LITERATURE LESSONS: March

COVID19

Analysis of a large (N=1,228,664) cohort of individuals who completed their primary COVID-19 vaccination series revealed an extremely low RISK OF SEVERE OUTCOME (respiratory failure, noninvasive ventilation, ICU admission) or death. Virtually all vaccinated individuals who did experience a severe outcome or who died had one or more of these risk factors: age ≥65 years, immunosuppression, obesity, diabetes, or chronic hepatic, respiratory, cardiac or renal disease.

TO READ MORE: Yek C, et al. Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series — 465 Health Care Facilities, United States, December 2020–October 2021. MMWR Morb Mortal Wkly Rep 2022;71:19–25. DOI: http://dx.doi.org/10.15585/mmwr.mm7101a4external icon.

A concise summary of currently available COVID therapeutics is worth a read. One take-away point: of the three ANTI-SPIKE MONOCLONAL ANTIBODY PREPARATIONS (bamlanivimab plus etesevimab, casirivimab plus imdevimab, and sotrovimab), only sotrovimab remains completely active against the Omicron variant. Another take-away point: nirmatrelvir-ritonavir is now authorized for emergency use for the treatment of mild to moderate COVID-19 in adult and pediatric patients (age ≥12 years and ≥40 kg) who are at high risk for progression and are within five days of symptom onset. In trials, this drug led to an 88% reduction in hospitalization or death compared to placebo. Finally, the FDA has issued an Emergency Use Authorization for molnupiravir (with similar conditions and restrictions as nirmatrelvir-ritonavir); however, molnupiravir is not recommended during pregnancy and is not yet authorized for children. Molnupiravir is associated with a 30% reduction in hospitalization or death compared to placebo.

TO READ MORE: Gandhi RT, et al. COVID-19 Therapeutics for Non-hospitalized Patients. JAMA. 2022, January 14. doi:10.1001/jama.2022.0335

Interestingly, the WHO recently made two rather STRIKING RECOMMENDATIONS.

1.  Countries should lift or ease international travel bans.

2. Countries and carriers should no longer require proof of COVID-19 inoculation for international travel.

TO READ MORE: World Health Organization (WHO). Statement on the tenth meeting of the International Health Regulations (2005) Emergency Committee regarding the coronavirus disease (COVID-19) pandemic. https://www.WHO.int. January 19, 2022. Accessed February 21, 2022.

ACCESSIBLE AT: https://www.who.int/news/item/19-01-2022-statement-on-the-tenth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-coronavirus-disease-(covid-19)-pandemic

The incidence of COVID-19 INFECTION AND RATE OF HOSPITALIZATION during both Delta and Omicron strain predominance was lowest among those who were both completely vaccinated and had received a booster.

TO READ MORE: Danza P, Koo TH, Haddix M, et al. SARS-CoV-2 Infection and Hospitalization Among Adults Aged ≥18 Years, by Vaccination Status, Before and During SARS-CoV-2 B.1.1.529 (Omicron) Variant Predominance — Los Angeles County, California, November 7, 2021–January 8, 2022. MMWR Morb Mortal Wkly Rep 2022;71:177–181. DOI: http://dx.doi.org/10.15585/mmwr.mm7105e1

A recent one-year study of 2126 WOMEN ATTEMPTING TO CONCEIVE spontaneously found that neither COVID-19 vaccination nor developing SARS-CoV-2 infection had any appreciable effect on fertility.

TO READ MORE: Wesselink AK, et al. A prospective cohort study of COVID-19 vaccination, SARS-CoV-2 infection, and fertility [published online ahead of print, 2022 Jan 20]. Am J Epidemiol. 2022;kwac011. doi:10.1093/aje/kwac011

PEDIATRIC DERMATOLOGY

PROGRESSIVE NODULAR HISTIOCYTOSIS is a rare papulo-nodular non-Langerhans cell histiocytosis. Treatment to date has been largely unsatisfactory. A case demonstrating striking response to very low dose baricitinib (1mg/day) is described.

TO READ MORE: Huang Y, Zhang Z, Zhu L, Chen Y. Treatment of Progressive Nodular Histiocytosis With Baricitinib. JAMA Dermatol. Published online January 19, 2022. doi:10.1001/jamadermatol.2021.5579

Establishing reliable DIAGNOSTIC CRITERIA FOR PSORIASIS in children and adolescents should result in more timely recognition and therapy. A study comparing 170 pediatric/adolescent psoriasis patients to 160 similarly aged individuals with other disorders found the following criteria to be most useful: persistent, well-demarcated erythema and scale involving the hairline, external auditory canal, extensor surfaces of the elbows and knees, umbilicus, crural folds, and diaper area along with a positive family history. The presence of any two of these criteria accurately identified psoriasis in 78% of children and adolescents and helped eliminate alternative diagnoses in 71% of study subjects.

TO READ MORE: Chalmers RJG. Recognizing psoriasis in children and adolescents: the DIPSOC study. Br J Dermatol. 2022;186(2):213-214. doi:10.1111/bjd.20825

INFECTIOUS DISEASES

Two to three itraconazole pulses (consisting of 6-10mg/kg/d each pulse separated by three weeks) led to complete resolution of TINEA CAPITIS in four pediatric patients. During the treatment period, there were no significant adverse events and no evidence of hepatic dysfunction.

TO READ MORE: Zhou YB, et. al. A novel itraconazole pulse therapy schedule in the treatment of tinea capitis in children. Clin Cosmet Investig Dermatol. 2021; November 25. doi:10.2147/CCID.S342203

The Moderna mRNA platform is being used in a novel approach towards production of an effective HIV VACCINE. The idea is to deliver HIV-specific antigens that are capable of triggering an immune response which is preventative or modulating. Earlier animal trials showed promise.

TO READ MORE: Foster R, Preidt R. First Shots Given in Trial of Moderna’s mRNA-Based HIV Vaccine. HealthDay News. February 2, 2022.

ACCESSIBLE AT: https://consumer.healthday.com/b-2-1-2656524361.html

RHEUMATOLOGIC DISEASES

A small (N=15) prospective, open-label phase 2 study showed that ustekinumab 90mg subcutaneously given at baseline and repeated at weeks 2, 4, 16, 28 and 40 was beneficial for the majority of BEHÇET’S DISEASE patients so treated. Absence of all oral and genital ulcers was seen in 60% of study subjects at week 24, with 10 of 11 responders maintaining response at week 52.

TO READ MORE: London J, et. al. Efficacy and safety of ustekinumab in Behçet disease: results from the prospective phase 2 STELABEC trial. J Am Acad Dermatol. 2021; December 2, 2021. doi:10.1016/j.jaad.2021.11.045

A retrospective study done in Texas compared 112 Black patients with DISCOID LUPUS ERYTHEMATOSUS to 71 non-Black DLE patients. Black patients were at increased risk of having scalp and ear involvement, severe dyspigmentation and scarring.

TO READ MORE: Joseph AK, et al. Discoid lupus erythematosus skin lesion distribution and characteristics in Black patients. Lupus Sci Med 2021;8e000514. Doi: 10.1136/lupus-2021-000514

Ultrasound and elastography are two tools sometimes used to evaluate patients with SYSTEMIC SCLERODERMA. The authors of a comprehensive literature review found marked heterogeneity in detailed methodology utilized. Nonetheless, B-mode ultrasound appeared to be relatively accurate in establishing the degree of skin thickening when compared to histologic findings. There was poor evidence correlating “stiffness” as reported by elastography with histologic findings.

TO READ MORE: Santiago T, et al. Ultrasound and elastography in the assessment of skin involvement in systemic sclerosis: A systematic literature review focusing on validation and standardization – WSF Skin Ultrasound Group. Semin Arthritis Rheum. 2022;52:151954. doi:10.1016/j.semarthrit.2022.151954

PSORIASIS

An interesting survey study disclosed that psoriatic patients–who are seeing their dermatology specialists already anyhow–would be in favor of the specialist MONITORING CARDIOVASCULAR RISK FACTORS (such as periodic lipid panels) and engaging in risk factor mitigation (such as encouraging proper diet and exercise or prescribing statins when indicated). However, dermatologists were not as enthusiastic about performing risk factor management.

TO READ MORE: Barbieri JS, et al. Analysis of Specialist and Patient Perspectives on Strategies to Improve Cardiovascular Disease Prevention Among Persons With Psoriatic Disease. JAMA Dermatol. Published online January 19, 2022. doi:10.1001/jamadermatol.2021.4467

ATOPIC DERMATITIS

Italian investigators compared young female patients with atopic dermatitis (AD) to matched psoriasis controls. The study concluded that women with moderate to severe AD were prone to significant flares of their disease in the premenstrual portion of the MENSTRUAL CYCLE. There was no correlation with the presence of the premenstrual syndrome or premenstrual dysphoric disorder.

TO READ MORE: Dal Bello G, et al. Variations of symptoms of atopic dermatitis and psoriasis in relation to menstrual cycle. J Am Acad Dermatol. 2021 Dec 15; doi: 10.1016/j.jaad.2021.12.014

CONTACT DERMATITIS

TO READ MORE: Atwater AR, et al. Medical adhesive allergens: Retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2018. J Am Acad Dermatol. 2021 Dec 5:S0190-9622(21)02927-3. doi: 10.1016/j.jaad.2021.11.055

HAIR AND NAILS

Severe and steroid resistant NAIL LICHEN PLANUS cleared completely with oral baricitinib, a selective JAK1/2 inhibitor, in a dose of 4mg daily.

TO READ MORE: Pünchera J, Laffitte E. Treatment of Severe Nail Lichen Planus With Baricitinib. JAMA Dermatol. 2022;158(1):107-108. doi:10.1001/jamadermatol.2021.5082

HIDRADENITIS SUPPURATIVA

A phase 2 multicenter, randomized, double-blind placebo-controlled study showed that the IL-17A and IL-17F blocker, BIMEKIZUMAB, performed better than placebo and adalimumab for moderate to severe hidradenitis patients (n = 73). Objective assessments were based on Hidradenitis Suppurativa Clinical Response (HiSCR) criteria at week 12.

TO READ MORE: Glatt S, et al. Efficacy and safety of bimekizumab in moderate to severe hidradenitis suppurativa. A Phase 2, double-blind placebo-controlled, randomized clinical trial. JAMA Dermatol 2021;157:1279-1288

(Editor’s note: Although this study was very promising, we await the results of a larger scale, longer duration study.)

CUTANEOUS ONCOLOGY, SURGERY AND LASERS

A retrospective Austrian study of 51 METASTATIC MELANOMA patients treated with ipilimumab and/or nivolumab or pembrolizumab disclosed that FDG PET/CT scan was of prognostic value. Metabolic parameters associated with this type of imaging, especially done three months after the first immunotherapy, were quite accurate in predicting three- and five-year overall survival.

TO READ MORE: Schweighofer-Zwink G, et al. Prognostic value of 2-[18F]FDG PET-CT in metastatic melanoma patients receiving immunotherapy. Eur J Radiol. 2022;146:110107. doi:10.1016/j.ejrad.2021.110107

Although there were some methodological shortcomings, a recent analysis of 25 publicly available SMARTPHONE APPS claiming to identify melanoma demonstrated highly variable and overall low accuracy and sensitivity. Use of such an app might give an individual a false sense of security, thereby preventing early detection and intervention.

TO READ MORE: Sun MD, et, al. Accuracy of commercially available smartphone applications for the detection of melanoma. Br J Dermatol. 2021, November 22. doi: 10.1111/bjd.20903

Retrospective analysis of just over 60,000 clinical stage I and II melanomas drawn from the National Cancer Database disclosed that ACRAL LENTIGINOUS MELANOMA was independently associated with sentinel lymph node positivity. This also means that such lesions are at relatively higher risk for regional  metastases.

TO READ MORE: Cheraghlou S, et al. Sentinel Lymph Node Biopsy Positivity in Patients With Acral Lentiginous and Other Subtypes of Cutaneous Melanoma. JAMA Dermatol 2022;158:51-58

DRUGS AND DEVICES

A randomized, double-blind, placebo-controlled phase 3 trial disclosed that, at week 24, 60% of patients treated for PRURIGO NODULARIS with dupilumab experienced itch reduction compared to only 18% of placebo recipients. Furthermore, 48% of dupilumab recipients achieved clear or almost clear skin, compared to only 18% of those receiving placebo.

TO READ MORE: Regeneron Pharmaceuticals. Second positive phase 3 Dupixent® (dupilumab) trial confirms significant improvements for patients with prurigo nodularis. Press Release. January 19, 2022. Accessed February 22, 2022.

GENERAL DERMATOLOGY

A small (N = 3), uncontrolled German study demonstrated rapid and sustained relief of PRURITUS ASSOCIATED WITH CHRONIC KIDNEY DISEASE by repeated intravenous infusions of naloxone (a mu-opioid receptor antagonist).

TO READ MORE: Pereira MP. Improvement of chronic kidney disease-associated pruritus after treatment with intravenous naloxone. JAMA Dermatol 2021;157:1380-1381

A comprehensive systematic review of medical literature (17 articles, 83,910 patients) disclosed that depression, as might be intuitively expected, was common among those with BULLOUS DISEASE. Depressive symptoms were seen in 40% to 80% of those with bullous disease; overt, mental health professional-verified depression was found in 11% to 28% of patients.

TO READ MORE: Pourali SP, et al. Bullous dermatoses and depression. JAMA Dermatol 2021;157:1487-1495.

(Editor’s note: Watch your patients with pemphigoid and pemphigus for signs of depression and secure mental health consultation as appropriate.)

During the pandemic, many practices established or enhanced TELEDERMATOLOGY capability, and patients were generally satisfied. However, a nationwide representative survey done in conjunction with Stanford University showed that in 2021, when compared to live face-to-face visits, patient overall satisfaction with telehealth fell to 43% (53% in 2020). Even more impressive, only 37% of respondents who used live video telemedicine for a minor illness reported higher satisfaction compared to in-person care, and only 28% of those using live video telemedicine for a chronic condition reported greater satisfaction when compared to in person visits.

TO READ MORE: DeSilva J, et al. Consumer adoption of telemedicine in 2021. Rockhealth Survey. December 13, 2021. Accessed February 22, 2022.

ACCESSIBLE AT: https://rockhealth.com/insights/consumer-adoption-of-telemedicine-in-2021/?mc_cid=f7e7061ed5&mc_eid=9cbd2c85b1

A large (N=340) multicenter, American retrospective review of acute GENERALIZED EXANTHEMATOUS PUSTULOSIS revealed a very small percentage (<10%) of such cases may be associated with renal or hepatic dysfunction. The majority of cases were associated with fever and neutrophilia, and 50% also developed eosinophilia. The most common trigger was exposure to antimicrobial medication.

TO READ MORE: Creadore A, et al. Clinical Characteristics, Disease Course, and Outcomes of Patients With Acute Generalized Exanthematous Pustulosis in the US. JAMA Dermatol 2022; January 5. doi: 10.1001/jamadermatol.2021.5390

A retrospective Danish analysis of patients with heretofore treatment resistant HAILEY-HAILEY DISEASE concluded that one to six sessions of superficial radiotherapy led to complete remission after just a single cycle, with three more patients entering remission after the second cycle of radiation.

TO READ MORE: Wulf HC, Wiegell SR. Treatment of Familial Benign Chronic Pemphigus With Superficial Radiotherapy. JAMA Dermatol. 2022, January 12. doi:10.1001/jamadermatol.2021.5491

A nationally representative cross-sectional online survey of 40,888 adults (age 18 to 85) revealed that the prevalence of VITILIGO is between 0.76% and 1.11%. This survey also suggested that some 40% of vitiligo is not currently diagnosed.

TO READ MORE: Gandhi K, et al. Prevalence of Vitiligo Among Adults in the United States. JAMA Dermatol. 2022;158(1):43-50. doi:10.1001/jamadermatol.2021.4724

ACNE

Two small matched groups of patients with acne-related POST-INFLAMMATORY HYPERPIGMENTATION were treated with either 50% glycolic or 30% salicylic acid peels every two weeks for six weeks. A blinded physician evaluator assessed photographs for degree of improvement. The glycolic acid peel produced a greater degree of pigmentary reduction.

TO READ MORE: Ravikumar B, et al. Efficacy of Alpha and Beta Hydroxy Acid Chemical Peels in Post acne Pigmentation: A Double Blinded, Randomized, Controlled Trial. J Clin Aesthet Dermatol 2022;15:48-52

ROSACEA

A comprehensive literature-based meta-analysis disclosed the intense pulsed light (IPL), pulsed dye laser (PDL) and neodymium: yttrium-aluminum-garnet (YAG) lasers were roughly equally efficacious in IMPROVING ERYTHEMA AND TELANGIECTASIA associated with rosacea.

TO READ MORE: Husein-ElAhmed H, Steinhoff M. Light-based therapies in the management of rosacea: a systematic review with meta-analysis. Int J Dermatol. 2022;61(2):216-225. doi:10.1111/ijd.15680