DRESS syndrome: Part II. Management and therapeutics
01 May 2013-Journal of The American Academy of Dermatology (J Am Acad Dermatol)-Vol. 68, Iss: 5, pp 7-9
TL;DR: In this paper, the appropriate management of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is paramount because it is associated with significant morbidity and mortality.
Abstract: The appropriate management of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is paramount because it is associated with significant morbidity and mortality. This syndrome shares clinical features with other dermatologic conditions, including other severe cutaneous drug reactions, requiring the clinician to carefully examine the proposed criteria to make the appropriate diagnosis. Once the diagnosis of DRESS syndrome has been established, the next step in management is immediate cessation of the causative medication(s). In cases in which the culprit drug is not obvious, clinicians must use their clinical judgment to select which medication to discontinue. They may also utilize patch or lymphocyte transformation tests to aid in identification when appropriate. Topical corticosteroids can be used for symptomatic relief, but systemic steroid therapy is generally required. Other immunosuppressants have also been employed in treatment and show promise in future therapy. Patients with DRESS syndrome should be managed in an intensive care or burn unit for appropriate care and infection control. In addition, appropriate specialists should be consulted based on the affected organ systems. Most patients recover completely after drug withdrawal and appropriate therapy. However, some patients with DRESS syndrome suffer from chronic complications and approximately 10% die, primarily from visceral organ compromise. Controlled clinical trials investigating the most appropriate therapies and their risks, particularly intravenous corticosteroids, are lacking, and would be invaluable in determining the optimal future treatment regimen for DRESS syndrome.
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TL;DR: Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid.
Abstract: Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the rapid development of nonfollicular, sterile pustules on an erythematous base. It is attributed to drugs in the majority of cases. Antibiotics are the most common cause of acute generalized exanthematous pustulosis; however, a wide variety of drugs has been associated with this condition. Typically, within 48 hours of ingesting the causative medication, there is acute onset of fever and pustulosis with leukocytosis. In severe cases there can be mucous membrane and systemic organ involvement. Histologic findings include intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils. Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid.
218 citations
Journal Article•
TL;DR: In this article, the authors describe the most common skin adverse drug reactions, including toxic epidermal necrolysis (TEN), drug reaction with Eosinophilia and systemic symptoms (DRESS), which can result in death.
Abstract: Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. Drug reactions are self-limited diseases and therefore, generally treatment is symptomatic. Prompt diagnosis, identification of, and early withdrawal of all suspect drugs are the most important preliminaries. The management of the patients must be undertaken in specialized intensive care units, with the same main types of therapy as for burns: warming of the environment, correction of electrolyte disturbances, administration of a high caloric enteral intake, and prevention of sepsis. Efficacy of drugs used in some case reports is difficult to evaluate: intravenous immunoglobulins, cyclosporin, cyclophosphamide, pentoxyfilline, and thalidomide have all been tried. Corticosteroid use is debated and is probably deleterious in late forms of TEN. For DRESS, corticoids are used in cases of life-threatening systemic impairment. Specific nursing care and adequate topical management reduce associated morbidity and allow a more rapid re-epithelialization of skin lesions. After healing, follow-up is needed for ophthalmologic and mucous membrane sequelae. Sunblocks are recommended. Testing for glycemia must be done. Avoidance of the responsible drug and chemically related compounds is essential for the patient and first-degree relatives.
211 citations
TL;DR: An overview of DRESS syndrome is provided, including clinical presentations, histopathological features, pathomechanisms, and treatments, as well as emerging studies have outlined the disease more clearly.
Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted. In recent years, emerging studies have outlined the disease more clearly, though several important questions remain unresolved. In this review, we provide an overview of DRESS syndrome, including clinical presentations, histopathological features, pathomechanisms, and treatments.
157 citations
TL;DR: Evidence exists that the presence of the HLA-B*58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide–oxypur inol–HLA-B*,58:00 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction.
Abstract: Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.
127 citations
TL;DR: This review highlights recent advances in the understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
Abstract: Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
123 citations
Cites background or result from "DRESS syndrome: Part II. Management..."
...Antiviral medications such as ganciclovir can be given in addition to steroids and/or IVIg in cases of severe disease with confirmation of viral reactivation [220]....
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...IVIg is one of the most commonly utilized therapies for SJS/TEN and is frequently the adjunctive therapy used for severe cases or pediatric patients [204]....
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...A trend identified in the same study also indicated that cyclosporine demonstrated better survival than IVIg [209]....
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...However, the premature discontinuation of a prospective study regarding the role of IVIg treatment occurred due to severe adverse effects [222]....
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...Plasmapheresis and other immunosuppressive drugs, such as cyclophosphamide, cyclosporine, interferons, muromonab-CD3, mycophenolate mofetil, and rituximab, may also be potential therapies [221]....
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References
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TL;DR: The term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is proposed, to decrease the ambiguity of the denomination of hypersensitivity syndrome.
Abstract: Since the first description by Saltzstein in 1959, the denomination of drug-induced pseudolymphoma was used to describe two cutaneous adverse drug reactions with a histological picture mimicking malignant lymphoma. On the basis of clinical presentation, this term includes two different patterns: (1) hypersensitivity syndrome which begins acutely in the first 2 months after the initiation of the drug and associates fever, a severe skin disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (hypereosinophilia, atypical lymphocytes) and organ involvement such as hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis. The cutaneous histological pattern shows a lymphocytic infiltrate, sometimes mimicking a cutaneous lymphoma, and the mortality rate is about 10%. When organ involvement exists, corticosteroids are often prescribed with dramatic improvement. Relapses may occur. (2) drug-induced pseudolymphoma which has a more insidious beginning with nodules and infiltrated plaques appearing several weeks after the beginning of the drug without constitutional symptoms. A pseudolymphoma pattern is seen on cutaneous histological slides. Complete improvement is usual after drug withdrawal, but a delayed lymphoma is possible. To decrease the ambiguity of the denomination of hypersensitivity syndrome, we propose the term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).
849 citations
TL;DR: Nicorandil may be associated with gastrointestinal ulceration and perforation of the terminal ileum: a possible complication of nicor andil therapy.
Abstract: ulceration. Dis Colon Rectum 2005; 48:1442–6. 4 Egred M, Andron M, Morrison WL. Nicorandil may be associated with gastrointestinal ulceration. BMJ 2006; 332:889. 5 King PM, Suttie SA, Jansen JO, Watson AJM. Perforation of the terminal ileum: a possible complication of nicorandil therapy. Surgeon 2004; 2:56–7. 6 Watson A, Al-Ozairi O, Fraser A et al. Nicorandil associated anal ulceration. Lancet 2002; 360:546–7.
802 citations
TL;DR: The definition of the various clinical patterns of patients with drug‐induced cutaneous side‐effects with systemic symptoms, and their possible relationships with the triggering medication, are improved to help in the identification of the causal drug in difficult situations when the patient is taking several drugs.
Abstract: Summary
Objective To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs.
Methods Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985–2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature.
Results Two hundred and sixteen patients with symptoms and signs consistent with cutaneous drug reactions with systemic symptoms were reported to the FPD during this period of time. Their pattern was similar to published data for these drugs, with fever, cutaneous eruption, hepatic abnormalities and eosinophilia being the most prominent but inconstant symptoms. There are clues suggesting that some particular lesional patterns may exist for some drugs.
Conclusions Although some trends emerge from these retrospective data, they suggest that no clear, unified outline can currently be defined for these multi-organ drug-induced reactions. Instead, a constellation of various symptoms and signs were recorded, that might be sorted in different patterns according to the causal drug, a finding that might indeed improve accurate identification of the causative drug in patients receiving several principal medications at a time. A national prospective study systematically collecting standardized data is required better to define the outlines of these severe adverse drug reactions and to evaluate prognostic data.
579 citations
TL;DR: The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro– from which one concludes to a previous in vivo reaction due to a sensitization, and the finding that drugs can directly interact with the T‐cell receptor, without previous metabolism or need to bind to proteins.
Abstract: Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.
558 citations
TL;DR: This syndrome should be regarded as a reaction induced by a complex interplay among several herpesviruses, antiviral immune responses, and drug-specific immune responses.
444 citations