases, including psoriasis. Genome screens in mouse models seem to indicate involvement of some of the equivalent chromosomal regions as for human disease. SUMMARY: The findings suggest that atopy in atopic dermatitis may be a secondary process, rather than the cause of the disease. The barrier function of the skin is seen not to be merely passive. Identification of the genes underlying atopic dermatitis is feasible and likely within a few years.
22. Leung DY, Soter NA.
Cellular and immunologic mechanisms in atopic dermatitis.
J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S1-S12. Review.
Atopic dermatitis is a chronic inflammatory skin disease that is frequently associated with respiratory allergies. Atopic dermatitis develops as a result of a complex interrelationship of environmental, immunologic, genetic, and pharmacologic factors. Efforts to understand the relative contributions of these factors have led to research seeking to identify the relevant effector cells and mediators involved in the pathogenesis of atopic dermatitis. These factors include the pattern of local cytokine release, the differentiation of helper T cells, multiple roles of IgE, skin-directed cell responses, infectious agents, and superantigens. This article reviews these cellular and immunologic mechanisms underlying atopic dermatitis and discusses how an understanding of their role in the inflammatory process may lead to improved treatments for atopic dermatitis.
23. Rystedt I.
Long term follow-up in atopic dermatitis.
Acta Derm Venereol Suppl (Stockh) 1985;114:117-120.
A long-term follow-up study (minimum 24 years) has been carried out on 955 individuals with a history of atopic dermatitis (AD), who in childhood had been in- or out-patients at the Department of Dermatology, Karolinska Hospital, Stockholm. 62% of the in-patients and 40% of the out-patients still had dermatitis at investigation. The most common site was the hands. Eczematous hand involvement in childhood had been of predominant importance for the occurrence of hand eczema in adult life. Both tabular and stepwise logistic regression analyses revealed that the prognostically unfavorable factors as regards healing were, in order of importance, severe (widespread) dermatitis in childhood, family history of AD, associated allergic rhinitis, and/or bronchial asthma (with allergic rhinitis as the dominant of these two factors), female sex and early age at onset. Fewer than 20% of the individuals with all these prognostic factors were healed at the time of investigation, whereas 85% of those with none of the factors were healed. Persistent dry/itchy skin in adulthood was also found to be associated with persistent or recurring AD to a significantly (p less than 0.001) higher degree than normal skin. As this factor cannot be used as a predictor in childhood, it was not included in the regression analyses.
