Home phototherapy in vitiligo

Transcription

1 Accepted: 29 May 2017 DOI: /phpp REVIEW ARTICLE Home phototherapy in vitiligo Tasneem F. Mohammad 1 Narumol Silpa-Archa 2 James L. Griffith 1 Henry W. Lim 1 Iltefat H. Hamzavi 1 1 Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA 2 Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Correspondence Iltefat H. Hamzavi, Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA. ihamzav1@hfhs.org Summary Vitiligo is a disorder characterized by the development of depigmented macules and patches. Narrowband ultraviolet B phototherapy is a standard of care treatment and is used both as monotherapy and in combination with other treatment modalities to induce repigmentation. Although phototherapy is safe and effective, its use is limited due to the significant time commitment required and associated costs. Home phototherapy is a safe and effective alternative to make phototherapy more accessible to patients. However, it is often underutilized due to lack of physician experience and comfort as well as misconceptions regarding its safety and efficacy. This article provides a brief overview of the use of phototherapy in vitiligo with a focus on home phototherapy in order to increase awareness and use of this treatment modality. KEYWORDS home phototherapy, narrowband ultraviolet B, phototherapy, pigmentation, vitiligo 1 INTRODUCTION Phototherapy is used for the treatment of several dermatologic diseases, including vitiligo. For many years, psoralen plus ultraviolet A (PUVA) was the primary form of photochemotherapy for vitiligo. However, the side effects of psoralen, which include nausea, vomiting, phototoxicity, and photocarcinogenicity, made this method of phototherapy less favorable than narrowband ultraviolet B (NB- UVB) therapy. First reported by Westerhof and Nieuweboer- Krobotova in 1997, NB- UVB was shown to be as effective as PUVA, but with fewer adverse effects, improved color match, and greater ease of administration. 1,2 Since then, NB- UVB has become the standard of care for vitiligo and can be administered using in- office or home phototherapy. Although convenient and cost effective, many questions have been raised regarding the safety and efficacy of home phototherapy. 3 This article aims to provide a brief review of phototherapy with a focus on home phototherapy in vitiligo to address misconceptions regarding the use of this form of therapy. 2 NB- UVB PHOTOTHERAPY 2.1 Light sources and lamps The light source used for NB- UVB phototherapy is the TL- 01 lamp (Philips, Eindhoven, the Netherlands), a phosphor- coated fluorescent bulb with an emission spectra between nm and peak emission at 311 nm. Compared to broadband ultraviolet B (BB- UVB) light, NB- UVB is associated with reductions in epidermal hyperplasia, sunburn cell formation, Langerhans cell depletion, and erythema. This is supported by the differences in the minimal erythema dose between BB and NB- UVB. In skin phototype I, the minimal erythema dose of NB- UVB is mj/cm 2 compared to mj/cm 2 with BB- UVB Phototherapy devices Multiple models of NB- UVB phototherapy devices exist. 5 The most common is the upright booth used for in- office phototherapy, which has bulbs and is ideal for wide areas of involvement. However, the intensity of light is less at the upper and lower ends of the bulbs. Patients with lesions on the lower legs should stand on a small stool to ensure adequate exposure. Other models, frequently used for home phototherapy, include single, double and triple paneled units, handheld wands, and hand and foot devices (Table 1). 5-9 Triple paneled units are most commonly prescribed for home phototherapy when a significant body surface area is involved, whereas handheld wands are prescribed for treatment of localized lesions. The variety of devices for phototherapy allows for personalized treatment plans, especially for localized areas of involvement. Photodermatol Photoimmunol Photomed. 2017;33: wileyonlinelibrary.com/journal/phpp 2017 John Wiley & Sons A/S. 241 Published by John Wiley & Sons Ltd

2 242 TABLE 1 Home phototherapy units 5-9 Model Type Use No. of lamps Features Daavlin UV Series -Full- length -Cabinet style - Treats entire body in 1 exposure - Generalized BSA involvement 12, 16 or 24 - Choice of digital timer or dosimeter - Custom- made platform elevates the patient to the level of the lamps - Lockout feature prevents unauthorized use. When activated, the user must enter a code to operate the unit - Removable safety key to prevent unauthorized use - Flex Dosimeter Control allows dosage to be entered by physician - UV sensor measures intensity of light emitted and adjusts treatment time to reflect variation in lamp output 7 Series -Full- length -Triple panel - Treat full body with 2 exposures - Generalized BSA involvement 8, 10 or 12 - Choice of digital timer or dosimeter - Lockout feature prevents unauthorized use. When activated, the user must enter a code to operate the unit - Removable safety key to prevent unauthorized use - Flex Dosimeter Control allows dosage to be entered by physician - UV sensor measures intensity of light emitted and adjusts treatment time to reflect variation in lamp output 4 Series - 4 ft single panel - Treatment area in - Localized BSA involvement 10 or 20 - Choice of digital timer or dosimeter - Removable safety key to prevent unauthorized use - Flex Dosimeter Control allows dosage to be entered by physician - UV sensor measures intensity of light emitted and adjusts treatment time to reflect variation in lamp output 1 Series -Single panel - Treatment area in - Hands and feet 4 - Choice of digital timer or dosimeter M series - Light box with lamps in base and hood - Hands and feet 10 - Choice of digital timer or dosimeter - Lockout feature prevents unauthorized use. When activated, the user must enter a code to operate the unit. - Removable safety key to prevent unauthorized use - Flex Dosimeter Control allows dosage to be entered by physician - UV sensor measures intensity of light emitted and adjusts treatment time to reflect variation in lamp output Dermapal -Handheld wand - Treatment area in - Scalp and localized lesions 1 - Available with scalp comb - Highly accurate timer National Biologic Foldalite III -Full- length (6 ft) - 4 folding panels - Treat full body with 1 exposure - Generalized BSA involvement 16 - Exact dosage ensured by automatic lamp shutoff at end of treatment -Failsafe circuitry - Key- locked on/off switch to prevent unauthorized use - Interior emergency on/off switch -Goggles included (Continues)

3 243 TABLE 1 (Continued) Model Type Use No. of lamps Features Panosol 3-D -Full- length -Triple panel - Treat full body with 2 exposures - Generalized BSA involvement 10 - Exact dosage ensured by automatic lamp shutoff at end of treatment - Failsafe circuitry in the event of power surges - Key- locked to prevent unauthorized use - Emergency on/off switch -Goggles included Panosol II - Full- length or 2 ft models -Single panel - Generalized BSA (full- length) or localized involvement (2 ft) Exact dosage ensured by automatic lamp shutoff at end of treatment - Failsafe circuitry in the event of power surges - Key- locked to prevent unauthorized use - Emergency on/off switch -Goggles included Hand/Foot II -Tabletop unit - Can put 2 units on tabletop cart for concurrent treatment of hands and feet - Hands and feet 8 - Exact dosage ensured by automatic lamp shutoff at end of treatment - Failsafe circuitry in the event of power surges - Key- locked to prevent unauthorized use - Emergency on/off switch -Goggles included Handisol II -Single panel - Treatment area in - Hands and feet 4 - Exact dosage ensured by automatic lamp shutoff at end of treatment - Failsafe circuitry in the event of power surges - Key- locked to prevent unauthorized use - Emergency on/off switch -Goggles included DermaLume 2x -Handheld device - Treatment area in - Scalp or localized areas 2 - Exact dosage ensured by automatic lamp shutoff at end of treatment -Failsafe circuitry - Key- locked to prevent unauthorized use - Emergency on/off switch - Comb serves as distance guard to keep skin safe -Goggles included Dermalite 90 -Handheld device - Treatment area in - Scalp or localized areas 1 - Comb serves as distance guard to keep skin safe - Comb, timer, UV Checker and goggles included Solarc Systems E Series -Full- length - 2 bulb units that can be combined to form single, double, triple or cabinet style panels - Generalized BSA involvement 4, 8, 12, 16 or 20 - Keyed switch lock to prevent unauthorized use - Digital countdown timer that allows dosage to be controlled and has a maximum setting of 20 min 1000 Series -Full- length -Single panel - Generalized BSA involvement 4, 6, 8 or 10 - Keyed switch lock to prevent unauthorized use - Digital countdown timer that allows dosage to be controlled and has a maximum setting of 20 min 500 Series - Single panel with removable hood - Treatment area in - Hands, feet and localized areas 2, 3 or 5 - Keyed switch lock to prevent unauthorized use - Digital countdown timer that allows dosage to be controlled and has a maximum setting of 20 min (Continues)

4 Mechanism of action TABLE 1 (Continued) Model Type Use No. of lamps Features - Scalp and localized lesions 2 - Keyed switch lock to prevent unauthorized use - Digital countdown timer that allows dosage to be controlled and has a maximum setting of 20 min 100 Series -Handheld device - Treatment area in UVBioTek - Generalized BSA involvement 16 - Emergency on/off switch - Equipped with acrylic safety shield to prevent direct contact with UV bulbs 1600B -Full- length -Cabinet style - Treats entire body in 1 exposure - Generalized BSA involvement 10 - Equipped with acrylic safety shield to prevent direct contact with UV bulbs Multidirectional -Full- length - Triple panel model - Treat full body with 2 exposures - Generalized BSA involvement 4, 6, 8 or 10 - Equipped with acrylic safety shield to prevent direct contact with UV bulbs 100B -Single panel - Dimension in -Localized areas 2 - Equipped with acrylic safety shield to prevent direct contact with UV bulbs 20B -Single panel - Dimension in - Hands, feet and localized areas 6 - Equipped with acrylic safety shield to prevent direct contact with UV bulbs Mobile- Lite - Single panel with removable hood - Dimension in BSA, body surface area; UV, ultraviolet. NB- UVB phototherapy induces disease stability by decreasing interleukin 17 and interleukin- 22 levels, which are secreted by T helper 17 cells that are increased in vitiligo. NB- UVB also leads to increased Fox P3 expression, which is a marker for T regulatory cells that are decreased in vitiligo. 10 Regarding repigmentation, NB- UVB acts through multiple mechanisms, including stimulating the activation, proliferation and migration of melanocytes from the outer root sheath of hair follicles to the epidermis. As such, there is often poor response to treatment in areas with fewer hair follicles, such as the hands and the feet. NB- UVB also increases expression of basic fibroblast growth factor and endothelin- 1 in keratinocytes, which induces melanocyte proliferation and migration. Increased levels of matrix metalloproteinase 2 and 9 and phosphorylated focal adhesion kinase stimulate melanocyte migration as well. 11 Finally, NB- UVB increases levels of tyrosinase and HMB 45 receptor expression on melanocytes, increasing melanin production Efficacy The efficacy of NB- UVB was demonstrated in 1997 by Westerhof and Nieuweboer- Krobotova where 67% (n=52/78) of subjects with extensive, generalized vitiligo repigmented with NB- UVB compared to only 46% (n=13/28) using PUVA, with fewer adverse effects and a faster rate of repigmentation. 1 In adults, several trials have shown the superiority of NB- UVB over PUVA. 2,13 A meta- analysis of non- surgical therapies for vitiligo showed that NB- UVB had fewer side effects and more patients achieving over 75% pigmentation at 68% compared to BB- UVB at 57% and PUVA at 51%. 13,14 NB- UVB also induces significant repigmentation with a good safety profile in children. 15,16 Factors associated with greater response to NB- UVB include location of vitiligo, recent disease onset with early treatment, longer treatment duration, darker skin type, and generalized vitligo. 15,17,18 Areas with greater follicular density, such as the face and neck, respond best to treatment. Bony prominences, acral, and mucosal sites typically have a poor response to NB- UVB phototherapy. 12,13,19 Although institutions have individual guidelines on the administration of NB- UVB phototherapy in vitiligo, no uniformly published guidelines exist. To address this gap, the Vitiligo Working Group developed phototherapy recommendations, which have recently been published (Table 2) Combination therapy (topical and systemic) Using other treatments with NB- UVB is common to enhance repigmenation (Table 3) 16,17 Because depigmentation can occur once phototherapy is discontinued, a rotational schedule of phototherapy may be required to maintain pigmentation. Topical therapies used with NB- UVB phototherapy include calcineruin inhibitors, vitamin D analogues, and pseudocatalase. Calcineurin inhibitors increase repigmentation when used with NB- UVB compared to NB- UVB alone, and are not associated with an increased risk of skin cancer. 21,22 Vitamin D analogues have been

5 245 TABLE 2 The Vitiligo Working Group phototherapy recommendations 20 Frequency of administration Optimal: 3 times per week Acceptable: 2 times per week Level of evidence: IIA Dosing protocol Initiate dose at 200 mj/cm 2 irrespective of constitutive skin type Increase by 10%-20% per treatment Fixed dosing based on skin type is another acceptable dosing strategy that takes inherent differences in the minimal erythema dose of various skin types into account Level of evidence: IB Maximum acceptable dose Face: 1500 mj/cm 2 Body: 3000 mj/cm 2 Maximum number of exposures SPT IV-VI: No limit SPT I-III: More data on the risk of cutaneous malignancy is needed before a recommendation can be made Course of NB- UVB Assess treatment response after exposures Minimum number of doses needed to determine lack of response: 48 exposures Due to the existence of slow responders, up to 72 exposures may be needed to determine lack of response to phototherapy Level of evidence: III Dose adjustment based on degree of erythema No erythema: Increase next dose by 10%-20% Pink asymptomatic erythema: Hold at current dose until erythema disappears then increase by 10%-20% Bright red asymptomatic erythema: Stop phototherapy until affected areas become light pink, then resume at last tolerated dose Symptomatic erythema (includes pain and blistering): Stop phototherapy until the skin heals and erythema fades to a light pink, then resume at last tolerated dose Level of evidence: IB Dose adjustment following missed doses 4-7 days between treatments: Hold dose constant 8-14 days between treatments: Decrease dose by 25% days between treatments: Decrease dose by 50% Over 3 wk between treatments: Restart at initial dose Device calibration or bulb replacement Decrease dose by 10%-20% Outcome measures to evaluate response Serial photography to establish baseline severity, disease stability, and response to treatment Validated scoring systems, such as the VASI or VETF, to quantify degree of response Level of evidence: IB Posttreatment recommendations Application of sunscreen Avoidance of sunlight (Continues) TABLE 2 (Continued) Topical products prior to phototherapy Avoid all topical products for 4 h EXCEPT mineral oil Mineral oil can be used to enhance light penetration in areas of dry, thickened skin, such as the elbows and knees Tapering NB- UVB after complete repigmentation has been achieved First month: Phototherapy twice weekly Second month: Phototherapy once weekly Third and fourth months: Phototherapy every other week After 4 mo: Discontinue phototherapy Follow- up SPT I-III: Yearly follow-up for total body skin examination to monitor for adverse effects of phototherapy, including cutaneous malignancy SPT IV-VI: No need to return for safety monitoring as no reports of malignancy exist with this group All patients: Return upon relapse for treatment Minimum age for NB- UVB in children Minimum age is when children are able to reliably stand in the booth with either their eyes closed or wearing goggles Typically around 7-10 y of age depending on the child Level of evidence: III Treatment of eyelid lesions Keep eyes closed during treatment, using adhesive tape if necessary Level of evidence: III Special sites Cover face during phototherapy if uninvolved Shield male genitalia Protect female areola with sunscreen prior to treatment, especially in SPT I-III Level of evidence: III Combination treatment for stabilization Oral antioxidants Topical treatments Oral pulse corticosteroids Level of evidence: IB Treatment of NB- UVB- induced skin changes Xerosis: Emollient or mineral oil Skin thickening: Topical corticosteroids or keratolytics NB- UVB, Narrowband ultraviolet B; SPT, skin phototype; VASI, Vitiligo Area Scoring Index; VETF, Vitiligo European Task Force Assessment Levels of evidence: Level IA evidence from meta- analysis of randomized controlled trials Level IB evidence from at least one randomized controlled trial Level IIA evidence from at least one controlled study without randomization Level IIB evidence from at least one other type of experimental study Level III evidence from nonexperimental descriptive studies, such as comparative studies, correlation studies, and case- control studies Level IV evidence from expert committee reports or opinions or clinical experience of respected authorities, or both. used successfully with NB- UVB in psoriasis, but studies on this combination in vitiligo are conflicting and require further studies. Due to the photoprotective nature of vitamin D analogues, use should be

6 246 TABLE 3 Combination therapies of NB- UVB and other medications Treatment response Combination therapy Mechanism Improved No significant difference Notes Benefits Limitations NB- UVB/ calcineurin inhibitors (tacrolimus/ pimecrolimus) Inhibit T cell activation Blocks production and release of proinflammatory cytokines 5 studies studies 25,26 Effect may be dose dependent (daily vs twice daily application) Face and neck are most responsive areas Few adverse effects Safe to use for extended periods Greasiness of tacrolimus may limit use in certain areas Costly medication May be associated with a burning sensation NB- UVB/topical corticosteroids Anti-inflammatory Immunomodulatory effects on T cells 2 studies 22,27 Useful for short courses of treatment Duration of use limited by side effects: telangiectasias, skin atrophy and striae NB- UVB/vitamin D analogues Receptors present on melanocytes and keratinocytes Restore calcium homeostasis Immunomodulatory effects on T cells 3 studies studies 22,31-36 NB- UVB/ pseudocatalase Replace depleted catalase levels Reduce H 2 O 2 mediated oxidative stress Restore calcium homeostasis 2 studies 37,38 2 studies 39,40 Activated by NB-UVB Not effective in acral areas Use in segmental vitiligo uncertain Only the formulation produced in Germany has shown any effect Costly to obtain original formulation NB- UVB/ Polypodium leucotomos extract Antioxidative properties: quench free radicals, lipid peroxidation and reactive oxygen species Immunomodulation of cell mediated immunity 1 study 41 Increased repigmentation in head and neck region Available over the counter Few adverse effects May be associated with mild pruritus and gastrointestinal discomfort NB- UVB/ alpha- liphoic acid Reduce oxidative stress Fatty-acid peroxyl and hydroxyl radical scavenger Inhibit lipoxygenase Promote glutathione synthesis 2 studies 42,43 Leads to earlier onset of repigmentation Available over the counter Few adverse effects NB- UVB/oral corticosteroids Anti-inflammatory Immunomodulatory effects on T cells 1 study 44 Minipulse dosing with oral betamethasone 0.5 mg/kg on 2 consecutive days weekly Combination therapy: NB-UVB>BB-UVB or PUVA Decreased risk of systemic side effects with minipulse dosing Longterm use limited by systemic side effects: weight gain, increased blood sugar and blood pressure and decreased bone density NB- UVB/ afamelanotide α-msh analogue in a controlled release formation Produces longer physiologic effects than parent molecule Stimulates melanin production 2 studies 45,46 Faster and deeper pigmentation of the face and neck More notable in darker skin phototypes Diffuse hyperpigmentation of normal skin Adverse effects: nausea, dizziness and headache Currently not commercially available α- MSH, alpha melanocyte stimulating hormone; BB- UVB, broad- band ultraviolet B; NB- UVB, narrow- band ultraviolet B; PUVA, psoralen with ultraviolet A.

7 247 avoided before phototherapy Patients with vitiligo have elevated levels of hydrogen peroxide (H 2 O 2 ) in their skin. Pseudocatalase degrades H 2 O 2 and can be combined with phototherapy for treatment of vitligo. Schallreuter et al. reported significant repigmentation using their formulation of pseudocatalase, but these results have not been reproducible. 27,28 Oral therapies used with phototherapy include antioxidants like Polypodium leucotomos extract, alpha- lipoic acid, and Ginkgo biloba. Polypodium leucotomos extract contains multiple polyphenols, which contribute to its immunomodulatory, antioxidant, and antiinflammatory properties. When used with NB- UVB, it increases the rate and degree of repigmentation of the head and neck compared to NB- UVB alone. 29 Alpha- lipoic acid, a supplement that stimulates melanocytes and has antioxidant and immunomodulatory activities, increased repigmentation when used with vitamin C, vitamin E, polyunsaturated fatty acids, cysteine monohydrate, and NB- UVB, compared to NB- UVB alone. 30 Ginkgo biloba is another over- the- counter antioxidant with benefit in inducing disease stability. 31,32 However, further studies on NB- UVB and ginkgo biloba are necessary. Daily dosing of prednisone or mini- pulse dosing of dexamethasone (4-6 mg two consecutive days a week) can be used with phototherapy to induce disease stability and repigmentation. 33 In addition, approximately onethird of patients are non- photoadaptors, meaning they do not exhibit a diminished erythema response to equivalent doses of NB- UVB upon subsequent irradiation. 34 As such, they cannot tolerate dose increases. Oral corticosteroids promote photoadaptation in this population. 35 Other options to increase treatment response in combination with phototherapy include surgical therapy and afamelanotide. Phototherapy is often used before or after cellular or tissue grafting to accelerate repigmentation and prevent new lesions. 36 Afamelanotide, an implantable alpha melanocyte- stimulating hormone analogue, significantly increased the rate and degree of repigmentation when combined with NB- UVB in patients with skin phototype IV- VI compared to NB- UVB alone. However, this medication is not yet commercially available HOME PHOTOTHERAPY Currently, few studies on the use of home phototherapy in vitiligo exist. Much of our knowledge is extrapolated from the psoriasis literature. 38 Although future research is needed, we can draw some preliminary conclusions regarding the safety and efficacy of home phototherapy in vitiligo. 3.1 Selection and administration To be considered for home phototherapy, patients must be good candidates for in- office phototherapy. Patients need to be motivated, able to comply with instructions, and return to clinic periodically for reevaluation. Absolute contraindications include a history of xeroderma pigmentosum or systemic lupus erythematosus. Relative contraindications are photodermatoses, immunosuppression, photodamaged skin, personal or family history of melanoma or multiple non- melanoma skin cancers, and claustrophobia. Use of photosensitizing medications is usually not a contraindication as most of these act in the UVA range. NB- UVB can also be used safely in children, pregnant females, and those with hepatic or renal disease. 39 Pregnant patients undergoing home phototherapy should be followed closely and extra caution should be used. Patients should complete a course of NB- UVB phototherapy to ensure treatment responsiveness, reliability following detailed instructions, and ability to follow- up in clinic. The consent performed prior to in- office phototherapy can be carried over for home phototherapy. However, institutional guidelines should be followed regarding this process. Administration of home phototherapy is similar to in- office phototherapy, with dose adjustments based on lesional erythema after treatment. Creating patient handouts with dose adjustments and instructions on how to handle missed doses is invaluable in facilitating patient understanding, ensuring compliance, and reducing adverse events (Figure 1). 3.2 Efficacy and safety One of the most well- known trials on home phototherapy is the PLUTO study, 40 the first multicenter, single- blinded, randomized, controlled trial comparing in- office vs. home NB- UVB phototherapy for the treatment of psoriasis. Patients in the home phototherapy arm were given a phototherapy schedule and an educational training session with a nurse. Subsequent dosing was adjusted by nurses, and the mean duration of phototherapy was 11 weeks compared to 14 weeks for inoffice phototherapy. At study completion, 70% of patients in the home phototherapy arm reached Psoriasis Area and Severity Index 50 compared to 73% in the in- office phototherapy arm, showing that home and in- office NB- UVB phototherapy were equally effective. There was no difference in the number of side effects. The total dose of NB- UVB administered, the measure of long- term safety, was slightly higher in the home phototherapy group, but not statistically significant. Based on a survey completed by participants, none of the subjects felt that home phototherapy was unsafe. 40 Cost was similar for both groups, with costs for the home phototherapy group including unit delivery, pick up, and home care. However, costs associated with time away from work were not considered. Once this variable was factored in, there was a significant cost advantage to home phototherapy. 41 Patient satisfaction was greater in the home phototherapy group, with equal Dermatology Life Quality Index scores and decreased burden of treatment. 40 Fewer studies have been performed on home phototherapy and vitiligo, but these have yielded similar results. A survey study from the Netherlands compared biweekly in- office vs. home phototherapy in 104 patients (57 home phototherapy and 32 in- office phototherapy). Results showed that home phototherapy patients received a greater number of treatments per week, with no significant difference in the cumulative dose. No significant difference was noted in the degree of pigmentation or adverse events between both groups. However, time investment was much lower in the home phototherapy group. 42 Another study compared home phototherapy with a handheld NB- UVB device 3 times per week to biweekly in- office excimer laser in subjects

8 248 3 Day/Week Home Phototherapy Instruc ons Vi ligo SAFETY: - Always wear eye protec on (unless told otherwise by your dermatologist) - Males must wear a jockstrap, and females apply sunscreen, SPF 30 or greater, to the nipples only (unless told otherwise by your dermatologist) - Anyone else in the room should wear UV eye protec on as well as full body skin protec on (clothing/sunscreen) - If clothing is worn during phototherapy, the exact same area should be covered at each session to prevent accidental burns to skin not exposed in the previous session. - Do NOT exceed the maximum treatment dose for the face or body. RISKS: - Sunburn or premature aging of the skin - Increased risk of skin cancer - Eye injury such as corneal burn and cataracts HOME TREATMENT INSTRUCTIONS: 3X WEEKLY (Monday, Wednesday, Friday) - If a triple panel model is being used, posi on the side panels at 45 degree angles - Stand 8 inches away from the light source. - Wear protec ve eye wear and protect genitals as stated under SAFETY For men, cover genitals and for women cover nipples with sunscreen (SPF 30 or greater). - On phototherapy days, do not apply any topical creams or ointments (medical or over-the-counter) before your treatment session. - A non-alcohol based moisturizer may be applied daily a er phototherapy to prevent dry skin. 1. Day 1 - MONDAY: Set mer to the me indicated for Level 1 in table below and treat the front-side of your body. Reset the mer and treat the back-side of your body. 2. Day 2 - WEDNESDAY: Repeat Day 1, except increase the dura on of treatment to the next level (i.e. Level 2) 3. Day 3 - FRIDAY: Increase dura on of treatment to the next level (i.e. Level 3) and treat front and back of body. 4. Con nue this pa ern of increasing to the next level at each treatment un l the maximum dose is reached or un l the light pink color of a pink carna on is achieved about one day a er phototherapy. Keep in mind pinkness/redness may develop hours a er exposure to this light source (NB-UVB). RE-EVALUATION: Regaining color is a very slow process. Re-evalua on for treatment response should occur only a er every treatments, but it may take up to 72 treatments before you will no ce a significant response without photographs. Before and a er photographs are helpful in this process. FIGURE 1 Henry Ford Hospital home phototherapy patient handout for vitiligo with localized vitiligo. Here, home phototherapy was more effective, although this difference was not statistically significant. There was, however, increased compliance with home phototherapy, with three subjects in the excimer treatment arm withdrawing from the study due to time constraints. Regarding safety, only 1 case of UVB- induced burn was noted in the home phototherapy group. 43 A study by Shan et al. examined the use of a home NB- UVB handheld device thrice weekly in 93 subjects with localized disease over 1 year. Repigmentation was observed 1 month after initiation of treatment and some subjects had complete repigmentation by 3 months. Dryness, pruritus, and a burning sensation were the most common side effects, but they did not lead to subject withdrawal. 44 Currently, no large, multicenter, randomized controlled trials comparing in- office vs. home phototherapy in vitiligo exist. The Hi- Light trial was a feasibility trial for a larger multicenter effort, which randomized 29 patients with non- segmental vitiligo to either the treatment group with 1 of 2 handheld NB- UVB home phototherapy devices or the placebo group, using sham irradiation. 45 Treatment

9 249 FIGURE 1 (Continued) 3 Day/Week Home Phototherapy Instruc ons Vi ligo Device Irradiance: 3 mw/cm2 Dosing *Dose Time Dosing *Dose Time Time Level # (mj/cm 2 ) (seconds) Level # (mj/cm 2 ) (seconds) (minutes) Star ng Dose: (mj/cm 2 ) min 50 sec Dosing Adjustments: (%) min 13 sec Maximum Dose for the Face: 1000 mj/cm min 38 sec Maximum Dose for the Body: 1800 mj/cm min 6 sec h p://teleflora.edgesuite.net/images/products/vl_ jpg *These doses are based on an irradiance of 3 mw/cm2 and may vary by device **Changes in treatment mes if treatments are missed: Length of me absent from phototherapy 1-2 Treatments 1-2 weeks 2-4 weeks >1 month **Dose Adjustments: Skin assessment No redness Mild redness - light pink Moderate redness Severe redness / blisters min 33 sec min 6 sec min 43 sec min 28 sec min 8 sec min 56 sec min 60 sec min 49 sec min 54 sec min 5 sec min 24 sec min 50 sec min 40 sec Adjustment in dose Maintain previous dose/level Decrease by 32% or 4 levels e.g. (10 to 6) Decrease by 65% or 11 levels e.g. (20 to 9) Re-start at ini al dose Dose adjustment Increase dose to next level Hold dose / level constant Decrease dose by 2 levels (4 to 2) Call physician lasted 4 months, with 3-4 sessions per week. At completion, 84% of subjects were compliant with their treatment regimen. Greater patient satisfaction was achieved with the treatment group, and the majority of subjects said they would recommend the handheld device, as it was easy to use, portable, compact, and convenient. As this was a feasibility trial, the duration was not long enough to assess repigmentation. However, this trial provided recommendations for future trials assessing home phototherapy in vitiligo, including recruitment through primary care, skin mapping of lesions to evaluate repigmentation, defining outcomes, minimal erythema dose testing prior to initiating phototherapy, training materials on how to operate home devices, and the inclusion of active treatments in all groups. 45 One of the main barriers to prescription of home phototherapy is concern over safety. Adverse effects of home phototherapy are similar to in- office phototherapy such as burning, erythema, xerosis, and pruritus; these are often treated using emollients or topical corticosteroids. Köebnerization may occur due to phototoxic reactions. With long- term use, photodamage and photoaging may occur. 39 Data regarding the risk of cutaneous malignancy with NB- UVB phototherapy in patients with vitiligo is mixed. 46,47 Patients at highest risk of side effects with home phototherapy are those who independently purchase units and self- administer phototherapy without physician oversight. However, most companies require a prescription to be written by a physician. Many devices are

10 250 equipped with safety features to prevent adverse events. These include controlled prescription timers, which allow for administration of a fixed a number of treatments after which a new code from the patient s physician is required, key- locked on/off switches, and timers limiting the length of treatment. Dosimeters to enable accurate dosing, safety shields, and failsafe switches also exist. 5 Physicians can track patient adherence by using an electronic data logger. 48 Support staff play a crucial role in keeping risks of home phototherapy to a minimum by providing patient education. This includes shielding special sites, wearing clothing with the same cut at each session, how to recognize adverse effects and when to contact their dermatologist, how to maintain a proper treatment distance and the importance of regular follow- up. As demonstrated by multiple studies, 40,42-45 when patients are educated regarding home phototherapy, the risks of adverse reactions are quite low and no greater than in- office phototherapy. A perceived lack of efficacy is another barrier to home phototherapy. Fifty- five percent of 367 surveyed dermatologists believed that in- office phototherapy was superior to home phototherapy, while 33% felt that greater risks were associated with home phototherapy. 49 However, previous studies show that home phototherapy is equally effective as in- office phototherapy, with greater adherence and decreased patient burden Lack of insurance coverage is a major barrier for this form of therapy, as many patients cannot afford a home unit without assistance. 50 Finally, many providers do not receive adequate training and are uncomfortable with prescribing home units. A survey administered at the Ninth Annual Dermatology Chief Residents meeting showed that only 35% of residents received training on the use and prescription of home phototherapy, while 73% had never prescribed home phototherapy during their training. 51 Another survey of dermatology residents showed that only 25% had didactics on home phototherapy and that no first- year residents and 17% of third- year residents were comfortable prescribing home phototherapy. 52 These educational gaps in residency become treatment gaps in practice, leading to the underutilization of home phototherapy. It is imperative that residency programs rectify these knowledge gaps and provide training on the use of home phototherapy. 4 CONCLUSION Based on the current literature, home phototherapy is a treatment option that should be considered in the management of vitiligo. Not only is it safe and effective, but it eases many hardships associated with in- office phototherapy. Although further studies on home phototherapy in vitiligo are necessary, there is a knowledge gap on home phototherapy among many providers, which needs to be addressed and further education provided. CONFLICTS OF INTEREST Dr. Mohammad is a sub- investigator for Allergan, Ferndale laboratories, and Estee Lauder. Dr. Hamzavi is a consultant for Chromaderm, Pfizer, and Johnson and Johnson and is an investigator for Estee Lauder, Allergan, Ferndale Laboratories, and Johnson and Johnson, and has received equipment from Johnson and Johnson, and is on the Ad Board of Aclaris. Dr. Lim is a consultant for Pierre Fabre, and an investigator for Estee Lauder, Ferndale, and Allergan. Drs. Griffith and Silpa- Archa have no relevant disclosures. REFERENCES 1. Westerhof W, Nieuweboer-Krobotova L. Treatment of vitiligo with UV- B radiation vs topical psoralen plus UV- A. Arch Dermatol. 1997;133: Yones SS, Palmer RA, Garibaldinos TM, Hawk JL. 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