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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 patients present with a prodromal phase, consisting of, malaise, sore throat, dysphasia, pruritus, cutaneous, burning sensation, or a combination of these symptoms
Most commonly involved organs are the liver, lungs, kidneys and blood abnormalities include lymphocytopenia, atypical lymphocytes, and eosinophilia.
This phase is followed by a morbilliform eruption that starts on the trunk and often face, and eventually spreads to more than 50% of the total body surface area.
Facial edema, which can accentuate or lead to new oblique earlobe creases is characteristic, and helps distinguish DRESS from uncomplicated morbilliform drug rashes.
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.
Estimated prevalence is approximately two cases per hundred thousand population and the incidence of one in 1000 to one in 10,000 cases in patient who received a medication, depending upon the causative agent.
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.
Aromatic anticonvulsants have the highest risk of association with DRESS, followed by allopurinol and sulfonamide antibiotics.
Allopurinol is associated with the longest disease, latency, and beta-lactam antibiotics and iodinated contrast media the shortest.
Elevated serum vancomycin trough levels in an age younger than 50 years associated within an increased risk of vancomycin related DRESS.
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.
Systemic involvement involves the hematologic, hepatic, renal, pulmonary, and cardiac systems: although involvement of nearly every organ system, including the endocrine, gastrointestinal, neurologic, ocular, and rheumatologic systems have occurred.
Studies found 36% of patients have involvement of one extra cutaneous organ, and 56% of patients have involvement or two or more organs.
Atypical lymphocytosis is the most frequent and earliest hematologic finding, whereas eosinophilia typically occurs later and tends to be persistent.
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 skin lesions are pleomorphic: urticarial, eczematous, lichenoid, exfoliative, erythrodermic, targeted, purpuric, vesicular, pusular or a combination.
56% of patients with DRESS have mucosal inflammation and erosion and 15% have mucositid involving more than one mucosal surface.
After the skin, the liver is the most frequently involved organ.
Liver function enzyme elevations are usually mild, but can be up to 10 times the upper limits of normal, with cholestatic pattern.
Antibiotics were the most common drug class implicated in liver dysfunction associated DRESS.
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 appearance of myocarditis may be delayed for months in some patients.
Pulmonary and myocardial involvement in DRESS are most frequently triggered by minocycline, although uncommon manifestations.
One in five patients have isolated kidney involvement.
Most cases of kidney involvement, have an isolated elevation in serum, creatinine or decrease in GFR, however, the most significant disease with proteinuria, older immature, or a combination can occur.
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.
Pulmonary manifestations with shortness of breath, dry cough, or both, develops in up to a third of patients with DRESS.
Pulmonary involvement may manifest as interstitial lung infiltrates, acute respiratory distress syndrome, and pleural effusions.
DRESS syndrome shares many characteristics in common with anticonvulsant hypersensitivity syndrome (AHS).
Referred 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.
Most fatalities the result of liver failure.
Worldwide mortality from DRESS ranges from 1.2 to 7.1%, and the US specific mortality of 5% was documented in 2019.
Ot accounts up to 23% of cutaneous drug eruptions in hospitalized patients.
Some patients have lymphadenopathy generalized.
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.
In the US five drugs account for most cases: allopurinol, vancomycin,lamatrigine, carbamzine and trimethoprin-sulfamethoxazole.
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.