Page 226 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 8-3 Integumentary System

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HEMOCHROMATOSIS

Hemochromatosis is a fairly common autosomal reces-
sive genetic disorder of iron metabolism that leads to
excessive iron absorption and eventually iron overload. Liver cirrhotic
Iron progressively accumulates in various tissues and brown
throughout the body, with the liver most severely Skin hyper-
affected. Most cases are caused by a genetic mutation Liver brown but pigmentation
in the hemochromatosis gene, HFE. This mutation is otherwise normal due to iron Iron deposits chiefly
carried by approximately 10% of the population. The deposition in liver cells, bile duct
disease signs and symptoms typically do not appear and melanin epithelium, and fibrous
until after child-bearing age, usually in the sixth or Skin Iron deposits chiefly over- bands; less in Kupffer
seventh decade of life. normal in Kupffer cells, less production cells
Clinical Findings: Caucasian males are the most fre- in liver cells
quently affected, and there is variability of carrier rates
among populations. For example, in Ireland the rate of
homozygosity for the C282Y mutation in HFE is 1 in
85 individuals. The overall incidence worldwide is
probably about 1 in 350.
The clinical manifestations of hemochromatosis
Spleen
patients who are homozygous for the mutated HFE Heart normal variable and Heart pigmented Spleen
gene can be quite variable. Classic hemochromatosis dark brown enlarged,
includes three main components: liver cirrhosis, diabe- slightly
tes, and generalized skin pigmentation. These symp- brown
toms are caused, respectively, by a persistent chronic
accumulation of iron in the liver and in the pancreas
and by iron deposition in the skin with increased Pancreas
normal,
melanin production. Cirrhosis is the main cause of no urinary Pancreas pigmented
morbidity and mortality, and it dramatically increases sugar and fibrotic, urinary Gastric
one’s risk for hepatocellular carcinoma. Gastric sugar ++++ mucosa
Cutaneous findings include a generalized bronze dis- mucosa pigmented
coloration of the skin. This diffuse pigmentation is one normal
of the first signs of the disease. This finding, along with
diabetes, has led to the name “bronze diabetes” to
describe the condition. Nails can be brittle and show
varying degrees of koilonychia. There is widespread
generalized hair thinning and loss, affecting all terminal
hair locations. Arthritis is a common finding in these
patients and can also be seen in asymptomatic hetero- Bone
zygous carriers of the disease. Bone marrow
Histology: Histology of the skin is not useful for marrow Lymph nodes relatively Lymph nodes
diagnosis. Liver biopsies show varying degrees of pigmented pigmented normal relatively normal
damage on a spectrum from fibrosis to cirrhosis. The
Prussian blue stain is used to accentuate the iron within
the hepatocytes and the cells of the biliary tract. There
is less iron accumulation in the Kupffer cells, which is Adrenal Pituitary Adrenal Pituitary
the direct opposite of the findings in states of iron cortex normal cortex pigmented
overload. normal pigmented
Pathogenesis: The HFE gene is located on the short Testis
arm of chromosome 6 and is mutated in this autosomal Gonads pigmented
recessive genetic disorder of iron metabolism. The normal and atrophic
most frequently encountered genetic mutation is the (azoospermia)
C282Y mutation. Normal iron regulation is dependent
on absorption of iron from dietary sources and normal
losses. Regulatory mechanisms allow for equalization of
iron absorption to balance the iron losses in normal Iron Overload Hemochromatosis
physiological states. The defect in HFE leads to abnor-
mal regulation of cellular uptake of iron as well as a loss
of regulation of ferritin levels. The result of the exces-
sive iron deposition is an increase in free radical oxygen
species and their destructive interactions with various single best predictor of morbidity and mortality in these chelation therapy with intravenous deferoxamine has
tissues. In the liver, this leads to fibrosis and eventually patients. The goal in most patients is to keep the hemo- been helpful for patients who cannot tolerate blood
cirrhosis. globin in the range of 12 g/dL. Other methods to removal procedures. Methods to try to decrease the
Treatment: Therapy requires removal of the exces- remove excessive iron include erythrocytapheresis and absorption of iron from the gastrointestinal tract can
sive iron. This is best accomplished by routine sched- iron chelation therapy. Erythrocytapheresis is a method also be attempted. These treatments have shown the
uled phlebotomy. Phlebotomy decreases the amount of by which predominantly red blood cells are removed best results if implemented before evidence of cirrhosis
iron stores and is used to attempt to prevent the pro- from the blood while the serum, white blood cells, and is present. The importance of genetic counseling
gression to cirrhosis. Prevention of cirrhosis is the platelets are returned to the patient’s bloodstream. Iron cannot be overemphasized.

212 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS