Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: 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: 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: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: 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: 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: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: 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: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: 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 (n = 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: 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.

Clinical Patterns and Morphology of COVID-19 Dermatology.

Coronavirus disease 2019 (COVID-19), an emergent disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the globe since its discovery in December 2019. Although first appreciated to cause pneumonia, numerous organ systems are now known to be involved. The objective of this article is to review the broad spectrum of cutaneous manifestations reported in association with SARS-CoV-2 infection. The most commonly reported cutaneous manifestations associated with COVID-19 infection include pernio (chilblain)-like acral lesions, morbilliform (exanthematous) rash, urticaria, vesicular (varicella-like) eruptions, and vaso-occlusive lesions (livedo racemosa, retiform purpura). It is important to consider SARS-CoV-2 infection in the differential diagnosis of a patient presenting with these lesions in the appropriate clinical context, as cutaneous manifestations may be present in otherwise asymptomatic individuals, or present before developing other symptoms of infection. With increased access to diagnostic testing, we are beginning to understand the utility and limitations of currently available assays.

Pyoderma gangrenosum associated with levamisole-adulterated cocaine in a c-ANCA positive patient.

Pyoderma gangrenosum (PG) is an inflammatory, ulcerative condition that is characterized by painful ulcers that commonly present on the lower extremities. Up to half of PG cases are associated with underlying systemic disease, including inflammatory bowel disease, various autoimmune conditions, and malignancy. Another well-known association is the manifestation of PG with recreational cocaine use, especially cocaine contaminated with the adulterant agent levamisole. Once utilized for its immunomodulatory capabilities, levamisole was withdrawn from the market in 2002. It has since been repurposed to potentiate the amphetamine-like effects and duration of cocaine and has reduced preparation cost. We present a 52-year-old woman with chronic maxillary sinusitis and cocaine use disorder presenting with a two-week history of painful ulcers on bilateral lower extremities, each with a purulent base and undermined, violaceous borders. Urine toxicology was positive for cocaine and serologic studies were positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and lupus anticoagulant. Underlying conditions, especially that of granulomatosis with polyangiitis, were considered and ultimately ruled out. The patient's lesions exhibited a marked response with a short course of oral corticosteroids, typical of PG associated with levamisole. This case highlights the crucial role that drug abstinence plays in the prevention of recurrence.

Distinguishing Cellulitis from Its Noninfectious Mimics: Approach to the Red Leg.

Cellulitis is a common clinical diagnosis in the outpatient and inpatient setting; studies have demonstrated a surprisingly high misdiagnosis rate: nearly one-third of cases are other conditions (ie, pseudocellulitis). This high rate of misdiagnosis is thought to contribute to nearly $515 million in avoidable health care spending in the United States each year; leading to the delayed or missed diagnosis of pseudocellulitis and to delays in appropriate treatment. There is a broad differential diagnosis for pseudocellulitis, which includes inflammatory and noninflammatory conditions of the skin. Accurate diagnosis of the specific condition causing pseudocellulitis is crucial to management, which varies greatly.

Inferior vena cava size is not associated with shock following injury.

BACKGROUND: The inferior vena cava (IVC) collapses with shock but may also be collapsed in volume-depleted patients in the absence of shock. The speed and availability of computed tomography (CT) make IVC measurement an attractive diagnostic modality for shock. The purpose of this study was to determine if IVC size following injury is associated with shock. METHODS: Retrospective data were collected on 272 trauma patients admitted to an adult trauma center from January 1 to December 31, 2012. Patients who met the highest-level activation criteria and underwent an abdominal CT scan during their initial resuscitation were included. All images were reviewed by two attending radiologists, and concordance was assessed using the Pearson correlation coefficient. The transverse (T) and anteroposterior (AP) diameters of the IVC were measured to calculate a T/AP ratio. Analysis of variance and χ were used to assess for a relationship between this ratio and various indices of shock. RESULTS: The mean (SD) age of the study cohort was 50 (21) years, mean (SD) Injury Severity Score (ISS) was 14 (9), 74% were male, and 96% sustained blunt trauma. The overall mean (SD) T/AP ratio was 1.81 (0.68). Patients with a shock index greater than 0.7 were significantly younger (43 [20] years vs. 55 [21] years, p < 0.0001), had a significantly lower mean arterial pressure (88 [15] mm Hg vs. 103 [18] mm Hg, p < 0.0001), and were more likely to be intubated (56% vs. 24%, p < 0.0001). However, IVC T/AP ratio was not significantly different among the cohort. Similarly, there was no association between IVC size and the need for urgent operation, angiography, emergent transfusion, hospital length of stay, or mortality. CONCLUSION: The static degree of IVC collapse is not associated with shock following injury. Therefore, measurement of IVC size by CT scan for patients with a T/AP ratio between 1 and 3.5 is not clinically relevant and cannot be used to predict mortality, shock, or impending shock. LEVEL OF EVIDENCE: Diagnostic test, level III.

Prolonged use of extracorporeal membrane oxygenation as a rescue modality following traumatic brain injury.

A 21-year-old male trauma patient presented after a motor vehicle crash, witnessed massive aspiration and sustained traumatic brain injury. On postinjury day 3, the patient progressed to adult respiratory distress syndrome (ARDS) refractory to all conventional therapies, prompting the use of extracorporeal membrane oxygenation (ECMO). After 5 days of ECMO support and 3 thrombosed oxygenators, systemic anticoagulation was initiated. After 20 days of ECMO, 15 of which required systemic anticoagulation, the patient was decannulated and transferred to a rehabilitation facility. The patient is currently home without any neurological deficits. Although controversial, ECMO may serve a role as a rescue therapy in ARDS when conventional therapies fail in the brain-injured patient.

Moderate weight loss is sufficient to affect thyroid hormone homeostasis and inhibit its peripheral conversion.

BACKGROUND: Thyroid hormones are important determinants of energy expenditure, and in rodents, adipose tissue affects thyroid hormone homeostasis via leptin signaling. The relationship between thyroid hormones and nutritional status in humans has been assessed primarily in drastic dietary or bariatric surgery interventions, while limited information is available on serial assessment of this axis during moderate, prolonged dietary restriction. METHODS: To evaluate the effects of moderate dietary restriction on thyroid hormone homeostasis, 47 subjects with a body mass index (BMI) of 25-45 kg/m(2) were enrolled in a longitudinal intervention study; 30 nonoverweight volunteers were also enrolled as controls. Overweight and obese subjects underwent a 12-month individualized dietary intervention aimed at achieving a 5-10% weight loss. RESULTS: The intervention resulted in a 6.3±0.9 kg (6.5±1.0%) weight loss. At baseline, thyrotropin (TSH) and T3 concentrations correlated significantly with fat mass (R=0.257, p=0.024 and R=0.318, p=0.005, respectively). After weight loss, T3 decreased significantly (from 112.7±3.1 to 101.8±2.6 ng/dL, p<0.001) in the absence of significant changes in TSH or free T4 (fT4). The decrease in serum T3 correlated with the decrease in weight (R=0.294, p<0.001). The T3:fT4 ratio decreased significantly (p=0.02) in individuals who lost >5% body weight. CONCLUSIONS: T3 concentration closely correlates with individual nutritional status, and moderate weight loss results in a decrease in T3 with minimal changes in other thyroid hormone homeostasis parameters. The data suggest that a decrease in peripheral conversion of the prohormone T4 into its hormonally active metabolite T3 is at least in part responsible for the observed changes in thyroid hormone homeostasis.

Atopic dermatitis: a disease caused by innate immune defects?

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last half century. A growing body of evidence suggests that there are a variety of defects in the innate immune system that collectively affect the development and severity of AD. The reduction in antimicrobial peptides, diminished recruitment of innate immune cells (PMNs, pDC, and NK cells) to the skin, epithelial barrier disruption, and TLR2 defects are just some of the credible explanations for AD patients' susceptibility to pathogens such as Staphylococcus aureus, herpes simplex virus, and vaccinia virus. Although the focus for several years has been to identify defects in the innate immune system that might explain AD patients' susceptibility to cutaneous pathogens, it has become clear that some innate immune defects might promote inflammation and thereby aggravate or even induce the development of AD. Here we review the innate immune system, and highlight many of the potential innate networks that may be important in AD patients susceptible to cutaneous pathogens.