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J.A.H. Eekhof, MD, PhD, Minor derm ailments: A. Knuistingh Neven, MD, PhD, S.P. Gransjean, medical student, and How good is the evidence W.J.J. Assendelft, MD, PhD Leiden University Medical for common treatments? Center, Leiden, The Netherlands Not very. This systematic review reveals that only a few [email protected] therapies have high-level research to support them

Practice recommendations o you use silver sulfadiazine for • Oral flucloxacillin is less effective than partial-thickness burns? If you local antibiotics for impetigo in limited ® DowdenDdo, you Health may be surprised Media to learn disease (level of evidence [LOE] 1a). that the evidence for its use in this situ- • Topical metronidazole and azelaic acid ation is conflicting. This was just one of are effective for rosaceaCopyright (LOE 1a).For personalthe findings ofuse our systematiconly review of • Betadine is effective for minor the methodologic quality and statistical infections following partial and clinical relevance of current therapies thickness burns (LOE 1b). for minor dermatologic ailments. • Terbinafine is effective against fungal Given that minor ailments, frequently In this Article infections of the nail (LOE 1a). dermatologic, account for 40% to 70% z Summary of • Miconazole is effective against of all consultations in family medicine,2,3 oral thrush (LOE 1a). guidelines based on better research are studies needed. This need is underscored by the Page E8 Level of evidence (LOE) increasing delegation of minor treatments 1a: Systematic reviews (with homogeneity) of randomized controlled trials (RCTs). to staff nurses, nurse practitioners, and 1a-: Systematic review of randomized trials displaying physician assistants, who should undergo worrisome heterogeneity. 1b: Individual RCT (with a narrow confidence interval). comprehensive training, preferably based 1b-: Individual RCT (with a wide confidence interval). on valid guidelines.4.5 Moreover, consul- 1c: All or none RCTs. 2a: Systematic reviews (with homogeneity) of cohort studies. tations for prevalent minor ailments of- 2a-: Systematic reviews of cohort studies displaying worrisome ten lead to prescriptions for medications, heterogeneity. thereby generating considerable costs.6,7 2b: Individual cohort study or low-quality RCTs (<80% follow- up). 2b-: Individual cohort study or low-quality RCTs (<80% follow- up/wide confidence interval). 2c: “Outcomes” research; ecological studies. z Methods 3a: Systematic review (with homogeneity) of case-control studies. The starting point for this review was 3a-: Systematic review of case-control studies with worrisome the textbook, Minor Ailments in Prima- heterogeneity. 6 3b: Individual case-control study. ry Care: An Evidence-Based Approach, 4: Case series (and poor-quality cohort and case-control which describes 119 minor ailments, studies). selected mainly on the basis of disease 5: Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles.” prevalence. We selected all dermatologic Source: Essential Evidence Plus. Levels of evidence.1 ailments (International Classification of

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Primary Care-code ‘S’) (N=42) (TABLE).5 ailments, where possible, into bacte- We searched the online data- rial infection, fungal infection, itch, and bases PubMed, Cochrane Controlled pain. Trials Register, and Clinical Evidence for We classified the efficacy of thera- articles relating to the treatment of these pies as yes, likely (if the result was not conditions. For each ailment, we used convincingly effective or based on small various search terms for indication and studies, or if the study objective was un- treatment.8 (See note at end of Methods clear), or no. Treatments with no trials section.) We excluded alternative (nonal- to support them are so identified. As to lopathic) and most preventive therapies whether the evidence was convincing, we because they are unusual in the daily indicated yes, no, or conflicting. practice of family medicine. Post hoc analysis. For trials with a We searched only for trials in which wide confidence interval and for thera- treatments were compared with placebo pies described as not clearly effective, we or a reasonable, accepted usual therapy. performed a post hoc power analysis to The search followed a hierarchy of evi- explore if the trial was underpowered.10 dence:8 systematic reviews (SRs), then We compared the number of subjects in

randomized controlled trials (RCTs), the study (n1) with the number we calcu- then other research articles (nonrandom- lated as necessary for the study to have

ized clinical trials, case series). When we sufficient power (n2). For all studies, we found a relevant SR published in 2004 or used standardized values (α=0.05 and

later, we did not search for a lower level b=0.20). If n1≥n2 we considered the study

of evidence (LOE). Instead, we restricted design accurate, and if n1< n2 we conclud- our subsequent search to RCTs published ed that the power was insufficient for the after the publication date of the SR.8 Two study to be able to answer its objectives. of the authors (SPG and JAHE) selected articles independently, based on article Further details on the following title and abstract. Disagreements in se- information are available from the fast track lection were discussed and consensus corresponding author: was reached. If an article contained rel- For limited • terms used in searching online evant first-line therapy, we also used the databases impetigo, local “related articles” option in PubMed to • post hoc power analysis antibiotic check for more sources. (See note at end • a summary of treatment ratio- of Methods section.) treatment is nales, therapies and their effec- To evaluate the methodologic qual- more effective tiveness, country where the re- ity of SRs and trials, we ranked articles search was undertaken, number than oral according to the method of infoPOEMs.8 of authors, and year of article (See key on page E1.) Two experienced flucloxacillin. publication for each dermato- researchers (JAHE and AKN) scored all logic ailment. articles independently. Consensus was reached in cases of disagreement.9 We deemed evidence convincing if the study z Results showed the intervention was effective and We collected 71 articles published in the if the LOE of the study was high (levels medical literature between January 1981 1a, 1b, or 2a). and July 2007.11-81 On average, we found Evaluating breadth of treatment ap- 2 articles per minor dermatologic ail- plication. To explore whether a treatment, with a range of 0 to 7. For 7 com- ment for a certain minor ailment could mon ailments, we found no studies on be applied to other ailments with similar therapies; for 13 ailments we found just symptoms and thus increase the strength 1 trial each. of the treatment’s rationale, we clustered For 20 of the 42 ailments, we found

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a SR of treatments (10 Cochrane reviews, Results varied. With partial thick- 5 Clinical Evidence, and 5 from other ness burns, evidence was conflicting on sources). Most articles describing RCTs the effectiveness and the harms of silver presented results with wide confidence sulfadiazine and several types of gauzes. intervals (LOEs 1b- and 2b-), mainly due For boils, we could find no trial about to small sample sizes. Eleven RCTs (14%) therapy. For both warts and mollusca had high dropout rates (LOE 2b or 2b-). contagiosa, Cochrane reviews were in- Seventy-four percent of all the trials conclusive on therapies commonly used were conducted in Europe and North in general practice. Evidence was also in- America. The United States (24%) and conclusive for treatments for paronychia, United Kingdom (25%) were the lar- polymorphic light eruption, and dog and gest contributors. Studies of Asian and cat bites. South American populations (eg, Indian, Nepalese, Iraqi, Brazilian) tended to focus on problems more prevalent in these z Clustering by treatment countries, such as lice and scabies. rationale For 26 of the 42 ailments, evidence Bacterial infections. We found trials on was unclear (no studies or studies with antibiotic therapy for 5 of the 12 mi- inconclusive evidence). Very few of the nor dermatologic ailments caused by therapies commonly used for minor or followed by bacterial infection. For dermatologic ailments are supported by the other 7, no trials were available. We high-level research evidence. Even some found evidence for the effectiveness of SRs included only methodologically poor treatment in 3 of the 11 indications (im- RCTs, which indicates that more research petigo, erythrasma, and rosacea). For is needed. the treatment of impetigo (in cases of A look at outcomes. The TABLE sum- limited disease), oral flucloxacillin is less marizes the effectiveness of therapies effective than local antibiotic treatment usually applied to minor dermatologic (LOE 1a). Betadine for minor infections ailments in daily practice. The columns after partial thickness burns is effective fast track present, in turn: (LOE 1b)or all other dermatological mi- Two systematic • the minor ailment, nor ailments in the bacterial infections • the treatments usually applied in category, the effectiveness of antibiotic reviews concluded daily practice, therapy was unclear. that oral • the number of studies found for Fungal infections. For 8 of the 9 ail- terbinafine these treatments, ments in which a fungal infection (yeast, is effective for • the condition at which treatment fungals, dermatophytes) was one of the was aimed, main reasons for therapy, we found trials fungal nail • whether the targeted condition on antimycotic treatment. There were 2 infections. belongs to 1 of the 4 categories SRs of oral therapy for fungal nail infec- of main symptoms, tions, both concluding that terbinafine • whether the study/studies is an effective antifungal therapy for the reported a positive effect for the condition. Miconazole is effective for in- treatment, fections with Candida albicans or derma- • whether the evidence for the tophytes (LOE 1a). effectiveness of a particular Itch. Itch was a main reason for treat- treatment was (according to ing 8 ailments. We found some trials for the authors) convincing, neutral lotion or oral antihistamines. We • whether the overall rating of also found evidence supporting use of lo- evidence was convincing, cal antihistamines for 2 of the 8 minor • and whether further studies are ailments. For 4 ailments, we found studies needed. with positive results for local application

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of steroids; we found no studies for oral all ailments exhibiting that condition. On steroids. We can therefore conclude that the basis of the treatment effect found local steroids are effective for ailments in for 4 ailments, we determined that local which itch is one of the main symptoms. steroids would most likely effectively re- Pain. For 5 ailments, relief from pain lieve itch associated with all minor der- was the main target of treatment. Trials, matologic ailments. For other conditions, however, did not focus on generic pain grouping by rationale for treatment did medications but on treatments aimed at not yield any extendable applications. specific causal pathways of the ailment Generally accepted treatments for (eg, antiviral treatment for the post- minor dermatologic ailments are insuf- herpetic pain of shingles). Therefore, we ficiently supported by research evidence. cannot draw generalizable conclusions This limitation contrasts dramatically on the treatment of pain in minor derma- with the body of evidence supporting tologic ailments. therapies in other aspects of family practice, reportedly having sufficient LOEs in the range of 50% to 80% of treat- z Post hoc power analysis ments.82,83 Given that minor ailments are Most of the 10 trials with LOE 1b- (and a substantial portion of a family physi- effectiveness of treatment described as no cian’s workload, and that other primary or likely) needed many more patients to care providers are increasingly treating reach a higher LOE. In only 2 trials,55,66 these ailments, definitive guidelines based the number of patients was sufficient. on high-quality research are needed. This Four of the 10 trials were missing infor- aspect of medical care deserves more at- mation that would have enabled us to tention from researchers and funding judge whether they were underpowered. agencies. n In 4 other trials, we considered the num- Correspondence ber of patients needed to prove treat- J.A.H. Eekhof, MD, PhD, Department of Public Health ment effectiveness (n2) unrealistic, and, and primary Care, leiden University medical Center fast track consequently, the therapy as very likely (LUMC), po box 9600, 2300 rC leiden, the Nether- lands; [email protected] Duct tape ineffective. Disclosure occlusion for The authors reported no potential conflict of interest rel- treating warts is z Conclusions evant to this article. ineffective. Study design was poor for more than half of the trials identified. And other studies References 1. Essential Evidence Plus. Levels of evidence. Avail- were so small as to lack statistical power. able at: http://www.essentialevidenceplus.com/ We found convincing evidence (SRs or product/ebm_loe.cfm?show=oxford. Accessed good RCTs) for the effectiveness of usual August 18, 2009. therapy for fewer than half of the ailments 2. Rambihar bv. [e-letter bmJ] 18 may 2001. Avail- able at: bmj.com/cgi/eletters/322/7296/1193. Ac- selected. Had we extended our search to cessed July 30, 2009. more databases, such as EMBASE and 3. Morris CJ, Cantrill JA, Weiss MC. GPs’ attitudes to CINAHL, we may have identified more minor ailments. Fam Pract. 2001;18:581-585. trials. However, it is unlikely we would 4. Pritchard A, Kendrick D. Practice nurse and health visitor management of acute minor illness in a gen- have arrived at a different conclusion, eral practice. J Adv Nurs. 2001;36:556-562. given that the number of relevant studies 5. Okkes IM, becker HW, bernstein rm, et al. the was so low in the databases we did search March 2002 update of the electronic version of ICPC-2. A step forward to the use of ICD-10 as a (PubMed, Cochrane library, Clinical Evi- nomenclature and a terminology for ICPC-2. Fam dence). Pract. 2002;19:543-546. We clustered ailments to determine if 6. Eekhof JAH, Knuistingh NA, verheij tJM, eds. Minor Ailments in Primary Care: An Evidence- a treatment aimed at a particular symp- Based Approach. Edinburgh/London: Elsevier But- tom or complication could be applied to terworth Heinemann; 2005.

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7. Salmon P. The potentially somatizing effect of clini- 25. Usha v, Gopalakrishnan Nair tv. A comparative cal consultation. CNS Spectr. 2006;11:190-200. study of oral ivermectin and topical permethrin 8. Assendelft WJJ, van tulder mW, Scholten rJ, cream in the treatment of scabies. J Am Acad Der- et al. De praktijk van systematische reviews. II. matol. 2000;42:236-240. Zoeken en selecteren van literatuur. [The practice 26. Zargari O, Golchai J, Sobhani A, et al. Comparison of systematic reviews. II. Searching and selection of the efficacy of topical 1% lindane vs 5% perme- of studies.] Ned Tijdschr Geneeskd. 1999;143:656- thrin in scabies: a randomized, double-blind study. 661. Indian J Dermatol Venereol Leprol. 2006;72:33-36. 9. Assendelft WJJ, Scholten RJ, van Eijk JT, et al. De 27. Medeiros I, Saconato H. Antibiotic prophylaxis for Praktijk van systematisch reviews. III. Methodolo- mammalian bites. Cochrane Database Syst Rev. gische beoordeling van onderzoeken. 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42. Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir 57. Warner RR, Schwartz JR, Boissy Y, et al. Dandruff with and without prednisone for the treatment of has an altered stratum corneum ultrastructure that herpes zoster. A randomized, placebo-controlled is improved with zinc pyrithione shampoo. J Am trial. The National Institute of Allergy and Infectious Acad Dermatol. 2001;45:897-903. Diseases Collaborative Antiviral Study Group. Ann 58. Altmeyer P, Hoffmann K. Loprox Shampoo Dosing Intern Med. 1996;125:376-383. Concentration Study Group. efficacy of different 43. Wood MJ, Johnson RW, McKendrick MW, et al. A concentrations of ciclopirox shampoo for the treat- randomized trial of acyclovir for 7 days or 21 days ment of seborrheic dermatitis of the scalp: results with and without prednisolone for treatment of of a randomized, double-blind, vehicle-controlled acute herpes zoster. N Engl J Med. 1994;330:896- trial. Int J Dermatol. 2004;43(suppl 1):9-12. 900. 59. 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Cochrane Database Syst Rev. 2002;(2):CD003584. 79. Crawford F. Athlete’s foot. BMJ Clin Evid. 75. Gupta AK, ryder JE, Johnson AM. Cumulative 2005;14:2000-2005. meta-analysis of systemic antifungal agents for 80. Knapik JJ, reynolds K, barson J. Influence of the treatment of onychomycosis. Br J Dermatol. an antiperspirant on foot blister incidence dur- 2004;150:537-544. ing cross-country hiking. J Am Acad Dermatol. 76. Davys HJ, Turner DE, Helliwell PS, et al. Debride- 1998;39:202-206. ment of plantar callosities in rheumatoid arthri- 81. Reynolds K, Darrigrand A, Roberts D, et al. Effects tis: a randomized controlled trial. Rheumatology. of an antiperspirant with emollients on foot-sweat 2005;44:207-210. accumulation and blister formation while walking in 77. van der Ham AC, Hackeng CA, Yo tI. the treat- the heat. J Am Acad Dermatol. 1995;33:626-630. ment of ingrowing toenails. A randomised compari- 82. Matzen p. How evidence-based is medicine? son of wedge excision and phenol cauterisation. J A systematic literature review. Ugeskr Laeger. Bone Joint Surg Br. 1990;72:507-509. 2003;165:1431-1435. 78. Rounding C, Bloomfield S. Surgical treatments for 83. Gill P, Dowell AC, Neal RD, et al. Evidence based gen- ingrowing toenails. Cochrane Database Syst Rev. eral practice: a retrospective study of interventions in 2005;(2):CD001541. one training practice. BMJ. 1996;312:819-821.

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Table The treatment of minor dermatologic ailments: What the research tells us Treatments for which sufficient positive evidence exists are highlighted in green; those for which negative evidence exists are highlighted in red.

Dermatological Category of treatment Was the Overall rating Are further minor ailment Target for target, according to Was treatment research of research studies (N*) Treatment treatment main symptoms effective? convincing?† evidence required? Oral antibiotics Infection 1. Partial thickness Bacterial infection No trials No Moderate Yes (flucloxacillin)11 (bacterial) burns (4) Gauze dressings11 Skin lesion Likely Conflicting Silver sulfadiazine11 Skin lesion No Conflicting Betadine12 Infection (bacterial) Bacterial infection Yes Yes Cooling13 Pain Pain No No Honey14 Pain Pain No No Neutral lotion Itch Itch No trials No 2. Polymorphic Poor Yes light eruption (4) Corticosteroids15,18 Itch Itch Yes Yes Oral antihistamines Itch Itch No trials No Sunscreens16,17 Preventive Yes No Local ointments Itch/rash Itch No trials No 3. Acute urticaria (2) Moderate Yes Oral antihistamines19 Itch/rash Itch Yes Yes Corticosteroids20 Itch/rash Itch Yes Yes Doxycycline Infection (bacterial) Bacterial infection No trials No 4. Insect bites None Yes and stings (0) Amoxicillin Infection (bacterial) Bacterial infection No trials No Oral antihistamines Pain/itch Itch No trials No Malathion21 Infection Yes Yes 5. Pediculosis (3) Good No Permethrin22 Infection Yes Yes Lindane Infection No trials No Combing23 Infection Yes Yes Permethrin25,26 Infection Yes Yes 6. Scabies (3) Good No Lindane24 Infection Yes Yes Benzyl benzoate Infection No trials No Malathion Infection No trials No Yes, for bites Dog and cat Oral antibiotics Infection 7. Bacterial infection to the hands. No Moderate Yes bites (1) (amoxicillin)27 (bacterial) No, for other bites Paraffin gauze Skin lesion No trials No 8. Abrasions (1) Poor Yes Non-adherent absorbent Skin lesion No trials No compress

Skin lesion/ Betadine Bacterial infection No trials No infection (bacterial) Honey2 Skin lesion Likely No Salicylic acid29 Lump on the skin Yes Yes 9. Warts (4) Moderate Yes Cryotherapy29 Lump on the skin No No Duct tape Yes, treatment Lump on the skin No occlusion30-32 was not effective Surgical procedures Lump on the skin No trials No Curettage33 Lump on the skin No trials No 10. Molluscum Poor Yes contagiosum (1) Liquid nitrogen33 Lump on the skin No trials No Fusidic acid cream33 Lump on the skin No trials No Betadine33 Lump on the skin No No

E vol 58, No 9 / September 2009 The Journal of Family Practice Minor derm ailments: Evidence for common treatments t

table (cont.) The treatment of minor dermatologic ailments: What the research tells us Treatments for which sufficient positive evidence exists are highlighted in green; those for which negative evidence exists are highlighted in red.

11. Furuncles (0) Hot compress Pain Bacterial infection No trials No None Yes Antibiotics Infection (bacterial) Bacterial infection No trials No Local fusidic acid 12. Impetigo (1) Infection (bacterial) Bacterial infection Yes Yes Good No or mupirocin34 Yes, but less 34 effective than Oral antibiotics Infection (bacterial) Bacterial infection Yes local treatment in limited disease

13. Pityriasis Selenium sulphide Infection Fungal infection No trials No Moderate Yes versicolor (2) Imidazole Infection Fungal infection No trials No Fluconazole35 Infection Fungal infection Yes No Itraconazole36 Infection Fungal infection Yes No Miconazole37,38 Infection Fungal infection Yes Yes 14. Intertrigo (2) Moderate Yes Hydrocortisone37 Infection Fungal infection No No Imidazole Infection (bacterial) Bacterial infection No trials No 15. Erythrasma (1) Good No Benzoic acid Infection (bacterial) Bacterial infection No trials No Erythromycin39 Infection (bacterial) Bacterial infection Yes Yes Acyclovir40 Infection (viral) Yes Yes 16. Shingles (6) Moderate/Good Yes Famcyclovir41 Infection (viral) Yes No Acyclovir + prednisolone42 Infection (viral) Yes No

43,44 Yes, treatment Corticosteroids Inflammation No was not effective Amitriptyline45 Pain Likely No 17. Pruritus in the Local emollients Itch Itch No trials No Moderate Yes elderly (1) Corticosteroids Itch Itch No trials No Local antihistamines Itch Itch No trials No Oral antihistamines46 Itch Itch Yes Yes 18. Xeroderma (0) Emollients Dry skin No trials No None Yes 19. Androgenic Wig Hair loss No trials No Moderate Yes alopecia (5) Finasteride49-51 Hair loss Yes Yes Minoxidil47,48 Hair loss Likely Conflicting 20. Alopecia Minoxidil52,53 Hair loss No No Moderate Yes areata (5) Oral prednisolone54 Hair loss Likely No Desoxymethasone55 Hair loss No No Betamethasone56 Hair loss Likely No 21. Dandruff (4) Zinc pyrithione57 Infection (yeast) Fungal infection Yes No Moderate Yes Ciclopirox58-60 Infection (yeast) Fungal infection Yes Yes Ketoconazole61 Infection (yeast) Fungal infection Yes Yes Selenium sulphide61 Infection (yeast) Fungal infection Yes Yes Corticosteroids61 Itch Itch Yes Yes 22. Seborrhoeic Zinc pyrithione57 Infection (yeast) Fungal infection Yes No Moderate Yes eczema (2) Ketoconazole61 Infection (yeast) Fungal infection Yes Yes Coal tar61 Infection (yeast) Fungal infection Yes Yes Selenium sulphide61 Infection (yeast) Fungal infection Yes No Corticosteroids61 Itch Itch Yes Yes

C O N T INU E D

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Category of Dermatological treatment target, Was the Overall rating Are further minor ailment Target for according to main Was treatment research of research studies (N*) Treatment treatment symptoms effective? convincing?† evidence required? 23. Herpes Sunscreens62 Prevention Yes Yes Good No labialis (1) Oral antivirals62 Infection (viral) Yes Yes Zinc oxide cream62 Skin lesion Likely No Topical antivirals Infection (viral) No trials No Topical antivirals Pain No trials No 24. Perioral Clean with water Prevention No trials No Poor Yes dermatitis (1) Topical metronidazole63 Infection Bacterial infection Likely No Tetracycline Infection Bacterial infection No No Less effective 25. Oral thrush (1) Nystatin64 Infection Fungal infection No Good No than miconazole Miconazole64 Infection Fungal infection Yes Yes 26. Salmon patch (0) No treatment is needed None No Hydroquinone, tretinoin, Skin irritation Yes No 27. Chloasma (3) Moderate Yes hydrocortisone combination65,66 Hydroquinone 67 Skin irritation Yes No Topical metronidazole68 Infection Bacterial infection Yes Yes 28. Rosacea (2) Moderate Yes Azelaic acid68 Infection Bacterial infection Yes Yes Zinc-sulphate69 Infection Bacterial infection Yes No Tetracycline68 Infection Bacterial infection Yes No Disinfectant liquid Infection Bacterial infection No trials - 29. Umbilical None Yes problems Antiseptic dressing Infection Bacterial infection No trials - To stop in infants (0) Silver nitrate No trials - granulations To stop Electrocauterization No trials - granulations Zinc oxide cream70 Skin lesion Yes Yes 30. Nappy rash (2) Moderate Yes Miconazole71 Infection Fungal infection Yes No Hydrocortisone Itch Itch No trials No Fish hook 31. Local extirpation Skin lesion No trials - None No in finger (0) Splinter under 32. Splinter removal Skin lesion No trials - None No nail (0) Subungual Discharging 33. Making a hole in the nail72 Likely No Moderate Yes hematoma (1) hematoma Terbinafine (oral) Infection No trials No 34. Brittle nails (0) None Yes Itraconazole (oral) Infection No trials No IInfection Bacterial 35. Paronychia (0) Antibiotics No trials No Poor Yes (bacterial) infection Drainage Discharging pus No trials No Antifungal cream Infection Fungal infection No trials No

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Category of Dermatological treatment target, Was the Overall rating Are further minor ailment Target for according to main Was treatment research of research studies (N*) Treatment treatment symptoms effective? convincing?† evidence required? Local treatment 36. Fungal infection Infection Fungal infection Yes Yes Good No (imidazole)73 of the nail (3) Oral terbinafine74,75 Infection Fungal infection Yes Yes Removing the excess Removing 37. Calluses Yes No None Yes callus76 callosity on the feet (1) Disinfectant ointment Infection No trials No Wedge excision77,78 Removing 38. Ingrown nail (2) Yes Yes Good Yes infected tissue Destruction Chemical ablation77,78 Yes Yes nail matrix Salicylic acid Resolution 39. Corns (1) No trials No None Yes callosity Excision76 Removing Yes No callosity Imidazole79 Infection Fungal infection Yes Yes 40. Athlete’s foot (1) Good No Imidazole + Fungal infection Infection/itch Yes Yes hydrocortisone79 /itch Itraconazole79 Infection Fungal infection Yes Yes 41. Foot blisters (2) Betadine Infection Bacterial infection No trials No Moderate Yes Reducing Antiperspirant 80,81 incidence Yes Conflicting of blisters 42. Plantar warts (4) Salicylic acid 29 Lump on the skin Yes Yes Moderate/ Yes good Cryotherapy 29 Lump on the skin No No Yes, treatment Duct tape Lump on the skin No was not occlusion30-32 effective Surgical procedures Lump on the skin No trials No

*N=Number of trials. † Convincing evidence taken as level of evidence 1a or 1b.