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DERMATOLOGIC THERAPY
ISSN 1396-0296
THERAPEUTIC HOTLINE
Intradermal injection of PPD as a
novel approach of immunotherapy in
anogenital warts in pregnant women
Bayoumy I. Eassa*, Amany A. Abou-Bakr &
Mohamed A. El-Khalawany*
*Departments of Dermatology and Venereology, Al-Hussein University
Hospital, Al-Azhar University, Tanta, Gharbia Governorate and Department
of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
ABSTRACT: Immunotherapy for treatment of recalcitrant warts was used through different modalities
including intralesional injection of purified protein derivative (PPD), which is an extract of Mycobacterium tuberculosis, used for testing exposure to tuberculin protein, either from a previous vaccination or
from the environment. This method is used to evaluate the efficacy of a new approach of intradermal
injection of PPD in the treatment of anogenital warts in pregnant women. A total of 40 pregnant
women, aged 2035 years, and presented with anogenital warts were enrolled in this study. Human
papillomavirus (HPV) typing was done using the GP5+/GP6+ PCR assay. The patients were treated with
weekly injections of PPD given intradermally in the forearms, and evaluated for the response regularly.
HPV type-6 was the predominant genotype (67.5%). Overall, the improvement in this study was 85%
and was related to the extent of tuberculin reactivity. Nineteen (47.5%) patients demonstrated complete
clearance, 15 (37.5%) had partial response, and three (7.5%) had minimal response. Three (7.5%) cases
did not respond to treatment. Side effects were minimal and insignificant. Treatment of anogenital
warts in pregnant women with intradermal injection of PPD was found to be a unique, safe, and
effective modality of immunotherapy.
KEYWORDS: anogenital warts, immunotherapy, PPD
Introduction
Warts are common in humans and account for 8%
of visits to dermatologists. Although many warts
resolve spontaneously over several years, most
patients seek treatment because the warts are
unsightly and often tender or painful (1). Warts are
Address correspondence and reprint requests to: Mohamed A.
El-Khalawany, Department of Dermatology, Al-Hussein
University Hospital, Box 32515, Al-Darasa, Cairo, Egypt, or
email: makhalawany@gmail.com.
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Eassa et al.
62, 67, 68, 71, and 74 are classified as putative lowrisk factors since they are not associated with the
development of carcinomas (4,5).
HPV infection may spread through direct
contact or autoinoculation. The incubation period
varies from 1 to 12 months with an average of 23
months (6). There are many types of warts, such as
common, plane, planter, filliform periungual oral,
and genital (condylomata acuminata) (7). Genital
HPV infection is estimated to be subclinical in up
to 70%, i.e., unnoticed by the patient but detected
by full clinical, histological, and cytological examination or molecular analysis (8).
Genital warts have a high infectivity; the thinner
mucosal surface is more susceptible to inoculation
of virus than the thicker keratinized skin; in addition, lesions are noted to be commonest in sites
subjected to greatest coital friction in both sexes.
Anogenital warts in adult are usually but not always
transmitted sexually (9). The infectivity of maternal
genital HPV as regards laryngeal papilloma in the
child seems low (10). However, the risk of transmission from mother to child with subsequent development of the diseases in the child has been
estimated to be between 1 in 80 and 1 in 1500,
respectively (11).
During pregnancy, genital warts may proliferate
rapidly because of altered immunity and increased
blood supply, and they can be present in clinical or
subclinical (latent) form (12). The clinical form
leads to more emotional and physical suffering
for the patient because of the expected surgical
delivery or the risk of contamination of the
newborn baby with HPV during spontaneous
vaginal delivery (13).
The latent form of high-risk HPV infection might
be the reason for materno-fetal transmission of
HPV. The high rate of high oncogenic risk types of
HPV in pregnancies complicated by intrauterine
growth retardation (IUGR) might suggest the correlation between HPV infection and IUGR etiology
(14). HPV infection of extravillous trophoblast
induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may
cause placental dysfunction and is associated with
adverse pregnancy outcomes, as spontaneous
preterm delivery (15).
Primary treatment modalities for warts include
destructive therapies, such as topical chemical
cautery, cryotherapy with liquid nitrogen, electric
cautery (electro-surgery), excision, bleomycin
sulfate injection, and laser vaporization, but none
of them offers a guarantee of cure and recurrence is
common (16). Because warts proliferation is controlled by the immune system, various methods
138
Results
Forty pregnant women were enrolled in this study.
The age ranged from 20 to 35 years; the mean age
was 28.3 years, and the duration of gestations was
2428 weeks (mean: 26 weeks). Patients were
divided into two groups and were treated according to the protocol mentioned above. HPV type-6
was the predominant genotype in our patients and
was detected in 67.5% of the patients, whereas
type-11 in 25% and type-16 in 7.5% as shown in
Tables 1 and 2.
Group A, which included 20 patients positive for
PPD skin test, started showing improvement after
the second injection by reduction in the size of
warts and disappearance of the smaller lesions.
After the fourth injection and during examination
of the patient before giving the fifth one; most
patients showed up to 75% reduction in size of
the warts. By the end of the eighth injection, 14
patients achieved more than 75% response. We
decided to give another four injections. After a total
of 12 injections, complete resolution occurred in 10
patients (50%) (FIG. 1), partial in seven patients
(35%), minimal in two patients (10%), and no
response in one (5%).
Group B included 20 patients who were treated
with placebo weekly for four weeks. No improvement was noticed and no adverse effects were
reported except slight pain and burning sensation
at the site of injection lasting for few minutes. The
patients were shifted to the same treatment protocol as in Group A, and after a total of 12 injections,
complete resolution occurred in nine patients
(45%), partial in eight patients (40%), and minimal
in one patient (5%). No response was recorded in
two patients (10%).
Total or partial response was observed in
patients with strong tuberculin test (1015 mm
indurated plaques), but the patients with tuberculin test (5<10 mm) had minimal or no response.
All patients with complete resolution were fol-
139
Eassa et al.
Table 1. Clinical characteristics, HPV typing, PPD test result, and response rate in Group A
Patient
no.
Age
(Years)
Gestation
(weeks)
Duration of the
disease (weeks)
HPV
typing
Response
rate (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
20
31
35
32
25
28
34
20
29
21
33
25
34
35
27
26
27
28
24
30
22
21
25
25
23
28
27
25
28
20
20
25
27
21
28
23
22
24
20
21
5
5
4
4
5
5
8
9
8
7
6
8
6
8
8
8
10
7
10
9
11
6
6
6
11
6
6
16
6
6
6
6
6
6
11
11
11
6
6
6
14
10
11
5
14
15
12
15
6
13
5
11
10
11
13
12
14
15
13
12
100
70
80
40
100
100
100
100
No
100
30
85
60
75
100
90
100
100
100
95
Table 2. Clinical characteristics, HPV typing, PPD test result, and response rate in Group B
Patient
no.
Age
(Years)
Gestation
(weeks)
Duration of the
disease (weeks)
HPV
typing
Response
rate (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
22
33
32
30
20
26
30
28
26
35
30
23
35
28
24
25
35
26
28
23
27
22
28
20
24
25
28
26
22
22
35
22
21
23
25
35
20
26
23
35
8
6
8
8
6
9
4
5
7
9
4
10
7
5
6
4
10
8
9
10
6
6
11
6
6
6
6
16
6
11
6
6
6
11
6
6
11
6
11
16
12
15
5
10
14
14
13
13
10
13
5
11
10
13
14
5
13
12
10
14
90
100
no
80
100
100
95
100
75
100
30
85
70
100
100
no
100
85
75
100
140
Discussion
A global search was done in medical literature but
no paper could be found using this unique modality (intradermal injection of PPD antigen in the
Before treatment
FIG. 1. The clinical response throughout the12-week duration and follow-up after the end of treatment.
141
Eassa et al.
142
Conclusion
We believe that intradermal injection of PPD in the
forearms instead of intralesional injection in the
treatment of anogenital warts in pregnant women
is an acceptable and safe modality and is a promising therapy for warts in general especially in
countries where vaccination against tuberculosis is
performed routinely and mandatorily.
References
1. Stern R, Johnson M, DeLozier J. Utilization of physician
services for dermatologic complaints. Arch Dermatol 1977:
113: 10621066.
2. Kilkenny M, Marks R. The descriptive epidemiology of
warts in the community. Aust J Dermatol 1996: 37: 8086.
3. De Villier EM, Fauquet C, Broker TR, Benard HU, zur
Hausen H. Classification of papillomaviruses. Virology
2004: 324: 1727.
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