For patients with PCT (and any other porphyria associated with photosensitivity), avoidance of sunlight—and any known precipitating factors—is essential. Hydroxychloroquine 200 mg can be given by mouth twice a week.33 Fresh blisters should be kept clean and free from infection.
In addition to symptom management, it is important to learn as much as possible about the family history of patients who have, or whom you suspect of having, any variant of this little-known genetic disease. Start with these 2 questions:
- Do you have family members who are unusually sensitive to the sun?
- Do you have any family members who always seem to be in the hospital but no one knows what’s wrong with them?
Hemochromatosis
Hereditary hemochromatosis (HH), also referred to as iron overload disease, is a little-known genetic disease that primarily affects Caucasians of Northern European descent, although other ethnic groups may also be affected.34,35
Iron is such a precious commodity that no mechanism has evolved for excreting it. During times of systemic infection, there is a tendency for the body to “hide” iron from invading bacteria, resulting in an increased serum and tissue ferritin—and causing chronic anemia if this continues for long periods of time. The balance of iron homeostasis depends on the regulation of iron absorption, which HH interferes with. In patients with HH, the excess iron builds up in the body, particularly in the liver, heart, pancreas, joints, and pituitary gland, and can cause tissue and organ damage.
Inheritance
Although our understanding of the mechanism by which HH occurs may not be complete, it appears that most cases involve a dysregulation of hepcidin, the major regulator of iron transfer. About 10% of white Americans are carriers of the disorder, which is autosomal recessive, and approximately 0.3% to 0.5% have the double mutation and are therefore at high risk for developing HH.34,35 In many cases, the disease does not develop until middle age.
Testing
HH often goes undetected for years. In some cases, routine lab tests that reveal a polycythemia with a high serum iron and a high ferritin and elevated liver enzymes are the first indication of a problem.
While iron studies can raise the suspicion of HH, however, pinning down the genetic mutation can be a little more complicated. The most common allele in Caucasians results from a C282Y mutation thought to be traced to a Celtic or Viking who lived several centuries ago. For this reason, patients with signs of iron overload who are of northern European ancestry are sometimes tested immediately for the gene associated with HH. Patients who present with cirrhosis may have had a liver biopsy before HH was suspected, and may be offered genetic testing, as well.36
Clinical presentation
Iron overload results in iron deposits in many tissues, with varying results: Infiltration of the liver can cause cirrhosis, infiltration of the pancreas can lead to diabetes, and infiltration of the skin results in a bronzed appearance. Diabetes is a primary complication when HH—sometimes referred to as “bronze diabetes”—goes untreated.37
Treatment
With the exception of a small amount of iron that is sloughed off in dead skin cells each day, bleeding is the only way to rid the body of excess iron. Most patients with HH can be treated with phlebotomy (See “A case for phlebotomized blood)”. One unit of whole blood is removed at approximately 2-week intervals until the serum ferritin is <20 ng/mL. This process takes about 13 months.38
Unlike other genetic disorders, HH can be completely controlled—provided it is detected before major organ damage occurs. Thus, it is particularly important that all family members of an individual diagnosed with HH—or found to be a carrier of the disorder—undergo genetic testing. They should also be asked whether they have (or have had) any relatives who frequently donate blood or have been told to give blood frequently.
A referral for genetic counseling may be indicated, not only for families affected by HH, but for those suspected of having (or carrying) other genetic disorders, as well.
A case for phlebotomized blood
The problem is straightforward: The United States has a shortage of donor blood, and phlebotomized blood from patients with hereditary hemochromatosis (HH) is available in large quantities—and is an excellent source of blood for patients with severe anemia. Yet blood banks often discard it.39
Sweden has used phlebotomies as a source of donor blood since 1984, with no ill effects.40 Until 1999, US blood banks were permitted to use blood from patients with HH, provided they indicated on the label that it came from a patient with the disorder. Since then, the US Food and Drug Administration (FDA) has permitted blood banks to apply for a variance permitting them to use this blood without labeling it as such. The standard safety measures apply to the phlebotomized blood, of course—and the change in this provision reflects the fact that blood from patients with HH is not harmful to recipients in any way.
The FDA maintains a list of establishments that have received such a variance (http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/RegulationoftheBloodSupply/Variances/ucm164649.htm) As of November 2011, there were more than 100 blood banks on that list.