Hemochromatosis Flashcards
How does hemochromatosis usually present?
Constitutional symptoms: lethargy, fatigue, susceptibility to infections.
Bronze-colored skin (hence “Bronze Diabetes” is colloquially used)
Liver issues (seen with elevated LFTs such as Alanine and Aminotransferases) leading to hepatomegaly and abdominal pain, eventually cirrhosis.
Endocrine gland disorders (pituitary, pancreas, thyroid):
Pituitary: loss of libido, erectile dysfunction, testicular atrophy, amenorrhea
Pancreas: alpha cell disruption leading to type II diabetes mellitus
Thyroid: hypothyroidism
Cardiomyopathy (HF, arrhythmias).
Arthralgia.
What are the known heart disorders that are caused by hemochromatosis?
Conduction abnormalities in patients with hemochromatosis are common. Myocardial dysfunction (e.g., cardiomyopathy) and/or direct accumulation of iron deposits within the conduction system (e.g., AV node, Bundle of His) can lead to cardiac arrhythmias. The most common cardiac arrhythmia is paroxysmal atrial fibrillation, but may also include sinus node dysfunction, complete AV block, atrial and ventricular tachyarrhythmias, and sudden cardiac death.
At what age are joints affected with hemochromatosis?
< 40 years old.
What is the genetic inheritance of hereditary hemochromatosis?
Autosomal recessive with incomplete penetrance.
Affected gene is on Chromosome 6 at the HFE gene.
The most common mutation is C282Y.
What is the most common cause for the acquired form of hemochromatosis?
Chronic blood transfusions.
Also: Alcohol use disorder, HCV, Non-alcoholic Fatty Liver Disease, porphyria
What is the most common joint affected with hemochromatosis?
2nd and 3rd metacarpophalangeal joints.
Also at the wrist.
how do the joints appear on x-ray with hemochromatosis?
Hook shaped osteophytes at the metacarpal heads.
Also with joint space narrowing and chondrocalcinosis.
What gender is most commonly affected by hemochromatosis?
Male.
Females are usually asymptomatic until menopause because menstruation is protective.
What is used to diagnose hemochromatosis?
Clinical presentation.
Iron overload:
-Elevated ferritin and transferrin.
-Patients with ferritin levels less than 500 ng/mL may be asymptomatic.
-Levels >300 ng/mL is diagnostic for nearly all patients.
-Premenopausal females >200 ng/mL is diagnostic
Genetics for definitive diagnosis.
Liver biopsy with Prussian Blue:
-Indicated with homozygous mutation of C282Y mutation, Serum ferritin >1000 ng/mL, and risk factors for liver cirrhosis
-Indicated to stage liver disease
what can be done to specifically treat arthropathy of hemochromatosis?
PO analgesics and therapeutic phlebotomy (Patients with ferritin levels less than 500 ng/mL may be monitored).
Hemochromatosis increases the risk of developing … ?
HCC
Increased risk of infection with Vibrio vulnificus, Yersinia enterocolitica, and Listeria.
How is Hemochromatosis managed?
Therapeutic phlebotomy or Iron chelation
Additional therapies:
-Dietary changes: Advise avoidance of iron and vitamin C supplements, avoid undercooked seafood, Encourage strict avoidance of alcohol. There is No need to reduce dietary iron.
-Proton pump inhibitors (PPIs) can be considered as an adjunct to phlebotomy because they can decrease iron absorption, however, only recommended for patients with a need for PPIs (e.g., GERD)
-Erythrocytapheresis is selective removal of red blood cells from the patient’s circulation is useful for patients with thrombocytopenia or hypoproteinemia
In what case would therapeutic phlebotomy be contraindicated?
Inability to tolerate the procedure (e.g., due to anxiety)
Iron-loading anemia evidenced by Low hemoglobin
Conditions sensitive to fluid shifts (e.g., end-stage liver disease, congestive heart failure)
If a patient has conditions where therapeutic phlebotomy is contraindicated but has hemochromatosis, what should be the treatment approach?
Provide medications that chelate (delete) iron (Fe): deFeroxamine, deFerasirox, deFeriprone
Check renal function prior to administration of chelating agents because of the risk of nephrotoxicity and renal accumulation.
These have significant adverse reactions:
Renal toxicity, hepatic toxicity, retinopathy, ototoxicity, neutropenia, agranulocytosis, gastrointestinal bleed, rash
Early intervention may improve … ?
Early treatment of iron overload may:
Improve fatigue and skin hyperpigmentation
Reverse early organ damage (e.g., elevated liver chemistries, early cardiomyopathy)
Increase life expectancy
It may be possible to prevent the progression of advanced complications (arthropathy, hypogonadism, diabetes, cirrhosis), but they cannot be reversed.
