Red man syndrome is an adverse reaction to the antibiotic vancomycin (Vancocin) that resembles an allergic reaction. It occurs because of the overstimulation of mast cells and basophils, which causes them to release histamine.
The primary symptoms are a red rash that itches. Other symptoms include a feeling of warmth and flushed skin.
Symptoms
The antibiotic vancomycin is used to treat serious bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). The medication prevents the bacteria from forming cell walls and blocks their growth. However, the drug can trigger a severe itchy rash. This reaction, known as red man syndrome or vancomycin flushing syndrome (VFS), is not common and can be dangerous if not treated promptly.
Symptoms of the reaction include itching, flushing, and redness of the skin. The itching and flushing usually affect the face, neck, and upper torso. It can also cause itching of the mouth and throat. Occasionally, patients may experience abdominal pain and chest pressure. If a patient experiences any of these symptoms, he or she should contact a healthcare provider immediately.
Medical research suggests that the underlying cause of red man syndrome is an overstimulation of mast cells that results in an inflammatory response that mimics anaphylaxis. Activated mast cells release histamine and other inflammatory mediators that are responsible for the resulting symptoms. The histamine released from degranulation of the mast cells causes a flushing sensation, and the itching is caused by the inflammatory mediators that are also being released.
In most cases, the rash associated with red man syndrome is mild and subsides soon after the infusion of the antibiotic has ended. In some patients, the rash is more severe and lasts longer. These more severe reactions are typically associated with higher doses of vancomycin and rapid infusion rates.
The first step in treating a case of red man syndrome is to stop administering the offending medication, in this case vancomycin. Antihistamines can help relieve the itching, and in more severe cases, epinephrine can be given to treat anaphylaxis. If possible, alternative antibiotics should be given to the patient, as these do not carry the same risk of red man syndrome. Keeping the skin moisturized can also help reduce the severity of the reaction. Medications that block histamines, such as hydroxyzine or diphenhydramine, can also be helpful. Taking these medications an hour before starting an infusion of vancomycin can prevent the onset of red man syndrome.
Diagnosis
Red man syndrome is a pseudo-allergic or adverse drug reaction with signs and symptoms that copy immunological allergies. It is usually triggered by the antibiotic vancomycin and occurs within 10-30 minutes after intravenous administration. The rash may appear on the face, neck, and upper middle part of the body. It also may cause a feeling of flushing, itching and other discomfort. Sometimes, a patient might experience fever, chills and headache. In rare cases, the skin might become thickened and ridged. In severe cases, nails might begin to chip or fall off.
In order to diagnose red man syndrome, the doctor should take a detailed history of symptoms and when they began. The timing of the onset and how they correlate to the infusion of the medication can help identify a potential link. In some cases, a skin biopsy might be required to confirm the diagnosis of red man syndrome. It might also be necessary to exclude other conditions with similar or identical symptoms. For instance, true anaphylaxis must be differentiated from red man syndrome because it is a more serious and life-threatening condition.
The first step of treatment for red man syndrome involves discontinuing the administration of the drug, most often vancomycin. The person is then given H1 and H2 antihistamines through an IV to reduce symptoms. If the symptoms persist, epinephrine auto-injectors might be needed to control anaphylaxis.
Although the exact mechanism of red man syndrome is not known, some experts believe that the rapid infusion of vancomycin causes degranulation of mast cells and basophils that results in the release of histamine independent of preformed IgE or complement. This histamine is responsible for the erythematous rash that is characteristic of red man syndrome.
Other antibiotics have been reported to cause red man syndrome as well, including the new glycopeptide antibiotic teicoplanin. Teicoplanin is less likely to cause the rash than vancomycin. Nevertheless, it is important to understand that all antibiotics can cause adverse reactions in certain patients. Therefore, the appropriate dose of any antibiotic should be based on a patient’s weight and other factors to minimize the risk of red man syndrome.
Treatment
Red man syndrome results from overstimulation of mast cells that stimulate an inflammatory and allergic response, resulting in the characteristic skin rash. The red rashes are associated with itching and the sensation of warmth or flushing in the face, neck, and upper body, with a more mild reaction occurring at the arms and legs. It can occur within 10-30 minutes after intravenous administration of vancomycin and will subside as soon as the drug is discontinued or the dose reduced to avoid the problem.
Because it can mimic symptoms of anaphylaxis, a physician must carefully evaluate the patient’s signs and symptoms and establish that the medication was the cause. This will involve the patient’s medical history, the timing of the reaction in relation to the drug administration, and exclusion of other causes of similar skin reactions or allergies. Antibiotics such as ciprofloxacin, amphotericin B, and rifampcin may also cause red man syndrome because they all can directly degranulate mast cells and basophils, which result in the release of histamine independent of preformed IgE or complement. The reaction is exacerbated when drugs such as opioid analgesics, muscle relaxants, or contrast dye are administered along with the antibiotics because they can also stimulate histamine release.
Fortunately, this reaction is not life-threatening and can be easily treated with antihistamines. The most common symptoms are a rash and itching in the face, neck, and upper chest and abdomen. Occasionally, the rash can spread to the arms and legs, although this is less common. It can also lead to a fever, chills, and itchy or watery eyes. Occasionally, the nails can become discolored or develop ridges and chip.
The best way to prevent this reaction is to ensure that patients are receiving the appropriate dose of medication, preferably in a slow infusion rate. Additionally, if the patient has been previously exposed to vancomycin, an antihistamine can be administered prior to infusion. This will not only reduce the onset of the reaction but can also prevent the patient from developing an allergy to the medication.
Prognosis
The prognosis for red man syndrome varies depending on the severity and specific case. Mild cases with minimal symptoms and quick resolution tend to have a more positive outcome. Symptoms that are accompanied by hypotension or a serious underlying condition such as cardiovascular disease may pose a greater risk of complications. Identifying factors that increase the likelihood of a severe reaction can help improve the patient’s outlook.
A common cause of this drug reaction is a rapid infusion rate during vancomycin administration. This can trigger a rapid release of histamine from mast cells and basophils, which mimics an allergic response to the antibiotic but differs in that it does not involve immunoglobulin antibodies.
Histamine is released by immune system cells and binds to special receptors found on the surface of skin’s sensory nerve fibers. This causes the skin to become itchy. This itchiness is often accompanied by the flushing sensation that is characteristic of red man syndrome. The rash and itching typically last several minutes to hours.
Another common symptom of red man syndrome is a feeling of warmth that can spread from the face to the chest and arms. This is due to the dilated blood vessels that result from histamine release. Some patients also experience watery eyes and tachycardia.
In addition to discontinuing the drug, doctors can provide relief from the symptoms of red man syndrome through oral antihistamine medications. The use of hydroxyzine has been shown to reduce the onset of the rash and itching. In some cases, physicians will pre-treat patients with a low dose of diphenhydramine before administering the first infusion of vancomycin to decrease their chances of experiencing this reaction.
It is important for patients to let their healthcare providers know if they are experiencing any of the symptoms of red man syndrome. It is recommended that they seek medical care immediately if they are. The doctor will stop the vancomycin infusion and will administer a medication to relieve the symptoms until the reaction subsides. They will then reintroduce the medication at a slower rate and adjust the dosage according to the patient’s individual needs.