Rare case of “red man” syndrome in a female patient treated with oral vancomycin for Clostridium difficile diarrhoea

Abstract

A 58-year-old Caucasian woman was admitted for knee replacement but during the postoperative period she developed sepsis due to pneumonia, which was treated with coamoxiclav and then piperacillin (for 2 weeks). She had renal failure, which needed haemofiltration. During her recovery she had diarrhoea due to Clostridium difficile, which was not controlled with metronidazole. Vancomycin was therefore given, but she developed urticarial erythematous skin rash and hence it was stopped. She was not on any other new medications and a vasculitic screen was negative. A dermatologist reviewed her file as well. The skin rash subsided after 2 weeks with topical emollients and chlorphenamine tablets. Her diarrhoea eventually settled and she went home well. Though classically described in men, this “red man” syndrome (features of urticarial erythematous rash due to oral vancomycin) has been previously reported in case reports and in literature reviews.

BACKGROUND

“Red man” syndrome is a recognised adverse reaction to intravenous vancomycin therapy. This case concerns an older woman who developed a red man syndrome reaction while on oral vancomycin therapy for Clostridium difficile toxin-caused diarrhoea. Isolated case reports exist recording this reaction in association with oral vancomycin therapy in patients with inflammatory bowel conditions or impaired renal function.

This case is important in the light of the increasing use of oral vancomycin to treat C difficile diarrhoea, a rising problem in the UK, and also its rarity in women.

CASE PRESENTATION

The patient, a 58-year-old Caucasian woman, was admitted originally for elective knee replacement but subsequently developed postoperative pneumonia (treated with coamoxiclav and then piperacillin) and renal impairment, which needed haemofiltration. She had a history of diabetes, osteoarthritis and hypertension. While recovering from this illness she developed diarrhoea, which was due to C difficile toxin.

The patient was moved out of the intensive care unit and renal functions were improving. After 4 days of metronidazole treatment as diarrhoea was still not improving, oral vancomycin was added. After 3 days she noticed a widespread urticarial erythematous rash (fig 1) on the stomach wall that slowly progressed.

Figure 1.

Erythematous urticarial rash.

Her renal functions still were improving and a vasculitic screen was requested. A dermatology review was requested and the opinion was that the rash appeared to be like that seen in red man syndrome. It was confirmed with nursing staff that no drug errors had been made and no vancomycin had been administered intravenously in error.

Vancomycin therapy was stopped immediately and regular antihistamines were prescribed. The rash then cleared and did not return. Rechallenge with oral vancomycin was not initiated. No other drug therapy was altered during this time, and no other potential allergens could be identified. Her diarrhoea did eventually stop. Unfortunately, despite our request, our laboratory did not perform a vancomycin level test.

INVESTIGATIONS

Renal functions, immunology screen for vasculitis and liver function tests were performed.

There was renal impairment with an estimated glomerular filtration rate (eGFR) of 18 ml/min/1.73 m². There was no evidence of thrombocytopoenia.

Stool culture showed C difficile toxin.

DIFFERENTIAL DIAGNOSIS

Drug rash, vasculitic rash, purpuric rash.

TREATMENT

Symptomatic and supportive treatment was given. Vancomycin was stopped.

OUTCOME AND FOLLOW-UP

On withdrawing the drug and with aid of topical skin creams and antihistamines the patient’s symptoms improved within 2 weeks; a dermatology review was requested and the opinion was that the rash appeared to be like that seen in red man syndrome.

DISCUSSION

A review of the literature^1,2 revealed a few (less than five) case reports describing rashes during oral vancomycin therapy, including one case of measurable serum vancomycin levels.

Vancomycin can cause two types of hypersensitivity reaction: the red man syndrome and anaphylaxis. Red man syndrome is thought to be an infusion-related reaction consisting of pruritus, an erythematous rash involving the face, neck and upper torso. Patients commonly experience the sensations of burning and itching. The incidence of red man syndrome varies between 3.7% and 47% in patients who are infected.

The red man syndrome seen in association with intravenous vancomycin administration is not a true allergic reaction. It appears to be due to vancomycin-induced histamine release without involvement of preformed antibodies. In a prospective, randomised, double-blind, placebo-controlled study in 30 patients who required vancomycin chemoprophylaxis before elective arthroplasty, oral pretreatment with either a histamine H1 receptor antagonist (diphenhydramine 1 mg/kg) or a histamine H2 receptor antagonist (cimetidine 4 mg/kg) significantly reduced the histamine-related adverse effects of rapid vancomycin infusion.

Although clinically significant serum concentrations can be obtained in patients treated with oral vancomycin who have concomitant C difficile colitis and renal failure, there has not been a clear correlation between these concentrations and any reported adverse sequelae.

LEARNING POINTS

• Drug rash can be quite disabling and multifactorial.

• Consider vasculitic rash when palpable.

• The opinion of dermatology colleagues is essential.