January 25, 2019

All of the 7 studies reported an increased likelihood of at least 1 extracutaneous infection among patients with atopic dermatitis.

Patients with atopic dermatitis (AD) have an increased risk for development of extracutaneous infections, in particular ear infection, strep throat, and urinary tract infection (UTI). Moreover, some studies have also suggested that AD may be associated with the development of certain potentially life-threatening infections, including septicemia, endocarditis, and meningitis. Findings from the study were published in the Journal of the American Academy of Dermatology.

The investigators sought to establish whether the occurrence of extracutaneous bacterial and mycobacterial infections is elevated among patients with AD. A total of 7 studies met inclusion criteria for the meta-analysis. All of the 7 studies reported an increased likelihood of at least 1 extracutaneous infection among patients with AD, including meningitis, endocarditis, encephalitis, sepsis, and bone and joint infections.

In pooled meta-analysis, the presence of AD in both children and adults was associated with significantly higher odds for the development of ear infection (odds ratio [OR] 1.29; 95% CI, 1.16-1.43; P <.0001), UTI (OR 2.31; 95% CI, 1.66-3.22; P <.0001), and strep throat (OR 2.31; 95% CI, 1.66-3.22; P <.0001), but not for pneumonia (OR 1.72; 95% CI, 0.75-3.98; P =.20), compared with control subjects.

No evidence of publication bias was detected among the studies that provided sufficient data for inclusion in the meta-analysis. A major limitation of this analysis, however, is the fact that individual-level data were not available.

The investigators concluded that future translational studies on this issue are warranted in order to confirm these relationships and to determine the exact causal mechanisms of the association between AD and increased extracutaneous infections. The associations reported in this meta-analysis are clinically relevant, as many of the infections identified are linked to significant pain and discomfort, lost school and work productivity, and have the possibility of being life threatening.

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Reference

Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extra-cutaneous bacterial and mycobacterial infections: a systematic review and meta-analysisJ Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.028

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January 24, 2019

Researchers treated patients with a microneedle fractional radiofrequency device to determine its safety and efficacy to treat facial acne scars.

The use of a microneedle fractional radiofrequency (MFR) system for the treatment of atrophic facial acne scars has demonstrated efficacy and safety among a group of Turkish patients, according to the results of a retrospective study conducted at the Dermato-Cosmetology Department of Uludag University Medical School in Bursa, Turkey, from 2014 to 2018. Findings from the analysis were published in the Journal of Cosmetic Dermatology.

The investigators sought to examine use of the MFR device among 9 patients with atrophic facial acne scarring. The severity of acne scars was classified via use of the Goodman and Barron’s Global Qualitative Acne Scarring Grading System, as follows: 1, macular; 2, mild; 3, moderate; and 4, severe. The number of MFR treatment sessions varied among the participants, from 1 to 5 (median, 3), with 4-week intervals between sessions. The efficacy of the device was evaluated by physicians’ global assessment and patients’ self-assessment scales at 4 weeks after the last treatment.

Of the 9 participants, 7 were women and 2 were men. The mean patient age was 31.33±11.09 (range, 17-50) years. Among the participants, 2 had mild, 4 had moderate, and 3 had severe facial acne scars. The mean age of the acne scars was 13.22±8.79 (range, 4-30) years. According to the predominant scar subtype, 3 patients had V-shaped scars, 3 had U-shaped scars, and 3 had M-shaped scars.

Clinical improvement of >25% has been reported among 77.7% (7 of 9) and 88.9% (8 of 9) of the patients, according to physicians’ global assessment and patients’ self-assessment, respectively. Better clinical improvement was attained in those with U-shaped atrophic acne scars (22.2% rated as good improvement according to patients’ self-assessment, and 11.1% rated as good or excellent improvement according to physicians’ global assessment) compared with patients with M-shaped and V-shaped scars.

No severe adverse effects, including scarring, pigmentation changes, and wound infection, were reported among patients treated with the MFR system.

The investigators reported favorable efficacy and safety among a group of Turkish patients with atrophic facial acne scars who were treated with the MFR device. Use of the system had the advantage of a quick return to daily life among treated patients. Additional studies are warranted in a large number of patients, including patients with all subtypes of acne scars, to further evaluate the efficacy of the MFR device. Combination therapies with the MFR system and other treatment methods should also be evaluated, particularly among patients with recalcitrant types of scars.

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Reference

Bulbul Baskan E, Akin Belli A. Evaluation of the efficacy of microneedle fractional radiofrequency in Turkish patients with atrophic facial acne scars [published online November 11, 2018]. J Cosmet Dermatol. doi: 10.1111/jocd.12812

January 24, 2019

Overall, 43.8% of the participants healed with the use of topical therapy alone within the 6-month treatment period.

The use of high-potency topical corticosteroid therapy in patients with pyoderma gangrenosum (PG) is an effective first-line treatment that avoids the possible adverse effects associated with the use of systemic therapies, according to the results of a recent study. The large prospective cohort study included secondary care patients in the United Kingdom. All participants had a clinical diagnosis of PG and were deemed suitable for topical treatment. Results were published in the Journal of the American Academy of Dermatology.^1,2  

The prospective cohort analysis was conducted alongside a randomized controlled trial of systemic treatments for patients with PG (the Study of Treatments for Pyoderma Gangrenosum Patients [STOP GAP]), in which oral prednisolone was compared with cyclosporine.^2,3

The investigators sought to estimate the efficacy of topical corticosteroids compared with the topical calcineurin inhibitor tacrolimus for the treatment of PG, a painful ulcerating disease for which the current evidence base regarding treatment is limited.^1,2 All participants received topical therapy following normal clinical practice (mainly classes I to III topical corticosteroids or tacrolimus 0.03% or 0.1%).² The primary study outcome was speed of healing on evaluation at 6 weeks. Secondary outcomes included the following: (1) proportion of patients healed by 6 months, (2) time to healing, (3) global assessment, (4) quality of life, (5) pain, (6) inflammation, (7) recurrence, and (8) treatment failure.²

A total of 67 patients were enrolled in the study. Of those participating, 49 patients received clobetasol propionate 0.05%, 10 patients received tacrolimus 0.03%, and 8 patients received other topical interventions. All participants were age 18 years or older.²

Overall, 43.8% of the participants healed with the use of topical therapy alone within the 6-month treatment period.^1,2 The initial ulcer size was a significant predictor of time to healing (hazard ratio 0.94; 95% CI, 0.88-1.00; P =.043).² Among the participants with PG, 15% experienced a recurrence of disease.^1,2 The median time to the healing of ulcers was 145 days.²

The investigators concluded that clobetasol propionate 0.05% demonstrated potential use as a first-line treatment for patients with PG, particularly those with small lesions.^1,2 Whether more severe PG will respond adequately to topical treatment alone requires further elucidation,² with larger ulcerations possibly requiring more intensive therapy.¹ A major limitation of the study was that it did not contain a randomized comparator.²

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References

1. Lake E. Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study [published online November 14, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.003

2. Thomas KS, Ormerod AD, Craig FE, et al; UK Dermatology Clinical Trials Network’s STOP GAP Team.  Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study[CM1] . J Am Acad Dermatol. 2016;75(3):940-949.

3. Ormerod AD, Thomas KS, Craig FE, et al; UK Dermatology Clinical Trials Network’s STOP GAP Team. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial. BMJ. 2015;350:h2958.

January 24, 2019

Poliosis may be induced among elderly persons with AA who have a poor melanocyte reservoir status.

Studies of poliosis — the regrowth of white hairs at the site of previous patches of AA — in patients with alopecia areata (AA) have been limited mostly to case reports of total or partial whitening with pigmented hair loss. In a retrospective analysis published in the Journal of the American Academy of Dermatology, investigators sought to characterize patients who had AA by comparing those with and without poliosis.¹

The medical records of 258 patients with AA who had visited Wonju Severance Christian Hospital, in Wonju, Korea, between March 2012 and June 2017 were examined retrospectively. All patients were divided into two subgroups: those with and those without poliosis. The demographic variables (age, gender, body mass index, smoking status, and alcohol use), comorbidities (diabetes mellitus, hypertension, and dyslipidemia), and disease-specific variables (age at onset of AA; extent, duration, recurrence, family history, and history of treatment of AA) of the two subgroups were then compared.

Overall, 13 of the 258 patients (5.04%) had poliosis. The average age of those in the poliosis subgroup was higher than the average age of those in the nonpoliosis subgroup. In addition, both the proportion of patients treated with diphenylcyclopropenone and the proportion of patients with less extensive lesions were higher in the poliosis group than in the nonpoliosis group. With respect to comorbidities, according to multivariate logistic regression analysis, only hypertension was significantly associated with poliosis (P =.032; adjusted P =.038).

In patients with AA, melanocyte-associated T-cell epitopes have been shown to behave like autoantigens. It is believed that hair whitening is caused by an interaction among various mechanisms, such as the dysregulation of signaling pathways and transcription factors in the microenvironment surrounding the hair follicle, including melanocyte stem cells, or by an imbalance in the management of oxidative stress.² Therefore, poliosis may be induced among elderly persons with AA who have a poor melanocyte reservoir status.

The investigators concluded that because the current analysis was conducted in a specific population of patients, future studies should consider genetic differences in the prevalence of AA and comorbidities according to ethnicity. Moreover, larger sample sizes need to be evaluated, given that the current study included only a small number of participants at a single institution.

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References

1. Lee YB, Jun M, Lee W-S. Alopecia areata and poliosis: a retrospective analysis of 258 cases [published online November 28, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.033

2. Harris ML, Fufa TD, Palmer JW, et al; NISC Comparative Sequencing Program. A direct link between MITF, innate immunity, and hair graying. PLoS Biol. 2018;16(5):e2003648.

January 23, 2019

The majority of the patients had mycosis fungoides, the most prevalent form of cutaneous T-cell lymphoma.

According to results of a retrospective, observational, noninterventionalist, multicenter Spanish case-series study designed to evaluate the role played by genetic polymorphisms in bexarotene-treated patients with cutaneous T-cell lymphoma (CTCL), screening of the APOA5 and APOC3 genotypes in these individuals may be a useful tactic for estimating triglyceride concentrations. Findings from the current analysis were published in JAMA Dermatology.

The investigators sought to examine the link between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE, and to evaluate the severity of hypertriglyceridemia among patients with CTCL receiving bexarotene therapy, as well as to optimize patient selection for treatment with bexarotene, based on the expected adverse effect profile.

The case series was performed at 12 university hospital dermatology departments in Spain between September 17, 2014, and February 17, 2015. A total of 125 patients with a confirmed diagnosis of CTCL who had received bexarotene for ≥3 months were enrolled in the study. Ultimately, 9 individuals were excluded because of missing analytic triglyceride data; thus, the final study group comprised 116 patients.

Data on demographic and cardiovascular risk factors were obtained for all participants. In addition, a complete blood analysis was performed, including a lipid profile, along with a genetic analysis from a saliva sample. The primary study outcome was the maximal triglyceride levels that were reported in association with the minor alleles of the polymorphisms being analyzed.

The mean patient age was 61.2±14.7 years; 59.5% of the participants were men, and 73.2% had mycosis fungoides, the most prevalent type of CTCL. While undergoing bexarotene treatment, 82.8% (96 of 116) of the participants developed hypertriglyceridemia, which was considered to be severe or extreme in 8.3% (8 of 96) of these patients.

Those individuals who carried minor alleles of the polymorphisms did not demonstrate any significant differences in baseline triglyceride levels. After bexarotene treatment, however, carriers of ≥1 of the 2 minor alleles of APOA5 c.1131T>C and/or APOC3 c.*40C>G had significantly lower concentrations of triglycerides compared with noncarriers of these minor alleles (241.59±169.91 mg/dL vs 330.97±169.03 mg/dL, respectively; P =.02), and were thus less likely to experience severe hypertriglyceridemia.

The researchers concluded that the findings from this study suggest that APO polymorphism investigation might prove beneficial in the clinical evaluation of bexarotene-induced hypertriglyceridemia in patients with CTCL and identification of the most suitable candidates for this treatment. Future studies aimed at exploring the sensitivity of these polymorphisms for predicting adverse outcomes to recognize which patients might need to discontinue treatment, or which will experience pancreatitis are warranted.

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Reference

Cabello I, Alia P, Pintó X, e al. Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-cell lymphoma treated with bexarotene. JAMA Dermatol. 2018;154(12):1424-1431.

January 22, 2019

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) often presents 8–12 days after drug exposure

A recently published case report describing a 27-year-old female patient with a history of polycystic ovary syndrome discusses a rare presentation of Stevens Johnson syndrome (SJS) involving vaginal pain and mucocutaneous desquamation following re-exposure to trimethoprim-sulfamethoxazole (TMP-SMX).

The patient, who presented to the clinical office complaining of dysuria, was diagnosed with a urinary tract infection and was prescribed TMP-SMX. After taking 4 doses of her medication, she presented to the emergency department (ED) complaining of left labial swelling and pain. She was diagnosed with left vulvovaginitis and was told to discontinue TMP-SMX since her urine cultures were negative. Two days later, the patient returned to the ED complaining of worsening vaginal pain and vulvar lesions but was discharged with a sitz bath and supportive care and urged to follow-up at the clinical office. At her follow-up appointment, she was reinitiated on TMP-SMX due to  “concerns of vulvar cellulitis with possible underlying abscess.”

“After she received 2 doses of TMP-SMX, the patient had new lip swelling, periorbital swelling, facial swelling, and formation of thick white plaque on her tongue and mouth,” the study authors reported. They added, “She also developed an erythematous papular pruritic rash on her hands, arms, soles of the feet bilaterally and papules were noted on the legs (up to thighs), feet, and abdomen.”

The study authors also noted that the patient experienced early vesicle formation, skin sloughing, significant erythema and edema in her genital region, a fever of 102°F, plaques on her tongue, and a painful maculopapular skin rash. The patient was diagnosed with SJS and transferred to the burn unit/ICU where she received intravenous immunoglobulin, supportive care, as well as wound care. The patient was discharged 11 days after being admitted to the hospital.

In their review, the study authors discussed several interesting features of this patient case, including the quick onset and development of SJS (6-12 hours vs 6 days to 2 weeks) as well as the unique presentation of the patient (vaginal pain/ mucocutaneous desquamation). They concluded, “This report shows that although SJS is a rare diagnosis, providers should consider SJS as a possible differential diagnosis as a cause of vaginal lesion after exposure to drugs.”

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Reference

Mergler R, Chuang M; Stevens Johnson Syndrome with Vaginal Pain and Lesions as Initial Presentation. Am J Case Rep 2018; 19:1519-1521 DOI: 10.12659/AJCR.912123

January 21, 2019

The investigators sought to describe switching patterns in dermatologic real-life daily practice among patients with psoriasis.

Among patients with psoriasis who require a switch in treatment, a change of therapeutic class appears to be more effective than a switch to an agent in the same therapeutic class, according to the results of a noninterventional, retrospective, multicenter analysis conducted at 11 volunteer dermatology centers in France. Findings from the study were published in Dermatologic Therapy.

The investigators sought to describe switching patterns in dermatologic real-life daily practice among patients with psoriasis. Efficacy was defined as achievement of ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) score, which was evaluated between 12 and 16 weeks after initiation of a new therapy. Patients enrolled in the study included those who were seen in routine daily practice and were being treated with infliximab, etanercept, adalimumab, or ustekinumab. A standardized case report form was filled out for each participant, which included the patient’s characteristics and clinical details, including all prior treatments.

A total of 1157 patients were included in the study, of whom 29.9% (346 of 1157) required a switch in treatment. The mean duration of treatment before the switch was 529.2 days for ustekinumab (range, 121-978 days), 450 days for etanercept (range, 13-2100 days), 431 days for adalimumab (range, 26-1729 days), and 424.2 days for infliximab (range, 4-1977 days; P =.21). When the first-line biologic agent was administered concomitantly with methotrexate, the mean duration of treatment was 530 days (range, 4-2100 days) compared with 439 days (range, 54-1638 days) when the biologic was administered as monotherapy (P =.14).

Switch in biologic agent, which was attributed to lack of efficacy, loss of therapeutic response, or adverse events, was considered effective in 71.9% of patients and ineffective in 28.1% of patients. Notably, switch efficacy was not known for 18 patients because of relocation or missing data.

The results provide a clearer understanding of the profile of patients with psoriasis who require a switch in their therapy, as patients were mostly men, were approximately 40 years of age on initiation of their first biologic agent, and were overweight (mean body mass index, 28 kg/m²). In addition, almost half of all individuals who switched had confirmed psoriatic arthritis.

The investigators concluded that the findings from this study are reflective of the high rate of comorbidities among patients with psoriasis and emphasize the role played by dermatologists in screening comorbidities among patients with psoriasis who require systemic therapy. This role is even more critical in the subpopulation of patients who require a switch from their first-line biologic therapy, regardless of the reason.

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Reference

Dabouz F, Khemis A, Barbe C, et al; Resopso network. Factors associated with successful switching between biologic therapies for the treatment of psoriasis in daily dermatological real-life practice: the Resoswitch study [published online November 28, 2018]. Dermatol Ther. doi: 10.1111/dth.12789

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