Topical salicylic acid, cryotherapy, and topical fluorouracil are effective for treating nongenital warts. (Strength of Recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs].) Fluorouracil is more expensive than salicylic acid and produces more adverse effects, such as pain and blisters. The combination of salicylic acid and cryotherapy may be better than either treatment alone, although salicylic acid may be more cost-effective than cryotherapy. Bleomycin and interferons should not be used to treat nongenital warts. (SOR: A, based on a meta-analysis.

Ainsworth, Carla

Feigenbaum, Alyson L.

St. Anna, Leilani

English

University of Missouri: MOspace

1290  American Family Physician www.aafp.org/afp	 Volume 84, Number 11 ◆ December 1, 2011Clinical QuestionWhat	 is	 the	 best	 therapy	 for	 treating	 non-genital	warts?Evidence-Based AnswerTopical	 salicylic	 acid,	 cryotherapy,	 and	topical	 fluorouracil	 are	 effective	 for	 treat-ing	 nongenital	 warts.	 (Strength	 of	 Rec-ommendation	 [SOR]:	 A,	 based	 on	 a	systematic	review	of	randomized	controlled	trials	[RCTs].)	Fluorouracil	 is	more	expen-sive	 than	 salicylic	 acid	 and	 produces	 more	adverse	 effects,	 such	 as	 pain	 and	 blisters.	The	combination	of	salicylic	acid	and	cryo-therapy	may	be	better	than	either	treatment	alone,	 although	 salicylic	 acid	 may	 be	 more	cost-effective	 than	 cryotherapy.	 Bleomy-cin	 and	 interferons	 should	 not	 be	 used	 to	treat	nongenital	warts.	(SOR:	A,	based	on	a	meta-analysis.)Evidence SummaryIn	 most	 healthy	 patients,	 viral	 warts	 will	resolve	without	treatment.	A	2006	Cochrane	review	 of	 21	 RCTs	 of	 various	 topical	 treat-ments	for	cutaneous	warts	found	an	average	placebo	response	rate	of	27	percent	(range	=	0	to	73	percent)	over	an	average	of	15	weeks	(range	=	four	to	24	weeks).1	TOPICAL SALICYLIC ACID Topical	 salicylic	 acid	 is	 inexpensive,	 well	tolerated,	 and	 effective	 for	 treating	 warts.	The	 same	 Cochrane	 review	 analyzed	 five	RCTs	of	salicylic	acid	(322	participants),	and	demonstrated	 a	 73	 percent	 cure	 rate	 with	salicylic	acid	compared	with	48	percent	with	placebo	 over	 a	 treatment	 period	 of	 six	 to	12	weeks	(number	needed	to	treat	[NNT]	=	4;	95%	 confidence	 interval	 [CI],	 3	 to	 7).1	 The	concentration	of	salicylic	acid	in	these	studies	ranged	from	17	to	60	percent.CRYOTHERAPYThe	Cochrane	review	also	analyzed	two	RCTs	(320	 participants)	 comparing	 cryotherapy	with	salicylic	acid	for	the	treatment	of	warts,	and	 found	 no	 statistically	 significant	 differ-ence	in	effectiveness.1	A	combination	of	cryo-therapy	and	salicylic	acid	may	be	better	than	either	treatment	alone.	In	the	Cochrane	anal-ysis,	 the	 NNT	 for	 combined	 therapy	 versus	cryotherapy	 alone	 (328	 participants)	 was	 8	(95%	 CI,	 5	 to	 50).	 The	 NNT	 for	 combined	therapy	 versus	 salicylic	 acid	 alone	 (318	 par-ticipants)	was	6	(95%	CI,	4	to	22).	Aggressive	cryotherapy	(e.g.,	double	or	30-second	freeze)	was	 more	 effective	 than	 gentle	 cryotherapy	(e.g.,	single	or	15-second	freeze)	in	a	subanal-ysis	of	four	RCTs	(592	participants;	NNT	=	5;	95%	 CI,	 3	 to	 7).1	 However,	 aggressive	 cryo-therapy	 caused	 more	 blistering	 and	 burning	than	salicylic	acid	or	gentle	freezing	(number	needed	to	harm	=	5;	95%	CI,	3	to	15).1	COST-EFFECTIVENESSA	 British	 study	 of	 various	 wart	 therapies	found	that	salicylic	acid	is	more	cost-effective	than	 cryotherapy.2	 Data	 on	 cost	 and	 cure	rates	 were	 obtained	 from	 various	 sources,	including	 published	 literature,	 patient	 sur-veys,	focus	groups,	and	expert	opinion.	When	compared	with	no	treatment,	the	incremen-tal	 cost	 (defined	 as	 cost	 for	 each	 1	 percent	increase	 in	 cure	 rate)	 for	 salicylic	 acid	 was	approximately	 $3.75.	 The	 incremental	 cost	for	cryotherapy	ranged	from	about	$5	to	$12,	depending	on	the	number	of	treatments.	OTHER TOPICAL AGENTS Data	 from	 the	 Cochrane	 review	 found	 that	topical	fluorouracil	was	no	better	than	topi-cal	salicylic	acid	for	curing	warts.1	Addition-ally,	 the	 cost	 of	 fluorouracil	 is	 more	 than	15	 times	 that	 of	 salicylic	 acid.3	 Fluorouracil	Treatment of Nongenital WartsALYSON	L.	FEIGENBAUM,	MD,	and	CARLA	AINSWORTH,	MD,	MPH,	Swedish Family Medicine, Seattle, WashingtonLEILANI	ST.	ANNA,	MLIS,	University of Washington Health Sciences Library, Seattle, WashingtonClinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medi-cine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recom-mendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).The complete database of evidence-based ques-tions and answers is copyrighted by FPIN. If interested in submit-ting questions or writing answers for this series, go to http://www.fpin.org or email: questions@fpin.org.A collection of FPIN’s Clinical Inquiries pub-lished in AFP is available at http://www.aafp.org/afp/fpin.FPIN’s Clinical InquiriesDownloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2011 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.Clinical InquiriesDecember 1, 2011 ◆ Volume 84, Number 11	 www.aafp.org/afp	 American Family Physician  1291in	combination	with	cryotherapy	may	cause	more	 pain	 and	 blistering	 than	 cryotherapy	alone.	 A	 double-blind	 RCT	 of	 80	 patients	compared	cryotherapy	plus	fluorouracil	with	cryotherapy	 alone	 and	 found	 a	 nonsignifi-cant	 trend	 toward	 more	 pain	 and	 blistering	associated	 with	 fluorouracil.	 The	 number	needed	 to	 harm	 was	 6	 (95%	 CI	 for	 blisters,	–3	to	25;	95%	CI	for	pain,	–3	to	87).4Two	 small,	 unblinded,	 and	 uncontrolled	studies	 of	 37	 and	 50	 participants	 suggest	that	 imiquimod	 (Aldara)	 may	 be	 effec-tive	 for	 treating	 recalcitrant	 warts.5,6	 The	authors	 reported	 total	 clearance	 of	 recalci-trant	warts	in	27	and	30	percent	of	patients	treated	 with	 imiquimod	 for	 a	 mean	 of	19	 and	 nine	 weeks,	 respectively.	 The	 effec-tiveness	 of	 treatment	 with	 duct	 tape	 is	unclear.	 In	a	prospective,	 randomized	 trial	of	61	patients,	duct	tape	seemed	more	effec-tive	 than	 cryotherapy,7	 but	 a	 double-blind	placebo-controlled	 study	 of	 80	 patients	found	no	difference.8	The	Cochrane	review	found	 insufficient	 evidence	 to	 support	intralesional	 bleomycin	 or	 interferons	 for	the	treatment	of	warts.1Recommendations from OthersAccording	to	the	American	Academy	of	Der-matology,	 warts	 may	 regress	 spontaneously,	and	treatment	varies	depending	on	the	 type	of	 wart	 and	 patient	 age.9	 Salicylic	 acid	 may	be	 preferred	 for	 treating	 warts	 in	 young	children,	and	it	can	be	applied	at	home.	For	adults	 and	 older	 children,	 cryotherapy	 is	generally	 preferred,	 but	 may	 take	 multiple	applications	over	weeks	to	months.9The authors thank E. Chris Vincent, MD, Swedish Family Medicine, Seattle, Wash., for his editing work on this paper.Copyright Family Physicians Inquiries Network. Used with permission.Address correspondence to Alyson L. Feigenbaum, MD, at f.alyson@gmail.com. Reprints are not available from the authors.Author disclosure: No relevant financial affiliations to disclose.REFERENCES	 1.	Gibbs	 S,	 Harvey	 I.	 Topical	 treatments	 for	 cutaneous	warts.	Cochrane Database Syst Rev.	2006;(3):CD001781.	 2.	Keogh-Brown	 MR,	 Fordham	 RJ,	 Thomas	 KS,	 et	 al.	 To	freeze	or	not	to	freeze:	a	cost-effectiveness	analysis	of	wart	treatment.	Br J Dermatol.	2007;156(4):687-692.		 3.	Red Book.	 Montvale,	 N.J.:	 Medical	 Economics	 Data;	2010:434,718.	 4.	Luk	NM,	Tang	WY,	Tang	NL,	et	al.	Topical	5-fluorouracil	has	 no	 additional	 benefit	 in	 treating	 common	 warts	with	 cryotherapy:	 a	 single-centre,	 double-blind,	 ran-domized,	 placebo-controlled	 trial.	 Clin Exp Dermatol.	2006;31(3):394-397.		 5.	Grussendorf-Conen	EI,	Jacobs	S,	Rübben	A,	Dethlefsen	U.	Topical	5%	 imiquimod	 long-term	treatment	of	cutane-ous	 warts	 resistant	 to	 standard	 therapy	 modalities.	Dermatology.	2002;205(2):139-145.		 6.	Hengge	UR,	Esser	S,	Schultewolter	T,	et	al.	Self-admin-istered	topical	5%	imiquimod	for	the	treatment	of	com-mon	warts	and	molluscum	contagiosum.	Br J Dermatol.	2000;143(5):1026-1031.		 7.	Focht	 DR	 III,	 Spicer	 C,	 Fairchok	 MP.	 The	 efficacy	 of	duct	 tape	 vs	 cryotherapy	 in	 the	 treatment	 of	 verruca	vulgaris	(the	common	wart).	Arch Pediatr Adolesc Med. 2002;156(10):971-974.		 8.	Wenner	R,	Askari	SK,	Cham	PM,	Kedrowski	DA,	Liu	A,	Warshaw	EM.	Duct	tape	for	the	treatment	of	common	warts	 in	adults:	a	double-blind	randomized	controlled	trial.	Arch Dermatol.	2007;143(3):309-313.		 9. American	 Academy	 of	 Dermatology.	 Warts.	 http://w w w.aad.org /publ i c / publ i cat ions /pamphlet s /	common_warts.html.	Accessed	April	12,	2010.	■

Treatment of Nongenital Warts

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Treatment of Nongenital Warts

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