With numerous therapeutic options available for chronic pruritus in atopic dermatitis, there is a need for structured, rational approaches to finding a treatment that will provide an individual patient with relief from itching.
In an published in the book series Advances in Experimental Medicine and Biology, Kalyani S. Marathe, MD, and William S. Farmer, BS, both of George Washington University in Washington, D.C., describe a "therapeutic ladder" approach designed to help clinicians and patients select treatments appropriately.
"Initially, practitioners should advise patients to employ non-pharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed," the authors wrote.
The first rung of the therapeutic ladder, according to the authors, is treatment with topical glucocorticoids and topical calcineurin inhibitors.
The second rung on the ladder includes more topical agents, including coal tar, menthol, capsaicin, and doxepin.
Once topical options have been exhausted, the authors said, the third rung would include systemic agents such as sedating or non-sedating antihistamines, oral glucocorticoids, or cyclosporine A.
If those primary systemic agents fail, the fourth and final rung in the therapeutic ladder for pruritus in AD includes neuromodulating or immunomodulating agents, such as immunosuppressants, SSRI/SNRIs, TCAs, and opioid receptor modulators.
Phototherapy has a place at each rung in the ladder as described by Farmer and Marathe, who say the treatment can provide "dramatic improvement" at each stage of treatment, including first line.
While this laddered approach seems simple in theory, determining the appropriate rung to select might be challenging in practice, particularly since pruritus can be so subjective.
To help guide clinical decisions, the authors recommend using the at each office visit. It rates the severity of the symptoms and assesses the temporal nature of the pruritus, location of the itch and palliation.
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.
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