Managing itch is multifactorial with a need to address the itch itself, but also contributing factors such as dry skin, inflammation, and scratch lesions. Basic therapy should be undertaken to address skin barrier dysfunction and includes the use of emollients, bath oils and avoiding any clinically relevant allergens. Beyond basic therapy, a range of topical and systemic treatment options are often used to help manage the itch associated with atopic dermatitis (Wollenberg et al., 2018).
Chronic pruritus, as seen in atopic dermatitis, is induced by the nonhistaminergic pathway (Mollanazar et al., 2016). Despite being used for decades, few randomised controlled trials (RCTs) have evaluated their efficacy in atopic dermatitis and those that have typically show a weak or no effect on pruritus. While the sedative effects of first-generation antihistamines may allow improved sleep, the evidence-base for an anti-pruritic effect of first- and second-generation antihistamines remains limited (Wollenberg et al., 2018).
As with systemic antihistamines, limited data is available on the use of topical formulations. A meta-analysis of four RCTs comparing topical antihistamines to vehicle (three evaluated doxepin 5% cream, one evaluated cromoglycate 4% lotion) identified a significant pooled reduction in pruritus of 27% (Sher et al., 2012). However, topical doxepin is associated with an increased risk of contact allergy and so is not licensed or used in Europe (Wollenberg et al., 2018).
Two topical calcineurin inhibitors, tacrolimus and pimecrolimus, are approved for the management of atopic dermatitis. Both have been shown to significantly reduce itch, with a 36% reduction compared to vehicle (Wollenberg et al., 2018). Importantly, topical calcineurin inhibitors are effective within 48 hours of application and show continued anti-pruritic effects with ongoing use. However, they are associated with burning/stinging upon application (Mollanazar et al., 2016).
Systemic corticosteroids are not anti-pruritic and their prolonged use in atopic dermatitis is not recommended due to their safety profile (Mollanazar et al., 2016).
While anti-inflammatory rather than anti-pruritic, topical corticosteroids have been shown to induce a rapid itch reduction in atopic dermatitis (Wollenberg et al., 2018). A meta-analysis of six RCTs found a 34% reduction in itch versus vehicle (Sher et al., 2012). However, a wide variety of topical corticosteroids with differing potencies and efficacies are available. Data suggests that moderate and high potency options are more effective than low potency topical steroids, but moderate and high potency options are similar (Mollanazar et al., 2016). While moderate use of topical corticosteroids should not have any systemic or local adverse events, patient concerns are common and should be addressed. By considering several factors such as potency, patient age and body area affected treatment can be optimised (Wollenberg et al., 2018). More information on the use of glucocorticosteroids in the treatment of atopic dermatitis can be found in the treatment options and guidelines sections.
IL-4 and IL-13 are important Th2 cytokines associated with pruritus in atopic dermatitis (Wong et al., 2017). Dupilumab, a recently approved monoclonal antibody against anti-IL-4 receptor α showed a 50% itch reduction in patients with moderate-to-severe atopic dermatitis (Beck et al., 2014).
IL-31 is believed to play a role in the development of atopic dermatitis and pruritus. A phase II study of an anti-IL31 receptor A antibody currently under development showed significant reductions in pruritus in patients with moderate-to-severe atopic dermatitis (Ruzicka et al., 2017).
Apremilast, an oral, small molecule phosphodiesterase (PDE) 4 inhibitor has been approved for the treatment of psoriatic arthritis and moderate-to-severe plaque psoriasis, but its development in atopic dermatitis has been halted (Wollenberg et al., 2018).
Multiple topical PDE4 inhibitors are currently under development for the management of atopic dermatitis (Wollenberg et al., 2018). Phosphodiesterase 4 regulates inflammatory cytokine production through the degradation of cyclic adenosine monophosphate (cAMP). In patients with atopic dermatitis, PDE4 activity is increased leading to reduced cAMP levels and increased inflammation.
One topical PDE4 inhibitor, crisaborole, was recently approved for the treatment of mild-to-moderate atopic dermatitis in patients two years and older in the U.S.A. but does not have a license in Europe (Wollenberg et al., 2018). A recent post-hoc analysis pooling data from two phase III trials saw significantly more patients report early improvement in pruritus with crisaborole than with vehicle (56.6% vs. 39.5%; p<0.001) (Yosipovitch et al., 2018). However, the efficacy of crisaborole compared to topical corticosteroids and calcineurin inhibitors remains uncertain (Wollenberg et al., 2018).
Use of narrowband UVB and UVA1 has been shown to be the most effective forms of UV therapy in multiple RCTs, including in the reduction of itch intensity. There is no anti-itch specific data for UV therapy though (Wollenberg et al., 2018).