Dermatologic manifestations of pediatric cardiovascular diseases: Skin as a reflection of the heart.

Cutaneous disease can often be an initial clue of an underlying cardiovascular disease. Many congenital conditions (ie, Noonan syndrome with multiple lentigines, Carney complex, and Fabry disease) and acquired conditions may present initially with specific cutaneous features that should prompt clinicians to conduct a full cardiac workup. Given the extensive number of conditions with both cardiovascular and cutaneous findings, this review will focus on diseases with cardiocutaneous pathology with hopes of raising clinician awareness of these associations to decrease morbidity and mortality, as several of these diseases often result in fatal outcomes.

Granuloma annulare: strengthening potential associations and pentoxifylline as a therapeutic option.

Granuloma annulare is frequently described in association with numerous systemic conditions and is often refractory to treatment. This retrospective review explored a large patient cohort to further strengthen associated comorbid conditions and assess response to different treatments in patients with granuloma annulare. This study found that patients with granuloma annulare frequently carried a diagnosis of hypothyroidism. Additionally, the highest rate of improvement in any treatment category was seen with pentoxifylline use. Thus, should be further explored as a first-line therapeutic option in the treatment of granuloma annulare.

Mycoplasma pneumoniae-associated mucositis complicated by herpes simplex virus dissemination and Staphylococcus Epidermidis bacteremia.

Prominent mucositis with minimal or no cutaneous involvement in the setting of Mycoplasma pneumoniae infection describes a clinical entity recently termed Mycoplasma-induced rash and mucositis (MIRM). About 81% of patients with MIRM experience complete resolution; however, the disease course in approximately 11% of patients is complicated by mucosal sequelae. We describe a patient with MIRM complicated by HSV dissemination and Staphylococcus epidermidis bacteremia and outline the management of mucocutaneous eruptions without systemic immunosuppressant agents.

Langerhans cell histiocytosis: A great imitator.

Langerhans cell histiocytosis (LCH) is an uncommon but serious inflammatory neoplasia that affects many organs, including the skin. Though uncommon, it should remain high on a clinician's differential diagnosis in treatment-resistant cases of conditions, such as seborrheic dermatitis, diaper dermatitis, arthropod bites, and many more. A thorough history nd physical examination for each patient can aid in the diagnosis; however, if clinically suspicious for LCH, a punch biopsy should be performed. Histologic evaluation of LCH is often enough to differentiate it from the many clinical mimickers. Characteristic findings include a histiocytic infiltrate with "coffee bean"-cleaved nuclei, rounded shape, and eosinophilic cytoplasm. Immunohistochemical stains, including CD1a, S100, and CD207 (langerin) are often needed for a definitive diagnosis. Electron microscopy also demonstrates the ultrastructural presence of Birbeck granules, but this is no longer needed due to immunohistochemical staining. Treatment is often necessary for LCH, if systemic involvement exists.

Dermatologic Sequelae Associated with Radiation Therapy.

Radiation therapy is a mainstay for the treatment of primary malignancies and metastatic disease and is associated with several dermatological adverse events that are underreported in the literature. The objective of this paper was to review the literature regarding cutaneous manifestations associated with radiation therapy in order to promote awareness of the cutaneous radiation therapy-associated adverse effects. This extensive literature review was performed using the Pubmed and Embase databases. Studies were reviewed for relevance and critical evidence pertaining to cutaneous manifestations of radiation therapy. The most commonly reported cutaneous sequelae associated with radiation therapy include radiation dermatitis, non-melanoma skin cancer, radiation-associated angiosarcoma, morphea, bullous pemphigoid, lymphangioma circumscriptum, and pseudosclerodermatous panniculitis. For many of these conditions, only case reports or case series exist and there is an absence of large-scale cohort studies. Despite these limitations, this review describes the wide range of dermatological adverse events associated with radiation therapy.

Compounding Benefits of Sentinel Lymph Node Biopsy for Perineal Melanoma: A Population-Based Retrospective Cohort Analysis.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) in the treatment of melanoma is known to provide valuable prognostic information. However, there is no literature describing an overall or disease-specific survival (DDS) benefit of SLNB. In the perineum, melanoma is often more advanced at presentation with current treatment guidelines translated from nonanatomic specific melanoma. As a result, there is little understanding surrounding the role of SLNB in melanoma of the perineum. Our objective is to better understand the therapeutic benefits of SLNB in perineal melanoma. METHODS: The Surveillance, Epidemiology, and End Results program is a large population-based cancer registry including survival data from millions of patients in the United States. The registry was used to generate patient data for analysis from 2004 to 2016. Inclusion criteria included melanoma of the perineum; Breslow depth of 0.80 mm or greater and less than 0.80 mm with ulceration; SLNB or no intervention; clinically negative nodal disease; and available overall survival data. RESULTS: For 879 patients from 2004 to 2016 with perineal melanoma, significant predictors of reduced survival include older than 75 years, Clark level IV-V, Breslow depth of greater than 4.00 mm, positive ulceration status, regional and distant nodal micrometastases, and clinically positive nodes on presentation. Aggregates for overall survival (OS) and disease-specific survival (DSS) were improved with implementation of SLNB. The 5-year survival rates with SLNB versus no SLNB were 54.0% and 43.0% for OS (P = 0.001) and 57.8% and 53.1% for DSS (P = 0.044). Stratification by Breslow depth yielded significant OS and DSS advantage for greater than 1.00 to 2.00 mm (21.3% benefit, P =0.021, and 16.8% benefit, P = 0.044) and greater than 4.00 mm (30.3% benefit, P = 0.005, and 21.0% benefit, P = 0.007) Breslow depths. CONCLUSIONS AND RELEVANCE: Sentinel lymph node biopsy may provide therapeutic benefits in addition to prognostic information for melanoma of the perineum through an increase in 5-year OS.

Hailey-Hailey Disease: An Update Review with a Focus on Treatment Data.

Hailey-Hailey disease is a rare blistering dermatosis first described in 1939 by the brothers Howard and Hugh Hailey. Its incidence is estimated at 1/50,000. The inheritance is autosomal dominant with complete penetrance, but a variable expressivity in affected family members. Clinically, Hailey-Hailey disease presents between the third and fourth decade as flaccid vesicles and blisters on erythematous skin, giving rise to erosions, fissures, and vegetations. Maceration and superinfections are frequent. The lesions are typically distributed symmetrically within intertriginous regions such as the retroauricular folds, lateral aspects of the neck, axillae, umbilicus, inguinal, and perianal regions. The disease is characterized by a chronic relapsing course with spontaneous remissions and multiple recurrences. Severe disease can be very frustrating and have a major psychological and social impact. Given the dearth of evidence-based guidelines and large clinical trials, the assessment of the efficacy and safety of treatments is difficult. Treatments include topical and systemic agents, and procedural therapy such as lasers and surgery. This review provides a systematic search of the literature with a focus on classical and emerging treatment options for Hailey-Hailey disease.

Histopathologic findings characteristic of CARD14-associated papulosquamous eruption.

BACKGROUND: Pathogenic mutations in caspase recruitment domain-containing protein 14 (CARD14) lead to CARD14-associated papulosquamous eruption, which shares clinicopathologic findings with psoriasis and pityriasis rubra pilaris. We aimed to describe distinguishing histopathologic features of CARD14-associated papulosquamous eruption. METHODS: This retrospective study examined the histopathologic features of specimens from patients with confirmed CARD14-associated papulosquamous eruption and adult patients with plaque psoriasis and pityriasis rubra pilaris. RESULTS: Lesional skin biopsies from patients with CARD14-associated papulosquamous eruption consistently showed alternating checkerboard parakeratosis and orthokeratosis, acanthosis without acantholysis, and dilated vessels in the dermal papillae, with some cases also showing follicular plugging. CONCLUSION: CARD14-associated papulosquamous eruption has a range of findings, with a predominance of features typically associated with pityriasis rubra pilaris.

Extramammary Paget disease.

In 1874, Sir James Paget first described Paget disease of the nipple, also known as mammary Paget disease. In 1889, extramammary Paget disease (EMPD) of the scrotum and penis was identified. Although mammary and extramammary Paget disease are both characterized by epidermal Paget cells and share a similar clinical presentation, their uniqueness lies in anatomical location and histogenesis. EMPD presents as an erythematous plaque on apocrine gland bearing areas (i.e. vulva, perineum, perianal region, scrotum, and penis) in older men and women. It can be a focal, multifocal, or an ectopic process. Immunohistochemical staining allows for differentiation between primary and secondary EMPD in addition to the many other disease entities that clinically resemble this malignancy. When diagnosing a patient with EMPD, a full history and physical should be performed given the possibility of an underlying malignancy. Surgical excision currently is first line therapy and the prognosis is often favorable. Recent advances within the field have examined the expression of chemokine receptors within tumors, which may be applicable in determining prognosis. This review addresses the history, epidemiology, pathogenesis, clinical presentation, histopathology, differential diagnosis, diagnosis, management, and new observations with respect to extramammary Paget disease.

Dermatologic manifestations associated with electronic cigarette use.

BACKGROUND: Electronic cigarette use continues to rise, yet there are no reviews summarizing dermatologic manifestations associated with electronic cigarettes in the literature. OBJECTIVE: To review the literature regarding cutaneous manifestations associated with electronic cigarette use and increase awareness of side effects associated with this rapidly developing public health epidemic. METHODS: The PubMed database was searched for related literature. All studies involving the effects of electronic cigarette use on the skin or mucosa were obtained and reviewed for evidence. RESULTS: Contact dermatitis, thermal injuries, and oral mucosal lesions have been reported with the use of electronic cigarettes. LIMITATIONS: The conclusions presented in individual case reports or series are not based on randomized controlled trials. CONCLUSION: Electronic cigarettes can present with harmful dermatologic manifestations.

CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris.

BACKGROUND: Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors. OBJECTIVE: We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14. METHODS: Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed. RESULTS: We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab. LIMITATIONS: Relatively small sample size. CONCLUSIONS: Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.

Black Hairy Tongue: Predisposing Factors, Diagnosis, and Treatment.

Black hairy tongue (BHT) is a benign condition commonly found among people who smoke, have poor oral hygiene, are immunocompromised, or have a medical condition limiting their ability to practice good oral hygiene. Though this condition is harmless, patients need to be educated on etiology as many common medications are associated with this condition. Patients being placed on certain antibiotics or antipsychotics should be educated on the importance of good oral hygiene or cessation of habits that promote BHT. Similarly, those with medical conditions increasing the risk for the development of BHT should schedule routine visits with their dentist or dental hygienist. Prognosis is good, and treatment consists of gentle brushing of the tongue, but many anecdotal reports exist demonstrating the use of medications or other products to treat this condition. This review addresses the epidemiology, clinical presentation, pathophysiology, etiology, histology, differential diagnosis, and treatment of BHT and lists all of the medications reported to cause this condition.

Risky business: Behaviors associated with indoor tanning in US high school students.

BACKGROUND: Understanding of associations between indoor tanning and risky health related behaviors such as sexual activity and substance abuse among high school students across the United States is incomplete. OBJECTIVE: To identify risky health related behaviors among high school students utilizing indoor tanning and analyze differences between state specific data. METHODS: Results from the Youth Risk Behavior Surveillance System (YRBSS) 2013 in 14 different states were analyzed. Participants were 90,414 high school students. Responses to questions assessing indoor tanning habits, sexual activity, and use of substances were analyzed. RESULTS: Sexual activity was associated with indoor tanning in 10 of 14 states, with Nebraska having the strongest association (adjusted odds ratio, 3.8; 95% CI, 2.4-6.2; p<0.001). Indoor tanning was also associated with use of alcohol, marijuana, ecstasy, cocaine, prescription medications, and cigarettes. LIMITATIONS: Only 15 states asked students about their personal history of indoor tanning use, and Minnesota was excluded from our analysis as they administered a non-YRBS questionnaire. Additionally, our study only analyzed results from the 2013 YRBS. Lastly, our data was analyzed in 14 individual data sets, giving a high likelihood of Type 1 error. CONCLUSIONS: High school students utilizing indoor tanning are more likely to engage in sexual activity and substance abuse as compared to students who do not utilize indoor tanning.

Cutaneous Squamous Cell Carcinoma: A Review of High-Risk and Metastatic Disease.

Non-melanoma skin cancer represents one-third of all malignancies and its incidence is expected to rise until the year 2040. Cutaneous squamous cell carcinoma (cSCC) represents 20 % of all non-melanoma skin cancer and is a deadly threat owing to its ability to metastasize to any organ in the body. Therefore, a better understanding of cSCC is essential to strengthen preventative measures and curable treatment options. Currently, research demonstrates that cSCC is diagnosed at a rate of 15-35 per 100,000 people and is expected to increase 2-4 % per year. With respect to metastatic cSCC, this disease is more common in men; people over the age of 75 years; and inhabitants of the south and mid-west USA. In 2010, the American Joint Committee on Cancer updated the Cancer Staging Manual's primary tumor designation to now include high-risk factors; however, factors such as immunosuppression and tumor recurrence were not included. Other staging systems such as Brigham and Women's Hospital have allowed for increased stratification of cSCC. High-risk cSCC is defined as a cSCC that is staged as N0, extends beyond basement membrane, and has high-risk features associated with sub-clinical metastasis. High-risk features are depth of invasion (>2 mm), poor histological differentiation, high-risk anatomic location (face, ear, pre/post auricular, genitalia, hands, and feet), perineural involvement, recurrence, multiple cSCC tumors, and immunosuppression. Epidermal growth factor receptor and nuclear active IκB kinase (IKK) expression are also predictive of metastatic capabilities. Clinically, the initial lesions of a cSCC tumor can present as a painless plaque-like or verrucous tumor that can ultimately progress to being large, necrotic, and infected. Tumors can also present with paresthesias or lymphadenopathy depending on the location involved. With respect to prognosis, metastatic cSCC is lethal, with several large studies demonstrating a mortality rate of >70 %. Therefore, treatment of metastatic cSCC is difficult and depends on the location involved and extent of metastasis. Treatment options include surgery, radiation therapy, chemotherapy, and any combination of the above. Surgery alone can be used for metastatic cSCC treatment, but is not as effective as surgery in conjunction with radiation therapy. Radiation therapy has some success as a monotherapy in low-risk or cosmetically sensitive areas such as the external ear, eyelid or nose. According to the 2013 National Comprehensive Cancer Network Guidelines, cisplatin as a single agent or combined with 5-fluorouracil hold the strongest support for the treatment of metastatic cSCC; however, the supporting evidence is inconsistent and a curative chemotherapeutic approach is still lacking. Epidermal growth factor receptor inhibitors are a newer class of agents being used in metastatic cSCC and hold some promise as a therapy for this disease. Other areas of interest in finding curative treatments for metastatic cSCC include p53, hypermethylation of specific genes, chromatin remodeling genes, and the RAS/RTK/PI3K pathway. This review addresses the epidemiology, staging, risk factors, clinical presentation, management, and new trends in the treatment of high-risk and metastatic cSCC.

Dermatology in Doximity.

Doximity, currently the largest online social networking service for United States (US) health care professionals and medical students, provides a wide variety of content to a large audience. In fact, its database includes 1,078,305 physicians in the US. It is therefore important to evaluate this content from time to time. Our objective is to analyze both the residency rankings and news content presented in Doximity, with respect to dermatology. The study compared the residency rankings created by Doximity to another dermatology residency ranking system that used a different algorithm. In terms of dermatology content, seven dermatology-related search terms were entered into the Doximity search query and data was collected on the first 20 "relevant" articles. Our study evaluated a total of 140 articles. The search term "skin cancer" yielded the most articles totaling 6,001. Informative articles were the most common type of article for each content item searched except for "dermatology", yielding research articles as the most common content type (70%). The search term "melanoma awareness" had the largest number of shares (19,032). In comparing dermatology residency rankings on Doximity with another ranking system that accounted for scholarly achievement, there was 50% overlap. In conclusion, it is vital to evaluate content on social media websites that are utilized by US medical students and health care professionals. We hope this information presented provides an up-to-date analysis on the quality of one particular social media platform.