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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
Public Health Service • U.S. Department of Health and Human Services
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National Institute of Arthritis and Musculoskeletaland Skin Diseases NIAMS/National Institutes of Health1 AMS CircleBethesda, MD 20892–3675
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Table of Contents
This booklet contains general information about alopeciaareata (al-oh-PEE-shah ar-ee-AH-tah). It describes whatalopecia is, its causes, and treatment options. Informationis also provided on current research. If you have furtherquestions after reading this booklet, you may wish todiscuss them with your doctor.
What Is Alopecia Areata?
Alopecia areata is considered an autoimmune disease, inwhich the immune system, which is designed to protect thebody from foreign invaders such as viruses and bacteria,mistakenly attacks the hair follicles, the tiny cup-shapedstructures from which hairs grow. This can lead to hair losson the scalp and elsewhere.
In most cases, hair falls out in small, round patches aboutthe size of a quarter. In many cases, the disease does notextend beyond a few bare patches. In some people, hair lossis more extensive. Although uncommon, the disease canprogress to cause total loss of hair on the head (referred to asalopecia areata totalis) or complete loss of hair on the head,face, and body (alopecia areata universalis).
What Causes It?
In alopecia areata, immune system cells called white bloodcells attack the rapidly growing cells in the hair follicles thatmake the hair. The affected hair follicles become small and
drastically slow down hair production. Fortunately, the stemcells that continually supply the follicle with new cells donot seem to be targeted. So the follicle always has the poten-tial to regrow hair.
Scientists do not know exactly why the hair follicles undergothese changes, but they suspect that a combination of genesmay predispose some people to the disease. In those who aregenetically predisposed, some type of trigger—perhaps avirus or something in the person's environment— brings onthe attack against the hair follicles.
Who Is Most Likely To Get It?
Alopecia areata affects an estimated four million Americansof both sexes and of all ages and ethnic backgrounds. Itoften begins in childhood.
If you have a close family member with the disease, your riskof developing it is slightly increased. If your family memberlost his or her first patch of hair before age 30, the risk toother family members is greater. Overall, one in five peoplewith the disease have a family member who has it as well.
Is My Hair Loss a Symptom of a Serious Disease?
Alopecia areata is not a life-threatening disease. It does notcause any physical pain, and people with the condition aregenerally healthy otherwise. But for most people, a disease
that unpredictably affects their appearance the way alopeciaareata does is a serious matter.
The effects of alopecia areata are primarily socially and emo-tionally disturbing. In alopecia universalis, however, loss ofeyelashes and eyebrows and hair in the nose and ears canmake the person more vulnerable to dust, germs, and foreignparticles entering the eyes, nose, and ears.
Alopecia areata often occurs in people whose family membershave other autoimmune diseases, such as diabetes, rheuma-toid arthritis, thyroid disease, systemic lupus erythematosus,pernicious anemia, or Addison's disease. People who havealopecia areata do not usually have other autoimmune dis-eases, but they do have a higher occurrence of thyroid disease,atopic eczema, nasal allergies, and asthma.
Can I Pass It on to My Children?
It is possible, but not likely, for alopecia areata to be inherit-ed. Most children with alopecia areata do not have a parentwith the disease, and the vast majority of parents with alo-pecia areata do not pass it along to their children.
Alopecia areata is not like some genetic diseases in which achild has a 50-50 chance of developing the disease if oneparent has it. Scientists believe that there may be a numberof genes that predispose certain people to the disease. It ishighly unlikely that a child would inherit all of the genesneeded to predispose him or her to the disease.
Even with the right (or wrong) combination of genes, alope-cia areata is not a certainty. In identical twins, who share allof the same genes, the concordance rate is only 55 percent.
In other words, if one twin has the disease, there is only a 55 percent chance that the other twin will have it as well.
This shows that other factors besides genetics are required to trigger the disease.
To learn more about the genes and other factors involved inalopecia areata risk, the National Institute of Arthritis andMusculoskeletal and Skin Diseases (NIAMS) is funding analopecia areata registry. The registry is an organized networkof five centers throughout the United States that will identifyand register patients with the disease and collect data andblood samples (which contain genes). Data, includinggenetic information, will be made available to researchersstudying the genetic basis and other aspects of disease anddisease risk. (For more information about the registry, see"How Can I Take Part In Research?" on page 16.)
Will My Hair Ever Grow Back?
There is every chance that your hair will regrow, but it may also fall out again. No one can predict when it mightregrow or fall out. The course of the disease varies from per-son to person. Some people lose just a few patches of hair,then the hair regrows, and the condition never recurs. Otherpeople continue to lose and regrow hair for many years. Afew lose all the hair on their head; some lose all the hair on
their head, face, and body. Even in those who lose all theirhair, the possibility for full regrowth remains.
In some, the initial hair regrowth is white, with a gradualreturn of the original hair color. In most, the regrown hair isultimately the same color and texture as the original hair.
What Can I Expect Next?
The course of alopecia areata is highly unpredictable, andthe uncertainty of what will happen next is probably themost difficult and frustrating aspect of the disease. You maycontinue to lose hair, or your hair loss may stop. The hairyou have lost may or may not grow back, and you may ormay not continue to develop new bare patches.
How Is It Treated?
While there is neither a cure for alopecia areata nor drugsapproved for its treatment, some people find that medica-tions approved for other purposes can help hair grow back,at least temporarily. The following are some treatments foralopecia areata. Keep in mind that while these treatmentsmay promote hair growth, none of them prevent new patchesor actually cure the underlying disease. Consult your healthcare professional about the best option for you.
•
Corticosteroids—Corticosteroids are powerful anti-
inflammatory drugs similar to a hormone called
cortisol produced in the body. Because these drugssuppress the immune system if given orally, they areoften used in the treatment of various autoimmunediseases, including alopecia areata. Corticosteroidsmay be administered in three ways for alopecia areata:
—
Local injections—Injections of steroids directly
into hairless patches on the scalp and sometimesthe brow and beard areas are effective in increas-ing hair growth in most people. It usually takesabout 4 weeks for new hair growth to become vis-ible. Injections deliver small amounts of cortisoneto affected areas, avoiding the more serious sideeffects encountered with long-term oral use. Themain side effects of injections are transient pain,mild swelling, and sometimes changes in pig-mentation, as well as small indentations in theskin that go away when injections are stopped.
Because injections can be painful, they may notbe the preferred treatment for children. After 1 or2 months, new hair growth usually becomes visi-ble, and the injections usually have to be repeatedmonthly. The cortisone removes the confusedimmune cells and allows the hair to grow. Largeareas cannot be treated, however, because the dis-comfort and the amount of medicine become toogreat and can result in side effects similar to thoseof the oral regimen.
—
Oral corticosteroids—Corticosteroids taken by
mouth are a mainstay of treatment for manyautoimmune diseases and may be used in moreextensive alopecia areata. But because of the riskof side effects of oral corticosteroids, such ashypertension and cataracts, they are used onlyoccasionally for alopecia areata and for shorterperiods of time.
—
Topical ointments—Ointments or creams con-
taining steroids rubbed directly onto the affectedarea are less traumatic than injections and, there-fore, are sometimes preferred for children. How-ever, corticosteroid ointments and creams aloneare less effective than injections; they work bestwhen combined with other topical treatments,such as minoxidil or anthralin.
•
Minoxidil (5%) (Rogaine*)—Topical minoxidil
solution promotes hair growth in several conditionsin which the hair follicle is small and not growing to its full potential. Minoxidil is FDA-approved fortreating male and female pattern hair loss. It mayalso be useful in promoting hair growth in alopeciaareata. The solution, applied twice daily, has beenshown to promote hair growth in both adults andchildren, and may be used on the scalp, brow, and
* Brand names included in this booklet are provided as examples only, and theirinclusion does not mean that these products are endorsed by the National Institutesof Health or any other Government agency. Also, if a particular brand name is notmentioned, this does not mean or imply that the product is unsatisfactory.
beard areas. With regular and proper use of the solu-tion, new hair growth appears in about 12 weeks.
•
Anthralin (Psoriatec)—Anthralin, a synthetic tar-
like substance that alters immune function in theaffected skin, is an approved treatment for psoriasis.
Anthralin is also commonly used to treat alopeciaareata. Anthralin is applied for 20 to 60 minutes("short contact therapy") to avoid skin irritation,which is not needed for the drug to work. When itworks, new hair growth is usually evident in 8 to 12weeks. Anthralin is often used in combination withother treatments, such as corticosteroid injections orminoxidil, for improved results.
•
Sulfasalazine—A sulfa drug, sulfasalazine has been
used as a treatment for different autoimmune disor-ders, including psoriasis. It acts on the immune sys-tem and has been used to some effect in patients withsevere alopecia areata.
•
Topical sensitizers—Topical sensitizers are medica-
tions that, when applied to the scalp, provoke anallergic reaction that leads to itching, scaling, andeventually hair growth. If the medication works, newhair growth is usually established in 3 to 12 months.
Two topical sensitizers are used in alopecia areata:squaric acid dibutyl ester (SADBE) and diphenylcy-clopropenone (DPCP). Their safety and consistencyof formula are currently under review.
•
Oral cyclosporine—Originally developed to keep
people's immune systems from rejecting transplantedorgans, oral cyclosporine is sometimes used to sup-press the immune system response in psoriasis andother immune-mediated skin conditions. But sup-pressing the immune system can also cause problems,including an increased risk of serious infection andpossibly skin cancer. Although oral cyclosporine mayregrow hair in alopecia areata, it does not turn thedisease off. Most doctors feel the dangers of the drugoutweigh its benefits for alopecia areata.
•
Photochemotherapy—In photochemotherapy, a
treatment used most commonly for psoriasis, a per-son is given a light-sensitive drug called a psoraleneither orally or topically and then exposed to anultraviolet light source. This combined treatment iscalled PUVA. In clinical trials, approximately 55 per-cent of people achieve cosmetically acceptable hairgrowth using photochemotherapy. However, therelapse rate is high, and patients must go to a treat-ment center where the equipment is available at leasttwo to three times per week. Furthermore, the treat-ment carries the risk of developing skin cancer.
•
Alternative therapies—When drug treatments fail to
bring sufficient hair regrowth, some people turn toalternative therapies. Alternatives purported to helpalopecia areata include acupuncture, aroma therapy,evening primrose oil, zinc and vitamin supplements,
and Chinese herbs. Because many alternative thera-pies are not backed by clinical trials, they may or maynot be effective for regrowing hair. In fact, some mayactually make hair loss worse. Furthermore, justbecause these therapies are natural does not mean thatthey are safe. As with any therapy, it is best to discussthese treatments with your doctor before you try them.
In addition to treatments to help hair grow, there are mea-sures that can be taken to minimize the physical dangers ordiscomforts of lost hair.
• Sunscreens are important for the scalp, face, and all
exposed areas.
• Eyeglasses (or sunglasses) protect the eyes from
excessive sun, and from dust and debris, when eye-brows or eyelashes are missing.
• Wigs, caps, or scarves protect the scalp from the sun
and keep the head warm.
• Antibiotic ointment applied inside the nostrils helps
to protect against organisms invading the nose whennostril hair is missing.
How Will Alopecia Areata Affect My Life?
This is a common question, particularly for children, teens,and young adults who are beginning to form lifelong goals
and who may live with the effects of alopecia areata formany years. The comforting news is that alopecia areata isnot a painful disease and does not make people feel sickphysically. It is not contagious, and people who have the dis-ease are generally healthy otherwise. It does not reduce lifeexpectancy and it should not interfere with the ability toachieve such life goals as going to school, working, marry-ing, raising a family, playing sports, and exercising.
The emotional aspects of living with hair loss, however, canbe challenging. Many people cope by learning as much asthey can about the disease; speaking with others who arefacing the same problem; and, if necessary, seeking counsel-ing to help build a positive self-image. To address quality-of-life issues for alopecia areata and all other skin diseases, theNIAMS sponsored a scientific meeting in September 2002on the burden of skin diseases.
How Can I Cope With the Effects of This Disease?
Living with hair loss can be hard, especially in a culture thatviews hair as a sign of youth and good health. Even so, mostpeople with alopecia areata are well-adjusted, contentedpeople living full lives.
The key to coping is valuing yourself for who you are, notfor how much hair you have or don't have. Many peoplelearning to cope with alopecia areata find it helpful to talkwith other people who are dealing with the same problems.
More than four million people nationwide have this disease
at some point in their lives, so you are not alone. If you wouldlike to be in touch with others with the disease, the NationalAlopecia Areata Foundation (NAAF) can help through itspen pal program, message boards, annual conference, andsupport groups that meet in various locations nationwide. Tofind contact information for NAAF and other organizationsthat can help people with alopecia areata, see "Where Can ILearn More About Alopecia Areata?" on page 17.
Another way to cope with the disease is to minimize itseffects on your appearance. If you have total hair loss, a wigor hairpiece can look natural and stylish. For small patchesof hair loss, a hair-colored powder, cream, or crayon appliedto the scalp can make hair loss less obvious by eliminatingthe contrast between the hair and the scalp. Skillfullyapplied eyebrow pencil can mask missing eyebrows.
Children with alopecia areata may prefer to wear bandanasor caps. There are many styles available to suit a child'sinterest and mood—some even have ponytails attached.
For women, attractive scarves can hide patchy hair loss; jewelry and clothing can distract attention from patchy hair;and proper makeup can camouflage the effects of lost facialhair. If you would like to learn more about camouflaging the cosmetic aspects of alopecia areata, ask your doctor ormembers of your local support group to recommend a cos-metologist who specializes in working with people whoseappearance is affected by medical conditions.
Is Research Close to Finding Better Treatments
or a Cure?
While a cure is not imminent, researchers are making head-way toward a better understanding of the disease. Thisincreased understanding will likely lead the way to bettertreatments for alopecia areata and eventually a way to pre-vent or even cure it.
Alopecia research ranges from the most basic studies of themechanisms of hair growth and hair loss in mice to testingmedications and ways to apply medications to help regrowhair in people. Both the National Institutes of Health andthe National Alopecia Areata Foundation support researchinto the disease and its treatment. Here are some areas ofresearch that hold promise.
•
Developing an animal model—This is a critical first
step toward understanding the disease, and muchprogress has been made. By developing a mouse witha disease similar to human alopecia areata, researchershope to learn more about the mechanism of the dis-ease and eventually develop immune system treat-ments for the disease in people.
•
Mapping genes—Scientists are studying the possible
genetic causes and mechanism of the disease both infamilies that have one or more persons with the dis-ease and in the general population. An understand-ing of the genetics of the disorder will aid in disease
prevention, early intervention, and development ofspecific therapies.
•
Studying hair follicle development—By studying
how hair follicles form in mouse embryos,researchers hope to gain a better understanding ofhair cycle biology that may lead to treatments for theunderlying disease process.
•
Targeting the immune system—Several new agents
found to be effective in treating psoriasis may proveto be effective in alopecia areata. These drugs workby blocking certain chemical messengers that play arole in the immune response, or by interfering withthe activity of white blood cells (called T-cells) thatare involved in the immune system's attack on hairfollicles. New therapies for treating other autoim-mune diseases like rheumatoid arthritis and lupusmay also benefit patients with alopecia areata.
•
Finding better ways to administer drugs—One
limitation of current topical therapies is getting thedrug to the source of the problem. Scientists are look-ing for a substance that penetrates the fat under theskin to deliver medication directly to hair follicles. In laboratory animals, topically applied synthetic sacs calledliposomes seem to fill the bill. Studies are still neededto show whether liposomes do the same for people.
•
Understanding cytokines—Chemical messengers
called cytokines play a role in regulating the body'simmune response, whether it is the normal responseto a foreign invader such a virus or an abnormalresponse to a part of the body. Researchers believethat by giving certain inflammation-suppressingcytokines, they may be able to slow down or stop the body's abnormal response to the hair follicles.
Because giving the cytokines systemically may causeadverse effects, they believe a topical medicationusing liposomes to get the agents to the root of thehair inside the follicle may be preferable.
•
Understanding stem cell biology—Epithelial stem
cells are immature cells that are responsible forregenerating and maintaining a variety of tissues,including the skin and the hair follicles. Stem cells inthe follicle appear to be spared from injury in alope-cia areata, which may explain why the potential forregrowth is always there in people with the disease.
By studying the biology of these cells, and theirimmediate offspring, which seem to be targeted bythe immune system, scientists hope to gain a betterunderstanding of factors that trigger the disease.
How Can I Take Part in Research?
A good place to start is the National Alopecia Areata Reg-istry sponsored by the NIAMS.
The registry, a network of five centers, will identify and regis-ter patients with the disease and collect information and bloodsamples (containing genes). Data, including genetic informa-tion, will be made available to researchers studying the geneticbasis and other aspects of the disease and disease risk.
The registry is seeking U.S. residents with alopecia areata,alopecia totalis, or alopecia universalis diagnosed by a derma-tologist. Although the registry itself will not be involved inany kind of treatment for alopecia areata, people who registerwill be made aware of studies for which they may qualify.
To take part in the registry, people don't have to live near ortravel to one of the five centers; however, they do have to meetsome requirements to participate. For more information, logonto the registry Web site at www.AlopeciaAreataRegistry.orgor have your doctor contact:
Madeline Duvic, M.D., Principal InvestigatorDepartment of DermatologyM.D. Anderson Cancer Center1515 Holcombe Boulevard, Box 434Houston, TX 77030Phone: 713–792–5999Fax: 713–794–1491E-mail:
[email protected]
Where Can I Learn More About Alopecia Areata?
You can get additional information through the followingorganizations:
National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS)
National Institutes of Health
1 AMS Circle
Bethesda, MD 20892–3675
Phone: 301–495–4484 or
877–22–NIAMS (226–4267) (free of charge)
National Center for Complementary and
Alternative Medicine Clearinghouse
P.O. Box 7923
Gaithersburg, MD 20898
Phone: 301–519–3153 or
888–644–6226 (free of charge)
TTY: 866–464–3615
Fax: 866–464–3616
E-mail:
[email protected]http://nccam.nih.gov
American Academy of Dermatology
P.O. Box 4014
Schaumburg, IL 60168–4014
Phone: 847–330–0230 or
888–462–DERM (3376) (free of charge)
Fax: 847–330–0500
www.aad.org
National Alopecia Areata Foundation
P.O. Box 150760
San Rafael, CA 94915–0760
Phone: 415–472–3780
Fax: 415–472–5343
E-mail:
[email protected]www.naaf.org
American Hair Loss Council
125 Seventh Street, Suite 625
Pittsburgh, PA 15222
Phone: 412–765–3666
Fax: 412–765–3669
www.ahlc.org
Acupuncture—a traditional Chinese system of healing in
which symptoms are relieved by inserting needles beneath
the skin at selected points and then stimulating the points by
rotating the needles or exposing them to heat or electrical
current.
Addison's disease—a condition that occurs when the adren-
al glands (a pair of glands situated on top of the kidneys) fail
to secrete enough corticosteroid hormones. Without treat-
ment, the disease can be fatal.
Alopecia areata—an autoimmune, often reversible disease
in which loss of hair occurs in sharply defined areas usually
involving the scalp or beard, but at times every hair on the
body.
Alopecia areata totalis—a form of alopecia areata character-
ized by the total loss of hair from the scalp and face.
Alopecia areata universalis—a form of alopecia areata in
which all hair on the scalp, face, and body is lost.
Aroma therapy—the therapeutic use of essential oils (highly
concentrated aromatic extracts distilled from a variety of aro-
matic plant materials including grasses, leaves, flowers, nee-
dles and twigs, fruit peels, wood, and roots) to promote the
health of body, mind, and spirit.
Autoimmune disease—a disease that results when the
immune system mistakenly attacks the body's own tissues.
Rheumatoid arthritis and systemic lupus erythematosus are
autoimmune diseases ("auto" means self).
Chemotherapy—the use of strong drugs to suppress the
immune system. Though originally associated with cancer
treatment, chemotherapy is used for many different diseases
involving the immune system.
Corticosteroids—potent anti-inflammatory hormones that
are made naturally in the body or synthetically (man-made)
for use as drugs. They are also called glucocorticoids. The
most commonly prescribed drug of this type is prednisone.
Cyclosporine—a strong drug that suppresses the immune
system. Originally developed to keep the body's immune
system from rejecting transplanted organs, cyclosporine is
being used increasingly in autoimmune diseases, including
(in rare cases) alopecia areata.
Diabetes—a disease in which the body does not produce or
properly use insulin, a hormone that is necessary to convert
sugar, starches, and other food into energy.
Evening primrose oil—the oil of a weedy plant containing
the essential fatty acid gamma linolenic acid (GLA), which
is converted into anti-inflammatory agents by the body.
Evening primrose oil is available as a nutritional supplement
and touted as a pain and inflammation reliever.
Hair bulb—a bulbous collection of actively growing cells
at the base of the follicle that constantly produces a strand
of hair.
Hair follicle—a small cup-shaped structure in the skin
from which hair grows. The cup is lined with cells and
connective tissue.
Immune system—a complex network of specialized cells
and organs that work together to defend the body against
attacks by "foreign" invaders such as bacteria and viruses. In
some rheumatic conditions, it appears that the immune sys-
tem does not function properly and may even work against
the body.
Liposome—a synthetic microscopic globule made of fatty
layers encapsulating drugs or other substances. Liposomes are
often used to deliver substances to the body's cells and tissues.
Pernicious anemia—a potentially dangerous form of ane-
mia, usually caused by an autoimmune process, which
results in a deficiency of vitamin B-12.
Rheumatoid arthritis—an autoimmune disease that
targets primarily the membrane lining the joints, leading
to pain, stiffness, swelling, and joint deformity.
Systemic lupus erythematosus—a chronic autoimmune dis-
ease of the connective tissue that can attack and damage the
skin, joints, blood vessels, and internal organs.
Topical sensitizers—medications that, when applied to the
scalp, provoke an allergic reaction that leads to itching, scal-
ing, and often hair growth. They include squaric acid
dibutyl ester and diphenylcyclopropenone.
The NIAMS gratefully acknowledges the assistance of George Cotsarelis, M.D.,
University of Pennsylvania Medical Center, Philadelphia; Vicki Kalabokes, Nation-
al Alopecia Areata Foundation, San Rafael, CA; Alan Moshell, M.D., NIAMS,
NIH; David Norris, M.D., University of Colorado Health Sciences Center, Denver;
and Vera Price, M.D., University of California, San Francisco, in the preparation of
this booklet. Mary Anne Dunkin was the author of this booklet.
The mission of the National Institute of Arthritis andMusculoskeletal and Skin Diseases (NIAMS), a part of theDepartment of Health and Human Services' National Insti-tutes of Health (NIH), is to support research into the causes,treatment, and prevention of arthritis and musculoskeletaland skin diseases, the training of basic and clinical scientiststo carry out this research, and the dissemination of informa-tion on research progress in these diseases. The NationalInstitute of Arthritis and Musculoskeletal and Skin DiseasesInformation Clearinghouse is a public service sponsored bythe NIAMS that provides health information and informa-tion sources. Additional information can be found on theNIAMS Web site at www.niams.nih.gov.
U.S. Department of Health and Human ServicesPublic Health ServiceNational Institutes of HealthNational Institute of Arthritis and Musculoskeletal and Skin Diseases
NIH Publication No. 03–5143February 2003
Source: http://wrightstatephysicians.org/derm/niams/Alopecia.pdf
How were new medicines discovered?David C. Swinney*‡ and Jason Anthony* Abstract Preclinical strategies that are used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. To investigate whether some strategies have been more successful than others in the discovery of new drugs, we analysed the discovery strategies and the molecular mechanism of action (MMOA) for new molecular entities and new biologics that were approved by the US Food and Drug Administration between 1999 and 2008. Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from the two approaches, respectively — in an era in which the major focus was on target-based approaches. We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.
DEMOCRATIC PEOPLE'S REPUBLIC OF KOREA 2015 HUMAN RIGHTS REPORT See endnote. EXECUTIVE SUMMARY The Democratic People's Republic of Korea (DPRK or North Korea) is an authoritarian state led by the Kim family for more than 60 years. Shortly after Kim Jong Il's death in late 2011, his son Kim Jong Un was named marshal of the DPRK and supreme commander of the Korean People's Army. Kim Jong Un's grandfather, the late Kim Il Sung, remains "eternal president." The most recent national elections, held in March 2014, were neither free nor fair. Authorities maintained effective control over the security forces. Citizens did not have the ability to change their government. The government subjected citizens to rigid controls over many aspects of their lives, including denial of the freedoms of speech, press, assembly, association, religion, movement, and worker rights. The government operated a network of political prison camps in which conditions were often harsh, life threatening, and included forced and compulsory labor. Defectors continued to report extrajudicial killings, disappearances, arbitrary detention, arrests of political prisoners, and torture. The judiciary was not independent and did not provide fair trials. There were reports of female victims of trafficking among refugees and workers crossing the border into China. Forced labor was practiced domestically, through mass mobilizations and as a part of the re-education system. NGOs noted that DPRK foreign contract workers also faced conditions of forced labor. The government made no known attempts to prosecute officials who committed human rights abuses. Impunity was a widespread problem. Section 1. Respect for the Integrity of the Person, Including Freedom from: a. Arbitrary or Unlawful Deprivation of Life There were numerous reports that the government committed arbitrary and unlawful killings.