A 25-year-old woman with newly diagnosed seizures comes to the emergency department with fever and skin rash. She had her first seizure 6 weeks ago, and an MRI of the brain revealed no structural lesions. She was started on phenytoin 4 weeks ago. Her temperature is 38.9 C (102 F). There is a diffuse confluent erythema involving 60% of the body, palpable generalized lymphadenopathy, and symmetrical facial swelling. The oral mucosa appears normal. Which of the following laboratory findings is most likely to be present in this patient?
This patient's cutaneous and systemic findings after starting a new medication are suggestive of a hypersensitivity reaction, in particular, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.
DRESS is a rare and potentially life-threatening drug reaction typically occurring 2-8 weeks after drug exposure. Commonly associated drugs include anticonvulsants (eg, phenytoin, carbamazepine), allopurinol, sulfonamides (eg, sulfasalazine), and antibiotics (eg, minocycline, vancomycin). Although the exact mechanism is unknown, it likely involves impaired drug detoxification along with drug-induced herpesvirus (eg, HHV-6) reactivation followed by T cell-mediated tissue injury.
Patients typically develop fever, generalized lymphadenopathy, facial edema, and diffuse morbilliform skin rash that can progress to a confluent erythema; mucosal involvement is often limited (in contrast with Stevens-Johnson syndrome/toxic epidermal necrolysis). Internal organ involvement is characteristic and can include the liver (elevated transaminases), kidney (acute interstitial nephritis), and lung (cough, dyspnea). Laboratory studies usually show eosinophilia. Clinical findings improve over several weeks following withdrawal of the drug.
(Choice A) Drug-induced antineutrophil cytoplasmic antibodies-associated vasculitis is most commonly linked to medications for hyperthyroidism (eg, propylthiouracil, methimazole) and hydralazine. Patients can develop constitutional symptoms, arthralgias/arthritis, and cutaneous vasculitis.
(Choice B) Blast cells with Auer rods indicate acute myeloid leukemia. Patients typically develop complications of pancytopenia, including fatigue (anemia), fever due to infection (neutropenia), and ecchymosis or epistaxis (thrombocytopenia).
(Choice C) Mixed cryoglobulinemia is a small- to medium-vessel vasculitis caused by circulating immunoglobulin-complement complexes that precipitate on refrigeration. It is typically associated with chronic inflammatory states (eg, systemic lupus erythematosus, hepatitis C) and can present with systemic findings (eg, fatigue, arthralgias, myalgias) and palpable purpura in the lower extremities due to cutaneous vasculitis.
(Choice E) Microangiopathic hemolytic anemia usually presents with anemia and fragmented red blood cells (schistocytes) on the peripheral smear. It has been associated with cancer chemotherapy drugs (eg, cisplatin, cyclophosphamide).
Educational objective:
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome typically occurs 2-8 weeks after exposure to high-risk drugs such as anticonvulsants (eg, phenytoin, carbamazepine), allopurinol, sulfonamides (eg, sulfasalazine), and antibiotics (eg, minocycline, vancomycin). Patients typically develop fever, generalized lymphadenopathy, facial edema, diffuse skin rash, eosinophilia, and internal organ dysfunction.