What is alopecia areata

Alopecia areata is also called autoimmune alopecia, is a common autoimmune skin disease, where  your body’s immune system attacks your hair cells, causing hair loss on the scalp, face and sometimes on other areas of your body. The term alopecia means hair loss. Alopecia areata represent an attack on the hair roots by the body’s own immune system. The hair loss can be total (including facial hair such as the eyelashes and eyebrows) or partial, resulting in a bald spot. Any disorder in which the body attacks its own cells is called an autoimmune disorder, and alopecia areata is an example of this kind of disorder. Alopecia areata affects people of all ages, both sexes and all ethnic groups can develop alopecia areata. Alopecia areata affects as many as 6.8 million people in the U.S. with a lifetime risk of 2.1%. Alopecia areata often first appears suddenly during childhood and young adults with one or more round bald patches appear suddenly, most often on the scalp, but it can be different for everyone who has it. The good news is that with alopecia areata, your hair follicles remain alive and hair can regrow at any time and those affected by alopecia areata sometimes experience regrowth of their hair. Hairs that do grow back often lack color or may be either temporarily or permanently white. This hypopigmentation is not seen in other forms of alopecia.

Key facts

• Alopecia areata is the third most common cause of hair loss.
• The lifetime risk in the general population is 1.7%.
• Alopecia areata represents a T-cell-mediated immune attack on the hair causing bald spots.
• The target allergen is related to melanin. Thus, patients with both black and white hair can preferentially loose the dark hair.
• About half of patients have onset of the alopecia before 15 years of age.
• About 10% of patients have nail changes including pitting, trachyonychia, and longitudinal ridging.
• A study of treatment with intralesional steroid Kenalog (triamcinolone acetonide) concentration showed 2.5 mg/mL to be just as effective as 5 or 10 mg/mL.
• Many studies have found Vitamin D levels to be lower in alopecia areata patients compared to controls.

Complications of alopecia areata

Alopecia areata patients are at risk for psychosocial consequences of their disease, such as depression and anxiety. Psychological support may be beneficial.

Alopecia areata patients should be assessed for atopy, vitiligo, thyroid disease, and other autoimmune conditions.

Figure 1. Alopecia areata

Figure 2. Alopecia areata in children (hair loss involving the eyebrows and eyelashes)

Who gets alopecia areata?

Alopecia areata can affect males and females at any age. Alopecia areata starts in childhood in about 50% of cases and before the age of 40 years in 80%. Lifetime risk is 1–2% and is independent of ethnicity.

• A family history of alopecia areata and/or of other autoimmune conditions is present in 10–25% of patients.
• At least 8 susceptibility genes have been detected.
• Patients with alopecia areata have higher than expected rates of thyroid disease, vitiligo and atopic eczema.
• There is increased prevalence in patients with chromosomal disorders such as Down syndrome.
• It’s possibly drug-induced when arising in patients on biologic medicines.

What is the prognosis for alopecia areata?

In 80% of patients with a single bald patch, spontaneous regrowth occurs within a year. Even in the most severe cases of alopecia totalis and alopecia universalis, recovery may occur at some future date.

Poor prognostic factors include:

• Extensive disease
• Bald patches persisting for more than 1 year
• Ophiasis pattern of hair loss
• Alopecia areata of the nails
• Onset of alopecia areata before puberty
• Family members with alopecia areata
• Personal or family history of other autoimmune diseases
• Down syndrome

New monoclonal antibody biologic agents targeting cytokine pathways offer promise for future treatment of alopecia areata.

Alopecia areata symptoms

Hair loss most commonly occurs on the scalp, but it can also target the eyebrows, eyelashes, beard, and other body sites. Symptoms may include the following:

• Round, patchy areas of non-scarring hair loss, ranging from mild to severe
  • Mild: 1–5 scattered areas of hair loss on the scalp and beard
  • Moderate: More than 5 scattered areas of hair loss on the scalp and beard
  • Severe: loss of all of the hair on the scalp and body
• Scalp burning (without redness), accompanying lesions
• Pitting and ridging of the fingernails

Several clinical patterns are described. More severe disease is associated with young age, concurrent atopic eczema, and chromosomal abnormalities.

Most patients have no symptoms, and a bald patch or thinning hair is noted incidentally, often discovered by a hairdresser. Other patients describe a burning, prickly discomfort in the affected areas—this is known as trichodynia.

Alopecia areata typically presents with round, bald spots on the scalp. The beard, eyebrows, or eyelashes may be affected but it is unusual for isolated lesions elsewhere on the body. One or more may be present at any one time. The exclamation point hair is characteristic and appears as a short terminal hair, tapered at the proximal end. There is no scarring, scale, or other alteration of the scalp skin.

The follicular openings are not lost in contrast to a scarring alopecia.

Patients may rarely go on to lose extensive amounts of hair of the scalp and body, but again, this is unusual. Most patients regrow their hair. The term alopecia totalis refers to patients who have lost all of their scalp hair. The term alopecia universalis refers to patients who have lost all hair on the scalp and body. All nasal hair may be lost and this can lead to increased nasal inflammation and irritation.

A new subtype of alopecia areata called “acute diffuse and total alopecia of the female scalp” has been described where the woman suffers complete hair loss within one month of presentation. The histology is that of alopecia areata except for a significant eosinophilic tissue infiltrate. Fortunately, the vast majority of these women do well with cosmetically acceptable hair regrowth at six months with or without steroid administration.

Patchy alopecia areata

Patch alopecia areata can affect any hair-bearing area, most often the scalp, eyebrows, eyelashes and beard.

Patchy alopecia areata has three stages:

1. Sudden loss of hair
2. Enlargement of bald patch or patches
3. Regrowth of hair

The bald areas may have a smooth surface, completely devoid of hair or with scattered “exclamation mark” hairs.

• Exclamation mark hairs are 2- to 3-mm in length, broken or tapered, with a club-shaped root. Microscopy shows a thin proximal shaft and normal caliber distal shaft.
• Regrowing hairs are often initially coloured white or grey; they may be curly when previously straight.
• It may take months and sometimes years to regrow all the hair.
• One patch can be falling out while another is regrowing.

Alopecia totalis

• Affects up to 5% of patients with autoimmune hair loss
• All or nearly all scalp hair is lost

Alopecia universalis

• Affects less than 1% of cases
• All hair or nearly all hair on the entire body is lost

Ophiasis

• Pattern of alopecia areata affecting occipital and lateral scalp
• Bald area can encircle scalp

Diffuse alopecia areata

• Sometimes called alopecia areata incognita
• Presents with sudden diffuse thinning of scalp hair
• Persisting hair tends to grey, thus descriptions of ‘turning white overnight’
• Positive hair pull test
• May be confused with telogen effluvium or hair loss due to medications

Alopecia areata of the nails

• Nail disease affects 10–50% of those with alopecia areata
• Regular pitting and ridging are the most common findings
• May also cause koilonychia, trachyonychia, Beau lines, onychorrhexis, onychomadesis, onycholysis and red spots on the lunula

Figure 3. Alopecia areata of fingernails (nail pitting)

Alopecia areata causes

Alopecia areata is classified as an autoimmune disorder. It is histologically characterized by T (lymphocyte) cells around the hair follicles. These CD8(+)NK group 2D-positive (NKG2D(+)) T cells release pro-inflammatory cytokines and chemokines that reject the hair. The exact mechanism is not yet understood.

The onset or recurrence of hair loss is sometimes triggered by:

• Viral infection
• Trauma
• Hormonal change
• Emotional/physical stressors

Moreover, sporadic cases of alopecia areata developing during anti-TNF-α therapy have been reported ¹. One third of the cases had a positive (personal or family) history of alopecia areata. Most of presented with rapid extensive alopecia areata, usually involving the ophiasis area. Prognosis was usually poor, with slight response to treatments. In the cases where anti-TNF-α therapy was maintained, the course did not seem to change.

Table 1. Alopecia areata associations

How can alopecia areata be prevented?

Scientists do not yet know how to prevent the onset of alopecia areata.

How is alopecia areata diagnosed?

Alopecia areata is diagnosed clinically. Although usually straightforward, additional tests are sometimes needed to confirm the diagnosis.

• Trichoscopy (use of a dermatoscope to examine hair and scalp)
• Skin biopsy (histopathology)

Alopecia areata treatment

There is not yet any reliable cure for alopecia areata and other forms of autoimmune hair loss. Because spontaneous regrowth is common in alopecia areata, and research has often been of poor quality, the effectiveness of reported treatments is mostly unknown.

• Observation
• Intralesional injection triamcinolone 2.5 mg/cc monthly
• Hydroxychloroquine
• Methotrexate or azathioprine
• Topical immunotherapy with diphenylcyclopropenone (DPCP) and anthralin
• Fexofenadine
• Measure Vitamin D and supplement if low.

Alopecia areata need not be treated as it is a benign condition and regrowth is typical. In fact, spontaneous remission occurs in up to 80% of patients with limited disease within a year. However, alopecia areata often causes great embarrassment and thus therapy is often desired to speed regrowth.

Intralesional steroids, first-line

Individual lesions may be injected with Kenalog (triamcinolone acetonide) every month. This usually induces hair regrowth for isolated areas although atrophy of the skin may occur. The injection should be done into the deep dermal/upper subcutaneous plane using a 30 gauge needle. One may cover several square centimeters of skin with one injection point by fanning out in various directions with the needle and injecting while with drawing. This helps distribute the medication more evenly than multiple small injection points. The maximum dose often cited is 20 mg per month, e.g., 8 mL of 2.5 mg/mL. In a double blind placebo controlled clinical trial comparing injection with 2.5, 5, and 10 mg/mL in alopecia areata of < 50% of the scalp, the 2.5 mg/mL concentration was just as effective as the 5 and 10 ².

Vitamin D

Deficient serum 25(OH)D (calcidiol or 25-hydroxyvitamin D) levels are present in patients with alopecia areata and inversely correlate with disease severity. Thus, screening patients and supplementing, if indicated, seems prudent ³. It would also be reasonable to screen patients for iron and zinc deficiency and supplement as appropriate ⁴.

Topical treatments

Several topical treatments used for alopecia areata are reported to result in temporary improvement in some people. Their role and efficacy are unknown. The hair may fall out when they are stopped. These include:

• Potent or ultrapotent topical steroids
• Minoxidil solution or foam
• Dithranol (anthralin) ointment

Any alopecia areata patient may benefit from a class 1 topical steroid for several months, although the area should be monitored for the development of atrophy. For example, topical clobetasol (given as a foam) grew modestly more hair than placebo in a double blind placebo controlled clinical trial.

Fexofenadine

Some use fexofenadine 120-180 mg/day for adults either as monotherapy or as an adjunct for other therapies. In a retrospective study of extensive alopecia treated with contact immunotherapy, the mean regrowth score of the fexofenadine group was 1.33 and that of the control 0.47 ⁵.

Topical Minoxidil

Minoxidil 5% is recommended by many, but its use is off-label in the US. In one study, topical minoxidil applied twice daily and nightly occluded with petrolatum for 1 year outperformed placebo modestly.

Topical Bimatoprost

A study in which 30 patients applied mometasone cream once daily or bimatoprost 0.03% solution (Lumigan, Allergan, 3 ml) twice daily to two separate patches of alopecia areata found that bimatoprost grew hair sooner and better than mometasone ⁶.

Alopecia Areata in a Child

• First-line 5% minoxidil and topical steroid (e.g., clobetasol, mometasone cream)
• Second-line, if extensive, immunocontact therapy
• Hydroxychloroquine
• Once over 10 years of age, or can tolerate, add intralesional triamcinolone as above
• Oral Tofacitinib did well in 8 patient 12-19 years of age with alopecia universals ⁷.

Alopecia of Eyebrows

• Intralesional steroid injection.
• Topical Bimatoprost.

Intralesional injection of steroid may be done by an ophthalmologist. Forty-one subjects with alopecia areata universalis without ocular disease applied 0.03% bimatoprost to the eyelid margin once a day over the course of 1 year ⁸. 43% of patients had moderate or total regrowth.

One may use intralesional triamcinolone 2.5 mg/mL every month, but the patient must accept the rare risk of ocular complications. For example, intralesional Kenalog (triamcinolone acetonide) 40 mg for vitiligo of the forehead (a much higher dose than would be used for alopecia areata) caused immediate stroke and blindness in a 15-year-old boy ⁹. One patient who had not had eyebrows for 20 years developed reasonable regrowth after several injections.

Intralesional triamcinolone 2.5 mg/mL may be injected every cm–about 0.1 mL per injection. When the patient returns often there is regrowth in tufts. One can then inject in between the tufts.

Treatment Options for Extensive Disease

Hydroxychloroquine

Hydroxychloroquine improved the clinical appearance in 5/9 children after 6 months ¹⁰. Patients were 12-16 years of age. A typical dose was 200 mg twice daily.

Systemic Steroids

Systemic steroids are usually only considered for extensive disease because of potential side effects. Most physicians agree that long-term systemic steroid treatment is not justified because of potential and actual adverse effects. In one study, pulse oral prednisone 300 mg every 4 weeks was used. Otherwise, one may give the steroid daily orally and taper to the lowest effective dose. Alternatively, Kenalog (triamcinolone acetonide) 60 mg intramuscular monthly x 3 may be tried but no more should be given and the patient risks the hair falling out once treatment is stopped.

Azathioprine

In a small study, 14 patients with alopecia universalis were treated with azathioprine 2.5 mg/kg body weight per day. Forty-three percent achieved complete regrowth at a mean of 4.7 months ¹¹ reviewed treatment of 31 patients and found regrowth greater than 50% was observed in 67.7% of patients, with the best responses observed in those with <5 years of disease progression (79%), age over 40 years (73.3%), male patients (72.8%), cumulative dose of methotrexate 1000-1500 mg, and multifocal alopecia areata (93%).

Topical immunotherapy with diphenylcyclopropenone and anthralin

Topical immunotherapy with diphenylcyclopropenone (DPCP) and anthralin of 25 patients with severe alopecia areata resulted in complete regrowth of hair in 72% ¹².

Topical Squaric Acid

The topical application of squaric acid dibutylester induces an allergic contact dermatitis and can grow hair both in adults and children. Various protocols exist, but one common approach is to first do an application on the arm to induce sensitivity and then one month later, start topical application of 5% squaric acid dibutylester on the affected areas of the scalp. Patients return monthly to monitor progress and for reapplication of the 5% if the hair is regrowing. If there is too much reaction (e.g., burning, blistering), the concentration is reduced to 2.5%. If no hair is growing, then the concentration can be increased to 10%.

Short Contact Anthralin

Inducing an irritant contact dermatitis can sometimes cause regrowth. Typically, one has the patient apply 1% anthralin for 1 hour and then wash off. The main side effect is irritation, but that is the goal. Rarely, there can be facial edema, vesicles, blisters, etc., if the reaction is too severe.

Tofacitinib and other JAK Inhibitors

Ninety patients with severe alopecia areata were treated with tofacitinib 5 mg twice daily for 2-3 months initially. Then, non-responders were eligible for pulse prednisone or higher doses of tofacitinib ¹³. Seventy-seven percent achieved a clinical response, with 58% achieving a greater than 50% improvement in SALT score over 4-18 months. There were no serious adverse events.

68% (9/13) pediatric patients with severe alopecia areata experienced clinically significant regrowth of hair in a study using tofacitinib (5 mg twice daily x 5 months) ¹⁴. Most of the patients studied had either alopecia universalis or totalis. No serious side effects were reported.

Topical 2% tofacitinib ointment applied twice daily (topical) had a modest effect, perhaps similar to clobetasol ointment under occlusion ¹⁵.

Oral ruxolitinib (a JAK1 and JAK2 blocker) led to almost complete hair regrowth in 3 alopecia areata patients in 5 months ¹⁶. In another study, 9/12 patients achieved at least 50% regrowth most by 6 months ¹⁷. Also Ruxolitinib-induced reversal of alopecia universalis in a patient with essential thrombocythemia ¹⁸.

Other Therapy

A wig or hair piece may be needed for more extensive disease. Patients with more diffuse hair loss, e.g., alopecia totalis or universalis, may desire more aggressive therapy. Intramuscular triamcinolone 40-60 mg or a tapering course of systemic steroids may be tried although controlled studies are lacking. Cyclosporin has been tried. Topical immunotherapy, with e.g., phenol, has been reported.

Adalimumab did not help alopecia areata in one report but did in another ¹⁹. Apremilast did not help 9 patients with severe alopecia areata ²⁰.

Treatment with platelet-rich plasma was studied in 45 patients with alopecia areata ²¹. Intralesional platelet-rich plasma grew more hair than intralesional triamcinolone 2.5 mg/mL or placebo without significant side effects. The platelet-rich plasma was prepared by drawing the patient’s own blood, centrifuging it for 8 minutes at 70 “G”s, and separating the platelet-rich plasma fraction.

A combination of the lipid lowering agents simvastatin and ezetimibe (which have immunomodulating effects) has been reported to be effective.

There is no convincing data to support the use of methotrexate, sulfasalazine, azathioprine, ciclosporin or phototherapy.

What else should be considered for alopecia areata?

Counselling

Some people with alopecia areata seek and benefit from professional counselling to come to terms with the disorder and regain self-confidence.

Camouflaging hair loss

Scalp

A hairpiece is often the best solution to disguise the presence of hair loss. These cover the whole scalp or only a portion of the scalp, using human or synthetic fibers tied or woven to a fabric base.

• A full wig is a cap that fits over the whole head.
• A partial wig must be clipped or glued to existing hair.
• A hair integration system is a custom-made hair net that provides artificial hair where required, normal hair being pulled through the net.
• Hair additions are fibers glued to existing hair and removed after 8 weeks

Styling products include gels, mousses and sprays to keep hair in place and add volume. They are reapplied after washing or styling the hair.

Eyelashes

Artificial eyelashes come as singlets, demilashes and complete sets. They can be trimmed if necessary. The lashes can irritate the eye and eyelids. They are stuck on with methacrylate glue, which can also irritate and sometimes causes contact allergic dermatitis.

Eyeliner tattooing is permanent and should be undertaken by a professional cosmetic tattooist. The colour eventually fades and may move slightly from the original site. It is extremely difficult to remove the pigment, should the result turn out to be unsatisfactory.

Eyebrows

Artificial eyebrows are manufactured from synthetic or natural human hair on a net that is glued in place.

Eyebrow pencil can be obtained in a variety of colors made from inorganic pigments.

Tattooing can also be undertaken to disguise the loss of eyebrows, but tends to look rather unnatural because of the shine of hairless skin.

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