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Background: Cryptococcus is an opportunistic infection acquired through inhalation from the environment, primarily affecting individuals with compromised immune systems. It typically leads to pneumonia upon passing through lung tissue. The infection can disseminate to various organs via the bloodstream, resulting in meningitis or encephalitis in the central nervous system. Disseminated Cryptococcus has been reported to involve the skin, liver, eyes, lymph nodes, bone marrow, spleen, kidneys, and intestines, significantly increasing morbidity and mortality. However, pancreatic involvement in Cryptococcus is relatively rare, and a few case reports have highlighted severe organ damage and high mortality rates. Case presentation: In this case report, we present the case of a 36-year-old Asian man who presented with a 2-week history of headaches and blurred vision in his right eye. Brain magnetic resonance imaging revealed multiple brain masses, along with a mass in the lower left lung field and a tumor in the pancreatic tail, as detected by chest computed tomography. Endoscopic ultrasound-guided fine needle biopsy and computed tomography-guided lung biopsy confirmed the diagnosis of disseminated cryptococcal infection involving the pancreas, lung, and brain. The patient's clinical condition improved following antifungal therapy. Additionally, we identified anti-granulocyte–macrophage colony-stimulating factor antibody as a risk factor for disseminated cryptococcal infection in this patient. Conclusion: Disseminated cryptococcosis can be a potentially lethal condition, as highlighted by previous literature. However, early diagnosis using contrast-enhanced harmonic endoscopic ultrasound and endoscopic ultrasound-guided biopsies, as well as prompt treatment as demonstrated in our case, can improve outcomes and prevent mortality. [ABSTRACT FROM AUTHOR]

We report a case of disseminated cryptococcosis, an uncommon fungal infection predominantly affecting the lungs and central nervous system, with the rare involvement of adrenal cryptococcosis, compounded by meningitis and pneumonia. The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Imaging via chest and abdominal CT scans revealed inflammation in the right lung’s middle lobe, splenomegaly, a splenic lesion, and a left adrenal mass, initially prompting considerations of pheochromocytoma. However, unilateral adrenalectomy and subsequent pathological examination disclosed extensive infiltration by inflammatory and multinucleate giant cells, with Periodic acid-Schiff (PAS) staining confirming the diagnosis. The identification of adrenal cryptococcosis was further supported by positive adrenal pus culture and significantly elevated capsular antigens in both serum and cerebrospinal fluid, at titers of 1:2560. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination. [ABSTRACT FROM AUTHOR]

A 76-year-old male diagnosed with sarcoidosis presented with atraumatic left anterior knee pain. Initial imaging of the left lower extremity revealed an eccentrically-based lytic lesion in the mid-distal femur with cortical erosion and an additional lytic lesion in the proximal tibia. Magnetic resonance imaging (MRI) demonstrated an aggressive lesion in the proximal tibia with surrounding marrow edema, cortical breach, and erosion into the distal patellar tendon. Given concern for metastatic bone lesions, a18-fluorodeoxyglucose positron emission tomography/computed tomography scan (FDG PET/CT) was performed which demonstrated concordant hypermetabolic lytic lesions at the left mid-distal femur and the left proximal tibia, as well as hypermetabolic diffuse lymphadenopathy. The patient was presumed to have metastatic lung cancer based on the presence of lung nodules. Due to concern for impending pathologic fracture, the patient underwent open biopsy with a plan for prophylactic fixation of both lesions. Intra-operatively, however, both lesions were found to contain pus, from which cultures ultimately grew Cryptococcus neoformans. This is a case of disseminated skeletal cryptococcosis masquerading as metastatic cancer in a patient without classic risk factors for disseminated cryptococcosis (defined as extrapulmonary evidence of infection). Classically, disseminated cryptococcosis is thought to occur in severely immunocompromised patients, such as those with human immunodeficiency virus (HIV) or organ transplant recipients. This case highlights the need to maintain a high index of suspicion in patients with underlying immunocompromising conditions, including less common conditions such as sarcoid, who present with bony lesions. This case report then discusses the diagnostic evaluation and treatment of disseminated skeletal cryptococcosis. [ABSTRACT FROM AUTHOR]

Background: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. Methods: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. Results: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). Conclusions: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted. [ABSTRACT FROM AUTHOR]

Abstract Background Cryptococcus is an opportunistic infection acquired through inhalation from the environment, primarily affecting individuals with compromised immune systems. It typically leads to pneumonia upon passing through lung tissue. The infection can disseminate to various organs via the bloodstream, resulting in meningitis or encephalitis in the central nervous system. Disseminated Cryptococcus has been reported to involve the skin, liver, eyes, lymph nodes, bone marrow, spleen, kidneys, and intestines, significantly increasing morbidity and mortality. However, pancreatic involvement in Cryptococcus is relatively rare, and a few case reports have highlighted severe organ damage and high mortality rates. Case presentation In this case report, we present the case of a 36-year-old Asian man who presented with a 2-week history of headaches and blurred vision in his right eye. Brain magnetic resonance imaging revealed multiple brain masses, along with a mass in the lower left lung field and a tumor in the pancreatic tail, as detected by chest computed tomography. Endoscopic ultrasound-guided fine needle biopsy and computed tomography-guided lung biopsy confirmed the diagnosis of disseminated cryptococcal infection involving the pancreas, lung, and brain. The patient’s clinical condition improved following antifungal therapy. Additionally, we identified anti-granulocyte–macrophage colony-stimulating factor antibody as a risk factor for disseminated cryptococcal infection in this patient. Conclusion Disseminated cryptococcosis can be a potentially lethal condition, as highlighted by previous literature. However, early diagnosis using contrast-enhanced harmonic endoscopic ultrasound and endoscopic ultrasound-guided biopsies, as well as prompt treatment as demonstrated in our case, can improve outcomes and prevent mortality.

Abstract We report a case of disseminated cryptococcosis, an uncommon fungal infection predominantly affecting the lungs and central nervous system, with the rare involvement of adrenal cryptococcosis, compounded by meningitis and pneumonia. The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Imaging via chest and abdominal CT scans revealed inflammation in the right lung’s middle lobe, splenomegaly, a splenic lesion, and a left adrenal mass, initially prompting considerations of pheochromocytoma. However, unilateral adrenalectomy and subsequent pathological examination disclosed extensive infiltration by inflammatory and multinucleate giant cells, with Periodic acid-Schiff (PAS) staining confirming the diagnosis. The identification of adrenal cryptococcosis was further supported by positive adrenal pus culture and significantly elevated capsular antigens in both serum and cerebrospinal fluid, at titers of 1:2560. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination.

Abstract Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Abstract Objective This study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals. Methods A total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agree Results Of the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus. Conclusion This study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.

Background: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. Methods: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). Results: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] − 5.4–27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI − 15.5–10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI − 1.5–8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. Conclusion: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required. [ABSTRACT FROM AUTHOR]

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals. Methods: A total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agree Results: Of the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus. Conclusion: This study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively. [ABSTRACT FROM AUTHOR]

Disseminated cryptococcosis, commonly linked to immunocompromised conditions like HIV infection, is exceedingly rare in immunocompetent individuals. This case report presents a rare case of disseminated cryptococcosis in an immunocompetent patient, who manifested with fever, weight loss, neurological manifestations, and distinct verrucous skin lesions. Mycological cultures and histopathological assessments were conducted, leading to the identification of Cryptococcus neoformans var. gattii within both lung and skin biopsies. This case highlights the significance of considering this yeast infection within immunocompetent individuals and the necessity for promptly initiating appropriate antifungal therapy to enhance patient outcomes.

Objective To explore the clinical features, diagnosis and treatment regimen of adrenal cryptococcosis so as to improve awareness of this disease for clinicians. Methods The clinical manifestations, laboratory indicators, imaging data and postoperative pathological results of a patient with adrenocortical insufficiency caused by Cryptococcus neoformans infection admitted to our hospital in June 2022 were collected and analyzed, and the related literature was reviewed. Results This patient presented with dizziness, fatigue, and multiple pigmentations throughout the whole body.Upper abdominal plain CT scan on June 24, suggested multiple nodular soft tissue shadows in the bilateral adrenal glands, and the scan on July 1 suggested mild inhomogeneous enhancement of bilateral adrenal nodules, which may be adrenal tumors.Retroperitoneal laparoscopic partial adrenalectomy was performed on July 13.Postoperative pathology indicated cryptococcosis.The antifungal treatment with itraconazole was stopped after 2 weeks by himself.In 3 months after the operation, CT revealed multiple adrenal masses on both sides, and itraconazole was taken again for treatment. Conclusion Patients with adrenal cryptococcosis usually have symptoms of adrenocortical insufficiency such as dizziness, fatigue, and multiple pigmentations throughout the whole body.Abdominal enhanced CT usually indicates adrenal nodules with inhomogeneous enhancement.The diagnosis depends on pathological examination, and antifungal therapy can be considered after adrenalectomy.

Cryptococcosis is a fungal infection that typically affects immunocompromised patients. It most commonly affects the lungs and may then disseminate to the central nervous system, bone, skin, and adrenal glands. Herein, we describe a 69-year-old man who presented with skin lesions as the initial manifestation of disseminated cryptococcosis. Initial workup led to an assumption that the patient was immunocompetent. Later in the clinical course, idiopathic depletion of CD4 T cells was discovered. This case highlights that disseminated cryptococcosis may present with cutaneous symptoms even when there is no evidence of pulmonary or central nervous system involvement and may be the first sign of an underlying cellular immune dysfunction.

Cryptococcosis is a systemic zoonotic disease that is challenging to diagnose based on clinical findings in cats and dogs due to the nonspecific nature of its clinical presentation. This case report aims to document the first confirmed case of disseminated cryptococcosis caused by Cryptococcus neoformans in a dog in Turkey and to highlight the potential link between natural disasters such as earthquakes and the emergence of zoonotic diseases in domestic animals. A two-and-a-half-year-old spayed female Cocker Spaniel presented with increased respiratory sounds, skin lesions, facial swelling and enlarged lymph nodes. These symptoms appear to be a complication of Demodex infestation due to the stress experienced by the dog following exposure to a severe earthquake. Diagnostic procedures including cytologic examination, fungal culture and DNA sequence analysis, which confirmed the infection was caused by C. neoformans. Due to the delay in the correct diagnosis of the disease, which, contrary to common data, started as an allergic reaction on the skin and was later diagnosed as a Demodex infestation, the dog died of severe respiratory failure during the treatment with itraconazole. The case highlights the critical role of veterinary emergency and critical care in the diagnosis and management of zoonotic diseases post-natural disasters. It also highlights the need for increased awareness and preparedness among veterinary professionals to address animal health challenges following such events. [ABSTRACT FROM AUTHOR]

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(1) Background: Cryptococcus neoformans is mostly known for causing meningitis, with or without disseminated disease. (2) Case presentation: An immunocompromised 75-year-old gentleman presented post renal transplant with generalized weakness, altered mental status, hypoxemia, and hyponatremia, and was found to have disseminated cryptococcal infection. After an initial improvement, the patient became suddenly hypotensive, and passed away soon after. The autopsy revealed widespread cryptococcal involvement, with the most severely affected organs being the brain, lungs, pancreas, adrenal glands, and spleen. The pancreas and one of the adrenal glands revealed diffuse granulomatous cryptococcal infection, with large areas of necrosis. The spleen also showed a large area of cryptococcal necrosis. In addition, the patient had chylous ascites, without histologically identifiable organisms. (3) Conclusions: This is a rare case of disseminated cryptococcal infection with severe necrotizing adrenalitis and pancreatitis, in addition to significant spleen, lung, and central nervous system involvement. The early recognition and treatment of the adrenal gland and pancreas cryptococcosis with surgical interventions may lead to better outcomes in affected patients. Furthermore, steroid treatment and diabetes mellitus may be risk factors for adrenal gland involvement. Additionally, clinicians should keep cryptococcal infection in their differential diagnosis for isolated adrenal gland and pancreas lesions. [ABSTRACT FROM AUTHOR]

A nearly 2‐year‐old, male, neutered pug was referred for a 1‐month duration of progressive gastrointestinal signs and lethargy, and possible seizure activity. Blood analyses before referral had shown marked increases in hepatocellular and hepatobiliary enzymes and increased pre‐prandial and post‐prandial bile acids, with normal bilirubin. Physical exam revealed a quiet mentation and blood analyses at the time of presentation found persistent increases in hepatic enzymes, and hypoalbuminaemia. Abdominal ultrasound identified intra‐abdominal free fluid and ileocolic lymphadenopathy. Cytology of the abdominal effusion, liver and abdominal lymph nodes identified organisms of the Cryptococcus genus. The dog had a positive Cryptococcus antigen lateral flow assay titre of 1:>10,000, confirming cryptococcosis. The dog was euthanased following diagnosis. This is the first report describing a case of disseminated cryptococcosis causing liver dysfunction in a veterinary species. Cryptococcus infection should be considered in a young dog presenting with gastrointestinal signs and liver enzymopathy. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a systemic zoonotic disease that is challenging to diagnose based on clinical findings in cats and dogs due to the nonspecific nature of its clinical presentation. This case report aims to document the first confirmed case of disseminated cryptococcosis caused by Cryptococcus neoformans in a dog in Turkey and to highlight the potential link between natural disasters such as earthquakes and the emergence of zoonotic diseases in domestic animals. A two-and-a-half-year-old spayed female Cocker Spaniel presented with increased respiratory sounds, skin lesions, facial swelling and enlarged lymph nodes. These symptoms appear to be a complication of Demodex infestation due to the stress experienced by the dog following exposure to a severe earthquake. Diagnostic procedures including cytologic examination, fungal culture and DNA sequence analysis, which confirmed the infection was caused by C. neoformans. Due to the delay in the correct diagnosis of the disease, which, contrary to common data, started as an allergic reaction on the skin and was later diagnosed as a Demodex infestation, the dog died of severe respiratory failure during the treatment with itraconazole. The case highlights the critical role of veterinary emergency and critical care in the diagnosis and management of zoonotic diseases post-natural disasters. It also highlights the need for increased awareness and preparedness among veterinary professionals to address animal health challenges following such events., Competing Interests: Declaration of competing interest The authors declared that there is no conflict of interest., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Key message Skin cryptococcosis often manifests as an umbilicated papule, and chest computed tomography findings of multiple nodules and cavities are also characteristic. The combination of characteristic cutaneous manifestations and radiological findings can help clinicians make an “at‐a‐glance” diagnosis of disseminated cryptococcosis.

Abstract Minimal invasive tissue sampling (MITS) technique detected HIV infection and disseminated cryptococcosis in an adult female with sudden death. A proper autopsy is essential to diagnose the exact cause of death and MITS can suffice in natural deaths.

A 49- year old immunocompetent male presented with a right flank abscess and was found to have disseminated cryptococcal disease. Treatment was initiated with a one-week intravenous regime of amphotericin B and flucytosine based on recent trial data that this is as effective, and less toxic, than the standard two weeks. After completion of intravenous treatment he was discharged with oral anti-fungals and is making a good recovery with ongoing follow up.

Abstract Background Transverse myelitis (TM) is due to inflammatory spinal cord injury with bilateral neurologic involvement, which is sensory, motor, or autonomic in nature. It may be associated with autoimmune disease, vaccination, intoxication and infections. The most common infection cause of TM is Coxsackie virus and Mycoplasma pneumoniae. The cryptococcosis is rare. We present the case of disseminated cryptococcosis revealed by transverse myelitis in an immunocompetent 55-year-old male patient. The literature review is also stated. Case presentation The 55-year-old man suffered from gradual numbness, weakness in both lower limbs and finally paralyzed in the bed. The thoracic spine Computed tomography (CT) was normal, but multiple nodules in the lung were accidentally discovered. Thoracic Magnetic Resonance Imaging (MRI) showed diffused thoracic spinal cord thickening and extensively intramedullary T2 hyper intensity areas. Gadolinium contrast enhanced T1WI showed an intramedullary circle-enhanced nodule at 9th thoracic level. Diagnosis was made by histological examination of the bilateral lung biopsy. The patient was treated successfully with systemic amphotericin B liposome and fluconazole and intrathecal dexamethasone and amphotericin B liposome. Conclusions This is a patient with disseminated cryptococcosis involving the lung, spinal cord and adrenal glands, which is rare in the absence of immunodeficiency.

(1) Background: Cryptococcus neoformans is mostly known for causing meningitis, with or without disseminated disease. (2) Case presentation: An immunocompromised 75-year-old gentleman presented post renal transplant with generalized weakness, altered mental status, hypoxemia, and hyponatremia, and was found to have disseminated cryptococcal infection. After an initial improvement, the patient became suddenly hypotensive, and passed away soon after. The autopsy revealed widespread cryptococcal involvement, with the most severely affected organs being the brain, lungs, pancreas, adrenal glands, and spleen. The pancreas and one of the adrenal glands revealed diffuse granulomatous cryptococcal infection, with large areas of necrosis. The spleen also showed a large area of cryptococcal necrosis. In addition, the patient had chylous ascites, without histologically identifiable organisms. (3) Conclusions: This is a rare case of disseminated cryptococcal infection with severe necrotizing adrenalitis and pancreatitis, in addition to significant spleen, lung, and central nervous system involvement. The early recognition and treatment of the adrenal gland and pancreas cryptococcosis with surgical interventions may lead to better outcomes in affected patients. Furthermore, steroid treatment and diabetes mellitus may be risk factors for adrenal gland involvement. Additionally, clinicians should keep cryptococcal infection in their differential diagnosis for isolated adrenal gland and pancreas lesions.

A 78-year-old man developed disseminated cryptococcosis with central nervous system involvement as encapsulated yeast cells were detected in transbronchial biopsy and skin biopsy specimens, and cerebrospinal fluid. Cryptococcus neoformans was confirmed by culture. He had been treated with low-dose prednisolone and methotrexate for rheumatoid arthritis. He started receiving antifungal therapy with intravenous liposomal amphotericin B followed by oral fluconazole. Methotrexate was discontinued. Approximately 4 months after the course of intravenous liposomal amphotericin B was completed, he complained of pain and swelling of the right wrist, which suggested that rheumatoid arthritis was worsening. Abatacept therapy was initiated along with antifungal therapy, and his symptoms relieved. After 24 months of antifungal therapy, although he was still receiving oral fluconazole, he was doing well and the serum cryptococcal antigen had become negative. Disseminated cryptococcosis is an important opportunistic infection associated with low-dose methotrexate for rheumatoid arthritis. Abatacept therapy may be feasible in strictly selected patients with rheumatoid arthritis complicated with cryptococcosis concomitantly with intensive anti-fungal therapy. [ABSTRACT FROM AUTHOR]

Disseminated cryptococcosis primarily affects immunosuppressed patients and has a poor outcome if diagnosis and treatment are delayed. Skin lesions are rarely manifest causing misdiagnosis. We present a case of cryptococcal cellulitis with severe pain in a kidney transplant recipient on long-term immunosuppressive therapy. Multiple organs were involved, and there was cutaneous dissemination of the lesions. Histopathology revealed abundant yeast-like cells with wide capsular halos in subcutaneous tissue, suggesting Cryptococcus spp. infection. Laser capture microdissection (LCM)-PCR on skin biopsies confirmed Cryptococcus neoformans var. grubii. A literature review of 17 cases of disseminated cryptococcosis with cutaneous cellulitis or panniculitis in HIV-negative individuals found that over half the patients (52.9%, 9/17) had a history of glucocorticoid therapy, and that the most common site was the legs (76.5%, 13/17). C. neoformans was the main pathogenic species, accounting for 88.2% (15/17) of cases. Fungal cellulitis should be included in the differential diagnosis of cellulitis that fails to respond to antimicrobial therapy in HIV-negative immunosuppressed individuals. Non-culture-based molecular techniques aid in rapid pathogen identification in histologically positive, unculturable specimens. [ABSTRACT FROM AUTHOR]

Cryptococcal disease is a rare but often serious infection in solid organ transplant recipients, commonly presenting as meningitis and pneumonia but can rarely cause myositis. We report the case of a 43‐year‐old female kidney transplant recipient with two previous graft failures requiring re‐transplantations who presented with a 1‐month duration of worsening unilateral leg pain, swelling, and shortness of breath. Blood cultures isolated Cryptococcus neoformans. A calf biopsy was performed and histopathology revealed myonecrosis with yeast forms consistent with Cryptococcus spp. Liposomal amphotericin B (LamB) was administered. Her course was complicated by hypoxemic respiratory failure with development of ground glass opacities on chest imaging. Work‐up revealed bacterial and C neoformans pneumonia and probable Pneumocystis jirovecii pneumonia (PJP) She received trimethoprim‐sulfamethoxazole and LamB and was discharged on fluconazole. Shortly thereafter she was re‐admitted with confusion, septic shock, and multi‐organ failure. Work‐up revealed PJP with subsequent development of cryptococcal meningitis. Despite aggressive management, she expired. Disseminated cryptococcal infection may manifest as myositis. Presence of cryptococcal infection is a marker of severe net state of immunosuppression (IS), hence, presence of other opportunistic infections is likely. Early recognition of cryptococcal infection, institution of targeted therapy, and IS reduction are important to improve overall survival. [ABSTRACT FROM AUTHOR]

Minimal invasive tissue sampling (MITS) technique detected HIV infection and disseminated cryptococcosis in an adult female with sudden death. A proper autopsy is essential to diagnose the exact cause of death and MITS can suffice in natural deaths. [ABSTRACT FROM AUTHOR]

This article discusses a case of disseminated cryptococcosis in an 88-year-old man who had previously received high-dose systemic steroid therapy for severe COVID-19 pneumonia. The patient developed swelling and redness in his left arm and was found to have Cryptococcus neoformans in his blood sample. Despite antifungal therapy, the patient passed away. The article emphasizes the importance of monitoring patients treated with steroids for COVID-19 and highlights the potential risks of prolonged immunosuppression. It also mentions that high-dose systemic steroid therapy has been used in Japan for severe lung diseases, including COVID-19, but its effectiveness and safety have not been established. [Extracted from the article]

Hypogammaglobulinemia is a rare complication of STAT1 gain-of-function (GOF) mutations. We report an adult patient diagnosed with hypogammaglobulinemia caused by B-cell depletion during the treatment of disseminated cryptococcosis. The patient carried the STAT1 GOF mutation (c.820C>T, p.R274W). The flow cytometric analysis of his bone marrow revealed that B-cell differentiation was blocked in the stages between pre-B1b and pre-B2 cells. On the other hand, his brother who carried the same mutation displayed normal B-cell counts, thereby indicating that the unrecognized variants in same or other gene might be associated with abnormal B-cell differentiation in the patients. In conclusion, impaired B-cell differentiation in the bone marrow can cause hypogammaglobulinemia in patients with STAT1 GOF mutations.

X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of patients to disseminated cryptococcal infections primarily due to CD40L deficiency that causes defective cross talk between T- and B-cells, thus preventing class switching. In HIGM syndrome, serum IgM levels are elevated with severe reduction in serum immunoglobulin G (IgG) and IgA levels. In addition, the expression of CD40L (CD154) on in vitro-activated T-cells is severely reduced or absent. Here, we describe a rare, and perhaps, the first reported case in India of a 3-year-old male child with X-linked HIGM immunodeficiency syndrome who developed disseminated Cryptococcosis. Evaluation of the serum IgG profile of the patient revealed increased serum IgM levels with reduced IgG and IgA levels. Both the frequency and the function of T-cells, primarily CD40L on activated T-cells, showed weak expression suggestive of HIGM syndrome.

Disseminated cryptococcosis, usually involving the lungs and central nervous system, carries a high risk of morbidity and mortality in immunocompromised hosts. In this report, we describe a case of miliary pulmonary cryptococcosis in a patient with acute myeloid leukemia, initially resembling miliary tuberculosis. The diagnosis of disseminated cryptococcosis was made based on transbronchial lung biopsy with subsequent detection of Cryptococcus neoformans in blood and cerebrospinal fluid. The patient was treated with liposomal amphotericin B as induction therapy, followed by fluconazole as consolidation and maintenance therapies thereafter. The infection was improved immediately, and he successfully underwent hematopoietic stem cell transplantation. The present case serves as a timely reminder that a radiological miliary pattern necessitates a thorough search for a definitive microbiological and histopathological diagnosis. [ABSTRACT FROM AUTHOR]

Hypogammaglobulinemia is a rare complication of STAT1 gain-of-function (GOF) mutations. We report an adult patient diagnosed with hypogammaglobulinemia caused by B-cell depletion during the treatment of disseminated cryptococcosis. The patient carried the STAT1 GOF mutation (c.820C>T, p.R274W). The flow cytometric analysis of his bone marrow revealed that B-cell differentiation was blocked in the stages between pre-B1b and pre-B2 cells. On the other hand, his brother who carried the same mutation displayed normal B-cell counts, thereby indicating that the unrecognized variants in same or other gene might be associated with abnormal B-cell differentiation in the patients. In conclusion, impaired B-cell differentiation in the bone marrow can cause hypogammaglobulinemia in patients with STAT1 GOF mutations. [ABSTRACT FROM AUTHOR]

Background: Transverse myelitis (TM) is due to inflammatory spinal cord injury with bilateral neurologic involvement, which is sensory, motor, or autonomic in nature. It may be associated with autoimmune disease, vaccination, intoxication and infections. The most common infection cause of TM is Coxsackie virus and Mycoplasma pneumoniae. The cryptococcosis is rare. We present the case of disseminated cryptococcosis revealed by transverse myelitis in an immunocompetent 55-year-old male patient. The literature review is also stated.Case Presentation: The 55-year-old man suffered from gradual numbness, weakness in both lower limbs and finally paralyzed in the bed. The thoracic spine Computed tomography (CT) was normal, but multiple nodules in the lung were accidentally discovered. Thoracic Magnetic Resonance Imaging (MRI) showed diffused thoracic spinal cord thickening and extensively intramedullary T2 hyper intensity areas. Gadolinium contrast enhanced T1WI showed an intramedullary circle-enhanced nodule at 9th thoracic level. Diagnosis was made by histological examination of the bilateral lung biopsy. The patient was treated successfully with systemic amphotericin B liposome and fluconazole and intrathecal dexamethasone and amphotericin B liposome.Conclusions: This is a patient with disseminated cryptococcosis involving the lung, spinal cord and adrenal glands, which is rare in the absence of immunodeficiency. [ABSTRACT FROM AUTHOR]

Disseminated cryptococcosis, commonly linked to immunocompromised conditions like HIV infection, is exceedingly rare in immunocompetent individuals. This case report presents a rare case of disseminated cryptococcosis in an immunocompetent patient, who manifested with fever, weight loss, neurological manifestations, and distinct verrucous skin lesions. Mycological cultures and histopathological assessments were conducted, leading to the identification of Cryptococcus neoformans var. gattii within both lung and skin biopsies. This case highlights the significance of considering this yeast infection within immunocompetent individuals and the necessity for promptly initiating appropriate antifungal therapy to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Disseminated cryptococcosis is a rare and fatal disease, and limited data exist regarding it in children. This study aimed to investigate the clinical characteristics of disseminated cryptococcosis in previously healthy children in China. Methods Hospitalized patients with disseminated cryptococcosis were enrolled during January 1996 to December 2015 in Beijing Children’s Hospital, Capital Medical University, China. Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated. Results A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls. Only 10 cases had a history of exposure to pigeon droppings. Fever, cough, and hepatomegaly were 3 main manifestations of disseminated cryptococcosis. However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P

Background: Cryptococcal infections have been mostly associated with immunocompromised individuals, 80–90% of whom have been HIV-positive patients. Increasingly, cryptococcal infections are being reported in cirrhotic patients who are HIV-negative. The underlying immunologic defects in cirrhotic patients seem to play an important role in predisposing them to cryptococcosis and affecting their morbidity and mortality. Case presentation: We present a case of disseminated cryptococcosis in an HIV-negative patient with underlying cirrhosis, who had rapid worsening of his hyponatremia with renal failure and was unable to recover, despite aggressive measures. Conclusion: Cryptococcus is a more common culprit of infections seen in cirrhotic patients than what it was previously known, and a high index of suspicion is required to diagnose these patients. Identification of poor prognostic factors, early diagnosis and intervention is crucial in the management of these patients.

Cryptococcus neoformans is an encapsulated yeast found worldwide.1 Patients with immunosuppression, including individuals with HIV/AIDS, transplant recipients and/or individuals with other T-cell mediated immunosuppression are more susceptible to becoming infected with Cryptococcus neoformans than immunocompetent individuals.2 This is a case report of a 66-year-old woman who presented to the emergency department with an unsteady gait and urinary incontinence. Magnetic resonance imaging (MRI) on presentation showed a large C5-C6 central disc protrusion. The patient underwent surgical repair and was treated with five days of IV steroids. Later in the course of her hospitalization, she had an unexplained increasing leukocytosis and tachycardia with witnessed episodes of unresponsiveness. She subsequently had a pulseless electrical activity cardiac arrest and succumbed despite resuscitative efforts. A post-mortem diagnosis revealed Cryptococcus neoformans fungemia and disseminated cryptococcosis involving multiple organs. Disseminated cryptococcosis primarily affects the central nervous system3, and thus this report presents a rare case of disseminated cryptococcosis involving multiple organs. [ABSTRACT FROM AUTHOR]

A 49- year old immunocompetent male presented with a right flank abscess and was found to have disseminated cryptococcal disease. Treatment was initiated with a one-week intravenous regime of amphotericin B and flucytosine based on recent trial data that this is as effective, and less toxic, than the standard two weeks. After completion of intravenous treatment he was discharged with oral anti-fungals and is making a good recovery with ongoing follow up. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a systemic mycosis caused by yeast like fungus Cryptococcus neoformans. The infection results from inhalation of fungal spores in soil, house dust and in pigeon and other bird excreta. Infection usually occurs in immunocompromised individuals with lung and central nervous system being common sites of involvement. Skeletal involvement usually occurs as a component of disseminated cryptococcosis. Isolated skeletal involvement is rare. Here, the author presents a case of isolated skeletal cryptococcosis in an immunocompetent patient who presented with severe back pain and leg pain. Possibility of Tuberculosis of spine was suggested clinically but histopathology showed cryptococcal granulomas. Patient was HIV seronegative and did not have any other co-morbid conditions. There were no lesions in lung or brain. Because of increasing incidence of crytpococcal infections in immunocompetent hosts it should be included in the differential diagnosis of tuberculosis. Spine and fungal cultures should also be done. In the absence of fungal cultures, histopathological examination including the special stains is useful for diagnosis.

Abstract We report a case of disseminated cryptococcosis in a 42-year old immunocompetent female. Prior to admission at Bugando Medical Center, the patient was attended at three hospitals for hypertension and clinically diagnosed malaria. Following diagnosis of disseminated Cryptococcus at our center, she was successfully treated with fluconazole but remained with visual loss. Blood cultures should be considered in the management of any adult presenting with fever to enable early detection of the least expected differentials like in this case. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a fungal disease which has been characterized by its identified risk groups. There are many risk factors identified. We present a surprising four cases of disseminated cryptococcosis in intravenous drug abuse (IVDA) patients in a short period of time and in one geographical area, this observation suggest that there may be a new association with IVDA and cryptococosis.

Disseminated cryptococcosis is infrequent in immunocompetent children. Pulmonary and central nervous system are the commonly involved sites of infection in an immunocompromised host. We report a fatal case of disseminated cryptococcosis in an immunocompetent host presenting as fever of unknown origin with miliary shadows on chest radiograph, mimicking tuberculosis. In countries with the heavy burden of tuberculosis, a high index of suspicion is needed for early diagnosis of its close mimics like disseminated cryptococcosis. [ABSTRACT FROM AUTHOR]

Purpose. A case report of fatal disseminated cryptococcosis in a patient treated with eculizumab is presented along with a review of literature suggesting a possible etiologic mechanism. Summary. A 23-year-old man with a history of minimal change nephrotic syndrome was hospitalized for acute kidney injury and abdominal pain and swelling. He was found to have disseminated pneumococcal disease, including peritonitis, bacteremia, and pulmonic endocarditis. The patient developed evidence of microangiopathic hemolytic anemia, leading to a diagnosis of atypical hemolytic uremic syndrome, and was started on eculizumab. The patient initially improved but developed septic shock 18 days after the first dose of eculizumab. All subsequent blood, respiratory, and intraabdominal cultures grew Cryptococcus neoformans. Twenty-eight days after the initial dose of eculizumab, the patient died. Autopsy findings demonstrated disseminated cryptococcosis, with infection noted in lung, myocardial, kidney, and liver tissues. Considering the complementdependent nature of host defenses against Cryptococcus species and available evidence regarding C. neoformans pathogenicity from studies of murine models, it was hypothesized that the patient's cryptococcosis and death were secondary to administration of eculizumab and consequent blockage of the C5 component of the complement cascade. Eculizumab is known to predispose recipients to infections with encapsulated organisms; however, this was believed to be the first reported case of infection with an encapsulated yeast possibly due to eculizumab use. Patients receiving eculizumab should be monitored closely for invasive cryptococcal infections. Conclusion. A 23-year-old man developed fatal disseminated cryptococcosis after treatment with eculizumab. [ABSTRACT FROM AUTHOR]

Infections occur more frequently in patients receiving biologics. However, cryptococcal infection is uncommon in patients receiving tocilizumab, an interleukin-6 inhibitor, in contrast to patients receiving tumor necrosis factor-α inhibitors. In this report, we describe a case of disseminated cryptococcosis in a 55-year-old man who was receiving tocilizumab every 2 weeks along with daily prednisolone and cyclosporine for Castleman's disease. He initially developed cellulitis on both upper limbs, and his condition worsened despite antibacterial therapy. Chest X-ray scanning and computed tomography demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was detected in blood, skin, and sputum cultures. He was diagnosed with disseminated cryptococcosis, and successfully treated with liposomal amphotericin B for a week followed by oral fluconazole for 11 months. The findings of this study indicate that cryptococcosis should be considered during the differential diagnosis of infection in patients receiving tocilizumab, especially in the presence of other risk factors for infections or a short tocilizumab dosing interval. [ABSTRACT FROM AUTHOR]

Key message: Skin cryptococcosis often manifests as an umbilicated papule, and chest computed tomography findings of multiple nodules and cavities are also characteristic. The combination of characteristic cutaneous manifestations and radiological findings can help clinicians make an "at‐a‐glance" diagnosis of disseminated cryptococcosis. [ABSTRACT FROM AUTHOR]