ARTICLE

Azithromycin Does Not Cure Pityriasis Rosea

Ahdi Amer, MD, Howard Fischer, MD

Wayne State University School of Medicine, the Carman and Ann Adams Department of Pediatrics, Childrens Hospital of Michigan, Detroit, Michigan

The authors have indicated they have no nancial relationships relevant to this article to disclose.

ABSTRACT
OBJECTIVES. Pityriasis rosea (PR) is a common skin disorder in children. Its cause is
unknown. A recent publication reported a 73% cure rate in patients with PR after
www.pediatrics.org/cgi/doi/10.1542/
treatment with erythromycin. To duplicate this result using a drug with fewer peds.2005-2450
adverse effects and greater biological half-life, we set out to study the effect of doi:10.1542/peds.2005-2450
azithromycin on PR. Azithromycin is an azalide antibiotic with a spectrum of
Key Words
antimicrobial activity very similar to that of erythromycin. pityriasis rosea, children, azithromycin
Abbreviation
DESIGN. We randomly assigned 49 children with PR to receive either azithromycin
PRpityriasis rosea
(12 mg/kg per day, up to a maximum of 500 mg/day) for 5 days or a similar- Accepted for publication Oct 20, 2005
appearing placebo. Study physicians were blinded to patients treatment type. Two Address correspondence to Howard Fischer,
pediatricians had to agree on the diagnosis of PR before patients could be enrolled. MD, Wayne State University School of
Medicine, the Carman and Ann Adams
Subjects were seen at follow-up visits 1, 2, and 4 weeks after starting treatment. Department of Pediatrics, Childrens Hospital
of Michigan, 3901 Beaubien Blvd, Detroit, MI
OUTCOME MEASURES. We measured the appearance of new lesions and resolution of 48201. E-mail: [email protected]
lesions. PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2006 by the
RESULTS. Rates of cure and of partial resolution were similar in the azithromycin and American Academy of Pediatrics

placebo groups.
CONCLUSION. Azithromycin does not cure PR.

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P ITYRIASIS ROSEA (PR) is an acute, inflammatory skin
disease that commonly affects children and adoles-
cents. Lesions may persist for 4 to 10 weeks and may be
the patients were enrolled and at all of the follow-up
visits.
This was a double-blind, placebo-controlled prospec-
pruritic. The first skin lesion to appear is called a herald tive study. Patients were randomly assigned to receive
patch and often appears on the trunk as a 2- to 5-cm azithromycin (n 25) or placebo (n 24). Only the
oval, scaly plaque. Within a week or two, smaller scaly study pharmacist was aware of study patients treatment
oval plaques appear, often in a Christmas tree distri- type. Treatment patients received azithromycin, 12
bution on the trunk.1 In dark-skinned patients, postin- mg/kg per day for 5 days. The maximum daily dose was
flammatory hyperpigmentation or hypopigmentation 500 mg/day of azithromycin; this was given to all of the
may be seen after the lesions resolve. Some epidemio- patients weighing 40 kg. Placebo patients received an
logic features (seasonal variation and clustering in com- appropriate volume, or number of tablets, of an identi-
munities) suggest that PR may be an infectious disease. cal-appearing and similar-tasting placebo.
At present, no etiologic agent has been identified. Patients were seen for follow-up at 1, 2, and 4 weeks
In 2000, Sharma et al2 published a study that showed after enrolling in the study. Standardized data collection
great success in inducing resolution of PR in a group of at each follow-up visit included: change in lesion num-
patients (most of whom were 21 years of age) by bers and size, presence of pruritus, medication adverse
treating with oral erythromycin for 2 weeks. They pro- effects, use of other treatments, and the presence of
duced complete resolution of lesions in 73% of their pigmentary changes. As in the diagnostic visit, the pa-
patients in a double-blind, placebo-controlled study, tient was evaluated by the 2 authors in most cases and
whereas there was no clearing within 2 weeks in any by 2 physicians in all of the cases. Digital photographs
patient in the placebo group. In a commentary a few were again taken. Patients were monetarily compen-
months later, the editor of a dermatology journal de- sated for attending follow-up visits. This study was ap-
scribed the findings of Sharma et al2 as remarkable and proved by the Wayne State University Human Investi-
unexpected. He stated that another study confirming gation Committee. Informed consent was obtained from
these results would be very useful.3 Others have ex- the parent accompanying the child.
pressed the same opinion.4 We undertook the following PR was considered completely resolved if areas in-
study to see whether these results could be replicated volved previously were neither scaly nor raised, and no
using azithromycin, an antibiotic with a longer biological new lesions had appeared. Erythema was not evident in
half-life and fewer gastrointestinal adverse effects than our patient population (100% black) at any time and
erythromycin. was not used as a criterion for disease activity. Partial
resolution meant a decrease in lesion number, scaliness,
METHODS or thickness but with active (ie, raised and scaly) lesions
Patients between 2 and 18 years of age with a diagnosis still present. No response (treatment failure) indicated
of PR were recruited from the General Pediatric Clinic, no change in the patients skin appearance. At each
Adolescent Clinic, and Emergency Department of Chil- follow-up visit, both examining physicians had to agree
drens Hospital of Michigan. Patients in the study had on the lesion resolution status of the patient. In cases of
the diagnosis of PR made by both authors in 80% of disagreement about resolution category, patients were
cases and by 1 study author and another experienced placed into the least-improved category of the 2 catego-
pediatrician in the remainder. Diagnosis was based on ries under consideration (eg, partial resolution over
characteristic PR features.1,5 Our patients had textbook complete resolution or no response over partial re-
cases of PR. No eruption seemed to be drug-related, sponse).
either by clinical appearance or by history. The study
authors have 45 combined years of experience practicing Statistical Analysis
pediatrics. If the 2 clinicians did not agree on the diag- We determined that to demonstrate a 30% cure rate
nosis of PR, the patient was not eligible for study enroll- with the active medication (versus no cure with pla-
ment. Exclusion criteria were receipt of an antibiotic cebo), each treatment arm needed 22 subjects. We had
within 2 weeks of the diagnosis of PR, a history of an adequate number of subjects to demonstrate such a
intolerance of azithromycin or erythromycin, or the treatment effect.
presence of lesions for 3 weeks at the time of diagnosis.
Patient data were collected at the time of the diagno- RESULTS
sis on standardized forms. These data included age, gen- There were 25 patients in the treatment (azithromycin)
der, race, duration of lesions, presence and location of group and 24 in the placebo group. Mean age was 8
the herald patch, number of lesions, presence of pruri- years in both groups. There were more boys (42% vs
tus, preceding upper respiratory infection, treatments 24%) in the azithromycin group. Lesions had been
used before the diagnosis, and history of PR exposure. present an average of 1.5 weeks before diagnosis in both
Digital photographs were taken of all of the lesions when groups. There were 2 patients in each group who had

PEDIATRICS Volume 117, Number 5, May 2006 1703

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lesions present for 3 weeks at the time of diagnosis TABLE 2 Results of the Treatment Intervention
(Table 1). Response Azithromycin Group Placebo Group P
Treatment with azithromycin had no influence on the (n 25 51%), n (%) (n 24 49%), n (%)
clinical course of PR in our patients. Fifteen patients in Complete resolution 15 (60) 10 (42) .275
the azithromycin group (60%) had complete resolution Partial resolution 7 (28) 7 (29)
of their lesions within 2 weeks of starting treatment. Ten No response 3 (12) 7 (29)
Combined complete 22 (88) 17 (71) .171
(42%) patients in the placebo group had complete res-
and partial
olution of their lesions within 2 weeks of starting treat- resolution
ment (P .275). Each treatment arm produced 7 pa-
tients with partial resolution. There were 3 failures at the
4-week follow-up visit in the azithromycin group and 7
in the placebo group. None of the outcomes reached mycin and found that the resolution rates for active drug
statistical significance (Table 2). When we combined and placebo resembled each other.
both complete and partial responders into a single group We do not think our nondermatologist status had an
and compared that group to the nonresponders, there influence on the validity of our diagnoses or judgment
was, again, no difference of statistical significance for about degree of response. Two physicians needed to
azithromycin treatment versus placebo (Fishers exact agree on each diagnosis and each response evaluation.
test, P .171). We reviewed our photographs at the end of the study
The proportion of patients with residual hyperpig- (before we broke the code of treatment assignment) to
mentation was 44% in the azithromycin group and 38% look for missed areas of disagreement. We found none.
in the placebo group. Hypopigmentation was seen in Azithromycin is a member of the azalide subclass of
12% of patients in the treatment group and 25% of macrolide antibiotics, of which erythromycin is the best-
patients getting placebo. Two patients in the placebo known agent. The range of microbes susceptible to
group and 1 in the treatment group reported an upper azithromycin is very similar to that of erythromycin,
respiratory infection before the onset of lesions. Two although azithromycin is less active against streptococ-
patients in the treatment group complained of stomach cus species and enterococci.7 Azithromycin has a long
ache, and 2 complained of diarrhea while receiving elimination half-life,7 and because of its high and persis-
azithromycin. There were no similar complaints in the tent tissue levels, a 5-day course of azithromycin is
placebo group. roughly equivalent to a 10-day course of erythromycin.8
Why might an antibiotic treat PR? There is presump-
DISCUSSION tive evidence that PR may be an infectious disease. In
We did not reproduce the results of Sharma et al.2 They addition, erythromycin is thought to have immuno-
treated a group of (presumably Indian) patients with modulating and antiinflammatory effects. The evidence
erythromycin and had a 73% cure rate in 2 weeks. None for an infectious etiology has been concisely summarized
of the placebo patients responded in the 2-week period. by Chuh et al6: (1) there is a distinct clinical course of
Their patients were alternately assigned (pseuorandom- events in PR (ie, herald patch followed by a secondary
ization; ref 6) to the 2 treatment arms. We treated a eruption followed by complete remission); this is similar
randomly assigned group of black children with azithro- to what is seen in many viral infections associated with
rashes; (2) most patients do not have a second attack, a
finding also seen in many viral diseases; (3) several
patients in the same environment or household may
TABLE 1 Patient Characteristics of the Azithromycin and Placebo develop PR; there is a report of 4 cases of PR occurring
Groups within 1 month on a whaling ship in the far north; (4)
Characteristic Azithromycin Group Placebo Group P there are reported associations of PR with respiratory
(n 25 51%) (n 24 49%)
infections and underprivileged economic status; and (5)
Age, n (%) contact plays a role; a survey showed that 4 times as
5 y 3 (12) 1 (4)
510 y 16 (64) 13 (54)
many dermatologists as otolaryngologists have had PR.
10 y 6 (24) 10 (42) Several organisms have been considered as potential
Mean age, y 8.0 8.4 etiologic agents of PR. Among viruses ruled out are
Male gender, n (%) 6 (24) 10 (42) cytomegalovirus,9 Epstein-Barr virus,9 parvovirus B19,9
Duration of lesions at diagnosis, wk 1.54 1.50 picornaviruses,6 and influenza and parainfluenza virus-
Reported upper respiratory 1 (4) 2 (8)
infection before onset of
es.6 Controversy exists about the role of human herpes-
lesions, n (%) virus 7.6,10 A critical review of the literature found insuf-
Pruritus, n (%) 23 (92) 17 (71) .056 ficient evidence to conclude that human herpesvirus 7
Residual hyperpigmentation, n (%) 11 (44) 9 (38) causes PR.4,6 No reliable evidence was produced by stud-
Residual hypopigmentation, n (%) 3 (12) 6 (25) .240 ies seeking to incriminate chlamydia, legionella, or my-

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coplasma infections.4,6 Erythromycin, azithromycin, and 4. Chuh AAT, Chan HHL. Prospective case-control study of chla-
clarithromycin have antiinflammatory effects.11 It has mydia, legionella and mycoplasma infections in patients with
pityriasis rosea. Eur J Dermatol. 2002;12:170 173
been speculated that these effects might contribute to-
5. Chuh AAT. Diagnostic criteria for pityriasis rosea: A prospec-
ward the action of erythromycin if any, in PR.4 tive case control study for assessment of validity [letter]. Eur
Acad Dermatol Vener. 2003;17:100 102
CONCLUSION 6. Chuh A, Chan H, Zawar V. Pityriasis rosea: evidence for and
Our study showed that a 5-day treatment with azithro- against an infectious etiology. Epidemiol Infect. 2004;132:
mycin did not modify the clinical course of PR. 381390
7. Hardman JC, Limbird LE, eds. Goodman and Gilmans The Phar-
macological Basis of Therapeutics. 10th ed. New York, NY:
ACKNOWLEDGMENTS
McGraw Hill; 2001:1251
This work was supported by a grant from Pfizer Inc. 8. Kucers A, Crowe SM, Grayson ML, Hoy JF, eds. The Use of
We thank Xiaoming Li, PhD, for help with statistical Antibiotics: A Clinical Review of Antibacterial, Antifungal and Anti-
analysis. viral Drugs. 5th ed. Oxford, United Kingdom: Butterworth-
Heinemann; 1977:655
REFERENCES 9. Chuh AAT. The association of pityriasis rosea with cytomega-
1. Hurwitz S. Clinical Pediatric Dermatology: A Textbook of Skin Dis- lovirus, Epstein-Barr virus and parvovirus B19 infections: a
orders of Childhood and Adolescence. 2nd ed. Philadelphia, PA: WB prospective case control study by polymerase chain reaction
Saunders Company; 1993:122123 and serology. Eur J Dermatol. 2003;13:2528
2. Sharma PK, Yadav TP, Gautam RK, Taneja N, Satyanarayana L. 10. Watanabe T, Kawamura T, Jacob SE, et al. Pityriasis rosea is
Erythromycin in pityriasis rosea: a double-blind, placebo- associated with both human herpesvirus-7 and human herpes-
controlled clinical trial. J Am Acad Dermatol. 2000;42:241244 virus-6. J Invest Dermatol. 2002;119:793797
3. Bigby M. A remarkable result of a double-masked; placebo- 11. Ianaro A, Ialenti A, Maffia P, et al. Anti-inflammatory activity
controlled trial of erythromycin in the treatment of pityriasis of macrolide antibiotics. J Pharmacol Exp Ther. 2000;292:
rosea. Arch Dermatol. 2000;136:775776 156 163

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Lohr S. New York Times. February 16, 2006
Noted by JFL, MD

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 Azithromycin Does Not Cure Pityriasis Rosea
Ahdi Amer and Howard Fischer
Pediatrics 2006;117;1702
DOI: 10.1542/peds.2005-2450

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright 2006 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
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 Azithromycin Does Not Cure Pityriasis Rosea
Ahdi Amer and Howard Fischer
Pediatrics 2006;117;1702
DOI: 10.1542/peds.2005-2450

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/117/5/1702

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright 2006 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
.

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