Parasites Induced Skin Allergy J Clin Med Res • 2010;2(6):247-255 Th2 cell phenotype and the selective loss of effector activity, against a background of regulatory T cells, alternatively ac- tivated macrophages, and Th2-inducing dendritic cells. The sum effect of these changes to host reactivity is to create an “anti-inflammatory” environment, which is most favorable to parasite survival [33]. In Echinococcus multilocularis in- fection, a combined Th1 and Th2 cytokine profile appears crucial for prolonged metacestode growth and survival. Vuit- ton has demonstrated that Th1 cytokines promote the initial cell recruitment around the metacestode and are involved in the chronicity of the cell infiltrate leading to a fully orga- nized periparasitic granuloma and its consequences, fibrosis and necrosis [25]. Meanwhile, the Th2 cytokines could be responsible for the inhibition of a successful parasite kill- ing, especially because of the “anti-inflammatory” potency of IL-10. This combination of various arms of the immune response results in a partial protection of both Echinococcus metacestode and host [25, 34]. However, it may also be con- sidered responsible for several complications of the disease. The Th2-related IgE synthesis and mast cell activation, well known to be responsible for anaphylactic reactions in cystic echinococcosis, are more rarely involved in ‘allergic’ com- plications in alveolar echinococcosis [25]. With regards to Anisakis simplex, it shares several epitopes with IL-4, impor- tant for the Th2 response development in human anisakiasis, where the parasite may modulate the Th1-Th2 dichotomy for its own benefit by mucosal inflammation control in an at- tempt to avoid the larval expelling [26]. An additional factor of the IgE response induction: the inhibition of complement pathway Apart from the increasing of the tissue permeability and lar- vae penetration, the induction of IgE response may have an additional advantage for the development of parasites in the hostile organism. In contrast to IgG, the IgE antibody does not activate the complement system. In animal experiments, IgG is shown to activate complement, and therefore, to kill the L3 larvae of Angiostrongylus cantonensis [35]. In vivo, however, the classic pathway activation can be avoided be- cause IgE does not interact with fraction C1 of the comple- ment [36]. Regarding the complement inhibition in humans, the larval L3 products of anisakis exercised a stronger ef- fect on the classical pathway than on the alternative one, constituting a mechanism to evade host defenses, similarly to other parasitic diseases. In this context, detailed studies revealed that larval products of Anisakis simplex act at the level of the C3 and C2 proteins, which are early components of the classical complement pathway [37, 38]. These find- ings suggest that parasites cannot “switch off” the humoral host immunity, but they could induce the Th2 profile. The Th2/IgE response may assure better survival possibilities for the parasites within the host due to parasitic avoidance of the complement pathway. Urticaria as symptom of parasite migration through the biological barriers Apart from parasitoses, the IgE response is also strongly as- sociated with pathogenesis of the immediate allergic diseas- es such as urticaria, angioedema, etc. Despite expectations, the association of the skin allergic reactions with presence of parasitic infections does not rely on hard data [7]. Recently, much evidence is collected about the interaction’s details be- tween the hosts and parasites, but fewer attempts are made to clarify the urticarial puzzle during parasitoses. Reflecting on these findings, it could be mentioned that urticaria is a skin manifestation, related to helminths or arthropods with a cutaneous phase: Schistosoma, Sarcoptes scabiei, as well as ticks and other blood sucking arthropods have been involved in Th2-based immunologic mechanisms [39, 40]. Among patients with toxocaral infection, an elevated ECP level was significantly associated with both cough and rhinitis, a high level of specific anti-toxocara IgE with itchy rashes [41]. Loeffler’s syndrome, which resembles the pathophysiologi- cal features of chronic asthma with its Th2-related immuno- logic feature, is related to ascaris and necator infection, both of which have an obligatory pulmonary phase [42]. Some helminths like necator and schistosoma have even both a cutaneous and pulmonary phase [43]. Such pathologies as larva migrans or cercarial dermatitis are also examples of the skin migration. Being attempts to find the suitable host environment, the parasitic induction of urticaria, atopic phe- notype, itching and the increased tissue permeability could favorise larvae migration and therefore, the completing of the parasitic life cycle [13, 16]. In the case of human ani- sakiasis, this would be a hopeless attempt to destroy hostile barriers (intestinal wall, etc) to search for the missed suitable environment, because they cannot develop within terrestrial mammalians. Consequently, the type I allergic reaction takes at least 2 to 6 hours to be triggered by alive larvae, while the ingestion of lyophilized larvae, or its equivalent in antigen, does not induce clinical symptoms in sensitized individuals [44, 45]. A similar scenario develops also within paratenic hosts during larvae migration in different visceral organs, like in case of Toxocara canis [46]. These data suggest that the development of allergic symptoms could be an active ef- fect of parasites and not only a host defense reaction. In some particular cases, IgE and IgG values will differ depending on the time relapsed between the parasitic contact and therefore on its developing phase [47]. During infection of mice with Litomosoides sigmodontis, female adult worms from prepatent infections protects mice injected with lipo- polysaccharide due to inhibition of the host Th1 response, whereas microfilariae worsen lipopolysaccharide-induced sepsis through the induction of the Th1-related cytokines in the peripheral blood [31]. Similarly to the immune modula- tion, Giardia lamblia can express different kinds of variant surface proteins (VSP). The giardial variant-type formation Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org 249