Treatment of systemic lupus erythematosus in 2006

Jean Sibilia^a,

^aRheumatology Department, Strasbourg Teaching Hospital-Hautepierre Hospital, 1, avenue Molière, 67098 Strasbourg cedex, France

Received 30 August 2006; accepted 6 September 2006. Available online 11 October 2006.

Abstract

After many barren years, conceptual advances and the introduction of new biotherapies are yielding improvements in the management of systemic lupus erythematosus (SLE). The result is a radical change in the management strategy. The main therapeutic advances rest on new discoveries (or rediscoveries), some of which are original. They can be summarized under 12 headlines.

- Smoking is inadvisable, as it promotes not only atheroma but also lupus flares.

- Hydroxychloroquine and conventional drugs (cyclophosphamide) are helpful provided they are used appropriately.

- Combined oral contraception and hormone replacement therapy may be less hazardous than previously thought, although caution remains in order.

- Drugs used in transplant recipients, such as mycophenolic acid, are generating optimism as treatments for SLE.

- Rituximab and new anti-B-cell drugs hold promise for the treatment of severe SLE.

- Efforts to develop an “etiologic” treatment for SLE based on type 1 (α/β) interferon blockade still face a number of obstacles.

- Peptide vaccines, whose main effect is stimulation of regulator T cells, hold promise—but confirmation is needed.

- Whether TNF antagonists can be used in lupus with skin and joint manifestations or in SLE is generating debate.

- Complement blockade for treating SLE and antiphospholipid syndrome is an attractive avenue of research.

- Numerous new immunotherapy modalities based on modulating intracellular signaling are being evaluated.

- In the most severe forms of SLE, autologous peripheral stem cell transplantation deserves consideration.

- A key component of the treatment of SLE is control of atheroma, which is among the most severe complications.

This rich harvest of new treatment possibilities can be expected to radically modify the prognosis of SLE, whose more aggressive forms remain severe.

Keywords: Systemic lupus erythematosus; Immunotherapy; Biotherapies; Rituximab; Hydroxychloroquine; TNF antagonists

Alopecia areata

Age from 2 years onwards
Have I got the right guidance?
This guidance covers the management of children and adults presenting with alopecia areata.
This guidance does not cover in detail the management of alopecia totalis or alopecia universalis.
There is separate PRODIGY guidance on Fungal (dermatophyte) skin infections and Seborrhoeic dermatitis.
The target audience for this guidance comprises healthcare professionals working within the NHS in England, who are providing first-contact or primary health care. This guidance is intended for use by generalist practitioners, rather than by practitioners with a Special Interest in Dermatology. Patient information leaflets (PILs) are intended to be printed and given to people with this condition. The Shared decision making section is designed to provide a focus for discussion during the consultation about the treatment options.

Changes
Last revised in May 2006
October-December 2005 - written. Validated in March 2006 and issued in May 2006.
Goals and outcome measures

Goals
• To diagnose alopecia areata correctly
• To ensure affected individuals understand the condition and the management options
Outcome measures
• Extent of hair regrowth

Background information
What is it?
• Alopecia areata is a chronic inflammatory condition which affects the hair follicles (and which can also affect the nails). It leads to partial hair loss that most commonly involves the scalp, eyebrows, eyelashes, or beard.
• Hair loss can be categorized by extent or pattern [Madani and Shapiro, 2000]:
o Patchy, limited hair loss is the most common presentation [Madani and Shapiro, 2000].
o Over 50% hair loss is generally considered as 'extensive' [Bolduc and Shapiro, 2001].
o Diffuse hair loss occurs occasionally but this is usually caused by other conditions.
o Alopecia totalis is total loss of scalp hair.
o Alopecia universalis is total loss of body hair.
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• Nail changes are estimated to affect 10-30% of people with alopecia areata, and may be present before, during, or after an episode of hair loss associated with alopecia areata [Papadopoulos et al, 2000; MacDonald Hull et al, 2003].
• Alopecia areata is non-scarring and the destruction of hair follicles is not permanent.
• The exact cause is unknown but the general consensus is that alopecia areata is a manifestation of a T-cell immune-mediated response in genetically predisposed individuals.
• A positive family history is found in up to 25% people with alopecia areata [Mitchell and Krull, 1984; Madani and Shapiro, 2000; BAD, 2004].
• Alopecia areata has been found to be associated with atopy and autoimmune diseases such as pernicious anaemia, thyroid disease (myxoedema), and vitiligo [Mitchell and Krull, 1984; Messenger, 2004].
• Environmental factors, including viral infection and stress, have also been suggested as possible causes but there is only anecdotal evidence to support these claims [Messenger, 2004].

How common is it?
• Alopecia areata is a relatively common condition and it has been estimated that it affects 0.15% of the UK population [Dobbins et al, 2003]. Other national and international estimates of the incidence of alopecia areata vary between 0.05% and 2% [Seiter et al, 2001; BAD, 2004; Messenger, 2004].
• The exact incidence and prevalence are unknown because people with mild disease and people with non-scalp involvement might never go to their doctor [Mitchell and Krull, 1984; Drake et al, 1992].
• Alopecia areata accounts for 2% of new dermatology outpatient clinic appointments in the UK and US [Fiedler and Alaiti, 1996; Madani and Shapiro, 2000; Dobbins et al, 2003].
• Alopecia areata can present at any age but children and adolescents are most commonly affected, with 60% of people developing their first patch before 20 years of age and the peak incidence occurring between 15 and 29 years of age [Madani and Shapiro, 2000; Bolduc and Shapiro, 2001]. People under the age of 16 years account for 20% of cases of alopecia areata [Sharma and Muralidhar, 1998].
• Alopecia areata affects both sexes equally and it is not known to show any racial preponderance [Dobbins et al, 2003; MacDonald Hull et al, 2003].

How do I know my patient has it?
History
• Typically, someone presenting with alopecia areata will report:
o An abrupt onset of patchy hair loss affecting any hair-bearing area (most commonly the scalp, eyebrows, eyelashes, or beard).
o Single or multiple patches of hair loss.
• In the area of hair loss some people will have experienced associated itching, burning, or tenderness.
• Factors which can help to confirm a diagnosis of alopecia areata include:
o Age of the patient
o Previous episodes of hair loss
o Family history
o Presence of atopy/autoimmune disease
• Factors which might suggest an alternative diagnosis include:
o Medical history (including any illness or infection within the past 6 months)
o Drug history
o Hair care routine
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o Diet
Examination
• Signs of alopecia areata (which might not always be present) [MacDonald Hull et al, 2003] include:
o Round, well-circumscribed, bald, and smooth patches on the scalp or within facial hair.
o Normal-coloured or slightly red skin without scarring (follicular markings are still present).
o Exclamation hairs (short broken hairs which taper proximally) might be seen around the the margin of the patches during active disease [Bertolino, 2000].
o Nail changes may occur - pitting, onycholysis (loosening), splitting, beau lines (transverse grooves), koilonychia (concave outer surface), or leukonychia (white patches under the nails) [Drake et al, 1992].
o Scaling may be present but its presence should raise the possibility of an alternative diagnosis (skin scrapings should be taken to exclude a fungal infection such as tinea capitis).
• To identify if there is active hair shedding, the 'pull test' can be performed at the periphery of a lesion. This involves grasping about 60 hairs between the finger and thumb and tugging gently but firmly. This test is positive (confirming active shedding) when 2-10 hairs are obtained [Shapiro and Madani, 1999; Madani and Shapiro, 2000; University of Texas at Austin, 2004].

Investigations
• Investigations are unnecessary in the majority of cases of alopecia areata [MacDonald Hull et al, 2003].
• Routine screening for possible associated autoimmune disease is not justified. However, if clinical signs or symptoms are suggestive of other autoimmune disorders, then further investigations may be appropriate (e.g. diffuse hair loss may be caused by hypothyroidism).
• If the diagnosis is in doubt, investigations that can be performed in either primary or secondary care include:
o Skin scrapings and fungal culture
o Systemic lupus erythematosus and syphilis serology
• Skin biopsies might be carried out in secondary care.

What else might it be?
• The most common differential diagnoses for patchy alopecia areata are tinea capitis and trichotillomania.
o Tinea capitis - a contagious fungal scalp infection mostly found in children (aged 4-14 years), who present with patchy hair loss and often complain of itch and scaling [University of Texas at Austin, 2004]. On examination, patches are irregular with erythema, scaling, and broken hairs, but they do not have the exclamation hairs or nail changes characteristic of alopecia areata. A kerion (a painful, boggy, and inflamed nodule) may be present on the head.
o Trichotillomania - a psychiatric condition which can be associated with obsessive-compulsive disorder, in which people pull their own hair out but often deny it [University of Texas at Austin, 2004]. In children it is more common in boys, but in adolescence it is more common in girls. Hair loss is asymmetrical and has an unusual shape, with broken hairs across the bald patch which are not easily removed. Single or multiple areas can be affected, including eyebrows and eyelashes. There is minimal or no inflammation.
• Other possible causes to consider include:
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o Androgenetic alopecia - there is a typical pattern of balding but shedding is not prominent and the pull test is negative.
o Scarring alopecia in its early stages [MacDonald Hull et al, 2003].
o Traction alopecia - hair loss secondary to hair styling techniques (e.g. tight braids, pony tails).
o Secondary syphilis - a moth-eaten, patchy hair loss is characteristic and appears 2-8 months after the primary syphilitic chancre-type lesions. Serology testing confirms the diagnosis.
o Systemic lupus erythematosus.
• Alopecia areata occasionally presents as diffuse hair loss. Many conditions can cause this but the main differential diagnoses are:
o Telogen effluvium - the most common form of diffuse alopecia. Generalized hair loss over the whole scalp occurs about 3 months after a significant event, such as physical or psychological stress [University of Texas at Austin, 2004]. Bitemporal recession is a common sign in women. Hair loss lasts for 3-6 months and then the hair regrows.
o Anagen effluvium (drug-induced) may mimic diffuse alopecia areata [MacDonald Hull et al, 2003].
o Female androgenic alopecia is the most common cause of diffuse hair loss in women.

Complications
• People with alopecia areata may suffer considerable psychological distress [MacDonald Hull et al, 2003], which can affect socializing and employment.
Prognosis
• Alopecia areata is an unpredictable disease with variable progression, and hair recovery may be complete, partial, or non-existent.
• The following stages of disease progression may be experienced:
o A single patch of hair loss which regrows in a few months, although hair loss may recur and most people have more than one episode of alopecia areata.
o Following the initial lesion, further patches can develop in the next 3-6 weeks; patches may become confluent if there is diffuse loss of other hair.
o There can be patches of regrowth at the same time as new patches are developing.
o When hair regrows it is initially fine and depigmented (white) before it returns to its original colour. Note: if regrowth of hair remains white it is important to consider vitiligo.
• In people with less than 40% or mild hair loss, if they receive no treatment, regrowth can be expected within in 1 year in up to 80% of people, as the condition is usually self-limiting [Bolduc and Shapiro, 2001; MacDonald Hull et al, 2003]. Therefore, the smaller the area of hair loss, the better the prognosis.
• Overall, 34-50% of people with alopecia areata recover in 1 year; almost all people with the condition experience more than one episode; and 14-25% progress to alopecia totalis or alopecia universalis [Ikeda, 1965; MacDonald Hull et al, 2003].
• A poor prognosis is associated with:
o Atopy
o Childhood-onset alopecia areata
o Chronic and extensive alopecia areata
o Down's syndrome
o Eyelash and/or eyebrow hair loss
o Family history of alopecia areata
o Ophiasis (alopecia areata of the scalp margin)
o Nail changes
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o Presence of other autoimmune disease

Management issues
Overview of management
• Exclude tinea capitis (especially in children) and trichotillomania.
• Establish whether hair loss is extensive or non-extensive (i.e. greater than or less than 50%) - we only recommend management options for hair loss on the scalp or face.
• Explain that alopecia areata is difficult to treat successfully and that hair loss is unpredictable, although in many cases the condition is self-limiting.
• In children and adolescents up to 16 years of age, unless the primary care professional is confident in managing this population, PRODIGY recommends that specialist advice should be sought before starting topical treatment.
• Consider referral for counselling and support, especially in people where visible hair loss is causing psychological distress.
• Consider primary care options, but referral to a dermatologist for consideration of secondary care options (e.g. intralesional corticosteroids, topical immunotherapy) may be more appropriate.
• In people with non-extensive alopecia areata (less than 50% hair loss), management options include:
o Watchful waiting with provision of reassurance (as spontaneous remission can occur after 3 months).
o Referral to dermatology for the consideration of intralesional corticosteroids.
o Topical corticosteroid or topical minoxidil in primary care if the person:
􀂃 Is waiting for referral
􀂃 Declines referral and only wants treatment in the primary care setting
• In people with extensive alopecia areata (more than 50% hair loss), alopecia totalis and alopecia universalis, management options include:
o Early referral to dermatology (topical immunotherapy is an effective treatment, but many dermatologists will not provide immunotherapy unless the risk/benefit assessment is favourable).
o Use of a topical corticosteroid or topical minoxidil in primary care while waiting for referral (although evidence of their effectiveness is limited in extensive hair loss).
o Watchful waiting, though spontaneous remission after 3 months is less likely than in people with non-extensive alopecia areata.
• Wigs may be a desirable option for some people (especially women). Advice on the different types
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of wigs available should be provided, but wigs can only be prescribed in secondary care.
• We are unable to make any recommendations on the use of alternative and complementary therapies (e.g. aromatherapy, massage, or relaxation) as there is insufficent published evidence of their use in people with alopecia areata.

What assessment do I need to make in somone with alopecia areata?
• An assessment should be made that includes the following:
o Age of the person
o Pattern and extent of the hair loss
o Rate of hair loss and duration of symptoms
o Previous episodes of hair loss and any treatment used
o The person's ideas, concerns, and expectations about the condition
o Psychological issues (e.g. any associated depression)
• Examination should include:
o Hair assessment - patch location and extent
o Pull test (to identify if there is active hair shredding and if further hair loss is likely)
• Estimating hair loss is useful to guide management [Olsen et al, 1999] and this can be done using several different methods, such as:
o Dividing the scalp into quarters
o Using a visual scale as an aid
• To identify if there is active hair shedding, the pull test can be performed at the periphery of a lesion. This involves grasping about 60 hairs between the finger and thumb and tugging gently but firmly. The test is positive (confirming active shedding) when 2-10 hairs are pulled out and this suggests that more hair loss can be expected [Shapiro and Madani, 1999; Madani and Shapiro, 2000; University of Texas at Austin, 2004].

What information should I give my patient with alopecia areata?
• Alopecia areata is an unpredictable condition, there is no satisfactory treatment, and it is difficult to treat successfully.
• Give reassurance, as non-extensive alopecia areata is often self-limiting and therefore a viable option is to 'watch and wait'. Extensive alopecia areata is less likely to be self-limiting than non-extensive alopecia areata.
• Hair regrowth may not be seen for at least 3 months, so if natural improvement is going to occur, it will often take time.
• Alopecia areata will have no effect on general health but can cause psychological distress.
• Drug treatment aims to induce hair growth, not cure it.
• If treatment is the preferred option, discuss the benefits and risks of each available option with the person.
• Topical treatments: if experimenting with the use of a topical preparation, try a corticosteroid for at least 3 months or minoxidil for 6 months. Note: it may take at least 3 months for hair to show any signs of regrowth, irrespective of whether the treatment has been effective or not.
• Intralesional corticosteroids are the most effective treatment for non-extensive hair loss but administration may be painful (they are not usually used in children as they are not well tolerated). Note: corticosteroids may be injected using a Dermo-Jet needle-less injector to minimize pain.
• Topical immunotherapy is the most effective treatment for extensive hair loss. However, it requires commitment in order to comply with the treatment episode and many dermatologists will not provide immunotherapy unless the risk/benefit assessment is favourable. 6
• When hair regrows it is initially fine and depigmented (white) before it returns to its original colour - inform people that hair can be dyed if it is slow to pigment.
• On sunny days, sunblock or a hat should be used to protect bald patches.
Counselling
• Alopecia areata can be a very distressing condition and has a number of psychological implications for people, especially children. They should have adequate counselling to explain the nature of the disease, its likely course, and the high rate of spontaneous remission.
o Some people may benefit from referral for counselling and support if hair loss is causing psychological distress.
o Affected individuals or parents of affected children often want a specialist opinion and this wish should be respected, even if the specialist has no more to offer in terms of treatment.
• All treatment options should be explained, along with their adverse effect profile. People need to be aware that alopecia areata itself will not damage their general health but that treatments may be toxic and potentially time-consuming.
• Support groups are available (for more information, see the Patient Information Leaflet).
How should I manage an episode of alopecia areata?
• Alopecia areata is difficult to treat successfully and recommended treatments aim to induce hair growth rather than cure the underlying cause [Madani and Shapiro, 2000].
• The following need to be taken into consideration when managing alopecia areata:
o Age - in children and adolescents up to 16 years of age, unless the primary care professional is confident in managing this population, PRODIGY recommends that specialist advice should be sought before starting a topical corticosteroid.
􀂃 Note: with children, secondary care use of intralesional corticosteroids is limited due to potential pain around injection sites, and the use of topical immunotherapy is controversial.
o Extent of hair loss - treatment selection will depend on whether there is extensive alopecia areata (more than 50% hair loss) or non-extensive alopecia areata (less than 50% hair loss).
o Patient preference for treatment method.

When should I consider referral?
• Consider specialist referral in the following situations:
o Diagnostic uncertainty
o Extensive disease, including alopecia totalis and alopecia universalis
o Pregnant or breastfeeding women
o If secondary care treatments are more appropriate
o If topical treatment initiated in primary care is not effective
o If a wig is required
Non-extensive alopecia areata (less than 50% hair loss)
• Many people with non-extensive alopecia areata experience a spontaneous remission, so consider giving no treatment as an option [Madani and Shapiro, 2000]. People should be advised that initial hair regrowth may not be seen for up to 3 months.
• If treatment is preferred: 7
o There is evidence that intralesional corticosteroids (ILCs) are the most effective treatment for non-extensive alopecia areata. For cosmetically unacceptable patches of hair loss, such as eyebrow involvement, ILCs may be the most suitable treatment option.
􀂃 Referral to a dermatologist is required [MacDonald Hull et al, 2003].
􀂃 See What treatments are not recommended for use in primary care? for more information.
o There is limited evidence to support the use of a topical corticosteroid, but it may be worth trying one in:
􀂃 Adults over 16 years of age (who are either waiting for referral or who have declined referral and want treatment in primary care only).
􀂃 Children, after discussion with a dermatologist where appropriate (ILC use is controversial as it is not well tolerated).
o There is limited evidence to support the use of topical minoxidil, but it may be worth trying in:
􀂃 Adults over 16 years of age who decline ILC treatment.
􀂃 Note: many experts do not recommend the use of minoxidil in children and adolescents under 16 years of age.
• Consider the need for counselling and psychological support, especially in people in whom areas of visible hair loss are causing psychological distress.

Topical corticosteroids
• Corticosteroids act as an immunosuppressant and topical preparations are widely used in alopecia areata.
• In primary care, where treatment options are limited in people with alopecia areata, topical corticosteroids may be worth trying (for more information, see Medicines management), although there is little good-quality evidence to support their use [Madani and Shapiro, 2000; Bolduc and Shapiro, 2001]. Of the trials that have been published, the drug or strength of corticosteroid used is often not available in the UK.
• In children and adolescents up to 16 years of age, unless the primary care professional is confident in managing this population, PRODIGY recommends that specialist advice should be sought before starting a topical corticosteroid.
• When treating adults over 16 years of age, the expert advice is to use a potent topical corticosteroid.
• Topical corticosteroids should be used continuously for at least 3 months before regrowth can be expected [Fiedler, 1992; Fiedler and Alaiti, 1996; Papadopoulos et al, 2000; Bolduc and Shapiro, 2001]. Hair loss may flare up despite treatment with a corticosteroid, but hair loss is minimized [Fiedler and Alaiti, 1996].
• When prescribing topical corticosteroids in primary care:
o Do not change any single treatment sooner than 3 months after starting treatment, as regrowth may first become evident at this time.
o Up to 6 months is a reasonable time for a trial of a treatment - if there is no response after 6 months an alternative treatment can be tried [Drake et al, 1992; Bertolino, 2000]. Note: cosmetic regrowth can take up to 1 year.
o A potent corticosteroid can be applied to the scalp because the thick skin reduces the penetration of the corticosteroid and hence its effectiveness. Note: this should still be applied for the minimum time necessary.
o For more information, see Medicines management.
• Some experts recommend combining a topical corticosteroid with topical minoxidil because the topical application of either agent alone might not be effective [Bolduc and Shapiro, 2001]. See What is the evidence for combining topical corticosteroid and topical minoxidil application? 8

Topical minoxidil
• Minoxidil is a peripheral vasodilator, originally used as an antihypertensive drug.
• Topical minoxidil solution is an option in primary care, although treating alopecia areata represents an off-licence use of minoxidil. The majority of experts do not recommend the use of minoxidil in children and adolescents under 16 years of age.
• Topical minoxidil is not available on the NHS - 2% and 5% strengths can be prescribed privately or are available for purchase over the counter with a recommendation from a medical practitioner.
• When prescribing topical minoxidil in primary care:
o If tolerated, it is best not to change the treatment sooner than 3 months after starting treatment as regrowth may first become evident at this time.
o Six months is recommended as a reasonable time for a trial of minoxidil, although there is little good-quality evidence to support its use - if there is no response after 6 months an alternative treatment can be tried [Drake et al, 1992; Bertolino, 2000]. Note: cosmetic regrowth can take up to 1 year.
o Stop minoxidil use if the hair regrows, as the likelihood is that this is a result of the natural history of the condition rather than the treatment. In some people, relapse will occur after discontinuing minoxidil and so further treatment courses and reassessment may be appropriate.
o For more information, see Medicines management.
• It may take 2-3 months for an initial response [Fiedler, 1992] and 1 year for a maximum response. A cosmetic response is maintained with continued total scalp application, although small patches of alopecia areata may redevelop [Fiedler and Alaiti, 1996].
• Some experts recommend combining topical minoxidil with a topical corticosteroid because the application of either alone might not be effective [Bolduc and Shapiro, 2001]. See What is the evidence for combining topical corticosteroid and topical minoxidil application? for more information.
Extensive alopecia areata (more than 50% hair loss), alopecia totalis and alopecia universalis
• Some people with extensive alopecia areata may experience spontaneous remission but, in general, the prognosis is poor [Madani and Shapiro, 2000].
• Early referral to a dermatologist is appropriate (unless the person does not want this). With increasing extent of hair loss, treatment preferences change. There is some evidence that topical immunotherapy (in the secondary care setting) is the most effective option for people with extensive alopecia areata [MacDonald Hull et al, 2003]. However, many dermatologists will not provide immunotherapy unless the risk/benefit assessment is favourable.
• There is no convincing evidence that topical corticosteroids or topical minoxidil are effective in people with extensive hair loss, but they may be considered in:
o People who are waiting for referral
o People who decline referral and only want treatment in primary care
• Consider the need for counselling and psychological support, especially in people where visible areas of hair loss are causing psychological distress.
• Wigs are a common treatment choice in people with alopecia areata. They can either be obtained on the NHS (via secondary care) or bought privately. For more information, see What treatments are not recommended for use in primary care?

How should I manage a relapse of alopecia areata?
• If a treatment has worked before, try that treatment again; similarly, avoid treatments that have not worked previously.
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• Consider prompt referral, as treatment with intralesional corticosteroids may help prevent progression.
What treatments are not recommended for use in primary care?
• Intralesional corticosteroids (ILCs) - there is evidence that this is the most effective treatment for non-extensive alopecia areata but referral to a dermatologist is required. ILCs are also the preferred treatment when the hair loss is in a cosmetically sensitive area (e.g. eyebrows) [MacDonald Hull et al, 2003].
• Topical immunotherapy - there is some evidence that topical immunotherapy (a secondary care treatment) is the most effective option for people with extensive alopecia areata [MacDonald Hull et al, 2003]. However, many dermatologists will not provide immunotherapy unless the risk/benefit assessment is favourable.
• Other treatment options for alopecia areata that are not recommended for use in primary care but which might be used in secondary care include:
o Topical dithranol
o Topical or systemic PUVA (psoralen plus ultraviolet A light)
o Oral corticosteroids
o Oral ciclosporin
o Oral minoxidil
o Wigs
o Dermatography
• Topical dithranol needs to be applied sufficiently frequently and in a high enough concentration to produce a brisk irritant reaction to be effective. Administration is cumbersome (it is applied at night to the whole scalp if the disease is widespread and left for 20-60 minutes prior to shampooing) and staining of clothes, skin, and fair hair can be a problem. A cosmetic response has been reported in 20-30% of people with non-extensive alopecia areata [Fiedler and Alaiti, 1996; Madani and Shapiro, 2000] and this may take up to 60 weeks to achieve.
• PUVA - this treatment has been suggested as being beneficial in alopecia areata [Fiedler and Alaiti, 1996]. Two to three treatments a week are required and the time to response is 20-40 sessions. A maximum response is generally achieved within 1 year, although variable responses and high relapse rates have been reported [Healy and Rogers, 1993; Madani and Shapiro, 2000]. However, PUVA is an unsatisfactory treatment option because of its adverse effect profile (nausea, pigment changes, risk of skin cancer).
• Oral ciclosporin is effective in extensive alopecia areata but its use is limited due to its adverse effect profile, and relapse occurs after discontinuation of treatment [Fiedler and Alaiti, 1996; Shapiro et al, 1997].
• Oral corticosteroids are not recommended for alopecia areata. Although there is some evidence that they are effective, the risks associated with their use outweigh any benefits. [Olsen et al, 1992; Perriard-Wolfensberger et al, 1993; Sharma and Muralidhar, 1998; Seiter et al, 2001].
• Oral minoxidil is not recommended for people with alopecia areata. Although there is some evidence that it is effective, the safety risks outweigh any benefits [Fiedler and Alaiti, 1996].
• Dermatography (tattooing) can be used to simulate eyebrows. One study with a 4-year follow-up showed that 77% had excellent results and 8% had good results with a cosmetic approach [Bolduc and Shapiro, 2001]. Two to three dermatography sessions lasting 1 hour are usually required.
• Wigs are a common treatment choice in patients with alopecia areata. They can be obtained on the NHS or bought privately.
o Acrylic wigs are cheaper than real hair, costing about £60 to £200, and are easier to look after. They can be itchy and hot and require frequent replacement.
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o Real-hair wigs are a better fit and are more socially acceptable, but are they are considerably more expensive than acrylic wigs. They last for 3-4 years but require more maintenance.
o NHS wigs can only be prescribed in secondary care. People who are categorized under certain NHS exemptions may be entitled to two subsidized wigs a year, but people will only qualify for a human-hair wig on prescription if they are allergic to acrylic or have a skin condition requiring the use of human-hair wigs [MacDonald Hull et al, 2003].

Complementary and other treatments
• Many other treatment modalities (e.g. aromatherapy, acupuncture and massage, and relaxation) have been used for alopecia areata but there is insufficient evidence on their efficacy for us to make any recommendations.
• For more information, see What is the evidence for complementary therapies and other treatments in alopecia areata?

Medicines management
Corticosteroids
Which topical corticosteroids and formulations are recommended for alopecia areata?
• Which formulation of corticosteroid?
o Topical gels, lotions, and scalp applications are formulated for use on hair-bearing areas such as the scalp, and expert opinion considers that these formulations are more user-friendly (easier to use, easier to wash out, and may cause less irritation).
o However, some dermatologists may prefer a different formulation (e.g. an ointment may be preferred where a more occlusive effect is required), and if a specific formulation is preferred by an individual patient, then it is important to take this into consideration too.
• In children and adolescents up to 16 years of age, PRODIGY recommends that specialist advice should be sought before starting a topical corticosteroid, unless the primary care professional is confident in managing alopecia areata in this population.
o Many dermatologists are happy to advise a short-term trial (2-3 months) of a topical corticosteroid of high potency in children.
• In adults, a potent topical corticosteroid is recommended (in line with expert opinion) and prescriptions for the following are included:
o Betamethasone dipropionate 0.05% lotion
o Betamethasone valerate 0.1% lotion
o Betamethasone valerate 0.1% scalp application
o Betamethasone valerate 0.12% foam
o Fluocinolone acetonide 0.025% gel
o Hydrocortisone butyrate 0.1% lotion
o Hydrocortisone butyrate 0.1% scalp application
o Mometasone furoate 0.1% scalp application
• Note: the alcohol content of these products varies and if someone reacts to one product, then it might be worth trying another preparation.

How should topical corticosteroroids be applied?
• In people with non-extensive alopecia areata, expert advice is to apply topical corticosteroids to the affected area only, rather than to the whole scalp.
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• Scalp - a potent corticosteroid can be used because the thick skin reduces the penetration of the corticosteroid and hence its effectiveness. Topical corticosteroids should still be applied sparingly however. Any fingertips and hands that have been in contact with the corticosteroid should be washed.
• Beard area - a moderately potent corticosteroid may be the most appropriate to use here because of the increased risk of skin atrophy.
• Eyebrows and eyelids - referral to secondary care is required for management. Topical corticosteroids should not be applied to these areas in primary care unless advised by a specialist.
• When applying topical corticosteroids to an area of alopecia areata, the surrounding hair should be dry.
• How much topical corticosteroid should be applied? As a practical guide, the quantity of solid-formulation topical corticosteroid to apply is often expressed in terms of fingertip units (FTUs) [MeReC, 1999]. Note: this is of no relevance to the use of scalp applications or topical lotions.
o One FTU is roughly equivalent to the amount of cream or gel that can be squeezed from a tube with a standard nozzle onto an adult index finger from the tip of the finger to the first crease.
o FTUs should be used together with body charts that show the number of FTUs required to cover each area of a child's or adult's body.
o As a rough guide, one FTU of topical corticosteroid is sufficient to treat a skin area about twice the size of the flat of the hand with the fingers together.
• When treating alopecia areata affecting the scalp, occlusion (e.g. a shower cap) can be used at night, and is recommended by some experts.
• Stop corticosteroid use if the hair regrows, as the likelihood is that this is due to the natural history of the condition.
• If there is no response after 3 months, reassess the management options.
What are the key contraindications and adverse effects of topical corticoteroids?
• Topical corticosteroids should be avoided in pregnant or breastfeeding women.
• Topical corticosteroids can exacerbate some conditions and so they are contraindicated [BNF 50, 2005] in people with areas of alopecia areata that are also affected by:
o Untreated bacterial, fungal, or viral skin lesions
o Acne
o Perioral dermatitis
o Plaque psoriasis
• If signs of hypersensitivity appear, application should be stopped immediately.
• Adverse effects of topical corticosteroids can be divided into localized effects (e.g. skin atrophy, exacerbation of skin infection, and acne at the site of application) and systemic adverse effects (e.g. hypophyseal-pituitary-adrenal [HPA] suppression).
o Reversible hypertrichosis on the face and neck may develop in young children [Fiedler and Alaiti, 1996].
• The risk of adverse effects is related to the potency of the topical corticosteroid, duration of use, and area of application (e.g. thin skin on the face) [BNF 50, 2005]. Adverse effects are most likely with potent or very potent topical corticosteroids when used in large quantities for prolonged periods.
• People should be advised that alcohol-based formulations are flammable, and that they must be allowed to dry naturally. People should not use a hairdryer and must keep away from open fires, flames, and cigarettes while the lotion is on.
• All people using topical corticosteroids in the medium to long term should be monitored for adverse effects, and children using long-term topical corticosteroids should have their growth curve monitored [Fiedler, 1992].
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Minoxidil
What is the availability of minoxidil?
• Topical minoxidil 2% and minoxidil 5% solutions have to be prescribed privately for alopecia areata as they can neither be prescribed on the NHS nor purchased over the counter (for alopecia areata).
• Over-the-counter topical minoxidil solution is only licensed for alopecia androgenetica, and therefore cannot be sold for alopecia areata, which is an off-licence use of the drug.
How should minoxidil be applied?
• Most experts do not recommend the use of minoxidil in children and adolescents under 16 years of age.
• In people with non-extensive alopecia areata, expert advice is to apply topical minoxidil to the affected area only.
• A dose of 1 ml minoxidil solution should be applied to the patch(es) of hair loss twice a day - the hair and scalp should be thoroughly dry prior to its application [ABPI Medicines Compendium, 2005a; ABPI Medicines Compendium, 2005b].
o For the night-time application, the solution should be applied more than 1 hour before bedtime to avoid spreading the solution onto the pillow (and therefore the face).
o Any fingertips and hands that have been in contact with minoxidil should be washed to avoid the development of mild hypertrichosis (unwanted non-scalp hair, including facial hair growth in women).
• Minoxidil may be applied via different applicator mechanisms (but people should avoid breathing in any mist) [ABPI Medicines Compendium, 2005a; ABPI Medicines Compendium, 2005b]:
o Pump-spray applicator - useful for large areas, six sprays represent a 1-ml dose
o Extended spray-tip applicator - useful for small areas, six sprays represent a 1-ml dose
o Rub-on applicator
• Stop minoxidil if the hair regrows, as the likelihood is that this is due to the natural history of the condition. In some people, relapse will occur after discontinuing minoxidil and so further treatment courses and reassessments may be appropriate.
• If there is no response after 6 months, then reassess the management options.

What are the key contraindications and adverse effects of topical minoxidil?
• Topical minoxidil is contraindicated in:
o People with treated or untreated hypertension
o Pregnant or breastfeeding women
o People with any scalp abnormality (including psoriasis and sunburn)
o People with a shaved scalp
• People with cardiovascular disease need careful consideration before topical minoxidil is used. Note: minoxidil is a peripheral vasodilator and the oral form is used as an antihypertensive drug.
• If chest pain or vasodilatory adverse effects develop, the person should be advised to stop using minoxidil and seek medical advice.
• Topical minoxidil is generally safe and easy to use, and it is well tolerated because systemic adverse effects are unlikely. Results from trials show that adverse effects are five times more commonly reported in women than in men.
• Topical minoxidil contains alcohol, which may cause eye irritation and burning. Note: bathe affected eye(s) with large amounts of cool tap water if affected in this way.
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• Some people experience hair shedding when minoxidil treatment is started, and changes in hair colour and/or texture have also been reported.
• Topical minoxidil contains propylene glycol as an excipient which has been known to cause skin irritation and itching.
• Discontinue minoxidil if the following adverse effects persist:
o Hypertrichosis (unwanted non-scalp hair, including facial hair growth in women)
o Local erythema
o Itching
o Dry skin/scalp
o Exacerbation of hair loss
[ABPI Medicines Compendium, 2005a; ABPI Medicines Compendium, 2005b]

Supporting evidence
Few treatments have been subject to randomized controlled trials and there are even fewer data available on long-term outcomes [MacDonald Hull et al, 2003; Messenger, 2004].
What is the evidence for topical corticosteroids in alopecia areata?
• There are few good-quality trial data (small sample sizes, high withdrawal rates) to support the use of topical corticosteroids in alopecia areata and trials have not been conducted using corticosteroids of mild potency [Madani and Shapiro, 2000; Bolduc and Shapiro, 2001]. Most experts believe that it is unlikely that a topical corticosteroid will prevent a patch of alopecia areata from extending.
• A two-part trial investigated the effect of fluocinolone acetonide 0.2% cream (Synalar HP®) versus placebo (vehicle component), each applied twice a day to half of the scalp, in 28 people with alopecia areata and alopecia totalis [Pascher et al, 1970]. The first part of the trial was a single-blind paired comparison in 15 people. This was followed by a second part, a double-blind study comparing the same agents in 13 people. With the two studies combined, the participants applied the topical preparations for at least 6 months.
o A satisfactory to excellent hair regrowth response was obtained in 17/28 people with fluocinolone.
o Of the 17 people who responded to fluocinolone, 12 retained regrowth satisfactorily for at least 3 months.
o Relapses occurred in 11/17 people, either during the trial or within 3 months of the end of the trial.
o Note: fluocinolone acetonide strengths available in the UK vary from 0.0025% to 0.025%, whereas fluocinolone acetonide 0.2% was used in this trial.
• A randomized controlled trial (RCT) (n = 70) investigated the effect of twice-daily application of topical desoximetasone cream (not available in the UK) for 12 weeks. There was a trend towards more hair regrowth in people using the topical corticosteroid but the rate of hair growth was not statistically significant compared with placebo [Charuwichitratana et al, 2000].
• Topical corticosteroids are considered by some to be largely ineffective in alopecia totalis (AT) and alopecia universalis (AU) [MacDonald Hull et al, 2003]. However, in a recent controlled trial, 28 people (19 with AT and 9 with AT/AU, none of whom had responded to topical immunotherapy) applied 2.5 g clobetasol propionate 0.05% ointment to one side of the scalp every night for 6 months (under occlusion with a plastic film), leaving the other side untreated and therefore acting as a control [Tosti et al, 2003].
o Initially, eight people (29%) were treated successfully but three relapsed and were not able to maintain hair regrowth.
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o Although only 18% of the participants therefore benefited from this very potent topical corticosteroid in the long term, the people in this trial had long-standing AT/AU with no previous treatment success.
• A small RCT (n = 61) compared betamethasone valerate (0.1%) foam with betamethasone dipropionate (0.05%) lotion, applied to the affected areas twice daily for 12 weeks [Mancuso et al, 2003]. Betamethasone valerate foam was consistently found to be better in terms of a hair regrowth score at 20 weeks' follow-up.
• The benefit of twice-daily application of betamethasone dipropionate 0.05% (the cream formulation rather than the lotion) has been reported by some experts [Fiedler and Alaiti, 1996] to be equivalent to the benefit reported with fluocinolone acetonide 0.2% cream [Pascher et al, 1970].

What is the evidence for topical minoxidil in alopecia areata?
• The effectiveness of minoxidil is considered to correlate with the extent of initial hair loss, although the evidence for minoxidil is variable. Most experts also believe that it is unlikely that topical minoxidil will prevent a patch from extending.
• A double-blind controlled trial compared placebo with topical 3% minoxidil solution in 30 people (age range 7-63 years) with extensive alopecia affecting 25-100% of the scalp [Price, 1987a; Price, 1987b]. After 12 weeks those in the placebo group were changed to minoxidil. Both placebo and intervention groups were treated for 64 weeks.
o After 12 weeks the minoxidil group showed some hair regrowth but this was not statistically significant.
o At the end of the trial, people with 100% scalp involvement (n = 9) showed no hair regrowth or only slight hair regrowth (one person was lost to follow-up), but of the 20 people with 25-99% hair loss, 13/20 had cosmetically acceptable or incomplete hair regrowth; 7/20 did not have acceptable regrowth.
o Minoxidil was found to be ineffective in people with 100% hair loss, or in people who had had alopecia areata for more than 10 years. In other people with hair loss, however, there was a 1 in 2 chance of cosmetically acceptable hair regrowth, although maintenance treatment is likely to be needed as hair loss began again 4 weeks after minoxidil was discontinued. Furthermore, five of the nine people who initially had cosmetically acceptable hair regrowth had further hair loss in the second year of treatment.
o A further comparison of 3% minoxidil and 5% minoxidil found that 5% minoxidil resulted in a greater number of responders and a faster response, but after 1 year of treatment the number of people with cosmetically acceptable results was similar in the two groups [Price, 1987b].
• A 1% minoxidil preparation (not available in the UK) was found to show benefit when compared with placebo in one double-blind study in people with patchy alopecia [Shi, 1986]. Further controlled trials comparing 1% minoxidil and 3% minoxidil have not confirmed these results however [Vestey and Savin, 1986; Price, 1987a; Ranchoff et al, 1989]. In a study comparing 1% minoxidil and 5% minoxidil the regrowth was more frequent in those using the 5% preparation but few people had cosmetically acceptable results nevertheless [Fiedler-Weiss, 1987].
• Minoxidil 5% solution appears to be more effective than weaker solutions, but the 5% solution may just have a quicker onset of action and there might be little real difference in the number of people who achieve a cosmetically acceptable response overall.
What is the evidence for combining topical corticosteroid and topical minoxidil application?
There is some evidence that combination therapies are better than monotherapy [Madani and Shapiro, 2000]. It is thought that the efficacy of topical minoxidil can be enhanced by combining it with a topical
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corticosteroid applied twice daily, or dithranol [Papadopoulos et al, 2000] and several combination strategies have been tried with variable results.
• A double-blind trial evaluated the use of topical minoxidil plus topical corticosteroid - twice-daily applications to the entire scalp of 5% minoxidil, followed 30 minutes later by 0.05% betamethasone (Diprosone®) [Fiedler, 1992].
o The percentages of people with severe, chronic, treatment-resistant alopecia areata who had fair to good regrowth at 16 weeks were:
􀂃 56% of people receiving combination therapy
􀂃 27% of people treated with topical minoxidil alone
􀂃 22% of people given topical corticosteroid alone
􀂃 13% of people given placebo
o A cosmetic response was seen in:
􀂃 16% of people with 100% scalp loss
􀂃 16% of people with 75-99% hair loss
􀂃 48% of people with 25-74% hair loss
􀂃 63% of people with 0-24% hair loss
• An open-label study of severe, treatment-resistant alopecia areata investigated the combination of 5% minoxidil twice daily plus dithranol (0.5% Dithrocream®) at night. Hair regrowth was seen in 78% of the study participants at 12 weeks, but by 24 weeks only 11% of people had cosmetically acceptable hair regrowth [Fiedler et al, 1990]. The initial response was found to be good but maintenance and cosmetic responses were poor, and the study was terminated early. Adverse effects were limited to irritant reactions.
What is the evidence for intralesional corticosteroids in alopecia areata?
• Intralesional corticosteroids (ILCs) are most suitable for non-extensive patches of hair loss that are cosmetically unacceptable on the scalp, beard, or eyebrows. ILCs stimulate hair regrowth at the site of injection [MacDonald Hull et al, 2003].
• In one trial comparing ILCs of different solubility, triamcinolone hexacetonide (more soluble) was compared with triamcinolone acetonide (less soluble) [Porter and Burton, 1971]. In the triamcinolone hexacetonide group (n = 11) tufts of hair grew in 33 out of 34 sites and in the triamcinolone acetonide group (n = 17) hair grew in 16 out of 25 sites. The effect was seen within 2-4 weeks, was temporary, and was found to last for about 9 months. The trial was neither randomized nor controlled and no statistical analysis was performed because of the small numbers. They concluded that triamcinolone acetonide might be less effective than triamcinolone hexacetonide.
• A study of 66 people with alopecia areata who were all treated with intralesional triamcinolone acetonide using a Porto-Jet (needle-less) injector found that 47/66 people (71%) showed regrowth of hair at 12 weeks after three injections, compared with 1/15 (7%) of the people injected with isotonic saline (i.e. the control treatment) [Abell and Munro, 1973]. Fourteen people (21%) had a relapse after the corticosteroid injections were stopped. The study was neither randomized nor double blind and was unable to confirm whether hair regrowth was due to the corticosteroid or to the natural history. ILCs were more useful in people with alopecia areata than in 18 additional people with alopecia totalis who were also treated.
• Other research has found that monthly injections of triamcinolone acetonide produced a better response in people with fewer than five patches less than 3 cm in diameter, compared with people who had more extensive alopecia areata [Kubeyinje, 1994]. Cosmetic regrowth was achieved in 35 of the 45 people with fewer than five patches (78%). The study had a small number of participants (n = 62), no controls, and there was no randomization.
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• Adverse effects include atrophy (which resolves when injections are discontinued), acne (which can be treated with topical acne treatments), and dose-related intermenstrual bleeding. If used near the eye there is a risk of cataracts and glaucoma [MacDonald Hull et al, 2003].
• Overall, ILCs are reported as being inappropriate or ineffective in people with rapidly progressive alopecia or extensive disease [Fiedler and Alaiti, 1996; MacDonald Hull et al, 2003].

What is the evidence for topical immunotherapy in alopecia areata?
• Topical immunotherapy is reported to be the most effective treatment for extensive alopecia areata [Madani and Shapiro, 2000] although it remains an unlicensed treatment and there have been few double-blind, randomized studies [MacDonald Hull et al, 2003].
• Topical immunotherapy involves the induction of an allergic contact dermatitis by topical application of a potent contact allergen, the most widely used being diphencyprone (DPCP). Initial regrowth is not expected for 12 weeks [Madani and Shapiro, 2000; Bolduc and Shapiro, 2001].
• A review of published studies of contact immunotherapy in people with alopecia areata concluded that 50-60% of people were reported as having achieved a cosmetically acceptable result over a period of about 6 months, although the range of response rates was very wide (9-87%) [Rokhsar et al, 1998]. Available data on long-term follow-up indicates a significant relapse rate.
• A large retrospective case series of 148 Canadian people with alopecia areata with more than 25% hair loss reported clinically significant improvement in 30% of people after 6 months, which increased to 78% after 32 months [Wiseman et al, 2001]. A cosmetically acceptable end point was achieved in 17% of people with alopecia totalis/universalis, in 60% of people with 75-99% hair loss, in 88% of people with 50-74% hair loss, and in 100% of people with 25-49% hair loss. Poor prognostic factors were early age of onset and extensive baseline hair loss. Three months was needed for significant hair regrowth and relapse was seen in 62% of people.
• Multiple treatments are needed but if no response is seen in 24 weeks treatment is discontinued [Madani and Shapiro, 2000.] Alternatively, the treatment can be tapered off gradually once cosmetically acceptable growth is achieved. Maintenance treatments are often required [Bolduc and Shapiro, 2001].

What is the evidence for complementary therapies and other treatments in alopecia areata?
• Although many alternative and complementary therapies have been used in alopecia areata, our literature search found only three randomized controlled trials.
• Aromatherapy with essential oils (thyme, rosemary, lavender, and cedarwood) massaged daily was compared with carrier oil in 86 people with alopecia areata and they were followed up after 3 months and 7 months [Hay et al, 1998]. Independently assessed photographic evidence was collected throughout the trial and any degree of improvement was measured using a six-point scale and computerized analysis of affected areas. Nineteen people in the active treatment group (n = 43) showed improvement, compared with six people in the control group (n = 41), which was a highly significant difference. However, the study had several limitations:
o It was not clear how long the treatment was given for.
o Thirteen people dropped out of the control group, reducing the impact of the apparent benefit achieved with aromatherapy.
o Some people had other types of treatment before the study was discontinued but no more details were provided.
o It is assumed that the treatment and intervention groups had similar baseline profiles in terms of extent and pattern of alopecia areata but details were not provided.
o Note: manufacturers of aromatherapy products are not bound by statutory monitoring or good manufacturing requirements and there is no formal recognized standardization of active ingredients in aromatherapy products.
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• Onion juice is thought to act by causing an irritant contact dermatitis. In a single-blind, placebo-controlled study of 62 people with non-extensive alopecia areata, onion juice (n = 45) was compared with tap water (n = 17) [Sharquie and Al Obaidi, 2002]. After 8 weeks, 20 out of 23 people who were applying onion juice (86%) had statistically significant hair regrowth, but 22 of the original 45 people in this group defaulted from the study. Onion juice was shown to be more effective than placebo but its usefulness is likely to be limited by the offensive smell and by non-compliance.
• Imipramine (75 mg daily) was compared with placebo in a double-blind, placebo-controlled trial that lasted 6 months [Perini et al, 1994]. Thirteen people with alopecia areata were enrolled in the study, seven receiving a serotonin reuptake inhibitor and six the placebo. After 3 months there was a significant improvement in the active treatment group - five of the seven people had hair regrowth, although only one person had cosmetically acceptable hair regrowth. There was no regrowth in the people in the placebo group. The study was limited by its small numbers and by the fact that all the study participants had experienced a stressful life event in the 6 months prior to the study; in addition, three participants had psychiatric conditions.

Scenario - Alopecia areata
Management recommendations
Which therapy?
• Exclude differential diagnoses - the most common are tinea capitis (especially in children) and trichotillomania.
• In children and adolescents up to 16 years of age, unless the primary care professional is confident in managing alopecia areata in this population, specialist advice should be sought before starting a topical corticosteroid.
• Establish whether hair loss on the scalp or face is extensive or non-extensive (i.e. greater than 50% or less than 50%).
• For non-extensive alopecia areata (less than 50% hair loss), management options include:
o Watchful waiting, with provision of reassurance (as spontaneous remission can occur after 3 months).
o Referral to dermatology for consideration of intralesional corticosteroids.
o Topical high-potency corticosteroid or topical minoxidil if the person is over 16 years of age and
􀂃 Is waiting for referral
􀂃 Declines referral, wanting treatment in primary care only
• With extensive alopecia areata (more than 50% hair loss), options include:
o Early referral to dermatology (topical immunotherapy is an effective treatment but a risk/benefit assessment has to be made prior to its use). Note: people with alopecia totalis and alopecia universalis should be routinely referred unless they decline this option.
o Topical corticosteroid or topical minoxidil may be used while awaiting referral (although evidence of their effectiveness is limited in extensive hair loss).
o Watchful waiting is an option but spontaneous remission after 3 months is less likely than in people with non-extensive alopecia areata.
• The pattern of hair loss and cosmetic appearance will influence the decision to refer (to dermatology and/or psychological services):
o If there is 20% patchy hair loss that is easily disguised by remaining hair and if it is not causing psychological distress, it could be managed by watchful waiting.
o If there is 20% patchy hair loss in visible areas that is not easily disguised and which is causing psychological distress, this would be more appropriately managed with intralesional corticosteroids (requiring referral) or topical treatment in primary care.
• People with asthma, eczema, or broken skin conditions: a water-based product is preferred.
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• A minimum of a 3-month trial of a topical treatment is recommended and if there is no response after 6 months it would be reasonable to try an alternative treatment.
Practical prescribing points
For further information please see the Medicines Compendium (www.medicines.org.uk) or the British National Formulary (www.bnf.org).

Topical corticosteroids
• Advise that topical corticosteroids should be used sparingly. In people with non-extensive alopecia areata they should only be applied to the affected areas.
• Give specific advice regarding the quantity of solid-formulation corticosteroid to apply. Where larger areas require treatment, explain and demonstrate the use of the fingertip unit (FTU).
• For an adult, one FTU of topical corticosteroid is sufficient to treat a skin area about twice the size of the area of the flat of the hand with the fingers closed.
• For a child aged from 1 year to 4 years, apply a third of the adult amount.
• Children using long-term topical corticosteroids should have their growth curve monitored.
• Any fingertips and hands that have been in contact with the corticosteroid should be washed.

Topical minoxidil
• Advise people with non-extensive alopecia areata to apply treatment to the affected areas only.
• Any fingertips and hands that have been in contact with minoxidil should be washed to avoid the development of unwanted non-scalp hair, including facial hair growth in women.
• Different modes of applicator are provided to aid topical use, the choice depending on the size of the area(s) affected.

Should I refer or investigate?
Refer?
• Consider specialist referral in the following situations:
o Diagnostic uncertainty
o Extensive disease, including alopecia totalis and alopecia universalis
o Pregnant or breastfeeding women
o If secondary care treatments are more appropriate
o If topical treatment initiated in primary care is not effective
o If a wig is required
Investigate?
• Investigations are unnecessary in the majority of people with alopecia areata [MacDonald Hull et al, 2003].
• Routine screening of possible associated autoimmune disease is not justified except if someone has e.g. diffuse hair loss, which may be caused by many other conditions including anaemia, herpes zoster, hypothyroidism, menopause, and psoriasis.
• If the diagnosis is in doubt, investigations that may be performed in either primary or secondary care include:
o Skin scrapings and fungal culture
o Systemic lupus erythematosus and syphilis serology 19
• Biopsies (e.g. incisional) may also be taken (in secondary care only).

Follow-up advice
• People with non-extensive alopecia areata who are managed in primary care should all be reviewed after about 3 months.
• If the condition becomes more extensive, if there are psychological issues that need to be addressed, or if ongoing support is required, then more regular review may be necessary.
• With topical corticosteroids:
o Stop the corticosteroid if the hair regrows, as the likelihood is that this is due to the natural history of the condition.
o If there is no response after 3 months, consider either a further 3-month trial or switching to an alternative topical preparation. If neither option is desirable, refer to a dermatologist.
o Anyone on medium- to long-term corticosteroids should be monitored for adverse effects, and children using long-term topical corticosteroids need to have their growth curve monitored.
• With topical minoxidil:
o If there is no response after 6 months, reassess the management options.
o Stop the minoxidil if the hair regrows, as the likelihood is that this is due to the natural history of the condition. In some people, relapse will occur after discontinuing minoxidil and so further treatment courses and reassessments may be appropriate.

Drug rationale
Drugs not included
• Many potential treatments for alopecia areata are usually only used in secondary care and are therefore not included: see What treatments are not recommended for use in primary care?
• Topical corticosteroid formulations other than gels, lotions, and scalp applications are not included as they may be less user-friendly for people with alopecia areata (e.g. ointments are greasy). Dermatologists recommend a variety of formulations and some may be preferred in different circumstances (e.g. an ointment may be preferred where a more occlusive effect is required [BNF 50, 2005]), and if a specific formulation is preferred by an individual patient, it is important to take this into consideration too.
• Mildly potent topical corticosteroids are not included for use on the scalp in adults as expert opinion recommends the use of potent topical corticosteroids in people with alopecia areata.
• Very potent topical corticosteroids are not included as they are reserved for use under specialist supervision in people with alopecia areata that has proved resistant to potent topical corticosteroids.
Drugs included
• Topical corticosteroid gels, lotions, and scalp applications are included as expert opinion considers that these formulations are more user-friendly than other formulations available (easier to use, easier to wash out, and may cause less irritation), and that they might be better tolerated. Some dermatologists may recommend the use of other formulations in different circumstances, and individual preferences should always be taken into consideration.
• In children and adolescents up to 16 years of age, PRODIGY recommends that specialist advice should be sought before starting a topical corticosteroid, unless the primary care professional is confident in managing alopecia areata in this population.
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• In adults, a potent topical corticosteroid is recommended (in line with expert opinion) and the following prescriptions are available (as a gel, lotion, or scalp application) on the NHS in England and are included:
o Betamethasone dipropionate 0.05% lotion
o Betamethasone valerate 0.1% lotion
o Betamethasone valerate 0.1% scalp application
o Betamethasone valerate 0.12% foam
o Fluocinolone acetonide 0.025% gel
o Hydrocortisone butyrate 0.1% lotion
o Hydrocortisone butyrate 0.1% scalp application
o Mometasone furoate 0.1% scalp application
• Note: the alcohol content of these products varies and if someone reacts to one product, then it may be worth trying another preparation.
• Topical minoxidil 2% and minoxidil 5% solutions are included as there is some limited evidence to support their use. A private prescription is required as minoxidil solution is not available for use on the NHS, and this might represent significant financial expense for people with alopecia areata.

Patient engagement
Shared decision making
• Alopecia areata is a common form of hair loss. In many cases small bald patches occur. In some cases total baldness occurs.
• Not treating this condition is a common option as there is a good chance that hair will regrow after 3 months or so. The more extensive the bald patches, the less likely it is that the hair will regrow.
• For alopecia areata where less than 50% of the scalp is affected, treatment options include:
o Referral to a skin specialist to consider steroid injections. This is probably the most effective treatment, but does not work in all cases.
o A topical steroid preparation or topical minoxidil. Hair regrowth only occurs in some cases with these treatments. You can also use one of these while you are waiting to see a specialist.
• For more extensive alopecia areata, treatment options include:
o Referral to a skin specialist to consider topical immunotherapy. This is probably the most effective treatment, but does not work in all cases.
o A topical steroid preparation or topical minoxidil. Hair regrowth only occurs in some cases with these treatments. You can also use one of these while you are waiting to see a specialist.
• For any topical treatment, a minimum 3-month trial is recommended. If there is no hair regrowth after 6 months, then it would be reasonable to try an alternative treatment.
• Wigs or hair extensions are an option.
© Crown Copyright 2006
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