The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia. Both first and second generation Janus kinase inhibitors have become promising treatment modalities for dermatologic conditions such as psoriasis, atopic dermatitis, alopecia areata, vilitigo, dermatomyositis, and graft-versus-host disease. Future promising areas of investigation include treatment of cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.
{"title":"Janus Kinase Inhibitors: A Review of Their Emerging Applications in Dermatology","authors":"A Cinats, E Heck, L Robertson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia. Both first and second generation Janus kinase inhibitors have become promising treatment modalities for dermatologic conditions such as psoriasis, atopic dermatitis, alopecia areata, vilitigo, dermatomyositis, and graft-versus-host disease. Future promising areas of investigation include treatment of cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 3","pages":"5-9"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36107690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Histamine is a key inflammatory player in the pathogenesis of urticaria, a mast-cell-driven disease characterized clinically by the development of wheals, angioedema, or both. Changes to the management of chronic spontaneous urticaria have recently been adopted due to increasing literature surrounding the efficacy and safety of up-dosing modern second-generation H1-antihistamines and the use of omalizamub, a biologic agent, as a third-line treatment. Given the prevalence of chronic urticaria and its impact on quality of life, this editorial aims to provide a summary of the proposed updated guidelines for the management of chronic urticaria as agreed upon at the 5th Consensus Conference on the Update and Revision of the EAACI/GA2LEN/EDF/WAO Guideline for Urticaria in Berlin in December 2016. The chronic urticaria treatment algorithm outlined here reflects the updates and revisions made by 43 international experts representing 40 societies from 25 countries. These guidelines have yet to be published and therefore will require approval by respective national and international boards before adoption.
{"title":"Chronic Urticaria: Following Practice Guidelines.","authors":"E P Westby, C Lynde, G Sussman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Histamine is a key inflammatory player in the pathogenesis of urticaria, a mast-cell-driven disease characterized clinically by the development of wheals, angioedema, or both. Changes to the management of chronic spontaneous urticaria have recently been adopted due to increasing literature surrounding the efficacy and safety of up-dosing modern second-generation H<sub>1</sub>-antihistamines and the use of omalizamub, a biologic agent, as a third-line treatment. Given the prevalence of chronic urticaria and its impact on quality of life, this editorial aims to provide a summary of the proposed updated guidelines for the management of chronic urticaria as agreed upon at the 5th Consensus Conference on the Update and Revision of the EAACI/GA<sup>2</sup>LEN/EDF/WAO Guideline for Urticaria in Berlin in December 2016. The chronic urticaria treatment algorithm outlined here reflects the updates and revisions made by 43 international experts representing 40 societies from 25 countries. These guidelines have yet to be published and therefore will require approval by respective national and international boards before adoption.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 3","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36107687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.
{"title":"Brodalumab: A Review of Safety.","authors":"S Rusta-Sallehy, M Gooderham, K Papp","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-tosevere plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publically available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 2","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35933094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.
{"title":"A Review of Fabry Disease.","authors":"B Chan, D N Adam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 2","pages":"4-6"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35933095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.
{"title":"New Treatments for Hereditary Angioedema.","authors":"Nathan M Johnson, Mariana A Phillips","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 1","pages":"6-8"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35756866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An increasing body of research indicates that dietary change may serve as a component of therapy for certain skin conditions. This includes conditions such as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain nutrients, foods, or dietary patterns may act as disease "triggers", while others may prove beneficial. Avoidance or elimination diets may be helpful in some conditions, although testing may be recommended first. In terms of beneficial effects, an eating pattern that emphasizes the consumption of whole foods over highly processed foods may help in the treatment of certain skin conditions, and will certainly help in the prevention of associated co-morbidities.
{"title":"Skin and Diet: An Update on the Role of Dietary Change as a Treatment Strategy for Skin Disease.","authors":"Rajani Katta, Mary Jo Kramer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An increasing body of research indicates that dietary change may serve as a component of therapy for certain skin conditions. This includes conditions such as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain nutrients, foods, or dietary patterns may act as disease \"triggers\", while others may prove beneficial. Avoidance or elimination diets may be helpful in some conditions, although testing may be recommended first. In terms of beneficial effects, an eating pattern that emphasizes the consumption of whole foods over highly processed foods may help in the treatment of certain skin conditions, and will certainly help in the prevention of associated co-morbidities.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"23 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35756865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting. Use of azelaic acid was associated with a significant reduction in inflammatory lesions, which persisted beyond the active treatment phase. Overall, azelaic acid 15% gel is an appropriate initial topical therapy for the treatment of moderate facial rosacea.
{"title":"Real-World Efficacy of Azelaic Acid 15% Gel for the Reduction of Inflammatory Lesions of Rosacea.","authors":"P J Wirth, M H Henderson Berg, N Sadick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting. Use of azelaic acid was associated with a significant reduction in inflammatory lesions, which persisted beyond the active treatment phase. Overall, azelaic acid 15% gel is an appropriate initial topical therapy for the treatment of moderate facial rosacea.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"22 6","pages":"5-7"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35211447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atopic dermatitis (AD) is the most common chronic inflammatory disease affecting 2-10% of adults and up to 15-30% of children. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are limited due to toxicity and side effects. Dupilumab, an interleukin (IL)-4 and IL-13 antagonist that limits type 2 T helper (Th2) driven inflammatory activity, is a promising therapeutic option. In clinical trials, it has demonstrated efficacy by reducing clinical activity and symptoms, and showed improvement in the AD genomic phenotype, including a significant reduction in Th2 chemokines and reversal of key epidermal markers of AD. It also has a favorable safety profile. This review discusses the role of dupilumab in treating Th2 related inflammation, and its efficacy and safety, as demonstrated in clinical trials. Dupilumab (Dupixent®) recently gained US FDA approval for patients with moderate-to-severe AD, and is poised to revolutionize the management of this chronic, relapsing condition.
{"title":"Dupilumab for Moderate-to-Severe Atopic Dermatitis.","authors":"R Vangipuram, S K Tyring","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is the most common chronic inflammatory disease affecting 2-10% of adults and up to 15-30% of children. Despite a rising prevalence, effective and safe therapeutics for patients with moderate-to-severe AD are limited due to toxicity and side effects. Dupilumab, an interleukin (IL)-4 and IL-13 antagonist that limits type 2 T helper (Th2) driven inflammatory activity, is a promising therapeutic option. In clinical trials, it has demonstrated efficacy by reducing clinical activity and symptoms, and showed improvement in the AD genomic phenotype, including a significant reduction in Th2 chemokines and reversal of key epidermal markers of AD. It also has a favorable safety profile. This review discusses the role of dupilumab in treating Th2 related inflammation, and its efficacy and safety, as demonstrated in clinical trials. Dupilumab (Dupixent®) recently gained US FDA approval for patients with moderate-to-severe AD, and is poised to revolutionize the management of this chronic, relapsing condition.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"22 6","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35566101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epidermal growth factor receptor (EGFR) inhibitors are part of an emerging class of anticancer medicines known as "targeted therapy," which target pathways more specific to neoplastic proliferation than traditional chemotherapeutic agents. Adverse effects of such treatments are thought to be less severe, but can still be significant. Because EGFR is preferentially expressed in epithelial tissues, including the skin and hair follicle, cutaneous side effects of these agents are quite common. Not only can these toxicities severely affect patients' quality of life, but in some specific instances, they can be associated with increased response to therapy. It is of paramount importance that clinicians familiarize themselves with and understand the basic management of the range of cutaneous adverse effects caused by these drugs.
{"title":"Epidermal Growth Factor Receptor Inhibitors: Cutaneous Side Effects and Their Management.","authors":"S Monjazeb, J Wilson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) inhibitors are part of an emerging class of anticancer medicines known as \"targeted therapy,\" which target pathways more specific to neoplastic proliferation than traditional chemotherapeutic agents. Adverse effects of such treatments are thought to be less severe, but can still be significant. Because EGFR is preferentially expressed in epithelial tissues, including the skin and hair follicle, cutaneous side effects of these agents are quite common. Not only can these toxicities severely affect patients' quality of life, but in some specific instances, they can be associated with increased response to therapy. It is of paramount importance that clinicians familiarize themselves with and understand the basic management of the range of cutaneous adverse effects caused by these drugs.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"22 5","pages":"5-7"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35492512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicotinamide, an amide form of vitamin B3, has shown the potential to treat a variety of dermatological conditions, including acne, rosacea, and atopic dermatitis. Recent studies have demonstrated the role of nicotinamide, in both topical and oral forms, as a chemopreventive agent against skin cancer. Its anti-carcinogenic role may be due to its ability to enhance DNA repair and prevent ultraviolet (UV)-induced immunosuppression, which is known to contribute to the progression of pre-malignant lesions. Furthermore, nicotinamide is a precursor of essential coenzymes for many important reactions in the body, including the production of nicotinamide adenine dinucleotide (NAD). NAD is a key coenzyme in the synthesis of adenosine triphosphate (ATP), which transports chemical energy within cells. Therefore, nicotinamide plays a significant role in supporting energy-dependent cellular processes, including DNA repair.
{"title":"Vitamin B Derivative (Nicotinamide)Appears to Reduce Skin Cancer Risk.","authors":"S Nazarali, P Kuzel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nicotinamide, an amide form of vitamin B3, has shown the potential to treat a variety of dermatological conditions, including acne, rosacea, and atopic dermatitis. Recent studies have demonstrated the role of nicotinamide, in both topical and oral forms, as a chemopreventive agent against skin cancer. Its anti-carcinogenic role may be due to its ability to enhance DNA repair and prevent ultraviolet (UV)-induced immunosuppression, which is known to contribute to the progression of pre-malignant lesions. Furthermore, nicotinamide is a precursor of essential coenzymes for many important reactions in the body, including the production of nicotinamide adenine dinucleotide (NAD). NAD is a key coenzyme in the synthesis of adenosine triphosphate (ATP), which transports chemical energy within cells. Therefore, nicotinamide plays a significant role in supporting energy-dependent cellular processes, including DNA repair.</p>","PeriodicalId":21829,"journal":{"name":"Skin therapy letter","volume":"22 5","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35338566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}