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    In atopic dermatitis, are you employing the therapeutic ladder approach?

     

    Systemic Therapies

    The choice of systemic agent can be challenging, due not only to the lack of randomized, controlled trials comparing one agent to another, but also due to the need for clinicians to consider patient factors including patient age, drug interactions, renal function and sedation.

    Antihistamines are widely used as an adjunct therapy, despite a lack of large, randomized trials confirming their anti-pruritic effects. Sedating antihistamines may be effective in improving sleep quality as well as reducing scratching during the night, which could help interrupt the AD scratch-itch cycle.

    Glucocorticoids have anti-inflammatory effects that are believed to suppress AD-related pruritus, though rebound flares after tapering are a concern, according to Farmer and Marathe. There are a few randomized, controlled trials supporting their use, including one showing that 4 weeks of combined nasal and oral beclomethasone in AD patients decreased pruritus significantly versus placebo. In another trial, 2 weeks of flunisolide nasal spray significantly reduced pruritus versus placebo, in children with severe AD.

    SSRIs, TCAs, and neural modulators may have a role in pruritus associated with AD. In particular, SSRIs including fluvoxamine, paroxetine, and sertraline have documented effectiveness for AD. Among TCAs, low-dose doxepin is used in patients with AD, but it’s effectiveness is “not predictable,” Farmer and Marathe said. Systemic neural modulators reduce pruritus by directly interacting with nerves, but efficacy is not well documented in clinical trials, they added.

    Several immunosuppressants have documented efficacy in pruritus from AD, according to the authors. One is dupilumab, the biologic that inhibits IL-4 and IL-13 and is approved for treatment of moderate-to-severe atopic dermatitis. In one study of dupilumab monotherapy, pruritus was reduced by 56% versus 15% for placebo at 12 weeks, while in a second monotherapy study, pruritus was reduced by 53% versus 8% at 12 weeks.

    Cyclosporine A can be used off-label for treating pruritus in AD patients, according to the authors. Research shows patients receiving the immunosuppressant had 55% reduction in pruritus after 6-8 weeks, though for half of patients, pruritus returned after treatment discontinuation.

    Due to potential for side effects, systemic therapies should be saved for situations where it is clear that topical therapies will not be effective, the authors emphasized.

     

    REFERENCES

    Kalyani S. Marathe and William S. Farmer. "Atopic Dermatitis: Managing the Itch," Part of the Advances in Experimental Medicine and Biology book series. First Online: 24 October 2017

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