Tape Strips Can Help Detect Abnormalities in AD Skin
A recent study showed minimally invasive tape strips can be used to characterize immune and epidermal barrier biomarkers in children with early-onset atopic dermatitis (AD).
“Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous AD phenotype,” the researchers said. “However, skin biopsies are not always feasible in children.”
The research group assessed tape strips for the ability to track cutaneous disease as a minimally invasive approach that could serve as a surrogate to whole-tissue biopsies. Sixteen tape strips were serially collected from lesional and nonlesional skin of 21 children with moderate to severe AD and normal skin of 30 children without AD. Main outcomes included gene and protein expression and were evaluated using quantitative real-time
polymerase chain reaction and immunohistochemistry.
Overall, 77 of the 79 evaluated immune and barrier gene products were detected in 70 of 71 tape strips. In addition, 53 of the 79 markers differentiated between children with AD from children without AD, the researchers said.
Compared with tape strips from normal skin, tape strips from AD skin showed significant increases in many cellular markers of T cells, AD-related dendritic cells, and key inflammatory, innate, and helper T (TH ) cell 2 genes. The researchers noted, for example, a significant difference between mean (SE) levels of IL-4 of -15.2 (0.91) and -19.5 (0.48) in lesional vs normal skin, respectively.
In addition, the researchers observed parallel decreases in epidermal barrier gene products and negative immune regulators. “For example, the decrease for [filaggrin gene] lesional was mean (SE) −2.9 (0.42) and for normal was 2.2 (0.45),” the researchers said. They also found associations between disease severity or transepidermal water loss and TH2 and TH17/TH22 products in lesional and nonlesional AD skin.
With the results of the study, the researchers concluded that the tape strips provided an alternative, minimally invasive method for serially evaluating AD-associated cutaneous biomarkers and that these strips may be useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.
Reference
Guttman-Yassky E, Diaz A, Pavel AB, et al. Use of tape strips to detect immune and barrier abnormalities in the skin of children with early-onset atopic dermatitis [published online October 9, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.2983
Nitric Oxide-releasing Topical May be Effective for Molluscum Contagiosum
A recent study found an investigational topical therapy, SB206 (berdazimer sodium gel coadministered with hydrogel), effectively treated molluscum contagiosum with good tolerability.
While there are numerous treatment options for molluscum contagiosum, none have been well-studied or approved by the FDA, the researchers said.
The group compared the efficacy and tolerability of topical SB206 in a 12-week, multicenter, phase 2, randomized, double-blind, vehicle-controlled clinical trial. A total of 256 participants (mean age, 7 years) were randomized to either twice-daily or once-daily topical SB206 or vehicle. Among the 217 participants who completed the full 12 weeks of treatment, the researchers found all molluscum contagiosum lesions cleared in 13.2%, 41%, and 35.2% of participants treated with either 4%, 8%, or 12% twice-daily SB206, respectively, and 41.9% of those treated with once-daily 12% SB206 compared with 20% of those treated with vehicle.
In participants treated with SB206, application-site erythema occurred in 10.6%, the researchers observed. Application-site reactions were the most common adverse events that led to treatment discontinuation, they added, and affected two participants in each twice-daily SB206 treatment group compared with zero participants in the vehicle and SB206 12% once-daily groups.
“Of the doses studied, SB206 12% applied once daily provided the best balance between [molluscum contagiosum] lesion clearance and tolerability,” the researchers concluded. “A larger study is needed to confirm [once-daily] SB206 12% efficacy and provide additional safety assessments.”
Reference
Hebert AA, Siegfried EC, Durham T, et al. Efficacy and tolerability of an investigational nitric oxide-releasing topical gel in patients with molluscum contagiosum: a randomized clinical trial [published online October 3, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.09.064
New Anti-IgE Antibody Deemed Effective for Chronic Spontaneous Urticaria
Ligelizumab, a next-generation high-affinity humanized monoclonal anti-IgE antibody, was found to be safe and effective for the treatment of chronic spontaneous urticaria, according to the findings of a recent study published in New England Journal of Medicine. These findings are promising, as most therapies available for chronic spontaneous urticaria do not result in complete control of symptoms, the researchers said.
In a phase 2b dose-finding trial, the researchers investigated the efficacy and safety of ligelizumab compared with omalizumab (Xolair) and placebo among 382 patients with moderate to severe chronic spontaneous urticaria that was inadequately controlled with H1-antihistamines at approved or increased doses, alone, or in combination with H2-antihistamines or leukotriene-receptor antagonists. Participants were randomly assigned to receive either a 24-mg, 72-mg, or 240-mg dose of ligelizumab, 300 mg of omalizumab, or placebo administered subcutaneously every 4 weeks for 20 weeks, or a single 120-mg dose of ligelizumab.
Hives, itch, and angioedema were monitored using weekly activity scores. The dose-response relationship for complete control of hives was the main objective, with the primary endpoint for achieving this response assessed at week 12. In addition, the researchers assessed safety throughout the study period.
“A dose–response relationship was established,” the group said of their findings. After 12 weeks of treatment, the researchers found 30%, 51%, and 42% of participants treated with 24 mg, 72 mg, and 240 mg of ligelizumab, respectively, had complete control of hives compared with 26% and 0% among participants in the omalizumab and placebo groups, respectively.
In addition, 30%, 44%, and 40% of participants treated with 24 mg, 72 mg, and 240 mg of ligelizumab, respectively, achieved complete control of symptoms compared with 26% and 0% in the omalizumab and placebo groups, respectively. No safety concerns associated with ligelizumab or omalizumab treatment were observed in the study, the researchers said.
“A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo,” the researchers concluded.
Reference
Maurer M, Giménez-Arnau AM, Sussman G, et al. Ligelizumab for chronic spontaneous urticaria. N Engl J Med. 2019;381(14):1321-1332. doi:10.1056/NEJMoa1900408
Severe Cutaneous Reaction Risk Very High in Some Allopurinol Users
Clinicians should be cautious when prescribing allopurinol for patients with gout and comorbid heart disease, as the medication is associated with higher risk for adverse cutaneous reactions, according to the findings of a recent study published in the Canadian Medical Association Journal.
The study also indicated this risk increased significantly among allopurinol users with comorbid chronic kidney disease and heart disease. Based on these findings, dermatologists should consider the possibility of allopurinol-caused drug reactions among patients with gout, heart disease, and chronic kidney disease.
Using population data, researchers analyzed the association between heart disease and risk of hospitalization for severe cutaneous adverse reactions among 130,325 individuals in British Columbia, Canada, between 1997 and 2015. They adjusted for known and purported risk factors as well as evaluated joint effects of combined clinical and demographic risk factors.
Overall, 109 hospital admissions for allopurinol-associated severe cutaneous adverse reactions were documented.
The researchers found that the multivariable risk was 1.55 for individuals with heart disease (95% CI, 1.01-2.37). Furthermore, patients with both heart disease and chronic kidney disease who initiated allopurinol dosage greater than 100 mg/d had an 11-fold higher risk, the researchers noted. Starting allopurinol at lower dosage among patients with heart disease and chronic kidney disease resulted in a five-fold reduction in this risk, they added.
Notably, the researchers found a 23-fold higher risk of allopurinol-associated severe cutaneous adverse reactions among older women with heart disease from regions with large Asian populations compared with younger men without heart disease from other regions.
“Heart disease is independently associated with risk of allopurinol-associated severe cutaneous adverse reactions, similar to chronic kidney disease, and low-dosage allopurinol initiation may substantially mitigate this risk,” the researchers concluded. “Risk factors for these rare but serious reactions should be considered when initiating allopurinol.”
Reference
Yokose C, Lu N, Xie H, et al. Heart disease and the risk of allopurinol-associated severe cutaneous adverse reactions: a general population-based cohort study. CMAJ. 2019;191(39):E1070-E1077. doi:10.1503/cmaj.190339
Psoriasis May Increase Cancer Risk
Psoriasis was associated with an increased risk of cancer incidence and cancer-related mortality, according to the findings of a recent study in JAMA Dermatology.
“The risk of cancer developing in people with psoriasis has raised some concern, with little clarity regarding differentiation in risk according to psoriasis severity,” the researchers said. They conducted a systematic review and meta-analysis of 58 observational studies that estimated the risk of cancer incidence or mortality among patients with psoriasis. Additionally, they calculated the pooled relative risk (RR) for cancer incidence and cancer-related mortality among patients with psoriasis compared to those without psoriasis.
Severe psoriasis and all severities of psoriasis were associated with an increased risk of overall cancer, the researchers said, with RR of 1.22 (95% CI, 1.08-1.39) and 1.18 (95% CI, 1.06-1.31), respectively. Additionally, they found associations for a range of site-specific cancers, including colon (RR 1.18; 95% CI, 1.03-1.35), colorectal (RR 1.34; 95% CI, 1.06-1.70), kidney (RR 1.58; 95% CI, 1.11-2.24), laryngeal (RR 1.79; 95% CI, 1.06-3.01), liver (RR 1.83; 95% CI, 1.28-2.61), lymphoma (RR 1.40; 95% CI, 1.24-1.57), non-Hodgkin lymphoma (RR 1.28; 95% CI, 1.15-1.43), keratinocyte (RR 1.71; 95% CI, 1.08-2.71), esophageal (RR 2.05; 95% CI, 1.04-4.07), oral cavity (RR 2.80; 95% CI, 1.99-3.93), and pancreatic (RR 1.41; 95% CI, 1.16-1.73).
The researchers found the overall cancer-related mortality risk was highest in patients with psoriasis (RR 1.22; 95% CI, 1.08-1.38). They also found severe psoriasis was associated with elevated liver (RR 1.43; 95% CI, 1.02-1.88), esophageal (RR 2.53; 95% CI, 1.87-3.41), and pancreatic cancer mortality.
“The heterogeneity of estimates was often very high despite stratification,” the researchers said. They also found marked attenuation of risk in studies that adjusted estimates for smoking, alcohol consumption, and obesity.
“These findings suggest that cancer is an important comorbidity in people with psoriasis, and dermatologists should be aware of this increased risk,” the researchers concluded. “Future research examining specific lifestyle factors, treatments, and the inflammatory processes that contribute to psoriasis may help provide additional information on the underlying mechanisms for the apparent increased cancer risk.”
Reference
Trafford AM, Parisi R, Kontopantelis E, Griffiths CEM, Ashcroft DM. Association of psoriasis with the risk of developing or dying of cancer: a systematic review and meta-analysis [published online October 16, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.3056