D-dimer and CoV-2 spike-immune complexes contribute to the production of PGE2 and proinflammatory cytokines in monocytes.

An overreactive inflammatory response and coagulopathy are observed in patients with severe form of COVID-19. Since increased levels of D-dimer (DD) are associated with coagulopathy in COVID-19, we explored whether DD contributes to the aberrant cytokine responses. Here we show that treatment of healthy human monocytes with DD induced a dose dependent increase in production of pyrogenic mediator, Prostaglandin E2 (PGE2) and inflammatory cytokines, IL-6 and IL-8. The DD-induced PGE2 and inflammatory cytokines were enhanced significantly by co-treatment with immune complexes (IC) of SARS CoV-2 recombinant S protein or of pseudovirus containing SARS CoV-2 S protein (PVCoV-2) coated with spike-specific chimeric monoclonal antibody (MAb) containing mouse variable and human Fc regions. The production of PGE2 and cytokines in monocytes activated with DD and ICs was sensitive to the inhibitors of ß2 integrin and FcγRIIa, and to the inhibitors of calcium signaling, Mitogen-Activated Protein Kinase (MAPK) pathway, and tyrosine-protein kinase. Importantly, strong increase in PGE2 and in IL-6/IL-8/IL-1ß cytokines was observed in monocytes activated with DD in the presence of IC of PVCoV-2 coated with plasma from hospitalized COVID-19 patients but not from healthy donors. The IC of PVCoV-2 with convalescent plasma induced much lower levels of PGE2 and cytokines compared with plasma from hospitalized COVID-19 patients. PGE2 and IL-6/IL-8 cytokines produced in monocytes activated with plasma-containing IC, correlated well with the levels of spike binding antibodies and not with neutralizing antibody titers. Our study suggests that a combination of high levels of DD and high titers of spike-binding antibodies that can form IC with SARS CoV-2 viral particles might accelerate the inflammatory status of lung infiltrating monocytes leading to increased lung pathology in patients with severe form of COVID-19.

Pyrogenic and inflammatory mediators are produced by polarized M1 and M2 macrophages activated with D-dimer and SARS-CoV-2 spike immune complexes.

Lung macrophages are the first line of defense against invading respiratory pathogens including SARS-CoV-2, yet activation of macrophage in the lungs can lead to hyperinflammatory immune response seen in severe COVID-19. Here we used human M1 and M2 polarized macrophages as a surrogate model of inflammatory and regulatory macrophages and explored whether immune complexes (IC) containing spike-specific IgG can trigger aberrant cytokine responses in macrophages in the lungs and associated lymph nodes. We show that IC of SARS-CoV-2 recombinant S protein coated with spike-specific monoclonal antibody induced production of Prostaglandin E2 (PGE2) in non-polarized (M0) and in M1 and M2-type polarized human macrophages only in the presence of D-dimer (DD), a fibrinogen degradation product, associated with coagulopathy in COVID-19. Importantly, an increase in PGE2 was also observed in macrophages activated with DD and IC of SARS-CoV-2 pseudovirions coated with plasma from hospitalized COVID-19 patients but not from healthy subjects. Overall, the levels of PGE2 in macrophages activated with DD and IC were as follows: M1≫M2>M0 and correlated with the levels of spike binding antibodies and not with neutralizing antibody titers. All three macrophage subsets produced similar levels of IL-6 following activation with DD+IC, however TNFα, IL-1ß, and IL-10 cytokines were produced by M2 macrophages only. Our study suggests that high titers of spike or virion containing IC in the presence of coagulation byproducts (DD) can promote inflammatory response in macrophages in the lungs and associated lymph nodes and contribute to severe COVID-19.

Tick-specific borrelial antigens appear to be upregulated in American but not European patients with Lyme arthritis, a late manifestation of Lyme borreliosis.

Borrelia burgdorferi (Bb) sensu lato, the etiologic agent of Lyme borreliosis, adapts to distinct environments in the mammalian host and the tick vector by differential gene expression. As a result, infected mice are not exposed to and rarely make antibodies to the set of antigens that are preferentially expressed in the tick, including outer surface protein A (OspA), Borrelia iron and copper-binding protein A (BicA), and OspD. Surprisingly, however, antibodies to OspA and BicA have been noted in American patients with Lyme arthritis. Here, we examined serum samples from 210 American patients and 66 European patients with a range of early or late manifestations of Lyme borreliosis and found that only American patients with Lyme arthritis commonly had antibody responses to OspA, BicA, and OspD. This suggests that infection with American but not European Borrelia strains often leads to concerted upregulation or derepression of tick-specific spirochetal antigens in these patients.

Building an Equity-Centered Ecosystem: University of Utah Health as a Microcosm.

Academic medicine, and medicine in general, are less diverse than the general patient population. Family Medicine, while still lagging behind the general population, has the most diversity in leadership and in the specialty in general, and continues to lead in this effort, with 16.7% of chairs identifying as underrepresented in medicine. Historical and current systematic marginalization of Black or African American, Latina/e/o/x, Hispanic or of Spanish Origin (LHS), American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and Southeast Asian individuals has created severe underrepresentation within health sciences professions. Over the last 30 years, the percentage of faculty from these groups has increased from 7 to 9% in allopathic academic medicine, with similar increases in Osteopathic Medicine, Dentistry, and Pharmacy, but all lag behind age-adjusted population means. Traditionally, diversity efforts have focused on increasing pathway programs to address this widening disparity. While pathway programs are a good start, they are only a portion of what is needed to create lasting change in the diversity of the medical profession as well as the career trajectory and success of underrepresented in medicine (URiM) health professionals toward self-actualization and positions of leadership. This article elucidates all parts of an ecosystem necessary to ensure that equity, diversity, and inclusion outcomes can improve.

TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi.

TRIF is an adaptor molecule important in transducing signals from intracellularly signaling Toll-like receptor 3 (TLR3) and TLR4. Recently, TLR2 was found to signal from intracellular compartments. Using a synthetic ligand for TLR2/1 heterodimers, as well as Borrelia burgdorferi, which is a strong activator of TLR2/1, we found that TLR2 signaling can utilize TRIF. Unlike TRIF signaling by other TLRs, TLR2-mediated TRIF signaling is dependent on the presence of another adaptor molecule, MyD88. However, unlike MyD88 deficiency, TRIF deficiency does not result in diminished control of infection with B. burgdorferi in a murine model of disease. This appears to be due to the effects of MyD88 on phagocytosis via scavenger receptors, such as MARCO, which are not affected by the loss of TRIF. In mice, TRIF deficiency did have an effect on the production of inflammatory cytokines, suggesting that regulation of inflammatory cytokines and control of bacterial growth may be uncoupled, in part through transduction of TLR2 signaling through TRIF.

Increasing the Representation of Black Men in Medicine by Addressing Systems Factors.

In 2015, data released by the Association of American Medical Colleges (AAMC) showed that there were more Black men applying and matriculating to medical school in 1978 than 2014. The representation of Black men in medicine is a troubling workforce issue that was identified by the National Academies of Sciences, Engineering, and Medicine as a national crisis. While premedical pathway programs have contributed to increased workforce diversity, alone they are insufficient to accelerate change. In response, the AAMC and the National Medical Association launched a new initiative in August 2020, the Action Collaborative for Black Men in Medicine, to address the systems factors that influence the trajectory to medicine for Black men. The authors provide a brief overview of the educational experiences of Black boys and men in the United States and, as members of the Action Collaborative, describe their early work. Using research, data, and collective lived experiences, the Action Collaborative members identified premedical and academic medicine systems factors that represented opportunities for change. The premedical factors include financing and funding, information access, pre-health advisors, the Medical College Admission Test, support systems, foundational academics, and alternative career paths. The academic medicine factors include early identification, medical school recruitment and admissions, and leadership accountability. The authors offer several points of intervention along the medical education continuum, starting as early as elementary school through medical school matriculation, for institutional leaders to address these factors as part of their diversity strategy. The authors also present the Action Collaborative's process for leveraging collective impact to build an equity-minded action agenda focused on Black men. They describe their initial focus on pre-health advising and leadership accountability and next steps to develop an action agenda. Collective impact and coalition building will facilitate active, broad engagement of partners across sectors to advance long-term systems change.

Disseminated cryptococcosis by biological therapy: We must manage the risk / Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Making 'Good Trouble': Time for Organized Medicine to Call for Racial Justice in Medical Education and Health Care.

"Never, ever be afraid to make some noise and get in good trouble, necessary trouble." - Representative John Lewis It is time now for organized medicine to make "good trouble" and call for racial justice in medical education and health care. It is also time to have an honest confrontation with reality in order to bring about racial healing and become anti-racist organizations. Using a racial justice framework, 4 elements described here can chart our course. Organized medicine must come together in solidarity to make "good trouble" and fight collectively for racial justice so that every community we serve can achieve their full health potential and achieve racial equity-that is, giving people what they need to enjoy full, healthy lives regardless of race.

Human Placental Trophoblasts Are Resistant to Trypanosoma cruzi Infection in a 3D-Culture Model of the Maternal-Fetal Interface.

Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas Disease (CD), is transmitted to humans by infected kissing bugs, blood transfusion, organ transplantation, and from mother-to-child. Congenital transmission is now considered an important route of CD spread in non-endemic countries where no routine testing of pregnant women for the disease is implemented. The main cellular mechanisms that lead to fetal infection by T. cruzi, despite the presence of a placental barrier, remain unclear. Mother-to-child transmission most likely occurs when bloodstream trypomastigotes reach the placental intervillous space and interact with the large cellular surface provided by the syncytioptrophoblasts. These highly specialized cells not only function as a physical obstacle between mother and fetus, but also modulate immune responses against pathogen infections. To overcome the limitations associated with the use of human fetal tissues, we employed a three-dimensional (3D) cell culture model to recreate the human placenta environment. In this system, the trophoblast-derived JEG-3 cell line is co-cultured with human brain microvascular endothelial cells attached to microcarrier beads in a rotating bioreactor. Here, we report that 3D culture of JEG-3/HBMEC spheroids promote JEG-3 cells differentiation revealed by the formation of syncytia and production of ß human chorionic gonadotropin and human placental lactogen (hPL). Under these growth conditions, we demonstrate that 3D-grown JEG-3 cells have reduced susceptibility to T. cruzi infection compared to JEG-3 cells grown in conventional tissue culture flasks. We also show that 3D-cultured JEG-3 cells release paracrine factors in the supernatant that prevent T. cruzi infection of non-trophoblastic cell lines. Our in vitro model of T. cruzi vertical transmission may help better understand the molecular processes by which parasites bypass the human placental barrier and could be exploited to evaluate therapeutics to reduce congenital CD.

Clinical correlations of grey matter reductions in the caudate nucleus of adults with attention deficit hyperactivity disorder.

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown decreased caudate volumes in individuals with attention deficit hyperactivity disorder (ADHD). However, most of these studies have been carried out in male children. Very little research has been done in adults, and the results obtained in children are difficult to extrapolate to adults. We sought to compare the volume of the caudate of adults with ADHD with that of healthy controls; we also compared these volumes between men and women. METHODS: We performed an MRI scan on 20 adults with ADHD (10 men and 10 women) aged 25-35 years and 20 healthy controls matched by age and sex. We used voxel-based morphometry with the DARTEL algorithm for image analyses. We used the specifically designed Friederichsen, Almeida, Serrano, Cortes Test (FASCT) to measure the severity of ADHD; both the self-reported (FASCT-SR) and the observer (FASCT-O) versions were used. RESULTS: The statistical parametric map showed a smaller region with low grey matter volume and a smaller concentration of grey matter in this region of the right caudate in ADHD patients than in health controls, both in the entire sample and within each sex. There was a significant correlation between the volume of this region of the caudate with the number of DSM IV-TR criteria, as well as with the total scores and most of the factors of the FASCT-SR and FASCT-O scales. A separate correlation analysis by sex gave similar results. LIMITATIONS: The study design was cross-sectional. CONCLUSION: The region of the right caudate with low grey matter volume was smaller in adults with ADHD in both sexes and was correlated with ADHD severity.

Gallbladder endometrioma associated with obstructive jaundice and a serous ovarian cystic adenoma.

The occurrence of pelvic endometriosis is not uncommon, but endometriosis of the gallbladder is extremely rare. To our knowledge, only one such case has previously been described in the literature. This report concerns another patient with gallbladder endometriosis, which formed two distinct lesions at the fundus of the organ. The clinicopathological findings and pathogenesis are discussed. Endometriosis should be considered in the differential diagnosis of a fertile woman with a painful mass, particularly if the mass is associated in size and tenderness with menstrual variability.

Achieving Gender Equity Is Our Responsibility: Leadership Matters.

Across academic medicine, and particularly among faculty and medical school leadership, the status quo is unacceptable when it comes to gender diversity, equity, and inclusion. The Association of American Medical Colleges has launched a bold gender equity initiative, endorsed by its Board of Directors, to implore academic medical institutions to take meaningful and effective actions.Defining what progress should look like to guide these actions is worth deeper exploration. It is not enough to measure the representation of different genders at various levels of leadership within our institutions. Research and experience we share suggests more must be done, especially for women of diverse racial and ethnic backgrounds. What is needed is a fundamental conversation about privilege, intersectionality across different backgrounds, and progress.Institutional leaders have a choice to make. Will we make gender equity a top priority system-wide because we recognize that doing so leads to organizational excellence? Do we understand that establishing a robust, comprehensive definition of gender equity and how it is practiced will result in better outcomes for all? And are we ready and able to prioritize and be accountable for efforts that are measurable, with clear definitions of progress; driven and reinforced by leadership directives; inclusive of all, including men as well as women of diverse backgrounds and orientations; and systemic rather than ad-hoc? Implementing such actions requires initiating difficult conversations, making conscious choices, and modeling best practices from leaders who have successfully made gender equity a priority.

A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease.

Chagas drug discovery has been hampered by a lack of validated assays to establish treatment efficacy in pre-clinical animal models and in patients infected with T. cruzi. Reduced levels of parasite secreted antigens in the blood of infected hosts could be used to demonstrate treatment efficacy. A published proteomic study of parasite secreted antigens identified the hypothetical protein Tc_5171 as a secreted antigen. In this report, we developed Tc_5171 specific antibodies and showed that the native protein was expressed by the three life cycle stages of the parasite. Anti-peptide antibodies were able to detect the parasite antigen in blood of infected mice during the acute and the chronic phase of infection. Benznidazole treatment of infected mice significantly reduced their blood antigen levels. Of clinical significance, patients diagnosed with Chagas disease, either asymptomatic or with cardiac clinical symptoms had significantly higher Tc_5171 antigen levels compared to endemic controls. Pair-wise analysis, before and after Benznidazole treatment, of patients with asymptomatic Chagas disease showed a significant reduction in antigen levels post treatment. Taken together, our results indicate that Tc_5171 could be used as a novel biomarker of Chagas disease for diagnosis and to assess treatment efficacy.

Teaching Medical Spanish to Improve Population Health: Evidence for Incorporating Language Education and Assessment in U.S. Medical Schools.

Introduction: Language concordance between patients and physicians is an important factor in providing safe and effective health care, with Spanish as the predominant and fastest growing non-English language in the United Sates. However, despite increasing demand for medical Spanish education, valid concerns about inadvertently increasing provider use of limited Spanish with patients, lack of knowledge of best practice in education and assessment, and lack of institutional support still present barriers to medical Spanish education in medical schools. Methods: The authors conducted a narrative review of existing literature that evaluates the link between medical Spanish education of physicians and language concordance. Results: Medical Spanish educational efforts, although increasing, are not consistently linked to learner assessment. The literature to date supports that for medical Spanish education to improve patient outcomes, it should be linked to assessment methodology that demonstrates improvement in language concordance with Spanish-speaking patients, and should include safety measures to prevent inadvertent communication errors. The authors review data for published medical Spanish postcourse language assessment strategies and provide recommendations to ensure responsible and competent use of medical Spanish skills. Conclusion: The authors propose three structural elements that should be considered when incorporating or enhancing medical Spanish education in medical schools: institutional endorsement of the role of medical Spanish education within a national health disparities context; precourse proficiency testing to establish student starting level; and learner postcourse communications skills and limitations assessment to provide individualized recommendations and assure patient safety.

Strategies for Teaching Linguistic Preparedness for Physicians: Medical Spanish and Global Linguistic Competence in Undergraduate Medical Education.

In accordance with Liaison Committee on Medical Education (LCME) curriculum content standards, medical schools are expected to teach physician communication skills and cultural competence. Given the sustained U.S. Spanish-speaking population growth, importance of language in diagnosis, and benefits of patient-physician language concordance, addressing LCME standards equitably should involve linguistic preparedness education. The authors present strategies for implementation of linguistic preparedness education in medical schools by discussing (1) examples of institutional approaches to dedicated medical Spanish courses that meet best practice guidelines and (2) a partnership model with medical interpreters to implement integrated global linguistic competencies in undergraduate medical curricula.

Current Demographic Status of Cardiologists in the United States.

Importance: Increasing cardiology workforce diversity will expand the talent of the applicant pool and may reduce health care disparities. Objective: To assess US cardiology physician workforce demographics by sex and race/ethnicity in the context of the US population and the available pipelines of trainees. Design, Setting, and Participants: This cross-sectional study used data from the Association of American Medical Colleges, the American Medical Association, and the American Board of Internal Medicine to stratify medical students, resident physicians, fellows, and cardiologists by sex and race/ethnicity. Additionally, proportional changes from 2006 through 2016 were assessed for adult and pediatric cardiology. Data analysis took place from August 2018 to January 2019. Main Outcomes and Measures: Percentage of cardiologists and trainees by sex and race/ethnicity in 2016, as well as changes in proportions between 2006 and 2016. Results: Despite a high percentage of female internal medicine resident physicians (10 765 of 25 252 [42.6%]), female physicians were underrepresented in adult general cardiology fellowships (584 of 2720 [21.5%]) and procedural subspecialty fellowships (interventional cardiology, 30 of 305 [9.8%]; electrophysiology, 24 of 175 [13.7%]). The percentage of female adult cardiologists slightly increased from 2006 through 2016 (from 8.9% to 12.6%; slope, 0.36; P < .001) but remained low. Female physicians made up a disproportionately higher number of pediatric residency positions (6439 of 8832 [72.9%]). Trends showed an increase in female pediatric cardiology fellows (from 40.4% to 50.5%; slope, 1.25; P < .001), which resulted in an increase in the percentage of female pediatric cardiologists (from 27.1% to 34.0%; slope, 0.64; P < .001). The percentages of members of underrepresented minority groups in adult and pediatric cardiology fellowships (from 11.1% to 12.4%; slope, 0.15; P = .01; and from 7.7% to 9.9%; slope, 0.29; P = .009; respectively) were low and increased only slightly over time. Additionally, members of underrepresented minorities made up less than 8% of practicing adult and pediatric cardiologists. Although Asian individuals are 5.2% of the US general population, they are not considered underrepresented because they are 22.1% of US medical school graduates (n = 4202 of 18 999), 38.1% of internal medicine resident physicians (n = 9618 of 25 252), 40.4% of adult cardiology fellows (n = 1098 of 2720), 19.9% of adult cardiologists (n = 5973 of 30 016), 22.6% of pediatric resident physicians (n = 1998 of 8832), 28.0% of pediatric cardiology fellows (n = 122 of 436), and 20.1% of pediatric cardiologists (n = 574 of 2860). Conclusions and Relevance: Female physicians remain underrepresented in adult cardiology, despite a robust pipeline of female medical students and internal medicine resident physicians. Women in pediatric cardiology are underrepresented but increasing in number. Members of several racial/ethnic minority groups remain underrepresented in adult and pediatric cardiology, and the percentages of trainees and medical students from these groups were also low. Different strategies are needed to address the continuing lack of diversity in cardiology for underrepresented minority individuals and women.

Restorative Justice as the Rx for Mistreatment in Academic Medicine: Applications to Consider for Learners, Faculty, and Staff.

The mistreatment of learners is an ongoing issue at U.S. medical schools. According to responses to the 2017 Association of American Medical Colleges Graduation Questionnaire, 39.3% of medical students nationally reported being mistreated. Many articles have been published on the topic of mistreatment at medical schools over the last 20 years. These articles have focused primarily on the definition of mistreatment, the impact of mistreatment, and initiatives put into place to help mitigate the problem. To date, very little attention has been paid to repairing the harm caused by mistreatment and rebuilding community trust. Academic medicine is in need of new forums of interaction to achieve more positive learning and workplace environments.The authors discuss restorative justice practices and the potential applications that they may have in academic medicine learning and workplace environments to serve vulnerable students, faculty, and staff who are targets of mistreatment. Restorative justice practices are used to convene groups of people to engage in substantive dialogue about consequential issues that impede community functioning. This process can help a group identify and gain mutual understanding of the personal and collective harm that has occurred, create the conditions that incentivize offenders to admit responsibility rather than deny or minimize the harm, and explore and define a set of problem-solving steps to address the harm and rebuild community trust.

Breaking the Silence: Time to Talk About Race and Racism.

Recent events in the United States have catalyzed the need for all educators to begin paying attention to and discovering ways to dialogue about race. No longer can health professions (HP) educators ignore or avoid these difficult conversations. HP students are now demanding them. Cultural sensitivity and unconscious bias training are not enough. Good will and good intentions are not enough. Current faculty development paradigms are no longer sufficient to meet the educational challenges of delving into issues of race, power, privilege, identity, and social justice.Engaging in such conversations, however, can be overwhelmingly stressful for untrained faculty. The authors argue that before any curriculum on race and racism can be developed for HP students, and before faculty members can begin facilitating conversations about race and racism, faculty must receive proper training through intense and introspective faculty development. Training should cover how best to engage in, sustain, and deepen interracial dialogue on difficult topics such as race and racism within academic health centers (AHCs). If such faculty development training-in how to conduct interracial dialogues on race, racism, oppression, and the invisibility of privilege-is made standard at all AHCs, HP educators might be poised to actualize the real benefits of open dialogue and change.

Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo / Disseminated cryptococcosis by biological therapy: We must manage the risk

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.