Farzam Gorouhi

Cutaneous and Mucosal Lichen Planus: A Comprehensive Review of Clinical Subtypes, Risk Factors, Diagnosis, and Prognosis

Lichen planus (LP) is a chronic inflammatory disorder that most often affects middle-aged adults. LP can involve the skin or mucous membranes including the oral, vulvovaginal, esophageal, laryngeal, and conjunctival mucosa. It has different variants based on the morphology of the lesions and the site of involvement. The literature suggests that certain presentations of the disease such as esophageal or ophthalmological involvement are underdiagnosed. The burden of the disease is higher in some variants including hypertrophic LP and erosive oral LP, which may have a more chronic pattern. LP can significantly affect the quality of life of patients as well. Drugs or contact allergens can cause lichenoid reactions as the main differential diagnosis of LP. LP is a T-cell mediated immunologic disease but the responsible antigen remains unidentified. In this paper, we review the history, epidemiology, and clinical subtypes of LP. We also review the histopathologic aspects of the disease, differential diagnoses, immunopathogenesis, and the clinical and genetic correlations.

Catecholamine stress alters neutrophil trafficking and impairs wound healing by β2 adrenergic receptor mediated upregulation of IL-6

Stress-induced hormones can alter the inflammatory response to tissue injury, however, the precise mechanism by which epinephrine influences inflammatory response and wound healing is not well defined. Here we demonstrate that epinephrine alters the neutrophil (PMN)-dependent inflammatory response to a cutaneous wound. Using non-invasive real-time imaging of genetically-tagged PMNs in a murine skin wound, chronic, epinephrine-mediated stress was modeled by sustained delivery of epinephrine. Prolonged systemic exposure of epinephrine resulted in persistent PMN trafficking to the wound site via an IL-6 mediated mechanism, and this in turn impaired wound repair. Further, we demonstrate that β2 adrenergic receptor-dependent activation of pro-inflammatory macrophages is critical for epinephrine-mediated IL-6 production. This study expands our current understanding of stress hormone-mediated impairment of wound healing and provides an important mechanistic link to explain how epinephrine stress exacerbates inflammation via increased number and lifetime of PMNs.

Crosstalk Between Adrenergic and Toll-Like Receptors in Human Mesenchymal Stem Cells and Keratinocytes: A Recipe for Impaired Wound Healing

Previous studies demonstrate that skin wounds generate epinephrine (EPI) that can activate local adrenergic receptors (ARs), impairing healing. Bacterially derived activators of Toll‐like receptors (TLRs) within the wound initiate inflammatory responses and can also impair healing. In this study, we examined the hypothesis that these two pathways crosstalk to one another, using EPI and macrophage‐activating lipopeptide‐2 (MALP2) to activate ARs and TLR2, respectively, in human bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neonatal keratinocytes (NHKs). BM‐MSCs exposed to EPI significantly (p < .05) increased TLR2 message (sevenfold BM‐MSCs), TLR2 protein (twofold), and myeloid differentiation factor 88 (MyD88) (fourfold). Conversely, activation of TLR2 by MALP2 in these cells increased β2‐AR message (twofold in BM‐MSCs, 2.7‐fold in NHKs), β2‐AR protein (2.5‐fold), phosphorylation of β‐AR‐activated kinase (p‐BARK, twofold), and induced release of EPI from both cell types (twofold). Treating cells with EPI and MALP2 together, as would be encountered in a wound, increased β2‐AR and p‐BARK protein expression (sixfold), impaired cell migration (BM‐MSCs‐ 21%↓ and NHKs‐ 60%↓, p < .002), and resulted in a 10‐fold (BM‐MSCs) and 51‐fold (NHKs) increase in release of IL‐6 (p < .001) responses that were remarkably reduced by pretreatment with β2‐AR antagonists. In vivo, EPI‐stressed animals exhibited impaired healing, with elevated levels of TLR2, MyD88, and IL‐6 in the wounds (p < .05) relative to nonstressed controls. Thus, our data describe a recipe for decreasing cell migration and exacerbating inflammation via novel crosstalk between the adrenergic and Toll‐like receptor pathways in BM‐MSCs and NHKs.

Prehospital hypertonic fluid resuscitation for trauma patients: A systematic review and meta-analysis

BACKGROUND Prehospital assessment of a patient’s circulation status and appropriate resuscitation with intravenous fluids plays a critical role in patients with obvious hemorrhage or systolic blood pressure below 90 mm Hg. OBJECTIVES We assessed the efficacy and safety of prehospital administration of crystalloids or colloids to improve the survival rate of trauma patients with acceptable safety profile. DATA SOURCES We searched SCOPUS, Embase, TRIP database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and PubMed as per search protocol from January 1, 1900 to February 12, 2015. STUDY ELIGIBILITY CRITERIA All randomized controlled trials were considered. PARTICIPANTS AND INTERVENTIONS All patients had penetrating or blunt trauma, excluding traumatic brain or thermal injuries. At least one of the comparators should be a crystalloid or colloid. STUDY APPRAISAL AND SYNTHESIS METHODS Detailed search strategy was developed and utilized. Duplicates were removed from the search results. We, the co-first authors (C.d.C. and F.G.), independently reviewed the article titles and abstracts to assess eligibility. Eligible articles were downloaded for full text review to determine inclusion in the review and analysis. We (C.d.C. and F.G.) performed a methodological quality assessment of each included article. The primary outcome was mortality. The secondary outcomes included adverse events, infections, multiple organ dysfunction score, and length of stay at the hospital. Heterogeneity was measured by I 2 value. An I 2 value greater than 50% was considered to be substantial heterogeneity. Fixed effect analysis and random effect analysis were performed when needed. RESULTS A total of nine trials (3,490 patients) were included in the systematic review, and six trials were included in meta-analyses. There were no significant differences between hypertonic saline with dextran and lactated Ringer’s solution in 1 day using two studies (2.91; 95% CI, 0.58–14.54; p = 0.19) and 28- to 30-day survival rates using another two studies (1.47; 95% CI, 0.30–7.18; p = 0.63). Adding dextran to hypertonic saline did not increase the survival rate (0.94; 95% CI, 0.65–1.34; p = 0.71). Overall, complications were comparable between all groups. LIMITATIONS The quality of some of the included studies is not optimal. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS There is no beneficial effect of hypertonic saline with or without dextran in general traumatic patients. Further trials to evaluate its benefit in patients with penetrating trauma requiring surgery are warranted. LEVEL OF EVIDENCE Systematic review and meta-analysis, level I.

A critical review of personal statements submitted by dermatology residency applicants.

Background. A strong personal statement is deemed favorable in the overall application review process. However, research on the role of personal statements in the application process is lacking. Objective. To determine if personal statements from matched applicants differ from unmatched applicants. Methods. All dermatology residency applications (n = 332) submitted to UC Davis Dermatology in the year of 2012 were evaluated. Two investigators identified the characteristics and recurring themes of content present in the personal statements. Then, both investigators individually evaluated the content of these personal statements in order to determine if any of the defined themes was present. Chi-square, Fishers exact, and reliability tests were used. Results. The following themes were emphasized more often by the matched applicants than the unmatched applicants as their reasons for going into dermatology are to study the cutaneous manifestations of systemic disease (33.8% versus 22.8%), to contribute to the literature gap (8.3% versus 1.1%), and to study the pathophysiology of skin diseases (8.3% versus 2.2%; P ≤ 0.05 for all). Conclusion. The prevalence of certain themes in personal statements of dermatology applicants differs according to match status; nevertheless, whether certain themes impact match outcome needs to be further elucidated.

Combination therapy of autologous adipose mesenchymal stem cell-enriched, high density lipoaspirate and topical timolol for healing chronic wounds.

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63‐year‐old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)‐enriched, high‐density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat‐killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro‐inflammatory interleukin‐6 and ‐8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC‐enriched, HDL with topical timolol for the healing of chronic venous leg ulcers. Copyright

Pancreatic acinar cell carcinoma–induced panniculitis

ACC: acinar cell carcinoma P ancreatic cancer is the fourth most common cause of cancer-related death among men and women in the United States. Every year, an estimated 43,090 people die of pancreatic cancer nationally. Pancreatic acinar cell carcinoma (ACC) is a rare form of pancreatic cancer that accounts for 1% to 2% of all pancreatic neoplasms. ACCs are generally asymptomatic and may be discovered incidentally when patients undergo work-up for general complaints such as abdominal pain. In the literature, investigators have reported a variety of systemic presentations of ACC. Herein, we report a patient with painful lower extremity nodules associated with pancreatic ACC.

In vitro Evaluation of a Surface Acoustic Wave Device on Epidermal Characteristics

The authors evaluate a novel Surface Acoustic Wave (SAW) device as to its effect on epidermal health. The SAW device is indicated for use in phonophoresis as well as epidermal tissue growth in wound care. In order to understand the clinical effect the authors evaluate an in vitro skin model for SAW effect and examine the cellular and subcellular changes that occur with this device. CK17 proliferation, changes in GAGs (Glycosaminoglycans) and neoangiogenesis were positively affected by the SAW device.

Evidence or Experience: That is the Question

This special issue does not intend to provide an explicit overview of all available evidence in the various fields of dermatology. Instead, it attempts to provide an efficient overview of the latest available evidence on selected topics. All dermatologists with different backgrounds need a periodic update on the available evidence and may not have the time to review each topic comprehensively. We all know that performing a comprehensive systematic review, such as a Cochrane review, entails many details, and reading such a review is not necessarily time efficient for busy practitioners. Thus, we emphasize the usefulness of the summary tables in this issue to present results of randomized trials and, more importantly, to provide general recommendations for each treatment modality. Practicing dermatologists may not be able to dedicate sufficient time to reading and reviewing the updated evidence. Therefore, it may be more useful for them to study summarized, updated, evidence-based reviews. The intention of this issue was to fulfill this need. We have often been asked why we believe in an evidence-based philosophy in the age of personalized medicine. The critical point that is frequently missed is that ‘‘Evidence-based medicine is not ‘cookbook’ medicine’’ [1]. You need to know the current evidence. You may need to know the quality of the studies as well as the strength of recommendations for therapeutic modalities; but you recommend it only after considering your experience, judgment, and common sense. Here, we would like to underscore some common misperceptions about evidencebased medicine. For example, underlying diseases are seldom discussed in evidence-based guidelines; therefore, it is the physician’s responsibility to customize treatment strategies for patients based on all the aspects, including but not limited to concurrent diseases, drug history, age, gender, ethnicity, social history, and, most importantly, patient preference [2]. Moreover, evidence-based medicine has its limitations. For instance, since therapeutic systematic reviews rely primarily on phase II and III randomized controlled trials, they may underestimate infrequent adverse events. Phase IV post-marketing surveillance studies can help detect these rare occurrences; however, they are often not available. Looking for all adverse effects may be more beneficial to patients, especially if they have genetic or environmental predisposing factors. Let us give you a rare clinical scenario: If a male patient has a paternal or maternal family history of BRCA gene mutation, his dermatologist should be more cautious in prescribing a lifelong finasteride treatment for his androgenetic alopecia and should monitor the patient for possible cancer-related signs or symptoms in the breast or other organs more often than in a patient with no relevant underlying risk factors. Such a clinical decision is not in any evidence-based guideline but is congruent with its principles. Additionally, anecdotal experience may be helpful, specifically if the literature lacks an appropriate systematic review. Unfortunately, this is commonly seen in dermatology. However, it is important to understand that even in the areas with no existing high-level evidence, the evidence-based approach is considered gold standard. F. Gorouhi (&) Department of Dermatology, University of California, Davis, 3301 C St. Suite 1400, Sacramento, CA 95816-3367, USA e-mail: farzam.gorouhi@ucdmc.ucdavis.edu