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Treatment of Molluscum Contagiosum with Cantharidin:A Practical Approach

Erin F.D. Mathes, MD; and Ilona J. Frieden, MD

ABSTRACT

M olluscum contagiosum is very com- mon. In this article we discuss the use of cantharidin as a treatment

option for molluscum contagiosum and give detailed information about distribution sources, how to apply it, and caveats regarding its use. Molluscum contagiosum is a common vi- ral disease of childhood caused by a poxvirus, which presents with small, firm, dome-shaped, umbilicated papules. It is generally benign and self-limited, with spontaneous resolution within 6 months to several years. Watchful waiting can often be an appropriate management strategy; however, some patients either desire or require treatment. Reasons for actively treating mol- luscum contagiosum may include alleviation of discomfort and itching (particularly in patients where an eczematous eruption — the so-called “molluscum eczema” — is seen in association) or in patients with ongoing atopic dermatitis where more lesions are likely to be present. Other reasons for treatment include limitation of spread to other areas and people, prevention of scarring and superinfection, and elimination

of the social stigma of visible lesions. No one treatment is uniformly effective. Treatment options include destructive therapies (curettage, cryotherapy, canthari- din, and keratolytics, among others), immu- nomodulators (imiquimod, cimetidine, and Candida antigen), and antivirals (cidofovir). In this article we discuss and describe our first- line treatment approach for those molluscum needing treatment — cantharidin.

Erin F. Mathes, MD, is Pediatric Dermatology Fellow, Department of Dermatology University of California, San Francisco. Ilona J. Frieden, MD, is Professor of Dermatology and Pediatrics, Depart- ments of Dermatology and Pediatrics University of California, San Francisco. Address correspondence to: Erin F. Mathes, MD, 1701 Divisadero St., Box 0316, San Francisco, CA 94143-0316; fax 415-353-7850; e-mail mathese@ derm.ucsf.edu. Dr. Mathes and Dr. Frieden have disclosed no rel- evant financial relationships. doi: 10.3928/00904481-20100223-03

For treatment, see page 125.

Editor’s note: Each month, this department features a discussion of an unusual diagnosis in genetics, radiology, or dermatology. A description and images are presented, with the diagnosis and an explanation of how the diagnosis was determined following. As always, your comments are welcome. E-mail pedann@slackinc.com.

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TREATMENT

Cantharidin

A recent review of evidence sup- porting various treatment options concluded that cantharidin may be the treatment of choice in young children

because it is painless and effective. 1 Cantharidin, a phosphodiesterase inhibitor that causes vesiculation of the skin, was originally derived from the blister beetle, but now is synthe- sized commercially. 2 Careful appli- cation to the skin typically results in

a small vesicle. Because molluscum

are very superficial skin lesions, ap- plication causes skin vesiculation, with extrusion of the molluscum

body, leading to the resolution of the lesion. 2 Although the evidence for the efficacy of cantharidin is mainly limited to retrospective case series, many physicians use cantharidin as

a treatment, and its use has a high

rate of parental (60% to 90%) and physician (92%) satisfaction. 1,3-8 In 1997, President Clinton ap- proved an amendment to the Food, Drug and Cosmetic Act of 1962 that provides that certain drug products may be compounded by a physician or pharmacist for individual patients. The Food and Drug Administration (FDA) has included cantharidin in the proposed list of bulk substances that physicians and pharmacists are

permitted to compound for use in in- dividual patients. 5

APPLICATION Treating molluscum with canthari- din is not technically difficult.Although there is a small risk for adverse effects, such as excessive blistering and scar-

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SIDEBAR 1.

 

Application Instructions (also see Figure 1 and Figure 2)

Treat only a few lesions (no more than four to five) at the first visit. In subsequent visits, treat no more than 12 to 15 lesions.

Try to get the child’s cooperation, explaining that the medication will not hurt. If the child is fearful and moving, assistance will be needed to apply without accidentally getting the medication on normal, unaffected skin.

Use the wooden end of a cotton applicator to apply a small drop of cantharidin directly to each lesion, taking care not to apply to the surrounding skin. If medication accidentally is applied to normal skin (as may happen in a moving infant), immedi- ately wash off the medication.

Allow the cantharidin to dry for at least 5 to 10 minutes to minimize the risk of spread to adjacent unaffected skin.

Attempting to wash off the medication is controversial. Some authors recommend doing so after 2 to 6 hours, but the polymer created by the collodion makes this dif- ficult. Another option is leaving the medication on overnight, only attempting to wash it off if visible blisters are noted a few hours later, although it is doubtful that this will actually halt the blistering effects.

SIDEBAR 2.

Helpful Hints

Gently shake the bottle, then stir with the applicator before applying to ensure an even concentration of cantharidin.

Do not treat intertriginous areas, or the face, initially. After determining typical response to medication, treatment in these areas can be considered:

For facial lesions, warn parents about the possibility of pigmentary alteration.

Do not treat lesions that are directly adjacent to the eye.

For intertriginous areas, warn parents about the greater risk of excessive blistering, especial- ly in hot weather. If the weather is very hot, limit the number of lesions treated to just a few.

Do not treat inflamed molluscum, at least initially, as they may resolve spontaneously.

If there was little or no response after the first treatment, at the next visit, advise the patient to leave the cantharidin on for longer, or not to wash it off at all.

Over-the-counter oral analgesics, such as ibuprofen or acetaminophen, may help with discomfort.

Topical petrolatum may help soothe irritated skin.Before applying petrolatum,make sure that the cantharidin has been thoroughly washed off. Liberal petrolatum application to areas with active cantharidin can cause spread of cantharidin and widespread blisters. 10

If surrounding dermatitis is present, treat it with 1% hydrocortisone ointment (over-the-counter).

ring, we (and others) believe the safety profile is sufficiently favorable to con- tinue using it for this purpose. 1,3-5,7,8 A major advantage over certain treat- ments, such as cryotherapy and curet-

tage, is that application of cantharidin is painless. Although pain (typically very minor) may occur several hours to a day later, children rarely associate this with their recent doctor visit, and

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SIDEBAR 3.

Anticipatory Guidance 11

Several hours after application, mild discomfort at the site of application occasionally occurs. This can be treated by using cool compresses and by administering over-the- counter analgesics, although, in our experience, this is rarely necessary.

One day after application, a small blister often forms, although, in some cases, only redness or mild crusting is noted. If the blister is tense and uncomfortable, draining with a sterilized needle may help diminish pain, although this is also rarely necessary.

Two to 4 days after application, the blister will crust or drain, leaving a superficial ero- sion. Apply an antibiotic ointment or sterile petrolatum to the eroded area to encour- age re-epithelialization.

Within 1 week, the area is typically healed, although postinflammatory erythema may persist for a week or two. In darker skin types, postinflammatory hyper- or hypopig- mentation may persist, at times for several months.

Scarring is rare. Occasionally, even untreated molluscum leave tiny pitted scars.

are usually willing to have the medica- tion applied on subsequent visits. We disagree with a recent review by Silverberg that suggested that can- tharidin should not be applied by pedi- atricians in their offices. 9 Pediatricians and family physicians perform many procedures that are more complicated than cantharidin application, such as splinting, venipuncture, lumbar punc- ture, intramuscular injection, lacera- tion repair, and incision and drainage. In this article, we give detailed instruc- tions regarding the use of cantharidin, including sources for purchasing, techniques for application, potential pitfalls and adverse effects, and billing codes for in-office treatment with this medication. We believe that with the following information and guidance, cantharidin can become a very useful tool for treating molluscum in the pri- mary physician’s office. Cantharidin is commercially avail- able in a 0.7% concentration, in a collodion base (see Table, page 127, for sources). This 0.7% formulation is strongly preferred for molluscum treatment over a more potent formu-

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lation, which combines a higher con- centration of cantharidin (1%) mixed with podophyllin and salycilic acid, and has a much greater risk for caus- ing excessive blistering, scarring, and even chemical cellulitis. Cantharidin can only be applied in a physician’s office and should never be dispensed to patients for

Cantharidin can only be applied in a physician’s office and should never be dispense to patients for self-application.

self-application (see Sidebar 1, page 125, and Figure 1, and Figure 2, page 127, for application instruc- tions). Most patients improve after one or two visits. 3,4,8 Complications include excessive blistering, pain, pruritis, and burning (see Figure 3, page 128, and Figure 4, page 128). Although some authors estimate that

and Figure 4, page 128). Although some authors estimate that Figure 1. Cantharadin bottle with applicators.

Figure 1. Cantharadin bottle with applicators.

these adverse effects occur in ap- proximately 6% to 46% of patients, in our experience, the rate is at the low end of this range. 3,4,8 Temporary erythema can occur in up to 37% of patients. 4,5 Care should be taken to avoid spreading the cantharidin to unaffected areas or to the eyes. There may be temporary pigment alteration that should resolve without scarring. Several “helpful hints” to use the medication effectively and minimize size effects are summarized in Sidebar 2 (see page 125). The first time can- tharidin is used, it is prudent to treat only three or four lesions to assess the individual patient’s response. Warn parents that although the medication is applied sparingly, there is a 1% to 5% chance of a larger blister developing. There is controversy regarding wheth- er the medication should be washed off a few hours after application. Some authors recommend this practice, but because cantharidin is dissolved in collodion, it forms a film upon drying, which is probably not easily removed with soap and water. 7 Follow-up visits to assess efficacy and perform further

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case challenges TABLE. Distribution Sources: How to Purchase for Medical Offices* Product Company Formulation
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TABLE.
Distribution Sources: How to Purchase for Medical Offices*
Product
Company
Formulation
Address/phone
E-mail/Website
Name
Dormer
Cantharone
Laboratories
0.7% canthari-
din in a col-
lodion base
91 Kelfield, Suite 5, Rexdale, On-
tario, Canada M9W 5A3; (416)
www.dormer.ca
242
6167; fax: 877 436 7637
0.7% cantharidin
in a collodion
base
997
Seguin, Hudson, Quebec,
Pharmscience/
Canthacur
Omniderm
Canada J0P 1H0; 450-458-0158;
fax: 450-458-7499
CustomerServicePaladin@pharmascience.com
Cantharidin
crystals and
608
13th Ave., Council Bluffs,
collodion base
Delasco
Cantharidin
IA 51501-6401; (800) 831-6273;
fax: (800) 320-9612
questions@delasco.com
sold separately
for in-office
compounding
3505 Austin Bluffs Parkway,
College
Compounded to
Cantharidin
Suite 101, Colorado Springs, CO
info@collegepharmacy.com**
Pharmacy
order
80918
*Cantharidin’s use is limited to in-office treatment by a physician. Please contact the suppliers for ordering requirements.
**Shipping to selected states only
treatments are typically scheduled ev-
ery 2 to 4 weeks. If patients have not
had any adverse reactions, more le-
sions can be treated than at the initial
visit. Individual lesions of molluscum
typically resolve after one treatment
but occasionally require retreatment,
particularly if they are large. In many
cases, after two to three treatments, the
molluscum will diminish in number
and gradually resolve. Sidebar 3 (see
page 126) outlines recommendations
for anticipatory guidance.
OTHER CONSIDERATIONS
Another problem that often
arises is the presence of so-called
“molluscum eczema,” a dermatitis
virtually identical to atopic derma-
titis, which preferentially occurs in
areas of skin where molluscum are
Figure 2. Application of cantharadin to molluscum.
present. Although the individual
molluscum can be treated with can-
tharidin, even in sites of dermati-
tis, the dermatitis itself should be
treated with a low to mid-potency
topical steroid to alleviate it and
prevent autoinnoculation with fur-
ther spread of the virus.
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    case challenges   Although there are few, random-   ized, prospective trials on
   

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Although there are few, random-

 

ized, prospective trials on treatments for molluscum, a recent large retro- spective study on cantharidin by Sil- verberg et al found that 90% of 300 patients cleared and an additional 8% improved in an average of 2.1 treatments. Parental satisfaction was 95%. 4,6 In their retrospective study of 110 patients, Cathcart et al found

a

96% efficacy after approximately

two treatments and a parental satis-

faction rate of 78%. 8 In contrast, in their prospective randomized trial of four treatment modalities, Hanna

et

al found that 36.7% of patients in

the cantharidin group were cured af- ter one visit, an additional 43% after two visits, and the remaining 20%

after three or more visits. The paren- tal satisfaction rate for cantharidin was 60%. The parental satisfaction for curettage (the preferred treat- ment modality in Hanna’s study) was almost 90%. 3 The practice envi- ronment in Hanna’s study is signifi- cantly different than most U.S. prac- tices because phamacologic sedation

is

available as needed for curettage.

In our experience, curettage is an ef- fective and acceptable treatment for older children, especially when it is difficult for the family to return for several more visits. The Current Procedural Termi-

nology (CPT) codes for billing for destruction of molluscum are well- established: CPT: 17110 (destruction of up to 14 lesions) and 17111 (de- struction of 15 or more lesions).

CONCLUSIONS With appropriate precautions and information provided, we believe that the use of this medication by pediatricians and other primary care

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  Figure 3. Chemical irritation from cantharidin application; this response is very unusual. Figure 4. Blisters

Figure 3. Chemical irritation from cantharidin application; this response is very unusual.

from cantharidin application; this response is very unusual. Figure 4. Blisters following cantharidin application; the

Figure 4. Blisters following cantharidin application; the amount of blistering is more than typically occurs.

the amount of blistering is more than typically occurs. Figure 5. Verruca vulgaris ring wart from

Figure 5. Verruca vulgaris ring wart from cantharadin application.

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views 2006, Issue 2. Art. No.: CD004767.

providers is safe and well within the technical expertise of any well- trained practitioner. Finally, although cantharidin is an excellent treatment option for mollus- cum, we do not recommend its use for common warts. For unknown reasons, the noninflammatory blisters caused by the medication can result in so- called “ring warts” (see Figure 5, page 128), leading to wart spread, rather than improvement.

2. Wolverton SE. Comprehensive Derma- tologic Drug Therapy. Philadelphia, PA:

DOI:10.1002/14651858.CD004767.pub2.

Saunders; 2001;532.

7. Coloe J, Morrell DS. Cantharadin use among pediatric dermatologists in the treat- ment of molluscum contagiosum. Pediatr Dermatol. 2009;26(4):405-408. 8. Cathcart S, Coloe J, Morrell DS. Parental satisfaction, efficacy, and adverse events in 54 patients treated with cantharidin for molluscum contagiosum infection. Clin Pediatr (Phila). 2008;48(2):161-165. 9. Silverberg NB. A practical approach to molluscum contagiosum. Part 2. Contem- porary Pediatrics. 2007;24(9):63-72.

3. Hanna D, Hatami A, Powell J, et al. A prospective randomized trial comparing the efficacy and adverse effects of four recognized treatments of molluscum con- tagiosum in children. Pediatr Dermatol.

2006;23(6):574-579.

4. Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum:

experience with cantharidin therapy in 300 patients. J Am Acad Dermatol.

2000;43(3):503-507.

5. Moed L, Shwayder TA, Chang MW. Cantharidin revisited: a blistering defense of an ancient medicine. Arch Dermatol.

10. Shah A, Treat J, Yan AC. Spread of can- tharidin after petrolatum use resulting in a varicelliform vesicular dermatitis. J Am Acad Dermatol. 2008;59(2 Suppl

REFERENCES

2001;137(10):1357-1360.

1. Brown J, Janniger CK, Schwartz CZ, Sil- verberg NB. Childhood molluscum conta- giosum. Int J Dermatol. 2006;45(2):93-99.

6. Van der Wouden JC, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database of Systematic Re-

1):S54-S55.

11. Cantharone brochure. www.dormer.ca. Dormer Laboratories, Canada.

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