Poppers Dermatitis: A Systematic Review on a Unique Form of Contact Dermatitis in the MSM Community.

There are certain demographic characteristics that may serve as risk factors for exposure to a contact allergen. Volatile alkyl nitrites, colloquially known as "poppers," are commonly inhaled by men who have sex with men (MSM) for their psychoactive and muscle-relaxing effects. They have been reported to cause either allergic contact dermatitis (ACD) or irritant contact dermatitis (ICD), termed "poppers dermatitis." We searched PubMed, Embase, and Web of Science to understand the patient population, clinical presentation, diagnosis, and clinical course of poppers dermatitis. Our search returned 13 articles detailing 18 patients total. Most patient cases were male (n = 13/15; 87%), of whom 5 were MSM. The reports on the remaining 8 men did not disclose their sexual behaviors. The chemicals deemed responsible for adverse cutaneous side effects included amyl nitrite (6/18; 33%), butyl nitrite (3/18; 167%), isobutyl nitrite (2/18; 11%), and an unspecified alkyl nitrite (7/18, 39%). The most common diagnosis was ICD (10/18; 56%). Only 3 patients underwent alkyl nitrite patch testing, with 2 testing positive for ACD. The most commonly involved anatomic sites were perinasal (13/18; 72%) and perioral regions (10/18; 56%). Rash morphology has been described as yellow crusting, impetigo-like, eczematous, vesicular, edematous, and erythematous. Ulceration can occur with direct skin contact to concentrated nitrite solution. Poppers dermatitis was often self-limited with complete resolution. Dermatologists should consider poppers dermatitis in those presenting with a characteristic midfacial rash, especially in MSM.

Allergic Contact Dermatitis and Patch Testing in Skin of Color Patients.

Objective: Skin of color patients face important health issues relevant to dermatologists, such as allergic contact dermatitis; however, there is a lack of information surrounding common allergens causing contact dermatitis that disproportionately affect skin of color patients, as well as interpreting patch testing in this population. Methods: Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles studying allergic and irritant contact dermatitis in skin of color patients. Results: The most common positive reactions in African American patients included PPD, balsam of Peru, bacitracin, fragrance mix, and nickel. The most common positive reactions in Hispanic patients included Carba mix, nickel sulfate, and thiuram mix. The most common positive reactions in Asian patients included nickel sulfate, fragrance mix, and potassium dichromate. When interpreting patch test results in patients with higher Fitzpatrick skin types, positive patch tests presented with lichenification and hyperpigmentation, rather than erythema and vesicles. Furthermore, characteristic bright red or pink hues for positive results may appear violaceous or faint pink. Conclusions: Awareness of the common allergens associated with allergic contact dermatitis in patients of skin of color can help guide patch testing as an important diagnostic tool. Further research must be conducted regarding contact dermatitis in this patient population, especially given the relative lack of data surrounding Hispanic, Asian and Pacific Islander, and Native American patients.

Allergic Contact Dermatitis in Sexual and Gender Minority Patients: Disparities and a Call to Action.

Objectives: Sexual and gender minority (SGM) patients face health issues relevant to dermatologists, such as allergic contact dermatitis (ACD); however, there is a lack of information surrounding common allergens causing ACD that disproportionally affect SGM patients. Methods: Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles studying ACD in the SGM population. Results: Common allergens associated with ACD in SGM patients include nitrates, fragrance mix, methylisothiazolinone, methylisothiazolinone-methylchloroisothiazolinone, topical antibiotics, and allergens seen in chest binders. Common anatomic sites included the chest, cheeks, perioral region, nasal orifices, and the anogenital region. Conclusions: Certain allergens and body sites affected by ACD are more common among the SGM community. This can help guide patch testing as a diagnostic tool. Further research must be conducted regarding ACD in SGM patients.

Allergic Contact Dermatitis in Sexual and Gender Minority Patients: Disparities and a Call to Action.

OBJECTIVES: Sexual and gender minority (SGM) patients face health issues relevant to dermatologists, such as allergic contact dermatitis (ACD); however, there is a lack of information surrounding common allergens causing ACD that disproportionally affect SGM patients. METHODS: Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles studying ACD in the SGM population. RESULTS: Common allergens associated with ACD in SGM patients include nitrates, fragrance mix, methylisothiazolinone, methylisothiazolinone-methylchloroisothiazolinone, topical antibiotics, and allergens seen in chest binders. Common anatomic sites included the chest, cheeks, perioral region, nasal orifices, and the anogenital region. CONCLUSIONS: Certain allergens and body sites affected by ACD are more common among the SGM community. This can help guide patch testing as a diagnostic tool. Further research must be conducted regarding ACD in SGM patients.

Regional variation in percutaneous absorption in in vitro human models: a systematic review.

Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous penetration, including anatomical region, although little is currently known regarding this parameter. Hence, the aim of this study was to summarize existing data on regional variation in percutaneous penetration in in vitro human models. PubMed, Embase, Web of Science, and US patent literature were explored, and relevant data collected. Eight eligible articles were identified, which together, explored 15 anatomical locations. Four investigations compared percutaneous penetration between scalp and abdominal skin, and all concluded that the former was more permeable. Within those four studies, 10 penetrants of varying physical/chemical properties were tested indicating that in those particular study conditions, anatomical location exerted a greater effect on percutaneous absorption than the physicochemical properties of the penetrants. In addition, torso area was less absorptive than scrotum in both studies in which these sites were compared. In conclusion, the scrotum and scalp appear to be highly susceptible to percutaneous absorption compared to other locations such as the abdomen. This is postulated to be largely due to the high density of hair follicles in these areas, enabling greater penetration via the appendageal pathway. However, there is a paucity of conclusive data regarding the penetrability of other anatomical locations. Investigations testing and ranking the susceptibility of different anatomical regions is of vital importance given the importance of (1) transdermal drug delivery and decontamination protocols and (2) understanding the underlying mechanisms and degree of these variances might aid our pharmacologic/toxicologic judgments.

Efficacy of water-only or soap and water skin decontamination of chemical warfare agents or simulants using in vitro human models: A systematic review.

Water-only or water and soap are widely recommended as preferred solutions for dermal decontamination. However, limited efficacy data exist. We summarized experimental studies evaluating in vitro efficacy of water-only or soap and water in decontaminating chemical warfare agents (CWA) or their simulants from human skin models. Embase, Covidence®, MEDLINE, PubMed, Web of Science, and Google Scholar were searched for articles using water-only or soap and water decontamination methods for removal of CWA/CWA simulants in in vitro human skin models. Data extraction was completed from seven studies, yielding seven contaminants. Water-only decontamination led to partial decontamination in all skin samples (100%, n = 81/81). Soap and water decontamination led to partial decontamination in all skin samples (100%, n = 143/143). Four studies found decontamination to either paradoxically enhance absorption of contaminants or their penetration rates, known as the "wash-in" effect. Despite recommendations, water-only or water and soap decontamination were found to yield partial decontamination of CWA or their simulants in all human in vitro studies. Thus, more effective decontaminating agents are needed. Some studies demonstrated increased or faster penetration of chemicals following decontamination, which could prove deadly for agents such as VX, although these findings require in vivo validation. Heterogeneity in experimental setups limits interstudy comparison, and it remains unclear when water-only or water and soap are ideal decontaminants, which requires more studies. Pending manuscripts will summarize in vivo human and animal efficacy data. International harmonized efficacy protocol should enable more efficient public health decisions for evidence-based public health decisions.

Did human evolution in skin of color enhance the TEWL barrier?

United States will soon be a nation of color; however, much of our knowledge of normal skin disease, and treatment thereof is based on white skin. We and others have attempted to elucidate any potential differences and advantages/disadvantages in skin function that have emerged during homo sapiens evolution post major migration from Eastern Africa. We investigated differences in one stratum corneum function by examining transepidermal water loss (TEWL) measurements in skin of color compared to Caucasian skin. TEWL, a measure of insensible water loss through stratum corneum, plays a major role in human survival. A comprehensive literature search was conducted to procure relevant papers that measured baseline TEWL in skin of color and Caucasian skin. The data show wide contradiction in results for all skin of color groups and white skin and, therefore, no conclusion can be made based on this question. We suggest this variation may be due to experimental confounding variables that impact TEWL quantification, such as anatomic site and sample size subject to further analysis and focus.

Unbearable transepidermal water loss (TEWL) experimental variability: why?

Despite the wide breadth of research, much disparity exists in transepidermal water loss (TEWL) research data-possibly due to uncontrolled experimental variables. We determined whether such experimental variables significantly impact TEWL studies and cause this disparity. An initial literature search regarding TEWL was performed to determine potential confounding variables. A subsequent search procured relevant and representative studies investigating the impact of these variables on TEWL. Variables, such as age, anatomic site, and temperature, impact TEWL and should be controlled for in TEWL studies. Other variables, such as smoking and menstrual cycle, have inconclusive results or do not provide sufficient data breadth to make a conclusion regarding its effect, if such an effect exists, on TEWL metrics. Therefore, these variables require further research to determine their potential impact on TEWL. Matching for as many experimental variables as possible may reduce the disparity in TEWL data/conclusions.

Ability of mathematical models to predict human in vivo percutaneous penetration of steroids.

Human skin is a common route for topical steroids to enter the body. To aid with risk management of therapeutic steroid usage, the US Environmental Protection Agency estimates percutaneous penetration using mathematical models. However, it is unclear how accurate are mathematical models in estimating percutaneous penetration/absorption of steroids. In this study, accuracy of predicted flux (penetration/absorption) by the main mathematical model used by the EPA, the Potts and Guy model based on in vitro data is compared to actual human in vivo data from our laboratory of percutaneous absorption of topical steroids. We focused on steroids due to the availability of steroid in vivo human data in our laboratory. For most steroids the flux was underestimated by a factor 10-60. However, within the group itself, there was an association between the Potts and Guy model and experimental human in vivo data (Pearson Correlation = 0.8925, p = 0.000041). Additionally, some physiochemical parameters used in the Potts and Guy equation, namely log Kp (Pearson Correlation = 0.7307, p = 0.0046) and molecular weight (Pearson correlation = -0.6807, p = 0.0105) correlated significantly with in vivo flux. Current mathematical models used in estimating percutaneous penetration/absorption did not accurately predict in vivo flux of steroids. Why? Proposed limitations to mathematical models currently used include: not accounting for volatility, lipid solubility, hydrogen bond effects, drug metabolism, as well as protein binding. Further research is needed in order to increase the predictive nature of such models for in vivo flux.

Efficacy of soap and water based skin decontamination using in vivo animal models: a systematic review.

Water-only or soap and water solutions are considered a gold standard for skin decontamination. However, there is lack of conclusive data regarding their efficacy. The aim of this study was to summarize in vivo animal model data on skin decontamination using water-only, and/or soap and water. Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles using water-only or soap and water decontamination methods in in vivo animals. Data extraction was completed from studies, representing three animal models, and 11 contaminants. Results demonstrated water-only decontamination solutions led to complete decontamination in 3.1% (n = 16/524) protocols, incomplete decontamination in 90.6% (n = 475/524) of protocols, and mortality in 6.3% (n = 33/524) of protocols. Soap and water decontamination solutions resulted in complete decontamination in 6.9% (n = 8/116) protocols, incomplete decontamination in 92.2% (n = 107/116) of protocols, and mortality in 6.9% (n = 8/116) of protocols. Although water only, or soap and water is considered a gold standard for skin decontamination, most papers investigated found that water only, and soap and water provided incomplete decontamination. Due to the insufficient data, and limitations that hinder the applicability of available data, evidence indicates that more contemporary studies investigating skin decontamination are needed, and compared to other model species, including humans, when practical.

Efficacy of water-based skin decontamination of occupational chemicals using in vitro human skin models: a systematic review.

Percutaneous absorption of chemicals is a potential route of topical and systemic toxicity. Skin decontamination interrupts this process by removing contaminants from the skin surface. Decontamination using water-only or soap and water solutions is the current gold standard despite limited efficacy data. A summary of studies evaluating their efficacy in decontaminating occupational contaminants from in vitro human skin models is presented. Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched for relevant articles and data extracted from 15 investigations that reported on 21 occupational contaminants, which were further classified as industrial chemicals, drugs, or pesticides. Water-only decontamination yielded no response in 4.3% (n = 6/140) and partial decontamination in 95.7% (n = 134/140) of skin samples. Soap and water decontamination yielded complete decontamination in 4.9% (n = 13/264) and partial decontamination in 95.1% (n = 251/264) of skin samples. Four studies (26.7%, n = 4/15) reported increased penetration rates or skin concentration of contaminants following decontamination, demonstrating a "wash-in" effect. Varying study methodologies hinder our ability to compare data and determine when water alone or soap and water are best used. International harmonized efficacy protocol might enhance our decontamination understanding and enable a more customized approach to decontamination clinical practice and research.

HPV Vaccination Status and Resolution of Warts in Pediatric Patients.

Background: Warts are a common dermatologic complaint with an increased incidence within the pediatric population. Warts are caused by multiple strains of the human papillomavirus (HPV). There is little research on how a patient's HPV immunization status affects the response to treatment of warts in pediatric patients. Aims: The purpose of this study is to investigate the relationship between HPV vaccination status and wart resolution. Materials and Methods: This is a retrospective chart review that investigates the relationship between response to routine treatment of warts and a subject's HPV vaccination status. Results: There was no significant relationship found between HPV vaccination status and resolution of warts (p = 0.797). However, there was a significant positive correlation between having the HPV vaccine and number of visits for the treatment of warts (r = 0.180, P = 0.024). Conclusion: This study did not show a significant correlation between HPV vaccination status and wart resolution, although it demonstrated a significant positive relationship between those immunized with the HPV vaccine and an increased number of treatment visits. Possible explanations for this unexpected correlation include the variation in HPV vaccine formulation, vaccination status, and frequency of office visits, since vaccinated patients are more likely to be compliant with office visits.

Prurigo pigmentosa in a patient with newly diagnosed type one diabetes with diabetic ketoacidosis.

Prurigo pigmentosa is a rare inflammatory cutaneous disorder associated with ketosis that resolves with reticulate hyperpigmentation. A 19-year-old man was admitted to the hospital with diabetic ketoacidosis. He also had developed reticulate papules coalescing into plaques over the posterior neck, back, and abdomen. Histopathological findings consistent with the clinical findings suggested the diagnosis of prurigo pigmentosa. After treatment with topical triamcinolone and oral doxycycline along with resolution of his ketosis after insulin administration, the patient's rash healed with reticulate hyperpigmentation.

Organic compounds percutaneous penetration in vivo in man: Relationship to mathematical predictive model.

Human skin is a common pathway through which chemicals in our environment enter the body. To aid with risk management of environmental chemicals, the US EPA utilizes mathematical models to estimate percutaneous penetration when experimental data is not available. Here, the accuracy of predicted flux by the Potts and Guy model based on in vitro penetration is compared to human in vivo data of percutaneous absorption of various organic compounds. For most chemicals, the flux was over- or underestimated by a factor 10-100. In vitro flux was significantly correlated to experimental human in vivo flux; however, the physiochemical parameters used in the Potts and Guy equation, Kp, Koctanol, and molecular weight, did not correlate significantly with in vivo flux. We discuss possible explanations for why the computer model did not accurately predict in vivo flux. Further research is needed with different types of chemicals encountered in the environment, and/or as used in clinical practice. This manuscript discusses limitations to the mathematical models currently used, and why the models should be further refined for use.