twenty-first issue
november 2, 2022
Patch testing in patients with allergic contact dermatitis to medical adhesives identifies specific allergens
Journal of the American Academy of Dermatology
Contact dermatitis? I don’t even have her number!
Adhesives are widely used across medical specialties and can pose dermatological challenges for some patients. Patients commonly experience irritant contact dermatitis in response to adhesives, but they can also experience allergic contact dermatitis (ACD) due to specific components of adhesives. Researchers sought to identify the most common triggers of ACD found in adhesives.
In a retrospective study, 43,722 patients from the North American Contact Dermatitis Group (NACDG) were patch tested from 2001-2018 with the NACDG screening series. In addition, they were tested with supplemental allergens and/or medical adhesive materials as indicated by patient history. The study cohort was composed of patients with a final diagnosis of ACD with a medical adhesive source to either the screening series or a supplemental allergen/material.; 313 patients met this inclusion criteria. The control group had patients with a diagnosis of ACD, but no medical adhesive source. The study found that study group patients were less likely to be male (OR, 0.58; 95% CI, 0.45-0.77) and/or less likely to be aged >40 years (OR, 0.76; 95% CI, 0.60-0.96). For the NACDG screening allergens, the most common positive patch test reactions were in response to colophony (80.7%), followed by balsam of Peru (3.9%), 2-hydroxyethyl methacrylate (2.7%), and carba mix (2.7%). Study group participants were more likely to have ACD on the trunk (OR, 2.12; 95% CI, 1.63-2.75) and leg (OR, 1.63; 95% CI, 1.20-2.21) and less likely to have involvement of the hands (OR, 0.76; 95% CI, 0.58-0.99), face (OR, 0.72; 95% CI, 0.54-0.96), eyelids (OR, 0.48; 95% CI, 0.30-0.77), and lips (OR, 0.47; 95% CI, 0.22-1.00). Importantly, of the 313 patients with medical adhesive contact allergy, 79 (25.2%) had at least 1 positive patch test reaction to a supplemental allergen/material and 54 (17.3%) only had positive reactions to supplemental allergens/materials.
Limitations: Patch testing may be prone to referral selection bias and may not represent the general population.
Main Takeaway: Colophony was by far the most commonly identified source of medical adhesive allergens (80.7%), followed by balsam of Peru (3.9%), 2-hydroxyethyl methacrylate (2.7%), and carba mix (2.7%). It is important to test supplemental allergens and materials in addition to the screening series to avoid missing additional contact allergens.
What are these medical adhesive allergens?
- Colophony: comes from the sap of coniferous trees and historically has been used in bandages and adhesives (although many modern bandages are pressure-sensitive, acrylate-based adhesives); a study in 2020 did still find that colophony based products were in 5 of 16 tested medical adhesive products
- Balsam of Peru: this is an aromatic liquid used for fragrance and flavoring; it cross reacts with benzoin (a balsamic resin used in adhesives) which is a reason that it is an important contact allergen
- 2-hydroxyethyl methacrylate: this is an acrylate used as an adhesive; many acrylate allergens are not part of the screening series, and this is another reason why it is important to include supplemental allergens when testing for ACD to adhesives
- Carba mix: this is a type of rubber accelerator, and rubber is used to formulate flexible base of bandages and medical adhesives
There is a unique population of low-density neutrophils in generalized pustular psoriasis
Journal of Investigative Dermatology
He’s just an average guy with the power to cause massive skin destruction– NeutroPhil!
Generalized pustular psoriasis (GPP) is a skin disorder characterized by widespread, neutrophilic pustules. Prior studies have linked GPP to dysregulation of the IL-36 immune pathway in the skin. To better understand disease pathogenesis, the authors studied the genes expressed in peripheral blood mononuclear cells (PBMCs) and neutrophils from 8 patients with GPP during acute flares and compared them to those from 8 patients with psoriasis vulgaris and 8 healthy control participants. During GPP flares, they identified:
- The gene expression signature of GPP cells were unique from the cells from psoriasis vulgaris and healthy controls. Overall, GPP was characterized by a neutrophil-dominant signature.
- A dramatic increase in CD66+, CD16+ low density neutrophils (LDNs). LDNs are a subset of neutrophils and have been implicated in diseases such as systemic lupus erythematosus.
- They looked at the genetic expression profiles of LDNs and normal density neutrophils and found that the transcriptional profiles between the two were distinct.
- In LDNs, they found a “hypoinflammatory phenotype” with enhanced release of neutrophil granule proteases.
- The authors speculate that GPP LDNs may contribute to the release of neutrophil granule proteases which may be important for IL-36 activation.
Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial
British Journal of Dermatology
Looking for a new acne treatment? Well this is zit!
The peroxisome proliferator-activated receptor-γ (PPARγ) is implicated in sebocyte differentiation, sebum production, and the inflammatory reaction, all of which contribute to the development of acne. N-acetyl-GED-0507-34-LEVO (NAC-GED) is a new topical medication which modulates PPARγ and thus may be useful in the treatment of acne.
This double-blind phase II randomized controlled trial evaluated both the efficacy and safety of 5% and 2% NAC-GED versus placebo (vehicle) when applied once daily for 12 weeks for facial acne in patients 12 – 30 years of age. To be eligible, total lesion count (TLC) at baseline of 20 – 100 and Investigator Global Assessment (IGA) score of 3-4 were required.
A total of 450 patients were assigned 1:1:1 to NAC-GED 5%, 2%, or vehicle [n=150, each]. Among NAC-GED users, there was a statistically significant reduction in TLC from baseline [NAC-GED 5%: -57.1%, p-value <0.001, NAC-GED 2%: -44.7%, p-value <0.001] when compared with vehicle [-33.9%]. Similarly, NAC-GED had higher rates of IGA success, defined as at least a two-score reduction (0 = clear, 1 = almost clear] as compared to placebo [NAC-GED 5%: 45%, 2%: 33%, vehicle 24%), though there was not a significant difference between 2% and vehicle. Adverse events occurred in 19% of patients prescribed NAC-GED 5% and vehicle, and in 16% of patients prescribed NAC-GED 2%, among which cold, headache, and sore throat were most common.
Limitations: The study period was 12 weeks, which may have not been sufficient time to detect significant acne improvement, or to observe relapse after discontinuation of therapy. This study was unable to control for factors that may contribute to acne development, such as dietary habits or BMI.
Main Takeaway: NAC-GED, a novel acne therapy targeting PPARγ, is both effective and safe for the treatment of facial acne in adolescents. This trial supports future, large-scale phase III trials.
The peroxisome proliferator-activated receptor-γ (PPARγ) is implicated in sebocyte differentiation, sebum production, and the inflammatory reaction, all of which contribute to the development of acne. N-acetyl-GED-0507-34-LEVO (NAC-GED) is a new topical medication which modulates PPARγ and thus may be useful in the treatment of acne.
This double-blind phase II randomized controlled trial evaluated both the efficacy and safety of 5% and 2% NAC-GED versus placebo (vehicle) when applied once daily for 12 weeks for facial acne in patients 12 – 30 years of age. To be eligible, total lesion count (TLC) at baseline of 20 – 100 and Investigator Global Assessment (IGA) score of 3-4 were required.
A total of 450 patients were assigned 1:1:1 to NAC-GED 5%, 2%, or vehicle [n=150, each]. Among NAC-GED users, there was a statistically significant reduction in TLC from baseline [NAC-GED 5%: -57.1%, p-value <0.001, NAC-GED 2%: -44.7%, p-value <0.001] when compared with vehicle [-33.9%]. Similarly, NAC-GED had higher rates of IGA success, defined as at least a two-score reduction (0 = clear, 1 = almost clear] as compared to placebo [NAC-GED 5%: 45%, 2%: 33%, vehicle 24%), though there was not a significant difference between 2% and vehicle. Adverse events occurred in 19% of patients prescribed NAC-GED 5% and vehicle, and in 16% of patients prescribed NAC-GED 2%, among which cold, headache, and sore throat were most common.
Limitations: The study period was 12 weeks, which may have not been sufficient time to detect significant acne improvement, or to observe relapse after discontinuation of therapy. This study was unable to control for factors that may contribute to acne development, such as dietary habits or BMI.
Main Takeaway: NAC-GED, a novel acne therapy targeting PPARγ, is both effective and safe for the treatment of facial acne in adolescents. This trial supports future, large-scale phase III trials.
Pediatric telogen effluvium patients have a range of triggers, including emotional stress and acute febrile illness
Journal of Pediatric Dermatology
Stress induced alopecia? Get outta hair!
Telogen effluvium (TE) is a diffuse, rapidly occurring non-scarring alopecia caused by alteration of the hair follicle cycle involving the anagen, catagen, and telogen phases. TE is often induced by a trigger that causes premature transition or duration of phases. Potential triggers include febrile illness, hemorrhage, dietary changes, nutritional deficiencies, emotional stress, vaccinations, and chemotherapy. Acute TE is self-limited, while chronic TE persists longer than 6 months. Patients present with hair thinning and may present with positive hair pull test and/or Beau’s lines on nails. While previous research has investigated TE in adult patients, few studies have investigated TE incidence, patient characteristics, and triggers in pediatric patients.
To better understand the epidemiology, exposures, and disease course of pediatric patients with TE, researchers conducted a retrospective single-center study of 76 children between ages 1 and 17 with acute and chronic TE. Average age of disease onset was 12.3 years old, and the patients were 88% female and 12% male. 32% of patients had additional non-dermatologic conditions, including asthma, anemia, thyroid disease, GI diseases, and attention deficit and hyperactivity disorder. 58% of patients had at least one associated trigger, with the most common triggers being emotional stress (18.4%), acute or febrile illness (14.5%), and nutritional deficiencies in iron, ferritin, or Vitamin D (11.9%). On exam, 42% of patients had diffuse thinning, and other hair loss patterns included bitemporal (2.6%) and vertex/crown distribution (2.6%). Observation (47.4%) was the most common treatment approach, although other treatments included topical steroid, minoxidil, vitamin supplementation, dietary counseling, fish oil supplementation, and counseling against harsh hair styling.
Limitations: Given the nature of this study, future studies are needed to elucidate the pathophysiologic mechanisms of associated triggers and establish greater evidence-based treatment approaches.
Main Takeaway: This study found that TE affects children of all ages in both acute and chronic forms, and patients demonstrate broad variability in presentation and age of onset. Work-up for common triggers is warranted.
