Serum Cryptococcal Antigen Titer Research Articles

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review.

Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course. We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed. Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence. Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.

An unusual case of reactivated latent pulmonary cryptococcal infection in a patient after short\u2010term steroid and azathioprine therapy: a case report

BackgroundCryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before.Case presentationA 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient’s history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed.ConclusionsAlthough rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.

Underlying Cryptococcal Diseases and the Correlation With Serum Cryptococcal Antigen Titers in Hospitalized HIV-Infected Patients Screened Positive for Cryptococcal Antigenemia.

Background: The prevalence of different underlying cryptococcal diseases in human immunodeficiency virus (HIV)-infected patients screened positive for cryptococcal antigenemia and the association between cryptococcal diseases and serum cryptococcal antigen (CrAg) titers were understudied.Methods: HIV-infected patients with CD4 < 200 cells/ul, admitted to the second hospital of Nanjing, Nanjing, China, from January 2016 to September 2019, were retrospectively analyzed. Integrated into routine HIV care, all these patients were screened for cryptococcal antigenemia with CrAg lateral flow assay. Positive patients received extensive laboratory and radiological studies to evaluate underlying cryptococcal diseases.Results: A total of 872 HIV inpatients were screened for serum CrAg. The prevalence of cryptococcal antigenemia in the study population was 10.3% (95% CI, 8.3–12.3%), 87.6% of which with cryptococcal antigenemia had clinically cryptococcal diseases. The prevalence of cryptococcal meningitis (CM), cryptococcemia and pulmonary cryptococcosis (PC) in patients with cryptococcal antigenemia were 58.4% (95% CI, 48.0–68.9%), 50.7% (95% CI, 39.1–62.2%), and 68.5% (95% CI, 58.7–78.4%), respectively. The median (range) serum CrAg titers in severe cryptococcal diseases (CM or cryptococcemia), localized PC (without co-existing CM or cryptococcemia) and isolated cryptococcal antigenemia were 1:2560 (1:10–1:2560), 1:20 (1:2–1:320), and 1:5 (1:2–1:320), respectively. Serum CrAg titers ≥1:320 were independently associated with CM (adjusted OR 26.88; 95%CI, 8.36–86.42). Severe cryptococcal diseases were found in all patients with serum CrAg titers ≥1:640. None of the patients with serum CrAg titers ≤ 1:5 had CM.Conclusion: The prevalence of cryptococcal antigenemia was high in HIV inpatients, supporting routine CrAg screening. Clinical cryptococcal diseases, most commonly the PC, existed in the majority of the patients with cryptococcal antigenemia. Since serum CrAg titer is correlated with cryptococcal disease severity, it may possibly guide anti-fungal treatment.

An Unusual Cause of Recurrent Pleural Effusion

Abstract Cryptococcus neoformans is a yeast that can cause severe infection in the immunocompromised. It is commonly associated with meningitis in patients with underlying HIV infection; however, infections can occur in other immunosuppressed hosts as well as the immunocompetent. Pulmonary disease is well described, but recurrent pleural effusion and empyema are rare. We describe a case in a non–HIV-infected, nontransplant cirrhotic patient presenting with recurrent pleural effusions and cryptococcal empyema. The patient is a 66-year-old man with cirrhosis, diabetes, and kidney disease who presented with 3 months of dyspnea complicated by recurrent pleural effusion and low protein ascites after treatment of hepatitis C virus. Routine cultures from multiple thoracenteses were unrevealing. Fungal culture ultimately grew C. neoformans/gattii. His serum cryptococcal antigen titer was 1:40, and chest imaging revealed several pulmonary nodules. He was admitted for evaluation of disseminated disease and central nervous system involvement, which was unremarkable. He was started on oral fluconazole 200 mg daily dosed for his renal function and was doing well in outpatient follow-up. Patients with cirrhosis tend to have a higher incidence of cryptococcal disease and are more likely to have disseminated infection with higher mortality. It is possible that deficiencies in complement and cytokine levels as well as leukocyte function may contribute to this increased risk. Effusions are an uncommon manifestation of pulmonary cryptococcosis and, as with the case in our patient, may resemble hepatic hydrothorax, leading to a delay in antifungal therapy. In conclusion, patients with liver disease have an increased risk of cryptococcosis. A high index of suspicion must be maintained for infection and should be considered in patients with recurrent effusions.

2272 A Case of Cryptococcal Hepatitis in HIV Patient With a Negative Serum Cryptococcal Antigen

INTRODUCTION: Infectious Cryptococcus neoformans occurs primarily in immunocompromised patients. The primary organ affected is the lungs, but CNS and skin involvement can also be seen. Disseminated Cryptococcosis can involve any organ in the body. However, hepatic involvement is rare. Here we offer a case of Cryptococcus hepatitis in a patient who presented with persistently elevated liver enzymes. CASE DESCRIPTION/METHODS: A 56-year-old Hispanic female with no known past medical history presented with fever, abdominal pain, nausea, unintentional weight loss, and diarrhea for two months. On physical examination, she was tachycardic with a heart rate of 110 bpm, and her abdomen was soft but tender to palpation in the right upper quadrant. Her liver function tests (LFTs) revealed elevated Aspartate Aminotransferase (AST) (415 U/L), elevated Alanine Aminotransferase (ALT) (201 U/L), elevated Alkaline Phosphatase (ALP) (763 U/L), normal total Bilirubin (0.9 mg/dl), and additional laboratory results in Table 1. Her HIV antigen screening was reactive, and absolute CD4 count was 22/ mcL. CT scan of the chest revealed two small calcified granulomas, for which she was started prophylactically on Azithromycin and TMP/SMZ. Over the course of her hospital stay, the patient's liver enzymes continued to trend upward while further workup ruled out hepatitis A, B, C, Wilson's disease, Hemochromatosis, AIH, PBC, PSC, other causes of viral hepatitis (CMV, EBV, HSV), with negative Histoplasma antibodies and negative serum Cryptococcal antigen titers. During the second week of hospitalization, her liver enzymes continued to rise with an ALP of 4046 U/L, AST of 407 U/L, and ALT of 276 U/L. With a persistent elevation of the liver enzymes without any definitive cause, an ultrasound-guided biopsy was warranted and performed. Pathology revealed Cryptococcal hepatitis (Figures 1 and 2), and the patient was started on a 15-day course of Amphotericin B with an 8-week course of Fluconazole 400 mg with LFTs nearly normalizing at 6 weeks. DISCUSSION: This case demonstrates an unusual manifestation of Cryptococcosis. Our patient did not present with the typical Cryptococcal pulmonary or central nervous system infection. As well, our patient's serum Cryptococcal antigen titers were negative, but biopsy results revealed Cryptococcal hepatitis, despite a very high sensitivity and specificity of the serum Cryptococcal antigen test. This case demonstrates the importance of maintaining a broad differential, specifically in immunocompromised patients.

NONRESOLVING PNEUMONIA: A RARE CASE OF PULMONARY CRYPTOCOCCOSIS IN AN IMMUNOCOMPETENT PATIENT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cryptococcus Neoformans is a serious fungal infection common to HIV, lung transplant, and otherwise immunocompromised patients. Infection in the immunocompetent (IC) host is rare. We present an IC patient with nonresolving pneumonia found to have a cryptococcal infection. CASE PRESENTATION: A 36-year-old Chinese female non-smoker, no past medical history with multiple Emergency Department (ED) visits in the past month for cough and shortness of breath treated with levofloxacin was referred to the ED again for outpatient findings of lung abscess on CT lung. Symptoms now included intermittent fevers, orthopnea, dyspnea on exertion, and weight loss. She endorsed cough with yellow sputum and small amounts of hemoptysis in the preceding days. Vitals, physical examination, and labs including CBC, BMP, lactate, and coagulation studies were unremarkable. CT Chest revealed large areas of consolidation in the RLL with multiple cavitary areas consistent with pneumonia with lung abscess. Admitted for necrotizing pneumonia, she received an empiric 7-day course of IV antibiotics. Blood and sputum cultures were negative, tuberculosis was ruled out via sputum. Viral testing revealed HIV negative with normal lymphocyte subset panels. Rheumatologic workup was unremarkable. Bronchoalveolar lavage samples stained positive for cryptococcus (Figure 1-3). Serum cryptococcal antigen titer was 1:128. There was no evidence of disseminated disease or CNS involvement on CT head or lumbar puncture. The patient was started on fluconazole with a plan for CT Chest in 6 months. DISCUSSION: Cryptococcus ranges from asymptomatic colonization to life threatening disseminated disease. Pulmonary infection with cryptococcus is uncommon in the IC patient. When present it is usually asymptomatic, but symptomatic disease can rarely occur. Because of this there is delay in treatment as symptoms may be present for days to weeks before the diagnosis is made. There are reports of disseminated infection leading to meningitis in an IC host(1)(2). In a retrospective study of disseminated cryptococcal infection in HIV noninfected patients mortality reached 63%(3). CONCLUSIONS: Our patient did not have any identifiable risk factors for Cryptococcus. It is not a disease isolated to HIV or immunocompromised patients. When assessing a patient with a nonresolving pneumonia it is crucial to have a broad differential. The life-threatening risk of pulmonary infection progressing to severe pneumonia with respiratory failure or extrapulmonic dissemination, particularly to the CNS, is why it is important to make a timely diagnosis and initiate appropriate treatment. Reference #1: Kerkering, TM, Duma, RJ, and Shadomy, S. The evolution of pulmonary Cryptococcus.Ann Intern Med. 1981; 94: 611-616 Reference #2: Chu HQ, Li HP, He GJ. Analysis of 23 cases of pulmonary cryptococcosis. Chin Med J (Engl) 2004;117:1425–1427 Reference #3: Chuang YM, Ho YC, Chang HT, Yu CJ, Yang PC, Hsueh PR. Disseminated cryptococcosis in HIV-uninfected patients. Eur J Clin Microbiol Infect Dis. 2008;27(4):307–310 DISCLOSURES: No relevant relationships by Ajay Adial, source=Web Response No relevant relationships by Trisana Cox, source=Web Response No relevant relationships by Rammohan Gumpeni, source=Web Response No relevant relationships by Asma Iftikhar, source=Web Response No relevant relationships by Tereza Izakovich, source=Web Response No relevant relationships by Priyank Trivedi, source=Web Response

Dynamic research of serum cryptococcal capsular polysaccharide antigen titer and chest CT of pulmonary cryptococcosis after antifungal therapy

Objective: To observe the dynamic changes of serum cryptococcal capsular polysaccharide antigen (CrAg) titer and chest CT of pulmonary cryptococcosis (PC) after antifungal therapy. Methods: A retrospective study was performed for patients with PC admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from January 2015 to April 2018. Serum CrAg titers and Chest CT examination were performed for all the cases before and after treatment. The difference between immunocompetent hosts group and immunocompromised hosts group were compared and analyzed. Results: Eighty-two patients with PC including 46 male (56.1%) and 36 (43.9%) female were enrolled. Fifty-two (63.4%) patients were proven PC and thirty (36.6%) patients were probable PC. Forty-five (54.9%) patients had underlying diseases. Fifty-four (65.9%) patients were immunocompetent hosts and twenty-eight (34.1%) patients were immunocompromised hosts. The mean duration of treatment was (7.9±2.4) months and the mean follow-up was (24.0±10.0) months. Improvement (≥75%) in chest CT were found in 64.8% of the cases in immunocompetent group and 67.9% in immunocompromised group after 6 months' treatment. Improvement (≥75%) was found in 88.9% of the cases with patchy infiltrates or consolidation and only 63.0% in nodular or mass-like type and mixed patterns of PC. The serum CrAg titer of 55 cases ranged from 1∶4 to 1∶160 before treatment (median 1∶40) and decreased for all cases after treatment. The serum CrAg titer became negative in 20 cases at last. Mean time of serum CrAg titer turning negative was (11.8±8.1) months. The serum CrAg titer became negative or decreased to 1∶1 in 24 cases after treatment cessation, of whom the serum CrAg titer ranged from 1∶5 to 1∶160 before treatment (median 1∶20). The serum CrAg titer of 31 cases ranged from 1∶4 to 1∶640 before treatment (median 1∶64), of whom the serum CrAg detections were still positive after treatment cessation, and CrAg titer was 1∶10 (ranged from 1∶2 to 1∶160). Conclusions: In PC, chest CT improves after antifungal treatment, and the infiltrates or consolidation type of PC resolves faster than nodular or mass-like shadows and mixed patterns in CT. The serum CrAg titer decreases after antifungal treatment.

Cryptococcal infections in solid organ transplant recipients over a 15-year period at a state transplant center.

The aim of this research paper was to determine the incidence, risk factors, and clinical outcome of solid organ transplant (SOT) recipients diagnosed and treated for cryptococcosis at our institution. Retrospective analysis of all patients with SOT diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015. Of 102 patients diagnosed with cryptococcal infection, 23 were SOT recipients. Renal transplant accounted for 22/23 cases, of which 13 had meningitis. The annual incidence of infection has risen significantly, and is now greater than 2/1000 prevalent renal transplant recipients. As expected, biochemical factors associated with meningitis include lower glucose on cerebrospinal fluid (CSF) analysis, median 2.4 vs 4.5mmol/L (P=.02); CSF white blood cell median 50 vs 1/μL (P<.001); CSF protein, median 950 vs 335mg/L (P=.04). Serum cryptococcal antigen titers were higher in the meningitis cohort, median 512 vs 32 (P=.03). Clinically, headache on admission (odds ratio: 9 [1.29-63.03], P=.03) and a prolonged length of stay (median of 36 vs 13days) in the meningitis cohort (P=.02) were significant. Cryptococcal infection in SOT recipients remains rare; however, there has been a marked increase in cases since 2014. This study reveals a need for increased vigilance for a potential emerging infectious disease. It furthermore highlights the need for ongoing research to further aid early diagnosis, prognostication, management, and screening cost-effectiveness.

Longitudinal Clinical Findings and Outcome among Cryptococcus gattii Patients in British Columbia

Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported. Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models. Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to <1:8 was 2.8 and 2.9 years, respectively. Cg-related and all-cause mortality among culture-confirmed cases at 12 months' follow-up was 23.3% and 27.2%, respectively. Cg-related mortality was associated with age >50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis. Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.

Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression.

Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined. SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria. Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07). We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.

Cryptococcal Necrotizing Fasciitis in a Patient After Renal Transplantation—A Case Report

A 50-year-old man, who had received an ABO-incompatible living related preemptive renal transplantation 1 year before, presented with painful lesions on both lower extremities and fever. At first, bacterial cellulitis was suspected and antibiotic therapy was initiated, but it was not effective. The serum cryptococcal antigen titer was 1:4,098, and pathologic examination of debrided tissue and wound pus culture revealed cryptococcal necrotizing fasciitis. Liposomal amphotericin B and fluconazole were started, and repeated debridement and skin grafting were performed. Because his graft function deteriorated because of antibody-mediated rejection and polyoma viral nephropathy, hemodialysis was induced on day 9 of hospitalization. During the treatment, he suffered repeated urinary tract infections, which were treated with antibiotics, and cytomegalovirus retinopathy, which was treated with ganciclovir. His cryptococcal necrotizing fasciitis was successfully cured by the combination of antimicrobial treatment and surgical procedures. He could walk with a cane and was discharged on day 298 of hospitalization. Cryptococcal necrotizing fasciitis in renal transplant recipients is so rare that only 14 cases have been reported. The mortality is not very high, but the prognosis of the patient is complicated by worsening of the cryptococcal infection of the central nervous system (CNS). Early detection and treatment to prevent spreading to other sites, especially the CNS or disseminated disease, is very important in cases of cryptococcal necrotizing fasciitis.

Importance of follow-up cerebrospinal fluid analysis in cryptococcal meningoencephalitis.

Cryptococcal meningoencephalitis represents a serious infection of the central nervous system, where reliable prognostic factors during the disease course are needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a German university hospital from 1999 to 2013 were analysed retrospectively. CSF parameters were analysed prior to therapy and during antifungal treatment and were compared between patients who survived or deceased. Fifteen patients clinically improved after antifungal therapy, while six patients died. No differences were observed between the outcome groups for the CSF parameters cell count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up examinations of serum cryptococcal antigen titer and CSF cell count have shown that these parameters cannot be used to monitor the efficacy of antifungal therapy as well. In contrast, the course of QAlb during therapy was indicative for the outcome as a possible prognostic marker. In patients with clinical improvement QAlb values were falling under therapy, while rising QAlb values were found in patients with fatal outcome indicating a continuing dysfunction of the blood-CSF barrier. In conclusion, our results indicate that, among the various CSF parameters, the course of QAlb presents a promising marker that might be used to monitor the efficacy of antifungal therapy.

Disseminated Cryptococcosis Presenting as Obstructive Jaundice in an Imunocompetent Pregnant Female

Purpose: A 22-year-old, gravid three, para two at 36 weeks of gestation presented with a 1-month history of right upper quadrant pain and jaundice. Past medical history notable for choledocholithasis and cholecystectomy. No fever, weight loss, or night sweats. No smoking, illicit drug use, or alcohol intake. Exam revealed scleral icterus and right upper quadrant tenderness. Vitals were stable. Labs: leukocytosis, microcytic anemia, mild transaminitis, and obstructive jaundice. Autoimmune, viral hepatitis panels, and HIV were negative. She delivered a healthy baby. CT chest and abdomen showed extensive systemic lymphadenopathy. MRCP and ERCP showed irregularities and dilatation of the intra and extra-hepatic bile ducts with common bile duct stricture. Biliary stent failed to resolve cholestasis. Liver biopsy therefore done, showed centrilobular cholestasis, portal edema, and necrosis with rare granulomas and eosinophils. Blood cultures and lymph node biopsies were positive for numerous yeast form Cryptococcus neoformans. Serum cryptococcal antigen titers markedly elevated at 1:4096. CSF analysis and culture was negative. Following antifungal therapy, follow-up ERCP showed free flow of bile and patient's LFT's and lymphadenopathy improved. Cryptococcosis is an opportunistic fungus affecting immune-compromised patients with an affinity to the CNS, skin, and lungs. We present an extremely rare case of disseminated cryptococcemia involving the biliary tree in an immunocompetent patient. Treatment for disseminated disease in pregnancy is induction with amphotericin or LFAmB with or without flucytosine for 2-4 weeks, followed by fluconazole for consolidation and maintenance, started after delivery. Prompt identification and treatment is important to prevent bad obstetric outcomes and mortality in this group.Figure: ERCP.Figure: Lymph node biopsy.

Cryptococcosis of lumbar vertebra in a patient with rheumatoid arthritis and scleroderma: case report and literature review

BackgroundAlthough cryptococcosis mainly occurs in the central nervous system and lungs in immunocompromised hosts, it can involve any body site or structure. Here we report the first case of primary cryptococcosis of a lumbar vertebra without involvement of the central nervous system or lungs in a relatively immunocompromised individual with rheumatoid arthritis and scleroderma.Case presentationA 40-year-old Chinese woman with rheumatoid arthritis diagnosed 1 year beforehand and with a subsequent diagnosis of scleroderma was found to have an isolated cryptococcal infection of the fourth lumbar vertebra. Her main complaints were severe low back and left leg pain. Cryptococcosis was diagnosed by CT-guided needle biopsy and microbiological confirmation; however, serum cryptococcal antigen titer was negative. After 3 months of antifungal therapy with fluconazole the patient developed symptoms and signs of scleroderma, which was confirmed on laboratory tests. After taking fluconazole for 6 months, the progressive destruction of the lumbar vertebral body had halted and the size of an adjacent paravertebral mass had decreased substantially. On discharge symptoms had resolved and at an annual follow-up there was no evidence of recurrence on the basis of symptoms, signs or imaging investigations.ConclusionAlthough cryptococcosis of the lumbar vertebra is extremely rare, it should be considered in the differential diagnosis for patients with lumbar vertebral masses to avoid missed diagnosis, misdiagnosis and diagnostic delay. Early treatment with antifungals proved to be a satisfactory alternative to surgery in this relatively immunocompromised patient. Any residual spinal instability can be treated later, once the infection has resolved.

Clinical Manifestations of Cryptococcus gattii Infection: Determinants of Neurological Sequelae and Death

Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05). Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.

Paradoxical cryptococcal immune reconstitution inflammatory syndrome in advanced chronic kidney disease

Cryptococcal-related immune reconstitution inflammatory syndrome (IRIS) is frequently seen in immunocompromised patients. A 45-year-old man with advanced chronic kidney disease (CKD) received intensive antifungal treatment for pulmonary cryptococcosis. Despite negative pleural effusion cultures and declining serum cryptococcal antigen titers, the patient presented with progressive pulmonary infiltration, intermittent fever, and elevated C-reactive protein. Steroids were given for suspected IRIS, and the clinical condition improved dramatically. This is the first report on paradoxical cryptococcal IRIS in a patient with advanced CKD.

Successful management of cryptococcosis of the bilateral adrenal glands and liver by unilateral adrenalectomy with antifungal agents: a case report

BackgroundCryptococcus species usually affect the central nervous system and lungs in immunocompromised hosts. Although the adrenal glands can be involved in disseminated cryptococcosis, primary adrenal insufficiency caused by the fungal infection is uncommon.Case presentationWe present a case of primary adrenal insufficiency with bilateral adrenal masses and liver invasion in a 43-year-old man with mild type 2 diabetes mellitus. Cryptococcosis was diagnosed by fine-needle aspiration biopsy of the liver mass. The serum cryptococcal antigen titer was elevated to 1:256. After 6 months of antifungal therapy with fluconazole and amphotericin B, the size of the liver mass was decreased, but no significant changes were observed in the bilateral adrenal masses and the serum cryptococcal antigen titer remained elevated at 1:128. To control the cryptococcosis, a laparoscopic left adrenalectomy was performed, followed by antifungal therapy. After the unilateral adrenalectomy, the size of the remaining right adrenal mass was reduced and the serum cryptococcal antigen titer declined to 1:4.ConclusionsThis is the first report describing adrenal cryptococcosis with adrenal insufficiency and liver invasion without central nervous system involvement. Adrenal cryptococcosis should be considered in the differential diagnosis for patients with bilateral adrenal masses with primary adrenal deficiency. Unilateral adrenalectomy was quite effective in controlling the cryptococcosis in this case. Even in patients with bilateral adrenal cryptococcosis, unilateral adrenalectomy should be an option for treatment of disseminated cryptococcosis.

Surveillance for Cryptococcus gattii in horses of Vancouver Island, British Columbia, Canada

In the last decade Cryptococcus gattii has emerged as an important human and animal pathogen in southwestern British Columbia (BC), Canada. When the disease initially emerged it was identified in humans and multiple animal species on the east coast of Vancouver Island. From fall 2003 until summer 2004, active surveillance was initiated to look for horses exposed to or infected with the organism by performing nasal cultures and serum antigen testing in horses residing within 10 km of known areas of environmental reservoirs of the fungus. Surveillance efforts were facilitated by local equine practitioners who were also encouraged to report clinical cases. Nasal colonization was identified in four of the 260 horses tested but none had a serum cryptococcal antigen titer. All positive horses were from the same geographic area near Duncan, BC. During the study period, a single horse was diagnosed with systemic cryptococcosis and euthanized; clinical and post mortem information is described. As this organism continues to disseminate in the Pacific Northwest it is important for veterinarians to be familiar with the disease as early diagnosis may enable more effective treatment.

Identifying Predictors of Central Nervous System Disease in Solid Organ Transplant RecipientsWith Cryptococcosis

Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed. Patients comprised a multicenter cohort of SOT recipients with cryptococcosis. Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001). CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.