A cross-sectional analysis of skin cancer risk in patients receiving narrow-band ultraviolet B phototherapy: an evaluation of 100 patients.

Narrow-band ultraviolet B (NB-UVB) phototherapy is an effective and widely used treatment modality for psoriasis and other inflammatory skin diseases. The carcinogenic effect of PUVA treatment has been investigated extensively, but there is very scarce data about the role of NB-UVB in the development of skin cancer. The aim of this study was to investigate the potential carcinogenic risk of NB-UVB therapy in various skin disorders. In this cross-sectional study, we evaluated 100 patients who had received whole-body NB-UVB treatment and 100 age- and sex-matched controls. Phototherapy unit database was used to identify patients. A total of 100 patients (53 males and 47 females) treated with NB-UVB and 100 controls were included in the study. The patient group revealed no cases of melanoma or non-melanoma skin cancer, while ten of them were found to have solar lentigines. Basal cell carcinoma in a patient and nine patients with solar lentigines were detected in the control group. There was no statistically significant difference between patient and control groups in terms of skin cancer and solar lentigines. This study does not provide evidence for an increased skin cancer risk in patients treated with NB-UVB phototherapy. However, we have detected the occurence of 10 cases of solar lentigines. Still, definitive prospective longitudinal studies with a greater number of patients and prolonged follow-up are required to specifically address skin cancer risk in relation to NB-UVB phototherapy.

Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos.

To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

Efficacy and safety of intense pulsed light with a KTP filter for the treatment of solar lentigines.

BACKGROUND: Optical energy-based devices, including intense pulsed light (IPL) and potassium titanyl phosphate (KTP) lasers achieve reduction of pigmented and vascular lesions in a relatively similar number of treatments. This study aimed to evaluate the efficacy and safety of an IPL with a "KTP-like" filter emitting a wavelength of 525-585 nm for the treatment of solar lentigines on the hands and face. METHODS: This was a single center, prospective, open-label clinical trial including 16 healthy Caucasian subjects (15 females, mean age, 55 years; skin types II and III) with hand and facial solar lentigines. Subjects were treated with three IPL treatment sessions with a KTP-like filter conducted at monthly intervals. Follow-up evaluations were performed 1, 3, and 6 months after the last treatment session. Overall pigmentation improvement, pigmentation clearance per lesion, adverse events, and subject tolerability to treatment were evaluated. RESULTS: Significant improvements in facial and hand pigmentation were noted at all follow-up visits (P < 0.0001). One month after the last treatment session, good to excellent outcomes were noted in 74.6% of treated facial areas and 90% of treated hand regions. Although the effect of treatment gradually declined in both treatment regions over the 6-month follow-up period, over 60% of subjects demonstrated good to excellent results at the study end. Clinical effectiveness was further confirmed by the reduction in Melanin Index (MI) following each treatment as compared to baseline. Downtime and complications were minimal. CONCLUSIONS: IPL treatment with a KTP-like filter is a well-tolerated and effective method for reducing facial and hand pigmentation. Lasers Surg. Med. 51:500-508, 2019. © 2019 Wiley Periodicals, Inc.

Efficacy and Safety of Topical Pidobenzone 4% as Adjuvant Treatment for Solar Lentigines: Result of a Randomized, Controlled, Clinical Trial.

BACKGROUND/OBJECTIVE: This study aims at the evaluation of the efficacy and safety of a combination therapy based on pidobenzone 4% and fractional CO2 laser or cryotherapy in the treatment of solar lentigines and the prevention of eventual posttreatment hyperchromia. METHODS: Efficacy was clinically evaluated by grading the pigmentation level with the Skin Tone Color Scale (STCS), and by grading patients' impression through a Visual Analog Scale (VAS). RESULTS: Our study shows that the associated treatment was safe and that it improves the therapeutic results on solar lentigines and prevents postiatrogenic hyperpigmentation compared with physical therapy alone. CONCLUSION: The combination of cryotherapy and pidobenzone 4% has been found to be the most useful treatment.

Objective assessment of intensive targeted treatment for solar lentigines using intense pulsed light with wavelengths between 500 and 635 nm.

BACKGROUND AND OBJECTIVES: Solar lentigines are commonly found in sun-exposed areas of the body including hands, neck, or face. This study evaluates the efficacy of an intense pulsed light (IPL) device, with wavelengths between 500 and 635 nm and delivered with a targeted tip, for the treatment of solar lentigines on Japanese skin. STUDY DESIGN/MATERIALS AND METHODS: Forty Japanese patients with solar lentigines received one IPL treatment with a targeted treatment tip that emits wavelengths between 500 and 635 nm and contact cooling. Pulses were delivered through a targeted tip to each lentigo until mild swelling and a gray color were observed. Digital photographs and gray level histogram values were taken pre- and post-treatment, and patient assessments were recorded post-treatment. RESULTS: Significant improvement was observed for all patients in digital photographs and mean values of gray level histograms (P < 0.0001). Ninety percent of patients reported satisfaction with the improvement of the treatment area and convenience of the procedure. Complications were minor and transitory, consisting of a slight burning sensation and mild erythema which resolved within 5 hours of treatment. No serious adverse events were observed. CONCLUSIONS: A short-wavelength IPL, delivered with a targeted tip and contact cooling, offers a highly efficacious treatment for solar lentigines in Japanese skin with minimal downtime and complications.

Triple combination as adjuvant to cryotherapy in the treatment of solar lentigines: investigator-blinded, randomized clinical trial.

BACKGROUND: Post-inflammatory hyperpigmentation is a frequent concern when treating solar lentigines. OBJECTIVES: To assess the safety and efficacy of a triple combination cream with fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05% as adjuvant to cryotherapy in the treatment of solar lentigines in hands dorsum, and in the prevention of post-inflammatory hyperpigmentation after cryotherapy. METHODS: This prospective, randomized, controlled, investigator-blinded, single-centre study enrolled 50 patients. Twenty-five patients received a 2-week daily triple combination cream plus sunscreen pre-treatment and 25 received sunscreen alone. After that, cryotherapy was performed in all patients followed by a 3-week recovery period. After this period, patients received the same initial treatment and were followed up for 8 weeks. Melanin and erythema levels of a target and a control lentigo were objectively measured using a narrowband reflectance spectrophotometer. Lentigines count, colour homogeneity and global improvement were also assessed. RESULTS: The number of solar lentigines reduced in the first 2 weeks only in patients who used the triple combination 25 ± 7 vs. 22 ± 8 (P < 0.0001), and reduced at the end of the study for both groups (P < 0.0001). The melanin levels also reduced in the first 2 weeks only in patients who used the triple combination 297 ± 69 vs. 273 ± 66 (P < 0.0001) and reduced at the end of the study for both groups (P < 0.0001). Erythema and residual blisters from cryotherapy were the reported adverse reactions. CONCLUSION: Triple combination cream can be used to enhance the resolution of solar lentigines, and to significantly reduce melanin levels and lentigines count, improving treatment results. It was well-tolerated and did not increase the occurrence of neither erythema nor other side-effects after the cryotherapy.

Protective effect of red orange extract supplementation against UV-induced skin damages: photoaging and solar lentigines.

BACKGROUND: Exposure of the skin to solar ultraviolet (UV) radiations causes important oxidative damages that result in clinical and hystopathological changes, contributing to premature skin aging. Hyperpigmented lesions, also known as age spots, are one of the most visible alterations in skin photoaging. Skin is naturally equipped with antioxidant systems against UV-induced ROS generation; however, these antioxidant defenses are not completely efficient during exposure to sunlight. Oral antioxidants are able to counteract the harmful effects of UV radiation and to strengthen the physiological skin antioxidant defenses. AIMS: The present study was performed to evaluate the in vivo skin photo-protecting and anti-aging effects of a red orange (Citrus sinensis varieties Moro, Tarocco and Sanguinello) extract supplementation. Previous studies showed that red orange extracts possess strong in vitro free radical scavenging/antioxidant activity and photo-protective effects on human skin. MATERIALS/METHODS: The photo-protective effects of red orange extract intake against UV-induced skin erythema and melanin production in solar lentigo was evaluated on healthy volunteers by an objective instrumental method (reflectance spectrophotometry). RESULTS: Data obtained from in vivo studies showed that supplementation of red orange extract (100 mg/daily) for 15 days brought a significant reduction in the UV-induced skin erythema degree. Moreover, skin age spots pigmentation (melanin content) decreased from 27% to 7% when subjects were exposed to solar lamp during red orange extract supplementation. CONCLUSIONS: Red orange extract intake can strengthen physiological antioxidant skin defenses, protecting skin from the damaging processes involved in photo-aging and leading to an improvement in skin appearance and pigmentation.

Multiple lentigines in areas of resolving psoriatic plaques after ustekinumab therapy.

The development of lentigines in areas previously involved by psoriasis has been reported in the literature, classically related to phototherapy but also to topical products. More recently, some authors have described several cases of lentigines appearing in resolving psoriatic plaques during or after treatment with anti-tumour necrosis factor (TNF) drugs used to treat severe plaque psoriasis, including adalimumab, etanercept, and infliximab. We report the case of a patient that developed multiple lentigines after clearance of the plaques of psoriasis receiving treatment with ustekinumab for his psoriasis.

[Dermocosmetic management of hyperpigmentations]. / Prise en charge dermo-cosmétique des hyperpigmentations.

Hyperpigmentations are very frequent situations that can have considerable impact on the quality of life of affected individuals. However, even if the esthetic prejudice they generate is undeniable, lentigo and melasma are benign conditions that require above all a risk-free management. In addition to the dermatological procedures (peeling, laser, etc.) and the topical drugs available to the dermatologist, there remains significant room for depigmenting dermocosmetic products. These products succeeded to transpose features of the classic pharmaceutical formula invented by Kligman from which they were inspired to the field of dermocosmetics. They comprise activators of epidermal turn-over, skin exfoliants, and active ingredients that interfere with the different stages of melanogenesis, without having the side effects of hydroquinone whose usage remains limited to the field of prescription drugs. Antioxidants are a particularly interesting addition because they participate in reducing cutaneous inflammation and efficiently complete the action of the other components of a depigmenting formula. It is important to remind the aggravating role that sun exposure has on hyperpigmentations. Therefore, measures of rigorous photoprotection are mandatory. Medical makeup, transitory or definite, is an interesting option for the management of hyperpigmentations. Consequently, depigmenting dermocosmetics, used in monotherapy but - most frequently - in combination with dermatological procedures, can be used in literally all types of hyperpigmentations with an efficacy that is dependent on the specific etiology. They are suited to be part of a treatment program that has to be adapted on a case-by-case basis.

NB-UVB (311-312 nm)-induced lentigines in patients with mycosis fungoides: a new adverse effect of phototherapy.

BACKGROUND: Lentigines are a common pigmentary disorder in adults and in patients treated by psoralen and ultraviolet A (PUVA) radiation. Their appearance following treatment with narrow-band ultraviolet B (NB-UVB) radiation has been reported in only two patients. OBJECTIVE: To describe the clinical and histological features of NB-UVB-induced lentigines their relation to dosimetry and the course of the eruption in patients with mycosis fungoides (MF). METHODS: The files of all patients with MF treated in our department in 2003-2010 were searched to identify those in whom lentigines appeared following monotherapy with NB-UVB radiation. RESULTS: Of the 73 patients with early stage MF identified, 10 met the study criteria. Lentigines were detected in skin previously involved by MF in seven patients, and in both involved and uninvolved skin in three patients. They appeared during therapy in three patients, after a mean of 56 exposures (range 50-61), and several months (mean 7.8) following completion of treatment in seven patients, after a mean of 69 exposures (range 32-157). Histopathological study of lesions from five patients revealed basal hyperpigmentation relative to adjacent normal-looking skin. Two lesions had a slight increased number of normal-looking melanocytes on immunohistochemical staining with melanoma cocktail. One lesion had elongated rete ridges. The lesions persisted throughout follow-up (mean 26.7 months) in 8 patients. CONCLUSIONS: Patients with MF treated with NB-UVB may acquire lentigines. As opposed to PUVA-induced lentigines which are a known common side-effect of long-term treatment, NB-UVB-induced lentigines are uncommon but appear earlier, even after a few months of treatment.

Hyperbaric oxygen improves ultraviolet B irradiation-induced melanin pigmentation and diminishes senile spot size.

BACKGROUND: The effects of exposure to hyperbaric oxygen on ultraviolet B (UVB) irradiation-induced melanin pigmentations of skins and on senile spot sizes of faces were investigated. METHODS: In the first experiment, male subjects were irradiated with UVB on their upper arms for inducing erythema and the subsequent melanin pigmentation. They were exposed to a hyperbaric environment at 1.25 atmospheres absolute (ATA) with 32% oxygen for 1 h/day, three times per week. In the second experiment, female subjects were exposed to a hyperbaric environment at 1.25 ATA with 32% oxygen for 1 h/day, two times per week. RESULTS: In the first experiment, melanin pigmentations lightened after 4 weeks of exposure to hyperbaric oxygen. In the second experiment, senile spot sizes became small after 12 weeks of exposure to hyperbaric oxygen. CONCLUSION: We concluded that exposure to hyperbaric oxygen used in this study accelerates both the fading in melanin pigmentation and the decrease in senile spot size.

Q-switched alexandrite laser treatment of oral labial lentigines in Chinese subjects with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by gastrointestinal hamartomatous polyps and visible mucocutaneous lentigines distributed in the oral and anal mucosa, hands, face, and nails. Although there are many reports regarding successful treatment of intestinal polyps of PJS, there is little information regarding treatment of lentigines. Q-switched lasers are the preferred method of treatment for benign melanocytic lesions. OBJECTIVE: To evaluate the efficacy of the Q-switched alexandrite laser (QSAL) in treating oral labial lentigines of PJS. METHODS AND MATERIALS: Fourteen cases of laser treatment of oral labial lentigines in patients diagnosed with PJS were studied between 2005 and 2008. All were treated using a single treatment with a QSAL with a 3-mm handpiece and a fluence of 4.0 to 9.0 J/cm(2). Retrospective analysis of the effect of QSAL was conducted. RESULTS: All 14 cases exhibited successful elimination of treated lentigines after one laser treatment. There were significant acute side effects. After a median 2-year follow-up, there were no recurrences or scars in treated sites. CONCLUSIONS: The QSAL provides effective treatment for removal of labial lentigines associated with PJS.

Reduction of pain and side effects in the treatment of solar lentigines with pneumatic skin flattening (PSF).

BACKGROUND: Energy densities utilized in the treatment of pigmented lesions such as solar lentigines with intense pulsed light systems are often limited by pain and post-treatment erythema and edema. The sensation of pain associated with the treatment is immediate and acute. Application of topical anesthesia is time-consuming, with only very moderate pain relief. OBJECTIVE: (a) To test pain reduction as well as the reduction of post-treatment erythema and edema when using pneumatic skin flattening (PSF). This new technology utilizes an evacuation chamber to generate skin compression and activates tactile neural receptors in the skin. The result is an afferent inhibition of pain transmission in the dorsal horn (the 'gate theory'). (b) To test the efficacy of PSF. METHODS: Twenty patients were treated for solar lentigines. The patients were treated by three different IPLs. The evaluation of acute pain and post-treatment erythema and edema was performed on all 20 patients: one to three sites per patient treated with PSF and the same number of control sites without PSF. Identical energies and IPL were applied to both sites on each patient. The pain evaluation was performed on a 10-level scale modified McGill Pain Questionnaire. The clinical response to treatment was also evaluated. RESULTS: All 20 patients completed the study and preferred the PSF treatment side over the non-PSF side. Substantial pain reduction was observed in 19/20 patients (95%). The average reduction of pain was by two levels, from very painful to very mild pain. Erythema reductions were observed on 14/18 (77%) patients and edema reduction on 8/9 (88%) patients. Treatment efficacy on PSF sites was identical to that of non-PSF sites. CONCLUSION: The pneumatic skin flattening (PSF) technology considerably reduces pain, erythema and edema in the treatment of solar lentigines by IPLs. Treatment efficacy is preserved. The enhanced safety of PSF enables the increase of energy density and the acceleration of results.

Case reports: clearance of lentigines in Japanese men with the long-pulsed alexandrite laser.

Benign pigmented lesions can be effectively treated with multiple modalities including lasers. The treatment of pigmented lesions in phototype IV skin is more complicated and challenging given the risk of pigmentation changes and scarring. We present the novel use of the long-pulsed Alexandrite 755 nm laser for the treatment of solar lentigines in sun-reactive phototype IV skin of patients of Japanese decent. Our Japanese patients cleared with one treatment with no pigmentary changes or scarring. No recurrences were noted to date. The long-pulsed Alexandrite 755-nm laser is a novel, safe, and effective treatment of solar lentigines in Japanese patients.

[Consensus document on bath-PUVA therapy. The Spanish Photobiology Group of the Spanish Academy of Dermatology and Venereology]. / Documento de consenso sobre la modalidad terapéutica del baño-PUVA. Grupo Español de Fotobiología de la Academia Española de Dermatología and Venereología.

Bath PUVA is a variant of phototherapy as efficacious as oral PUVA therapy that avoids many of the adverse effects associated to this treatment. Nevertheless, the special features and the specialized equipment required for its employment have limited its application in the dermatologic clinics of our country. Following the trend initiated after the publication of the consensus document on oral PUVA therapy and narrow band (NB) UVB therapy, the Spanish Photobiology Group from the Spanish Academy of Dermatology and Venereology has developed a therapeutic guideline for bath PUVA therapy based on the literature review and the experience of its members. The document aims to be a practical reference guide for those dermatological centres that include phototherapy among their services. It reviews the concept and indications of this type of treatment and proposes recommendations concerning therapeutic procedures, drug associations of interest and prophylaxis and management of adverse effects.

Objective evaluation of the effect of intense pulsed light on rosacea and solar lentigines by spectrophotometric analysis of skin color.

BACKGROUND: To date, intense pulsed light (IPL) has been applied to various skin diseases, but there have been few objective evaluations of its efficacy. OBJECTIVE: The aim of this study was to perform objective evaluations of the effect of the IPL system on rosacea and solar lentigines. METHODS: Twelve patients with rosacea were treated with IPL at the wavelength of 550 to 670 nm, three times every 4 weeks, and the skin color was determined with L(*)a(*)b(*) color space using a spectrophotometer. In addition, 18 patients with solar lentigines were treated once, and the lightness L(*) was determined. RESULTS In all of 6 erythematotelangiectatic rosacea patients and in 5 of 6 papulopustular rosacea patients, each of the L(*)a(*)b(*) values of the posttreated lesions approached those of normal skin areas (efficacy rate, 91.6%). The mean level of the L(*)a(*)b(*) values improved significantly after treatment and particularly in the erythematotelangiectatic rosacea patients. In 12 of 18 patients with solar lentigines, the lightness L(*) was elevated after treatment (efficacy rate, 66.6%). CONCLUSION: As demonstrated by spectrophotometric analysis of skin color, IPL at the wavelength of 550 to 670 nm is effective for rosacea and solar lentigines, particularly most useful for erythematotelangiectatic rosacea.