Case Report

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An 18-year-old woman was referred for evaluation of a possible immunodeficiency causing recurrent toxic shock syndrome. Her problems began in August 1988 when she had a sore throat, nasal congestion, and a low-grade fever followed by development of a punctate, macular erythematous rash on her neck, wrists, and forearms. This rash progressed rapidly to confluent erythema over the trunk and extremities, including the palms and soles. She also developed angioedema of the hands and face, a temperature of 40 °C, nausea and vomiting, profound fatigue, myalgia, diffuse arthralgias, and orthostatic hypotension. She was hospitalized and treated with antibiotics and intravenous fluids. Resolution of symptoms occurred over the next 48 to 72 hours, followed by skin desquamation, most prominently on the palms and soles. Similar episodes occurred in November 1988 and in September, October, November, and December 1989. No clear association of these episodes with menstruation was observed. Multiple cultures of the throat, axilla, groin, vagina, and rectum grew only normal flora.

In a detailed history, the patient reported that her episodes were preceded by symptoms associated with upper respiratory infection. She recalled taking over-the-counter cold preparations at the time of at least three of the episodes; her symptoms developed 4 to 6 hours after taking these medications. However, she took a different product each time. The active and inactive ingredients of each of these three products were reviewed. The only components common to all three were pseudoephedrine and sucrose (Table 1). It was thought that her symptoms might represent an adverse reaction to pseudoephedrine. This possibility was discussed with the patient, and we decided to challenge her with pseudoephedrine. She was instructed to take no medications for at least 2 weeks. On the day of the challenge, physical examination was essentially normal; she had no skin abnormalities and she was not menstruating. She was given 60 mg of pseudoephedrine orally. Five and a half hours later, she developed an erythematous pinpoint macular rash starting on the anterior neck and quickly spreading to confluence. This rash was associated with a sensation of heat and burning pain, nausea, light-headedness, and fatigue. The rash quickly progressed to involve the whole body, including the palms of the hands and soles of the feet. Pulse was 72 beats/min and blood pressure was 134/78 mm Hg in the supine position and 120 beats/min and 124/70 mm Hg in the upright position. Her temperature rose from 36.4 °C to 38.2 °C. She later developed protracted vomiting. The patient was admitted to the hospital and received intravenous fluid replacement. Her course was uneventful and symptoms began to resolve within 24 hours. One week later, she had desquamation of the skin on her palms and soles. At no time did she have involvement of the mucous membranes.

The patient was instructed to avoid all pseudoephedrine-containing products and remained symptom-free until approximately a year later when she inadvertently took an over-the-counter cough syrup that contained pseudoephedrine. She had previously used the same brand of non-pseudoephedrine-containing cough syrup with no problems. Within 6 hours of ingesting the pseudoephedrine-containing cough syrup, she developed the same symptoms, which again resolved within 48 hours after supportive measures were taken. Since then, she has diligently examined the list of ingredients on products before ingestion. She has been symptom-free for about 2 years.

Discussion

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Pseudoephedrine is an effective decongestant and is widely used. Side effects from pseudoephedrine use are rare and generally center on central nervous system excitation or cardiac dysrhythmias (reviewed in reference 4). Fixed drug eruptions have been reported to occur in response to pseudoephedrine [5-7]. Our patient's reaction was unique because of the predominance of the systemic symptoms.

Pseudoephedrine is widely used in many over-the-counter preparations. Most patients do not consider over-the-counter preparations as medications and thus neglect to report ingestion of such products. On the other hand, it is not unusual for physicians to overlook such ingestion when obtaining a patient's history. Our case shows the importance of obtaining a meticulous drug history and of maintaining a high index of suspicion for adverse drug reactions when searching for the cause of unusual clinical syndromes.