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Literature Lessons – September

Including the latest on acne, atopic dermatitis, COVID-19, contact dermatitis, cutaneous oncology, drugs and devices, infectious disease, psoriasis, and more.

GENERAL DERMATOLOGY

A recent retrospective study at Children’s Hospital of Colorado involving 190 patients showed that PRIOR AUTHORIZATIONS failed to reveal any inappropriate prescribing but did delay therapy, leading to potentially avoidable health care utilization (emergency department visits, hospitalization).

TO READ MORE: Constant BD, et al. Delays Related to Prior Authorization in Inflammatory Bowel Disease. Pediatrics. 2022;149(3):e2021052501. doi:10.1542/peds.2021-052501.

Editor’s note: In my opinion, the entire prior authorization process is deeply flawed and needs significant reform.

PEDIATRIC DERMATOLOGY

A recent CDC authored study concluded that, between 2015 and 2020, more adolescents were receiving human papillomavirus (HPV) VACCINATION. The percentage of those aged 13 to 17 who received at least one dose of the vaccine rose from 56% to 75%, and the proportion who completed the full vaccine series increased from 40.3% to 59.3%.

TO READ MORE: Lu PJ, et al. Human Papillomavirus Vaccination Trends Among Adolescents: 2015 to 2020. Pediatrics. 2022;150(1):e2022056597. doi:10.1542/peds.2022-056597.

Editor’s note: A factor found to facilitate HPV vaccination was medical provider recommendation. In dermatology, we see adolescents frequently for things like acne, eczema, and warts. OUR recommendation could help reinforce this positive trend going forward.

A systematic review of 122 reports involving 1032 PEDIATRIC ALOPECIA AREATA patients found that the use of potent topical steroids was not only the most frequent intervention but also was justified by available literature. The second most common intervention was contact immunotherapy utilizing either diphenylcyclopropenone (DPCP) or squaric acid dibutyl ester (SADBE). Most other treatments were either ineffective or rarely used. The evidence for either topical or systemic JAK inhibitor use was severely limited in the pediatric population, although this is done (off-label) in some academic centers.

TO READ MORE: Barton VR, et al. Treatment of pediatric alopecia areata: A systematic review. J Am Acad Dermatol. 2022;86(6):1318-1334. doi:10.1016/j.jaad.2021.04.077.

A retrospective Turkish study of PEDIATRIC URTICARIA identified a “trigger” in 46% of patients. Triggers included: infections (18%), drugs (11%), foods (8%), infections and drugs (3%), insects (3%), and seasonal pollen (1%). The most common infections associated with acute urticarial included: upper respiratory tract infections (74.5%), urinary tract infections (13.2%), gastroenteritis (8.2%), and otitis media (4.1%). Severe urticaria was associated with recurrent bouts of hives.

TO READ MORE: Bezirganoglu H, et al. The common triggers of urticaria in children admitted to the pediatric emergency room [published online ahead of print, 2022 May 6]. Pediatr Dermatol. 2022;10.1111/pde.15020. doi:10.1111/pde.15020.

PSORIASIS

Mindera Health’s product, Mind.Px, is a machine-learning based test which helps predict a patient’s response to a given class of biologic drug therapy with a positive predictive value of 91%. The test consists of a painless patch placed on psoriasis patients’ skin for 5 minutes. The RNA gathered by the patch is utilized to analyze over 7000 biomarkers to determine the OPTIMAL BIOLOGIC THERAPY.

SOURCE: Strober BE, et al. Dermatologist concordance with a precision medicine test for the selection of psoriasis biologic treatment. Poster, presented at the San Diego Dermatology Symposium, March 11-13, 2022.

Using global data and sophisticated meta-analytic methodology, investigators concluded that the global PREVALENCE OF THE METABOLIC SYNDROME among patients with psoriasis was 32% (95% confidence interval [26-38%). The risk for metabolic syndrome was much less—approximately 9%—in children and adolescents. Comparing geographic sites, North America had the lowest overall prevalence of 26%.

TO READ MORE: Liu L, et al. Global prevalence of metabolic syndrome in patients with psoriasis in the past two decades: current evidence [published online ahead of print, 2022 Jun 6]. J Eur Acad Dermatol Venereol. 2022;10.1111/jdv.18296. doi:10.1111/jdv.18296.

Investigators recently utilized data from the U.S. FDA Adverse Event Reporting System (2016-2021) to screen for drugs associated with NEW ONSET OR WORSENING OF PRE-EXISTING PSORIASIS. Prednisone, tocilizumab, hydroxychloroquine and (surprisingly) dupilumab were the most often implicated drugs. There was also a suggestion that PD-1 inhibitors (such as nivolumab) may be emerging drugs associated with psoriasis.

TO READ MORE: Learned C, et al. Psoriasis adverse events and associated medications as reported in the US Food and Drug Administration’s Adverse Event Reporting System from 2016 to 2021. JAAD Int. 2022;7:144-145. Published 2022 Apr 18. doi:10.1016/j.jdin.2022.03.010.

The question of DISTURBED SLEEP in association with psoriasis was recently investigated in 334 subjects compared to 126 non-psoriatic controls. Among psoriasis patients, sleep duration was shorter and sleep quality diminished. The presence of anxiety and depression was a better predictor of sleep disturbance than itching, although pruritus at bedtime was a contributing factor to poor sleep.

TO READ MORE: Sahin E, et al. Prevalence and factors associated with sleep disturbance in adult patients with psoriasis. J Eur Acad Dermatol Venereol. 2022;36(5):688-697. doi:10.1111/jdv.17917.

ATOPIC DERMATITIS

This retrospective analysis of 162 patients treated in academic centers in Korea and the U.S. found that 88.3% of those with pre-existing FACIAL DERMATITIS improved following initiation of dupilumab therapy. Only 4.3% of such patients worsened following dupilumab. Six out of 25 patients (24%) who had no pre-existing facial involvement developed new onset facial dermatitis. It was felt that concurrent withdrawal of topical corticosteroids may be possibly responsible.

TO READ MORE: Ahn J, et al. Facial Erythema in Patients with Atopic Dermatitis Treated with Dupilumab- A Descriptive Study of Morphology and Etiology. J Eur Acad Dermatol Venereol. 2022, Jun 13. doi: 10.1111/jdv.18327.

CONTACT DERMATITIS

To determine if some PRODUCTS/TOPICAL MEDICATIONS are a cause of dermatitis, a repeated open application test may be utilized. The current study suggests strongly that such a test should be done for at least 10 consecutive days in order to capture positive reactions.

TO READ MORE: Amsler E, et al. What is the optimal duration for a ROAT? The experience of the French Dermatology and Allergology group (DAG). Contact Dermatitis. 2022;87(2):170-175. doi:10.1111/cod.14118.

This is a massive 16-year study of OCCUPATIONAL CONTACT DERMATITIS done by the North American Contact Dermatitis Group. A key takeaway point is that personal service providers (e.g., hair stylists, building cleaning/service individuals, food service workers, and hospital employees) are among the most likely to develop occupational contact dermatitis. Gloves are a common source of occupational contact dermatitis. About 20% of those with occupational contact dermatitis would have been inadequately assessed if only standard patch testing had been done without the use of occupation-specific supplemental allergens or substances.

TO READ MORE: DeKoven JG, et al. Occupational contact dermatitis: Retrospective analysis of North American Contact Dermatitis Group Data, 2001 to 2016. J Am Acad Dermatol. 2022;86(4):782-790. doi:10.1016/j.jaad.2021.03.042.

The contact allergen of the year is ALUMINUM, even though allergic contact dermatitis due to this metal is relatively uncommon. The most frequent modes of sensitization include allergen-specific immunotherapy and vaccines containing aluminum. Aluminum sensitivity manifests as either pruritic subcutaneous nodules at vaccination and immunotherapy injections sites, or as dermatitis where aluminum-containing sunscreens or antiperspirants are applied.

TO READ MORE: Bruze M, et al. Aluminum-Allergen of the Year 2022. Dermatitis. 2022;33(1):10-15. doi:10.1097/DER.0000000000000836.

ROSACEA

A recent manuscript suggested that rosacea is more common among individuals with SKIN OF COLOR than might be expected. Skin “sensitivity” consisting of facial stinging and burning in response to a wide variety of over-the-counter products might be an early clue. Adequate skin examination, especially against a dark blue background, may be useful to detect subtle erythema and telangiectasias. Regular use of sunscreen and moisturizer mitigates against rosacea in skin of color.

TO READ MORE: Alexis A, et al. Improving Rosacea Outcomes in Skin of Color Patients: A Review on the Nuances in the Treatment and the Use of Cleansers and Moisturizers. J Drugs Dermatol. 2022;21(6):574-580. doi:10.36849/JDD.6838.

Editor’s note: Rosacea in skin of color is not a new concept!

SEE: Rosen T, Stone MS. Acne rosacea in blacks. J Am Acad Dermatol. 1987;17(1):70-73. doi:10.1016/s0190-9622(87)70173-x.

INFECTIOUS DISEASES

A large-scale retrospective Danish study covering a 20-year period conclusively found that incident HERPES ZOSTER was not associated with an increased risk of subsequent dementia.

TO READ MORE: Johannesdottir Schmidt SA, et al. Incident Herpes Zoster and Risk of Dementia: A Population-Based Danish Cohort Study [published online ahead of print, 2022 Jun 8]. Neurology. 2022;10.1212/WNL.0000000000200709. doi:10.1212/WNL.0000000000200709.

Although topical OZENOXACIN (a quinolone) is only FDA approved for impetigo, it was found to be beneficial for paronychia, folliculitis, and secondarily infected trauma. It is applied twice daily for five days.

TO READ MORE: García Ron G, et al. New therapeutic applications of ozenoxacin in superficial skin infections. Dermatol Reports. 2021;14(2):9289. Published 2021 Aug 5. doi:10.4081/dr.2021.9289.

The incidence of SCABIES has risen dramatically during the last two years in Spain. Long periods spent only at home might have facilitated transmission and difficulty accessing medical care might have been responsible for delays in diagnosis and treatment. Clinical resistance to permethrin has become apparent.

PRESENTATION BY: Yolanda Gilaberte, MD, PhD, Spanish Academy of Dermatology and Venereology, 49th Congress, Malaga, June 1-4.

Editor’s note: This supports similar published observations from Germany and Italy.

In the Western Hemisphere, SPOROTRICHOSIS is most common in South America (Brazil, Peru) and in Mexico. Among the 124 articles and corresponding 12,568 patients in this study, 11.62% of cases were reported in North America. Though other species exist, most clinical cases are due to Sporothrix schenckii. Agriculture work or gardening pose the highest risk for acquisition. Exposure to contaminated animal mucosal secretions or animal scratches or bites (e.g., from a cat) also poses a risk. Lymphocutaneous disease is the most common manifestation, although cutaneous and visceral disseminated disease occurs in immunocompromised individuals. Culture remains the gold standard diagnostic maneuver.

TO READ MORE: Hernández-Castro R, et al. Epidemiology of Clinical Sporotrichosis in the Americas in the Last Ten Years. J Fungi (Basel). 2022;8(6):588. Published 2022 May 30. doi:10.3390/jof8060588.

PYTHIOSIS is a rare but emerging fungal infection, usually due to Pythium insidiosum. This pathogen is worldwide in distribution, with Western Hemisphere cases being reported from: United States, Mexico, Haiti, and Costa Rica. This infection follows exposure to freshwater environments, and primarily involves skin and subcutaneous tissue or the ocular/orbital region. The morphology is characterized as necrotic, exophytic lesions, resembling those caused by more common saprophytes. Due to a lack of ergosterol in the fungal cell membrane, azole and allylamine antifungal drugs may be only partially effective to ineffective. Aggressive surgical management is typical.

TO READ MORE: Perkins MJ, et al. Severe skin and soft tissue pythiosis acquired in a hot spring in the southwestern United States, a case report and review of North American cases. Travel Med Infect Dis. 2022;48:102349. doi:10.1016/j.tmaid.2022.102349.

Beware! PROLONGED MASK WEARING can lead to atypical tinea faciei (tinea incognito). This erythematous papular eruption can mimic allergic contact dermatitis to some portion of the mask.

TO READ MORE: Cunningham EP, et al. Tinea incognito “mask”erading as allergic contact dermatitis due to COVID-19 facial covering in children. Pediatr Dermatol. 2022;39(2):326-327. doi:10.1111/pde.14911.

HAIR AND NAILS

A recent systematic literature review revealed increased use of surgical approaches other than amputation to treat NAIL SQUAMOUS CELL CARCINOMA. The review encompassed 404 patients who were included in 15 manuscripts. Mohs surgery is superior to wide local excision in terms of recurrence rate. However, when bone is already involved, amputation appears to be optimal.

TO READ MORE: Ning AY, et al. Treatment Options and Outcomes for Squamous Cell Carcinoma of the Nail Unit: A Systematic Review. Dermatol Surg. 2022;48(3):267-273. doi:10.1097/DSS.0000000000003319.

A single-center retrospective review of TRACTION ALOPECIA patients (N=167) disclosed, as expected, that the majority of those affected were Black and female, with a median age of 31. Over half the patients presented 1 to over 5 years after onset. Sixty-three percent improved following multimodality interventions. Professional counseling was found to be beneficial.

TO READ MORE: Santa Lucia G, et al. Traction alopecia: Neglected in women and children of color [published online ahead of print, 2022 May 28]. J Am Acad Dermatol. 2022;S0190-9622(22)00882-9. doi:10.1016/j.jaad.2022.05.039.

A retrospective Vietnamese review found that elevated serum interleukin (IL)-17A levels correlate with ALOPECIA AREATA when compared to matched controls. More severely affected individuals and those with concurrent nail changes had the highest serum IL-17A levels, suggesting a possible therapeutic pathway.

TO READ MORE: Thi Thuy Le T, et al. Increased serum interleukin- 17A levels correlate with disease severity and poor prognostic factors in patients with alopecia areata. Dermatol Reports. 2021;14(2):9398. Published 2021 Oct 27. doi:10.4081/dr.2021.9398.

CUTANEOUS ONCOLOGY, SURGERY AND LASERS

A Dutch study involving 539 patients (median age 78) indicated that medical burden following treatment for BASAL CELL CARCINOMA in older patients is NOT related solely to age. Rather a higher burden is seen in older patients who are “frail.” Indication that the patient is at risk for post-operative complications include inability to perform activities of daily living, dependency, larger tumor diameter, and polypharmacy.

TO READ MORE: van Winden MEC, et al. Predictors of surgical treatment burden, outcomes, and overall survival in older adults with basal cell carcinoma: Results from the prospective, multicenter BATOA cohort. J Am Acad Dermatol. 2022;86(5):1010-1019. doi:10.1016/j.jaad.2021.05.041.

A retrospective review at the University of Alabama of 1,000 consecutive patients (1,318 nonmelanoma skin cancers) who underwent MOHS SURGERY found that 1.7% were found to be “inappropriate” according to current criteria.

TO READ MORE: Stancut E, et al. Institutional Adherence to Current Mohs Surgery Appropriate Use Criteria With Reasons for Nonadherence and Recommendations for Future Versions. Dermatol Surg. 2022;48(3):290-292. doi:10.1097/DSS.0000000000003369.

A retrospective observational study found that higher tuna and non-fried fish dietary intake was associated with an increased risk of both in-situ and invasive MELANOMA. Investigators speculated contaminants in fish, such as polychlorinated biphenyls, dioxins, arsenic, and mercury, might explain their results.

TO READ MORE: Li y, et al. Fish intake and risk of melanoma in the nih-aarp diet and health study. Cancer Causes Control. 2022;33(7):921-928. Doi:10.1007/s10552-022-01588-5.

Editor’s note: A critical deficiency in the study was a failure to account and correct for any differences in risk factors for melanoma, such as mole count, hair color, history of severe sunburn, and sun-related behavior.

HIDRADENITIS SUPPURATIVA

A previous multinational, prospective study demonstrated that combination of preoperative, perioperative, and postoperative adalimumab enhanced the result of extensive SURGICAL RESECTION. This new manuscript calls into account some potential shortcomings of the previous report, being especially critical of the lack of analysis of time to postoperative healing between those receiving adjunctive adalimumab and those receiving placebo.

TO READ MORE: Guillem P, Perat C, Vlaeminck-Guillem V. Can Adalimumab Reduce the Extent of Hidradenitis Suppurativa Surgery? JAMA Surg. 2022;157(6):552-553. doi:10.1001/jamasurg.2022.0083.

DRUGS AND DEVICES

The Post-Finasteride Syndrome Foundation petitioned the FDA in 2017 to order discontinuation of the sale of FINASTERIDE or to include far stronger warnings. In June 2022, the FDA denied the petition for discontinuation but has agreed to require additional warnings regarding suicidal ideation or suicide.

SOURCE: Levine D. FDA requires disclosure of suicide risk for anti-baldness drug. Reuters. June 10, 2022.

RHEUMATOLOGIC DISEASES

In a 363-patient placebo-controlled study, DEUCRAVACITINIB statistically outperformed placebo for the treatment of systemic lupus erythematosus (SLE). Deucravacitinib is a selective TYK-2 Janus Kinase inhibitor which ultimately reduces elaboration of Type 1 interferons, key drivers of SLE pathology. Safety was deemed equivalent to placebo.

TO READ MORE: Morand E, et al. LB0004 Efficacy and safety of deucravacitinib, an oral selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus : A Phase 2, randomized, double-blind, placebo-controlled study. Ann Rheum Dis. 2022;81:209.

Children and adolescents suffering from DERMATOMYOSITIS are often overwhelmed by the seriousness of their disorder and how it will alter their lifestyle going forward. Anxiety and depression are common in this group, and virtually all should have access to mental health services.

SOURCE: McCann L. What do adult Rheumatologists need to know about inflammatory myositis when young people transition to adult care? Presented at: EULAR 2022 Congress; June 1-4, 2022 (virtual meeting).

A case series described DISCOID LUPUS ERYTHEMATOSUS limited to the periorbital regions, most commonly involving a single upper or lower eyelid. Diagnosis is nearly always delayed (11-60 months), the problem being ascribed to contact dermatitis or eczema. Anti-nuclear antibody is typically positive, but in low titer. Antimalarial therapy is usually beneficial.

TO READ MORE: Theisen E, et al. Periorbital discoid lupus erythematosus: A retrospective study. JAAD Case Rep. 2022;25:78-82. Published 2022 Jun 2. doi:10.1016/j.jdcr.2022.05.024.

COVID19

One potential consequence of all COVID-19 vaccinations is the occurrence of INCIDENTAL IPSILATERAL AXILLARY ADENOPATHY. Especially among those with risk factors for breast cancer or lymphoma, this benign reactive lymphatic hyperplasia can result in extensive and costly diagnostic testing.

TO READ MORE: Zhou W, et al. Frequency and Outcomes of Ipsilateral Axillary Lymphadenopathy After COVID-19 Vaccination. JAMA Netw Open. 2022;5(6):e2216172. Published 2022 Jun 1. doi:10.1001/jamanetworkopen.2022.16172.

According to Harvard authors, the recent OMICRON strain of SARS-CoV-2 (BA.2.12.1) and emerging strains (BA.4 and BA.5) are capable of escaping neutralizing antibodies induced by both the current COVID-19 vaccinations and by natural infection due to prior viral variants. We obviously need new, modified vaccines!

TO READ MORE: Hachmann NP, et al. Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5. N Engl J Med. 2022;387(1):86-88. doi:10.1056/NEJMc2206576.

During the COVID-19 pandemic, there has been a notable increase in the use of ANTIBIOTICS. One in three attendees in emergency departments with a primary diagnosis of COVID-19 received an antibiotic, while 24% of similar patients seen in an ambulatory outpatient setting received an antibiotic. Azithromycin prescriptions accounted for just over 50% of all antibiotics given, followed by doxycycline, amoxicillin and levofloxacin. These trends were seen among Medicare recipients.

TO READ MORE: Tsay SV, et al. Antibiotic Prescriptions Associated With COVID-19 Outpatient Visits Among Medicare Beneficiaries, April 2020 to April 2021. JAMA. 2022;327(20):2018-2019. doi:10.1001/jama.2022.5471.