Managing Recalcitrant Warts: Facts about Bacillus Calmette-Guerin (BCG), Mycobacterium Indicus Pranii (Mw Vaccine), and Purified Protein Derivative (PPD) as Immunotherapy — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Managing Recalcitrant Warts: Facts about Bacillus Calmette-Guerin (BCG), Mycobacterium Indicus Pranii (Mw Vaccine), and Purified Protein Derivative (PPD) as Immunotherapy
Department of Dermatology, Diwaniyah Teaching Hospital, Diwaniyah, Iraq
,
Department of Dermatology, Diwaniyah Teaching Hospital, Diwaniyah, Iraq
1 Department of Dermatology, Diwaniyah Teaching Hospital, Diwaniyah, Iraq
2 Department of Dermatology, Diwaniyah Teaching Hospital, Diwaniyah, Iraq
Recalcitrant warts can accurately be defined as warts that persist after six months of conventional therapy. Up to one-third of non-genital warts, especially periungual and plantar warts, become recalcitrant. Traditional treatment options for warts include topical salicylic acid, cryotherapy, and electrocautery; however, patients with recalcitrant warts remain a major therapeutic challenge. There is evidence that immunotherapy can clear recalcitrant warts if traditional treatment fails. Given this, clinical studies published in PubMed and Google Scholar that used Bacillus Calmette-Guerin (BCG), Mycobacterium Indicus Pranii (Mw vaccine), and purified protein derivative (PPD) as immunotherapy for wart, were reviewed in this study. Neither of these treatments has been subjected to a randomized controlled trial, thus to date, there are no standardized protocols to use them. Our review highlights the scientific facts in the clinical applications of the previous options to treat recalcitrant warts and investigate the differences among them, concerning efficacy, adverse effects, dosage, and route of administration.
KeywordsRecalcitrant WartsBCG VaccineMycobacterium W VaccinePPD (Purified Protein Derivative)
Bravo, I.G. and Felez-Sanchez, M. (2015) Papillomaviruses; Viral Evolution, Cancer, and Evolutionary Medicine. Evolution, Medicine, and Public Health, 2015, 32-51.
Braaten, K.P. and Laufer, M.R. (2008) Human Papillomavirus (HPV), HPV-Related Disease, and the HPV Vaccine. Reviews in Obstetrics & Gynecology, 1, 2-10.
Lipke, M.M. (2006) An Armamentarium of Wart Treatments. Clinical Medicine & Research, 4, 273-293.
Weber, C.A. and Hoffman, K.M. (2013) How to Treat Recalcitrant Warts. Podiatry Today, 26, 68-73.
Grussendorf-Conen, E.I. and Jacobs, S. (2002) Efficacy of Imiquimod 5% Cream in the Treatment of Recalcitrant Warts in Children. Pediatric Dermatology, 19, 263-266. https://doi.org/10.1046/j.1525-1470.2002.00083.x
Schianchi, R., Brena, M. and Veraldi, S. (2018) Treatment of Common Recalcitrant Warts with Topical Formic Acid. International Journal of Dermatology, 57, e3-e4. https://doi.org/10.1111/ijd.13811
Shumer, S.M. and O’Keefe, E.J. (1983) Bleomycin in Treatment of Recalcitrant Warts. Journal of the American Academy of Dermatology, 9, 91-96. https://doi.org/10.1016/S0190-9622(83)70112-X
Nofal, A., Nofal, E., Yosef, A. and Nofal, H. (2015) Treatment of Recalcitrant Warts with Intralesional Measles, Mumps, and Rubella Vaccine: A Promising Approach. International Journal of Dermatology, 54, 667-671. https://doi.org/10.1111/ijd.12480
Gaston, A. and Garry, R.F. (2012) Topical Vitamin A Treatment of Recalcitrant Common Warts. Virology Journal, 9, 21. https://doi.org/10.1186/1743-422X-9-21
Moniem, E.A., Genedy, R.M. and Moussa, R. (2016) Oral Zinc Sulfate in the Treatment of Recalcitrant Warts. Egyptian Journal of Obesity, Diabetes and Endocrinology, 36, 34-38.
Laftah, Z. and Bashir, S. (2017) Treatment of Recalcitrant Viral Warts with a CO2 Laser. Journal of the American Academy of Dermatology, 76, AB267. https://doi.org/10.1016/j.jaad.2017.04.1036
Chandrashekar, L. (2011) Intralesional Immunotherapy for the Management of Warts. Indian Journal of Dermatology, Venereology and Leprology, 77, 261-263. https://doi.org/10.4103/0378-6323.79694
World Health Organization (2018) BCG Vaccine: WHO Position Paper, Feb 2018 Recommendations. Vaccine, 36, 3408-3410. https://doi.org/10.1016/j.vaccine.2018.03.009
Internal Clinical Guidelines Team (UK) (2016) Tuberculosis: Prevention, Diagnosis, Management and Service Organization. National Institute for Health and Care Excellence (UK), London.
Immunisation against Infectious Disease—The Green Book (2013) Public Health England, Chapter 32. https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book
McShane, H. (2011) Tubeculosis Vaccines: Beyond Bacilli Calmette-Guerin. Philosophical Transactions of the Royal Society B Biological Sciences, 366, 2782-2789. https://doi.org/10.1098/rstb.2011.0097
Van-Dunem, J.C.V.D., Rodrigues, L.C., Alencar, L.C.A., Militao-Albuquerque, M.F.P. and de Alencar Ximenes, R.A. (2015) Effectiveness of the First Dose of BCG against Tuberculosis among HIV-Infected, Predominantly Immunodeficient Children. BioMed Research International, 2015, Article ID: 275029.
Mostaan, S., Yazdanpanah, B., Moukhah, R., Hozouri, H.R., Rostami, M., Khorashadizadeh, M., et al. (2016) Adverse Effects of BCG Vaccine 1173 P2 in Iran: A Meta-Analysis. Advanced Biomedical Research, 5, 99. https://doi.org/10.4103/2277-9175.183659
WHO (1995) Statement on BCG Revaccination for the Prevention of Tuberculosis. Bulletin of World Health Organization, 73, 805-806.
Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L.A., Ifrim, D.C., Saeed, S., et al. (2012) BacilleCalmette-Guerin Induces NOD2-Dependent Nonspecific Protection from Reinfection via Epigenetic Reprogramming of Monocytes. Proceedings of the National Academy of Sciences of the United States, 109, 17537-17542. https://doi.org/10.1073/pnas.1202870109
Bothamley, G.H., Cooper, E.d., Shingadia, D. and Mellanby, I. (2003) Tuberculin Testing before BCG Vaccination. BMJ, 327, 243-244.
ten Dam, H.G., Toman, K., Hitze, K.L. and Guld, J. (1976) Present Knowledge of Immunization against Tuberculosis. Bulletin of the World Health Organization, 54, 255-269.
Dye, C. (2013) Making Wider Use of the World’s Most Widely Used Vaccine: BacilleCalmette-Guérin Revaccination Reconsidered. Journal of the Royal Society Interface, 10, Article ID: 20130365. https://doi.org/10.1098/rsif.2013.0365
Ahmad, N.A., Abd Hamid, H.A., Sahril, N., MohdYusoff, M.F., Naidu, B.M., et al. (2013) BacilleCalmette-Guerin (BCG) Revaccination: Is It Beneficial for Tuberculosis Control? Open Access Scientific Reports, 2, 656.
Sterne, J.A., Rodrigues, L.C. and Guedes, I.N. (1998) Does the Efficacy of BCG Decline with Time since Vaccination? International Journal of Tuberculosis and Lung Disease, 2, 200-207.
Hatherill, M., Geldenhuys, H., Pienaar, B., Sulaiman, S., Chheng, P., Debanne, S.M., et al. (2014) Safety and Reactogenicity of BCG Revaccination with Isoniazid Pretreatment in TST Positive Adults. Vaccine, 32, 3982-3988. https://doi.org/10.1016/j.vaccine.2014.04.084
Rodrigues, L.C., Pereira, S.M., Cunha, S.S., Genser, B., Ichihara, M.Y., et al. (2005) Effect of BCG Revaccination on Incidence of Tuberculosis in School-Aged Children in Brazil. The BCG-REVAC Cluster-Randomised Trial. The Lancet, 366, 1290-1295. https://doi.org/10.1016/S0140-6736(05)67145-0
Nofal, A., Yosef, A. and Salah, E. (2013) Treatment of Recalcitrant Warts with Bacillus Calmette-Guérin: A Promising New Approach. Dermatologic Therapy, 26, 481-485. https://doi.org/10.1111/dth.12019
Kumar, P. and Das, A. (2014) Excellent Response to Intralesional Bacillus Calmette-Guérin Vaccine in a Recalcitrant Periungual Wart. Journal of Cutaneous and Aesthetic Surgery, 7, 234-235. https://doi.org/10.4103/0974-2077.150788
Jagati, A., Agarwal, S., Parmar, K.S., Shah, B.J. and Tank, J. (2017) A Prospective Interventional Study of 50 Patients to Assess the Effectiveness and Safety of Intralesional Reconstituted Bacille Calmette Guerin Immunotherapy in Treatment of Warts. International Journal of Applied Research, 3, 37-41.
Sharquie, K.E., Al-Rawi, J.R., Al-Nuaimy, A.A. and Radhy, S.H. (2008) BacilleCalmetteGuérin Immunotherapy of Viral Warts. Saudi Medical Journal, 29, 589-593.
Metawea, B., El-Nashar, A.R., Kamal, I., Kassem, W. and Shamloul, R. (2005) Application of Viable Bacillus Calmette-Guerin Topically as a Potential Therapeutic Modality in Condylomata Acuminata. The Journal of Urology, 65, 247-250. https://doi.org/10.1016/j.urology.2004.09.025
Zaheer, S.A., et al. (1993) Combined Multidrug and Mycobacterium w Vaccine Therapy in Patients with Multibacillary Leprosy. The Journal of Infectious Diseases, 167, 401-410. https://doi.org/10.1093/infdis/167.2.401
Rahman, S.A., Singh, Y., Kohli, S., Ahmad, J., Ehtesham, N.Z., Tyagi, A.K. and Hasnain, S.E. (2014) Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis. mBio, 5, e02020. https://doi.org/10.1128/mBio.02020-14
Rahman, S.A., Singh, Y., Kohli, S., Ahmad, J., Ehtesham, N.Z., Tyagi, A.K. and Hasnain, S.E. (2015) Reply to “Mycobacterium indicus pranii” Is a Strain of Mycobacterium Intracellulare: “M. indicuspranii” Is a Distinct Strain, Not Derived from M. intracellulare, and Isan Organism at an Evolutionary Transition Point between a Fast Grower and Slow Grower. mBio, 6, e00352. https://doi.org/10.1128/mBio.00352-15
Gupta, K.R. and Gupta, A. (2006) Concise Encyclopaedia of India. Volume 3, Atlantic Publishers & Distributors, 917.
Singh, I.G., Mukherjee, R., Talwar, G.P. and Kaufmann, S.H. (1992) In Vitro Characterization of T Cells from Mycobacterium w-Vaccinated Mice. Infection and Immunity, 60, 257-263.
Gupta, A., Geetha, N., Mani, J., Upadhyay, P., Katoch, V.M., Natrajan, M., et al. (2009) Immunogenicity and Protective Efficacy of “Mycobacterium w” against Mycobacterium Tuberculosis in Mice Immunized with Live versus Heat-Killed M. w by the Aerosol or Parenteral Route. Infection and Immunity, 77, 223-231. https://doi.org/10.1128/IAI.00526-08
Meena, J.K., Malhotra, A.K., Mathur, D.K. and Mathur, D.C. (2013) Intralesional Immunotherapy with Mycobacterium w Vaccine in Patients with Multiple Cutaneous Warts: Uncontrolled Open Study. JAMA Dermatology, 149, 237-239. https://doi.org/10.1001/jamadermatol.2013.866
Talwar, G.P. (1999) An Immunotherapeutic Vaccine for Multibacillary Leprosy. International Reviews of Immunology, 18, 229-249. https://doi.org/10.3109/08830189909043027
Gupta, S., Malhotra, A.K., Verma, K.K. and Sharma, V.K. (2008) Intralesional Immunotherapy with Killed Mycobacterium w Vaccine for the Treatment of Ano-Genital Warts: An Open Label Pilot Study. Journal of the European Academy of Dermatology and Venereology, 22, 1089-1093. https://doi.org/10.1111/j.1468-3083.2008.02719.x
Singh, S., Chouhan, K. and Gupta, S. (2014) Intralesional Immunotherapy with Killed Mycobacterium indicus pranii Vaccine for the Treatment of Extensive Cutaneous Warts. Indian Journal of Dermatology, Venereology and Leprology, 80, 509-514. https://doi.org/10.4103/0378-6323.144145
Garg, S. and Baveja, S. (2014) Intralesional Immunotherapy for Difficult to Treat Warts with Mycobacterium w Vaccine. Journal of Cutaneous and Aesthetic Surgery, 7, 203-208. https://doi.org/10.4103/0974-2077.150740
Higuchi, K. (2011) QFT Test and TST Test in Diagnosis of TB Infection. Nihon Rinsho, 69, 1378-1383.
Laura, M., Helen, R.S. and Ibrahim, A. (2015) Diagnosis and Management of Latent Tuberculosis Infection. Cold Spring Harbor Perspectives in Medicine, 5, a017830. https://doi.org/10.1101/cshperspect.a017830
Navak, S. and Achariva, B. (2012) Mantoux Test and Its Interpretation. Indian Dermatology Online Journal, 3, 2-6. https://doi.org/10.4103/2229-5178.93479
Khadka, P., Koirala, S. and Thapaliya, J. (2018) Cutaneous Tuberculosis: Clinicopathologic Arrays and Diagnostic Challenges. Dermatology Research and Practice, 2018, Article ID: 7201973.
Cohn, D.L., et al. (2000) Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. American Journal of Respiratory and Critical Care Medicine, 161, S221-S247.
Arend, S.M., Engelhard, A.C.F., Groot, G., de Boer, K., Andersen, P., Ottenhoff, T.H.M., et al. (2001) Tuberculin Skin Testing Compared with T-Cell Responses to Mycobacterium tuberculosis-Specific and Nonspecific Antigens for Detection of Latent Infection in Persons with Recent Tuberculosis Contact. Clinical and Diagnostic Laboratory Immunology, 8, 1089-1096.
Ahmad, S. (2010) New Approaches in the Diagnosis and Treatment of Latent Tuberculosis Infection. Respiratory Research, 11, 169.
Pai, M., Denkinger, C.M., Kik, S.V., Rangaka, M.X., Zweiling, A., Oxlade, O., et al. (2014) Gamma Interferon Release Assays for Detection of Mycobacterium Tuberculosis Infection. Clinical Microbiology Reviews, 27, 3-20. https://doi.org/10.1128/CMR.00034-13
Abd-Elazeim, F.M., Mohammed, G.F., Fathy, A. and Mohamed, R.W. (2014) Evaluation of IL-12 Serum Level in Patients with Recalcitrant Multiple Common Warts, Treated by Intralesional Tuberculin Antigen. Journal of Dermatological Treatment, 25, 264-267. https://doi.org/10.3109/09546634.2013.768760
Youssef, S.S., Diab, H., NaeemSallam, M.A. and Ahmed, A. (2009) Evaluation of IL2 and IFN γ mRNA Gene Expression in Resistant Genital and Plantar Warts, Treated by Intralesional Tuberculin.
Sharquie, K.E., Al-Rawi, J.R., Noaimi, A.A. and Majly, W.H. (2016) Tuberculin as Intralesional Therapy for Viral Warts-Single-Blind, Split, Placebo, Controlled Study. Journal of Cosmetics, Dermatological Sciences and Applications, 6, 191-198. https://doi.org/10.4236/jcdsa.2016.65024
Wananukul, S., Chatproedprai, S. and Kittiratsacha, P. (2009) Intralesional Immunotherapy Using Tuberculin PPD in the Treatment of Palmoplantar and Periungual Warts. Asian Biomedicine, 3, 739-743.
Amirnia, M., Khodaeiani, E., Fouladi, D.F. and Masoudnia, S. (2016) Intralesional Immunotherapy with Tuberculin Purified Protein Derivative (PPD) in Recalcitrant Wart: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial Including an Extra Group of Candidates for Cryotherapy. Journal of Dermatological Treatment, 27, 173-178. https://doi.org/10.3109/09546634.2015.1078871
Eassa, B.I., Abou-Bakr, A.A. and El-Khalawany, M.A. (2011) Intradermal Injection of PPD as a Novel Approach of Immunotherapy in Anogenital Warts in Pregnant Women. Dermatologic Therapy, 24, 137-143. https://doi.org/10.1111/j.1529-8019.2010.01388.x
Albugami, M., Tashkandi, A. and Al Rashed, A. (2009) Difficulties in Diagnosing Tuberculosis in Pregnancy. Annals of Saudi Medicine, 29, 154. https://doi.org/10.4103/0256-4947.51804
Podder, I., Bhattacharya, S., Mishra, V., Sarkar, T.K., Chandra, S., Sil, A., Pal, S., Kumar, D., Saha, A., Shome, K., Bandyopadhyay, D. and Das, N.K. (2017) Immunotherapy in Viral Warts with Intradermal Bacillus Calmette-Guerin Vaccine versus Intradermal Tuberculin Purified Protein Derivative: A Double-Blind, Randomized Controlled Trial Comparing Effectiveness and Safety in a Tertiary Care Center in Eastern India. Indian Journal of Dermatology, Venereology and Leprology, 83, 411. https://doi.org/10.4103/0378-6323.193623
Shaheen, M.A., Salem, S.A., Fouad, D.A. and El-Fatah, A.A. (2015) Intralesional Tuberculin (PPD) versus Measles, Mumps, Rubella (MMR) Vaccine in Treatment of Multiple Warts: A Comparative Clinical and Immunological Study. Dermatologic Therapy, 28, 194-200. https://doi.org/10.1111/dth.12230
Moubasher, A.E.A., Hassan, O.M., Youssef, E.M.K. and Sabek, M.M.A. (2016) Intralesional Injection of Purified Protein Derivatives versus Zinc Sulfate 2% in Recalcitrant Palmar and/or Plantar Warts. Journal of the Egyptian Women’s Dermatologic Society, 13, 151-158.
Saoji, V., Lade, N.R., Gadegone, R. and Bhat, A. (2016) Immunotherapy Using Purified Protein Derivative in the Treatment of Wart: An Open Uncontrolled Trial. Indian Journal of Dermatology, Venereology and Leprology, 82, 42-46. https://doi.org/10.4103/0378-6323.171650
Nimbalkar, A., Pande, S., Sharma, R. and Borkar, M. (2016) Tuberculin Purified Protein Derivative Immunotherapy in the Treatment of Viral Warts. Indian Journal of Drugs in Dermatology, 2, 19-23. https://doi.org/10.4103/2455-3972.184103
Pande, S., Sontakke, A. and Tayade, B.O. (2016) Purified Protein Derivative for Viral Warts and Interpretation of Tuberculin Skin Tests and Interferon Gamma Release Assay for Diagnosis of Tuberculosis in India. Indian Journal of Drugs in Dermatology, 2, 73-74. https://doi.org/10.4103/2455-3972.196165
Sterling, J.C., Handfield-Jones, S. and Hudson, P.M. (2001) Guidelines for the Management of Cutaneous Warts. British Journal of Dermatology, 144, 4-11. https://doi.org/10.1046/j.1365-2133.2001.04066.x