TITAN II MISSILE VETERANS HEALTH AND WELLNESS

Alopecia Areata from UDMH exposure in animals

Below are the files on alopecia areata and its prevalence in the US population at 0.1% to 0.2%.

This is also a T-Cell connected problem.

Alopecia Areata: eMedicine Dermatology

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eMedicine Specialties > Dermatology > Diseases of the Adnexa

Alopecia Areata

Author: Chantal Bolduc, MD, FRCP(C), Assistant Professor, Department of

Dermatology, University of Montreal

Coauthor(s): Harvey Lui, MD, FRCPC, Professor and Head, Department of

Dermatology and Skin Science, Vancouver General Hospital, University of British

Columbia; Medical Director, The Skin Centre, Lions Laser Skin Centre and

Psoriasis and Phototherapy Clinic, Vancouver General Hospital; Jerry Shapiro,

MD, FRCP(C), Clinical Associate Professor, Department of Medicine, Division of

Dermatology, University of British Columbia, Canada

Contributor Information and Disclosures

Updated: Sep 27, 2010

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Overview

Differential Diagnoses & Workup

Treatment & Medication

Follow-up

Multimedia

References

Keywords

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Learn more Introduction

Background

Alopecia areata is a recurrent nonscarring type of hair loss that can affect any

hair-bearing area. Clinically, alopecia areata can manifest many different

patterns. Although medically benign, alopecia areata can cause tremendous

emotional and psychosocial distress in affected patients and their families.

Pathophysiology

The exact pathophysiology of alopecia areata remains unknown. The most widely

accepted hypothesis is that alopecia areata is a T-cell–mediated autoimmune

condition that is most likely to occur in genetically predisposed individuals.1

Autoimmunity

Much evidence supports the hypothesis that alopecia areata is an autoimmune

condition. The process appears to be T-cell mediated, but antibodies directed to

hair follicle structures also have been found with increased frequency in

alopecia areata patients compared with control subjects. Using

immunofluorescence, antibodies to anagen-phase hair follicles were found in as

many as 90% of patients with alopecia areata compared with less than 37% of

control subjects. The autoantibody response is heterogeneous and targets

multiple structures of the anagen-phase hair follicle. The outer root sheath is

the structure targeted most frequently, followed by the inner root sheath, the

matrix, and the hair shaft. Whether these antibodies play a direct role in the

pathogenesis or whether they are an epiphenomenon is not known.

Histologically, lesional biopsy findings of alopecia areata show a

perifollicular lymphocytic infiltrate around anagen-phase hair follicles. The

infiltrate consists mostly of T-helper cells and, to a lesser extent,

T-suppressor cells. CD4+ and CD8+ lymphocytes likely play a prominent role

because the depletion of these T-cell subtypes results in complete or partial

regrowth of hair in the Dundee experimental bald rat (DEBR) model of alopecia

areata. The animals subsequently lose hair again once the T-cell population is

replete. The fact that not all animals experience complete regrowth suggests

that other mechanisms likely are involved. Total numbers of circulating T

lymphocytes have been reported at both decreased and normal levels.

Studies in humans also reinforce the hypothesis of autoimmunity. Studies have

shown that hair regrows when affected scalp is transplanted onto SCID (severe

combined immunodeficiency) mice that are devoid of immune cells. Autologous T

lymphocytes isolated from an affected scalp were cultured with hair follicle

homogenates and autologous antigen-presenting cells. Following initial regrowth,

injection of the T lymphocytes into the grafts resulted in loss of regrown

hairs. Injections of autologous T lymphocytes that were not cultured with

follicle homogenates did not trigger hair loss.

A similar experiment on nude (congenitally athymic) mice failed to trigger hair

loss in regrown patches of alopecia areata after serum from affected patients

was injected intravenously into the mice. However, the same study showed that

mice injected with alopecia areata serum showed an increased deposition of

immunoglobulin and complement in hair follicles of both grafted and nongrafted

skin compared with mice injected with control serum, which showed no deposition.

In addition, research has shown that alopecia areata can be induced using

transfer of grafts from alopecia areata–affected mice onto normal mice. Transfer

of grafts from normal mice to alopecia areata–affected mice similarly resulted

in hair loss in the grafts.

Clinical evidence favoring autoimmunity suggests that alopecia areata is

associated with other autoimmune conditions, the most significant of which are

thyroid diseases and vitiligo (see History).

In conclusion, the beneficial effect of T-cell subtype depletion on hair growth,

the detection of autoantibodies, the ability to transfer alopecia areata from

affected animals to nonaffected animals, and the induction of remission by

grafting affected areas onto immunosuppressed animals are evidence in favor of

an autoimmune phenomenon. Certain factors within the hair follicles, and

possibly in the surrounding milieu, trigger an autoimmune reaction. Some

evidence suggests a melanocytic target within the hair follicle. Adding or

subtracting immunologic factors profoundly modifies the outcome of hair growth.

Genetics

Many factors favor a genetic predisposition for alopecia areata. The frequency

of positive family history for alopecia areata in affected patients has been

estimated to be 10-20% compared with 1.7% in control subjects.1 The incidence is

higher in patients with more severe disease (16-18%) compared with patients with

localized alopecia areata (7-13%). Reports of alopecia areata occurring in twins

also are of interest. No correlation has been found between the degree of

involvement of alopecia areata and the type of alopecia areata seen in

relatives.

Several genes have been studied and a large amount of research has focused on

human leukocyte antigen. Two studies demonstrated that human leukocyte antigen

DQ3 (DQB1*03) was found in more than 80% of patients with alopecia areata, which

suggests that it can be a marker for general susceptibility to alopecia areata.

The studies also found that human leukocyte antigen DQ7 (DQB1*0301) and human

leukocyte antigen DR4 (DRB1*0401) were present significantly more in patients

with alopecia totalis and alopecia universalis.2,3,4

Another gene of interest is the interleukin 1 receptor antagonist gene, which

may correlate with disease severity. Finally, the high association of Down

syndrome with alopecia areata suggests involvement of a gene located on

chromosome 21.

In summary, genetic factors likely play an important role in determining

susceptibility and disease severity. Alopecia areata is likely to be the result

of polygenic defects rather than a single gene defect. The role of environmental

factors in initiating or triggering the condition is yet to be determined.

Cytokines

Interleukin 1 and tumor necrosis factor were shown to be potent inhibitors of

hair growth in vitro. Subsequent microscopic examination of these cultured hair

follicles showed morphologic changes similar to those seen in alopecia areata.

Innervation and vasculature

Another area of interest concerns the modification of perifollicular nerves. The

fact that patients with alopecia areata occasionally report itching or pain on

affected areas raises the possibility of alterations in the peripheral nervous

system. Circulating levels of the neuropeptide calcitonin gene-related peptide

(CGRP) were decreased in 3 patients with alopecia areata compared with control

subjects. CGRP has multiple effects on the immune system, including chemotaxis

and inhibition of Langerhans cell antigen presentation and inhibition of

mitogen-stimulated T-lymphocyte proliferation.

CGRP also increases vasodilatation and endothelial proliferation. Similar

findings were reported in another study, in which decreased cutaneous levels of

substance P and of CGRP but not of vasoactive intestinal polypeptide were found

in scalp biopsy specimens. The study also noted a lower basal blood flow and

greater vasodilatation following intradermal CGRP injection in patients with

alopecia areata compared with control subjects. More studies are needed to shed

light on the significance of these findings.

Viral etiology

Other hypotheses have been proposed to explain the pathophysiology of alopecia

areata, but more evidence is needed to support them. Alopecia areata was

believed to possibly have an infectious origin, but no microbial agent has been

isolated consistently in patients. Many efforts have been made to isolate

cytomegalovirus, but most studies have been negative.5 Frequency

United States

Prevalence in the general population is 0.1-0.2%. The lifetime risk of

developing alopecia areata is estimated to be 1.7%. Alopecia areata is

responsible for 0.7-3% of patients seen by dermatologists.6,7 International

Worldwide prevalence of alopecia areata is the same as that in the United

States.

Mortality/Morbidity

Alopecia areata is a benign condition and most patients are asymptomatic;

however, it can cause emotional and psychosocial distress in affected

individuals. Self-consciousness concerning personal appearance can become

important. Openly addressing these issues with patients is important in helping

them cope with the condition.

Race

All races are affected equally by alopecia areata; no increase in prevalence has

been found in a particular ethnic group.

Sex

Data concerning the sex ratio for alopecia areata vary slightly in the

literature. In one study including 736 patients, a male-to-female ratio of 1:1

was reported.8 In another study on a smaller number of patients, a slight female

preponderance was seen.

Age

Alopecia areata can occur at any age from birth to the late decades of life.

Congenital cases have been reported. Peak incidence appears to occur from age

15-29 years. As many as 44% of people with alopecia areata have onset at younger

than 20 years. Onset in patients older than 40 years is seen in less than 30% of

patients with alopecia areata.

Clinical

History

The natural history of alopecia areata is unpredictable. Extreme variations in

duration and extent of the disease occur from patient to patient. Alopecia

areata most often is asymptomatic, but some patients (14%) experience a burning

sensation or pruritus in the affected area. The condition usually is localized

when it first appears. Of patients with alopecia areata, 80% have only a single

patch, 12.5% have 2 patches, and 7.7% have multiple patches. No correlation

exists between the number of patches at onset and subsequent severity. Alopecia

areata most often affects the scalp (66.8-95%); however, it can affect any

hair-bearing area. The beard is affected in 28% (males; see first image below),

eyebrows in 3.8%, and extremities in 1.3% of patients (see second image below).

More than one area can be affected at once.

Alopecia areata affecting the beard.

[ CLOSE WINDOW ]Alopecia areata affecting the beard.

Alopecia areata affecting the arms.

[ CLOSE WINDOW ]Alopecia areata affecting the arms.

Localized alopecia areata: Episodes of localized (<50% involvement) patchy

alopecia areata usually are self-limited; spontaneous regrowth occurs in most

patients within a few months, with or without treatment.

Extensive alopecia areata: Extensive (>50% involvement) forms of alopecia

areata are less common. Alopecia totalis or alopecia universalis are reported

to occur at some point in 7% of patients; alopecia areata involving more than

40% hair loss is seen in 11%. The proportion of patients with alopecia totalis

appears to decrease with every decade of life.

In 30% of patients with alopecia totalis, complete hair loss occurred within

6 months after onset of disease. Sharma et al9 reported a mean progression

period to alopecia totalis of 4 months after onset. The natural evolution of

alopecia totalis is unpredictable, but recurrences of alopecia areata (not

necessarily alopecia totalis) are expected.

In a study involving 736 patients,8 the relapse rate was 90% over 5 years.

One percent of children and 10% of adults can experience long-lasting

regrowth. Forty-four percent of children and 34% of adults experience a

significant period of normal or near-normal hair growth. Twenty-two percent

of children and 34% of adults do not experience regrowth.

Associated conditions: Because some of the entities associated with alopecia

areata occur uncommonly in the general population, a large number of patients

with alopecia areata need to be examined to confirm whether an increased

prevalence of these conditions exists among patients with alopecia areata.

Unfortunately, most studies are performed on small groups; therefore, the data

should be interpreted carefully.

Atopic dermatitis is seen in 9-26% of patients with alopecia areata. In the

general population, the prevalence of atopic dermatitis in children in

temperate developed countries varies from 5-20%. In adults, the prevalence

decreases to 2-10%. Some authors have found atopy to be a poor prognostic

factor for alopecia areata.

Vitiligo is seen with an incidence varying from 1.8-3% compared with 0.3% in

control subjects. Also see Vitiligo.

Clinically evident thyroid disease was found in 0.85% of 1700 patients with

alopecia areata.10 The prevalence of thyroid disease determined on a

clinical or laboratory basis varies among studies from 0.85-14.7%. The

incidence of thyroid disease in control subjects is estimated to be 0.17-2%.

The presence of microsomal antibodies is found in 3.3-16% of patients.

Antibodies can be found with or without signs or symptoms of thyroid

disease, but patients with positive autoantibodies have a higher incidence

of functional abnormalities found on thyroid-releasing hormone tests (26% vs

2.8%). The incidence of thyroid microsomal and thyroglobulin antibodies in

control subjects is 7%. Other studies have not supported these results. A

study in 100 patients with alopecia areata failed to find an increased

incidence of circulating autoantibodies, including mitochondrial and

thyroglobulin antibodies.

Collagen-vascular diseases have been found in 0.6-2% of patients with

alopecia areata, while the incidence in control subjects is 0.17%. The

incidence of alopecia areata in 39 patients with lupus erythematous was 10%

in a study by Werth et al,11 in contrast to 0.42% of general dermatologic

patients.

Diabetes mellitus was found to be more common in control subjects (1.4%)

than in patients with alopecia areata (0.4%).12 The occurrence of alopecia

areata may protect against the appearance of type I diabetes mellitus.

However, the incidence of type I diabetes mellitus was significantly higher

in relatives of patients with alopecia areata compared with the general

population.

Alopecia areata is seen in 6-8.8% of patients with Down syndrome, but only

0.1% of patients with alopecia areata have Down syndrome. The high frequency

of alopecia areata in patients with Down syndrome suggests that a genetic

linkage for alopecia areata may exist on chromosome 21.

Anxiety, personality disorders, depression, and paranoid disorders are seen

with increased prevalence varying from 17-22% of patients, and the lifetime

prevalence of psychiatric disorders is estimated to be 74% in patients with

alopecia areata. Psychiatric problems are seen in both children and adults.

No association has been made between the severity of the psychiatric

disorder and that of alopecia areata.

Stressful life events within the 6-month period preceding episodes of

alopecia areata were significantly higher in patients with alopecia areata

compared with patients with androgenetic alopecia or tinea capitis.13 Major

stress factors (eg, death in family) were reported in 12% of patients.

Others associations in some studies include pernicious anemia, myasthenia

gravis, ulcerative colitis, lichen planus, and Candida endocrinopathy

syndrome.

Precipitating factors: A precipitating factor can be found in 15.1% of

patients with alopecia areata. Major life events, febrile illnesses, drugs,

pregnancy, trauma, and many other events have been reported, but no clear

conclusions can be drawn. Despite these findings, most patients with alopecia

areata do not report a triggering factor preceding episodes of hair loss.

Physical

The presence of smooth, slightly erythematous (peach color) or normal-colored

alopecic patches is characteristic. The presence of exclamation point hairs (ie,

hairs tapered near proximal end) is pathognomonic but is not always found. A

positive result from the pull test at the periphery of a plaque usually

indicates that the disease is active, and further hair loss can be expected.

Additionally, hair loss on other hair-bearing areas also favors the diagnosis.

The most common presentation is the appearance of one or many round-to-oval

denuded patches. No epidermal changes are associated with the hair loss.

Alopecia areata can be classified according to its pattern. Hair loss most often

is localized and patchy (see image below).

Patchy alopecia areata.

[ CLOSE WINDOW ]Patchy alopecia areata.

A reticular pattern occurs when hair loss is more extensive and the patches

coalesce. An ophiasis pattern occurs when the hair loss is localized to the

sides and lower back of the scalp (see image below).

Ophiasis pattern of alopecia areata.

[ CLOSE WINDOW ]Ophiasis pattern of alopecia areata.

Conversely, sisaipho (ophiasis spelled backwards) pattern occurs when hair loss

spares the sides and back of the head (see image below).

Sisaipho pattern of alopecia areata.

[ CLOSE WINDOW ]Sisaipho pattern of alopecia areata.

Alopecia totalis occurs with 100% hair loss on the scalp (see image below).

Alopecia totalis.

[ CLOSE WINDOW ]Alopecia totalis.

Alopecia universalis occurs with complete loss of hair on all hair-bearing

areas. Alopecia areata usually is focal; however, it can be diffuse, thereby

mimicking telogen effluvium (TE) or the type of androgenetic alopecia seen in

women (see image below).

Diffuse alopecia areata.

[ CLOSE WINDOW ]Diffuse alopecia areata.

See also Androgenetic Alopecia and Telogen Effluvium.

Dermoscopy

Dermoscopic findings have been reported to be helpful in the diagnosis of

difficult cases of alopecia areata.

The presence of yellow dots seems to be a specific feature of alopecia

areata and has been reported to be present in 95% of patients, regardless of

their disease stages. Following histopathological correlation, these yellow

dots represent degenerated follicular keratinocytes and sebum contained

within the ostium of hair follicles. Although occasionally seen in advanced

male-pattern hair loss, yellow dots are not seen in cases of female-pattern

hair loss, scaring alopecia, or telogen effluvium.

Other dermoscopic signs reported include black dots, tapering hairs, broken

hairs, and clustered short vellus hairs.

Nail involvement

Nail involvement is found in 6.8-49.4% of patients and most commonly is seen

in patients with severe forms of alopecia areata.

Pitting is the most common finding.

Several other abnormalities have been reported (eg, trachyonychia, Beau

lines, onychorrhexis, onychomadesis, koilonychia, leukonychia, red lunulae).

Fingernails predominantly are affected.

Causes

The true cause of alopecia areata remains unknown. The exact role of possible

factors needs to be clarified (see Pathophysiology).

No known risk factors exist for alopecia areata, except a positive family

history.

The exact role of stressful events remains unclear, but they most likely

trigger a condition already present in susceptible individuals, rather than

acting as the true primary cause.