Jonette E. Keri

Guidelines of care for the management of acne vulgaris

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

IMPORTANCE Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00847912.

Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: A randomized clinical trial

Importance Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration clinicaltrials.gov Identifier: NCT00847912

Effect of Tetracyclines on the Development of Vascular Disease in Veterans with Acne or Rosacea: A Retrospective Cohort Study

TO THE EDITOR Tetracyclines are commonly used for the treatment of acne and rosacea. In addition to their antibacterial properties, tetracyclines are increasingly being studied for other properties, such as their anti-inflammatory properties (Jackson et al., 1999; Meier, 2000; Sho et al., 2004; Griffin et al., 2005; Tessone et al., 2006; Hackmann et al., 2008; RomeroPerez et al., 2008; Griffin et al., 2010). One can hypothesize that these qualities may have secondary benefits and a protective effect on other organ systems. We sought to test the hypothesis that tetracyclines used in acne and rosacea patients may have secondary benefits on the cardiovascular system, specifically, a decreased odds ratio of developing vascular diseases. After approval by the Institutional Review Board at the Miami Veterans Affairs Health System, we used the electronic medical records from the veterans integrated service network-8 (which includes the Veterans Affairs medical centers of Bay Pines, Miami, West Palm Beach, Tampa, North Florida/South Georgia, and San Juan) to perform a retrospective observational cohort study and identify patients with the diagnosis of acne or rosacea using the International Classifications of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes during the period of 1 July 2004 through 30 June 2010, allowing for at least 18 months of follow-up. We excluded any patient who had been diagnosed with vascular disease before prescription of a tetracycline, or before the diagnosis of acne/rosacea. Demographic, clinic, and pharmacy data were extracted. Vascular disease was defined and identified using the ICD-9 codes for cardiovascular disease, cerebrovascular disease, atherosclerosis, and aortic aneurysm with or without rupture/dissection. In a multiple logistic regression model, age, sex, and comorbidities (see Table 1) were included as covariates. The Hosmer–Lemeshow test was performed to assess goodness-of-fit. P-values were reported as two sided. Statistical analyses were performed using SAS software (Version 9.2, SAS Institute, Cary, NC). In total, 13,847 patients matched our inclusion and exclusion criteria (Figure 1). Patients were further subdivided—to those with prior treatment with a tetracycline, and those without tetracycline treatment (control). Demographics can be found in Table 1. There were similar race profiles between control and treatment groups within both the acne and rosacea sets (data not shown). Similar rates of comorbidities were found between study and control groups (Table 1). Of those rosacea patients who were treated with a tetracycline, 12.56% patients developed a new diagnosis of vascular disease compared with 17.15% of the control group. Overall, rosacea patients who were prescribed a tetracycline had an odds ratio of 0.69 for the development of vascular disease when compared with those not prescribed a tetracycline (odds ratio 0.69 in the univariate model, 95% confidence interval (CI) 0.61–0.79, Po0.05; odds ratio 0.78 in the multivariate model, 95% CI 0.68–0.89, Po0.05) (Table 1). Acne patients showed an odds ratio of 0.79 (95% CI 0.62–1.02) in a univariate model; however, the results were not statistically significant, and did not persist with the multivariate model. The effect of treatment duration (o3 months, 3–12 months, 412 months of daily dosing with a tetracycline) was explored; however, the group sizes were too small to make meaningful conclusions (data not shown). Cumulative dose effect was not explored, nor was daily dosage. A statistically significant decrease was found in the development of new aortic aneurysms in rosacea patients treated with doxycycline (P1⁄4 0.007) (Table 1), although the number of cases was quite small. Other vascular diagnoses were not analyzed individually. We found a potential association between the administration of tetracyclines and a decreased odds ratio for the development of vascular disease in veterans with rosacea. This study further contributes to the body of literature supporting an association between chronic low-grade inflammation and cardiovascular disease (Prodanowich et al., 2005; Wang et al., 2012). One can conjecture that the stabilization or inhibition of matrix metalloproteinases by tetracyclines has a beneficial effect on the vascular wall and/or calcifications in arteries. We did not detect any benefit of tetracyclines in acne patients, possibly due to the inherent demographics of acne patients. The average age of our acne patients may be too young to LETTERS TO THE EDITOR

Treatment of Acne Keloidalis Nuchae: A Systematic Review of the Literature

Acne keloidalis nuchae (AKN) is a chronic inflammatory condition that leads to fibrotic plaques, papules and alopecia on the occiput and/or nape of the neck. Traditional medical management focuses on prevention, utilization of oral and topical antibiotics, and intralesional steroids in order to decrease inflammation and secondary infections. Unfortunately, therapy may require months of treatment to achieve incomplete results and recurrences are common. Surgical approach to treatment of lesions is invasive, may require general anesthesia and requires more time to recover. Light and laser therapies offer an alternative treatment for AKN. The present study systematically reviews the currently available literature on the treatment of AKN. While all modalities are discussed, light and laser therapy is emphasized due to its relatively unknown role in clinical management of AKN. The most studied modalities in the literature were the 1064-nm neodymium-doped yttrium aluminum garnet laser, 810-nm diode laser, and CO2 laser, which allow for 82–95% improvement in 1–5 sessions. Moreover, side effects were minimal with transient erythema and mild burning being the most common. Overall, further larger-scale randomized head to head control trials are needed to determine optimal treatments.

The role of nicotinamide in acne treatment

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti‐inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patients baseline or performed similarly to another standard‐of‐care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first‐line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.

Rosacea and cardiovascular disease: Is there an association?

treating rosacea with an oral tetracycline lowered the incidence of vascular events. Patients with rosacea that were prescribed a tetracycline had a favorable odds ratio for the development of vascular disease compared with those not prescribed a tetracycline (odds ratio 0.69 in the univariate model, 95% confidence interval 0.61-0.79, P \ .05; odds ratio 0.78 in the multivariate model, 95% confidence interval 0.68-0.89, P\.05). Although the results are preliminary and should be confirmed using other patient populations, it is proposed that the anti-inflammatory properties of tetracyclines may have beneficial secondary effects on the cardiovascular system of veterans with rosacea. It is yet unclear if the observed effect was because of the direct effect of the use of a tetracycline, or improvement associated with the systemic treatment of rosacea itself. It is possible that systemically treating the rosacea may constitute a risk factor reduction, much like improving body mass index can reduce the risk of heart disease. Although it is unclear how tetracyclines may benefit the cardiovascular system, matrix metalloproteinases (MMPs) are influential in the pathology of both rosacea and CVD. Tetracyclines inhibit MMP activity, therefore it would follow that treating one disease may have benefits on both organ systems. MMP-2 and MMP-9, both of which tetracyclines inhibit, are enzymes that degrade the basement membrane of capillaries. Doxycycline has been shown to defend capillary wall and connective tissue integrity, reduce hypersensitivity to vasodilatory stimuli, prevent leakage of capillaries, and inhibit cytokines involved in inflammation and erythema, all of which is seen in rosacea. 4 There are also data that 90-day subantimicrobial-dose doxycycline lowers serum C-reactive protein over a 2-year period in postmenopausal women. 5 Although there are limitations to retrospective reviews, the data by Dosal et al 2 do raise some questions about how we should approach our patients with rosacea, especially in a current clinical environment where systemic treatment of rosacea is under scrutiny for bacterial resistance concerns.

Laser Hair Removal in a Patient with Vitiligo

A 32-year-old woman with vitiligo was treated with 755 nm Gentlase laser hair removal, in an area of normal skin and an area of vitiliginous skin. The area of normal skin responded with hair reduction of 89% after four laser treatments, but the hair on the vitiliginous area did not respond. No Koebner phenomenon was observed after treatment.

Effectiveness of photopneumatic technology: a descriptive review of the literature

Usage of photopneumatic technology has recently increased for treatment of different skin conditions such as acne, keratosis pilaris (KP), and rosacea. Photopneumatic devices combine gentle negative pressure with broad band pulsed light simultaneously to attack multiple targets in the skin for better treatment outcomes. In this literature review, we evaluate the efficacy of photopneumatic therapy on treatment of acne, keratosis pilaris (KP), and rosacea.

Treatment of seborrheic dermatitis: a comprehensive review

Abstract Seborrheic dermatitis (SD) is a chronic, recurring inflammatory skin disorder that manifests as erythematous macules or plaques with varying levels of scaling associated with pruritus. The condition typically occurs as an inflammatory response to Malassezia species and tends to occur on seborrheic areas, such as the scalp, face, chest, back, axilla, and groin areas. SD treatment focuses on clearing signs of the disease; ameliorating associated symptoms, such as pruritus; and maintaining remission with long-term therapy. Since the primary underlying pathogenic mechanisms comprise Malassezia proliferation and inflammation, the most commonly used treatment is topical antifungal and anti-inflammatory agents. Other broadly used therapies include lithium gluconate/succinate, coal tar, salicylic acid, selenium sulfide, sodium sulfacetamide, glycerin, benzoyl peroxide, aloe vera, mud treatment, phototherapy, among others. Alternative therapies have also been reported, such as tea tree oil, Quassia amara, and Solanum chrysotrichum. Systemic therapy is reserved only for widespread lesions or in cases that are refractory to topical treatment. Thus, in this comprehensive review, we summarize the current knowledge on SD treatment and attempt to provide appropriate directions for future cases that dermatologists may face.