MEDICAL POLICY

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APPENDIX
HISTORY

Light Therapy for Vitiligo

Number 2.01.525

Effective Date August 16, 2013

Revision Date(s) 08/12/13

Replaces 2.01.86 and 2.01.518 (in part)

Policy

PUVA for the treatment of vitiligo which is not responsive to other forms of conservative therapy (e.g., topical corticosteroids, coal/tar preparations, and ultraviolet light) may be considered medically necessary.

Targeted phototherapy is considered medically necessary for the treatment of vitiligo.

Related Policies

2.01.47

Light Therapy for Psoriasis

2.01.518

Light Therapies for Eczema, Atopic Dermatitis and Mycosis Fungoides

Policy Guidelines

The duration and number of treatments depends on the type, number, and location of the lesions; skin type; type of therapy and the dosage.

PUVA

During a course of PUVA therapy, the patient needs to be assessed on a regular basis to determine the effectiveness of the therapy and the development of side effects. These evaluations are essential to ensure that the exposure dose of radiation is kept to the minimum compatible with adequate control of disease. Therefore, PUVA is generally not recommended for home therapy.

Repigmentation may begin after 15 to 25 treatments of PUVA. When effective, significant follicular pigmentation occurs after 6 months of therapy with 8-10 treatments per month. However, some patients will need 150 to 200 PUVA treatments over 12 to 24 months to complete treatment.

Narrow-band UVB

Narrow-band UVB is typically administered 2 to 3 times per week for several months.

There is no specific CPT code for laser therapy for vitiligo. It should currently be reported using an unlisted CPT (96999) but the CPT codes for laser therapy for psoriasis (96920-96922) might be used.

Description

Light therapy for vitiligo includes both targeted phototherapy and photochemotherapy with psoralen plus ultraviolet A (PUVA). Targeted phototherapy describes the use of ultraviolet light that can be focused on specific body areas or lesions. PUVA uses a psoralen derivative in conjunction with long wavelength ultraviolet A (UVA) light (sunlight or artificial) for photochemotherapy of skin conditions.

Background

Vitiligo is an idiopathic skin disorder that causes depigmentation of sections of skin, most commonly on the extremities. Depigmentation occurs because melanocytes are no longer able to function properly. The cause of vitiligo is unknownbut most research suggests it is an autoimmune disease. The most common form of the disorder is non-segmental vitiligo (NSV) in which depigmentation is generalized, bilateral, symmetrical, and increases in size over time. In contrast, segmental vitililgo (SV) also called asymmetric or focal vitiligo, covers a limited area of skin. The typical natural history of vitiligo involves stepwise progression with long periods in which the disease is static and relatively inactive, and relatively shorter periods in which areas of pigment loss increase.

There are numerous medical and surgical treatments aimed at decreasing disease progression and/or attaining repigmentation. Topical corticosteroids, alone or in combination with topical vitamin D3 analogs, is a common first-line treatment for vitiligo. Alternative first-line therapies include topical calcineurin inhibitors, systemic steroids, and topical antioxidants.

Treatment options for vitiligo recalcitrant to first-line therapy include, among others, psoralens with ultraviolet A and targeted light therapy. PUVA uses a psoralen derivative in conjunction with long wavelength ultraviolet A light (sunlight or artificial) for photochemotherapy of skin conditions. Psoralens are tricyclic furocoumarins that occur in certain plants and can also be synthesized. They are available in oral and topical forms. Oral PUVA is generally given 1.5 hours before exposure to UVA radiation. Topical PUVA therapy refers to directly applying the psoralen to the skin with subsequent exposure to UVA light. With topical PUVA, UVA exposure is generally administered within 30 minutes of psoralen application.

Potential advantages of targeted phototherapy include the ability to use higher treatment doses and to limit exposure to surrounding tissue. Broadband (BB)-ultraviolet B (UVB) devices, which emit wavelengths from 290 to 320 nm have been largely replaced by narrowband (NB)-UVB devices. NB-UVB devices eliminate wavelengths below 296 nm, which are considered erythemogenic and carcinogenic but not therapeutic. Original NB-UVB devices consisted of a Phillips TL-01 fluorescent bulb with a maximum wavelength (lambda max) at 311 nm. Subsequently, xenon chloride (XeCl) lasers and lamps were developed as targeted NB-UVB treatment devices; they generate monochromatic or very narrow band radiation with a lambda max of 308 nm. Targeted phototherapy devices are directed at specific lesions or affected areas, thus limiting exposure to the surrounding normal tissues. They may therefore allow higher dosages compared to a light box, which could result in fewer treatments.

Regulatory Status

In 2001, an XeCl excimer laser (XTRAC™ by PhotoMedex) received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for the treatment of skin conditions such as vitiligo. The 510(k) clearance has subsequently been obtained for a number of targeted UVB lamps and lasers, including newer versions of the XTRAC system including the XTRAC Ultra™, the VTRAC™ lamp (PhotoMedex), the BClear™ lamp (Lumenis), the 308 excimer lamp phototherapy system (Quantel Medical) and the Excilite™ and Excilite µ™ XeCl lamps. The intended use of all of these devices includes vitiligo among other dermatological indications.

The oral psoralen products Oxsoralen-Ultra (methoxsalen soft gelatin capsules) and 8-MOP (methoxsalen hard gelatin capsules) have been approved by the FDA; both are made by Valeant Pharmaceuticals. Topical psoralen products have also received FDA approval e.g., Oxsoralen (Valeant Pharmaceuticals).

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application

N/A

Rationale

This policy was created in 2012 with a search of the MEDLINE database through March 2013. Following is a summary of the key literature published to date.

Targeted Phototherapy

In 2010, Whitton and colleagues published a Cochrane review of randomized controlled trials (RCTs) on treatments for vitiligo. (1) The investigators searched the literature through November 2009 and identified 5 trials on excimer laser therapy. None of these trials included a control group of individuals who did not receive excimer therapy, so the effect of laser therapy cannot be isolated. Four trials compared the combination of excimer laser therapy and a topical therapy to excimer lasers alone or excimer lasers plus a placebo topical treatment. The fifth trial compared different frequencies of excimer laser treatment (once, twice, or three times weekly). Whitton stated that the majority of analyses showing statistically significant differences were from studies that assessed combination interventions. The authors concluded that this review has found some evidence from individual studies to support laser treatment for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures.  They agreed that there was a need for high quality randomized trials using standardized measures and which also address quality of life.

In order to adequately evaluate the impact of laser treatment or other targeted phototherapy treatment on vitiligo RCTs are needed that include a comparison group of patients who receive a treatment other than targeted phototherapy (i.e. an alternative treatment, no treatment, or sham treatment). Two RCTs of this type have been published by the same research group in Italy, and their findings are described below. These trials were not included in the Whitton et al. Cochrane review.

In 2012, Nistico and colleagues published a non-blinded RCT that included 53 patients with localized and generalized vitiligo. (2) Patients were randomly assigned to one of 3 treatments for 12 weeks: 1) Excimer laser plus vitamin E (n=20); 2) excimer laser plus topical 0.1% tacrolimus ointment and vitamin E (n=20); 3) vitamin E only (control group, n=13). All patients in the 2 excimer laser groups completed treatment; 1 patient in the control group dropped out. Before and after treatment, 2 independent clinicians rated clinical response; 51-75% repigmentation was considered a ‘good’ response and >75% repigmentation was considered an ‘excellent’ response. The proportion of patients with a good or excellent response was 11/20 (55%) in the laser plus vitamin E group, 14/20 (70%) in the laser E plus tacrolimus plus vitamin E group, and 0 in the control group. The rate of good or excellent response did not differ significantly between the groups that received excimer laser therapy with and without topical treatment (p=0.36). The response rate was significantly better in both groups receiving laser treatment compared to the control group (p<0.001).

The Italian research group also published a similar 12-week study in 2009 in which topical 4% khellin ointment was used instead of tacrolimus ointment. (3) This study included 48 patients (16 per group), of which 45 (94%) completed treatment. The proportion of patients with a good or excellent response (see definitions above) was 14/16 (88%) in the excimer laser plus vitamin E group, 14/16 (88%) in the excimer laser plus khellin plus vitamin E group, and 1/16 (6%) in the vitamin E only (control) group. The clinical response rates in the 2 groups receiving laser treatment were significantly higher than in the control group.

In 2012, El-Zawahry and colleagues in Egypt published findings of a study comparing ultraviolet A (UVA) treatment and targeted narrowband ultraviolet B (NB-UVB) phototherapy in 40 patients with vitiligo. Phototherapy sessions occurred 3 times a week for 12 weeks. The primary efficacy outcome was change in the Vitiligo Area Scoring Index (VASI) before and after treatment. After the 36 treatment sessions, the median percent change in VASI score was 0% (range: -13.3% to 37.5%) in the UVA group and -6.7% (range: -50.9% to 26.4%) in the NB-UVB group. The difference between groups was statistically significant, favoring the NB-UVB group (p=0.000). Several secondary outcomes also favored the NB-UVB group. For example, a significantly higher proportion of patients in the NB-UVB were judged by a blinded physician to have a moderate to excellent response compared to patients in the UVA group (80% vs. 25%, p=0.000).

Psoralens with Ultraviolet A (PUVA)

The 2010 Cochrane review of trials on treatments for vitiligo, discussed above in the section on targeted phototherapy, identified 10 RCTs evaluating oral PUVA. (1) Two trials assessed oral PUVA alone, and 8 assessed PUVA in combination with other treatments e.g., calcipotriol, azathioprine, polypodium leucotomos, khellin, or surgical treatment. Seven of the 8 studies used 9 methoxypsoralen. Six trials were identified on oral PUVA plus sunlight; 2 of these used placebo as the comparison. Due to differences among studies, findings of trials on oral PUVA and on oral PUVA plus sunlight were not pooled.

An earlier meta-analysis of treatments for vitiligo was published in 1998 by Njoo and colleagues. (4) A pooled analysis of 2 RCTs on oral unsubstituted psoralen plus sun for generalized vitiligo (total n=97) found a statistically significant treatment benefit of active treatment compared to placebo (pooled odds ratio [OR]: 19.9, 95% confidence interval [CI]: 2.4 to 166.3). A pooled analysis of 3 RCTs, 2 on oral methoxsalen plus sun and 1 on oral trioxsalen plus sun (total n=181) also found a significant benefit of active treatment versus placebo on generalized vitiligo (OR: 3.8, 95% CI: 1.3 to 11.3). All studies were published prior to 1985, had relatively small sample sizes (confidence intervals were wide), and used sun exposure rather than artificial UVA.

A 2007 RCT, using a psoralen formulation available in the U.S., was published by Yones and colleagues. (5) The study used data on 56 patients in the U.K. who had non-segmental vitiligo. Outcome assessment was blinded. Patients were randomly assigned to receive twice-weekly treatments with methoxsalen hard gelatin capsules (8-MOP) psoralen plus UVA (n=28) or narrow band (NB)-ultraviolet B (UVB) therapy (n=28). The NB-UVB treatments were administered in a Waldmann UV500 cabinet containing 24 Phillips 100 NB-UVB fluorescent tubes. In the PUVA group, the starting dose of irradiation was 0.5 J/cm2, followed by 0.25 J/cm2 incremental increases if tolerated. Patients were evaluated after every 16 sessions and followed for up to 1 year. Treatment was discontinued if there was complete or near complete resolution of vitiligo, no or minimal improvement after 32 treatments, completion of 200 lifetime treatments, or upon patient request. All patients were included in the analysis. The median number of treatments received was 49 in the PUVA group and 97 in the NB-UVB group. At the end of treatment, the median improvement body surface area with vitiligo (BSA-V) was 23% in the PUVA group and 61% in the NB-UVB group. In addition, 5 of 25 (20%) of patients in the PUVA group and 8 of 25 (32%) in the NB-UVB group had at least 75% improvement in BSA-V at the end of follow-up. The authors did not provide p-values in their outcome table. They stated though, that the difference in improvement in BSA-V did not differ significantly between groups. A total of 24 (96%) patients in the PUVA group and 17 (68%) in the NB-UVB group developed erythema at some point during treatment; this difference was statistically significant, p=0.02.

There is some evidence from randomized studies, mainly those published prior to 1985, that PUVA is more effective than placebo for treating vitiligo.

Summary

Light therapy for vitiligo includes both targeted phototherapy and PUVA. Most published RCTs evaluating targeted phototherapy for vitiligo treated patients in all groups with targeted phototherapy and thus the effect of phototherapy treatment cannot be isolated. There are 2 small RCTs, both from the same research group, which found that excimer laser treatment produced better results than a vitamin E control group. British guidelines on vitiligo do not specifically address targeted phototherapy, although they do state that if phototherapy is used for treating nonsegmental vitiligo, NB-UVB should usually be used in preference to oral PUVA.

There is some evidence from randomized studies, mainly those published prior to 1985, that PUVA is more effective than placebo for treating vitiligo. PUVA for vitiligo is recommended in British guidelines for adults who do not respond to more conservative treatments. Based on the available evidence and clinical guidelines, PUVA may be considered medically necessary in patients with vitiligo who have not responded adequately to conservative therapy.

Practice Guidelines and Position Statements

In 2008, a guideline on the diagnosis and management of vitiligo was published by several organizations in the U.K. including the British Association of Dermatologists, the Royal College of Physicians of London, and the Cochrane Skin Group. (6) The guideline included the following statements:

PUVA therapy should be considered for treatment of vitiligo only in adults who cannot be adequately managed with more conservative treatments. PUVA is not recommended in children. (Grade of recommendation D, Level of evidence 4)

If phototherapy is to be used for treating nonsegmental vitiligo, NB-UVB should usually be used in preference to oral PUVA. (Grade of recommendation A, Level of evidence 1+)

A trial of PUVA therapy should be considered only for adults with widespread vitiligo, or localized vitiligo associated with a significant impact on patient's QoL (quality of life). Ideally, this treatment should be reserved for patients with darker skin types. (Grade of recommendation D, Level of evidence 3)

Before starting PUVA treatment, patients should be made aware that there is no evidence that this treatment alters the natural history of vitiligo. They should also be made aware that not all patients respond, and that some body sites, such as the hands and feet, respond poorly in all patients. They should also be informed of the limit to the number of treatments due to possible side-effects. (Grade of recommendation D, Level of evidence 3)

American Academy of Dermatology

The American Academy of Dermatologists does not have a current guideline on the treatment of vitiligo, although their website lists NB-UVB and excimer laser as treatments for vitiligo. They state a 70% effectiveness rate with excimer laser, with the highest effectiveness on the face and lowest effectiveness for hands and feet.

Medicare National Coverage

No national coverage determination.

References

  1. Whitton ME, Pinart M, Batchelor J et al. Interventions for vitiligo. Cochrane Database Syst Rev 2010; (1):CD003263.
  2. Nistico S, Chiricozzi A, Saraceno R et al. Vitiligo treatment with monochromatic excimer light and tacroliums: results of an open randomized controlled study. Photomed Laser Surg 2012; 30(1):26-30.
  3. Saraceno R, Nistico S, Capriotti E et al. Monochromatic excimer light 308nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study. Dermatol Ther 2009; 22(4):391-4.
  4. Njoo MD, Spuls PI, Bos JD et al. Nonsurgical repigmentation therapies in vitiligo. Arch Dermatol 1998; 134(12):1532-40.
  5. Yones SS, Palmer RA, Garibaldinos TM et al. Randomized double-blind trial for treatment of vitiligo. Arch Dermatol 2007; 143(5):578-84.
  6. Gawkrodger DJ, Ormerod AD, Shaw L et al. Therapy Guidelines and Audit Subcommittee, British Association of Dermatologists, Clinical Standards Department, Royal College of Physicians of London, Cochrane Skin Group, Vitiligo Society. Guideline for the diagnosis and management of vitiligo. Br J Dermatol 2008; 159(5):1051-76. Available online at: http://www.guidelines.gov/. Last accessed June 3, 2013.
  7. American Academy of Dermatology.Vitiligo: Diagnosis, Treatment and Outcome. http://www.aad.org/skin-conditions/dermatology-a-to-z/vitiligo/diagnosis-treatment. Last accessed June 3, 2013.
  8. Blue Cross and Blue Shield Association. Light Therapy for Vitiligo. Medical Policy Reference Manual, Policy 2.01.86, 2012.
  9. El-Zawahry BM, Bassiouny DA, Sobhi RM et al. A comparative study on efficacy of UVA1 vs. narrow-band UVB phototherapy in the treatment of vitiligo. Photodermatol Photoimmunol Photomed 2012; 28(2):84-90.

Coding

Codes

Number

Description

CPT

96912

Photochemotherapy; psoralens, and ultraviolet A (PUVA)

 

96920

Laser treatment for inflammatory skin disease (psoriasis); total area less than 250 sq cm

 

96921

Laser treatment for inflammatory skin disease (psoriasis); 250 sq cm to 500 sq cm

 

96922

Laser treatment for inflammatory skin disease (psoriasis); over 500 sq cm

 

96999

Unlisted special dermatological service or procedure

ICD-9 Procedure

99.83

Other phototherapy (includes photochemotherapy)

ICD-9 Diagnosis

709.01

Vitiligo

ICD-10-CM
(effective 10/01/14)

L80

Vitiligo

ICD-10-PCS
(effective 10/01/14)

6A600ZZ; 6A601ZZ

Extracorporeal therapies, physiological systems, phototherapy skin, codes for single and multiple

Type of Service

DME

 

Place of Service

Inpatient
Outpatient

Physician’s Office

 

Appendix

N/A

History

Date

Reason

07/10/12

New policy, add to Medicine section. Policy content referencing vitiligo previously contained in 2.01.518 has been removed is now reflected within this policy. Treatment of vitiligo with PUVA or targeted phototherapy, previously considered cosmetic, may now be considered medically necessary. Approximate durations of treatment added to Policy Guidelines.

09/07/12

Update coding section – ICD-10 codes are now effective 10/01/14.

08/16/13

Replace policy. Policy updated with literature review. Reference added. No change to policy statement.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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