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Skin disease: current and new therapies

Thomas F Poyner
MB BS FRCP(Lond) FRCP(Glasg) MRCGP DPD
GP
Stockton-on-Tees
Founder member
Primary Care Dermatology Society
E:thomas.poyner@gp-a81002.northy.nhs.uk

Skin disease doesn't always fit into neat compartments. However, a wide range of skin problems are seen in general practice.

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Sensitive facial skin
Patients complaining of sensitive facial skin is something most GPs and nurses have come across. A study has confirmed its existence and shown that this common problem is associated with a dry skin and blushing/flushing.(1)

Eczema
Patients are used to hydrocortisone cream, which has been available over the counter for some time, and the moderate potency steroid clobetasone butyrate is now also available without a prescription. It is indicated as a short-term treatment for the control of atopic, primary irritant and allergic eczema in adults and children over 12 years of age. The cream is supplied in a 15g tube and should be used for seven days only, then medical advice sought if further therapy is required. The limited duration of use and the small pack size should act as safeguards to inappropriate use. If pharmacists have a range of effective cosmetically acceptable dermatological therapies they could provide a quick point of access for patients.

When children with atopic eczema need treatment from a doctor, there has always been the query of which potency of topical steroid to prescribe. It has been demonstrated that a short burst of potent topical corticosteroid is just as effective as prolonged use of a milder preparation.(2) There are many anecdotal reports of the benefits of a consultation with a nurse who has dermatological expertise for children with atopic eczema. However, a single consultation does not seem to have a major impact on their quality of life.(3) Perhaps we should be considering multiple consultations for those with moderate or severe eczema.

Immunomodulatory agents
Doctors are often anxious about using a topical steroid on children and when treating the face, neck and flexures of adults. Immunomodulatory agents appear to provide a topical therapy with comparable therapeutic potency to that of topical steroids without significant local or adverse effects.(4) They inhibit the cells that produce cytokines, which are mediators of inflammation and are associated with flares of eczema.

Tacrolimus is a macrolide that is produced by a fungus. Tacrolimus 1% ointment has been used to treat atopic dermatitis in children and adults. Sites that have been treated successfully include the face and neck. It has a potency comparable to that of a moderately potent or potent steroid. The use of topically applied tacrolimus ointment has shown great promise, with excellent efficacy and safety profiles superior to the systemic use of this agent.(5) When tacrolimus was used to treat atopic dermatitis, pruritus was markedly improved within three days and the only adverse event was mild transient skin irritation. Patients can experience a temporary sensation of warmth or burning.(6)

Permicrolimus is derived from ascomycin, which again is produced from a fungus. It has been studied as a treatment for eczema in children and adults.(7) It may have a future role in treating mild to moderate atopic eczema. Unlike topical steroids, there is no risk of atrophy.(8)

Azathioprine is used in secondary care to treat patients with severe atopic dermatitis. This drug is effective in some patients, but for others it can cause serious myelotoxicity. The efficacy and risk of side-effects of azathioprine are related to a key enzyme in its metabolism. This enzyme is known as thiopurine methyl transferase (TPMT). Pretreatment measurement of this enzyme is becoming more readily available. Its measurement is now considered essential by some as a means of identifying those patients at high risk of bone marrow failure (one in 300), in whom azathioprine should be avoided or given in substantially lower doses.(9)

Urticaria
Urticaria is a common dermatological problem that responds to antihistamines such as chlorpheniramine; however, sedation limits the acceptability and use of these medications. Sedation is especially important for certain occupations such as flight crew. This led to the development of a second generation of less sedative oral antihistamines. Work from the Drug Safety Research Unit has looked to see whether all of these second-generation antihistamines are truly nonsedating. The four second-generation antihistamines investigated were loratadine, cetirizine, fexofenadine and acrivastine. All these compounds were found to have a low risk of sedation. Fexofenadine and loratadine may be more appropriate for people working in safety-critical jobs.(10)

Research into antihistamines has continued with new third-generation antihistamines being derived from existing molecules. From loratidine has come its major metabolite, desloratadine, and this drug has been shown to be a safe and effective treatment for chronic idiopathic urticaria.(11) From cetirizine has come its isomer, levocetirizine. Desloratadine and levocetirizine need only to be given in half the dose of their parent compounds. Whilst many patients with urticaria respond to the first antihistamine prescribed, others are more difficult to control and need a whole repertoire.

Acne
Topical antibiotics are a well-recognised treatment for inflamed lesions. Clindamycin has been used for many years to treat acne, and recently a clindamycin zinc combination product has become available. Retinoid-like drugs can be used as part of a treatment regimen to treat comedones and even prevent microcomedones, which can act as precursor lesions on what appears to be normal skin.

Psoriasis
It is interesting to find that there is no firm evidence on which to base treatment of guttate psoriasis.(12) Over recent years the vitamin D analogues such as calcipotriol and tacalcitol have become firstline therapy for treating plaque psoriasis in primary care. There is now another drug, calcitriol, which is the natural active form of vitamin D3. It is indicated for mild to moderate psoriasis and is available in an ointment formulation that is used twice daily.

We have become accustomed to using vitamin D analogues in combination with topical steroids. Different drugs in combination can have different modes of action and can be more effective than either drug alone. If one tries to use the two drugs separately, the stability of one or both drugs may be affected and compliance may be poor. Calcipotriol and betamethasone dipropionate in a combination product produce a more rapid response than either drug alone and have fewer side-effects.(13)
 
The treatment of psoriasis should involve more than prescriptions, and a cognitive-behavioural symptom management programme is also beneficial.(14)

Methotrexate is used long term in controlling extensive psoriasis. However, it can cause serious liver damage, and overreliance on liver function tests alone can result in cases being missed. Liver biopsy has been advocated by some as a means of monitoring for liver damage; however,performing routine liver biopsies is not without significant morbidity and mortality. A new blood test called the type III Procollagen assay (PIIINP-0) may go some way towards reducing the need for liver biopsies.(15)

Superficial skin infections

Impetigo
In a recent study patients were treated with topical povidone-iodine, along with either fusidic acid or placebo. The researchers found that fusidic acid was more effective than the placebo, and they also questioned the value of povidone-iodine alone as a treatment for impetigo because of low cure rates and high rate of adverse events.(16)

Head lice
Consultations for head lice and claims of treatment failures are a common problem in primary care. Head lice were collected from school children in four centres at Loughborough, Exmouth, Leeds and South Shields. The data from this study suggested that head lice resistance to over-the-counter products containing synthetic insecticides (permethrin, phenothrin and malathion) is present in many parts of England.(17) This study also suggested that resistance is starting to develop to carbaryl in head lice in Leeds and that extensive use of this product would lead to significant resistance.

Anogenital warts
Imiquimod is a new secondline treatment for anogenital warts. This is available as a 5% cream, which is applied three times weekly for 8-16 weeks.(18) Imiquimod can cause soreness and irritation in up to 50% of patients. It should be avoided in pregnancy.

Hair: too much or too little
Finasteride lowers dihydrotestosterone (DHT), which is an apparent cause of hair loss in males. Giving this drug once daily in a dosage of 1mg can help maintain hair growth. It is available only on private prescription.

The drug has an excellent safety profile, and drug- related adverse events occur in less than 2% of men; these include decreased libido, erectile dysfunction and ejacularapy. In a two-year study of men agetion disorders, all of which resolve on cessation of thed 18-41, 83% of men maintained their hair or experienced a net increase in hair.(19)

Finasteride is not indicated in women or children, and women should not handle crushed or broken tablets when pregnant, because finasteride could cause abnormalities of the external genitalia of a male fetus.

There is a new topical treatment for unwanted facial hair in females.(20) Eflornithine is an ornithine decarboxylase inhibitor, an enzyme found in the hair follicle that is needed for hair growth. A thin layer of cream is applied twice daily. Because the drug is not a depilatory, patients are likely to need to continue using hair-removing methods. A response may been seen as early as 4-8 weeks, but if no improvement is seen after six months the treatment should be stopped. On cessation of therapy, hair growth returns to normal after eight weeks.

Actinic keratoses
Actinic keratoses present as scaly papules on sun- exposed sites. They are common and rarely can progress to a skin malignancy. They are a common cause of referral to secondary care as treatment is not always easy in primary care. Current treatments include cryotherapy, curettage and topical chemotherapy with 5-fluorouracil or photodynamic therapy.

Recently a gel containing 3% diclofenac in 2.5% hyaluronan has been introduced. This treatment has been shown to be effective and to be well tolerated.(21) The gel is applied to affected areas twice daily for 8-12 weeks. Some patients may experience irritation, but this is usually mild and transient. The optimal therapeutic effect may not be evident for up to 30 days post-treatment.

Skin cancer
The introduction of the two-week rule for certain skin malignancies has created a significant workload. It has been suggested that teledermatology may be a useful triage tool.(22) The UK guidelines for the management of cutaneous melanoma were published recently.(23) These advise that patients with lesions suspicious of melanoma should be referred urgently to a dermatologist or surgeon with an interest in pigmented lesions. The guidelines also recommend that if a patient has a lesion removed by their general practitioner that is subsequently reported as a melanoma they should be referred immediately to a specialist.(23)
 
Delivery of care
There has been a radical rethink of how dermatological services may be provided in the future. Highlighted areas include the need to move care nearer to the patient and a desire to improve the primary-secondary care interface. Action on Dermatology had 106 bids for pilot sites.(24) High-priority areas were exploring the GP specialist role and the use of nurses with specialist skills in providing long-term support for patients with chronic skin conditions.

The Action on Dermatology bids underwent an exhaustive assessment process, and there were 16 successful sites. The successful sites had a multitude of ideas, many of which overlapped. These included continuing medical education for primary care staff and the creation of new posts for GPs and nurse specialists.

A baseline skills assessment of local primary care services was seen as a good starting point. Treatment protocols and referral guidelines were thought to be useful. Changing the way those in primary and secondary care work was put forward, with integrated care pathways and multidisciplinary clinic teams. Clinics were popular with triage clinics, nurse-led community-based clinics and rapid-access pigmented lesion clinics suggested. Modern technology will feature (eg, electronic referrals, digital imaging and teledermatology).

NICE referral guidelines
NICE has produced a guide to appropriate referral from general to specialist services.(25) This document will stimulate local discussions on how to ensure the appropriate transfer of patients from general to specialist services. Topics include acne, atopic eczema in children and psoriasis.

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References

  1. Willis CM, Shaw S, de Lacharriere O, et al. Sensitive skin: an epidemiological study. Br J Dermatol 2001;145:258-63.
  2. Thomas KS, Armstrong S, Avery A, et al. Randomised controlled trial of short bursts of a potent topical steroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema. BMJ 2002,324:768-71.
  3. Chinn DJ, Poyner T, Sibley G. Randomised controlled trial of a single dermatology nurse consultation in primary care on the quality of life of children with atopic eczema.Br J Dermatol 2002;146:432-9.
  4. Smith CH. New approaches to topical therapy. Clin Exp Dermatol 2000;25:567-74.
  5. Lawrence ID. Tarcolimus (FK506): experience in dermatology. Dermatol Ther 1998;5:74-84.
  6. Ruzicka T, Asmann T, Homey B. Tacrolimus: the drug for the turn of the millennium? Arch Dermatol 1999;135:374-80.
  7. Harper J, Green A, Scott G, et al. First experience of topical SDZ ASM 981 in children with atopic dermatitis. Br J Dermatol 2001;144:781-7.
  8. Queille-Roussel C, Paul C, Duteil L, et al. The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin 4 weeks: a randomized, double-blind controlled study.Br J Dermatol 2001;144:507-13.
  9. Meggitt SJ, Reynolds NJ. Azathioprine for atopic dermatitis.Clin Exp Dermatol 2001;26:369-75.
  10. Mann R D, Pearce G L, Dunn N, et al. Sedation with non-sedating antihistamines: four prescription-event monitoring studies in general practice. BMJ 2000;320:1184-7.
  11. Ring J, Hein R, Gauger A, et al. Once-daily desloratidine improves the signs and symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study. Int J Dermatol 2001;40:1-5.
  12. Chalmers RJ, O'Sullivan T, Owen CM, et al. A systematic review of treatment for guttate psoriasis. Br J Dermatol 2001;145:891-4.
  13. Douglas WS, Poulin Y, Decroix J, et al. A new calcipotriol/betamethasone formulation. Acta Derm Venereol 2002;82:1-5.
  14. Fortune DG, Richards HL, Kirby B, et al. A cognitive-behaviour symptom management programme as an adjunct in psoriasis therapy. Br J Dermatol 2002;146:458-65.
  15. Boffa MJ, Smith A, Chalmers RJ,et al. Serum type III procollagen aminopeptide for assessing liver damage in methotrexate treated patients. Br J Dermatol 1996;135:538-44.
  16. Koning S, van Suijlekom-Smit LW, Nouwen JL, et al. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial. BMJ 2002;324:203-6.
  17. Downs AMR, Stafford KA, Hunt LP, et al. Widespread insecticide resistance in head lice to the over-counter Pediculoides in England and the emergence of carbaryl resistance. Br J Dermatol 2002;146:88-91.
  18. Snoeck R, Bossens M, Parent D,et al. Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection. Clin Infect Dis 2001;33(5):597-602.
  19. Kaufman K, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenic alopecia. J Am Acad Dermatol 1998;39(4 Pt 1):578-89.
  20. Shapiro J, Lui H. Vaniqa-eflornithine 13.9% cream. Skin Ther Lett April 2001;6(7):1-3,5.
  21. Rivers JK, Arlette J, Shear N, et al. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002;146:94-100.
  22. Jolliffe VML, Harris DW, Morris R, et al. Can we use video images to triage pigmented lesions? Br J Dermatol 2001;145:904-10.
  23. Roberts DLL, Anstey AV, Barlow RJ, et al. UK guidelines for the management of cutaneous melanoma. Br J Dermatol 2002;146:7-17.
  24. Evans N. Action on Dermatology Progress Report. British Association of Dermatologists Newsletter 4(6):16.
  25. NICE Referral Advice. A guide to appropriate referral from general to specialist services. London: National Institute for Clinical Excellence; 2001.

Resources
Primary Care Dermatology Society
PO Box 6
Princes Risborough
Bucks HP7 9XD
National Eczema Society
Hill House
Hillgate Hill
London N19 9XD
T:020 7281 3553
W:www.eczema.org
Acne Support Group
Howard House
The Runway
South Ruislip
HA4 6SE
W:www.m2w3.com/ace
W:www.stopspots.org
British Dermatological Nursing Group
BAD House
19 Fitzroy Square London 1P 5HQ

Events
Primary Care Dermatology Society
14-15 September 2002
Scottish meeting.
PCDS has meetings throughout the year. For further details contact the Primary Care Dermatology Society
PO Box 6
Princes Risborough
Bucks HP7 9XD
Congress of European Academy of Dermatology and Venereology
3-7 October 2002
Prague
E:eadv@guarant.cz
American Academy of Dermatology Annual Meeting
21-26 March 2003
San Francisco