Overview and update on biologic therapy for moderate-to-severe hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety.

The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum.

Importance: Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis. Current knowledge of this rare disease is limited owing to a lack of validated diagnostic criteria and large population studies. Objective: To evaluate the association of age with the clinical presentation and comorbidities of pyoderma gangrenosum. Design, Setting, and Participants: This was a multicenter retrospective cohort study performed at tertiary academic referral centers in urban settings. Adults (≥18 years) who were evaluated and diagnosed as having pyoderma gangrenosum at the Brigham and Women's and Massachusetts General Hospitals from 2000 to 2015 and the University of Pennsylvania Health System from 2006 to 2016 were included. Main Outcomes and Measures: Patient demographics, clinical features, medical comorbidities, and treatment. Results: Of the 356 validated cases of pyoderma gangrenosum included in the study, 267 (75%) were women and 284 (84.8%) were white. The mean (SD) age at presentation was 51.6 (17.7) years. Pathergy was recorded in 100 patients (28.1%). A total of 238 patients (66.9%) had associated medical comorbidities: inflammatory bowel disease in 146 patients (41.0%); inflammatory arthritis in 73 patients (20.5%); solid organ malignant neoplasms in 23 patients (6.5%); hematologic malignant neoplasms in 21 patients (5.9%); and hematologic disorders, specifically monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and polycythemia vera in 17 patients (4.8%). When stratified by age, pathergy was more common in patients 65 years or older (36.3% vs 24.3%; P = .02). Inflammatory bowel disease was the only medical comorbidity that was more common in patients younger than 65 years (47.7% vs 26.6%; P < .001), while a number of medical comorbidities were more common in those 65 years or older, including rheumatoid arthritis (13.3% vs 6.2%; P = .03), ankylosing spondylitis (1.8% vs 0%; P = .04), solid organ malignant neoplasms (13.3% vs 3.3%; P < .001), hematologic malignant neoplasms (9.7% vs 4.1%; P = .04), and the aforementioned hematologic disorders (10.6% vs 2.1%; P < .001). Conclusions and Relevance: Although clinical presentation in this large cohort was similar between different age groups, disease associations varied by age. The findings of this study may allow for a more focused, age-specific evaluation of patients with pyoderma gangrenosum.

Adverse Reactions to Biologics in Psoriasis.

Psoriasis is a chronic autoimmune disease which affects millions of people worldwide. Not only can psoriasis itself be debilitating and significantly reduce an individual's quality of life, but it is also a risk factor for other systemic disorders, such as metabolic syndrome, cardiovascular disease, and malignancy. Tremendous strides were made in the treatment of psoriasis during the mid-to-late-20th century, including the emergence of topical corticosteroids and vitamin D analogs, methotrexate, systemic retinoids, and phototherapy. However, it was not until 2004 with the advent of systemic biologic agents, which precisely target components of the immune system involved in the pathophysiological process of psoriasis, that the primary treatment benchmark increased from 50% improvement in the Psoriasis Area and Severity Index (PASI 50) to PASI 75, PASI 90, and even PASI 100, or complete resolution of cutaneous disease. Today, many patients receiving biologic therapy routinely experience greater than 75% or 90% reduction in cutaneous disease burden and a significant improvement in overall quality of life. These biologic agents are generally well-tolerated and safe but, like any medication, have associated adverse effects, some of which are predictable based on the effects of immune modulation, animal model studies, and human populations with known cytokine deficiencies. Going forward, it will be important to carefully monitor the safety profiles of these agents in both clinical trials and post-marketing surveillance registries to ensure long-term safety. It is reassuring that large safety registries are consistent in demonstrating an improved safety profile with newer and emerging biologic therapies.

Update on biologic safety for patients with psoriasis during pregnancy.

Biologic agents have become more common to treat patients with psoriasis, but concerns about their effect on pregnancy and lactation often preclude this treatment during these time periods. During the past decade, we have gained a much better understanding of the course of psoriasis during pregnancy and the safety of the use of biologic agents during pregnancy and lactation. Under certain circumstances, biologic agents can be considered appropriate treatment options for patients who are pregnant or lactating.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

Early release of high-sensitive cardiac troponin during complex catheter ablation for ventricular tachycardia and atrial fibrillation.

BACKGROUND: Radiofrequency ablation results in intentional cardiac injury. We aimed to assess the kinetics of cardiac injury as measured by cardiac troponin release following ventricular ablation and atrial ablation. METHODS: Patients undergoing ablation for ventricular tachycardia (VT) with structural heart disease (19 patients) or atrial fibrillation (AF, 24 patients) were prospectively enrolled. High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) were measured before ablation as well as 30 min, 60 min, 90 min, 120 min, 4 h, 8 h, and 24 h after applying the first ablation lesion. RESULTS: Median ablation time, power used, and energy delivered were 28 min, 39 W, and 69,713 J in VT ablations and 55 min, 29 W, and 95,425 J in AF ablations, respectively. Release of hs-cTnT occurred promptly with both, but reached greater levels earlier for ventricular compared to atrial ablation (hs-cTnT after 30 min 191 vs. 31 ng/l, after 1 h 467 vs. 80 ng/l; hs-cTnI after 30 min 132 vs. 30 ng/l, after 1 h 331 vs. 76 ng/l; p < 0.001 for all comparisons). After 24 h, levels were similar (hs-cTnT 1325 vs. 1303 ng/l, p = 0.92; hs-cTnI 2165 vs. 1996 ng/l, p = 0.55). Levels of hs-cTnT after 24 h correlated well with the energy delivered in AF ablations (r = 0.81 and r = 0.75, p < 0.001), but not in VT ablations (r = 0.35 and r = 0.44, p = ns). CONCLUSIONS: Evidence of cardiac injury as indicated by the release of hs-cTnT and hs-cTnI occurs early with atrial and ventricular ablation. Higher early levels are observed in ventricular ablations, but levels are similar after 24 h. The extent of total troponin release seems to correlate well with the amount of energy delivered in AF ablations, but not in VT ablations.