JEADV
DOI: 10.1111/jdv.12762
ORIGINAL ARTICLE
Laser (755 nm) and cryotherapy as depigmentation treatments for vitiligo: a comparative study N. van Geel,* L. Depaepe, R. Speeckaert Department of Dermatology, Ghent University Hospital, Ghent, Belgium *Correspondence: N. van Geel. E-mail: [email protected]
Abstract Background Depigmentation therapy can be an option in adults with extensive and refractory vitiligo. Remaining pigmented patches can be removed using depigmentation creams (monobenzyl ether of hydroquinone 20%), laser therapy or cryotherapy. In contrast to cream treatment, laser therapy and cryotherapy are fast and targeted methods, capable of destroying melanocytes selectively on one specific area. Up till now, controlled trials comparing laser and cryotherapy as depigmenting treatment in vitiligo are lacking. Material and methods We performed a retrospective comparative study in 22 generalized vitiligo patients. Thirty-one pigmented test regions were exposed to cryotherapy and 20 to 755 nm laser therapy. The mean surface area per test region was 3.55 cm² and number of treatments per test region was limited to one single session in 84.3% and varied up to four sessions (2.0%). Results Overall no significant difference in the capacity to induce depigmentations was observed between cryotherapy (46.7%) and laser therapy (42.9%) after one treatment. The percentage of induced depigmentation was significantly different according to the body location (P = 0.005) with best results on the trunk, followed by the arms, face, neck and less on the hands. Variables that positively influenced depigmentation results were a younger age of vitiligo onset (P = 0.012), skin type V (P < 0.001) and clinical presence of Koebner’s phenomenon (P = 0.039). Despite initial failure after one treatment, repetitive treatment sessions on eight test areas resulted in successful depigmentation. Side-effects were restricted to cryotherapy and concerned mainly hyperpigmentation in the face. Conclusion To our knowledge, this is the first study comparing head-to-head depigmentation strategies intra- and inter-individually. We could demonstrate that in general laser and cryotherapy are equally effective in inducing depigmentations in generalized vitiligo patients. Retreatment of the same area may be required in case of initial failure. Received: 12 June 2014; Accepted: 5 September 2014
Conflicts of interest None.
Funding sources This research was supported by a research grant to N. van Geel from the Scientific Research Foundation-Flanders (FWO Senior Clinical Investigator: No. 1.8.315.12).
Introduction Vitiligo is a common acquired pigmentary disorder, affecting approximately 1% of the world population. The management of vitiligo is still often frustrating for both the patient and physician and the effect of vitiligo on the quality of life can be significant.1,2 The exact origin of vitiligo is unknown, although there is accumulating evidence for a major aetiologic role of melanocyte-specific cytotoxic T cells in progressive vitiligo.3 Perilesional T cells of vitiligo lesions have been shown to target melanocytedifferentiation antigens (e.g. Mart-1, Tyrosinase, gp100) and be able to efficiently eliminate melanocytes in a skin explant model.4 Increasing genetic evidence has been provided for
JEADV 2015, 29, 1121–1127
immune-based melanocyte elimination in vitiligo by genomewide association studies. Interestingly, several players in both the innate (e.g. NLRP-1, XBP-1), adaptive immune system (e.g. MHC, CTLA-4) and some melanocyte-specific genes (e.g. MC1R, region near TYR) have been found to be associated with vitiligo.5,6 Commonly used conventional treatments include phototherapy [narrowband ultraviolet B and psoralen with ultraviolet A (PUVA)], local steroids, calcipotriol and more recently topical immunomodulators (tacrolimus and pimecrolimus).2,7 Repigmentation occurs mostly in a perifollicular pattern.8 This reflects the melanocyte reservoir which is believed to be present around
© 2014 European Academy of Dermatology and Venereology
Geel et al.
1122
the hair follicle containing immature melanocytes and melanocyte stem cells.9,10 Another less important mechanism of repigmentation consists of remaining undestroyed lesional and perilesional melanocytes that repopulate vitiligo lesions.11 Nonetheless, in long-standing vitiligo this melanocyte reservoir may be exhausted, leading to an irreversible state of depigmentation. Therefore, in adult patients with extensive and refractory vitiligo, depigmentation therapy can be an option too.2,7 The presence of remaining pigmented areas can cause pronounced cosmetic disfigurements, especially when located on visible areas such as the face and the hands. Remaining pigmented patches can be removed using depigmentation creams (monobenzyl ether of hydroquinone 20%; MBEH), laser therapy or cryotherapy.7 Bleaching (MBEH) creams are worldwide the most used form of depigmentation therapy.12 Although MBEH may lead to a satisfying degree of depigmentation, it is debatable due to safety concerns, reported side-effects and long duration of treatment. Furthermore, treatment can fail or it can induce undesired depigmentations in non-treated areas. In contrast, laser therapy and cryotherapy are fast and targeted methods, capable of destroying melanocytes selectively on one specific area. Up till now, controlled trials comparing laser and cryotherapy as depigmenting treatment in vitiligo are lacking. The primary purpose of the current retrospective study was to compare the usefulness of 755 nm laser therapy and cryotherapy as depigmentation treatment in vitiligo inter- and intra-individually. The secondary aim was to investigate the influence of different clinical variables (e.g. body localization, body surface area (BSA) involvement, skin type, Koebner’s phenomenon) on treatment response and to evaluate possible side-effects of both techniques.
Hospital. Data collection was obtained from patients who underwent a trial session (test treatment) with cryotherapy and/ or 755 nm laser therapy on a small area of remaining pigmented skin between March 2008 and March 2014. All patients had recalcitrant extensive generalized vitiligo or cosmetic severely disfiguring vitiligo on visible areas such as the face and the hands. They were all seeking a depigmentation of remaining cosmetically disfiguring pigmented skin. Exclusion criteria were combination therapies (e.g. both techniques on the same area; combination of laser/cryotherapy with bleaching creams or any other topical treatment). General characteristics were retrieved from the patients’ medical file (age, gender, age of onset of vitiligo, disease activity, family history of vitiligo), personal and family history for autoimmune/autoinflammatory diseases (thyroid disease, diabetes mellitus type 1, alopecia areata, psoriasis, pernicious anaemia, rheumatoid arthritis, systemic lupus erythematosus and Addison’s disease). To estimate the total BSA involvement we used the flat palm of the hand as 1% rule (the palm of a hand including fingers equals 1% of the total body surface). To evaluate Koebner’s phenomenon (KP) we used the assessment and classification method as recently introduced by the Vitiligo European Task Force group.13 Evaluation was performed by the patient’s history [Koebner’s phenomenon type 1 (KP1)] and based on clinical examination [Koebner’s phenomenon type 2A/B (KP2A: lesions on friction areas, KP2B: linear, artefactual lesions)]. KP2A was assessed in all patients at the hip region. In addition a sub-grading system for KP2A and B (grading: +; ++; +++) was also used corresponding to the degree of presentation. If assessment was unreliable or not possible due to the extreme extent of the lesions this was recorded separately.
Methods
Set-up of the trial sessions
Subjects
This is a retrospective, monocentre comparative trial conducted at the department of Dermatology of the Ghent University
We used cryotherapy and Alexandrite (755 nm) laser therapy (Candela Alex TriVantage, Candela Corporation, Wayland, Massachusetts, USA) on 1 or 2 small test regions (e.g. 3–4 cm2) per body locations of interest. Cryotherapy was performed by
Figure 1 Cryotherapy was performed by gently rolling three times over the test area with a cotton tip which was dipped into liquid nitrogen.
JEADV 2015, 29, 1121–1127
© 2014 European Academy of Dermatology and Venereology
Depigmentation therapy vitiligo
gently rolling three times over the test area with a cotton tip which was dipped into liquid nitrogen (Fig. 1). Alexandrite laser treatment was carried out using a 3-mm spot size. Eight to 10 J/cm² was used according to the skin type of the patient (similar skin reaction were pursued). No specific after-care was used. In test areas with multiple treatments sessions, the same depigmentation method was used in each session. Clinical evaluation of the test regions was performed at baseline, and during the follow-up period. Photographs were taken using a digital camera (Nikon, Brussels, Belgium). Side-effects were recorded during each visit.
1123
Test areas
In total, 51 pigmented test regions were exposed to cryotherapy or 755 nm laser therapy. Cryotherapy was used on 31 and laser therapy on 20 test areas respectively. Characteristics of the test areas are summarized in Table 2. The amount of treatments per test region was limited to one single session in 84.3%, two sessions in 7.8%, three in 5.9% and four sessions in one patient (2.0%). Intra-individual comparison could be performed in 42 (82.4%) lesions, present in 16 (72.7%) patients. Treatment evaluation
Evaluation of depigmentation
Digital clinical pictures were used to evaluate the capacity to induce depigmentation and to assess the percentage of depigmentation per test area. Treatment results were subsequently classified according to a grading system from 0 to 6 (0 = no effect, 1 =
DOI: 10.1111/jdv.12762
ORIGINAL ARTICLE
Laser (755 nm) and cryotherapy as depigmentation treatments for vitiligo: a comparative study N. van Geel,* L. Depaepe, R. Speeckaert Department of Dermatology, Ghent University Hospital, Ghent, Belgium *Correspondence: N. van Geel. E-mail: [email protected]
Abstract Background Depigmentation therapy can be an option in adults with extensive and refractory vitiligo. Remaining pigmented patches can be removed using depigmentation creams (monobenzyl ether of hydroquinone 20%), laser therapy or cryotherapy. In contrast to cream treatment, laser therapy and cryotherapy are fast and targeted methods, capable of destroying melanocytes selectively on one specific area. Up till now, controlled trials comparing laser and cryotherapy as depigmenting treatment in vitiligo are lacking. Material and methods We performed a retrospective comparative study in 22 generalized vitiligo patients. Thirty-one pigmented test regions were exposed to cryotherapy and 20 to 755 nm laser therapy. The mean surface area per test region was 3.55 cm² and number of treatments per test region was limited to one single session in 84.3% and varied up to four sessions (2.0%). Results Overall no significant difference in the capacity to induce depigmentations was observed between cryotherapy (46.7%) and laser therapy (42.9%) after one treatment. The percentage of induced depigmentation was significantly different according to the body location (P = 0.005) with best results on the trunk, followed by the arms, face, neck and less on the hands. Variables that positively influenced depigmentation results were a younger age of vitiligo onset (P = 0.012), skin type V (P < 0.001) and clinical presence of Koebner’s phenomenon (P = 0.039). Despite initial failure after one treatment, repetitive treatment sessions on eight test areas resulted in successful depigmentation. Side-effects were restricted to cryotherapy and concerned mainly hyperpigmentation in the face. Conclusion To our knowledge, this is the first study comparing head-to-head depigmentation strategies intra- and inter-individually. We could demonstrate that in general laser and cryotherapy are equally effective in inducing depigmentations in generalized vitiligo patients. Retreatment of the same area may be required in case of initial failure. Received: 12 June 2014; Accepted: 5 September 2014
Conflicts of interest None.
Funding sources This research was supported by a research grant to N. van Geel from the Scientific Research Foundation-Flanders (FWO Senior Clinical Investigator: No. 1.8.315.12).
Introduction Vitiligo is a common acquired pigmentary disorder, affecting approximately 1% of the world population. The management of vitiligo is still often frustrating for both the patient and physician and the effect of vitiligo on the quality of life can be significant.1,2 The exact origin of vitiligo is unknown, although there is accumulating evidence for a major aetiologic role of melanocyte-specific cytotoxic T cells in progressive vitiligo.3 Perilesional T cells of vitiligo lesions have been shown to target melanocytedifferentiation antigens (e.g. Mart-1, Tyrosinase, gp100) and be able to efficiently eliminate melanocytes in a skin explant model.4 Increasing genetic evidence has been provided for
JEADV 2015, 29, 1121–1127
immune-based melanocyte elimination in vitiligo by genomewide association studies. Interestingly, several players in both the innate (e.g. NLRP-1, XBP-1), adaptive immune system (e.g. MHC, CTLA-4) and some melanocyte-specific genes (e.g. MC1R, region near TYR) have been found to be associated with vitiligo.5,6 Commonly used conventional treatments include phototherapy [narrowband ultraviolet B and psoralen with ultraviolet A (PUVA)], local steroids, calcipotriol and more recently topical immunomodulators (tacrolimus and pimecrolimus).2,7 Repigmentation occurs mostly in a perifollicular pattern.8 This reflects the melanocyte reservoir which is believed to be present around
© 2014 European Academy of Dermatology and Venereology
Geel et al.
1122
the hair follicle containing immature melanocytes and melanocyte stem cells.9,10 Another less important mechanism of repigmentation consists of remaining undestroyed lesional and perilesional melanocytes that repopulate vitiligo lesions.11 Nonetheless, in long-standing vitiligo this melanocyte reservoir may be exhausted, leading to an irreversible state of depigmentation. Therefore, in adult patients with extensive and refractory vitiligo, depigmentation therapy can be an option too.2,7 The presence of remaining pigmented areas can cause pronounced cosmetic disfigurements, especially when located on visible areas such as the face and the hands. Remaining pigmented patches can be removed using depigmentation creams (monobenzyl ether of hydroquinone 20%; MBEH), laser therapy or cryotherapy.7 Bleaching (MBEH) creams are worldwide the most used form of depigmentation therapy.12 Although MBEH may lead to a satisfying degree of depigmentation, it is debatable due to safety concerns, reported side-effects and long duration of treatment. Furthermore, treatment can fail or it can induce undesired depigmentations in non-treated areas. In contrast, laser therapy and cryotherapy are fast and targeted methods, capable of destroying melanocytes selectively on one specific area. Up till now, controlled trials comparing laser and cryotherapy as depigmenting treatment in vitiligo are lacking. The primary purpose of the current retrospective study was to compare the usefulness of 755 nm laser therapy and cryotherapy as depigmentation treatment in vitiligo inter- and intra-individually. The secondary aim was to investigate the influence of different clinical variables (e.g. body localization, body surface area (BSA) involvement, skin type, Koebner’s phenomenon) on treatment response and to evaluate possible side-effects of both techniques.
Hospital. Data collection was obtained from patients who underwent a trial session (test treatment) with cryotherapy and/ or 755 nm laser therapy on a small area of remaining pigmented skin between March 2008 and March 2014. All patients had recalcitrant extensive generalized vitiligo or cosmetic severely disfiguring vitiligo on visible areas such as the face and the hands. They were all seeking a depigmentation of remaining cosmetically disfiguring pigmented skin. Exclusion criteria were combination therapies (e.g. both techniques on the same area; combination of laser/cryotherapy with bleaching creams or any other topical treatment). General characteristics were retrieved from the patients’ medical file (age, gender, age of onset of vitiligo, disease activity, family history of vitiligo), personal and family history for autoimmune/autoinflammatory diseases (thyroid disease, diabetes mellitus type 1, alopecia areata, psoriasis, pernicious anaemia, rheumatoid arthritis, systemic lupus erythematosus and Addison’s disease). To estimate the total BSA involvement we used the flat palm of the hand as 1% rule (the palm of a hand including fingers equals 1% of the total body surface). To evaluate Koebner’s phenomenon (KP) we used the assessment and classification method as recently introduced by the Vitiligo European Task Force group.13 Evaluation was performed by the patient’s history [Koebner’s phenomenon type 1 (KP1)] and based on clinical examination [Koebner’s phenomenon type 2A/B (KP2A: lesions on friction areas, KP2B: linear, artefactual lesions)]. KP2A was assessed in all patients at the hip region. In addition a sub-grading system for KP2A and B (grading: +; ++; +++) was also used corresponding to the degree of presentation. If assessment was unreliable or not possible due to the extreme extent of the lesions this was recorded separately.
Methods
Set-up of the trial sessions
Subjects
This is a retrospective, monocentre comparative trial conducted at the department of Dermatology of the Ghent University
We used cryotherapy and Alexandrite (755 nm) laser therapy (Candela Alex TriVantage, Candela Corporation, Wayland, Massachusetts, USA) on 1 or 2 small test regions (e.g. 3–4 cm2) per body locations of interest. Cryotherapy was performed by
Figure 1 Cryotherapy was performed by gently rolling three times over the test area with a cotton tip which was dipped into liquid nitrogen.
JEADV 2015, 29, 1121–1127
© 2014 European Academy of Dermatology and Venereology
Depigmentation therapy vitiligo
gently rolling three times over the test area with a cotton tip which was dipped into liquid nitrogen (Fig. 1). Alexandrite laser treatment was carried out using a 3-mm spot size. Eight to 10 J/cm² was used according to the skin type of the patient (similar skin reaction were pursued). No specific after-care was used. In test areas with multiple treatments sessions, the same depigmentation method was used in each session. Clinical evaluation of the test regions was performed at baseline, and during the follow-up period. Photographs were taken using a digital camera (Nikon, Brussels, Belgium). Side-effects were recorded during each visit.
1123
Test areas
In total, 51 pigmented test regions were exposed to cryotherapy or 755 nm laser therapy. Cryotherapy was used on 31 and laser therapy on 20 test areas respectively. Characteristics of the test areas are summarized in Table 2. The amount of treatments per test region was limited to one single session in 84.3%, two sessions in 7.8%, three in 5.9% and four sessions in one patient (2.0%). Intra-individual comparison could be performed in 42 (82.4%) lesions, present in 16 (72.7%) patients. Treatment evaluation
Evaluation of depigmentation
Digital clinical pictures were used to evaluate the capacity to induce depigmentation and to assess the percentage of depigmentation per test area. Treatment results were subsequently classified according to a grading system from 0 to 6 (0 = no effect, 1 =
