Subject(s)
Dermatology , Internship and Residency , Curriculum , Dermatology/education , Education, Medical, Graduate , HumansSubject(s)
Boron Compounds/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Dermatitis, Atopic/drug therapy , Dermatologic Agents/therapeutic use , Administration, Cutaneous , Administration, Topical , Dose-Response Relationship, Drug , Eczema/drug therapy , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely pruritic papulovesicular eruption over extensor surfaces such as the knees, elbows, lower back, buttocks, and neck. Patients are instructed to adhere to a gluten-free diet for purposes of improving their skin disease and gluten-sensitive enteropathy; this is the only treatment that lowers risk of enteropathy-associated T cell lymphoma. Patients who adhere to a strict gluten-free diet often have remission of their skin disease over months to years. Dapsone is a rapid and extremely effective first-line treatment option and often used while transitioning to a gluten-free diet. Aside from gluten-free diet and dapsone, second-line treatment options include sulfapyridine, sulfasalazine, and colchicine. Some patients have difficulty adhering to a gluten-free diet or develop intolerable side effects to systemic therapies. Furthermore, there is limited data on the use of the second-line treatments. Recent studies have shed light on the role of JAK-STAT-dependent pathways in the pathogenesis of dermatitis herpetiformis. We present a patient treated with tofacitinib, 5mg twice daily, an oral JAK1/3 inhibitor, who demonstrated clinical improvement of DH and control of new lesion development.
Subject(s)
Celiac Disease/complications , Dermatitis Herpetiformis/drug therapy , Piperidines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Aged , Celiac Disease/diet therapy , Dapsone/therapeutic use , Dermatitis Herpetiformis/diet therapy , Dermatitis Herpetiformis/etiology , Dermatitis Herpetiformis/pathology , Diet, Gluten-Free , Drug Administration Schedule , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 3/antagonists & inhibitors , Male , Patient Compliance , Remission Induction/methods , Treatment OutcomeABSTRACT
Introduction: Biologics have transformed the management of moderate-to-severe psoriasis. The risk of developing a malignancy during treatment is an important consideration, and many studies have been conducted to determine the magnitude of this risk. However, there is little research on the use of biologic treatment in psoriasis patients with a history of established malignancy. Methods: We preformed a retrospective chart review of patients with psoriasis and a history of malignancy that were treated with biologics or apremilast. A list was created containing the 690 patients with psoriasis who were treated in our clinic with biologics or apremilast between January 1st, 2012 and May 31, 2018. The charts were examined, and 16 patients were found to have a history of malignancy excluding non-melanoma skin cancer. Results: Sixteen patients met criteria to be included in this review. The average time from cancer diagnosis to initiation of biologics or apremilast was 4.7 years, and 9 patients (56%) started treatment within five years. Three patients (19%) received concurrent cancer therapy during biologic treatment. None of the 16 patients had recurrence or progression of their cancer noted clinically or radiographically during biologic or apremilast treatment. Most patients had improvement of their psoriasis. Discussion: The data reviewed here show successful treatment on biologics despite concurrent malignancy, though confirmatory research is needed. J Drugs Dermatol. 2019;18(4):387-390.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biological Products/therapeutic use , Neoplasms , Psoriasis/drug therapy , Thalidomide/analogs & derivatives , Female , Humans , Male , Middle Aged , Retrospective Studies , Thalidomide/therapeutic use , Treatment OutcomeSubject(s)
Antibodies, Monoclonal/therapeutic use , Drug Approval , Hidradenitis Suppurativa/diagnosis , Hidradenitis Suppurativa/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized , Cohort Studies , Female , Follow-Up Studies , Humans , Injections, Subcutaneous , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome , United States , United States Food and Drug Administration , Young AdultABSTRACT
BACKGROUND: Discoid lupus erythematosus (DLE) and dermatomyositis (DM) are inflammatory autoimmune diseases that manifest primarily in the skin but can be linked to systemic complications. Although there is an in-depth understanding of the clinical presentation of these two diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients. OBJECTIVE: An understanding of the pathogenesis of each disease in greater detail will lead to newer targeted medications with less morbidity. This review article endeavors to substantiate the use of new treatments which target the JAK-STAT pathway while elaborating on the immunopathology as well. METHODS: PubMed was searched for relevant review articles, case reports, case series reports, randomized clinical trials (RCTs), basic science articles. Appropriate key terms and MeSH terms were utilized in the search. Clinicaltrials.gov was used to find relevant and current clinical trials being conducted in DLE and DM patients. RESULTS: A review of the literature supports the proposal that though there are likely many components and pathways involved in the destruction of keratinocytes, the Th1 cell immune response and specifically the JAK-STAT signaling pathway is common to both DLE and DM. CONCLUSION: Although further study is needed to determine the efficacy and benefits of JAK inhibitors over conventional therapy, these medications should be considered in refractory cases.
Subject(s)
Dermatomyositis/metabolism , Interferon Type I/metabolism , Interferon-gamma/metabolism , Janus Kinases/metabolism , Lupus Erythematosus, Discoid/metabolism , STAT Transcription Factors/metabolism , Animals , Dermatomyositis/drug therapy , Humans , Janus Kinases/antagonists & inhibitors , Lupus Erythematosus, Discoid/drug therapy , Protein Kinase Inhibitors/therapeutic use , Signal Transduction/drug effectsABSTRACT
Maintaining blood-brain barrier integrity and minimizing neuronal injury are critical components of any therapeutic intervention following ischemic stroke. However, a low level of vitamin D hormone is a risk factor for many vascular diseases including stroke. The neuroprotective effects of 1,25(OH)2D3 (vitamin D) after ischemic stroke have been studied, but it is not known whether it prevents ischemic injury to brain endothelial cells, a key component of the neurovascular unit. We analyzed the effect of 1,25(OH)2D3 on brain endothelial cell barrier integrity and tight junction proteins after hypoxia/reoxygenation in a mouse brain endothelial cell culture model that closely mimics many of the features of the blood-brain barrier in vitro. Following hypoxic injury in bEnd.3 cells, 1,25(OH)2D3 treatment prevented the decrease in barrier function as measured by transendothelial electrical resistance and permeability of FITC-dextran (40 kDa), the decrease in the expression of the tight junction proteins zonula occludin-1, claudin-5, and occludin, the activation of NF-kB, and the increase in matrix metalloproteinase-9 expression. These responses were blocked when the interaction of 1,25(OH) )2D3 with the vitamin D receptor (VDR) was inhibited by pyridoxal 5'-phosphate treatment. Our findings show a direct, VDR-mediated, protective effect of 1,25(OH) )2D3 against ischemic injury-induced blood-brain barrier dysfunction in cerebral endothelial cells.
