The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Loss of function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell mediated immune responses and can promote IgE mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

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Background: Positive staining for SOX10 and the S100 protein are often used in the evaluation of challenging melanocytic neoplasms including melanoma in patient samples. SOX-10 positivity of non-melanocytes in re-excision specimen could complicate the evaluation of invasive melanoma with an invasive desmoplastic component.Therefore, quantifiable data regarding the positivity of SOX-10 in scars will help dermatopathologists to better identify false positive staining.Methods: A retrospective analysis was performed on 50 re-excision specimens from 2013 to 2017, with a diagnosis of squamous cell carcinoma (SCC) or squamous cell carcinoma in situ (SCCIS). Blocks of re-excision specimens containing scars were stained for SOX-10; results were evaluated by a board-certified dermatopathologist. The sum of the five highest numbers of high-power field (HPF) counts as a proxy for "SOX-10 stain factor," and cell morphological features were analyzed. MART-1 and CD68 immunohistochemical staining was performed to study possible lineage of these SOX-10 positive cells.Results: All 50 specimens showed varying degrees of SOX-10 positivity for histiocytes. SOX-10 positive histiocytes were present in 86% of re-excision scar tissues, of which 71.3% had spindle-shaped or angulated nuclei, and 61.8% had nuclear sizes larger than typical lymphocytes (7 μm). Within the same area of scars, CD68 staining was floridly positive, where as MART-1 staining was overwhelmingly negative.Conclusions: This study illustrates a potential diagnostic pitfall of using SOX-10 to evaluate re-excision specimens of melanocytic neoplasms and also suggests a previously undescribed staining pattern in scars of SOX-10 positive cells that are not melanocytes. We postulate that such SOX-10 positive cells may represent a small fraction of histiocytes routinely found in scar tissue. K E Y W O R D SCD68, dermal dendritic cell, desmoplastic melanoma, histiocytes, immunohistochemical stains, MART-1, scars, SOX-10

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