A female patient in her early 30s visited the outpatient department for follow-up. She was referred to the dermatology department with a primary complaint of itching, redness, and skin allergy on the face, neck, shoulder, breast, stomach, and back. She also complained of breast tenderness, discomfort, and loss of taste. She had a history of recently diagnosed PCOS and type 2 DM for the last seven years. The eruption had begun over the breast and abdomen, with redness that progressed to her neck, face, and back region. The development of widespread, rash-like lesions measuring 5–6 cm in diameter and varying in size, even spreading to the trunk, is shown in
On interviewing the patient, the medical and family history revealed that her mother had experienced the same reaction in adulthood. The patient had a past medical history of uncontrolled DM over the last seven years, as well as migraine, and she was allergic to dust mites, pollen, mold, and ground nuts. She was on oral gliclazide 3 mg daily and a tablet containing a combination of caffeine 100 mg, ergotamine 1 mg, paracetamol 250 mg, and prochlorperazine 2.5 mg (SOS). The patient had been taking this combination of drugs for the last 6–7 years. For the last 4 days, she had been on glimepiride 2 mg, voglibose 0.2 mg, and metformin 500 mg SR daily for DM. Her physician had changed antidiabetic medications because she did not respond well to gliclazide 3 mg daily.
The EMM reaction with various-shaped lesions had appeared in the first weeks of treatment when she began the alternative medications of glimepiride 2 mg, voglibose 0.2 mg, and metformin 500 mg (SR) daily with oral clomiphene citrate 100 mg. Vitamin D 10,000 IU twice weekly and calcium 1,250 mg twice daily had also been prescribed for PCOS.
The patient was physically diagnosed with maculopapular rash following EMM, but no other abnormality or deformity was found. On the recommendation of a gynecologist, dermatologist, and endocrinologist, a differential diagnosis and the following tests were performed: pregnancy test, TSH test for hypothyroidism, prolactin for hyperprolactinemia, total testosterone for evaluation of ovarian tumor, total testosterone for hyperthecosis, DHEA-S for adrenal tumor, 24-hour urine free cortisol for Cushing’s syndrome, fasting blood glucose, HbA1c for diabetes, and 75 g oral glucose tolerance test for insulin resistance or glucose intolerance. The patient’s blood pressure was normal at 120/70 mmHg.
After 2 hours, the glucose level was 285 mg/dL, indicating diabetes with insulin resistance. The testosterone value of 147 ng/dL was normal. The DHEA-S value of 18.7 µmol/L showed no adrenal tumor. An elevated level of prolactin was found, confirming mild hyperprolactinemia. The 17-hydroxyprogesterone test was normal at <6 nmol/L, and the 24-hour urine free cortisol was also normal. Other investigations, such as the urine examination and chest x-ray, were as expected. On evaluation, no clinical sign of systemic lupus erythematosus was found. The anti-nuclear antibody test was negative. An x-ray of the abdomen showed no evidence of gallstones or pancreatic calcification. No evidence of pancreatic necrosis or dilatation of the intrahepatic ducts was seen on an ultrasound of the abdomen. Three cutaneous punch biopsies were also performed. The skin biopsy of the target lesion revealed intraepithelial edema associated with exocytosis. The biopsy of the breast sample showed severe edema and polymorphonuclear infiltrate in the superficial dermis. The presence of high CD1+ immune-labeled cells was also observed (
After 20 days of discontinuation of the combination of glimepiride, voglibose, metformin, and clomiphene citrate, a re-challenge test was performed after obtaining patient consent. Six hours after the first dose was administered, mild eruptions developed with itching and redness of the neck and face, loss of taste, and chest tiredness and discomfort. The patient declined to give other samples for biopsy due to a lack of money and time. One day after drug administration, the reaction became more severe and spread over the neck and breast. Treatment was initiated, and the patient recovered.
The patient’s vital signs, electrolyte levels, and FBC were monitored daily. The progression of skin rashes was also observed daily. The treatment included the oral antihistamine levocetirizine 5 mg, β-methasone dipropionate 0.05% ointment, methylprednisolone 32 mg/ day for five days, and topical calamine lotion at night. The dose of methylprednisolone was reduced to 16 mg after 5 days then to 8 mg after another 5 days. On assessing this adverse drug reaction (ADR), oral glimepiride, voglibose, and metformin, when prescribed with clomiphene citrate, were the suspected drugs. However, the breast tenderness or discomfort was caused only by oral clomiphene citrate 100 mg. The combination of glimepiride 2 mg, voglibose 0.2 mg, and metformin 500 mg SR daily was stopped immediately when it was confirmed as the cause of the ADR. A causality assessment of the ADR was conducted using the Naranjo scale. On examination, an ADR was found probable and caused by the combination of glimepiride, voglibose, and metformin. Vitamin D and calcium were assessed as having no role in this ADR.
The patient had been taking glimepiride 2 mg, voglibose 0.2 mg, and metformin 500 mg SR daily, along with clomiphene citrate 100 mg. On follow-up, the signs subsided when this combination was withdrawn and treatment was initiated; the patient began to recover.