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Keywords:

  • laser therapy;
  • optical diagnostics;
  • phototherapy;
  • skin of color

Abstract

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

Background/purpose: Patients with skin of color present unique challenges and opportunities for dermatologists in their disease states as well as their response to treatment. There are differences in dosing for patients with skin of color using standard phototherapeutic approaches as well as unique disease states that may respond to newer phototherapeutic options. Lastly, there are optical diagnostic options that allow investigators to differentiate erythema and pigmentation in a quantitative manner for clinical research purposes.

Methods: Review of the current literature with regard to vitiligo, hidradenitis suppurativa and optical diagnostic methods.

Conclusions: Practitioners need to be aware of the various phototherapy and laser therapy options for patients with skin of color. New discoveries for the use of visible light as a form of treatment are on the horizon, and optical diagnostic techniques such as diffuse reflectance spectroscopy and colorimetry may add value clinically and within the research realm as objective measures of pigmentation and erythema.

One of the most well-known classification schemes in dermatology, the Fitzpatrick skin phototype, is often used to categorize the pigmentation of skin. The focus of this scheme considers the ability of the skin to tan and its propensity for sunburn. While this differentiates darkly pigmented skin (also called ‘skin of color’) from skin of lighter pigmentation, it only scratches the surface of the various dermatologic challenges associated with skin of color. There are a unique set of disease states present in patients with skin of color that may be very uncommon or of limited impact for other patients of lighter skin types, and it is important for dermatologists to have a thorough understanding of these diseases so that they are not overlooked among the patient population.

In this article, we will overview some of the dermatological disorders associated with skin of color that we see in our institution and provide a review of the laser and phototherapy options for these conditions. We will also discuss the use of optical diagnostics as a new tool in diagnosing and managing diseases in skin of color.

Vitiligo

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

Vitiligo is perhaps one of the most disfiguring conditions and is an area of significant concern for patients of color. It is caused by the destruction of melanocytes through a currently unknown mechanism but likely to be immune based, which leads to hypopigmented and depigmented macules and patches. It affects approximately 1% of the population of the United States, with varying rates worldwide (1).

Phototherapy options

Phototherapy options for vitiligo typically involve some form of ultraviolet radiation. Psoralen plus ultraviolet A (PUVA) has been a mainstay in the treatment of vitiligo for many decades (2). Narrow band ultraviolet B (NBUVB) was first used in the treatment of vitiligo in 1997 (3), and has been shown to be an effective treatment in recent years (4–8). NBUVB has been shown to improve pigmentation more effectively than PUVA. Both treatments are ineffective on the hands and feet (2). Yones and colleagues published similar findings in a randomized double-blind trial of 50 patients, which showed a >50% improvement in repigmentation for 64% of the patients receiving NBUVB. In comparison, only 36% of the patients receiving PUVA showed >50% improvement. In addition, the repigmented areas in the patients receiving PUVA were a poor color match to unaffected skin (9).

As with any treatment, NBUVB has its share of adverse side effects but for the most part has been shown to be a safe modality. The most acute of these is phototoxicity from the ultraviolet radiation. Transient hyperpigmentation has also been noted (10). One possible consideration may be an increased chance for non-melanoma skin cancer (NMSC) in Fitzpatrick skin types I and II in patients with vitiligo. This is likely independent of artificial UV radiation exposure. In 2009, a retrospective review of 477 vitiligo patients determined that there was a non-statistically significant increased risk of NMSC among vitiligo patients when compared with the US average (11). All patients were baseline Type I or II skin and none had received UV phototherapy for their vitiligo. However, no skin cancers were reported in vitiligo patients with darker pigmented skin. This observation is unusual, given the assumption that the lack of pigment would increase the risk of skin cancer as it does in albinism (12).

Another phototherapy modality available for vitiligo is the excimer laser, a monochromatic 308 nm high-intensity light source. It has been shown in multiple studies to be an effective treatment for vitiligo, with a faster repigmentation rate, and less incident irradiation to unaffected areas (13–15) than NBUVB. The excimer laser has been shown in studies to cause quicker and more thorough repigmentation than NBUVB (16,17). Neither study, however, used a validated scoring method, nor were body locations of the affected regions considered. As stated earlier, the hands and feet tend not to respond while the face has a much better response.

Newer, more objective measures of repigmentation can facilitate clinical study validation. In 2004, Hamzavi et al. (8) published a study on the effectiveness of NBUVB in treating vitiligo using a novel quantitative metric, the Vitiligo Area Scoring Index, or VASI. The VASI uses the surface of the palm to approximate 1% of the body's surface area, and then determines the degree of depigmentation (or repigmentation after treatment) within each ‘hand unit’ of vitiligo on the body. This allowed the total pigmentation level of the affected areas to be determined in a quantitative and parametric manner. This would allow for the reporting of the degree of response for the average patient. This is much more intuitive than the non-parametric system, which only allows one to stipulate the degree of repigmentation in a subgroup of a population. For example, the VASI score stated the average degree of repigmentation to be 43% in areas receiving NBUVB as compared with an average repigmentation rate of 3% at the control sites (8). Meanwhile, the non-parametric system used by Yones et al. (9) stated that 64% of patients achieved >50% repigmentation, which is much more difficult to interpret for most patients and physicians.

Prognostic factors

The clinical subtype of vitiligo has a substantial impact on the prognosis of the condition. According to a retrospective study in 2007, patients with skin phototypes III–V gain more benefit when using NBUVB for the treatment of vitiligo than those with less pigmented skin. In addition, facial lesions (excluding perioral) show the best response to treatment, and the outcomes are improved in patients who respond within the first month of treatment (18). Although there are no prospective studies that confirm these findings, the author's clinical experience is aligned with the authors of this report.

When dosing the treatment regimen for vitiligo, it is important to take into consideration the dynamics of each patient's response. In addition to pigmentation, the effect of photoadaptation may also need to be taken into account. Photoadaptation refers to the phenomenon in which higher doses of radiation are required to cause a similar effect within the skin. In a study in 2007, Rivard et al. (19) describe a method of measuring the amount of photoadaptation that takes place within individuals undergoing phototherapy for vitiligo. The minimal erythema dose (MED) was measured on the individuals before and after treatment. In approximately two-thirds of the patients, the MED after treatment was higher than before, indicating that photoadaptation had taken place. The remaining one-third of the study participants either showed very little change in MED or showed a decrease in the MED after treatment (19). In a follow-up study, Hexsel et al. (20) reported very similar findings, with two-thirds of the patients showing photoadaptive patterns. In addition, the authors investigated the rate of DNA damage due to UVB radiation by measuring changes in the levels of cyclobutane pyrimidine dimers (CPDs) in normal skin vs. vitiliginous skin. The number of CPDs per megabase was approximately 40% higher in vitiliginous skin both at baseline and at 24 h post-exposure. In contrast, the rate of DNA repair, measured as the mean percent of CPDs cleared after 24 h, was equivalent in both vitiliginous and normal skin (20). The conclusions from this study were that alternate-day dosing is safest and that patients who do not photoadapt are likely poor candidates for phototherapy.

Adjuvant therapy

There are a number of adjuvant therapies that have been shown to have good results when used in combination with phototherapy. Most of these are small uncontrolled studies, but they can shed some light on future treatment options. The use of the 5-fluorouracil with an erbium:YAG laser has been shown to be effective in treating periungal vitiligo, which is resistant to most phototherapy options (21). Tacrolimus, an immunomodulator, has been shown to have superior results when used with an excimer laser than the laser alone, when used on UV-resistant areas such as the bony prominences and extremities (22). Recalcitrant vitiligo on the face has been noted to respond to an excimer laser when it is paired with hydrocortisone butyrate (23). There is also evidence for the role of topical antioxidants in vitiligo therapy. A randomized, double-blind trial of betamethasone and catalase/dismutase superoxide (C/DSO) showed that C/DSO showed comparable results as betamethasone when used on vitiligo lesions (24).

Calcipotriene, a synthetic analog of 1,25-dihydroxyvitamin D3, also has potential for adjuvant therapy in vitiligo. A study in 2004 showed increased pigmentation when using calcipotriene in combination with NB-UVB (25). A similar study from Turkey, however, showed no statistically significant improvement when using calcipotriene with NB-UVB (26). Larger studies are needed to be more certain of its effects.

Summary

In order for phototherapy to be successful, many different factors must be taken into consideration. Patients should have stable vitiligo, without recent progression of their disease. Phototherapy options show better results in certain sites, such as the neck, trunk, face, and limbs; acral vitiligo is less likely to respond to treatment. When considering photoadaptation, it may be impossible to know whether a patient is a photoadapter before starting treatment. However, it should become clear as therapy progresses. Patients must be able to commit to a minimum of 1 month of treatment, as most phototherapy regimens require 1 month to show results for minimal repigmentation. NB-UVB has been shown in many studies to have good results, with favorable color match and duration. The excimer laser yields similar results, although it has been shown to respond quicker than NB-UVB. Adjuvant therapy should not be used as a first-line therapy; rather, if no change has occurred within 6 weeks of monotherapy, adjuvant treatments may be considered. It may take several iterations to determine what combination works best for each patient.

Hidradenitis suppurativa (HS)

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

Follicular disorders, such as pseudofolliculitis barbae and dissecting cellulitis, are also associated with skin of color (27,28). Within this group, HS is one of the most disfiguring and agonizing. HS is a disease found in the intertriginous areas of the body, such as the axilla, groin, and inframammary regions. It is a chronic, recurrent condition in which painful nodules and abscesses form on the skin and may later progress to fistulae and severe scarring. The pathogenesis is thought to involve inflammation around hair follicles, which leads to comedogenesis. The increased inflammation and comedone eventually causes a rupture of the follicular infundibulum, which leads to an inflammatory nodule. These develop into abscesses when inflamed and eventually to sinus tracts and scarring (29–33).

Treatment options

Because of the clinical appearance of HS, topical and systemic antibiotics are used in its treatment. However, cultures rarely show a relevant organism. Most antibiotics have been shown to only have a mild to moderate effect, and recurrence often occurs once treatment has been completed (34,35). Other systemic agents, such as immunosuppressive agents (36–39), oral retinoids (40), and hormonal therapies (41–44), have all been used to treat HS with varying success. None of these treatments, however, help to alleviate the condition to a sufficient degree once sinus tracts and scarring have taken place. In those situations, surgery is the standard of care. However, the long recovery time, risk for subsequent infection, and recurrence rates make surgery a less attractive option (45–50).

Energy-based/phototherapy options

Energy-based devices are also an option for HS. Most of these studies are case reports but have led to better controlled studies. Non-ablative radiofrequency devices have been shown to cause dermal and subcutaneous heating, which lead to some relief of the condition (51). A 1450 nm diode laser can improve HS after four treatments, but causes minimal changes to areas of scarring and sinus tracts (52). Photodynamic therapy in conjunction with aminolevulinic acid has been noted to show clearance of 75–100% of patients (53). CO2 laser stripping with healing through secondary intention has been shown to be an effective alternative to surgery in removing chronic lesions, with a low recurrence rate (54).

One of the newer treatment modalities for HS is the long-pulsed Nd:YAG laser, which has been used in the past for hair removal. The justification for the use of this laser in this condition is based on a report that showed good results in the treatment of dissecting cellulitis (55). In 2009, Tierney et al. (56) published a randomized-controlled trial for the use of the long-pulsed Nd:YAG laser in the treatment of moderate to severe HS (Hurley stages II–III). Patients were given topical antibiotics on one half of their body (control), and treated with a 1064 nm long-pulsed Nd:YAG laser plus topical antibiotics on the treated side. The Hidradenitis Suppurativa Lesion, Area and Severity Index (HS-LASI) (29), was used to quantitatively determine the extent to which the lesions changed after treatment. After 3 months of treatment, the severity of HS decreased by 65.3%, averaged over all treated anatomic sites, as compared with a decrease of 7.5% for control sites (56) (Figs 1 and 2).

image

Figure 1.  Left inguinal area of a patient with hidradenitis suppurativa before treatment.

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Figure 2.  Left inguinal area of the same patient after treatment with an Nd:YAG laser.

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Visible light

Ultraviolet light has been a mainstay in dermatological therapy for several decades. The effect of UV light on pigmentation and inflammatory disorders is well known. UV light, however, is not the only type of radiation that can cause a reaction within the skin. Apart from laser radiation, which is a particularly strong form of visible light radiation limited to a specific wavelength, broadband visible light has been shown to have an effect on the pigmentation of the skin. The degree of the effect appears to be influenced by the baseline pigment of the subject and thus the present literature, which is tilted toward studies with lighter skinned patients, may not be able to identify the impact of visible light upon pigmentation. In a recent study, 40 min of broadband visible light (at doses of 160, 320, and 480 J/cm2) led to immediate pigment darkening (Fig. 3). It was also shown to cause an increase in oxyhemoglobin, clinically apparent as erythema. The oxyhemoglobin level (and, subsequently, the erythema level) increased as the dose increased, but diminished over time eventually (weeks) regardless of the dose. There were no apparent long-term effects from the light treatments (57).

image

Figure 3.  From left to right: pigmentation from visible light at doses of 480, 320, and 160 J/cm2.

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Determining the effect of visible light on the skin through the use of spectroscopic analysis allows for a better understanding of how the skin changes due to exposure to sunlight, which contains both visible and ultraviolet light. In addition, this opens up more potential for the use of visible light as a therapeutic tool for the treatment of skin disease.

Optical diagnostics

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

In addition to using light as a treatment modality, photobiology can use light to study the skin and obtain detailed information about the clinical course of a disease. This is accomplished by augmenting the visual exam with a number of different modalities. Polarized light photography uses filters to either block or allow reflected light from the surface of skin (58). This can help to elucidate surface features such as texture, elevation, and scaling from tissue characteristics such as telengiectasias, pigmentary changes, and inflammation (59).

Diffuse reflectance spectroscopy works by measuring the frequency spectrum of reflected light from the skin. It uses a light source coupled with a spectrometer to compare the reflected light to the absorption spectrum of known chromophores and thus determine a quantitative measure of the substances within the skin (Figs 4 and 5). Measurement of the amount of melanin and oxyhemoglobin, for example, can be performed to determine pigmentation and erythema levels, respectively (60,61).

image

Figure 4.  Diffuse reflectance spectroscopy setup, from left to right: laptop, spectrometer with a calibration plate, halogen light source, and probe.

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Figure 5.  Using the DRS probe on the back of a patient's neck.

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Colorimetry also uses spectroscopy, but uses specific wavelength filters on the reflected light to quantify the color of skin using the Commision International d'Eclairage (CIE) Lab color system (Figs 6 and 7). This system attempts to represent colors in a similar fashion as the human eye perceives color; the colors are quantified based on their lightness value (L*), amount of green or red (a*), and amount of blue or yellow (b*). Colorimetry offers an indirect measure of erythema as a change in the a* component within the CIE-Lab color system. Hence, colorimetry is useful in measuring conditions that are related to dermal blood content, such as port wine stains (62). In addition, pigmentary disorders can be more quantitatively analyzed; the L* and b* values have been found to correlate well with the skin color (63). Thus, objective measurement of the skin tone is possible in pigmentary disorders such as vitiligo (64).

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Figure 6.  Colorimetry setup, from left to right: laptop and Konica–Minolta colorimeter.

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Figure 7.  Using the colorimeter on the back of a patient's neck.

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The reliability and reproducibility of the measurements from these instruments provide an advantage over traditional methods of visual inspection and description. The limitations of qualitative analysis of pigmentation and erythema can be overcome using these techniques, and results from previous studies may be validated in a much more effective fashion. One direct benefit of this method was shown in the visible light studies, where the investigator noted that the effects of pigmentation were actually found to be due to erythema in UVA1-irradiated sites while actual increased melanin was found to be the cause in sites irradiated with visible light (57). This technique is also commonly used to quantify pigment due to conditions such as melasma (65).

Conclusion

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

Skin of color represents a unique set of challenges for the dermatologist, not just in the varied conditions that skin of color is associated with, but also in the treatment choices that are available for use. Many current treatments are not indicated for patients with darker skin pigmentation, or cause unwanted effects, such as hypo- or hyperpigmentation. Photomedicine has much to offer for patients with skin of color, and practitioners should be cognizant of the new treatment options as well as diagnostic and investigative tools being studied.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References

Disclosures: Unrestricted grant from Johnson and Johnson Consumer Companies Skillman, NJ, USA, The Livingood Fund and The Shahani Fund. Dr. Hamzavi is a principal investigator for studies funded by Dow Pharmaceuticals, Abbott, Pfizer and Cipher, as well as a consultant for Kythera.

References

  1. Top of page
  2. Abstract
  3. Vitiligo
  4. Hidradenitis suppurativa (HS)
  5. Optical diagnostics
  6. Conclusion
  7. Acknowledgements
  8. References