this report describes a case of systemic amyloidosis that began with severe refractory orthostatic hypotension , the most invalidating feature of autonomic nervous system involvement . we describe a case of amyloid light - chain ( al ) amyloidosis in a 73-year - old woman whose most invalidating feature was severe refractory orthostatic hypotension ( oh ) , associated with dysphagia and diarrhea . after otorhinolaryngologist evaluation , gastroenteric endoscopic studies , abdomen ultrasound , and brain nuclear magnetic resonance imaging ( mri ) scan , the diagnosis was unknown . during one of them , cardiac junctional rhythm was detected , and a pacemaker was implanted . on admission , clinical examination showed severe oh ( systolic blood pressure [ sbp ] dropping down to 70 mmhg ) with unmodified heart rate ( hr ) . furthermore , mild right ocular ptosis and labial commissure deviation were present , in addition to right leg hyposthenia . blood tests depicted normocytic anemia ( hb 11 g / dl ) , a rise in cholestasis indexes ( alkaline phosphatase 201 ui / l ; gamma - glutamyl transferase 328 ui / l with normal bilirubin ) and hypoalbuminemia ( 2.7 g / dl ) . a tilt table test demonstrated the absence of autonomic reflexes with severe blood pressure drop ( sbp up to 55 mmhg and diastolic blood pressure [ dbp ] up to 28 mm hg ) without hr modification when reaching upright position [ figure 1 ] . an electromyography ( emg ) identified a typical pattern of chronic bilateral l5-s1 radiculopathy , excluding any diagnostic abnormality for polyneuropathy . because of the persistence of dysphagia , endoscopic evaluation was repeated , and the histological examination of a hyperemic gastric antrum pointed out perivascular deposits positive to congo red staining , identified as amyloid at immunochemistry . a multisystemic disease became evident : renal involvement with proteinuria ( 2.5 g/24 h ) , autonomic nervous system involvement characterized by oh , gastrointestinal disease with malabsorption and dysphagia , bone femoral lytic lesions , and cardiovascular disease . in particular , an electrocardiogram showed the first - degree atrioventricular blockage and frequent supraventricular extrasystole [ figure 2a ] , and a cardiac ultrasound pointed out a thickness of the left ventricle wall , diffuse myocardial hyperechogenicity , and mild pericardial effusion [ figure 2b ] . finally , bence jones proteinuria together with small monoclonal component igg kappa and monoclonal light chains lambda at serum protein electrophoresis were found . bone marrow biopsy unveiled a plasma cellular infiltrate ( 5%10% ) and perivascular amyloid depositions . all these data allowed the diagnosis of al amyloidosis , promptly treated with melphalan and dexamethasone . as for oh , fludrocortisone and midodrine were started but resulted ineffective . during hospitalization and even after discharge , the most invalidating symptom was severe refractory oh while the massive cardiac involvement was probably responsible for the sudden fatal outcome not long after discharge . tilt test registration . the figure shows the recording of systolic blood pressure , diastolic blood pressure , and heart rate in clinostatic and sitting position ( passive orthostatic position not performable because of severe presyncopal symptoms ) during a tilt test . in sitting position , an immediate reduction in systolic blood pressure to 55 mmhg and diastolic blood pressure to 28 mmhg is evident , without any change in the heart rate , which remains stable at 76 beats / min electrocardiogram ( a ) and cardiac ultrasound , ( b ) the figure shows the 12-lead electrocardiogram pointing out the first - degree atrioventricular blockage ( panel a ) . in panel b , cardiac ultrasound ( parasternal long - axis view ) depicts left ventricle wall thickness , diffuse myocardial hyperechogenicity , and mild pericardial effusion we describe an uncommon cause of neurogenic oh that urges to take amyloidosis into consideration in the differential diagnosis of autonomic disturbances . in fact , despite its low incidence ( approximately 610 cases per million person - years ) , its consequences can be massive . systemic amyloidosis is characterized by the extracellular tissue deposition of insoluble fibrils as a result of protein misfolding . these tissue deposits may be responsible for progressive failure in several organs . in al , amyloidosis mixed sensory and motor peripheral neuropathy and/or autonomic neuropathy account for 20% and 15% of the cases , respectively . in fact , this process promotes nerve injury by direct compression or by accumulation of fibrils in vasa nervorum walls , leading to autonomic neuropathy and neurogenic oh . autonomic dysfunction , including oh , is frequently associated with polyneuropathy at an advanced stage . on electrophysiological studies , motor conduction velocity and compound muscle action potential of either median or tibial nerves are significantly decreased in both patients with or without signs of neuropathy . in our patient , the autonomic involvement manifested with refractory oh was doubtless the most invalidating aspect , but also the only neurological symptom associated with a clear result of an instrumental investigation . in literature , a single case of pure autonomic failure without the involvement of peripheral nerves due to primary amyloidosis is described . in our case , despite the emg was not suggestive of polyneuropathy , an involvement of the third and seventh cranial nerves can not be excluded since neither a nerve biopsy nor a brain mri has been performed . renal involvement is often present ( 70% occurrence ) , frequently as asymptomatic proteinuria or nephrotic syndrome . restrictive cardiomyopathy is seen in 60% of cases , consequent to the thickening of the interventricular septum and ventricular wall because of light chain infiltration . other cardiac manifestations include sudden death or syncope due to arrhythmia or heart block and rarely angina or infarction due to accumulation of amyloid in the coronary arteries . in our case , restrictive cardiomyopathy led to severe diastolic dysfunction and consequent heart failure while the recurrent syncope and junctional rhythm urged the implantation of a pacemaker . gastrointestinal disease is less common , being clinically evident in 1% of cases and having a histological documentation in 8% . its manifestations include bleeding ( due to vascular fragility ) , gastroparesis , bacterial overgrowth , malabsorption , and intestinal pseudo - obstruction resulting from dysmotility . dysphagia and diarrhea were two important features for the final diagnosis in our patient that resulted from a gastrointestinal biopsy . approximately 10% of patients affected by al amyloidosis have coexisting multiple myeloma , but in our case , bone marrow plasma cellular infiltration was only 510% ; conversely , bence jones proteinuria , small monoclonal component igg kappa , monoclonal light chains lambda , and femoral osteolytic lesions were found . the management of al amyloidosis varies , depending on whether the patient is eligible for high - dose melphalan , followed by autologous hematopoietic cell transplantation . in our case , alternatives are melphalan / dexamethasone combination therapy and bortezomib , the latter was avoided in our case due to its highly hypotensive effect . al amyloidosis median survival varies from 4 to 6 months , in presence of cardiac and hepatic failure , to 5 years in case of limited organ involvement . in the case , we describe the massive cardiac involvement was probably responsible of the sudden fatal outcome . sp contributed in clinical data collection and discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . rl contributed in clinical data collection and discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . la contributed in clinical data collection and discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . lb contributed in clinical data discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . mr contributed in clinical data discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . ap contributed in clinical data collection and discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . sf contributed in clinical data discussion , conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work .
we discuss here an uncommon condition of neurogenic hypotension in the context of immunoglobulin light chain ( amyloid light - chain ) amyloidosis . 
 the most serious feature was autonomic nervous system impairment , mainly characterized by severe refractory orthostatic hypotension , which became progressively invalidating , forcing the patient to bed . 
 moreover , since the systemic involvement of the disease , the patient presented also diarrhea , dysphagia , asthenia , peripheral edema because of gastrointestinal , and kidney dysfunction . eventually , the massive myocardial depression and infiltration led to a fatal outcome .