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Refers to drug rash with eosinophilia and systemic symptoms (DRESS).
A severe cutaneous drug corruption characterized by fever, rash, lymphadenopathy, internal organ involvement, and hematologic abnormalities.
Most commonly involved organs are the liver, lungs, kidneys and blood abnormalities include lymphocytopenia, atypical lymphocytes, and eosinophilia.
Nonspecific presentation.
It is frequently asymptomatic early and considerable time passes after the initial drug exposure, making diagnosis difficult.
Typically presents within 1-2 months of drug initiation.
Pathogenesis is unclear and it may have a genetic origin.
Studies report that reactivation of human herpesvirus 6 and 7, Epstein-Barr virus, and cytomegalic virus can occur at the onset of the syndrome.
Drugs commonly associated include: antiepileptic agents, allopurinol, sulfa drugs, antibiotics, and psychotropic medications.
Incidence estimated to be 1 per 1000-10,000 individuals exposed to commonly used drugs.
Mortality rate estimated to be 10-20%.
The acronym Drug Reaction with Eosinophila and Systemic Symptoms (DRESS)
Characterized by an extensive rash, fever, lymphadenopathy, hematologic abnormalities, hepatitis, and involvement of the kidneys, lungs, heart, or pancreas.
Diagnosis based on a history of diffuse rash occurring 2-8 weeks after exposure to a new medication, associated with fever, lymphadenopathy, diffuse morbilliform rash, facial edema, atypical lymphocytosis, peripheral eosinophilia, elevated liver function tests.
The heart is affected and 4-27% of patients, which causes an inflammatory myocarditis and this important to recognize cardiac involvement early because it can be fatal it in up to 50% of cases.
The onset of symptoms is often delayed, occurring 2–6 weeks after drug initiation.
Acute liver injury is the most common internal organ manifestation and usually follows a cholestatic pattern of injury.
Most patients have full hepatic function recovery.
DRESS syndrome shares many characteristics in common with anticonvulsant hypersensitivity syndrome (AHS).
Ref2242ed to as drug-induced hypersensitivity syndrome (DIHS).
Kidney injury is common and generally mild.
Ocular involvement is extremely rare.
The incidence of DRESS has been estimated to be between 1 in 1,000 and 1 in 10,000 drug exposures.
It carries a mortality rate of 10–20%, with most fatalities the result of liver failure.
Skin biopsy findings are variable and considerably overlap with other skin pathologies.
Skin biopsy findings include spongiosis, acanthosis, interface vacuolization, lymphocyte infiltration, and dermal edema.
The most common biopsy finding is perivascular infiltration with lymphocytes, granulocytes, and eosinophils.
Eosinophils act by binding antibody bound cells and release contents of cytotoxic granules, which is the mechanism whereby they cause organ damage in the heart, liver, and lungs.
Treatment consists of supportive therapy, corticosteroids, and antihistamines.
Discontinuation of the offending drug is the most critical step in management.
Fluid management may be beneficial, and the patient should be treated similarly to a burn patient.
Considered an idiosyncratic reaction.
Three potential causative factors have been identified 1) a defect in drug metabolism resulting in the failure to eliminate toxic reactive intermediates, 2) reactivation of human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), or cytomegalovirus (CMV), which may serve as a trigger for the reaction, and 3) a genetic predisposition that alters immune response.
The RegiSCAR program criteria for DRESS Sx: an acute rash, fever above 38°C, lymphadenopathy at two sites, involvement of at least one internal organ, and abnormalities in lymphocyte and eosinophil counts.
A Japanese consensus group criteria for DRESS Sx: The diagnosis requires meeting seven of the nine criteria in this system or all of the first five: a maculopapular rash developing > 3 weeks after drug initiation, clinical symptoms continuing > 2 weeks after stopping therapy, fever > 38°C, liver abnormalities (ALT > 100 IU/L) or other organ involvement, leukocytosis, atypical lymphocytes, eosinophilia, lymphadenopathy, or HHV-6 reactivation.
More than 50 drugs have been linked to DRESS syndrome.
Most common drugs associated with DRESS syndrome include: anticonvulsants, sulfa derivatives, antidepressants, nonsteroidal anti-inflammatory drugs, and antimicrobials.
Nevirapine, a nonnucleoside reverse transcription inhibitor for the treatment of human immunodeficiency virus reported to be associated with DRESS Sx.
Agents involved include: benzodiazepines, bupropion, amitriptyline, mirtazapine, phenytoin, carbamazine, and phenobarbital.
A diagnosis of DRESS syndrome should be considered in any patient with severe rash, fever, eosinophilia or lymphocytic changes.
Prompt recognition, supportive therapy and initiation of corticosteroids, may prevent or minimize additional organ system involvement.
Long-term sequelae includes permanent liver and kidney damage, development of autoimmune conditions including hemolytic anemia, diabetes, autoimmune thyroid disease, and vitiligo.
Recurrence is as high as 25%, and can be spontaneous, associated with viral reactivation, or caused by medications including unrelated compounds.
Reactivation can occur particularly with human herpesvirus 6 (HHV-6).
HHV-6 reactivation is detected in around 60% of patients and is associated with more severe organ involvement.
HHV-6 reactivation is thought to play a role in the waxing and waning course of DRESS syndrome.
Management universally, is cessation of the causative agent.
Use of corticosteroids is widely accepted, but lacks controlled study efficacy.
Systemic corticosteroids therapy is considered a mainstay of therapy when there is involvement of internal organs.
Recent agents include intravenous immunoglobulins, plasma exchange, cyclosporine, cyclophosphamide, but little information is available.
Intravenous IgG immunoglobulins have some success but is associated with a high risk of adverse reactions and should be avoided.