Keywords: Atopic dermatitis, Elderly, Narrow-band ultraviolet B.

TO THE EDITOR

The prevalence of atopic dermatitis (AD) in elderly patients is gradually increasing in developed countries [1]. In this paper, we report cases of elderly Japanese patients with AD who were treated in our hospital with narrow-band ultraviolet B (UVB, wavelength: 311 ± 2 nm) phototherapy and discuss its utility as an adjunctive treatment for AD in older adults. We describe two instructive cases in detail, then summarize clinical characteristics of the AD and the efficacy of phototherapy for these cases and four additional cases in Table 1.

Phototherapy regimens consisted of intensive treatment (three to five irradiation sessions per week) and/or maintenance treatment (one irradiation session every one to four weeks). As a practical consideration, rather than measuring the minimal erythema dose (MED) in each case as is often done, we simply began the first irradiation treatment for each patient with a dose of between 0.30 and 0.40 Joule (J)/cm² (approximately half the value of the average MED in the Japanese population [2]), on only in a small area of the skin lesions. We then increased the dose by 0.05 J/cm² at each subsequent treatment until the optimal dose was achieved, as determined by effective therapeutic response without adverse effects (e.g., marked irritation). The assessment of therapeutic effects was defined as follows: clinical remission, disappearance of skin lesions in more than 95% of observed lesional areas for at least three months with standard treatments and maintenance treatment of narrow-band UVB; clinical improvement, disappearance of skin lesions in more than 95% of observed lesional areas for at least three months with standard treatments and maintenance treatment of narrow-band UVB and either oral corticosteroids (betamethasone, ≤0.5 mg/day) or cyclosporine (≤50 mg/day); minor improvement, mild to moderate improvement of lesional areas with standard treatments and narrow-band UVB (intensive and/or maintenance treatments), with or without oral corticosteroids/cyclosporine; and ineffective. The standard treatments comprised regular application of moisturizers and/or emollients in combination with topical corticosteroids and tacrolimus, as well as oral antihistamines/cytokine-inhibitors [3]. Topical tacrolimus was used for non-irradiated areas of skin lesions except for on the days of irradiation treatments.

Case 1: A 64-year-old man presented with refractory eczematous erythema on the face (atopic red face), and lichenified eczema with localized prurigo-forming papules on the trunk and extremities (Figure 1a). Serum laboratory tests revealed a prominent immunoglobulin (Ig) E-allergic status. A biopsy of the lichenified eczema revealed a chronic eczematous reaction with inflammatory cell infiltrates, including numerous IgE-positive mast cells (MCs), cluster of differentiation (CD) 11c+ dendritic cells (DCs), and CD1a+ DCs [4]. Previous treatments with standard therapies and oral corticosteroids had achieved only moderate improvements. We therefore administered narrow-band UVB phototherapy, which, after 12 irradiation sessions, resulted in clinical remission of his refractory AD (Figure. 1b), allowing for withdrawal of oral corticosteroids.

Case 2: A 76-year-old man presented with chronic eczema on the face and lichenified eczema and/or nummular-form eczema on the trunk and upper extremities. Laboratory data indicated IgE-allergic status. Skin biopsy showed allergic-type infiltration of the lichenified eczema by IgE+ MCs, IgE+ CD11c+ DCs, and IgE+ CD1a+ DCs. He had a history of hepatitis C, in remission since interferon therapy in his 50s. He had achieved moderate improvement of AD through standard treatments and oral corticosteroids or cyclosporine, but decreasing the doses of these resulted in AD relapse. We therefore administered narrow-band UVB phototherapy concomitantly with ongoing oral corticosteroids or cyclosporine. Clinical improvement of the AD was observed at least once following phototherapy (combined with standard treatments and occasional use of oral cyclosporine). However, when we increased the dosage of narrow-band UVB to 1.00 J/cm² (in an effort to achieve clinical remission without oral cyclosporine), the patient experienced marked deterioration at the areas of the phototherapy, with emergence of severe eczema. We therefore discontinued phototherapy.

Some older patients have difficulty managing AD using only standard treatments, as a diminishing ability to perform normal activities of daily living may inhibit adequate administration of topical medications. Therefore, for moderate to severe cases of AD, powerful anti-inflammatory treatments like oral corticosteroid or cyclosporine may be used in concert with the standard treatments [1]; however, underlying conditions (e.g., hypertension, renal dysfunction, and diabetes mellitus) in elderly patients with AD may preclude the use of such treatments.

In the presented cases (Table 1), we used narrow-band UVB phototherapy as an adjunctive treatment. Given its potent anti-inflammatory effects, we expected this treatment to provide substantial relief from, or even cure AD. Using phototherapy, we achieved a favorably therapeutic outcome for at least one in every six cases, and induced clinical remission in two (cases 1 and 3) of the six cases (33%). In these two cases, long-term clinical remission (³6 months) was also observed after cessation of the phototherapy. One case (case 2) experienced a flare-up of eczema following the 1.00 J/cm² dose of narrow-band UVB, so we discontinued his phototherapy. This exacerbation was likely due to exceeding the patient’s non-identified MED-dose, resulting in an irradiation-induced flare-up. Previous reports indicate that narrow-band UVB phototherapy is not effective for treating acute severe exacerbations of AD [5], so following this event, we only performed irradiation at doses over 0.70 J/cm² in a few select AD patients.

A recent study [6] demonstrated that the immunomodulatory effects of narrow-band UVB phototherapy for AD are achieved via suppression of the immune pathways of T-helper (Th)2, Th22, and Th1 cells and the associated decrease of inflammatory infiltrating cells such as CD1a+ DCs, CD11c+ DCs, and Fc epsilon receptor type 1 (FcεR1)+ cells in the lesional skin. In AD, complexes of IgE and FcεR1 on the surface of IgE+ MCs, IgE+ CD1a+ DCs, and IgE+CD11c+ DCs may capture large amounts of allergens resulting in induction of IgE-mediated immediate, late-phase, and even ‘delayed-type’ hypersensitivity [1]. Thus, we speculate that the efficacy of narrow-band UVB phototherapy for elderly patients with AD in our hospital is due to suppressions of both T-cell-activities and IgE-mediated allergic reactions in AD.

1. Tanei R, Hasegawa Y (2016) Atopic dermatitis in older adults: a viewpoint from geriatric dermatology. Geriatr Gerontol Int 16: 75-86.

2.  Horio T (2003) Phototherapy and photochemotherapy. In: Tamaki K, et al, eds. Comprehensive handbook of clinical dermatology, Vol. 2. Tokyo: Nakayamashoten,   p170-180 (in Japanese).

3.   Saeki H, Furue M, Furukawa F, Hide M, Ohtsuki M, Katayama I, et al. (2009) Guidelines for management of atopic dermatitis. J Dermatol 36: 563-577

4.  Tanei R, Hasegawa Y, Sawabe M (2013) Abundant immunoglobulin E-positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly. J Eur Acad Dermatol Venereol 27: 952–60.

5.   Morita A (2005) Newly developed phototherapy for atopic dermatitis. Allergol Int 54: 175-80.

6.   Tintle S, Shemer A, Suárez-Fariñas M, Fujita H, Gilleaudeau P, et al. (2011) Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol 128: 583-593.

7.    Hanifin JM, Thurston M, Omoto M Cherill R, Tofte SJ, et al. (2001) The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol 10: 11-18.