Oral Smoothened Inhibitors for Gorlin Syndrome: A Clinical Review.

BACKGROUND: Although smoothened inhibitors (SMOi) have demonstrated efficacy in the management of basal cell carcinoma (BCC), no guidelines are available on how to utilize SMOi in the treatment of Gorlin syndrome (GS). OBJECTIVE: Assess the clinical response to SMOi in GS, provide practical guidance for clinicians, and identify areas for future research. METHODS: Alongside a comprehensive search of Medline and Google Scholar for systemic therapies related to Gorlin Syndrome (GS), expert opinion was specifically sought to provide detailed guidance on the use of SMOi in the management of GS. RESULTS: Intermittent dosing of SMOi and daily dosing had similar efficacy. Intermittent dosing resulted in better compliance with therapy. However, lack of tolerability limited long-term use of SMOi. LIMITATIONS: There are few studies solely on the use of SMOi in GS. Included studies often had a subgroup of GS patients. CONCLUSION: While the adverse events of SMOi, such as vismodegib and sonidegib, may result in their discontinuation during treatment of GS, intermittent dosing may improve compliance. Further research is needed to identify dosing strategies that minimize tumor burden while mitigating side effects to achieve maximum compliance.

Efficacy and safety of the enzymatic mixture - Lipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study.

Purpose: To study the effect of the enzymatic mixture: Lipase, Collagenase and Hyaluronidase in the treatment of submental fat. Methods: A monocentric prospective cohort study including 10 female patients, aged between 18 and 65 years old, who received treatment for submental fat with a mixture of Lipase, Collagenase, and Hyaluronidase. The treatment protocol consisted of one treatment session every 21 days for a total of 3 sessions. In each session, 4 ml of the enzymatic mixture (1 ml of Collagenase GH PB20, 1 ml of Hyaluronidase PB 3000 and 2 ml of Lipase PB 500) + 2 ml of Lidocaine 2% were injected in the submental fat (SMF). Efficacy was assessed four weeks after the last session. Co-Primary Outcome was defined as the improvement of ≥ 1-point in Clinician-Reported and Patient-Reported Sub-mental Fat Rating Scales (CR-SMFRS and PR-SMFRS). Secondary Outcomes included score reductions in Patient-Reported Sub-mental Fat Impact Scale (PR-SMFIS), ≥10% reduction in submental fat pad thickness by ultrasound, and Subject Self-Rating Scale (SSRS) responses of 4, 5, or 6. Results: The Co-Primary outcome was achieved in 9 out of 10 patients. A considerable reduction of 22.8% in the PR-SMFIS was observed. Furthermore, 9 out of 10 patients expressed overall satisfaction with the treatment. Submental fat reduction of more than 10% was observed in 9 out of 10 patients in neutral position and in all patients in flexed position. Adverse effects were only limited to local reactions. Conclusion: The enzymatic mixture of Lipase, Collagenase and Hyaluronidase is an effective and safe minimally-invasive method for the reduction of SMF that can be used alone or in conjunction with other treatment modalities.

Acquired ichthyosis: a clinical review.

Acquired ichthyosis (AI) is a rare, nonhereditary cutaneous disorder that has been associated with numerous neoplastic, infectious, drugs, endocrine, metabolic, autoimmune, and malabsorptive diseases. Review all demographical, clinical, histological, and therapeutic features of AI and focus on all reported associated diseases. We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles on AI, with no limits on publication date, participant age, sex or nationality. Eighty-four articles were included. Total number of included patients was 167 patients with a mean age at presentation of 39 years [range 0.5-85] and a sex ratio M:F of 5:2. The most common malignancy associated with AI is Hodgkin's lymphoma. AI occurred before, simultaneously or after the onset of malignancy or systemic disease. The severity of AI depends on the severity of the underlying disorder and regresses once the disease goes into remission and may also be a marker of disease recurrence or relapse. 8% have been reported to be drug related and all occurred weeks to months after drug intake and resolved after stopping or decreasing the dose of the drug. Data were derived from case reports and observational studies. Limitations include the accuracy of published data, potential patient selection, and reporting bias. AI can be associated with numerous systemic diseases and drugs. Physicians should be particularly alert to these associations to provide adequate screening and management of patients with AI.

Pediatric Keloids and Review of the Efficacy of Current Treatment Modalities.

BACKGROUND: Keloids and hypertrophic scars are the result of excessive fibroblast proliferation and collagen deposition in the wound healing process, leaving patients with irritating and cosmetically displeasing lesions. Despite there being numerous modalities for treatment, keloids are notoriously recalcitrant to therapy and recurrence rates are high. OBJECTIVE: Because many keloids begin to develop during childhood and adolescence, it is important to better understand which treatment options may be best suited toward the pediatric population specifically. METHODS: We reviewed 13 studies that focus specifically on effectiveness of treatment options for keloids and hypertrophic scars in the pediatric population. These studies cover 545 keloids in 482 patients, all aged 18 and younger. RESULTS: Many treatment modalities were used, with multimodal treatment being the most common (76%). There were 92 instances of recurrence, with a total recurrence rate of 16.9%. CONCLUSION: Data from the combined studies suggest that keloid development is less common before adolescence and that higher rates of recurrence are observed among patients who have received monotherapy compared with those who received multimodal treatments. More well-designed studies with standardized ways of assessing outcomes are needed to expand our understanding on how to optimally treat keloids in the pediatric population.

Combination Approaches to Hand Rejuvenation: A Review of the Literature and Discussion.

BACKGROUND: Various noninvasive/minimally invasive modalities for hand rejuvenation exist, and the efficacy and safety of these procedures as both monotherapy and same-day procedures is increasingly being studied. OBJECTIVE: To review data on the efficacy and safety of hand rejuvenation modalities and suggest a practical combination approach for these procedures. METHODS: The PubMed database was queried for peer-reviewed articles regarding hand rejuvenation techniques, including chemical peels, laser and light sources, sclerotherapy, autologous fat transfer, and injectable volumetric fillers. RESULTS: Chemical peels have been studied the least, with most studies evaluating the use of fillers and laser/light-based devices. Most studies reported overall good results with high patient satisfaction. Satisfaction rates were lower in laser/light-based treatments compared with other modalities. Transient erythema, edema, or pain after procedures was common; most studies did not report serious postprocedure complications. Importantly, there was no significant increase in adverse effects after same-day procedures. CONCLUSION: Using same-day procedures allows practitioners to address hand rejuvenation from different aspects, seems to improve outcomes, and reduces time spent in the office for patients. The authors suggest a practical framework for combining cosmetic approaches to achieve the most optimal outcome for hand rejuvenation.

Merkel cell carcinoma: Epidemiology, disease presentation, and current clinical practice outcomes.

Using the National Cancer Database, we introduce the findings of a retrospective investigation of the largest cohort of cases with Merkel cell carcinoma (N = 20,829). A decreasing proportion of stage I (P = .0004) and stage II (P = .0065) Merkel cell carcinoma among skin cancers was complemented by an increasing proportion of stage III disease (P < .0001). A predominance of non-Hispanic White (96.4%), male (62.6%) patients with a mean age of 74.5 ± 10.8 years and Medicare coverage (73.5%) was observed. Stage I was the most common presenting stage at diagnosis (29.2%), followed by stages II (12.7%), III (11.0%), and IV (3.8%). Most Merkel cell carcinoma tumors grew outside the head and neck (53.4%) and showed a nodular growth pattern (66.0%) but no extracapsular lymph node (90.5%) or lymphovascular involvement (63.8%). Narrow-margin excision and radiation therapy (RT) were used in 75.2% and 56.3% of tumors, respectively. Wide-margin excision lead to improved overall survival (P < .001) versus narrow-margin excision, particularly in stage III (difference in the median overall survival rate [ΔmOS], 23.7 months; P < .001). RT showed a significant OS benefit (P =.006), most pronounced in stage II (ΔmOS, 37.8 months) followed by stage I (ΔmOS, 16.1 months; P < .001). The survival benefit with primary-site RT (ΔmOS, 24.0 months) was higher than that with primary-site/lymph node RT (ΔmOS, 5.2 months; P < .001). Wide-margin excision independently predicted improved OS (hazard ratio, 0.577; 95% CI, 0.403-0.826; P = .003) versus narrow-margin excision and RT predicted better OS (hazard ratio, 0.608; 95% CI, 0.424-0.873; P = .007) versus no RT on multivariable analysis.

Social media voices on the treatment of skin psoriasis with biologics.

Social media is an outlet for patients to share medical experiences with a large audience. However, the impact of such content on individual patient treatment decisions has yet to be fully explored. We characterized patient experiences posted on social media surrounding biologic use for skin psoriasis. We analyzed content from YouTube, Instagram, and TikTok and identified patient experiences with a variety of biologics, most commonly Humira (20.7%), Cosentyx (14.0%), and Stelara (14.0%). The biologic was described as burdensome in about half of all videos/posts (46.4%), and the most commonly cited reasons included adverse effects or abnormal blood tests (12.8%), cost or insurance issues (11.7%), lack or loss of efficacy (11.7%), and pain with injection or injection site reaction (11.7%). Nevertheless, the majority (60.9%) of videos/posts reported an overall positive experience with a biologic for their skin psoriasis, which may inspire reluctant patients to try a biologic recommended by their physician.

Pediatric discoid lupus erythematosus: Short report.

Pediatric discoid lupus erythematosus (DLE) is a rare inflammatory skin disorder. This article aims to review all the available clinical and therapeutic data on reported cases of pediatric DLE. A systematic review of the literature was conducted using Pubmed and Embase with no limitation on publication date, sex, or nationality. Thirty-two articles were included with 201 cases, a mean age of 8.9 years (2 months-16 years) and an F:M ratio of 1.8. Lesions were located on the head and neck in 58.5% and were disseminated in 36.5% of the cases. Associated symptoms were pruritus (10.1%) and alopecia (8.7%). 12% progressed to systemic lupus erythematosus (SLE) and 14.5% had concurrent SLE. The only statistically significant predictor for progression to SLE was the onset of symptoms before or at the age of 10 years (p = 0.004). Treatments consisted mainly of sunscreens (26.3%), topical corticosteroids (24.3%), and oral antimalarials (25.3%). Retrospective nature of the included studies, small sample size, short duration of follow-up and limited data on the patients' demographics. Pediatric DLE affects mostly the head and neck, with a female predominance, a possible association with inflammatory and autoimmune diseases, and overall good treatment response and prognosis.

Lichen Planus Pigmentosus Associated with Topical Olive Oil Application.

A 45-year-old brown-skinned woman presented with a 5-year history of asymptomatic grayish brown lesions on the face, arms, and legs. She had no medical history of previous diseases or contact dermatitis. She revealed that she had used olive oil all over her body for the last 8 years every other day. Physical examination showed multiple, well-defined, oval-shaped, dark brown, smooth-surfaced macules with no elevated active borders (Figure 1). There were no associated lesions on the nails, scalp, or mucosae. Serologic tests for autoantibodies and hepatitis A, B, and C virus infections were non-reactive. A patch test for olive oil was also negative. A skin biopsy revealed epidermal atrophy, orthokeratosis, basal cell vacuolation, and a band-like lymphocytic infiltrate in the upper portion of the dermis with abundant colloid bodies and pigmentary incontinence in the papillary dermis (Figure 2). A diagnosis of lichen planus pigmentosus (LPP) was confirmed, and betamethasone butyrate propionate was applied for 2 months over the lesions, with a limited therapeutic effect. Clinical improvement was seen only after she discontinued the olive oil application (Figure 3).

Management of Darier disease: A review of the literature and update.

Darier disease (DD) is a rare type of inherited keratinizing disorder with no definitive therapeutic approach. The objective of this study is to provide a detailed literature review of all the available treatment modalities of Darier disease, including those that are both surgical and non surgical, to compare their efficacies and to propose a novel therapeutic approach. A complete search of the literature for all articles describing the different treatments of Darier disease, with no restrictions on patients' ages, gender or nationalities, was performed with the use of PubMed. A total of 68 articles were included in the study: 3 prospective studies, 44 case reports/case series and 21 letters/correspondences/clinical images. The treatments described were topical, oral or physical. Retinoids (isotretinoin, tazarotene and adapalene) and fluorouracil were the two most effective topical treatments. Oral retinoids were the most effective oral therapy and were prescribed in the cases of generalized Darier disease. For localized and resistant skin lesions, physical therapies including surgical excision, dermabrasion and CO2 laser ablation were the first line choices. Limitations of this article include the inability to verify the accuracy of the published data, the relatively small sample size, the absence of randomized controlled clinical trials and possible unidentified confounding factors in various studies. In every therapeutic approach to Darier disease, consideration of patient comorbidities, disease distribution, severity and treatment accessibility is essential. Large and randomized clinical trials are necessary for the comparison of the efficacy and the safety of all the treatments of Darier disease and settling a consensus for management.

Nonsurgical Methods for Penile Augmentation: A Systematic Review.

BACKGROUND: There is no standardized approach for nonsurgical techniques for penile augmentation despite the increase of demand for this intervention. OBJECTIVE: To compare the efficacy and safety between different injection techniques. MATERIALS AND METHODS: On October 8, 2019, a literature search was performed on PubMed, Embase, Ovid, and Cochrane database. All articles describing penile augmentation were included. RESULTS: Thirteen studies were included in this article with a total of 1,311 patients. Five studies were prospective cohort. The most commonly described technique was hyaluronic acid fillers with a total of 4 articles and 205 patients. The mean injected volume ranged from 20 to 40 mL. In all included studies, a minority of patients had side effects, but some had disabling complications. CONCLUSION: There are no defined clinical guidelines for penile augmentation techniques implemented yet. Hyaluronic acid seems to be safe, efficient, and with a high satisfaction score. Further randomized control trials are warranted. EBM LEVEL OF EVIDENCEBASED MEDICINE: 2a.

Comparison of gabapentin and doxepin in the management of uremic pruritus: A randomized crossover clinical trial.

Gabapentin and doxepin are well-known treatments of uremic pruritus in hemodialysis patients but no head-to-head studies were conducted to date. The aim of this trial is to compare the efficacy and the tolerability of gabapentin and doxepin in the treatment of uremic pruritus in hemodialysis patients. A single-blind crossover randomized trial was conducted that included hemodialysis patients with uremic pruritus. Patients were randomized to receive 10 mg doxepin daily or 100 mg gabapentin for 4 weeks and the two groups were treated conversely for another 4 weeks after a 4-week washout period. Eighty-five patients were screened for eligibility. Thirty-one met the inclusion criteria and four were excluded. Sixteen patients agreed and signed the consent and two withdrew from the study. VAS scores at baseline were 6.71 and 6.14, and dropped to 0.57 and 2.35 at week 4 in the gabapentin and doxepin groups, respectively. Mean scores of the 5-Domain Itch Scale (5-D) at baseline were 14.71 and 14.64, and dropped to 5.78 and 7.57 at week 4 in the gabapentin and doxepin groups, respectively. Mean scores of the Dermatology Life Quality Index (DLQI) at baseline were 9.6429 and 8.7857, and dropped to 0.71 and 3.35 at week 4 in the gabapentin and doxepin groups, respectively. Reductions in Visual Analog Scale (VAS), 5-D and DLQI were statistically significant (P < .05). No serious side effects were recorded. Limitations of this study include single-blind design, small number of included cases and lack of placebo control. Gabapentin was more effective than doxepin in decreasing uremic pruritus severity and improving quality of life of these patients.