Download PDF - The Dermatologist

Supported by Stiefel Laboratories, Inc.
Extensions
An Educational Newsletter for Physician Assistants and Nurse Practitioners in Dermatology
The Scientific Panel on
Antibiotic Usage in
Dermatology (SPAUD)
Part II: Continuation of A Summary Report
On Usage Patterns, Management Challenges
and Recommendations
By James Q. Del Rosso, D.O., F.A.O.C.D.
T
he following is Part
II of the summary
report based on the
meeting of The Scientific
Panel on Antibiotic Use in
Dermatology, held in Las
Vegas, NV, on April 22,
2006. The faculty for the
program included James
Q. Del Rosso, D.O. (Chairman), Dirk Elston, M.D.,
Jan Hirschmann, M.D.,
James Leyden, M.D., and
Guy Webster, M.D. Part I
of the summary report was
published in the last issue
of Extensions.
Antibiotic Use in
Skin and Soft
Tissue Infections
• Impetigo, both bullous and non-bullous, is
now caused primarily by
S. aureus. Topical mupirocin, some oral cephalosporins such as cephalexin and cefdinir, oral
amoxicillin-clavulanate,
and some oral macrolide
antibiotics are efficacious
in treating this condition, although S. aureus
SPRING 2007
resistance to erythromycin is very high in many
communities.1,2
• Systemic treatment
should be effective against
S. aureus. Amoxicillin-clavu-
• Acute flares of atopic
dermatitis are effectively
treated with topical corticosteroids of appropriate
potency based on disease
severity. Systemic antibi-
Acute flares of atopic dermatitis
are effectively treated with
topical corticosteroids of
appropriate potency based on
disease severity.
lanate and oral cephalosporins such as cephalexin
and cefdinir have been
shown to be more efficacious than amoxicillin and
penicillin, respectively.
Cephalexin and cefdinir
are active in impetigo
caused by erythromycinresistant S. aureus.3,4
Incision and drainage
are vital components of
treatment when abscesses
are present.5-7
otics as monotherapy without corticosteroid treatment for atopic dermatitis
does not contribute significantly to efficacy of the
eczematous
dermatitis
itself. Antibiotics are indicated when infection is
clearly present.
Chronic suppressive antibiotic therapy, either topical or oral, is not recommended in the management of atopic dermatitis.8
Editors’ Message
elcome to the SPRING 2007
Extensions. Our purpose in bringing
you this newsletter is to provide you with
timely, relevant clinical information to help
you provide the best care to your patients.
In the lead section of this issue, beginning on
this page, we report on highlights of the newly
formed Scientific Panel of Antibiotic Usage in
Dermatology (SPAUD), which focuses on
usage patterns, management challenges and
prescribing recommendations for dermatologic use
of antibiotics.
This issue’s Sound
Bites gives insight into the
new American Acne and
Rosacea Society with
information on how to join.
In addition, Sound Bites
highlights pediatric rosacea Dr. James Del Rosso
and discusses whether
superficial peels affect
sebum secretion.
In the litSCAN column we
offer a synopses of studies
that researched topical treatments for hypertrophic
scars, whether melanocytic
Dr. Roger Ceilley
nevi are influenced by pregnancy, and more.
Lastly, we also offer an interesting Case of
the Month. Turn to page 6 to try to diagnose
this patient’s condition.
You are invited to submit a succinctly written summary of an interesting case accompanied by a digital photograph. Send it to:
[email protected].
Please forward to us any comments or
suggestions you have regarding Extensions.
We hope to consistently achieve our objectives of providing a publication that is enjoyable to read, educational and clinically useful.
W
Professionally yours,
James Q. Del Rosso, D.O., F.A.O.C.D.
Roger I. Ceilley, M.D.
Co-editors
2
Current Approaches
to Antibiotic
Selection in
Uncomplicated Skin
and Soft Tissue
Infections
Tackling the
Anterior Nares and
Other Sites of
Colonization:
Implications for the
Dermatologist
• Uncomplicated skin and
soft tissue infections (USSI) are
frequently diagnosed clinically
and are often not cultured in
ambulatory clinic patients.
When cultures are tabulated,
gram-positive organisms dominate. Staphylococcus aureus and
coagulase-negative species are
the majority followed by streptococcal infections. Enterococci
and Pseudomonas aeruginosa are
more common in complicated
skin and soft tissue infections.9
• Erysipelas, a form of cellulitis,
has high morbidity. It is characterized by diffuse erythema with
a cliff-like border and without
subtle gradations of erythema.
Relapse rates approach 25%,
especially on lower extremities.
Treatments should target
patients at high risk for recurrence. Many patients with lower
extremity involvement elicit stasis
changes and decreased lymphatic flow, and many exhibit interdigital tinea pedis.
In a study of patients with
≥three episodes within the prior
2 years, I.V. penicillin for four
10-day courses per year (or erythromycin for penicillin-allergic
patients), and methods to
enhance lymphatic drainage
such as pneumatic compression
demonstrated one recurrence
over a 2-year follow-up.10
• Minor skin and soft tissue
infections may still be empirically treated with oral antibiotic
therapy including beta-lactam
drugs (eg, cephalosporins,
semisynthetic
penicillins),
macrolides or clindamycin.11
• The most frequently prescribed oral antimicrobials for
USSI include:12
■ oral cephalosporins
(>50%)
■ amoxicillin/clavulanic
acid
■ macrolides
■ anti-staphylococcal
penicillins
■ fluoroquinolones.
• In an evaluation of
S. aureus carriage from different body sites in the general
population, persistent nasal
carriers and perineal carriers
produced the highest organism loads, while other sites
were less heavily colonized and
more likely to be transient. A
strong direct correlation was
found between colonization
rates for the hand and nose in
both the general population
and in nasal carriers. The anterior nares is the most frequently involved carriage site.13
• A nasal MRSA colonization
study showed a 10-fold increase
in the same community over 3
years, suggesting an overall
increase in carriage rates.14
• In one study, when nonnasal carriers were artificially
inoculated with a mixture of
S. aureus strains, they were
able to eliminate the inoculated strains and did not become
carriers. Persistent carriers
selected the original resident
strain from the mixture and
demonstrated an inherent
propensity for carriage.15
• A study of U.S. soldiers
showed 3% (24/812) were colonized with CAMRSA. Of those,
38% (9/24) developed soft tissue infection over 2 months vs.
3% colonized with methicillinsensitive S aureus infection.16
• Nasal S. aureus carriage
ranges from 39% to 82% in
atopic dermatitis.17 Two studies found that nasal colonization correlated with greater
disease severity.18,19
• Nasal carriage of MRSA was
shown to correlate with bacteremia and infections of vascular access sites for dialysis and
postoperative wound infections.20
• In a double-blind, placebocontrolled trial of MRSA carriers (nares=60%; groin=38%,
skin=62%) subjects used
chlorhexidine skin cleansing
and were treated with topical
mupirocin or placebo to anterior nares for 5 days. MRSA
eradication from all sites was
25% in the mupirocin +
chlorhexidine group and 18%
in the placebo/chlorhexidine
group. Nasal eradication was
44% and 23% respectively.21
nance treatment once adequate disease control is
achieved. If antibiotics are
used chronically to sustain
long-term maintenance of
therapeutic response, concomitant use of BPO is recommended to limit emer-
Some antibiotics such as
tetracyclines have
anti-inflammatory activity and
may be clinically appropriate in the
management of some
inflammatory dermatoses.
• An in vitro study comparing povidone iodine, benzalkonium chloride, chlorhexidine gluconate and ethanol
showed 70% ethanol to be
most effective against MRSA.
It eradicated both sensitive
and resistant strains in
<3 minutes.22
• Switching from chlorhexidine gluconate 4% to triclosan 1% reduced new
MRSA cases per week from
3.4 to 0.14 (p<0.0001).22
Preliminary SPAUD
Consensus Statement
Acne and Rosacea
• Antibiotic monotherapy,
especially prolonged use, is
not recommended in the treatment of acne vulgaris.
Prolonged topical or oral
antibiotic therapy for acne vulgaris is best accompanied by
use of BPO to optimize efficacy and mitigate emergence of
less sensitive P. acnes strains.
• Combination use of
BPO, a topical and/or oral
antibiotics
and
topical
retinoids for acne is rational
with the latter being applicable for long-term mainte-
gence of antibiotic resistance
(ie, Propionibacterium acnes).
Whenever possible, the
duration of chronic oral
antibiotic therapy for acne or
rosacea should be limited as
much as is clinically feasible.
• Oral antibiotics have characteristically been used for the
past four to five decades for
rosacea; however, efficacy of
oral agents such as tetracyclines
is probably related to antiinflammatory effects more so
than antibiotic activity in this
disorder. Anti-inflammatory
effects of oral tetracyclines,
especially doxycycline and
minocycline, are also believed
to contribute to the improvement of acne.
• Some antibiotics such as
tetracyclines have anti-inflammatory activity and may be
clinically appropriate in the
management of some inflammatory dermatoses.
• Emergence of less-sensitive P. acnes, commensal
organisms, and potentially
pathogenic
bacteria
in
patients undergoing chronic
antibiotic therapy, especially
with an oral agent, warrants
further study regarding
issues related to antibiotics
commonly prescribed by dermatologists, especially for
chronic use.
• Although topical and oral
antibiotic
therapy
may
impact the microbiologic
activity of skin and nares,
data are more limited with
topical antibiotic use, especially with regard to clinical
significance. Further study is
needed to better differentiate implications that may be
clinically significant to both
individual patients and the
general population.
• Presence of less-sensitive
P. acnes organisms contribute
to decreased efficacy of antibiotic treatment in some
patients, especially if a high
density of less-sensitive strains
are present. However, oral
antibiotics such as doxycycline
and minocycline, and topical
clindamycin, have continued
to maintain efficacy in many
patients, especially when used
in appropriate combination
with other agents (ie. BPO,
topical retinoids).
Fluoroquinolones are not
generally recommended as
empiric first-line therapy for
USSI due to the availability
of other effective agents, and
the need to preserve their
efficacy in the treating infections where oral options are
more limited (ie, gramnegative pathogens such as
P. aeruginosa).
• Many skin and soft tissue
infections caused by CAMRSA
present as abscesses.
Overall, the most important predictor of effective
response to treatment is
appropriate incision and
drainage, even in cases when
the initial empiric oral antibiotic therapy is not active
against CAMRSA. If culture
and sensitivity confirms
CAMRSA after incision and
drainage, the need to use an
oral antibiotic active against
CAMRSA is based on the
patient’s clinical response.
• Topical mupirocin may be
used to eradicate both methicillin-sensitive and methicillinresistant nasal S. aureus carriage; however, therapy should
Many skin and soft tissue
infections caused by CAMRSA
present as abscesses.
Skin and Soft Tissue Infections
• Most uncomplicated skin
and soft tissue infections
(USSI) seen in ambulatory
clinical practice are caused
by staphylococci and streptococci. Oral cephalosporins
active against these organisms (ie. cephalexin, cefdinir) are the most common
agents prescribed by dermatologists for USSI and exhibit favorable efficacy and safety profiles. There are no oral
cephalosporins that exhibit
activity against CAMRSA or
P. aeruginosa.
be intermittent. Chronic use
may contribute to emergence
of mupirocin-resistant S. aureus.
Both high-level and low-level
mupirocin resistance may be
significant with regard to therapeutic effectiveness of the drug.
Preoperative
Prophylactic
Antibiotic Therapy
• Overall, the need for preoperative prophylactic systemic antibiotic therapy in
patients undergoing dermatologic surgical procedures (ie.
biopsies, excisions) involving
non-contaminated or non-
infected skin has not been
substantiated by a strong body
of scientific evidence, including both prevention of endocarditis or postoperative
wound infection.
Acknowledgement: The SPAUD
meeting is sponsored by Physician
Resources and is supported in
part through the following educational grantors: CollaGenex
Pharmaceuticals, Medicis Pharmaceuticals, and Stiefel Laboratories. The SPAUD faculty gratefully acknowledges the support of
these companies in this unprecedented dermatologic initiative.
Submitted for Publication.
11.
12.
13.
14.
15.
References
1.
Bass JW, Chan DS, Creamer KM.
Comparison of oral cephalexin,
topical mupirocin and topical bacitracin for treatment of impetigo.
Ped Infect Dis J. 1997;16:708-709.
2.
Booth JH, Benrimoj SI. Mupirocin
in the treatment of impetigo. Int J
Dermatol. 1992;31:1-9.
3.
Dagan
R,
Bar-David Y.
Comparison of amoxicillin and
clavulanic acid (augmentin) for the
treatment of nonbullous impetigo.
AJDC 1989;143:916-918.
4.
Demidovich CW, Wittler RR,
Ruff ME et al. Impetigo: Current
etiology and comparison of penicillin, erythromycin and cephalexin therapies. AJDC. 1990;144:
1313-1315.
5.
Rutherford WH, Calderwood JW,
Hart D, Merret JD. Antibiotics in
surgical treatment of septic lesions.
Lancet.1970;May 23:1077-1080.
6.
Llera JL, Levy RC. Treatment of
cutaneous abscess:A double-blind
clinical study. Ann Emer Med.
1985;14:15-19.
7.
Macfie J, Harvey J.The treatment
of acute superficial abscesses: a
prospective clinical trial. Br J Surg.
1977;64:264-266.
8.
Hanifin JM, Rogge JL.. Staphylococcal infections in patients
with atopic dermatitis. Arch
Dermatol. 1977;113:1383-1386.
9.
Hedrick J. Acute bacterial skin
infections in pediatric medicine:
current issues in presentation and
treatment. Pediatr Drugs. 2003;5
Suppl 1: 35-46.
10. Allard P, Stucker M et al. Cyclical
16.
17.
18.
19.
20.
21.
22.
intravenous antibiotics as an effective therapy concept in chronic
recurrent erysipelas. Hautarzt.
1999;50:34-38.
Stevens DL, Bisno AL, Chambers
HF et al. Practice guidelines for
the diagnosis and management of
skin and soft-tissue infections. Clin
Infect Dis. 2005;41:1373-1406.
IMS Data: 2003.
Wertheim HFL, Melles DC,Vos
MC et al.The role of nasal carriage
in Staphylococcal aureus infections.
Lancet Infect Dis. 2005;5:751-762.
Creech CB, Kernodle DS et al.
Increasing rates of nasal carriage of
methicillin-resistant Staphylococcus
aureus in healthy children. Pediatr
Infect Dis J. 2005;24:617-621.
Nouwen J, Boelens H, van
Belkum A, Verbrugh H. Human
factor in Staphylococ-cus aureus
nasal carriage. Infect Immun.
2004;72:6685-6688.
Ellis MW, Hospenthal DR et al.
Natural history of communityacquired
Methicillin-resistant
Staphylococcus aureus colonization
and infection in soldiers. Clin
Infect Dis. 2004;39:971-979.
Roth HL.Atopic dermatitis revisited. Int J Dermatol. 1987;26:139-149.
Gilani SJK, Gonzalez M, Hussain I,
Finlay AY, Patel GK. Staphylococcus
aureus re-colonization in atopic
dermatitis; beyond the skin. Clin
Exp Dermatol. 2004;30:10-13.
Hon KL, Lam MC, Leung TF, et
al. Clinical features associated with
nasal Staphylococcus aureus colonisation in chinese children with
moderate-to-severe atopic dermatitis. Ann Acad Med Singapore.
2005;34:602-605.
Chiang
FY,
Climo
M.
Staphylococcus aureus carriage and
healthcare-acquired infection. Curr
Infect Dis Rep. 2002;4:498-504.
Harbarth S, Dharan S, Liassine N, et
al. Randomized, placebo-controlled double-blind trial to evaluate the efficacy of mupir-ocin for
eradicating carriage of Methicillinresistant Staphylococcus aureus.
Antimicrob Agents Chemother.
1999;43:1412-1416.
Webster J. Handwashing in a
neonatal intensive care nursery:
product acceptability and effectiveness of chlorhexidine gluconate 4%
and triclosan 1%. J Hosp Infect.
1992;21:137-141.
3
Sound Bites
Excerpts from scientific journals
and highlights of a new society
devoted to acne and rosacea
research and treatment.
By James Q. Del Rosso, D.O., F.A.O.C.D.
AMERICAN ACNE & ROSACEA SOCIETY:
STIMULATING INTEREST IN TWO
COMMON DERMATOLOGIC DISORDERS
The American Acne &
Rosacea Society (AARS), a
new organization dedicated
to furthering education and
research related to both of
these common disorders,
recently completed its second educational meeting on
February
2,
2007
in
Washington, DC.
The society provides an educational newsletter and will
soon be kicking off a major public relations campaign to
heighten public awareness
about these disorders and the
importance of appropriate dermatologic care.
The current President of the
organization is Hilary Baldwin,
M.D., the President-Elect is
James Del Rosso, D.O., and the
Secretary-Treasurer is Lee
Zane, M.D.
Physician assistants and
nurse practitioners who are
employed by dermatologists
4
For more
information,
please contact
the AARS
Executive
Director,
Cindy Froelich
(contact
information
below).
are encouraged to join the
AARS. For more information,
please contact the AARS
Executive Director, Cindy
Froehlich, at [email protected]. The following items
are excerpted from the first
AARS newsletter issue published in January 2007. ■
DO SUPERFICIAL PEELS AFFECT
SEBUM SECRETION?
Superficial chemical peels
using agents such as glycolic
acid and salicylic acid are
often utilized in the treatment of acne vulgaris.
Applications of low concentrations of glycolic acid and
alpha-hydroxy acid (AHA)
reduce corneocyte adhesion;
higher concentrations promote epidermolysis.
Salicylic acid, a component
of Jessner’s solution, is a
“desmolytic agent”, thus producing detachment of corneodesmosomes leading to
desquamation of corneocytes.
Salicylic acid has been reported to have a stronger
comedolytic effect than AHAs.
When asked by a patient,
“Will the peels make my face
less oily?”, it now appears that
the answer is “no” based on a
recent study.
• Patients (mean age 25.2
years) with mild to moderate
facial acne vulgaris underwent peeling with glycolic
acid 30 % (n=27) or Jessner’s
solution (n=11) on two separate occasions 2 weeks apart.
• The objective of the
study was to assess the
impact of superficial peeling
on sebum secretion with
each preparation.
• Before and 2 weeks after
completion of each peel,
sebum levels of the forehead, nose, cheeks and chin
were measured using a
sebumeter. Sebum levels
were measured at least
5 hours after facial washing
in order to measure the
plateau level (“casual level”).
• The same blinded investigator performed the measurement of sebum levels in a controlled room environment
(temperature and humidity).
• Superficial facial peeling with
either glycolic acid 30% or
Jessner’s solution did not significantly affect sebum secretion after
two repetitive applications separated by 2 weeks.
• The impact of the two
types of peels on sebum
secretion were not significantly different. ■
Source: Lee SH, et al.
JEADV. 2006;20:964-968.
PEDIATRIC ROSACEA
Pediatric rosacea is rare.
The phymatous form has
not been reported in children. However, occasional
cases, including one report
of rosacea fulminans (pyoderma faciale) appears in
the literature.
• The differential diagnosis
of pediatric rosacea includes
multiple entities, such as
acne vulgaris and demodicidosis. The latter has been
seen in neonates and
immunocompromised children with either leukemia or
HIV infection.
• Other entities in the differential diagnosis of pediatric
rosacea include childhood sarcoidosis, periorificial dermatitis and granulomatous periorificial dermatitis. The latter
entity has also been referred
to as facial Afro-Caribbean
childhood eruption, presenting as pink to yellow brown
monomorphous
papules
affecting the perioral, periocular and perinasal regions in
prepubertal children. ■
Source: Kroshinsky D, et
al. Dermatologic Therapy.
2006;19:196-201.
litSCAN
Clinically Significant Abstracts from
Current Medical and Surgical
Dermatologic Literature.
By Roger I. Ceilley, M.D.
Are Melanocytic Nevi Influenced
by Pregnancy?
Zampino MR, Corazza M, et al.
Dermatol Surg. 2006;32:1497-1504.
• Subjective clinical changes
of pigmented skin lesions have
been reported in 10.5% and
32.5% of pregnant women.
• Dermoscopic parameters,
total dermoscopic score
(TDS), and the sizes of nevi
showed some variability during pregnancy.
• These changes were transient as the nevi recovered their
prior appearance after delivery.
• Results also indicate an
intrinsic influence of pregnancy that may induce structural
modifications without influencing the size of the nevi.
• Progressive lightening of
the nevi resulted at the end of
pregnancy and after delivery. ■
Topical Treatments for Hypertrophic Scars
Zurada JM, Kriegel D, Davis IC.
J Amer Acad Dermatol. 2006;55:1024-1031.
• Topical therapies for
hypertrophic scars have
become increasingly popular
because of their ease of use,
comfort,
noninvasiveness,
and relatively low cost.
• Results showed no single,
optimal modality that can
eliminate or prevent hypertrophic scarring.
• Products in the United
States containing onion
extract do not improve scar
cosmesis or symptomatology
when compared with a petrolatum-based ointment.
• Imiquimod 5% cream has
been shown to improve the
quality of new hypertrophic
scars after surgery in a preliminary clinical trial, but further studies are necessary.
• Silicone ointment or gel
alone is less effective than silicone sheeting.
• Vitamin E may be detrimental to wound healing
and often leads to contact
dermatitis and is therefore
not recommended. ■
Imiquimod 5% cream has been
shown to improve the quality of
new hypertrophic scars
after surgery.
Fractional Photothermolysis: Treatment of
Facial and Nonfacial Cutaneous
Photodamage with a 1,550-nm ErbiumDoped Fiber Laser
Wanner M, Tanzi EL, Alster T.
Dermatol Surg. 2007;33:23-28.
• The nonablative 1,550-nm
erbium doped fiber laser is an
effective treatment for facial
and non-facial photodamage,
rhytides, and dyspigmentation with a favorable recovery
and side effect profile.
• In this study, 51% to 75%
improvement in photodamage at the 9-month follow-up
was achieved in 73% and 55%
of facial and non-facial skin
treated, respectively.
• Side effects were limited
to transient erythema and
edema in the majority of
patients. No prolonged pigmentary changes or scarring
were observed.
• Patient satisfaction surveys
mirrored the observed clinical effects.
• The noninvasive nature of
fractional photothermolysis
treatment, along with an excellent side effect profile, makes
this an attractive alternative to
ablative laser techniques.
Patient
satisfaction
surveys mirrored
the observed
clinical effects.
• Demand continues to
grow for minimally invasive
techniques to treat photodamage, and dermasurgeons
are continually challenged to
produce effective treatment
while minimizing post treatment recovery. ■
Pacemakers and Implantable Cardiac
Defibrillators in Dermatologic Surgery.
Matzke TJ, Christenson LJ, et al.
Dermatol Surg. 2006;32:1155-1161.
• 173 patients with pacemakers and 13 with implantable cardiac defibrillators (ICDs) undergoing dermatologic surgery
had no documented complications from electrosurgery.
• Recommended precautions
have included preoperative cardiology evaluation to identify
patients hemodynamically dependent on pacemakers.
• Electrosurgery can result
in pacemaker malfunction by
oversensing, inhibiting firing
or triggering of rapid firing,
device reprogramming, battery depletion, or direct damage to the device.
• Inhibition is the most
common side effect and
occurs when electromagnetic interference (EMI) is
misinterpreted as physiologic cardiac activity, resulting in the pacemaker not
sensing to fire.
• To lower the risk of prolonged inhibition of device
output from EMI, demand
pacemakers may be reprogrammed to an asynchronous
(fixed) mode that does not
sense electrical activity and
fires at a fixed rate.
• The care of patients with
ICDs requires special consideration. The authors published
recommendations regarding
electrosurgery in patients with
cardiac devices. ■
*Authors note: In our practice,
hot cautery with a disposable
cautery unit and pressure is a satisfactory alternative for most patients
with pacemakers/defibrillators.
5
Case of the
Month
Follicular Mucinosis
By Roger I. Ceilley, M.D., and Sandra E. Coady, P.A.-C.
Case Study
A 49-year-old Caucasian female presented with a 3-month history of
an enlarging, red lesion that arose suddenly on her left pre-auricular
region. She complained that the lesion was very itchy, and treatment
with 1% hydrocortisone cream provided no relief.
Examination revealed an erythematous, slightly indurated plaque
without ulceration, crusting, or scabbing (Fig. 1). Exam of the head and
neck revealed no anterior cervical or jugulodigastric lymph node
enlargement. Physical exam was otherwise noncontributory. No new
lesions were found when she was examined 1 month later; however,
examination 2 months later revealed three more lesions present on her
head and neck (Fig. 2).
Diagnosis and Discussion
Two 4-mm punch biopsies were performed. Histology showed that
both biopsies were similar with large amounts of primary follicular
mucin associated with wide separation of follicular epithelial cells and
mucinous microcyst formation.
Perifollicular mononuclear inflammation was seen, and adjacent
dermis showed a mix of perivascular and interstitial inflammatory cells
in which lymphocytes predominated. A few scattered eosinophils were
also seen. Cytologic atypia was not appreciated. The clinical-pathologic correlation led to the diagnosis of follicular mucinosis.
Follicular mucinosis — also known as alopecia mucinosa — was
first reported by Pinkus in 1957.1 The eruption consists of papules and
or indurated plaques that show distinct histologic changes in the hair
follicles. These changes can lead to hair loss, which is generally the
first outward sign of involvement. This condition also causes mucinous material to accumulate in the hair follicles and sebaceous
glands, resulting in an inflammatory and degenerative condition.
Occasionally, mucinous material can be expressed out of active
lesions.
These plaques and papules are frequently pruritic and may occur
as an isolated area or in clusters.2 The face, neck, and scalp are the
most frequently affected sites, although these lesions may appear on
any part of the body.3 The disorder is more frequent in males. The
alopecia is generally reversible unless follicular destruction and scarring have occurred.
There are three subsets of follicular mucinosis.
1. The most common subtype is seen in a younger age group (<40
years), with a tendency for head, neck, and upper arms involvement.
Spontaneous resolution generally occurs in 2 months to 2 years.
2. A second subtype occurs in persons >40 years and tends to
present with numerous larger lesions that are more widespread, and
of a chronic nature.
3. The third subtype is associated with mycosis fungoides (MF), the
most common form of cutaneous T-cell lymphoma. This subtype may
occur at any age, and lesions tend to be numerous and widespread.
It is estimated that 15% to 30% of patients with follicular mucinosis
will have associated MF, which may be diagnosed histologically by the
presence of atypical lymphocytes. The dermatopathologist should
6
FIGURE 1
FIGURE 2
carefully analyze any specimen with follicular mucinosis for features
of MF, and if found, the patient must undergo further evaluation.
Histopathology
Follicular mucinosis, also known as alopecia mucinosa is a disease process defined histopathologically by mucin deposition in hair
follicles and sebaceous glands which then undergo degeneration.
The pathogenesis of FM is unknown.1
Treatment
No histologic findings of MF were seen in the biopsy from our
patient, so this case most likely represents the second subtype of
follicular mucinosis.
Our patient was treated with multiple intralesional triamcinolone
2.5 mg/cc injections. Other forms of therapy are being considered.
There is no definitive treatment for follicular mucinosis. Most
cases will resolve on their own within 2 to 24 months of initial presentation, though other subtypes are more recalcitrant. Treatments
for follicular mucinosa include topical, intralesional and systemic
corticosteroids as well as PUVA, radiation therapy, isotretinoin, dapsone, and minocycline.1
Pediatric and primary chronic follicular mucinosis generally disappear within 2 years, while secondary follicular mucinosis (especially
when it appears with mycosis fungoides) persists and has the least
favorable prognosis.2
References
1. Mucinoses, Rebora, A. and Rongioletti, F. in Dermatology. Eds Bolognia
Jean L, Jorizzo Joseph L, Rapini Ronald R. 2003. Mosby. pp.656-657.
2. Gerstner Gervaise L, Lebwohl Mark G: Alopecia Mucinosa 2006; 1-10
eMedicine.
3. Cutaneous Manifestations of Internal Disease, Habif, Thomas P. In Clinical
Dermatology, Fourth edition. 2004. Mosby;p.894.
Brief Summary
Duac® Topical Gel
(clindamycin, 1% - benzoyl peroxide, 5%)
ForDerm atologicalUse Only.
NotforOphthalm ic Use.
RxOnly
INDICATIONS AND USAGE
Duac TopicalGelis indicated forthe topicaltreatm entofinflam m atory
acne vulgaris.
Duac TopicalGelhas notbeen dem onstrated to have any additional
benefitwhen com pared to benzoylperoxide alone in the sam e vehicle
when used forthe treatm entofnon-inflam m atory acne.
CONTRAINDICATIONS
Duac TopicalGelis contraindicated in those individuals who have
shown hypersensitivity to any ofits com ponents orto lincom ycin.Itis
also contraindicated in those having a history ofregionalenteritis,
ulcerative colitis,pseudom em branous colitis,orantibiotic-associated
colitis.
W ARNINGS
ORALLY AND PARENTERALLY ADM INISTERED CLINDAM YCIN HAS
BEEN ASSOCIATED W ITH SEVERE COLITIS W HICH M AY RESULT IN
PATIENT DEATH.USE OF THE TOPICAL FORM ULATION OF
CLINDAM YCIN RESULTS IN ABSORPTION OF THE ANTIBIOTIC FROM
THE SKIN SURFACE.DIARRHEA,BLOODY DIARRHEA,AND COLITIS
(INCLUDING PSEUDOM EM BRANOUS COLITIS)HAVE BEEN
REPORTED W ITH THE USE OF TOPICAL AND SYSTEM IC
CLINDAM YCIN.STUDIES INDICATE A TOXIN(S)PRODUCED BY
CLOSTRIDIA IS ONE PRIM ARY CAUSE OF ANTIBIOTIC-ASSOCIATED
COLITIS.THE COLITIS IS USUALLY CHARACTERIZED BY SEVERE
PERSISTENT DIARRHEA AND SEVERE ABDOM INAL CRAM PS AND
M AY BE ASSOCIATED W ITH THE PASSAGE OF BLOOD AND M UCUS.
ENDOSCOPIC EXAM INATION M AY REVEAL PSEUDOM EM BRANOUS
COLITIS.STOOL CULTURE FOR Clostridium difficile AND STOOL
ASSAY FOR Clostridium difficile TOXIN M AY BE HELPFUL
DIAGNOSTICALLY.W HEN SIGNIFICANT DIARRHEA OCCURS,THE
DRUG SHOULD BE DISCONTINUED.LARGE BOW EL ENDOSCOPY
SHOULD BE CONSIDERED TO ESTABLISH A DEFINITIVE DIAGNOSIS
IN CASES OF SEVERE DIARRHEA.ANTIPERISTALTIC AGENTS SUCH
AS OPIATES AND DIPHENOXYLATE W ITH ATROPINE M AY PROLONG
AND/OR W ORSEN THE CONDITION.DIARRHEA,COLITIS AND
PSEUDOM EM BRANOUS COLITIS HAVE BEEN OBSERVED TO BEGIN
UP TO SEVERAL W EEKS FOLLOW ING CESSATION OF ORAL AND
PARENTERAL THERAPY W ITH CLINDAM YCIN.
M ild cases ofpseudom em branous colitis usually respond to drug
discontinuation alone.In m oderate to severe cases,consideration
should be given to m anagem entwith fluids and electrolytes,protein
supplem entation and treatm entwith an antibacterialdrug clinically
effective againstClostridium difficile colitis.
PRECAUTIONS
General:Forderm atologicaluse only;notforophthalm ic use.
Concom itanttopicalacne therapy should be used with caution because
apossible cum ulative irritancy effectm ay occur,especially with the use
ofpeeling,desquam ating,orabrasive agents.
Theuse ofantibiotic agents m ay be associated with the overgrowth of
nonsusceptible organism s,including fungi.Ifthis occurs,discontinue
use ofthis m edication and take appropriate m easures.
6.Duac TopicalGelcan be stored atroom tem perature up to 25°C
(77°F)forup to 2 m onths.Do notfreeze.Keep tube tightly closed.
Keep outofthe reach ofsm allchildren.Discard any unused product
after2 m onths.
Keep tube tightly closed.Keep outofthe reach ofsm allchildren.
7.Before applying Duac TopicalGelto affected areas,wash the skin
gently,rinse with warm water,and patdry.
Carcinogenesis,M utagenesis,Im pairm entofFertility:Benzoyl
peroxide has been shown to be a tum orprom oterand progression
agentin a num berofanim alstudies.The clinicalsignificance ofthis is
unknown.
2.This m edication should notbe used forany disorderotherthan that
forwhich itwas prescribed.
3.Patients should notuse any othertopicalacne preparation unless
otherwise directed by theirphysician.
4.Patients should reportany signs oflocaladverse reactions to their
physician.
5.Duac TopicalGelm ay bleach hairorcolored fabric.
®
StiefelLaboratories,Inc.
CoralGables,FL 33134
833185 Rev.0504
Benzoylperoxide in acetone atdoses of5 and 10 m g adm inistered
twice perweek induced squam ous cellskin tum ors in transgenic TgAC
m ice in a study using 20 weeks oftopicaltreatm ent.
Genotoxicity studies were notconducted with Duac TopicalGel.
Clindam ycin phosphate was notgenotoxic in Salm onella typhim urium
orin a ratm icronucleus test.Benzoylperoxide has been found to cause
DNA strand breaks in a variety ofm am m alian celltypes,to be
m utagenic in Salm onella typhim urium tests by som e butnotall
investigators,and to cause sisterchrom atid exchanges in Chinese
ham sterovary cells.Studies have notbeen perform ed with Duac
TopicalGelorbenzoylperoxide to evaluate the effecton fertility.
Fertility studies in rats treated orally with up to 300 m g/kg/day of
clindam ycin (approxim ately 120 tim es the am ountofclindam ycin in
the highestrecom m ended adulthum an dose of2.5 g Duac TopicalGel,
based on m g/m 2)revealed no effects on fertility orm ating ability.
Your Choice is Clear
TM
Pregnancy:Teratogenic Effects:Pregnancy Category C:Anim al
reproduction studies have notbeen conducted with Duac TopicalGelor
benzoylperoxide.Itis also notknown whetherDuac TopicalGelcan
cause fetalharm when adm inistered to a pregnantwom an orcan affect
reproduction capacity.Duac TopicalGelshould be given to a pregnant
wom an only ifclearly needed.
Developm entaltoxicity studies perform ed in rats and m ice using oral
doses ofclindam ycin up to 600 m g/kg/day (240 and 120 tim es the
am ountofclindam ycin in the highestrecom m ended adulthum an dose
based on m g/m 2,respectively)orsubcutaneous doses ofclindam ycin
up to 250 m g/kg/day (100 and 50 tim es the am ountofclindam ycin in
thehighestrecom m ended adulthum an dose based on m g/m 2,
respectively)revealed no evidence ofteratogenicity.
Nursing W om en:Itisnotknown whetherDuac TopicalGelis secreted
into hum an m ilk aftertopicalapplication.However,orally and
parenterally adm inistered clindam ycin has been reported to appearin
breastm ilk.Because ofthe potentialforserious adverse reactions in
nursing infants,a decision should be m ade whetherto discontinue
nursing orto discontinue the drug,taking into accountthe im portance
ofthe drug to the m other.
Pediatric Use:Safety and effectiveness ofthis productin pediatric
patients below the age of12 have notbeen established.
ADVERSE REACTIONS
During clinicaltrials,allpatients were graded forfacialerythem a,
peeling,burning,and dryness on the following scale:0 = absent,1 =
m ild,2 = m oderate,and 3 = severe.The percentage ofpatients thathad
sym ptom s presentbefore treatm ent(atbaseline)and during treatm ent
were as follows:
REFERENCES:
1. IMS Data, Oct. 2006.
2. Duac [Prescribing Information]. Stiefel Laboratories, Inc.,
2004.
Localreactions with use ofDuac TopicalGel
% ofpatients using Duac TopicalGelwith sym ptom present
Com bined results from 5 studies (n = 397)
Clindam ycin and erythrom ycin containing products should notbe used
in com bination.In vitro studies have shown antagonism between these
two antim icrobials.The clinicalsignificance ofthis in vitro antagonism
is notknown.
1.Duac TopicalGelis to be used as directed by the physician.Itis for
externaluse only.Avoid contactwith eyes,and inside the nose,
m outh,and allm ucous m em branes,as this productm ay be irritating.
U.S.PatentNos.5,466,446,5,446,028,5,767,098,and 6,013,637
PatentPending
8.Excessive orprolonged exposure to sunlightshould be lim ited.
To m inim ize exposure to sunlight,a hatorotherclothing should
beworn.
Avoid contactwith eyes and m ucous m em branes.
Inform ation forPatients:Patients using Duac TopicalGelshould
receive the following inform ation and instructions:
Dispensing Instructions forthe Pharm acist:Dispense Duac
TopicalGelwith a 60 day expiration date and specify “Store at
room tem perature up to 25°C (77°F).Do notfreeze.”
Before Treatm ent(Baseline)
During Treatm ent
M ild
M oderate
Severe
M ild
Erythem a
28%
3%
0
26%
Peeling
6%
<1%
0
Burning
3%
<1%
0
Dryness
6%
<1%
0
M oderate Severe
5%
0
17%
2%
0
5%
<1%
0
15%
1%
0
(Percentages derived by # subjects with sym ptom score/# enrolled
Duac subjects,n = 397).
HOW SUPPLIED
Duac™ (clindam ycin,1% -benzoylperoxide,5% )TopicalGelis
available in a 45 gram tube -NDC 0145-2371-05.
Priorto Dispensing:Store in a cold place,preferably in a refrigerator,
between 2°C and 8°C (36°Fand 46°F).Do notfreeze.
Duac is a registered trademark of Stiefel Laboratories, Inc.
Your Choice is Clear and Make the Clear Choice are trademarks
of Stiefel Laboratories, Inc.
#
1
Am erica’s
FastestGrowing
Rx Acne1
Medication
Im pressive results.
Proven tolerability.
2
For topical BPO/antibiotic acne therapy,
TM
YourChoice isClear
TM
Make the ClearChoice
IM P O R TA N T S A FETY IN FO R M A TIO N
D uac TopicalG elis indicated forthe topicaltreatm entofinflam m atory acne.
D uac TopicalG elis w elltolerated.Side effects m ay include erythem a,
peeling,burning,and dryness.
D uac TopicalG elis contraindicated in patients w ho have show n
hypersensitivity to any ofits com ponents orlincom ycin,and in those w ith a
history ofregionalenteritis,ulcerative colitis,orantibiotic-associated colitis.
D iarrhea,bloody diarrhea,and colitis have been reported w ith the use of
topicalclindam ycin.D iscontinuation is recom m ended ifsignificantdiarrhea
develops.
Please see accom panying Brief Sum m ary of Prescribing Inform ation.
© 2007,StiefelLaboratories,Inc. D TG -74-2006-U SA U .S.Patent N os.5,466,446,5,446,028,5,767,098,and 6,013,637 Patents Pending
HMP Communications
83 General Warren Blvd., Suite 100
Malvern, PA 19355
www.stiefel.com
PRSRT STD
US POSTAGE
PAID
BENSALEM, PA
PERMIT #182