PEDICULOSIS

Updated recommendations for pediatric head lice (May 2015)

Pediculosis capitis is a common condition that can lead to physical discomfort and social stigmatization. An update to the 2010 clinical report on head lice published by the American Academy of Pediatrics incorporates new therapies (spinosad and topical ivermectin), clarifies diagnosis and treatment protocols, and provides guidance for the management of children with pediculosis capitis in the school setting [5]. Examples of major points in the update include recommendations that no child should be excluded from school because of head lice or nits and that pyrethroids remain reasonable first-line therapies for primary treatment of pediculosis capitis in communities where resistance to pyrethroids is unproven

Topical pediculicides — Topical insecticides are the initial treatment of choice for pediculosis capitis. Examples of these agents include pyrethroids (permethrin, pyrethrins), malathion, benzyl alcohol, spinosad, topical ivermectin, and lindane. Pyrethrins may be combined with piperonyl butoxide, an ingredient that inhibits pyrethrin catabolism in the louse and improves efficacy.

The mechanisms of action of pyrethroids, malathion, spinosad, topical ivermectin, and lindane involve neurotoxic effects on lice. Benzyl alcohol 5% lotion is a newer treatment option that functions via asphyxiation of the parasite.

Topical pediculicides should be applied according to the package instructions. Hair conditioners should not be used prior to application; these products may result in reduced efficacy [28]. In addition, rinsing of topical pediculicides from the hair should be performed over a sink rather than in a shower or bath to limit skin exposure [27]. Warm water is preferred over hot water to minimize vasodilation and systemic absorption [27].

Skin irritation is a potential side effect of topical pediculicides. Topical corticosteroids or oral antihistamines may be useful for reducing symptoms of skin irritation when necessary [27].

Pyrethroids 

The scalp should be saturated with the pediculicide after the hair has been washed with shampoo, rinsed with water, and towel dried. The pediculicide remains on the hair for 10 minutes before rinsing off with water. A second treatment is indicated in 7 to 10 days, since resistance patterns have led to reduced ovicidal activity of pyrethroids [8,28]. One study of permethrin found lice-free rates of 83 percent on day 2, decreasing to 46 percent on day 8 before a second treatment, and then increasing to 78 percent on day 9 after the second treatment and staying there on day 15 [30].

More than three applications of the same product within two weeks is not recommended. Prescription strength permethrin (5%) is also available, but is not more effective than the over the counter preparation [7].

Malathion

Malathion lotion 0.5% is available by prescription in the United States and over the counter in the United Kingdom. In the United States, malathion is available as a product that includes terpineol, an ingredient with additional pediculicidal properties.

One in vitro study found that malathion 0.5% with terpineol was most effective at killing head lice, compared with pyrethroids and lindane [31]. However, the treatment time with malathion is longer than other topical pediculicides. The lotion is left in place for 8 to 12 hours before washing off [32]. A single application of malathion is sufficient for most patients. If live lice are visualized seven to nine days after treatment, a second treatment should be performed.

Some studies have suggested that shorter application times may also be effective [33,34]. In one small, investigator-blinded, randomized trial, lice were eradicated in 98 percent of patients treated with one or two 20 minute applications of malathion with terpineol [35].

Malathion is malodorous and its vapor is irritating to the eyes, which are unfavorable features for some patients. The potential flammability of the product due to the presence of alcohol has also been a concern; however, injuries have not been reported [33].

Benzyl alcohol 

The mechanism of action of benzyl alcohol 5% lotion involves the asphyxiation of lice. After the benzyl alcohol component paralyzes the louse respiratory sphericles in an open state, the mineral-oil containing vehicle obstructs the sphericles.

When treating pediculosis capitis, benzyl alcohol 5% lotion is applied for 10 minutes with saturation of the scalp and hair, and then rinsed off with water. Information on the amount of the product to apply based is provided in the package insert; long hair requires larger amounts. The treatment is repeated after seven days. Benzyl alcohol lotion may cause irritation of the skin, scalp, and eyes, as well as transient numbness at the site of application.

Spinosad 

Two manufacturer-sponsored phase 3, multicenter, randomized trials compared the efficacy and safety of spinosad 0.9% cream rinse with permethrin 1% cream rinse plus nit combing [39]. Patients who had residual live lice seven days after an initial treatment were instructed to repeat application of the same therapy. After treatment, approximately 85 percent of spinosad-treated subjects were lice free, compared with approximately 44 percent of those treated with permethrin. Individuals treated with spinosad were also less likely to require a second application.

Spinosad is supplied as a 0.9% topical suspension. Therapy with spinosad involves application of the product to completely cover the scalp and hair. The hair should be dry prior to treatment. After application is completed, spinosad should be left on for 10 minutes. Subsequently, the scalp and hair should be thoroughly rinsed with warm water to completely remove the product. Shampooing of the hair can be performed at any time after treatment. Treatment should be repeated if live lice remain seven days after the initial application.

Topical ivermectin 

The primary efficacy end point in both trials was the number of index patients (youngest household member with at least three live lice detected on examination) who were louse-free at days 2, 8, and 15. A combined analysis of the trial results revealed that among the index patients, 131 of 138 (95 percent) treated with topical ivermectin and 46 of 147 (31 percent) treated with the placebo lotion were free of live lice on day 2. By day 15, live lice were absent in 74 and 18 percent of patients, respectively. In addition, patients in the topical ivermectin group were more likely to be free of pruritus on day 2; 67 versus 43 percent denied pruritus. Adverse events were infrequent and occurred at similar rates in both groups.

Topical ivermectin therapy is administered via a single application to dry hair. As with malathion, a single application is sufficient because topical ivermectin has both ovicidal and pediculicidal properties. The lotion should thoroughly coat the hair and scalp. The lotion is rinsed off with water after 10 minutes.

Topical ivermectin generally is well tolerated. Potential adverse effects include ocular irritation, dry scalp, and a burning sensation on the skin [40,41]. The safety of ivermectin in infants under the age of six months is not established.

Lindane 

Lindane toxicity — Lindane is an organochlorine insecticide that inhibits neurotransmission in parasitic arthropods. Neurologic toxicity resulting in seizures and death has been reported in humans following topical lindane therapy [42]. Most reports of these events have occurred after prolonged or repeated application of lindane, but in rare cases, have followed a single application [42].

Although the drug has been banned in some countries and the state of California [43] and the American Academy of Pediatrics no longer recommends use of this therapy [27], lindane shampoo and lotion remain available by prescription elsewhere in the United States. The US FDA has placed a black box warning on the drug labels, cautioning that lindane shampoo and lotion should only be used as a second-line treatment in patients who cannot tolerate or have failed other therapies for the treatment of scabies or lice. Lindane is contraindicated in patients with skin disorders that may lead to increased systemic absorption (eg, atopic dermatitis, psoriasis). Other contraindications for the use of this drug are addressed separately. Detail about specific interactions is available by using the Lexi-Interact program included with UpToDate.

If used, lindane should be given only as single application; retreatment should be avoided. Other measures to minimize toxicity include:

• Prescribe one ounce of lindane lotion or shampoo to treat an average adult; no more than two ounces should be prescribed.
• Lindane shampoo prescribed for pediculosis capitis should be washed off after four minutes.
• Caregivers applying the drug to patients should wear gloves that are less permeable to lindane (nitrile, latex, neoprene, or sheer vinyl). Natural latex gloves should not be used. Caregivers should thoroughly wash their hands after application.

Choosing a pediculicide

Pediculicide resistance — Head louse resistance to topical insecticides is a growing concern [44]. Resistance to particular agents varies geographically [28,29,31,45-50]. As an example, in an in vitro study, lice from South Florida had greater resistance to lindane, permethrin 1%, and pyrethrin with piperonyl butoxide than lice from Panama [31]. Only a United States formulation of malathion 0.5% exhibited similar efficacy in both locations.

Resistance to malathion appears to be less prevalent in the United States than in the United Kingdom [28]. It is unclear whether this is due to the history of limited use of the drug in the US, or that the US formulation of malathion also contains terpineol, a chemical with pediculicidal properties. In one in vitro study in Britain, fewer lice died after four hours of exposure to malathion 0.5% in isopropanol than after 30 minutes of exposure to the US product (42 versus 96 percent) [51].

A mutation in the louse kdr allele that results in decreased sensitivity of neuronal voltage gated sodium channels has been proposed as the primary mechanism for pyrethroid resistance [52]. However, this theory is brought into question by a study that found a poor correlation between mutations in kdr and treatment failure [53]. Resistance to malathion occurs via increased production of enzymes that metabolize malathion and decreased sensitivity of neuronal acetylcholinesterase to the drug [28]. Other pathways for resistance may also be involved. The mechanism of action of benzyl alcohol (louse asphyxiation) may make this agent less susceptible to the development of resistance than the topical neurotoxic agents [1].

Pediculicide selection — Variation in the prevalence of resistance to topical pediculicides makes it difficult to uniformly recommend one agent over another. Several direct comparisons of agents have been published, including the following:

• In a 2007 United States randomized trial, both a gel and lotion formulation of malathion 0.5% with terpineol were superior to permethrin 1% for the treatment of pediculosis capitis [54].
• A 2002 in vitro study in the United States reported that malathion 0.5% with terpineol was superior to pyrethroids, and that lindane was least effective [31]. Among the pyrethroids, a product containing pyrethrin, piperonyl butoxide, and benzyl alcohol was the most effective, followed by permethrin 1%, and pyrethrin with piperonyl butoxide.
• Spinosad was more effective than permethrin 1% in two phase three manufacturer-sponsored randomized trials [39]. (See ‘Spinosad’ above.)

Benzyl alcohol and topical ivermectin have not been compared with other agents, but appear to be effective for the majority of patients.

In addition to efficacy, several factors may affect the selection of a pediculicide.

●Ease of administration and risks: Malathion requires longer application times, is malodorous, and is more expensive than pyrethroids. In addition, the drug has the potential for flammability and may cause respiratory depression if ingested. Unlike malathion, benzyl alcohol has a mildly pleasant odor. Lindane is a less favorable choice due to a risk for neurologic side effects and its relatively poor efficacy.