Massive variceal hemorrhage secondary to presinusoidal portal hypertension due to arsenic poisoning IRENE M. SZULER, MD; C. NOEL WILLIAMS, FRCP[C], FACP; J. THOMAS HINDMARSH, MD, MRC PATH, FRCP[C]; HOSOON PARK-DINCSOY, MD
Arsenic hepatic toxicity is rare. A 64-year-old man who had ingested a proprietary preparation containing arsenic for 55 years was admitted to hospital with massive hemorrhage from the upper gastrointestinal tract secondary to bleeding esophageal varices. Presinusoidal sclerosis, a recognized sequel to long-term arsenic ingestion, was present, and the characteristic skin pigmentation and hyperkeratosis of chronic arsenic poisoning were striking. We report this case to draw attention to the serious side effects resulting from ingestion of an antiasthmatic remedy containing arsenic trioxide that we believe to be still in use in North America. Case report A 64-year-old man had been healthy except for insulin-dependent diabetes mellitus of 15 years' duration. On the morning of his admission to hospital he lost consciousness after breakfast and, on regaining it, assumed he had been unconscious for several minutes. He had no recollection of the onset of the episode and disregarded it, since it resembled several of his rare hypoglycemic epiFrom the departments of medicine and pathology, Daihousie University and the Victoria General Hospital, Halifax Reprint requests to: Dr. C. Noel Williams, 5849 University Ave., Halifax, NS B3H 1W2
sodes. Before leaving for work he experienced a powerful urge to defecate and was partially incontinent of a large melena stool en route to the bathroom, whereupon he again temporarily lost consciousness. He was admitted to a local hospital. On the third hospital day he vomited approximately 1500 mL of bright red blood, which caused his hemoglobin concentration to fall by 4 g and necessitated immediate blood transfusion. On the fifth hospital day roentgenography after a barium swallow revealed "questionable esophageal varices"; hematemesis followed, necessitating further transfusion. Emergency esophagogastroscopy disclosed varices in the distal 5 to 6 cm of the esophagus. He was transferred to our hospital for further management. The man stated that he had felt well until 5 days prior to transfer. He had not experienced nausea, abdominal pain or heartburn. His appetite was normal, he had maintained his ideal body weight, and his diabetes mellitus was well controlled by daily injections of insulin. There was no history of ingestion of salicylate or other ulcerogenic drugs, and he was a lifelong abstainer from alcoholic beverages. Asthma had been diagnosed when he was 9 years old, as had allergies to hay and ragweed. He had not experienced any acute asthmatic epi-
168 CMA JOURNAL/JANUARY 20, 1979/VOL. 120
sodes since his youth, a fact he attributed to the prophylactic use of an old patent medicine, Overseas Asthma Relief, which he had been taking daily since age 9. He had initially been instructed to take a teaspoonful three times daily, and for the year before admission had taken a tablespoonful each night. He had smoked a pipe since age 35 years but had never smoked cigarettes. He had no cough, wheeze or dyspnea. There was no family history of diabetes mellitus or peptic ulcer. The man worked as a pipe fitter for a steel company, with which he had been employed for 40 years. There was no evidence of encephalopathy or stigmata of chronic liver disease. He was mildly dehydrated. There was no sign of active bleeding. Chest examination revealed good air entry, vesicular breath sounds with prolonged expiration and end-expiratory rhonchi. His abdomen was not tender, the liver span was 8 cm, the spleen was not palpable and there was no ascites. Rectal examination showed soft tarry black stools. Absent ankle jerks and vibration sense in his legs, with intact position and other senses, suggested mild peripheral neuropathy. The characteristic skin manifestations of chronic arsenic ingestion were present. Macular pigmentation resembling minute freckles was seen about the outer aspect of the shoulders to just
below the axillary fold (Fig. 1). Minute areas of depigmentation were scattered between the freckles. Irregular keratoses on the sides of the fingers and the palms (Fig. 2), warty lesions on the back of the fingers,
and a large irregular hyperkeratotic lesion on one sole were noted. The hand lesions were best appreciated when the patient's hands were shaken; the characteristic feeling is often the initial clue to the diagnosis.
FIG. 1-Characteristic areas of pigmentation and depigmentation over scapula.
FIG. 2-Classic hyperkeratoses on side of finger and on palm.
The asthma medication contained, according to the dispensing pharmacist, potassium iodide, camphor water, gentian root in an alcohol base and 18 mL of I % arsenic trioxide (Fowler's solution) in a total volume of 224 mL. The estimated total amount of arsenic ingested over 55 years, at six bottles per year, was approximately 55 g. The hemoglobin concentration was 12.1 g/dL, the leukocyte count 7.0 x 109/L, the platelet count 275 x 109/L and the erythrocyte sedimentation rate 19 mm/h. On several occasions the serum concentrations of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, 'yglutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase and bilirubin were normal, as were the prothrombin and partial thromboplastin times. In the serum the albumin value was 3.0 g/dL, the globulin value 2.3 g/dL and the aiantitrypsin value 380 (normal 150 to 275) mg/dL. A VRDL test was negative. Barium contrast roentgenograms of the upper gastrointestinal tract showed esophageal varices, and their presence was confirmed by celiac axis arteriography (Fig. 3). Esophageal varices were also seen by esophagoscopy, when no other abnormality could be found to account for the bleeding. Roentgenograms of the chest and pulmonary function tests showed changes compatible with chronic airways obstruction. A specimen of liver obtained by percutaneous biopsy showed sinusoidal collagenosis and portal fibrosis. Assays revealed an arsenic content of 11.7 parts per million (ppm) (normal less than 1) in hair and 16.7 ppm (normal less than 1) in nail clippings. On the 22nd hospital day a prophylactic splenorenal venous shunt of the Warren type was established. Two wedge biopsies were performed on the inferior edge of the liver; one specimen underwent special histochemical studies and estimation of arsenic content, and the other underwent histologic examination. The microscopic appearance of the liver biopsy specimen was one of precirrhosis with sinusoidal colla-
CMA JOURNAL/JANUARY 20, 1979/VOL. 120 169
genosis, angiomatous change of the parenchyma and portal fibrosis with perilobular fibrosis (Fig. 4). No arsenic was demonstrated by histochemical processing of an unfixed liver specimen, and assay of the liver tissue yielded a normal concentration of arsenic (less than 0.3 ppm by dry weight). The patient remained well after discharge and had suffered no further gastrointestinal bleeding 12 months later.
cirrhosis following prolonged ingestion of arsenic, in some of which there was improvement following discontinuation of the toxin. Arsenic was once extensively used therapeutically - alone in the treatment of syphilis, and in Fowler's solution against certain skin disorders.
It was also used in the processing of beer in Britain and as a poison for insects attacking fruits and vegetables, for rodents and for humans. Hutchinson3 in 1895 and Hamberger4 in 1900 described patients who had ascites following prolonged usc of Fowler's solution, and Weir5 in
Discussion Our patient presented with massive hemorrhage from the upper gastrointestinal tract due to bleeding esophageal varices; he had portal hypertension secondary to noncirrhotic presinusoidal fibrosis. There were no clinical stigmata to suggest cirrhosis, liver function was excellent, and wedge biopsy of the liver confirmed the absence of cirrhosis. Chronic arsenic poisoning is insidious. Early symptoms are nonspecific weakness, anorexia and, occasionally, nausea, vomiting and diarrhea or constipation. More common signs are diarrhea and classic skin pigmentation, with hyperkeratosis of palms and soles and circumscribed edema of lower eyelids and ankles. Peripheral neuropathy with mainly sensory involvement may occur; it was, slight in our patient and could have resulted from diabetes mellitus. Our patient had ingested an estimated 55 g of arsenic trioxide over 55 years and had the characteristic skin changes of arsenic toxicity. In addition, the arsenic content of both hair and nails was more than 11 times the normal. We have no explanation for the lack of an increased concentration of arsenic in the liver; in one of Morris and associates' two cases there was an increased concentration.1 Viallet and colleagues2 did not record the arsenic content of the liver in their case. The three main forms of hepatic damage attributed to arsenic are cirrhosis,.11 malignant liver disease11'13 and noncirrhotic portal hypertension.1'2'14'15 There have been many cases reported of ascites, anasarca or
FIG. 3-Celiac axis arteriogram demonstrating esophageal varices.
FIG. 4-Sinusoidal collagenosis, portal fibrosis and angiomatous changes seen in specimen from wedge biopsy of liver (reticulin; X80).
170 CMA JOURNAL/JANUARY 20, 1979/VOL. 120
1930 described two patients with cirrhosis who had been taking Fowler's solution for long periods. Sturrock6 and Reynolds,7 in 1900 and 1901 respectively, described an outbreak of liver disease in beer drinkers in the north of England, where arsenopyrite had been added to catalyse the production of sulfuric acid used to hydrolyse starch in beer production; their disease was directly related to the amount of arsenic in the beer. Stockman8 in 1921 reported a case of cirrhosis with ascites after the ingestion of arsenic in a bromide mixture, and Cannon9 in 1936 described a young woman with an enlarged liver who had ingested fruits and vegetables sprayed with an arsenical pesticide. Luchtrath'0 reported in 1972 that cirrhosis had decreased among German vintners since arsenical pesticides were banned 30 years earlier. Baldridge" and others described cirrhosis in patients being treated with arsenic for syphilis. Arsenic has been shown to induce malignant hepatic tumours,12"' including diffuse, hyperplastic hemangioendothelioma, metastasizing sarcomatous hemangioendothelioma and malignant hemangioendothelioma of multicentric origin. Noncirrhotic portal hypertension, which was present in our patient, has been described in only four previous reports. Zeegen and associatesTM in 1970 described a series of 44 patients with portal hypertension, 4 of whom had been taking arsenic. Viallet and colleagues2 reported in abstract form the case of a man who had taken arsenic in the treatment of psoriasis for 12 years before portal hypertension developed in the absence of histologic evidence of cirrhosis. An explanation for this unusual picture was summarized in the report by Morris and associates' of two patients who had been treated with Fowler's solution for 3 and 22 years. Liver specimens from these two patients showed portal tract fibrosis and an increased number of portal veins, but no evidence of cirrhosis. Wedged hepatic vein pressures were essentially normal, while the intrasplenic pressure was high, which indicated that the obstruction to portal flow
was in the portal tracts. It was suggested that arsenic had damaged the intrahepatic portal veins. Arsenic may also have been responsible for the portal hypertension in a woman described at a clinicopathologic conference.15 In most of the descriptions of noncirrhotic portal hypertension arsenic trioxide, as in Fowler's solution, has been implicated. However, arsenic-contaminated water in India has been reported to produce a similar clinical picture.'6 In current therapeutics arsenic is of importance only in the treatment of amebiasis and certain tropical disorders. However, it is widely found in natural sources and can contaminate water and food. Water can be dangerously contaminated if it runs through the soil around abandoned gold mines, since gold extraction leaves much arsenic in the soil. Several such areas are recognized; one of the most famous is Antofagasta, Chile, another is a province in Taiwan, and an area just outside Halifax has recently been identified and studied following the diagnosis of chronic arsenic poisoning in several individuals.'7 Herbal preparations for the symptomatic relief of asthma have long been used in the Eastern world. The mechanism by which arsenic has this effect is unknown. Our patient had moderate airways obstruction and had taken Overseas Asthma Relief throughout his life; despite the lack of use of conventional antiasthmatic drugs he had had no exacerbations of asthma since his youth. With the identification of obvious sources of arsenic, exposure to this element in medications has been nearly eliminated in the Western world. In Singapore, however, arsenic poisoning was recently found to be caused by the use of local or imported traditional Chinese antiasthmatic herbal preparations, the most toxic being the Sin Lak asthmatic pill.18 Overseas Asthma Relief was patented in 1926 in Nova Scotia and was distributed throughout North America. Since it may still be in use, physicians should be aware of its hazards.
We thank Dr. Barry Ross for dermatologic consultation, and Dr. R.E. Jarvis of the department of chemical engineering, University of Toronto, for analysing the arsenic content of the liver. References 1. Moiuus JS, SCHMID M, NEWMAN 5, et al: Arsenic and noncirrhotic portal hypertension. Gastroenterology 66: 86, 1974 2. VIALLET A, GUILLAUME E, C6if J, et al: Presinusoidal portal hypertension following chronic arsenic ingestion (abstr). Gastroenterology 62: 177, 1972 3. HUTCHINSON J: Case illustrating effects of arsenic. Arch Surg 6: 386, 1895 4. HAMBERGER LP: Arsenical pigmentation and keratosis. Johns Hopkins Med J 11: 87, 1900 5. WEIR JF: Cirrhosis associated with chronic inorganic arsenical poisoning.
Mayo Clin Proc 5: 173, 1930 6. STuRROCK AC: A note on certain forms of beer poisoning. Br Med J 2: 1815, 1900 7. REYNOLDS ES: An account of the epidemic outbreak of arsenical poisoning occurring in beer drinkers in the north of England and the Midland counties in 1900. Lancet 1: 166, 1901 8. STOCKMAN R: Chronic arsenic poisoning. Edinb Med J 27: 1, 1921 9. CANNON AB: Chronic arsenical poisoning: symptoms and sources. NY State J Med 36: 219, 1936 10. LUCHTRATH H: Cirrhosis of the liver in chronic arsenical poisoning in vintners. Ger Med Mon 2: 127, 1972 11. BALDRIDGE CW: Relationship between antisyphilitic treatment and toxic cir-
rhosis. Am J Med Sci 188: 685, 1934 12. Rom F: Arsen, Leber, Tumoren. Hamangioendotheliom. Z Krebsforsch 61: 468, 1957 13. REGELSON W, KIM U, OsPINo J, et al: Haemangioendothelial sarcoma of liver from chronic arsenic intoxication by Fowler's solution. Cancer 21: 514,
1968 14. ZEEGEN R, STANSFELD AG, DAWSON AM, et al: Prolonged survival after portal decompression of patients with non-cirrhotic intrahepatic portal hypertension. Gut 11: 610, 1970 15. NEALE G, AZZOPARDI JG: Chronic arsenical poisoning and non-cirrhotic portal hypertension - a case for diag-
nosis. Br Med J 4: 725, 1971 16. DATTA DV: Arsenic and non-cirrhotic portal hypertension (C). Lancet 1:
433, 1976 17. HINDMARSH JT, MCLETCHIE OR, HEFFERNAN LPM, et al: Electromyographic abnormalities in chronic environmental arsenicalism. J Anal Taxi-
col 1: 270, 1977 18. TAY CII, SEAM CS: Arsenic poisoning from anti-asthmatic herbal prepara-
tions. Med J Aust 2: 424, 1975
CMA JOURNAL/JANUARY 20, 1979/VOL 120 171
Arsenic hepatic toxicity is rare. A 64-year-old man who had ingested a proprietary preparation containing arsenic for 55 years was admitted to hospital with massive hemorrhage from the upper gastrointestinal tract secondary to bleeding esophageal varices. Presinusoidal sclerosis, a recognized sequel to long-term arsenic ingestion, was present, and the characteristic skin pigmentation and hyperkeratosis of chronic arsenic poisoning were striking. We report this case to draw attention to the serious side effects resulting from ingestion of an antiasthmatic remedy containing arsenic trioxide that we believe to be still in use in North America. Case report A 64-year-old man had been healthy except for insulin-dependent diabetes mellitus of 15 years' duration. On the morning of his admission to hospital he lost consciousness after breakfast and, on regaining it, assumed he had been unconscious for several minutes. He had no recollection of the onset of the episode and disregarded it, since it resembled several of his rare hypoglycemic epiFrom the departments of medicine and pathology, Daihousie University and the Victoria General Hospital, Halifax Reprint requests to: Dr. C. Noel Williams, 5849 University Ave., Halifax, NS B3H 1W2
sodes. Before leaving for work he experienced a powerful urge to defecate and was partially incontinent of a large melena stool en route to the bathroom, whereupon he again temporarily lost consciousness. He was admitted to a local hospital. On the third hospital day he vomited approximately 1500 mL of bright red blood, which caused his hemoglobin concentration to fall by 4 g and necessitated immediate blood transfusion. On the fifth hospital day roentgenography after a barium swallow revealed "questionable esophageal varices"; hematemesis followed, necessitating further transfusion. Emergency esophagogastroscopy disclosed varices in the distal 5 to 6 cm of the esophagus. He was transferred to our hospital for further management. The man stated that he had felt well until 5 days prior to transfer. He had not experienced nausea, abdominal pain or heartburn. His appetite was normal, he had maintained his ideal body weight, and his diabetes mellitus was well controlled by daily injections of insulin. There was no history of ingestion of salicylate or other ulcerogenic drugs, and he was a lifelong abstainer from alcoholic beverages. Asthma had been diagnosed when he was 9 years old, as had allergies to hay and ragweed. He had not experienced any acute asthmatic epi-
168 CMA JOURNAL/JANUARY 20, 1979/VOL. 120
sodes since his youth, a fact he attributed to the prophylactic use of an old patent medicine, Overseas Asthma Relief, which he had been taking daily since age 9. He had initially been instructed to take a teaspoonful three times daily, and for the year before admission had taken a tablespoonful each night. He had smoked a pipe since age 35 years but had never smoked cigarettes. He had no cough, wheeze or dyspnea. There was no family history of diabetes mellitus or peptic ulcer. The man worked as a pipe fitter for a steel company, with which he had been employed for 40 years. There was no evidence of encephalopathy or stigmata of chronic liver disease. He was mildly dehydrated. There was no sign of active bleeding. Chest examination revealed good air entry, vesicular breath sounds with prolonged expiration and end-expiratory rhonchi. His abdomen was not tender, the liver span was 8 cm, the spleen was not palpable and there was no ascites. Rectal examination showed soft tarry black stools. Absent ankle jerks and vibration sense in his legs, with intact position and other senses, suggested mild peripheral neuropathy. The characteristic skin manifestations of chronic arsenic ingestion were present. Macular pigmentation resembling minute freckles was seen about the outer aspect of the shoulders to just
below the axillary fold (Fig. 1). Minute areas of depigmentation were scattered between the freckles. Irregular keratoses on the sides of the fingers and the palms (Fig. 2), warty lesions on the back of the fingers,
and a large irregular hyperkeratotic lesion on one sole were noted. The hand lesions were best appreciated when the patient's hands were shaken; the characteristic feeling is often the initial clue to the diagnosis.
FIG. 1-Characteristic areas of pigmentation and depigmentation over scapula.
FIG. 2-Classic hyperkeratoses on side of finger and on palm.
The asthma medication contained, according to the dispensing pharmacist, potassium iodide, camphor water, gentian root in an alcohol base and 18 mL of I % arsenic trioxide (Fowler's solution) in a total volume of 224 mL. The estimated total amount of arsenic ingested over 55 years, at six bottles per year, was approximately 55 g. The hemoglobin concentration was 12.1 g/dL, the leukocyte count 7.0 x 109/L, the platelet count 275 x 109/L and the erythrocyte sedimentation rate 19 mm/h. On several occasions the serum concentrations of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, 'yglutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase and bilirubin were normal, as were the prothrombin and partial thromboplastin times. In the serum the albumin value was 3.0 g/dL, the globulin value 2.3 g/dL and the aiantitrypsin value 380 (normal 150 to 275) mg/dL. A VRDL test was negative. Barium contrast roentgenograms of the upper gastrointestinal tract showed esophageal varices, and their presence was confirmed by celiac axis arteriography (Fig. 3). Esophageal varices were also seen by esophagoscopy, when no other abnormality could be found to account for the bleeding. Roentgenograms of the chest and pulmonary function tests showed changes compatible with chronic airways obstruction. A specimen of liver obtained by percutaneous biopsy showed sinusoidal collagenosis and portal fibrosis. Assays revealed an arsenic content of 11.7 parts per million (ppm) (normal less than 1) in hair and 16.7 ppm (normal less than 1) in nail clippings. On the 22nd hospital day a prophylactic splenorenal venous shunt of the Warren type was established. Two wedge biopsies were performed on the inferior edge of the liver; one specimen underwent special histochemical studies and estimation of arsenic content, and the other underwent histologic examination. The microscopic appearance of the liver biopsy specimen was one of precirrhosis with sinusoidal colla-
CMA JOURNAL/JANUARY 20, 1979/VOL. 120 169
genosis, angiomatous change of the parenchyma and portal fibrosis with perilobular fibrosis (Fig. 4). No arsenic was demonstrated by histochemical processing of an unfixed liver specimen, and assay of the liver tissue yielded a normal concentration of arsenic (less than 0.3 ppm by dry weight). The patient remained well after discharge and had suffered no further gastrointestinal bleeding 12 months later.
cirrhosis following prolonged ingestion of arsenic, in some of which there was improvement following discontinuation of the toxin. Arsenic was once extensively used therapeutically - alone in the treatment of syphilis, and in Fowler's solution against certain skin disorders.
It was also used in the processing of beer in Britain and as a poison for insects attacking fruits and vegetables, for rodents and for humans. Hutchinson3 in 1895 and Hamberger4 in 1900 described patients who had ascites following prolonged usc of Fowler's solution, and Weir5 in
Discussion Our patient presented with massive hemorrhage from the upper gastrointestinal tract due to bleeding esophageal varices; he had portal hypertension secondary to noncirrhotic presinusoidal fibrosis. There were no clinical stigmata to suggest cirrhosis, liver function was excellent, and wedge biopsy of the liver confirmed the absence of cirrhosis. Chronic arsenic poisoning is insidious. Early symptoms are nonspecific weakness, anorexia and, occasionally, nausea, vomiting and diarrhea or constipation. More common signs are diarrhea and classic skin pigmentation, with hyperkeratosis of palms and soles and circumscribed edema of lower eyelids and ankles. Peripheral neuropathy with mainly sensory involvement may occur; it was, slight in our patient and could have resulted from diabetes mellitus. Our patient had ingested an estimated 55 g of arsenic trioxide over 55 years and had the characteristic skin changes of arsenic toxicity. In addition, the arsenic content of both hair and nails was more than 11 times the normal. We have no explanation for the lack of an increased concentration of arsenic in the liver; in one of Morris and associates' two cases there was an increased concentration.1 Viallet and colleagues2 did not record the arsenic content of the liver in their case. The three main forms of hepatic damage attributed to arsenic are cirrhosis,.11 malignant liver disease11'13 and noncirrhotic portal hypertension.1'2'14'15 There have been many cases reported of ascites, anasarca or
FIG. 3-Celiac axis arteriogram demonstrating esophageal varices.
FIG. 4-Sinusoidal collagenosis, portal fibrosis and angiomatous changes seen in specimen from wedge biopsy of liver (reticulin; X80).
170 CMA JOURNAL/JANUARY 20, 1979/VOL. 120
1930 described two patients with cirrhosis who had been taking Fowler's solution for long periods. Sturrock6 and Reynolds,7 in 1900 and 1901 respectively, described an outbreak of liver disease in beer drinkers in the north of England, where arsenopyrite had been added to catalyse the production of sulfuric acid used to hydrolyse starch in beer production; their disease was directly related to the amount of arsenic in the beer. Stockman8 in 1921 reported a case of cirrhosis with ascites after the ingestion of arsenic in a bromide mixture, and Cannon9 in 1936 described a young woman with an enlarged liver who had ingested fruits and vegetables sprayed with an arsenical pesticide. Luchtrath'0 reported in 1972 that cirrhosis had decreased among German vintners since arsenical pesticides were banned 30 years earlier. Baldridge" and others described cirrhosis in patients being treated with arsenic for syphilis. Arsenic has been shown to induce malignant hepatic tumours,12"' including diffuse, hyperplastic hemangioendothelioma, metastasizing sarcomatous hemangioendothelioma and malignant hemangioendothelioma of multicentric origin. Noncirrhotic portal hypertension, which was present in our patient, has been described in only four previous reports. Zeegen and associatesTM in 1970 described a series of 44 patients with portal hypertension, 4 of whom had been taking arsenic. Viallet and colleagues2 reported in abstract form the case of a man who had taken arsenic in the treatment of psoriasis for 12 years before portal hypertension developed in the absence of histologic evidence of cirrhosis. An explanation for this unusual picture was summarized in the report by Morris and associates' of two patients who had been treated with Fowler's solution for 3 and 22 years. Liver specimens from these two patients showed portal tract fibrosis and an increased number of portal veins, but no evidence of cirrhosis. Wedged hepatic vein pressures were essentially normal, while the intrasplenic pressure was high, which indicated that the obstruction to portal flow
was in the portal tracts. It was suggested that arsenic had damaged the intrahepatic portal veins. Arsenic may also have been responsible for the portal hypertension in a woman described at a clinicopathologic conference.15 In most of the descriptions of noncirrhotic portal hypertension arsenic trioxide, as in Fowler's solution, has been implicated. However, arsenic-contaminated water in India has been reported to produce a similar clinical picture.'6 In current therapeutics arsenic is of importance only in the treatment of amebiasis and certain tropical disorders. However, it is widely found in natural sources and can contaminate water and food. Water can be dangerously contaminated if it runs through the soil around abandoned gold mines, since gold extraction leaves much arsenic in the soil. Several such areas are recognized; one of the most famous is Antofagasta, Chile, another is a province in Taiwan, and an area just outside Halifax has recently been identified and studied following the diagnosis of chronic arsenic poisoning in several individuals.'7 Herbal preparations for the symptomatic relief of asthma have long been used in the Eastern world. The mechanism by which arsenic has this effect is unknown. Our patient had moderate airways obstruction and had taken Overseas Asthma Relief throughout his life; despite the lack of use of conventional antiasthmatic drugs he had had no exacerbations of asthma since his youth. With the identification of obvious sources of arsenic, exposure to this element in medications has been nearly eliminated in the Western world. In Singapore, however, arsenic poisoning was recently found to be caused by the use of local or imported traditional Chinese antiasthmatic herbal preparations, the most toxic being the Sin Lak asthmatic pill.18 Overseas Asthma Relief was patented in 1926 in Nova Scotia and was distributed throughout North America. Since it may still be in use, physicians should be aware of its hazards.
We thank Dr. Barry Ross for dermatologic consultation, and Dr. R.E. Jarvis of the department of chemical engineering, University of Toronto, for analysing the arsenic content of the liver. References 1. Moiuus JS, SCHMID M, NEWMAN 5, et al: Arsenic and noncirrhotic portal hypertension. Gastroenterology 66: 86, 1974 2. VIALLET A, GUILLAUME E, C6if J, et al: Presinusoidal portal hypertension following chronic arsenic ingestion (abstr). Gastroenterology 62: 177, 1972 3. HUTCHINSON J: Case illustrating effects of arsenic. Arch Surg 6: 386, 1895 4. HAMBERGER LP: Arsenical pigmentation and keratosis. Johns Hopkins Med J 11: 87, 1900 5. WEIR JF: Cirrhosis associated with chronic inorganic arsenical poisoning.
Mayo Clin Proc 5: 173, 1930 6. STuRROCK AC: A note on certain forms of beer poisoning. Br Med J 2: 1815, 1900 7. REYNOLDS ES: An account of the epidemic outbreak of arsenical poisoning occurring in beer drinkers in the north of England and the Midland counties in 1900. Lancet 1: 166, 1901 8. STOCKMAN R: Chronic arsenic poisoning. Edinb Med J 27: 1, 1921 9. CANNON AB: Chronic arsenical poisoning: symptoms and sources. NY State J Med 36: 219, 1936 10. LUCHTRATH H: Cirrhosis of the liver in chronic arsenical poisoning in vintners. Ger Med Mon 2: 127, 1972 11. BALDRIDGE CW: Relationship between antisyphilitic treatment and toxic cir-
rhosis. Am J Med Sci 188: 685, 1934 12. Rom F: Arsen, Leber, Tumoren. Hamangioendotheliom. Z Krebsforsch 61: 468, 1957 13. REGELSON W, KIM U, OsPINo J, et al: Haemangioendothelial sarcoma of liver from chronic arsenic intoxication by Fowler's solution. Cancer 21: 514,
1968 14. ZEEGEN R, STANSFELD AG, DAWSON AM, et al: Prolonged survival after portal decompression of patients with non-cirrhotic intrahepatic portal hypertension. Gut 11: 610, 1970 15. NEALE G, AZZOPARDI JG: Chronic arsenical poisoning and non-cirrhotic portal hypertension - a case for diag-
nosis. Br Med J 4: 725, 1971 16. DATTA DV: Arsenic and non-cirrhotic portal hypertension (C). Lancet 1:
433, 1976 17. HINDMARSH JT, MCLETCHIE OR, HEFFERNAN LPM, et al: Electromyographic abnormalities in chronic environmental arsenicalism. J Anal Taxi-
col 1: 270, 1977 18. TAY CII, SEAM CS: Arsenic poisoning from anti-asthmatic herbal prepara-
tions. Med J Aust 2: 424, 1975
CMA JOURNAL/JANUARY 20, 1979/VOL 120 171
