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.