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Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
Original Article
Frequency of
radiotherapy
cutaneous
manifestations
of
Humaira Maryum*, Zarnaz Wahid**, Ijaz Ahmed***, M. Zafar Alam*
*Department of Dermatology, Hamdard University, Karachi
**Department of Dermatology, Dow University of Health Sciences, Karachi
*** Department of Dermatology, Ziauddin University, Karachi
Abstract Objective To determine different types of cutaneous manifestations secondary to ionizing radiation
therapy in patients treated for various malignancies.
Patients and methods The cross-sectional study was conducted on patients attending outpatient
department of Dermatology and Oncology, Civil hospital Karachi, from 1 st May 2006 till 31st
August 2006. Patients belonging to both sexes and all age groups fulfilling the selection criteria
were enrolled. After an informed consent, selected patients were subjected to a detailed history and
clinical examination. A clinical diagnosis of different radiation-induced skin changes was made.
Relevant investigations, biochemical profile and skin biopsy were done where required. All the
findings were recorded, compiled, tabulated and analyzed. The type of radiation, dosage and
duration of treatment was also recorded.
Results 100 patients comprising 35 (35%) males and 65 (65%) females completed the study.
Minimum age of presentation was 11 years and maximum 82 years, the mean age being 46.36 (SD
14.46). All the patients were receiving external beam therapy. Minimum radiation dose at which
skin lesions appeared was 500cGy while maximum 7000cGy. Maximum number of patients
developed cutaneous lesions in the dose range between 3100cGy to 6000cGy. Pigmentation (64%)
was the most common cutaneous change followed by erythema (45%), epilation (42%), moist
desquamation (26%) and oral mucositis (11%). Scalp alopecia, xerostomia, dry desquamation,
ulceration, telangiectasia, atrophy and necrosis followed in a descending frequency. Amongst the
enrolled subjects 31 patients (31%) were classified as suffering from acute radiodermatitis while
another 11 as chronic radiodermatitis (11%).
Conclusion Radiation therapy produces significant cutaneous manifestations on skin, pigmentary
changes, erythema and epilation being the most common. Moist desquamation, oral mucositis,
xerosis and scalp alopecia are seen less often. Severe changes which may lead to the interruption of
therapy are seen less commonly.
Key words
Radiation therapy, radiodermatitis, moist desquamation, dry desquamation, xerostomia, mucositis,
pigmentation.
Introduction
Radiation therapy is used in a majority of cancer
patients at some point during their treatment. It
Address for correspondence
Prof. Ijaz Ahmed
Department of Dermatology, Ziauddin
University, Karachi
E mail: [email protected]
is well-known that the radiations used to kill
cancer cells can also damage normal tissues in a
treatment field leading to side effects. Goal of
radiation therapy is to balance the effects in
order to maximize destruction of cancer cells
and minimize normal tissue damage.1,2 Ionizing
radiations constitute energy sufficiently strong to
remove an orbital electron from an atom. These
371
Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
radiations can have an electromagnetic form,
such as a high energy photon or a particulate
form, like an electron, proton, neutron or alpha
particles. High energy radiation is either
delivered to the tumor through a machine (a
linear accelerator) known as external beam
radiotherapy, or by means of a radiation source
placed in contact with the tumor, known as
brachytherapy. Most patients tolerate the applied
dose of radiotherapy with no or moderate side
effects. However, 5 to 10% of all individuals
show increased tendency to develop skin
reactions.3 Radiation confers significant, dosedependent cutaneous sequelae, including
erythema, desquamation, ulceration, alopecia,
decreased skin elasticity, thickened and fibrotic
skin and delayed wound healing.3-5 These
cutaneous side effects are painful, aesthetically
unpleasant, affect quality of life, and may
influence treatment adherence, tolerance, and
schedule.4,6
Radiation therapy targets rapidly dividing cells,
and because skin is characterized by rapid cell
proliferation, it is often affected by such
treatment.7 Adverse cutaneous effects of
radiotherapy can be divided into acute
radiodermatitis, chronic radiodermatitis and
other benign skin reactions, as well as some late
complications like skin malignancies. Acute
radiodermatitis occurs during the first 3 weeks
of radiotherapy while chronic radiodermatitis
develops few weeks after initiation of
radiotherapy. Acute radiation dermatitis
manifests as a spectrum of symptoms that range
from no cutaneous changes to the most severe
clinical disease which include hemorrhage,
ulceration, and necrosis.8,9 Between these
extremes, patients may experience erythema,
depilation, pruritus, dyspigmentation, dry
desquamation, patchy moist desquamation
limited to intertriginous areas, confluent and
widespread moist desquamation, edema, and
alopecia. Alopecia can become permanent in the
chronic phase due to perifollicullar fibrosis.8,9
Less commonly reported reactions are
pemphigus vulgaris, pemphigus foliaceus and
bullous pemphigoid. Squamous cell carcinoma
and basal cell carcinoma are well documented
late sequelae.
Studies are being conducted worldwide to assess
the cutaneous manifestations of radiotherapy.
However, statistical data on the subject is
lacking in our part of the world as no work has
been done in this regard. The study was aimed to
determine different types of cutaneous
manifestations secondary to ionizing radiation
therapy in patients treated for various
malignancies.
Patients and methods
The cross-sectional study was conducted on
patients attending outpatient department of
Dermatology and department of Oncology, Civil
hospital, Karachi. The study spanned from 1st
May 2006 till 31st August 2006 completed over
a period of 4 months. Patients were selected on
the basis of already defined exclusion and
inclusion criteria by non-probability convenient
sampling.
Patients belonging to both sexes and all age
groups were enrolled for the study. Only patients
developing skin changes after exposure to
radiation therapy were included. All the patients
were receiving external beam radiotherapy i.e.
photon and electron type of energy. Patients
having any primary dermatosis and those with
skin manifestations due to other systemic
diseases were excluded. Patients with
dermatoses secondary to any systemic or topical
treatment were also ruled out.
372
Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
All the patients were subjected to a detailed
history and clinical examination comprising
general,
systemic
and
dermatological
examination. A clinical diagnosis of different
radiation-induced skin changes was made.
Relevant investigations like scraping for fungus,
swabs for culture and Tzanck smear were
performed in doubtful cases. Biochemical
profile and skin biopsy were done where
required. The type of radiation, dosage and
duration of treatment was also recorded.
A predesigned proforma was used to record
different findings. All the findings were
compiled, tabulated and analyzed using the
software SPSS.
Results
A total of 100 patients were enrolled in the study
belonging to both sexes. There were 35 (35%)
males and 65 (65%) females. Minimum age of
presentation was 11 years and maximum 82
years, the mean age being 46.36±14.46 years.
Table 1 reveals the type of energy used. Seventy
one (71%) patients were on photon therapy
comprising 29 males (41%) and 42 females
(59%). Seven (7%) patients were receiving
electron beam therapy including 5 males (71%)
and 2 females (29%). Of the remaining 22
patients, 1 male (5%) and 21 females (95%)
were initially treated with photon therapy
followed by electron beam.
Correlation between the dose of radiation and
onset of cutaneous changes can be appreciated
from Table 2. Minimum radiation dose at which
skin lesions appeared was 500cGy while
maximum 7000cGy. Only one patient suffered
from skin lesions at the minimum dosage.
Maximum number of patients developed
cutaneous lesions in the dose range 3100cGy to
6000cGy.
Table 1 Type of radiation (n=100).
Type of radiation Male
Female
(n=35)
n=65)
N (%)
N (%)
Photon
29 (41%) 42 (59%)
Electron
5 (71%)
2 (29%)
Photon + electron
1 (5%)
21 (95%)
Table 2 Dose of radiation (n=100).
Dose range
Male
Female
cGy
(n=35)
(n=65)
500-1000
1
3
1100-2000
0
2
2100-3000
7
5
3100-4000
9
16
4100-5000
1
23
5100-6000
11
13
6100-7000
6
3
Total
n&%
71
7
22
Total
(N & %)
4
2
12
25
24
24
9
Table 3 Skin manifestations due to radiotherapy
(n=100).
Skin manifestation
Male
Female
Total
N (%)
n%
n&%
Pigmentation
26 (41) 38 (59)
64
Erythema
20 (44) 25 (56)
45
Epilation
22 (52) 20 (48)
42
Moist desquamation 17 (65)
9 (35)
26
Oral mucositis
8 (72)
3 (28)
11
Xerosis
2 (29)
5 (71)
7
Scalp alopecia
1 (14)
6 (86)
7
Xerostomia
1 (17)
5 (83)
6
Dry desquamation
3 (60)
2 (40)
5
Ulceration
1 (20)
4 (80)
5
Telangiectasia
2 (50)
2 (50)
4
Atrophy
0
2 (100) 2
Necrosis
1 (50)
1 (50)
2
Change of sensation 0
2 (100)
2
Fibrosis
0
1 (100)
1
Radiation induced skin changes are presented in
Table 3. It can be appreciated that pigmentation
was the most common cutaneous change seen in
our study (64%) comprising 26 males (41%) and
38 females (59%). Erythema followed with a
frequency of 45% i.e. 20 males (44%) and 25
females (56%). Epilation (42%), moist
desquamation (26%) and oral mucositis (11%)
were seen less frequently. Scalp alopecia,
xerostomia, dry desquamation, ulceration,
telangiectasia, atrophy and necrosis were also
seen in a descending frequency (Table 3).
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Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
Amongst the enrolled subjects 31 patients (31%)
were classified as suffering from acute
radiodermatitis while another 11 as chronic
radiodermatitis (11%). All the patients with
acute
radiodermatitis
presented
with
pigmentation, erythema and epilation. Moist
desquamation was seen in 26 (84%) followed by
dry desquamation 5 (16%), ulceration 5 (16%)
and necrosis in 1 patient (3%). Likewise
pigmentation and epilation was a feature in all
the patients with chronic radiodermatitis
followed by telangiectasia in7 (64%) and scaling
in 7 (64%), atrophy in 6 (54%), and fibrosis and
necrosis in 1 patient (9%) each.
Discussion
Radiation therapy is a commonly used and
clinically important treatment for a variety of
malignancies but can impart injury to healthy
skin.4 Approximately 85% of patients treated
with radiation therapy will experience a
moderate-to-severe skin reaction.10 The goal of
radiation therapy is to balance the effects in
order to maximize destruction of cancer cells
and minimize normal tissue damage. The side
effects that each patient experiences are directly
related to several factors, including: site of
treatment, volume of irradiated tissue, total
radiation dose, elapsed treatment time and daily
fraction size.11 Macmillan et al.12 added to the
knowledge on the risk factors for skin
breakdown.
The present study was aimed to determine
different types of cutaneous manifestations
secondary to ionizing radiation therapy in
patients treated for various malignancies.
Correlation between the dose of radiation and
onset of cutaneous changes in our study can be
appreciated by the appearance of skin lesions at
a minimum radiation dose 500cGy while
maximum 7000cGy.
Pigmentation was the most common skin finding
in our study. Braun-Falco et al.13 found mild to
moderate pigmentation in more than one third of
their similar series of patients. The frequency
was significantly higher in our study i.e. 65%.
However, the results can vary from one study to
another depending upon study design and
setting. Moreover, the extent of pigmentation
can be influenced by the dose and duration of
radiation therapy.11 Erythema at the site of
irradiation followed next in frequency to
pigmentation. Hanks et al.14 reported a
comparable frequency in a similar set of
patients. Majority of our patients developed
erythema at a dose of 3000 to 6000 cGy, which
is similar to the dosage described in the past
study.14 Hanks et al.14 also suggested the
comparable maximum dose for development of
erythema. Yamazaki et al.11 have already
defined erythema to be dependent on the total
dose of irradiation. Hanks et al.14 reported mild
erythema in 48%of their patients while 40%
patients developed moderate erythema and brisk
erythema in (12%) at a dose of up to 5040cGy.
Therefore, the frequency and severity of
erythema in our study is comparable to the past
study.14 Likewise the radiation dose responsible
for erythema in our study is also consistent with
the report from Hanks et al.14 Epilation was seen
in a significant number of patients in our study.
The well-known complication of radiotherapy
has been reported from time to time. Yesudian et
al.15 claims that epilation (hair loss) may occur
on any hair bearing of skin with doses above 1
Gy. Yesudian et al.15 also pointed out that
fractioned radiation dosage can prevent the
development of permanent hair loss until dose
exceeds 45 Gy.
Moist desquamation, using current radiotherapy
techniques, is a frequent consequence of radical
doses of radiotherapy.16,17 Moist desquamation
374
Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
was also seen in our patients. Hanks et al.14
reported the frequency of moist desquamation to
be 20% in a similar series of patients. Therefore,
the finding in our study is almost consistent with
the study mentioned.14 On the contrary, SnijdersKeitholz et al.15 reported moist desquamation as
an acute side effect in all their patients studied.
Oral mucositis also featured in our patients.
Allal et al.19 also observed mucositis as an acute
reaction in young subjects as well as in elderly.
However, workers have observed mucositis in
almost all their patients irradiated for head and
neck tumours.20,21 Therefore, the frequency of
mucositis also depends upon the region
irradiated and can vary from one study to
another.11 Xerosis has been claimed as a side
effect of radiotherapy from time to time.22
Xerosis also featured in our study. Wilson et
al.23 reported xerosis as a finding in acute as
well as chronic radiodermatitis. Therefore the
finding in our study is comparable to the reports
in literature.22,23 Scalp alopecia observed in our
study had a frequency less than that reported by
Lawenda et al.24 However, the findings can vary
from one study to another depending upon study
design and setting.11 Xerostomia although seen
in our patient had a frequency less than that
reported by Shaharyar et al.25 i.e. 13.6%.
However, the study was confined to only those
patients who were irradiated for head and neck
tumors. Allal et al.19 also observed xerostomia as
a chronic reaction in young subjects as well as in
elderly. Dry desquamation was seen in a smaller
number of our series of patients. However, the
finding is comparable to that reported by
Seegenschmiedt et al.22 Radiogenic ulcers were
also a feature in our study and Landthaler et al.26
also reported ulceration in 9.5% radiation fields.
Again the development of such side effects
depends upon duration and dose of radiation.11
Therefore, our findings are comparable to the
reports in literature.11
Atrophic changes were seen with a much lesser
frequency i.e. skin atrophy and telangiectasia.
Tsang et al.27 reported similar atrophic changes
(skin atrophy and telangiectasia) in 6 (11%) of
54 patients in a series of patients. Therefore, the
frequency of these changes was less than that in
study mentioned. Change of sensation and
fibrosis were the least frequent side effects seen
in our study. Seegenschmiedt et al.22 reported
these changes with frequencies comparable to
those in our study.
This study shows the frequency of various
cutaneous side effects of radiotherapy in our part
of the world. These changes were seen with a
variable frequency. These skin changes have
been reported world-over in various studies. Our
findings are consistent with those shown in
research previously done with few variations.
Radiation therapy is an important treatment
modality in the management of cancers.
Therefore, concerned physicians should be
vigilant
to
manage
these
cutaneous
complications
in
collaboration
with
dermatologists to prevent permanent skin
damage and disfigurement.
Conclusion
Radiation therapy is an important treatment
modality in the management of cancers and
produces significant side effects on skin.
Pigmentary changes, erythema and epilation
being the most common. Moist desquamation,
Oral mucositis, xerosis and scalp alopecia are
seen less often. Xerostomia, dry desquamation
and ulceration are seen with further lower
frequency.
Atrophic changes like atrophy,
fibrosis and telangiectasia are seen occasionally.
375
Journal of Pakistan Association of Dermatologists 2013; 23 (4): 371-377.
Radiodermatitis can be divided as acute and
chronic disease as determined by the duration of
its onset. Severe changes which may lead to the
interruption of therapy are seen less commonly.
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