Perianal warts are brought on by the human papillomavirus (HPV), which affects the genital and anal regions and is spread through sexual contact. Ablation therapies are just one of the many therapeutic alternatives available for the treatment of Perianal warts, but the most of them are inherently uncomfortable, may leave scars, and cannot stop recurrence. [1,2]

Immunotherapy, a more recent therapeutic strategy, has been applied to treat Perianal warts with encouraging results. This includes immunotherapy using pure protein derivative (PPD) intralesional injections. PPD acts as an immunomodulator and boosts the immune system against lesions both nearby and far from the injection site. PPD immunotherapy stimulates cell-mediated immunity by stimulating NK cells, Th1 cells, and cytokine production, which is part of the immunotherapeutic agent's mode of action. This therapy provides long-lasting immunity with few negative effects. [1,3]

A sterile protein extract from Mycobacterium TB is known as a purified protein derivative. Injections of purified protein derivative antigens into the lesion trigger an immune response against both HPV and M. tuberculosis, causing the wart to recover. [1,3]

Immunotherapy has a low recurrence rate compared to conventional therapy, which has a recurrence rate of 20–30%. Eight months following treatment with no recurrence is the longest observation period of PPD treatment for Perianal warts that has been documented.

This case report aims to demonstrate the effectiveness, safety, and recurrence rate in long after intralesional injection of PPD as a treatment for Perianal warts in adult male.

A 23-year-old male adult presented to the Department of Dermatology with complaints of asymptomatic multiple skin coloured raised lesions in the perianal area for the last 2 weeks. Lesions were asymptomatic. His sexual history revealed frequent episodes of receptive anal intercourse. Clinical examination demonstrated multiple verrucous papules and plaques in the perianal area.

Case Description

A 23-year-old male adult presented to the Department of Dermatology with complaints of asymptomatic multiple skin coloured raised lesions in the perianal area for the last 2 weeks. Lesions were asymptomatic. His sexual history revealed frequent episodes of receptive anal intercourse. Clinical examination demonstrated multiple verrucous papules and plaques in the perianal area. Figure 1

General physical examination and systemic examination was normal. The patient underwent biochemical tests and virology assessment for investigations for HIV, HBsAG, Anti HCV) which were found to be non-reactive.

Patient was planned immunotherapy with intradermal purified protein derivatives in the dose of 10 TU /0.1 ml to be given 2 weekly for a maximum of 5 injections. A volume of 0.1 ml of PPD was given intradermally with an insulin syringe into the middle third of the right forearm after cleaning with 70% alcohol. After two weeks of first follow up, more than 90% of warts had regressed. Second session heralded complete clearance of lesions. Patient has been on regular follow up and even after three months, there had been no recurrence. Figure 2

One of the most frequent clinical signs of HPV infection in the vaginal area, which largely affected industrialized nations, is perianal warts. There is significant evidence linking these warts to anogenital malignancies. Men and women between the ages of 25 and 29 have the highest rate of perianal warts, respectively. [1,4]

Men who have sex with men (MSM) have an HPV seroprevalence that is roughly 2–6 times greater than that of heterosexual men, and it has been linked to 80–85% of anal malignancies. Anal warts are more prevalent in MSM who have engaged in condom-free anogenital contact or other anal-piercing sexual conduct, and their occurrence is ten times higher in HIV patients. Genital contact, early coitarche, multiple sex partners, and a history of STIs are a few more variables that increase the chance of HPV infection. Both sexual and non-sexual methods can be used to transmit genital HPV. HPV is very contagious and can spread between sexual partners even when no visible warts are present. [1,5]

The contour look of papules or verrucous, which can be flat or pedunculated, is highly diverse in the clinical form of Perianal warts. The lesion may be white, pink, purple, red, or skin-colored, or it may have other colors or patterns. Usually,   the   characteristics  of  skin  lesions are 

  Figure 1: Baseline

Figure 2:                            

Wart recurrence is a common issue because the main treatments for Perianal warts up to this point have focused on removing the warts rather than treating the underlying infection. However, a patient's preference, convenience, the expertise of the doctor, cost, and side effects can all be taken into account while deciding on a Perianal warts therapy. [1,4]

Perianal warts can be treated surgically using electrocautery, excision surgery, cryotherapy, laser, and other methods, as well as non-surgically with podophyllin, podophyllotoxins, trichloroacetic acid, and immunotherapy. Anal warts may be treated with electrocautery, excision surgery, cryotherapy, and trichloroacetic acid. However, a number of studies have noted that the therapy's side effects include pain, burning, crust, ulceration, infection, and permanent scarring. Immunotherapy is an established treatment option with a lesser likelihood of forming scar tissue and a reasonably low recurrence rate. [1,4,5]

An effective biological treatment against infections, cancer, and other disorders is immunotherapy. Cimetidine, imiquimod, interferons, Candida albicans antigens, measles, mumps, rubella (MMR), intralesional vitamin D, Bacillus-Calmette-Guerin (BCG), and PPD are a few immunotherapy medications that have been used in the past to treat Perianal warts. These medications work by triggering the immune system's defense against the warts' HPV-induced proliferation. [1,3]

PPD is safe and effective for treating persistent warts (including multiple warts, large lesions, palmoplantar, periungual, and vaginal kinds) intralesionally, according to several studies. To boost the immune response against HPV infection on the injection site and distant lesions, intralesional immunotherapy, such as PPD injection, has been utilized to completely eradicate all warts. The proinflammatory cytokines interferon gamma (IFN-) and interleukin (IL)-12, which have a T-helper 1 pattern, are released when PPD generates a robust systemic immune response, activating cytotoxic T cells and natural killer (NK) cells to fight HPV infection. [1,4,5]

Numerous studies have been done to evaluate the efficiency of PPD versus other immunotherapies for warts. In this instance, a dose of 10 TU/0.1 ml was administered twice weekly for a total of 5 injections. After washing with 70% alcohol, 0.1 ml of PPD was injected intradermally using an insulin syringe into the middle third of the right forearm. More than 90% of warts had returned after the first two weeks of follow-up. Complete elimination of lesions was announced by the second session. Even after three months of consistent follow-up care for the patient, there had been no recurrence. [1,4]

Less chance of scarring and a lower recurrence rate are immunotherapy's key benefits. Rashes, swelling, pain or discomfort at the injection site, and fever have all been reported as frequent PPD adverse effects in studies. The emergence of painful nodules that could grow into blisters or abscesses at the injection site is a serious adverse effect that may occur; however the occurrence was uncommon. Eight months following treatment, prior research on anogenital and common warts revealed no recurrence. In our trial, the side effect was slight pain at the injection site for PPD, but it quickly subsided and did not return even three months later. [1,5]

Overall, Intradermal PPD appears to be an effective, safe, and acceptable treatment modality for perianal warts. It is easy to perform, easily available, inexpensive, easy to use, well-tolerated mode of treatment with minimal side effects and carries the advantage of patient compliance and high patient satisfaction.

Conflict of Interest

None declared

Funding

No funding sources

Ethical Approval

The study was approved by the Institutional Ethics Committee of Civil Hospital, Nurpur

1. Achdiat, Pati Aji et al. "Success of Intralesional Purified Protein Derivative Immunotherapy in the Treatment of Anogenital Warts: A Case Report." Journal of Experimental Pharmacology, 2022, pp. 131–135. https://orcid.org/0000-0002-6924-0833.

2. Eassa, Bayoumy I., Amany A. Abou-Bakr, and Mohamed A. El-Khalawany. "Intradermal Injection of PPD as a Novel Approach of Immunotherapy in Anogenital Warts in Pregnant Women." Dermatologic Therapy, vol. 24, no. 1, 2011, pp. 137–143. https://doi.org/10.1111/j.1529-8019.2010.01388.x.

3. Saoji, Vikrant et al. "Immunotherapy Using Purified Protein Derivative in the Treatment of Warts: An Open Uncontrolled Trial." Indian Journal of Dermatology, Venereology and Leprology, vol. 82, 2016, p. 42. doi:10.4103/0378-6323.171650.

4. Nimbalkar, Ajay et al. "Tuberculin Purified Protein Derivative Immunotherapy in the Treatment of Viral Warts." Indian Journal of Drugs in Dermatology, vol. 2, no. 1, 2016, p. 19. https://ijdd.in/article.asp?issn=2455-3972;year=2016;volume=2;issue=1;spage=19;epage=23;aulast=Nimbalkar.

5. Jaiswal, Amit et al. "Immunotherapy with PPD in Treatment of Warts: An Open Labelled Study from Western Uttar Pradesh." IP Indian Journal of Clinical and Experimental Dermatology, vol. 5, no. 1, 2019, pp. 41–45. https://www.academia.edu/download/63471003/IJCED-5-1-41-4520200530-3830-8eu63n.pdf