VITILIGO

By Gary M. White, MD
Vitiligo


Vitiligo is a condition in which the skin loses all of its color in well-defined patches.

Age of Onset

Vitiligo may occur at any age, but onset from 10-30 is typical. Any patient over 40 years of age who develops what looks like vitiligo should have a complete skin examination to exclude melanoma (see melanoma-associated vitiligo). In children, halo nevi are often associated. Vitiligo may develop in children under 3 years of age and these patients tend to have more extensive and progressive disease [J Am Acad Dermatol. 2015 Sep;73(3):467].

Associations

Associated conditions include sensorineural hearing loss, congenital nevi, halo nevi, Graves disease, Hashimoto thyroiditis, autoimmune conditions (e.g., pernicious anemia), stem cell transplantation and a reduced risk of skin cancer.

Clinical

Vitiligo is characterized by sharply demarcated, completely white (depigmented) patches. They usually start small and expand. The acral areas and the face are commonly involved. In general, there are two clinical variants of vitiligo. The classic type is acquired in late childhood or adulthood and is symmetric. A less common variant is segmental vitiligo which tends to have its onset early in life and is asymmetric (often involving a dermatome).  Depigmentation in the mouth may occur (for a picture, see Indian J Dermatol 2015;60:103).

Active vs Stable Vitiligo

Stable vitiligo appears a completely depigmented patches with sharp borders. Active (spreading) vitiligo in contrast has less well defined borders comprised of hypo but not depigmented skin. Woods light helps in identification showing a marginal gray edging [JAAD 2017;76;856]. Trichrome, pentachrome and inflammatory raised border and confetti-like depigmentation are also variants of active (spreading) vitiligo. Confetti-like pigmentation is defined as the presence of numerous 1-5 mm depigmented macules in groups, usually at the borders of existing lesions and not predominantly in a follicular or perifollicular location [JAAD 2015;73;272]. Marginal or inflammatory vitiligo is defined as vitiligo with raised, inflammatory borders Dermatology Online Journal 21(3)).

Hypochromic Vitilgo

Hypochromic vitiligo is an uncommon variant of vitiligo that seems to be limited to individuals with dark skin types (V and VI) [Br J Dermatol. 2015;172:716-21]. Hypopigmented macules and patches in the seborrheic areas of the face and neck is most typical. The scalp and trunk may have lesions as well.

Precipitating Factors

Any chemical exposure to e.g. hydroquinones, catechols, phenols or mercaptoamines should be excluded (see chemical leukoderma). Patients with metastatic melanoma treated with pembrolizumab or interferon therapy [JAAD 1996;35;650] may develop vitiligo and in fact, this occurrence is associated with response to therapy. Vitiligo occuring in the radiation port of radiotherapy has been reported.

Differential Diagnosis

If the areas are completely depigmented, a postinflammatory hypopigmented process is excluded. However, a chemical leukoderma from exposure to hydroquinones, catechols, phenols or mercaptoamines may be indistinguishable from vitiligo. Every patient should be quizzed about potential exposure to depigmenting chemicals, e.g., chemicals at work, germicides, and pesticides. See chemical leukoderma.

Workup

Every patient should have a TSH, ANA and Vitamin D level measured. Several studies have found the following incidence: Vitamin D insufficiency 55%, thyroid disease 18.5%, and elevated ANA in 12.4% of patients with vitiligo.

Vitiligo Seems to Protect Against Skin Cancer

After adjusting for confounders, patients with vitiligo had a 3-5-fold lower probability of developing melanoma, BCC and SCC. However, treatment with UVB or PUVA negated this effect [JAAD 2014;71;1110].

Vitiligo and Congenital Nevi

In one study [BJD 2015;172;1052] congenital nevi (CMN) were present in 3.3% of patient's with vitiligo (non-segmental) vs only 1.0% of the control population. The presence of halo nevi was significantly higher and age of onset of vitiligo was significantly lower in the presence of CMN. Halo formation around the CMN, as observed in 30.3% of cases, was associated with a higher diameter of the CMN.

Halo Nevi

In one study of 208 children with vitiligo [Ped Derm 2016;33;44], 55 (26%) had at least one halo nevus. In that study, the presence of a halo nevus does not significantly alter the risk of disease progression or response to treatment.

Hearing and Vitiligo

Approximately 15% of patients with vitiligo have some sort of sensorineural hearing loss. Even in patients with normal hearing, bilateral cochlear dysfunction is common in both segmental and classic vitiligo [BJD 2015, 172: 406–411].

Treatment

Tacrolimus or a potent topical steroid are first-line therapy for vitiligo. In some situations the potent topical steroid has a slightly higher response rate, but the tacrolimus is safer as it does not cause skin atrophy.

Combination Therapy

In one review, narrowband UVB (NB-UVB) combined with a class I topical steroid gave the vast majority of patients at least 75% regimentation over 6 months [Dermatol There 2008;21: Suppl 1:S24]. To prevent against atrophy, it is recommended to alternate therapy with the topical steroid, e.g., clobetasol every other week with tacrolimus during the off weeks.

Tacrolimus

Tacrolimus is applied BID to involved areas for 2-3 months. If beneficial, therapy may continue for years. If no results are seen, switching to a potent topical steroid is recommended. Once repigmentation is achieved, twice weekly tacrolimus is effective at preventing relapse [J Invest Dermatol 2014 Dec 18].

Topical Steroids

Topical steroids may be tried for 2-4 months to see if repigmentation may be achieved. Care must be taken to assure that atrophy does not occur. However, limiting clobetasol use to 2 months at a time seems safe and effective. For example, facial vitiligo in children has been treated with clobetasol ointment BID for 2 months, then vaseline for 2 months, then clobetasol for 2 months. Fifty-eight percent responded with > 50% repigmentation. No atrophy was seen. Tacrolimus BID for 6 months had the same response rate of 58% for the face. On the body, however, clobetasol was more effective than tacrolimus, 39% vs 23%. [Br J Dermatol. 2011 Sep;165(3):626-32.]. Some recommend clobetasol every other week alternating with tacrolimus every other week.

Intralesional Steroids

Intralesional Kenalog worked extremely well in a study of 9 patients. Only one patient developed atrophy. Triamcinolone acetonide 3 mg/mL was injected every 0.5 cm. The treatment was repeated monthly with an average treatment duration of 4 months [JAAD Volume 71, Issue 2, Pages 391–393, August 2014].

Phototherapy

Narrowband UVB repigmented vitiligo by 43% (as measured by the VASI score) with 3/week treatments for 60 treatments total or 6 months--whichever came first.   Combining NB-UVB with topical steroids gives even better results (see Combination Therapy above). Home units can be very convenient for patients, increasing compliance.

PUVA and broad band UVA therapy are effective as well. In a study of PUVA vs. BB-UVA (15 mJ/cm2/session) [Clin and Exp Derm 2013;38;830], results were comparable.

High-Intensity Medium-Band (304-312 nm) Ultraviolet B

High-Intensity Medium-Band (304-312 nm) Ultraviolet B using the Dualight UV120-2 (Theralight, Carlsbad, CA) caused some repigmentation in 90% of patches and greater that 50% repigmentation in 54% of patches after a mean of 20 sessions [PD 2017;34;266].

Prostaglandin F2 Alpha Analogs

The prostaglandin F2 Alpha Analogs: Latanoprost (Xalatan), Bimatoprost (Latisse), and Tafluprost (Zioptan), are being investigated for use in vitiligo, especially the periocular variant [Int J Dermatol 2015;54:587-93]. They can be combined with NB-UVB. For glaucoma, these agents are applied once a day nightly. For vitiligo, once a day and twice a day application to the depigmented areas is being investigated.

JK Inhibitors

A 53-year-old woman with vitiligo was nearly cleared after 5 months treatment with tofacitinib, a Janus kinase inhibitor. The initial dose was 5 mg every other day, increased after 3 weeks to 5 mg/day. There were no side effects and laboratory monitoring was normal. This single case report is very encouraging. More studies are being anticipated. [JAMA Dermatol 2015;151;1110]. One patient experienced rapid skin repigmentation on oral ruxolitinib [JAAD 2016;74;370]. Topical ruxolitinib 1.5% cream BID provided a 23% improvement in mean VASI score in 11 patients with vitiligo [JAAD 2017;76;1054].

Afamelanotide

Afamelanotide is an implantable analog of alpha-melanocyte stimulating hormone that increases the efficacy of NB-UVB in the treatment of vitiligo. A multicenter, randomized trial involving 55 patients with vitiligo treated with afamelanotide and NB-UVB or NB-UVB alone found that regimentation at day 168 was 48.6% in the combination group compared with 33.2% in the monotherapy group [JAMA Dermatol. 2015 Jan;151(1):42-50.]. One concern however is that the drug can cause darkening of the skin, increasing the overall visibility of the vitiligo.

Mini Punch Grafting

Mini punch grafting for treating drug-resistant vitiligo stable for at least a year had about a 70% regimentation rate in one study [JAAD Apri 2014]. It may be done for segmental vitiligo as well.

Laser

Treatment of vitiligo with the 308-nm excimer laser showed good repigmentation in many patients with the best response occurring on the face and in newer lesions [JEADV 2017;31;337].

Photocil

Photocil cream filters out non-therapeutic wavelengths but allows therapeutic wavelengths with a peak at 308 nm to pass. It is applied to the affected areas with regular sunscreen elsewhere followed by sunlight 3 times a week. In one study, there was 48% repigmentation vs. 3% for placebo [Derm Therapy 2014;18;214].

Halting Rapid Progression

Oral methotrexate, oral steroids (e.g. in one study, dexamethasone pulse 4 mg Saturday and Sunday only for up to 8 weeks in adults. For children, 2 mg was used.) and IM steroids (e.g. kenalog 60 mg IM monthly x 3) have both been used to halt the progression of "unstable" vitiligo [Dermatology. 2015 Sep;231(3):286-90]. Pseudocatalase doesn't seem to be effective.

Minocycline 100 mg/day over say 6 months or longer has been used with benefit [Indian J Dermatol Venereol Leprol. 2014;80:29-35].

Complete Depigmentation

Topical monobenzyl ether of hydroquinone (monobenzone 20% cream) is an effective and safe treatment for depigmentation of extensive vitiligo in patients that desire permanent depigmentation [BJD 2015;172;1662]. It is usually applied as a 20% concentration once a day to areas where complete depigmentation is desired. Time to complete depigmentation was on average 10 months in the above study. Therapy is continued for years as repigmentation after the end of treatment occurs in most patients, with sun exposure being the most common trigger for repigmentation. Sunscreen use in the treated areas is therefore recommended.

Additional Pictures

Vitiligo Vitiligo Vitiligo Vitiligo

Vitiligo

Repigmentation often starts about the hair follicles.
Repigmentation in Vitiligo

Segmental Vitiligo Courtesy Michael O. Murphy, MD
Segmental Vitiligo

Squamous cell carcinoma in a patient with vitiligo. (Skin cancers are 3x less likely in patients with vitiligo)
Squamous cell carcinoma in a patient with vitiligo Squamous cell carcinoma in a patient with vitiligo

Vitiligo and psoriasis coexistant.
Vitiligo and psoriasis

Follicular vitiligo
Follicular Vitiligo

Trichrome Vitiligo
Trichrome Vitiligo

If you see confetti-like vitiligo on the upper body or face of an older adult, think of melanoma-associated vitiligo.
Melanoma associated vitiligo

References

Confetti-like vitiligo which has been reported as a sign heralding rapid progression. For a picture, see JAAD 2015;73;272.
Camouflaging Vitiligo. For a picture, see JAAD November 2014 Volume 71, Issue 5, Pages 935–940.

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