hemochromatosis and hair loss
hemochromatosis and hair loss

HEMOCHROMATOSIS AND HAIR LOSS

Hereditary hemochromatosis is a genetic disorder characterised by uninhibited intestinal absorption of dietary iron, resulting in an increase in total body iron stores.  Like most animals, humans have no way to excrete excess iron.

Sufficient levels of iron are critical for the production of red blood cells.  Red blood cells deliver oxygen to the hair follicles and iron deficiency hair loss is common in women of a child bearing age.  When your body produces less blood cells than it needs, it will divert blood supply to essential organs.   When blood flow to the scalp is reduced, the hair follicle will go in to resting phase and more hairs will shed from the scalp daily than usual.  This will eventually lead to less hair coverage over the scalp.

Whilst iron deficiency is detrimental to hair health, too much iron is toxic to cell membranes and tissues.  When there is an overload of iron, excess iron is deposited in organs (such as the heart and liver) and leads to a decline in function.  This decline in functions effcts hormones that regulate mood, energy and metabolism.  Excess iron can also lead to organ damage and disruption of normal blood circulation and digestion and nutrient availability.

Hereditary hemochromatosis and hair loss

Adapted from – Recognition and Management of Hereditary Hemochromatosis [1]

IRON DEFICIENCY VS IRON OVERLOAD

Iron is highly reactive and leads to oxidative damage in the body.  Whilst iron is normally bound by ferritin to prevent this highly reactive element causing damage to the body, reactions with oxygen can lead to the relaease of iron into the tissues of the body and cell membranes.  These factors combined can lead to a gradual loss of hair.

Most of the damage caused by hemochromatosis is thought to occur in the liver.  Appropiate liver function is required for healthy hair growth and once liver function starts to decline, there will inevitably be a loss of hair.

Iron overload affects hair growth directly in a number of ways:

Itchy scalp – Pruritus or itch is defined as an unpleasant sensation of the skin that provokes the urge to scratch. It is a characteristic feature of many  systemic diseases.  Pruritus may be present in patients with hemochromatosis where the levels of iron in blood and tissues are elevated [2] or when the skin is dehydrated.  Persistent scratching can break the skin or remove growing tissue.

Epidermal dehydration – As well as a lowered basal metabolic rate iron overload can also lead to dry, thickened skin.  For normal hair growth, the hair follicle must be housed in a suitably hydrated epidermis. Water is essential for the normal functioning of the skin, especially its outer layer, the stratum corneum. Loss of water from the skin is normally carefully regulated, a function dependent on the complex nature of the stratum corneum (outermost layer of the epidermis). The retention of water in the stratum corneum is dependent on natural moisturising factors and intercellular lipids orderly arranged to form a barrier to prevent epidermal water loss. The water content of the stratum corneum is necessary for proper keratin cell development within the hair fibre.

Accumulation of iron in the sebaceous glands – When iron accumulates in a gland or organ it can have an inhibitory effect.  When there are high levels of iron in sebaceous glands in can lead to a reduction of function.

The sebaceous glands are microscopic glands that secrete an oily matter onto the skin.  They help with the removal of old skin cells on the scalp, they keep the scalp hydrated by providing a waterproof top layer on the stratum corneum and lubricates the hair fibre.  The oily matter secreted onto the scalp is made up of wax esters and squalene and act as a barrier to microbes that might penetrated the skin and the hair follicle.  The sebaceous glands also supply vitamin E to the scalp, clinical trials have shown this fatty vitamin is essential for hair growth.

Reduced blood circulation – Adequate blood flow is essential for the delivery of nutrients to the hair follicle.  The keratin cells that make up the hair fibre are particularly dependant on blood flow the hyperactive hair follicle stem cells that drive hair growth will gradually slow their activity as blood flow declines.

Increased oxidative damage – Unbound iron is a highly reactive element and high levels of iron will lead to higher levels of oxidative damage to all tissue.  This damage can occur to DNA, lipids and proteins.  DNA provides the information that tells the cell when and how to produce keratin, if DNA is damaged this may lessen or completely prevent the manufacture of keratin within the hair fibre.  Oxidative damage can also occur to the growing hair fibre that is still within the epidermal layer.

Decreased collagen production – Iron overload tends to reduce collagen production by interrupting the synthesis of proteoglycans. Type II collagen increases after iron depletion therapy in patients with hemochromatosis [3].

Hemochromatosis and hair loss

DIAGNOSING HEMOCHROMATOSIS IN WOMEN

The main pathophysiological functions of hemochromatosis include: (1) altered function of either: Human factors engineering protein, hepcidin antimicrobial peptide, transferrin receptor 2 protein or solute carrier family 40 member 1 protein, (2) decreased expression of the iron inhibitory hormone hepcidin, (3) an increased absorption of dietary iron in the duodenum, (4) physical and mental symptoms due iron overload in tissue [4].  Although most patients with hemochromatosis have two faulty C282Y genes (80%-85%), other regularly identified mutations include an aspartate substitution for histidine at position 63 (H63D) and a cysteine substitution for serine at position 65 (S65C).

Early diagnosis in the general population has been problematic for clinicians due to the wide-ranging and non-specific classic symptoms of hemochromatosis.  Diagnosis techniques to identify the condition currently include genetic screening, and measurement of serum iron markers.  Genetic screening, transferrin saturation and serum ferritin are often used to screen for hemochromatosis, but in women of childbearing age, this may not be a reliable tool.

hemochromatosis diagnosis flow chart

TESTING FOR HEMOCHROMATOSIS; SPECIFICITY VS SENSITIVITY

All diagnostic tests have a balance of sensitivity and specificity.  Sensitivity is the ability of a test to correctly identify patients with a disease and the specificity relates to the ability of a test to show a patient does not have a disease.  Transferrin saturation is a ratio determining the percentage of transferrin bound (saturated) in a complex with iron. Ferritin is produced by the liver and is the main storage site of iron.  By looking at how iron is bound by transferrin and ferritin it allows practitioners to have an idea of whether the levels of iron in the body are too high and whether this is due to hemochromatosis.

A diagnostic value of above 200 µg/L for serum ferritin and above 45% for transferrin saturation indicates hemochromatosis.  In women, a ferritin level of 200 µg/mL or higher has a sensitivity of 66% and a specificity of 85% in detecting hemochromatosis, clinical research points to a sexual bias in serum ferritin levels that leads to under diagnosis in women [5].  Ferritin tends to rise with inflammation but can also be lowered with heavy periods so this may delay diagnosis.  Transferrin saturation indicates a need for further genetic testing but with a cut off point of 45%, one study showed this test failed to detect 33% of cases [5].

IRON REDUCTION THERAPY FOR THE IMPROVEMENT OF HEMOCHROMATOSIS SYMPTOMS

There are a number of therapies that can be undertake under medical supervision to lower iron levels in the body:

Iron chelation therapy – this involves taking oral or injected medication that binds to excess iron and removes it from the body.  A challenge of chelation therapy is to balance adequately the levels of iron being excreted from the body.  The dose of medication must be careful adjusted over time as iron levels fall.  Another major challenge is adherence to the chelation schedule, treatment interruption of will negatively effect therapeutic success.  A lack of lowered serum ferritin does not necessarily mean chelation therapy is unsuccessful as inflammation may be a secondary cause of high ferritin levels.

Venipuncture / therapeutic phlebotomy – This procedure removes blood from the body with the specific intention of reducing iron overload.  This is the most common way of treating hemochromatosis.  Normally, blood is taken at regular intervals until total iron is reduced and ferritin levels reach normal levels.

REDUCING THE RISK OF HAIR LOSS FROM HEMOCHROMATOSIS

Whilst men tend to suffer more symptoms specific to hemochromatosis such liver fibrosis, women who have untreated hemochromatosis suffer more from non-specific symptoms such as severe fatigue, arthritis and hair loss [6]. Only 30-60% of females with two C282Y genes exhibit symptoms of iron overload and end organ damage affects only 1% of females with hemochromatosis.

Early detection and treatment of hemochromatosis will reduce the likelihood of end organ damage.  Iron depletion via venipuncture or chelation is usually able to reverse conditions associated with the accumulation of iron. Disease progression can be slowed when ferritin is reduced to 50-100 µg/L [4].

In 2007, Canadian researchers concluded that hemochromatosis is a “common and relatively simple genetic disease to treat.”

With treatment, hair loss due to the condition is likely to be temporary, especially with early diagnosis and effective management.

REFERENCES

  1. Brandhagen, D.J., Fairbanks, V.F. and Baldus, W., 2002. Recognition and management of hereditary hemochromatosis. American family physician, 65(5), p.853.
  2. Nestler, J.E., 1983. Hemochromatosis and pruritus. Annals of internal medicine, 98(6), pp.1026-1026.
  3. Richette, P., Eymard, C., Deberg, M., Vidaud, D., De Kerguenec, C., Valla, D., Vicaut, E., Bardin, T. and Henrotin, Y., 2010. Increase in type II collagen turnover after iron depletion in patients with hereditary haemochromatosis. Rheumatology, 49(4), pp.760-766.
  4. Bacon, B.R., Adams, P.C., Kowdley, K.V., Powell, L.W. and Tavill, A.S., 2011. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md.)54(1), 328.
  5. Adams, P.C., Reboussin, D.M., Press, R.D., Barton, J.C., Acton, R.T., Moses, G.C., Leiendecker-Foster, C., McLaren, G.D., Dawkins, F.W., Gordeuk, V.R. and Lovato, L., 2007. Biological variability of transferrin saturation and unsaturated iron-binding capacity. The American journal of medicine120(11), 999.
  6. Moirand, R., Adams, P.C., Bicheler, V., Brissot, P. and Deugnier, Y., 1997. Clinical features of genetic hemochromatosis in women compared with men. Annals of internal medicine127(2), 105 – 110.

MORE ARTICLES