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Topic:Immunoglobulin E

Immunoglobulin E (IgE) is an antibody class involved in the immune response of horses, particularly in allergic reactions and parasitic infections. It binds to allergens and triggers the release of inflammatory mediators from mast cells and basophils. Elevated levels of IgE are often associated with hypersensitivity disorders, such as insect bite hypersensitivity (IBH) in horses. This page assembles peer-reviewed research studies and scholarly articles that investigate the production, regulation, and clinical implications of Immunoglobulin E in equine health, including its role in allergic conditions and potential as a diagnostic marker.
Production of seven monoclonal equine immunoglobulins isotyped by multiplex analysis.
Veterinary immunology and immunopathology    February 19, 2013   Volume 153, Issue 3-4 187-193 doi: 10.1016/j.vetimm.2013.02.010
Keggan A, Freer H, Rollins A, Wagner B.Horses have 11 immunoglobulin isotypes: IgM, IgD, IgA, IgE, and seven IgG subclasses designated as IgG1-IgG7, each of which are distinguished by separate genes encoding the constant heavy chain regions. Immunoglobulin (Ig) isotypes have different functions during the immune response and pathogen-specific isotypes can be used as indicators for immunity and protection from disease. In addition to existing monoclonal antibodies to various equine Igs, quantification of the individual isotypes requires pure isotype standards. In this report, we describe a fusion between X63-Ag8.653 mouse myeloma ce...
Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcɛRI.
Veterinary immunology and immunopathology    February 11, 2013   Volume 153, Issue 1-2 10-16 doi: 10.1016/j.vetimm.2013.01.008
Sabban S, Ye H, Helm B.The binding of immunoglobulin E (IgE) to its high-affinity receptor (FcɛRI) is the central protein interaction in IgE-mediated allergic reactions. The cross-linking of the IgE/FcɛRI complex, through cognate allergens, on the surface of mast cells and basophil cells results in mediator release, and thus leads to the symptoms of type I hypersensitivity responses in mammals. To develop a baseline value for subsequent equine anti-allergy drug and vaccine research, the interaction of equine IgE with its high-affinity FcɛRI receptor was investigated following the cloning and expression of equine ...
Immunogenomic analysis of insect bite hypersensitivity in a model horse population.
Veterinary immunology and immunopathology    January 3, 2013   Volume 152, Issue 3-4 260-268 doi: 10.1016/j.vetimm.2012.12.013
Vychodilova L, Matiasovic J, Bobrova O, Futas J, Klumplerova M, Stejskalova K, Cvanova M, Janova E, Osickova J, Vyskocil M, Sedlinska M, Dusek L....Equine insect bite hypersensitivity (IBH) is a seasonal IgE-mediated dermatosis caused by bites of insects of the genus Culicoides. A familial predisposition for the disease has been shown but, except for the MHC, the genes involved have not been identified so far. An immunogenomic analysis of IBH was performed in a model population of Old Kladruby horses, all living in the same environment. Clinical signs of IBH were used as phenotypic manifestation of IBH. Furthermore, total serum IgE levels were determined in the sera of these horses and used as an independent phenotypic marker for the immu...
Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity.
Veterinary immunology and immunopathology    November 19, 2012   Volume 151, Issue 1-2 147-156 doi: 10.1016/j.vetimm.2012.11.007
Meulenbroeks C, van der Meide NM, Zaiss DM, van Oldruitenborgh-Oosterbaan MM, van der Lugt JJ, Smak J, Rutten VP, Willemse T.Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFNγ, FoxP3 and CD3(ζ)) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the s...
Equine IgE responses to non-viral vaccine components.
Vaccine    October 23, 2012   Volume 30, Issue 52 7615-7620 doi: 10.1016/j.vaccine.2012.10.029
Gershwin LJ, Netherwood KA, Norris MS, Behrens NE, Shao MX.Vaccination of horses is performed annually or semi-annually with multiple viral antigens, either in a combination vaccine or as separate injections. While this practice undoubtedly prevents infection from such diseases as rabies, equine influenza, West Nile virus, and equine herpes virus, the procedure is not without repercussions. Hypersensitivity reactions, including fatal anaphylactic shock, after vaccination, although uncommon, have increased in incidence in recent years. Studies reported herein document the development of IgE antibodies against non-target antigen components of equine vir...
Reaginic antibodies from horses with recurrent airway obstruction produce mast cell stimulation.
Veterinary research communications    August 12, 2012   Volume 36, Issue 4 251-258 doi: 10.1007/s11259-012-9534-x
Moran G, Folch H, Henriquez C, Ortloff A, Barria M.Reaginic antibodies (IgE and some IgG subclasses) and mast cells play important roles in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. The cross-linking of the receptor initiates a coordinated sequence of biochemical and morphological events that results in exocytosis of secretory granules containing pre-formed inflammatory mediators, secretion of newly formed lipid mediators, and secretion of cytokines. Previously, several studies have invest...
Culicoides obsoletus extract relevant for diagnostics of insect bite hypersensitivity in horses.
Veterinary immunology and immunopathology    July 23, 2012   Volume 149, Issue 3-4 245-254 doi: 10.1016/j.vetimm.2012.07.007
van der Meide NM, Meulenbroeks C, van Altena C, Schurink A, Ducro BJ, Wagner B, Leibold W, Rohwer J, Jacobs F, van Oldruitenborgh-Oosterbaan MM....Insect bite hypersensitivity (IBH) is an allergic dermatitis in horses caused by the bites of Culicoides species. The aim of the present study was to evaluate the applicability of whole body extracts of C. obsoletus (the main species found feeding on horses in the Netherlands), C. nubeculosus (rarely found in The Netherlands) and C. sonorensis (typical for North America) for diagnosis of IBH in horses in The Netherlands. Blood and serum samples of 10 clinically confirmed IBH affected and 10 healthy control horses were used to evaluate the IgE titers (ELISA) against the Culicoides whole body ex...
Inhalant horse allergens and allergies: a review of the literature.
Military medicine    July 20, 2012   Volume 177, Issue 7 877-882 doi: 10.7205/milmed-d-12-00038
Arseneau AM, Hrabak TM, Waibel KH.A wealth of literature exists regarding common allergies to household pets such as cat or dog. Allergy to horse, however, is infrequently discussed in the medical literature despite significant sensitization rates among urban-dwelling subjects without direct exposure to horses. A literature search was conducted in PubMed and additional references were collected from surveying the references of the pulled articles. This review summarizes aspects of IgE-mediated horse allergy including the prevalence and mechanisms for sensitization, clinical presentation, molecular characterization of the major...
Immunoglobulin genes and diversity: what we have learned from domestic animals.
Journal of animal science and biotechnology    June 20, 2012   Volume 3, Issue 1 18 doi: 10.1186/2049-1891-3-18
Sun Y, Liu Z, Ren L, Wei Z, Wang P, Li N, Zhao Y.This review focuses on the diversity of immunoglobulin (Ig) genes and Ig isotypes that are expressed in domestic animals. Four livestock species-cattle, sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including μ, δ, γ, ϵ, and α. Two poultry species (chickens and ducks) express three IgH isotypes, μ, υ, and α, but not δ. The κ and λ light chains are both utilized in the four livestock species, but only the λ chain is expressed in poultry. V(D)J recombination, somatic hypermutation (SHM), and gene conversion (GC) are three distinct mechanisms by which immunog...
Evaluation of IgE levels against Culicoides nubeculosus allergens in Belgian warmblood horses.
Communications in agricultural and applied biological sciences    May 9, 2012   Volume 77, Issue 1 218-222 
Peeters LM, Janssens S, Schaffartzik A, Marti E, Buys N.No abstract available
Equine insect bite hypersensitivity: what do we know?
Veterinary immunology and immunopathology    April 3, 2012   Volume 147, Issue 3-4 113-126 doi: 10.1016/j.vetimm.2012.03.017
Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C.Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin...
Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses.
Veterinary immunology and immunopathology    February 18, 2012   Volume 146, Issue 2 125-134 doi: 10.1016/j.vetimm.2012.02.007
Wagner B, Hillegas JM, Babasyan S.CD23, also called FcεRII, is the low-affinity receptor for IgE and has first been described as a major receptor regulating IgE responses. In addition, CD23 also binds to CD21, integrins and MHC class II molecules and thus has a much wider functional role in immune regulation ranging from involvement in antigen-presentation to multiple cytokine-like functions of soluble CD23. The role of CD23 during immune responses of the horse is less well understood. Here, we expressed equine CD23 in mammalian cells using a novel IL-4 expression system. Expression resulted in high yield of recombinant IL-4/...
Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.
Veterinary immunology and immunopathology    December 1, 2010   Volume 140, Issue 1-2 63-74 doi: 10.1016/j.vetimm.2010.11.016
Heimann M, Janda J, Sigurdardottir OG, Svansson V, Klukowska J, von Tscharner C, Doherr M, Broström H, Andersson LS, Einarsson S, Marti E....Equine insect bite hypersensitivity (IBH) is a seasonally recurrent, pruritic skin disorder caused by an IgE-mediated reaction to salivary proteins of biting flies, predominantly of the genus Culicoides. The aim of this study was to define T cell subsets and cytokine profile in the skin of IBH-affected Icelandic horses with particular focus on the balance between T helper (Th) 1, Th2 and T regulatory (Treg) cells. Distribution and number of CD4+, CD8+ and Forkhead box P3 (FoxP3)+ T cells were characterized by immunohistochemical staining in lesional and non-lesional skin of moderately and seve...
IgE, IgGa, IgGb and IgG(T) serum antibody levels in offspring of two sires affected with equine recurrent airway obstruction.
Animal genetics    November 26, 2010   Volume 41 Suppl 2 131-137 doi: 10.1111/j.1365-2052.2010.02122.x
Scharrenberg A, Gerber V, Swinburne JE, Wilson AD, Klukowska-Rötzler J, Laumen E, Marti E.Equine recurrent airway obstruction (RAO) is a chronic lower airway disease of the horse caused by hypersensitivity reactions to inhaled stable dust, including mould spores such as Aspergillus fumigatus. The goals of this study were to investigate whether total serum IgE levels and allergen-specific IgE and IgG subclasses are influenced by genetic factors and/or RAO and whether quantitative trait loci (QTL) could be identified for these parameters. The offspring of two RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease status, and total serum IgE levels and specifi...
Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity.
Veterinary immunology and immunopathology    October 15, 2010   Volume 139, Issue 2-4 200-209 doi: 10.1016/j.vetimm.2010.10.015
Schaffartzik A, Marti E, Torsteinsdottir S, Mellor PS, Crameri R, Rhyner C.Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an allergic dermatitis of the horse. The aim of our study was to identify, produce and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus relevant for IBH by phage surface display technology. A cDNA library constructed with mRNA derived from C. nubeculosus salivary glands was displayed on the surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH-affected horses. Ten cDNA inserts encoding putat...
Equine neonates have attenuated humoral and cell-mediated immune responses to a killed adjuvanted vaccine compared to adult horses.
Clinical and vaccine immunology : CVI    October 13, 2010   Volume 17, Issue 12 1896-1902 doi: 10.1128/CVI.00328-10
Ryan C, Giguère S.The objectives of this study were to compare relative vaccine-specific serum immunoglobulin concentrations, vaccine-specific lymphoproliferative responses, and cytokine profiles of proliferating lymphocytes between 3-day-old foals, 3-month-old foals, and adult horses after vaccination with a killed adjuvanted vaccine. Horses were vaccinated intramuscularly twice at 3-week intervals with a vaccine containing antigens from bovine viral respiratory pathogens to avoid interference from maternal antibody. Both groups of foals and adult horses responded to the vaccine with a significant increase in ...
Detection of reaginic antibodies against Faenia rectivirgula from the serum of horses affected with Recurrent Airway Obstruction by an in vitro bioassay.
Veterinary research communications    September 3, 2010   Volume 34, Issue 8 719-726 doi: 10.1007/s11259-010-9440-z
Morán G, Folch H, Araya O, Burgos R, Barria M.Reaginic antibodies, mainly of the IgE and some IgG subclasses, play an important role in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of RAO. However, whereas immunological aspects of RAO have been extensively studied, the precise sequence of events is still not well understood and role of IgE in this disease still remains controversial. Therefo...
Respiratory allergy induced by exclusive polysensitization to serum albumins of furry animals.
European annals of allergy and clinical immunology    July 23, 2010   Volume 42, Issue 3 127-130 
Liccardi G, Dente B, Restani P, Senna G, Falagiani P, Ballabio C, D'Amato G.In this report we describe un unusual case of exclusive allergic sensitization to furry animals, as a possible study model to speculate about different modalities ofsensitization to allergens of common and less common mammalian species. A 27-year-old woman referred in our Allergological Centre for the occurrence of conjunctival and severe respiratory symptoms after contact with several animals such as cats, dogs, rabbits, horses, cows etc. Patient underwent clinical and anamnestic evaluation including a detailed information on the modality of exposure to different furry animals. Skin-prick-tes...
Cloning, production and characterization of antigen 5 like proteins from Simulium vittatum and Culicoides nubeculosus, the first cross-reactive allergen associated with equine insect bite hypersensitivity.
Veterinary immunology and immunopathology    April 28, 2010   Volume 137, Issue 1-2 76-83 doi: 10.1016/j.vetimm.2010.04.012
Schaffartzik A, Marti E, Crameri R, Rhyner C.Insect bite hypersensitivity (IBH) is an IgE-mediated seasonal dermatitis of the horses associated with bites of Simulium (black fly) and Culicoides (midge) species. Although cross-reactivity between Simulium and Culicoides salivary gland extracts has been demonstrated, the molecular nature of the allergens responsible for the observed cross-reactivity remains to be elucidated. In this report we demonstrate for the first time in veterinary medicine that a homologous allergen, present in the salivary glands of both insects, shows extended IgE cross-reactivity in vitro and in vivo. The cDNA sequ...
Skin prick test to horse should be included in the standard panel for the diagnosis of respiratory allergy.
Journal of investigational allergology & clinical immunology    March 18, 2010   Volume 20, Issue 1 93-94 
Liccardi G, Salzillo A, Piccolo A, D'Amato G.No abstract available
Intradermal testing of horses with and without insect bite hypersensitivity in The Netherlands using an extract of native Culicoides species.
Veterinary dermatology    February 25, 2010   Volume 20, Issue 5-6 607-614 doi: 10.1111/j.1365-3164.2009.00832.x
Sloet van Oldruitenborgh-Oosterbaan MM, van Poppel M, de Raat IJ, van den Boom R, Savelkoul HF.Intradermal tests using a Culicoides nubeculosus extract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch species C. obsoletus and C. pulicaris. Thirteen pairs of horses were tested, each pair consisting of one horse with IBH and the other a healthy control. Each horse was injected intradermally with 0.1 mL of three concentrations of Culicoides whole body extract (1 : 1000 w/v, 1 : 10,000 w/v and 1 : 25,000 w/v), histamine solution (0.01 mg/mL, po...
Effects of dexamethasone and hydroxyzine treatment on intradermal testing and allergen-specific IgE serum testing results in horses.
Veterinary dermatology    February 25, 2010   Volume 20, Issue 5-6 615-622 doi: 10.1111/j.1365-3164.2009.00837.x
Petersen A, Schott HC.To determine whether dexamethasone or hydroxyzine affect intradermal testing (IDT) and allergen-specific IgE serum testing (ASIST) results in horses, these tests were performed serially in five horses without signs of atopic dermatitis before and after treatment with the drugs. IDT consisted of saline, histamine (1:100,000 w/v) and eight commercial extracts; results were evaluated as subjective scores by comparison to saline (0) and histamine (4) and as objective measurement of wheal diameter (mm). After baseline testing, dexamethasone (20 mg) was administered intramuscularly daily for 7 days....
Induction of interleukin-4 production in neonatal IgE+ cells after crosslinking of maternal IgE.
Developmental and comparative immunology    December 16, 2009   Volume 34, Issue 4 436-444 doi: 10.1016/j.dci.2009.12.002
Wagner B, Stokol T, Ainsworth DM.Transfer of maternal IgE antibodies to the neonate with the colostrum has been described in different mammalian species. Previous work in horses has shown that IgE bound to the surface of neonatal basophils is solely of maternal origin. However, the functional role of the maternal IgE transfer remained unclear. We hypothesized that maternal IgE mediates the onset of innate IL-4 production in equine neonatal basophils. Intracellular IL-4 production was measured in PBMC of newborn and older foals by flow cytometric analysis. A small population of IL-4(+) cells was observed in the peripheral bloo...
In vitro bioassay to detect reaginic antibodies from the serum of horses affected with recurrent airway obstruction.
Veterinary research communications    December 10, 2009   Volume 34, Issue 1 91-99 doi: 10.1007/s11259-009-9334-0
Morán G, Burgos R, Araya O, Folch H.In horses, Recurrent Airway Obstruction (RAO) is an allergic disease that involves IgE mediated Type I Hypersensitivity responses. The development of this type of allergy involves a series of events that begins with reaginic antibodies, mainly IgE and some IgG subclasses. These reaginic antibodies bind with high affinity, via the Fc portion, to FcepsilonRI receptors on the membrane of mast cells and basophils. Once bound, environmental allergens cross-link the antibodies, which results in mast cell degranulation leading to the production of histamine and other chemical mediators that act toget...
Insect bite hypersensitivity in the horse: comparison of IgE-binding proteins in salivary gland extracts from Simulium vittatum and Culicoides nubeculosus.
Veterinary immunology and immunopathology    September 24, 2009   Volume 132, Issue 1 62-67 doi: 10.1016/j.vetimm.2009.09.016
Hellberg W, Mellor PS, Torsteinsdóttir S, Marti E.Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis of horses caused by bites of insects such as Culicoides or Simulium spp. The aim of the present study was to compare the IgE-binding pattern of sera of IBH-affected horses to Culicoides nubeculosus and Simulium vittatum salivary gland extracts (SGE). Individual IgE responses to proteins of S. vittatum and C. nubeculosus SGEs were evaluated in 15 IBH-affected and three healthy horses on immunoblots. Fourteen out of the 15 IBH-affected but none of the healthy horses showed individual IgE binding patterns to seven and six m...
IgE in horses: occurrence in health and disease.
Veterinary immunology and immunopathology    September 23, 2009   Volume 132, Issue 1 21-30 doi: 10.1016/j.vetimm.2009.09.011
Wagner B.Since the initial characterization of IgE by Ishizaka et al. (1966), IgE was described in several mammalian species. In horses, a single gene encoding the IgE heavy chain constant region (IGHE gene) exists per haploid genome and several allelic variants of the equine IGHE gene were found. IgE occurs in its soluble form in equine serum and physiological concentrations of total IgE are around 1000-fold higher in normal horse than in normal human serum. Maternal IgE is enriched in the colostrum and transferred to the neonatal foal after birth. Foals do not produce detectable concentrations of end...
Cloning of IgE-binding proteins from Simulium vittatum and their potential significance as allergens for equine insect bite hypersensitivity.
Veterinary immunology and immunopathology    September 23, 2009   Volume 132, Issue 1 68-77 doi: 10.1016/j.vetimm.2009.09.017
Schaffartzik A, Weichel M, Crameri R, Björnsdóttir TS, Prisi C, Rhyner C, Torsteinsdóttir S, Marti E.Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of Culicoides and sometimes Simulium spp. The aim of this investigation was to identify Simulium allergens associated with IBH. A phage surface display cDNA library expressing recombinant Simulium vittatum salivary gland proteins was screened using sera of IBH-affected horses sensitized to S. vittatum salivary gland proteins as shown in immunoblot, resulting in the identification of seven cDNAs encoding IgE-binding proteins. The deduced amino acid sequences of these proteins showed sequence similarities to a...
Sensitization of skin mast cells with IgE antibodies to Culicoides allergens occurs frequently in clinically healthy horses.
Veterinary immunology and immunopathology    September 23, 2009   Volume 132, Issue 1 53-61 doi: 10.1016/j.vetimm.2009.09.015
Wagner B, Miller WH, Erb HN, Lunn DP, Antczak DF.IgE antibodies are mediators of mast cell degranulation during allergic diseases. The binding of IgE to its high-affinity IgE receptor on mast cell surfaces is called "sensitization" and precedes the development of clinical allergy. Previously, intradermal injection of anti-IgE or the anti-IgG(T) antibody CVS40 induced immediate skin reactions in horses. This suggested that both IgE and IgG(T) sensitize equine skin mast cells. Here, we investigated sensitization to allergen and with IgE or IgG(T) in clinically healthy horses of different age groups. In addition, immediate skin reactions to Cul...
Increased IL-4 and decreased regulatory cytokine production following relocation of Icelandic horses from a high to low endoparasite environment.
Veterinary immunology and immunopathology    July 9, 2009   Volume 133, Issue 1 40-50 doi: 10.1016/j.vetimm.2009.07.002
Hamza E, Torsteinsdottir S, Eydal M, Frey CF, Mirkovitch J, Brcic M, Wagner B, Wilson AD, Jungi TW, Marti E.Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides spp. IBH does not occur in Iceland where Culicoides are absent. However, following importation into continental Europe where Culicoides are present, >or=50% of Icelandic horses (1st generation) develop IBH but
Dietetic effects of oral intervention with mare’s milk on the Severity Scoring of Atopic Dermatitis, on faecal microbiota and on immunological parameters in patients with atopic dermatitis.
International journal of food sciences and nutrition    May 21, 2009   Volume 60 Suppl 7 41-52 doi: 10.1080/09637480802249082
Foekel C, Schubert R, Kaatz M, Schmidt I, Bauer A, Hipler UC, Vogelsang H, Rabe K, Jahreis G.In a double-blind, placebo-controlled crossover trial, 23 patients consumed 250 ml mare's milk or placebo for 16 weeks. The aim was to examine the effects of mare's milk on the characteristics of atopic dermatitis (AD), on faecal microbiota and on clinical and immunological parameters. The intensity of AD was examined using the Severity Scoring of Atopic Dermatitis (SCORAD) index. During the mare's milk period, the mean SCORAD value of patients (n=23; 17 females, 6 males) decreased from 30.1 to 25.3 after 12 weeks (P<0.05) and to 26.7 after 16 weeks (P<0.1). In a subgroup (n=7) the SCORA...