Pigmented actinic lichen planus: a case report.

Actinic lichen planus (ALP) is a rare photosensitive subtype of lichen planus (LP) with four major forms recognized: annular, pigmented (melasma-like), dyschromic, and classic lichenoid. The prevalence is highest among dark-skinned younger females residing in tropical and subtropical regions. There are very few reports of ALP across Europe, with most of the cases among individuals living in warm countries or in people of Middle Eastern and Indian ancestry. We report a case of a 68-year-old white man that presented with a 9-year history of a mildly pruritic solitary hyperpigmented patch on the tip of his nose. Histopathological examination demonstrated signs of classic LP with epidermal atrophy, pigmentary incontinence, and signs of solar elastosis. Based on these findings, a diagnosis of pigmented ALP was established. Topical pimecrolimus and tretinoin along with rigorous photoprotection proved effective, with mild residual hyperpigmentation after 6 months of treatment. Many differential diagnostic possibilities should be considered for such a lesion. Nevertheless, a biopsy and correlation of histopathological and clinical findings can shorten the time from onset to a proper diagnosis. Treating both the hyperpigmented and inflammatory component of this dermatosis is necessary, as well as strict long-term photoprotection to prevent recurrences.

Refractory solar lentigines successfully treated with 532-nm nanosecond Nd:YAG Vasculature Salvage Laser Surgery (VSLS) system: Case series.

BACKGROUND: Solar lentigo, a common epidermal hyperpigmented lesion found in sun-exposed areas, results from the proliferation of melanocytes and the accumulation of melanin. Although various treatments for solar lentigo have been explored, they often lead to complications, including prolonged erythema and post-inflammatory hyperpigmentation (PIH), posing significant concerns. OBJECTIVES AND METHODS: This study evaluated the safety and efficacy of the Vasculature Salvage Laser Surgery (VSLS) system. We treated six Korean patients, each with solar lentigo, in a single session using the 532-nm nanosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) VSLS system, with follow-up periods ranging from 3 to 10 weeks. RESULTS: The treatment led to the complete removal of pigmented lesions in all patients without resulting in PIH, even in cases where previous laser treatments had failed. The only side effect observed was mild erythema, which resolved over the long term in most instances. CONCLUSIONS: The VSLS system emerges as a safe and effective treatment for pigmented lesions, including refractory solar lentigines. Nonetheless, additional studies are required to verify its long-term efficacy.

Postoperative risk assessment of post-inflammatory hyperpigmentation and the efficacy of delayed prevention following 532 nm Q-switched Nd:YAG laser treatment of solar lentigines: a randomized controlled study.

BACKGROUND: Although post-inflammatory hyperpigmentation (PIH) is a common adverse event following laser procedures, studies evaluating its risk remain limited. OBJECTIVE: To analyze PIH risk after 532 nm Q-switched Nd:YAG laser (QSNYL) treatment for solar lentigines and examine the efficacy of triple combination cream (TCC) for its prevention. METHODS: In this single center, investigator-blinded, randomized controlled study, participants with solar lentigo either received TCC or emollient from 2 weeks post-QSNYL treatment. The occurrence of PIH was determined by three independent and blinded dermatologists. In vivo skin measurements and sun exposure questionnaires were examined to evaluate the risk of PIH. RESULTS: A total of 28 patients with 67 solar lentigines were included in the analysis. In the control group, PIH occurred in 55.3% of the lesions. Risk factors for the occurrence of PIH were the increased erythema at weeks 2 (OR, 1.32; p = 0.035) and outdoor activity during 1-5 pm (OR, 8.10; p = 0.038). Treatment with TCC from 2 weeks post-QSNYL treatment significantly decreased the incidence of PIH (31.0% vs. 55.3%, p = 0.048). CONCLUSION: Post-laser erythema and outdoor activity at the daytime are prognostic factors for the occurrence of PIH. Administering TCC could be considered for the prevention of PIH in high-risk patients.

Topical Steroids Sold as Fade Creams in Beauty Supply Stores: A Danger for Cosmetic Consumers.

Topical corticosteroids are used extensively in dermatology. Class 1 high potency topical steroids (HPTS) can result in unwanted side effects such as skin hypopigmentation, atrophy, and acneiform eruptions. HPTS are only legally available by prescription to ensure appropriate use in the United States (US). The authors have noticed a recent increase in patients presenting with steroid acne after buying HPTS products in beauty supply stores. These products are marketed as fade creams to treat hyperpigmentation and uneven skin tone. We assessed skincare products containing HPTS (clobetasol or betamethasone) in 33 beauty supply stores in Miami, FL; Washington, DC; and Baltimore, MD. Out of 33 beauty supply stores, 14 (42.42%) contained HPTS skincare products, and they were all located in Miami. Out of 15 stores visited in Miami, 14 (93.33%) contained skincare products with clobetasol, and 5 (33.33%) contained skincare products with both clobetasol and betamethasone. Of the stores selling HPTS skincare products, the number of different brands available ranged from 1 to 7, with an average of 4.21 different brands per store. Our study reveals that HPTS are readily available in over-the-counter skincare products in many beauty supply stores. HPTS skincare products were only available in one of three cities suggesting there may be a regional supplier distributing these products. It may also indicate that there is less oversight of retail stores in Miami with HPTS products. More studies are needed to quantify the availability of these products in different locations throughout the US. Further Studies can help identify this problem and raise awareness among consumers of the dangers of HPTS skincare products in beauty supply stores. J Drugs Dermatol. 2024;23(9):709-712. doi:10.36849/JDD.7608.

Treatment of Acne Vulgaris-Associated Post-Inflammatory Dyschromia With Combination of Non-Ablative Laser Therapy and Topical Antioxidants.

Acne can cause disfiguring sequelae, such as scarring, post-inflammatory erythema (PIE), and post-inflammatory hyperpigmentation (PIH). These post-inflammatory dyschromias pose a significant psychological burden on patients. This burden disproportionately affects skin of color (SOC) patients and can be the most distressing aspect of acne in SOC patients with skin types IV to VI. Multiple non-ablative lasers are used in the treatment of acne-related PIE and PIH. Combination therapies have shown promise in conditions such as rosacea, acne, and post-inflammatory dyschromia. Addressing both the inflammatory and scarring components of acne is key. Given the role of oxidation in the inflammatory cascade, including antioxidants could be an efficacious adjuvant with non-ablative lasers. This is a single-site, randomized, controlled clinical study of 25 subjects with skin types I to VI with facial PIE and/or PIH from acne. The primary objective was to investigate the clinical efficacy of non-ablative laser therapy followed by the topical application of Silymarin/Salicylic Acid/L-Ascorbic Acid/Ferulic Acid (SSAF) or control in the improvement in oily skin patients with facial PIE and PIH due to acne lesions. There was a statistically significant decrease in PIH and intralesional melanin in patients treated with a combination SSAF and non-ablative laser therapy. Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density. This was even more strikingly marked in the SOC subjects, potentially providing an energy-based device (EBD)-based therapy in this population. Limitations of this study include small sample size and length of post-treatment follow-up. J Drugs Dermatol. 2024;23(9):769-773. doi:10.36849/JDD.8309.

Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries).

BACKGROUND: Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic. METHODS: In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors. RESULTS: Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations. CONCLUSION: Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity.

Semaxanib, a VEGF inhibitor, suppresses melanogenesis by modulating CRTC3 independently of VEGF signaling.

BACKGROUND: Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib. OBJECTIVE: To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib. METHODS: Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. In vivo studies were conducted using an epidermis-humanized transgenic mouse model and ex vivo human skin tissues. RESULTS: Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B-stimulated ex vivo human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes. CONCLUSION: Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.

Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

H Syndrome: Three New Cases from Morocco.

A 19-year-old girl presented with symmetric and bilateral hyperpigmentation, an indurated lesion that initially appeared on the axillary fold at the age of 14, which then extended to the lower back, anterior aspect of both thighs, and popliteal fold. No hypertrichosis was observed (Figure 1).The patient was the youngest of the four children, born from the first-degree consanguineous marriage. She was born at full term and weighed 2,420 g at birth. No similar patient was present in the family. The patient experienced delayed motor acquisition and stature growth (3rd percentile) until the age of 4. Right hypoacusis was diagnosed at the age of 6. She developed hallux valgus, flexion contracture of the fin-gers and toes, barrel deformity of the anterior thorax, and recurrent fever. The laboratory tests, including fasting blood glucose, -triglycerides, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were normal. Her abdominal, pelvic, and transthoracic ultrasound scans were normal, with no hepatosplenomegaly, lymphadenopathy, or cardiac abnormalities. Histologic analysis demonstrated patchy acanthosis of the epidermis, with orthokeratotic hyperkeratosis. Keratinocyte hyperpigmentation and spongiosis at certain areas were observed with moder-ate inflammation because of the infiltration of lymphocytes, histiocytes, and plasma cells. Immunohistochemical analysis showed macrosialin (CD68+) and common gamma chain (γc) CD132. Germline mutations in the SLC29A3 gene were not analyzed. The patient was prescribed dermocorticoids with depigmentation therapy, which demonstrated moderate clinical evolution.

INDIVIDUAL ARTICLE: Skincare in Skin of Color: A Comprehensive Approach to Preprocedure, Intraprocedure, and Postprocedure.

Hyperpigmentation, uneven skin tone, textural changes, and dull skin are common cosmetic concerns in skin of color. Other signs of aging, including fine lines, deeper wrinkles, and skin laxity, also occur but may present in later decades. In-office procedures such as laser treatments, energy devices, toxins, fillers, and chemical peels are useful options for addressing the most common cosmetic concerns in skin of color patients. Skincare can play an important role in improving cosmetic outcomes when used in conjunction with in-office procedures. With the availability of these approaches, clinicians can now integrate in-office procedures with skincare strategies to offer patients with skin of color a comprehensive treatment plan that meets their needs. J Drugs Dermatol. 2024;23:8(Suppl 1):s5-10.

Two cases of imatinib induced oral pigmentation affecting the palate.

BACKGROUND: Medication-related oral pigmentation is a unique yet benign finding in the dental setting. As new antineoplastic agents emerge, it is likely that this documented manifestation will continue to grow. CASE DESCRIPTION: Here, we describe two case presentations of imatinib-related hyperpigmentation of the palate. Both patients had been on imatinib, an antineoplastic agent for 10-14 years and presented with asymptomatic diffuse blue-black discoloration of the hard palate. Both cases demonstrated biopsy-proven pigment changes localized to the superficial connective tissue with evidence of melanin and hemosiderin deposits. Of note, this is a benign finding that does not require intervention. CONCLUSION: These two cases illustrate intraoral findings associated with imatinib. Increased awareness of this side effect will enable clinicians to appropriately council patients regarding the benign nature of this process.

Dermatological Conundrum: Puzzling Pigmentation in Vitamin B12 Deficiency and Addison's Disease.

We report a case series of two patients who had similar skin pigmentation but were caused by vitamin B12 deficiency and Addison's disease. We further discuss the pathophysiology of skin hyperpigmentation in both of these disorders and the response to treatment. Our case report highlights the importance of the identification of simple bedside clinical signs to diagnose reversible causes of skin pigmentation.

Treatment of Iron-Induced Cutaneous Hyperpigmentation With Energy-Based Devices.

OBJECTIVES: Iatrogenic cutaneous siderosis is a well-recognized dermatologic complication after parenteral iron infusion. The condition manifests as discrete, hyperpigmented patches near the site of injection. Most cases do not resolve spontaneously, leading to significant aesthetic and psychological distress to patients. A recent case of iatrogenic cutaneous siderosis at our institution prompted a systematic review of the efficacy of energy-based devices previously reported in the treatment of this condition. METHODS: PubMed and Cochrane databases were searched for all peer-reviewed articles published using the following search terms: "iron OR heme OR hemosiderosis OR siderosis" and "hyperpigmentation OR staining OR tattoo." Articles reporting on energy-based devices in the treatment of iron-induced hyperpigmentation were included. RESULTS: A total of seven articles and 54 total patients were included in this review. All patients, including the patient treated at our institution, were female, with an average age of 44 years. Hyperpigmentation was most commonly associated with intravenous iron infusion (48/54, 89%), on the arm or forearm (44/54, 81%), and used for the treatment of underlying iron deficiency anemia (54/54, 100%). The application of six different nanosecond or picosecond quality-switched laser systems was reported in the treatment of cutaneous siderosis, with wavelengths ranging from 532 to 1064 nm. Spot sizes varied between 2 and 7 mm, with energy fluences spanning 0.5-40 J/cm2 depending on both the device and spot size. Outcomes were measured after an average of 5.4 laser treatments and 10.4 months, with over half of all reported patients experiencing complete clearance (27/50, 54%). Our patient received treatment in three test areas with picosecond alexandrite 785 nm, nanosecond Nd:YAG 532 nm, and picosecond Nd:YAG 532 nm devices. The nanosecond Nd:YAG 532 nm treated area demonstrated the greatest improvement, and the entire arm was subsequently treated with this device. CONCLUSIONS: Despite the often intractable nature of iatrogenic cutaneous siderosis, laser surgery is a reasonable and safe treatment modality for patients seeking cosmetic improvement of this dyschromia. Dermatologists should be aware of this entity and the efficacy of the energy-based devices currently in our armamentarium. A combination approach may need to be utilized with different wavelengths and pulsed widths to target iron pigment in both dermal and subcutaneous layers.

Exploring Fractional Pigment Toning: A Novel Approach for Treating Benign Pigmented Lesions in Asian Patients With Fitzpatrick Skin Types III-V.

BACKGROUND/OBJECTIVE: Laser therapy has emerged as a widely favored treatment option for solar lentigines (SL). However, a significant challenge associated with this treatment, particularly among individuals with darker skin tones, is the notable risk of postinflammatory hyperpigmentation (PIH) induction. In response to these concerns, the authors conducted a prospective, self-controlled study to comprehensively evaluate the safety and effectiveness of 532-nm picosecond laser, both with and without a microlens array (MLA), for the management of SL in patients with Fitzpatrick skin types (FST) III-V. METHODS: Twenty-seven patients with FST III-V and bilateral SL on the face underwent randomized treatment. One side of the face was treated with a 532-nm picosecond laser coupled with an MLA, utilizing the fractional pigment toning (FPT) technique, while the other side received treatment without the MLA, following the conventional technique (CT). The FPT technique utilized a 9-mm spot size with a fluence of 0.47 J/cm2 for two passes covering 40% of the area. In contrast, the CT used a 4.5-mm handpiece with fluence ranging from 0.3 to 0.7 J/cm2. Patients received a single treatment and were evaluated for pigment clearance, occurrence of PIH, and other adverse effects at 2 weeks, 1, 3, and 6 months posttreatment. RESULTS: Twenty-seven participants completed the study protocol. Analysis of pigment clearance, measured via 3D photography, showed significant improvement from 2 weeks to 6 months posttreatment for both the FPT technique (p < 0.001) and CT (p = 0.004). PIH occurred in 64%, 80%, 96%, and 88% of cases on the CT side, compared to 8%, 32%, 36%, and 16% on the FPT technique side at 2 weeks, 1, 3, and 6 months posttreatment, respectively. The incidence of PIH was significantly lower on the FPT technique side compared to the CT side throughout the follow-up periods. Additionally, transient and mild hypopigmentation occurred in one participant (4%) on the FPT technique side and in five participants (20%) on the CT side. No other adverse effects were observed during the study. CONCLUSIONS: The 532-nm picosecond laser emerges as a safe and efficacious treatment modality for SL in individuals with FST III-V. Particularly noteworthy is the efficacy of the FPT technique, which demonstrates comparable effectiveness while significantly reducing the incidence of PIH compared to the CT.

Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.