SUMMARY Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 248-252 248 Original Article Treatment of Molluscum Contagiosum with 10% Potassium Hydroxide Solution Atiya Rahman 1, Aisha Akhtar 1, Saadia Tabassum 2,Rana Shakil Ahmad 3 1. Department of Dermatology, Combined Military Hospital Lahore & CMH Lahore Medical College; 2. Department of Dermatology, Aga Khan University Hospital, Karachi;3.Clinical Research Executive Abstract Background: To determine the efficacy and safety of topical 10% potassium hydroxide solution in the treatment of molluscum contagiosum (MC) . Methods: An open, prospective, non-randomized study of one year duration was conducted using 10% KOH solution to treat MC. Twenty eight patients completed the study. A total of seven appointments were planned; one baseline and six follow-up visits. 10% KOH was applied to molluscum lesions daily till the lesions resolved or till 3 months had elapsed. Results: Twenty eight patients, among which 22 were children, completed the study. The mean age of patients was 10.6 years. The total lesion count in the patients varied from 5 – 94, with the mean lesion count of 22.14 SD +_ 18.32. There was complete resolution of lesions in 20 (71.4%) of patients , 4 (14.3) had a near complete, 2 (7.1%) had partial and 2 (7.1%) patients had no improvement. 82% patients tolerated the treatment well with no side effects. Conclusion:10% KOH solution is an effective and well tolerated treatment for MC. It is less painful and cost-effective as compared to many well- established therapeutic modalities. It has the advantage of ease of application at home making it an acceptable and feasible option for the treatment of MC. Key Words: Molluscum contagiosum, Potassium hydroxide, Efficacy. Introduction Molluscum Contagiosum (MC) is among the most common viral skin infections. Common treatment options include destructive therapy, topical therapy and immunotherapy. Destructive therapy is poorly tolerated because of pain on application. In addition, these therapies are expensive and have inconvenience of application in hospital setting. MC is among the most common viral skin infections , occurring in approx 2-8% of children.1,2 It is caused by a member of the Poxvirus family, the genus Molluscipox virus. The virus is transmitted by close physical contact, autoinoculation, and fomites.MC presents as asymptomatic, discrete, smooth, flesh-coloured, dome- shaped papules with central umbilication.1 The lesions can be numerous and recurrent. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection.3Treatment options include destructive therapy, topical therapy, immunotherapy and oral therapy.1 Destructive treatment modalities include curettage, cryotherapy, expression or pricking with a sterile needle, electrodesiccation, photodynamic therapy, and laser ablation.4,5Among topical therapies different chemical agents, like cantharidin,6 povidone- iodine,7 potassium hydroxide,8 tretinoin,9 and imiquimod10 have been used with variable success. Immune modulating agents include interferon alpha, imiquimod and cimetidine.1 Destructive therapy is poorly tolerated in children because of pain on application. In addition, these therapies are expensive and have inconvenience of application in hospital setting. Patients and Methods An open, prospective, non-randomized study of one year duration was conducted at Dermatology Department of Combined Military Hospital, Lahore using 10% KOH solution to treat MC. Sample size of 28 cases was estimated using 95% confidence interval and 14% deviation acceptance with a percentage of complete response in 85% in the previous studies. A total of seven appointments were planned; one baseline and six follow-up visits. During the baseline visit thorough history and dermatological examination was carried out. Cases were studied for number of lesions, their site, any eczematous change, presence of pain or pruritus. First application of 10% KOH solution was performed with the patient or parent closely observing the procedure and was advised to apply the drug in a similar way at home Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 248-252 249 twice daily. Six follow-up visits were planned at the end of week 1, 2, 4, 6, 8 and 12. The medication was to be applied till the lesions resolved or till 3 months had elapsed. KOH applied on the skin initiates an inflammatory response leading to lesion clearance. The number of lesions, their site, crusting , erythema , erosions , pain , pruritus , improvement of lesion were documented. The clinical response to treatment was assessed using the methods devised by Marsalet al and Capriotti et al. 11,12 The patients were divided into 4 groups on the basis of improvement of MC lesions. Group 4= complete cure; Group 3= near complete response (with less than 5 MC lesions all over the body) ;Group 2= partial response (less than 60% of the lesions since the baseline visit and more/equal than 5 lesions);Group 1= poor response (>60% of the lesions since baseline visit). Patients whose lesions cleared up before 3 months were documented and were discharged from the study having attained “complete cure”. At the end of 3 months final assessment was made . Results Twenty eight patients, 22 children and 6 adults completed the study. Age of patients ranged from 2 years to 36 years and the mean age was 10.6 years ± 8.96. Eleven (39.3%) patients were female and 17 (60.7%) were male. The duration of MC lesions varied from 2 – 39 weeks, with a mean duration of 8.6 weeks (Table 1). Twelve (42.9%) of the patients gave positive family history in a first degree relative. The total lesion count in the patients varied from 5 – 94, with the mean lesion count of 22.14 SD +_ 18.32. 32.2% patients had been treated previously with other therapeutic modality (17.9% with cryotherapy and 14.3% with phenolization) but had unsatisfactory response. Successful 10% KOH solution application to MC initiates an inflammatory response consisting of erythema, crusting, erosion and usually associated with a mild stinging or pruritus(Figure 1). There was complete resolution of lesions in 20 (71.4%) of patients , 4 (14.3%) had a near complete, 2 (7.1%) had partial and 2 (7.1%) patients had no improvement (Table 2). Complete cure was seen in majority of patients in age group2 to 20 years (Table 3;Figure 1- 4).Duration of disease could prolong the response time for the patients as it has strong effect on treatment and improvement in patients with a significant value (Table 4). There was no significant effect noted for other demographical factors like age, gender and site of disease. An equal distribution was observed on evaluation on different sites, but most commonly the lesions were present on multiple sites; 16(57%) of cases ( Table 1:Distribution of the characteristics in study population (n=28) Mean Percentages Age 10.60±8.96 Gender Male 11(39.3%) Female 17(60.7%) Family history Yes 12(42.9%) No 16(57.1%) Duration of disease 8.57±9.36 Site of disease Head & neck 5(17.9%) Trunk 3(10.7%) Upper limb 1(3.6%) Lower limb 2(7.1%) Genitalia 1(3.6%) Multiple sites 16(57.1%) Table 2:Percentage improvement in the disease grades of the patients Response No Percentage 1. Poor Response 2 7.1 2. Partial Response 2 7.1 3. Near Complete Response 4 14.4 4. Complete Cure 20 71.4 Table 3: Impact of demographical variables on the study outcome Improvement grades Total P-value Group 1: Poor Response Group 2:Partial Response Group 3: Near Complete Response Group 4: Complete Cure Gender Female 0 0 1 10 11 0.273 .0% .0% 25.0% 50.0% 39.3% Male 2 2 3 10 17 100.0% 100.0% 75.0% 50.0% 60.7% Age group 2-20 year 1 2 2 17 22 0.267 50.0% 100.0% 50.0% 85.0% 78.6% >20 year 1 0 2 3 6 50.0% .0% 50.0% 15.0% 21.4% Table 5).Majority of the patients (82%) tolerated the treatment well with no side effects. 2 (7.1%) developed contact dermatitis after application of KOH; 3 (10.7%) patients developed secondary bacterial infection requiring oral antibiotic therapy. Four patients developed transient post-inflammatory hypopigmentation once the lesions cleared; this resolved within a month of stopping KOH application.The hypopigmentation settled after the completion of study duration with no further treatment. Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 248-252 250 Table 4:Stratification of the improvement with respect to family history and duration of disease Improvement Grades Total P- value Group 1: Poor Response Group 2: Partial Response Group 3: Near Complete Response Group 4: Complet e Cure Family History Yes 1 1 1 9 12 0.887 50.0% 50.0% 25.0% 45.0% 42.9% No 1 1 3 11 16 50.0% 50.0% 55.0% 75.0% 57.1% Duration of disease 2-12 year 1 0 3 19 23 0.000 50.0% .0% 75.0% 95.0% 82.1% 13-23 year 0 2 0 0 2 .0% 100.0% .0% .0% 7.1% >23 year 1 0 1 1 3 50.0% .0% 25.0% 5.0% 10.7% Table 5: Improvement according to body site Improvement Grades Total Site of lesion Group 1 Poor Response Group 2. Partial Response Group 3. Near Complete Response Group4. Complet e Cure p-value Head & Neck 0 0 0 5 5 0.667 .0% .0% .0% 25.0% 17.9% Trunk 0 0 0 3 3 .0% .0% .0% 15.0% 10.7% Upper limb 0 0 0 1 1 .0% .0% .0% 5.0% 3.6% Lower 0 1 0 1 2 .0% 50.0% .0% 5.0% 7.1% Genitalia 0 0 0 1 1 .0% .0% .0% 5.0% 3.6% Multiple sites 2 1 4 9 16 100.0% 50.0% 100.0% 45.0% 57.1% Discussion MC is a common viral infection that frequently affects children of school going age. It is thought that using community bathing facilities/swimming pools or siblings using the same washing sponges or towels spreads the infection.11In healthy patients, cutaneous MC is a self-limiting disease that often spontaneously resolves in 6 to 9 months, usually without scarring. Quality of life is a factor to consider when deciding whether or not to treat a paediatric patient as he or she may suffer chastisement from peers at school if the lesions are visible. Not treating paediatric infections also carries the risk of the disease spreading to others, and this consideration may favour the option of treatment over benign neglect.13 Conditions like atopic dermatitis may cause widespread development of MC, making it imperative to treat the lesions promptly. Destructive treatment options like curettage, expression or pricking with a sterile needle, electrodessication and laser ablation are not well- tolerated by children because of pain and are expensive. Among drugs that are applied topically imiquimod has been found to be of limited efficacy. In a study spanned over more than 10 yrs in USA it was found that it has been prescribed in only 7% of the patients of MC.10 KOH has been used in varying strengths; 2.5%, 5%, 10% and 20%. The rationale for using the lower strengths is to minimize its side effects, especially reducing irritant effects on face. The exact mechanism by which KOH clears MC lesions is not clear. It appears that topical application of KOH digests keratin and induces inflammation; this in turn stimulates innate and cell-mediated immune response that inhibits MC-induced immunosuppression and eliminates the infection of MC. Considering the same mechanism of action KOH has been successfully used in warts.14-16 Short et al, conducted a double blind, randomized, placebo-controlled study comparing 10% KOH solution with a placebo.17 The end point of their study was the complete clearance of the lesions. They recruited 20 patients (10 in each group), age ranging from 2 – 12 years. They excluded patients with facial lesions. 2 (20%) of the patients complained of severe stinging sensation and developed severe inflammatory response and 2 (20%) reported transient post inflammatory hyperpigmentation. 70% of their patients’ lesions were cleared with 10% KOH. Only 20% of the patients in the placebo group cleared the lesions at the end of the study. In our study the majority of the patients (82%) tolerated the drug well. Fig 1:Signs of inflammation after application of 10% KOH solution Fig 2: 6 year old boy, baseline Fig 3 Same patient, after 2 weeks of treatment Fig 4:Same patient, at 8 weeks of treatment, mostly resolved lesions, 2 healed crusted lesions at the base of the neck and post inflammatory hypopigmentation at few sites Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 248-252 251 7% developed contact dermatitis at the site of application but it was easily managed by the use of low potency topical steroids. In a similar study Handjani et al8 compared 10% KOH with cryotherapy, whose efficacy for treating MC is well established. The two groups had 15 patients each. Age varied from 1 – 24 years. 86.6% in the KOH group had complete clearance as compared to 93.3% in the cryotherapy group (p>0.05). Post inflammatory hyperpigmentation was noticed more commonly with cryotherapy. A study on 2 different concentrations of KOH (2.5% and 5%) was conducted.18 out of the 29 patients recruited in the study 25 completed it; 13 in 2.5% group and 12 in 5% group. 11 (44%) of the patients had lesional clearance at the end of the study. 8 of these patients were in the 5% treatment group and 3 were in the 2.5% KOH group. This difference was statistically significant (p < 0.047). There were no statistical differences between the two groups with respect to side-effects (p = 0.682). We have used higher percentage 10% KOH solution and achieved better efficacy. We would suggest against using concentration of KOH lesser than 10%.Al Sudanyet al19have compared 10% KOH with 25% podophyllin solution. They found 64% of their patients were cleared of MC lesions at the end of the study. However, the study duration was 4 weeks. We present the case that had their patients continued the medication the percentage of patients cleared of MC could have increased. In Pakistan, Qureshi et al have used 10% KOH to treat their MC patients. 20 They have compared its efficacy with cryotherapy. The mean age of their patients was 20.53 years. A later incidence peak in young adults is attributable to sexual transmission with lesions more common in genital area.21 80% of their patients achieved clinical clearance of the lesions. They did not find statistically significant difference in the clearance of the lesions amongst the patients receiving two different treatment modalities, indicating 10% KOH has the same efficacy as cryotherapy. The patients in our study were predominantly children, unlike their study based mainly on adults. Therefore, our study sheds light on how 10% KOH solution treats children, the age group mainly affected by MC. Side effects like severe stinging sensation and hypopigmentation has been reported with 10% KOH use.22In our study 82% of the patients tolerated the topical medicament well. Only a few patients developed contact dermatitis, secondary infection and hypopigmentation at the site which resolved with the passage of time. In contrast, destructive therapies like cryotherapy and electrodessication are associated with much higher chances of burning, pain and pigmentary changes which can last for a long time.23-25In our setup where patients come from far flung areas, it is difficult for them to have regular follow up for hospital based treatment. A treatment modality which is economical, acceptable, efficacious and easily tolerated is the need of the hour. Conclusion 1.10% KOH solution is an effective treatment for MC. 2. It has the advantage of ease of application at home making it a good and feasible option in the treatment of MC. References 1. Forbat E, Al-Niaimi F, Ali FR. Molluscum Contagiosum: Review and Update on Management. PediatrDermatol. 2017 ;34(5):504-15. 2. Scheinfeld N. Treatment of molluscum contagiosum: a brief review and discussion of a case successfully treated with adapelene. Dermatol Online J. 2007 ;13(3):15-18. 3. van der Wouden JC, van der Sande R, Kruithof EJ. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017 17; 5: 4767-70. 4. Sterling J. Treatment of warts and molluscum: what does the evidence show? CurrOpinPediatr. 2016 ;28(4):490-99. 5. Shahriari M, Makkar H, Finch J. Laser therapy in dermatology: Kids are not just little people. ClinDermatol. 2015 ;33(6):681-86. 6. Moye V, Cathcart S, Burkhart CN. Beetle juice: a guide for the use of cantharidin in the treatment of molluscum contagiosum. DermatolTher. 2013 Nov-;26(6):445-51. 7. Capriotti K, Stewart K, Pelletier J. Molluscum Contagiosum treated with dilute povidone-iodine.J Clin Aesthet Dermatol. 2017 ;10(3):41-45. 8. Handjani F, Behazin E, Sadati MS. Comparison of 10% potassium hydroxide solution versus cryotherapy in the treatment of molluscum contagiosum: an open randomized clinical trial. J Dermatolog Treat. 2014 ;25(3):249-50. 9. Rajouria EA, Amatya A, Karn D. Comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for Molluscum Contagiosum in children. Kathmandu Univ Med J (KUMJ). 2011 Oct-Dec;9(36):291-4. 10. Farhangian ME, Huang KE, Feldman SR. Treatment of Molluscum Contagiosum with Imiquimod in the United States.PediatrDermatol. 2016;33(2):227-28. 11. Marsal MJR, Cruz I, Teixido C, Diez O. Efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscumcontagiosum: Randomized clinical trial: Research protocol BMC Infectious Diseases 2011, 11:278-81 12. Capriotti K, Stewart K, Pelletier J. Molluscum Contagiosum Treated with Dilute Povidone-Iodine. Journal of clinical and Aesthetic Dermatology. 2017; 10 (3): 41 - 45. 13. Olsen JR, Gallacher J, Finlay AY, Piguet V, Francis NA. Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort study.Lancet Infect Dis. 201515(2):190-95 14. de Abreu Camargo CL, Walter BeldaWJr, Fagundes LJ.A prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of https://www.ncbi.nlm.nih.gov/pubmed/28884917 http://www.ncbi.nlm.nih.gov/pubmed?term=%22Scheinfeld%20N%22%5BAuthor%5D javascript:AL_get(this,%20'jour',%20'Dermatol%20Online%20J.'); https://www.ncbi.nlm.nih.gov/pubmed/?term=Sterling%20J%5BAuthor%5D&cauthor=true&cauthor_uid=27269886 https://www.ncbi.nlm.nih.gov/pubmed/27269886 Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 248-252 252 genital warts in men. An Bras Dermatol. 2014;89(2):236- 40. 15. Loureiro WR, Cacao FM, Belda W Jr, Fagundes LJ, Romiti R. Treatment of genital warts in men with potassium hydroxide. Br J Dermatol. 2008;158:180-82. 16. Allen AL, Siegfried EC. Management of warts and molluscum in adolescents. Adolesc Med.2001; 12: 229-42. 17. Short KA, Fuller C, Higgins EM. Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum. Pediatric Dermatology. 2006, 23 (3): 279–81 18. Uçmak D, Akkurt MZ, Kacar SD, Sula B, Arica M. Comparative study of 5% and 2.5% potassium hydroxide solution for molluscum contagiosum in children. CutanOculToxicol. 2014 ;33(1):54-59. 19. Nameer K. Al-Sudany A,Dler R. Abdulkareem. A comparative study of topical 10% KOH solution and topical 25% podophyllin solution as home-based treatments of molluscum contagiosum. Journal of Dermatology & Dermatologic Surgery. 2016; 20: 107–14. 20. Qureshi A, Zeb M, Jalal-Ud-Din M, Sheikh ZI. Comparison of efficacy of 10% potassium hydroxide solution versus cryotherapy in treatment of molluscum contagiosum. J Ayub Med Coll Abbottabad. 2016 ;28(2):382-85. 21. Hanson, D., Diven, D.G.,. Molluscum contagiosum. Dermatol Online J 2003; 9 (2) 2-5. 22. Can B, Topaloglu F, Kavala M, Turkoglu Z, Zindanci I. Treatment of pediatric molluscum contagiosum with 10% potassium hydroxide solution. J Dermatolog Treat. 2014 ;25(3):246-48. 23. Hughes CM, Damon IK, Reynolds MG (2013) Understanding US healthcare providers’ practices and experiences with molluscum contagiosum. PLoSONE 8(10): e76948. 24. Whetmore SJ. Cryosurgery for common skin lesions. Treatment in family physicians' offices.Canadian Family Physician. 1999; 45: 964-74. 25. Al-Mutairi N, Al-Doukhi A, Al-Farag S, Al-Haddad A. Comparative study on the efficacy, safety, and acceptability of imiquimod 5% cream versus cryotherapy for molluscum contagiosum in children. Pediatr Dermatol. 2010 ;27(4):388- 94. https://www.ncbi.nlm.nih.gov/pubmed/?term=Al-Doukhi%20A%5BAuthor%5D&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/?term=Al-Farag%20S%5BAuthor%5D&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/?term=Al-Haddad%20A%5BAuthor%5D&cauthor=true&cauthor_uid=19804497 https://www.ncbi.nlm.nih.gov/pubmed/19804497