sign in sign up
<<
Home , Keloid

clinical Treating common

Lawrence Leung Options and evidence

excellent review has been written by Jablonska Background et al;5 and a brief summary of the various types of Nongenital warts are a common condition seen in general practice, affecting patients common warts is given in Table 1 (Figure 1–4). of all ages. There are many treatment options and patients often self medicate with remedies from folklore or tradition before presenting to their doctor. Pathogenesis Objective With a minor breach in the epithelial surface, This article attempts to summarise the quality of different treatments and to provide HPV enters the epithelial cells via putative recommendations and a quick reference for treating common warts. surface receptors and proliferates. This results Discussion in persistent viral infection with metaplasia Many common warts will resolve spontaneously but others are recalcitrant and often of keratinocytes, which gradually accumulate require ongoing treatment beyond first line measures. Without definite guidelines for keratohyalin granules6 and are sloughed off.4 treating recalcitrant warts, it is important for the general practitioner to consider the As these virally infected keratinocytes are not available evidence for efficacy and contraindication of the various treatment options. destroyed, the HPV virions are rarely exposed to Keywords: warts; skin diseases; treatment; salicylic acid; the Langerhans cells of the skin, and therefore evade being cleared by systemic immunity. This facilitates the viral persistence and continual growth of the . Diagnostic features and Nongenital cutaneous warts are commonly differential diagnoses seen in general practice with an overall Cutaneous warts often present as localised flat prevalence of 7–10%1 and a peak age of or dome shaped with well demarcated presentation of 12–16 years.1–2 They are edges. Histological findings include epidermal most commonly found on the hands and acanthosis, papillomatosis, feet but can also be found on the face, and parakeratosis with elongated rete ridges eyelids and torso. The causative agent is often curving toward the centre of the wart. human papilloma virus (HPV). Without treatment, one-third of cutaneous warts will resolve spontaneously within 3 months and two-thirds within 2 years.3 Myrmecia warts often persist despite repeated treatments and become recalcitrant warts. There is no consensus on the prevalence of, and most effective treatment for, recalcitrant warts. Classification of nongenital cutaneous warts There are over 100 identified types of HPV;4 Figure 1. Myrmecia warts on the ball of the most common types of cutaneous warts are calcaneum. These are painful. Notice the 2,4 typical round appearance with pitting when type 1, 2, 3, 4, 7, 10, 27 and 57. Cutaneous keratinised plates were removed warts can present in various forms and sizes. An

Reprinted from Australian Family Physician Vol. 39, No. 12, december 2010 933 clinical Treating common warts – options and evidence

Capillary vessels are often prominent and may are used to feed the wart. While most cutaneous seek treatment. With a record of existence going be thrombosed, giving the pathognomonic brown warts tend to be exophytic and painless (ie. back to the ancient Greeks and Romans, the dots at the centre of the lesion when the warts are grow out of and above the skin), those affecting common wart in no way lacks curative options, pared down. Due to the continuous viral induced the palm and soles are often endophytic (ie. including hypnotherapy;8 garlic;9 duct tape;7 fig hyperkeratotic changes, the surface papillary grow inwards into the skin) and lead to and tree latex;10 oral zinc sulphate;11 oral histamine lines of the skin are disrupted resulting in a rough discomfort. When several warts with different 2 receptor antagonist;11 cautery;7 hyfrecation;7 surface. Most lesions are of skin colour but can morphologies cluster together, a mosaic wart is surgical removal;12 salicylic acid;2,7 liquid 4 7 13 appear black due to thrombosed capillaries which formed. Due to the myriad of morphologies and nitrogen ; local ; CO2 wide area of possible distribution, cutaneous laser;3 YAG laser;12 pulsed dye laser;14 intense warts have to be differentiated from other skin pulsed light (IPL);15 topical imiquimod;16 topical conditions such as seborrhoeic , callous, 5-;17 squaric acid;18 intralesional , , mole, injection of bleomycin;19 ;2 candida , keratoacanthoma and cutaneous horn.7 antigen 1;20 measles, mumps and rubella (MMR) vaccine;21 and autoimplantation of wart Treatment options materials.22 Detail of each treatment modality Most cutaneous warts are self limiting and is beyond the scope of this article and readers resolve within 2 years. When they pose are referred to Lipke’s excellent reviews.7 discomfort or aesthetic problems, patients often Classification of quality of evidence (Table 2) Figure 2. Common warts on the sole of the foot with irregular hyperkeratosis. These are Table 1. Categories of common warts with their HPV subtypes relatively painless Type HPV Morphology Mode of regression type

Myrmecia 1 Round keratinised lesions found Vascular extravasation warts commonly on pressure point of and haemorrhage (Figure 1) foot, often painful endophytic with minimal growth with central pit when inflammatory infiltrate central hyperkeratotic plate removed

Common 2, 4, 57 Flat or raised papules or nodules Cellular inflammatory warts with irregular hyperkeratotic infiltrate involving (Figure 2) surfaces commonly found on the lymphocytes, dorsum of hand and periungually, natural killer cells and and can involve the sole of the macrophages Figure 3. Butcher’s wart from a food handler foot or face – often painless. with the exophytic cauliflower morphology Lesions can converge to form on the lateral aspect of the digit. Notice the mosaic warts and can be coexistence of plane warts on the dorsum and base of the finger endophytic Butcher’s 7 Found exclusively in butchers Vascular extravasation warts and meat handlers, cauliflower- and minimal (Figure 3) like exophytic lesions found on inflammation both sides of the hand but rarely periungually

Plane warts 3, 10 Multiple flat papules with Simultaneous (Figure 4) relatively smooth but inflammatory hyperkeratotic surfaces found on infiltration of the hand and face, often painless mononuclear cells and brought on by Koebner phenomenon

Intermediate 10, 27 Intermediate morphology Simultaneous Figure 4. Multiple plane warts on dorsum of warts between common and plane inflammatory reaction hand. Notice the papular appearance which warts found mostly on dorsum of can be smooth or hyperkeratotic hands in the immunosuppressed

934 Reprinted from Australian Family Physician Vol. 39, No. 12, december 2010 Treating common warts – options and evidence clinical and recommendations (Table 3) according to the 3 months and two-thirds disappear in 2 years’ plantar warts and should be used with caution United States Preventive Services Task Force are rule. Should the wart persist, the best initial for lesions around the eye. When patients applied to a summary of treatment options and treatment is salicylic acid (evidence I-A), which present with common warts it is likely they evidence in Table 4. has clear evidence of advantage over placebo. have already tried salicylic acid or even liquid Next in line would be cryotherapy with liquid nitrogen at home with no result. In such cases, Fresh warts nitrogen (evidence I-B), which has not been the GP can pursue more aggressive liquid nitrogen For lesions that on initial presentation have mild shown to be superior over other treatments cryotherapy, which has longer contact time with or no symptoms, the general practitioner can such as salicylic acid or placebo. Liquid nitrogen paring down to the base and increased risks of choose to observe the ‘one-third disappear in may have better efficacy than salicylic acid for pain and blistering. Intralesional immunotherapy or chemotherapy, laser and electrosurgery are Table 2. Classification of quality of evidence better reserved as second line treatments and are not recommended for common warts at initial Level of Quality of evidence evidence presentation. Level I Evidence obtained from at least one properly designed randomised Best practice for treating fresh controlled trial (RCT) common warts Level II-1 Evidence obtained from well designed controlled trials without Nonfacial lesions are best treated with a salicylic randomisation acid gel, cream or instant dry film preparation. Level II-2 Evidence obtained from well designed cohort or case control analytic Commercial brands come in various strengths studies, preferably from more than one centre or research group from 15–40%. Apply on alternate days with Level II-3 Evidence obtained from multiple time series with or without the contact time of 8 hours, adding occlusive dressing intervention. Dramatic results in uncontrolled trials might also be (adhesive bandage or plastic wrap) if necessary regarded as this type of evidence to enhance effects. If no improvement is observed Level III Opinions of respected authorities, based on clinical experience, after 6 weeks, proceed to liquid nitrogen descriptive studies, or reports of expert committees application with four sets of five freeze-thaw Adapted from United States Preventive Services Task Force. Available at www.ahrq. cycles per treatment, to be repeated fortnightly. gov/clinic/uspstfix.htm Lesions with hyperkeratinisation should either be pared down with a scalpel or rubbed with a pumice stone in warm water before treatment. Table 3. Recommendations: United States Preventive Services Task Force For facial lesions, salicylic acid application Level Recommendations is not recommended because of the possibility Level A Good scientific evidence suggests that the benefits of the of scarring. They are best treated in the practice clinical service substantially outweigh the potential risks. with liquid nitrogen. Apply the liquid nitrogen Clinicians should discuss the service with eligible patients with a fine nozzle spray or cottonwool tip with Level B At least fair scientific evidence suggests that the benefits of two sets of five freeze-thaw cycles to be repeated the clinical service outweigh the potential risks. Clinicians fortnightly. If lesions do not resolve within 3 should discuss the service with eligible patients months, or after five rounds of liquid nitrogen Level C At least fair scientific evidence suggests that there are treatment, the warts are considered refractory or benefits provided by the clinical service, but the balance recalcitrant. between benefits and risks are too close for making general lesions that are resolved with initial recommendations. Clinicians need not offer it unless there are treatments can recur and they are treated as fresh individual considerations lesions, albeit with a lower chance of success. Level D At least fair scientific evidence suggests that the risks of the lesions with unusual morphology, bleeding clinical service outweigh the potential benefits. Clinicians or pigmentation should be biopsied to exclude should not routinely offer the service to asymptomatic patients possible malignancy. Level I Scientific evidence is lacking, of poor quality, or is conflicting, such that the risk versus benefit balance cannot be assessed. Recalcitrant warts Clinicians should help patients understand the uncertainty surrounding the clinical service When warts fail to resolve after repeated treatments, they are considered recalcitrant. There Adapted from United States Preventive Services Task Force. Available at www.ahrq. is no consensus for the definition of recalcitrant gov/clinic/pocketgd09/gcp09app.htm#ApA warts but as a general rule, they can be described

Reprinted from Australian Family Physician Vol. 39, No. 12, december 2010 935 clinical Treating common warts – options and evidence as warts that fail five rounds of first line human immunodeficiency virus infections.28 immunotherapy (eg. interferon and MMR treatment (salicylic acid or liquid nitrogen). Plantar there are no definite guidelines for treating vaccine). These are not first line treatments warts are notorious for becoming recalcitrant. recalcitrant warts and available options for common warts and should be administered Certain immunosuppressed conditions create a include destruction treatments (eg. laser and only with prior training or in a specialist higher risk of developing recalcitrant warts, these electrosurgery), intralesional chemotherapy (eg. centre so that possible side effects can be include acute leukemia,25 organ transplant26,27 and bleomycin and 5-fluorouracil) and intralesional monitored. A preferred option of the author is

Table 4. Summary of treatment and evidence for common warts

Method Level of evidence Comments Salicylic acid2 I-A Benefits are established as compared to placebo but only modest. Most trials look at use of salicylic acid in combination with other agents Liquid nitrogen cryotherapy2,23 I-B Overall evidence is inconclusive to suggest a therapeutic advantage of cryotherapy over other topical treatments or placebo. Aggressive cryotherapy may be more effective but is offset by more pain and blistering Intralesional interferon2,23 I-C Trials use various forms of (alfa, beta, gamma). Intralesional injections are often painful and overall evidence of use is insufficient Intralesional bleomycin I-C Cochrane review of trials used various dosages and concentrations with different delivery systems, but none show sufficient evidence of beneficial use2 I-B More recent studies showed significant benefits as compared to cryotherapy19 Intralesional candida II-3B Data from case series and isolated reports. No RCT yet. Suggested use in antigen1,20 the more recalcitrant types of warts Intralesional MMR vaccine21 I-B One RCT and one time series executed with recalcitrant plantar warts. Efficacy for other types of warts still unknown Autoimplantation of wart II-3C Only one intention-to-treat series reported significant effects. No RCT material22 available Topical 5-fluorouracil2 I-C Efficacy significant with one study using cream preparation in children, but overall evidence becomes limited when pooled with other studies Intralesional 5-fluorouracil24 I-B One double blind RCT using a 5-fluorouracil mixture of epinephrine and lidocaine Topical podophyllin7 II-2D Good efficacy from older case series in 1970s, not recommended now for toxicities. No known RCT Topical imiquimod16 II-2C Approved for use in genital warts, only two case studies of efficacy for plantar warts. Evidence is still lacking Topical squaric acid18 II-3C Intention to treat studies showed efficacy in children and cases of recalcitrant wart, known risks of Duct tape2 I-I Perhaps the most controversial of all treatments, modest efficacy from an RCT in school children is later refuted by another RCT in adults. Evidence is too conflicting to suggest benefit 14 Laser (CO2 and YAG) I-C Good efficacy from intention to treat case series especially with recalcitrant warts and in children. The only RCT does not show evidence of benefit over conventional treatment Intense pulsed light15,30 I-I One case study combines photosensitiser with IPL and shows efficacy, another RCT using IPL alone shows no efficacy. Evidence is lacking Electrosurgery II-1C Good efficacy from case reports with known risks of scarring and deep (electrodessication, tissue damage. One controlled trial compares electrocoagulation with electrocoagulation and infrared coagulation with no difference, no known RCT. Often used for cautery)7 recalcitrant warts Surgical excision7 II-3D No RCTs so far, generally not recommended as first line treatment due to scarring, pain and high rate of recurrence – up to 30%

936 Reprinted from Australian Family Physician Vol. 39, No. 12, december 2010 Treating common warts – options and evidence clinical electrodessication (hyfrecation) of the lesion 2006;3:CD001781. Autoimplantation therapy for multiple warts. Indian J Dermatol Venereol Leprol 2009;75:593–5. under local anaesthesia, which often results in 3. sterling JC, Handfield-Jones S, Hudson PM. Guidelines for the management of cutaneous warts. 23. damstra RJ, van Vloten WA. Cryotherapy in the clearance after a single treatment. However, Br J Dermatol 2001;144:4–11. treatment of condylomata acuminata: a controlled this option is contraindicated in patients with 4. handisurya A, Schellenbacher C, Kirnbauer R. study of 64 patients. J Dermatol Surg Oncol Diseases caused by human papillomaviruses (HPV). J 1991;17:273–6. poor (eg. uncontrolled diabetes Dtsch Dermatol Ges 2009;7:453–66. 24. yazdanfar A, Farshchian M, Fereydoonnejad M. or peripheral vascular diseases), keloid tendency 5. Jablonska S, Majewski S, Obalek S, et al. Cutaneous Treatment of common warts with an intralesional or patients with pace makers. It is also not warts. Clin Dermatol 1997;15:309–19. mixture of 5-fluorouracil, lidocaine, and epinephrine: 6. Gross G, Pfister H, Hagedorn M, et al. Correlation a prospective placebo-controlled, double-blind rand- recommended for lesions on the face. between human papillomavirus (HPV) type and his- omized trial. Dermatol Surg 2008;34:656–9. tology of warts. J Invest Dermatol 1982;78:160–4. 25. tobin AM, Cotter M, Irvine AD, et al. Successful Best practice for treating recalcitrant 7. lipke MM. An armamentarium of wart treatments. treatment of a refractory verruca in a child with acute warts Clin Med Res 2006;4:273–93. lymphoblastic leukaemia with topical cidofovir. Br J 8. Phoenix SL. Psychotherapeutic intervention for Dermatol 2005;152:386–8. Destructive options include aggressive numerous and large viral warts with adjunctive hyp- 26. sandoval M, Ortiz M, Diaz C, et al. Cutaneous mani- nosis: a case study. Am J Clin Hypn 2007;49:211–8. festations in renal transplant recipients of Santiago, cryotherapy (maximum paring down with 9. dehghani F, Merat A, Panjehshahin MR, et al. Chile. Transplant Proc 2009;41:3752–4. scalpel and longer freezing time of 6 seconds Healing effect of garlic extract on warts and corns. 27. dharancy S, Catteau B, Mortier L, et al. Conversion to instead of the usual 3 seconds), hyfrecation Int J Dermatol 2005;44:612–5. sirolimus: a useful strategy for recalcitrant cutaneous 10. bohlooli S, Mohebipoor A, Mohammadi S, et viral warts in liver transplant recipient. Liver Transpl with local anaesthesia, laser treatment and al. Comparative study of fig tree efficacy in the 2006;12:1883–7. thermocoagulation. treatment of common warts (verruca vulgaris) vs 28. lowe S, Ferrand RA, Morris-Jones R, et al. Skin disease among human immunodeficiency virus- subject to availability 5-fluorouracil or cryotherapy. Int J Dermatol 2007;46:524–6. 11. stefani M, Bottino G, Fontenelle E, et al. Efficacy infected adolescents in Zimbabwe: a strong indicator bleomycin can be administered either topically or comparison between cimetidine and zinc sulphate in of underlying HIV infection. Pediatr Infect Dis J intralesionally, preferably in a specialist setting. the treatment of multiple and recalcitrant warts. An 2010;29:346–51. 29. dubina M, Goldenberg G. Viral-associated nonmela- lesions with unusual morphology, bleeding Bras Dermatol 2009;84:23–9. 12. tosti A, Piraccini BM. Warts of the unit: surgi- noma skin cancers: a review. Am J Dermatopathol or pigmentation should be biopsied to exclude cal and nonsurgical approaches. Dermatol Surg 2009;31:561–73. possible malignancy. 2001;27:235–9. 30. Kalil CL, Salenave PR, Cignachi S. Hand warts 13. huo W, Gao XH, Sun XP, et al. Local hyperthermia at successfully treated with topical 5-aminolevulinic 44 degrees C for the treatment of plantar warts: a acid and intense pulsed light. Eur J Dermatol Summary randomized, patient-blinded, placebo-controlled trial. 2008;18:207–8. Common nongenital warts are common and may J Infect Dis 2010;201:1169–72. 14. sethuraman G, Richards KA, Hiremagalore RN, et al. persist despite active treatment. Salicylic acid is Effectiveness of pulsed dye laser in the treatment the best evidence based treatment for warts on of recalcitrant warts in children. Dermatol Surg initial presentation and can be complemented by 2010;36:58–65. 15. togsverd-Bo K, Gluud C, Winkel P, et al. Paring and liquid nitrogen cryotherapy. For recalcitrant warts, intense pulsed light versus paring alone for recalci- choices vary depending on availability and the trant hand and foot warts: a randomized clinical trial training of the GP. The expected efficacy must be with blinded outcome evaluation. Lasers Surg Med 2010;42:179–84. balanced against costs and possible side effects. 16. mitsuishi T, Wakabayashi T, Kawana S. Topical It is advisable to perform skin biopsy for suspicious imiquimod associated to a reduction of heel hyper- keratosis for the treatment of recalcitrant mosaic lesions where necessary in order to exclude plantar warts. Eur J Dermatol 2009;19:268–9. diagnoses such epidermodysplasia verruciformis 17. moore AY. Clinical applications for topical 5-fluoro- and verrucous carcinoma, which are HPV induced uracil in the treatment of dermatological disorders. J 29 Dermatolog Treat 2009;20:328–35. squamous cell carcinomas of the skin. 18. hama N, Hatamochi A, Hayashi S, et al. Usefulness Author of topical immunotherapy with squaric acid dibutyl- ester for refractory common warts on the face and Lawrence Leung MBBChir, BChinMed, MFM(Clin), neck. J Dermatol 2009;36:660–2. FRACGP, FRCGP(UK), is Assistant Professor, 19. dhar SB, Rashid MM, Islam A, et al. Intralesional Department of Family Medicine, Queen’s bleomycin in the treatment of cutaneous warts: University, Kingston, Ontario, Canada. a randomized clinical trial comparing it with [email protected]. cryotherapy. Indian J Dermatol Venereol Leprol 2009;75:262–7. Conflict of interest: none declared. 20. summers P, Richards-Altmon P, Halder R. Treatment of recalcitrant verruca vulgaris with candida antigen References in patient with human immunodeficiency virus. J 1. clifton MM, Johnson SM, Roberson PK, et al. Drugs Dermatol 2009;8:268–9. Immunotherapy for recalcitrant warts in children 21. nofal A, Nofal E. Intralesional immunotherapy of using intralesional mumps or Candida antigens. common warts: successful treatment with mumps, Pediatr Dermatol 2003;20:268–71. measles and rubella vaccine. J Eur Acad Dermatol 2. Gibbs S, Harvey I. Topical treatments for cuta- Venereol 2010 [Epub ahead of print]. neous warts. Cochrane Database Syst Rev 22. shivakumar V, Okade R, Rajkumar V.

Reprinted from Australian Family Physician Vol. 39, No. 12, december 2010 937