CL Renz

CM Thompson

DP Healy

Henry Gray

JM McCullough

L Bergerin

Lori

MP Wilhelm

Phillippa Bailey

R Fekety

RA Lucas

S Aradhvula

T Toyoguchi

English

PubMed

Bailey, Pippa

Gray, Harry

Explore Bristol Research

An elderly woman with 'Red Man Syndrome' in association with oral vancomycin therapy: a case report

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BioMed CentralCases Journal
ssOpen AcceCase Report
An elderly woman with 'Red Man Syndrome' in association with oral 
vancomycin therapy: a case report
Phillippa Bailey*1 and Henry Gray2
Address: 1Frenchay Hospital, Frenchay Park Road, Bristol, BS16 1LE, UK and 2Southmead Hospital, Westbury-on-Trym, Bristol, BS10 5NB, UK
Email: Phillippa Bailey* - drpip@doctors.org.uk; Henry Gray - gray.harry@googlemail.com
* Corresponding author    
Abstract
Introduction: 'Red Man Syndrome' is a recognized adverse reaction to intravenous vancomycin
therapy. This case concerns an elderly woman who developed a 'Red Man Syndrome' reaction
whilst on oral vancomycin therapy for Clostridium difficile (C difficile) diarrhoea. Isolated case
reports exist recording this reaction in association with oral vancomycin therapy in patients with
inflammatory bowel conditions or impaired renal function, of which this patient had both.
Case Presentation: An 82 year old Caucasian woman who developed C. difficile diarrhoea after
co-amoxiclav therapy for a urinary tract infection. She was treated with oral vancomycin therapy
during which she developed a widespread erythematous rash in keeping with that of 'Red Man
Syndrome'. This rash resolved on stopping the oral vancomycin.
Conclusion: 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. It also calls us to review our understanding of the
mechanism of the 'Red Man Syndrome' reaction. It is possible that significant absorption of orally
administered vancomycin occurs in the presence of an inflammatory bowel condition.
Background
Vancomycin and Red Man Syndrome
Vancomycin can cause two types of hypersensitivity reac-
tion – 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 complain
of the sensations of burning and itching. Agitation, dizzi-
ness, headaches, chills, fever and perioral paresthesia are
also described. The incidence of red man syndrome varies
between 3.7% and 47% in infected patients [1].
The 'Red Man Syndrome' seen in association with intrave-
nous vancomycin administration is not a true allergic
reaction. It appears to be due to vancomycin-induced his-
tamine release without involvement of preformed anti-
bodies [2]. In animal models, vancomycin provokes
histamine release from rat peritoneal mast cells [3]. There
is evidence of reduced side effects associated with vanco-
mycin when antihistamines are given with therapy. In a
prospective, randomized, double-blind, placebo-control-
led study in 30 patients who required vancomycin chem-
oprophylaxis before elective arthroplasty, oral pre-
treatment 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 [4].
Published: 18 August 2008
Cases Journal 2008, 1:111 doi:10.1186/1757-1626-1-111
Received: 4 July 2008
Accepted: 18 August 2008
This article is available from: http://www.casesjournal.com/content/1/1/111
© 2008 Bailey and Gray; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
Cases Journal 2008, 1:111 http://www.casesjournal.com/content/1/1/111Hypothesized mechanism of reaction
It is generally understood that systemic bioavailability of
orally administered vancomycin is negligible [5]. In one
study, after 7 doses of oral vancomycin 250 mg every 8
hours in healthy volunteers, no vancomycin concentra-
tions were detected in serum (sensitivity limit 0.64 micro-
grams/ml) or urine [6].
However, the presence of an inflammatory bowel process
can result in increased absorption of oral vancomycin [7].
In patients with pseudomembranous colitis and severe
renal failure, several studies have revealed that orally
administered vancomycin may occasionally reach thera-
peutic concentrations in serum and even pose a risk of sys-
temic toxicity [8,9].
In one of these case reports an anephric girl with C. diffi-
cile pseudomembranous colitis received oral vancomycin
250 mg every 6 hours. She developed unexplained fever
and encephalopathy. Sustained serum vancomycin con-
centrations of 34 micrograms/ml were recorded, with Cer-
ebrospinal fluid (CSF) concentrations of 4.3 microgram/
ml. Discontinuation of the drug, along with haemodialy-
sis caused the serum concentration to fall to 24 micro-
gram/ml with resolution of the symptoms [9].
Case presentation
The patient, an 82 year old Caucasian woman, was admit-
ted to hospital with confusion. She had a number of active
medical problems, including atrial fibrillation, ischaemic
heart disease, chronic kidney disease, hypertension and
osteoarthritis. Six years prior to admission she had under-
gone a right hemicolectomy for Dukes B colorectal carci-
noma.
During admission she was diagnosed as having a urinary
tract infection (UTI). Prior to admission her general prac-
titioner had treated the patient with a 3 day course of tri-
methoprim 200 mg bd. On admission to hospital, urine
culture was positive for Escherichia. coli and she was pre-
scribed a 5 day course of oral co-amoxiclav 625 mg tds.
Four days following completion of this course of antibiot-
ics, she developed diarrhoea, which was positive for
Clostridium difficile toxin. Metronidazole 400 mg tds was
prescribed immediately. The patient's diarrhoea wors-
ened, she was opening her bowels 7 times daily with a
Bristol Stool classification Type 7 stool. After five days of
oral metronidazole therapy, oral vancomycin 250 mg qds
was started.
Four days after oral vancomycin therapy was instigated,
the patient developed a widespread pruritic, confluent,
erythematous rash over her chest, back, neck and thighs.
She also complained of a severe headache. 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 regu-
lar 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 inden-
tified.
On admission the patient had Chronic Kidney Disease
(CKD) stage 2. When she developed C. difficile diarrhoea
the patient developed acute-on-chronic renal failure, with
renal function deteriorating to an equivalent of CKD stage
3. Some case reports of patients developing 'Red Man Syn-
drome' in association with oral vancomycin therapy have
involved patients with impaired renal function, suggest-
ing that reduced excretion of any systemically absorbed
vancomycin may contribute to developing the reaction.
Unfortunately, despite our request, vancomycin levels
were not performed by our laboratory.
The reaction seen in our patient seemed to be the same as
that seen previously with intravenous vancomycin admin-
istration – the 'Red Man Syndrome'. Review of the litera-
ture reveals a number of existing case reports describing
rashes during oral vancomycin therapy, including one
case of measurable serum vancomycin levels. All cases we
became aware of have been described in patients in the
presence of colitis or impaired renal function.
Discussion
As described, this reaction is thought to be associated with
intravenous administration of the drug, but there are iso-
lated case reports of 'Red Man Syndrome' in association
with intraperitoneal and oral administration of vancomy-
cin [8,10,11].
Conclusion
With increasing incidence of C. difficile pseudomembra-
nous colitis, and the increased use of oral vancomycin
therapy to treat it, reporting of cases of possible 'Red Man
Syndrome' is essential. From our literature review, cases
have only been reported in patients with an inflammatory
bowel process. It cannot necessarily be concluded that
inflammatory bowel processes are required to allow the
absorption of vancomycin. It is true that it is only in these
cases possible 'Red Man Syndrome' has been reported but
oral vancomycin has few indications for use.
It causes us to question the mechanism of this drug reac-
tion. Does the presence of an inflammatory bowel process
allow vancomycin absorption, resulting in significantPage 2 of 3
(page number not for citation purposes)
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serum concentrations of the drug, made more significant
if there is reduced renal excretion? Alternatively, is the
presence of vancomycin in the gut able to cause histamine
release without systemic absorption? With increasing use
of oral vancomycin, recording of possible 'Red Man Syn-
drome', with measurement of serum vancomycin concen-
trations, is essential.
Consent
Written informed consent was obtained from the patient
for publication of this case report. A copy of the written
consent is available for review by the Editor-in-Chief of
this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
HG collected the details of the case and recorded the
patient data including microbiology specimens and renal
function. PB was the major contributor in researching and
writing the manuscript. Both authors read and approved
the final manuscript.
Acknowledgements
With thanks to Dr Cameron Kennedy, Consultant Dermatologist, Bristol 
Royal Infirmary, Bristol for his opinion on our patient's rash.
References
1. Lori , Wazny D, Behnam D: Desensitization protocols for vanco-
mycin hypersensitivity.  Ann Pharmacother 2001, 35:1458-1464.
2. Healy DP, Sahai JV, Fuller SH, Polk RE: Vancomycin-induced his-
tamine release and 'red man syndrome': comparison of 1
and 2 hour infusions.  Antimicrob Agents Chemother 1990,
34(4):550-4.
3. Toyoguchi T, Ebihara M, Ojima F, Hosoya J, Shoji T, Nakagawa Y: His-
tamine release induced by antimicrobial agents and effects
of antimicrobial agents on vancomycin-induced histamine
release from rat peritoneal mast cells.  J Pharm Pharmacol 2000,
52(3):327-31.
4. Renz CL, Thurn JD, Finn HA, Lynch JP, Moss J: Oral antihistamines
reduce the side effects from rapid vancomycin infusion.
Anesth Analg 1998, 87(3):681-5.
5. Fekety R, Siva J, Kauffman C, Buggy B, Deery HG: Treatment of
antibiotic-associated Clostridium difficile colitis with oral
vancomycin: comparison of two dosage regimens.  Am J Med
1989, 86:15-9.
6. Lucas RA, Bowtle WJ, Ryden R: Disposition of vancomycin in
healthy volunteers from oral solution and semi-solid matrix
capsules.  J Clin Pharm Ther 1987, 12:27-31.
7. Wilhelm MP, Estes L: Vancomycin Mayo Clin Proc 1999, 74:928-35.
8. Bergerin L, Boucher F: Possible red-man syndrome associated
with systemic absorption of oral vancomycin in a child with
normal renal function.  Ann Pharmacotherapy 1994, 28(5):581-584.
9. Thompson CM, Long SS, Gilligan PH: Absorption of oral vanco-
mycin:possible associated toxicity.  Int J Pediatric Nephrol 1983,
4(1):1-4.
10. McCullough JM, Dielman DG, Peery D: Oral vancomycin-induced
rash: case report and review of the literature.  DICP 1991,
25(12):1326-8.
11. Aradhvula S, Manian FA, Hafidh SA, Bhutto SS: Significant absorp-
tion of oral vancomyin in a patient with clostridium difficile
colitis and normal renal function.  South Med J 2006,
99(5):518-20.Page 3 of 3
(page number not for citation purposes)


Crossref

Bhutto SS: Significant absorption of oral vancomyin in a patient with clostridium difficile colitis and normal renal function. South Med J

Deery HG: Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens.

Desensitization protocols for vancomycin hypersensitivity. Ann Pharmacother

Disposition of vancomycin in healthy volunteers from oral solution and semi-solid matrix capsules.

Estes L: Vancomycin Mayo Clin Proc

Histamine release induced by antimicrobial agents and effects of antimicrobial agents on vancomycin-induced histamine release from rat peritoneal mast cells.

Oral antihistamines reduce the side effects from rapid vancomycin infusion. Anesth Analg

Oral vancomycin-induced rash: case report and review of the literature. DICP

PH: Absorption of oral vancomycin:possible associated toxicity.

Possible red-man syndrome associated with systemic absorption of oral vancomycin in a child with normal renal function. Ann Pharmacotherapy

Vancomycin-induced histamine release and 'red man syndrome':

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2527496

An elderly woman with 'Red Man Syndrome' in association with oral vancomycin therapy: a case report

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