Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Introduction

Psoriasis is a chronic inflammatory cutaneous disorder that can significantly affect patient quality of life (QoL). Although the exact pathogenesis remains to be elucidated, immunologic abnormalities with an increase in immune mediators are likely primary contributing factors. Most patients have mild disease that can be adequately managed by topical therapy. However, a subset of the psoriatic population with severe disease requires phototherapy and/or systemic treatment. Due to its chronic and recalcitrant course, a combinational approach (including topical, systemic, and nondrug interventions) is often necessary for successful long-term management.

Of the conventional systemic agents, acitretin, cyclosporine, and methotrexate are the most commonly used. In the new era of biologics, these agents remain as valuable therapeutic options for severe psoriasis. Recent studies have also provided insights into enhanced efficacy and safety when these drugs are used in combination with the biologics. A review of these conventional systemic antipsoriatic agents will be discussed.

As family physicians frequently serve on the frontlines of patient care and are instrumental in managing comorbidities associated with psoriasis, it may be helpful to be aware of more aggressive approaches. However, because systemic treatment carries a higher risk for adverse effects, moderate to severe cases are best co-managed with dermatologists, who are more familiar with the use of these agents.

Disease Overview

• Psoriasis is a common multisystem disease that affects the skin and may involve the joints.
• Immune dysregulation of T cells results in overactivation, triggering an inflammatory response that leads to the accelerated production of epidermal cells.
• Build-up of the epidermis produces red, scaly, and well demarcated plaques of variable size.
• Psoriasis can affect any part of the body, including the scalp, elbows, knees, lower back, and nails, but the face is usually unaffected.
• Chronic lesions, particularly of the hands and feet, can result in persistent dryness, hyperkeratosis (thickening of the other layer of the skin), itching, fissuring, and infection.

Prevalence

• Genetic factors increase disease susceptibility.
• It affects about 2-3% of the general population.1
• Up to 35% of people with psoriasis have moderate to severe disease.²
• It may eventually progress to the joints (arthritis). Up to 30% of Canadians with psoriasis develop psoriatic arthritis.³

Types of Psoriasis⁴

• Plaque – chronic plaque psoriasis is the most common variant, affecting more than 80% of the psoriatic patient population.⁵
• Guttate – multiple small (5-15 mm) red lesions are round or oval, and drop-like in shape. Lesions appear suddenly and will typically cover the trunk, arms, legs, face, and scalp. It is often associated with streptococcal infection.
• Inverse – also known as flexural psoriasis occurs in the creases and folds of the skin, such as the armpits, groin, and under the breasts. The lesions are characterized by smooth, well defined red patches, but scaling is generally minimal or absent.
• Pustular – a rare form that can be localized to the palms and soles or become generalized. Although pustules are seen, they do not indicate an infection.
• Erythrodermic – a very rare form; most of the skin’s surface is affected by inflammation, redness, and scaling. It can be fatal due to associated complications.

Severity Assessment

• Psoriasis Area Severity Index (PASI) is widely used in clincial trials.
• One common method for measuring psoriasis severity is based on the percentage of affected body surface. For example, one palm-sized lesion represents 1% of body surface area (BSA).⁴
  • Mild psoriasis affects <3% of BSA.
  • Moderate psoriasis affects 3%-10% of BSA.
  • Severe psoriasis affects >10% of BSA.
• The measure of social, emotional, and fuctional impairment resulting from psoriasis is critical.
• The Dermatology Life Quality Index (DLQI) questionnaire is a commonly used tool to assess patient reported outcomes.
• In a questionnaire study, investigators assessed the extent of psychosocial comorbidity and functional impairment in 43 psoriasis patients.⁶
  • About 48% of psoriasis patients reported adverse impacts on social functioning, leading to decreased work efficiency in 51% and to workplace distress in 63%.⁶
  • Stress in the home environment and interpersonal relationships were reported by 70%.⁶

Comorbidities

• Psoriasis can significantly impact a patient’s QoL, e.g., loss of productivity, depression, and an increased incidence of malignancy.⁷
• Associated comorbidities include cardiovascular disease and metabolic syndrome, which may be linked to the underlying chronic inflammation.
• Psoriasis patients have demonstrated an increased prevalence of obesity, dyslipidemia, and insulin resistance.

Treatment Rationale

Formulation of an effective treatment strategy will depend on several factors, including findings from diagnostic investigations, extent and severity of psoriasis, treatment history, age, and patient preferences. Aside from achieving tangible improvements, the adopted therapeutic approach must also minimize QoL impairment, such as discomfort, disability, and heighten self-consciousness, which can lead to social avoidance behaviours. Consequently, early diagnosis and ongoing medical and adjunctive care are crucial for controlling chronicity and disease severity.

Biologics represent the newest class of antipsoriatic agents, although their advent has revolutionized the treatment of moderate to severe psoriasis, long-term safety remains to be established and their high cost can be prohibitive. The common traditional systemic agents (i.e., acitretin, cyclosporine, and methotrexate) continue to have a place in the management of severe psoriasis and novel combined uses have emerged.

Acitretin

Acitretin is a second generation aromatic retinoid (a vitamin A
derivative). Acitretin is prescribed mainly for men and also for post-menopausal women. Due to its teratogenic potential, premenopausal women are generally excluded as treatment candidates. Acitretin’s mechanism of action includes inhibiting cell replication by controlling cellular differentiation within the epidermis. It reduces inflammation and influences the growth rate of skin cells.

Advantages and Benefits

• Convenient once daily oral dosing.
• Very helpful as an adjunct to phototherapy.
• Acitretin may be the safest oral systemic agent for psoriasis, apart from its teratogenic risk that persists 2-3 years following treatment discontinuation.⁸
• Highly effective for treating pustular (including palmoplantar psoriasis) or erythrodermic forms of psoriasis; less effective as monotherapy for plaque psoriasis.
• Acitretin usually does not cause organ damage, which is a side-effect with other medicines (such as methotrexate and cyclosporine), therefore, it can be used for long-term maintenance therapy.
• Unlike other systemic therapies for psoriasis, it does not suppress the immune system.
• Relatively safe for long-term treatment.
• For psoriasis patients with a history of melanoma, acitretin should be considered as a therapeutic option.

Risks and Side-Effects

• Onset of response is usually 2-4 months.
• Combination treatment with phototherapy or biologic agents is superior to monotherapy.
• Side-effects include dryness and irritation of the skin, lips, eyes, nose, and mucous membrane surfaces. Frequent use of a moisturizer is essential to help reduce the irritation.
• Other adverse side-effects include elevation of cholesterol and triglyceride levels, liver toxicity, bone changes, and alopecia.
• As birth defects can occur with retinoids, acceptable method(s) of birth control must be practiced by and discussed with the patient. Because of its relatively long bioelimination, even following treatment cessation, female patients must continue to avoid pregnancy for the next 2-3 years.
• The main issue with compliance is to minimize side-effects through inclusion of topical agents and phototherapy.
• Due to the medication’s drying effects, starting with a lower dose may ease the intensity.

Cyclosporine

Cyclosporine is an immunosuppressant that is also frequently used in organ transplantation. Although it is a very effective antipsoriatic agent, cyclosporine is generally reserved for patients with severe, disabling, or recalcitrant psoriasis (also referred to as a crisis drug), owing to its cost and potentially serious side-effect profile (e.g., renal impairment). Cyclosporine offers rapid disease control in severe cases by suppressing the body’s immune system and slowing the rapid production of skin cells.

Advantages and Benefits

• Treatment is administered orally 1-2 times daily.
• Onset of effect is rapid (4-8 weeks); improvement is often seen within the first 4 weeks.
• Highly effective for severe psoriasis, especially helpful for treating acute flare-ups.
• It can be used intermittently in short-term courses or combined with other topical and systemic therapies.
• Multiple short courses are prescribed to reduce the potential for toxicity.

Risks and Side-Effects

• Long-term use leads to kidney damage, although the damage is often reversible with treatment cessation.
• Total duration of therapy should not exceed 1-2 years to avoid severe adverse systemic effects.
• Regular assessments through blood and urine tests, and blood pressure monitoring are required throughout treatment.
• Rebounds are common if the dosage is tapered or when the medication is stopped.
• Side-effects include flu-like symptoms, nausea, diarrhea, hair growth, high blood pressure, numbness and tingling, and kidney damage.
• Because cyclosporine suppresses the body’s immune system, there is an increased risk of infections and certain cancers, such as skin cancer and lymphomas, but reported incidences usually involve use in organ transplantation where the medication is administered long-term and at higher doses.
• Cyclosprine cannot be used at the same time with psoralen + UVA (PUVA) or UVB phototherapy, methotrexate or other immunosuppressive agents, coal tar, or radiation therapy.
• As a potent immunosuppressive agent, increasing the risk of skin cancer, patients being treated with cyclosporine should be advised to take sun-protective measures, i.e., as applying a broad-spectrum sunscreen daily and wearing long-sleeved clothing and hats.

Methotrexate

Methotrexate (MTX) is an antimetabolite drug that has been in use since the 1950s. It continues to be one of the most widely prescribed drugs for treating severe psoriasis. MTX is effective against diseases that are affected by abnormally rapid cell growth (e.g., psoriasis, rheumatoid arthritis, and cancer). It helps to control psoriasis by reducing immune responses and slowing joint destruction. MTX is usually given after other medications have been tried unsuccessfully.

• The mechanism of action is the interference with DNA synthesis repair and cellular reproduction.
• Antifolate agents, such as MTX, impair the function of folic acid (a B vitamin) that is essential for cellular activity.
• MTX is usually administered orally once weekly at doses ranging from 2.5-25 mg or occasionally by injection.
• It can be administered either as a single dose or in a split dose 12 hours apart for 3 doses.

Advantages and Benefits

• Reasonably effective, convenient dosing, and relatively inexpensive
• Improvements are noticeable following 6-8 weeks of therapy.
• MTX can be used for longer periods of time in comparison with other agents (such as cyclosporine), but patients must be regularly monitored for potentially serious side-effects.
• MTX can also enhance the effect of UVB phototherapy.

Risks and Side-Effects

• Side-effects include headache, skin irritation (itch and rash), hair loss, mouth sores, upset stomach, nausea, low white blood cell count, and fatigue.
• Long-term MTX use can cause serious liver damage. Routine blood tests assessing hepatic function may not detect the damage, hence, a liver biopsy may be necessary every 1.5-2 years while undergoing treatment.
• Long-term risks include birth defects, kidney damage, bone marrow toxicity, and bone marrow suppression (rare, but potentially life-threatening).
• There are many drugs (e.g., non-steroidal anti-inflammatory drugs) that can adversely interact with MTX.
• MTX can cause birth defects and miscarriages, resultantly, women with child-bearing potential taking the drug must use a reliable method of contraception.
• To mitigate the risk of liver damage, patients must be advised not to consume alcohol while on therapy.

Phototherapy

• For generalized psoriasis, UVB phototherapy offers an effective option that allows both rapid disease control and long-term maintenance.8
• Narrowband UVB may be more effective than broadband.
• Use of low doses of acitretin enhances both therapeutic benefits of UVB and PUVA.
• MTX may also improve the effect of UVB.
• Phototherapy in combination with acitretin not only improves efficacy, but may also reduce long-term side-effects and the number of required treatments.
• For patients unresponsive to phototherapy or who find the treatment schedule too demanding, MTX can be an effective alternative.

Conclusion

Effective ongoing management of patients with severe psoriasis requires knowledge of available therapies, including mechanism of action, potential toxicity, and appropriate monitoring. Combinational, rotational, and sequential therapeutic methods that aim to improve overall efficacy while reducing the toxicity of the chosen medications are the goals of treatment. Optimal patient care also requires continued education and support, as well as addressing quality of life concerns. It is important to encourage patients to be involved in therapeutic decision-making and to report any side-effects that they are experiencing, in order that symptoms can be mitigated with dose adjustments, the addition of other treatments, or even temporary discontinuation of therapy.

References

1. Griffiths CE, et al. Lancet 370(9583):263-71 (2007 Jul 21).
2. Thomas VD, et al.J Am Acad Dermatol 53(2):346-51 (2005 Aug).
3. The Arthritis Society. Psoriatic Arthritis.
4. National Psoriasis Foundation. Facts about psoriasis.
5. Pathirana D, et al. J Eur Acad Dermatol Venereol 23(Suppl 2):1-70 (2009 Oct).
6. Gaikwad R, et al. Indian J Dermatol Venereol Leprol 72(1):37-40 (2006 Jan-Feb).
7. Gottlieb AB, et al. J Dermatolog Treat 19(1):5-21 (2008).
8. Feldman S. Dermatol Online J 6(1):4 (2000 Sep).

Introduction

Hand dermatitis (HD) is a common skin disorder affecting individuals of all ages. HD broadly refers to any type of inflammation involving the skin of the hands that is characterized by a combination of redness, itching, scaling, and fissuring. Both genetic and environmental risk factors are important in its etiology. HD is well known for its recalcitrance, typically following a chronic relapsing course that progresses in severity and may resist conventional treatment. However, recent advances, particularly for chronic severe disease, have broadened the therapeutic landscape. A thorough understanding of pathogenesis, heritability, diagnosis, therapeutic options, and patient-related factors will aid in improving acute and long-term management, as well as treatment outcomes. For this review, the terms eczema and dermatitis are used interchangeably and refer to the same condition.

Prevalence and Prognosis

Most adult patients with dermatitis have involvement of the hands.

• An estimated 7-12% of the general population is affected by HD.¹
  • Approximately 5-7% of HD patients have chronic severe disease and 2-4% are refractory to topical treatment.²
• Prevalence is considerably higher among certain occupational groups, e.g., domestic workers, hairdressers, health care professionals, and workers in the agricultural, food-related, mechanical, metallurgic, or printing industries.
• HD is also twice as likely to occur in women than in men.³
• Strongest negative prognostic factors include extent of involvement, history of childhood dermatitis, and disease onset at < 20 years of age.⁴

Causes and Risk Factors

• Exogenous and endogenous factors contribute to the etiology of HD. This multiplicity makes identification of all causative elements very difficult.
• HD commonly progresses on a chronic path, even with avoidance of the initially implicated trigger.²
• Personal/familial history of atopy (asthma, allergic rhinitis, atopic dermatitis).
• HD can be caused or aggravated by occupational exposure from working in wet conditions, frequent hand washing, or using irritative substances.
  • Severity of occupational HD is associated with prolonged sick leave and increased risk of job loss.⁵

Common Variants of Hand Dermatitis

An epidemiologic HD study observed irritant contact
(35%), allergic contact (19%), and atopic (22%) dermatoses
to be the most commonly classified forms; 15% of patients
had unclassified eczema.⁶

Irritant Contact Dermatitis (ICD)

• ICD is caused by repeated or prolonged exposure to contactants, which inhibits epidermal barrier repair.
• Substances that can induce reactions: water, soaps, detergents, cleansers, solvents, degreasers, lubricants, oils, coolants, food products, fiberglass dust, metals, plastics, and resins, as well as mechanical trauma.
• Symptoms are usually symmetrical and affect the dorsal fingertips and webspaces.

Allergic Contact Dermatitis (ACD)

• Making a distinct diagnosis between ICD and ACD can be difficult.
• Reactivity occurs when previously sensitized individuals are re-exposed to the antigen.

Treatment

Despite its prevalence and considerable disease burden, there are very few well-designed randomized controlled trials
(RCTs) evaluating therapies for chronic hand dermatitis (CHD). Resultantly, most therapeutic recommendations are based
on personal physician experience and the limited number of small studies. The EDEN survey by van Coevorden et al.
assessed HD studies conducted between 1977 to 2003 and confirmed a lack of RCTs, with most exhibiting poor methodology
and quality of reporting.⁷ Consequently, this dearth of evidence-based data fails to sufficiently guide therapeutic decisionmaking.
The absence of clarity is even more evident for severe CHD, as therapeutic options are further restricted.⁸

Topical Agents

Topical treatments may be used in combination or with systemic or light therapies.

Emollients

• The regimented use of emollients contributes to repair of the skin barrier.
• Adequate moisturization can support pharmacologic treatment by reducing the need for topical corticosteroids or immunomodulators, and mitigating side-effects from drug therapy.

Corticosteroids

• Topical steroids are used to reduce inflammation and are a mainstay of therapy.
• Ointments are generally more effective and contain fewer preservatives and additives than creams.
• The thick stratum corneum (e.g., palms, palmar aspects of fingers, and around nails) often requires higher potency preparations, such as clobetasol propionate 0.05% ointment 1-2 times daily for a few weeks and then 2-3 times a week thereafter, as needed.
• Topical steroids should be used on affected areas twicedaily until improvement is seen, then the dosage may be tapered to intermittent use for maintenance therapy.
• A poor response may indicate a corticosteroid allergy.
• Cross-reactions between groups of corticosteroids and flares with systemic steroids may complicate therapy.
• Limitations can include tachyphylaxis, skin atrophy, and systemic side-effects, especially if used long-term.

Topical Calcineurin Inhibitors (TCIs)

• TCIs are nonsteroidal immunomodulators that exert anti-inflammatory effects.
• Pimecrolimus and tacrolimus are beneficial when conventional agents fail or are unsuitable.
• Pharmacokinetic activities of TCIs include skin absorption, but they do not enter the bloodstream.
• Onset of effect is slower than corticosteroids.
• Common side-effects of TCIs include mild and transient itching and burning upon application.

Salicylic Acid and Coal Tar

• These agents are sometimes prescribed for hyperkeratotic areas to help soften skin, reduce thickness, and improve penetration of medications.
• Salicylic acid can cause irritation.
• Tars can have an unpleasant odour and cause irritation and staining. Potential carcinogenicity is also a concern.

Systemic Agents

Antihistamines

• Sedating antihistamines (e.g., hydroxyzine or diphenhydramine) may be useful adjuncts when taken at bedtime for intractable itch, especially during flares.

Antibiotics

• Oral/topical antibiotics are used to treat infected lesions.
• Most infections are caused by Staphylococcus aureus colonization. Cephalexin is commonly prescribed at the dose of 500mg 4 times daily for 7 days.

Oral Corticosteroids

• Oral corticosteroids are effective in a short course for treating acute or widespread outbreaks.
• Prednisone may be initially prescribed at 0.5-1mg/kg or 20-40mg, then tapered over several weeks. Patients must be given information on side-effects (e.g., avascular necrosis of the hip) and precautions during dispensing.
• Long-term use is rarely advisable due to undesirable and potentially harmful side-effects.

Oral Immunosuppressive Agents for Severe HD

• Azathioprine may be used in AD, pompholyx, and psoriasis.
  • Side-effects include elevated liver enzymes, leucopenia, infections, and sun sensitivity.
  • Rare side-effects from long-term use include squamous cell cancers and non-hodgkins lymphoma.
• Cyclosporine suppresses inflammatory responses.
  • Long-term use can lead to severe side-effects, including organ damage.
• Methotrexate (MTX) has an immunomodulatory effect and is usually taken at a dose of 7.5-20mg weekly.
  • Side-effects of MTX include nausea, vomiting, diarrhea, liver fibrosis and cirrhosis, pulmonary fibrosis, and pancytopenia, as well as other severe adverse effects from long-term use.
  • Folic acid is generally co-prescribed, as this may reduce MTX associated side-effects.
  • During MTX treatment, alcohol avoidance is essential to prevent liver damage.
• Mycophenolate mofetil (MMF) may be used for patients who are nonresponsive or inadequate responders to other HD therapies.
  • There are concerns over MMF’s teratogenicity and long-term carcinogenicity.

Phototherapy (Light Therapy)

For severe or treatment resistant HD, narrowband UVB light or oral/bath psoralen + long-wave UVA light therapy (PUVA)
are helpful due to their local immunosuppressive effect.

• Long-term use of UV light therapies can cause skin damage and increase cancer risk.
• Patients may consider the required time commitment to be inconvenient.
• Access to clinic-based phototherapy may be limited.

Therapeutic Advance for CHD

One of the few adequately controlled studies, which
represents the largest HD trial to date, explored the oral use
of alitretinoin in severe CHD refractory to standard care.¹
The investigation provides much-needed evidenced-based
data and demonstrates the therapeutic potential for this nonimmunosuppressive
agent.

Alitretinoin (9-cis retinoic acid) is a new oral retinoid
that received regulatory approval in Canada in November
2009. It is the only systemic agent that is indicated for the
treatment of adults with severe CHD that is refractory to
high-potency topical steroids.

• Two randomized, double-blind, placebo-controlled, multicenter trials involving over 1300 patients treated with alitretinoin demonstrated significant clinical improvements in moderate to severe CHD.^1,9
• One study assessing once-daily use for 12 weeks showed a dose-dependent improvement in 53% of HD patients, who exhibited up to 70% mean reduction in disease signs and symptoms.⁹
• A second study looking at once-daily use for up to 24 weeks reported 48% of alitretinoin-treated patients achieved clear or almost clear hands, with up to 75% median reduction in disease signs and symptoms, compared with 17% of placebo. After cessation of therapy, the median time to relapse was 5.5-6.2 months.¹
• Alitretinoin was well-tolerated. Side-effects were dose-dependent and included headache, flushing, mucocutaneous events (e.g., dryness of the skin, lips, and eyes), hyperlipidemia, and decreased levels of freethyroxine and thyroid stimulating hormone.
• For most patients, the recommended starting dose is 30mg for up to 24 weeks, depending on response.¹⁰ A starting lower dose of 10mg daily may be tried in patients exhibiting unacceptable adverse reactions to the higher dose.¹¹
• Alitretinoin is an endogenous retinoid, with concentrations returning to normal range within 1-3 days after treatment cessation. It is rapidly eliminated and does not accumulate in the body.¹¹
• As with all systemic retinoids, alitretinoin is teratogenic and requires strict monitoring when used in women of childbearing potential. Pregnancy testing and the use of acceptable methods of contraception are required just prior to, during, and 1 month after therapy.

Self-Care Tips for Patients

An essential part of HD management is to restore the normal skin barrier function by regularly moisturizing with emollients,
both during and in between flares. Lifestyle modifications and patient self-care are critical components for successful
ongoing management and minimizing adverse effects on quality of life (QoL).

• Use mild cleansers instead of harsh or perfumed soaps.
• Maintain the regimented use of bland moisturizers (e.g., petrolatum).
• Avoid products containing fragrances and preservatives.
• Bathe with warm water and limit the duration.
• If triggers are known, avoidance is a central HD management strategy.
• Reduce exposing hands to water, cleaning products, and aeroallergens by wearing gloves (wear cotton gloves under latex/rubber to absorb perspiration).
• Use barrier creams and practice glove hygiene to reduce antigen exposure and severity of skin reactions.
• Scratching can cause cracks to form, allowing bacteria to enter the damaged epidermis and result in infection.
• Antipruritic strategies include applying a cold compress to the affected area, keeping fingernails short, and using OTC products containing hydrocortisone.
• Avoid skin contact with fruits, vegetables, and raw meats.
• If possible, wear vinyl gloves to shampoo hair.
• Remove rings before wet-work or hand washing, as they can trap moisture and irritants.
• Efforts aimed at reducing stress are beneficial for controlling HD. Psychological stress may cause immunological changes that can aggravate HD.
• For education and social support, patients may benefit from interactions with national organizations or web-based social networks.

Conclusion

Formulation of an effective treatment strategy will depend on many factors, including findings from diagnostic investigations,
extent and severity of HD, treatment history, age, and patient preferences. Aside from achieving tangible improvements,
the adopted therapeutic approach must also minimize QoL impairment from sleep interference, discomfort, disability, and
heighten self-consciousness, which can lead to social avoidance behaviors. Consequently, early diagnosis and ongoing
medical and adjunctive care are crucial for controlling chronicity and disease severity.

There is a significant unmet need for pharmacologic agents that are effective in the long-term management of severe CHD.
Present treatment options are plagued with side-effects and unable to induce sustained periods of remission. However,
the recent introduction of alitretinoin has broadened the therapeutic options and improved the outlook for patients who
are unresponsive to conventional therapies. Within the framework of patient care, pharmacists play an integral role by
counseling on adjunctive OTC medications, drug side-effects, proper usage, and tips for daily management. Such efforts
directed at patient education convey practical advice and reinforce both the rationale and aims of prescribed therapies,
which can help to optimize treatment outcomes.

References

1. Ruzicka T, et al. Br J Dermatol 158(4):808-17 (2008 Apr).
2. Diepgen, et al. Contact Dermatitis 47:203-10 (2007).
3. Meding B, et al. Acta Derm Venereol 69(3):227-33 (1989).
4. Meding B, et al. J Invest Dermatol 124(5):893-7 (2005 May).
5. Cvetkovski RS, et al. Br J Dermatol 152(1):93-8 (2005 Jan).
6. Meding B. Acta Derm Venereol Suppl (Stockh) 153:1-43 (1990).
7. van Coevorden AM, et al. Br J Dermatol 151(2):446-51 (2004 Aug).
8. Robertson L. Skin Therapy Lett 14(3):1-5 (2009 Mar).
9. Ruzicka T, et al. Arch Dermatol 140(12):1453-9 (2004 Dec).
10. Health Canada. Notice of Decision for Toctino (2009 Nov 13).
11. The electronic Medicines Compendium (eMC) on alitretinoin (Toctino®). Available at: http://emc.medicines.org.uk/ medicine/21177/SPC/Toctino+10mg+and+30mg+soft+capsules/. Accessed March 25, 2010.

1 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
2 Skin Care Centre Pharmacy, Vancouver, BC, Canada

Introduction

Head lice infestations (Pediculosis humanus capitis) are most prevalent during childhood in industrialized countries. It is estimated to occur in about 1-3% of children aged 6-12 years.¹ Greater susceptibility is associated with girls, which is likely attributed to close contact play and the sharing of objects.² Infestations are caused by direct physical contact with humans or fomites carrying live lice. Head lice infestations do not pose health risks, nor are they indicative of poor hygiene. Instead, active infestations signal the onset of a potentially widespread nuisance in schools and homes, and may subject affected individuals and their family members to stigmatization within their community. Diagnostic accuracy, decontamination, and topical therapy are required for containment and eradication.

Facts on Head Lice

• Adult lice are 2-4 mm long (about the size of a sesame seed). These wingless insects cannot jump or fly. Hence, hair-to-hair contact represents the primary mode of transmission.
  • Lice can crawl rapidly (about 6-30 cm per minute).
  • They can adapt their colour to their surroundings, making detection by visual inspection difficult.
  • Lice survive by sucking blood from their host every 3-6 hours and they cannot miss several consecutive meals.²
  • After mating, an adult female louse can lay 5-6 eggs daily for 30 days.³
• Eggs (nits) are laid on the hair shaft closest to the scalp.
  • Nits are very small and oval-shaped, and they range in colour from white to tan or silver to grey.
  • Nits are located near the scalp owing to the warmer temperature and close proximity to their eventual food supply.
• Nymphs (hatched immature lice) require 9-12 days to reach adulthood.

Symptoms

• Most infestations are asymptomatic, but persistent itching occurring near the back of the head and/or around the ears is commonly the first noticeable symptom. Sleeplessness, red marks, excoriations, and rash can also occur.
• Pruritis may be experienced 2-6 weeks after the first infestation; itching may occur sooner (1-2 days) in future infestations due to prior sensitization to antigens present in lice saliva during the initial exposure.

Diagnosis

Early detection of head lice is important for reducing its communicable potential. Diagnositic accuracy can be challenging
and requires experience and expertise, as lice can readily evade detection by their rapid mobility and minimal visibility.
Additionally, nits can resemble dandru., scabs, hair spray droplets, or other debris.⁴

• An active infestation is de.ned by the presence of 10 or more live lice.⁵
• The discovery of nits alone without live lice does not indicate infestation; about 10-30% of nits do not hatch.⁶
• Overdiagnosis by healthcare professionals is common, whereby extinct or inactive infestations are determined to be
• active infestations and pharmacologic intervention is unnecessarily initiated.⁵
• Once an active infestation has been confirmed, alert and screen everyone in the household and close contacts.

Methods of Detection

Although visual inspection is easier to perform, wet combing with conditioner (WCWC) remains the most reliable method of detection.^1,6

WCWC Method for Head Lice Detection⁶

• Apply a liberal amount of conditioner (white is best) to dry hair, soaking strands from scalp to ends.
• Remove tangles with a regular bright light-coloured comb.
• Start behind the ears and comb each section of hair.
• Place the lice comb (a special fine-tooth comb) against the scalp and pull to the end of the hair.
• Check the comb for lice after each pull.
• Wipe the comb with a tissue each time and look for lice.
• Place the tissue in a plastic bag.
• Check all the hair over the entire head.
• Repeat combing every section of hair at least 5 times.
• When finished, tie the plastic bag with the soiled tissues and discard in the garbage.
• If live lice are detected, all traces of conditioner must be washed from the hair prior to treatment.

Manual Removal

Manual removal of lice and nits is recommended for children Manual removal and daily lice combing serve as useful adjunctive measures. These nonpharmacologic approaches aid in reducing pediculicidal resistance, which is a concern in topical insecticidal use.

Environmental Decontamination

Because lice can survive away from a human host for 3-4 days, implementing fomite control strategies can eliminate potential sources of transmission and minimize reinfestation.

• Personal items used or worn by an infested person during the 3 days before treatment should be machine laundered in hot
• water (e.g., linens, blankets, pillows, stuffed toys, and clothing), then placed in a dryer using a hot setting for 20 minutes.
• Objects that cannot be washed should be stored in a tightly-wrapped plastic bag for 2 weeks or in a freezer for 24 hours.
• Soak combs (including lice comb) and hairbrushes in very hot water for 20 minutes or in rubbing alcohol for 1 hour.
• Vacuum carpets, furniture, and mattresses that the infested person came into contact with.
  • Extensive cleaning is unnecessary as the survivability of head lice away from the scalp is limited.
• Insecticidal sprays have not been shown to be effective.
• Children should be permitted to return to school after appropriate treatment; strict no-nit policies are unnecessary.^4,5,7

Topical Treatment

Topical treatment (Table 1) is recommended only when live lice are found. To prevent reinfestation, it is advisable to treat all infested family members and close contacts immediately and on the same day.⁶

Key Points of Topical Treatment

• Permethrins (synergized pyrethrins) are considered first-line therapies and most preparations are available OTC.
• Available pediculicides are not 100% ovicidal. Consequently, for all topical therapies, two treatments (7-10 days apart) are necessary to eradicate the nymphs that are hatched from nits not killed by the first treatment.
• Depending on the pediculicide, specific application to either wet or dry hair is required.
• Adequate saturation and treatment duration are essential for penetration of lice and nits by the active agent.
• The medication should be applied not only to the scalp and along the hair shaft, but also to the back of the ears and neck.
• Patients should not wash their hair for 1-2 days after the treatment is rinsed off.
• The presence of live lice after treatment does not indicate failure, as it can take up to 24 hours for the parasites to die.
• The most common side-effects from topical therapies include itchiness, mild skin irritation, and redness.
  • Post-treatment itching is not an indication of reinfestation.
• Many proposed alternative or natural treatments, such as tea tree oil, petroleum jelly, peanut butter, and mayonnaise have not been clinically proven to be effective.

Treatment Failure

The most common reasons for treatment failure include:

• Misdiagnosis
• Improper use (e.g., not saturating hair from scalp to ends or not leaving the product on long enough)
• Not repeating the treatment after 7-10 days or reapplication too soon after initial application
• Pediculicidal resistance
• Inadequate manual removal of nits
• Repeat exposure to lice (reinfestation)

Improper management of an active infestation poses considerable costs to a family as:⁸

• the child may not be permitted to attend school and may be ostracized and stigmatized.
• the parent may be required to take time off from work or pay for alternate care.
• the family must commit time and financial resources for eradication and prevention of reinfestation.

Conclusion

Although head lice infestation is not as prevalent in Canada as in developing countries, it remains a common communicable problem that carries substantial costs, both financial and social, for affected individuals. Given their favourable safety and efficacy profiles, permethrins and synergized pyrethrins remain first-line treatments for Pediculosis capitis.^3,4,6,7 Diagnositic accuracy and appropriate management, as well as education aimed at reducing transmission, are central for eradication and minimizing the suffering and treatment-related costs for those impacted.

References

1. Jahnke C, et al. Arch Dermatol 145(3):309-13 (2009 Mar).
2. Meinking TL. Curr Probl Dermatol 11(3):73-118 (1999 May-Jun).
3. Burkhart CN. Lancet 361(9352):99-100 (2003 Jan 11).
4. Centers for Disease Control and Prevention. Fact sheet: head lice. Available at: http://www.cdc.gov/lice/head/factsheet.html. Accessed August 12, 2009.
5. Position statement from Infectious Diseases and Immunization Committee, Canadian Paediatric Society. Paediatr Child Health 13(8):692-704 (2008 Oct).
6. District Health Authority Public Health Services of Nova Scotia. Guidelines for treatment of pediculosis capitis (head lice), August 2008.
7. Diamantis SA, et al. Dermatol Ther 22(4):273-8 (2009 Jul-Aug).
8. Boivin M. Webmodule: Skin clinic vignettes – infestations. Head lice and scabies. rxBriefCase (2009 May).

1. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA
2. Division of Dermatology, University of Western Ontario, London, ON, Canada
3. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Background

The number of patients with psoriasis is increasing, while the number of medical dermatologists is shrinking. There are more than 1 million psoriasis patients in Canada, with 620,000 visits to a health care professional in 2006 for treatment of this condition. Approximately 35% of these visits were with dermatologists; the remainder was handled primarily by family practitioners.

Disease Severity

There are a wide range of definitions of disease severity for psoriasis. In light of the various measures that are currently available, patients can be separated into two categories: those treated with local (topical) therapy and those treated with systemic therapy. This article will deal with topical therapy.

Topical Treatment Options and the Treatment Triangle

Topical medications, either as monotherapy or in combination, are the most commonly prescribed treatments by both dermatologists and family practitioners. The treatment triangle brings together evidence-based medicine, patient preference, and the physician’s expertise in order to determine the most appropriate treatment approach. Given the increasingly limited access to dermatologists, adequate education on all available treatment options must be provided to family practitioners in order for them to adequately manage the psoriatic population in Canada.

Commonly Used Topical Antipsoriatic Therapies

• Emollients/ Keratolytics
• Topical Steroids
• Tars
• Anthralin
• Tazarotene
• Calcipotriol
• Calcipotriol + Betamethasone Dipropionate
• Calcineurin inhibitors

Emollients

The use of emollients improves the skin barrier function by restoring hydration and forming a protective layer that guards against infection and other irritants. Additional benefits include:

• improvement of itching
• removal of superficial scales, resulting in a smoother appearance to the skin
• improvement of penetration of other topical medications.

Topical Corticosteroids

Corticosteroids are potent compounds widely used for their
anti-inflammatory, immunosuppressive and antiproliferative
effects.

• Efficacy and safety have been confirmed when used as monotherapy in short-term courses and when given intermittently for more lengthy periods.
• Studies have shown improved efficacy when applied in the late afternoon or evening.

Tar

Tar slows the proliferation of skin cells and reduces inflammation, itching and scaling. While tar compounds are very effective for treating scalp psoriasis, they have several limitations:

• They are odiferous.
• They can irritate and stain.
• They can cause folliculitis.
• There is concern that they may be carcinogenic.

Anthralin

Anthralin reduces the rapid acceleration of skin growth, as seen in psoriasis.

• An effective treatment for mild-to-moderate disease, however, patients are slow to respond.
• Skin irritation and staining are common side-effects.
• Its availability is limited and is rarely used by outpatients.

Tazarotene

• It is a retinoid with the ability to mediate skin cell proliferation and differentiation
• It is mostly used in non-psoriasis indications
• It may cause irritation to psoriatic lesions
• Its effects can be enhanced when used in combination with topical corticosteroids, calcipotriol and phototherapy.

Calcipotriol

• A vitamin D analogue that acts to modulate both epidermal proliferation and differentiation.
• Twice daily application has been shown to be more effective than tar, short contact anthralin, and some corticosteroids.

Compounding

Use of calcipotriol in combination with steroids enhances efficacy. However, compounding should be used with caution. Ad hoc mixtures of calcipotriol plus steroids (including betamethasone dipropionate and betamethasone valerate) have been shown to be unstable. The valerate steroid activity disappeared within 24 hours, while the dipropionate steroid activity was more than one-third depleted after only 4 weeks.

Calcipotriol plus Betamethasone Dipropionate

• Available as a stable commercial preparation.
• Phase III trials involving more than 6,000 psoriasis patients have demonstrated clear or almost clear responses in 50% of those treated after 4 weeks of therapy.
• Reduction in Psoriasis Area and Severity Index (PASI) score was consistent throughout the study population: approximately 40% after 1 week and 70% after 4 weeks. The PASI is a visual rating system that is determined by assessing the amount of body surface area affected by psoriasis, redness, thickness, and degree of scaling.
• Response rates were uniform across patients of differing age, sex, races, and baseline disease severity.
• Combination therapy with calcipotriol and betamethasone dipropionate can enhance the rate and degree of improvement for patients undergoing treatment with UVB, PUVA, methotrexate, cyclosporine, retinoids, or alefacept.
• The addition of calcipotriol and betamethasone dipropionate can have a dose sparing effect, reducing some of the side-effects produced by many antipsoriatic treatments.
• Many dermatologists agree that including calcipotriol and betamethasone dipropionate in combination therapy produces synergistic effects.
• Can be considered as first-line topical therapy due to once daily application, quick onset of action, and favorable safety and efficacy profiles over 52 weeks of “as needed” use.

Topical Calcineurin Inhibitors

• Calcineurin inhibitors are immunosuppressive agents that interfere with T-cell signaling and affect the body’s inflammatory responses.
• Studies have indicated therapeutic benefits for psoriasis, especially on the face, and in the groin and skin folds.

Noncompliance and Nonadherence

Noncompliance or nonadherence to treatment can influence outcomes in all disease states. They unquestionably lower response to treatment, and this is of particular concern with topical medications. When the illness has the severity potential of psoriasis, physicians need to find treatment options that best suit each patient.

There is no reliable method to ensure or improve compliance in patients with psoriasis. Some clinical strategies to promote compliance include:

• encouraging patient feedback and input surrounding their treatment.
• selecting fast-acting topical therapies.
• selecting treatments that facilitate ease of use, i.e., once-daily dosing.
• referring patients to national organizations for support.

Conclusion

Advancements in topical antipsoriatic therapies have provided safer and more effective treatment options, especially when used in combination. Consequently, much research is underway to investigate novel treatment combinations for psoriasis in the hope that it will provide further enhancements in efficacy that will lead to improved patient compliance.

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Background

Microcomedones are the precursors to all acne lesions. Topical therapies, such as retinoids, have the ability to substantially reduce their number, thereby disrupting the pathways that lead to the development of both inflammatory and noninflammatory acne lesions.

Retinoids naturally occur in the human body and are implicated in the regulation of a variety of physiologic processes. Their mechanism of action can be explained by their interaction with cell receptors. This cellular interactivity, as it relates to acne, involves controlling and slowing the turnover of skin cells, reducing sebum secretion and inhibiting inflammatory responses. Retinoids can access the skin through systemic modes of administration, as well as through metabolism when applied topically. The effects of retinoids on epidermal proliferation, pigment maturation, and collagen production make them important for treating a number of skin conditions, and as such, they are used extensively.

Approved Topical Retinoids

Naturally occurring retinoids

• All-trans retinol (used in over-the-counter cosmeceuticals)
• All-trans retinoic acid (tretinoin)
• Alitretinoin (US FDA approved for AIDS-related Kaposi’s sarcoma)*

Synthesized retinoids

• Adapalene
• Tazarotene
• Bexarotene (US FDA approved for cutaneous lymphoma)*

* Not available in Canada

Histological Changes Following Prolonged Use of Topical Retinoids

• Epidermal thickening of atrophic skin
• Elimination of dystrophic keratinocytes, including actinic damaged cells
• Dispersal of melanin granules, such as those seen in sun damaged skin
• New dermal collagen formation
• Angiogenesis, which may be seen as telangiectasias
• Comedolysis, which breaks down comedones

Tretinoin

Tretinoin was introduced as the first topical retinoid in the 1970s. A number of products containing tretinoin have been developed since; each unique formulation incorporates specific bases and delivery systems, and includes claims of enhanced efficacy and reduced irritancy. Topical tretinoin is approved in various jurisdictions for the treatment of acne, well as for photodamage and anti-aging.

Mechanism of Action

• Activates DNA, normalizing gene expression, affecting cell differentiation and keratinization of the follicular epithelium,
  preventing comedone production, and triggering the lysis of existing comedones.
• Affects cell growth and differentiation, thereby providing the potential for this agent to improve fine lines, wrinkles, mottled pigmentation and skin roughness. Topical tretinoin has been shown to increase procollagen1 production, which plumps up the epidermis in those with depressed scars and wrinkles.
• Inhibition of the toll-like receptor 2 receptors, which are activated by P. acnes, may explain the significant antiinflammatory effects seen in acne.
• Tretinoin, unlike systemic isotretinoin, does not have a direct effect on the sebum production.

Pharmacology

Only 1%-2% is absorbed in normal skin. However, absorption may be 15 times greater if dermatitis is present. There is minimal uptake into the dermis.

• Tretinoin is an active metabolite that does not require conversion.
• It is found normally in plasma.
• It is excreted in the hepatic system, as well as removed by skin desquamation.

Approved Indications for Use

• Acne
• Photoaging

Contraindications

• Nursing
• Pregnancy, at risk Category C, is a relative contraindication. Despite five case reports, there is no clear evidence that topical retinoids are harmful to the fetus. However, it is prudent to avoid, especially in the first trimester.

Precautions

• Exercise care when using with other photosensitizing drugs, e.g., tetracyclines and thiazides.
• Tretinoin can cause photosensitivity. Instruct patients to avoid unnecessary or prolonged exposure to sunlight, and wear sunscreen and protective clothing.
• Tretinoin can also cause skin irritation and hypo- or hyperpigmentation.

Patient Compliance Can Be Influenced by Product Selection

Skin irritation is a significant concern, especially for eczematous patients, whose skin is already hypersensitive from existing topical treatments; and further exacerbation by retinoids is not likely to gain compliance. Minimize irritation by selecting a tretinoin formulation that is combined with a vehicle most suitable for the patient’s skin type. A special microsphere waterbased gel delivery system where the tretinoin is delivered to the epidermis more slowly and evenly can be less irritating. This delivery system also allows more predictable sustained applications to be used in the skin. These new water-based gels
must be distinguished from alcohol-based gels.

Other options to improve tolerance for other bases include:

• Using a cream base rather than an alcohol-based gel.
• Initially using a lower concentration of the retinoid.
• For those with oily skin, an aqueous gel might reduce an oily appearance.
• Patients with dry skin, do better by avoiding the traditional alcohol gels.

In the initial phase of treatment, it must be made clear to the patient that the acne can increase or appear to worsen. This perception is common even if there is an actual reduction in acne counts. Visible improvement may be noted after 2 weeks of treatment, but the appearance may be worse for the first few weeks. However, it is important for the sake of compliance to explain that significant improvement may take up to 2–3 months to occur.

Advice to the Patient to Enhance Compliance

Quantity:

• Applying a small amount of the topical medication, i.e., about the size of a pea to form a thin, almost imperceptible layer, may reduce irritation.

Use a moisturizer:

• Areas such as the nasolabial folds, as well as those below the corners of the mouth, are more easily irritated. Adding a noncomedogenic moisturizer before or after the application can reduce irritation.

Dry skin:

• Applying tretinoin to dry, nonmoistened skin is advised. If irritation continues to be a problem, apply tretinoin to an unwashed face; this allows the skin’s protective oils to build.

Time of application:

• Some dermatologists recommend that anti-acne products with the potential to irritate
  should be applied in the early evening to avoid the occlusive effect of the sleeping face on the pillow.

Contact time:

• Reducing contact time by washing the topical off with a gentle cleanser a few minutes after application may also reduce irritation. Contact time can be gradually increased as tolerated. When using the microsphere technology, this strategy may not be as relevant because the tretinoin is released more slowly onto the skin.

Frequency of application:

• Initially, the application of the retinoid every 2–3 days will reduce irritation.

Area of application:

• It is important that the retinoid be applied not just on individual spots, but all over the affected area to prevent the formation of new lesions.

Expectations for rate of response:

• It must be made clear to the patient that the acne can increase or look as if it is increasing over the first few weeks. This perception is common even when the actual acne counts are reducing. For the sake of continued compliance the patient must understand that significant improvement may take 2–3 months to be seen, and it may take up to 6 months to see maximum benefit.

How long is treatment required?

• Acne is a chronic condition so the patient must understand that longterm treatment is required, even after improvement has been achieved. Microcomedones are the first events occurring in acne formation and these invisible lesions can be prevented by continued topical retinoid use.

Photoprotection:

• Sun avoidance or sun protection must be encouraged as tretinoin thins the stratum corneum, and allows greater entry of UV light into the skin.

Benefits

All acne patients can benefit from topical retinoids:

• As a first-line treatment for those with comedonal acne
• Mixed comedonal and inflammatory acne will benefit
• For mild-to-moderate inflammatory acne

Patients with severe acne can be helped by topical tretinoin once the severity of the acne has been diminished by systemic therapy. It can be used to reduce recurrence. Cystic acne needs systemic therapy, but topical retinoids, following the use of oral isotretinoin, may reduce recurrences by preventing the formation of microcomedones, as well as using the collagen
enhancing properties to hasten the repair of depressed areas of the skin.

Conclusion

Topical retinoids are the cornerstone of acne therapy and they can be used across the entire spectrum of acne severity. Selecting the most suitable retinoid formulation, as well as dispensing proper advice in terms of drug application, can improve patient compliance. It is also important to establish realistic patient expectations with regard to the rate of improvement in order to ensure compliance and increase the chances of achieving treatment success.

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Case History

She had recently been prescribed a topical retinoid, however, she believed she was allergic to it. She wore make-up to conceal her problem and was very embarrassed by her appearance. Her job requires her to be in contact with the public, and she confessed to being very impatient with the rate of treatment response.

Further questioning revealed that her periods were regular and she was not taking oral contraceptives (OCPs). She had a history of eczema and adverse reactions to some topical products. The patient was not taking any medications that could aggravate acne (e.g., lithium, phenytoin). She confirmed that her make-up was oil-free and non-comedogenic.

Clinical Assessment

The patient was asked to remove her make-up. Closer examination revealed the presence of inflamed papules with some comedones that were located mainly on the cheeks and forehead; there were many whiteheads and no blackheads; and the background skin appeared normal. (See Figure 1.)

Figure 1: Examination revealed the presence of inflamed papules with some comedones, many whiteheads, no blackheads and normal appearing background skin.

It is unlikely that the patient has a retinoid allergy. Her reaction began within 48 hours of using a retinoid product, producing skin redness, scaling, and sensitivity, but no swelling of the eyelids. Moreover, she had no previous exposure to retinoids. The evidence indicated that it was an irritant rather than an allergic reaction.

Diagnostic Features

Acne

• Non-inflammatory lesions (comedones)
• Inflammatory lesions (papules & pustules)
• Scarring (examine using tangential light)
• May have significant psychological impact.

Rosacea

• Fair complexion
• Flushing, telangiectasias
• Background redness, which eventually becomes permanent
• Papules and pustules in the central face
• Absence of comedones

Perioral Dermatitis

• Most prevalent in young women and adolescents.
• Scaling, erythema, and papulopustular lesions – may have small vesicles.
• Papules are small and avoid the vermillion border.
• Usually situated around the mouth, chin, and nasolabial folds.

Treatment Options

It was difficult for the patient to accept retinoid treatment as an option because of her recent experience. Moreover, she wanted to avoid systemic therapy, at least initially, and could not afford the light or laser treatments.

Recommendation

With this patient profile, a topical antibiotic-BP combination was recommended.

Practical Tips for Application of Combination Therapy

• Apply a small amount (pea sized) to the face in the evening.
• Apply to dry skin that has not been washed recently.
• If the product is irritating, short contact application can be used, such as washing off after 2-3 minutes.
• Warn of potential for bleaching clothes.
• It is reasonable to expect about a 25% improvement after 1 month.
• Acne may flare in the first few weeks, so the patient needs to be warned.
• This is not photosensitizing.

Discussion

In general, laboratory assessments are not necessary if the patient’s periods are regular. She is not taking an OCP so this could be a future avenue of treatment if she is unresponsive to topicals.

It is reasonable for the patient to be prescribed a combined product such as BP plus an antibiotic, to be applied once daily in the evening to decrease inflammation and reduce the number of lesions. In conjunction, a once-daily application of a topical retinoid may need to be introduced later, probably using short contact initially, i.e., leave on for a few minutes and then wash off the product.

Acne patients should return for a 2-month follow-up visit to check for compliance and proper application of topical preparations. The first sign of improvement is a reduced number of new lesions and this frequently occurs, but it may not be enough to be noticed by the patient. If, after another 2 months, further improvement is not seen, adding a systemic drug may be necessary. If scarring is seen, then a more aggressive treatment may be warranted. A multifaceted approach is required in assessing and successfully treating acne due to the range of causes, symptoms, and available treatment options. Since patient compliance is a concern, a great deal of attention must be given to the methods available to minimize the chance of irritation. In the opinion of the author, this may be the single most important factor influencing the success of topical therapy in acne.

Benzoyl Peroxide

• Considered to be the most frequently used topical treatment for acne.
• Acts as a potent antibacterial and converts to benzoic acid on the skin.
• Is safe and effective, especially for inflammatory acne.
  • Lowers Propionibacterium acnes (P. acnes) by 98%.
  • Lowers free fatty acids by 50%.
  • Reduces the size and number of comedones.
  • Strengths of 2.5% and 5% can be as effective as 10%, depending on the formulation.
• Is as effective as topical antibiotics against papules/ pustules.
• Is effective against comedones, but less so than the retinoids.
• Precautions include dryness, warm sensation, tingling, stinging and bleaching of colored fabrics.

Topical Antibiotics

Topical antibiotics, e.g., clindamycin and erythromycin, reduce P. acnes on the skin and in hair follicles.

• Very effective, but concerns about antibiotic resistance make their use as a single agent less acceptable.
• Anti-inflammatory; reduces P. acnes.
• Lacks comedolytic effects, therefore has limited use as a single treatment; more useful in a combined treatment regimen.

Combination Therapy

Acne is caused by multiple pathogenic factors; combination therapy can increase the chances of treatment success.

• BP/clindamycin
• BP/erythromycin
• Has synergistic effects.
• Can produce less irritation.
• BP appears to inhibit antibiotic resistance to topical clindamycin and erythromycin.

Retinoids

• Effective for mild-to-moderate acne.
• Include tretinoin, tazarotene, adapalene.
• Exhibit comedolytic, anticomedogenic, antiinflammatory, and antibacterial properties.
• Have been shown to prevent the formation of comedones.
• It is essential to advise patients of the importance of sunscreen protection.

1. La Clinique de Dermatologie, Moncton, NB, Canada
2. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Background

Human papillomavirus (HPV) is a very common sexually-transmitted disease that is associated with a number of benign, premalignant, and frankly malignant lesions of the anogenital tract. In Canada, its prevalence varies depending on a number of risk factors, but appears to be highest in people between 15-25 years of age. [Varela A, et al. Skin Therapy Lett – US FP Ed 1(2): 1-3 (2007 winter).] ThSkin The introduction of a relatively new immunomodulator, and the approval of a vaccine significantly improves treatment options in managing this condition.

Condyloma Acuminatum (anogenital warts) is a common form of HPV infection. The majority of these are due to infection with HPV 6 or 11, and are clinically benign. Genital warts are usually asymptomatic, but can cause pruritus, bleeding, or mild burning. The warts present as:

• small, verrucous papules
• discrete, sessile, smooth-topped papules or nodules
• large exophytic masses

Lesion color can range from flesh-colored to pink to reddish brown, and often they are multifocal. Lesion distribution generally corresponds with the areas of highest friction during sexual activity.

Risk Factors

• The number of sexual partners over a lifetime
• The sexual promiscuity of the sexual partners
• Correlations between oral contraceptives and smoking have been reported.[Trottier H, et al. Vaccine 24 Suppl 1:S1-15 (2006 Mar).] However, the literature has not consistently supported such findings.

Pathogenesis

The virus is inoculated directly into the epidermal layers of the skin through epithelial defects, especially with maceration. Genital infections are primarily contracted through sexual contact. These infections can then be transmitted to newborns via passage through the infected birth canal. [Kaye JN, et al. J Gen Virol 77(Pt 6):1139-43 (1996 Jun).]

Diagnosis

• Primarily made by visual inspection.
• For hard to detect lesions, particularly on the cervix, a 5% acetic acid solution can be applied to the suspected area. After a few minutes, the condylomata should appear as white patches on the mucosa. These changes are not diagnostic for HPV.
• A biopsy may be useful if:
  • diagnosis is uncertain.
  • lesions do not respond to standard therapy.
  • the disease worsens during therapy.
  • the patient is immunocompromised.
  • the warts are pigmented, indurated, fixed, bleeding, or ulcerated. [CDC. Genital Warts Treatment Guidelines 2006.

Differential Diagnosis

• Molluscum contagiosum
• Benign penile pearly papules
• Hymenal remnants
• Bowenoid papulosis
• Seborrheic keratosis
• Syphilitic condyloma lata
• Skin tags
• Squamous cell carcinoma
• Verrucous carcinoma (Giant condyloma of Buschke-Lowenstein)
• Vulvar dysplasia
• Linear epidermal nevus
• Lichen nitidus
• Angiokeratomas
• Milium
• Fordyce spots

In the majority of patients, treatment can induce wart-free periods; if left untreated, warts may resolve on their own, remain unchanged, or increase in size or number. Treatment can reduce, but does not eliminate, HPV infection. The choice of treatment should be guided by the preference of the patient, the available resources, and the health provider’s experience. No single treatment is ideal for all patients or all warts. The majority of patients require a course of therapy rather than a single treatment, and improvement will generally be seen within 3 months. [CDC. Genital Warts Treatment Guidelines 2006.] Before beginning any treatment, it is essential to screen patients for other sexually-transmitted diseases.

Most treatment modalities treat the symptom of the disease (warts) versus the disease itself. However, imiquimod, goes further by inciting an immunologic response, thereby providing a field effect in clinical and subclinical HPV.

There are three treatment modalities:

• Antiproliferative agents
• Destruction/excision therapies
• Immunomodulatory therapy
• Combination therapies

Antiproliferative Therapies

• Podophyllin resin 10%-25%
  • provider-administered
• Podophylox 0.5% solution or gel
  • can be applied by the patient
  • does not contain the mutagenic substances found in podophyllin resin.

Destruction/Excision Therapies

• Local cryotherapy is the most common destructive mode.
  • It is safe during pregnancy.
• Application of topical trichloracetic acid
• Electrocautery
• Ablative laser treatment
• Excision by scissor, curette, or scalpel
• All of these options have a risk of scarring.

Immunomodulatory Therapy

• Imiquimod
• Approved by Health Canada in 1999.
• Topical cream – administered by patient.
• Self-administration improves patient compliance.
• Enhances the cytotoxic immune response, which is usually seen as an inflammatory response.
• Applied directly to the affected skin 3 times per week for up to 16 weeks. Initially the frequency of applications can be reduced if the patient is over concerned by the degree of inflammation.
• Acts to reduce the viral load, thereby reducing recurrence rates to very low levels.
• A significant advantage is the ability to affect subclinical lesions.
• Is more effective in women than in men possibly because warts are more commonly found on mucosal skin.

Combination Therapy

• Often monotherapy can be inadequate for treating anogenital warts. Combination therapy can provide a better result.
• Treatment with imiquimod followed by excision of residual lesions may provide long-term clearance of anogenital warts in those patients for whom monotherapy was insufficient.[Carrasco D, et al. J Am Acad Dermatol 47(4 Suppl):S212-6 (2002 Oct).]

Figure 1: Algorithm for treatment of suspect lesions. [Adapted from Varela A, et al. Skin Therapy Lett – US FP Ed 1(2):1-3
(2007 Winter).] TCA= trichloroacetic acid

Prophylaxis

A quadrivalent HPV recombinant vaccine is now available in Canada, and is indicated in girls and women aged 9-26 years for the prevention of diseases caused by HPV types 6, 11, 16, and 18, which include genital warts, cervical cancer and other neoplasias of the cervix, vagina and vulva. It should be administered IM as three separate 0.5ml doses. Studies with this vaccine are now ongoing in males. Another bivalent HPV vaccine (for HPV types 16 and 18) is currently under review with Health Canada. There is no evidence for effectiveness in treating those who already have genital warts.

Conclusion

Most HPV infections are asymptomatic and can spontaneously clear on their own. However if treatment is required, there are a number of antiproliferative, destructive, immunomodulatory modalities available. Combination therapies have been shown to be advantageous. In general, the response time can be expected within 3 months of therapy. Patients should be evaluated throughout the course of therapy for treatment response and side-effects, and treatment should be changed if substantial improvement is not seen within that time frame. Cryotherapy combined with imiquimod appears to be very commonly used. A quadrivalent HPV recombinant vaccine is now available for girls and women 9-26 years of age, and a bivalent vaccine is under review with Health Canada. While not of benefit to those already infected, future generations may be spared considerable burden from external genital warts due to the development, approval, and release of HPV polyvalent vaccines. Not only does the vaccination largely prevent incident external genital warts, but it also protects against genital tract HPV-associated neoplasia.

Department of Dermatology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

The Organism

Malassezia are lipophilic yeasts that are normal commensals on the skin surface. Named after French microbiologist Louis Charles Malassez (1842-1909), there are seven species of these yeasts, which were previously called Pityrosporum. They usually form colonies in the skin in late childhood and adult life, but can be found in some neonates. The conditions described in this article are either caused by the Malassezia itself or from some kind of immunological or toxic reaction to the organism.

Malassezia can cause:

• Dandruff
• Adult seborrheic dermatitis
• Pityriasis versicolor
• Pityrosporum (Malassezia) folliculitis

The treatment recommendations are based on evidence-based medicine, physician experience, and patient preference.

Dandruff

What It Is

• Also known as pityriasis capitis. Caused by M. globosa which produces oleic acid from its action on sebum, it is an irritant to skin.
• This is the mild end of the spectrum of seborrheic dermatitis. It is very common, with white scaling on the scalp but no inflammatory reaction, as seen in true seborrheic dermatitis.

Treatment

• Shampoos active against Malassezia yeasts are usually sufficient for this condition. These shampoos can be either antifungal, keratolytic (salicylic acid), or cytostatic (coal tar).
  They can be used daily until control is achieved, and then the frequency can be reduced to prn (often 1-3 times a week).

Antiyeast shampoos

• Over-the-counter (OTC)
  • Zinc pyrithione (Head & Shoulders®) Zinc pyrithione shampoos have been developed in recent
    years to ensure that particle size, shape, and adherence of
    the therapeutic molecule give improved bioavailability,
    and therefore greater effectiveness. Cosmetically elegant
    shampoos are now produced with great acceptance
    by consumers.
  • Selenium sulfide (Selsun®) – very actively antifungal
  • Ketoconazole (Nizoral®)

• Prescription
  • Ciclopirox shampoo (Loprox®)

Seborrheic Dermatitis

What It Is

• A common (5% prevalence) chronic relapsing rash seen in adults
• Quite well-defined erythematous lesions that do not cross the hair line of the scalp
• Accompanied by a greasy looking scale
• Located on the scalp, medial eyebrows, in and around the ears, central chest, and upper back. It may also be found in the intertriginous areas. Rarely, it is generalized.
• More extensive and inflammatory variants are seen in patients with AIDS.

Risk Factors

• Neurological conditions, e.g., poststroke, Parkinsonism
• HIV-AIDS
• Antipsychotic drugs

Differential Diagnosis

• Scalp:
  • Scalp Psoriasis
    • Well-defined lesions that may extend beyond the hairline. The scale is more silvery than the greasy yellowish-brown colour seen in seborrheic dermatitis. May have involvement in other typical sites. Central facial involvement uncommon. It may
      sometimes be impossible to distinguish the two conditions.
  • Tinea Capitis
    • Usually seen in children. There is a spectrum of appearance ranging from mild scaling to boggy plaques.
• • Atopic Dermatitis
    • May be aggravated on the face, neck, and upper chest by Malassezia yeast.

• Face:
  • Facial Rosacea
    • Central face with papules and pustules. Flushing always present. Nasolabial and paranasal scale not usually present but blepharitis is seen in both. The two conditions quite frequently coexist. Systemic lupus does not exhibit papules and pustules.
  • Intertriginous Seborrheic Dermatitis
    • Erythrasma, intertrigo, psoriasis

Treatment

• The selection of therapy depends on the effectiveness, ease of use, and cosmetic acceptability of the products. The face, scalp, and chest are the most common sites of involvement.

Evidence-Based Therapy

• Evidence-Based Therapy
• Oral and topical ketoconazole, and hydrocortisone are first-line treatments.
• Lithium succinate ointment, 15% propylene glycol in water.
• Zinc pyrithione shampoo (Head & Shoulders®)

Suggested Therapy

• Gain control of facial dermatitis with topical ketoconazole cream. Hydrocortisone 1% cream can be added if necessary.
• OTC: Antiyeast shampoos, e.g., zinc pyrithione (Head & Shoulders®) can be used in the shower, first on the scalp in the usual way, and then rubbing the lather onto the face and chest if necessary and left on for 30-60 seconds before washing off. If this is not effective, other antiyeast shampoos can be tried in a similar fashion. Patients often prefer treating this condition in the shower rather than by applying creams.
• If the scalp is unresponsive to topical steroid solutions, gels and shampoos can be used on the scalp (e.g., betamethasone valerate solutions [e.g., Betnovate®] flucinonide gels, clobetasone shampoo [Clobex®]).
• The use of immunomodulators such as pimecrolimus cream (Elidel®) has been found to be helpful for the control of facial seborrheic dermatitis that is unresponsive to other therapy. Tacrolimus ointment (Protopic®) has also been found to be helpful.

Pityriasis Versicolor

What It Is

• Infection confined to the trunk and proximal limbs when the yeast transforms into hyphae. Hair and nails are never involved.
• Fine scaly patches of varying color, red, brown, and white; usually in young adults. Seen on the upper trunk, neck, upper arms, and occasionally the scalp.
• Hypopigmented patches, caused by the yeast, produce azelaic acid, which inhibits melanin production. The hypopigmentation may last for months after the yeast overgrowth has been controlled. Occasionally the condition remits spontaneously.
• The diagnosis is confirmed by the appearance of spores and hyphae (spaghetti and meatballs) on KOH exam of skin scrapings of the scale.

Risk Factors

• Sun exposure
• Pregnancy
• Sweating
• Cushing’s syndrome
• Interestingly, it is not more common in HIV-AIDS

Differential Diagnosis

• Vitiligo is commonly seen on the face, hands and genitals. There is no scale present. Much more complete depigmentation. Frequent hyperpigmentation at the edges of the lesions, which often vary in size. Depigmentation of hair can occur.
• Other conditions to consider are tinea corporis and postinflammatory hypopigmentation.

Treatment

• The erythematous and brown patches tend to respond quickly to therapy.
• Hypopigmented lesions are slow to respond, persisting long after the yeast infection has cleared. Sun exposure may be required to stimulate repigmentation.
• High recurrence rate, especially for those who exercise and sweat regularly. Maintenance treatment is often required, especially in the summer months.

Evidence-Based Therapy

• Topical antifungal creams, i.e., ketoconazole, clotrimazole, and terbinafine have been shown to be effective. Ketoconazole shampoo is also effective.
• Oral itraconazole (200mg daily for 1 week), ketoconazole (400mg single dose, repeated in 1 week) and fluconazole (Diflucan®) (150mg-300mg weekly for 1 month) have been shown to be effective.
• Propylene glycol 50% in water b.i.d. for 2 weeks.
• 1% zinc pyrithione shampoo applied in the shower and left on for 5 minutes.
• Selenium sulfide 2.5% lotion daily and left on for 10 minutes for 1 week.
• A combination of honey, olive oil, and beeswax in equal parts used t.i.d. has been shown to be effective.

Suggested Therapy

• Patients can be given a choice of oral or topical therapy. The surface areas are large, making the application of antifungal creams difficult and costly.
• Most will clear with the OTC shampoos such as zinc pyrithione or ketoconazole applied in the shower and left on for a few minutes before being washed off.
• Selenium sulfide shampoos can be irritating.
• Those with very extensive or resistant involvement can opt for systemic therapy. It must be noted that oral terbinafine is ineffective for this condition. A short course of ketoconazole or fluconazole can be used at the doses shown above. Oral ketoconazole can be hepatotoxic, but is not thought a problem for such short courses.

Pitysporum (Malassezia) Folliculitis

Seen in Three Scenarios

• Back and upper chest involved with itchy papules and pustules.
• Associated with seborrheic dermatitis on the upper trunk.
• Multiple pustules on the face and trunk in HIV+ individuals

Treatment

• Treat the underlying condition.
• Topical antiyeast creams are recommended.
• If no response to oral antifungals, treat as discussed for
  pityriasis versicolor.

The skin has evolved to protect us from the harmful effects of ultraviolet light. Sunscreens were first developed to prevent sunburns by blocking UVB; they allowed us to prolong our time in the sun, but that resulted in increased exposure to UVA. Most modern sunscreens
attempt to block the whole spectrum of UV light, however not all so-called broad spectrum sunscreens protect skin from the whole range of UVA.

A Comparison on UVA and UVB

Long-term Effects on the Skin

Most of us know that sun exposure has immediate positive and negative effects on the skin. The medium and longer term effects are negative. Positive effects include a sense of warmth, pleasure and Vitamin D production.

Photosensitive Rashes

These occur only when activated by UV light. Most of them are brought on by UVA. Photosensitive rashes (detailed below) can be thought of as:

1 – Idiopathic reactions to UV light
(Polymorphous light eruption – PLE)

The timing of the onset of the rash in relation to sun exposure and its duration, as well as the type of reaction produced on the skin, is key to making the diagnosis. As always there is some variation.

2 – Phototoxic and photoallergic skin reactions

There are a number of drugs and chemicals that can produce a reaction in the skin. These can be either phototoxic or photoallergic reactions.

3 – UV aggravation of existing conditions

There are many pre-existing conditions that are aggravated by sunshine. Some of the important light aggravated conditions are:

Polymorphous Light Eruption

Sun Exposure Causes
Rash starts within hours of exposure and lasts for days even with no further sunshine. Solar urticaria is seen within minutes of exposure. Rash can be seen in the form of papules, papulovesicles or plaques, hence the term polymorphous. Plaques are less commonly seen.		Polymorphous light eruption (PLE) Mostly caused by UVA Occurs in early spring or summer, and often during vacation periods Is mostly symmetrical, red papules and plaques. Occurs in exposed areas but not necessarily all the exposed areas Occurs in 10%-20% of the population May be confused for allergic reaction to sunscreen Skin tends to be less reactive to sun as the summer progresses. The type of rash tends to remain constant for each patient.		Treatment of PLE Sun avoidance and protection with broad spectrum sunscreen (UVA and UVB) Topical steroids and antihistamines UVA and UVB light therapy may help some at the start of the season, which can harden the skin and prevent the reaction. Hydroxychloroquine, 400mg daily for 2 weeks in the spring or before a vacation may help

Photoxic vs. Photoallergic Reactions

Phototoxic drugs or chemicals

• Sunburn-like
• Usually seen within hours
• Usually caused by UVA

Includes tetracyclines, sulfa, amioderone, fursomide, naproxen, piroxicam, chlorpromazine, ciprofloxacin, thiazides

Photoallergic reactions

• An eczema like reaction. Can be thought of as a delayed hypersensitivity type reaction.
• Causes: Sunscreens, fragrances/aftershave (like musk ambrette, sandalwood oil), chlorhexidine

Phytophotodermatitis

• A special type of reaction to topical contact with a sensitizer called psoralen contained in a number of plants.
• UVA plus psoralen will produce a blistering reaction often seen in streaks; a brown pigmentation is produced
• which may last for months.
• Plants containing psoralen are responsible including lime, yarrow, cow parsley, celery, lemon, fig

Photoprotection

Should be encouraged to prevent the immediate, medium and long-term ill effects of excessive sun exposure. Some sun exposure is desirable for vitamin D production.

Two ways to encourage photoprotection:

1. Sun avoidance

• Avoid the sun between 10am and 3pm.
• Try to stay in the shade.
• Wear protective, tightly woven clothes and a broad brimmed hat.

2. Sun protection

• Use a Broad-spectrum sunscreen in a sufficientquantity.
• SPF = the ratio of minimal erythema dose (MED) of protected skin/MED of unprotected
• skin. This is a crude biological measure.
• The SPF factor is calculated using 2mg/cm2 of sunscreen. Most people apply only 25-50% of this.
• Reapply sunscreen every 2 hours; UVL causes some chemical sunscreens to become inactive over time.

Sunbed Tan

• Very popular, producing good, even colour.
• Contain dihydroxyacetone (DHA); reacts with amino acids containing keratin. DHA concentration varies from 2%-6%; higher numbers give a darker colour.
• DHA has an SPF of 2%-3%. Some have a low SPF screen added that lasts only a few hours.
• Coloured skin does not provide protection against photodamage.
• Bronzers are dyes that are added to the skin; can be washed off.
• Beta-carotene, tyrosine, tanning accelerators such as psoralen are not recommended.

Sunscreen Use

• Broad spectrum only should be used.
• SPF related to UVB protection only; does not provide a reference to UVA protection.
• All sunscreens have UVB protection; reflected in the SPF.
• If skin sunburns in 10 minutes, properly applied sunscreen at SPF 15 means skin will burn in 150 minutes.
• Physical screens reflect light; chemical screens absorb UV, converting energy into heat
• SPF15 blocks 87.5% of UVB and SPF 50 blocks 98% of UVB.

Sunscreen Choices

Sunscreen with full spectrum UVA protection contains:

Avobenzone (Parsol 1789), Mexoryl Sx, and Zinc oxide working together. The first two have slightly different peaks of protection. Titanium Dioxide, Dioxybenzone Methyl anthranilate and Octocrylene provide UVA protection, but not along the whole spectrum. Some recommended general sunscreens: Ombrelle® 30, 45, 60, cream and lotion. (This broad spectrum sunscreen was pioneered in Canada); Anthelios® 30, 45, 60; Neutrogena® Heathy Defense Sunblocks 30, 45 with parsol.

Special sunscreens:
Lip protection: SCC is more commonly seen in men and women who don’t wear lipstick:
Ombrelle® Lip Balm SPF30; RoC Minesol® Lipstick SPF 20; Neutrogena Stick 30; Antherpos ® SPF 50. For joggers these can also be used above the eyebrows to prevent the screen from entering the eyes. Can also be used on the nose.

Spray for athletes, or for people with hairy or oily skin: Ombrelle® Sport Spray 15; Coppertone ® Sport 15 and 30; Neutrogena® Healthy Defense Spray 30.

Faculty of Medicine, University of British Columbia, Vancouver, Canada

Diagnostic Features of Eczema or Atopic Dermatitis (AD)

Diagnostic Features of Eczema or Atopic Dermatitis (AD): a chronic relapsing condition in patients with a personal or family history of atopy. Usually starts before the age of 2 years and usually improves or resolves in older children and adults.

• Itching must be present to make the diagnosis
• Dry Skin is always present
• Typical Rash Location varies with age of patient. Infants: face usually involved. Diaper area and axilla usually clear. Extensor arms and legs involved due to friction from crawling. Children 4-10 years: flexures, sides of the neck, earlobes.
• Inflammed Skin usually seen
• Secondary Infection – Staphylococcus aureus very common, molluscum and herpes infections often more extensive

Treatment: Self-help and Medical Treatments

1. Patient Self-help – Patients may not improve if triggers are not removed

Aggravating/Trigger Factors to be Avoided

• Skin irritants such as soap, bubble bath, detergents, fabric softeners and perfumed products.
• Frequent bathing, especially if not followed by moisturizers. Sweating may exacerbate pruritus.
• Skin infection will tend to promote AD
• Food allergies can play a role in a small percentage of young patients with AD (e.g. eggs, milk, nuts, peanuts, fish, shellfish,
• wheat, and soy account for over 90% of food allergies)
• Environmental allergens such as house dust mites

Self-Help
1. Use a mild cleanser; 2. Moisturize often; 3. Hydrocortisone; 4. Cool bathing; 5. Use perfume free products; 6. Oral antihistamines; 7. Avoid triggers

Mild Cleansers

• Mild soap or nonsoap cleanser like Spectrojel®, Spectroderm®, Cetaphil®, plain white Dove®
• Emulsifying ointment USP (ask pharmacist)

Moisturizers
Use at least 250mg of cream/ week. Must be thick like butter or greasy like petroleum (e.g., Vaseline® Petroleum Jelly, Aquaphor® ointment, Creamy Vaseline®, 25% water in Hydrophilic Petrolatum, Aqueous cream, Aveeno® cream, unscented cold cream, Eucerin® cream, Cetaphil® cream, Cliniderm® cream)

2. Medical Treatment

Relief and suppression of eczema flares check list:

• Itch Relief – Dry Skin Therapy – Inflammation Suppression
• with anti-inflammatories
• Infection Control

Itch Relief
Oral-sedating antihistamines at bedtime. Hydroxyzine, Benadryl®, start at low dose and increase as tolerated. Moisturize and use topical anti-inflammatory. Wet compresses using gauze or face cloth dipped in tepid water, rung out and then laid on oozing skin is soothing.

Long-term Control by Preventing New Flares

Control of a flare may be easier than motivating a patient to continue intermittent use of an anti-inflammatory or to regularly moisturize the skin and avoid triggers. Using anti inflammatory topicals at the first signs and symptoms can minimize the use of medication and give smoother control of the disease.

Dry Skin

Frequent moisturizing especially within 2-5 minutes after bathing and when skin is wet. Most patients under moisturize. Check the quantity used. Use a minimum of 250mg/week (more if possible).

Anti-inflammatory Drugs
Corticosteroids and Calcineurin inhibitors are useful for shortand long-term use.

Topical Corticosteroids (TCS)

• Gold standard of treatment for AD
• Quick acting anti-inflammatory action. Potency from mild to very potent.
• General rule is that one uses the lowest potency possible for control of the disease. Goal is to be off the steroid more often than on the steroid.
• Useful for flare prevention.
• In conjunction with calcineurin inhibitors, they have a role
• as rescue medication when severe flares develop.
• Low potency corticosteroids are best used in the skin folds, face and neck.
• Moderate potency steroids are needed for thick lichenified eczema in older children and for acute flares on the body.
• Side-effects such as skin atrophy, tachyphlaxis, and adrenal suppression can occur but these are usually seen if the drug is used for too long, too often, or too much especially on the face folds, or inner thigh. Very young and old patients are more at risk. No harm will come from using potent corticosteriods for short periods, i.e., days at a time.
• Two issues of concern are steroid phobia by patients and
  steroid allergy:
  a) Steroid phobia — patients need to understand that the
  body naturally produces steroids and that side-effects are unlikely if topical steroids are used appropriately.
  b) Steroid allergy – Uncommon. Patch testing is required to confirm.

Topical Calcineurin Inhibitors
Pimecrolimus (Elidel™ 1% cream) Nonsteroid approved for short- and long-term intermittent use in mild-to-moderate AD over 2 years of age. Guidelines suggest use when other standard treatments fail or there is concern regarding risk of side-effects.

• Rapid relief (1-2 weeks) due to targeted anti-inflammatory action
• Used in practice to bring AD under control and also intermittently thereafter at first signs and symptoms of disease activity to prevent flare-ups. Topical corticosteroids can also be used but some physicians reserve them for more severe flares.
• Well-controlled studies in infants, children and adults demonstrate significant reduction in incidence of flares with the use of corticosteroids.
• Long-term studies show efficacy and safety in infants from 3-23 months, but it is not approved for this age range.
• Burning or stinging can be a problem but the likelihood is usually relative to disease severity. Patients do much better if warned of this transient effect.
• Long term safety – see Author’s Comment on recent FDA advisory.

Tacrolimus (Protopic™0.03% and 0.1%ointment) Non-steroid approved for short-term intermittent use in moderate- to-severe atopic AD over 2 years of age (0.03% >2yrs, 0.1% >15yrs). Guidelines suggest use when other standard treatments fail or concern regarding risk of side effects.

• Rapid relief (1-2 weeks) due to targeted anti-inflammatory action
• Used in practice to bring AD under control and also intermittently thereafter at first sign of disease activity or flare. TCS could be used as rescue medications for severe flares
• Long-term studies show safety and efficacy in > 2yr old.
• Burning or stinging can be a problem but the likelihood is usually relative to disease severity.
• Long term safety – see Author’s Comment on FDA advisory.

Infection Control

Clinical experience shows that AD may respond to anti Staph antibiotics even when there are no signs of a typical impetigo. Localized AD with probable secondary infection (swab if in doubt) use mupirocin cream, fucidic acid cream/ointment or oral cloxacillin or cephalosporin if widespread.

Authors’ Comments

Recently asked question: What is the role of calcineurin inhibitors in the control of eczema following the recent FDA Health Advisory?

It is the authors’ opinion that the recent Advisory about calcineurin inhibitors increasing the risk of cancer is based more on fear than fact. Granted that long-term use of oral immunosuppressive agents, such as in the transplant population, does raise the incidence of lymphoma, the degree of suppression is dose related. Rates of lymphoma and skin cancers in clinical trials and postmarketing surveillance reveal cancer rates that are much lower than would be expected in a control population. Evidence shows that both pimecrolimus and tacrolimus have very low systemic absorption when used topically as recommended for AD. Animal studies using oral formulations showed a higher rate of lymphoma, but at very high doses. What is clear is that people with AD have very significant disease that impacts most negatively on their quality of life. For the physician and patient there is no option other than to treat this disabling condition. With any medication there are always potential risks, but based on the available information the benefits of these medications far outweigh the risks. Resistant cases have been treated with UV light, azathioprine, cyclosporine, mycophenolate mofetil and systemic steroids.

It is significant that in a recent survey of leading dermatologists in North America and Europe conducted and published by Skin Therapy Letter© the majority of these doctors reported that they will not change their habit of prescribing topical calcineurin inhibitors, but are now likely to spend a little more time counseling and informing their patients who show concern.