Literature Lessons

A single center retrospective analysis compared 7,361 biological drug recipients with 74,910 matched patients. There was not an increased risk of COVID-19 infection or an increased risk of COVID-19-related mortality among the biologic drug recipient cohort. Prominent among the drugs received were adalimumab (28.4%), infliximab (15.6%), and etanercept (11.9%), as well as rituximab (15.6%) and dupilumab (8.6%). The majority of individuals in the study were being treated for rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and atopic dermatitis. This supports dermatologists to not proactively stop biologic drugs in their patients who are already using them. This study also suggests that, if a patient requires and qualifies for a biologic agent, he/she should receive an appropriate biologic drug during the COVID-19 pandemic.

TO READ MORE: Pahalyants V, et al. Immunosuppressive biologics did not increase the risk of COVID-19 or subsequent mortality: a retrospective 1 matched cohort study from Massachusetts. J Am Acad Dermatol.2021; Aug 28; doi: 10.1016/j.jaad.2021.08.065.

One in every 500 Americans have now died of COVID-19, deaths having increased due to the contagious Delta variant, with the number of deaths through mid-September, 2021 now exceeding those for all of 2020. USA Today, Sep 1, 2021.

The worldwide COVID-19 pandemic has disrupted the flow of resources, the availability of medical manpower, and the pharmaceutical supply chain to significantly impact efforts to combat the spread of HIV and increase in drug-resistant tuberculosis.

TO READ MORE: The Global Fund, 20 Years of Impact. Accessible at: https://theeglobalfund.org/en/results

A comprehensive meta-analysis of studies of hydroxychloroquine administered as either post-exposure prophylaxis or as part of acute care management strongly supports discontinuation of utilization of this drug for COVID-19.

TO READ MORE: Hennekens CH, et al. Updates on hydroxychloroquine in prevention and treatment of COVID-19. Am J Med. 2021; Aug 23; doi: 10.1016/j.amjmed.2021.07.035.

A nationally representative Mental Health America poll found that during the COVID-19 pandemic and mostly directly due to same, 93% of health care workers said they experienced stress in the past three months, 86% reported anxiety, 77% reported frustration, 76% reported exhaustion and/or burnout, and 75% said they were overwhelmed.

TO READ MORE: https://mhanational.org/issues/state-mental-health-america

Data gathered from three months of a CDC online COVD-19 Self-Checker (Feb-May, 2021) suggested that loss of taste and/or smell was more closely associated with these signs and symptoms: congestion, a runny nose, cough and fever, than with positive COVID-19 tests. Loss of taste and smell may not be a reliable predictor of COViD-19 infection.

TO READ MORE: Koyama AK, et al. Symptoms reported with new onset of loss of taste or smell in individuals with and without SARS-CoV-2 infection. JAMA Otolaryngol Head Neck Surg. 2021; Sep 2. doi: 10.1001/jamaoto.2021.2239.

COVID-19

The multi-state Providence Healthcare System medical records were evaluated during the two years pre-COVID-19 vaccination and since the institution of vaccination. The mean monthly incidence of both myocarditis and pericarditis increased following the administration of mRNA COVID-19 vaccines. Myocarditis developed rapidly, mostly among younger patients, primarily after the second vaccination. By contrast, pericarditis largely affected older patients later, after either the first or second vaccine dose. Most cases eventually resolved without residual defect.

TO READ MORE: Diaz GA, et al. Myocarditis and pericarditis after vaccination for COVID-19. JAMA. 2021;326(12):1210-1212.

Very few states (five total) allow minors to consent to medical interventions, including vaccination. Some have vigorously advocated to allow older minors (14-17) to consent to COVID-19 vaccination, but this would require legislative action.

TO READ MORE: Morgan L, et al. COVID-19 vaccination of minors without parental consent: respecting emerging autonomy and advancing public health. JAMA Pediatr. 2021;175(10):995-996. Compared to those who are not vaccinated, fully vaccinated patients who still contract COVID-19 are more likely to develop “long haul” complications. These include:  cardiac arrhythmia, joint pain, Type 2 diabetes, liver disease, sleep disturbances, and mood or anxiety disorders. To read more: Reuters Health Medical News, 2021; October 28.

(Editor’s note: Although the authors make the point that decision-making processes in older minors often parallel those of their parents/guardians, I think the emergence of side effects—see above—and confusion over the booster issue, makes it less likely that a minor can truly make an “informed” decision. This is a slippery slope, in my opinion.)

PEDIATRIC DERMATOLOGY

A comprehensive registry for pediatric melanoma has disclosed that atypical Spitz nevi/Spitzoid melanoma most often arises on the extremities in younger patients; these lesions carry a better prognosis. Conventional melanomas (which resemble those in adults) arise at a median age of 13 and often carry either BRAFV600E or TERT promoter mutations. Patients with melanoma arising in a giant congenital nevus harbor NRASQ61 mutations, and have a poorer prognosis.

TO READ MORE: Pappo AS, et al. A prospective, comprehensive registry that integrates the molecular analysis of pediatric and adolescent melanocytic lesions. Cancer. 2021; July 6. doi: 10.1002/cncr.33750.

A surveillance study used a pre-pandemic/post-pandemic control design with data from eight health systems in six states (California, Oregon, Washington, Colorado, Minnesota, and Wisconsin) to compare childhood vaccination rates for a variety of standard immunizations. Throughout 2020, the rates of vaccination, in all pediatric age groups, remained lower than expected and lower than rates for comparable time periods in 2019.

TO READ MORE: DeSilva MB, et al. Association of the COVID-19 pandemic with routine childhood vaccination rates and proportion up to date with vaccinations across 8 U.S. health systems in the vaccine safety datalink. JAMA Pediatr. 2021; October 7. doi:10.1001/jamapediatrics.2021.4251.

INFECTIOUS DISEASES

Vegetative (or hypertrophic) genital herpes is virtually always seen in conjunction with HIV infection. The authors report a case of acyclovir-resistant vegetative HSV-2 infection without any evidence of HIV infection or other immunosuppression. Treatment with topical imiquimod, oral thalidomide (150 mg/day), and topical compounded 1% cidofovir was eventually successful.

TO READ MORE: Hu J, et al. Vulvar pseudotumoral acyclovir-resistant herpes in an HIV-negative, non-immunosuppressed patient: a therapeutic challenge. Int J Women’s Dermatol. 2021; June 20. doi: 10.1016/j.ijwd.2021.06.002.

(Editor’s note: Biopsy is indicated to distinguish between vegetative herpes and squamous cell carcinoma.)

A recent retrospective study at UCSF of scabies (N=103) showed that post-treatment itch occurs in many patients (in this study 34%), and lasted a relatively long time (in this study a median of 52.5 days). Topical corticosteroids and NB-UVB were commonly used to treat the condition.

TO READ MORE: Chiu L, et al. Management of common scabies and post-scabetic itch in adults: lessons learned from a single-center retrospective cohort study. Int J Women’s Dermatol. 2021; Sep 12. doi: 10.1016/j.ijwd.2021.09.001.

Facial and non-facial leishmaniasis patients (N=134) were compared in an Israeli study. Those with facial lesions tended to be younger and female. In all other respects, however, lesions behaved similarly regardless of location.

TO READ MORE: Moser RY, et al. Comparison between cutaneous leishmaniasis patients with facial and non-facial lesions. Int J Dermatol. 2021; Sep;60(9):1109-1113.

A deficiency or mutated version of the protein Optineurin (OPTN) may allow herpes viruses, especially the omnipresent HSV-1, to invade the central nervous system. Based on mouse experiments, this then leads to a neurodegenerative disorder, which mimics human Alzheimer’s disease.

TO READ MORE: Ames, J, et al. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Nat Commun. 12, 5401 (2021). doi: 10.1038/s41467-021-25642-z.

What do you tell a patient who has herpes zoster about the likelihood of a recurrence? In a large scale, retrospective Australian study, 3.9% of those with shingles developed another episode, generally two to three years after the initial one. Factors favoring recurrence include immunosuppression, female gender, and younger age at first outbreak.

TO READ MORE: Qian J, et al. Risk of recurrent herpes zoster in a population-based cohort study of older adults. J Am Acad Dermatol. 2021; 85:611-618.

The Italian authors point to an increase in scabies during the COVID pandemic, in line with several other prior publications. This might be due to the “stay at home” and “work from home” policies adopted in many countries, leading to more extended and closer contact with family members and other cohabitants.

TO READ MORE: De Lucia M, et al. Scabies outbreak during COVID-19: an Italian experience. Int J Dermatol. 2021;60:1307-1308.

A pediatric case of tinea faciei due to Trichophyton benhamiae was associated with contact with pet guinea pigs. This is an emerging zoophilic pathogen, mostly associated with guinea pigs.

TO READ MORE: Iznardo H, et al. Tinea faciei from trichophyton benhamiae from a pet guinea pig. JAMA Dermatol. 2021;157:1115.

Swedish researchers from KTH Royal Institute of Technology and Karolinska University Hospital have developed a new wound hydrogel, which kills virtually all gram positive and gram negative bacteria. Furthermore, it induces the production of natural antimicrobial peptides and reduces inflammation. It is also totally biodegradable and non-toxic. The hydrogel is a dendritic polymer based on polyethylene glycol and propionic acid. This may revolutionize the management of diabetic, stasis, and vascular ulcers, as well as superficial traumatic wounds.

TO READ MORE: Fan Y, et al. Dendritic hydrogels induce immune modulation in human keratinocytes and effectively eradicate bacterial pathogens. J Am Chem Soc. 2021; October 12. doi: 10.1012/jacs.1c07492.

A novel way to search for mites is to do a scabies prep from the hyponychium using the blunt end of a hyfrecator tip. Debris (including mites, eggs, or scybala) might accumulate there due to scratching, and the use of the hyfrecator tip is an atraumatic way of sampling that area.

TO READ MORE: Oberdorfer K and Moossavi M. Cutis. 2021;108:228-229.

RHEUMATOLOGIC DISEASES

The “deck-chair sign” consists of an erythematous truncal eruption sparing both intertriginous areas and transverse skin folds. Three cases are well documented where this sign was present early in the course of dermatomyositis.

TO READ MORE:  Int J Dermatol. 2021;60:e367-368. doi: 10.1111/ijd.15491

COSMETIC DERMATOLOGY

This nationally representative survey study did not find a difference between adult men and women in terms of frequency of indoor tanning. However, men chose indoor tanning facilities with fewer rules and often used home tanning units. Men who are frequent tanners may also be prone to binge alcohol drinking and smoking.

TO READ MORE: Feng J, et al. Sex differences in indoor tanning habits and location. J Am Acad Dermatol. 2021;85(2):466-468.


PSORIASIS

A short report from Greece noted 14 patients with very mild psoriasis who flared into generalized disease following either mRNA or adenovirus COVID-19 vaccination. Mean time after vaccination until psoriasis flare was 10.36 days.

TO READ MORE: Sotiriou E, et al. Psoriasis exacerbation after COVID-19 vaccination: a report of 14 cases from a single centre. J Eur Acad Dermatol Venereol.2021; Aug 7. doi: 10.1111/jdv.17582.

TO READ MORE: Akbulut TO, et al. Drug survival and predictor factors for discontinuation of methotrexate in psoriasis: a real–life multicenter study. Int J Dermatol. 2021;60:11140-1147.

A retrospective analysis based upon the Optum electronic claims database clearly suggests that the development of psoriatic arthritis is more common among those with more severe cutaneous disease.

TO READ MORE: Merola JF, et al. Incidence and prevalence of psoriatic arthritis in patients with psoriasis stratified by psoriasis disease severity: retrospective analysis of a US electronic health records database. J Am Acad Dermatol. 2021; Sep 18. doi: 10.1016/j.jaad.2021.09.019.

A report from Turkey analyzed 649 patients who were started on methotrexate as their first systemic treatment for psoriasis. Methotrexate was continued for a median of 15 months, which is short compared to most biologic drugs. Early nausea and vomiting predicted that the drug would be discontinued quickly.

Italian investigators conducted a meta-analysis of 25 observational cohort studies looking for an association between psoriasis and lymphohematological malignancies. Collectively, the studies included more than 2.5 million patients who were followed from 1.5 to 30 years. Psoriasis patients, in these studies, had an increased risk of Hodgkin lymphoma, Non-Hodgkin lymphoma, and CTCL/Mycosis fungoides. There was also some evidence of association with leukemia and multiple myeloma, although the hazard ratio was lower.

TO READ MORE: Bellinato F, et al. Risk of lymphohematologic malignancies in patients with chronic plaque psoriasis: a systematic review with meta-analysis. J Am Acad Dermatol. 2021; Aug 4. doi: 10.1016/j.jaad.2021.07.050.

A prospective 52-week study involving 45 patients with both plaque and nail psoriasis showed over 50% improvement in Nail Psoriasis Severity Index (NAPSI) following Apremilast therapy (dose 30mg BID).

TO READ MORE: Muñoz-Santos C, et al. Apremilast improves quality of life and ultrasonography parameters in patients with nail psoriasis: a prospective cohort study. J Dermatol. 2021; Aug 12. doi: 10.1111/1346-8138.16074.

 ATOPIC DERMATITIS

A British cohort of 11,000 children was followed to age 10. Those with severe atopic dermatitis were twice as likely to suffer from depression. All degrees of atopic dermatitis were associated with “internalizing behaviors” by age 4, including headaches or stomachaches, and excessive worrying and signs of low self-esteem.

TO READ MORE: Kern C, et al. Association of atopic dermatitis and mental health outcome across childhood. a longitudinal cohort study. JAMA Dermatol. 2021; Sep 1. doi: 10.1001/jamadermatol.2021.2657.

Two British pediatric cohorts (N=30,905) were followed from birth (1958 and 1970) until the year 2016. Of those who developed atopic dermatitis, about 10% had the disorder persist into midlife. No specific early life exposures (or lack thereof) could be identified that predisposed to persistent atopic dermatitis.

TO READ MORE: Abuabara K, et al. Patterns of atopic eczema disease activity from birth through midlife in two British birth cohorts. JAMA Dermatol. 2021; Oct 1. doi: 10.1001/jamadermatol.2021.2489. (Editor’s note: This is further verification that atopic dermatitis doesn’t always “go away” as the child ages.)

A retrospective Danish study showed that, once started, both methotrexate and azathioprine were continued as therapies for atopic dermatitis in almost the exact same percentage at one, two, and four years. For both drugs, adverse events led to discontinuation (methotrexate, 25%; azathioprine, 41%). Both drugs equally improved sleep quality.

TO READ MORE: Elsgaard S, et al. Drug survival of systemic immunosuppressive treatments for atopic dermatitis in a long-term pediatric cohort. Int J Women’s Dermatol. 2021; July 22. doi: 10.1016/j.ijwd.2021.07.005.

The third report of transient but significant alcohol-induced facial flushing concomitant with starting dupilumab therapy for atopic dermatitis gives rise to the possibility that dupilumab, in some patients, may interfere with the alcohol detoxification mechanisms.

TO READ MORE: Brownstone ND, et al. Dupilumab-induced facial flushing after alcohol consumption. Cutis. 2021;108:106-107

A U.S. cross-sectional, nationally representative study showed that children with atopic dermatitis were more likely to be chronically absent (>15 days/year) from school than children with psoriasis. Children with psoriasis were not more likely to be chronically absent from school than children without skin disease. In parallel, parents of children with atopic dermatitis were also more likely to miss work due to caregiving for their offspring.

TO READ MORE: Chang BT and Silverberg JI. Association of pediatric atopic dermatitis and psoriasis with school absenteeism and parental work absenteeism, a cross-sectional United States population-based study. J Am Acad Dermatol. 2021; 85:885-892.

CONTACT DERMATITIS

Irritable bowel syndrome (IBS) might be due to an inflammatory reaction to select foods. Following patch testing to identify suspected allergens, 19 patients were followed for three to four months after avoiding those foods with a positive patch test. Results found that 78.9% of the 19 study participants reported improvement in their global IBS symptoms.

TO READ MORE: Stierstorfer MB, Toro B. Patch test-directed dietary avoidance in the management of irritable bowel syndrome. Cutis. 2021;108:91-95. (Editor’s note: If this were confirmed in a larger series, it would amount to a major advance in our ability to deal with IBS.)


HAIR AND NAILS

Isotretinoin has been found to increase the growth rate and decrease the thickness of the nail plate, these effects increasing over a six-month period. Pre-existing nail health should be assessed before isotretinoin administration.

TO READ MORE: Ozcelik S and Killic FA. Effects of isotretinoin on the growth rate and thickness of the nail plate. Int J Dermatol. 2021;60:1258-1262.

In the first large-scale study on the subject, gender-affirming hair removal (electrolysis, laser) in transgender individuals was associated with improved mental health, including decreased mental distress and reduced suicidal ideation.

TO READ MORE: Lee MS, et al. Association between gender-affirming hair removal and mental health outcomes. JAMA Dermatol. 2021;157:1120-1122.

HIDRADENITIS SUPPURATIVA

A prospective, multicenter, 12-week European study involving 238 patients demonstrated objective improvement in hidradenitis patients who received an oral tetracycline or clindamycin plus rifampicin. The HiSCR (Hidradenitis Suppurativa Clinical Response) was achieved in 40.1% of those who received tetracycline, doxycycline, or minocycline and in 48.2% of those who received the combination regimen.

TO READ MORE: van Straalen KR, et al. The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: results of a prospective European cohort study. J Am Acad Dermatol. 2021;85(2):369-378.

A comprehensive review and meta-analysis not unexpectedly found that about half of hidradenitis patients suffer some form of sexual dysfunction. The latter is often accompanied by overt depression and low self-esteem.

TO READ MORE: Seetan K, et al. Sexual dysfunction in patients with hidradenitis suppurativa: a systematic review and meta-analysis. J Clin Aesthet Dermatol. 2021;14(8):61-65.

CUTANEOUS ONCOLOGY, SURGERY, AND LASERS

A single center review of 164 cases initially diagnosed as superficial basal cell carcinoma (BCC) disclosed that 37% were found (at excision or during Mohs surgery) to have a more aggressive component. The message is that management of superficial BCC should take into account the possibility of a deeper, undiagnosed, aggressive BCC subtype.

TO READ MORE: Sohn GK, et al. Characteristics of superficial basal cell carcinomas containing more aggressive subtypes on final histopathologic diagnosis. J Drugs Dermatol. 2021;20(8):874-879.

A comprehensive Australian analysis of actinic keratosis (AK) topical field therapy (involving the face and scalp) concluded that treatments with high complete clearance rates in the short run (three to six months) may have much lower complete clearance rates at one year, undermining the precise goal of a durable reduction in incidence of AKs and skin cancer.

TO READ MORE: Sinclair R, et al. A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies. Australas J Dermatol. 2021;May;62(2):119-123. doi: 10.1111/ajd.13447. (Editor’s note: This pessimistic but realistic study suggests we should routinely repeat topical field therapies as a matter of best practice.)

DRUGS AND DEVICES

PADCEV® (enfortumab vedotin-ejfv) is an antibody-drug conjugate designed to treat cancer expressing Nectin-4, generally bladder cancer. This drug has now been strongly linked to cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Should a patient receiving this therapy call and report a “rash,” this should be considered URGENT, and the patient seen or referred to an emergency department immediately.

TO READ MORE: Nguyen MN, et al. Postmarketing cases of enfortumab vedotin—associated skin reactions reported as Stevens-Johnson syndrome or toxic epidermal necrolysis. JAMA Dermatol. 2021; Sep 8. doi: 10.1001/jamadermatol.2021.3450.

Harvard researchers have developed a low projected cost (<$25), self-contained, battery power point of care device that can detect all known variants of COVID-19 from a saliva sample in about an hour. The device is also easily modified to detect other respiratory pathogens.

TO READ MORE: Abbasi J. Point-of-care SARS-CoV-2 variant diagnostic in development. JAMA 2021;326(10):901.

GENERAL DERMATOLOGY

Investigators did not find an increased risk of venous thromboembolic events among 158,123 patients with inflammatory skin conditions (including psoriasis, atopic dermatitis, hidradenitis, alopecia areata, and vitiligo) compared to a large cohort of matched patients without cutaneous inflammatory disorders.

TO READ MORE: Schneeweiss MC, et al. Incidence of venous thromboembolism on patients with dermatologist-diagnosed chronic inflammatory skin diseases. JAMA Dermatol. 2021;157(7): 805-816.

Despite a positive Phase 2 study (Br J Dermatol. 2021 May 3. doi: 10.1111/bjd.20431), which suggested therapeutic activity of rilzabrutinib, an oral Bruton tyrosine kinase inhibitor, in pemphigus, a larger Phase 3 study unfortunately failed to meet either primary or key secondary endpoints.

TO READ MORE: Sanofi provides an update on Phase 3 study evaluating rilzabrutinib for the treatment of pemphigus. Available at: https://www.sanofi.com/en/media-room/press-releases/2021/2021-09-09-07-00-00-2293920

Of 1563 biopsy-proven skin malignancies at a single U.S. institution, 51% were discovered by dermatologists during a total body skin examination (TBSE). Melanomas discovered on TBSE had a mean Breslow depth of 0.53 mm compared to 1.04 mm for those identified by patients themselves or by their primary care provider. TBSE can be prioritized to highest risk patients, but clearly carries significant benefit.

TO READ MORE: Jiang A, et al. Skin cancer discovery during total body skin examinations. Int J Women’s Dermatol. 2021; May 30;7(4):411-414. doi: 10.1016/j.ijwd.2021.05.005.