Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Treatment of Atopic Dermatitis, Dermatophytes, and Syphilis by Indigenous Peoples Prior to 1850.

The Iroquoian and Algonquian-speaking Peoples of North America discovered numerous natural treatments to dermatological conditions long prior to European settlement. Anthropological evidence suggests that treatments for atopic dermatitis, dermatophyte infections, and syphilitic lesions were derived from Sassafras albidum, genus Salix trees, and Sassafras officinale. Literature suggests these medicinal properties are attributed to the naturally abundant safrole, salicylic acid, and ascorbic acid in these flora. Numerous instances of these natural medicinal discoveries later being implemented into European literature reaffirms the impact of Indigenous medicine on contemporary dermatology.

Real-World Moderate-to-Severe Hidradenitis Suppurativa: Decrease in Disease Burden With Adalimumab.

BACKGROUND: Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited. OBJECTIVES: To measure the impact of adalimumab on moderate-to-severe HS patients' health-related quality of life (HRQoL) and work productivity. METHODS: In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician's practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6-10, medium; ≥11, high). RESULTS: From baseline to weeks 24 and 52, all PRO overall scores improved significantly (P ≤ .0023). The number of patients reporting "good disease control" and "complete disease control" increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin "tenderness" and "itchiness" improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders. CONCLUSION: At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients.

Case Report of Patient With Erythropoietic Protoporphyria and Basal Cell Carcinoma Diagnoses.

BACKGROUND: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. There is a clear association between BCC development and ultraviolet (UV) radiation. Erythropoietic protoporphyria (EPP) is an inherited porphyria disorder that is a result of protoporphyrin accumulation, typically manifesting with phototoxicity. CASE SUMMARY: We report a case of a 24 year-old man with both EPP and BCC diagnoses. At the age of 4 years, the patient was diagnosed with EPP. The patient presented with a BCC on his nose at age 24 years, despite sun avoidance as the primary treatment for his EPP diagnosis. CONCLUSION: Consider the diagnosis of BCC in a patient with EPP, despite sun avoidance.

Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: A case report.

Vandetanib is an oral tyrosine kinase inhibitor with cutaneous adverse effects that include the development of acne. We present a patient who underwent vandetanib therapy for stage IV medullary thyroid cancer in conjunction with the use of doxycycline for acne that developed. After vandetanib use, blue-grey pigmentation developed in the acne on his face, chest, back, and arms, which darkened after the use of doxycycline. We review the literature to report that this blue-grey hyperpigmentation was likely vandetanib-induced but may have been the result of both drugs being used in combination.

A Review of the Efficacy and Safety for Biologic Agents Targeting IL-23 in Treating Psoriasis With the Focus on Tildrakizumab.

Psoriasis is a chronic and debilitating inflammatory immune-mediated skin disorder. Several cytokines including interleukin (IL)-23 were demonstrated to play a central role in the pathogenesis of this disease. Treatment options for psoriasis range from topical to systemic modalities, depending on the extent, anatomical locations involved and functional impairment level. Targeting cytokines or their cognate receptors that are involved in disease pathogenesis such as IL-12/23 (i.e., targeting the IL-12p40 subunit shared by these cytokines), IL-17A, IL-17F, IL-17RA, and TNF-α using biologic agents emerged in recent years as a highly effective therapeutic option for patients with moderate-to-severe disease. This review provides an overview of the important role of IL-23 signaling in the pathogenesis of psoriasis. We describe in detail the available IL-23 inhibitors for chronic plaque psoriasis. The efficacy, pharmacokinetic properties, and the safety profile of one of the most recent IL-23 biologic agents (tildrakizumab) are evaluated and reviewed in depth.

Skin care and hygiene among healthcare professionals during and after the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 pandemic has necessitated enhanced protection against viral transmission among healthcare professionals, particularly relating to handwashing and personal protective equipment. Some of these requirements may persist for years to come. They bring associated concerns around skin hygiene and general care, with damage to the face and hands now a well-documented consequence among healthcare professionals. This review assesses optimal skin care during the severe acute respiratory syndrome coronavirus 2 pandemic and in the "new normal" that will follow, identifies current knowledge gaps, and provides practical advice for the clinical setting. Regular, systematic hand cleaning with soap and water or an alcohol-based hand rub (containing 60%-90% ethanol or isopropyl alcohol) remains essential, although the optimal quantity and duration is unclear. Gloves are a useful additional barrier; further studies are needed on preferred materials. Moisturization is typically helpful and has proven benefits in mitigating damage from frequent handwashing. It may be best practiced using an alcohol-based hand rub with added moisturizer and could be particularly important among individuals with pre-existing hand dermatoses, such as psoriasis and eczema. Face moisturization immediately prior to donning a mask, and the use of dressings under the mask to reduce friction, can be helpful dermatologically, but more work is required to prove that these actions do not affect seal integrity. Nonetheless, such measures could play a role in institutional plans for mitigating the dermatologic impact of transmission control measures as we exit the pandemic.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

Low-dose subcutaneous immunoglobulin is an effective treatment for autoimmune bullous skin disorders: A case report.

Intravenous immunoglobulin is a recognized treatment in recalcitrant autoimmune bullous diseases. Infusions are administered monthly over 1-5 days in the hospital setting and associated with mild to severe infusion-related systemic effects, in part due to the high doses necessary to induce and achieve remission. We present a case series of four patients with bullous diseases treated successfully with low-dose subcutaneous IgG who achieved remission with maintenance therapy. Patient-administered smaller, more frequent doses of IgG into subcutaneous tissue more closely mimics the body's own antibody production and produces a more stable serum trough level. Subcutaneous IgG is a novel treatment approach in bullous diseases which can induce a state remission.

Nonprescription acne vulgaris treatments: Their role in our treatment armamentarium-An international panel discussion.

BACKGROUND: Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. OBJECTIVES: This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. METHODS: The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. RESULTS: All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. CONCLUSION: The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Incidence and anatomic presentation of cutaneous malignant melanoma in central Canada during a 50-year period: 1956 to 2005.

BACKGROUND: Incidence rates of cutaneous malignant melanoma (CMM) have increased worldwide. Long-term studies examining rates and anatomic site-specific incidence on a population-based level are infrequent. OBJECTIVE: We sought to examine the historical changes in the incidence and anatomic site presentation of CMM during a 50-year period in Manitoba, Canada. METHODS: Using population-based data, all first diagnoses of CMM reported between 1956 and 2005 were identified. Age-specific rates, age-standardized incidence rates, and anatomic sites were recorded. RESULTS: Incidence rates of CMM slowed for each sex beginning in 1981 for female patients and 1992 for male patients. Annual percent change revealed decreasing rates among male patients younger than 40 years (1992-2005: -5.3% [P = .03]) and female patients younger than 40 years (1987-2005: -1.8% [P = .15]). Similarly, middle-aged individuals (age 40-59 years) also had diminished annual percent change (men 1992-2005: 0.6% [P = .65]; women 1983-2005: -0.3% [P = .68]). The annual percent change for older men and women (60-79 and > or =80 years) continued to increase. Anatomic site-specific analyses revealed that the trunk was the most frequent site of CMM for young male patients (<60 years) whereas the lower extremities were the most common among young female patients (<60 years). Incidence rates for each site, however, are slowing. Among those aged 60 years and older, the rates for each anatomic site increased. LIMITATIONS: Determining changes in tumor thickness would have been useful in determining whether the nature of tumors have changed over time; however, this is not recorded in our registry. CONCLUSION: The rates of CMM are slowing; however, this change is confined to younger individuals. Anatomic site-specific CMMs are changing; rates among older individuals continue to increase for both sexes.

Risk factors for skin cancer and solid tumors in newly diagnosed patients with chronic lymphocytic leukemia and the impact of skin surveillance on survival.

A retrospective analysis on 587 patients with chronic lymphocytic leukemia (CLL) assessed risk factors for skin cancer and the influence of skin cancers on survival and incidence of solid tumors (STs). Patients underwent skin surveillance and were followed for a median of 6.65 years. The relative risk for skin cancer increased prior to CLL diagnosis rising 4-fold one-year post-diagnosis. Independent predictors for skin cancer were male gender (p = .0001), age ≥70 years (p = .0036) and prior chemotherapy (p = .0116). There was no increase in mortality from skin cancer and neither skin cancer nor chemotherapy increased the risk for a ST. The development of a ST was an independent predictor of survival (p < .0001) and 43% of deaths were related to STs. Thus, regular skin surveillance can prevent increased mortality from skin cancer, but not STs, in CLL. Close skin monitoring is required for elderly males who received chemotherapy.

Use of oral miltefosine for cutaneous leishmaniasis in Canadian soldiers returning from Afghanistan.

Old world cutaneous leishmaniasis (CL) is caused by Leishmania major and Leishmania tropica, and is endemic to several Asian and Middle-Eastern countries where the rates of infection can be substantial. CL is one of the most common vector-transmitted parasitic infections in Afghanistan. Six cases of CL in Canadian soldiers returning from Afghanistan are reported in the present study. Their lesions did not improve with fluconazole therapy, and the organism demonstrated in vitro resistance. Oral miltefosine seemed effective.

Risk of second primary cancer and death following a diagnosis of nonmelanoma skin cancer.

Cancer-free patients diagnosed with a first primary nonmelanoma skin cancer (NMSC) offer an opportunity for studying the risk of a second primary cancer without the confounding effect of systemic treatment. The objective of the study was to estimate the risk of second primary cancer in people with a history of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) and the risk of dying in cancer patients with a NMSC history. BCC and SCC cases diagnosed between 1956 and 2000 in Manitoba, Canada were followed-up for second primaries (other than NMSC). Standardized incidence and mortality ratios (SIR and SMR) were calculated. Men [SIR, 1.06; 95% confidence interval (95% CI), 1.02-1.10] and women (SIR, 1.07; 95% CI, 1.02-1.12) with a BCC history as well as men (SIR, 1.15; 95% CI, 1.08-1.22) with a SCC history were at greater risk of a second primary cancer. Overall, the increased risk was observed only in the first 4 years following a NMSC, although it remained increased for specific cancer sites. The risk remained higher in all age groups up to 75 years of age. People with a history of BCC (males: SMR, 1.09; 95% CI, 1.04-1.14; females: SMR, 1.24; 95% CI, 1.16-1.32) or SCC (males: SMR, 1.18; 95% CI, 1.09-1.27; females: SMR, 1.55; 95% CI, 1.35-1.79) had a greater risk of death following their second primaries. Even if NMSC patients are at greater risk of a second cancer, it is not recommended to follow them up beyond the generally accepted periodic examination of the skin.

Trends of nonmelanoma skin cancer from 1960 through 2000 in a Canadian population.

Nonmelanoma skin cancer (NMSC) is the most common malignancy diagnosed in Caucasian populations, but little is known about its occurrence in Canada. We sought to determine the historical change of the occurrence and risk of NMSC. All first diagnoses of NMSC reported in Manitoba between 1960 and 2000 were identified. Rates were reported as well as lifetime risk of developing the disease. Basal cell carcinoma was the predominant form of NMSC, accounting for 79% of all NMSCs. The annual percentage change of basal cell and squamous cell carcinoma increased 2.4%, mainly in people older than 40 years of age from the early 1970s to 2000. The lifetime risk of being diagnosed with NMSC increased by two to three times in the 1990s compared to the 1960s. We concluded that because of the potentially high impact of NMSC on resource utilization and treatment-related costs as well as its easily preventable character, priority should be given to prophylactic measures.

Topical 5% imiquimod in the treatment of lentigo maligna.

BACKGROUND: Standard treatment for lentigo maligna (LM) is surgical excision with 5 to 10 mm margins. This can be cosmetically disfiguring. Imiquimod locally induces Toll-like receptors to release cytokines that destroy neoplastic melanocytes. OBJECTIVE: The off-label use of topical 5% imiquimod cream may provide an alternative to surgery. This study reviews the use of imiquimod to treat LM. METHODS: A 5-year retrospective and prospective chart analysis was conducted. Pretreatment biopsies confirmed the diagnosis. Treatment was individualized for each patient. Posttreatment biopsies and dermoscopy determined clearance of LM. RESULTS: Twenty-seven patients were reviewed. There were 20 responders (74.1%) and 7 failures. The mean tumor size (area of an ellipse) was 6.69 cm2, and the mean treatment duration was 17.68 weeks. Neither the size of the tumor (p  =  .86) nor treatment duration (p  =  .18) was related to resolution of the lesion. CONCLUSION: Imiquimod is an effective treatment for LM that provides patients with a cosmetically favorable outcome when standard surgery is not an option.