Etiopathogenesis Of Atopic Dermatitis :

Malek Fathi Abou Agwa

Atopic dermatitis (AD) remains a puzzlin disorderi.nwhich a variety of factors are involved i the initiationand evolution of the disease. These factorsare the consequence of specific multiple abn- rmalitieswhich could all together account for the eti, pathogenesisof AD.The term AD is now commonly accepted afte : avariety of synonyms. Although it opens to Cl .ticismit appears to be the best name of the diseasE Recently,Rajka, 1983 proposed his own definiti In”Atopic dermatitis is a specific dermatitis i theabnormality reacting skin of atopic individua s,resulting in itch with its sequalae,as well. s ineczematous inflammation”.The true incidence of AD could not be det. rmined.Some new data reflected a raised incidence in tnfantsand in cold and dry geographical areas. On tl ~ otherhand ,the occurence of the disease in hot lndhumid areas is also well· known. Seen from·a. 9 .obaLaspect the real prevalence of AD has changed t ,causemore people than formerly now have access to rr !dicalcare. In addition, some environmental Lnf Lue .cesmay also contribute to the increased occurenc , ofAD. Discussing the different theories postul .tedfor the etiopathogenesis of AD through analys s ofthe different data and correlation between th setheories, could clarify the most supportive e iologicaltheory.The genetic theory was supported by the p sitivefamilial history being encountered in nearly 11cases of AD and t~e association of AD cases w thasthma, rhinitis and hay fever. The associat on ofAD with other congenital defects with derma to ogicalor systemic is one of the proofs given for th stheory. The specific mode of inheritance in Dhas not yet been defined. This was explained bythe fact that what is inherited is not a skin diseasebut a tendency to pruritus which become evidenton exposure of the skin to stressful Lrrt rnalor external environment.The physiologic theory is generally governe, bythe dry skin of the atopic patients. Several factorswere considered in explanation of suchdrynes: forexample decreased sweating, decerased TWL, de, ~ea-.sed sebum, decreased cohesion between corne oc- tes,epidermal vasculature changes and excessive sc ling.Remissions and exacerbations of the disease wi h seasonal variations is a good support of the p ysiologictheory in atopic patients. Sweating ,rovokingstimuli as physical exercise shows the im .ortanceof sweat training therapy in AD, both are corr latedpositively with the physiologic theory. The e ’idenceof different surface lipids composition, as we I asthe isolation of staphylococcus aureus in high r incidencecould be attributed to the physiologic theory.The autonomic imbalance theory with beta a .renergicblokade (Szentivanyis theoryl968) resu ts ininhibition of beta adrenergic receptors, activ .tionof alpha adrenergic and cholinergic receptors. Thebeta adrenergic inhibition will result in incr ·asedneurons exci tabili ty, decreased threshold of C .taneousitching and increased intracellular cAMP with .bnormalcell proliferation and inhibition of epidermal mitosis.This will be manifested clinically by lichenif cationand pruritus. The increased activity of the a phaadrenergic receptors will activate the vascula . reactionand pilomotor smooth muscle reaction. Th.s ismanifested clinically by different grades of ~ .llor,white dermographism (vascular theory) together withfollicular keratosis of the skin. The active :ion ofcholinergic receptors will directly affect t ie sweatglands with clinical presentation of oligo/ar lidroseswith subsequent dry skin (physiologic theory)Accordingly, lymphocytes, polymorphonuclear ] ,ucocytesand even m st cells could be affected ~ .th thechanges in different enzymes and histamine. :gElevel was proved to be highly increased (Imml ioLoqd ctheory). The most accepted explanation of tt .stheory is that the fundamental abnormality cc lId bean inherited (genetic theory)or acquired .defe :t inadenyl cyclase enzyme.being that identified t)· the betaadrenergic receptors. This could be happened withreduced synthesis, partial blockage and defec .iveenzyme molecule.The immunologic theory expanded several i munologicalabnormalities in AD patients. Such a ,normalitiesare not only due to defects in the hum ral orcellular immunity or defects in autonomic bal nce butalso they are more likely to be factors assoc atedwith disease activity and severity.The immunological mechanism necessitates hepresence of an allergen. Several allergens w reidentified in atopic patients. Sun exposure, foodsinhalents, danders lipid solvents, irritants, nd allfactors leading to dry skin. The allergenica lyactive material finds its way to the target c, 11where in the first stage it causes atopic sen: itizationto be followed by atopic reaction. By a- Jpicsensitization, the allergen enters through na ur a Lportal to react with reagin forming cell. Rei :linproduced ”f Lxe s II to reacting cell (example rna: t cell)containing inactive or bound mediator, for exe nple,histamine. By a.:opic reaction, the antigen a< ’linenters by natural portal and contacts reagin j i.xedto reacting cell. Antigen reagin reaction cal sesrelease of mediator for example, histamine c orrtainedin mast cell granules. Mediator exert!pharmacologic effect on shock organ to cause ! rmptoms,Although 19E is the most common high Lmmi 10-globulin detected in AD, but there is no doub1 that19E antibodies and atopic anaphylactic suscep1 lbilityare a concomitant phenomenon of AD and nc -the fundamental disorder. 19E directly or inc -rectly through abnormal immune regulation is c msideredto be responsible for a rapid start 01itching, its continuity and/or persistence. J ,soit shares in the production.of the inflammatoz rreactions of the skin with all its clinical me Iifestationsknown as late cutaneous reaction (] rt.ephase of the immediate type)of immunological eaction.This phenomenon is based on the release of mediatorsfrom surface of mast cells or basophils durin’ an IgE -anti-IgE reaction. Different authors discuss. j therole of IgE in AD with several arguments a qa i i st andseveral arguments with, but no body could den orneglect the role of IgE in AD. Reports on Chi 1gesin other immunoglobulins are fewer but statin~ themarked increase of IgG, moderate increase of l JM,normal value of IgA and decreased IgD levels.The delayed hypersensitivity or cell mediat !dimmune response (CMI) in AD was long discussecSuppression of T cell function is the main fac corwith all its results. Clinically it enhances :heinflammatory process responding to exogenous alergensfor example, viral,fungal and bacterial. Also.( car ) through T cell population versus 19B evelwith resultant high proportion of lymphocytes aving19B bound to their membranes. Suppression of cellfunction also results in increased sensitivity ofT cell to cAMP and histamine with all its clin calreplications.The vascular theory is positively argumented {iththe abnormal vascular responses to variety oj stimulirising from physiological, environmental, gel ~ticor immunological factors, these reactions Lnr ludeskin pallor, changes in skin temperature, val aeonstrictiontendency in areal circulation and I ~itedermographism. Some altered pharmacologic r. ~ctionscould be contributed to these vascular man.i.f. stations.Acetyl choline with an altered pharmacologic reactionresult in the del~yed blanch phenomenon whicJ occursfrequently in patients with AD. Other alter, ~ pharmacologicalreaction in AD patients is recor, ed aswith histamine prostaglandin, brady kinin, erotinin,kalikenin and catecholamine.The psychoclogical theory plays some part in theinitiation, aggrevation or perpetuation of t e disease.The personality trait in AD was reg rdedin the past as a fixed and irrevocable featu e.-In fact, the personality deviation observed n ADis considered as a result not a cause. The oleof maternal rejection in AD is not clear but itis of great importance in contribution to thseverity of the disease. Thevpsychological lspectsof AD were considered by some authors in the , :mtextsof immunology, where emotional effects has prj ved tohave a great incidence in the immune system a: :1manifestedin skin diseases.Correlations between different lines of tr. atanent;followed in AD and the etiopathogenesis of th. diseaserevealed a very positive correlation suppo.r t Li :J themultifactorial opinion in etiology of the dis, ’!se.In conclusion. the etiology of AD could n01 beattributed to only one theory, but a group of theoriescorrelated and interacting with each other cal beconsidered the ideal etiopathogenesis of the ( isease.These include the genetic, the physiological, theautonomic, the immunological, the vascular, tl ~ alteredpharmacologic and the psychological. Tl ~setheories act and/or interact with resulting Lr oaLancein the autonomic system presenting the main f, ~turesof the disease. This comes into conclusion tl ~t theprimary and predisposing is the genetic theor~ Themost mastering theory is the autonomic theory Theclinical manifestations of the disease are th, directexpression of the autonomic ”disturbances. Th idealtreating regime should include drug, supporti e andimmunologic therapy.