Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo

BACKGROUND: Recent advances in the pathophysiology of vitiligo have demonstrated defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may be involved in the regulation of melanin synthesis, and receptors for 1,25-dihydroxyvitamin D3 have been demonstrated on melanocytes. OBJECTIVES: We conducted an open study to determine the efficacy and tolerability of calcipotriol cream as monotherapy and in conjunction with psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. METHODS: Twenty-six patients with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and four were placed on combination treatment with twice-daily topical calcipotriol 50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly. RESULTS: Treatment was well tolerated at all sites and no adverse effects were reported. After a therapy time of 3-9 months (mean 6 months), 77% (17 of 22) of those treated with monotherapy showed 30-100% improvement, and three of the four patients on combination treatment showed good response. CONCLUSIONS: Topical calcipotriol appears to be an effective and well-tolerated treatment for vitiligo and can be safely used in conjunction with PUVA, but controlled studies are necessary to exclude the possibility of spontaneous repigmentation.     

Blue vitiligo following intralesional injection of psoralen combined with ultraviolet B radiation therapy

A 23‐year‐old Chinese man presented with a 16‐month history of white patches on his abdomen and neck. He had previously received an intralesional injection of psoralen along with narrowband psoralen ultraviolet B radiation (PUVB) therapy. Blue macules had appeared in and around the injection sites 1 week later. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches. Histological examination revealed an absence of epidermal melanocytes and pigment in the basal layer, as well as deposition of melanophages between collagen bundles or surrounding blood vessels and appendages in the middle and lower parts of the dermis. A diagnosis of blue vitiligo was made. The blue colour faded gradually over time. Our case provides direct evidence to support the previous surmise that PUVB can contribute to blue vitiligo. To our knowledge, this is only the fourth reported case of blue vitiligo in the English literature.     

Endothelin-1 is significantly elevated in plasma of patients with vitiligo treated with psoralen plus ultraviolet A

BACKGROUND: Recent evidence suggests that systemic psoralen plus ultraviolet A (PUVA) therapy may have a stimulatory effect on melanocytes, not only locally but also systemically. Aim. We aimed to assess endothelin-1 (ET-1), a potent melanocyte mitogen, in plasma of PUVA-treated paients with vitiligo. METHODS: ET-1 was sequentially assessed (using ELISA) in patients with nonsegmental vitiligo treated with PUVA (n = 20), at 8, 16 and 24 h following the PUVA session. Evaluations took place at 0, 1 and 3 months of therapy. Patients with psoriasis (n = 15) treated identically and healthy subjects not receiving any therapy (n = 15) served as controls. Vitiligo Area Scoring Index (VASI) and Psoriasis Area Severity Index (PASI) scores were simultaneously evaluated. RESULTS: ET-1 was significantly lower in vitiligo than in psoriasis at month 0 (8.2 +/- 3.6 vs. 13.7 +/- 5.4 pg/mL; P = 0.03) and it was significantly higher in both than in healthy controls at all time points of the PUVA sessions (P < 0.001). In vitiligo, it significantly increased at month 3 at 8 (8.2 +/- 3.6 vs. 10.8 +/- 2.7 pg/mL; P = 0.02) and 16 h (8.2 +/- 3.6 vs. 11.5 +/- 3.9 pg/mL; P < 0.01), whereas in psoriasis, it significantly decreased at month 3 at 8 (13.7 +/- 5.4 vs. 3.5 +/- 0.4 pg/mL; P < 0.01) and 16 h (13.7 +/- 5.4 vs. 6.3 +/- 4 pg/mL; P = 0.01). In contrast to psoriasis, sequential values of vitiligo revealed insignificant variance (P > 0.05). VASI score significantly decreased at month 3 (19 +/- 9.6 vs. 11.9 +/- 7.3; P < 0.01), whereas PASI score significantly decreased at months 1 (38.2 +/- 16.1 vs. 13.8 +/- 3; P < 0.05) and 3 (38.2 +/- 16.1 vs. 7 +/- 2.6; P = 0.03). There was a significant indirect correlation of ET-1 with VASI score (P < 0.01) and a significant direct correlation with PASI score (P < 0.01). CONCLUSION: Systemic PUVA therapy in vitiligo may have a generalized mitogenic effect on melanocytes through the release of ET-1 into the circulation.     

Effects of psoralen plus ultraviolet A irradiation on cultured epidermal cells in vitro and patients with vitiligo in vivo

BACKGROUND: Both psoralen plus ultraviolet (UV) A (PUVA) and narrowband UVB (NB-UVB) irradiation are effective treatments for vitiligo vulgaris. However, the mechanisms of PUVA and NB-UVB in repigmentation are not thoroughly clarified. Our previous results showed that NB-UVB irradiation directly promotes melanocyte (MC) migration and stimulates MC proliferation via keratinocytes (KCs). OBJECTIVES: In the present study, we used NB-UVB as a reference for comparison to investigate the immediate effects of PUVA on MC proliferation and migration. METHODS: Cultured MCs and KCs were treated with PUVA or irradiated with NB-UVB. The direct impact of PUVA treatment on MCs was assessed in terms of its effect on MC proliferation and migration. The indirect effect of PUVA treatment and NB-UVB irradiation on MC proliferation via KCs was also investigated. The activities of matrix metalloproteinase (MMP)-2 and MMP-9, known for their influence on cell migration, were evaluated in the PUVA-treated MC and KC supernatants. The concentrations of MC mitogens/growth factors in the PUVA-treated KC supernatants were also determined. In addition, the serum levels of MC mitogens/growth factors in healthy controls, in patients with active vitiligo and in patients with repigmenting vitiligo after PUVA treatment were determined to elucidate the mechanisms of how PUVA induces vitiligo repigmentation in vivo. RESULTS: Our results demonstrated that PUVA treatment did not significantly stimulate the release of MC mitogens/growth factors from KCs. The migration of MCs was also not enhanced after PUVA treatment. The expression of MMP-2 activity in supernatants derived from PUVA-treated MCs was significantly increased as compared with the control group. However, neither MMP-2 nor MMP-9 activity in KC supernatants was stimulated by PUVA treatment. In contrast to NB-UVB, immediate effects of PUVA on MC proliferation and migration were not observed in this study. Sera from patients with repigmenting vitiligo after PUVA treatment contained higher levels of basic fibroblast growth factor, stem cell factor and hepatocyte growth factor as compared with healthy controls and patients with active vitiligo. CONCLUSIONS: Our results indicate that in addition to immune suppression, PUVA treatment creates a favourable milieu for promoting the growth of MCs in patients with vitiligo instead of directly stimulating the regrowth of MCs. Based on our results, we propose that in the active stage of vitiligo, PUVA treatment is the therapy of choice to slow down the destruction of MCs and to create a favourable environment for MCs to survive. In the stable stage of vitiligo, NB-UVB irradiation should be used to stimulate the proliferation and migration of MCs directly.     

Eye protection for ultraviolet B phototherapy and psoralen ultraviolet A patients

Background/purpose: We tested eye protection used for phototherapy patients. The study also established current practice concerning eye protection in a sample of UK phototherapy units. Methods: The ultraviolet (UV) transmission spectra of 30 ‘UV protective’ contact lenses were measured at 5 nm intervals between 290 and 400 nm. Sunglasses, small UV goggles and UV visors were tested between 270 and 420 nm. We surveyed the use of eye protection during phototherapy in 78 UK phototherapy units. Results: All samples of sunglasses, eye protection goggles, visors and sunglasses comfortably passed previously published arbitrary limits of acceptability. Most contact lenses showed some protection in the UVB, but most had little or no UVA protection. Of 78 UK phototherapy units 21 (33%) use tinted goggles during UV exposures, two (3%) use a visor only, 28 (43%) use both and nine (14%) use clear plastic (probably polycarbonate) goggles. Conclusions: UV transmission for sunglasses and contact lenses is lower compared with samples tested 10 years ago. All samples of glasses, goggles and visors tested provided adequate protection in the UV range according to published arbitrary limits of acceptability. Most contact lenses did not provide significant UV protection in the UVA range.     

Cream psoralen plus ultraviolet A therapy for granuloma annulare

BACKGROUND: Treatment modalities for granuloma annulare (GA) often remain unsatisfactory or can be accompanied by potentially hazardous side-effects. Psoralen plus ultraviolet (UV) A (PUVA) bath photochemotherapy has been reported to be highly effective in the treatment of GA. Another form of topical PUVA therapy, using 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as bath PUVA therapy in the treatment of palmoplantar dermatoses. OBJECTIVES: To assess the efficacy of cream PUVA photochemotherapy in patients with GA. METHODS: Five patients with GA were treated. The diagnosis was confirmed by pretreatment skin biopsies. Cream PUVA therapy was performed four times a week: the mean number of treatments was 26 (range 17-40) and mean cumulative UVA dose was 55.9 J cm-2 (range 18.2-109.2). RESULTS: Cream PUVA photochemotherapy induced significant clinical improvement (one patient) or clearance (four patients) of GA in all patients. Clearance was documented clinically and histopathologically. CONCLUSIONS: Cream PUVA phototherapy can be highly effective in patients affected by localized forms of GA.     

Case of localized scleroderma successfully treated with bath psoralen and ultraviolet A therapy

The patient was a 12-year-old girl with linear scleroderma distributed on the right abdomen, dorsal aspect of the right thigh, lower leg and foot. The initial regimen of oral prednisolone and methotrexate, or i.v. methylprednisolone failed in the treatment of the scleroderma. Then bath psoralen and ultraviolet A therapy (bath-PUVA) therapy of 0.2 J–4.0 J/cm² daily to total doses 62.8 J/cm² combined with oral prednisolone was started. After bath-PUVA therapy, regression of the skin sclerosis was observed, the possible mobile range of the right ankle was increased and histological examination confirmed improvement of the sclerosis. The successful results of bath-PUVA therapy in this case suggest its utility for localized scleroderma.     

Flegel's disease treated with psoralen ultraviolet A

Flegel's disease is an uncommon condition which causes asymptomatic keratotic papules on the limbs. It usually develops in the fourth or fifth decade. Therapeutic options are limited to emollients, topical 5-fluorouracil and retinoids, but none of these treatments is consistently helpful. We report a patient with Flegel's disease who responded to psoralen ultraviolet A treatment.     

Amyloid deposition after psoriasis therapy with psoralen and long-wave ultraviolet light

Histologic examination of skin from 52 patients under continued treatment with methoxsalen and long-wave ultraviolet irradiation (PUVA) disclosed small superficial dermal deposits in six subjects who had completed one year of therapy and in six subjects who had completed two years of therapy. These deposits, by light and electron microscopic criteria, are similar to those of lichen amyloidosus. Amyloid deposition should be regarded as a possible complication of PUVA therapy.     

The use of Janus kinase inhibitors and narrowband ultraviolet B combination therapy in non-segmental vitiligo

Vitiligo is a depigmentation disorder of the skin that occurs secondary to the destruction of melanocytes by an immune-mediated process. Vitiligo clinically presents with depigmented macules and patches, most commonly on the face, acral sites, and genitalia. It can be characterized as generalized or localized based on distribution. The localized form can be further divided into segmental (linear, band-like, or Blaschkoid) and non-segmental vitiligo. The classical treatment of vitiligo includes topical steroids, pulsed oral steroids in unstable vitiligo, phototherapy, a combination of steroid therapy and phototherapy, surgical grafting, as well as intentional depigmentation therapy in severe cases. However, recent advances in understanding the immune mechanisms implicated in the pathogenesis of vitiligo have led to the use of an FDA-approved topical Janus kinase (JAK) inhibitors for vitiligo. Despite this novel therapy advancement, we recommend the addition of narrowband ultraviolet B (NB-UVB) to JAK inhibitors in patients with extensive and progressive lesions, or those not fully responsive to JAK inhibitor monotherapy.