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. University of British Columbia Student Health Services, Vancouver, Canada
2. Department of Dermatology and Skin Science, University of British Columbia, and The Pediatric Allergy Dermatology Centre (PADC), Vancouver, Canada

Background

The social, economic, and educational impact of head lice infestations is considerable. It is most commonly seen in school-aged children, and girls are more commonly affected than boys. New therapeutic options are now available that may help clinicians to keep ahead of lice.

Infestation

• Caused by the obligate ectoparasite Pediculus humanus capitis; can survive for 1–2 days away from the scalp.
• Transmission most commonly occurs through:
• Close physical contact, especially head-to-head contact
• Fomites, such as hats.
• Transfer is optimal when hairs are relatively stationary and parallel, i.e., while children are at rest.
• Eggs are glued to the hair close to the scalp in egg castings, or nits. Nits within 1cm of the scalp should be counted as a sign of active infestation.

Clinical Presentation

• Most common symptom is pruritus.
• Occurs due to sensitization to either louse salivary or fecal antigens.
• May be so intense that excoriations and secondary bacterial infection may occur.
• Diagnostic gold standard is finding a live louse or nymph on the scalp, or a viable egg attached to the hair. Microscopic examination of the nit may aid in this determination.
• Nits alone are not proof of active infection.
• Not finding a louse does not completely rule out infestation.
• Louse combs increase the diagnostic yield.

Treatment Options

Pediculicides: Neurotoxic Agents

• Includes permethrin, permethrin-based products, malathion, and lindane.
• Not recommended for children < 2 years of age. Off-label use based on clinical judgement.
• Avoid hair conditioner before applying; it may coat the hair and protect the lice and nits.

Permethrin-based Products

• OTC extracts of natural pyrethrins from chrysanthemums combined with piperonyl butoxide to increase stability and effect.
• Neurotoxic to lice, but not ovicidal; even after two treatments viable lice and eggs may remain.
• Contraindicated in patients allergic to ragweed, chrysanthemums, or other permethrin products.

Permethrin 1%

• Historically considered standard treatment; however issues of resistance have made it necessary to explore new alternatives.
• It is a poorly absorbed synthetic pyrethrin with pediculicidal and ovicidal activity.
• Leaves a residue on the hair and remains active for 2 weeks following application.
• Wash hair, rinse with water, towel dry, then apply to entire scalp and hair for 10 minutes and rinse out. Treat again 7-10 days later.

Malathion 0.5%

• Can be applied for 10 minutes or overnight and repeated in 1 week.
• Can cause stinging of the skin and eyes.
• Should be used with caution:
  • base is flammable.
  • may lead to respiratory depression if ingested (there are no reported cases).
• No significant resistance has been reported in the US.

Lindane 1% Lotion

• Second-line treatment to be used as an alternative when other treatments have failed.
• Has limited ovicidal activity; kills lice by causing CNS stimulation and respiratory paralysis.
• Higher side-effect potential including neurotoxicity and bone marrow suppression.
• Contraindicated in children < 2 years, pregnant women, and nursing mothers.

Oral Agent – Ivermectin

• An antihelminthic drug and effective pediculicide
• Suggested for off-label use in the treatment of head lice at a dosage of 200ìg/kg, to be repeated in 7-10 days.
• Possible neurotoxicity is a concern; safety and efficacy remain to be established.
• No resistance has been reported to date and it may be used after failure with topical pediculicides.
• May be useful for extensive infestations or infestations with multiple types of ectoparasites.
• Should not be used in children weighing < 15kg.

Non-neurotoxic Pediculicides

• Exoskeleton Integrity Dehydration Pediculicides
• This is new nonpesticide, nonprescription, behind-thecounter product containing isopropyl myristate 50% and ST-cyclomethicone 50% (Resultz™).
• Recently approved by Health Canada for the treatment of lice in persons aged 4 years and older.
• Works by dissolving the waxy exoskeleton that covers the lice.
• Apply first to dry hair, scalp, and the nape of the neck, leave in place for 10 minutes, then rinse. Repeat in 1 week.
• Phase II clinical trials document a higher success rate (no live lice) compared with traditional pediculicides (57% isopropyl myristate 50% and ST-cyclomethicone 50% vs. 22% with .33% pyrethrin + 4% piperonyl butoxide; 77.1% isopropyl myristate 50% and ST-cyclomethicone 50% vs. 20% with permethrin 1%). [Data on file – Altana Pharma.]
• Other phase II studies showed a 97% (28 of 29 patients) success rate.[Kaul N, et al. In vivo efficacy and safety of an experimental pediculicide rinse. Presented at: the 63rd Annual Meeting of the American Academy of Dermatology, New Orleans, Feb 2005.]
• Well tolerated with mild local erythema or pruritus being the main side-effect.

Dry-on Suffocation Based Pediculicide

• Originally marketed as Nuvo® Lotion; it was later discovered to be Cetaphil® Gentle Skin Cleanser.
• Reported 96% success rate when applied to the scalp, dried with a hair dryer (for ~30 minutes), and removed during the next day’s bath.[Pearlman DL. Pediatrics 114(3):e275-9 (2004 Sep).]
• Reviews found that the study did not use proper methods of diagnosing lice, was anecdotal, and was not a welldesigned, randomized control study.[Roberts RJ, et al. Lancet 365(9453):8-10 (2005 Jan); Burkhart CG, et al. J Am Acad Dermatol 54(4):721-2 (2006 Apr).]
• Given encouraging preliminary results, further study is warranted.

Mechanical

• Nit combing is labor intensive and somewhat painful; should not be used alone.
• Application of a 8% formic acid rinse or a 1:1 mixture of white vinegar and water followed by combing with a nit comb can aid in nit removal.
• The only treatment recommended for children < 2 years of age.

Environmental Interventions

• Decontaminate clothing, linen and towels by washing in hot water (60°C) or dry-cleaning.
• Treat combs and brushes with boiling water, alcohol, bleach, or soak in a disinfectant solution (e.g., 2% Lysol^®).
• Examine all household members and close contacts and treat concurrently if infested.
• Notify the school.
• Treat bedmates prophylactically.

Treatment Categories

Treatment Failures and Resistance

Resistance to permethrin and lindane is common in populations where these pediculicides have been heavily used. Treatment failures can also be a result of reinfestation from:

• an untreated classmate
• an inadequate quantity of pediculicide applied
• the improper duration of product application.

A second treatment of the prescribed pediculicide should be administered 7-10 days after the start of treatment to kill all active stages of the louse. Resistance should be suspected if live lice are still present 2-3 days after the second application of a product has been used correctly and no other cause for failure can be identified.

• If lice are present after 2 correctly applied treatments, resistance is certain.
• Resistant infestations should be treated with an agent from a different class of pediculicides

Conclusion

Lice have developed resistance to some pediculicides and it is expected that with ongoing use, these pediculicides will probably become less effective. These products can still be used effectively to treat nonresistant lice. New products are now available in Canada that may prove to be equal to or more effective/safe than the standard neurotoxic pediculicides, while
at the same time minimize the problem of treatment-resistant lice.

1. University of British Columbia Student Health Services, Vancouver, Canada
2. Department of Dermatology and Skin Science, University of British Columbia,
and The Pediatric Allergy Dermatology Centre (PADC), Vancouver, Canada

ABSTRACT

Pediculosis capitis, or head lice, is a world-wide public health concern affecting persons of all ages and socioeconomic backgrounds. It is caused by Pediculus humanus capitis, an obligate ectoparasite that lives on human hair and feeds on the blood from the skin. Upon diagnosis, treatment should be initiated, since established infestations with head lice generally do not spontaneously resolve. Chemical pediculicides are currently the standard treatment, however, issues of resistance have made it necessary to explore new alternatives. If an infestation is resistant to these drugs, then the physician should consider treating with an agent from a different class of pediculicides or, potentially, with newer nonpediculicides.

Key Words:
pediculosis capitis, head lice, pediculicide

In the US, the number of head lice infestations annually is estimated between 6–12 million among children 3–12 years of age.¹ The social, economic and educational impact of head lice infestations is considerable. In the US, the total direct costs for treatment and indirect costs for lost wages, educational programs, and school and nursing home monitoring programs have been estimated at more than $1 billion annually.²

Infestation is most common in school-aged children with girls being more commonly affected than boys. African-American children are less often affected; this variation is thought to be the result of differences in the hair shaft structure, which may be oval shaped and thus more difficult for a louse to grasp.¹ Transmission of head lice most commonly occurs through close physical contact, especially head-to-head contact, but fomites, such as hats also play a role. Louse transfer has been found to be optimal when hairs are relatively stationary and parallel, suggesting that louse transmission is more likely to occur while children are at rest, than during periods of vigorous play.³

Head lice infestation is caused by the obligate ectoparasite Pediculus humanus capitis, a wingless, elongated, dorsoventrally flattened insect. The adult louse feeds 4–5 times/day and can normally only survive for 1–2 days away from the scalp. Eggs are glued to the hair in egg castings, or nits, close to the scalp and can survive up to 10 days away from the human host. Lice typically lay nits within 1–2mm of the scalp and for practical purposes, nits within 1cm of the scalp should be counted as a sign of active infestation.⁴

Clinical Presentation

Although some children with infestation are asymptomatic, the most common symptom is pruritus, which occurs due to sensitization to either louse salivary or fecal antigens and may be so intense that excoriations and secondary bacterial infection may occur.⁵

Many children with an active infestation will, on exam, have nits attached to their hair and some live lice on their scalp. The diagnostic gold standard for head lice is finding a live louse or nymph on the scalp or a viable egg attached to the hair.⁵ Nits alone are not proof of active infection because some of these represent hatched empty shell casings or nonviable eggs that may retain a viable appearance for weeks after death. Microscopic examination of the nit, or use of a hand lens, may aid in this determination.⁴ Since lice move rapidly, not finding a louse does not completely rule out infestation. The use of louse combs increases the diagnostic yield.³ If head lice is diagnosed, then it should be treated, since established infestations, in general, do not spontaneously resolve.

Treatment

The ideal treatment agent for lice would be free of harmful chemicals, readily available without a prescription, easy to use, and inexpensive.⁵ Chemical pediculicides are currently the standard treatment.

Prior to the emergence of resistance, the treatment of choice in North America was permethrin 1% due to its safety and efficacy. Unfortunately resistance to permethrin and lindane is common in populations where these pediculicides have been heavily used.³ To illustrate this, the insecticidal activity of pyrethroids in the mid 1980s was 100%, but by 2000 it had decreased to only 28%.⁶ Conversely Meinking, et al., in a recent study, showed 1% lindane was the slowest and least effective pediculicide with no lice eradicated after 10 minutes (the recommended application time), and killing only 17% of lice after 3 hours.⁷ Malathion (Ovide^®, Taro Pharmaceuticals), which had not been used extensively in the US, has performed well in permethrin-resistant populations.³ Lice resistance to both pyrethrin and malathion has been documented in the UK (Downs, et al. showed a 64% failure rate for malathion).⁸ The pattern of resistance in an area generally follows the pattern of pediculicide use, and this geographic variation in sensitivities further reinforces the belief that lice adapt to toxins and develop resistance with ongoing exposure.

Treatment Failures

While treatment failures may be due to drug resistance, it is important to recognize many treatment failures are a result of reinfestation from an untreated classmate, inadequate quantity of pediculicide applied, or improper duration of product application.4 A recent paper suggested that a second treatment of the prescribed standard pediculicides (except permethrin) should be administered ideally 10 days after the start of treatment to kill all active stages of the louse.⁹ However, in practice many physicians retreat in 7 days instead of 10. Resistance should be suspected after the second treatment if live lice are still present 2-3 days after a product has been used correctly and no other cause for failure can be identified.1 If lice are present after 2 correctly applied treatments, resistance is certain.¹ Resistant infestations should be treated with an agent from a different class of pediculicides or with newer nonpediculicide agents.

Since permethrin resistance may be a relative phenomenon, some clinicians will use higher concentrations and longer durations of contact in an attempt to overcome this resistance. Whether increasing the permethrin concentration from 1% to 5% and leaving it on overnight affects the cure rate is unclear. Certainly this pattern of treatment may cause a higher rate of skin irritation, but longer contact with the same products is already used with other ectoparasites, such as scabies.

‘No nit’ policies exclude children from school unnecessarily and are not recommended.⁴ The presence of nits alone should not be the basis for exclusion of children from school. The child should be allowed to return to school or child care facilities after proper treatment.⁵

Myths and Facts

Myths about head lice are abundant and belief in these myths is often why treatments are not used properly and why people believe their lice treatment has failed. (See Table 1.)

Standard Pediculicides: Neurotoxic Agents

These agents are historically considered the standard treatment and have been the most effective treatment for head lice. This category of pediculicides is not recommended for children under 2 years of age and off-label use of these products for patients in this age range is based on clinical judgment.⁵ These products should be applied to the entire scalp. Because hair conditioner may coat the hair and protect the lice and nits, it should be avoided before product application.⁷

Permethrin

Permethrin 1% (Nix^®) is a poorly absorbed synthetic pyrethrin with pediculicidal and ovicidal activity. It blocks sodium channel repolarization of the louse neuron resulting in respiratory paralysis and death. By leaving a residue on the hair, it remains active for 2 weeks following application.⁵ After washing hair, rinsing with water, and towel drying, it is applied to the scalp and hair for 10 minutes and then rinsed out. To ensure a cure, many practitioners recommend a second treatment approximately 1 week later as any eggs not killed by first treatment will be hatching.

Permethrin-based Products

Permethrin-based products include over-the-counter (OTC) extracts of natural pyrethrins from chrysanthemums combined with piperonyl butoxide to increase stability and effect. These products are neurotoxic to lice but not ovicidal and even after two treatments viable lice and eggs may remain. These products are contraindicated in patients who are allergic to ragweed, chrysanthemums, or other permethrin products.⁵

Malathion

Malathion is an organophosphate cholinesterase inhibitor that causes respiratory paralysis of the louse. It is a fast acting pediculicide that presently has the highest ovicidal activity. It binds to the sulfur atoms of the hair, accounting for its residual effect. Malathion 0.5% can be applied for 10 minutes or overnight and repeated in 1 week. It has an unappealing odor and can cause stinging of the skin and eyes.⁵ This product should be used with caution, as its base is flammable and may lead to respiratory depression if ingested (although there are no reported cases).⁴ Currently significant resistance to this agent has not been reported in the US, but may occur with ongoing use as seen in other countries.⁸

Lindane

Lindane (gamma benzene hexachloride) 1% lotion is pediculicidal but it has limited ovicidal activity. This organochloride kills lice by causing CNS stimulation and respiratory paralysis. Given lindane’s increased side-effect potential including neurotoxicity and bone marrow suppression, it is considered a second-line treatment.5 Lindane remains on the market as an alternative when other treatments have failed. It is contraindicated in children under 2 years, pregnant women, and nursing mothers.

Oral Agents

Ivermectin

Ivermectin, an antihelminthic drug, has been suggested for off-label use in the treatment of head lice at a dosage of 200ìg/kg, repeated in 7-10 days to kill newly hatched nymphs.11 It is an effective pediculicide and the mechanism of action is thought to be on the symbiotic gram-negative bacteria that are required to digest blood. With the concern of possible neurotoxicity, the safety and efficacy of this agent for head lice remains to be established.³ No resistance has been reported to date and it may be used after failure with topical pediculicides. Treatment with this agent may benefit patients with extensive infestations or infestations with multiple types of ectoparasites.³ Oral ivermectin should not be used in children weighing less than 15kg.⁴ Topical ivermectin holds some promise but warrants further study.³

TMP/SMX

Oral TMP/SMX has been shown to be effective in small studies of off-label use.5 It presumably works by destroying the gut flora of the louse, thereby interfering with its ability to synthesize vitamin B and ultimately causing death.5 Combination therapy with topical agents may improve it’s efficacy.

Non-neurotoxic Agents

Exoskeleton Integrity Dehydration Pediculicides

A new nonpesticide product containing isopropyl myristate 50% and ST-cyclomethicone 50% (Resultz™, Altana) works by dissolving the waxy exoskeleton of the louse, dehydrating them and eventually leading to their death. The first application is applied to dry hair, the scalp, and the nape of the neck; it is left in place for 10 minutes and then rinsed. A second application, 1 week later is recommended.

Based on safety and efficacy data, Health Canada has recently approved this nonprescription behind the counter product for the treatment of lice in persons aged 4 years and older. Phase II clinical trials document a higher success rate (no live lice) when compared with traditional pediculicides (57% Resultz™ vs. 22% with RID^®; 77.1% Resultz™ vs. 20% with permethrin 1%).¹⁷ Other Phase II studies have documented a 97% (28 of 29 patients) success rate.¹⁶ In studies to date, the product was well tolerated with mild local erythema or pruritus being the main side-effect (8 of 29 patients).¹⁶ Phase III clinical trials are pending. Isopropropyl myristate is a water-insoluble organic ester used as an emulsifier and emollient in low concentrations in cosmetic products such as oils, creams, lotions, makeup, lipstick, deodorants, sun screens, hair products, and nail lacquer removers.¹⁸

Dry-on Suffocation-Based Pediculicide

Nuvo^® Lotion, or dry-on suffocation-based pediculicide (DSP) (later found to be Cetaphil^® Gentle Skin Cleanser) was reported to have success rate of 96% when applied to the scalp, dried with a hair dryer (for approximately 30 minutes), and removed during the next day’s bath.¹² It was reported to work by suffocating the louses’ spiracles or breathing holes, causing death by suffocation. As reviewed in The Lancet13 and other sources,^14,15 the study did not use proper methods of diagnosing lice, was anecdotal, and was not a well-designed randomized control study. Nevertheless, the concept is novel and there may be a significant beneficial effect; therefore further studies are warranted.

Nit Agents

Further knowledge of the nit sheath, the glue by which the egg is attached to human hair, or the nit laying process may lead to the production of future treatment agents.¹⁹

Mechanical Removal

Mechanical nit removal as a treatment modality is not an appropriate method of lice eradication when used alone.20 Some authors believe that mechanical removal of nits after treatment with a pediculicide remains an important adjunct.³ Application of an 8% formic acid rinse or a 1:1 mixture of white vinegar and water followed by combing with a nit comb can aid in the removal of nits. Nit combing is the only treatment recommended for children < 2 years of age. It is labor intensive and somewhat painful.²¹

Environmental Interventions

Clothing, linen and towels should be decontaminated by hot water washing (60°C) or dry-cleaned. Combs and brushes should be treated with boiling water, alcohol, bleach, or soaked in a disinfectant solution (for example 2% Lysol^®).

All household members and close contacts should be examined and treated concurrently if infested; and the school should be notified. Bedmates should be treated prophylactically. Furniture disinfection is unnecessary since head lice generally die within 1–2 days when separated from a person.⁵

Alternative Treatments

Naturopathic products including herbal shampoos, occlusive agents (e.g., mayonnaise, margarine, and olive oil), kerosene or gasoline are largely unproven or ineffective.22 There is no evidence that the occlusive products suffocate lice and they have no pediculicidal or ovicidal effects.²² Kerosene or gasoline should never be used due to flammability and extreme hazard. Another “natural” remedy is Chick-Chack^®, containing coconut oil, anise oil, and ylang ylang oil.³ Published data is sparse and caution should be advised until more data is available.

Conclusion

Lice have developed resistance to some pediculicides and it is expected that with ongoing use these pediculicides will probably become less effective. These products can still be used effectively to treat nonresistant lice. Resistance should be suspected if live lice are still present 2–3 days after a product has been used correctly and no other cause for treatment failure can be identified. If lice are present after 2 correctly applied treatments, resistance is almost certain. Resistant infections should be treated with an agent from a different class of pediculicides or with newer non-neurotoxic agents. New products are presently in the process of being developed and tested. Over time these products may prove to be equal to or more effective/safe than the standard neurotoxic pediculicides, while at the same time minimize the problem of treatment resistant lice.

References

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3. Elston DM. Drugs used in the treatment of pediculosis. J Drugs Dermatol 4(2):207-11 (2005 Mar-Apr).
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17. Data on file – Altana Pharma.
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