patients with collagen vascular disease ( cvd ) such as rheumatoid arthritis , systemic lupus erythematosus , scleroderma , polymyositis , and dermatomyositis , are known to be sensitive to ionizing radiation 19 .
irradiation to the lung in patients with interstitial pneumonia ( ip ) is also considered a relative contraindication because ip is a risk for severe radiation - induced pneumonitis 10 . meanwhile , in general , irradiation of extrapulmonary sites in ip patients is not contraindicated . here , we report a patient with bladder cancer and mild ip who received pelvic irradiation and showed unexpectedly severe adverse effects that followed by the onset of polymyositis and fatal exacerbation of ip .
a 70-year - old japanese man with bladder cancer ( ct1n0m0 ) presented to the radiation oncology department in march 2014 .
he had ip , which had been controlled stable with prednisolone ( 10  mg / day ) since 2010 .
a chest computed tomography ( ct ) revealed ground - glass opacity in the subpleural region ( figs.1 and 2 ) .
spirometry test results showed a restrictive pattern ( vital capacity , 55% ; forced expiratory volume 1.0 , 76% ) . although he was diagnosed as being tolerable for surgery under general anesthesia , he refused surgery and selected radiotherapy for his bladder cancer .
he had a previous history of spinal canal stenosis and cataract in the left eye , however , he did not have a medical history indicative of a risk for severe radiation toxicity including diabetes mellitus .
radiotherapy targeting the bladder and pelvic lymph node regions was initiated , with a daily fraction of 2  gy . however , he developed urinary tract pain and erythema in the radiation field much earlier than expected ( i.e. , within the first week ) .
alpha - blockers , loxoprofen , intravesical infusion of lidocaine , and betamethasone valerate ointment were ineffective . in the third week
, he showed grade 3 urinary tract pain , grade 3 radiation dermatitis ( assessed using the common terminology criteria for adverse events , version 4.0 ) , and needed to urinate every 5 to 10  min .
thus , radiotherapy was terminated at 34  gy , much less than the target bladder dose of 60  gy .
, he was admitted to our hospital with proximal muscle weakness , which had worsened over the previous 2  weeks .
iu / l ) and c - reactive protein ( 3.66  mg / dl ) levels , myogenic changes in the left deltoid and biceps brachii on electromyography , a high signal in the proximal muscles on magnetic resonance imaging ( short - ti inversion recovery ) , and the presence of autoantibodies against aminoacyl - trna synthetase ( anti - ars antibodies ) led to a diagnosis of polymyositis .
meanwhile , ct ( chest through pelvis ) showed no signs of infection or progression of cancer .
an increased dose of prednisolone ( 60  mg / day ) over 1  month improved the muscle weakness and ck levels ( 639 
chest ct showed extensive areas of ground - glass opacity and consolidation , suggesting an acute exacerbation of ip ( fig.3 ) . despite maximum medical therapy , including prednisolone pulse ( 1  g / day ) and cyclophosphamide , he died 1  week later .
we conducted radiotherapy to this patient because he had not presented with any symptoms suggestive of cvd .
although we could not identify the specific reason of the severe adverse effects during radiotherapy , the following onset of polymyositis suggested that the patients had vulnerability to ionizing radiation . to the best of our knowledge ,
this is the first case reported in the literature of unexpectedly severe adverse reactions to radiotherapy followed by the onset of cvd .
the current case suggests that unexpectedly severe adverse effects after radiotherapy can be an alarm of cvd onset , which enables the prediction and early intervention of the cvd .
notably , cvd - associated ip can precede the appearance of systemic cvd symptoms by many years ; sometimes by more than 5  years 12,13 .
these findings are consistence with our case which had a 4-year history of ip before the onset of polymyositis . in such cases
, it is impossible to distinguish cvd - associated ip from other types of ip ( e.g. , drug - induced ip or idiopathic ip ) because the clinicopathological findings of cvd - associated ip show wide variation 1113 . at the time of radiotherapy
however , there may be a considerable number of patients with ip - preceding cvd who are at risk of unexpectedly severe toxicity after radiotherapy .
anti - ars antibody - positive polymyositis and dermatomyositis are strongly associated with ip 15 . of note , 2950% of anti - ars
antibody - positive ip - associated cases polymyositis and dermatomyositis are ip - preceding type 15 . taken together ,
these findings suggest that measurement of anti - ars antibody levels in ip patients prior to radiotherapy may help predict severe radiation toxicity associated with the late onset of polymyositis or dermatomyositis .
cvd markers such as antinuclear antibody were not evaluated in the stable ip period . in summary ,
careful observation for the  alarm  adverse effects of radiotherapy , especially in ip patients , may lead to the prediction and early intervention of the cvd .
written informed consent was obtained from the patient s next of kin for publication of this case report and accompanying images .
 key clinical messageinterstitial pneumonia ( ip ) sometimes precedes collagen vascular disease ( cvd ) onset . a patient with bladder cancer and 
 mild ip received pelvic irradiation and experienced unexpectedly severe urinary toxicity followed by polymyositis onset and fatal ip exacerbation . 
 careful observation for  alarm adverse effects  of radiotherapy in ip patients may help predicting cvd onset . 
Introduction
Case Report
Discussion
Informed Consent
Competing Interests