Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterized by fever, skin rash, hematological abnormalities, and systemic involvement such as hepatitis. DRESS usually presents 2–6 weeks after drug initiation. DRESS should be suspected on clinical grounds in the setting of the introduction of new drug therapy and is most commonly described after the introduction of aromatic anticonvulsants, allopurinol, or antiretroviral therapies. We describe here a case of DRESS due to phenytoin exposure with complete resolution on drug discontinuation. Our patient developed DRESS with a skin rash, lymphadenopathy, and markedly abnormal liver enzymes, 4 weeks after drug initiation following drainage of a brain abscess. He was initially diagnosed as having a recurrence of the abscess or sepsis of another origin. It is important to recognise the possibility of DRESS in this setting, as a good outcome depends on the immediate withdrawal of the offending drug. A mortality rate of up to 10% has been described in unrecognised cases.
Several cutaneous reactions to medication with variable onset and manifestations occur after drug exposure [
RegiSCAR criteria for the likelihood of DRESS syndrome.
No | Yes | Unknown | |
---|---|---|---|
(1) Fever > 38.5°C | −1 | 0 | −1 |
(2) Enlarged lymph nodes (>2 sites, >1 cm) | 0 | 1 | 0 |
(3) Atypical lymphocytes | 0 | 1 | 0 |
(4) Eosinophilia | 0 | 0 | |
0.7–1.49 × 109/L or 10–19.9% | 1 | ||
>1.5 × 109/L or ≥20% | 2 | ||
(5) Skin rash | 0 | 0 | |
Extent > 50% | 0 | 1 | 0 |
At least 2 of: edema, infiltration, purpura, scaling | −1 | 1 | 0 |
Biopsy suggestive of DRESS | −1 | 0 | 0 |
(6) Internal organ involvement | 0 | 0 | |
One | 1 | ||
2 or more | 2 | ||
(7) Resolution in >15 days | −1 | 0 | −1 |
(8) At least 3 investigations negative for alternative cause | 0 | 1 | 0 |
Final score: <2 No case; 2-3 possible case, 4-5 probable case; >5 definite case.
A 47-year-old male patient presented to a metropolitan hospital with a new onset of fever, headache, right-sided weakness, and dysphasia. His background included a history of paranoid schizophrenia and cannabis abuse. The patient strongly denied the use of injectable drugs. His only medication was longstanding depot risperidone injections. He was a smoker with no known allergies. A computerized tomography (CT) of the brain revealed a 2 × 3 cm mass in the medial left frontal lobe consistent with the diagnosis of a brain abscess. Initial biochemistry and a complete blood count were normal, including liver enzyme tests. Successful neurosurgical drainage of the brain abscess was undertaken in theatre. Cultures taken from the abscess material grew
Three weeks after admission to the rehabilitation unit (day 27), the patient developed fever (38.4 degrees Celsius). Blood cultures were undertaken, a chest X-ray (CXR) ordered, and a CT scan of his brain repeated which showed a reduced abscess cavity compared to his previous study. A day later the patient developed erythema over his upper torso, malaise and rigors. On the recommendation of the general medical unit on take in the hospital, the patient was commenced on antibiotic therapy (vancomycin), and his biochemistry repeated. The results of the biochemistry revealed deranged liver enzymes (Figure
Liver enzymes show an acute rise on day 27, with gradual normalization by day 69 (42 days after the initial rise).
The patient is presented as a case of DRESS. He expressed typical features of DRESS with skin rash, lymphadenopathy, raised liver enzymes, and atypical lymphocytes, three and a half weeks after commencement onto phenytoin, which is the suspected culprit drug. He did not develop overt hypereosinophilia, which is defined in DRESS as being above 0.7 × 109/L [
Naranjo score for the likelihood of an adverse drug reaction.
Yes | No | Unknown | |
---|---|---|---|
(1) Previous conclusive reports on this reaction | 1 | ||
(2) Did the adverse event appear after suspected drug given? | 2 | ||
(3) Did the adverse reaction improve when the drug was discontinued or a specific antagonist given? | 1 | ||
(4) Did the adverse reaction appear when the drug was readministered? | 0 | ||
(5) Are there alternative causes that could have caused the reaction? | −1 | ||
(6) Did the reaction reappear when a placebo was given? | 0 | ||
(7) Was the drug detected in any body fluid in toxic concentrations? | 0 | ||
(8) Was the reaction more severe when the dose was increased or less severe when decreased? | 0 | ||
(9) Did the patient have a similar reaction to the same or similar drugs in any previous exposure? | 0 | ||
(10) Was the adverse event confirmed by any objective evidence? | 1 |
Final score: >9 Definite ADR; 5–8 probable ADR; 1–4 possible ADR; <0 doubtful ADR.
Anticonvulsant therapies, particularly those with an aromatic ring structure such as carbamazepine, phenytoin, and phenobarbital have been recognised as precipitants for DRESS syndrome, in what used to be termed anticonvulsant hypersensitivity syndrome [
The proposed pathogenesis of DRESS relates to an abnormal immune response in a genetically susceptible individual [
The disease occurs along a spectrum of severity, which depends to some degree on early recognition and discontinuation of the offending drug. A skin rash, usually an erythematous, maculopapular rash occurred in 99% of cases of DRESS described in the literature [
The major differential diagnoses include septicaemia, autoimmune diseases including vasculitides and adult Still’s disease, tick borne diseases, and viral disease, including viral hepatitis and virus hemorrhagic fevers (in the appropriate context). These conditions should be excluded in all cases of suspected DRESS, either through relevant history or serology. Demonstration of herpes viruses, particularly herpes virus type 6 (HHV-6 infection), is suggestive of the diagnoses and may be a cofactor in the pathogenesis of DRESS [
Treatment is withdrawal of the offending drug or drugs. Corticosteroids and intravenous immunoglobulins have been given in individual cases [
Our patient fit the criteria for DRESS and showed improvement soon after discontinuation of his phenytoin. He was discharged home from the acute medical ward within a week, following drug withdrawal without the need for further rehabiltative treatment. Levetiracetam was initiated in order to replace the phenytoin. He remained on ceftriaxone at the recommendation of the infectious diseases unit and was followed up in the outpatient department with no recurrence of fever or other symptoms. The patient remained well a year following the above hospitalisation with complete normalisation of inflammatory markers and liver enzymes.