• Alopecia areata overview - introduction
• Alopecia areata overview - clinical features
• Alopecia areata overview - diagnosis
• Alopecia areata overview - pathology
• Alopecia areata overview - treatment
• Alopecia areata overview - references

Alopecia areata overview - introduction

Alopecia areata (AA) is a non-scarring, inflammatory, hair loss disease that is seen in men, women and children. This condition is commonly manifested by patchy areas of complete hair loss on the scalp and other body parts. In severe cases, alopecia areata can progress to complete loss of all body hair. While not a life threatening condition, Alopecia areata is nevertheless serious because of the psychologically and sociologically devastating effects the hair loss can have on the victim.

The characteristics of the hair loss disease we now know to be alopecia areata (AA) were first described by Cornelius Celsus in 30 A.D. Celsus described two forms of alopecia, using the Greek word alopekia, literally translating as “fox mange”. Alopecia areata has been given many different names throughout history. However, the actual term "alopecia areata" was first used by Sauvages in his "Nosologica Medica", published in the eighteenth century. In past times, alopecia areata was thought to be caused by stress, infectious agents, or hormonal disruption. The hypothesis that the disease is autoimmune in nature and affects genetically susceptible individuals was first mooted in the mid 20th century.

Normally, hair growth in each hair follicle occurs in a cycle. There are three main phases of the hair growth cycle; Anagen, Catagen and Telogen. Anagen is the active growth phase when hair fiber is produced. This is followed by catagen, a period of controlled regression of the hair follicle. Ultimately the hair follicle enters telogen where it is in a so-called resting state.

Alopecia areata primarily affects the hair follicle as it enters the anagen phase. Studies indicate that the initial event in the development of alopecia areata is the premature precipitation of anagen follicles into the telogen state or resting state of the hair follicle cycle. Most commonly, hair follicles exit anagen, enter catagen, and then shed the hair fiber upon entering telogen. The follicles may then proceed back into the next anagen growth phase but, as a result of the continued activity of the disease, produce poor aberrant hair fiber. Such follicles are described as being in a dystrophic anagen state. Some researchers believe the hair follicles continue indefinitely to oscillate between several rapid cycles of dystrophic anagen and telogen states. Others believe many of the follicles are eventually arrested in telogen.

The factors that trigger the onset of alopecia areata and the mechanisms of its development are still shrouded in mystery.

• Autoimmunity: Evidence gathered on the basis of several indirect and direct observations suggest that an immune-mediated pathogenesis is involved in the onset of alopecia areata. The immune system, which is designed to protect the body from virus and bacteria, mistakenly attacks the hair follicles, leading to hair loss.
• Genetic predisposition: Studies show that some people are genetically predisposed towards the development of alopecia areata corroborated by the fact that there is a higher frequency of a family history of alopecia areata in people who are affected.
• Environmental triggers: Vaccines, desensitizing injections, exposure to chemicals can precede alopecia areata development. Some dermatologists suggest general viral or bacterial infections may prompt the immune system into an inappropriate response against hair follicles in susceptible people.
• Stress and anxiety: There have been a number of reports on individual cases where clearly defined sudden stressful events have resulted in abnormal hair loss.
• Abnormal keratinocytes have also been suggested as potential targets in the affected hair follicles.

Alopecia areata overview - clinical features

Alopecia areata can present in many different forms. Most frequently, it develops as a single patch of hair loss a centimeter or two in diameter in any hair-bearing region but more commonly on the scalp. The first one or two patches may expand in size and other patches of hair loss may subsequently develop. Alopecia areata may be manifest as one of several distinct patterns of hair loss:

• Round or oval patches of hair loss
• Loss of all terminal scalp hair (alopecia totalis)
• Loss of all scalp and body hair (alopecia universalis)
• Ophiasis (band-like) pattern of hair loss

Alopecia areata may also develop at particular sites such as skin nevi. Nevi are spots of skin with properties different from surrounding skin, and perinevoid alopecia areata is characterized by alopecia areata like lesions around pigmented nevi.

In early active alopecia areata, the hair cycle is disrupted and there is an abnormal shift in the expected ratio of anagen, telogen and catagen hair follicles. Hairs that fall out appear to have "roots" and are observed to be telogen hairs when examined under the microscope.

Short, 1 to 2-mm fractured hairs can frequently be seen at the active margins of alopecia areata. These hairs are commonly described by the clinician as exclamation-mark hairs because these characteristic hairs fracture at their distal end and taper proximally to a pencil point, giving them the appearance of an exclamation mark. Hairs that are less severely damaged may continue in anagen but produce dystrophic hairs as described earlier.

Alopecia areata commonly affects pigmented hairs and is less able to attack un-pigmented or white hairs. Alopecia areata runs an unpredictable course and may last many years with some re-growth, or it may cycle through expression and remission. In some cases, it may only last for a short period and normal hair growth can be quickly re- established within months. Because of partial telogen-to-anagen conversion, the initial re-growth in alopecia areata may consist of short, white, "fuzzy" hairs.

Some people with alopecia areata may experience changes in hair color during, or after, an episode of hair loss and at times these color changes can be permanent. The phenomena that pigmented hairs are more frequently affected by alopecia areata and that re-growing hair is often initially white are still not explained scientifically.

Anywhere between 10% and 66% of people with alopecia areata also have aberrant nail formation, with nail pitting the most common finding. Several other nail abnormalities such as longitudinal ridging, brittle nails, spotting of the lunulae, (the small crescent-shaped structure or marking at the base of a fingernail that resembles a half-moon), koilonychias (a deformity characterized by concavity of the outer surface of the nail), onycholysis (the separation or loosening of a fingernail or toenail from its nail bed) and onychomadesis (complete shedding of a fingernail or toenail), have been reported. Nail abnormalities can precede, follow or occur concurrently with hair loss.

Alopecia areata overview - diagnosis

At present, there is no conclusive diagnostic test for alopecia areata. Dermatologists deduce alopecia areata by a process of elimination of other hair loss causes and close examination of the lesion itself. Hair pull tests are sometimes conducted at the margins of lesions. For a more definitive diagnosis, dermatologists sometimes need to take a small skin biopsy for microscopic examination to see whether there is focal inflammation of the hair follicles.

The differential diagnosis of alopecia areata includes tinea capitis, traction alopecia, trichotillomania, pressure-related alopecia, and loose anagen syndrome. Some of the cicatricial alopecias such as aplasia cutis and pseudope1ade, and metastatic disease may be confused with alopecia areata. Although most of these conditions can usually be distinguished from alopecia areata by history and clinical examination, in some cases a biopsy may be necessary to confirm diagnosis.

Alopecia areata overview - pathology

Lymphocytic infiltrates and granulomatous inflammation have been observed around late anagen hairs as well as within the hair follicle in the acute progressive stage of alopecia areata. The inflammatory cell infiltrate is primarily composed of activated T lymphocytes, with the presence of CD4, CD8 and Langerhans' cells. The inflammatory infiltrate may also be present above the hair follicle bulb and may invade follicular streamers (stelae), but does not typically invade the bulge area, the region where the arrector pili muscle inserts into the hair follicle and where hair follicle stem cells are situated. This probably explains why follicles are not destroyed in alopecia areata. If the stem cells are still intact, then damage to the hair follicles can be repaired via stem cell proliferation.

Some studies document the presence of eosinophils in all stages of alopecia areata within the fibrous tracts and the peribulbar infiltrate, whereas others have shown evidence of mast cells in addition to the lymphocytic infiltrate. Pigment incontinence may be seen at the apex of the dermal papilla, and some of the pigment may be retained in follicular streamers.

Three different patterns of hair follicle cellular degeneration have been observed in acute alopecia areata, including necrosis, apoptosis, and dark cell transformation. Another type of follicular degeneration described in alopecia areata is a circumscribed cystic change in the supra-bulbar region above the dermal papilla.

Using both light and electron microscopic techniques, most of the nail changes seen in alopecia areata have been found to be related to changes within the proximal matrix.

Alopecia areata overview - treatment

Treatment approach is based on criteria like age and extent of disease. There is no strong evidence to suggest that drug-induced remissions or therapies alter the long term course of alopecia areata. Treatment may promote hair growth, but the underlying alopecia areata is still present. For this reason treatment has to be continued to have a continued hair growth promoting effect. Potentially everyone with alopecia areata is capable of re-growing hair even after many years of hair loss. However, there is no permanent cure for alopecia areata and there is no universally proven therapy for inducing remission.

Corticosteroids are so far the most popular form of treatment for patchy alopecia areata as they are known to exert a strong inhibitory effect on the activation of T lymphocytes. Steroids can be administered in three different ways; topically as a cream or lotion, intralesional as local injections into the bald patches, and systemically either as injections into a muscle or taken orally. Each of these approaches bears different rates of success and side effects.

• Topical creams are available with several different commercial trade names and with different concentrations of steroids. They are applied only to the regions of hair loss and they are the mildest form of steroid treatment. Response to topical steroids in therapeutic trials has been mixed. The risk of systemic absorption and the potential associated side effects must be evaluated during long-term treatment.
• Intralesional steroid injection is an accepted compromise between topical application and systemic administration. It involves the injection of a steroid solution (usually triamcinolone) just below the epidermis, where the associated inflammatory infiltrate is present. It can take up to 2 – 6 weeks before noticeable hair growth develops. Side effects can include pain from the injections and atrophy of the skin around the injection site. This atrophy is usually reversible unless the region has been repeatedly injected over time. Again, there is a risk of associated side effects by way of systemic absorption if injected doses are too high or too frequent. The steroids usually promote a temporary re-growth of hair and subsequent relapse when the treatment is stopped.
• Oral corticosteroid treatment is usually only a treatment of last resort because of the potential for serious side effects. Short term courses of oral corticosteroids called “pulse” treatments are often used in an attempt to limit side effects.
• Some studies indicate that a combination of topical, intralesional and short term oral corticosteroids is effective therapy.

Alopecia areata can be treated with contact sensitizers like diphenylcyclopropenone (DCP) or squaric acid dibutylester (SADBE) in Europe and Canada, though they are not approved for use in the USA. First hair growth is usually visible after 8-12 weeks of initial treatment, and weekly treatments are necessary for complete hair re-growth. Side effects of this kind of treatment include a mild eczematous reaction and enlargement of retroauricular lymph nodes.

Researchers in the field of medicine are striving to determine improved future treatment modalities, which may be immunosuppressive or immunomodulatory in nature. Effective treatment of alopecia areata is currently the subject of several laboratory investigations focusing on biologic drugs, new selective immunosuppressive drugs, and even some initial investigations into gene therapy (though gene therapy for alopecia areata will take many years to develop). Successful testing of the efficacy of the newly developed therapeutic agents in patients with alopecia areata may lead to the introduction of novel therapies for this immune-mediated disease of the hair follicle, or at least define a treatment method that can protect the hair follicle from the injurious effects of inflammation.

Alopecia areata overview - references

• Freyschmidt-Paul P, Happle R, McElwee KJ, Hoffmann R. Alopecia areata: treatment of today and tomorrow. J Investig Dermatol Symp Proc. 2003 Jun;8(1):12-7. PMID: 12894988
• McElwee KJ, Freyschmidt-Paul P, Sundberg JP, Hoffmann R. The pathogenesis of alopecia areata. J Investig Dermatol Symp Proc. 2003 Jun;8(1):6-11. PMID: 12894987
• McElwee KJ, Hoffmann R. Alopecia areata. Clin Exp Dermatol. 2002 Jul;27(5):410-7. PMID: 12190642
• Freyschmidt-Paul P, Hoffmann R, Levine E, Sundberg JP, Happle R, McElwee KJ. Current and potential agents for the treatment of alopecia areata. Curr Pharm Des. 2001 Feb;7(3):213-30. PMID: 11311114
• McElwee KJ, Tobin DJ, Bystryn JC, King LE Jr, Sundberg JP. Alopecia areata: an autoimmune disease? Exp Dermatol. 1999 Oct;8(5):371-9. PMID: 10536963