Blair, Janis E.

Abstract Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides-endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. Lay Summary Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management.

Abstract We report 8 cases of coccidioidomycosis associated with ruxolitinib treatment. Among 135 patients living in the coccidioidal-endemic region receiving ruxolitinib, 5 cases were diagnosed after starting and 4 had extrathoracic dissemination. Periodic serological screening while on ruxolitinib is warranted for patients residing in the coccidioidal-endemic region.

AbstractCoccidioidomycosis is an infection caused by the geographically restricted dimorphic fungus, Coccidioides. Coccidioidomycosis occurs endemically in the southwestern and western United States, mainly in focused regions of Arizona and California where the incidence is highest, and in Central and South America. Patients with impaired immunity, especially those with impaired cellular immunity, are at higher risk of severe and disseminated disease. In this review, we describe the fungal ecology and mycology, epidemiology, pathophysiology, and normal immune defenses to Coccidioides as well as address current concepts in diagnosis, treatment, and continued care of patients with pulmonary coccidioidomycosis. We also present and answer our most frequently asked questions regarding patients with primary pulmonary coccidioidomycosis.

Abstract Background Making the decision to stop antifungal therapy in patients with coccidioidomycosis can be challenging in patients with risk factors for relapsed infection. Spherulin-based coccidioidal skin testing was re-introduced to the market in 2014 and approved for the detection of delayed-type hypersensitivity in patients with a history of pulmonary coccidioidomycosis Methods We searched electronically for patients who had a spherulin skin test placed in our institution from January 1, 2015 through March 1, 2017, and then included patients age 18 years and older who met the definition for confirmed or probable pulmonary coccidioidomycosis. A retrospective chart review was conducted, and included details of clinical illness, antifungal treatment, serology, and chest imaging Results From January 1, 2015 to August 31, 2017, 172 patients with coccidioidomycosis had a spherulin skin test placed. We included for further study the 129 patients who had primary pulmonary coccidioidomycosis, followed for a median of 18 months (range 0–50 months); 56 (43.4/%) were male, 108 (85.7/%) Caucasian, median age was 55 years (range18–89).19/12914.7%)) were smokers, 14/129 (10.9%) were diabetic, 2 patients had HIV (1.6%) and 15/129 (11.6) we immunocompromised without HIV. 116/129(89.9%) % received antifungal treatment. Median time from illness to skin test was 13.5 months (range 0–78). Eighty-nine of 129 patients (69%) had a positive skin test, 40 (31%) had a negative test. Antifungal treatment was subsequently discontinued in 75/89 (84%), and one patient (1.2%) with a positive test, experienced relapsed infection. Among 30/40 with negative CST, antifungals were discontinued and none relapsed. Conclusion The presence of delayed-type hypersensitivity to coccidioidomycosis, manifested by a positive spherulin skin test, was associated with discontinuation of antifungal therapy, and a low percentage of relapsed infection. Disclosures All authors: No reported disclosures.

AbstractThe care of primary pulmonary coccidioidomycosis remains challenging. Such infections produce a variety of signs, symptoms, and serologic responses that cause morbidity in patients and concern in treating clinicians for the possibility of extrapulmonary dissemination. Illness may be due to ongoing fungal growth that produces acute inflammatory responses, resulting in tissue damage and necrosis, and for this, administering an antifungal drug may be of benefit. In contrast, convalescence may be prolonged by other immunologic reactions to infection, even after fungal replication has been arrested, and in those situations, antifungal therapy is unlikely to yield clinical improvement. In this presentation, we discuss what findings are clinical indicators of fungal growth and what other sequelae are not. Understanding these differences provides a rational management strategy for deciding when to continue, discontinue, or reinstitute antifungal treatments.

Abstract Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Intact cellular immunity is critical to the control of this infection. A recently released reformulated spherulin antigen (Spherusol; Nielsen BioSciences, Inc.) was approved to detect delayed-type hypersensitivity, which implies the presence of cellular immunity, to Coccidioides species. We aimed to summarize our experience with this test in patients with primary pulmonary coccidioidomycosis. We retrospectively reviewed clinical data for all patients with primary pulmonary coccidioidomycosis who had a Coccidioides (spherulin) skin test (CST) placed at our institution between January 1, 2015, and August 31, 2017. During the study period, 172 patients had a CST placed, and 122 met our inclusion criteria for proven or probable pulmonary coccidioidomycosis. Of these 122, 88 (72.1%) had a positive CST result and 34 (27.9%) had a negative result. In the positive CST group, 74 of the 79 treated patients (93.7%) had antifungal treatment stopped, 1 of whom (1.4%) had relapsed infection. In contrast, 27 of the 33 treated patients in the negative CST group (81.8%) had their antifungal treatment stopped, and none had a relapse. Seven patients overall (5.7%), all of whom had a positive CST, experienced mild local adverse reactions to the CST. Although previous controlled studies of CST showed sensitivity and specificity greater than 98%, our real-world experience with the CST showed lower rates of positivity. Negative CST results did not predict relapse with antifungal agent withdrawal.

Background An increasing number of residents and fellows have children during training. However, little is known about the specific experience of cardiology fellows who become parents during training. Methods and Results A 66‐question Internet‐based survey about experiences of pregnancy during graduate medical training was administered between May 1 and July 15, 2013, to all trainees (N=1516) in the Mayo School of Graduate Medical Education across 3 academic sites. Questions explored the experiences of new mothers, fathers, and their fellow trainees. There were 644 survey respondents overall (response rate, 42%), and of 73 cardiovascular trainees, 29 (10 women [35%]) completed the survey. Of those surveyed, 59% reported having children. All trainee mothers reported making alterations to their training schedule due to pregnancy and maternity leave. Twenty percent of trainee fathers also reported changing their training because of their partner's pregnancy. Of trainees with children, 41% reported difficulty completing research because of pregnancy and childcare obligations. Nontrainee mothers were significantly more likely to breastfeed beyond 6 months compared with trainee mothers ( P =0.018). A perceived stigma attached to pregnancy was reported by 62% of trainees. Both male and female trainees felt that their programs did not promote pregnancy‐related schedule flexibility. Conclusions Our study shows that both men and women entering parenthood during cardiology training often have to change their schedule, research, and career path. Cardiology training programs should focus on curriculum design and supportive parenthood policies to both avoid negative stigma and optimize fellowship training during this time period.

Coccidioidomycosis is a common infection in the western and southwestern United States as well as parts of Mexico and Central and South America and is due to the soil-dwelling fungi Coccidioides. Central nervous system (CNS) infection is an uncommon manifestation that is nearly always fatal if untreated. The presentation is subtle, commonly with headache and decreased mentation. The diagnosis should be considered in patients with these symptoms in association with a positive serum coccidioidal antibody test. The diagnosis can only be established by analysis of cerebrospinal fluid (CSF), which typically demonstrates a lymphocytic pleocytosis, hypoglycorrhachia, elevated protein, and positive CSF coccidioidal antibody. Cultures are infrequently positive but a proprietary coccidioidal antigen test has reasonable sensitivity. Current therapy usually begins with fluconazole at 800 mg daily but other triazole antifungals also have efficacy and are often used if fluconazole fails. Triazole therapy should be lifelong. Intrathecal amphotericin B, the original treatment, is now reserved for those in whom triazoles have failed. There are several distinct complications of CNS coccidioidal infection, the most common of which is hydrocephalus. This is nearly always communicating and requires mechanical shunting in addition to antifungal therapy. Other complications include cerebral vasculitis, brain abscess, and arachnoiditis. Management of these is difficult and not well established.

AbstractBackgroundFluconazole is the most commonly used antifungal treatment for various forms of coccidioidomycosis. Although we had anecdotally observed a high proportion of patients reporting cutaneous adverse effects associated with fluconazole treatment, this observation was not well described in the medical literature, and we were unsure of the additional effect of the arid desert environment of Arizona.MethodsWe performed a one‐time, voluntary survey of patients with coccidioidomycosis and compared the responses of patients treated with fluconazole with those of untreated patients.ResultsFrom January 1, 2015, to August 22, 2017, 62 fluconazole‐treated and 35 untreated patients with coccidioidomycosis provided consent and were enrolled in the study; demographics were similar between the two groups. Among the 62 fluconazole‐treated patients, daily dosages ranged from 200 mg to 800 mg. However, most (44/62, 71%) took 400 mg daily, the typical dose for the treatment of coccidioidomycosis. The median fluconazole treatment duration at the time of study participation was 6 months. When compared with untreated patients, those taking fluconazole had more moderate to severe dry lips (74.2% [46/62] vs. 23.5% [8/34]; P < 0.001), dry skin (45.8% [27/59] vs. 22.9% [8/35]; P = 0.03), and alopecia (31.1% [19/61] vs. 11.4% [4/35]; P = 0.004).ConclusionsFor the treatment of coccidioidomycosis, patients receiving fluconazole reported significantly more severe cutaneous effects, including dry lips, dry skin, and alopecia, than untreated patients. Our findings identify an association but do not prove causality.