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ePaper created 2014-09-15, 12:31:02 | version 1.32.01
Historically, corticosteroids were advocated, but after reports with a negative outcome in the 80s of last century, they were increasingly regarded as harmful and even detrimental by some authors. Building on J.S. Pasricha’s use of pulse therapy with dexamethasone/cyclophosphamide for pemphigus in 1988, the group around Van der Meer reappraised the use of corticosteroids in SJS/TEN.[1] The assumption was that the negative general opinion was due to the fact that low-dose corticosteroids, administered for too long and too late in the process, are hardly therapeutically effective, raise the risk of infection and possibly have a negative effect on wound healing. The rationale was that a short course of high-dose corticosteroids, administered earlier in the process, might possibly influence the immune-mediated cascade, leading to massive apoptosis. We developed an overall treatment protocol with high-dosed pulse therapy with 1.5mg/kg bodyweight dexamethasone on three consecutive days, and reported a low mortality.[2] Although the controversy on treatment modalities has not been settled, the general opinion is less negative nowadays and this protocol has become widely followed. Current opinion is that systemic corticosteroids are clearly deleterious in the late stage of SJS/TEN while in the early stage their benefits are not yet evidenced. Derived from Van der Meer’s propagation of pulse therapy, Jonkman embarked on the first randomized double-blind clinical trial in pemphigus (PEMPULS), and found that pulse therapy did not appear to have any benefit in pemphigus above standard therapy with prednisolon and azathioprine.[3] The study on cADR in general and severe cADR such as acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms in particular, has led to the appointment of Kardaun as head of the Reference Center for Cutaneous Adverse Drug Reactions in the Netherlands.[4,5] Besides a national role in treatment, this has resulted in cooperation with a leading multinational study group (RegiSCAR), as well as multiple publications, in particular on classification problems in severe cADR and a thesis on severe cADR.[6] References 1. Meer JB van der. On behalf of the TEN working group. Stevens-Johnson-syndroom en toxische epidermale necrolyse; therapiebeleid bij deze levensbedreigende ziekten. Ned Tijdschr Geneeskd 1996; 140: 1538-43. 2. Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. Acta Derm Venereol 2007; 87: 144-8. 3. Mentink LF, Mackenzie MW, Tóth GG, et al. Randomized controlled trial of adjuvant oral dexamethasone pulse therapy in pemphigus vulgaris: PEMPULS trial. Arch Dermatol 2006; 142: 570-6. 4. Kardaun SH, Kuiper H, Fidler V, et al. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol 2010; 37: 1220-9. 5. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 2007; 156: 609-11. 6. Kardaun SH. Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN). In: SH Kardaun ed. Severe cutaneous adverse drug reactions, challenges in diagnosis and treatment. Thesis, Groningen, 1st ed. Oisterwijk: BOXPress; 2012. p.31-56. 55 BWEADVSMGFINCORR:Opmaak 1 21-07-2014 17:40 Pagina 55