Clinical Oncology (1992) 4:331-332 © 1992 The Royal College of Radiologists
Clinical Oncology
Case Report Enhanced Normal Tissue Response to Radiation in a Patient with Discoid Lupus Erythematosus A. J. Rathmell and R. E. Taylor D e p a r t m e n t of R a d i o t h e r a p y a n d Oncology, C o o k r i d g e Hospital, Leeds LS16 6 Q B , U K
Abstract. We report the case of a patient with discoid lupus erythematosus who developed a severe skin reaction whilst undergoing mantle irradiation for non-Hodgkin's lymphoma. Widespread moist desquamation occurred after a skin dose of only 17 Gy and was associated with an abscopal response outside the treatment area. The case illustrates the need for extreme caution when administering radiotherapy to patients with discoid or systemic lupus erythematosus. Keywords: Discoid lupus erythematosus; Skin reaction; Radiotherapy
CASE HISTORY A 45-year-old female patient (Caucasian, fair complexion with no vitiligo, dark hair) presented in July 1988 with cervical and axillary lymphadenopathy in association with night sweats and 7 kg loss in weight. Biopsy showed a diffuse large cell nonHodgkin's lymphoma. Staging investigations (including CT scanning and bone marrow examination) were negative and she was considered to have Stage IIB disease. She had a past history of chronic discoid lupus erythematosus (CDLE) diagnosed clinically 25 years previously and subsequently confirmed by skin biopsy. The latter demonstrated all the typical features of the condition, as discussed below. She had never developed any systemic involvement, although her antinuclear factor titre was positive at a dilution of 1 in 500 and anti double-stranded DNA antibodies were also present. The principal manifestation of the condition was that of marked photosensitivity of the facial skin, necessitating the use of sun screens during the summer months. She had required only the occasional use of topical steroids and at the time of diagnosis of the lymphoma the general condition of her skin was good. Chemotherapy for the lymphoma was instituted using the CHOP regime but
Correspondence and offprint requests to: Dr A. J. Rathmell, Senior Registrar, Department of Radiotherapy and Oncology, Cookridge Hospital, Leeds LS16 6QB, UK.
unfortunately she experienced severe nausea and vomiting following the first course and refused to have any further chemotherapy. She did however agree to undergo a course of radiotherapy and she commenced treatment with an anterior and posterior mantle field arrangement in December 1988. Treatment was carried out on an 8 MV linear accelerator at 150 cm FSD with shaped lung-shielding blocks. Both anterior and posterior fields (equally weighted) were treated daily and the prescribed dose was 40 Gy (central mid-plane) in 20 daily fractions of 2 Gy. The central separation was 18.5 cm with a maximum of 20.5 cm (inferior edge) and minimum of 14.0 cm (axillae). No bolus was used and the skin dose was calculated to be 1.06-1.21 Gy per fraction. The patient was given our usual skin care instructions, namely to wash daily with warm water, dry carefully with a soft towel and avoid all skin care products other than baby powder. The first week of treatment proceeded uneventfully but by the time she had received 8 fractions she had developed marked erythema in the unshielded areas of the treatment volume and was prescribed topical steroids. Treatment continued but the skin reaction rapidly worsened; after 15 fractions she had florid erythema and was starting to develop moist desquamation in both axillae. Treatment was stopped at this point, after a midplane dose of 30 Gy and a skin dose of 15.918.15 Gy. The skin reaction continued to progress during the following week and she developed widespread areas of moist desquamation around the axillae and neck. There was some spread of reaction to the shielded areas of skin and in addition she developed severe facial erythema in a 'butterfly' distribution above the treated area. The reaction gradually settled (accompanied by extensive desquamation) over the next 6 weeks with conservative management, including topical, but not systemic, steroids. The clinical photographs (Figs. 1 and 2) were taken 25 days after the cessation of radiotherapy and show the extensive area of desquamation, the relative sparing beneath the lung blocks and the 'abscopal' reaction affecting the facial skin. After recovering from the effects of treatment the patient remained well and in remission for 1 year before developing an abdominal relapse. She eventually died of her lymphoma in March 1991.
P
, '~22¢
Fig. 1. Extensive desquamatlon following limited mantle irradiation.
Fig. 2. Abscopal response affecting facial skin.
DISCUSSION Lupus erythematosus (LE) is an autoimmune connective tissue disorder associated with a variety of circulating antinuclear antibodies. The condition may involve the skin alone (chronic discoid lupus erythematosus, CDLE) or may involve additional organs such as lung and kidneys (systemic lupus erythematosus, SLE). The skin lesions are characterized histologically by hyperkeratosis, plugging of follicular orifices, liquefaction degeneration of the basal layer, epidermal thinning, chronic inflammatory infiltration and telangiectasia.
332 Photosensitivity is a well known feature of both forms of the condition, but an increased sensitivity of normal tissues to ionizing radiation is not a recognized association and there are very few previous reports on the subject. A report by Ben-Chetrit et al. [1] suggested that total lymphoid irradiation (20 Gy in 2 Gy fractions) used therapeutically in the mana g e m e n t of SLE could lead to excessive toxicity but the side-effects described were systemic rather than cutaneous. Strober et al. treated ten patients in a similar fashion and e n c o u n t e r e d no significant toxicity [2]. Olivotto et al. reported a case of fatal pelvic necrosis occurring in a patient with SLE who received external b e a m radiotherapy for carcinoma of cervix but did not describe the skin reaction [3]. W e were unable to find any previous references in the literature which clearly d o c u m e n t excessive skin reactions m patients with LE. Normal skin reactions during mantle irradiation tend to be maximal in the lateral neck and axillae where separations are smallest and, in the case of axillae, where the skin is m o r e sensitive. E v e n in these areas, however, the skin reaction at completion of a mantle has rarely progressed beyond erythema and mild dry d e s q u a m a t i o n , although occasionally small areas of moist d e s q u a m a t i o n arise in the axillae if the arms have been adducted during treatment. T h e early and severe skin
A . J . Rathmell and R. E. Taylor reaction described in this case, with spread to shielded areas and with an abscopal response on the face, was clearly pathological. The patient had not received c h e m o t h e r a p y for 7 weeks prior to radiation and an enhanced skin reaction following Adriamycin is said not to occur if the interval between the drug and radiation is greater than 1 week [4]. Hence, the presence of C D L E seems to be the only explanation for the excessive reaction. Olivetto et al. suggested that endarteritis might be responsible for the possible reduced normal tissue tolerance in patients with SLE [3], but other conditions associated with e n h a n c e d radlosensitivity, such as ataxia telangeiectasia, are known to have defects of chromosomal repair mechanisms as the underlying cause [5]. The photosensitivity experienced by patients with L E is thought to be due in part to an interaction between ultraviolet light and cellular D N A such that critical antigenic sites are exposed for interaction with auto-antibodies and it is possible that a similar m e c h a n i s m is responsible for X-irradiation effects. A significant e n h a n c e m e n t of normal tissue response to radiation appears to occur only rarely in patients with LE, but it seems prudent to exercise extra caution when such patients require radiotherapy treatment, and to monitor acute reactions closely. Where enhanced skin reactions are observed it would be interesting to perform
skin biopsies, c h r o m o s o m a l fragility studies and monitoring of auto-antibody levels in order to gain more insight into the underlying mechanisms.
Acknowledgement. W e would like to thank Julie Povall from the D e p a r t m e n t of Medical Physics for performing the calculations and p h a n t o m m e a s u r e m e n t s required to determine the skin dose received by this patient.
References 1. Ben-Chetrit E, Gross DJ, Braverman A, et al Total lymphoid irradiation m refractory systemic lupus erythematosus. Ann Intern Mcd 1986;105:58-60. 2. Strober S, Field E, Hoppe RT, et al. Treatment of intractable lupus nephritis with total lymphoid irradiation. Ann Intern Med 1985,102:450-8. 3. Olivotto IA, Fairey RN, Gillies JH, et al. Fatal outcome of pelvic radiotherapy for carcinoma of the cervix in a patient with systemic lupus erythematosus Clin Radiol 1989;40:83-4. 4. Phihps TL. Tissue toxicity of radiation-drug interactions. In Sokol GH, Malckel RP, editors Radiation-drug interactions. New York: Wiley, 1980:187 5. Hanawalt PC, Sarasm A. Cancer-prone hereditary diseases with DNA processing abnormahties Trends Genet 1986;2:124-9.
Received for pubhcauon March 1992 Accepted following revtston May 1992
Clinical Oncology
Case Report Enhanced Normal Tissue Response to Radiation in a Patient with Discoid Lupus Erythematosus A. J. Rathmell and R. E. Taylor D e p a r t m e n t of R a d i o t h e r a p y a n d Oncology, C o o k r i d g e Hospital, Leeds LS16 6 Q B , U K
Abstract. We report the case of a patient with discoid lupus erythematosus who developed a severe skin reaction whilst undergoing mantle irradiation for non-Hodgkin's lymphoma. Widespread moist desquamation occurred after a skin dose of only 17 Gy and was associated with an abscopal response outside the treatment area. The case illustrates the need for extreme caution when administering radiotherapy to patients with discoid or systemic lupus erythematosus. Keywords: Discoid lupus erythematosus; Skin reaction; Radiotherapy
CASE HISTORY A 45-year-old female patient (Caucasian, fair complexion with no vitiligo, dark hair) presented in July 1988 with cervical and axillary lymphadenopathy in association with night sweats and 7 kg loss in weight. Biopsy showed a diffuse large cell nonHodgkin's lymphoma. Staging investigations (including CT scanning and bone marrow examination) were negative and she was considered to have Stage IIB disease. She had a past history of chronic discoid lupus erythematosus (CDLE) diagnosed clinically 25 years previously and subsequently confirmed by skin biopsy. The latter demonstrated all the typical features of the condition, as discussed below. She had never developed any systemic involvement, although her antinuclear factor titre was positive at a dilution of 1 in 500 and anti double-stranded DNA antibodies were also present. The principal manifestation of the condition was that of marked photosensitivity of the facial skin, necessitating the use of sun screens during the summer months. She had required only the occasional use of topical steroids and at the time of diagnosis of the lymphoma the general condition of her skin was good. Chemotherapy for the lymphoma was instituted using the CHOP regime but
Correspondence and offprint requests to: Dr A. J. Rathmell, Senior Registrar, Department of Radiotherapy and Oncology, Cookridge Hospital, Leeds LS16 6QB, UK.
unfortunately she experienced severe nausea and vomiting following the first course and refused to have any further chemotherapy. She did however agree to undergo a course of radiotherapy and she commenced treatment with an anterior and posterior mantle field arrangement in December 1988. Treatment was carried out on an 8 MV linear accelerator at 150 cm FSD with shaped lung-shielding blocks. Both anterior and posterior fields (equally weighted) were treated daily and the prescribed dose was 40 Gy (central mid-plane) in 20 daily fractions of 2 Gy. The central separation was 18.5 cm with a maximum of 20.5 cm (inferior edge) and minimum of 14.0 cm (axillae). No bolus was used and the skin dose was calculated to be 1.06-1.21 Gy per fraction. The patient was given our usual skin care instructions, namely to wash daily with warm water, dry carefully with a soft towel and avoid all skin care products other than baby powder. The first week of treatment proceeded uneventfully but by the time she had received 8 fractions she had developed marked erythema in the unshielded areas of the treatment volume and was prescribed topical steroids. Treatment continued but the skin reaction rapidly worsened; after 15 fractions she had florid erythema and was starting to develop moist desquamation in both axillae. Treatment was stopped at this point, after a midplane dose of 30 Gy and a skin dose of 15.918.15 Gy. The skin reaction continued to progress during the following week and she developed widespread areas of moist desquamation around the axillae and neck. There was some spread of reaction to the shielded areas of skin and in addition she developed severe facial erythema in a 'butterfly' distribution above the treated area. The reaction gradually settled (accompanied by extensive desquamation) over the next 6 weeks with conservative management, including topical, but not systemic, steroids. The clinical photographs (Figs. 1 and 2) were taken 25 days after the cessation of radiotherapy and show the extensive area of desquamation, the relative sparing beneath the lung blocks and the 'abscopal' reaction affecting the facial skin. After recovering from the effects of treatment the patient remained well and in remission for 1 year before developing an abdominal relapse. She eventually died of her lymphoma in March 1991.
P
, '~22¢
Fig. 1. Extensive desquamatlon following limited mantle irradiation.
Fig. 2. Abscopal response affecting facial skin.
DISCUSSION Lupus erythematosus (LE) is an autoimmune connective tissue disorder associated with a variety of circulating antinuclear antibodies. The condition may involve the skin alone (chronic discoid lupus erythematosus, CDLE) or may involve additional organs such as lung and kidneys (systemic lupus erythematosus, SLE). The skin lesions are characterized histologically by hyperkeratosis, plugging of follicular orifices, liquefaction degeneration of the basal layer, epidermal thinning, chronic inflammatory infiltration and telangiectasia.
332 Photosensitivity is a well known feature of both forms of the condition, but an increased sensitivity of normal tissues to ionizing radiation is not a recognized association and there are very few previous reports on the subject. A report by Ben-Chetrit et al. [1] suggested that total lymphoid irradiation (20 Gy in 2 Gy fractions) used therapeutically in the mana g e m e n t of SLE could lead to excessive toxicity but the side-effects described were systemic rather than cutaneous. Strober et al. treated ten patients in a similar fashion and e n c o u n t e r e d no significant toxicity [2]. Olivotto et al. reported a case of fatal pelvic necrosis occurring in a patient with SLE who received external b e a m radiotherapy for carcinoma of cervix but did not describe the skin reaction [3]. W e were unable to find any previous references in the literature which clearly d o c u m e n t excessive skin reactions m patients with LE. Normal skin reactions during mantle irradiation tend to be maximal in the lateral neck and axillae where separations are smallest and, in the case of axillae, where the skin is m o r e sensitive. E v e n in these areas, however, the skin reaction at completion of a mantle has rarely progressed beyond erythema and mild dry d e s q u a m a t i o n , although occasionally small areas of moist d e s q u a m a t i o n arise in the axillae if the arms have been adducted during treatment. T h e early and severe skin
A . J . Rathmell and R. E. Taylor reaction described in this case, with spread to shielded areas and with an abscopal response on the face, was clearly pathological. The patient had not received c h e m o t h e r a p y for 7 weeks prior to radiation and an enhanced skin reaction following Adriamycin is said not to occur if the interval between the drug and radiation is greater than 1 week [4]. Hence, the presence of C D L E seems to be the only explanation for the excessive reaction. Olivetto et al. suggested that endarteritis might be responsible for the possible reduced normal tissue tolerance in patients with SLE [3], but other conditions associated with e n h a n c e d radlosensitivity, such as ataxia telangeiectasia, are known to have defects of chromosomal repair mechanisms as the underlying cause [5]. The photosensitivity experienced by patients with L E is thought to be due in part to an interaction between ultraviolet light and cellular D N A such that critical antigenic sites are exposed for interaction with auto-antibodies and it is possible that a similar m e c h a n i s m is responsible for X-irradiation effects. A significant e n h a n c e m e n t of normal tissue response to radiation appears to occur only rarely in patients with LE, but it seems prudent to exercise extra caution when such patients require radiotherapy treatment, and to monitor acute reactions closely. Where enhanced skin reactions are observed it would be interesting to perform
skin biopsies, c h r o m o s o m a l fragility studies and monitoring of auto-antibody levels in order to gain more insight into the underlying mechanisms.
Acknowledgement. W e would like to thank Julie Povall from the D e p a r t m e n t of Medical Physics for performing the calculations and p h a n t o m m e a s u r e m e n t s required to determine the skin dose received by this patient.
References 1. Ben-Chetrit E, Gross DJ, Braverman A, et al Total lymphoid irradiation m refractory systemic lupus erythematosus. Ann Intern Mcd 1986;105:58-60. 2. Strober S, Field E, Hoppe RT, et al. Treatment of intractable lupus nephritis with total lymphoid irradiation. Ann Intern Med 1985,102:450-8. 3. Olivotto IA, Fairey RN, Gillies JH, et al. Fatal outcome of pelvic radiotherapy for carcinoma of the cervix in a patient with systemic lupus erythematosus Clin Radiol 1989;40:83-4. 4. Phihps TL. Tissue toxicity of radiation-drug interactions. In Sokol GH, Malckel RP, editors Radiation-drug interactions. New York: Wiley, 1980:187 5. Hanawalt PC, Sarasm A. Cancer-prone hereditary diseases with DNA processing abnormahties Trends Genet 1986;2:124-9.
Received for pubhcauon March 1992 Accepted following revtston May 1992
