Prurigo nodularis through the years
The term prurigo, originating from pruire (itching), was coined by Ferdinand von Hebra in 1850, characterizing typical itching papules and nodules induced by scratching Citation[1]. Since then, various eponyms have arisen. Ernest Henri Besnier (1860) described a chronic lichenoid flexural form of atopic dermatitis still known as prurigo of Besnier Citation[2]. In 1909, Hyde described an intractable chronic eruption characterized by numerous persistent pruritic nodules, mainly on the extremities Citation[1,3]. To date, Hyde’s prurigo or prurigo nodularis is the genuine chronic form of prurigo Citation[4]. Prurigo nodularis is generally regarded as a variety of eczema; in many cases there is a history of atopic dermatitis. Prurigo nodularis can be associated with an atopic background; 60–80% of patients with prurigo nodularis are atopic and up to 46% have atopic dermatitis Citation[3,5]. The atopic type of prurigo nodularis or prurigo form of atopic dermatitis is accompanied by cutaneous hypersensitivity to environmental allergens with the presence of allergen-specific IgE Citation[6].
Prurigo nodularis: a difficult disease to treat
The prurigo form of atopic dermatitis often represents a therapeutic challenge; most cases of the prurigo form of atopic dermatitis are therapy resistant and patients will be subjected to various types of treatment. Topical treatments include corticosteroids, coal tar and bath phototherapy. Systemic treatments include cyclosporine, chloroquine, naltrexone, dapsone, thalidomide and photochemotherapy (PUVA). Today, narrowband 311-nm ultraviolet B (NB-UVB) phototherapy is widely recognized as an effective treatment modality for patients with chronic atopic dermatitis Citation[7].
The benefit of conventional phototherapy is limited in prurigo nodularis
Narrowband 311-nm ultraviolet B phototherapy is effective against moderate-to-severe atopic dermatitis, and is well tolerated by most patients Citation[7,8]. The main disadvantage of photo(chemo)therapy is that the whole body surface is exposed to UV radiation, and not merely the affected areas. In patients with lesions restricted to relatively small surface areas, such as in prurigo nodularis, a targeted NB-UVB therapy is required.
Targeted UVB therapy: the excimer laser for localized inflammatory skin disorders
In contrast to conventional phototherapy, the excimer laser offers the opportunity to selectively direct treatment to lesional skin using high doses of UVB. The excimer laser was invented in 1970 and introduced for eye surgery in 1981. In 1997, the 308-nm xenon chloride (XeCl) excimer laser was introduced for the treatment of psoriasis Citation[9]. Afterwards, an increasing number of indications were reported to improve by such a treatment. For localized psoriasis vulgaris, the excimer laser was found to be more effective than NB-UVB Citation[10]. The main advantages of the excimer laser were comparable or higher efficacy with fewer treatments and even a lower cumulative dose than NB-UVB Citation[10].
The excimer laser in atopic dermatitis
Recently, the 308-nm XeCl excimer laser has been introduced as a new option in the area of UVB phototherapy for atopic dermatitis Citation[11,12]. While there is fair evidence to support the use of the excimer laser in psoriasis and vitiligo, there is poor evidence for its use in atopic dermatitis. Nevertheless, the US FDA approved the excimer laser for the treatment of atopic dermatitis. To date, one controlled study and several uncontrolled open case series demonstrate the efficacy of the excimer laser in atopic dermatitis.
Recently, we published a randomized controlled trial comparing the efficacy and safety of excimer laser therapy with once-daily application of a very potent topical corticosteroid (clobetasol propionate 0.05% ointment) in patients with the prurigo form of atopic dermatitis Citation[13]. The favorable results from this pilot study suggest that the excimer laser can safely and effectively be used in the treatment of the prurigo form of atopic dermatitis, and might be a good alternative to topical corticosteroids Citation[13].
Obviously, the more resistant and localized forms of atopic dermatitis are the best candidates to benefit from such a targeted UVB treatment. Therefore, it is puzzling that only a single controlled study is published on the treatment of the prurigo form of atopic dermatitis with the excimer laser. Another clinical presentation of atopic dermatitis that seems suitable for this laser treatment is lichen simplex chronicus Vidal. Similar to the prurigo form of atopic dermatitis, it is relatively resistant to topical therapy and generally restricted to a confined surface area. Again, only a series of cases of lichen simplex chronicus successfully treated with the excimer laser have been reported so far.
Pros & cons of the excimer laser for the treatment of atopic dermatitis
The main advantage of the use of the excimer laser in atopic dermatitis, the targeted treatment, is also a shortcoming, especially in widespread atopic dermatitis. The therapy is too time consuming to treat large areas. Moreover, in large areas it is difficult to memorize which parts have already been treated at the session, resulting in an unwanted second pass and over dosage, with acute side effects of painful burning and blisters.
Progressing atopic dermatitis may also cause problems as the UVB dose is increased stepwise in each lesion up to a multiple of the minimal erythema dose. In case of newly developing lesions, exposure of a previously untreated lesion to such a high dose will result in acute side effects.
Depending on the device, the beam diameter can be adjusted from 1 to 2.5 cm to fit the size of the lesions. Thereby, higher doses of UVB can be used, as the nonlesional skin, which has a lower minimal erythema dose than lesional skin, is not exposed to UVB. Compared with conventional 311-nm UVB therapy, the number of treatments can be considerably reduced by using higher doses. In psoriasis, it has been demonstrated that even a single high-dose 308-nm treatment can result in remissions of psoriasis Citation[14]. Moreover, the frequency of the treatments can be reduced to once or twice a week.
Similar to 311-nm narrowband UVB, we have to be aware of the long-term side effects of carcinogenesis and skin aging. While the lower number of treatments and the lower cumulative dose is advantageous, single doses are generally higher in the excimer laser regimen. At present we do not know what these specific regimes entail for the risk of carcinogenesis and skin aging. Obviously, the precise targeting of affected areas, leaving adjacent skin unexposed to UVB radiation, decreases the total exposure considerably. This is a major advantage with regard to the long-term safety.
A cosmetic drawback is the hyperpigmentation that develops, particularly in patients with darker skin types. In our previous study, blinding of the observer was lost due to sustained hyperpigmentation at 3 and 6 months after the end of treatment with the excimer laser Citation[13]. This is of particular interest for future randomized blinded studies. Another obvious drawback is the cost of the treatment, which results from the relatively high costs for purchase and maintenance of the device. Moreover, treatment has to be administered by a trained care giver. To date, studies on the cost–effectiveness of the excimer laser for the treatment of the prurigo form of atopic dermatitis are lacking, as are studies on the optimal regimen (once- or twice-weekly; conventional or accelerated dose increase; and combination with topical therapy).
Summarizing, for patients with the prurigo form of atopic dermatitis resistant to first-line topical therapy, the 308-nm excimer laser may be a good alternative and an additional option within the second-line therapies. Since currently available therapies for patients with the prurigo form of AD are not very effective, we underline the need for new treatment modalities, such as the excimer laser. Randomized controlled trials are necessary to demonstrate the efficacy and optimal regimen of the 308-nm XeCl excimer laser, as well as its cost–effectiveness.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
- Wallengren J. Prurigo: diagnosis and management. Am. J. Clin. Dermatol.5, 85–95 (2004).
- Besnier EH. [First note and preliminary observations as an introduction into the study of prurigo diasthetiques]. Ann. Dermatol. Syphiligr. (Paris)3, 634–648 (1892).
- Rowland Payne CM, Wilkinson JD, McKee PH, Jurecka W, Black MM. Nodular prurigo – a clinicopathological study of 46 patients. Br. J. Dermatol.113, 431–439 (1985).
- Eczema, lichenfication, prurigo and erythroderma. In: Rook’s Textbook of Dermatology. Burn T, Breathnach S, Cox N et al. (Eds). Wiley-Blackwell, NJ, USA, Vol. 1, 44–48 (2004).
- Miyachi Y, Okamoto H, Furukawa F et al. Prurigo nodularis. A possible relationship to atopy. J. Dermatol.7, 281–283 (1980).
- Tanaka M, Aiba S, Matsumura N et al. Prurigo nodularis consists of two distinct forms: early-onset atopic and late-onset non-atopic. Dermatology190, 269–276 (1995).
- Der-PetrossianM, Seeber A, Honigsmann H et al. Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis. Br. J. Dermatol.142, 39–43 (2000).
- Reynolds NJ, Franklin V, Gray JC et al. Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomized controlled trial. Lancet357, 2012–2016 (2001).
- Bónis B, Kemény L, Dobozy A, Bor Z, Szabó G, Ignácz F. 308 nm UVB excimer laser for psoriasis. Lancet350(9090), 1522 (1997).
- Novák Z, Bónis B, Baltas E et al. Xenon chloride ultraviolet B laser is more effective in treating psoriasis and in inducing T cell apoptosis than narrow-band ultraviolet B. J. Photochem. Photobiol.67, 32–38 (2002).
- Kardorff B, Honig-d’Orville I, Wahlen M, Dorittke P. Treatment of the prurigo form of atopic eczema/dermatitis in adults with 308nm excimer laser. Kosmetische Medizin.24(1) (2003).
- Baltás E, Csoma Z, Bodai L et al. Treatment of atopic dermatitis with the xenon chloride excimer laser. J. Eur. Acad. Dermatol. Venereol.20(6), 657–660 (2006).
- Brenninkmeijer EE, Spuls PI, Lindeboom R et al. Excimer laser vs. clobetasol propionate 0·05% ointment in prurigo form of atopic dermatitis: a randomized controlled trial, a pilot. Br. J. Dermatol.163(4), 823–831 (2010).
- Asawanonda P, Anderson RR, Chang Y, Taylor CR. 308-nm excimer laser for the treatment of psoriasis: a dose–response study. Arch. Dermatol.136, 619–624 (2000).