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Antibiotics are among the most common causes of drug-induced liver injury worldwide. Amoxicillin/clavulanic acid and nitrofurantoin are the most common culprits while tetracyclines are a rare cause of liver injury. Among tetracyclines, minocycline has been reported more frequently than doxycycline, which is an extremely rare cause of drug-induced liver injury. We present a healthy 28-year-old male patient from rural United States who was taking doxycycline for Lyme disease. After five days of therapy, he developed nausea, vomiting, fatigue, and significant transaminitis consistent with a hepatocellular pattern of liver injury. After a thorough workup which ruled out other causes such as infection, autoimmune diseases, liver malignancy, and vascular, structural, and metabolic disorders, his liver injury was attributed to doxycycline. We reached the diagnosis also by demonstrating a consistent temporal association between doxycycline intake and liver injury and the patient recovered completely with the cessation of doxycycline. Recognition of doxycycline as a cause of drug-induced liver injury should be considered in patients utilizing this antibiotic. Doxycycline, unlike minocycline, has a short latency period. Early recognition and discontinuation of doxycycline in our patient resulted in the complete resolution of symptoms and transaminitis preventing further morbidity and mortality.
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BACKGROUND: Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients' demographics, clinical manifestations, diagnosis, management, and outcome. METHODS: We performed a systematic review of the literature using MEDLINE and LILACS databases. We searched for articles published in the period from January 1990 to December 24, 2022, to identify patients who developed liver abscesses due to Aspergillus spp. RESULTS: Our search yielded 21 patients all of whom had invasive aspergillosis confirmed on liver biopsy. Of these patients 81% were adults, and 60% were males. The majority (86%) of patients were immunocompromised and 95% had symptomatic disease at the time of diagnosis. The most common symptoms were fever (79%), abdominal pain (47%), and constitutional symptoms (weight loss, chills, night sweats, fatigue) (38%). Liver enzymes were elevated in 50%, serum galactomannan was positive in 57%, and fungal blood cultures were positive in only 11%. Co-infection with other pathogens preceded development of apsergillosis in one-third of patients, and the majority of the abscesses (43%) were cryptogenic. In the remaining patients with known source, 28% of patients developed liver abscess through dissemination from the lungs, 19% through the portal vein system, and in 10% liver abscess developed through contiguous spread. The most common imaging modality was abdominal computerized tomography done in 86% of patients. Solitary abscess was present in 52% of patients while 48% had multiple abscesses. Inadequate initial empiric therapy was prescribed in 60% of patients and in 44% of patients definite treatment included combination therapy with two or more antifungal agents. Percutaneous drainage of the abscesses was done in 40% of patients, while 20% required liver resection for the treatment of the abscess. Overall mortality was very high at 38%. CONCLUSION: Further studies are urgently needed for a better understanding of pathophysiology of liver aspergillosis and for developement of newer blood markers in order to expedite diagnosis and decrease mortality.
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Antifúngicos , Aspergilosis , Aspergillus , Absceso Hepático , Humanos , Absceso Hepático/microbiología , Aspergillus/aislamiento & purificación , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Antifúngicos/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Huésped InmunocomprometidoRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.
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(1) Background: Cardiomyopathy in celiac disease or celiac cardiomyopathy (CCM) is a serious and potentially life-threatening disease that can occur in both adults and children. However, data supporting the causal relationship between celiac disease (CD) and cardiomyopathy (CMP) are still inconsistent. The aim of this study was to review and synthesize data from the literature on this topic and potentially reveal a more evidence-based causal relationship. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to search Medline, Embase, and Scopus databases from database inception until September 2023. A total of 1187 original articles were identified. (3) Results: We identified 28 CCM patients (19 adult and 9 pediatric) with a mean age of 27.4 ± 18.01 years. Adult patients with CCM were predominantly male (84.2%) while pediatric patients were predominantly female (75%). The most common comorbidities associated with CCM were anemia (75%) and pulmonary hemosiderosis (20%). In 35% of patients, CCM occurred before the diagnosis of CD, while in 48% of patients, CCM and CD were diagnosed at the same time. Diagnosis of CD preceded diagnosis of CCM in only 18% of patients. Diagnosis of CCM is often delayed with an average, from the onset of symptoms to diagnosis, of 16 months. All patients were treated with a gluten-free diet in addition to guideline-directed medical therapy. At 11-month follow-up, cardiovascular improvement was seen in 60.7% of patients. Pediatric mortality was 33.3%, while adult mortality was 5.3%. (4) Conclusions: Clinicians should be aware of the possible association between CD and CMP, and we recommend CD work-up in all patients with CMP who have concomitant anemia. While we identified only 28 cases in the literature, many cases might go unreported due to a lack of awareness regarding CCM. A high degree of clinical suspicion and a prompt diagnosis of CCM are essential to minimizing the risks of morbidity and mortality, as the combination of a gluten-free diet and guideline-directed medical therapy can improve clinical outcomes.
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LEVEL OF EVIDENCE: 4, Descriptive quality improvement project.
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Hospitales , Mejoramiento de la Calidad , Humanos , PolíticaRESUMEN
BACKGROUND Immunotherapy is a novel treatment offering an alternative to traditional chemotherapeutic agents for different malignancies. Hematologic adverse reactions (HARs) related to immune checkpoint inhibitors (ICIs) are uncommon. Pure red cell aplasia (PRCA) is a rare hematologic complication of ICI therapy in metastatic melanoma with significant mortality risk despite treatment with steroids or immunosuppressive therapy. For unexplained acute anemia after exclusion of other causes, performing bone marrow biopsy is imperative to diagnose PRCA and rule out involvement of bone marrow by primary tumor. HARs can occur during ICI therapy or even after ICI therapy is stopped. ICI rechallenge, even after the development of HARs, is considered in some patients with good response to treatment of HARs from ICIs. Recurrence of HARs with the same or different type of reaction is seen in some patients. CASE REPORT Two cases of ICI-induced PRCA were confirmed on bone marrow biopsy after dual ICI treatment with nivolumab and ipilimumab in metastatic melanoma. In case 2, PRCA was successfully treated with steroids and later rechallenged with single-agent nivolumab, causing mild ICI-induced immune thrombocytopenia, which did not require treatment with steroids. CONCLUSIONS It is crucial to increase clinician awareness of the possibility of PRCA development not only during treatment with ICI but also after finishing treatment with ICI; there is high mortality associated with missing an opportunity to diagnose and treat PRCA on time with favorable results. ICI rechallenge can be considered in patients who showed response to immunotherapy, especially those with limited alternative therapeutic options.
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Melanoma , Aplasia Pura de Células Rojas , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/tratamiento farmacológico , Nivolumab/efectos adversos , Aplasia Pura de Células Rojas/inducido químicamente , Aplasia Pura de Células Rojas/tratamiento farmacológico , Aplasia Pura de Células Rojas/diagnóstico , Esteroides/uso terapéuticoRESUMEN
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.
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Amiodarona , Fibrilación Atrial , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Anciano de 80 o más Años , Humanos , Masculino , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Ataxia/inducido químicamente , Ataxia/diagnóstico , Ataxia/tratamiento farmacológico , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/tratamiento farmacológico , Mareo/inducido químicamente , Mareo/tratamiento farmacológico , Temblor/inducido químicamente , Informes de Casos como AsuntoRESUMEN
Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a common pathogen in the neonatal period, causing meningitis and sepsis. In non-pregnant adults it is an unusual cause of meningitis. We report about an elderly female with several risk factors for invasive GBS infection who developed GBS meningoencephalitis one month after treatment for COVID-19 upper respiratory tract infection. The patient presented with mania, and the classic triad of headache, neck stiffness, and fever was absent which contributed to the delay in diagnosis. Following initiation of treatment with intravenous ceftriaxone she attained full recovery, and her behavior returned to baseline. This case illustrates an unusual presentation of an emerging infection and should alert clinicians about this presentation. By reporting this case we want to raise awareness about mania as a presenting feature of meningoencephalitis. This should lead to more timely diagnosis and better outcomes for future patients.
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Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney.
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Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.
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Lyme disease (LD) is the most common tick-borne illness across the United States, caused by the bacterium Borrelia burgdorferi sensu lato and transmitted to humans by the bite of infected Ixodes ticks. Jamestown Canyon Virus (JCV) is an emerging mosquito-borne pathogen found mostly in the upper Midwest and Northeastern United States. Co-infection between these two pathogens has not been previously reported since it would require the host to be bitten by the two infected vectors at the same time. We report a 36-year-old man who presented with erythema migrans and meningitis. While erythema migrans is a pathognomonic sign of early localized Lyme disease, Lyme meningitis does not occur in this stage but in the early disseminated stage. Furthermore, CSF tests were not supportive of neuroborreliosis, and the patient was ultimately diagnosed with JCV meningitis. We review JCV infection, LD, and this first reported co-infection to illustrate the complex interaction between different vectors and pathogens and to emphasize the importance of considering co-infection in people who live in vector-endemic areas.
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Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, hence significant efforts have been made to establish behavior and risk factors associated with CVD. The American Heart Association proposed a 7-metric tool to promote ideal cardiovascular health (CVH). Recent data demonstrated that a higher number of ideal CVH metrics was associated with a lower risk of CVD, stroke, and mortality. Our study aimed to perform a systematic review and meta-analysis of prospective studies investigating the association of ideal CVH metrics and CVD, stroke, and cardiovascular mortality (CVM) in the general population. Medline and Scopus databases were searched from January 2010 to June 2022 for prospective studies reporting CVH metrics and outcomes on composite-CVD, coronary heart disease, myocardial infarction, stroke, and CVM. Each CVH metrics group was compared to another. Twenty-two studies totaling 3,240,660 adults (57.8% men) were analyzed. The follow-up duration was 12.0 ± 7.2 years. Our analysis confirmed that a higher number of ideal CVH metrics led to lower risk for CVD and CVM (statistically significant for composite-CVD, stroke, and CVM; p < 0.05). Conclusion: Even modest improvements in CVH are associated with CV-morbidity and mortality benefits, providing a strong public health message about the importance of a healthier lifestyle.
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Anaplasma phagocytophilum is an obligate intracellular, Gram-negative pathogen, causative agent of Human Granulocytic Anaplasmosis (HGA). HGA usually manifests as a non-specific febrile illness, accompanied by evidence of leucopenia, thrombocytopenia, and an alteration in liver enzymes. Neurologic manifestations of anaplasmosis are rare and rarely reported. We describe a 62-year-old man who developed encephalitis due to an Anaplasma phagocytophilum infection. The patient favorably responded to intravenous doxycycline and recovered without neurological sequela. In the tick endemic area, clinicians should have a high index of suspicion for tick-borne diseases in patients presenting with neurological deficits. A prompt diagnosis and treatment lead to improvements in morbidity and mortality.
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Anaplasma phagocytophilum is an emerging, Gram-negative, and obligate intracellular pathogen that is infrequently implicated as a causative agent of community-acquired pneumonia. In this paper, we report about an immunocompetent patient from the community who presented with fever, cough, and shortness of breath. Chest X-ray and CT showed bilateral lung infiltrates. Extensive workup for other common and uncommon causes of pneumonia was positive for anaplasmosis. The patient recovered completely with doxycycline therapy. In our literature review, we find that in 80% of reported cases of anaplasmosis pneumonia, empiric treatment did not contain doxycycline, which in some cases led to acute respiratory distress syndrome. Clinicians in tick-borne disease endemic regions should be aware of this unusual presentation of anaplasmosis in order to be able to select appropriate antimicrobial regimens and initiate timely management.
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Nintedanib is a tyrosine kinase inhibitor that was approved for the treatment of patients with idiopathic pulmonary fibrosis in 2014. The most common side effect of Nintedanib is diarrhea, and thrombocytopenia is a rare side effect of Nintedanib. The exact mechanism is unknown, and the literature lacks case reports of this phenomenon. Here, we report the case of a patient who developed thrombocytopenia 12 weeks after starting treatment with Nintedanib. The patient underwent an extensive work up for infectious, hematological, autoimmune, and neoplastic diseases. The patient's thrombocytopenia resolved following cessation of Nintedanib. This case is significant as it reports a rare side effect that might have detrimental consequences if not recognized and treated timely. Additionally, the onset of thrombocytopenia was delayed, 3 months after the initiation of Nintedanib. We also highlight the various literature regarding drug-induced thrombocytopenia and explore the necessary work-up needed to exclude other potential diagnoses. We hope to advocate for multidisciplinary teams to be aware of patients with pulmonary fibrosis on Nintedanib so that this adverse effect can be recognized promptly.
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Fibrosis Pulmonar Idiopática , Trombocitopenia , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Indoles/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológicoRESUMEN
Suppurative portal vein thrombosis (pylephlebitis) is an uncommon condition usually associated with an intra-abdominal infection or inflammatory process. In this study, we aimed to synthesize data on previously published cases according to the PRISMA guidelines. A total of 103 patients were included. Patients were more commonly male (71.8%) and had a mean age of 49 years. The most common infection associated with pylephlebitis was diverticulitis (n = 29, 28.2%), and Escherichia coli was the most isolated pathogen (n = 21, 20.4%). Blood cultures were positive in 64 cases (62.1%). The most common site of thrombosis was the main portal vein (PV) in 59 patients (57.3%), followed by the superior mesenteric vein (SMV) in 40 patients (38.8%) and the right branch of the PV in 30 patients (29.1%). Sepsis developed in 60 patients (58.3%). The mortality rate in our review was 8.7%, and independent risk factors for mortality were the presence of pertinent comorbidities (OR 5.5, p = 0.02), positive blood cultures (OR 2.2, p = 0.02), and sepsis (OR 17.2, p = 0.049).
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Background: Pericarditis caused by Methicillin-resistant Staphylococcus aureus (MRSA) is a rare infection, often seen in patients with chronic kidney disease, immunosuppression, or previous pericardial disease. The presentation can be dramatic with acute illness leading to septic and/or obstructive shock due to pericardial tamponade. Occasionally disease can have a more protracted, indolent, subacute clinical course. Case report: We report a case of a 57-year-old male patient with a previous history of smoking and moderate alcohol use who presented with progressive dyspnea and cough. He was found to have a disseminated MRSA infection with pericarditis complicated by pericardial tamponade. Urgent pericardiocentesis yielded 1.1 liters of purulent fluid that grew MRSA. MRSA was also isolated from the blood and pleural fluid. The patient underwent left thoracotomy, decortication, and pericardial window and completed 3 weeks of intravenous vancomycin therapy, concluding in an excellent outcome. Conclusion: Bacterial pericarditis is an exceptionally rare form of pericarditis which been traditionally associated with chronic medical conditions requiring a prolonged healthcare stay. However, it has lately been observed in healthy individuals with social habits such as smoking and alcohol consumption. Bacterial pericarditis must be recognized in a timely fashion and managed aggressively to prevent a devastating outcome. A multidisciplinary approach is advised, which includes a combination of pericardial drainage and aggressive antibiotic therapy. Such treatment often yields a positive outcome and good long-term prognosis.
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Myocarditis is an infrequent complication of influenza infection that is most often diagnosed clinically in the setting of confirmed influenza infection and elevated cardiac enzymes. Pericarditis can also occur in cases of influenza myocarditis and may require pericardiocentesis for tamponade. Patients with fulminant myocarditis have cardiogenic shock; however, echocardiographic findings may be subtle, showing a preserved ejection fraction and diffuse left ventricular wall thickening (compared to baseline) due to inflammatory edema. Recognizing these echocardiographic findings in the appropriate clinical setting facilitates the early recognition of fulminant myocarditis. Therefore, we report a case of fulminant influenza A myocarditis in healthy 37-year-old women complicated by transient left ventricular wall thickening and tamponade, highlighting the importance of early diagnosis and supportive management for a successful outcome.
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Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%).
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Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.