Red Man Syndrome

Background

Red man syndrome (RMS) is an adverse reaction associated with the rapid intravenous (IV) infusion of vancomycin, a glycopeptide. It is characterized by flushing, erythema (redness), and pruritus (itching) primarily affecting the upper body, often the face, neck, and torso—hence the name. RMS is not a true allergic reaction but rather an anaphylactoid response mediated by histamine release from mast cells. It typically occurs during or shortly after infusion and resolves quickly once the infusion is slowed or stopped. Similar reactions can occur with other glycopeptides like teicoplanin, though less commonly.

Signs and symptoms

The hallmark symptoms of red man syndrome include:

• Intense flushing and erythema of the face, neck, upper chest, and arms (resembling a severe sunburn).
• Pruritus (itching), which can be widespread.
• Hypotension (low blood pressure), which may lead to dizziness or fainting.
• Tachycardia (rapid heart rate) and, in severe cases, chest pain or dyspnea (shortness of breath).
• Rarely, more severe manifestations like angioedema or bronchospasm.

Symptoms usually begin within 4-10 minutes of starting the infusion and can last from 20 minutes to several hours, depending on the infusion rate and dose.

Causes

Red man syndrome is primarily caused by the rapid IV administration of vancomycin. The reaction is dose- and rate-dependent:

• Higher doses (e.g., >500 mg) or rapid infusion (e.g., over less than 60 minutes) increase the risk.
• It may also occur with other drugs that trigger mast cell degranulation, such as certain opioids (e.g., morphine) or contrast media.
• Risk factors include a history of previous RMS episodes, atopic conditions, or concurrent use of drugs that enhance histamine release.

Mechanism

RMS results from non-immunologic mast cell degranulation, leading to the release of histamine and other vasoactive mediators. Vancomycin directly stimulates mast cells and basophils, causing histamine release without involving IgE antibodies. This distinguishes it from true anaphylaxis. The reaction is more pronounced with impure or older formulations of vancomycin, though modern preparations have reduced incidence.

Diagnosis

Diagnosis is primarily clinical, based on the timing and symptoms during vancomycin infusion. It is differentiated from true vancomycin allergy (which involves IgE-mediated hypersensitivity) by:

• Lack of urticaria or systemic involvement in mild cases.
• Resolution upon slowing the infusion, without need for epinephrine.
• Negative skin testing for allergy.

Monitoring vital signs during infusion can aid in early detection.

Treatment

Management is supportive and focuses on alleviating symptoms:

• Immediately slow or stop the vancomycin infusion.
• Administer antihistamines (e.g., diphenhydramine 25-50 mg IV) to block histamine effects.
• For hypotension, provide IV fluids and, if severe, vasopressors.
• In rare severe cases, corticosteroids or epinephrine may be used, though this is uncommon.

Most episodes resolve without long-term sequelae.

Prevention

Preventive measures include:

• Infusing vancomycin slowly: At least 60 minutes for 1 g, or longer for higher doses (e.g., 2 hours for 2 g).
• Premedication with antihistamines (e.g., diphenhydramine) and/or H2 blockers (e.g., ranitidine) for patients with prior RMS.
• Using alternative antibiotics if repeated reactions occur, though desensitization protocols exist for necessary vancomycin use.

See also

• Vancomycin