BACKGROUND: warts or verrucae are the cutaneous maifestations caused by human papilloma virus. They are common benign presenting complaints attending to the OPD of dermatology. The treatment of wart posses a therapeutic challenge, as a result multiple modalities are existing for the treatment of cutaneous warts, which is cumbersome and may result in cosmetic disfigurement, chances of recurrences. Thus, immunotherapy is evolving promising treatment in cutaneous warts by inducing host cell mediated immunity towards HPV resulting in clearance and to prevent the recurrences.
AIM: Our study is aimed to evaluate the efficacy of lesional vitamin D3 injections and normal saline intralesional injections on cutaneous warts .
MATERIALS AND METHODS: This is a randomised control trials in cutaneous warts conducted in a tertiary care centre, mamata general hospital , khammam. 26 patients with cutaneous warts were randomly divided into 2groups. Group A received lesional injection of vitamin D3 every 3 weeks untill the improvement in the size of warts .group B was received normal saline injections as a control. The maximum of 3 these sessions were carried in both groups. Statistical analysis was done by unpaired T test (P <0.05)
RESULTS : 76.92% of the patient showed a significant reduction in size of wart with vitamin D3 injection ,while 15.38% of patients with normal saline .This therapy was well tolerated except for the pain during the injections .
CONCLUSION: Our study’s results focus a new insight in the treatment response in reduction of the size of cutaneous warts
KEY WORDS: Immunotherapy, VitaminD3, Warts , Normal saline, Intralesional .
Introduction
Cutaneous warts are the common benign condition caused by human papilloma virus(HPV) usually self-limiting papillomas (1,2).treatment have been based on destructive methods such as cryotherapy, photodynamic therapy, pulsedyelasers, kerotolytics like salicylic acid, immune stimulation( dinitrochloro benzene, interferons) or antimitotic effects( bleomycin, florouracil)(3). Because currently available treatment often fail and chances of recurrences. To overcome this complication immunotherapy is evolving and more popular treatment for cutaneous warts by inducing the host cell mediated immunity. Various topical and intralesional agents are used as immuotherapy of warts such as imiquimod ,mycobacterium w (MW),BCG, MMR vaccines, candida antigens , trichophyton skin antigens(4,5,6,7,8,9). Our study not only focus on new treatment but also try to see the response and chances of recurrences in the cutaneous warts.
MATERIAL AND METHODS
This was a randomised control trial conducted in the department of dermatology in the mamata general hospital in period of six months from November 2016 to May 2017. A total of 26 patients were enrolled for the study , they were subjected to complete workup including detailed history and examination of lesions. Pregnant , Lactating mothers , Immunosuppressed patients, history of intake of immune modulators, immunosuppressive drugs were excluded. We included patients of age group 14 to 60 years in the study. We explained the procedure to all the patients, written and informed consent were obtained from them before the commencement of the study. Approval was obtained from the institutional ethical committee. Patients of the study were equally divided into group A and group B. No prior sensitization dose was given to any of these patients. Group A received 0.2 ml/7.5mg of injection vitamin d3(arachitol-3l) using a insulin syringe at the base of a single wart and the session was repeated every three weeks for three sessions. Group B received 0.2 ml of 0.84% normal saline at the base of the wart , this session was also repeated as above. Photographs were captured at each visit to check the treatment response. Improvement of response was graded as Excellent response – 75% , Good response – 51 to 75%, Partial response -26 to 50%, Poor response – <25 %. Patients were followed up for 3 months after the last injection.
RESULTS
Our study included a total of 26 patients for treatment of warts among them 10 were females and 16 were males .Male to female ratio 1.8:1. Mean age 26.6 +/- 5.5 years. The mean duration of wart is 3.2 +/- 1.61 mean years. Treatment response to the vitamin D3 is tabulated.
TABLE-1
Response GROUP A (13)- vit D3 GROUP B (13)- NS
Excellent 10(76.92%) –
Good – –
Partial 1(8%) –
Poor 2(15.38%) 2(15.38%)
Nill – 11
Maximum response was seen after 7 weeks of therapy. Immunotherapy was well tolerated by the patients except for pain during injections followed by edema of the lesion, no other serious complications were observed. Statistical analysis was done by unpaired T test and P = <0.05. A significant reduction in size of wart was seen with vitamin D3 than normal saline.
Figure 1.
a.Initial lesion before start of intralesional injection of vitamin D3;
b. after three weeks
c. after twelve weeks
a. b. c.
Figure 2.
a.Initial lesion before intralesional injection;
b.after three weeks
c. after twelve weeks
a. b. c.
DISSCUSSION
Warts are the common viral infection on skin and mucosa and are prevalent world wide. Warts are caused by HPV (DNA virus), which has more than 100 strains . Some warts may spontaneously disappear while others persist and spread on other body sites provoking physical and emotional stress to the patient(10).
Warts treatment depends on two main therapeutic options , the first line is conventional destructive and aggressive methods which includes treatment with chemical cautery, cryotherapy, electrocautery, surgical excision, laser ablation and second line of treatment includes immunotherapy which is based on activation of immune system to deal with HPV virus and suppress its activity. Such therapy applied topically, intralesionally or systemic administration (11).
Intralesional Immunotherapy utilises the immune system to mount a delayed type of hypersensitivity response to various antigens and also to wart tissue. Immunotherapy associated with production of Th1 cytokines that activate cytotoxic and natural killers to eradicate HPV infection. This clears not only local warts also distant warts unlike traditional wart therapy(12).
Some authors have directly injected antigen to the largest wart without performing a preliminary intradermal testing. Warts are injected intralesionally using an insulin syringe which is held parallely to the skin surface bevel facing upwards . This therapy is repeated every 3 weeks until complete clearance of warts for a maximum of three treatments with or without response(13). In our study patient subjected with vitamin D3 treatment every three weeks for a maximum of 3 sessions which is co-related with the above study.
We adopted this study with vitamin D3 due to economical price, easy availability and good compliance to the patient. An active form of vitamin D3 has been used for treatment of psoriasis vulgaris. It is well known that vitamin D3 analog have biological action in epidermal cell regulation, cell proliferation and modulation of cytokine production. Recent evidence demonstrate an effect on cell death, tumour invasion, angioma and cancer regulation (14). Intralesional vitamin D3 was first introduced by Aktas et al. for the treatment of plantar warts.(15 ).
The effect of vitamin D3 on verrucae by TLR activation of human macrophages, upregulates the expression of vitamin D receptors and vitamin D1 hydroxylase gene leading to antimicrobial peptide action(16). Topical vitamin D3 derivative used in a case of infant with ano-genital wart and also used to treat the warts in three immunocompromised patients of SLE , HIV and renal transplant recipients(17)
Intralesional saline is generally used as placebo control for treatment of cutaneous warts(18). In some study patients were subjected to intralesional saline in a cutaneous wart showing a zero response (19).
Our study results showed 76.92% clearance of cutaneous wart with intralesional injections of vitamin D3 ,which is co-related with the Kavya et al. (20)
Conclusion
Injection vitamin D3 is more effective in treatment of verrucae. This immunotherapy has better patient compliance, good therapeutic response without cosmetic disfigurement and capable of preventing recurrences. Thus, our observation open avenues of further randomised trials for the establishment of role of vitamin D3 in cutaneous warts.
Financial support and sponsorship :
Nil.
Limitations of study :
As the study has a small sample size.
Conflicts of interest :
There are no conflicts of interest.