Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

Oral candidiasis and seborrheic dermatitis in an 8-year-old female with a heterozygous variant of the IL-17RC gene.

An 8-year-old female with chronic oral candidiasis and severe seborrheic dermatitis was found to have a heterozygous mutation (p.R14X c.40 C>T) of the IL-17RC gene, which was predicted to possibly represent a new pathogenic variant via truncation or nonsense-mediated mRNA decay. Given previously reported IL-17RC-related disorders are autosomal recessive, we would expect an affected individual to have two mutated alleles whereas our patient was heterozygous. Given the overlapping clinical picture, this variant could be responsible for altered immunity against both Candida and Malassezia species. This is the first report to our knowledge of chronic oral candidiasis and severe seborrheic dermatitis in a patient with a heterozygous variant (p.R14X c.40 C>T) for the IL-17RC gene.

Distinguishing annular pustular psoriasis from subcorneal pustular dermatosis-A diagnostic dilemma in a 10-year-old boy.

Subcorneal pustular dermatosis (SPD) and annular pustular psoriasis (APP) are very rare in childhood and difficult to differentiate both clinically and histopathologically. We report the case of a 10-year-old male with a 9-year history of erythematous scaly annular plaques with scattered pustules on the trunk. Although initially diagnosed as SPD, a lack of response to dapsone, presence of spongiosis on histology, and early age of disease onset led to consideration of APP. The patient was subsequently treated with adalimumab 80 mg weekly and completely cleared. This case illustrates the overlapping features of SPD and APP and suggests that the two disorders may represent a spectrum of the same disease.

Limitations in the literature regarding Mohs surgery and staged excision for melanoma: A critical review of quality and data reporting.

BACKGROUND AND OBJECTIVES: The literature supporting Mohs micrographic surgery and staged excision in treating primary cutaneous melanoma is growing but has not been critically reviewed for bias. METHODS: Articles concerning Mohs micrographic surgery and staged excision for melanoma were assessed using modified "Risk of Bias in Non-randomized Studies of Interventions" (ROBINS-I) criteria, which measures bias in 7 categories. RESULTS: Forty-seven of 48 (97.9%) studies reviewed had serious or critical bias. None were randomized controlled trials. The most frequent cause of critical bias was poorly defined outcomes. The least frequent form of bias observed was change in intervention. LIMITATIONS: The modified ROBINS-I criteria cannot account for all study limitations. Modification of the criteria leads to some degree of subjectivity. CONCLUSION: The current body of literature suffers from limitations due to serious or critical bias in 1 or more ROBINS-I criteria. Local recurrence rate definitions are often poorly defined or not defined at all. Longer follow-up times, clear tumor classifications, and prospective, randomized study designs are necessary to improve the quality of future research.

Emerging therapeutics in the management of connective tissue disease. Part II: Dermatomyositis and scleroderma.

The management of connective tissue diseases is dramatically evolving with the advent of biologics and novel oral systemic therapeutics. Despite involvement in the care of these complex patients, there is a knowledge gap in the field of dermatology regarding these emerging agents. The second article in this continuing medical education series discusses new and emerging therapeutics for dermatomyositis and scleroderma that target cells, intracellular signaling pathways, and cytokines.

Statins are associated with increased risk of squamous cell carcinoma of the skin: a whole-population study from Iceland.

Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case-control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. These are high-quality registers which include all cancer diagnoses, as well as every prescription in the country. Cases included all first-time histologically confirmed diagnoses of (BCC), in situ squamous cell carcinoma (SCCis) and invasive SCC between 2003 and 2017. Each case was paired with 10 age- and sex-matched controls. Multivariate conditional logistic regression analysis was performed. Four thousand seven hundred patients with BCC, 1167 patients with SCCis and 1013 patients with invasive SCC were identified and paired with 47,292, 11,961 and 10,367 controls, respectively. Overall statin use was associated with an increased risk of invasive SCC and SCCis but not BCC (adjusted OR [95% CI]: 1.29 [1.11-1.50]; 1.43 [1.24-1.64]; 1.03 [0.95-1.12], respectively). Subgroup analysis demonstrated that statins were significantly associated with invasive SCC and SCCis in patients over 60, but not in those under 60. Atorvastatin was only associated with an increased risk of SCCis; whereas, simvastatin was associated with an increased risk of both invasive SCC and SCCis. This whole-population study of Iceland demonstrates that statin exposure is associated with increased risk of SCC, but not BCC, in a low UV environment. The reasons are unclear, but our results may suggest that individuals receiving atorvastatin and simvastatin have differing levels of baseline keratinocyte cancer risk or that properties of a statin other than 'statin intensity' affect association with SCC.

Pacinian corpuscle hyperplasia: A review of the literature.

OBJECTIVE: Pacinian corpuscle hyperplasia typically presents as a tender nodule on the volar aspect of the palm or digit, often after trauma. Histologically, it presents as one to multiple normal-sized to enlarged Pacinian corpuscles in the deep dermis or subcutaneous adipose tissue. Given its rarity, its pathogenesis is debated and nomenclature is poorly defined. Herein, we present a case of Pacinian corpuscle hyperplasia and review the current literature. METHODS: A literature review was conducted using PubMed with the following search terms: Pacinian corpuscle hyperplasia, Pacinian corpuscle neuroma, Pacinioma, Pacinian corpuscle hypertrophy, and heterotopic Pacinian corpuscles. All case reports and case series were reviewed for histopathologic evidence of true Pacinian corpuscle hyperplasia. Cadaveric studies, cases without true Pacinian corpuscles, and noncutaneous cases were excluded from our analysis. RESULTS: Sixty patients with Pacinian corpuscle hyperplasia of the hands and feet (65 cases, some with >1 location) were reviewed. The mean age of presentation was 49.5 years, and women accounted for 60% of cases. Pain was the most commonly reported symptom (55 of 65 cases; 84.6%). Forty-five cases (69.2%) were localized to a digit, most commonly the second digit (17 of 65 cases; 26.2%), and 18 of 65 cases (27.6%) affected the palm, primarily the distal palm. Surgical excision was curative in 50 of 65 cases (76.9%). CONCLUSION: Although relatively uncommon, Pacinian corpuscle hyperplasia should be considered in the differential diagnosis of a tender nodule on the digit or distal palm, particularly after trauma.

Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.

BACKGROUND: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. METHODS: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). LIMITATIONS: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSION: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study.

BACKGROUND: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. OBJECTIVES: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). METHODS: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. RESULTS: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). LIMITATIONS: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSIONS: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.

An update on the microbiology, immunology and genetics of seborrheic dermatitis.

The underlying mechanism of seborrheic dermatitis (SD) is poorly understood but major scientific progress has been made in recent years related to microbiology, immunology and genetics. In light of this, the major goal of this article was to summarize the most recent articles on SD, specifically related to underlying pathophysiology. SD results from Malassezia hydrolysation of free fatty acids with activation of the immune system by the way of pattern recognition receptors, inflammasome, IL-1ß and NF-kB. M. restricta and M. globosa are likely the most virulent subspecies, producing large quantities of irritating oleic acids, leading to IL-8 and IL-17 activation. IL-17 and IL-4 might play a big role in pathogenesis, but this needs to be further studied using novel biologics. No clear genetic predisposition has been established; however, recent studies implicated certain increased-risk human leucocyte antigen (HLA) alleles, such as A*32, DQB1*05 and DRB1*01 as well as possible associations with psoriasis and atopic dermatitis (AD) through the LCE3 gene cluster while SD, and SD-like syndromes, shares genetic mutations that appear to impair the ability of the immune system to restrict Malassezia growth, partially due to complement system dysfunction. A paucity of studies exists looking at the relationship between SD and systemic disease. In HIV, SD is thought to be secondary to a combination of immune dysregulation and disruption in skin microbiota with unhindered Malassezia proliferation. In Parkinson's disease, SD is most likely secondary to parasympathetic hyperactivity with increased sebum production as well as facial immobility which leads to sebum accumulation.

Long-term outcomes after coronary artery bypass surgery in patients with diabetes.

OBJECTIVES: Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications. METHODS: This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes. RESULTS: Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27-4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P < 0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P < 0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53-2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23-1.75). CONCLUSIONS: Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up.