Alopecia
Diseases

Author: Gianpiero Pescarmona
Date: 03/10/2007

Description

DEFINITION

The disease definition according to a specific consensus conference or to The Diseases Database based on the Unified Medical Language System (NLM)

Also the link to the corresponding Mesh term has to be created

DatabaseLink
Wikipedia"URL":
The Diseases Database"URL":
OMIM"URL":

EPIDEMIOLOGY

age, sex, seasonality, etc

SYMPTOMS

DIAGNOSIS

histopathology
radiology
NMR
laboratory tests

PATHOGENESIS

PATIENT RISK FACTORS

Vascular

Genetic

Acquired

Hormonal

Genetic

Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. 1997
J Invest Dermatol. 1997 Sep;109(3):296-300.
Sawaya ME, Price VH.

Department of Medicine, University of Florida, Gainesville 32610, U.S.A.

In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.

Acquired

Skin disorders and thyroid diseases.

TISSUE SPECIFIC RISK FACTORS

anatomical (due its structure)

vascular (due to the local circulation)

physiopathological (due to tissue function and activity)

Cadherin 23 is a component of the tip link in hair-cell stereocilia

RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. 2001

Interactions of the vitamin D receptor with the corepressor hairless: analysis of hairless mutants in atrichia with papular lesions. 2007

A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu. 2006

  • Abstract
    A novel autosomal recessive mutant was produced using N-ethyl-N-nitrosourea mutagenesis. The characteristics of the mutant mice included progressive irreversible hair loss within a month of birth, wrinkled skin, and long curved nails. Linkage analysis revealed that the causative gene is linked to D14Mit193 on chromosome 14. Sequence analysis of the complete cDNA of the candidate gene, hairless (Hr), identified a homozygous G-to-T transition at nucleotide 3572, leading to the substitution of glycine by tryptophan, designated Gly960Trp. This missense mutation occurs in the vicinity of repression domain 3 of the hairless protein (HR). This allele was named Hr(m1Enu). The relative amounts of Hr mRNA and HR protein determined by real-time PCR and Western blot analyses, respectively, were slightly elevated in the mutant mice. Quantitative real-time PCR analysis revealed the increased expression of Kc1 and Vdr in the mutant mice, whereas the expression of Nrs1 and Krtap16-6 was decreased. These results suggest that the Gly960Trp substitution in HR protein in Hr(m1Enu) mice may alter the function of HR as a transcriptional corepressor.

COMPLICATIONS

THERAPY

Cadherin 23 is a component of the tip link in hair-cell stereocilia

RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. 2001

Interactions of the vitamin D receptor with the corepressor hairless: analysis of hairless mutants in atrichia with papular lesions. 2007
m

Comorbidity profiles among patients with alopecia areata: The importance of onset age, a nationwide population-based study. 2011

Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dermatology, National Yang-Ming University, Taipei, Taiwan.
Abstract
BACKGROUND:
Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by onset age has rarely been reported.

OBJECTIVE:
We sought to clarify the role of atopic and autoimmune diseases in AA, thereby better understanding its pathogenesis.

METHODS:
A total of 4334 patients with AA were identified from the National Health Insurance Database in Taiwan from 1996 to 2008. A national representative cohort of 784,158 persons served as control subjects.

RESULTS:
Among patients with AA, there were significant associations with vitiligo, lupus erythematosus, psoriasis, atopic dermatitis, autoimmune thyroid disease, and allergic rhinitis. Different ages at onset resulted in disparate comorbidities. Increased risk of atopic dermatitis (odds ratio [OR] 3.82, 95% confidence interval 2.67-5.45) and lupus erythematosus (OR 9.76, 95% confidence interval 3.05-31.21) were found in childhood AA younger than 10 years. Additional diseases including psoriasis (OR 2.43) and rheumatoid arthritis (OR 2.57) appeared at onset age 11 to 20 years. Most atopic and autoimmune diseases were observed at onset ages of 21 to 60 years. With onset age older than 60 years, thyroid disease (OR 2.52) was highly related to AA. Moreover, patients with AA had higher risk for more coexisting diseases than control subjects.

LIMITATIONS:
We could not differentiate hypothyroidism from hyperthyroidism.

CONCLUSIONS:
AA is related to various atopic and autoimmune diseases. Different associated diseases in each onset age group of AA can allow clinician to efficiently investigate specific comorbidities.

Comments
2013-02-13T12:04:25 - Eugenio Malvicino

Hormones, Molecules and Drugs which are associated with hair growth

Introduction

Hair growth is influenced by many things, including our general health, nutritional status, minerals in your body, medications, and hormones. Hair loss can be due to antidepressants, deficit of hormones, hypoxia, blood pressure medications, low iron, low zinc, chemotherapy, crash dieting, infection or hig fever.
Normally, hair growth has three phases: the anagen phase(growth phase) , the catagen phase(resting phase) and the telogen phase(sloughing phase).

Growth phases

Hormones

  • Thyroid hormones

Hormonally induced hair loss takes place when 5-alpha reductase starts to convert the hormone testosterone on the scalp to its less useful version, dihydrotestosterone, or DHT.Then DHT attacks the hair follicle, and shrinks it, even making it disappear entirely. Hair becomes thinner and finer, and may stop growing entirely. This conversion of testosterone to DHT seems to be sped up in some patients with hyperthyroidism or hypothyroidism, and may be the cause of hair loss that continues for thyroid patients, despite what is considered sufficient thyroid treatment.
Here there is an abstract about the influence of the Euthyroidism:

Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation.2008

But we have to pay attention because also Hyperthyroidism could cause hair loss, and it is demonstrated by this research:

Endocrine controls of primary adult human stem cell biology: Thyroid hormones stimulate keratin 15 expression, apoptosis, and differentiation in human hair follicle epithelial stem cells in situ and in vitro.2010

  • Estrogens

An other important class of hormones are the Estrogens which serves to reduce body hair and promote the growth of the hair on your head, unlike the male hormones testosterone and DHT (androgens), which promote hair loss on your head and an increase in body hair. If you possess normal levels of estrogen the risk of having female pattern baldness is reduced. However, if there is an estrogen deficiency, which occurs during peri-menopause and menopause, or if the estrogen levels plummet after giving birth or stopping medication, it will impact own hair.
Oral contraceptives contain the hormone estrogen which stimulates and prolongs the growth phase of hair follicles. That is why pregnant women, who have high concentrations of estrogen, often have especially healthy and abundant hair. However, when the anagen is prolonged by estrogen, and the hair does eventually shed, which is a normal part of the growing process, more hairs than usual will be sloughed off.
According to Dr. Frederick R. Jelovsek, M.D., M.S., about 10 percent of the hairs will reach the resting phase at the same time when a woman is taking oral contraceptives or during pregnancy. This is a higher percentage than normal. About three months after the resting stage begins, the sloughing phase starts. Somewhere between 50 and 100 hairs will be lost each day for a while, which is more than is normally shed at one time. You are shedding the extra hair that the estrogen created.
If a woman stops taking oral contraceptives or, in the case of a menopausal woman, quits taking hormone replacement therapy (HRT), this will prompt hair loss because her body no longer has that extra boost of estrogen.

Estrogen

When your body is getting extra estrogen, during pregnancy or via HRT or oral contraceptives, a woman will actually have more hair than normal. After she gives birth, the estrogen levels eventually return to normal and the excess hair goes into the resting stage, which is called catagen phase, and the excess hairs will fall out about three months after giving birth.
Scientists point out that losing the excess hairs that were grown because of excess estrogen is not a big deal; however, if hair loss occurs in the "normal" hairs, not in the excess ones, new hairs may not grow back in and this is considered a form of estrogen-related hair loss.

In this abstract is showed the reason why estrogen raised the number of our hairs:

Estrogen Leads to Reversible Hair Cycle Retardation through Inducing Premature Catagen and Maintaining Telogen.2012

Molecules

  • Iron

The hair growth is also influenced by the level of iron, because it’s the component of the Hemoglobin which delivers the oxigen to the tissutes. Normal levels of iron allow the straight oxigenation of the scalp and the hair follicles guaranteed the right number of our hair. Iron deficiency is less common in men and postmenopausal women than in women of childbearing age.
A double-blind, placebo-controlled study, carried out over eight years by French researchers, tested the impact of a daily dose of antioxidants on 13,000 healthy subjects, including 7,886 women, and allowed researchers to provide conclusive evidence that iron deficiency and iron depletion are factors in hair loss. Data from 3,759 pre-menopausal women showed that 48 percent suffered from iron deficiency or iron depletion. Among post-menopausal women only 23 percent had lower than normal levels of ferritin because iron loss is often due to menstruation and pregnancy. Researchers cross-referenced data concerning hair loss and iron reserves, as measured by the amount of ferritin in the blood. They were able to show that pre-menopausal women in the 'severe hair loss' category had significantly lower iron reserves than women who did not suffer from excessive hair loss. Foods rich in iron include liver, kidney, mussels, oysters, lean beef, lentils, beans, spinach, prunes, and raisins.


The study plubished by the European Journal of Dermatology( Volume 17, Number 6, 507-12, November-December 2007, Investigative report) showed this association:
Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. The aim of our study was to assess this relationship in a very large population of 5110 women aged between 35 and 60 years. Hair loss was evaluated using a standardized questionnaire sent to all volunteers. The iron status was assessed by a serum ferritin assay carried out in each volunteer. Multivariate analysis allowed us to identify three categories: “absence of hair loss” (43%), “moderate hair loss” (48%) and “excessive hair loss” (9%). Among the women affected by excessive hair loss, a larger proportion of women (59%) had low iron stores (<\; 40 µg/L) compared to the remainder of the population (48%). Analysis of variance and logistic regression show that a low iron store represents a risk factor for hair loss in non-menopausal women.

  • Oxigen

The most important molecole of nourishment for the scalp and the hair is the Oxigen, delivered by the iron as we see formerly. The oxigen is kept by the environment thanks to the exstrinsic respiration; but if we have respiration diseases like asthma, the levels of oxigen decrease.
Asthma is associated with hair loss because their mitochondrions have less oxigen than normal and they aren’t able to produce ATP for the hair growth and compromised cellular repair mechanisms.
Generally it is the Hipoxya that reduce the pressure of oxigen and subsequently the reduction of the nourishment of the hair, in fact when you smoke the oxygen deficiency in your blood weakens the hair follicles, leading to dryness of the scalp and hair loss.
Also, uncontrolled diet that is high in saturated fat causes accumulation of cholesterol inside your arteries resulting in less oxygen in your blood stream.

  • Minerals, Vitamins and Proteins

Minerals are important factors for the regular and normal hair growth in fact a mineral or vitamin deficiency is at the root of your hair loss, you simply need to correct the deficiency. Maybe it's the result of improper digestion, or perhaps you're not absorbing the necessary vitamins and minerals as well as you need to. I want to show some examples:
-deficiency in ZINC can contribute to hair shedding, because without zinc and other related minerals, your hair shafts weaken, causing hair breakage and slow hair regrowth. Zinc benefits for hair include promotion of cell reproduction, tissue growth, and repair of broken tissues. Zinc also maintains the oil-secreting glands that are attached to your hair follicles, decreasing their chances of falling off. More studies need to be conducted to establish that zinc supplements will help with hair loss, but it is said that zinc gluconate at a dose level of 50 or 60 mgs per day for two weeks is recommended.
Here an abstract that demonstrated this correlation:

The Therapeutic Effect and the Changed Serum Zinc Level after Zinc Supplementation in Alopecia Areata Patients Who Had a Low Serum Zinc Level. 2009

- SILICA is a common component of the body. It is found in connective tissues, muscle tissue, bone, nails and hair. Silica helps strengthen hair and makes it less likely for hair to become brittle and develop split ends. Silica helps retain moisture in hair, creating shinier strands. It helps also strengthen hair and prevents or reduces hair loss.
-Hair loss occurs when the diet is inadequate in the B VITAMINS, especially B6, biotin, inositol and folic acid. Biotin is a B vitamin and is present in foods like eggs and liver. Biotin is a major component in the natural hair manufacturing process; it is essential to not only grow new hair, but it also plays a major role in the overall health of skin and nails. However, it would take a huge amount of eggs and liver to provide you with the 5 milligrams of biotin that you would need for healthy hair and nails. A biotin supplement can provide your body with the necessary amount of biotin it needs to promote hair growth and prevent hair loss without additional calories and without having to eat liver.
-European studies have found that SOY PROTEIN reinforces hair and stimulates its growth. In one study, the hair growth increased by 15 percent only eating tofu and soy milk which are good sources of soy protein. Other good sources of protein are low-fat cheese, eggs, fish, beans, brewer's yeast and yogurt.

Drugs

The last part of this research want to describes the most common medicines against the hair loss:

  • Minoxidil (Rogaine) : This topical medication is available over the counter and no prescription is required. It can be used in men and women. It works best on the crown, less on the frontal region. Minoxidil is available as a 2%solution, 4% solution, an extra-strength 5% solution, and a new foam or mousse preparation. Rogaine may grow a little hair, but it's better at holding onto what's still there. There are few side effects with Rogaine. The main problem with this treatment is the need to keep applying it once or twice a day, and most men get tired of it after a while. In addition, minoxidil tends to work less well on the front of the head, which is where baldness bothers most men. Inadvertent application to the face or neck skin can cause unwanted hair growth in those areas.
  • Finasteride (Propecia) : This medication is FDA approved for use in only men with androgenic hair loss. Although not FDA approved in women, it has been used "off label" in women with androgenic hair loss who are not pregnant or planning to become pregnant while on the medication. Finasteride is in a class of medications called 5-alpha reductase inhibitors. It is thought to help reduce hair loss by blocking the action of natural hormones in scalp hair follicles. Propecia is a lower-dose version of a commercially available drug called Proscar that helps shrink enlarged prostates in middle-aged and older men. Women, especially those who are or may become pregnant, should not handle finasteride capsules. Touching the contents of the capsules may potentially harm a male fetus and females who accidentally touch leaking capsules should wash the area to avoid side effects. Propecia 1 mg tablets are available by prescription and taken once daily. Propecia may grow and thicken hair to some extent for some people, but its main use is to maintain hair that's still there. Studies have shown that this medication works well in some types of hair loss and must be used for about six to 12 months before full effects are determined. This medication does not "work" in days to weeks, and its onset of visible improvement tends to be gradual. It may be best for men who still have enough hair to retain but also can help some regrow hair. Possible but very unlikely side effects include impotence or a decreased sex drive. Studies have shown that these side effects were possibly slightly more common than seen in the general population and are reversible when the drug is stopped. Taking Propecia once a day seems to be easier than applying minoxidil, but the prospect of taking a pill daily for years doesn't sit well with some. There's also the cost, about $70-$100/month, which is generally not reimbursed by most health insurers.
  • Dutasteride (Avodart) : it has recently been used as "off label" to treat hair loss in men. It is FDA approved and primarily used to treat an enlarged prostate (bening prostatic hyperplasia or BPH) only in men. Dutasteride is similar to finasteride (Propecia, Proscar) and is in a class of medications called 5-alpha reductase inhibitors. Dutasteride may help in hair loss by blocking the production or binding of a natural substance in the scalp hair follicles. Although not FDA approved in women, it has been used "off-label" in women with androgenic hair loss who are not pregnant or planning to become pregnant while taking the medication. Women, especially those who are or may become pregnant, should not handle dutasteride capsules. Touching the contents of the capsules may potentially harm a male fetus and females who accidentally touch leaking capsules should wash the area with soap and water immediately. There is a six-month clearance time required after taking this medication before being permitted to donate blood.
  • Bimatoprost : a group of topical medications called prostaglandin analogs have recently began undergoing testing for potential hair regrowth. They may be used in men and women. These drugs are not currently FDA approved for scalp hair loss. Currently these are primarily used for eyelash enhancement. One of the new medications is called Bimatoprost. Further testing and studies are required to assess the efficacy of these products in scalp hair loss. Bimatoprost solution (Latisse) has just been started to be used off-label for help in selected cases of hair loss. It is currently FDA approved for cosmetic eyelash enhancement. Studies have shown it can treat hypotrichosis (short or sparse) of the eyelashes by increasing their growth, including length, thickness, and darkness. This medication is also commercially available as Lumigan, which is used to treat glaucoma. It is not known exactly how this medication works in hair regrowth, but it is thought to lengthen the anagen phase (active phase) of hair growth. Interestingly, during routine medical use of Lumigan eye drops for glaucoma patients, it was serendipitously found that eyelashes got longer and thicker in many users. This led to clinical trials and the approval of cosmetic use of Latisse for eyelashes.

About the future

Finally I want to show one of the last discovers in this field because it might be the starting point of the complete knowledge about this disease and an innovative kind of therapy that could be recovered from baldness:

* The scientists at the University of Pennsylvania believe they have discovered the cause of alopecia in a molecole that destroys the hair follicles. George Cotsarelis announced to be in talks with several pharmaceutical companies to develop treatments that may be available within two years. Dr. Cotsarelis has found with his team of dermatologists that the prostaglandin D2 (PGD2) arrests the growth of hair follicles. The link between genetics and alopecia is known for a long time but was never identified the specific cause.
When the team analyzed the scalps of bald men were found PGD2 levels three times higher in areas where the hair was becoming thinner.

Previous work conducted by the same research team had found that bald men have cells that can make your hair grow but whose maturation was blocked. It is thought, therefore, that PGD2, through a receptor called GPR44, lock up the ripening stopping the process of hair growth.
In laboratory tests on mice and the compound arresting hair growth.

The prostaglandin D2 can be blocked and inhibited in a natural way through the therapy HairOzone™ included in the medical protocol injective bSBS™, thanks to the combination of genomics and regenerative medicine enables it to act progressively stimulating the stem cells of the skin and hair follicles favoring the production of a healthy hair and quality. Acts on the follicles during miniaturization which often reverses the balding process, its action also reaches the subcutaneous atrophied follicles.
Thanks to DNA testing can speak directly to the heart of the problem and identify the genetic predisposition of the individual. The accuracy of the test YourLife™ -™HairLife included in the protocol biogenesis Bulbar has absolute precision and allows the post Biologist targeted therapies and the highest chance of success.

  • Research has shown that the application of certain frequencies of light (in the red and green spectrums) can increase the amount of oxygen in the scalp and overcome the hypoxia caused by the effects of DHT. Over time, a series of light treatments will build up large stores of energy for tissue and vascular (blood flow) regeneration. The purpose of the red and green light in combination is to reoxygenate the tissue and allow local cellular energy production to resume hence stimulating hair re-growth.
2011-05-16T16:07:38 - Gianpiero Pescarmona

Zn gluconate???

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