Causes of Injury and Litigation in Cutaneous Laser Surgery: An Update From 2012 to 2020.

OBJECTIVE: To identify common causes of injury and liability claims related to cutaneous laser surgery from 2012 to 2020. MATERIALS AND METHODS: Search of online national legal database of public legal documents regarding cutaneous laser surgery litigation. RESULTS: From 2012 to 2020, 69 cases of liability claims due to a cutaneous laser surgery device were identified. Of these, 49 (71%) involved a nonphysician operator (NPO); 12 incidents (17%) involved non-core physician operators performing the procedure; 6 cases (9%) involved a plastic surgeon operator; and 2 cases (3%) involved a dermatologist operator. Laser hair removal was most litigated (44 cases, 64%), followed by laser skin rejuvenation (20 cases, 30%). Thirty-six of 69 cases had a discernible outcome, 53% (n = 19) rendered judgements in favor of the plaintiff, with a mean indemnity payment of $320,975 (range, $1,665-$1.5 million). CONCLUSION: Previous work evaluating trends in laser surgery litigation from 1985 to 2012 identified increasing injury and legal action when performed by NPOs. Data from this study are consistent with these previous findings. Both studies demonstrate that NPOs account for most cases of legal action with an increasing proportion of cases being performed by NPOs. In this study, unsupervised NPOs comprise nearly three-quarters of laser surgery lawsuits, but the data may underestimate the frequency of injury and litigation caused by unsupervised NPOs.

Pediatric Laser Therapy in Pigmented Conditions.

Advances in laser therapy have led to novel therapeutic approaches to common pediatric skin conditions. As a non-invasive alternative to surgical options, laser therapy is efficacious in treating a broad range of conditions, from vascular and pigmented lesions to tattoo and hair removal. This paper reviews the basic mechanics of laser therapy, its role in common pigmented pediatric dermatoses, and special considerations for this unique age group.

A molecular mechanism for IL-4 suppression of loricrin transcription in epidermal keratinocytes: implication for atopic dermatitis pathogenesis.

Skin barrier defects play an important role in atopic dermatitis (AD) pathogenesis. Loricrin, an important barrier protein suppressed in human AD, is down-regulated by IL-4 in keratinocytes. However, the molecular mechanism is unknown. Since loricrin transcription requires p300/CBP, and Stat6 also recruits this common coactivator for its stimulated factors, we hypothesize that IL-4-activated Stat6 competes for the available endogenous p300/CBP, leading to loricrin transcription inhibition. First, we showed that loricrin is suppressed in the skin of IL-4 transgenic mice, an AD mouse model. In human keratinocytes, IL-4 down-regulation of loricrin is abrogated by a pan-Jak inhibitor, suggesting that the Jak-Stat pathway is involved. To further investigate the downstream molecular mechanism, we transfected HaCat cells with a loricrin promoter and then treated them with either IL-4 or vehicle. Not surprisingly, IL-4 greatly suppressed the promoter activity. Interestingly, this suppression was prevented when we knocked down Stat6, indicating that Stat6 participates in IL-4 regulation of loricrin. A Stat6-specific inhibitor confirmed the knockdown study. Finally, IL-4 suppression of loricrin was reversed with transfection of a CBP expression vector in a dose-dependent manner. Taken together, for the first time, we delineate a molecular mechanism for IL-4 down-regulation of loricin expression in human keratinocytes, which may play an important role in AD pathogenesis.

Diacerein inhibits the pro-atherogenic & pro-inflammatory effects of IL-1 on human keratinocytes & endothelial cells.

We investigated IL-1-induced regulation of genes related to inflammation and atherogenesis in human keratinocytes and endothelial cells, and if 'diacerein', an oral IL-1 inhibiting drug currently approved for use in osteoarthritis, would reverse IL-1's effects on these cells. Primary human keratinocytes and coronary artery endothelial cells were treated with either IL-1α or IL-1ß, with and without diacerein. Using PCR-array, we assessed differential gene-expression regulated by IL-1 and diacerein. We identified 34 pro-atherogenic genes in endothelial cells and 68 pro-inflammatory genes in keratinocytes significantly (p<0.05) regulated at least 2-fold by IL-1, in comparison to control. Diacerein completely or partially reversed this regulation on almost all genes. Using ELISA, we confirmed diacerein's ability to reverse IL-1-driven gene-regulation of 11 selected factors, at the protein level. The results support a novel idea that diacerein acts as an inhibitor of the pro-atherogenic and pro-inflammatory effects of IL-1. Diacerein may have therapeutic applications to diminish IL-1-induced skin inflammation in psoriasis and attenuate IL-1-induced development of atherosclerosis. Further investigation into diacerein's effect on skin inflammation, atherogenesis and cardiovascular risk in animal models or humans is warranted.

Malignant syphilis: ostraceous, ulceronecrotic lesions in a patient with human immunodeficiency virus.

We present a 36-year-old HIV-positive man with a sixweek history of spreading, ulcerative, and necroticcutaneous lesions. Laboratory and histopathologicexamination revealed syphilis. This case of malignantsyphilis, also known as lues maligna, is an uncommonvariant of this sexually transmitted infection. This casehighlights the importance of including malignantsyphilis in the differential diagnosis of patientspresenting with a disseminated ulcerative andnecrotic rash, especially in individuals with HIV.

Therapeutic Synergy, Neutrality, and Antagonism: Combination Treatment in Dermatology.

Dermatologists frequently employ combination therapy to treat various diseases, but the evidence to support the use of such combinations is often lacking. Synergy is an appealing although somewhat ambiguous concept in medicine. Utilizing synergy allows clinicians to provide the most efficacious combination of treatments to patients, while potentially minimizing adverse effects and reducing the development of drug resistance. Definitions of synergy vary, but ultimately converge on finding a therapeutic advantage in combining treatments. Here we discuss the concept of 'therapeutic synergy', which can be defined as an increase in the efficacy of a combination of treatments in comparison to any of its individual parts alone. We review the concept of therapeutic synergy in dermatology by discussing some of the evidence regarding combination therapies utilized in the management of atopic dermatitis, acne vulgaris, psoriasis, and cutaneous lupus erythematosus. Further meaningful investigation of therapeutic synergy and its applications in dermatology should be undertaken.

J Drugs Dermatol. 2016;15(10):1203-1207.

Differential expression of inflammation-related genes in IL-4 transgenic mice before and after the onset of atopic dermatitis skin lesions.

IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD), a common chronic inflammatory skin disease. We have generated IL-4 transgenic (Tg) mice by over-expressing IL-4 in the epidermis. These mice spontaneously develop chronic pruritic inflammatory skin lesions, which meet the clinical and histological diagnostic criteria for human AD. Systemic survey of immune-related genes in this mouse model, however, has not been performed. In this study, we utilize PCR array technique to examine hundreds of inflammation-related genes in the IL-4 Tg mice before and after the onset of skin lesions as well as in their wild type (WT) littermates. Only those genes with at least 2-fold up-regulation or down-regulation and with a P-value of less than 0.05 in comparison to WT controls were identified and analyzed. In the skin lesions, many chemokines, pro-inflammatory cytokines, and other AD-related factors are dysregulated compared to the wild type mice. Particularly, CXCL5, IL-1ß, IL-24, IL-6, oncostatin M, PTGS2, FPR1 and REG3γ are up-regulated several hundred-fold. In the pre-lesional group that shows no obvious skin abnormality on clinical observation, 30 dysregulated genes are nevertheless identified though the fold changes are much less than that of the lesional group, including CCL6, CCL8, CCL11, CCL17, CXCL13, CXCL14, CXCR3 and IL-12Rß2. Finally using ELISA, we demonstrate that 4 most dramatically up-regulated factors in the skin are also elevated in the peripheral blood of the IL-4 Tg mice. Taken together, our data have identified hundreds of dysregulated factors in the IL-4 Tg mice before and after the onset of skin lesions. Future detailed examination of these factors will shed light on our understanding of the development and progression of AD and help to discover important biomarkers for clinical AD diagnosis and treatment.

Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management.

IMPORTANCE: Atopic dermatitis (AD) is a common skin condition treated by dermatologists, allergists, pediatricians, and primary care physicians. Several treatment guidelines and therapeutic parameters exist for the management of this disease. Health care professionals may be unaware of guidelines created by specialty organizations other than their own. OBJECTIVE: To review, compare, and contrast the most recent AD management guidelines. EVIDENCE REVIEW: The guidelines for AD management published by the American Academy of Dermatology 2014 work group were compared with those created by the 2012 Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. International guidelines created by the 2012 European Task Force on Atopic Dermatitis and the 2013 Asia-Pacific Consensus Group for Atopic Dermatitis were also considered. FINDINGS: Several differences among the guidelines suggest that there may be disparity in the perceptions of AD between US dermatologists and allergists and health care professionals in other areas of the world. There are notable differences among the guidelines regarding the recommendations for the use of diluted bleach baths, vitamin D, and environmental modifications. CONCLUSIONS AND RELEVANCE: Comparison of different guidelines may ultimately augment knowledge of treatment strategies and enhance realization of biases in the understanding and management of AD.

Association of Vitiligo and Alopecia Areata With Atopic Dermatitis: A Systematic Review and Meta-analysis.

IMPORTANCE: Previous studies found conflicting results as to whether atopic dermatitis (AD) is increased in patients with vitiligo and alopecia areata (AA). OBJECTIVE: To compare the prevalence of AD between patients with either vitiligo or AA and those without these disorders by performing a meta-analysis of observational studies. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, Google Scholar, and a manual search of 12 additional journals between 1946 and April 5, 2014. STUDY SELECTION: Observational studies published in any language that compared the prevalence of AD among patients with and without either vitiligo or AA. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent investigators. Quality of evidence was assessed using the Newcastle-Ottawa Scale and Methodological Evaluation of Observational Research checklist. A meta-analysis of studies assessing AD, vitiligo, and/or AA was performed using a fixed-effects model to estimate pooled odds ratios (ORs). Subset analyses were performed for childhood vs adult-onset vitiligo and alopecia totalis or alopecia universalis vs patchy alopecia. MAIN OUTCOMES AND MEASURES: Self-reported and/or physician-diagnosed AD, vitiligo, and AA. RESULTS: In total, 16 studies of vitiligo and 17 studies of AA were included in the review. In the pooled analysis of the studies that included control patients without vitiligo (n = 2) and control patients without AA (n = 3), patients with vitiligo (Cochran-Mantel-Haenszel OR, 7.82; 95% CI, 3.06-20.00, P < .001) or AA (OR, 2.57; 95% CI, 2.25-2.94, P < .001) had significantly higher odds of AD than did control patients without these disorders. Pooled analysis of 3 studies found higher odds of AD in patients with early-onset vitiligo (<12 years) compared with those with late-onset vitiligo (OR, 3.54; 95% CI, 2.24-5.63, P < .001). Pooled analysis of 4 studies found higher odds of AD in patients with alopecia totalis or alopecia universalis compared with those with patchy alopecia (OR, 1.22; 95% CI, 1.01-1.48, P = .04). CONCLUSIONS AND RELEVANCE: Patients with either vitiligo, especially early-onset disease, or AA, especially alopecia totalis or alopecia universalis, have significantly increased risk for AD.

Interleukin-4 up-regulation of epidermal interleukin-19 expression in keratinocytes involves the binding of signal transducer and activator of transcription 6 (Stat6) to the imperfect Stat6 sites.

Interleukin-19 (IL-19) plays an important role in asthma by stimulating T helper type 2 (Th2) cytokine production. Interestingly, IL-4, a key Th2 cytokine, in turn up-regulates IL-19 expression in bronchial epithelial cells, so forming a positive feedback loop. In atopic dermatitis (AD), another Th2 disease closely related to asthma, IL-19 is up-regulated in the skin. We propose to use IL-4 transgenic (Tg) mice and human keratinocyte culture to delineate the molecular mechanisms involved in the up-regulation of IL-19 in AD. IL-19 is similarly up-regulated in the skin of IL-4 Tg mice as in human AD. Next we show that IL-4 up-regulates IL-19 expression in keratinocytes. Interestingly, the up-regulation was suppressed by a pan-Janus kinase (Jak) inhibitor, suggesting that the Jak-signal transducer and activator of transcription (Jak-STAT) pathway may be involved. Dominant negative studies further indicate that STAT6, but not other STATs, mediates the up-regulation. Serial 5' deletion of the IL-19 promoter and mutagenesis studies demonstrate that IL-4 up-regulation of IL-19 in keratinocytes involves two imperfect STAT6 response elements. Finally, chromatin immunoprecipitation assay studies indicate that IL-4 increases the binding of STAT6 to its response elements in the IL-19 promoter. Taken together, we delineate the detailed molecular pathway for IL-4 up-regulation of IL-19 in keratinocytes, which may play an important role in AD pathogenesis.

Ultrasound-guided intranodal lymphangiography followed by thoracic duct embolization for treatment of postoperative bilateral chylothorax.

BACKGROUND: Percutaneous thoracic duct embolization (TDE) is a safe, effective, and minimally invasive option for treating chylothorax. A recent report demonstrated the feasibility of ultrasound-guided intranodal lymphangiography as an alternative to pedal lymphangiography for visualization of the thoracic duct, promising relative technical ease and decreased procedure time for TDE. METHODS: We report a case of postoperative bilateral chylothorax treated with ultrasound-guided intranodal lymphangiography followed by TDE. RESULTS: Intranodal lymphangiography resulted in rapid opacification of the abdominal lymphatics, permitting technically successful primary and secondary embolization procedures. Deployment of metallic coils and liquid embolic agents within the thoracic duct produced rapid clinical and radiographic improvement. CONCLUSION: Intranodal lymphangiography is a reliable, reproducible, and less technically challenging alternative to pedal lymphangiography.