What are the causes of Vancomycin (Vancomycin hydrochloride) skin reactions, also known as Red man syndrome?

From the Guidelines

Vancomycin can cause Red Man Syndrome, a skin reaction typically presenting as flushing, rash, and pruritus, due to histamine release from mast cells and basophils, particularly when infused too rapidly. To prevent or minimize these reactions, administer vancomycin at a slower infusion rate (over 1-2 hours rather than rapid infusion) as suggested by the study 1. The study recommends that Vancomycin dosages should be infused during the course of at least 1 h to reduce the risk of histamine-release “red man” syndrome.

Consideration of premedication with diphenhydramine (25-50 mg orally or IV) 30-60 minutes before infusion may be beneficial, although the evidence for this is not strong 1. If Red Man Syndrome occurs, stop the infusion immediately, administer antihistamines, and once symptoms resolve, restart at a slower rate. Other serious skin reactions associated with vancomycin include linear IgA bullous dermatosis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which require immediate discontinuation of the drug and dermatology consultation.

Some key points to consider:

• Vancomycin skin reactions can be severe and require immediate attention
• Histamine release from mast cells and basophils is the primary cause of Red Man Syndrome
• Slower infusion rates can help prevent or minimize these reactions
• Patients with a history of vancomycin skin reactions should have this clearly documented in their medical records, and alternative antibiotics should be considered when appropriate
• The use of premedication with antihistamines or glucocorticoids is not well supported by the evidence 1, but may be considered in certain cases.

From the FDA Drug Label

Infusion-Related Events During or soon after rapid infusion of vancomycin hydrochloride for injection, patients may develop anaphylactoid reactions, including ... flushing of the upper body ("red neck") Rapid bolus administration (e.g., over several minutes) may be associated with ... reactions

The causes of Vancomycin (Vancomycin hydrochloride) skin reactions, also known as Red man syndrome, include:

• Rapid infusion of the drug
• Anaphylactoid reactions These reactions usually resolve within 20 minutes but may persist for several hours. Such events are infrequent if vancomycin hydrochloride for injection is given by a slow infusion over 60 minutes 2, 2.

From the Research

Causes of Vancomycin Skin Reactions

The causes of Vancomycin skin reactions, also known as Red man syndrome, can be attributed to several factors, including:

• Hypersensitivity reactions, which can be pseudoallergic or allergic in nature 3
• Immune-mediated delayed hypersensitivity reactions, characterized by skin rashes accompanied by peripheral eosinophilia 4
• Release of histamine and other mediators, leading to symptoms such as flushing, erythema, and pruritus 3

Types of Vancomycin Skin Reactions

Various types of skin reactions have been reported with Vancomycin use, including:

• Morbilliform eruption
• Erythroderma
• Acute generalized exanthematous pustulosis
• Linear immunoglobulin A bullous dermatosis
• Toxic epidermal necrolysis 5
• Stevens-Johnson syndrome, a rare but severe reaction 6
• Red man syndrome (RMS), characterized by flushing, erythema, and pruritus 3, 7

Risk Factors and Associations

Certain risk factors and associations have been identified with Vancomycin skin reactions, including:

• Male sex, which is associated with a higher likelihood of RMS documentation 7
• Black race, which is associated with a lower likelihood of RMS documentation 7
• Severe renal insufficiency, which has been linked to an increased risk of Vancomycin reactions 6