Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Hemochromatosis Douglas Ashinsky MD To cite this article: Douglas Ashinsky MD (1992) Hemochromatosis, Postgraduate Medicine, 91:4, 137-145, DOI: 10.1080/00325481.1992.11701249 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701249
Published online: 17 May 2016.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Technology Sydney]
Date: 23 July 2016, At: 01:13
Hemochromatosis It's more than skin-deep
Douglas Ashinsky; MD
Downloaded by [University of Technology Sydney] at 01:13 23 July 2016
Preview In a patient with hemochromatosis, excess iron is deposited in parenchymal tissue. Skin hyperpigmentation and damage to organs, including the liver and heart, often result. In this article, Dr Ashinsky describes a case in which diagnosis was made by laboratory testing and examination of liver biopsy specimens. Appropriate therapy led to rapid improvement in the patient's condition.
A 55-year-old woman presented at the physician's office complaining of progressive weakness, shortness ofbreath, nocrurnal dyspnea, and nausea. She also described a feeling that all her heartbeats were not going into her hands. Past medical history was unremarkable. Atrial fibrillation with hypotension was discovered, and she was admitted to the hospital. On admission, the patient's blood pressure was 90/50 mm Hg, heart rate 120 beats per minute and irregular, and respirations 20/min at rest. Her skin was ashen. Veins were markedly distended to the angle of jaw while she sat upright, and hepatojugular reflux was present. There was a bilateral decrease in breath sounds in the lower half of the chest with dullness and egophony. Cardiac rhythm was irregularly irregular without murmurs, gallops, or thrills. The liver was enlarged and palpable about 6 em below the costal margin. The spleen was not palpable. Pitting edema was present in both legs.
Laboratory srudies revealed the following values: hemoglobin 15.5 g!dL, hematocrit47.5%, mean corpuscular volume 104 J..Lm1, white blood cell count 9,000/mm3, reticulocyte count 8.8%, platelet count 95,000/mm3, serum urea nitrogen 55 mg!dl, serum creatinine
• A PERPLEXING CASE
1.5 mgldl, and serum glucose 231 mgldl. Prothrombin time was increased to 19 seconds, but partial thromboplastin time was normal. Serum electrolytes were within normal range. Creatine kinase levels were normal. Liver function values were elevated as follows: alanine aminotransferase (formerly
VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE • HEMOCHROMATOSIS
called SGP1} 84 U/L, aspartate aminotransferase (formerly called SCOT) 121 U /L, and alkaline phosphatase 183 U/L. Arterial blood gas srudies demonstrated pH of7.37, Pco2 of29 mm Hg, Po2 of70 mm Hg, and a calculated bicarbonate level of 16 mEq/L while the patient was breathing room air. Chest films revealed a markedly enlarged heart with bilateral pleural effusion. An electrocardiogram showed atrial fibrillation with a rapid ventricular response. Normal sinus rhythm was restored with administration of digoxin and procainarnide hydrochloride. Therapy with supplemental oxygen, a diuretic, and an angiotensin-converting enzyme inhibitor was begun, and the patient's condition rapidly improved. Liver function values and prothrombin time remained elevated. Fibrinogen level was low and levels of fibrin degradation products were elevated, but the patient showed no signs of bleeding. An echocardiogram showed dilated cardiomyopathy of both ventricles and a small amount of pericardia! effusion. Abdominal ultrasound revealed bilateral pleural effusion, ascites, and prominence of the inferior vena cava and middle hepatic veins. Examination of a blood smear revealed mild rouleaux formation and normocytic and target cells. Vitamin B12 and folate levels were continued
137
Downloaded by [University of Technology Sydney] at 01:13 23 July 2016
PERPLEXING CASE CONTINUED
normal, but the serum iron level was elevated to 169 J.Lg/dl, total iron-binding capacity was decreased to 195 J.Lg/dl, and the serum ferritin level was extremely high at 5,51 0 ng! mL. A diagnosis of hemochromatosis with liver failure and cardiac disease was then considered. At this point it was discovered that hemochromatosis had recently been diagnosed in the pa. ' stster. . nents Magnetic resonance imaging of the abdomen showed increased deposits of iron in the liver and pancreas, consistent with hemochromatosis. Also noted were an irregular contour of the liver and a prominent spleen, consistent with cirrhosis. Histologic study ofliver biopsy specimens confirmed the diagnosis of hemochromatosis. A catheter was inserted for infusion of deferoxarnine mesylate, and biweekly phlebotomies were begun. After several phlebotomies, the patient was discharged from the hospital with normal sinus rhythm and no evidence of congestive heart failure. Phlebotomies Douglas Ashinsky, MD Dr Ashinsky is medical attending physician, Overlook Hospital, Summit, New Jersey, and Muhlenberg Regional Medical Center, Plainfield, New Jersey. He is also assistant instructor of medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey.
138
were continued three times a week for 1 month, then two times a week The patient's condition has continued to improve.
Discussion Hemochromatosis is a disease in which there is an inappropriate increase in intestinal absorption of iron. This results in deposition of iron in parenchymal cells of the liver, pancreas, skin, heart, spleen, pituitary and other endocrine glands, and bones. The inherited form of the disease is called idiopathic hemochromatosis. Secondary hemochromatosis is caused by disorders that promote iron overload.l.2 Hemochromatosis, also known as bronze diabetes or pigment cirrhosis, was first named by von Recklinghausen in 1889. He believed that hemosiderin, the ironstorage pigment that causes the disease, was derived from blood. After reviewing autopsy cases, Sheldon in 1935 postulated that hemochromatosis was due to an inborn error in the metabolism of iron. 2 The gene frequency for idiopathic hemochromatosis in AngloSaxons is about 5%. The carrier (heterozygote) frequency is 1Oo/o, and the disease (homozygote) frequency is 0.3%. The inherited allele is located on chromosome 6 and is closely linked to the HLA-A
locus. It has also been associated with the histocompatibility locus antigens HLA-A3, HLA-B7, HLA-B 14, and HLA-All. This association is useful in the examination of family members of a patient with idiopathic disease. 3 Hemochromatosis is found 5 to 10 times more ofren in men than in women, because women lose blood through menstruation and pregnancy. Most patients are between 40 and 60 years of age when symptoms develop, and the disorder is rarely seen in those under age 20. 3 Patients usually present with hepatomegaly, skin pigmentation, splenomegaly, ascites, arrhythmia, congestive heart failure, jaundice, arthropathy, and loss of body hair. 23 Hyperpigmentation is caused by an increase in the number of melanocytes and a thinning of the epidermis. Iron deposits stimulate melanin production and alter epidermal thickness. 3 Cardiac manifestations are common in hemochromatosis and typically are present at the time of diagnosis. An electrocardiogram may demonstrate arrhythmia, low voltage, or repolarization abnormalities. An echocardiogram and cardiac catheterization data usually show restrictive cardiomyopathy, and chest films may reveal cardiomegaly and increased pulcontinued
HEMOCHROMATOSIS • VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE
-vicodin®~ ~~ habit~bltatrale 5rng (Waning: May be
111• • •
,IIIO
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Hemochromatosis Douglas Ashinsky MD To cite this article: Douglas Ashinsky MD (1992) Hemochromatosis, Postgraduate Medicine, 91:4, 137-145, DOI: 10.1080/00325481.1992.11701249 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701249
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Technology Sydney]
Date: 23 July 2016, At: 01:13
Hemochromatosis It's more than skin-deep
Douglas Ashinsky; MD
Downloaded by [University of Technology Sydney] at 01:13 23 July 2016
Preview In a patient with hemochromatosis, excess iron is deposited in parenchymal tissue. Skin hyperpigmentation and damage to organs, including the liver and heart, often result. In this article, Dr Ashinsky describes a case in which diagnosis was made by laboratory testing and examination of liver biopsy specimens. Appropriate therapy led to rapid improvement in the patient's condition.
A 55-year-old woman presented at the physician's office complaining of progressive weakness, shortness ofbreath, nocrurnal dyspnea, and nausea. She also described a feeling that all her heartbeats were not going into her hands. Past medical history was unremarkable. Atrial fibrillation with hypotension was discovered, and she was admitted to the hospital. On admission, the patient's blood pressure was 90/50 mm Hg, heart rate 120 beats per minute and irregular, and respirations 20/min at rest. Her skin was ashen. Veins were markedly distended to the angle of jaw while she sat upright, and hepatojugular reflux was present. There was a bilateral decrease in breath sounds in the lower half of the chest with dullness and egophony. Cardiac rhythm was irregularly irregular without murmurs, gallops, or thrills. The liver was enlarged and palpable about 6 em below the costal margin. The spleen was not palpable. Pitting edema was present in both legs.
Laboratory srudies revealed the following values: hemoglobin 15.5 g!dL, hematocrit47.5%, mean corpuscular volume 104 J..Lm1, white blood cell count 9,000/mm3, reticulocyte count 8.8%, platelet count 95,000/mm3, serum urea nitrogen 55 mg!dl, serum creatinine
• A PERPLEXING CASE
1.5 mgldl, and serum glucose 231 mgldl. Prothrombin time was increased to 19 seconds, but partial thromboplastin time was normal. Serum electrolytes were within normal range. Creatine kinase levels were normal. Liver function values were elevated as follows: alanine aminotransferase (formerly
VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE • HEMOCHROMATOSIS
called SGP1} 84 U/L, aspartate aminotransferase (formerly called SCOT) 121 U /L, and alkaline phosphatase 183 U/L. Arterial blood gas srudies demonstrated pH of7.37, Pco2 of29 mm Hg, Po2 of70 mm Hg, and a calculated bicarbonate level of 16 mEq/L while the patient was breathing room air. Chest films revealed a markedly enlarged heart with bilateral pleural effusion. An electrocardiogram showed atrial fibrillation with a rapid ventricular response. Normal sinus rhythm was restored with administration of digoxin and procainarnide hydrochloride. Therapy with supplemental oxygen, a diuretic, and an angiotensin-converting enzyme inhibitor was begun, and the patient's condition rapidly improved. Liver function values and prothrombin time remained elevated. Fibrinogen level was low and levels of fibrin degradation products were elevated, but the patient showed no signs of bleeding. An echocardiogram showed dilated cardiomyopathy of both ventricles and a small amount of pericardia! effusion. Abdominal ultrasound revealed bilateral pleural effusion, ascites, and prominence of the inferior vena cava and middle hepatic veins. Examination of a blood smear revealed mild rouleaux formation and normocytic and target cells. Vitamin B12 and folate levels were continued
137
Downloaded by [University of Technology Sydney] at 01:13 23 July 2016
PERPLEXING CASE CONTINUED
normal, but the serum iron level was elevated to 169 J.Lg/dl, total iron-binding capacity was decreased to 195 J.Lg/dl, and the serum ferritin level was extremely high at 5,51 0 ng! mL. A diagnosis of hemochromatosis with liver failure and cardiac disease was then considered. At this point it was discovered that hemochromatosis had recently been diagnosed in the pa. ' stster. . nents Magnetic resonance imaging of the abdomen showed increased deposits of iron in the liver and pancreas, consistent with hemochromatosis. Also noted were an irregular contour of the liver and a prominent spleen, consistent with cirrhosis. Histologic study ofliver biopsy specimens confirmed the diagnosis of hemochromatosis. A catheter was inserted for infusion of deferoxarnine mesylate, and biweekly phlebotomies were begun. After several phlebotomies, the patient was discharged from the hospital with normal sinus rhythm and no evidence of congestive heart failure. Phlebotomies Douglas Ashinsky, MD Dr Ashinsky is medical attending physician, Overlook Hospital, Summit, New Jersey, and Muhlenberg Regional Medical Center, Plainfield, New Jersey. He is also assistant instructor of medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey.
138
were continued three times a week for 1 month, then two times a week The patient's condition has continued to improve.
Discussion Hemochromatosis is a disease in which there is an inappropriate increase in intestinal absorption of iron. This results in deposition of iron in parenchymal cells of the liver, pancreas, skin, heart, spleen, pituitary and other endocrine glands, and bones. The inherited form of the disease is called idiopathic hemochromatosis. Secondary hemochromatosis is caused by disorders that promote iron overload.l.2 Hemochromatosis, also known as bronze diabetes or pigment cirrhosis, was first named by von Recklinghausen in 1889. He believed that hemosiderin, the ironstorage pigment that causes the disease, was derived from blood. After reviewing autopsy cases, Sheldon in 1935 postulated that hemochromatosis was due to an inborn error in the metabolism of iron. 2 The gene frequency for idiopathic hemochromatosis in AngloSaxons is about 5%. The carrier (heterozygote) frequency is 1Oo/o, and the disease (homozygote) frequency is 0.3%. The inherited allele is located on chromosome 6 and is closely linked to the HLA-A
locus. It has also been associated with the histocompatibility locus antigens HLA-A3, HLA-B7, HLA-B 14, and HLA-All. This association is useful in the examination of family members of a patient with idiopathic disease. 3 Hemochromatosis is found 5 to 10 times more ofren in men than in women, because women lose blood through menstruation and pregnancy. Most patients are between 40 and 60 years of age when symptoms develop, and the disorder is rarely seen in those under age 20. 3 Patients usually present with hepatomegaly, skin pigmentation, splenomegaly, ascites, arrhythmia, congestive heart failure, jaundice, arthropathy, and loss of body hair. 23 Hyperpigmentation is caused by an increase in the number of melanocytes and a thinning of the epidermis. Iron deposits stimulate melanin production and alter epidermal thickness. 3 Cardiac manifestations are common in hemochromatosis and typically are present at the time of diagnosis. An electrocardiogram may demonstrate arrhythmia, low voltage, or repolarization abnormalities. An echocardiogram and cardiac catheterization data usually show restrictive cardiomyopathy, and chest films may reveal cardiomegaly and increased pulcontinued
HEMOCHROMATOSIS • VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE
-vicodin®~ ~~ habit~bltatrale 5rng (Waning: May be
111• • •
,IIIO
