Difficult to control atopic dermatitis
- Ulf Darsow1, 2Email author,
- Andreas Wollenberg3,
- Dagmar Simon4,
- Alain Taïeb5,
- Thomas Werfel6,
- Arnold Oranje7,
- Carlo Gelmetti8,
- Ake Svensson9,
- Mette Deleuran10,
- Anne-Marie Calza11,
- Francesca Giusti12,
- Jann Lübbe11,
- Stefania Seidenari12,
- Johannes Ring1, 2 and
- the European Task Force on Atopic Dermatitis / EADV Eczema Task Force
© Darsow et al.; licensee BioMed Central Ltd. 2013
Received: 20 November 2012
Accepted: 4 March 2013
Published: 14 March 2013
Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial / antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. “Eczema school” educational programs have been proven to be helpful.
Atopic dermatitis (AD, atopic eczema, eczema) is an inflammatory, chronically relapsing, and intensely pruritic skin disease occurring often in families with atopic diseases (atopic dermatitis, bronchial asthma and/or allergic rhino-conjunctivitis) . Less than 10% are regarded as severe cases because of disease intensity and extent (SCORAD > 40) or refractory to treatment. Reasons for severe courses of AD are based on individual (e.g. genetic, barrier function, allergies) risc factors and sometimes on therapeutic problems like misunderstandings with regard to topical treatment. Management of exacerbated AD is a therapeutic challenge, as it requires efficient short-term control of acute symptoms, without compromising the overall management plan that is aimed at long-term stabilization, flare prevention, and avoidance of side effects.
The role of contact allergy in AD patients is frequently underestimated [3, 4]. The frequency of contact sensitization in AD, ranging from 41% to 64% according to recent observations, supports the importance of systematic patch testing in atopic patients, adults and children. The most common contact sensitizers are metals, fragrance, preservatives, dyes, neomycin, and lanolin, but contact allergy to topical glucocorticosteroids is also not rare in AD patients.
Contact sensitization may worsen the skin condition of AD patients and influence the course of the disease. Moreover, sensitized AD subjects may respond to very low concentrations of contact allergens, because of their impaired skin barrier function and hyper-reactivity to irritant stimuli enhancing contact reactions.
Topical anti-inflammatory treatment
The use of wet-wrap dressings with (diluted) corticosteroids for up to 14 days (usually applied for 3 days) is a safe crisis intervention treatment of severe and/or refractory AD with temporary systemic bioactivity of the corticosteroids as the only reported serious side-effects [5, 6]. By tradition, anti-inflammatory topical therapy has been administered to lesional skin only and has been stopped or tapered down once visible lesions were cleared. This traditional, reactive approach has in the last years been challenged by the proactive treatment concept, which is defined as a combination of pre-defined, long-term, low dose, anti-inflammatory treatment applied to previously affected areas of skin in combination with liberal use of emollients on the entire body and a predefined appointment schedule for clinical control examinations [7, 8].
Topical corticosteroids (TCS) are a first line anti-inflammatory treatment, applied on inflammatory skin lesions according to needs (pruritus, sleeplessness, new flare). Proactive therapy for flare prevention is also possible with TCS.Topical corticosteroids are grouped by potency, which should be known to prescribers. Potent and very potent corticosteroids (group III and IV) are more likely to cause depression of adrenal function than group I (mild) and II (moderate strength) treatments, but their systemic effects will decrease more quickly due to more rapid restitution of the skin barrier [9, 10]. However, potency ranking of topical steroids in some countries including the US is the reverse of the European system with class I (superpotent) to class VII (low potency). For severe AD, group II and group III (EU system) glucocorticosteroids are recommended. Itch is the key symptom for evaluation of response to treatment, and tapering should not be initiated before the itch has disappeared. Dose tapering should be gradual in order to avoid withdrawal rebound. Tapering strategies consist in using a less potent corticosteroid on a daily base, or keeping a more potent one while reducing the frequency of application (intermittent regimen).
Topical calcineurin inhibitors
Both topical calcineurin inhibitors (TCI), tacrolimus ointment (0.1% and 0.03%) and pimecrolimus cream (1%), are licensed for topical eczema treatment. Various aspects of these drugs have been reviewed in detail . The efficacy of both formulations has been demonstrated against placebo in clinical trials for short term [12, 13] and long term use of these substances [14, 15]. In addition, proactive tacrolimus ointment therapy has been shown to be safe and effective for up to one year in reducing the number of flares and improving the quality of life in adult patients and children [16, 17]. The anti-inflammatory potency of 0.1% tacrolimus ointment is similar to a corticosteroid with intermediate activity , while the latter is clearly more active than 1.0% pimecrolimus cream .
Systemic antihistamines (anti H1) are widely used in acute flares against itch, however few controlled studies are available . Antihistamines may be helpful in decreasing pruritus and permit sleep during flares. In this setting, sedative anti H1 molecules such as hydroxyzine are recommended by clinicians as helpful. Concerning the newer non-sedating H1R specific antihistamines, controlled studies did not show significant effects on eczema.
Anti-bacterial and antimycotic therapy
A number of defects in innate and adaptive immunity may explain the high rate of cutaneous colonization with Staphylococcus aureus (up to 90% in moderate to severe eczema) in AD . There is evidence that a decrease in microbiome diversity is associated with an increased colonization with S. aureus as well as increase in disease activity. Antibiotic eradication of S. aureus may therefore not always be an appropriate long-term strategy, especially with regard to the increasing prevalence of antibiotic resistance [22–24]. In particular topical antibiotics should not be used for longer periods in the treatment of AD. There is evidence for an association of S. aureus-derived superantigens with disease exacerbation [25, 26], supporting early observations that the density of S. aureus colonization in AD is significantly correlated with clinical severity , and that patients with severe AD may improve (but not be cured) by anti-staphylococcal treatment . In general, improvement of eczema by anti-inflammatory therapy (i.e. TCS, TCI, UV) decreases S. aureus colonization.
Other secondary infections, such as yeasts, dermatophytes, and streptococcal infections have also been implicated as disease factors in AD (for a review, see ). Intense, fleshy erythema in skin folds of children with a flare of AD may warrant a search for streptococcal skin infection. In general, signs of secondary infections should be treated if present. Ketoconazole and ciclopiroxolamine are proposed for topical treatment of “head and neck” AD, often associated with Malassezia sympodialis superinfection [29, 30].
Except UVA1, which was shown to be effective in managing AD flares, phototherapy is not indicated in the acute stages of AD, but apt to treat chronic, pruritic, lichenified forms. However, it should not be prescribed in patients who experienced a worsening of their dermatosis during sun exposure. Usually, phototherapy is part of a total treatment plan in addition to topical anti-inflammatory and antimicrobial therapy. As second-level treatment it is used especially in adults. Phototherapy in children younger than 12 years should not be applied under normal circumstances.
Broadband UV (UVA+UVB = 290–400 nm)
Narrow-band UVB (nbUVB = peak:311–313 nm)
UVA1 (340–400 nm).
nbUVB has been indicated for chronic-moderate forms of AD  and is currently preferred to broadband UV because it is less erythemogenic, while high dose UVA1 has been prescribed for more severe phases .
Systemic anti-inflammatory therapy
Non-response to adequately applied topical therapy is rare, and systemic anti-inflammatory treatment should be limited to severe cases in which the potential of topical treatment (or of patient compliance) has been exhausted. An actual overview of the different options has been published . Corticosteroids are rapidly effective, but should only be used for a few weeks, for severe acute exacerbations, because of the many long term side-effects. In severe chronic cases consider starting another systemic anti-inflammatory therapy while tapering the corticosteroid.
The usefulness of both cyclosporin (3–5 mg/kg/day) and azathioprine (2.5 mg/kg/day) has been well documented in clinical trials with children and adults [33–36]. Cyclosporin A therapy is rapidly effective, but has a narrow therapeutic index and requires a close follow-up of renal function. It is an approved substance for systemic treatment of AD in many countries and is frequently used for systemic immunosuppressive therapy in AD.
Azathioprine has a slower onset of action and is not always well tolerated. Low TPMT (thiopurinemethyltransferase) activity is associated with an increased myelotoxicity of azathioprine, but patients at risk can be identified by pre-treatment screening for TMTP activity .
Mycophenolate mofetil (2g/day) seems to offer a comparatively more favourable safety profile and its usefulness in severe AD is documented in both prospective and retrospective studies [37–39], but remains to be assessed in larger randomized trials.
Methotrexate is used by many clinicians as an alternative treatment. Only a few studies have documented its effect and more randomised trials are needed .
Biologic agents (biologicals) present new therapeutic tools in the treatment of recalcitrant AD. They specifically target inflammatory cells and mediators, respectively, and thus may inhibit pathogenically relevant pathways. A number of case reports and pilot studies have been published recently, however representative, randomized, placebo controlled studies evaluating the efficacy and safety of biologicals in AD are still not available. Approaches resulting in reduced T cell activation using agents such as alefacept (fusion protein of lymphocyte function antigen (LFA)-3 (CD58) and immunoglobulin (Ig)G, rituximab (anti-CD20 antibody) and efalizumab (anti-CD11a antibody, no longer available) have been shown to be effective in selected patients with moderate to severe AD and were mentioned in guidelines [2, 41–44].
Educational programs and counselling
In the last decade, education programs for patients and parents were established in different countries in Europe, but also in North and South America (see http://www.opened-dermatology.com). Standardized interdisciplinary programs involving dermatologists, paediatricians, psychologists / psychosomatic counsellors, and dietary counselling have been demonstrated to support the improvement of subjective and objective symptoms, and optimize medication use in patients, and result in a significant gain in quality of life . Participation in one of these programs is highly encouraged.
European Task Force on Atopic Dermatitis / EADV Eczema Task Force: O. Baadsgaard, Hellerup, Denmark; T. Bieber, Bonn, Germany; E. Bonifazi, Bari, Italy; C.A.F.M. Bruijnzeel-Koomen, Utrecht, The Netherlands; A. M. Calza, Geneva, Switzerland; M. Deleuran, Aarhus,Denmark; U. Darsow, Munich, Germany; J. De la Cuadra, Valencia, Spain; L. De Raeve, Brussels, Belgium; T.L. Diepgen, Heidelberg, Germany; P. Dupuy, Castanet Tolosan, France; G. Fabrizi, Rome, Italy; C. Gelmetti, Milan, Italy; A. Giannetti, Modena, Italy; U. Gieler, Gießen, Germany; F. Giusti, Modena, Italy; J. Harper, London, England; E.A. Holm, Copenhagen, Denmark; M. Kägi, Zürich, Switzerland; O. Kekki, Tampere, Finland; B. Kunz, Hamburg, Germany; R. Lever, Glasgow, Scotland; J. Lübbe, Geneva, Switzerland; A.B. Olesen, Aarhus, Denmark; A. P. Oranje, Rotterdam, The Netherlands; Y. de Prost, Paris, France; G. Rajka, Oslo, Norway; T. Reunala, Tampere, Finland; J. Revuz, Créteil, France; J. Ring, Munich, Germany; S. Seidenari, Modena, Italy; D. Simon, Bern, Switzerland; M. Song, Brussels, Belgium; J.F. Stalder, Nantes, France; A. Svensson, Malmö, Sweden; A. Taïeb, Bordeaux, France; D. Tennstedt, Brussels, Belgium; K. Turjanmaa, Tampere, Finland; C. Vestergaard, Aarhus, Denmark; T. Werfel, Hannover, Germany; A. Wollenberg, Munich, Germany
- Handbook of atopic eczema. Edited by: Ring J, Przybilla B, Ruzicka T. 2006, Heidelberg: Springer, 2Google Scholar
- Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, Gieler G, Lipozencic J, Luger T, Oranje AP, Schäfer T, Schwennesen T, Seidenari S, Simon D, Ständer S, Stingl G, Szalai S, Szepietowski JC, Taïeb A, Werfel T, Wollenberg A, Darsow U: Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis) Part I. J Eur Acad Dermatol Venereol. 2012, 26: 1045-1060. 10.1111/j.1468-3083.2012.04635.x.View ArticlePubMedGoogle Scholar
- Manzini BM, Ferdani G, Simonetti V, Donini M, Seidenari S: Contact sensitization in children. Contact Dermatitis. 1998, 15: 12-17.Google Scholar
- Mortz CG, Andersen KE: Allergic contact dermatitis in children and adolescents. Contact Dermatitis. 1999, 41: 121-130. 10.1111/j.1600-0536.1999.tb06102.x.View ArticlePubMedGoogle Scholar
- Devillers AC, Oranje AP: Efficacy and safety of 'wet-wrap' dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature. Br J Dermatol. 2006, 154: 579-585. 10.1111/j.1365-2133.2006.07157.x.View ArticlePubMedGoogle Scholar
- Schnopp C, Holtmann C, Stock S, Remling R, Fölster-Holst R, Ring J, Abeck D: Topical steroids under wet-wrap dressings in atopic dermatitis-a vehicle-controlled trial. Dermatology. 2002, 204: 56-59. 10.1159/000051811.View ArticlePubMedGoogle Scholar
- Wollenberg A, Bieber T: Proactive therapy of atopic dermatitis -an emerging concept. Allergy. 2009, 64: 276-278. 10.1111/j.1398-9995.2008.01803.x.View ArticlePubMedGoogle Scholar
- Van der Meer JB, Glazenburg EJ, Mulder PG, Eggink HF, Coenraads PJ: The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic Dermatitis Study Group. Br J Dermatol. 1999, 140: 1114-1121.View ArticlePubMedGoogle Scholar
- Feiwel M, Munro D, James V: Effect of topically applied 0.1% betamethasone valerate ointment on the adrenal function of children. Thirteenth congress of International Dermatology. 1968, Berlin: Springer, 202-204.Google Scholar
- Walsh P, Aeling J, Huff L, Weston W: Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids. J Am Acad Dermatol. 1993, 29: 501-503. 10.1016/S0190-9622(08)82011-7.View ArticlePubMedGoogle Scholar
- Bornhövd E, Burgdorf WHC, Wollenberg A: Macrolactam immunomodulators for topical treatment of inflammatory skin diseases. J Am Acad Dermatol. 2001, 45: 736-743. 10.1067/mjd.2001.117525.View ArticlePubMedGoogle Scholar
- Ruzicka T, Bieber T, Schöpf E, Rubins A, Dobozy A, Bos J: A short-term trial of tacrolimus ointment for atopic dermatitis. N Engl J Med. 1997, 337: 816-821. 10.1056/NEJM199709183371203.View ArticlePubMedGoogle Scholar
- Van Leent EJ, Graber M, Thurston M, Wagenaar A, Spuls PI, Bos JD: Effectiveness of the ascomycin macrolactam SDZ ASM 981 in the topical treatment of atopic dermatitis. Arch Dermatol. 1998, 134: 805-809. 10.1001/archderm.134.7.805.View ArticlePubMedGoogle Scholar
- Reitamo S, Wollenberg A, Schöpf E, Perrot JL, Marks R, Ruzicka T: Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. Arch Dermatol. 2000, 136: 999-1006. 10.1001/archderm.136.8.999.View ArticlePubMedGoogle Scholar
- Meurer M, Fölster-Holst R, Wozel G, Weidinger G, Jünger M, Bräutigam M: Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Dermatology. 2002, 205: 271-277. 10.1159/000065863.View ArticlePubMedGoogle Scholar
- Wollenberg A, Reitamo S, Girolomoni G, Lahfa M, Ruzicka T, Healy E, Giannetti A, Bieber T, Vyas J, Deleuran M: Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy. 2008, 63: 742-750.View ArticleGoogle Scholar
- Thaci D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, Van Der Valk P, Buckova H, Sebastian M, Schuttelaar M, Ruzicka T: Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol. 2008, 159: 1348-1356. 10.1111/j.1365-2133.2008.08813.x.View ArticlePubMedGoogle Scholar
- Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Friedmann P: Efficacy and safety of tacrolimus ointment compared with hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002, 109: 547-555. 10.1067/mai.2002.121832.View ArticlePubMedGoogle Scholar
- Luger T, Van Leent E, Graeber M, Hedgecock S, Thurston M, Kandra A: SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br J Dermatol. 2001, 144: 788-794. 10.1046/j.1365-2133.2001.04134.x.View ArticlePubMedGoogle Scholar
- Diepgen TL: Long-term treatment with cetirizine of infants with atopic dermatitis: a multi-country, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol. 2002, 13: 278-286. 10.1034/j.1399-3038.2002.01047.x.View ArticlePubMedGoogle Scholar
- De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA: Atopic dermatitis: a disease caused by innate immune defects. J Invest Dermatol. 2009, 129: 14–30-22.View ArticlePubMedGoogle Scholar
- Lübbe J: Secondary infections in patients with atopic dermatitis. Am J Clin Dermatol. 2003, 4: 641-654. 10.2165/00128071-200304090-00006.View ArticlePubMedGoogle Scholar
- Shah M, Mohanraj M: High levels of fusidic acid resistant Staphylococcus aureus in dermatology patients. Br J Dermatol. 2003, 148: 1018-1020. 10.1046/j.1365-2133.2003.05291.x.View ArticlePubMedGoogle Scholar
- Niebuhr M, Mai U, Kapp A, Werfel T: Antibiotic treatment of cutaneous infections with Staphylococcus aureus in patients with atopic dermatitis: current antimicrobial resistances and susceptibilities. Exp Dermatol. 2008, 17: 953-957. 10.1111/j.1600-0625.2008.00734.x.View ArticlePubMedGoogle Scholar
- Bunikowski R, Mielke M, Skarabis H, Worm M, Anagnostopoulos I, Kolde G: Evidence for a disease-promoting effect of staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol. 2000, 105: 814-819. 10.1067/mai.2000.105528.View ArticlePubMedGoogle Scholar
- Zollner T, Wichelhaus T, Hartung A, Von Mallinckrodt C, Wagner T, Brade V: Colonization with superantigen-producing staphylococcus aureus is associated with increased severity of atopic dermatitis. Clin Exp Allergy. 2000, 30: 994-1000. 10.1046/j.1365-2222.2000.00848.x.View ArticlePubMedGoogle Scholar
- Hauser C, Wuethrich B, Matter L: Staphylococcus aureus skin colonization in atopic dermatitis. Dermatologica Helvetica. 1985, 170: 35-View ArticleGoogle Scholar
- Breuer K, Haussler S, Kapp A, Werfel T: Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol. 2002, 147: 55-61. 10.1046/j.1365-2133.2002.04872.x.View ArticlePubMedGoogle Scholar
- Lintu P, Savolainen J, Kortekangas-Savolainen O, Kalimo K: Systemic ketoconazole is an effective treatment of atopic dermatitis with IgE-mediated hypersensitivity to yeasts. Allergy. 2001, 56: 512-517. 10.1034/j.1398-9995.2001.056006512.x.View ArticlePubMedGoogle Scholar
- Mayser P, Kupfer J, Nemetz D, Schäfer U, Nilles M, Hort W, Gieler U: Treatment of head and neck dermatitis with ciclopiroxolamine cream - results of a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2006, 19: 153-158. 10.1159/000092596.View ArticlePubMedGoogle Scholar
- Williams HC, Grindlay DJ: What's new in atopic eczema? An analysis of the clinical significance of systematic reviews on atopic eczema published in 2006 and 2007. Clin Exp Dermatol. 2008, 33: 685-688. 10.1111/j.1365-2230.2008.02906.x.View ArticlePubMedGoogle Scholar
- Akhavan A, Rudikoff D: Atopic dermatitis: systematic immunosuppressive therapy. Semin Cutan Med Surg. 2008, 27: 151-155. 10.1016/j.sder.2008.04.004.View ArticlePubMedGoogle Scholar
- Berth-Jones L, Finlay A, Zaki I, Tan B, Goodyear H, Lewis-Jones S: Ciclosporin in severe childhood atopic dermatitis: a multicentre study. J Am Acad Dermatol. 1996, 34: 1016-1021. 10.1016/S0190-9622(96)90281-9.View ArticlePubMedGoogle Scholar
- Van Joost T, Heule F, Korstanje M, Van-den-Broek M, Stenveld H, Van-Vloten W: Ciclosporin in atopic dermatitis: a multicentre, placebo-controlled study. Br J Dermatol. 1994, 130: 634-640. 10.1111/j.1365-2133.1994.tb13111.x.View ArticlePubMedGoogle Scholar
- Murphy LA, Atherton D: A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 2002, 147: 308-315. 10.1046/j.1365-2133.2002.04922.x.View ArticlePubMedGoogle Scholar
- Berth-Jones J, Takwale A, Tan E, Barclay G, Agarwal S, Ahmed I: Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol. 2002, 147: 324-330. 10.1046/j.1365-2133.2002.04989.x.View ArticlePubMedGoogle Scholar
- Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke W-H, Kaufmann R, Zollner T: Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol. 2001, 137: 870-873.PubMedGoogle Scholar
- Heller M, Shin HT, Orlow SJ, Schaffer JV: Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patients. Br J Dermatol. 2007, 157: 127-132. 10.1111/j.1365-2133.2007.07947.x.View ArticlePubMedGoogle Scholar
- Murray ML, Cohen JB: Mycophenolate mofetil therapy for moderate to severe atopic dermatitis. Clin Exp Dermatol. 2007, 32: 23-27.PubMedGoogle Scholar
- Goujon C, Berard F, Dahel K, Guillot I, Hennino A, Nosbaum A, Saad N, Nicolas JF: Methotrexate for the treatment of adult atopic dermatitis. Eur J Dermatol. 2006, 16: 155-158.PubMedGoogle Scholar
- Simon D, Wittwer J, Kostylina G, Buettiker U, Simon HU, Yawalkar N: Alefacept (lymphocyte function-associated molecule 3/IgG fusion protein) treatment for atopic eczema. J Allergy Clin Immunol. 2008, 122: 423-424. 10.1016/j.jaci.2008.06.010.View ArticlePubMedGoogle Scholar
- Moul DK, Routhouska SB, Robinson MR, Korman NJ: Alefacept for moderate to severe atopic dermatitis: a pilot study in adults. J Am Acad Dermatol. 2008, 58: 984-989. 10.1016/j.jaad.2008.02.007.View ArticlePubMedGoogle Scholar
- Simon D, Hösli S, Kostylina G, Yawalkar N, Simon HU: Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol. 2008, 121: 122-128. 10.1016/j.jaci.2007.11.016.View ArticlePubMedGoogle Scholar
- Darsow U, Wollenberg A, Simon D, Taïeb A, Werfel T, Oranje A, Gelmetti C, Svensson A, Deleuran M, Calza AM, Giusti F, Lübbe J, Seidenari S, Ring J for the European Task Force on Atopic Dermatitis / EADV Eczema Task Force: ETFAD / EADV Eczema Task Force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol. 2010, 24: 317-328. 10.1111/j.1468-3083.2009.03415.x.View ArticlePubMedGoogle Scholar
- Staab D, Diepgen TL, Fartasch M, Kupfer J, Lob-Corzilius T, Ring J: Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial. BMJ. 2006, 332: 933-938. 10.1136/bmj.332.7547.933.PubMed CentralView ArticlePubMedGoogle Scholar
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