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class=\u0022kwd\u0022\u003EExclusive Article - For home page\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ERick Hoekzema, MD, PhD, Free University and Academic Medical Center, Amsterdam, The Netherlands, discussed 2 recently published studies that provide insight into relatively new dermatologic conditions. The first was a retrospective study of a series of patients with clinical features of urticarial dermatitis (UD) [Hannon GR et al. \u003Cem\u003EJ Am Acad Dermatol\u003C\/em\u003E. 2014]. The second study discussed cutaneous side effects seen in patients treated with V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors [Vanneste L et al. \u003Cem\u003EJ Eur Acad Dermatol Venereol\u003C\/em\u003E. 2014]. Prof Hoekzema focused on the ramifications of these findings, particularly the need for careful monitoring of patients following BRAF inhibitor treatment.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn a 2006 article, Kossard and colleagues [\u003Cem\u003EArch Dermatol\u003C\/em\u003E. 2006] reported that patients presenting with urticarial plaques and papules had features resembling urticaria; however, the individual lesions lasted \u0026gt; 24 hours and often for days. Kossard et al. concluded that UD \u201cseems to be a useful histological and clinical term for a subset of the dermal hypersensitivity reaction pattern.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EProf Hoekzema also further discussed the retrospective 6-year review of clinical and laboratory evaluations (including histology), as well as the final diagnosis and associations for 146 patients with clinical features of UD who were seen at the Mayo Clinic during 2006 through 2012 [Hannon GR et al. \u003Cem\u003EJ Am Acad Dermatol\u003C\/em\u003E. 2014]. UD was confirmed in 70 patients, 40 of whom also had histopathologic results concordant with Kossard\u0027s description of UD. Of these 40 patients, 10% had a history of malignancy within 4 months of UD onset, prompting the investigators to question whether UD can be paraneoplastic and whether there is a need for malignancy screening in recalcitrant cases. The investigators concluded that UD is characterized by both urticarial and eczematous lesions, and patients with UD can have an array of diagnoses including various subtypes of dermatitis, drug eruptions, bullous pemphigoid, and scabies.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EProf Hoekzema believes UD does not represent a disease entity but a reaction pattern, both clinically and histologically. Although idiopathic UD may exist, he sees it as a diagnosis of exclusion for which underlying common causes such as medication reaction and pemphigoid need to be excluded first.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EBRAF inhibitors prolong survival in patients with BRAF\u003Csup\u003EV600E\u003C\/sup\u003E-positive metastatic melanoma by 3 to 4 months by way of a disruption in the mitogen-activated protein kinase (MAPK) signaling pathway [Chapman PB et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2011]. Growth factors that bind to the receptor tyrosine kinase activate the MAPK pathway. Overactivation of the transcription factor associated with this pathway stimulates cell growth that can lead to cancer development in keratinocytes. BRAF inhibitors prevent overactivation and proliferation in malignant cells. However, the cause of epidermal proliferation (including squamous cell carcinomas, keratoacanthomas, and verrucous keratoses) is a paradox that is not fully understood. Although he did not discuss this paradox in detail, Prof Hoekzema suggested a recent review by Holderfield and colleagues [\u003Cem\u003EBr J Cancer\u003C\/em\u003E. 2014] as further reading.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EIn a second study, Vanneste and colleagues [\u003Cem\u003EJ Eur Acad Dermatol Venereol\u003C\/em\u003E. 2014] reported the significant cutaneous adverse events (AEs) associated with BRAF\u003Csup\u003EV600E\u003C\/sup\u003E treatment when used to treat patients with a BRAF mutant (V600E, V600K, V600R) metastatic melanoma. Of the 20 patients treated with BRAF inhibitors, 11 (58%) developed cutaneous side effects and 10 (42%) had \u0026gt; 1 cutaneous AE. The major side effect was verrucous papillomas observed in 8 (42%) patients after 1 to 12 weeks. Other effects are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12127\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12127\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12127\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EPrevalence and Timing of Cutaneous Side Effects Following BRAF Treatment\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EPatient education (especially the need for photoprotection) and early identification and management can minimize these AEs and allow the patient to continue BRAF treatment without interruption and often without dose reduction. These patients should be treated by a team that includes a dermatologist; close and consistent cutaneous follow-up may be required. In those patients with unmanageable cutaneous AEs, combination therapy with a mitogen-activated protein kinase kinase (MAP2K) inhibitor helps decrease the incidence. Thus, the use of other inhibitors of the MAPK cascade or inhibition of other signaling pathways may be helpful in the management of these toxicities.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EHok Bing Thio, MD, PhD, The Erasmus University Medical Center, Rotterdam, The Netherlands, surveyed a series of new therapeutic approaches to treating skin disease.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EAfter 15 years of innovations in gene therapy, only 1 patient with an inherited skin disorder has been successfully treated in a clinical trial [Abdul-Wahab A et al. \u003Cem\u003ESemin Cutan Med Surg\u003C\/em\u003E. 2014]. Prof Thio attributed this to the fact that multiple genes are often involved in skin disorders.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EImmunotherapeutics have been very successful in benign and malignant skin diseases [O\u0027Shea JJ et al. \u003Cem\u003ECell\u003C\/em\u003E. 2014]. For instance, inhibition of interleukin (IL)-17A, implicated in the pathogenesis of autoimmune disorders, reduces psoriasis symptoms [Patel DD et al. \u003Cem\u003EAnn Rheum Dis.\u003C\/em\u003E 2013]. Besides psoriasis and psoriatic arthritis (PsA), IL-17 is implicated in rheumatoid arthritis and Beh\u00e7et disease. Five biological drugs for silencing psoriasis are in clinical use and more are in the pipeline [Crow JM. \u003Cem\u003ENature\u003C\/em\u003E. 2012].\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EApremilast is a small molecule that modulates the production of proinflammatory and anti-inflammatory mediators and inhibits the intracellular signal transducing protein phosphodiesterase-4 [Schafer PH et al. \u003Cem\u003ECell Signal\u003C\/em\u003E. 2014; McCann FE et al. \u003Cem\u003EArthritis Res Ther\u003C\/em\u003E. 2010; Schett G et al. \u003Cem\u003ETher Adv Musculoskelet Dis.\u003C\/em\u003E 2010]. Apremilast appears to be a potential new agent for the treatment of both rheumatoid arthritis and PsA.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EThere are already a variety of established immunomodulatory therapies for patients with multiple sclerosis (MS) and several new treatments are in or have recently completed clinical trials [Cross AH, Naismith RT. \u003Cem\u003EJ Intern Med.\u003C\/em\u003E 2014]. Although many of these therapies have potential in the treatment of dermatologic conditions, at least 1 treatment for MS (dimethylfumarate) has emerged from the successful treatment of psoriasis.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EIn one study, more complete suppression of immunoglobulin E (IgE) with ligelizumab, a novel high-affinity humanized monoclonal IgG1\u03ba anti-IgE, proved superior to omalizumab in suppressing skin-prick wheal responses to an allergen [Arm JP et al. \u003Cem\u003EClin Exp Allergy\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EKIT, BRAF, MAP2K, and extracellular signal-regulated kinase inhibitors that block mutations in the MAPK pathway are proving effective in the treatment of metastatic melanoma. Such mutations lead to oncogenic cell proliferation and loss of apoptosis function. The anti-cytotoxic T lymphocyte A4 antibody, ipilimumab, which prevents downregulation of the immune system, can lead to significant increases in survival for patients with metastatic melanoma, whereas nivolumab, a fully human IgG4 monoclonal antibody, blocks ligand activation of PD-1, a protein called programmed cell death that is important for apoptosis [Ledford H. \u003Cem\u003ENature\u003C\/em\u003E. 2014 (vol 7494)].\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EEpigenetic mutations in basal keratinocytes in the epidermis caused by the sun may promote hyperproliferative precancerous keratinocytes. Topical applications of agents such as 5-fluorouracil, imiquimod, and ingenol mebutate are used with success to treat superficial skin cancer, primarily actinic keratosis and basal cell carcinomas [Micali G et al. \u003Cem\u003EJ Am Acad Dermatol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EProf Thio went on to discuss other agents with the potential to treat dermatologic conditions. Brimonidine, a highly selective \u03b12-adrenerigc agonist, reduces erythema of rosacea through direct cutaneous vasoconstriction [Fowler J et al. \u003Cem\u003EJ Eur Acad Dermatol Venereol\u003C\/em\u003E. 2014]. Demodex folliculorum is the most common human ectoparasite. Because rosacea is linked to the presence of this parasite, it can be treated with ivermectin, especially when combined with metronidazole (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Salem DA. \u003Cem\u003EInt J Infect Dis.\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/37\/29\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Comparison of Invermectin and Invermectin Plus Metronidazole on Mite Density\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1651019326\u0022 data-figure-caption=\u0022Comparison of Invermectin and Invermectin Plus Metronidazole on Mite Density\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/37\/29\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/37\/29\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/37\/29\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12126\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EComparison of Invermectin and Invermectin Plus Metronidazole on Mite Density\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECombination treatment comprises invermectin plus metronidazole.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EAdapted from \u003Cem\u003EInternational Journal of Infectious Diseases\u003C\/em\u003E, 17:e343\u2013e347. Salem DA et al, Evaluation of the efficacy of oral ivermectin in comparison with ivermectin-metronidazole combined therapy in the treatment of ocular and skin lesions of \u003Cem\u003EDemodex folliculorum\u003C\/em\u003E, Copyright 2013, with permission from International Society for Infectious Diseases.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-22\u0022\u003EAccording to Prof Thio, the role of gastrointestinal and cutaneous microbiota in healthy skin and in inflammatory and allergic skin diseases is also an area of scientific interest [Maccaferri S et al. \u003Cem\u003EDig Dis.\u003C\/em\u003E 2011]. As an example, he highlighted a study showing that consuming a candy that contained 2.1% kimchi-derived \u003Cem\u003ELactobacillus plantarum\u003C\/em\u003E K8 cell lysate can improve skin barrier function and repair [Kim H et al. \u003Cem\u003EJ Microbiol Biotechnol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/37\/29.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzlwkp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlwkp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlwkp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}