By: Catherine Joachin
Introduction
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially lethal hypersensitivity to one or several drugs. It is a late-onset, enduring reaction with a 10% mortality rate and no established diagnostic criteria (Husain, Reddy & Schwartz, 2013). Patients with this condition frequently present with a morbilliform rash, but dermatologic and systemic manifestations can vary.
Symptoms
Eosinophilia refers to high amounts of eosinophils in the blood, suggesting the presence of an allergen, cancer, or parasite. The most common symptom seen in children and adults with DRESS syndrome is a cutaneous eruption akin to measles referred to as a morbilliform rash (Takenaka & Nishizawa, 2020). This inflammation is characterized by severe redness that predominantly covers the face and upper body in the earlier stages of the condition and later spreads to the lower extremities, but this rash has the potential to spread to all surfaces of the skin (Husain, Reddy & Schwartz, 2013). Patients may suffer from a fever and pruritus (itchy skin) preceding skin eruption.
DRESS syndrome can seriously impact several organ systems, with the liver being the most commonly affected, often with hepatitis. In extreme cases, hepatic necrosis (liver cell death) can lead to liver failure, the primary cause of death in DRESS syndrome (Husain, Reddy & Schwartz, 2013).
People afflicted with DRESS syndrome may also encounter renal, cardiac, hematologic, pulmonary, gastrointestinal, neurological, and endocrine complications. Nervous system symptoms typically develop 2 to 4 weeks post-onset and include meningitis and encephalitis (Husain, Reddy & Schwartz, 2013). Neurological symptoms are rare but may manifest in the form of headaches, seizures, cranial nerve palsies, and muscle weakness (Calle et al., 2023).
Causes
While DRESS syndrome can be caused by a variety of medications, certain drugs carry a higher risk of triggering DRESS or specific systemic complications. Minocycline is commonly implicated in cardiac, pulmonary, and hepatic pathologies, while renal complications are mostly attributed to allopurinol, carbamazepine, and dapsone (Husain, Reddy & Schwartz, 2013). Similarly, phenytoin plays a role in liver problems, ampicillin in cardiac complications, and dapsone in kidney problems (Husain, Reddy & Schwartz, 2013). Of note, research suggests that HHV-6 (human herpesvirus-6) reactivation, a neurotropic virus causatively linked to hepatitis flare, may also be associated with neurological symptomatology.
How does this relate to epilepsy?
Infection with HHV-6 has been associated with encephalitis, temporal lobe epilepsy, and febrile seizures (Bartolini et al., 2019). In DRESS syndrome, HHV-6 reactivation has been linked to fever, gastrointestinal and respiratory problems, in addition to seizures (Calle et al., 2023). Antiepileptics (e.g., carbamazepine and phenytoin) have also been identified as the most frequently implicated drugs in DRESS syndrome (Calle et al., 2023). Therefore, epilepsy may present in patients with DRESS syndrome as a result of underlying immunosuppressive responses to some drugs.
Diagnosis and Treatment
Ruling out conditions that share clinical features with DRESS syndrome, such as Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and erythroderma, is particularly important because this condition is particularly severe and life-threatening (Husain, Reddy & Schwartz, 2013). The onset of cutaneous eruption in DRESS syndrome typically starts later (at around 2 to 6 weeks) and lasts several weeks more than in other allergic reactions, viral infections or skin diseases (Husain, Reddy & Schwartz, 2013). Another clinically distinctive feature is the presence of lymphocytes in affected skin areas, suggesting an adaptive immune response to medication (Calle et al., 2023). Observing if such cells are present in infected tissue can help in diagnosis when the culprit drug is not easily identifiable.
Ideally, treatment of DRESS syndrome starts with the immediate withdrawal of the causative drug. Corticosteroid therapy can be provided to alleviate symptoms of cutaneous eruption, although less widespread treatment options can be considered for those who fail to respond to systemic steroids (Husain, Reddy & Schwartz, 2013). In cases presenting with exfoliative dermatitis, patients may benefit from treatment in intensive care or burn units (Husain, Reddy & Schwartz, 2013). Specialized care may also be administered to address systemic symptoms related to organ complications. Overall, the prognosis is generally favorable, with most patients recovering after the removal of the culprit drug and supportive therapy; however, some patients may endure life-long complications or die (Husain, Reddy & Schwartz, 2013).
Conclusion
DRESS syndrome (or drug reaction with eosinophilia and systemic symptoms syndrome) is a serious allergic reaction to certain drugs that can lead to widespread skin rashes, fever, and multiple organ dysfunction. Less common symptoms such as shortness of breath, headaches, and seizures may manifest as a result of systemic problems. The majority of patients with this condition recover; however, a small subset live with chronic complications or die.
References
Bartolini, L., Theodore, W. H., Jacobson, S., & Gaillard, W. D. (2019). Infection with HHV-6 and its role in epilepsy. Epilepsy Research, 153, 34–39. https://doi.org/10.1016/j.eplepsyres.2019.03.016
Calle, A. M., Aguirre, N., Ardila, J. C., & Cardona Villa, R. (2023). DRESS syndrome: A literature review and treatment algorithm. The World Allergy Organization Journal, 16(3), 100673-. https://doi.org/10.1016/j.waojou.2022.100673
Husain, Z., Reddy, B. Y., & Schwartz, R. A. (2013). DRESS syndrome: Part I. Clinical perspectives. Journal of the American Academy of Dermatology, 68(5), 693.e1-. https://doi.org/10.1016/j.jaad.2013.01.033
Husain, Z., Reddy, B. Y., & Schwartz, R. A. (2013). DRESS syndrome: Part II. Management and therapeutics. Journal of the American Academy of Dermatology, 68(5), 709.e1-9; quiz 718–720. https://doi.org/10.1016/j.jaad.2013.01.032
Takenaka, D., & Nishizawa, T. (2020). Morbilliform drug eruptions caused by trimethoprim–sulfamethoxazole. BMJ Case Reports, 13(9), e238255-. https://doi.org/10.1136/bcr-2020-238255
