Janus Kinase and Tyrosine Kinase Inhibitors in Dermatology: A Review of Their Utilization, Safety Profile and Future Applications.

Janus kinase inhibitors, also commonly referred to as JAK inhibitors, are a novel drug class that target and block cytokine signaling mediated by the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, thereby regulating immune response and cell growth. Although JAK inhibitors are mainly used for rheumatological conditions such as rheumatoid arthritis, their application in the field of dermatology is actively being investigated. Tofacitinib is US FDA-approved for psoriatic arthritis and showing promise for treating psoriasis. Most recently, regulatory approvals for the US were gained by ruxolitinib as a first-inclass, selective, topical therapy for atopic dermatitis and oral upadacitinib for active psoriatic psoriasis. Additionally, abrocitinib and upadacitinib have demonstrated efficacy in atopic dermatitis and are pending FDA approval for this indication. The therapeutic potential of JAK inhibitors in dermatological conditions such as alopecia areata, psoriasis, atopic dermatitis, vitiligo, and dermatomyositis are showing promising results in clinical trials. Adverse events for JAK inhibitors seem to be similar to that of biologic drugs. Common adverse effects include increased risk of infections and thromboembolic events. Further investigation is needed to not only better understand the safety profile of JAK inhibitors, but also their full utility within the field of dermatology.

Topical Diacerein Ointment for Epidermolysis Bullosa Simplex: A Review

Epidermolysis bullosa (EB) is a group of rare mucocutaneous fragility disorders often presenting in infancy and early childhood with painful blistering of the skin and mucous membranes. The severity of EB blister burden varies by disease subtype. Studies have shown that patients with generalized severe epidermolysis bullosa simplex (EBS), a variant characterized by extreme fragility, develop blisters in the setting of overproduced, mutated K14 protein, a component of the intermediate filament integral in keratinocyte stability, and constitutive activation of interleukin (IL)-1 , a pro-inflammatory cytokine that promotes the hyperproliferation of keratinocytes. Diacerein, a rhein prodrug and anthraquinone, has been shown to reduce expression of K14 and inhibit IL-1 converting enzyme. In clinical trials, topical 1% diacerein was shown to be an effective and safe, non-invasive treatment for patients suffering from EBS. This review examines the clinical trials of topical diacerein and its role in EBS. Diacerein ointment was granted US FDA Rare Pediatric Disease designation in May 2018 and Fast Track development designation in August 2018.

Glycopyrronium Tosylate (Qbrexza) for Hyperhidrosis

Hyperhidrosis is a condition characterized by excessive sweat production beyond which is physiologically necessary for thermal regulation. Affecting over 4.8% of the United States population, studies have shown that severe primary hyperhidrosis interferes with daily activities and can be considered intolerable, negatively impacting a patient's quality of life. Glycopyrronium tosylate is a topical anticholinergic agent that reduces sweat production by blocking the activation of acetylcholine receptors in peripheral sweat glands. In clinical trials, topical glycopyrronium tosylate, a pre-moistened cloth containing 2.4% glycopyrronium solution, was shown to be an effective, safe and non-invasive treatment for patients suffering from primary hyperhidrosis. This review examines the clinical trials of topical glycopyrronium tosylate and its role in primary hyperhidrosis. Glycopyrronium tosylate was recently US FDA-approved (as of June 2018) to manage patients with primary axillary hyperhidrosis.