DRESS Syndrome · What Is It, Symptoms, Diagnosis, and More

DRESS syndrome is triggered by certain medications, with the most common culprits being anticonvulsants, antibiotics, and allopurinol. The most common anticonvulsants include carbamazepine, phenytoin, phenobarbital, sodium valproate, and lamotrigine. Antibiotics include sulfonamides (e.g., sulfasalazine, dapsone), minocycline, metronidazole, dapsone, and vancomycin. Allopurinol is a medication used to prevent or lower uric acid levels in the blood and is commonly used to treat gout. Other less common triggers include anti-viral agents (e.g., nevirapine, abacavir), non-steroidal anti-inflammatory drugs (e.g. celecoxib, ibuprofen), and antiplatelet medication (e.g., clopidogrel).  

The specific underlying mechanisms of this condition remain unknown; however, the pathogenesis is thought to involve an interplay between medications, viruses, and the immune system, primarily mediated by T-cells. Individuals carrying specific mutations in genes that encode drug detoxification enzymes have been shown to have a higher risk of DRESS. Lastly, reactivation of viral herpes infections (e.g., human herpesvirus 6 [HHV-6], HHV-7, Epstein-Barr virus [EBV], cytomegalovirus [CMV]) have been detected in those with DRESS syndrome.  

The signs and symptoms of DRESS syndrome include a pruritic, maculopapular rash that can look morbilliform, or measles-like, and distributed symmetrically over the torso and extremities. In darker skin colors, the eruption may appear deep red, maroon, violaceous, or brown. In lighter skin colors, the eruption may be any shade of pink or red, and fading eruptions may appear violaceous. The rash typically develops 2 to 6 weeks after starting the responsible drug, often covers 50% of the total body surface, and can progress to patches and plaques that are confluent, or merge together. Less commonly, pustules and vesicles can be seen.  

Additionally, a common feature of DRESS syndrome is facial swelling, and hematologic abnormalities are often also seen, including eosinophilia (i.e., high levels of eosinophils in the blood), leukocytosis (i.e., high white blood cell count), and neutrophilia (i.e., high levels of neutrophils in the blood).  

Systemic symptoms associated with DRESS include fever, which can precede the rash; fatigue; and painless enlarged lymph nodes, usually at more than two sites. In severe disease, organ systems can be affected, commonly the liver, causing hepatitis; the heart, resulting in myocarditis; lungs, causing interstitial pneumonitis; kidneys, causing interstitial nephritis; and brain, resulting in encephalitis.  

DRESS syndrome is diagnosed through a clinical evaluation by a clinician, such as a dermatologist, and gathering additional data through laboratory testing. There is no standard for DRESS diagnosis, but diagnostic criteria have been proposed by various research groups.   

Proposed criteria include: 

1. Presence of a drug eruption;  

1. Hematologic abnormalities (e.g., eosinophilia);  

1. Systemic manifestations (i.e., adenopathy, hepatitis); and

1. Fever >100.4°F.  

Laboratory studies that can be conducted to support a diagnosis of DRESS include liver function tests to look for elevated alanine transaminase (ALT) and aspartate transaminase (AST); a complete blood count (CBC) to look for leukocytosis with eosinophilia and atypical lymphocytes; urinalysis; and renal function tests (e.g., creatinine, blood urea nitrogen) to look for kidney involvement. A skin biopsy may be done which reveals a perivascular lymphocytic infiltration in the papillary dermis, with eosinophils, atypical lymphocytes, and spongiosis, or intercellular edema.  

DRESS syndrome is treated by a multidisciplinary team often including dermatologists, and depending on whether organ systems are affected, gastroenterologists, cardiologists, nephrologists, and hematologists. The primary treatment for DRESS syndrome is to identify and stop the offending medication as soon as possible. Any new drugs taken in the 2 months prior to onset of symptoms may be considered as culprits. Depending on the severity of DRESS, topical steroids may be used to treat those with mild disease whereas systemic corticosteroids (e.g., prednisone) have been used in those with severe disease or signs and symptoms of internal organ involvement. Supportive measures can also be used including wound care, replacing fluids lost through the impaired skin barrier, and using warming blankets to maintain temperature.  

Other medical therapies that have been used for DRESS syndrome include cyclosporine, intravenous immunoglobulin (IVIG), mycophenolate mofetil, rituximab, plasmapheresis, and cyclophosphamide. It is important to identify and promptly treat DRESS syndrome, as it has a 10% mortality rate, most commonly from liver failure.