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DOI: 10.1111/jocd.13272
ORIGINAL CONTRIBUTION
Dalia R. Shaldoum MBBCh1 | Ghada F. R. Hassan MD2 | Eman H. El Maadawy MD2 |
Gamal M. El-Maghraby MD3
1
MBBCh. Faculty of medicine, Tanta
University Abstract
2
Dermatology and Venereology, Faculty of Background: Many therapeutic modalities were reported for the treatment of warts;
medicine, Tanta University, Tanta, Egypt
however, no single treatment is completely effective.
3
Pharmaceutical Technology, Faculty of
pharmacy, Tanta University, Tanta, Egypt
Objective: To evaluate the efficacy of intralesional injection of MMR vaccine vs vita-
min D in treatment of warts.
Correspondence
Ghada Fawzy Rezk Hassan, 1 Asmaa bent
Patients and Methods: A total of 60 patients were included in the study divided
Abi-Bakr street, Neseem street, end of into two groups. Group A received intralesional MMR vaccine into largest wart, and
Moheb street, Al-Mahalla Al-Kobra, El-
Gharbia, Egypt.
group B received intralesional vitamin D3 into each lesion with maximum of five
Email: ghadafawzy53@yahoo.com warts treated in one session. A maximum of six sessions was done every 3 weeks in
both groups. Follow-up was done for 6 months for any recurrence.
Results: In group A: complete response in 80%, partial response in 6.67%, minimal
response in 6.67%, and no response in 6.67% of patients. About 60% of patients
with multiple warts showed complete clearance of distant untreated warts. In group
B: complete response in 66.7%, partial response in 6.67%, minimal response in 20%,
and no response in 6.67% of patients. There was no significant difference between
both groups. No recurrence was observed in both groups in the follow-up period.
Conclusions: Immunotherapy by both intralesional MMR vaccine and vitamin D3 is
simple, well-tolerated, effective, and cost-benefit modalities for the treatment of
warts.
KEYWORDS
1 | I NTRO D U C TI O N and viewed as socially unacceptable when located on visible areas
(eg, hands and face). 3
Warts are caused by infection of the epidermis with human pap- Many destructive and immunotherapeutic treatments that have
illomavirus (HPV). HPVs are divided into separate genotypes. variable success rates are available for warts. The current destruc-
Different HPV types may preferentially infect either cornified tive therapeutic options for cutaneous warts include cryotherapy,
stratified squamous epithelium of skin or uncornified mucous electrocauterization, surgical excision, laser ablation, bleomycin
membranes.1 Some warts may spontaneously disappear, while intralesional injection, topical agents, such as 5FU/salicylic acid,
others persist and can spread on other body sites. 2 Warts can be more recently, topical treatment cantharidin, podophyllotoxin, and
painful depending on their location (eg, soles and near the nails) salicylic acid.4 They have their own limitations, such as suboptimal
efficacy, associated adverse effects, and high recurrence rates in ex- mepecaine 3% (ampoule of 1.8 mL). A few minutes later, 0.4 mL of
5
tensive warts. vitamin D3 (5 mg/2mL equivalent to 20 000 IU cholecalciferol) solu-
About immunotherapy, 2 various intralesional antigens that have tion was slowly injected into the base of each wart using an insulin
been used for cutaneous warts including the measles, mumps, ru- syringe. A maximum of five warts were treated per patient in one
bella (MMR) vaccine,6 skin test antigens (mumps, candida,7 tricho- session. The maximum total amount of vitamin D3 injected in one
phyton), Bacillus of Calmette and Guerin (BCG) vaccine, tuberculin, session was 5 mg. Injections were performed every 3 weeks until
and Mycobacterium w (Mw) vaccine.5 It is postulated to achieve its complete clearance or for a maximum six treatment sessions.
result by stimulating a cell-mediated immune response via recruit- In both groups A and B, the surface area and number of warts
ment of various immune cells (ie, neutrophils, lymphocytes) and re- were noted and lesions were photographed. With follow-up, the
lease of cytokines (eg, TNF-α, IL-1, IL-6, IFN-γ, GM-CSF). Though it is response to treatment and approximate decrease in size of warts
injected intralesionally, the sensitization it produces may also result was recorded and history of adverse effects was taken. Complete
in clearance of noninjected distant warts.7 So, mumps-measles-ru- response (CR) for complete disappearance of the warts and return
bella (MMR) vaccine results in regression of warts via immunomod- of normal skin markings (100%), partial response (PR) for more than
ulation and induction of immune system for destroying virus and the 50% improvement, minimal response (MR) for less than 50% im-
infected host cells.6,8 provement, and no response (NR) for stable disease (0%). Resolution
The vitamin D has multiple physiological and pharmacological of distant untreated warts was recorded. The percentage of im-
effects mediated by action of the vitamin D receptors (VDRs). VDR provement ranged from 0% to 100% according to size of regression
activators have been shown to inhibit cell replication and have im- of warts. Follow-up was done every month for six months after last
munomodulatory properties. It has been suggested that vitamin D session to detect any recurrence.
derivatives exert their effects via diverse mechanisms, including reg-
ulation of epidermal proliferation, inhibition of hyperkeratosis, and
induction of apoptosis and anti-inflammatory actions.9-12 2.1 | Statistical analysis
Data were fed to the computer and analyzed using IBM SPSS soft-
2 | M E TH O DS ware package version 20.0 (v 16; SPSS Inc, Chicago, IL, USA).
Abbreviations: FE, Fisher exact for chi-square test; MW, P, P values for Mann-Whitney test; t, P, t
and P values for Student t test; χ2, P, χ2 and P values for chi-square.
complete response after 6 sessions. The patients who showed partial A. While dystrophy, swelling and vasovagal attack occurred only in
response reached it after 6 sessions. All other patients who showed group B. Regarding the recurrence, all cured patients in both groups
minimal or no response received 6 sessions, so there was no relation did not show any recurrence within the follow-up period which ex-
between response and increasing number of sessions. On the other tended for 6 months after the end of treatment sessions.
hand in group B, 14 patients (46.7%) showed complete response after There was a statically significant negative correlation be-
2 sessions, 4 patients (13.3%) showed complete response after 3 tween the response and the number of treatment sessions with P
sessions, and two patients (6.7%) showed complete response after 4 value = .001* in the group B only (Figure 5), and no statically sig-
sessions. The patients who showed partial response reached it after nificant correlation was found in group A. There were no significant
six sessions. There was significant relationship between number of correlations between the response and either age, sex, duration of
treatment sessions and response in group B (Table 3). There was sig- the disease, or type of warts in each group (Table 4).
nificant difference between the two groups regarding the number of
sessions, as those who received intralesional vitamin D3 needed less
number of treatment sessions to get complete response, Figure 5. 4 | D I S CU S S I O N
In group A, minimal pain occurred in 24 (80%) patients and min-
imal erythema in 30 (100%) patients. In group B, minimal pain oc- Cutaneous warts are prevalent conditions in dermatology caused
curred in 20 (66.7%) patients, minimal erythema in 12 (40%) patients, by the human papilloma virus (HPV). Treatment is almost difficult,
nail dystrophy in 2 (6.7%) patients with periungual warts, swelling and most of the modalities are destructive resulting in scarring
in 4 (13.3%) patients, and mild symptoms of vasovagal attacks in 8 and are associated with recurrences. Destructive modalities such
(26.7%) patients. No significant difference was found between the as electrical and chemical cautery are painful procedures diffi-
two groups except erythema which was significantly higher in group cult to be utilized in children.13 Intralesional immunotherapy by
|
4 SHALDOUM et al.
B (III) B (IV)
A (III) A (IV)
F I G U R E 1 B, Before treatment (group A), male patient aged 27 years old, he had verruca in multiple sites (BI, II, III, IV). T = target wart. A,
After treatment (group A), the same patient after 4 sessions with complete response of target and other distant warts
antigens like BCG, candida, trichophyton, and MMR makes the im- Na et al 8 recorded only 26.5% of complete response, 25.0% with
mune system able to produce a type 1 helper T cell (TH 1)–medi- partial response, and no response in 48.5%. Lower recorded value
ated delayed-type hypersensitivity response to various antigens, of success of treatment with MMR were also reported in Saini et
including HPV that accelerates destruction of virus and infected al13 where 6.9% showed no response, 22.84% with minimal re-
13
host cells. It can also eradicate the distant wart. Intralesional vi- sponse, 59.77% with partial response, and 26.44% with complete
tamin D3 may also affect the warts via regulating epidermal cell resolution.
10
proliferation and differentiation, inhibiting hyperkeratosis, and The mean of number of treatment sessions needed in the cur-
also through effect on different cytokines as vitamin D has im- rent study to reach complete response was 5.47 ± 0.64 sessions in
mune-regulatory actions.14 group A. But in Nofal et al15 study, the average number of treat-
In group A (MMR group), 80% showed complete response, ments to achieve complete response was 3.25 and 5.38 sessions,
6.67% had partial response, 6.67% had minimal response, and respectively. With agreement with the previous studies, in the
6.67% had no response. In Nofal et al15 study, complete response present study, there was no statistically significant relationship
occurred in 63%, partial response in 23%, and no response in 14%, between the therapeutic response to MMR vaccine and the age
which was in agreement with the present study. On the contrary, of the patients. 8,13,15
SHALDOUM et al. |
5
A (I) A (II)
Abbreviations: χ2, P: χ2 and P values for chi-square test; MC, Monte Carlo for chi-square test; t, P, t
and P values for Student t test; MMR, measles, mumps, and rubella; Vit D, vitamin D.
*Statistically significant at P ≤ .05
Percentage of improvement
rs P rs P
F I G U R E 5 Correlation between percentages of improvement to disappearance of the wart within three months, without pain or
with number of sessions in group B
other side effects and no recurrence within the 9 months since its
disappearance.
done by Raghukumar et al18 and Kavya et al19 recurrence was ob- According to our best knowledge, the current study is the first
served in 3.33% and in one patient, respectively. study to compare MMR vaccine and vitamin D3 intralesional injec-
Other study was done by Imagawa and Suzuki,11 where vitamin tions as therapeutic options for warts, and from the results, we can
D3 derivatives were used topically in treatment of warts in which conclude that: MMR vaccine and vitamin D3 intralesional injections
local application of (maxacalcitol ointment 25 μg/g) three times a are simple, effective, safe, office technique, well-tolerated, and
day was advised. In some cases, the subjects were advised to apply cost-efficient modalities in the treatment of different types of warts
gauze smeared with approximately a 1 mm thickness of the oint- even if recalcitrant or multiple. It is easy to administer in outpatient
ment after a bath and leave it on until they bathed the next day. clinics.
In all patients, the warts successfully disappeared within 2 weeks MMR vaccine needed more sessions of treatment to show com-
to 6 months of the start of treatment without pain or other side plete clearance of warts, and clearance of distant untreated warts
effects. was reported, while vitamin D3 needed less number of session treat-
10
Another case report done by Moscarelli et al showed that ments to show complete clearance of warts and no clearance of
local application of activated vitamin D (gauze wet with calcitriol distant untreated warts were found. Both modalities of treatments
0.5 μg solution) at least two times a day and the advice to reapply showed a decreased risk of recurrence which is a big problem that
a gauze wet with calcitriol 0.5 solution after each hand washing led faces both the patients and the dermatologists.
|
8 SHALDOUM et al.