Cutaneous Sarcoidosis Induced by Laser Therapy: Case Report and Review of the Literature.

BACKGROUND: Sarcoidosis, characterized by non-caseating epithelioid granulomas, presents diagnostic and therapeutic challenges. METHOD: Here we present a 38-year-old woman who exhibited erythematous and infiltrated skin lesions on her facial region following fractional laser treatment. RESULTS: Histological analysis confirmed cutaneous sarcoidosis. Initial interventions with topical clobetasol and oral chloroquine provided transient relief. Subsequent outpatient management comprised topical tacrolimus and clobetasol, as well as systemic methotrexate, later substituted with prednisone. Gradual tapering resulted in lesion reduction. CONCLUSIONS: This case underscores the intricate nature of cutaneous sarcoidosis and the necessity for personalized therapeutic approaches. The association with cosmetic procedures highlights the importance of understanding potential triggers. The presented case highlights and reminds the medical community that lasers are not only used for therapeutic purposes but can also induce specific responses through laser therapy. Notably, while laser therapy is frequently employed in treating cutaneous sarcoidosis, its role in inducing sarcoidosis warrants further investigation.

Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies.

BACKGROUND: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2). OBJECTIVE: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data. METHODS: Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study. RESULTS: Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events. CONCLUSIONS: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018).

Risk of cardiovascular disorders in hidradenitis suppurativa patients: a large-scale, propensity-matched global retrospective cohort study.

BACKGROUND: Patients with hidradenitis suppurativa (HS) often suffer from comorbid diabetes, metabolic syndrome, and hyperlipidemia and, therefore, are susceptible to the development of cardiovascular diseases (CVDs). Moreover, systemic inflammation plays a vital role in the development of atherosclerosis. The creation of atherosclerotic plaque is characterized by endothelial dysfunction driven by elevated concentrations of interleukin (IL)-1, IL-6, and IL-18 among others, as well as tumor necrosis factor (TNF) alpha. METHODS: This study aimed to assess the risk of HS patients developing CVDs. We performed a large-scale, propensity-matched global retrospective cohort study analyzing the risk of development of CVDs in patients suffering from HS. The analysis included 144,100 HS patients with 144,100 healthy controls (HC). The cohorts were matched regarding demographics and history of diseases relevant to CVDs, e.g., diabetes, obesity, and nicotine dependence. A total of 90 cardiovascular disorders were identified. The identification of cardiovascular disorders was based on ≥1% appearance of the event, based on absolute numbers, in both cohorts. RESULTS: Before the matching, HS patients displayed a higher frequency in excess weight or obesity (25 vs. 14.4%, respectively), nicotine dependence, and diabetes mellitus, but lower odds of primary hypertension in comparison to healthy controls. A total of 47 CVDs are associated with an increased risk of onset in HS patients. Although the highest hazard ratio (HR; 2.1; 95% CI: 1.95-2.269) was found for unspecified heart failure, the HS cohort was exceptionally predisposed to developing myocardial infarction (HR: 2.06; 95% CI: 1.88-2.27) and an acute embolism and deep vein thrombosis of the lower extremity (HR: 1.93; 95% CI: 1.74-2.14). CONCLUSIONS: This is the most extensive study on the association of HS with CVDs. We demonstrated that HS patients are at significantly greater risk of developing various CVDs compared to matched controls, with heart failure being the most common one.

Acne influences life-changing decisions among young adults.

BACKGROUND: Acne is a chronic inflammatory disease predominantly affecting young people. This study was undertaken to assess the impact of acne in young adults on their major life-changing decisions (MLCD), paying attention to the relationships between major life-changing decisions profile (MLCDP) and Quality of Life (QoL), feeling of stigmatization and acceptance of the disease. METHODS: The study was performed on 213 young people diagnosed with acne. A variety of questionnaires were employed to measure the clinical and psychological aspects of acne. RESULTS: The majority of patients (N.=148, 73.3%) reported at least one MLCD that acne affected in any way (mean number 2.9±3.2, range: 0-18). The most common MLCD influenced by acne appeared to be a decision of changing eating habits (N.=132, 65.3%), followed by changing habits associated with smoking and alcohol (N.=85, 42.1%) and deciding to be more active physically (N.=61, 30.2%). The total score of MLCDP ranged from 0 to 33 points (mean 5.41±6.23 points). MLCDP total score significantly correlated with clinical acne severity (P=0.006), QoL (P<0.001), stigmatization (P<0.001) and illness acceptance (P<0.001). CONCLUSIONS: Acne has an important impact on life-changing decisions in young adults. MLCDP correlates with impaired QoL, level of stigmatization and degree of illness acceptance. This should be taken into consideration in the holistic approach to acne patients.

Extra-Anogenital Giant Cutaneous Squamous Cell Carcinomas.

Extra-anogenital giant cSCCs are rare but have worse outcomes compared to smaller tumors. Prompted by limited data, the authors conducted a retrospective study to gather more information about giant cSCCs to optimize clinical care. We identified seven cases of giant cSCCs from a review of cSCC cases treated in the Unit of Dermatosurgery between 2016 and 2022. Most patients were male (85.71%) with a mean age of 80.29 ± 12.22 years. UV radiation was the most common risk factor (five cases) followed by smoking (three cases) and hidradenitis suppurativa (one case). Most giant cases were located in the head area (71.4%) and the diameter of lesions ranged from 6 to 18 cm. All patients corresponded to tumor stage T3, and 42.86% of patients had lymph node metastases. Surgical excision was the treatment of choice in most cases (85.71%), while a combination of cemiplimab and RP1 was used in some cases due to the ineffectiveness of treatment or contraindications to other therapies. The authors emphasize the importance of early detection and prevention of modifiable risk factors, such as UV radiation, and a multidisciplinary approach to treatment. Other therapies, including immunotherapy, may become increasingly important.

Five decades of the use of botulinum toxin in ophthalmology.

Botulinum toxin (BoNT) has been known for over 50 years. It has conquered many areas of medicine and has become indispensable in contemporary medicine. Now, BoNT is used to treat at least 26 conditions in six medical specialties. Although the use of BoNT began in strabology, it became the gold standard for many ophthalmologic pathologies. The present review of the literature focuses on the use of BoNT in ophthalmology and treatment of the following conditions: blepharospasm, facial hemispasm, facial palsy, spastic entropion, strabismus, endocrine orbitopathy, convergence spasm, and facial trauma. We conclude that nearly half a century of experience in utilizing BoNT in ophthalmology ensured a satisfactory level of effectiveness and safety for patients with many pathologies. Areas of future research include the application of BoNT in new selected indications, the development of the route of application without injections, and the development of long-acting BoNT forms for patients who require repeated long-term treatment.

Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials.

BACKGROUND: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis. OBJECTIVE: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials. METHODS: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy). RESULTS: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders. CONCLUSIONS: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years.

Psoriasis is a chronic inflammatory skin condition. Many available treatments for psoriasis are injected, but can be inadequate in terms of effectiveness, and/or cause serious side-effects. Deucravacitinib is a recently approved oral medicine that interferes with an enzyme involved in inflammation called 'tyrosine kinase 2' (TYK2). Deucravacitinib has been shown to improve psoriatic patches and symptoms (such as itching) through 1 year in two global clinical trials in adults with moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2). This study was an analysis of the safety and efficacy of deu­cravacitinib for up to 2 years. To do this, the researchers used data from approximately 1500 people who completed both trials and continued into an ongoing, long-term extension trial (POETYK LTE). Overall, there were no new side-effects, and the number, type and severity of side-effects, as well as the number of patients who stopped treatment because of these side-effects, remained low. The most frequent side-effects included common cold symptoms and COVID-19. Rates of shingles and serious side-effects were comparable to rates reported in the real world. Improvements in psoriasis symptoms seen at 1 year were maintained for up to 2 years in patients receiving deucravacitinib treatment from the start of PSO-1 or PSO-2, or who crossed over from placebo to deucravacitinib at 4 months. Long-term treatment with deucravacitinib improved psoriasis symptoms and resulted in mostly mild side-effects. The study findings suggest that deucravacitinib could be a well-tolerated and effective treatment for people with psoriasis.

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus.

INTRODUCTION: Chronic pruritus (CP) is a common symptom defined as a sensation that provokes the desire to scratch and which lasts for at least 6 weeks. CP remains a problem for up to 21.3% of renal transplant recipients (RTRs). Our research aimed to establish the possible association between serum levels of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) and the presence and intensity of CP in RTR. METHODS: The study was performed on a group of 129 RTRs, who were divided according to the presence or absence of pruritus in the previous 3 days. The assessment of pruritus was performed with the use of a numeric rating scale (NRS), 4-Item Itch Questionnaire (4IIQ), and Itchy Quality of Life (Itchy QoL). A total of 129 blood samples with a volume of 9 ml were drawn from RTRs during the monthly routine control. Serum levels (pg/mL) of NT-4 and BDNF were measured by the ELISA. RESULTS: Pruritic RTRs have statistically significantly higher serum concentrations of NT-4 serum level compared to non-pruritic RTRs (229.17 ± 143.86 pg/mL and 153.08 ± 78.19 pg/mL [p = 0.024], respectively). Moreover, a statistically significant difference between pruritic and non-pruritic RTRs with healthy controls was shown (p < 0.001 and p < 0.001, respectively). Although there was a numerically higher serum concentration of BDNF in pruritic RTRs (32.18 ± 7.31 pg/mL vs. 31.58 ± 10.84 pg/mL), the difference did not reach statistical significance. No statistically significant difference was also seen in BDNF serum levels between RTRs and healthy controls. Furthermore, there was a statistically significant, positive correlation between serum concentration of NT-4 and NRS score (p = 0.008, r = 0.357). CONCLUSIONS: The results indicate higher NT-4 serum concentration in RTRs with pruritus compared to RTRs without pruritus. Furthermore, the study revealed a statistically significant, positive correlation between the serum concentration of NT-4 and NRS score.

Hidradenitis suppurativa and follicular occlusion syndrome: Where is the pathogenetic link?

The follicular occlusion tetrad complex encompasses several entities (hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp, and pilonidal cyst) that share common clinical features, risk factors, and pathophysiology. Follicular occlusion is a crucial triggering mechanism in the etiology in each of these disorders, leading to development of distinctive skin lesions such as deep-seated nodules, abscesses, comedones, and draining sinuses, often with accompanying scarring. Despite the fact that the follicular occlusion tetrad components manifest multiple similarities, they also exhibit many differences among themselves and require individual approaches and treatment.

Non-multiple medium-sized congenital melanocytic nevi: to excise or to follow up?

Introduction: Congenital melanocytic nevi (CMN) are benign lesions composed of clonal proliferations of melanocytes. Although medium-sized CMN are common and generally remain benign throughout a person's lifetime, they may be precursors of melanoma. There is a limited number of studies focused on the risk of melanoma in solitary, medium-sized, congenital melanocytic nevus; therefore, the incidence of malignant transformation and guidelines for treatment are not well established. Aim: Prompted by the limited data, we conducted this study to gather more information about medium-sized CMN, to optimize clinical care. We share our analysis of surgically removed medium-sized CMN. Material and methods: A total of 10 patients with non-multiple, medium-sized, congenital melanocytic nevus were included in this study. Lesions were removed using surgical procedures. Results: In most of the cases the reason for excision of the medium-sized CMN was evolution of the lesion or aesthetic considerations reported by the patients. In 2 cases, due to the large size of the lesions, serial excisions were performed, while other CMN were removed surgically using simple excision technique. Eight of 10 medium-sized CMN were histologically described as benign, and 2 cases of malignant transformations were reported. Conclusions: According to our clinical experience and knowledge, we recommend managing patients on an individual basis, taking into consideration multiple clinical attributes. In our opinion, long-lasting observation is the management of choice, and if there is need of surgery, we recommend total simple or staged excision depending on nevus size.

Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review.

Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.