arsenic is an element that has raised concern from both the environmental and human health standpoints since the dawn of civilization . chronic exposure , most commonly , is due to prolonged ingestion of water containing elevated levels of arsenic . a report in 2001 , has stated that around 150 million people are at risk from arsenic - contaminated ground water in the combined areas of west bengal and its neighboring country , bangladesh . dyspnea may occur in chronic arsenicosis due to heart failure , because of atherosclerotic hypertensive heart diseases , arsenic - induced restrictive pulmonary diseases , and portopulmonary hypertension . in this case , we found isolated pulmonary arterial hypertension as the cause of dyspnea in a patient with chronic arsenicosis . a 24-year - old , married girl , from the nadia district of west bengal , india , presented to us with progressive dyspnea for the last six months . she presented to us with dyspnea of grade 4 , as per the modified medical research council ( mmrc ) grading of dyspnea . she had cyanosis , resting oxygen saturation ( spo2 ) 81% , a pulse rate of 102/minute , blood pressure of 100/60 mmhg , and a respiratory rate of 26/minute . the internal jugular veins were engorged and pulsatile . bilateral pitting pedal edema was present . on examination of her palm , hyperkeratosis and raindrop pigmentation was seen [ figure 1 ] . examination of the respiratory system revealed no abnormality . on examination of her cardiovascular system , we found tachycardia and a loud pulmonary component of the second heart sound . she was given oxygen at the rate of 6 liters / minute through a face mask . the routine blood investigation showed hemoglobin 9.1 g / dl , total leukocyte count 11,400/cubic millimeter , with neutrophil 80% , lymphocytes 17% , eosinophils 2% , and monocytes 1% ; urea 23 mg / dl and creatinine 0.8 mg / dl ; and sodium 133 meq / l , potassium 3.7 meq / l , and calcium 9.3 mg / dl . her enzyme - linked immunosorbent assay ( elisa ) for human immunodeficiency virus ( hiv ) 1 and 2 antigen testing was negative . echocardiography revealed a grossly enlarged right ventricle and dilated right atrium , with intact an interatrial septum and interventricular septum and grade 3 tricuspid regurgitation , with a measured mean pulmonary artery systolic pressure of 65 mmhg , which established the diagnosis of pulmonary arterial hypertension . transesophageal echocardiography ( tee ) was also performed , but failed to reveal any intracardiac shunt [ figure 2 ] . doppler - ultrasonography ( doppler - usg ) of the abdomen revealed no evidence of portal hypertension . we sent her hair , nail , and drinking water from her residence to the school of tropical medicine in kolkata for arsenic estimation and the report revealed 0.12 mg / l arsenic in the water sample ( safe limit of arsenic content in drinking water is 0.05 mg / l in india and 0.01 mg / l , as per the world health organization statement ) , 2.66 g / g in her hair , and 6.10 g / g in her nail . high - resolution computed tomography ( hrct ) scan of her thorax did not reveal any parenchymal abnormality . on computed tomography ( ct)-angiography we found no embolus in the the pulmonary vasculature , but an enlarged main pulmonary artery trunk [ figure 3 ] . subsequently , we planned to have investigations for connective tissue disorders ( ctd ) , in order to detect the etiology of the pulmonary arterial hypertension ( pah ) . however , all our workups , including anti - centromere antibody , anti - ds dna antibody , anti - ro , anti - u3 and u1 rnp , and anti - phospholipid antibody were negative . after all these investigations we were in fact left with the idiopathic or heritable form of pah . we then took her family history in detail , but failed to illicit any history suggestive of pah in her family , even after repeated enquiry . serum analysis for bone morphogenetic protein receptor 2 ( bmpr-2 ) gene and activin receptor kinase - like 1 ( alk-1 ) gene failed to detect any mutation . thus , with the exclusion of all possible causes of pah in the present case , we concluded that chronic arsenicosis may be responsible for pah in this case . hyperkeratosis and raindrop pigmentation of the palm transesophageal echocardiography showing an enlarged right atrium and a right ventricle with intact interatrial septum and interventricular septum ct angiography showing an enlarged main pulmonary artery arsenicosis is a multi - system disorder , with virtually no system exempted from its involvement . . peripheral vascular disease , hypertension , ischemic heart disease , non - cirrhotic portal hypertension , hepatomegaly , peripheral neuropathy , respiratory involvement , bad obstetrical outcome , hematological disturbances , and diabetes mellitus are among the other clinical features linked to arsenic toxicity . the proposed mechanism of arsenic - induced hypertension is accelerated atherosclerosis due to monoclonal expansion of smooth , production of reactive oxygen species , upregulation of inflammatory signals , and platelet aggregation . respiratory manifestations of arsenicosis include chronic obstructive pulmonary disease ( copd ) , bronchiectasis , and pulmonary fibrosis . pulmonary arterial hypertension , as per literature , can occur in arsenicosis , secondary to copd , lung fibrosis , and portal hypertension . pulmonary hypertension has been defined as an increase in mean pulmonary arterial pressure ( pap ) , 25 mmhg at rest , as assessed by right heart catheterization ( rhc ) . however , we measured pulmonary artery systolic pressure by applying the formula ( pa systolic pressure = tricuspid regurgitation pressure gradient + estimated right atrial pressure ) . theoretically , the calculation of mean pap from pa systolic pressure is possible ( mean pap = 0.61  pa systolic pressure + 2 mmhg ) . we excluded ctd by clinical examination and auto - antibody profile , left heart diseases by echocardiography , intra - cardiac shunt by tee , portal hypertension by doppler usg , pulmonary embolism by ct - angiography , as the probable causes of pah . in our workups we got no evidence of portal hypertension , copd or interstitial lung diseases causing pah . however , literature revealed many mechanisms causing endothelial dysfunction of systemic arteries like reactive oxygen species generation and inflammatory cascades mediated by cytokines in chronic arsenicosis patients . on the basis of the above - mentioned mechanisms , we proposed that pah in the present case might be due to chronic arsenic exposure and its toxicity . careful attention to such cases in the future would provide more evidence of an association between the two conditions .
chronic arsenic exposure causes cutaneous effects like hyperkeratosis , peripheral vascular disease , hypertension , ischemic heart disease , non - cirrhotic portal hypertension , hepatomegaly , peripheral neuropathy , respiratory involvement , bad obstetrical outcome , hematological disturbances , and diabetes mellitus . here 
 we present a case of a 24-year - old lady , with chronic exposure to arsenic , presenting to us with progressive dyspnea . 
 we found pulmonary arterial hypertension ( pah ) as a cause of her dyspnea . 
 pah can occur in arsenicosis , secondary to arsenic - induced chronic obstructive pulmonary disease ( copd ) , lung fibrosis , and portal hypertension , which we excluded by appropriate investigations in our case . 
 we also excluded a familial or heritable form of pah . 
 thus , with the exclusion of all these secondary causes of pah , as well as a hereditary cause , we came to a conclusion that this pah might be due to chronic arsenic exposure . to the best of our knowledge , 
 no case of pah in chronic arsenicosis has been reported to date .