CASE REPORT:
A 69-year-old female patient was referred to our department by the internal medicine department for lesions of the oral mucosa. The patient was a housewife living with her husband in an urban setting, mother of 6 daughters, and had no prior travel history. She had no history of smoking, alcohol consumption, or illicit drug use. No allergies were identified.
Her medical history revealed type-2 diabetes for 17 years, hypertension for 10 years, dyslipidemia, and Gout disease. She had a surgical history of coronary artery bypass surgery 11 years earlier and cholecystectomy 17 years earlier. Medications involved metformin (Glucophage®), Glibenclamide (Diabenil®), Captopril (Tensopril®), Isosorbide dinitrate (Pensordil®), Propranolol (Normocardil®), Fluvastatin (Lescol®), Aspirin®, and Colchicine® . She started taking Allopurinol® 6 weeks before hospitalization. No history of drug hypersensitivity reactions was identified.
A week before her hospitalization, the patient developed chills with unrecorded fever. The following day, the patient noticed bluish spots on the lower limbs with a very important edema on the lips. She consulted the emergency department where she had an unspecified symptomatic treatment, without improvement. Then, the patient consulted a dermatologist who prescribed Corticosteroid (Solupred® 20mg) as a mouthwash and referred the patient to the internal medicine department where she was hospitalized.
On the first day of admission to the internal medicine department, the patient was conscious and well-oriented. The initial recorded temperature was 38.7°C, blood pressure was 120/70 mmHg, pulse was 67 beats/minutes, and weight was 72 kg. Physical examination showed the presence of a confluent erythematous maculopapular rash, diffused all over the body (feet, legs, stomach, chest, back), and sparing the face, scalp, palms, and soles. (Figure 1, 2). Nikolsky’s sign was negative. No lymphadenopathy was present. On auscultation, the chest was clear on both sides. The patient’s heart had a regular rate and rhythm. The remainder of the examination was without abnormalities. In the department of dental medicine, oral examination showed the presence of a painful erosive cheilitis, crusty lesions on both lips, and confluent ulcerations across the labial mucosa (Figure 3). These aspects were reminiscent of those seen in some bullous drug eruption (Erythema multiforme, Stevens-Johnson syndrome…) but Nikolsky’s sign was negative. Antibodies (Amoxicillin 2g per days) were prescribed to avoid infection of the lesions. Local corticosteroid therapy (Solupred as a mouthwash), antalgic, and chlorhexidine-based mouthwash were also prescribed. Oral biopsy was scheduled.
Complete blood count (CBC) showed a normal number of white blood cells (WBCs) of 10.28*10^3/mm3 with 9.4% lymphocytes, 11.3% monocytes, and16.1% (1.65*10^3/mm3) eosinophils, corresponding to a moderate eosinophilia. C -reactive protein was elevated at 13 mg/L. Results of tests for serum electrolytes, hemoglobin, hematocrit, and sedimentation rate were normal.
Serology for hepatitis B and hepatitis C was negative. Urine and blood cultures were also negative. Uric acid level was high. Similarly, high levels of Serum glucose and triglyceride were noted.
Skin biopsy was performed and it showed necrotic keratinocytes and a subepidermal perivascular inflammatory infiltrate, consisting of lymphocytes and eosinophils (Fig 4). This histological aspect was in accordance with drug eruption (toxiderma).
Based on the patient’s history, clinical presentation, and biological tests, diagnosis of cutaneous adverse drug reaction was made. Systemic corticosteroid therapy (Solupred 20mg) was therefore started. The most likely etiology was allergic response to Allopurinol. Infectious and immunological etiologies were eliminated.
On the seventh day of admission, the patient had an alteration in her renal function and decompensation of diabetes, with blood glucose level rising from 7.0 (mmol/l) to 9.8. Creatinine level increased to 116 μmol/l. Liver function tests showed a low albumin level (31 g/l), an abnormal coagulation panel with an international normalized ratio (INR) of 1.3, and transaminitis (AST: 47 IU/L; ALT: 43 IU/L), all indicating an alteration in hepatic function.
Diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) was therefore made.
Five days after corticosteroid therapy, an improvement in both cutaneous and oral lesions was noted (Fig 5).Three years later, the patient was rehospitalized with similar mucocutaneous lesions after automedication using Allopurinol.