Applied Evidence

Prurigo nodularis: Picking the right treatment

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Naltrexone. As an opioid antagonist, naltrexone is able to block endogenous opiates from binding to central opioid receptors and causing the sensation of pruritus. Accordingly, oral naltrexone can be used to treat PN, as shown in an open-label clinical trial in which 9 out of 17 patients (53%) achieved high antipruritic effect, defined as a reduction of pruritic symptoms by at least half.18

When selecting naltrexone to treat PN, prescribe a daily dose of 50 mg for an average of 4.7 months; up to 20 months of treatment may be required. If tachyphylaxis occurs, consider increasing the dose to 50 mg twice a day. Most patients should notice some level of antipruritic efficacy and varying degrees of lesion flattening, softening, or healing. However, exacerbation after therapy discontinuation may occur in 41% of patients. Adverse medication effects include fatigue, nausea, and dizziness.18

Oral naltrexone, gabapentin, or pregabalin may be needed for widespread or treatment-resistant prurigo nodularis.

Gabapentin and pregabalin. In response to a report of a case series in which 4 patients with PN responded well to gabapentin,19 Mazza et al20 conducted a prospective study of pregabalin treatment for 30 patients with PN. Both gabapentin and pregabalin inhibit calcium influx and subsequent excitatory neurotransmitter release, the mechanism by which they likely decrease pruritus in patients with PN.20 In the pregabalin study, 23 out of 30 patients (77%) experienced complete resolution of pruritic symptoms and a reduction of prurigo nodules in number or flattening. The recommended dosage of pregabalin is 25 mg 3 times daily for 3 months, after which time clinical progress is assessed. If a patient is not lesion-free, continue pregabalin at a maintenance dose of 50 mg/d for up to 2 years. Adverse effects typically include headache, sedation, and dizziness.20

When to refer a dermatologist

Refer patients to a dermatologist if initial clinical findings suggest a need for further work-up to rule out primary cutaneous diseases, or if the therapies discussed (TABLE8-10,15-20) yield unsatisfactory results. Dermatologists can provide more advanced treatments that require close monitoring, such as phototherapy,21-24 cyclosporine,25 or thalidomide.26-28 Based on multiple case series and case reports, as well as our own personal experience (FIGURE 2), thalidomide is efficacious in treating PN. However, thalidomide is typically reserved for cases that are severe and treatment-recalcitrant due to the drug’s high cost, teratogenicity (pregnancy category X), and potentially irreversible peripheral neuropathy.29

Putting Tx options into practice

In addition to ruling out potential causes of pruritus and determining the best treatment for each individual with PN, assess for and appropriately treat any psychiatric comorbidities, which are often a psychological component of PN.

Localized PN. Start with topical corticosteroids under occlusion for localized PN. To avoid complications of long-term topical corticosteroid use, including dermal atrophy, periodically switch to a steroid-sparing agent, such as calcipotriol ointment or topical pimecrolimus. Less evidence is available to support the efficacy of tacrolimus ointment in PN treatment. Topical capsaicin is not as practical as other topical treatments since it needs to be applied 4 to 6 times daily. Oral antihistamines and montelukast may be added to the therapeutic regimen if there is a chronic pruritic component related to the lesions themselves or an underlying atopic diathesis fueling the itch-scratch cycle.

Widespread or treatment-resistant PN. Prescribe naltrexone, gabapentin, or pregabalin for more widespread disease or lesions resistant to conservative therapies. If you suspect a primary cutaneous disease as the underlying cause of pruritus or if topical and oral therapies do not achieve the desired therapeutic effect, refer to a dermatologist for further work-up and treatment.

How we would manage the case presented in the introduction. We would start the 43-year-old on topical corticosteroids under occlusion and periodically substitute calcipotriol ointment. (Given the unease that some patients might feel with the black-box warning on topical calcineurin inhibitors, we would likely try calcipotriol ointment as a courtesy before suggesting topical calcineurin inhibitors.) We would also prescribe an oral antihistamine at the start, given that her history of seasonal allergies and childhood asthma increases her chances of having an atopic component causing or exacerbating her disease. However, assessing her response to topical therapies before initiating an oral antihistamine would also be an appropriate strategy.

Unfortunately, PN is typically a chronic and often treatment-resistant disease with disappointing recurrence rates. As we learn more about the pathophysiology of PN, more effective therapies will hopefully emerge to improve the quality of life for these patients.

Michael Saco, MD, Department of Dermatology & Cutaneous Surgery, University of South Florida, 13330 Laurel Drive, Tampa, FL 33612; [email protected]


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