Approach Considerations
Current available treatments of prurigo nodularis have had mild-to-moderate success at best. Often, combinations of several medications or physical modalities may be used in an attempt to control this process. Habit reversal therapy for the itch-scratch cycle associated with prurigo nodularis may be helpful and can be administered by dermatology nurses trained in this therapy. [26]
A 2020 article proposes a diagnostic and treatment algorithm that includes the following [27] :
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An initial assessment of core symptoms
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A detailed dermatologic history
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A detailed clinical examination
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Treatment outcomes as reported by the patient
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A diagnostic workup
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Recommended therapies
Topical Care for Prurigo Nodularis
Topical, oral, and intralesional corticosteroids have all been used in prurigo nodularis in attempts to decrease inflammation and sense of itching and to soften and smooth out firm nodules. The improvement with corticosteroids is variable, and corticosteroids are sometimes not helpful. The response may be improved with the use of occlusive dressings or soak-and-smear therapy. Intralesional corticosteroid (usually triamcinolone acetonide) treatment is commonly used in resistant cases of limited extent. Triamcinolone acetonide concentrations as low as 2.5 mg/mL may be effective, although more scarred pruriginous lesions may require higher concentrations. A total dose of 20 mg (8 mL of 2.5 mg/mL) for adults every 3-4 weeks is safe for patients without diabetes mellitus or hypertension. An 8-am serum cortisol test can be performed if concerns exist about adrenal suppression. [28]
Menthol, phenol, pramoxine, capsaicin cream, [29, 30] vitamin D-3 ointment, [31] and topical anesthetics are some other topical agents used to reduce pruritus. Treatment with DuoDerm or other occlusive therapies has been suggested to flatten skin lesions while at the same time preventing patients from directly scratching nodules. [32]
For steroid-unresponsive patients or those with lesions on thin skin, a few case reports and small studies have shown efficacy of the topical immunomodulators tacrolimus and pimecrolimus.
Phototherapy treatment has limited studies showing potential benefits and efficacy but psoralen plus ultraviolet (UV)–A (PUVA), broadband UV-B, narrowband UV-B, excimer laser, and UV-A have been used with success, with no evidence that any modality is superior to the other. [33] Consider the adverse effects of prolonged UV exposure before such treatment. Monochromatic 308-nm light therapy may be helpful for recalcitrant lesions, [34] although this modality may be more useful in atopic dermatitis. [35] The combination of UV-B 308-nm excimer light and bath PUVA therapy may be effective in the treatment of prurigo nodularis. Resistant nodules have been successfully treated with excimer lasers as well. [36, 33] UV-A1 has also been reported to benefit lichen simplex chronicus and prurigo nodularis. [37]
Systemic Care for Prurigo Nodularis
Antihistamines, anxiolytics, opiate receptor antagonists, and thalidomide are oral medications other than steroids used for prurigo nodularis. Thalidomide [38, 39, 40] has been shown to aid in several severe dermatoses, including prurigo nodularis with or without associated HIV disease. [41, 42, 43] Severe teratogenic effects are well known and documented, and all women of childbearing age should be on adequate birth control methods. Patients taking thalidomide have an increased risk of peripheral neuropathy and sedation is common. Approximately 20% of patients on thalidomide develop peripheral neuropathy within the first year on the medication. [44] Options to reduce and avoid potential adverse effects of thalidomide are to treat with a sequential combination of thalidomide with UV-B therapy or thalidomide followed by its analogue lenalidomide to shorten the treatment length for thalidomide. [18] Lenalidomide is 2000 times more potent than thalidomide. [44] Lenalidomide as a single treatment can be an option for patients with prurigo nodularis that is recalcitrant to thalidomide and other therapies. Lenalidomide is also not without its risk, as it can cause myelosuppression more frequently than thalidomide and has an increased risk for thromboembolic events. The benefit of lenalidomide is that peripheral neuropathy is less frequent and the risk for thromboembolic events can be mitigated by taking aspirin with lenalidomide. [44] Studies on thalidomide and lenalidomide are all small case studies with low power, but treatment with these medications has yielded positive results with moderate-to-significant improvement in the majority of the cases. [18]
Multiple small case studies showed potential for the use of methotrexate, a folic acid antagonist widely used for autoimmune inflammatory disorders such as psoriasis. [45, 46] Low-dose parenteral methotrexate reduced the pruriginous nature of the lesions and has shown potential for long-term remission. [45, 46]
A 2019 systematic review of evidence-based treatments for prurigo nodularis reported promising evidence for pregabalin, amitriptyline, paroxetine, fluvoxamine, and neurokinin-1 receptor antagonists and suggested that higher-power studies and randomized controlled trials are needed. [47]
Several studies have reported successful treatment with dupilumab and nemolizumab. [48, 49, 50]
Anecdotally, gabapentin has been reported to benefit lichen simplex chronicus and prurigo nodularis for some cases. [51, 52] Sedation is the main problem with this generic medication.
Substance P (SP) is a major mediator of pruritus. It binds to the neurokinin receptor 1 (NKR1). The NKR1 antagonist aprepitant is marketed for prevention of chemotherapy-induced nausea and vomiting and for prevention of postoperative nausea and vomiting and may benefit patients with prurigo nodularis. [53]
Studies suggest that pruritus may arise from an imbalance of the mu- and kappa-opioid receptor system activity in either the skin or the central nervous system. Stimulation of kappa-opioid receptors by their agonists inhibits pruritus. Kappa-opioid receptors agonists bind to kappa-opioid receptors on keratinocytes and cutaneous and/or central itch neurones. Nalfurafine, a selective kappa-opioid receptor agonist, is approved for the treatment of chronic pruritus in Japan. [54]
Surgical Care for Prurigo Nodularis
Cryotherapy with liquid nitrogen helps reduce pruritus and flatten skin lesions. [55, 56] This modality can be particularly helpful in upper limb and trunk lesions for patients with diabetes mellitus or in patients with hypertension to minimize adverse effects of intralesional and highly potent topical corticosteroids. Thirty-second thaw cycles with 2-4 treatments are recommended, depending on the size of the lesion. Understanding the risks of scarring and change in pigmentation (especially in darker-skinned individuals) is important. Cryotherapy may be combined with other modalities (eg, intralesional corticosteroids).
Pulsed-dye laser therapy may help reduce the vascularity of individual lesions.
Consultations
Pay special attention to patients with prurigo nodularis. Take a careful history of immune compromise or other internal disease. Refer patients to an internist or a family physician for possible further investigation and examination. Some patients benefit from psychiatric referral once underlying dermatologic and medical disorders have been excluded. [57]
Activity
Instruct prurigo nodularis patients to minimize touching, scratching, and rubbing affected areas.
Long-Term Monitoring
Monitor patients with prurigo nodularis for the following:
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Signs of improvement
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Resistance to treatment
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Development of symptoms or signs of underlying medical or psychiatric conditions
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Atypical lesions meriting skin biopsy
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Use of alternative therapies that may actually worsen atopic dermatoses
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Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
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Prurigo nodularis. Courtesy of Jeffrey Meffert, MD.
