Minocycline side effects rare, but can be severe

National report - A case report of a young girl who developed pseudotumor cerebri (PTC) after a course of minocycline to treat acne has prompted clinicians to review appropriate therapy for acne vulgaris to avoid serious adverse events.

The case report involves a patient who developed pseudotumor cerebri, or idiopathic intracranial hypertension.

The case

A fundus oculi examination indicated bilateral papilledema. No abnormal findings were seen by magnetic resonance imaging of the brain. A spinal tap was not obtained because there were no signs of neurological infection. The diagnosis was PTC secondary to minocycline administration.

Patients with PTC typically complain of headache accompanied by dizziness, nausea or visual defects. PTC is characterized by intracranial pressure exceeding 250 mmHg without the presence of a lesion or infection. The bulging of anterior fontanels in infants and papilledema and abducens nerve paresis in older children and adults are the common features.

PTC is a condition that is typically encountered in young overweight women between ages 20 and 45 years. The incidence in a normal population is one to two cases per 100,000 persons. That figure rises to 19 to 21 per 100,000 cases among obese women who are in the reproductive age group.

In the case of the patient in this case report, the minocycline was discontinued, and systemic corticosteroids and acetazolamide were administered as therapy. Clinical signs of PTC disappeared after six weeks of treatment, and there was no permanent neurological damage. The patient's acne also improved significantly.

Treatment revisited

Two years later, the patient's acne recurred. Therapies such as topical retinoids, benzoyl peroxide and antibiotics were administered, as were oral macrolides, but did not produce the desired results. The patient requested a course of oral isotretinoin, which has been associated with teratogenicity in humans and has the potential to produce PTC as well.

"I was concerned about the possibility of another episode of PTC," says Vincenzo Bettoli, M.D., an assistant professor of dermatology at the University of Ferrara in Ferrara, Italy, and author of this case report.

"The patient's mother was a neurologist and could check on the status of the girl and the psychological discomfort of the patient. We concluded that we could run the risk of prescribing oral isotretinoin."

The therapy was administered at a low dosage, considering the previous episode of PTC. The dosage was initially 10 mg per week for two weeks, titrated to 20 mg per week for two weeks. The dosage climbed gradually to a maximum of 20 mg per day. The total dosage administered was 51 mg per kg, which fully cleared the patient's acne.

The patient was continually tested for any neurological changes that would indicate PTC during and post treatment, but no symptoms were observed.

"In our experience, we have not seen other patients who have followed such a sequence of events," Dr. Bettoli notes, referring to the patient's adverse reaction to the original medication.

"Minocycline is a drug that rarely produces side effects, but can have severe side effects when they do occur."

The case report has put oral isotretinoin under a new light for the treating dermatologist who sees a patient with acne, according to Dr. Bettoli.

"For the patient's severe acne in this case, oral isotretinoin was the right choice," Dr. Bettoli tells Dermatology Times. "If we were going to use tetracyclines, the choice of therapy would be based on the side-effect profile. The data in the literature support equivalent efficacy of doxycycline, limecycline and minocycline. Minocycline would be a choice after doxycycline and limecycline because of the possibility of severe side effects. If a patient had moderate acne, we would use oral antibiotics."

Dr. Bettoli adds that the case report suggests that the mechanism of PTC induction is different between minocycline and oral isotretinoin. Minocycline is more lipophilic than other tetracyclines, penetrates the blood-brain barrier more readily and attains greater cerebrospinal fluid level.