Skin-Related Quality of Life During Autoimmune Bullous Disease Course.

Importance: Autoimmune bullous diseases (AIBDs) are chronic relapsing-remitting conditions with significant morbidity. Skin-related quality of life (SRQL) may vary by AIBD subtype and disease type. Disease severity and flare severity can be difficult to define; SRQL can offer a key insight. Objectives: To investigate the Skindex-16 score as an SRQL measure in AIBD subtypes during flare and nonflare states and to evaluate Skindex-16 construct validity. Design, Setting, and Participants: This retrospective cross-sectional study was conducted from September 1, 2016, to February 1, 2020, among 192 patients at the University of Utah Health autoimmune dermatology clinic with pemphigoid, pemphigus, dermatitis herpetiformis, and linear immunoglobulin A disease. Patients had an encounter-associated diagnosis, Skindex-16 scores, and self-reported flare status. Statistical analysis was performed from March 2022 to June 2023. Exposure: Autoimmune bullous disease subtype and patient-reported flare status. Main Outcomes and Measures: Skindex-16 domain scores (emotions, symptoms, and functioning; range, 0-100, where 0 indicates no effect on SRQL and 100 maximum effect) and individual item scores were described by disease and flare status. Flare scores were expected to be higher by at least the standard error of measurement (SEm). Convergent validity was assessed using Spearman correlation among Skindex-16 scores, serologic titers, and other patient-reported outcome measures. Floor or ceiling domain scores (<20% of sample scoring either lowest or highest possible domain scores, respectively) were assessed for Skindex-16. Structural validity was assessed using confirmatory factor analysis (CFA). Results: The study included 192 patients with 212 visits (median age, 68 years [IQR, 58-76 years]; 123 of 212 women [58.0%]) with Skindex-16 scores (64 in flare state and 148 in nonflare state). Median Skindex-16 domain scores were higher for all disease categories among patients in the flare state compared with those in the nonflare state (pemphigoid [emotions: flare, 52.4 (IQR, 38.1-69.0); nonflare, 7 (IQR, 0-17); symptoms: flare, 37.5 (IQR, 29.2-58.0); nonflare, 13 (IQR, 0-25); functioning: flare, 26.7 (IQR, 10.0-56.7); nonflare, 0 (IQR, 0-3)]; pemphigus [emotions: flare, 54.8 (IQR, 31.0-81.0; nonflare, 0 (IQR, 0-19); symptoms: flare, 58.3 (IQR, 41.7-70.8); nonflare, 4 (IQR, 0-12.5); functioning: flare, 26.7 (IQR, 13.3-83.3); nonflare, 0 (IQR, 0-3.33)]; dermatitis herpetiformis [emotions: flare, 72.6 (IQR, 34.7-90.5); nonflare, 14.3 (IQR, 2.4-26.2); symptoms: flare, 69 (IQR, 31.3-85.4); nonflare, 12.5 (IQR, 0-29.2); functioning: flare, 38.3 (IQR, 5.0-63.2); nonflare, 0 (IQR, 0-13.3)]. This difference exceeded SEm cut points. Cronbach α was greater than 0.80 for all domains and AIBDs. Moderate or low correlations were seen with desmoglein 1 and bullous pemphigoid 180 titers. Moderate correlation existed between Skindex-16 and Patient-Reported Outcomes Measurement Information System Depression scores (emotions: ρ = 0.40; symptoms: ρ = 0.41; functioning: ρ = 0.48), and strong correlation existed between Skindex-16 and patient-reported disease severity (emotions: ρ = 0.71; symptoms: ρ = 0.73; functioning: ρ = 0.66). Floor domain scores greater than 20% were seen among patients in the nonflare state, but ceiling domain scores were rare (<10% for all domains); CFA model fit was poor. Conclusions and Relevance: In this cross-sectional study, SRQL was highly associated with flare of AIBDs. Skin-related quality of life was worse during periods without flare among patients with pemphigoid and dermatitis herpetiformis compared with pemphigus, highlighting residual SRQL morbidity. Skindex-16 showed good construct validity, but the poor CFA model fit needs further research. Clinical measurement of SRQL in AIBDs can add critical disease-severity information.

Questions raised by a case of adult-onset linear nodular scleroderma.

Morphea presenting clinically with nodular or keloidal skin changes is extremely rare. Nodular scleroderma or keloidal morphea presenting in a linear distribution is even more uncommon. We present an otherwise healthy young woman with unilateral, linear, nodular scleroderma and review the somewhat confounding earlier literature in this area. To date, this young woman's skin changes have proven refractory to oral hydroxychloroquine and ultraviolet A1 phototherapy. Several aspects of this case including the patient's family history of Raynaud disease, her nodular sclerodermatous skin lesions, and the presence of U1RNP autoantibodies raised concern about her management with respect to future risk of developing systemic sclerosis.

The effect of an electronic medical record intervention on hydroxychloroquine prescribing habits and surveyed providers' opinions of the 2016 American Academy of Ophthalmology guidelines in the rheumatology and dermatology practices of an academic institutionle.

BACKGROUND: Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines. METHODS: Data were collected pre-intervention (June 2017-January 2019) and post-intervention (March 2019-April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher's exact tests for comparisons of proportions between groups. RESULTS: Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%). CONCLUSIONS: At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers' familiarity with these guidelines.

Examining Dermatologist Use and Opinions of Ultraviolet Radiation for Cosmetic and Medical Purposes.

BACKGROUND: The commercial tanning industry has opposed efforts to educate the public on the risks of tanning as well as attempts to restrict minors' access to tanning services. Despite a paucity of supporting literature, statements from the tanning industry claiming that dermatologists routinely use in-office phototherapy for cosmetic treatments and refer patients to tanning salons have successfully derailed and defeated legislation in many states. OBJECTIVE: This study aims to evaluate dermatologist referrals for ultraviolet radiation for cosmetic and medical purposes via tanning beds or phototherapy, as well as their opinions on tanning, legislation, and ultraviolet radiation counseling practices. DESIGN: The study was conducted using a 10-question anonymous survey. SETTING: The participants were surveyed during meetings of three regional dermatologic societies. PARTICIPANTS: One hundred and fifty-two dermatologists attending society meetings participated in the study. MEASURES: The authors measured physician referrals, opinions, and recommendations regarding ultraviolet exposure. RESULTS: Zero physicians (0/152) recommended tanning salons for cosmetic reasons. These 152 dermatologists referred 458 (417 adult, 41 pediatric) out of an estimated 809,369 patients (0.057%) to tanning salons for medical treatment. Of these physicians, 76 out of 152 and 15 out of 152 reported referring at least one adult or one pediatric patient, respectively, within the last year. All respondents supported ultraviolet tanning legislation and discouraged cosmetic tanning. CONCLUSION: These findings directly contradict the assertion that dermatologists use ultraviolet radiation for cosmetic purposes or routinely refer patients to tanning salons. This study underscores the complex nature of ultraviolet radiation, as dermatologists infrequently utilize ultraviolet radiation for medical purposes and unanimously support restrictive legislation. In addition, these dermatologists counsel against cosmetic tanning and list tanning bed use among their highest concerns with regard to the health of pediatric patients.

Crystal structure of the inverse crown ether tetra-kis-[µ2-bis-(tri-methyl-sil-yl)amido]-µ4-oxido-dicobalt(II)disodium, [Co2Na2{µ2-N(SiMe3)2}4](µ4-O).

The title compound, [Co2Na2{µ2-N(SiMe3)2}4](µ4-O), (I), represents a new entry in the class of inverse crown ethers. In the mol-ecule, each Co atom is formally in the oxidation state +II. The structure contains one half of a unique mol-ecule per asymmetric unit with the central µ4-oxido ligand residing on an inversion center, leading to a planar coordination to the Na and Co atoms. In the crystal, bulky tri-methyl-silyl substituents prevent additional inter-actions with cobalt. However, weak inter-molecular Na⋯H3C-Si inter-actions form an infinite chain along [010]. The structure is isotypic with its Mg, Mn and Zn analogues.

Protonolysis and amide exchange reactions of a three-coordinate cobalt amide complex supported by an N-heterocyclic carbene ligand.

A three-coordinate cobalt species, IPrCoCl{N(SiMe3)2} [1; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene], was synthesized by the reaction of {IPrCoCl2}2 with NaN(SiMe3)2. Compound 1 is a useful starting material for low-coordinate (IPr)Co species. 1 reacts with 2,6-di-tert-butyl-4-methylphenol (BHT-H) via aminolysis of the Co-N bond to generate a three-coordinate phenoxide complex, IPrCoCl(O-2,6-(t)Bu2-4-MeC6H2) (2). The reaction of 1 with 2,6-diisopropylaniline (NH2DIPP) generates IPrCoCl(NHDIPP) (4), which undergoes disproportionation to form a mixture of 4, {IPrCoCl2}2, and IPrCo(NHDIPP)2 (3). The same product mixture is formed by the reaction of 1 with Li[NH(DIPP)], which unexpectedly proceeds by amide exchange. Compound 3 was synthesized independently by the reaction of {IPrCoCl2}2 with 4 equiv of Li[NH(DIPP)]. The reaction of 1 with the bulkier lithium 2,6-dimesitylanilide (LiNHDMP) also proceeds by amide exchange to generate IPrCoCl(NHDMP) (5), which is stable toward disproportionation. Compounds 1 and 2 exhibit trigonal-planar geometries at cobalt in the solid state. The solid-state structure of 3 also contains a trigonal-planar cobalt center and exhibits close Co---H contacts involving the methine hydrogen atoms of the NH(DIPP) groups in the axial positions. The solid-state structure of 5 features an interaction between cobalt and a flanking aryl group of the anilide ligand, resulting in pyramidalization of the cobalt center.

Cutaneous lupus erythematosus.

Cutaneous lupus erythematosus is a heterogeneous autoimmune condition that can significantly impact quality of life. Treatment is focused on reducing clinical inflammation and preventing scarring. The choice of treatment should be guided based on the severity of disease. Mild or localized disease can be treated with sun protection and topical agents. Antimalarials are the initial treatment of choice if systemic therapy is required. Patients with severe or unresponsive disease can also be treated with a number of other immunomodulating or immunosuppressive agents. Clinicians should be aware of their potential adverse effects and appropriate dosing.

Evaluation of reliability, validity, and responsiveness of the CDASI and the CAT-BM.

To properly evaluate therapies for cutaneous dermatomyositis (DM), it is essential to administer an outcome instrument that is reliable, valid, and responsive to clinical change, particularly when measuring disease activity. The purpose of this study was to compare two skin severity DM outcome measures, the Cutaneous Disease and Activity Severity Index (CDASI) and the Cutaneous Assessment Tool-Binary Method (CAT-BM), with the Physician Global Assessment (PGA) as the "gold standard". Ten dermatologists evaluated 14 patients with DM using the CDASI, CAT-BM, and PGA scales. Inter- and intra-rater reliability, validity, responsiveness, and completion time were compared for each outcome instrument. Responsiveness was assessed from a different study population, where one physician evaluated 35 patients with 110 visits. The CDASI was found to have a higher inter- and intra-rater reliability. Regarding construct validity, both the CDASI and the CAT-BM were significant predictors of the PGA scales. The CDASI had the best responsiveness among the three outcome instruments examined. The CDASI had a statistically longer completion time than the CAT-BM by about 1.5 minutes. The small patient population may limit the external validity of the findings observed. The CDASI is a better clinical tool to assess skin severity in DM.

Connective tissue panniculitis: lupus panniculitis, dermatomyositis, morphea/scleroderma.

Panniculitis is an uncommon cutaneous manifestation of connective tissue diseases. Our discussion will include panniculitis occurring in the setting of lupus erythematosus, dermatomyositis, and scleroderma/morphea. These subtypes of panniculitis are unified by an active inflammatory stage of the disease that can progress to develop scarring, atrophy, and calcifications. Treatment is most effective if initiated during the active phase of the disease and often requires systemic therapy because of the location of the inflammation. Antimalarials are the initial treatment of choice for most cases of lupus erythematosus panniculitis, whereas corticosteroids in combination with other steroid-sparing immunosuppressive agents are the first-line treatment for panniculitis in patients with dermatomyositis. The appropriate treatment for panniculitis in the setting of morphea/scleroderma varies based on clinical severity.

A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes.

We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis.

Observations of psoriasis in the absence of therapeutic intervention identifies two unappreciated morphologic variants, thin-plaque and thick-plaque psoriasis, and their associated phenotypes.

Psoriatic plaque thickness is a clinical measure of psoriasis severity. We have observed that patients tend to revert to a baseline thickness of psoriatic plaques when in an untreated state, and hypothesized that other features of psoriasis could associate with this trait. Data prospectively collected on 500 participants in the Utah Psoriasis Initiative were used for the study. In response to a question assessing plaque thickness when disease was at its worst, 144 (28.8%) reported thick plaques, 123 (24.6%) reported thin plaques, and 233 (46.6%) reported intermediate thickness. For patients with "worst-ever" disease at enrollment (n=122), there was significant correlation of thickness between assessment by the patient and the physician (r=0.448, P-value 0.01). Thick plaques associated with male gender, increased body mass index, nail disease, psoriatic arthritis, larger plaques, more body sites, and greater total body surface area affected. Thin plaques associated with eczema, guttate psoriasis, and skin cancer. We suggest that this is preliminary evidence that plaque thickness is an easily measured trait that associates with other clinical features of psoriasis, and that stratification on this phenotype may be useful in further defining the genetic basis of this disease.

Impact of obesity and smoking on psoriasis presentation and management.

OBJECTIVE: To study the impact of obesity and smoking on psoriasis. DESIGN: Cross-sectional study. SETTING: University of Utah Department of Dermatology clinics. PATIENTS: A case series of patients with psoriasis enrolled in the prospective Utah Psoriasis Initiative (UPI) (which carefully performs phenotyping of patients with psoriasis) was compared with 3 population databases: the Behavioral Risk Factor Surveillance System of the Utah population, the 1998 patient-member survey from the National Psoriasis Foundation, and 500 adult patients who attend our clinics and do not have psoriasis (non-psoriatic population). RESULTS: The prevalence of obesity in patients within the UPI population was higher than that in the general Utah population (34% vs 18%; P<.001) and higher than that in the non-psoriatic population attending our clinics. Assessment of body image perception with a standardized diagram in the UPI group resulted in the median body image score of normal weight at 18 years of age and the onset of psoriasis, but it changed to overweight at the time of enrollment in the UPI. Thus, obesity appears to be the consequence of psoriasis and not a risk factor for onset of disease. We did not observe an increased risk for psoriatic arthritis in patients with obesity; furthermore, obesity did not positively or negatively affect the response or the adverse effects of topical corticosteroids, light-based treatments, and systemic medications. The prevalence of smoking in the UPI population was higher than in the general Utah population (37% vs 13%; P<.001) and higher than in the non-psoriatic population (37% vs 25%; P<.001). We found a higher prevalence of smokers in the obese population within the UPI than in the obese population within the Utah population (25% vs 9%; P<.001). CONCLUSIONS: Patients with psoriasis attending the University of Utah Dermatology Clinics were more likely to be obese and to smoke compared with non-psoriatic patients and more likely to be obese compared with other large cohorts with psoriasis. Smoking appears to have a role in the onset of psoriasis, but obesity does not. The high prevalence of obesity and smoking in a psoriasis cohort has not been previously noted; if confirmed, it supports the prediction that a significant portion of patients with psoriasis will have the comorbid conditions and public health issues of those with obesity and smoke.

Clinical germline genetic testing for melanoma.

Clinical genetic testing for mutations in CDKN2A (cyclin-dependent kinase inhibitor 2A), a melanoma susceptibility gene, is now available. The International Melanoma Genetics Consortium advocates that genetic testing for CDKN2A should be done only as part of a research protocol. Experience with genetic testing for other cancer-susceptibility genes indicates that CDKN2A testing has enormous potential for the prevention and detection of a deadly disease. However, clinicians need to understand the benefits and shortcomings of clinical CDKN2A testing so that it can be used advantageously. Here, we examine whether CDKN2A meets the recommendations of the American Society of Clinical Oncology (ASCO) for cancer-susceptibility genetic testing. Although genetic testing for hereditary melanoma should, whenever possible, occur within research protocols, it might be successfully done outside of research protocols if attention is paid to selection, education, and counselling needs of patients; valid test interpretation; and the changing of medical management in appropriate individuals.

Characterization of bleomycin lung injury by nuclear magnetic resonance: correlation between NMR relaxation times and lung water and collagen content.

The response of the NMR relaxation times (T(1), CPMG T(2), and Hahn T(2)) to bleomycin-induced lung injury was studied in excised, unperfused rat lungs. NMR, histologic, and biochemical (collagen content measurement) analyses were performed 1, 2, 4, and 8 weeks after intratracheal instillation of saline (control lungs) or 10 U/kg bleomycin sulfate. The control lungs showed no important NMR, water content, histologic, or collagen content changes. The spin-spin relaxation times for the fast and intermediate components of the CPMG decay (T(2f) and T(2i), respectively) increased 1 week after bleomycin injury (acute inflammatory stage) and then progressively decreased during the following 2-8 weeks (i.e., with the development of the chronic, fibrotic stage of the injury). The slow component (T(2s)) showed no significant changes. The response of T(1) and the slow component of the Hahn T(2) was, on the whole, similar to that of CPMG T(2f) and T(2i). T(1) changes were very small. Lung water content increased 1 week after injury. Histologic and biochemical assessment of collagen showed that collagen content was close to control at 1 week, but markedly increased at 2, 4, and 8 weeks. T(1) and T(2) data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T(2)) reflect the structural changes associated with bleomycin injury. The prolonged T(2) relaxation times observed in the acute stage are related to the presence of edema, whereas the subsequent decrease in these values marks the stage of the collagen deposition (fibrotic stage). CPMG-T(2) and Hahn-T(2) measurements can be valuable as a potentially noninvasive method for characterizing bleomycin-induced lung injury and pathologically related lung disorders.