Comment on "Skin disease of the breast and nipple" [Letter]
Diagnostic work-up and treatment in patients with pyoderma gangrenosum: retrospective analysis of US insurance claims-based data
Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and "real-world" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population.
014 Differential gene expression in lesional skin may signify immune-mediated lung parenchymal damage in dermatomyositis patients [Meeting Abstract]
Dermatomyositis (DM) is an autoimmune connective tissue disease that most commonly affects skin and muscles. Clinical manifestations can be protean, with some patients experiencing skin-limited disease while others develop serious systemic complications including interstitial lung disease (ILD). While both T cell-mediated and humoral immune dysregulation have been purported to play a role in manifesting said end-organ damage, our understanding of immunophenotypic prognostic factors associated with the development of ILD in DM patients remains limited. Thus, we sought to identify potential biomarkers that might be differentially expressed in lesional skin obtained from DM patients with versus without ILD. Utilizing NanoString technology, we assessed differential mRNA expression of 800 immune-related genes in formalin-fixed, paraffin-embedded lesional skin samples obtained from five DM patients with ILD compared to five DM patients without ILD. Among 42 highly regulated genes, 10 were significantly (p<0.05) upregulated in DM patients with ILD: CD44, NFKBIZ, CD24, EGR1, DEFB103B, CCL18, CCL22, CXCL2, S100A8 and S100A9. Notably, serum levels of S100A8/A9 heterodimer (an endogenous ligand of Toll-like receptor 4) are known to correlate with clinical severity in patients with DM-associated ILD, thereby supporting NanoString's utility in identifying salient genes associated with end-organ damage in DM. We also identified several novel genes downregulated in patients with DM-associated ILD that play a role in autophagy and adaptive immune activation: CLEC7, LEF1, KLRC2, BTLA, MUC1, and TCF7. Taken together, our results begin to characterize an immune-related gene expression signature in lesional DM skin that may be associated with comorbid ILD. While validation experiments are ongoing, the identification of biomarkers of systemic disease in lesional DM skin not only has the potential for risk stratifying DM patients at the time of tissue diagnosis but may provide novel targets for early intervention against DM-associated ILD.
Prominent dyspigmentation in a patient with dermatomyositis and TIF1-Î³ autoantibodies [Case Report]
Clinical Characteristics, Disease Course, and Outcomes of Patients With Acute Generalized Exanthematous Pustulosis in the US
Importance/UNASSIGNED:Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series. Objective/UNASSIGNED:To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. Design, Setting, and Participants/UNASSIGNED:A retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. Main Outcomes and Measures/UNASSIGNED:Patient demographic characteristics, clinical course, suspected causative agent, treatment, and short- and long-term outcomes. Results/UNASSIGNED:Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 Â°C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were Î²-lactam antimicrobials, 51 (33.8%) were non-Î²-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (nâ€‰=â€‰12), none of which was suspected to be due to AGEP. Conclusions and Relevance/UNASSIGNED:This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.
Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States
Importance/UNASSIGNED:Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. Objective/UNASSIGNED:To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. Design, Setting, and Participants/UNASSIGNED:A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. Main Outcomes and Measures/UNASSIGNED:The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. Results/UNASSIGNED:Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). Conclusions and Relevance/UNASSIGNED:Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.
Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States
Importance/UNASSIGNED:Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. Objective/UNASSIGNED:To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. Design, Setting, and Participants/UNASSIGNED:This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. Main Outcomes and Measures/UNASSIGNED:The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. Results/UNASSIGNED:Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (nâ€‰=â€‰128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. Conclusions and Relevance/UNASSIGNED:In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.
Profound leukemia cutis in a patient with relapsed T-cell acute lymphoblastic leukemia [Case Report]
Disseminated Cryptococcosis [Case Report]
Evaluating the Contributions of Dermatologists in the Management of Systemic Sclerosis: A Retrospective Analysis [Letter]
Systemic Sclerosis (SSc) is an autoimmune condition characterized by cutaneous sclerosis and the potential for internal organ involvement.1 Given the multisystem nature of SSc, multiple disciplines are often involved in its management. However, while the skin is affected in more than 90% of patients,2 dermatologists are variably involved in the management of SSc, potentially first evaluating patients only late in the disease course, or at times not at all.