Assessing the Discriminatory Ability of Diagnostic Criteria for Ulcerative Pyoderma Gangrenosum and Its Mimickers.

This comparative effectiveness research study assesses the discriminatory ability of diagnostic criteria for pyoderma gangrenosum.

Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed a role for PCSK9 in regulating immune responses. Using RNA-Seq-based variant discovery, we identified a possible psoriasis-susceptibility locus at 1p32.3, located within PCSK9 (rs662145 C > T). This finding was verified in independently acquired genomic and RNA-Seq data sets. Single-cell RNA-Seq (scRNA-Seq) identified keratinocytes as the primary source of PCSK9 in human skin. PCSK9 expression, however, was not uniform across keratinocyte subpopulations. scRNA-Seq and IHC demonstrated an epidermal gradient of PCSK9, with expression being highest in basal and early spinous layer keratinocytes and lowest in granular layer keratinocytes. IL36G expression followed the opposite pattern, with expression highest in granular layer keratinocytes. PCSK9 siRNA knockdown experiments confirmed this inverse relationship between PCSK9 and IL36G expression. Other immune genes were also linked to PCSK9 expression, including IL27RA, IL1RL1, ISG20, and STX3. In both cultured keratinocytes and nonlesional human skin, homozygosity for PCSK9 SNP rs662145 C > T was associated with lower PCSK9 expression and higher IL36G expression, when compared with heterozygous skin or cell lines. Together, these results support PCSK9 as a psoriasis-susceptibility locus and establish a putative link between PCSK9 and inflammatory cytokine expression.

Real-world utilization of Delphi consensus diagnostic criteria for suspected pyoderma gangrenosum.

We found that the systematic use of Delphi consensus diagnostic criteria resulted in substantial changes in management patterns in cases of suspected pyoderma gangrenosum (PG), including a reduction in systemic corticosteroid use, and significantly improved clinical outcomes. This improvement may have resulted from a combination of reduced misdiagnosis, optimized management and reduced iatrogenic harm. Increased utilization of validated diagnostic criteria for PG could optimize provider heuristics, increase diagnostic accuracy, and optimize management and clinical outcomes.

Bile Acids Improve Psoriasiform Dermatitis through Inhibition of IL-17A Expression and CCL20-CCR6-Mediated Trafficking of T Cells.

Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.

Social media (SoMe) enhances exposure of dermatology articles.

Social media (SoMe) refers to a variety of virtual platforms used to enhance sharing of information. To evaluate the influence of SoMe with regards to views and downloads of published dermatology articles, we conducted a retrospective study from July 2020-March 2021 examining articles published on Instagram and Twitter under Dermatology Online Journal (DOJ) accounts and compared these with type-matched and issue-matched articles that were not posted on social media. During this time period, 163 total articles of the three types used for social media (Case Report, Case Presentation, and Photo Vignette) were published in DOJ and 15 were promoted via SoMe. Utilization of SoMe demonstrated a significant (P<0.0001) positive effect with regards to both views (175.5±16.4) and downloads (31.5±4.0) over matched articles not published on SoMe. Similar trends illustrating the positive effect of SoMe on readership have been previously observed in the field of dermatology as well as other medical specialties. Most direct accessions to articles arrived via Instagram rather than Twitter, diverging from previous studies on SoMe use in medical journals. Social media, in particular Instagram, can be a successful platform to enhance the exposure of peer-reviewed medical information.

Glycan biomarkers of autoimmunity and bile acid-associated alterations of the human glycome: Primary biliary cirrhosis and primary sclerosing cholangitis-specific glycans.

We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Glycopeptides associated with disease severity were also identified. Multinomial regression modelling was employed to construct and validate multi-analyte diagnostic models capable of accurately distinguishing PBC, PSC, and healthy controls from one another (AUC = 0.93 ± 0.03). Finally, to investigate how disease-relevant environmental factors can influence glycosylation, we characterized the ability of bile acids known to be differentially expressed in PBC to alter glycosylation. We hypothesize that this could be a mechanism by which altered self-antigens are generated and become targets for immune attack. This work demonstrates the utility of the MRM method to identify diagnostic site-specific glycan classifiers capable of distinguishing even related autoimmune diseases from one another.

Clinical features of recurrent Mycoplasma pneumoniae-induced rash and mucositis.

BACKGROUND/OBJECTIVES: The characteristics of patients experiencing recurrent Mycoplasma pneumoniae-induced rash and mucositis (MIRM) are not well understood. We aimed to characterize patients with recurrent disease by comparing the demographics, skin and mucosal involvement, seasonality, and treatment to those with single episodes (isolated MIRM). METHODS: This retrospective case series screened all patients seen by our dermatology inpatient consult service from September 2014 to March 2020. Cases were selected based on laboratory and clinical criteria that confirmed a diagnosis of MIRM. RESULTS: We identified 13 patients with MIRM: 5 who experienced recurrence (38%) and 8 with isolated, single episodes without recurrence. Mean age was 13.6 years for initial episodes in the recurrent patients compared to 11.7 in patients with isolated episodes. All 5 recurrent MIRM patients were male (compared with 75% of isolated MIRM patients) and predominantly Black (60%, compared with 25%). Most episodes overall (isolated and recurrent) occurred from the months of October to February. Recurrences after initial MIRM episode had less severe skin and mucosal findings, often involving only one mucous membrane, less frequent need for hospital admission, and shorter duration of hospital stay. Prophylactic treatments and treatments beyond supportive care were of unclear value. CONCLUSIONS: Some characteristics of MIRM differ between patients with recurrent and isolated disease. Clinicians should be aware of the potential for recurrence, which occurred in 38% of our cohort. Although recurrences after initial MIRM episode tended to be less severe, there is still potential for prolonged hospitalizations with recurrent episodes. More evidence is needed regarding effective preventive and treatment regimens in patients with recurrent MIRM.

Gonococcal osteomyelitis in a pediatric patient with disseminated gonococcal infection: Implications for antimicrobial management.

We report a case of a female teenager with gonococcal septic arthritis of the right shoulder that also caused osteomyelitis of the humeral head. Infection with Neisseria gonorrhoeae is a frequently diagnosed sexually transmitted infection in the sexually active teenage population and disseminated gonococcal infection (DGI) is the most common systemic manifestation of acute gonorrhea. DGI commonly involves acute arthritis, tenosynovitis and dermatitis with less common complications of endocarditis, hepatitis and meningitis. In contrast, osteomyelitis has only rarely been reported as a result of gonococcal infection. Clinicians need to be aware of this unusual manifestation of DGI as a prolonged duration of antimicrobial treatment may be needed to assure complete resolution of this infection.