Toll-Like Receptors and Contact Dermatitis.

Contact dermatitis (CD) is a common cutaneous inflammatory condition that affects millions of people worldwide. Xenobiotic agents are frequently encountered in substances used in everyday life, making it difficult to avoid personal and occupational exposure. Toll-like receptors (TLRs) are transmembrane receptors that modulate the innate immune system in response to tissue injury or infection. TLRs play a key role in the pathophysiology of contact dermatitis. TLR signaling is involved in three major forms of CD: protein CD, allergic contact dermatitis (ACD), and irritant CD. Of the 10 TLRs found in humans, three play an important role in ACD. This makes TLRs a useful potential therapeutic target to consider against CD. In this review, we discuss the role of TLRs in CD and summarize current and emerging treatments for CD that target TLRs.

Safety assessment for nail cosmetics: Framework for the estimation of systemic exposure through the nail plate.

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.

Editors and Journals: Part II-Relationship between the Editor-in-Chief and the Owner of the Journal: The Consequences When Editorial Independence Dissolves.

A symbiotic relationship between the editor and the owner of a medical journal is important for the journal to fulfill successfully the expectations of its readers and authors. Editorial freedom and transparency by owner of the journal are important qualities that enable the editor to provide valid scientific information in an unbiased manner. Unresolved impedance of editorial freedom or the persistent lack of transparency or both frequently results in untenable consequences for editor and often a substantial defamation of the journal's credibility. Unfortunately, misguided and inappropriate behavior by a medical society or the publication owner repeatedly occurs with the same devastating effect for the editor: prompt, unanticipated, and unjustified termination of the position at the journal. Alternatively, conditions imposed by a journal's owner may lead to the resignation of the editor because of untenable conditions. Because the owner does not have to account for its actions and there is no recourse for the editor, currently there seems to be no effective measures to prevent this tragic sequence of events in the future.

Editors and Journals: Part I-Responsibilities And Expectations Of Editors: Who Is the Editor and Why an Editor?

Important components of a medical journal include its readers, authors, editor, and owner. Editor is the individual to whom the journal is branded. The editor determines the journal's published content and establishes its caliber. The success of a journal depends on the general and specific responsibilities of the editor toward its readers, authors, and owner. For a journal to maintain its stature of excellence, the expectations of the editor-including editorial independence-must be preserved; therefore, in the best interest of the journal, the owner must provide unequivocal support to the editor.

The 2-Methoxymethyl Modification of p -Phenylenediamine Reduces the Sensitization Risk for Hairdressers to Hair Dyes-An Occupational Hand Exposure-Based Risk Assessment.

BACKGROUND: Allergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p -phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis. OBJECTIVE: The aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers. METHODS: Hand exposure of hairdressers (N = 11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons. By accounting for wet work and uneven hand exposure, the daily hand exposure was derived and compared with the occupational acceptable exposure level (AEL), that is, the sensitization induction threshold of ME-PPD adjusted for interindividual variability among workers. RESULTS: The daily hand exposure to ME-PPD was 1.6 µg/cm 2 , and the occupational AEL was 215 µg/cm 2 . The ratio of hand exposure to AEL was calculated as the margin of safety (MOS) against occupational sensitization. For ME-PPD, the MOS of 134 indicates a low likelihood of sensitization versus PPD and PTD with MOS values of 2.7 and 5.9, respectively. CONCLUSIONS: Our data predict that the use of ME-PPD in professional hair color products improves the protection of hairdressers against hair dye-related contact allergy versus the use of PPD and PTD.

Patterns of Allergic Contact Dermatitis in African Americans in a Major Metropolitan Area Over a 10-Year Period.

BACKGROUND: Differences in patterns of allergic contact dermatitis (ACD) among underrepresented minority populations are not well studied. OBJECTIVE: The aim of the study was to investigate patterns of ACD in African American and White patch-tested patients in a distinct metropolitan area over a 10-year period. METHODS: We conducted a retrospective review of 297 ACD patients patch tested from 2009 to 2019. Differences in allergen frequency, relevance, and sources of exposure were evaluated. Fisher exact test analyses were performed to examine these differences. RESULTS: Among 297 patients, 215 were White and 47 were African American. The most common sensitizers differed between the 2 groups. African American patients also reacted with statistically significant greater frequency to disperse dye blue (P = 0.019) and textile dye mix (P = 0.001). The most common source of positive patch tests for all patients was personal care products (72%). Occupational allergy was greater in African American male patients, and personal care product exposure was greater in White male patients (P = 0.009). CONCLUSIONS: Our study highlights the differing patterns of sensitization seen in African American and White patients. This is likely due to differences in personal care product use or occupational allergy. Additional studies with larger sample sizes are needed to expand upon these differences.

Patch testing: Uses, systems, risks/benefits, and its role in managing the patient with contact dermatitis.

Patch testing is the gold standard diagnostic tool for cell-mediated type IV hypersensitivity reactions like allergic contact dermatitis. Sensitized individuals have primed antigen-specific T lymphocytes that cause a reaction when antigens are applied to the skin owing to prior sensitization. Patch testing can be used in the adult and pediatric populations, but it is contraindicated in patients with a known history of severe allergic reactions to suspected allergens, generalized active dermatitis, or extensive eczema. Patch test systems can be a comprehensive panel (70-80 allergens), but they can also be targeted and limited to a more common allergen series (35 allergens). The decision for allergen selection should be based on an accurate patient history, physical examination, and availability of allergens. Measurement and interpretation of the test results requires training and experience, as well as consideration of relevance and clinical history. Patch testing is generally considered safe with just a few known complications: excited skin syndrome, active sensitization, and rarely anaphylaxis or other cutaneous complications. Appropriately pretesting patient education can help to mitigate some of these complications. Based on patch testing results, patients should be educated regarding proper allergen avoidance measures to resolve symptoms of allergic contact dermatitis.

Radiation and Hyperthermia Combination Therapy for Recalcitrant Verruca Vulgaris.

A 47-year-old white woman presented to our clinic complaining of recalcitrant warts on her trunk and extremities. She had an extensive past medical history including immunodeficiency of unknown origin, pulmonary hypertension, rheumatoid arthritis, and systemic lupus erythematosus, for which she was being treated with chronic immunosuppressive therapy with methylprednisolone and belimumab. The patient had previously failed treatments at an outside facility with liquid nitrogen, trichloroacetic acid, topical cidofovir, imiquimod, topical 5-fluorouracil, intralesional candida antigen, pulsed-dye laser (Vbeam Perfecta), surgical excision, and photodynamic therapy. (SKINmed. 2019;17:68-71).

Cutaneous metastases of pancreatic neuroendocrine carcinoma.

Neuroendocrine carcinomas with distant metastases are rarely reported in the literature, with cutaneous metastases being among the most infrequently reported sites. The importance of distinguishing metastatic neuroendocrine carcinoma (NEC) from primary neuroendocrine carcinoma in the skin, or Merkel cell carcinoma (MCC), has been stressed in the literature, with CK20 positivity traditionally being reported as the key diagnostic feature of MCC. Our case not only serves as one of the few reported cases of cutaneous metastases of a visceral NEC, but also serves to caution providers as to the use of CK20 positivity as an absolute diagnostic feature. We present a case of a 67-year-old female with widespread cutaneous metastases of a pancreatic NEC. Immunohistochemical staining revealed CK20 positivity, despite visceral origin of the primary tumor. This case serves to highlight not only a rare presentation of cutaneous metastases of a pancreatic neuroendocrine carcinoma, which has yet to be reported in the literature, but also serves as the only report of a pancreatic NEC with CK20 positivity, providing evidence for cautionary use of CK20 staining for diagnostic purposes, particularly for visceral NECs which have been under-represented in the literature.