While there’s no “one” answer to the question of the relationship between alopecia areata and stress and no experimental proof, dermatologist and researcher Dr. Maria Hordinsky of the University of Minnesota offers some hypotheses.

Dr. Horinsky answers the question: “Can stress cause the hair loss of alopecia?”

Gina’s Kolata’s NY Times article today is a timely “lesson” for the alopecia areata community. Genes are not stable. They change. They become inactive and they die.  Genes are highly complex and unpredictable. All sorts of things happen that are not understood. For everyone, but especially for those who believe that the naming and locations of a few genes for alopecia areata is a slam dunk or  straight line from point A to point B, please read here about the nature of genes in another disease.  The same degree of uncertainties, mutating, life and death of genes applies to all diseases, including AA.

Clinical Review: Management of Alopecia Areata.
Published July 31, 2010

M J Harries, J Sun, R Paus, and L E King, Jr
Management of alopecia areata
BMJ 2010; 341: c3671

A comprehensive review of the treatments currently in use for treating  alopecia areata, totalis and universalis.; referenced and offering statistical data on the efficacy of various approaches. Ask your doctor or medical librarian for a copy of this article. Discuss the findings with your dermatologist and decide together which if any of the treatments you might consider in an attempt for regrowth. Of particular interest are the relapse rates and the results of therapies used both alone and in combination with each other.

This article reminds that the biological agents (alefacept, efalizumab and etanercept) are not effective for alopecia areata patients. Those are the randomised controlled drug trials promoted as beacons of hope for patients with much fanfare over the past decade. BGDL advises a temperate wait and see approach to any clinical trial; not just for alopecias but for any disease.  The results are not in until they’re in.

The Editor’s Summary (July 1, 2010 Nature magazine) puts it simply.

“The genetic basis of alopecia areata, a common autoimmune disease that causes disfiguring hair loss due to the collapse of immune privilege of the hair follicle, is largely unknown.”  Key words that follow in the editor’s summary are “association study”, “implies the involvement”,  and “significant associations”.

So here at BGDL we say:  continue to use all your best and beautiful Alopecia Options ™; help us grow so we can help you get you connected to other women; and from time to time check back at the progress of aforementioned associations and decide how you’re going to live beautifully and confidently today while others keep looking down that more distant and elusive road.

At the founding of BGDL , medical and research updates were frequently posted both here and on social networking sites where questions and discussions frequently arise. This was purposeful -  to correct misinformation and better educate on what’s accurate and what’s  media hype.

Going forward, the work I do to assess research news and post links to this information will appear only on this blog. To locate all postings about research, click on the research tag below.           - Thea Chassin, founder and president BGDL

I cannot take claim for this and I don’t even know who to attribute it to. Though it was originally written in reference to new genetic markers for mental illness, it applies equally and perfectly to the super-caffeinated news coverage of a hair loss gene this week.

“The thing to keep in mind is that genetics is often just a predisposition to a problem, not a 100% indicator that something will develop. It’s good that some scientists are trying to isolate genes. It’s also good that other scientists are learning how environmental factors activate and deactivate certain genes; especially interesting is the possibility (as with some research on autism and fever) that genes that get switched in one direction can reverse direction during the lifespan. Intake of vitamins (especially vitamin D, the only vitamin whose creation is primarily endogenous) and nutrients, environmental toxins, and psychosocial stress all interact with our genes in ways that are not yet clear. It seems that new branches of science should be created that focus on the connections between disparate research and theories. There seems to be way too much compartmentalization and specialization where this type of research is concerned.”

It’s simple. Because in a news cycle like we’re in right now with a recently published genetics study  about the identification of genes for hair loss, women feel worse than ever. Yes, worse than ever. Consider this:

#1) Researchers have been identifying genes for all kinds of diseases in labs around the world for a very long time and with ever more exacting  tools.

#2) The identification of genes, while noble and hard work, is light-years away from anything to do with finding treatments and cures. Look at the history.

#3) Not one iota of this work, as earnest as it is, helps a woman living with alopecia areata today.

#4) The oft heard expectation  that if THEY will find a cure, if THEY would be more interested in hair loss as a problem, then I will feel better. This belief is long held for many and a giant step in the wrong direction. Actually, not a step at all. It cements women into immobility, wallowing in self pity, unable to take charge of their lives.

#5) Because in comments pouring out below the hair loss gene blogs,  women still lament their sadness for feeling ” freakish”, “abnormal”,”strange” and worse. They want someone to fix them. It doesn’t work that way.

#6) Because we know how to push that self-talk not just to the back burner.  We know how to get it off your stove.

Did you ever provide DNA (blood sample) and survey answers for the long form of the NAAR (National Alopecia Areata Registry) in the US?

Did your questionnaire include that you’re of  European ancestry?

If you did, then your DNA might have been used in the study, published this week in Nature, which used DNA only from people who self-reported European heritage.

Title: “Genome-wide association study in alopecia areata implicates both innate and adaptive immunity” .

Cautious patience advised: not a clinical trial, not a cure, not a treatment, not a proof.  Geneticists work hard on all kinds of diseases and find ever newer ways to identify and tag genetic material.  Improved technologies make identification ever more detailed.

How many diseases have modern day cures even with the tagging of genetic markers, decades of research and sometimes even boatloads of funding?

The biotech company Follica gets mentioned sometimes in the alopecia areata community even though they are not researching hair growth products for alopecia areata. Some of Follica’s research and development utilizes  the hair growth research of  Dr. George Cotsarelis (University of Pennsylvania) who is a known dermatology researcher who has done investigations about alopecia areata, so that confuses some folks. The confusion was amplified when mainstream media went all out loudly and indiscriminately in 2008 to parrot Follica’s press releases for new discoveries, patents and sizable equity financing for hair growing products. The buzz worked, but it came across on TV to the public as if it was applicable to all forms of hair loss.

Follica’s hair growth focus is on male and female pattern baldness known as androgenic alopecia. For Follica news and their latest round of equity financing, read more.

While the NAAR page on the MD Anderson website states “Nearly 2% of people in the United States, many of them children, suffer from alopecia areata, a skin disorder that causes hair to fall out in patches….” this very recent  update (February 2010, Journal of the American Academy of Dermatology) makes it clear that the prevalence of the condition is 0.1% 0.2% in the United States.

It would be more accurate for the MD Anderson site to say that the lifetime risk is 2%.

This week attention is on the announcement of a new “hair loss” gene in a study led by Dr. Angela Christiano of Columbia University - revealed previously in scientific meetings and published in the journal Nature this week.

The researcher’s personal interest in and search for a hair loss gene started in the late 1990’s as reported in the NY Times. At that time, her quest led to a family in Pakistan with the hereditary condition Hypotrichosis Simplex and an observation about chromosome 8.  Since then additional DNA analysis has yielded expanded data.  The news this week is on a mutation of chromosome 18.

How does this relate to alopecia areata? There is no connection. But since it’s in the news this week, it’s a teaching moment….especially because just the other night the mother of an adult child with AA had this exchange:

Mother excitedly:  “They found the hairloss gene!!”

Chassin: “It’s not all that new and there’s nothing about it that helps alopecia areata patients”

Mother: “But it’s true! It’s all over the news today! They found the gene.”

(sigh)

For a long time, genetics researchers at Columbia University ( USA) , Haddassah-Hebrew University Medical Center (Israel) and other sites have tried to learn about the genes of hairloss. One thing is sure -  It’s not one gene. It’s a complex of traits. As a little background to the news this week about the genes of hair loss,  here’s info from 2005 to help put into perspective how complex it is and how far today’s news of “may” “could” and “further study” is from finding good treatments and cures.

You might have the view if you live in the United States that the only research being funded and performed or even that the only research of value are the few and minimally funded studies supported by a national foundation based in the US.

Scientists on many continents, especially in genetics labs, are trying to learn about the genes of people with alopecia areata compared to  control groups without aa.  Here’s one published in the Journal Autoimmunity in 2008 about a genetic study from Kuwait University in Kuwait. It’s written for other geneticists, not the general population, so it’s very technical, but knowing that this work takes place helps demonstrate the global range of scientists looking at aa.

We encourage people with alopecia areata being  part of the NAAR (National Alopecia Areata Registry). We also like to point out the kinds of studies we’re finding where researchers utilized registry data. While most research doesn’t end up with important results that lead to cures of anything, there’s a theory that looking at the genes of families like those in this study can broaden “understanding”.

“Familial Alopecia Areata and Chronic Thrombocytopenia”

Alopecia areata (AA) has a strong hereditary component and is associated with a number of other autoimmune diseases. There is no established relationship between AA and any of the congenital thrombocytopenias. Read more…

Case in point: today a blog alert pops up with a bold font headline that a major USA ivy-league university’s researchers have identified a gene for inherited baldness. It refers to a famous science magazine and gives the issue month.  It says that funding was provided in part by a well known alopecia research funding source. So you might assume this has something major to do with current alopecia research. BUT…a bit more exploration and a read of the original article reveals that publication was in 1998. The baldness being discussed is a rare recessive trait of 11 members of a Pakistani family where hair fails to grow after an infant’s ritual head shave at one week of age and members are born without eyebrows or eyelashes. Genetic studies are valuable, but “news” must be taken in context.

In the blog, the principal investigator is quoted…remember this is 1998…”The discovery of this new gene gives us endless possibilities that may allow us to effectively treat hair loss and possibly baldness within the next five years.” Whether this is an accurate quote or not, I don’t know….but there are too many who still believe if it’s in print it must be so!

So…the point is this: understand that there’s context and follow back to the original source when seeing hair loss genetic “discoveries” on the internet. And try to get the whole story whenever you see any bold face announcement “We found a gene!”

You’ve probably seen some numbers about AA, but they don’t tell the whole story. The  lifetime risk of having some form of alopecia areata is estimated to be nearly 2% (1.7%)….nearly 5 million in the US by today’s census. Lifetime risk means the percentage  of people who have a chance to have any type of AA( including transient episodes) over their entire life. That does not mean that nearly 2% of the current US population currently have a form of the disease.

The prevalence of alopecia areata is far lower…how many people currently have it.  That estimate is 0.1% to 0.2% of the population. Big difference.

This article was researched using patient surveys collected in the NAAR ( National Alopecia Areata Registry) a multi-center data collection project based at MD Anderson in Texas. History of atopy or autoimmunity increases risk of alopecia areata.

And at the bottom here, you’ve got a list of the scientific meeting presentations and published articles using the NAAR database. Just keep in mind that the identification of genetic locations (loci) and alleles (markers) is not a straight path to anything having to do with treatment. Kind of like zebras and oranges.

Presented below is the concluding paragraph and final sentence in the February, 2010 JAAD (Journal of the American Academy of Dermatology) feature article “Alopecia Areata Update: Part II Treatment”. (Italics and bolding added)

“There has been little progress in the treatment of AA in  the past decade, and ILCSs are still the preferred method of treatment for most patients. Newer topical and systemic agents (eg. biologics) have been tried, but the outcomes have been unattractive. We are still in need of developing treatment options for refractory cases and for specific hair-bearing sites ( ie eyelashes) where treatment choices are almost nonexistent. Because of higher psychiatric morbidity in patients with AA, psychosocial support is a valuable tool in any management plan.

Thank you to authors  Alkhalifah, Alsantali, Wang,  McElwee, and Shapiro for the inclusion of this important statement in this prestigious journal.

We never ask you to send money for research and leave you stranded with no follow up. In fact, we don’t ever ask you to send your money to research at all.

What do we do? Bald Girls Do Lunch is the leader in providing primary sources and tools so you really know what dermatological science is learning about AA,where it’s headed, and where it has totally dead ended.

A terrific new knowledge tool:

February, 2010, Journal of the American Academy of Dermatology ( Vol 62, Issue 2, Pages 191-202)
Alopecia Areata Update: Part II: Treatment.

Click here for the abstract.

Ask your dermatologist or medical librarian to make you a copy of the full article including Part I.

(Click on ‘research’ and ‘treatment’ tags to see more updates in the blog)

If you follow alopecia areata research, you’ve no doubt heard about the “mouse model”…..the ones who develop alopecia areata. Actually, mouse models are not new, but there’s a special type bred at the Jackson Laboratories in Maine. Here’s a lot of info about these AA mice and how researchers can order specific strains.

You’ve also likely heard about  “infiltrates” and ” lymphocytes”. What’s especially nice about this page are the cross-sectional photos of hair follicles showing magnification of lymphocyte infiltrates around the follicle bulbs. And here’s even more info about the Jackson technique that induces AA symptoms through surgical grafting from one mouse to another.

In 2008 the news releases were afire including coverage on the  network morning talk shows that a baldness cure was “right around the corner” courtesy of the start-up Follica using a novel scientific discovery by Dr. George Cotsarelis at UPenn.  Standing by our advice then, we still say “Don’t hold your breath.”

Here’s the latest.

A brief summary of alopecia areata cause and treatments. I like the photos.

One photo depicts  how bare an area of the scalp can become…the characteristically totally smooth patch of hairless terrain. The other shows the appearance of finger nail pitting or the ’sandpaper’ appearance  a common condition in many alopecia areata patients.

It’s a small scientific study( 42 patients) putting Bexarotene gel 1% on half the head of alopecia areata patients.  The gel can be irritating and cannot be used if pregnant or getting pregnant.
Some people had some regrowth. Based on this study, the authors think their hypothesis has merit for further study possibly including a placebo.

Here’s the full report.

Intralesional corticosteroid injections continue to be the standard treatment for adults with patchy alopecia < 50% scalp involvement. Filed in October 2009 (clinicaltrials.gov) and not yet recruiting, this study  in Asia proposes to compare steroid injections with Botox injections and compare the results of hair regrowth.

Is there no limit to what will be tried?

Just over 20 years ago (1988)  the Canadian Veterinary Journal  published the report of alopecia areata in a Holstein cow.

Topical tacrolimus (Protopic) has FDA approval and is commonly used for dermatitis and psoriasis. It’s action on T-cells  (types of white blood cells known as lymphocytes) made it a natural for trials on alopecia areata patients, AA also being a T-cell mediated condition. Dr. Kevin McElwee summarizes the results on an AA study and describes where research might next look to further test its effectiveness. Read more…..

User friendly, 22 pages and free (your tax dollars at work).  Order the newly revised Questions & Answers About Alopecia Areata from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH).

The open label, non-randomized efficacy study using Plaquenil (hydrocholroquine) lead by Drs. Hordinsky (University of Minnesota) and Kalish (State University of New York at Stony Brook) was completed in January, 2008.  The clinical trial used 16 patients of both sexes ages 18 and over with severe scalp alopecia areata with and without loss of body hair. Statistical analysis was performed on sections of the scalp to determine if there was any significant regrowth compared to pre-treatment images.

The results are not yet published.

Want to know more about the role of T-lymphocytes, neuropeptides, immunomodulatory agents and a whole lot more basic science?

Here’s a source: Journal of Investigative Dermatology Symposium Proceedings(2004)9,73-78;doi:10.1111/j.1087-0024.2004.00835.x
Autoimmunity: Alopecia Areata
Maria Hordinsky and Marna Ericson, Dep. of Dermatology, University of Minnesota, Minneapolis, Minnesota

The incidence of vitilgo is estimated to be 1% of the US population.
The incidence of people with alopecia areata who also have vitiligo is 3%-8%

Source: Majumder, PP, Das, SKLICC: A genetic model for vitiligo. Am J Hum Gen 43: 119–125, 1988

From the University of British Columbia, noted dermatologist and hair researcher Dr Jerry Shapiro has proposed a clinical trial using intradermal injections of Botox (Botulinum toxin A) to stimulate hair growth in patients with alopecia areata. The proposed  interventional  study is designed as randomized and double blind ( subject and investigator) using a placebo control.

The hypothesis:  that intralesional injections of Botulinum Toxin A can be used as a treatment for AA. Potential points of action of this treatment include changes in neurotransmitters, which either directly or via neuroimmunologic mechanisms influence cytokines (proteins that serve as messengers between cells)  that are responsible for the hair growth arrest in alopecia areata.

From the 2009 annual meeting of the International Society for Stem Cell Research comes a presentation about a tiny study at the University of Cairo (dermatology researcher Marwa Fawzi)  using 8 children with extensive alopecia areata.  At no small cost of pain, here’s what the kids were subjected to: bits of skin with hair follicles were removed, grown in a lab for stem cell multiplication and a month later injected in numerous locations back into bald areas of the scalp.

 

Ouch for an adult! double ouch on a child! Result  6 months later?  5 children had 50% hair increase, 2 had less than 50% and one had none. New skin samples showed that injected stem cells had a stimulating affect on previously dormant follicles. No report of long term results.

 

Why would someone do this study on children? It’s reported that a new study will include 30 children. It’s hard enough to endure the difficulties of a bald childhood without 1) being  subjected to the pain of scalp injections and 2) running  the risk of deep disappointment when scalp hair fails to regrow. 

 

For the well being of children, is this kind of study really “helpful” as this reporter says or a recipe for additional emotional stress?

 

Source

 

 

 

 

 

The future dims further for treatments - another reason why BGDL is passionately helping women live beautifully and successfully today.

Dermatology Times reports on the study by Dr. Bruce Strober of the  New York University Medical Center’s Department of Dermatology who conducted a randomized, double-blind, placebo-controlled 12-week trial with alefacept (Amevive) in patients with chronic severe alopecia areata.

“According to Dr. Strober, trial results were resoundingly unsuccessful. There was no difference between the treated group and the placebo group, and there was a very low level response in both groups.” Click here to read more.

Genes Show Limited Value in Predicting Diseases which also means limited value in new treatments - and this is for common diseases.  So you can imagine how vastly remote genome research  is for a condition like alopecia areata.

Research for alopecia has not been able to accomplish very much that is useful for good treatments. That’s why BGDL depends on your donations of any size to help run programs like our beauty events and lunches that help women today.

Raptiva ( efalizumab) a treatment for moderate to severe plaque psoriasis was the drug to be tested by a Northwestern University clinical trial for use on patients with severe alopecia areata.

No more.

The trial has been cancelled. These warnings on Raptiva for ties to a rare brain infection , PML, (progressive multifocal leukoencephalopathy) were issued by the FDA today.

Incredibly, a prominent alopecia organization website was still as of March 3, 2009  encouraging alopecia areata patients to sign up to be in this now aborted Raptiva clinical trial. It was funded by Genentech with no funding from the NIH.

You gotta ask: how does a clinical trial get that far that it gets approval to proceed with a drug like this on healthy people just wanting to grow hair?  What if it had recruited and someone with alopecia areata had become irreversibly ill?

Update April 8, 2009

Genentech announces the removal of  all Raptiva from the US market.

Click here for Reuters report in the New York Times

From the Cochrane Skin Group, University of Nottingham ( UK)

Authors: Delamere FM,Sladden MM, Dobbins HM, Leonardi-Bee J.

“Authors’ Conclusions: Few treatments for alopecia areata have been well evaluated in randomised trials. We found no RCTs on the use of diphencyprone, dinitrochlorobenzene, intralesional corticosteroids or dithranol although they are commonly used for the treatment of alopecia areata.

Similarly, although topical steroids and minoxidil are widely prescribed and appear to be safe, there is no convincing evidence that they are beneficial in the long-term. Most trials have been reported poorly and are so small that any important clinical benefits are inconclusive. There is a desperate need for large well conducted studies that evaluate long-term effects of therapies on quality of life.”

Abstract of conclusions from  “Interventions for alopecia areata”, Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004413

The clinical trial using alefacept for alopecia areata is completed and the results have been summarized in Skin & Allergy News:  September 2008 ( vol 39, issue 9, page 2). Principal research collaborator is Maria K. Hordinsky, MD.

The purpose of this study was to examine prospectively the safety and efficacy of alefacept in the treatment of subjects with severe alopecia areata of the scalp. Common features between psoriasis and alopecia areata, including immunologic and therapeutic aspects, suggested that alefacept, which has been shown to be a safe and statistically significant beneficial therapeutic modality for the treatment of psoriasis, may have therapeutic value in alopecia areata.

Full text reported in Skin and Allergy News:  Alefacept Fails Alopecia Areata Test

Results abstract:— Alefacept fared no better than placebo in treating chronic, severe alopecia areata in a 12-week double-blind, randomized study of 45 adults. Patients with at least a 6-month history of alopecia areata with 50%–95% scalp involvement were randomized to receive a single weekly intramuscular injection of either placebo or 15 mg of alefacept (Amevive) for 12 weeks, followed by a 12-week observation period.

 It was announced in a press release by Allergan Inc. on 12/3/08 that the drug Lumigan, currently approved to treat glaucoma, is close to FDA approval for cosmetic use as an eyelash growth enhancer for upper lashes - but don’t get excited if you have extensive loss due to AA. It had been discovered in clinical studies that a side effect in glaucoma patients was the growth of longer, darker and fuller lashes. The FDA posted a review of the drug on its Web site Wednesday ahead of a Friday review by an outside panel of medical experts. The advisory panel is being asked to vote on whether it thinks Latisse ( the proposed brand name) should be approved. The FDA usually follows its panels’ advice. If approved, the product would be the first FDA-approved product sold for eyelash enhancement.

Two pilot studies were done with alopecia areata volunteers at the  University of California San Francisco using Lumigan or Xalatan on patients with greater than 50 percent eyelash loss and concluded that it was not effective. No study has yet been done on AA patients with less than 50 percent loss. These pilot studies were a joint effort of the UCSF departments of dermatology and opthalmology with principal investigators Drs. Price and Stamper.

And as with all drugs, there will be risks and the potential for serious side effects in some people.

Click here for FDA briefing documents.