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Red Man Syndrome - Causes, Symptoms, Treatment, and Prevention

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Red man syndrome is a hypersensitive reaction caused by the infusion of Vancomycin antibiotics for bacterial infections.

Written by

Dr. Osheen Kour

Medically reviewed by

Dr. Basuki Nath Bhagat

Published At November 25, 2022
Reviewed AtJuly 31, 2023

Introduction

Red man syndrome, now known as Vancomycin flushing Syndrome (VFS), is a red rash caused by the Vancomycin antibiotic infusion and not because of an allergic reaction to the drug. Red rashes appear on the face, neck, and middle area of the body of an infected person. Vancomycin flushing syndrome is usually associated with a high rate of infusion treatment with Vancomycin. The Vancomycin drug is a commonly used antibiotic in treating postoperative wound infections, endocarditis, central line-associated bloodstream infections, and bacterial infections. The flushing reaction can be produced after the dose infusion within 10 minutes or can occur up to seven days after Vancomycin therapy. The responses are usually caused by intravenous injection and rarely intraperitoneal or oral doses.

What Are the Causes of Red Man Syndrome?

  • The red man syndrome was believed to be caused due to unhealthy or impure environmental conditions. Later due to repeated incidences, it was found to be associated with Vancomycin infusion, which leads to overstimulation of some immune cells in the person's body.

  • Mast cells responsible for allergic reactions in the body get overstimulated due to Vancomycin antibiotics and produce histamine. This histamine causes symptoms resembling the red man syndrome, which is the blood flushing in the body and not an allergic reaction.

What Are the Symptoms of Red Man Syndrome?

  • Flushing of blood or red rashes on the neck, face, and upper body.

  • Low blood pressure.

  • Fever and chills.

  • Dizziness.

  • Headache.

  • Weakness.

  • Nausea and vomiting.

  • Itching.

  • Increased heart rate.

  • Swelling under the skin (angioedema).

  • Chest and back pain.

  • Muscle spasm.

  • Fatigue.

  • Dehydration.

  • Swelling in lymph nodes.

  • Pruritus.

How Can We Treat Red Man Syndrome?

  • If a person develops symptoms during the treatment procedure, the doctor immediately stops the infusion of Vancomycin antibiotic.

  • A person is then given an H1 and H2 antihistamine therapy orally or intravenously, such as Diphenhydramine and Ranitidine.

  • If the symptoms are severe and hypotension also occurs, then saline infusion is given along with antihistamine through an intravenous route to the person.

  • If anaphylaxis shows symptoms like breathing difficulty, altered mental status, stridor, or hives, Epinephrine auto-injector treatment can be started immediately.

How Can We Prevent Red Man Syndrome?

  • Antihistamine therapy can be given before starting treatment with a Vancomycin antibiotic. This can reduce the symptoms and risk of developing redness and itchy skin.

  • Diphenhydramine can also be given to a person before infusing the first dose of Vancomycin to prevent the syndrome.

  • This treatment is effective only if given an hour before the treatment.

  • Another measure can be taken by giving a person the Vancomycin antibiotic infusion in small and frequent doses for better tolerance.

What Is the Differential Diagnosis for Red Man Syndrome?

Red man syndrome or Vancomycin flushing reaction produces symptoms similar to anaphylactic shock and must be differentiated from this condition. Both anaphylactic shock and red man syndrome show symptoms such as hypotension, red or erythematous rashes, and pruritus. Anaphylactic shock is usually mediated by IgE antibodies and occurs due to prior exposure, showing reactions like hives, stridor, bronchospasm, and wheezing. In contrast, red man syndrome is caused by intravenous infusion of Vancomycin as the first reaction to antibiotic therapy.

What Are the Other Antibiotics Producing Red Man Syndrome Symptoms?

Antibiotic treatments with drugs such as Rifampicin, Ciprofloxacin, Amphotericin B, and Teicoplanin can also cause red man syndrome in a person. This is because these drugs can cause the degranulation of mast cells and produce histamine, just like Vancomycin antibiotic drugs. Some other medicines can also cause the syndrome, like muscle relaxants, contrast dyes, or opioid analgesics, because of their potential to release histamine on consumption.

What Are the Uses of Vancomycin Antibiotics?

Vancomycin can be used for the following reasons:

  • Treatment of severe allergic reactions caused by gram-positive bacteria.

  • It can also be used for treating endocarditis by using antibiotic prophylaxis.

  • Vancomycin can also be used to treat pseudomembranous colitis in cases where metronidazole therapy is not very effective.

  • It can also be given as an intravitreal injection for treating endophthalmitis to give gram-positive bacterial coverage for the disease.

  • It can also be used in major surgical prophylaxis procedures, such as prosthesis implantation.

  • Vancomycin can also be given to a person resistant to penicillin and multi-drug therapy or severely allergic to penicillin antibiotics.

What Are the Symptoms Produced by Vancomycin Intravenously?

Rare symptoms produced by Vancomycin are:

  • Bleeding gums.

  • Black stool.

  • Cough.

  • Lightheadedness.

  • Blood in stool and urine.

  • Hearing loss.

  • Pale skin.

  • Loss of balance.

  • Lower back pain.

  • Trouble in hearing.

  • Weakness and tiredness.

  • Red spots on the skin.

  • Buzzing and ringing sounds in the ears.

  • Difficult and painful urination.

What Are the Other Adverse Effects of Vancomycin Antibiotic Drugs?

Vancomycin is extensively used to treat various bacterial infections, but it can also produce some serious adverse effects, such as:

  • Ototoxicity (hearing loss) with high or excessive doses and underlying causes like hearing loss or taking any ototoxic agent.

  • Nephrotoxicity (kidney damage) usually causes renal impairment and renal failure and increases the creatinine level in the kidneys during therapy.

  • Neutropenia (low white blood cells) occurs during the treatment with Vancomycin and subsides as soon as the treatment is completed.

  • Eosinophilia (high eosinophil count).

  • Phlebitis or vasculitis (blood vessel inflammation).

Conclusion

Red man syndrome is a drug reaction caused by Vancomycin infusion, and the symptoms produced can be seen clinically by the doctor during treatment therapy. The syndrome does not require any laboratory examination for diagnosis. The redness on the skin surface is produced by the release of histamine from mast cells which can cause redness to flush over the skin surface. The condition can be managed clinically, and the person affected must be adequately informed and educated by the physician. The prognosis of red man syndrome with treatment and supportive care is usually excellent.

Frequently Asked Questions

1.

Is Red Man Syndrome an Allergy?

Yes, red man syndrome is an allergy. It is an anaphylactoid reaction caused by the rapid infusion of the glycopeptide antibiotic vancomycin. It results in a pruritic, erythematous rash of the face, neck, and upper torso, involving the extremities to a lower degree.

2.

How to Treat Red Man Allergy?

Treatment includes: 
- Mild cases: Antihistamines such as diphenhydramine.
- Moderate to severe cases: diphenhydramine and ranitidine intravenously. Normal saline bolus to treat hypotension. Alternatives to vancomycin can be used once symptoms reside. 
- In case of anaphylaxis: Treatment for anaphylaxis is started, and the patient is taken for emergency care. Epinephrine is used as early treatment.

3.

What Are the Predisposing Factors of Red Man Allergy?

The predisposing factors are:
- Receiving Vancomycin infusions rapidly.
- People under the age of 40
- History of vancomycin flushing syndrome.
- Antibiotics such as ciprofloxacin or rifampin, analgesics, and muscle relaxants.

4.

What Are the Major Adverse Effects of Vancomycin?

The major adverse effects of vancomycin are: intravenous effects
- Nephrotoxicity.
- Hypotension.
- Hypersensitivity reactions such as anaphylaxis.
- Red man syndrome is associated with rapid infusions of vancomycin.
Oral route effects:
- Abdominal pain and nausea.
- Dysguesia or distorted sense of taste.
- Peripheral edema
- Fatigue.
- Headache.
- Diarrhea.
- Flatulence.
- Vomiting.
- Urinary tract infection.
- Fever.
Rare side effects:
- Increased serum creatinine.
- Red man syndrome
- Interstitial nephritis.
- Ototoxicity.
- Nephrotoxicity.
- Thrombocytopenia.
- Vasculitis. 

5.

Does Red Man Syndrome Resemble DRESS?

DRESS- drug reaction with eosinophilia and systemic symptoms. It is a severe drug-induced syndrome reaction characterized by fever, lymphadenopathy, transaminitis, kidney injury, and rash. It is often seen after a vancomycin injection and masquerades as red man syndrome. 

6.

Can Vancomycin Be Given Through the Intravenous Route?

Yes. Vancomycin injection is available in powder form, fluid is added, and an injection is given intravenously. The IV is infused slowly for at least 60 minutes every six or twelve hours.

7.

How Does Allergy Rash Appear?

The rashes appear as maculopapular rash, urticaria, linear IgA bullous dermatitis, and red man syndrome- erythematous rash on the face, neck, and upper torso (extremities).

8.

What Are the Bactericidal Effects of Vancomycin?

Vancomycin is bactericidal against intestinal bacteria and certain selective infections. A choice of drug for serious staphylococcal infections where penicillins and cephalosporins cannot be used. It works by binding to peptide precursors in the bacterial cell wall, preventing cross-linking of peptidoglycan side chains and thereby inhibiting cell wall synthesis.

9.

What Are the Contraindications for Vancomycin Use?

Contraindications to vancomycin are
- A few clinical considerations during patient care.
- Elderly patients are prone to vancomycin toxicity due to age-related changes in renal function, the volume of distribution, and accumulation.
- Vancomycin is not used in pregnancy unless the benefits outweigh the risks.
- Intravenous administration of vancomycin excreted in breast milk. Hence, breastfeeding mothers should consult their physician. 
- The reduced renal function causes vancomycin to accumulate in the body, thereby increasing the adverse effects.
- Prolonged use of vancomycin can cause drug resistance.
- Administration of other medications along with vancomycin increases the adverse effects and toxicity.

10.

To Which Class of Drugs Does Vancomycin Belong?

Vancomycin belongs to the cell-wall synthesis inhibitor class of antimicrobial medications. It is a tricyclic glycopeptide antibiotic derived from Streptococcus orientalis.

11.

Does Vancomycin Affect the Heart?

Patients scheduled for cardiac surgery often receive vancomycin as a prophylaxis to reduce postoperative staphylococcal wound infection. In a few cases, vancomycin depressed cardiac function.

12.

Does Vancomycin Have Serious Effects on the Kidneys?

Vancomycin has been reported to cause renal failure or nephrotoxicity with intravenous administration. Recent studies have shown that renal toxicity is lower than expected.

13.

What Makes Vancomycin an Effective Drug?

Vancomycin is a broad-spectrum glycopeptide antibiotic against gram-positive bacteria; it is effective because it inhibits methicillin-resistant Staphylococcus aureus. In addition, it binds to wall-building protein peptides, is active against both pathogens and is poorly absorbed from the intestinal tract.
Dr. Basuki Nath Bhagat
Dr. Basuki Nath Bhagat

Family Physician

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red man syndromevancomycin flushing syndrome
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