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Literature Lessons – November

Including the latest on psoriasis, atopic dermatitis, infectious disease, hidradenitis suppurativa, rheumatologic diseases, and more.

GENERAL DERMATOLOGY

Topical ivermectin 1% cream (Soolantra) proved effective as an INSECT REPELLANT in this small (N = 2) observational case report. The bites averted were due to “No-See-Ums” or tiny, seasonal mosquito-like insects. 

TO READ MORE: Liu D, et al. Novel Use of Topical Ivermectin for the Prevention of Facial Insect Bites. J Drugs Dermatol. 2022 Aug 1;21(8):906-907. doi: 10.36849/JDD.6432. PMID: 35946968.

Since the onset of the COVID-19 pandemic, the use of TELEDERMATOLOGY has significantly increased. The authors point out that this modality may be associated with serious disadvantages in skin of color. These include potential reduced access to the internet and requisite hardware, inherent concern about privacy and lack of direct interaction with the provider, and misdiagnosis or missed additional diagnoses (such as acrolentiginous melanoma). 

TO READ MORE: Sanchez C, et al. Teledermatology and Skin of Color Patients. J Drugs Dermatol. 2022 Jul 1;21(7):793-794. doi: 10.36849/JDD.6860. PMID: 35816062.

In order to help combat the opioid epidemic, dermatologists should LIMIT OPIOID PRESCRIBING and consider the use of non-narcotic analgesics whenever possible. This review of 24 studies involving over 52 million patients disclosed that between 34% to 87.5% of patients received an opioid prescription following a dermatologic procedure (most commonly Mohs surgery). However, a great many patients either did not fill the opioid prescription or did not take all prescribed doses. Use of opioids in non-procedural dermatology (e.g., for herpes zoster) was highly variable. 

TO READ MORE: Pourali SP, et al. Are we contributing to the opioid epidemic? A systematic review on systemic opioid use in dermatology. Int J Dermatol. 2022 Sep;61(9):1056-1068. doi: 10.1111/ijd.16011. Epub 2021 Dec 6. PMID: 34870325.

A case report describes and illustrates the resolution of steroid and ketoconazole-resistant facial SEBORRHEA following the application of ruxolitinib 1.5% cream twice daily. 

TO READ MORE: Pope E, et al. Topical ruxolitinib in the treatment of refractory facial seborrheic dermatitis. JAAD Case Rep. 2022 Apr 23;24:59-60. doi: 10.1016/j.jdcr.2022.04.003. PMID: 35619595; PMCID: PMC9127103.

PEDIATRIC DERMATOLOGY

A cross-sectional study was conducted in the United Kingdom and Germany of 235 individuals (age 6 – 89) with TUBEROUS SCLEROSIS COMPLEX AND FACIAL ANGIOFIBROMAS. The online survey study revealed that the severity of impact on quality of life and psychosocial well-being correlated with the severity of facial lesions. Facial angiofibromas were found to be most troublesome in social situations and at school, and least troublesome at home. Study subjects were embarrassed by or self-conscious of their facial angiofibromas. Anxiety and depression were common among those with tuberous sclerosis complex and facial angiofibromas. Severe facial angiofibromas were associated with both itch (66%) and pain (45%). Sixty-seven percent of those treated with topical rapamycin/sirolimus found this modality to be “very” or “somewhat” successful. 

TO READ MORE: Monaghan M, et al. Impact of facial angiofibromas in tuberous sclerosis complex and reported efficacy of available treatments. Front Med (Lausanne). 2022 Aug 29;9:967971. doi: 10.3389/fmed.2022.967971. PMID: 36106321; PMCID: PMC9467435.

Editor’s note: 0.2% topical sirolimus gel (Hyftor) was FDA approved in March, 2022, for twice daily application to facial angiofibromas in those 6 years of age and older.

A well-referenced commentary highlights how reliance on SOCIAL MEDIA and obsession with “selfie” pictures and videos facilitate adverse psychologic sequelae among adolescents. Social media also contributes to body dysmorphic disorder (BDD) among adolescents, and dermatologists asked to perform cosmetic procedures are encouraged to screen such young patients for BDD. Anxiety, depression, decreased quality of life, and even suicidal ideation may result from social media participation. 

TO READ MORE: Gherlone N, et al. Adolescents Seeking Cosmetic Treatment as a Consequence of Social Media Pressure: Treatment for the Problem of Aging or the Problem of the Ages? Skinmed. 2022 Aug 31;20(4):255-257. PMID: 35976014.

PSORIASIS

Investigators utilized deidentified Optum Electronic Health Record Data from 2015-2020 to examine the course of 1535 patients with generalized PUSTULAR PSORIASIS. Two-hundred-seventy-one of these patients accounted for 513 flare episodes over the study period. Most common therapeutic interventions included topical corticosteroids, opioid agents, and an assortment of other systemic agents (methotrexate, cyclosporine, and oral steroids). Of note, a quarter of documented pustular psoriasis flare episodes were not associated with any dermatologic intervention. 

TO READ MORE: Zema CL, et al. Understanding Flares in Patients With Generalized Pustular Psoriasis Documented in US Electronic Health Records. JAMA Dermatol. 2022 Oct 1;158(10):1142-1148. doi: 10.1001/jamadermatol.2022.3142. PMID: 35947363; PMCID: PMC9366655.

ATOPIC DERMATITIS

A long-term extension of the original pivotal study showed that daily ABROCITINIB (100 mg or 200 mg dose) was beneficial regardless of prior response or lack of response to dupilumab. Most importantly, among dupilumab non-responders, Eczema Area and Severity Index 75 (EASI75) was achieved in 80% (dose 200 mg/day) and 67.7% (dose 100 mg/day) of subjects. The EASI75 response rate with abrocitinib was even better among subjects who had previously responded to dupilumab. 

TO READ MORE: Shi VY, et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J Am Acad Dermatol. 2022 Aug;87(2):351-358. doi: 10.1016/j.jaad.2022.04.009. Epub 2022 Apr 16. PMID: 35439608.

Analysis of a large (nearly 5000) birth cohort study disclosed that being OVERWEIGHT (or obese) at age 5 was associated with an increased risk of atopic dermatitis later in life (ages 9 and 15). This might be attributable to release of proinflammatory cytokines from adipose tissue. However, having atopic dermatitis early in childhood was not associated with obesity in later childhood or in adolescence. 

TO READ MORE: Manjunath J, et al. Association of obesity in early childhood with atopic dermatitis in late childhood and adolescence. J Am Acad Dermatol. 2022 Aug;87(2):426-427. doi: 10.1016/j.jaad.2021.08.048. Epub 2021 Sep 4. PMID: 34487780.

Ninety relatively stable adult atopic dermatitis patients were split into three groups (N = 30 each) of DUPILUMAB dosing. One group maintained at conventional dosage (300 mg/2 weeks); one group doubled the dosing interval (300 mg/4 weeks); and the final group increased the dosing interval variably (300 mg/6-8 weeks). Disease severity did not increase among those who received a tapering lowered dose, although itch severity had a transient increase. Disease severity biomarkers, such as CCL17 and CCL18, remained low in all three groups. This study shows that, in appropriate patients, dupilumab dosing interval can be lengthened without ill effect. 

TO READ MORE: Spekhorst LS, et al. Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis. Allergy. 2022 Nov;77(11):3398-3407. doi: 10.1111/all.15439. Epub 2022 Jul 29. PMID: 35837880.

COSMETIC DERMATOLOGY

In a nicely referenced Mexican meta-analysis, the authors conclude that the best treatments for KERATOSIS PILARIS (off the face) are twice daily application of lactic acid (typically 10%) followed by twice daily application of salicylic acid (typically 5%). Use of the 1064-nm Nd:YAG laser was judged the third most effective therapy, up to Fitzpatrick type IV skin tone. A final recommended intervention was topical tacrolimus ointment (0.1%). 

TO READ MORE: Suástegui-Rodríguez I, et al. Keratosis Pilaris Treatment: Evidence from Intervention Studies. Skinmed. 2022 Aug 31;20(4):258-271. PMID: 35976015.

ROSACEA

A small (N = 13) Taiwanese study demonstrated that weekly intramuscular injections of HYDROXOCOBALAMIN (vitamin B12) reduced both persistent erythema and episodic flushing among the rosacea patients studied. 

TO READ MORE: Huang YW, et al. Hydroxocobalamin: An Effective Treatment for Flushing and Persistent Erythema in Rosacea. J Clin Aesthet Dermatol. 2022 Jun;15(6):42-45. PMID: 35783562; PMCID: PMC9239126.

CONTACT DERMATITIS

About half of those who have worn MASKS frequently during the COVID19 pandemic develop some form of facial dermatosis. This includes acne, eczema, pressure injury, contact allergy, or simply persistent itching. This conclusion was based on a review of 37 qualifying publications. 

TO READ MORE: Justin LYS, et al. Facial dermatoses induced by face masks: A systematic review and meta-analysis of observational studies. Contact Dermatitis. 2022 Dec;87(6):473-484. doi: 10.1111/cod.14203. Epub 2022 Sep 2. PMID: 35980367; PMCID: PMC9539048.

INFECTIOUS DISEASES

Aside from skin and mucosal lesions, MONKEYPOX is often accompanied by and may present with a variety of systemic complaints. These include malaise (~73%), fever (72%), chills (~69%), headache (65%), lymphadenopathy (64%), myalgia (~62%), and generalized pruritus (60%). Those who acquired monkeypox via receptive anal intercourse may also present with rectal pain, pus, or blood on stools, and overt rectal bleeding. There are over 53,000 cases globally and over 20,000 cases in the United States. 

TO READ MORE: Monkeypox Signs and Symptoms. CDC. Last reviewed September 7, 2022. Accessed December 6, 2022. Monkeypox | Poxvirus | CDC

This large multicenter prospective study of MONKEYPOX done in Spain, indicates that close personal contact during sexual activity is the main route of spread. Also of note: lesion location correlates with type of sexual activity. For example, receptive anal intercourse is associated with perianal skin lesions and proctitis. Oral sex is associated with perioral skin lesions and tonsilitis. Researchers analyzed 181 confirmed cases; 174 were men and 166 self-identified as men who have sex with men. 

TO READ MORE: Tarín-Vicente EJ, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022 Aug 27;400(10353):661-669. doi: 10.1016/S0140-6736(22)01436-2. Epub 2022 Aug 8. PMID: 35952705; PMCID: PMC9533900.

Although the absolute number of MONKEYPOX cases continues to rise, the rate of increase appears to have slowed. In a recent survey, 48% of men who have sex with men have reduced their number of sex partners, 50% have reduced their one-time sexual encounters, and 50% have reduced sexual encounters with partners met on dating apps or at sex parties. 

TO READ MORE: Delaney KP, et al. Strategies Adopted by Gay, Bisexual, and Other Men Who Have Sex with Men to Prevent Monkeypox virus Transmission – United States, August 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 2;71(35):1126–30. doi: 10.15585/mmwr.mm7135e1. PMID: 36048582; PMCID: PMC9472779.

During the COVID-19 pandemic, the incidence of MUCORMYCOSIS has increased. This may be due, in part, to various degrees of pulmonary damage related to COVID-19 or to the use of steroids and Janus kinase (JAK) inhibitors to treat the disease. It may also be due to seemingly mundane items, such as nasal mucosal damage related to repeated COVID-19 diagnostic swab tests. Cutaneous mucormycosis has protean manifestations, including indurated plaques or tender nodules which progress to necrosis and eschar formation, purpuric papules, and cellulitic lesions. Diagnosis depends upon direct exudate smear, fungal culture, skin biopsy, and PCR of tissue samples. Administration of amphotericin B or isavuconazole along with thorough surgical debridement is therapeutic. 

TO READ MORE:  Hatami P, et al. Serious health threat of mucormycosis during the ongoing COVID-19 pandemic: what dermatologists need to know in this regard. Int J Dermatol. 2022 Aug;61(8):979-981. doi: 10.1111/ijd.16101. Epub 2022 Jan 30. PMID: 35094397.

Individuals who practice in locales with a high incidence of LYME DISEASE should recognize that this may present as an inflammatory plaque with prominent dusky, vesiculobullous lesions. A series of three cases from New England is presented. 

TO READ MORE: Doughty H, et al. Vesiculobullous Lyme disease: A case series. JAAD Case Rep. 2022 Apr 25;24:56-58. doi: 10.1016/j.jdcr.2022.04.001. PMID: 35619594; PMCID: PMC9127143.

The global burden of tuberculosis (TB) is on the rise, according to both the WHO and CDC. This means that CUTANEOUS TB still exists, especially in developing countries. Considering the recent massive influx of undocumented immigrants, every dermatological practitioner should review how TB presents on the skin. This article points out that a substantial number of cutaneous TB cases occur in children and beautifully illustrates representative lesions of lupus vulgaris, scrofuloderma, tuberculosis verrucosa cutis, and tuberculous dactylitis. 

TO READ MORE: Singal A, et al. Clinicoepidemiological characteristics of cutaneous tuberculosis in 1458 Indian patients: a retrospective analytical study from a tertiary care center. Int J Dermatol. 2022 Aug;61(8):1012-1022. doi: 10.1111/ijd.16267. Epub 2022 May 17. PMID: 35583803.

A retrospective analysis of patients with a diagnosis of BULLOUS PEMPHIGOID over an 8-year period was compared to a cohort of matched controls. More than 17% of the bullous pemphigoid patients had a documented diagnosis of scabies within three years, while only 4.2% of the control group had had scabies. This study suggests that, at least among adults, having scabies increases the risk of developing bullous pemphigoid in the near future. 

TO READ MORE: Rozenblat M, et al. Bullous Pemphigoid and Scabies: Is There an Association? J Drugs Dermatol. 2022 Sep 1;21(9):1009-1011. doi: 10.36849/JDD.4900. PMID: 36074509.

HAIR AND NAILS

Although based on a small, retrospective study (N = 8), an Italian investigator reported rapid improvement in NAIL PSORIASIS among patients treated with tildrakizumab. At week 6, there was a mean Nail Psoriasis Severity Index (NAPSI) improvement of 40.6% and at week 20, the mean NAPSI improvement was a notable 90%. Six out of 8 patients had minimal disease at week 20. 

TO READ MORE: Brunasso A. Nail Psoriasis Improvement During Tildrakizumab Therapy: A Real-Life Experience. J Drugs Dermatol. 2022 Aug 1;21(8):914-916. doi: 10.36849/JDD.6828. PMID: 35946963. 

Editor’s note: A phase 3b study with tildrakizumab in nail psoriasis is underway.

Several cases of ALOPECIA AREATA are presented documenting excellent response to dilute intralesional triamcinolone acetonide (2.5 mg/mL) when combined with lidocaine and 1:100,000 epinephrine. It is theorized that the epinephrine, via vasoconstriction, decreases the rate of clearance of the injected corticosteroid. 

TO READ MORE:  Stratulat E, et al. Unique Treatment for Alopecia Areata Combining Epinephrine With an Intralesional Steroid. Cutis. 2022 Aug;110(2):105-108. doi: 10.12788/cutis.0580. PMID: 36219645.

CUTANEOUS ONCOLOGY, SURGERY AND LASERS

Using data obtained for Medicare recipients from 2009-2018, investigators found that the incidence of one or more ACTINIC KERATOSIS was 29.3% in this multi-year cohort. That translated into 28,656 per 100,000 person-years. 

TO READ MORE:  Navsaria LJ, et al. Incidence and Treatment of Actinic Keratosis in Older Adults With Medicare Coverage. JAMA Dermatol. 2022 Sep 1;158(9):1076-1078. doi: 10.1001/jamadermatol.2022.2555. PMID: 35895043; PMCID: PMC9330251.

A small (N = 25) retrospective Korean study demonstrated that application of 5% imiquimod 3 times weekly resulted in 68% of subjects obtaining complete resolution of classic KERATOACANTHOMAS (1.0-1.6 cm diameter). The median time until complete resolution was 73 days. 

TO READ MORE: Lee JW, et al. Therapeutic efficacy of topical imiquimod cream on keratoacanthoma: A retrospective single-center study. J Am Acad Dermatol. 2022 Sep;87(3):671-674. doi: 10.1016/j.jaad.2021.08.037. Epub 2021 Aug 30. PMID: 34474080.

HIDRADENITIS SUPPURATIVA 

A recent study suggested that JAK INHIBITORS, specifically upadacitinib (15-30 mg/day), may be beneficial for hidradenitis. All patients received 5 mg daily for four weeks, and if they failed to achieve hidradenitis suppurativa clinical response (HiSCR) at week 4, received the higher 30 mg daily dose. Responders maintained their benefit through 24 weeks of therapy. 

TO READ MORE:  Kozera E, et al. Real-world safety and clinical response of Janus kinase inhibitor upadacitinib in the treatment of hidradenitis suppurativa: A retrospective cohort study. J Am Acad Dermatol. 2022 Dec;87(6):1440-1442. doi: 10.1016/j.jaad.2022.07.047. Epub 2022 Aug 4. PMID: 35934210.

Editor’s note: No JAK inhibitor is yet approved for hidradenitis in the United States.

A comprehensive literature review disclosed that hidradenitis suppurativa (HS) is associated with CONCOMITANT INFLAMMATORY ARTHRITIS. Specifically, there was an increased prevalence of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis among HS patients compared to the general population. Probable risk factors included male gender, age under 30, severe HS, and administration of adalimumab and infliximab. 

TO READ MORE: Hanna N, et al. Incidence, prevalence, and predictors of inflammatory arthritis in patients with hidradenitis suppurativa: a systematic review and meta-analysis. Int J Dermatol. 2022 Sep;61(9):1069-1079. doi: 10.1111/ijd.15860. Epub 2021 Aug 25. PMID: 34432308.

DRUGS AND DEVICES

In August, the FDA issued warning letters to three companies who are selling UNAPPROVED NEW DRUGS claiming that they lead to “mole and skin tag removal.” The FDA reasserted that skin lesions need to be evaluated and treated by appropriate health care professionals. In addition, the FDA also issued June warning letters to a dozen companies who persist in selling OTC skin lightening agents which contain hydroquinone. As of September 23, 2020, skin lightening products containing hydroquinone which are not FDA approved were ordered to be removed from the marketplace. The FDA cited the risks of skin reactions and exogenous ochronosis associated with hydroquinone products, reasserting that they must be used only under medical supervision. 

TO READ MORE: Warning letter: Amazon.com and FDA works to protect consumers from potentially harmful OTC skin lightening products. FDA. April 19, 2022. Accessed December 6, 2022.

RHEUMATOLOGIC DISEASES

In a randomized, double-blind phase 2 trial, various dosages of oral deucravacitinib (3 mg BID, 6 mg BID and 12 mg QD) outperformed placebo for improvement in SYSTEMIC LUPUS ERYTHEMATOSUS. This held true across a variety of validated measures including British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), and systemic lupus erythematosus (SLE) Responder Index. 

TO READ MORE: Pike M, et al. POSTER: Efficacy and safety of deucravacitinib, an oral selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a phase 2, randomized, double-blind, placebo-controlled study. European Academy of Dermatology and Venereology Congress. September 7-10, 2022, Milan. 

Editor’s note: Deucravacitinib appears to be a promising drug for systemic lupus erythematosus, although optimal dosing remains to be elucidated.

COVID19

According to a Kaiser Foundation study, 10 million to 33 million adults age 18-64 suffer from LONG COVID, including malaise, persistent fatigue, dyspnea, cardiovascular abnormalities, headaches, and mental health impairment (brain fog). Just under a third have symptoms that last at least a year, and a half either no longer work or work fewer hours. 

TO READ MORE: Burns A. What are the Implications of Long COVID for Employment and Health Coverage? Kaiser Family Foundation (Kff.org), August 1, 2022. Accessed December 6, 2022.

Independent of other known risk factors (such as smoking, asthma, obesity, and hypertension), it appears that significant psychological distress BEFORE infection predisposes to LONG COVID. Depression, anxiety, perceived stress, and loneliness increase the risk of long Covid by 32% to 46%, according to a large scale American prospective study. 

TO READ MORE: Wang S, et al. Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions. JAMA Psychiatry. 2022 Nov 1;79(11):1081-1091. doi: 10.1001/jamapsychiatry.2022.2640. Erratum in: JAMA Psychiatry. 2022 Sep 28;: PMID: 36069885; PMCID: PMC9453634.

Although the drug has been linked to rebound phenomena, NIRMATRELVIR-RITONAVIR (Paxlovid) has also proven quite beneficial during the omicron COVID-19 surge. It reduced the risk of death by 79% and decreased hospitalization by 73% among those aged 65 and older. 

TO READ MORE: Arbel R, et al. Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge. N Engl J Med. 2022 Sep 1;387(9):790-798. doi: 10.1056/NEJMoa2204919. Epub 2022 Aug 24. PMID: 36001529; PMCID: PMC9454652.

Some lessons regarding COVID-19 testing: PCR tests carry a low risk of false negative results (1%) but home rapid antigen tests carry around a 15% risk of false negatives. Tests tend to be positive during rapid viral proliferation, and therefore may well be negative if performed immediately upon the onset of symptoms. Mucous is not the testable material, but rather the nasal cavity lining cells. The nose should be blown before the swab is inserted. Flowflex performs best, followed by BinaxNow, followed by all other brands. 

TO READ MORE:  Reddy S. Can you trust that at-home COVID test result? What five tests in 24 hours taught me. Wall Street Journal. August 24, 2022.