LITERATURE LESSONS : July

GENERAL DERMATOLOGY

The Ichthyosis Scoring System is a new, validated means of assessing the severity of either genetic or acquired ichthyosis. It takes into account the degree of erythema and scaling in several body surface areas. This should help determine who is eligible for clinical trials, as well as ongoing objective evaluation of therapeutic success.

TO READ MORE: Sun Q, et al. Development and Initial Validation of a Novel System to Assess Ichthyosis Severity. JAMA Dermatol. 2022;158(4):359-365. doi:10.1001/jamadermatol.2021.5917.

Editor’s note: Like the EASI and PASI, a universal scoring system will tell us how well new drugs for ichthyosis perform.

While varicose veins are typically of cosmetic concern, they can be symptomatic. VARICOSE VEINS are associated with muscle cramps, peripheral edema, pain after sitting or standing for protracted periods, pruritus around one or more veins, and the development of stasis ulcers at or near the ankle.

TO READ MORE (about symptomatic varicose veins): Streed J. Could leg pain be due to varicose veins? Mayo Clinic News Network, May 3, 2022. Available at: https://newsnetwork.mayoclinic.org/discussion/could-leg-pain-be-due-to-varicose-veins.

OZONE can be delivered in a variety of ways, including within an aqueous or oil preparation or via a bag containing ozone placed on the skin. Ozone primarily acts as a direct anti-infective and as an antioxidant. There is some evidence that ozone may help treat primary cutaneous infections and disorders known for microbial aberrations (acne, atopic dermatitis). Ozone may also help stimulate wound healing in chronic ulcers (diabetic, stasis). However, the quality of the evidence available to date provides neither sufficient justification nor reliable procedural details to recommend ozone treatment for skin diseases. This remains an area available for additional study.

TO READ MORE: Oliveira Modena DA, de Castro Ferreira R, Froes PM, Rocha KC. Ozone Therapy for Dermatological Conditions: A Systematic Review. J Clin Aesthet Dermatol. 2022;15(5):65-73.

A retrospective two-site study of almost 300 BULLOUS PEMPHIGOID  patients seen during a 6-year period disclosed three separate clinical clusters. The first group was older, had fewer blisters, minimal to no mucosal involvement and demonstrated anti-BP230 antibodies. The second group was younger, had moderate severity (<100 blisters), mucosal involvement in 38%, and 70% had only anti-BP180 antibodies. The final cluster were younger patients with severe disease (>100 blisters), frequent (91%) mucosal involvement and 74% with only anti-BP180 antibodies. This final group was comprised of patients with the most difficult disease to control, leading to the most frequent relapses.

TO READ MORE: Guerrois F, et al. Bullous pemphigoid: three main clusters defining three outcome profiles [published online ahead of print, 2022 Apr 25]. J Am Acad Dermatol. 2022;S0190-9622(22)00695-8. doi:10.1016/j.jaad.2022.04.029.

ACNE

It is worth remembering that adolescents with acne may well be highly influenced by MISINFORMATION derived from the internet. For example, antibiotics and isotretinoin may be characterized as poisonous. The root cause of acne may be erroneously attributed to Candida toxins or drinking fluoridated water. A vegan diet may be proposed as an acne “cure-all.” Adolescent blind acceptance of information from the internet may interfere with any therapeutic plan due to non-adherence.

TO READ MORE:  O’Connor C, et al. Spotting fake news: a qualitative review of misinformation and conspiracy theories in acne vulgaris [published online ahead of print, 2022 Apr 18]. Clin Exp Dermatol. 2022;10.1111/ced.15222. doi:10.1111/ced.15222.

ROSACEA

A systematic review and meta-analysis of 39 studies including more than 9100 patients found, not unexpectedly, that erythematotelangiectatic and papulopustular rosacea were the MOST COMMON VARIETIES seen in clinical practice. Phymatous rosacea accounted for only 7% of cases and was more common in men.

TO READ MORE:  Barakji YA, et al. Assessment of Frequency of Rosacea Subtypes in Patients With Rosacea: A Systematic Review and Meta-analysis [published online ahead of print, 2022 Apr 6]. JAMA Dermatol. 2022;e220526. doi:10.1001/jamadermatol.2022.0526.

PEDIATRIC DERMATOLOGY

In a retrospective case series (N=47) of pediatric GRANULOMA ANNULARE at a single urban academic institution, there was a very high prevalence of atopic conditions. None of the pediatric study subjects developed diabetes. Most lesions, as expected, presented on the extremities. While topical steroids relieved pruritus, they did not hasten lesion involution.

TO READ MORE: Cruz SA, et al. The Clinical Presentation and Comorbidities Associated with Granuloma Annulare in the Pediatric Population: A Retrospective Study. Skinmed. 2022;20(1):24-28. Published 2022 Feb 28.

PSORIASIS

In a dose-ranging Phase 2 study of SONELOKIMAB, an IL-17A and IL-17F blocker, clinical efficacy was demonstrated. This new agent is novel in that it is a nanobody, about one-tenth the size of a typical monoclonal antibody.

TO READ MORE: Papp KA, et al. IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study [published correction appears in Lancet. 2021 Jun 5;397(10290):2150]. Lancet. 2021;397(10284):1564-1575. doi:10.1016/S0140-6736(21)00440-2.

A Korean retrospective study focusing on 800 generalized PUSTULAR PSORIASIS patients over a 14-year period disclosed that co-existing renal or hepatic disease, prior myocardial infarction, and concomitant diabetes mellitus put such individuals at high risk for severe disease, including admission to an intensive care unit.

TO READ MORE: Ohn J, et al. Identifying patients with deteriorating generalized pustular psoriasis: Development of a prediction model [published online ahead of print, 2022 May 2]. J Dermatol. 2022;10.1111/1346-8138.16383. doi:10.1111/1346-8138.16383.

Investigation of fecal samples revealed that psoriasis patients who are not systemically treated have lower GUT MICROBIAL DIVERSITY than carefully matched non-psoriatic controls and household cohabitants of the psoriasis study patients.

TO READ MORE:  Todberg T, et al. Patients with psoriasis have a dysbiotic taxonomic and functional gut microbiota [published online ahead of print, 2022 Mar 15]. Br J Dermatol. 2022;10.1111/bjd.21245. doi:10.1111/bjd.21245.

Editor’s note: Is this somehow etiologic or an epiphenomenon, the result of systemic inflammation?

ATOPIC DERMATITIS

An Israeli retrospective population-based cohort study involving 58,582 adult atopic dermatitis patients noted that two doses of the BNT162b2 mRNA COVID-19 VACCINE reduced the risk of infection, hospitalization, and death by 80%, 92%, and 96%, respectively. The most interesting thing about this study was that protection afforded by the vaccine remained the same among adult atopics who continued to receive immunosuppressive drugs, including azathioprine, mycophenolate, methotrexate, cyclosporine, and dupilumab.

TO READ MORE: Kridin K, et al. Determinants and Effectiveness of BNT162b2 mRNA Vaccination Among Patients with Atopic Dermatitis: A Population-Based Study. Am J Clin Dermatol. 2022;23(3):385-392. doi:10.1007/s40257-022-00672-5.

A British retrospective population-based cohort study over a 10-year period analyzed over 173,000 adult and pediatric atopic dermatitis patients. Compared to nearly 695,000 controls from the same primary care database, those with atopy had a higher baseline prevalence of AUTOIMMUNE DISEASE (5.8% versus 4.3%). The atopic patients also had a higher incidence of new onset autoimmune disease, especially those with severe atopic dermatitis. Specifically, those with atopic dermatitis were likely to develop psoriatic and rheumatoid arthritis, Sjogren syndrome, Crohn disease and ulcerative colitis, vitiligo, alopecia areata, pernicious anemia, and autoimmune hypothyroidism.

TO READ MORE: de Lusignan S, et al. Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study [published online ahead of print, 2022 Apr 22]. J Allergy Clin Immunol. 2022;S0091-6749(22)00547-4. doi:10.1016/j.jaci.2022.03.030.

COSMETIC DERMATOLOGY

Although the metabolic syndrome was numerically more common among a cohort of patients with MELASMA, the difference was not statistically significant. There was no difference in metabolic parameters such as BMI between MELASMA patients and matched controls. Fasting insulin levels were higher in the melasma cohort, reaching statistical significance. The connection between melasma and metabolic derangement is weak, at best.

TO READ MORE: Gore Karaali M. Metabolic Syndrome in Melasma: A case-control study [published online ahead of print, 2022 May 12]. J Cosmet Dermatol. 2022;10.1111/jocd.15076. doi:10.1111/jocd.15076.

HAIR AND NAILS

Dermoscopic frontal and occipital scalp findings were compared between women with female pattern ANDROGENETIC ALOPECIA, TELOGEN EFFLUVIUM, and matched normal controls. Most notably, androgenetic alopecia was characterized by excessive hair diameter diversity, and the presence of vellus hairs and yellow dots. Telogen effluvium was more commonly associated with perifollicular scaling.

TO READ MORE:   Bains P, et al. Comparison of Dermoscopic Findings in Female Androgenetic Alopecia and Telogen Effluvium and Female Controls in a Tertiary Care Center. J Clin Aesthet Dermatol. 2022;15(5):29-34.

An online survey disclosed that the vast majority of licensed NAIL TECHNICIANS had some training in detecting acral skin cancers (including acral lentiginous melanoma) and routinely referred suspicious lesions to dermatologists for evaluation. Nail professionals also were willing and eager to obtain additional training to increase their confidence and skill levels in this endeavor.

TO READ MORE: Joseph AK, et al. Knowledge, attitudes, and behaviors of nail technicians in detecting acral lentiginous melanoma [published online ahead of print, 2022 May 9]. J Cosmet Dermatol. 2022;10.1111/jocd.15068. doi:10.1111/jocd.15068.

HIDRADENITIS SUPPURATIVA

A retrospective U.S. cohort study revealed that select INFLAMMATORY MARKERS can accurately reflect hidradenitis disease severity. The most reliable predictive parameters included: elevated C-reactive protein (CRP), total leukocyte and absolute neutrophil count, and counts of eosinophils, basophils, and monocytes.

TO READ MORE: Andriano TM, et al. Serum inflammatory markers and leukocyte profiles accurately describe hidradenitis suppurativa disease severity [published online ahead of print, 2022 May 11]. Int J Dermatol. 2022;10.1111/ijd.16244. doi:10.1111/ijd.16244.

Editor’s note: I wonder if serially following CRP, for example, could be used to predict flares before they are clinically apparent, leading to more intensified intervention?

CUTANEOUS ONCOLOGY, SURGERY AND LASERS

According to a recently published Swedish study, younger (18-39) and older (> 70) melanoma patients feel like they don’t get enough INFORMATION from their health care providers. Middle-age melanoma patients (40-69) are generally satisfied with the quantity and quality of information given to them by the health care provider.

TO READ MORE: Tufvesson SH, et al. Perception of information to Swedish melanoma patients in routine clinical practice – a cross-sectional survey. BMC Cancer 2022;22(1):159. doi: 10.1186/s12885-022-09208-w

A fascinating case of classic KAPOSI SARCOMA with only transient response to radiotherapy demonstrated marked and sustained improvement following daily oral administration of 10 mg propranolol. The low dose was well tolerated.

TO READ MORE: Salido-Vallejo R, et al. Treatment With Oral Propranolol for Refractory Classic Cutaneous Kaposi Sarcoma [published online ahead of print, 2022 May 11]. JAMA Dermatol. 2022;10.1001/jamadermatol.2022.1278. doi:10.1001/jamadermatol.2022.1278.

Editor’s note: As the authors point out, propranolol appears to be an attractive alternative in patients with thick, multiple, or symptomatic lesions when topical treatment is inadequate and/or radiotherapy and chemotherapy simply are not suitable.

A large cross-sectional study involving ASIAN AMERICANS from the National Health Interview Survey database disclosed that all subgroups were more likely to seek shade, wear long clothing to the ankles, and wear long-sleeved shirts but less likely to use sunscreen compared to non-Asian/non-Hispanic Whites. Those of Chinese ancestry were more likely to apply sunscreen and wear a hat compared to other Asian subgroups.

TO READ MORE: Supapannachart KJ, et al. Skin Cancer Risk Factors and Screening Among Asian American Individuals. JAMA Dermatol. 2022;158(3):260-265. doi:10.1001/jamadermatol.2021.5657.

A longitudinal Italian study followed a cohort of women with VULVAR MELANOSIS for several decades. Despite the fact that in nearly 1 out of 3 lesions increased in size or underwent color changes, no malignant degeneration was noted.

TO READ MORE: De Giorgi V, et al. Clinical and Dermoscopic Features of Vulvar Melanosis Over the Last 20 Years. JAMA Dermatol. 2020;156(11):1185-1191. doi:10.1001/jamadermatol.2020.2528.

DRUGS AND DEVICES

Can a patient who asserts penicillin allergy safely receive a cephalosporin? This study, based on a systematic review and meta-analysis of 77 publications (6147 patients) found that the vast majority of penicillin-allergic individuals can, indeed, receive CEFAZOLIN without adverse incident. Of those who were deemed penicillin allergic, only 0.7% were found to be cefazolin sensitive. Among the small group of those with a historical allergy to cefazolin, 3.7% were found to be penicillin allergic.

TO READ MORE: Sousa-Pinto B, et al. Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin: A Systematic Review and Meta-analysis. JAMA Surg. 2021;156(4):e210021. doi:10.1001/jamasurg.2021.0021.

National spending on drugs rose by 12% in 2021, largely related to COVID-19 vaccine and treatment costs. Despite an overall increase in DRUG SPENDING, the cost per prescription on average was flat or slightly declining. Out-of-pocket costs for prescription drugs increased substantially, creating a significant financial burden for select subsegments of the U.S. population.

TO READ MORE: IQVIA Institute for Human Data Science. The Use of Medicines in the U.S. 2022. April 21, 2022. Accessed at: https://www.iqvia.com/insights/the-iqvia-institute/reports/the-use-of-medicines-in-the-us-2022.

INFECTIOUS DISEASES

Twenty-seven INPATIENTS WITH BODY LICE and 81 inpatients without were included in an analysis done at the University of California, San Francisco. As one might predict, those infested with the obligate blood-sucking ectoparasites had a mean 2.5 g/dL lower hemoglobin level. This may be one cause of anemia in marginalized populations, such as the homeless.

TO READ MORE: Rudd N, et al. Association of Body Lice Infestation With Hemoglobin Values in Hospitalized Dermatology Patients [published online ahead of print, 2022 Apr 20]. JAMA Dermatol. 2022;e220818. doi:10.1001/jamadermatol.2022.0818.

To date, INFECTIOUS FILOVIRUSES (such as Ebola) have only been found in Africa. However, the Lloviu virus, a very close genetic relative of Ebola, has now been found–both serologically and via direct viral isolation–from bats in both Spain and Hungary. This poses the possibility of a zoonotic spread to humans (spelunkers for example). This novel virus might logically be expected to be both lethal and contagious, based on its similarity to Ebola. Remdesivir has proven effective against Lloviu virus in-vitro.

TO READ MORE: Kemenesi G, et al. Isolation of infectious Lloviu virus from Schreiber’s bats in Hungary. Nat Commun. 2022;13(1):1706. Published 2022 Mar 31. doi:10.1038/s41467-022-29298-1 and Görföl T, et al. Lloviu Virus in Europe is an Emerging Disease of Concern. Ecohealth. 2022;19(1):5-7. doi:10.1007/s10393-021-01574-4.

Investigators have discovered a new molecule, GASDERMIN A, which causes a specific type of programmed skin cell death, called pyroptosis, when faced with certain recognized pathogens, such a Group A Streptococci. The researchers hope to harness this novel protein to induce cell death in diseased skin (such as necrotizing fasciitis) without harming uninfected cells and eliminating the need for debilitating surgical debridement.

TO READ MORE: LaRock, D.L., Johnson, A.F., Wilde, S. et al. Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes. Nature 605, 527–531 (2022). https://doi.org/10.1038/s41586-022-04717-x.

RHEUMATOLOGIC DISEASES

Researchers at the University of Michigan have found that both lesional and normal-appearing skin of LUPUS patients contains elevated levels of Type 1 interferons in keratinocytes and fibroblasts compared to matched skin samples from healthy individuals. The same is true of circulating monocytes. The investigators speculate that this keeps the skin in a “primed” state so that small provocations can lead to the rapid development of inflammation.

TO READ MORE: Billi AC, et al. Nonlesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation. Sci Transl Med. 2022;14(642):eabn2263. doi:10.1126/scitranslmed.abn2263.