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.

2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towards multiple cancers. Here, we report that topically applied 2HF inhibits the growth of intradermal implants of melanoma in immunocompetent mice. 2HF induced apoptosis and inhibited the growth of the human SK-MEL-24 as well as murine B16-F0 and B16-F10 melanoma cell lines in vitro. Apoptosis was associated with depletion of caspase-3, caspase-9, and PARP1 in B16-F0 and SK-MEL-24 cells. Caspase-9 and MEKK-15 were undetected even in untreated B16-F10 cells. Signaling proteins TNFα, and phospho-PDGFR-β were depleted in all three cell lines; MEKK-15 was depleted by 2HF in SK-MEL-24 cells. 2HF enhanced sunitinib (an MEK and PDGFR-β inhibitor) and AZD 2461 (a PARP1 inhibitor) cytotoxicity. 2HF also depleted the Ral-regulated, stress-responsive, antiapoptotic endocytic protein RLIP76 (RALBP1), the inhibition of which has previously been shown to inhibit B16-F0 melanoma growth in vivo. Functional inhibition of RLIP76 was evident from inhibition of epidermal growth factor (EGF) endocytosis by 2HF. We found that topically applied 2HF–Pluronic Lecithin Organogel (PLO) gel inhibited B16-F0 and B16-F10 tumors implanted in mice and caused no overt toxicity despite significant systemic absorption. 2HF treatment reduced phospho-AKT, vimentin, fibronectin, CDK4, cyclinB1, and BCL2, whereas it increased BIM and phospho-AMPK in excised tumors. Several cancer signals are controlled by endocytosis, a process strongly inhibited by RLIP76 depletion. We conclude that 2HF–PLO gel may be useful for topical therapy of cutaneous metastases of melanoma and could enhance the antineoplastic effects of sunitinib and PARP1 inhibitors. The mechanism of action of 2HF in melanoma overlaps with RLI76 inhibitors.

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

Scabies is a contagious skin infestation caused by tiny mites.The microscopic, 8-legged human itch mite digs into the skin to feed and lay eggs; however, it cannot survive outside human skin for more than 2 to 3 days. Scabies is transmitted by direct person-to-person contact or through objects that carry the mites, such as clothing and bedding. Scabies can affect anyone but is most common in children and crowded populations, such as jails, refugee camps, and nursing homes. Because scabies is a human parasite, household pets are typically not affected. Most people with scabies have fewer than 100 mites. However, the itching and rash can be everywhere.Norwegian scabies, or crusted scabies, is a severe infestation of hundreds to thousands of mites that appears as a thick, yellow-gray crust on the skin. It occurs in elderly people or those with disabilities who cannot scratch or feel the itch. It also occurs in those with weakened immune systems.

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Establishing accurate symptomatology associated with novel diseases such as COVID-19 is a crucial component of early identification and screening. This case report identifies an adult patient with a history of clotting dysfunction presenting with rare cutaneous manifestations of COVID-19, known as ‘COVID-19 toes’', previously described predominantly in children. Additionally, this patient presented with possible COVID-associated muscle spasticity of the lower limbs, as well as a prolonged and atypical timeline of COVID-19 infection. The rare occurrence of ‘COVID-19 toes’' in this adult patient suggests that her medical history could have predisposed her to this symptom. This supports the coagulopathic hypothesis of this manifestation of COVID-19 and provides possible screening questions for patients with a similar history who might be exposed to the virus. Additionally, nervous system complaints associated with this disease are rare and understudied, so this novel symptom may also provide insight into this aspect of SARS-CoV-2.

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