Overview of Safety, Efficacy, and Patient Counseling for Ruxolitinib in Treating Atopic Dermatitis.

Ruxolitinib, a Janus kinase (JAK) inhibitor, has been used orally for over a decade in the treatment of myelofibrosis. The immunosuppressive and anti-inflammatory properties of ruxolitinib have made it an attractive treatment option for several dermatologic conditions, such as atopic dermatitis, psoriasis, alopecia areata, and vitiligo. In October 2021, US Food and Drug Administration approved ruxolitinib as the first topical JAK inhibitor for treating atopic dermatitis. Recent studies have demonstrated its efficacy for both visible manifestations and itch of atopic dermatitis. These results indicate that topical ruxolitinib could be used as a long-term glucocorticoid for treating atopic dermatitis. While more studies are required to compare it to classic topical treatments of atopic dermatitis, topical ruxolitinib has a promising future in the field of dermatology. (SKINmed. 2023;21:40-43).

Localized Bullous Pemphigoid Following Orthopedic Surgery.

Bullous pemphigoid is an autoimmune condition whereby the immune system forms antibodies that target the skin, resulting in the formation of blisters in a generalized and symmetric pattern. Localized bullous pemphigoid can occur in special circumstances. Here, we describe two patients that developed localized bullous pemphigoid in one lower extremity following orthopedic surgery. We propose that underlying edema following orthopedic surgery is a potential trigger for localized bullous pemphigoid.

Occupationally Related Nickel Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 1998-2016.

BACKGROUND: The epidemiology of nickel allergy in occupational settings is not well understood. OBJECTIVE: The aim of the study was to characterize occupationally related nickel allergy (ORNA). METHODS: This is a retrospective cross-sectional analysis of 44,378 patients patch tested by the North American Contact Dermatitis Group from 1998 to 2016. Characteristics of individuals with ORNA were compared with those with non-ORNA (NORNA). RESULTS: A total of 7928 (18.2%) individuals were positive to nickel sulfate 2.5%. Two hundred sixty-eight (3.4%) had ORNA. As compared with NORNA, ORNA was statistically associated with the male sex (41.0% vs 12.9%, P < 0.001), a diagnosis of irritant contact dermatitis (22.4% vs 12.0%, P < 0.001), and no history of eczema (81.7% vs 75.7%, P = 0.0217). The most common sites of ORNA dermatitis were hand (39.9%) and arm (18.1%), which were significantly more common than in NORNA (P < 0.0001). Sixteen industry categories and 22 occupation categories were identified for ORNA; the most common industries were durable goods manufacturing (24.6%) and personal services (15.7%), and the most frequent occupations were hairdressers/cosmetologists/barbers (14.3%), machine operators (9.3%), and health care workers (7.1%). Overall 30% of ORNA occupations were in metalworking. Of 215 ORNA sources identified, instruments/phones/other equipment (16.3%), vehicles/machinery (15.8%), and tools (15.3%) were the most common. CONCLUSIONS: Occupational nickel allergy is distinct from nonoccupational nickel allergy.

Epidemiology of nickel sensitivity: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data 1994-2014.

BACKGROUND: Nickel is a common allergen. OBJECTIVE: To examine the epidemiology of nickel sensitivity in North America. METHODS: Retrospective, cross-sectional analysis of 44,097 patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. Nickel sensitivity was defined as a positive patch test for nickel. We evaluated the frequency of nickel sensitivity and patient demographics. For each positive reaction to nickel, we tabulated clinical relevance, occupational relatedness, and exposure sources. RESULTS: The average frequency of nickel sensitivity was 17.5% (1994-2014). Nickel sensitivity significantly increased over time (from 14.3% in 1994-1996 to 20.1% in 2013-2014 [P < .0001]). Nickel-sensitive patients were significantly more likely to be female, young, nonwhite, and atopic (have eczema and asthma) and/or have dermatitis affecting the face, scalp, ears, neck, arm, or trunk (P values ≤ .0474). Overall, 55.5% of reactions were currently clinically relevant; this percentage significantly increased over time (from 44.1% in 1994-1996 to 51.6% in 2013-2014 [P < .0001]). The rate of occupational relatedness was 3.7% overall, with a significant decrease over time (from 7.9% in 1994-1996 to 1.9% in 2013-2014 [P < .0001]). Jewelry was the most common source of nickel contact. LIMITATIONS: Tertiary referral population. CONCLUSIONS: Nickel allergy is of substantial public health importance in North America. The frequency of nickel sensitivity in patients referred for patch testing has significantly increased over a 20-year period.

Can Sunscreens Harm Coral Reefs? Addressing Environmental Concerns and Offering Practical Recommendations.

The crucial role sunscreen plays in preventing sunburns, photoaging, and skin cancer is unquestionable, and as a result, it is incumbent upon dermatologists to influence patients to appropriately use sunscreens. In addition to explaining the benefits of sunscreen use and how to properly use sunscreen, dermatologists must also address possible barriers or concerns that patients may have regarding sunscreen. One concern that has gained increasing media attention in the recent years has been the environmental impact of sunscreens, especially the impact on coral reefs. There is strong evidence that some sunscreen ingredients, especially oxybenzone, are harmful to corals if the concentration in water is high. In some situations, primarily related to the number of swimmers and the geography of the shoreline, concentrations of oxybenzone far exceed the levels shown to be harmful to corals. As advocates for our patients' skin health, we need to be prepared to address this issue when asked, so that patients do not forgo sunscreen use in an effort to protect corals. This article will review evidence regarding the effects of sunscreen ingredients on corals and will provide practical guidance for counseling patients on how to select sunscreens that minimize the potential for harm to coral reefs.

Chlorine Dioxide Complex Cleanser: A New Agent With Rapid Efficacy for Keratosis Pilaris.

Chlorine dioxide complex™ is a new molecule to dermatology that is a unique, non-toxic, broad spectrum anti-microbial and keratolytic compound. Chlorine dioxide has been used as an antiseptic in industrial settings for decades, primarily in water treatment facilities for municipal water supplies and food preparation. The compound has exceptional antiseptic properties with no known potential for development of resistance. It is a true keratolytic and anti-inflammatory, but is non-toxic to human tissue due to its unique mechanism of action. Chlorine dioxide's use in consumer products was previously limited because it is inherently an unstable molecule that had to be used quickly after it was produced. However, the recent development of a complexed form of chlorine dioxide that retains its antimicrobial and keratolytic activity has allowed the development of products (AsepticMD, Aseptic Plus, Nashville, TN) that take advantage of the properties of this unique molecule. Here we report a case series demonstrating its efficacy as a cleanser in keratosis pilaris. J Drugs Dermatol. 2018;17(5):554-556.

Epidemiology of pediatric nickel sensitivity: Retrospective review of North American Contact Dermatitis Group (NACDG) data 1994-2014.

BACKGROUND: Nickel is a common allergen responsible for allergic contact dermatitis. OBJECTIVE: To characterize nickel sensitivity in children and compare pediatric cohorts (≤5, 6-12, and 13-18 years). METHODS: Retrospective, cross-sectional analysis of 1894 pediatric patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. We evaluated demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources. RESULTS: The frequency of nickel sensitivity was 23.7%. Children with nickel sensitivity were significantly less likely to be male (P < .0001; relative risk, 0.63; 95% confidence interval, 0.52-0.75) or have a history of allergic rhinitis (P = .0017; relative risk, 0.74; 95% confidence interval, 0.61-0.90) compared with those who were not nickel sensitive. In the nickel-sensitive cohort, the relative proportion of boys declined with age (44.8% for age ≤5, 36.6% for age 6-12, and 22.6% for age 13-18 years). The most common body site distribution for all age groups sensitive to nickel was scattered/generalized, indicating widespread dermatitis. Jewelry was the most common source associated with nickel sensitivity (36.4%). LIMITATIONS: As a cross-sectional study, no long-term follow-up was available. CONCLUSIONS: Nickel sensitivity in children was common; the frequency was significantly higher in girls than in boys. Overall, sensitivity decreased with age. The most common source of nickel was jewelry.

Cutaneous Delayed-Type Hypersensitivity to Surfactants.

BACKGROUND: Repeated and prolonged use of surfactants can cause irritant as well as allergic contact dermatitis. OBJECTIVE: This study reports the frequency of positive patch test results to surfactants tested on the North American Contact Dermatitis Group screening series including cocamidopropyl betaine (CAPB), amidoamine (AA), dimethylaminopropylamine (DMAPA), oleamidopropyl dimethylamine (OPD), and cocamide diethanolamide (CDEA), and correlations of positive reactions between CAPB and the other surfactants. METHODS: This was a retrospective analysis of 10 877 patients patch tested between 2009 and 2014 to the surfactants CAPB, AA, DMAPA, OPD, and CDEA. Frequencies of positive reactions to these surfactants were calculated, and trends of reactivity between the surfactants analyzed. CONCLUSIONS: The OPD had the highest rate of positive patch reactions (2.3%) followed by DMAPA (1.7%), and CAPB (1.4%). The AA and CDEA had the lowest rate of positive reactions (0.8%). There was a high degree of overlap in positive patch tests between the surfactants. The CDEA was the least likely to coreact with another surfactant.

Potential role of reduced environmental UV exposure as a driver of the current epidemic of atopic dermatitis.

The basis for the sudden and dramatic increase in atopic dermatitis (AD) and related atopic diseases in the second half of the 20th century is unclear. The hygiene hypothesis proposes that the transition from rural to urban living leads to reduced childhood exposure to pathogenic microorganisms. Hence instead of having the normal TH1 bias and immune tolerance because of repeated exposure to pathogens, urban dwellers have TH2 cell immune activity and atopic disease in a more sterile environment. Various other environmental exposures have been implicated in the explosion of AD (and atopic disorders in general), including breast-feeding, tobacco smoking, alcohol consumption, and exposure to domesticated furry pets. Notably, the key role of a compromised barrier of neonatal skin as a predisposing factor in the development of childhood AD has recently been demonstrated. In this article we review the salubrious effects of suberythemogenic doses of UVB irradiation for the skin barrier. We then discuss how the lack of sufficient UVB exposure could have contributed to the rapid increase in the incidence of AD in developed countries. This hypothesis offers a separate but not competing partial explanation, which should be viewed as not discounting the role of the etiopathogenic factors that also could influence the prevalence of atopic disorders.

Granulomatous Rosacea and Periorificial Dermatitis: Controversies and Review of Management and Treatment.

Granulomatous rosacea and periorificial dermatitis are common skin conditions affecting the face. This article examines the historical origin, causes, clinical presentation, and management strategies for these entities.

Systemic contact dermatitis to foods: nickel, BOP, and more.

Systemic contact dermatitis (SCD), a cutaneous reaction that is a direct manifestation of systemic exposure to a known allergen in a sensitized individual, has been increasingly recognized as a cause of persistent cutaneous contact dermatitis that is refractory to conventional therapies. While SCD in response to drugs has been described well in the literature, SCD to allergens in common foodstuffs is a less well-articulated phenomenon. Several foods that are universally consumed throughout the world contain potent allergens including nickel, balsam of Peru, trace metals, urushiol, and sesquiterpene lactones as well as a host of others that may cause a distinctive clinical picture. In this review article, the authors review the typical presentation and prevalence of SCD to foods, pathophysiology, the most common offensive ingestible food allergens, several appropriate diets, and effectiveness of dietary avoidance for situations in which SCD is suspected.

Bier spots are an under-recognized cutaneous manifestation of lower extremity lymphedema: a case series and brief review of the literature.

Bier spots represent a benign vascular mottling characterized by multiple irregular white macules along the extensor surfaces of the arms and legs. They have been reported in a variety of diverse conditions with no consistent disease association. We have identified a novel association between these physiologic anemic macules and lower extremity lymphedema. Eleven patients between 23 and 70 years of age (5 male and 6 female) were diagnosed with Bier spots as evidenced by reversible white macules ranging from 3 to 8 mm in diameter on the extensor portions of the feet, ankles, and calves. The thighs were affected as well in 2 morbidly obese subjects. We suspect that these lesions are not uncommon in lymphedema but are simply under-recognized.

Delocalization of Endogenous A-kinase Antagonizes Rap1-Rho-α2C-Adrenoceptor Signaling in Human Microvascular Smooth Muscle Cells.

The second messenger cyclic AMP (cAMP) plays a vital role in the physiology of the cardiovascular system, including vasodilation of large blood vessels. This study focused on cAMP signaling in peripheral blood vessels, specifically in human vascular smooth muscle (microVSM) cells explanted from skin punch biopsy arterioles (also known as resistance vessels) of healthy volunteers. Using these human microVSM we recently demonstrated cAMP activation of exchange protein activated by cAMP (Epac), the Ras-related small GTPase Rap1A, and RhoA-ROCK-F-actin signaling in human microVSM to increase expression and cell surface translocation of functional α2C-adrenoceptors (α2C-ARs) that mediate vasoconstriction. Protein-protein association with the actin-binding protein filamin-2 and phosphorylation of filamin-2 Ser2113 by cAMP-Rap1A-Rho-ROCK signaling were necessary for receptor translocation in these cells. Although cAMP activated A-kinase in these cells, these effects were independent of A-kinase, and suggested compartmentalized A-kinase local signaling facilitated by A-kinase anchoring proteins (AKAPs). In this study we globally disrupted A-kinase-AKAP interactions by the anchoring inhibitor decoy peptide Ht31 and examined the effect on α2C-AR expression, translocation, and function in quiescent microVSM treated with the adenylyl cyclase activator and cAMP elevating agent forskolin. The results show that Ht31, but not the control peptide Ht31-P, reduced forskolin-stimulated Ser133 phosphorylation of A-kinase substrate CREB, reduced α2C-AR mRNA levels, reduced cell surface translocated receptors, and attenuated agonist-triggered receptor functional responses. Together, the results suggest that compartmentalized cAMP signaling elicits a selective cellular response in microVSM, which may have relevance to arteriole physiological function and responses.

Low-nickel diet scoring system for systemic nickel allergy.

BACKGROUND: Consumption of nickel in the diet leads to spongiotic dermatitis in a dose-related fashion in individuals who are allergic to nickel. Dietary modification to reduce nickel intake leads to resolution of this dermatitis. OBJECTIVE: This study aims to create an evidence-based, user-friendly diet to assist patients in reducing dietary nickel intake. METHODS: Food and Drug Administration data on the nickel content of foods were combined with serving size information to calculate the upper limit of nickel per serving for a variety of foods. Based on these calculations, a point system was created that allows patients to reduce their nickel intake below the typical threshold for elicitation of the spongiotic dermatitis. CONCLUSIONS: A simplified point-based diet can help patients with dermatitis due to dietary nickel consumption.

Henoch-Schönlein purpura-like presentation in IgA-dominant Staphylococcus infection - associated glomerulonephritis - a diagnostic pitfall.

BACKGROUND: In children and adults, Henoch-Schönlein purpura (HSP) has a characteristic clinical presentation that includes a purpuric lower extremity skin rash, IgA-dominant glomerulonephritis, and abdominal and joint pain. A similar clinical presentation can be seen in adults who have a systemic infection with methicillin-resistant Staphylococcus aureus. It is critically important to distinguish the IgAdominant glomerulonephritis of HSP from the IgA-dominant glomerulonephritis of staphylococcal infection, because HSP may need to be treated with corticosteroids and immunosuppressives, while Staphylococcus infection-associated glomerulonephritis requires antibiotics. DESIGN: We searched our renal biopsy database for cases of Staphylococcus infection-associated IgA-dominant glomerulonephritis, to identify those with an HSP-like presentation. Their clinical, laboratory, and biopsy findings are reviewed. RESULTS: Between 2004 and 2011, we identified 37 patients with culture-proven Staphylococcus infection-associated glomerulonephritis. Of these, 8 (22%) had an HSP-like presentation manifested by lower extremity purpuric skin rash. Mesangial IgA and C3 deposits were consistent findings on kidney biopsy. Crescents were uncommon. Four of the 8 patients received glucocorticoid (steroid) therapy for a presumed diagnosis of HSP. Renal function worsened in 3 patients, and 1 patient ultimately improved but developed sepsis during the course. Overall, renal outcome was poor in 71% of the cases despite mild chronic renal injury in the biopsy. CONCLUSION: In adult patients with an HSPlike presentation, a high index of suspicion for underlying Staphylococcal infection is warranted. Blood cultures are frequently negative. Cultures from the site of infection should be performed. Steroid treatment did not improve outcomes. Renal outcomes were frequently poor.

Pregnancy and dermatologic therapy.

Dermatologists should be familiar with medication safety in pregnancy to be able to prescribe safely and confidently to pregnant women or women who may become pregnant during the course of treatment for dermatologic conditions. Topical medications should be considered first-line therapy for pregnant women, but certain systemic medications are safe to use in pregnancy and may be prescribed if necessary. Dermatologic surgery may be performed during the second trimester of pregnancy with proper positioning, but elective procedures should be delayed until the postpartum period.

Warfarin-induced Venous Limb Gangrene.

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene.