Optical coherence tomography for assessment of epithelialization in a human ex vivo wound model.

The ex vivo human skin wound model is a widely accepted model to study wound epithelialization. Due to a lack of animal models that fully replicate human conditions, the ex vivo model is a valuable tool to study mechanisms of wound reepithelialization, as well as for preclinical testing of novel therapeutics. The current standard for assessment of wound healing in this model is histomorphometric analysis, which is labor intensive, time consuming, and requires multiple biological and technical replicates in addition to assessment of different time points. Optical coherence tomography (OCT) is an emerging noninvasive imaging technology originally developed for noninvasive retinal scans that avoids the deleterious effects of tissue processing. This study investigated OCT as a novel method for assessing reepithelialization in the human ex vivo wound model. Excisional ex vivo wounds were created, maintained at air-liquid interface, and healing progression was assessed at days 4 and 7 with OCT and histology. OCT provided adequate resolution to identify the epidermis, the papillary and reticular dermis, and importantly, migrating epithelium in the wound bed. We have deployed OCT as a noninvasive tool to produce, longitudinal "optical biopsies" of ex vivo human wound healing process, and we established an optimal quantification method of re-epithelialization based on en face OCT images of the total wound area. Pairwise statistical analysis of OCT and histology based quantifications for the rate of epithelialization have shown the feasibility and superiority of OCT technology for noninvasive monitoring of human wound epithelialization. Furthermore, we have utilized OCT to evaluate therapeutic potential of allogeneic adipose stem cells revealing their ability to promote reepithelialization in human ex vivo wounds. OCT technology is promising for its applications in wound healing and evaluation of novel therapeutics in both the laboratory and the clinical settings.

Efficacy of Nd:YAG laser therapy for the treatment of verrucae: a literature review.

Verrucae are benign epithelial proliferations, characteristically 1-20 mm in diameter, caused by human papilloma virus (HPV) infection occurring on the skin and mucosa (Photomed Laser Surg 33(6):338-42, 2015; Lasers Med Sci 29(3):1111-6, 2014). Prevalence of verrucae is 5-20% in children and young adults with peak incidence reported during teenage years (Lasers Med Sci 29(3):1111-6, 2014; J Am Acad Dermatol 22(4):547-66, 1990; J Korean Med Sci 24(5):889-93, 2009). Patients often express significant displeasure with quality of life due to this cosmetic insecurity, as well as functional problems and physical discomfort when they occur on palms of hands and soles of feet. Traditional therapeutic options for warts, such as topical salicyclic acid, topical imiquimod, bleomycin injections, cryotherapy, surgical excision, and electrocautery, have proven somewhat effective but often lead to high recurrence rates or scarring (Photomed Laser Surg 33(6):338-42, 2015). Laser therapy offers an alternative solution by employing selective tissue destruction with minimal risks. We performed a broad literature search in PubMed to obtain all available published articles that studied the treatment of verrucae on the skin with 1064-nm neodymium-doped yttrium aluminum garnet laser. This laser is specifically suited for verruca treatment due to its deeply penetrating 1064-nm wavelength and relatively low risk of pigmentation changes in dark skin types (Photomed Laser Surg 33(6):338-42, 2015). Laser therapy is effective in the treatment of verrucae and has enabled clinicians to provide direct, targeted treatment of warts.

Efficacy of fractional lasers in treating alopecia: a literature review.

Hair loss stemming from different types of alopecia, such as androgenic alopecia and alopecia areata, negatively affects over half the population and, in many circumstances, causes serious psychosocial distress. Current treatment options for alopecia, such as minoxidil, anthralin, and intralesional corticosteroids, vary efficacy and side effect profiles. It is known that low-level laser/light therapies (LLLT), or photobiomodulations, such as the US FDA-cleared HairMax Lasercomb®, He-Ne laser, and excimer laser, are relatively affordable, user-friendly, safe, and effective forms of treatment for hair loss. While less is known about the effectiveness of fractional lasers for combating hair loss, research suggests that by creating microscopic thermal injury zones, fractional lasers may cause an increase in hair growth from a wound healing process, making them potential therapeutic options for alopecia. A literature review was performed to evaluate the effectiveness of fractional lasers on hair regrowth. The specific fractional laser therapies include the 1550-nm nonablative fractional erbium-glass laser, the ablative fractional 2940-nm erbium:YAG laser, and the ablative fractional CO2 fractional laser. Additional randomized controlled trials are necessary to further evaluate the effectiveness of the lasers, as well as to establish appropriate parameters and treatment intervals.

Utilization of Optical Coherence Tomography in the Evaluation of Cherry Hemangiomas.

Cherry hemangiomas are common vascular proliferative lesions that can be concerning from a cosmetic perspective. Laser therapy is often used to eradicate cherry hemangiomas, but some lesions require multiple treatments or do not resolve at all. The suboptimal response to laser treatment may be due to limitations in penetration depth by vascular lasers such as the pulsed dye laser. Optical coherence tomography is a low-energy, light-based imaging device that can evaluate the depth and extent of vascular lesions such as cherry hemangiomas by allowing visualization of tissue structure and blood vessel architecture, which cannot be appreciated by clinical or dermatoscopic examination alone. We present optical coherence tomography images of a cherry hemangioma to demonstrate the precision and resolution of this imaging modality. Optical coherence tomography provides valuable information that has the potential to predict response to laser therapy without unnecessary attempts. Future prospective studies will determine its value for this purpose.

J Drugs Dermatol. 2016;15(6):713-714.

The picosecond laser for tattoo removal.

The prevalence of tattoos continues to grow as modern society's stigma towards this form of body art shifts towards greater acceptance. Approximately one third of Americans aged 18-25 and 40 % of Americans aged 26-40 are tattooed. As tattoos continue to rise in popularity, so has the demand for an effective method of tattoo removal such as lasers. The various colors of tattoo inks render them ideal targets for specific lasers using the principle of selective photothermolysis. Traditional laser modalities employed for tattoo removal operate on pulse durations in the nanosecond domain. However, this pulse duration range is still too long to effectively break ink into small enough particles. Picosecond (10-12) lasers have emerged at the forefront of laser tattoo removal due to their shorter pulse lengths, leading to quicker heating of the target chromophores, and consequently, more effective tattoo clearance. Recent studies have cited more effective treatment outcomes using picosecond lasers. Future comparative studies between picosecond lasers of various settings are necessary to determine optimal laser parameters for tattoo clearance.

Lasers and nevus of Ota: a comprehensive review.

Nevus of Ota is a benign dermal melanocytic nevus that typically affects Asian children and women. The nevus presents as unilateral blue-gray hyperpigmented macules and patches scattered along the first and second divisions of the trigeminal nerve. Individuals with nevus of Ota experience emotional and psychosocial distress related to cosmetic disfigurement and often look for treatment options. Unfortunately, even when treated early, lesions of nevus of Ota are still difficult to treat. The use of lasers for the treatment of nevus of Ota lesions has become helpful in the management of dermal nevi. Currently, Q-switched (QS) lasers have been the most studied and demonstrated positive results for treatment of nevus of Ota. The purpose of this review article is to summarize the clinical efficacy and side effects associated with QS lasers and the treatment of nevus of Ota lesions.

Laser and light-based treatments of venous lakes: a literature review.

Venous lake is a benign vascular malformation commonly seen in elderly patients, typically arising in sun-exposed areas of the body. Patients often seek treatment to prevent recurrent bleeding or because they find the lesion cosmetically unacceptable. Venous lake may negatively affect quality of life, due to the cosmetic disfigurement it can create and the resulting psychological distress. Traditional treatments, such as surgical excision, cryosurgery, sclerotherapy, and electrocoagulation, result in varying degrees of success and can cause discomfort. Laser- and light-based treatment modalities may offer a safe and effective alternative, as numerous studies have shown their benefit in the treatment of venous lakes, particularly with the long-pulsed 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG). Although various types of lasers and lights have been studied, there remains a lack of general consensus as to which one is the superior laser modality. Further studies that establish standardized protocols to compare the results of using different types of laser treatments are warranted.

Sorafenib-induced Facial Acneiform Eruption.

Sorafenib is a multikinase inhibitor that is used to treat hepatocellular carcinoma by inhibiting tumor cell growth and angiogenesis. Cutaneous adverse events of sorafenib are commonly reported, with alopecia and hand-foot skin reactions most frequently encountered. Acneiform eruptions represent rare adverse events that have only been reported at high doses of sorafenib. We present a patient who started low dose sorafenib for hepatocellular carcinoma and subsequently developed a fulminant facial acneiform eruption in the absence of other cutaneous adverse events. Treatment included topical clindamycin and tretinoin with some improvement. Facial acneiform eruption represents a rare consequence of sorafenib that has not previously been described at low doses. Additionally, acneiform papules in the absence of other cutaneous adverse events is unusual. The cutaneous mechanism is not well understood but may be related to indirect epidermal growth factor receptor inhibition or direct cytotoxic effects on eccrine glands. Topical treatment produces only minimal improvement in patients who continue sorafenib therapy. Discontinuation of the drug is usually unwarranted except in special circumstances.

Hypomyopathic Dermatomyositis Presenting with Idiopathic CD4 T-lymphocytopenia and Delayed Anti-MDA5 Positivity.

A 47-year-old Haitian male with no known past medical history was admitted to the hospital for gradually progressive dyspnea, nonproductive cough, and weight loss. He also endorsed a one-year history of joint pains. He was febrile and tachycardic and in mild respiratory distress. Other pertinent physical examination findings included diffuse inspiratory crackles, digital ulcers, and symmetric swelling of the wrists, elbows, shoulders, and knees. He was found to have a right basilar consolidation on chest computed tomography (CT) and was placed on antibiotics for presumptive pneumonia. His CD4 count was 158 cells per microliter despite testing negative for human immunodeficiency virus (HIV). A thorough infectious workup was unrevealing, and he did not improve with antibiotics. He had a weakly positive anti-nuclear antibody (ANA) with an otherwise negative rheumatologic workup. Creatinine kinase and aspartate aminotransferase were mildly elevated in the absence of overt muscle weakness. A myositis panel, including melanoma differentiation-associated protein five (anti-MDA5) antibody, was negative at the time. He was discharged on a short course of prednisone without a definitive diagnosis. He returned several months later with worsening respiratory symptoms. At this time, a lung biopsy revealed interstitial lung disease. Repeat myositis panel demonstrated anti-MDA5 positivity. The patient was also found to have new-onset non-ischemic heart failure with reduced ejection fraction. A diagnosis of hypomyopathic dermatomyositis was made based on clinical, laboratory, and imaging findings. The patient was restarted on prednisone, and mycophenolate mofetil was subsequently initiated for maintenance therapy.

Diagnosis and Management of Pearly Penile Papules.

Pearly penile papules (PPP) are common, benign lesions that appear on the corona of the glans penis during adolescence or early adulthood. Despite their benign nature, PPP are known to cause significant distress because of their resemblance to sexually transmitted infections such as condyloma acuminata. PPP can be clinically distinguished based on their uniform, dome-shaped papules that orient in one to two rows around the glans penis. There is no association between PPP and sexually transmitted infections, and treatment is generally reserved for patients with excessive concern. Physicians should be aware of this distinction in order to adequately reassure anxious patients. For patients who still desire treatment after counseling, cryotherapy and laser therapy represent two reliable treatment options with low rates of recurrence.

Laser and Light Treatments for Hair Reduction in Fitzpatrick Skin Types IV-VI: A Comprehensive Review of the Literature.

Unwanted facial and body hair presents as a common finding in many patients, such as females with hirsutism. With advances in laser and light technology, a clinically significant reduction in hair can be achieved in patients with light skin. However, in patients with darker skin, Fitzpatrick skin types (FST) IV-VI, the higher melanin content of the skin interferes with the proposed mechanism of laser-induced selective photothermolysis, which is to target the melanin in the hair follicle to cause permanent destruction of hair bulge stem cells. Many prospective and retrospective studies have been conducted with laser and light hair-removal devices, but most exclude patients with darkly pigmented skin, considering them a high-risk group for unwanted side effects, including pigmentation changes, blisters, and crust formation. We reviewed the published literature to obtain studies that focused on hair reduction for darker skin types. The existing literature for this patient population identifies longer wavelengths as a key element of the treatment protocol and indicates neodymium-doped yttrium aluminum garnet (Nd:YAG), diode, alexandrite, and ruby lasers as well as certain intense pulsed light sources for safe hair reduction with minimal side effects in patients with FST IV-VI, so long as energy settings and wavelengths are appropriate. Based on the findings in this review, safe and effective hair reduction for patients with FST IV-VI is achievable under proper treatment protocols and energy settings.

Vascular Features of Nail Psoriasis Using Dynamic Optical Coherence Tomography.

BACKGROUND: Nail psoriasis is a painful and disfiguring nail disease that often leads to invasive biopsies. Dermoscopy of the hyponychium can be useful in the diagnosis showing twisted coiled vessels. Structural features of nail psoriasis have been described with optical coherence tomography (OCT). OBJECTIVES: To investigate vascular features of nail psoriasis using dynamic OCT. METHODS: This was an observational, prospective, controlled study in which psoriasis patients with psoriatic nail changes and healthy control patients underwent OCT imaging of the distal nail plate and proximal nail fold. Vertical and horizontal OCT images were analyzed to describe structural and vascular features and to quantify blood flow at depth. RESULTS: Sixteen psoriatic nails and 16 control nails were included. Psoriatic nails had significantly increased blood flow in the proximal nail fold at depths of 0.72 mm (p = 0.035) and 0.76 mm (p = 0.027). Nail thickness was significantly greater in psoriatic nails compared to control nails (p = 0.0016). Compared to control nails, psoriatic nails had dilated, disorganized blood vessels superficially in the proximal nail fold. LIMITATIONS: The main limitation of our study is the relatively small sample size. CONCLUSIONS: OCT can identify structural and vascular features specific to nail psoriasis.

Hedgehog Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal Cell Carcinoma: A Systematic Review and Pooled Analysis of Interventional Studies.

IMPORTANCE: Hedgehog pathway inhibitors (HPIs) were made available by US Food and Drug Administration approval in 2012 for vismodegib and 2015 for sonidegib. Both target the Smoothened molecule and are indicated for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC). OBJECTIVE: To evaluate clinical experience with HPIs, including efficacy and adverse effects. DATA SOURCES: We conducted a systematic review in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EMBASE, using search terms "vismodegib," "sonidegib," "Erivedge," "Odomza," "basal cell carcinoma," and "BCC." STUDY SELECTION: We included clinical trials, retrospective medical record reviews, and prospective case series that used HPIs for the treatment of laBCC or mBCC in human subjects. Individual case reports and limited, retrospective case series were excluded from our review. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 2 reviewers on a predesigned, standardized form. MAIN OUTCOMES AND MEASURES: The following data were recorded: number of patients with laBCC or mBCC, dose and frequency of drug administration, median duration of treatment, clearance and recurrence rates, and adverse effects. RESULTS: Eleven vismodegib articles (published between 2009 and 2015) met criteria for inclusion, and 8 articles were able to be pooled for analysis. The 8 pooled articles included 744 total patients with 704 patients clinically evaluable. Sonidegib did not yield enough publications for a formal analysis. Objective response to vismodegib for laBCC had a weighted average of 64.7% (95% CI, 63.7%-65.6%); complete response averaged 31.1% (95% CI, 30.4%-31.8%). Objective response for mBCC was 33.6% (95% CI, 33.1%-34.2%); complete response averaged 3.9% (95% CI, 3.3%-4.4%). Median duration of therapy was 35.8 weeks (95% CI, 35.1-36.5 weeks). CONCLUSIONS AND RELEVANCE: In a systematic review of HPIs for laBCC and mBCC, vismodegib, but not sonidegib, had enough studies to warrant a pooled analysis. Vismodegib was identified to have a significant, consistent effect on the median duration of therapy of laBCC and mBCC. While mBCC responses are superior to any traditional approach, the response rate for laBCC might be considered in the context of other standard treatment options including surgery and radiation therapy.

5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Comprehensive Review of the Literature.

Hypertrophic (HTSs) and keloid scars are common dermatological complaints produced by disruption of the normal wound-healing process. Despite a wide array of therapeutic options available to treat these lesions, HTSs and keloids continue to pose a significant challenge to clinicians in everyday practice. The chemotherapeutic drug 5-fluorouracil (5-FU) is a well-known treatment option reserved for recalcitrant HTSs and keloid lesions. We present clinicians with a comprehensive review of the published data concerning the use of 5-FU in the treatment of HTSs and keloids. The current evidence suggests that 5-FU is a safe and practical alternative for the treatment of HTSs and keloids as it may substantially improve the appearance of proliferative scars and reduce the chance of recurrence. This therapeutic option is most effective in conjunction with adjuvant therapy such as corticosteroids. Additional randomized controlled clinical trials with large sample sizes should be conducted to corroborate the existing efficacy and safety data in patients with HTSs and keloids.

Laser and Light Treatments for Striae Distensae: A Comprehensive Review of the Literature.

Striae distensae (SD) are common dermatologic lesions that often arise as a result of rapid weight change, certain endocrine conditions, or prolonged exposure to steroids. SD initially present as raised edematous plaques (striae rubra), after which they become white and atrophic (striae alba) owing to local breakdown and reorganization of collagen and elastin. There currently exists no reliable treatment option, though numerous topical applications have been attempted. Lasers and light represent emerging noninvasive therapies that have demonstrated some success targeting vascular chromophores in striae rubra and stimulating collagen and elastin production in striae alba. An extensive literature review was performed to gather all available articles studying laser and light treatments for SD. Lasers and light can significantly improve the appearance of both striae rubra and striae alba. Generally, striae rubra are more responsive to therapy and can be treated successfully with a variety of lasers without major adverse effects. Fractional lasers exhibit the strongest results for striae alba repigmentation and collagen induction, and several other lasers produce temporary repigmentation. Lasers in combination with other modalities such as topical agents and additional energy devices have also demonstrated promising preliminary results; however, large comparative studies are necessary to validate these outcomes.

Origin of the Zika virus revealed: a historical journey across the world.

BACKGROUND: Zika virus (ZIKV) is an arbovirus within the Flaviviridae family, the recent spread of which has promoted public concern. METHODS: This study outlines the clinical features, potential for teratogenicity, diagnosis, and treatment of ZIKV infection. RESULTS: Zika virus is transmitted through the bite of an infected Stegomyia (= Aedes) mosquito, blood transfusion, sexual intercourse, and perinatal routes. Infection has been characterized as mildly symptomatic. Symptoms include mild fever, headache, arthralgia, myalgia, non-purulent conjunctivitis, and a pruritic maculopapular rash. It is rarely life-threatening, but both Guillain-Barré syndrome and fetal microcephaly have been reported. ZIKV belongs to the same family as bovine viral diarrhea virus, which causes hydrocephalus and microcephaly in newborn calves, and hepatitis C virus, which can be vertically transmitted in human pregnancies, and hence there remains concern for potential similarities. Diagnostic methods include polymerase chain reaction performed in blood samples during infection, and in urine and saliva. Pregnant women undergo antibody testing for immunoglobulin M. Treatment involves supportive care, and acetaminophen and antihistamines to control symptoms. CONCLUSIONS: Although there was no evidence of the circulation of ZIKV in the Western hemisphere prior to 2014, the global spread of Stegomyia aegypti and increases in urban populations and international travel have fostered its evolution. Adherence to current guidelines for the prevention of ZIKV transmission is especially relevant in regions experiencing ongoing outbreaks. Concern for microcephaly in newborns warrants further investigation into the potential long-term effects of ZIKV infection, especially in relation to reproductive health and mother-fetus transmission.