Rare Case of Cryptococcal Meningitis in Non-HIV Patient with Mantle Cell Lymphoma Associated with Acalabrutinib (Tyrosine Kinase Inhibitor)

Cryptococcus neoformans infections are more common among immunosuppressed individuals, causing the most widespread opportunistic CNS infection among HIV-positive patients [1]. Specifically, those with cellular immunosuppression, such as patients with HIV positive CD4 counts less than 100. When a patient presents with atypical symptoms, it can be difficult to diagnose due to its infrequent presentation in HIV negative patients. Due to the rarity of encounters in HIV-negative patients, when atypical symptoms are present, it poses a diagnostic challenge. Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin B-cell lymphoma that is known to be associated with cellular immunosuppression [2]. This demonstrates the need for early diagnosis and recognition of cryptococcal infections and as a physician should be vigilant to diagnose cryptococcal who is on Acalabrutinib with MCL [3]. CLL patients receiving ibrutinib should be evaluated for cryptococcal infection, which is potentially life threatening if overlooked [4]. Meningitis caused by Cryptococcus mainly presents with fever and altered mental status but in this case, our patient 78-year-old male with mantle cell lymphoma, undergoing a regimen of Rituximab-Bendamustine (BR) in combination with acalabrutinib (TKI), presented with hypotension to ED in June 2021. Cryptococcal infection in patient receiving ibrutinib were mostly reported in patients with Chronic lymphocytic leukemia, who have poor immune reconstitution. Here we are reporting case of cryptococcal meningoencephalitis in patient with MCL on acalabrutinib which is never reported before.

Clinical features of invasive fungal disease in children with no underlying disease

There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.

Disseminated cryptococcal infection in a lymphoma suspected patient

Cryptococcus neoformans is an opportunistic pathogen, mainly responsible for meningitis in immunodeficient individuals. We report a rare case of dessiminated cryptococcosis in a six years old boy, patient was being evaluated for lymphoma. In the present case the causative agent was Cryptococcus neoformans. It was diagnosed through Bactec, aerobic blood culture bottle. The cause of hospitalization of the patient was fever with abdominal pain. Blood and CSF culture revealed the presence of Cryptococcus neoformans which was further confirmed by urease test and corn meal tween agar (CMT). In the present case fungus was unusually isolated earlier from blood culture rather than cerebrospinal fluid. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5784 How to cite this:Khursheed N, Umer A, Adnan F. Disseminated cryptococcal infection in a lymphoma suspected patient. Pak J Med Sci. 2022;38(2):430-432. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5784 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Case Report of SLE Patients with Cryptococcosis in Nongkhai Hospital

Background: Cryptococcal infection, especially cryptococcal meningitis, is the most common cause of central nervous system (CNS) infection with a high mortality rate in patients with systemic lupus erythematosus (SLE). The clinical features of cryptococcal meningitis may be non-specific, which may lead to miss or delay diagnosis and treatment. Objective: To collect the case series of SLE patients with cryptococcosis treated in Nongkhai Hospital between 2013 and 2021 and compared it with other studies. Materials and Methods: The medical records of SLE patients (ICD-10 M320-M329) with cryptococcal infection (ICD-10 B450-B459) treated in Nongkhai Hospital between 2013 and 2021 were reviewed and collected onto a medical record form. The following information were obtained, gender, occupation, age at SLE diagnosis, age of onset, duration of disease, comorbid or risks, previous infection, SLE disease activity, glucocorticoids, and immunosuppressors administered before or at infection diagnosis, cryptococcosis clinical manifestations, laboratory data, Cerebrospinal fluid (CSF) findings, antifungal agents used, and outcomes. Results: Six hundred thirty-six patients with SLE were identified and six patients developed cryptococcosis. Five patients had cryptococcal meningitis and one patient had cryptococcocemia. Fever and headache were the symptoms of all patients. CSF cryptococcal antigen was positive in five patients. Antifungal therapy was initiated as soon as the diagnosis was confirmed in all patients. Five patients (83.3%) recovered completely, and one patient was against the advice. Conclusion: The present study suggested that SLE patients presenting with fever and headache along with a history of moderate to high dose steroids and immunosuppressants administration should always be suspected of cryptococcal infection and cryptococcal meningitis. Meanwhile, CSF cryptococcal antigens are the effective screening tools to establish an early diagnosis. Accordingly, early appropriate treatment is crucial for a favorable outcome. Keywords: Cryptococcal infection; Cryptococcosis; Cryptococcal meningitis; SLE; Lupus

Cryptococcal Infection with Ruxolitinib in Primary Myelofibrosis: A Case Report and Literature Review

Cryptococcus neoformans (CN) is an encapsulated yeast that causes disseminated and potentially life-threatening in immunocompromised hosts. We present a patient with primary myelofibrosis on ruxolitinib who developed disseminated disease due to CN. The report underscores the importance of suspecting infections with intracellular pathogens in immunosuppressed patients on ruxolitinib.

Mycotic Pseudotumor of the Breast Secondary to Cryptococcal Infection: Report of Three Rare Cases and Literature Review

Breast masses in clinical practice are often investigated primarily for neoplastic conditions. Breast fungal infections are unusual, and few cases have been reported in the literature. The differential diagnosis for a breast mass should not be limited to neoplastic conditions as there are treatment implications. The correct diagnosis is associated with reduced and unwanted cases of surgical intervention. We describe 3 cases of cryptococcal infection of the breast that clinically masqueraded as breast malignancies.

310. Cryptococcal Infection Following COVID-19 infection in Solid Organ Transplant Recipients: A Case Series

Background Fungal infections have been identified with or following SARS-CoV-2 infection, most commonly COVID associated pulmonary aspergillosis. Cryptococcus species are ubiquitous in the environment and the third most common invasive fungal infection following Solid Organ Transplant (SOT). We describe four cases of concurrent or subsequent cryptococcal infection within 90 days following COVID-19 infection. Methods We conducted a retrospective study of patients presenting with proven cryptococcosis either concurrently or within 90 days following COVID-19 diagnosis. Cases were identified March 2020 through May 2021. All were seen at the University of Alabama in Birmingham, a regional referral and comprehensive transplant center. Exemption for this review was approved by our IRB. Results Four cases were identified, all were SOT recipients. Case details are provided in Table 1. No patients required ICU level care at any point. COVID-19 treatment included 10 days of increased steroids for 3 patients, remdesivir for 2, and 1 received no treatment for COVID-19. In contrast to the typical time-course for cryptococcal infection post-SOT (median time approx. 500 days post-transplant), three patients were greater than 2 years post-transplant and were without rejection or recent changes in immunosuppression. Patient 1 was less than 6 months post liver-kidney transplant and was diagnosed at time of admission with concurrent COVID-19 and cryptococcal pneumonia. Infection was disseminated in the other 3 cases including positive blood cultures in 2 patients and cryptococcal meningitis (CM) in 2 patients. CM cases presented later following COVID-19 and had the longest delay between symptom onset (headache, neurologic symptoms) and CM diagnosis. One patient had CM 8 years prior, but had done extremely well off fluconazole for over 6 years prior to this recurrence. All patients are doing well at most recent follow-up evaluations. Table 1. Summary of Cases Conclusion We describe the first case series with a temporal association between SARS-CoV-2 infection and cryptococcosis. All cases were immunocompromised due to SOT. Some symptoms were attributed to post-COVID syndrome leading to significant delays in diagnosis for those patietns, highlighting the importance of considering this association for at-risk patients. Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant)

1376. Cryptococcal Infection Presenting Solely as a Pleural Effusion

Background Cryptococcal infections are frequently seen in immunosuppressed hosts. To date, few cases of cryptococcal infections presenting solely as pleural effusion have been described in liver transplant recipients. To our knowledge, this is the first case of cryptococcal pleuritis presenting with acute respiratory failure early post liver transplant. Methods 51- year old male with non- alcoholic cirrhosis complicated by chronic right hydrothorax underwent deceased donor liver transplantation with methylprednisolone induction. A week later, he developed acute respiratory failure requiring intubation. Pleural fluid was exudative with lymphocyte predominance; aerobic culture grew C. neoformans. Serum cryptococcal antigen was initially negative (prozone phenomenon was excluded) and subsequently turned positive titer 1:16. He was started on liposomal amphotericin and flucytosine, but developed acute kidney injury; induction therapy was changed to fluconazole with flucytosine for 2 weeks followed by fluconazole consolidation for 8 weeks. He remains on maintenance therapy. Donor serum cryptococcal antigen was negative, and recipients of other organs from the donor were clinically well. Results Pleural effusions are common in cirrhotic patients with ascites from hepatic hydrothorax. Although rare, Cryptococcal infection can manifest as isolated pleural effusion. Our patient was diagnosed with Cryptococcal empyema early post-transplant, though likely had subclinical or latent infection pre-transplant; evaluation for donor-derived infection was negative. Diagnosis of isolated pleural disease may be missed if only serum Cryptococcal antigen is tested, as antigen may not be detectable. Diagnosis is mainly established by pleural fluid culture and may be delayed, as pleural fluid is not routinely cultured when effusions are attributed to hepatic hydrothorax. Cryptococcal antigen in the pleural fluid may have a better diagnostic yield. Conclusion Cryptococcal infection should be considered in patients with cirrhosis and liver transplant recipients presenting with pleural effusion without any other abnormalities on chest imaging. Diagnosis may be missed if only serum cryptococcal antigen is used. Disclosures All Authors: No reported disclosures