By Madison Abbs, PharmD and Alexandria Taylor, PharmD, BCPS
Patient Case: Patient is a 23-year-old female presenting to the emergency room from urgent care with rash on her back, chest, and face. She notes that the rash is progressively spreading down her trunk and extremities. She reports fever, chills, and body aches. The patient was prescribed sulfamethoxazole-trimethoprim 7 days prior for suspected perirectal abscess.
Vitals: Temperature- 101 F, blood pressure- 132/71 mmHg, heart rate- 103 bpm, weight- 115.9 kg
Table 1. Four Types of Hypersensitivity Reactions and Offending Agents (1)
SJS= Steven Johnson’s Syndrome; TEN= Toxic Epidermal Necrolysis
Background
Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS) is a rare, life-threatening, delayed hypersensitivity reaction that occurs due to repeated exposure to an offending agent. DRESS accounts for 10-20% of reported cutaneous reactions, most often reported using the FDA (Food and Drug Administration) Adverse Drug Event Reporting System (FAERS). Common offending agents include allopurinol, aromatic antiepileptics (phenytoin, carbamazepine), vancomycin, sulfonamides, and mexiletine, among several others.
Diagnosis and Scoring Systems
DRESS typically presents with a morbilliform rash (characterized by red, flat lesions), fever, and swelling within one to six weeks of ingesting the culprit agent. Consequences of untreated DRESS with continued exposure to the offending agent include pulmonary and hepatic failure, leading to mortality in 2-10% of patients. Lab abnormalities may include leukopenia, leukocytosis, eosinophilia, thrombocytopenia, and anemia.(2) DRESS is diagnosed using one of two scoring systems: The European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) and The Japanese Research Committee on Severe Cutaneous Adverse Reaction (J-SCAR). A 2022 study showed that using the RegiSCAR scoring system, 98.3% of cases were correctly diagnosed. In contrast, the same study showed that J-SCAR criteria failed to diagnose a significant proportion of DRESS cases (48.9%) due to the use of more specific diagnosis criteria.(3)
Treatment
Treatment of DRESS is based on severity of symptoms at presentation but includes a combination of antihistamines and corticosteroids, in addition to the cessation of the offending agent. Introducing new medications at diagnosis should be avoided, especially empiric antibiotics. Initial therapy includes supportive care such as fluids, electrolytes, and pain control. Patients with mild DRESS symptoms and no systemic organ involvement can be treated with antihistamines and high potency, topical corticosteroids such as clobetasol or betamethasone. For more severe cases of DRESS with organ involvement, systemic glucocorticoids are recommended. A moderate to high dose (0.5 to 1 mg/kg per day using actual body weight) of prednisone or prednisone equivalents is given until clinical improvement and then tapered over 8 to 12 weeks.(4) The efficacy of systemic glucocorticoids for the treatment of DRESS has not been evaluated in randomized control trials, but case reports indicate clinical benefit. In general, primary literature on DRESS treatment is lacking. It is important to add medications that caused DRESS for a patient to their allergy list and avoid future exposure to the offending agent.
Back to our patient: Utilizing the RegiSCAR scoring system, the patient scored a four, indicating probable DRESS as a result of sulfamethoxazole-trimethoprim therapy.
Figure 1. Patient’s Rash Presentation in Emergency Department on Day One
Treatment course:
In emergency department, she was given:
• 10 mg IV dexamethasone (~0.5 mg/kg prednisone equivalent)
• 25 mg IV diphenhydramine
• 1 g oral acetaminophen
During admission, patient was treated with:
• 25 mg oral diphenhydramine x2 doses
• 40 mg oral famotidine x2 doses
• One dose of prednisone 60 mg (~0.5 mg/kg prednisone equivalent)
At discharge, she was prescribed:
• Methylprednisolone dose pack (Day 1: 24 mg, Day 2: 20 mg, Day 3: 16 mg, Day 4: 12 mg, Day 5: 8 mg, Day 6: 4 mg)
○ Total of 8 days of steroid therapy
○ Lower dose and shorter duration than recommended in the literature
• Diphenhydramine 25 mg as needed for itching
3 Takeaways for the Ambulatory Care Pharmacist
Utilizing validated scoring systems is important in the diagnosis of cutaneous reactions
Removal of offending agent and immediate treatment with antihistamines and systemic corticosteroids is key to preventing fatal symptoms
Adding offending agents to the patient’s allergy list is important in prevention of future occurrences
1. Marwa K, Kondamudi NP. Type IV Hypersensitivity Reaction. [Updated 2022 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
2. Santiago LG, Morgado FJ, Baptista MS, Gonçalo M. Hypersensitivity to antibiotics in drug reaction with eosinophilia and systemic symptoms (DRESS) from other culprits. Contact Dermatitis. 2020;82(5):290-296.
3. Sasidharanpillai S, Ajithkumar K, Jishna P, et al. RegiSCAR DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Validation Scoring System and Japanese Consensus Group Criteria for Atypical Drug-Induced Hypersensitivity Syndrome (DiHS): A Comparative Analysis. Indian Dermatol Online J. 2022;13(1):40-45. Published 2022 Jan 24.
4. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part II. Management and therapeutics. J Am Acad Dermatol. 2013;68(5).
Madison Abbs, PharmD
PGY1 Pharmacy Resident
University of Pittsburgh Medical Center St. Margaret Hospital
Alexandria Taylor, PharmD, BCPS
Hospital Clinical Pharmacist
University of Pittsburgh Medical Center St. Margaret Hospital
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