Postinflammatory Hyperpigmentation Following Mohs Micrographic Surgery: An Observational Study.

IMPORTANCE: Functional and cosmetic outcomes following Mohs micrographic surgery (MMS) are poorly studied in individuals with skin of color (SOC). Postinflammatory hyperpigmentation (PIH) may be long-lasting and highly distressing. SOC individuals are particularly susceptible to PIH following procedures.  Objective: To characterize factors that contribute to the development of PIH following MMS in SOC. DESIGN: This retrospective study included 72 SOC individuals with 83 cases of keratinocyte carcinoma treated with MMS between August 2020 and August 2021 at a single medical center in the Bronx, New York. RESULTS: Postinflammatory hyperpigmentation following Mohs micrographic surgery was more common in Fitzpatrick skin types (FST) IV to V (48.0%) compared to FST I to III (18.2%; P=0.006). Grafts and granulation resulted in higher rates of PIH compared to linear repairs and flaps (87.5% vs 30.7%; P=0.003). Cases with postoperative complications resulted in higher rates of PIH compared to cases without (81.8% vs 29.2%; P=0.001). In a subset analysis of linear repairs, polyglactin 910 as a subcutaneous suture produced a higher rate of PIH compared to poliglecaprone 25 (46.2% vs 7.1%; P=0.015).  Conclusions and Relevance: Individuals with SOC (FST IV to V) are more likely to develop PIH following MMS. Grafts and granulation lead to PIH more often than linear repairs and flaps. Postoperative complications significantly increase the risk of PIH. Surgeons should consider these risk factors during surgical planning in an effort to mitigate PIH in SOC individuals. Studies with larger sample sizes are indicated.  J Drugs Dermatol. 2024;23(5):316-321. doi:10.36849/JDD.8146.

[Inflammatory dermatoses in skin of color]. / Entzündliche Dermatosen auf pigmentierter Haut.

Acne, rosacea, atopic dermatitis, and psoriasis vulgaris are common inflammatory dermatoses. Of note, the epidemiology and clinical presentation of these common dermatologic diseases varies considerably between people with different colors of skin. Yet, most dermatology textbooks present and describe the clinical pictures of White people. To provide excellent dermatological care for all patients, it is of central importance to know the epidemiology and recognize key clinical characteristics of these diseases in patients with skin of color (SOC). In acne, cultural habits of Blacks (use of steroid-based lighteners, comedogenic hair care products) may lead to manifestation of specific forms of acne. In addition, postinflammatory hyperpigmentation and keloids pose particular therapeutic challenges in this patient group. Atopic dermatitis in Asians shows a clinical and histological picture that is similar to psoriasis in Whites. By contrast, atopic dermatitis manifests on the extensor side in Black people. Due to the difficulty of recognizing erythema in SOC, the severity of the respective inflammatory diseases in these individuals is often underestimated. The treatment of acne, rosacea, atopic dermatitis, and psoriasis does not differ between people of different skin colors. The exception is the necessary therapy for postinflammatory hyperpigmentation in all the inflammatory dermatoses mentioned, and for keloids in acne.

Facial skin characteristics and concerns in Indonesia: A cross-sectional observational study.

BACKGROUND: Facial skin characteristics and appearance vary according to ethnicity. While much of this knowledge is derived from the Caucasian population, lately there have been efforts to gain such understanding in various regions in Asia.  In this paper, we have built an understanding of such features in Indonesia. In Indonesia, a section of females wears a traditional veil (hijab) to cover the scalp and part of face. The influence of the hijab on facial skin attributes was also investigated. METHODS: In a cross-sectional observational study design involving 419 female volunteers in Jakarta, Indonesia, facial skin attributes (colour, radiance, hydration, trans-epidermal water loss [TEWL], wrinkles, fine lines, pores, and sebum levels) and conditions (melasma, post-inflammatory hyperpigmentation (PIH), solar lentigines/ senile lentigines, seborrheic keratoses and acne) were assessed by trained operators and dermatologists using standard validated instruments and scales. RESULTS: With age, facial skin colour showed darkening in cheek; forehead on the other hand showed slight lightening. The skin evenness and radiance decreased, substantially. Aging attributes measured in terms of lines, wrinkles, and under-eye dark circles showed deterioration with age; the decline was progressively faster than colour change. Facial image data analysis corroborated these findings. Skin hydration remained similar across the age groups even though the skin barrier function measured in terms of TEWL improved with age. Sebum levels in the skin were similar up to the age of 50 but declined in the next group of 50-60 year. Pore severity increased with age. Melasma, seborrheic keratosis and PIH showed a high prevalence (>∼50%) at the young age group (20-30 years), itself. Melasma prevalence attained 100% in the age group of 41-50 year and onwards, and its severity similarly showed a steady rise with age. PIH on the other hand showed a steady decline with age. Solar lentigines prevalence (∼30%) did not change much across age groups, and the severity scores were similar in age groups up to 50 year but increased substantially in 51-60-year age groups. Seborrheic keratosis was similar (∼47%) in age groups up 20-40 year but steadily increased in upper age groups. Its severity was similar in the age groups of 20-30 year and 31-40 year but showed a two-fold increase in subsequent age groups. Acne was 10% in the age group of 20-30 year and declined gradually to 0.7% in the 51-60-year age group. Hijab wearers showed slight protection in skin colour darkening and improvement of evenness and radiance but were similar on aging (fine lines and wrinkles on crow's feet, under eye and peri-oral areas) markers to non-wearers. In general, in majority of age-groups, hijab wearers showed a higher prevalence of melasma, solar/senile lentigines, seborrheic keratosis and PIH.

Adverse Events of Nonablative Lasers and Energy-Based Therapies in Subjects with Fitzpatrick Skin Phototypes IV to VI: A Systematic Review and Meta-Analysis.

BACKGROUND: Although there is an abundance of literature on nonablative laser and energy-based therapies for the management of skin conditions, adverse events are inconsistently addressed and range widely across studies. Fitzpatrick skin phototypes (SPTs) IV to VI are believed to be at higher risk. OBJECTIVES: The aim of this study was to determine the types and rates of adverse events in nonablative laser and energy-based therapies among patients with SPTs IV to VI. METHODS: Articles addressing nonablative laser and energy-based therapies for skin rejuvenation and acne scarring in patients with SPTs IV to VI that provided data on adverse events were included. The pooled prevalence of each adverse event was calculated. To determine whether age, treatment indication, SPT, and device type influenced incidence, subgroup and meta-regression analyses were performed. Heterogeneity was evaluated with the I2 statistic. RESULTS: Forty-three studies were included in the meta-analysis. The sample size was 1654, and the median age of subjects was 39.4 years. The most common adverse events were postinflammatory hyperpigmentation (PIH) (rate, 8.1%) and prolonged erythema (rate, 0.6%). The rate of PIH was significantly higher for diode and erbium-doped lasers compared with intense pulsed light and radiofrequency. PIH correlated positively with SPT, laser density, and total energy delivered. CONCLUSIONS: Although the overall rate of adverse events in nonablative laser and energy-based therapies for SPTs IV to VI is low, the incidence of PIH is not insignificant. Certain lasers, such as diode, Q-switched Nd:YAG, and erbium-doped lasers, tend to have higher rates of PIH, whereas intense pulsed light and radiofrequency have minimal risk. Higher SPTs and higher energy deliverance correlate positively with the incidence of PIH.

Superficial X-ray-induced hyperpigmentation in postoperative keloid radiotherapy: A study of 70 keloids to identify clinical features and risk factors.

BACKGROUND: Postoperative radiation is one of the most effective treatments for keloid. Radiation-induced hyperpigmentation is, however, a concern for both patients and dermatologists. AIMS: To identify clinical features and risk factors of superficial X-ray-induced hyperpigmentation in postoperative keloid radiotherapy. PATIENTS/METHODS: From November 2019 to November 2020, 70 keloids in 55 patients were treated with superficial X-ray after surgery. Patient data and treatment-related parameters were collected. Follow-up photographs were taken one month after radiotherapy. Three independent dermatologists assessed photographs for pigmentation. The clinical characteristics and severity of pigmentation were summarized. Logistic regression was used to analyze the risk factors associated with occurrence and severity of hyperpigmentation. RESULTS: The pigmentation was a well-defined rectangular brown macule consistent with the unprotected area that involves normal skin, and 82.9% of keloids displayed pigmentation induced by superficial X-ray at one month after treatment. All keloids of trunk appeared to be mild-to-moderately hyperpigmented (100%); 92.89% of limb keloids displayed mainly severe pigmentation. Keloid location was an independent risk factor for the incidence and severity of pigmentation. Longer incision length was also predictive of increased hyperpigmentation severity. CONCLUSIONS: Superficial X-ray-induced hyperpigmentation was common and severe in postoperative keloid radiotherapy. The incidence and severity of pigmentation can be predicted by the location and incision length of the keloid.

Comparison of Fractional Picosecond 1064-nm Laser and Fractional Carbon Dioxide Laser for Treating Atrophic Acne Scars: A Randomized Split-Face Trial.

BACKGROUND: To date, no studies have compared the fractional picosecond 1064-nm laser (FxPico) and fractional carbon dioxide laser (FxCO2) for the treatment of acne scars. OBJECTIVE: To compare the efficacy and safety between FxPico and FxCO2 for treating facial atrophic acne scars. MATERIALS AND METHODS: Twenty-five Asian patients with mild to moderate atrophic acne scars underwent single sessions of randomized split-face treatment with FxPico and FxCO2. Clinical efficacy was assessed by photographs, skin imaging analysis, and patient satisfaction. The adverse events were recorded on every visit. Skin biopsies were performed immediately and 3 months after treatment. RESULTS: The physician improvement scores for skin texture and atrophy significantly increased on the FxPico sides, but no significant difference was observed between FxPico and FxCO2. Skin imaging also showed significant improvement on both sides for scar volume. Postinflammatory hyperpigmentation (PIH) was not reported on FxPico sides, whereas 6 patients (24%) experienced mild PIH on FxCO2 sides. Immediate post-FxPico skin biopsy revealed laser-induced optical breakdown with photoacoustic columns. Collagen and elastic fibers increased at 3 months after both treatments. CONCLUSION: FxPico was as effective as FxCO2 in treating atrophic acne scars, correlating with evidence of tissue remodeling with more safety profiles.

Defining dose constraints for catheter insertion sites to minimize toxicity after interstitial breast brachytherapy.

PURPOSE: The purpose of this study was to define dose constraints for catheter insertion sites to minimize probability of prominent post-therapy skin marks after interstitial breast brachytherapy. METHODS AND MATERIALS: Forty patients who had undergone interstitial breast brachytherapy were studied at followup at least 2 years after the procedure. Their implant marks were compared with background skin and areola and scored as Gr0 = invisible (same color as surrounding skin), Gr1 = darker than surrounding skin but lighter than areola or hypopigmentation, and Gr2 = same color as areola or darker. Highest point doses received in each plane of implant and their corresponding closest distances from clinical target volume, 85% isodose, and closest catheter dwell point were used for analysis. A logistic regression was performed to ascertain effects of various dosimetric parameters on the probability of Gr2 marks. Receiver operating characteristic curve was generated to derive cutoffs. RESULTS: A total of 280 dose points were studied. Median values for various parameters were 1.4 Gy (0.24-3.74) for Dose max and 1.6 cm, 1.5 cm, and 1.0 cm for Dist CTV min, Dist Iso min, and Dist Dwell min, respectively. On logistic regression, increasing Dose max alone was associated with an increased likelihood of developing Gr2 marks. Each unit increase of Dose max increased probability of development of Gr2 skin marks by 5.0% (2.391-10.328). Receiver operating characteristic analysis also showed greatest odd ratio (8.0), sensitivity (74.8%), and specificity (73%) for Dose max. CONCLUSIONS: It seems prudent to restrict dose to catheter insertion sites for better cosmesis.

Comparing the Efficacy of Radiofrequency Ablation Versus Laser Ablation for Chronic Venous Insufficiency in the Lower Extremities: a Vietnamese Report.

INTRODUCTION: Chronic venous insufficiency (CVI) is a chronic condition, triggered by reflux through the saphenous vein network. AIM: To determine the efficacy of endovenous laser ablation (LA) and radiofrequency ablation (RFA) for CVI treatment in the lower extremities, at the Bach Mai Radiology Center. METHODS: This retrospective study was approved by the institutional review board of Bach Mai Hospital. The study recruited 49 people, from August 2016 to April 2018, with recurrent venous insufficiency in the lower extremities and measured 56 ablated veins. RESULTS: In this study, 8 patients (10 veins, with a mean diameter of 5.83 ± 0.96 mm) were treated with RFA, and 41 patients (46 veins, with a mean diameter of 7.96 ± 3.47 mm) were treated with LA. The occlusion rates for LA- and RFA-treated veins were very effective, at 95.7% and 90%, respectively. No significant differences in occlusion rates or clinical improvements were observed between the two ablation methods. On the first day post-treatment, the visual analog score (VAS) value for the LA group was significantly higher than that for the RFA group. Furthermore, ecchymosis, 1 day after treatment, and hyperpigmentation, paresthesia, and numbness, 1 month after treatment, were only observed in the LA group. CONCLUSION: Both LA and RFA were minimally-invasive and safe therapies. No serious complications requiring further interventions were reported and the treatment effectively improved the clinical symptoms of patients. Based on our study, we recommend that RFA should be considered for moderate dilated saphenous vein cases, whereas LA should be indicated for large dilated saphenous vein cases, with or without aneurysm.

Calf Reduction by Partial Resection of Gastrocnemius Using a Suction-Assisted Cartilage Shaver.

BACKGROUND: Long-term aesthetic reduction of the legs in Asians is gaining increasing popularity among cosmetic patients. Current treatment options include botulinum toxin injection, radiofrequency, neurectomy, and total, subtotal, or partial muscle resection of the gastrocnemius. Partial resection using Kelly forceps was introduced in 2000. This article presents the use of a suction-assisted cartilage shaver to perform partial resection, describing the procedures and shaver modifications and evaluating its use. METHODS: A retrospective review of 71 cases with a minimum 6-month follow-up (average, 36.5 months; range, 6 to 160 months) was performed. Twenty partial calf reductions were performed with a short shaver, 27 with a long shaver, and 24 with an endoscope-guided long shaver. RESULTS: Mean reduction of calf circumference was 2 cm (range, -1 to 6 cm); the mean preoperative and postoperative calf circumferences were 35.8 cm and 33.8 cm, respectively. Mean tissue reduction per calf was 110 g (range, 25 to 300 g).Two patients developed larger calves after surgery, one because of weight gain and the other because of weight training. Complications included surface irregularity (n = 4, 5.6 percent), numbness over the lateral ankle or lateral foot (n = 9, 12.7 percent), hematoma clot requiring surgical evacuation (n = 11, 15.5 percent), prolonged seroma (n = 2, 2.8 percent), and left ankle plantar-flexion contracture due to tight, sustained postsurgery bandaging (n = 1, 1.5 percent). Scar-related complications were hyperpigmentation (n = 6, 8.5 percent), depressed scars (n = 5, 7 percent), and hypertrophic scars (n = 2, 2.8 percent). CONCLUSIONS: Short, long, and endoscope-guided long suction-assisted cartilage shavers for partial resection of calf muscles can be used effectively to reduce the calf. Several mostly treatable complications were noted. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Clinical Characteristics and Disease Course in Black Patients With Lymphomatoid Papulosis: A Case Series

INTRODUCTION: Lymphomatoid papulosis (LyP) is a CD30+ T-cell lymphoproliferative disorder (LPD) presenting as a recurrent eruption of papules and nodules which resolve spontaneously. CD30+ LPD prevalence in African American (AA)/Black patients is lower compared to White patients. CD30+ LPD has been recently reported to have worse outcomes in AA patients compared to White patients. METHODS: A retrospective chart review identified eight AA patients with LyP. We describe our experience with these eight patients and review the literature on similar cases. RESULTS: In half of the eight included patients, lesions occurred 1-4 years before they were diagnosed. In six patients (75%), resolution of the lesions resulted in hyperpigmented macules and scars. Five patients (63%) had also mycosis fungoides. Most of the patients who were followed (4/7, 57%) did not have complete resolution at their last visit, despite different treatment approaches. Discussion: Our results highlight that although LyP has an indolent course in AA/Black patients, residual hyperpigmentation and scars frequently occur, highlighting the need for better treatments of this lymphoproliferative disorder in this specific population. J Drugs Dermatol. 2020;19(1):89-91. doi:10.36849/JDD.2020.4602

Scar Assessment After Breast Reconstruction: Risk Factors for Hypertrophy and Hyperpigmentation in Asian Patients.

BACKGROUND: Breast scars after breast reconstruction can be hypertrophic and/or hyperpigmented, especially in Asian patients, whose skin is thicker and has increased melanin. Few studies have focused on breast scars after breast reconstruction, and the risk factors for an abnormal breast scar remain unknown. METHODS: We examined 257 Asian patients who underwent an immediate 2-stage unilateral implant-based breast reconstruction. Vascularity, hypertrophy, and hyperpigmentation of the patients' breast scars were assessed at 1 year postoperatively. Risk factors for an abnormal scar were analyzed statistically. Analyzed patient factors included age, body mass index, incision site (frontal or lateral), breast size (the weight of the resected specimen), skin necrosis at the initial operation (expander placement), and adjuvant therapy. RESULTS: At 1 year postoperatively, 161 patients (63%) showed normal vascularity, 77 patients (30%) showed mild vascularity, 18 patients (7%) showed moderate vascularity, and 1 patient (0.4%) showed severe vascularity. No patient factors were correlated with vascularity. Thirty-two patients (12%) showed hypertrophy, and the rate of hypertrophy was significantly higher in the patients with a lateral incision (n = 59) compared with those with a frontal incision (n = 198) (28.8% vs 7.6%, P < 0.01). Even in the frontal incision group, a lateral part of the frontal scar was likely to be hypertrophic. Forty-six patients (18%) showed hyperpigmentation, and the rate of hyperpigmentation was significantly higher in the patients with skin necrosis (n = 47) at the initial operation than those without skin necrosis (n = 210) (57.4% vs 9.0%, P < 0.01). Large breast was also a risk factor for hyperpigmentation due to its higher frequency of skin necrosis. CONCLUSIONS: In Asian patients who undergo breast reconstruction, the use of a lateral incision is a risk factor for hypertrophy, and skin necrosis at the initial operation is a risk factor for hyperpigmentation at the breast scar.

Comparison of a picosecond alexandrite laser versus a Q-switched alexandrite laser for the treatment of nevus of Ota: A randomized, split-lesion, controlled trial.

BACKGROUND: Novel picosecond lasers have been available for various pigmentary disorders. However, there are limited data directly comparing picosecond lasers and Q-switched lasers for treatment of nevus of Ota. OBJECTIVE: To compare the efficacy and safety of a picosecond alexandrite laser (PSAL) with a Q-switched alexandrite laser (QSAL) for the treatment of nevus of Ota. METHODS: Each lesion of 56 enrolled participants was split into 2 parts and randomly assigned to either the PSAL or QSAL treatment arm. Each lesion was treated in up to 6 sessions in 12-week intervals. Efficacy and safety were determined using blinded visual evaluation and self-report at each follow-up visit. RESULTS: The PSAL arm achieved a significantly better clearance (5-point scale, PSAL 4.53 vs QSAL 4.0) with fewer sessions (PSAL 5.26 vs QSAL 5.87) and less severe pain (Visual Analog Scale, PSAL 5.61 vs QSAL 6.40). Patients were more satisfied with PSAL than QSAL (Likert scale, 4.5 vs 4.0). Occurrences of postinflammatory hyperpigmentation (PSAL 26% vs QSAL 34%) and hypopigmentation (PSAL 21% vs QSAL 47%) were also lower in PSAL than QSAL arm. LIMITATIONS: Lack of objective assessments and outcome measures. CONCLUSION: PSAL demonstrated better clinical results and fewer adverse events than QSAL for the treatment of nevus of Ota.

Outcomes and prognostic factors in African American and black patients with mycosis fungoides/Sézary syndrome: Retrospective analysis of 157 patients from a referral cancer center.

BACKGROUND: The prevalence of mycosis fungoides/Sézary syndrome (MF/SS) is higher in the black population than in the white population in the United States and worse outcomes have been observed in black patients. OBJECTIVE: To describe the outcomes and to identify prognostic factors in African American and black patients with MF/SS. METHODS: Clinical features and follow-up data were analyzed in 157 self-identified African American or black patients seen during 1994-2018. RESULTS: We included 122 patients with early stage MF and 35 patients with advanced-stage disease (median follow-up of 25 months). Overall, >80% of the patients who died from disease or progressed had erythema or hyperpigmentation without hypopigmentation. Patients with hypopigmentation, either as the sole manifestation or in combination with other lesions, had better overall survival (P = .002) and progression-free survival (P = .014). Clinical stage, TNMB classification, plaque disease, and elevated serum lactate dehydrogenase were also significantly associated with outcomes. Demographic and socioeconomic parameters were not associated with prognosis. LIMITATIONS: A retrospective study at a single cancer center. CONCLUSION: MF/SS manifestations and outcomes in African American and black patients are heterogeneous. Demographic and socioeconomic factors do not seem to have a prognostic role, while clinical characteristics might help in the stratification of risk of progression and shorter survival, allowing for individually tailored therapeutic interventions.

A Prospective Randomized Controlled Study of Oral Tranexamic Acid for the Prevention of Postinflammatory Hyperpigmentation After Q-Switched 532-nm Nd:YAG Laser for Solar Lentigines.

BACKGROUND AND OBJECTIVES: Q-switched (QS) 532-nm Nd:YAG laser is one of the treatment options for solar lentigines (SLs). However, the high incidence of postinflammatory hyperpigmentation (PIH) is concerning, especially in dark-complexioned skin. Tranexamic acid (TA) can decrease melanogenesis and has been used to treat melasma. The aim of this study is to evaluate the efficacy and safety of oral TA for PIH prevention and clearance in patients with SL treated with QS 532-nm Nd:YAG laser. STUDY DESIGN/MATERIALS AND METHODS: Forty patients with SL treated with QS 532-nm Nd:YAG laser were enrolled in this randomized controlled trial. They were randomly assigned to be receive oral TA 1,500 mg daily or placebo for 6 weeks. Results were evaluated by blinded investigators using digital photographs, dermatoscopy, colorimetry, physician grading scores, and patient satisfaction scores at baseline, 2nd, 4th, 6th, and 12th weeks. RESULTS: The incidence of PIH, relative melanin value, lightness index, and clinical improvement scores were not significantly different between the two groups. However, the TA group had a significantly lower incidence of dermatoscopic finding of pigmented granules, which correspond to PIH at 6th and 12th weeks (P = 0.038 and 0.013, respectively). Homogenous light brown pigmentation under dermatoscopy was significantly associated with higher clinical improvement. CONCLUSIONS: Oral TA therapy starting at the first day postlaser treatment is not effective for PIH prevention after QS 532-nm Nd:YAG laser in SL. However, PIH clearance, as assessed dermatoscopically, is significantly improved by oral TA at 6th and 12th week. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Drug-Induced Hyperpigmentation: Review and Case Series.

BACKGROUND: Hyperpigmentation is a common dermatologic problem that may have substantial impact on the patient, since it affects the appearance and quality of life, and may influence treatment adherence. There are few studies of drug-induced hyperpigmentation. METHODS: We studied drug-induced hyperpigmentation in patients attending an outpatient dermatology clinic in the Western Area of Valladolid (Spain) from August 1, 2017 to April 20, 2018. RESULTS: The incidence of drug-induced hyperpigmentation was 1.31% in patients attending a first dermatology consultation in the study period. Of the 16 patients, 8 were taking more than 1 drug. The most frequent drugs identified were nonsteroidal anti-inflammatory agents (25%), antihypertensive agents (18.75%), antimalarials (12.5%), antibiotics, antineoplastic agents, psychoactive agents, simvastatin, allopurinol, amiodarone and mucolytic (6.25% each). Hyperpigmentation was found in the mucosa in 25% of patients and in photograph-exposed areas in 37.5%. DISCUSSION: Diagnosing drug-induced hyperpigmentation is a dermatologic challenge. A differential diagnosis with hyperpigmentation caused by endocrine and metabolic disorders, the most closely-related disorders to drug-induced hyperpigmentation, and with hyperpigmentation of idiopathic origin, should be conducted. Drug-induced hyperpigmentation is a relatively frequent reason for consultation, especially in polypharmacy patients. The sample may have been biased as many patients receiving treatments frequently associated with drug-induced hyperpigmentation, such as antineoplastic drugs, are diagnosed and treated by other specialties, such as oncologists. CONCLUSION: Family physicians and specialists should consider drugs as a cause of hyperpigmentation to facilitate the correct diagnosis and treatment.

Hyperpigmentation and higher incidence of cutaneous malignancies in moderate-high PCB- and dioxin exposed individuals.

Polychlorinated biphenyls (PCB) are well known persistent and toxic environmental pollutants. Our aim was to identify effects of moderate-high exposure to dioxin-like (dl) and non-dioxin-like (ndl)-PCBs on the skin in order to provide more insight in the pathophysiological effects of these compounds. We performed a dermatological examination on 92 former workers from a transformer recycling company with known elevated serum PCB and/or dioxin (polychlorinated dibenzo-p-dioxin/polychlorinated dibenzo-p-furan (PCDD/F)) levels. In addition, we performed a skin cancer screening over a period of seven years (2010-2016) on resp. 268, 271, 210, 149, 92, 129 and 79 participants. We found a higher incidence of acne and malignancies of the skin (malignant melanoma, basal cell carcinoma and mycosis fungoides) in the workers compared to normal population. The probability of having hyperpigmentation on the skin was statistically significantly higher in workers with higher sumPCBs- (OR:1.09(1.12-2.17)), dioxin-like (dl)-PCBs- (OR:1.56(1.12-2.17)) and dioxin (PCDD/Fs) (OR:1.09(1.02-1.16)) levels. Age was a confounding factor in this model. Formation of hyperpigmentation could be an indicator for (moderate-high) exposure to toxic compounds like PCBs. The higher incidence of cutaneous malignancies found in the workers might be associated with PCB- and dioxin exposure, warranting further investigation on larger cohorts.

A multicentre, open, investigator-initiated phase IV clinical trial to evaluate the efficacy and safety of ingenol mebutate gel, 0·015% on the face and scalp, and 0·05% on the trunk and extremities, in Korean patients with actinic keratosis (PERFECT).

BACKGROUND: Ingenol mebutate gel is a novel, field-directed topical treatment for actinic keratosis (AK). Most pivotal studies have targeted Western populations. No clinical study has been conducted to investigate its efficacy and safety in Asian populations. OBJECTIVES: To evaluate the efficacy and safety of ingenol mebutate gel for treating AK of face/scalp and trunk/extremities in a large Asian (Korean) population. PATIENTS AND METHODS: In this multicentre, open-label, interventional, parallel-group, prospective phase IV study (PERFECT, trial registration no.: NCT02716714), the eligible patients were allocated into either the face/scalp or the trunk/extremities group, according to their selected treatment area location. After application of ingenol mebutate gel, the participants were followed up for 6 months. The primary efficacy endpoint was complete clearance (CC) of AK lesions in the selected treatment area at day 57. Quality of life was evaluated using Skindex-29. Safety endpoints included local skin responses, scar, pigmentation, pain and adverse events. RESULTS: In total, 78·1% [95% confidence interval (CI) 66·86-86·92%] of subjects had CC at day 57, with 76·6% (95% CI 64·31-86·25%) in the face/scalp group and 88·9% (95% CI 51·75-99·72%) in the trunk/extremities group. Among them, CC was sustained in 88·9% (48 of 54, 95% CI 77·37-95·81%) at month 6. The local skin responses significantly increased 1 day after the treatment compared with baseline, and decreased afterwards. Among the total subjects, 7·8% (6 of 77) had hyperpigmentation on the application area. Scars were not reported. CONCLUSIONS: Ingenol mebutate is effective for the treatment of AK in Asians, with tolerable safety profiles.