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Ibuprofen Risks of Stevens Johnson Syndrome (SJS / TEN)

  • Erythema Multiforme (Stevens-Johnson Syndrome) (Infectious Diseases)...Erythema multiforme (also known as Stevens-Johnson syndrome [SJS]) and toxic epidermal necrolysis (TEN) are often confused in the medical literature. In ...
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    Causes of Stevens Johnson Syndrome (SJS / TEN)

     

    Video: Allergic reaction made her face peel off

    In 2005, Eva Uhlin was on vacation with her family when she fell ill with toxic epidermal necrolysis, a rare allergic reaction to over-the-counter pain medication.

    She shares her story along with her father, Lars Uhlin, and dermatologist Dr. Jeanine Downie.

     

    Stevens Johnson Syndrome (SJS / TEN) Treatment and Outcomes

     

    Luis Fernando Ramírez, Pascal Demoly

    Allergy Unit, Inserm U657, University Hospital of Montpellier; Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, 34295 Montpellier cedex 05, France

     

    While there is no standard treatment, the management of fluid and electrolyte requirements and antibiotics in case of a sepsis are of most importance. Other drugs given in addition to supportive care, such as corticosteroids, thalidomide, ciclosporin A, high-dose intravenous immunoglobulins, TNF antagonists are often used on an individual basis, but, there are few proper evaluations of these treatments. To date, a specific therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis that has shown efficacy in controlled clinical trials unfortunately does not exist (6).

    In the present study, 6 patients had Stevens-Johnson syndrome and 1 toxic epidermal necrolysis. They were rapidly treated with high-dose glucocorticosteroids (more than 5 mg/kg) with good results. None of the patients died. Side effects were acceptable (1 hypokaliemia, 1 bradycardia without any consequences). Systemic glucocorticosteroids were in fact the standard treatment until the early 1990’s, with little evidence until a small retrospective monocenter study suggesting that a short course of high dose dexamethasone may be of benefit (7) in 12 patients included over a period of 10 years. The EuroSCAR retrospective case-control study concluded however, that glucocorticosteroids did not show a significant effect on mortality in comparison with supportive care only (8). Controlled studies are indeed needed, including more severe patients, given the example of intravenous immunoglobulins which were shown to be dramatically effective in case reports and some non-controlled clinical studies and still remain controversial, because of studies with negative or even opposite results (6).


    References


    1. Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME. Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev. 2008;7:598-605.


    2. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes JN, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35-44.


    3. Díaz J, Bonilla D, Ramírez AF, Herrera M, Ramírez LF, Serrano C. Dosis altas de corticoides sistémicos en pacientes con síndrome de Stevens-Johnson y necrolisis epidérmica tóxica: descripción de siete casos y revisión de la literatura. Rev Col Dermatol. 2011;19:13-9


    4. Sekula P, Liss Y, Davidovici B, Dunant A, Roujeau JC, Kardaun S, Naldi et al. Evaluation of SCORTEN on a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis included in the RegiSCAR Study. J Burn Care Res. 2011;32:237-45.


    5. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11:349-56.


    6. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39.


    7. Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. Acta Derm Venereol. 2007;87:144-8.


    8. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008;58:33-40.

     

    Treating Stevens-Johnson syndrome and toxic epidermal necrolysis with high doses of glucocorticosteroids

    Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced diseases with a low incidence but high mortality. Numbers come mainly from large cohorts such as the European Registry of Severe Cutaneous Adverse Reactions (EuroSCAR study, http://regiscar.uni-freiburg.de) and others.

    Thus, the annual incidences of Stevens-Johnson syndrome and toxic epidermal necrolysis are estimated to be between 1.2 to 6 and 0.5 to 1.2 cases per million inhabitants, respectively1. Mortality rate has been estimated as high as 30-50% for toxic epidermal necrolysis and lower in Stevens-Johnson syndrome patients (5%).

    The most commonly associated drugs include antimicrobial sulphonamides, betalactams, anticonvulsants (except valproic acid), allopurinol, nevirapine, and oxicam-NSAIDS (such as piroxicam)(1,2). Most, but not all, cases occur within the first 8 weeks of drug exposure.


    In Colombia, no such data are available. But assuming that the incidence is the same as in Europe and the USA, at least 75 cases occur each year in Colombia.
    Stevens-Johnson syndrome and toxic epidermal necrolysis are considered to be the same disease but of different severities across a spectrum, with their distinction largely based on the degree of skin detachment: 1-10% (Stevens-Johnson syndrome), 10-30% (overlap syndrome) and >30% (toxic epidermal necrolysis).

    The most important aspects in the diagnosis include the detachment of at least 1% of the body surface area in addition to the involvement of at least one mucous membrane, together with an appropriate temporal relationship to the implicated drug.


    Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis.

    Ideally, the diagnosis should be made by a physician with adverse drug reaction experience, and this was the case in the study published in this journal issue where the authors treated with high dose corticosteroids 7 patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (3).

    Severity and prognosis are linked to clinical extension, a rapid recognition of the disease, prompt withdrawal of the culprit drugs and appropriate supportive care, ideally in an intensive care unit. Severity is currently best appreciated using the SCORTEN (4), a severity-of-illness score for Stevens-Johnson syndrome and toxic epidermal necrolysis based on a minimal set of well-defined variables calculated within 24 hours of admission. In the present study the initial SCORTEN of the patients is unknown.

    Very few risk factors have been identified so far. Clearly some drugs are more prone to Stevens-Johnson syndrome and toxic epidermal necrolysis and some HLA B alleles play a role in some ethnies. For example, a strong association between carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis has been described for HLA-B*1502 in a Han Chinese population (5).

    In European and Japanese patients, HLA-B*1502 does not seem to be a risk factor, highlighting the importance of ethnicity in genetic predisposition. Collecting data from every country may help to better dissect the pathophysiology and better understand this disease.


    Stevens-Johnson syndrome and toxic epidermal necrolysis is a life threatening condition and therefore supportive care is an essential part of the therapeutic approach. Early referral to burn centers increases the survival rate.

    What is Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis?

     

    Acta Dermatovenerol Croat. 2011 Mar;19(1):73.

    Side Effects in Dermatology. The File of Adverse Reactions of Medicines (FARM) Ninth edition. International Medical Publishers b. v., Naarden, The Netherlands, 2009. Pages 152, soft cover. ISBN 978-90-5884-004-2.

    Abstract

    In their daily routine, dermatovenereologists frequently encounter various drug side effects. Therefore, the new edition of this small but very useful book is highly welcome.

    The ninth edition marks the 36th anniversary of the appearance of the book Side Effects in Dermatology. Guide to Adverse Drug Reactions. As new drugs appear daily on the market, so ever new drug reactions are being reported.

    However, the editors note that, tending to be as concise as possible, they tried to update rather than extend the references. Side effects due to local application of drugs on the skin are not included in this guide unless the side effects are systemic in nature.

    A special chapter entitled List of Cutaneous Adverse Reactions brings numerous side effects manifesting on the skin in alphabetical order, from acanthosis nigricans through xerosis.

    The fourth chapter consisting of some 60 pages offers extensive list of drugs along with the most common cutaneous side effects and accompanied by respective references. Whenever possible, references are as a rule limited to one recent reference on a particular adverse reaction.

    A special chapter is dedicated to some clinical manifestations, i.e. acneiform eruptions, alopecia, hypotrichosis, hypertrichosis and hirsutism.

     

    Drug induced hypersensitivity syndrome (DIHS), eczematous and exanthematous types of drug eruptions, exfoliative dermatitis, fixed drug eruptions, granulomatous drug reactions (GDR), lichenoid and lupus-like drug reactions are described.

     

    There also are descriptions of pseudolymphomas and some forms of lymphoma that may develop as manifestations of hypersensitivity to some drugs. According to localization, drug side effects manifesting as nail and oral lesions, photosensitivity, hyper- and hypopigmentation, psoriasis induction or exacerbation, purpura and scleroderma-like reactions, urticaria and vascular reactions are presented.

    The book offers thorough descriptions of severe cutaneous adverse reactions (SCAR), i.e. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

    The last, sixth chapter brings 1893 references (first author, journal name, year, volume and pages).

    This excellent handbook should find place in the library of every dermatovenereologist, however, it will certainly prove highly useful also to every medical practitioner.