Frequency of cutaneous manifestations of radiotherapy.
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
May 2006 till 31
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.
Radiation therapy radiodermatitis moist desquamation dry desquamation xerostomia mucositis pigmentation.
Radiation therapy is used in a majority of cancer patients at some point during their treatment. It 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.12 Ionizing radiations constitute energy sufficiently strong to remove an orbital electron from an atom. These 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 dose- dependent 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.Radiation therapy targets rapidly dividing cells and because skin is characterized by rapid cellproliferation it is often affected by suchtreatment.7 Adverse cutaneous effects ofradiotherapy 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.89 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.89Less 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 methodsThe cross-sectional study was conducted on patients attending outpatient department of Dermatology and department of Oncology Civilhospital Karachi. The study spanned fromMay 2006 till 31August 2006 completed overa 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 All the patients were subjected to a detailedhistory and clinical examination comprisinggeneral systemic and dermatologicalexamination. A clinical diagnosis of differentradiation-induced skin changes was made. Relevant investigations like scraping for fungus swabs for culture and Tzanck smear wereperformed in doubtful cases. Biochemical profile and skin biopsy were done where required. The type of radiation dosage and duration of treatment was also recorded. 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.
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 46.3614.46 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 receivingelectron 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###Total
###N (%)###N (%)
Photon###29 (41%) 42 (59%)###71
Electron###5 (71%)###2 (29%)###7
Photon + electron###1 (5%)###21 (95%)###22
Table 2 Dose of radiation (n=100).
cGy###(n=35)###(n=65)###(N and %)
Table 3 Skin manifestations due to radiotherapy (n=100).
Skin manifestation Male###Female###Total
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
Necrosis###1 (50)###1 (50)###2
Change of sensation 0###2 (100)###2
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).
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.
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 1Gy. 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.1617 Moist desquamation 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 Snijders- Keitholz 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.2021 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.22Xerosis 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.2223 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.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%) of54 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.
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.
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.
1. Pignol JP Olivotto I Rakovitch E et al. A multi-center randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol. 2008;26:2085-92.2. Lee JH Kay CS Maeng LS et al. Theclinical features and pathophysiology of acute radiation dermatitis in patients receiving tomotherapy. Ann Dermatol.2009;21:358-63.3. Salvo N Barnes E Van Draanen J.Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature. Curr Oncol. 2010;17:94-112.4. Thanik V Chang C Zoumalan R. A novel mouse model of cutaneous radiation injury. Plast Reconstr Surg. 2011;127:560-8.5. Jagetia G Rajanikant G. Acceleration of wound repair by curcumin in the excisionwound of mice exposed to different doses of fractionated [gammar] radiation. Int Wound J. 2012;9:76-92.6. Okunieff P Xu J Hu D. Curcumin protectsagainst radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radial Oncol Biol Phys. 2006;65:890-8.7. Ryan JL. Ionizing radiation: the good the bad and the ugly. J Invest Dermatol.2012;132:985-93.8. Pommier R Gomez F Sunyach MP et al.Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Oncol.2004;22:1447-53.9. Hymes S Strom E Fife C. Radiation dermatitis: clinical presentation pathophysiology and treatment 2006. J Am Acad Dermatol. 2006;54:28-46.10. Markouizou A Koliarakis N ParaskevaidisM et al. Radiation dermatitis: implicated factors clinical aspects possible prevention and medical care. J BUON. 2007;12:463-70.11. Yamazaki H Yoshida K Kobayashi K et al.Assessment of radiation dermatitis using objective analysis for patients with breast cancer treated with breast-conserving therapy: influence of body weight. Japanese J Radiol. 2012;30:486-91.12. Macmillan MS Wells M MacBride S et al.Randomized comparison of dry dressings versus Hidrogel in management of radiation- induced moist desquamation. Int J Radiat Oncol Biol Phys. 2007;68:864-72.13. Braun-Falco O Schultze U Meinhof WGoldschmidt H. Contact radiotherapy of cutaneous hemangiomas: therapeutic effects and radiation sequelae in 818 patients. Arch Dermatol Res. 1975;253:237-47.14. Hanks SH Lyons JA Crowe J et al. Theacute effects of postoperative radiation therapy on the transverse rectus abdominis myocutaneous flap used in immediate breast reconstruction. Int J Radiol Oncol Biol Phys.2000;47:1185-90.15. Yesudian P. Hair India 2010. Int J Trichol.2010;2:77-8.16. Richardson J Smith JE McIntyre M et al.Aloe vera for preventing radiation-induced skin reactions: a systematic literature review. Clin Oncol (R Coll Radiol).2005;17:478-84.17. Bourgeois JF Gourgou S Kramar A et al.Radiation-induced skin fibrosis after treatment of breast cancer: profilometric analysis. Skin Res Technol. 2003;9:39-42.18. Snijders-Keiholz T Trimbos JB Hermans J Leer JW. Management of vulvar carcinoma radiation toxicity results and failure analysis in 44 patients (1980 1989). Acta Obstet Gynaecol Scand. 1993;72:668-73.19. Allal AS Maire D Becker M Dulguerov P.Feasibility and early results of accelerated radiotherapy for head and neck carcinoma in the elderly patients. Cancer. 2000;88:648-52.20. Cawley MM Benson LM. Current trends in managing oral mucositis. Clin J Oncol Nursing. 2005;9:584-92.21. Rashad UM. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol. 2010;123:223-8.22. Seegenschmiedt MH Olschewski T Guntrum F. Radiotherapy optimization in early stage Dupuytren's contracture: first results of a randomized clinical study. Int J Radiat Oncol Biol Phys. 2001;49:785-98.23. Wilson LD Jones GW Kim D et al.Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol. 2000;43:54-60.24. Lawenda BD Gagne HM Gierga DP et al.Permanent alopecia after cranial irradiation: dose response relationship. Int J Radiat Oncol Biol Phys. 2004;60:879-87.25. Shahayar Khan NH Hafeez M Alauddin Z.Five year survival results of locallyadvanced nasopharyngeal carcinoma treated with radiotherapy. J Coll Physician Surg Pak. 1999;9:413-5.26. Landthaler M Hagspiel HJ Braun-Falco O.Late irradiation damage to the skin caused by soft X-ray radiation therapy of cutaneous tumours. Arch Dermatol. 1995;131:182-6.27. Tsang RW Liu FF Wells W Payne DG.Lentigo maligna of the head and neck. Results of treatment by radiotherapy. Arch Dermatol. 1994;130:1008-12.
|Printer friendly Cite/link Email Feedback|
|Publication:||Journal of Pakistan Association of Dermatologists|
|Date:||Dec 31, 2013|
|Previous Article:||A study on clinical manifestations of tuberous sclerosis.|
|Next Article:||Comparative evaluation of autologous serum skin test and autologous plasma skin test in chronic urticaria.|