a broad and heterogeneous group of syndromes may result from this process , since any type , size , and location of blood vessel may be involved .
vasculitis and its consequences may be the primary or sole manifestation of a disease ; alternatively , vasculitis may be a secondary component of another primary disease like infection , malignancy and rheumatic disease .
beside systemic vasculitis , non bacterial thrombotic endocarditis ( nbte ) could be a paraneoplastic manifestation of malignancy too .
the cardiac conditions most commonly resulting in nbte are mitral regurgitation , aortic stenosis , aortic regurgitation , ventricular septal defects , and complex congenital heart disease .
nbte also arises as a result of a hypercoagulable state ; this phenomenon gives rise to the clinical entity of marantic endocarditis ( uninfected vegetations seen in patients with malignancy and chronic diseases ) and to bland vegetations complicating systemic lupus erythematosus and the antiphospholipid antibody syndrome .
the patient is 34 y / o man presented with episodic painless purple discoloration and linear ungual hemorrhage of fingers and toes , associated with paresthesia since a month ago .
he also complained of 10 - 15 mins morning stiffness and 4 kg weight loss during previous month .
he had a few episodes of vertigo and because of the following symptoms he went to neurologist .
brain mri which was done ( figure 1 ) and the patient was referred to rheumatologist for more evaluation .
mri findings were : multiple hyper signal lesions in periventricular and subcortical with involvement of subcortical mfibers in parietal lobe , preserving basal gangelia , thalamus and corpus callosum , the possibility of demyelinating disease should be considered he had history of left eye amblyopia since childhood , lumbar disc herniation 10 years ago and unilateral varicocele surgery last year .
he took no medications and he did not smoke or use illicit drugs . he was married and worked as a salesman . on examination , bp : 115/70 , pr : 76/min , t : 37.2 oral , rr : 16/min .
subungual hemorrhage was seen in nearly all fingers plus a purple patch on the left sole .
tte was done before admission and was normal . a complete blood count and results of liver function tests
serum creatinin level was 1.6mg / dl and urine analysis revealed proteinuria and hematuria ( table 1 ) . under the clinical suspicion of systemic vasculitis , methylprednisolone and cyclophosphamide
chest ct scan was done and right sided pleural effusion with multiple small nodules in right lung parenchyma was seen ( figure 2 ) .
pleural fluid analysis was exudative ( table 2 ) , so imipenem and ciprofloxacin were started and because of the possibility of underlying malignancy , cytologic analysis of pleural fluid was requested . 
 
chest computed tomography showed right side pleural effusion pleural fluid analysis on the fourth day of admission , he suddenly experiences a very severe right flank pain .
u / a and cbc revealed hematuria and leukocytosis ( wbc=17500 ) and abdominopelvic ct scan findings were infracted zones in both kidneys , suggestive for systemic vasculitis or embolic process ( figure 3 ) .
abdominopelvic computed tomography showed hypo dense areas suggestive for kidney infarction transthorasic echocardiography was repeated and this time a large size mass ( 12 * 5 mm ) was seen on aortic valve that was suggestive for vegetation , so antibiotics were changed to cefazoline , ampicillin and gentamycin . during
the next days hemoglobin level dropped to 11.3gr / dl and due to thrombocytopenia and abnormal coagulation tests and fragmented rbcs in peripheral blood smear , subclinical dic was suggested and ffp and packed cell were transfused and renal biopsy was canceled .
two days later right hemi paresis was evolved and on examination right hemiparesia without any sphinctral dysfunction or sensory abnormality was detected .
this time brain mri revealed evidence of one hyper signal lesion in left hemisphere of cerebellum ( figure 4 ) .
brain mri showed a hyper signal lesion in left hemisphere of cerebellum transesophageal echocardiography confirmed aortic vegetation on rcc ( 7 * 5 mm ) . on suspicion of underlying malignancy ,
whole body bone scan was done and findings were increased uptake in posterior ribs and spine , suggestive for metastasis .
result of cytologic examination on pleural fluid revealed severe mesothelial hyperplasia with cytologic atypia and ihc report was suggestive for adenocarcinoma with suspected origin of upper gi , pancreas or testis and lung and colon were low likely ( negative for ttf 1 and positive for ck 7 ) . at first ,
patient was candidate for vats ( video assisted thoracic surgery ) but due to ihc report and patient unwillingness , vats was canceled and searching for other sources of metastasis was started . during the admission , because of worsened dyspnea and orthopnea and exudative pleural fluid , chest tube was inserted .
the results of serum tumor markers were bhcg < 1 u / l ( normal<10 ) , afp=3.5iu / ml ( normal=0 - 10 ) , psa=0.2ng / ml ( normal = upto4 ) , ca19 - 9=66.9u / ml ( normal=0 - 36 ) , cea=5.8ng / ml ( normal = non smoker < 3.4 ) .
ultrasound of both testicles was normal and abdominopelvic ct was unremarkable for malignancy . finally under the diagnosis of metastatis of unknown primary ,
patient had been feeling better after starting therapy and after a few sessions of physiotherapy , he was able to walk .
the patient was presented with multi organ involvement such as skin , brain and kidney that was suggestive of systemic disease . as we discussed below
, the main possible diagnosis was overlapping of systemic vasculitis and endocarditis and it 's embolic complications , as manifestations of underlying malignancy .
systemic vasculitis is in two categories ; primary or secondary , but in our patient , due to negative results of rheumatologic panel , secondary vasculitis associated with primary diseases like malignancy or infection was more compatible with the patient .
leukocytoclastic venulitis confined to the skin is the most common finding ; however , widespread systemic vasculitis may occur but it is an uncommon presentation . 
 
exudative pleural effusion with positive cytology made this hypothesis more prominent and led us searching for the most common sites of metastatic pleural effusion such as lung carcinoma , breast carcinoma and lymphoma .
bma / bmb ( bone marrow aspiration and biopsy ) and absence of organomegaly or lymphadenopathy , lymphoma was not an appropriate possibility .
as ihc report was low likely for lung , being the origin of metastasis , we tried to find other origins such as pancreas , testis and upper gi , but all results were unremarkable for malignancy .
endocarditis : our patient suffered from skin lesions that were compatible with janeway and subungual hemorrhage and led us to endocarditis , either bacterial or nonbacterial thrombotic endocarditis ( nbte ) .
cardioembolism is responsible for 20% of ischemic stroke and among the causes of cardioembolism , endocarditis was considered in this patient , responsible for the acute cerebellar stroke and kidney infarctions and due to the size and location of vegetation , nbte was more compatible with the patient .
finally due to elevated ca 19 - 9 and nodularity in right lung , chemotherapy drugs were selected in a way that they could cover pancreas and lung .
 secondary systemic vasculitis and nonbacterial endocarditis are rare events . 
 we report a case presented with different manifestations of underlying malignancy such as systemic vasculitis , non bacterial endocarditis and dic ( disseminated intravascular coagulopathy ) . 
 efforts to find the source of malignancy was unsuccessful and due to patient 's unwillingness for further evaluation , finally under the diagnosis of metastatic disease of unknown primary , patient is receiving cyclic chemotherapy . 
INTRODUCTION
CASE PRESENTATION
Final Diagnosis
DISCUSSION