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A. Tosti et al. (eds.)Hair and Scalp Treatmentshttps://doi.org/10.1007/978-3-030-21555-2_9

9. Alopecia Areata: Clinical Treatment

Norma Elizabeth Vazquez-Herrera¹ and Antonella Tosti²

(1)

Tecnológico de Monterrey, Hospital San José, Monterrey, Nuevo León, Mexico

(2)

Fredric Brandt Endowed Professor of Dermatology, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

Antonella Tosti

Email: atosti@med.miami.edu

Keywords

Alopecia areataTreatmentSteroidsClobetasolIntralesional steroidsSystemic steroidsPrednisonePrednisoloneDexamethasonePulse therapyTopical immunotherapySquaric acid2,3-Dyphenylcyclopropenone (DPCP)AnthralinPhototherapyExcimer laserUVA-1UVB-nbCyclosporineMethotrexateAzathioprineSulfasalazineJAK inhibitorsTofacitinibRuxolitinibBaricitinibMinoxidilProstaglandin F2a analogsVitamin D3Ezetimibe/simvastatinPlatelet-rich plasmaFexofenadineEbastineAromatherapyLatanoprostBimatoprostTravoprost

How to Choose the Best Treatment for Your Patient?

There are factors that will guide the clinician to choose the most suitable therapeutic regimen for each patient. Here is a list of important ones to consider:

1.

Age of the patient: Some systemic medications may represent an unjustified risk in the pediatric population. In addition, children have low tolerance to pain and treatment such as intralesional steroids can cause a lot of stress. On the other hand, geriatric patients may use a number of drugs, and clinicians should be aware of possible interactions.
2.

Extent of the disease: While localized disease may improve spontaneously or with local treatments, extensive alopecia usually requires the use of systemic drugs or immunotherapy.
3.

Disease progression: Active and rapidly progressive disease may benefit from more aggressive interventions such as oral steroids or immunosuppressants.
4.

Personal coping with disease: Emotional support increases compliance to treatment. Understanding the patients’ needs will help in choosing the best treatment plan. Dedicating some time to discussing camouflage options, patient support organizations, and psychological/group therapy may provide great help for the patient (Fig. 9.1).
5.

Compliance: Treatment success requires good compliance. Some treatments can be done at home but may require daily application of topicals; other treatments can be done at the office but require frequent visits. Patients and doctor should discuss realistic options.
6.

Cost of medication/insurance coverage: Treatment of alopecia areata is often long lasting, and the disease frequently relapses. This topic is clearly of utmost importance for treatment adherence.

../images/440271_1_En_9_Chapter/440271_1_En_9_Fig1_HTML.jpg — Fig. 9.1

A patient with alopecia areata totalis treated with scalp micropigmentation

Therapeutic strategies must be directed as either immunosuppressive or immunomodulating and may consist of monotherapy or combination therapy. The strategy should be different depending on age and chronicity of the disease. Table 9.1 describes treatment strategies in different cases of alopecia areata, and Table 9.2 describes treatment in special areas (beard, eyebrows, and eyelashes).

Table 9.1

Treatment in alopecia areata in children and adults

Age 0–10 years old	Age > 10 years old
Localized ^a First line: Topical corticosteroids or excimer laser Second line: Topical immunotherapy, anthralin, or phototherapy Extensive ^b First line: Topical immunotherapy, anthralin, or phototherapy Second line: Pulse systemic steroids or topical minoxidil Alopecia areata totalis/universalis First line: Topical immunotherapy or anthralin Second line: Phototherapy	Localized First line: Topical corticosteroids or intralesional corticosteroids Second line: Topical immunotherapy or anthralin Third line: Phototherapy or excimer laser Extensive First line: Topical immunotherapy, anthralin, or phototherapy Second line: Topical corticosteroids with occlusion^c or pulse oral steroids Third line: Oral tofacitinib 5 mg twice a day Alopecia areata totalis/universalis First line: Topical corticosteroids with occlusion^c or topical immunotherapy Second line: Oral tofacitinib 5 mg twice a day Third line: Phototherapy, combination therapy^d

Age 0–10 years old

Age > 10 years old

Localized ^a

First line: Topical corticosteroids or excimer laser

Second line: Topical immunotherapy, anthralin, or phototherapy

Extensive ^b

First line: Topical immunotherapy, anthralin, or phototherapy

Second line: Pulse systemic steroids or topical minoxidil

Alopecia areata totalis/universalis

First line: Topical immunotherapy or anthralin

Second line: Phototherapy

Localized

First line: Topical corticosteroids or intralesional corticosteroids

Second line: Topical immunotherapy or anthralin

Third line: Phototherapy or excimer laser

Extensive

First line: Topical immunotherapy, anthralin, or phototherapy

Second line: Topical corticosteroids with occlusion^c or pulse oral steroids

Third line: Oral tofacitinib 5 mg twice a day

Alopecia areata totalis/universalis

First line: Topical corticosteroids with occlusion^c or topical immunotherapy

Second line: Oral tofacitinib 5 mg twice a day

Third line: Phototherapy, combination therapy^d

^aLocalized: <50% hair loss

^bExtensive: ≥50% hair loss

^c14 or older

dCombination therapy: systemic steroids as induction and corticosteroid-sparing agent/DMARDs

Table 9.2

Treatment alopecia areata affecting beard/eyelashes/eyebrows

Beard	Eyebrows^a	Eyelashes
First line: Topical corticosteroids, topical minoxidil, topical prostaglandin agonists^b Second line: Phototherapy, excimer laser Third line: Topical immunotherapy, anthralin, 2% topical tofacitinib	First line: IL corticosteroids^c, topical corticosteroids, topical minoxidil, topical prostaglandin agonists. Second line: Topical immunotherapy, excimer laser Third line: 2% topical tofacitinib	First line: Topical corticosteroids, topical prostaglandin agonist Second line: 2% topical tofacitinib

Beard

Eyebrows^a

Eyelashes

First line:

Topical corticosteroids, topical minoxidil, topical prostaglandin agonists^b

Second line:

Phototherapy, excimer laser

Third line:

Topical immunotherapy, anthralin, 2% topical tofacitinib

First line:

IL corticosteroids^c, topical corticosteroids, topical minoxidil, topical prostaglandin agonists.

Second line:

Topical immunotherapy, excimer laser

Third line:

2% topical tofacitinib

First line:

Topical corticosteroids, topical prostaglandin agonist

Second line:

2% topical tofacitinib

^aSteroid treatment in eyebrows requires careful application and ophthalmologic monitoring before, during, and after treatment

^bTopical prostaglandin agonists: latanoprost, bimatoprost, and travoprost

^cIL, intralesional corticosteroids, 2.5 mg/mL concentration

Since the cause of alopecia areata is unknown,the authors believe that there is no need for extensive laboratory or imaging studies. Association with dental “foci” or other infections has never been confirmed and screening for autoimmune diseases is not routinely necessary. Parents often ask about the risk of relapses after vaccination; the only vaccine that has been associated with onset of alopecia areata is the hepatitis B vaccine.

Steroids: Topical, Intralesional, Systemic

Topical steroid therapy is the first-line treatment in pediatric patients and in localized alopecia areata of recent appearance in adults. In these cases, we suggest prescribing a high-potency steroid, such as clobetasol propionate 0.05% as gel, foam, or solution. Only in adults, in cases of extensive or acute alopecia areata, high-potency steroids in cream formulation may be used under occlusion at night and rinsed in the morning, at a daily dosage not higher than 2.5 g per day, which corresponds to 5 fingertip units (FTU) [1] (Figs. 9.2 and 9.3).

../images/440271_1_En_9_Chapter/440271_1_En_9_Fig2_HTML.jpg — Fig. 9.2

Hair regrowth with topical potent steroids under occlusion therapy. Note presence of ecchymosis due to scalp atrophy

../images/440271_1_En_9_Chapter/440271_1_En_9_Fig3_HTML.jpg — Fig. 9.3

Severe scalp atrophy in a child treated with long-term topical steroids

One FTU is the amount of topical steroid that is squeezed out from a standard tube along an adult’s fingertip from the very end of the finger to the first crease in the finger and is equivalent to 0.5 g of steroid.

Intralesional corticosteroid therapy is a first-line treatment for localized patchy alopecia in adults and may be used as a third-line alternative in children older than 10 years of age who do not respond to other noninvasive therapies. However, injections are painful and might cause important distress to patients, particularly in children. It can also be used in alopecia areata of the beard and eyebrows (see Chap. 2 for treatment modality). Doses in different steroid presentations are discussed in Table 9.3.

Table 9.3

Intralesional steroid dosing in alopecia areata

	Steroid	Dose	Efficacy
Scalp	TA	2.5–10 mg/cc^a	42.99–92%
	BD	1.25 mg/cc	44.4%
	HA	25 mg/cc
Eyebrows, beard, and other body parts	TA	2.5 mg/cc

TA triamcinolone acetonide, BD betamethasone dipropionate, HA hydrocortisone acetate

^aIn the scalp, a dose of 2.5 mg/cc has been shown to be equally effective to previous higher concentration doses

Look for trichoscopic signs of inflammation (broken hairs, black dots, and exclamation sign hairs) to decide where to inject. Consider the patient unresponsive after 6 months of treatment if there is no regrowth . Side effects include cutaneous atrophy, folliculitis, hypo- or hyperpigmentation, pustules, and telangiectasia (Figs. 9.4 and 9.5). Glaucoma and cataracts may occur when treating periocular areas; thus, ophthalmologic consultation before, during, and after treatment is highly recommended [2–4].

../images/440271_1_En_9_Chapter/440271_1_En_9_Fig4_HTML.jpg — Fig. 9.4

Scalp atrophy after intralesional steroids

../images/440271_1_En_9_Chapter/440271_1_En_9_Fig5_HTML.jpg — Fig. 9.5

Gluteal atrophy after superficial steroid injections

Systemic therapy is a possible option in case of acute rapid progressing alopecia areata. It may also be used in localized but very active cases. Systemic steroids are not a good option in alopecia totalis/universalis as response is poor. Response varies from 11% to 88%, with relapse rates of 28–100%. Side effects associated with pituitary-adrenal axis suppression prohibit long-term treatments; therefore, relapse rates are high. If you choose to use systemic steroids as an initial approach, you need to plan maintenance with other systemic/local treatments with a better safety profile. Pulse therapy is the preferred treatment, but there are no studies comparing results with different steroids or regimens. Always prescribe alendronate, calcium, and vitamin D3 when you prescribe systemic steroids for more than 1 month to prevent osteoporosis.

Tables 9.4, 9.5, and 9.6 summarize the different treatment modalities in systemic steroid therapy (oral, IV, and IM administration).

Table 9.4

Oral steroid therapy

	Scheme	Efficacy	Relapse
Prednisone	5 mg/kg (300 mg) oral prednisone once a month for 3–6 months	82%	0%
Dexamethasone	Dexamethasone 2 mg twice a week for 6 months	75%	16%
Dexamethasone	Dexamethasone 0.5 mg/day for 6 months	37%	75%
Prednisolone	80 mg for 3 consecutive days once every3 months	66%	33%
	300 mg pulses at 4-week intervals	58%	N/A
	200 mg once weekly	34%	25%
	0.5 g daily for 5 days	11%	N/A
	1000 mg pulses (AA totalis and universalis)	42%	N/A

Table 9.5

Intramuscular steroid therapy

	Scheme	Efficacy	Relapse
Triamcinolone	40 mg once a month for 6 months followed by 40 mg once every 1.5 months for 1 year	74%	46%
Triamcinolone	40 mg every 4 weeks for a maximum of 6 months, followed by immunotherapy to reduce relapse	63%	47.11

Table 9.6

Intravenous steroid therapy

		Efficacy rate	Relapse rate
Methylprednisolone	Adults: 500 mg QD or 250 mg BID over a period of 1 hour on 3 consecutive days per month for three courses	20–80%	16.7–100%
Methylprednisolone	Children: 8–20 mg/kg over a period of 1 hour on 3 consecutive days per month for three courses	25–67%	40–81%
Prednisolone	Adults: 100 mg QD on 3 consecutive days per month for three courses	73%	30%
Prednisolone	Adults: 2 g single-dose IV	11%	N/A

Corticosteroid-Sparing Agents/Disease-Modifying Antirheumatic Drug (DMARD)

Since systemic corticosteroids are not recommended for long-term treatment, different corticosteroid-sparing agents may be used. The main action of these agents involves the inhibition of lymphoid proliferation. Cyclosporine (Cya), methotrexate, and azathioprine have shown different levels of efficacy as both monotherapy and combination therapy with systemic steroids. The authors rarely utilize Cya because dosages required to treat alopecia areata are high (6 mg/kg/day), results are not consistent, and the safety profile is a concern. We utilize methotrexate (15 mg a week plus folic acid) in association with systemic steroids, keeping in mind that results from this treatment are not fast. We don’t have personal experience with sulfasalazine, which has been utilized with success in some studies [5–11]. Mycophenolate mofetil and topical calcineurin inhibitors are not effective.

Tables 9.7 and 9.8 summarize different treatment schemes that have been published using monotherapy and combination therapy with cyclosporine, methotrexate, azathioprine, and sulfasalazine.

Table 9.7

Monotherapy with corticosteroid-sparing agents

	Dose	Duration	Efficacy	Relapse	Side effects
Cyclosporine	6 mg/kg/day	3–27 months	50–53%	20–100%	Gastrointestinal symptoms, hypertrichosis, hypertension, weight gain, headache/dizziness, nephrotoxicity
Methotrexate	10–15 mg/week	28 weeks	64–89%	31–73%	Transient elevated transaminases, persistent nausea, and lymphocytopenia
Azathioprine	2.5 mg/kg/day	10 months	43%	14.30%	Diarrhea, elevation of liver enzymes, pancreatitis, and bone marrow suppression
Sulfasalazine	3 g/day	6 months	25.60%	N/A	N/A