DRESS syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.; Kiran Singh, M.D. [2]

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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe adverse drug reaction. The exact pathogenesis of DRESS syndrome is poorly understood, but it is thought that genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites following drug administration and subsequent activation of immunologic reactions. The incidence of DRESS syndrome is approximately 10 to 100 per 100,000 drug exposures with a case-fatality rate of approximately 10%. DRESS syndrome has been reported among patients of all age groups with neither gender nor racial predilection. Common symptoms of DRESS syndrome include rash and fever. DRESS syndrome is characterized by a prolonged latency period (2-8 weeks following the administration of triggering drug). If left untreated, DRESS syndrome self-resolves following the discontinuation of the triggering drug in the majority of cases, but clinical manifestations may persist up to 3 months. Complications of DRESS syndrome include visceral organ involvement and development of chronic autoimmune diseases. Common physical examination findings of patients with DRESS syndrome include high-grade fever, diffuse exanthematous eruption (commonly exfoliative dermatitis), lymphadenopathy, facial edema, abdominal tenderness, and hepatomegaly. Laboratory findings of patients with DRESS syndrome usually differ depending on the organ involvement. Common Lab findings include anemia, eosinophilia, atypical lymphocytosis, monocytosis, thrombocytopenia, and elevated anti-HHV6 antibodies (viral reactivation). Drug withdrawal is the first step in the management of DRESS syndrome. Supportive care is considered the mainstay of therapy, and hospitalization and administration of pharmacologic agents is usually necessary. Medical therapy for the management of DRESS syndrome usually include topical and/or systemic corticosteroids, antipyretic agents, and symptomatic management of exfoliative dermatitis (fluids, nutritional support, management of electrolyte imbalances, and sepsis prevention).

The early descriptions of DRESS syndrome were made in the 1940s and 1950s. The term DRESS syndrome was first coined by Helene Bocquet, a French dermatologist, in 1996.

There is no classification system established for DRESS syndrome.

The exact pathogenesis of DRESS syndrome is poorly understood. It is thought that an interaction between genetic and environmental factors is responsible for the development of DRESS syndrome. Genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions. A post-viral reaction (T-cell cross-reacion) has also been postulated due to the high incidence of viral reactivation following DRESS syndrome. On histopathological analysis of skin biopsy, DRESS syndrome is not characterized by a specific finding. Common histopathological findings include non-specific lymphocytic and eosinophilic infiltration with involvement of the papillary dermis and evidence of epidermotropism.

DRESS syndrome is an adverse drug reaction. Common causes of DRESS syndrome include anticonvulsants, allopurinol, antiviral agents, and antibiotics, but virtually all drugs may cause DRESS syndrome.

DRESS syndrome must be differentiated from other diseases that cause fever, rash, and visceral involvement, such as exanthematous pustulosis, psoriasis, Still’s disease, toxic epidermal necrolysis, Stevens-Johnson syndrome, lymphoma, serum sickness, drug-induced liver injury, and Staphylococcal scalded skin syndrome.

The incidence of DRESS syndrome is approximately 10 to 100 per 100,000 drug exposures. The case-fatality rate of DRESS syndrome is approximately 10%. DRESS syndrome has been reported among patients of all ages with no gender or racial predilection.

There are no established risk factors in the development of DRESS syndrome. Possible risk factors in the development of DRESS syndrome include positive family history and rapid dose escalation of the triggering agent.

Screening for DRESS syndrome in the general population is not recommended.

DRESS syndrome is characterized by a prolonged latency period (2-8 weeks following the administration of triggering drug). If left untreated, DRESS syndrome self-resolves following the discontinuation of the triggering drug in the majority of cases, but clinical manifestations may persist up to 3 months and the long-term sequelae have not yet been identified. Complications of DRESS syndrome include visceral organ involvement and long-term autoimmune diseases. The prognosis of DRESS syndrome is generally good, and the case-fatality rate is approximately 10%. Factors associated with worse prognosis have not yet been established.

There is no gold standard for the diagnosis of DRESS syndrome. Two diagnostic criteria have been proposed: The RegiSCAR criteria and the Japanese Consensus Group criteria.

Common symptoms of DRESS syndrome rash and fever.

Common physical examination findings of patients with DRESS syndrome include high-grade fever, diffuse exanthematous eruption, lymphadenopathy, facial edema, abdominal tenderness, and hepatomegaly.

Laboratory findings of patients with DRESS syndrome usually differ depending on the organ involvement. Common Lab findings include anemia, eosinophilia, atypical lymphocytosis, monocytosis, and thrombocytopenia.

Other diagnostic studies for DRESS syndrome include elevated anti-HHV-6 antibody due to viral reactivation, positive lymphocyte activation test, patch testing, and possibly rechallenging of the suspected drug.

Drug withdrawal is the first step in the management of DRESS syndrome. Supportive care is considered the mainstay of therapy, and hospitalization and administration of pharmacologic agents is usually necessary. Medical therapy for the management of DRESS syndrome usually include topical and/or systemic corticosteroids, antipyretic agents, and symptomatic management of exfoliative dermatitis (fluids, nutritional support, management of electrolyte imbalances, and sepsis prevention). Additional therapies have been attempted with variable success, including the use of N-acetylcysteine, intravenous immunoglobulins, and cyclosporin.

There are no established measures for the primary prevention of DRESS syndrome. Primary prevention measures may include slow dose escalation of drugs (e.g. anticonvulsants), genetic counseling to patients with affected relatives, and in vitro impaired detoxification testing.

Secondary preventive measures to avoid DRESS syndrome include avoidance of drug re-exposure, screening for cross-reacting agents using in vitro lymphocyte toxicity assays, and possibly desensitization techniques.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

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The early descriptions of DRESS syndrome were made in the 1940s and 1950s. The term DRESS syndrome was first coined by Helene Bocquet, a French dermatologist, in 1996.

• DRESS syndrome was first described by Saltzstein in 1959. However, it is thought that DRESS syndrome may have described earlier since the 1940s following the introduction of hydantoin and reports of hydantoin-induced lymphadenopathy.^[1]
• Initially, DRESS syndrome was occasionally termed either drug-induced pseudolymphoma given its clinical presentation that often mimics lymphoma or anticonvulsant hypersensitivity syndrome given its association with use of anticonvulsant agents.^[2][3]
• The term DRESS syndrome was first coined by Helene Bocquet, a French dermatologist, in 1996.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

There is no classification system established for DRESS syndrome.

• There is no classification system established for DRESS syndrome.
• To view the classification of drug eruptions, of which DRESS syndrome belongs to, click here.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

The exact pathogenesis of DRESS syndrome is poorly understood. It is thought that an interaction between genetic and environmental factors is responsible for the development of DRESS syndrome. Genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions. A post-viral reaction (T-cell cross-reacion) has also been postulated due to the high incidence of viral reactivation following DRESS syndrome. On histopathological analysis of skin biopsy, DRESS syndrome is not characterized by a specific finding. Common histopathological findings include non-specific lymphocytic and eosinophilic infiltration with involvement of the papillary dermis and evidence of epidermotropism.

The exact pathogenesis of DRESS syndrome is poorly understood. It is thought that an interaction between genetic and environmental factors is responsible for the development of DRESS syndrome.

• Genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions.^[1] DRESS syndrome is more common among slow acetylators.^[2]
• The variation of the incidence of DRESS syndrome across families and ethnicities may suggest a significant role for genetics in the pathogenesis of DRESS syndrome.^[3]
• DRESS syndrome is associated with certain human leukocyte antigen (HLA), such as:^[4][5][6][7]

• HLA-B*1502
• HLA-B*1508
• HLA-B*5701
• HLA-B*5801

• It is thought that toxic accumulation of metabolites results in the activation of interleukin-5 (IL-5), which results in the activation of eosinophils and the downstream inflammatory cascade.^[8][9][1]
• It is unknown how drug interactions are associated with viral activation and clinical manifestations of DRESS syndrome, but expansion of both virus-specific and non-specific T-cells is often observed with DRESS syndrome and herpes virus reactivation (e.g. CMV, EBV, HHV6, and HHV-7) is common among patients with DRESS syndrome. Accordingly, it has been postulated that in addition to the clonal expansion of drug-specific T-cells, antiviral T-cells may cross-react with drugs and result in concomitant expansion of viral-specific T-cells.^[10]

DRESS syndrome is not characterized by a specific finding on histopathological analysis of skin biopsy. The following findings may be present:^{[11][12][13][14]}

• Non-specific lymphocytic infiltration, typically in the perivascular superficial dermis
• Abundance of eosinophils
• Band-like infiltrate of atypical lymphocytes
• Involvement of the papillary dermis
• Dermal edema
• Spongiosis
• Acanthosis
• Vacuolization
• Epidermotropism that resembles mycosis fungoides

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2], Yazan Daaboul, M.D., Serge Korjian M.D.

DRESS syndrome is an adverse drug reaction. Common causes of DRESS syndrome include anticonvulsants, allopurinol, antiviral agents, and antibiotics, but virtually all drugs may cause DRESS syndrome.

• DRESS syndrome is an adverse drug reaction.
• Classically, DRESS syndrome has been associated with anticonvulsant agents, but virtually all drugs may cause DRESS syndrome.

The following drugs have commonly been associated with DRESS syndrome:

The following drugs have also been reported to be associated with DRESS syndrome:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

DRESS syndrome must be differentiated from other diseases that cause fever, rash, and visceral involvement, such as exanthematous pustulosis, psoriasis, Still’s disease, toxic epidermal necrolysis, Stevens-Johnson syndrome, lymphoma, serum sickness, drug-induced liver injury, and Staphylococcal scalded skin syndrome.

Differential diagnoses of DRESS syndrome include the following:

• Acute generalized exanthematous pustulosis
• Angioimmunoblastic lymphadenopathy
• Autoimmune hepatitis
• Cholecystitis
• CMV mononucleosis
• Dermatitis
• Drug-induced liver injury
• Drug-induced nephrotoxicity
• EBV mononucleosis
• Gilbert syndrome
• Hypereosinophilic syndrome
• Kawasaki disease
• Lymphoma
• Psoriasis
• Serum sickness
• Staphylococcal scalded skin syndrome
• Stevens-Johnson syndrome
• Still’s disease
• Toxic epidermal necrolysis
• Vasculitis
• Viral exanthem
• Viral hepatitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

The incidence of DRESS syndrome is approximately 10 to 100 per 100,000 drug exposures. The case-fatality rate of DRESS syndrome is approximately 10%. DRESS syndrome has been reported among patients of all ages with no gender or racial predilection.

• The incidence of DRESS syndrome is approximately 10 to 100 per 100,000 drug exposures.^[1]

• The case-fatality rate of DRESS syndrome is approximately 10%.

• DRESS syndrome affects patients of all ages and has been reported among pediatric, adult, and elderly patients.^[1]
• In modest-sized observational studies and case series:

• The median age for the development of DRESS syndrome is approximately 40-50 years among adult patients.^[2][3]
• The median age for the development of DRESS syndrome is approximately 10-12 years among pediatric patients.^[4]

• There is no gender predilection to the development of DRESS syndrome.

• There is no racial predilection to the development of DRESS syndrome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

There are no established risk factors in the development of DRESS syndrome. Possible risk factors in the development of DRESS syndrome include positive family history and rapid dose escalation of the triggering agent.

• There are no established risk factors for the development of DRESS syndrome.
• Possible risk factors in the development of DRESS syndrome include:

• Positive family history for DRESS syndrome^[1][2]
• Rapid dose escalation of the triggering drug^[3]

To view the list of drugs that are associated with DRESS syndrome, click here.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.

Please help WikiDoc by adding content here. It’s easy! Click here to learn about editing.

Screening for DRESS syndrome in the general population is not recommended.

• Screening for DRESS syndrome in the general population is not recommended.

To view primary preventive measures to avoid DRESS syndrome, click here. To view secondary preventive measures to avoid DRESS syndrome, click here.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

DRESS syndrome is characterized by a prolonged latency period (2-8 weeks following the administration of triggering drug). If left untreated, DRESS syndrome self-resolves following the discontinuation of the triggering drug in the majority of cases, but clinical manifestations may persist up to 3 months and the long-term sequelae have not yet been identified. Complications of DRESS syndrome include visceral organ involvement and long-term autoimmune diseases. The prognosis of DRESS syndrome is generally good, and the case-fatality rate is approximately 10%. Factors associated with worse prognosis have not yet been established.

• DRESS syndrome is characterized by a prolonged latency period.
• Clinical manifestations of DRESS syndrome are usually delayed. Earliest manifestations may appear 2-8 weeks following the administration of triggering drug.
• Initially, patients usually develop non-specific signs and symptoms, namely fever and rash that involves the face, upper trunk, and upper extremities, making the early diagnosis of DRESS syndrome difficult upon patient presentation.
• Additional clinical manifestations follow, and patients may subsequently develop lymphadenopathy, visceral disease (typically liver involvement), and worsening of the skin eruption.
• The nature of the visceral involvement is thought to be associated with the identity of the triggering drug:^[1]

• Hepatic and GI involvement has been associated with abacavir
• Renal involvement has been associated with allopurinol
• Pulmonary involvement has been associated with abacavir and minocycline

• If left untreated, DRESS syndrome self-resolves following the discontinuation of triggering drug in the majority of cases, but clinical manifestations may persist up to 3 months and the long-term sequelae have not yet been identified.

• Organ involvement is considered the most important complication of DRESS syndrome.
• Complications of DRESS syndrome include the following:

• Hepatitis and hepatic necrosis
• Acute interstitial nephritis
• Chronic kidney disease
• Pneumonitis
• Eosinophilic pneumopathy
• Eosinophilic myocarditis
• Pleuritis
• Pericarditis
• Myositis
• Uveitis
• Pancreatitis
• Encephalitis
• Meningitis

• Long term complications often include the development of autoimmune diseases, such as:

• Autoimmune hemolytic anemia
• Graves’ disease
• Insulin-dependent diabetes mellitus

• The prognosis of DRESS syndrome is generally good.
• The case-fatality rate of DRESS syndrome is approximately 10%. Mortality is most commonly due to fulminant hepatic failure.
• Factors associated with worse prognosis of DRESS syndrome have not yet been established. Early drug discontinuation has been suggested as a favorable prognostic factor^[2], whereas extent of affected body surface area is thought to be a poor prognostic factor.
• Administration of corticosteroid therapy has not been demonstrated to be associated with reduced risk of death, ^[3], but patients who do not undergo slow corticosteroid tapering (over several weeks) are thought to be at an increased risk of relapse.

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