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Microscopic photographs of Cryptococcus neoformans . A) Gray, mucoid colonies, highly suspicious of Cryptococcus spp., growing in solid media. B) Direct examination of colonies in suspension.
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Background
Cryptococcal meningoencephalitis is an opportunistic infection that predominantly affects immunocompromised patients. Hyper immunoglobulin M syndrome is a primary immunodeficiency syndrome that increases susceptibility to several opportunistic infections. Here, we report a case of cryptococcal meningoencephalitis in the context of hyper...
Similar publications
Cryptococcosis is a global invasive mycosis, commonly encountered in patients with HIV/AIDS with low CD4 counts, diabetics, organ and stem-cell transplant recipients , malignancies, and other patients with immuno-suppression. The presentation depends on which organ is usually involved although multi-organ involvement may be present. Here, we descri...
Introduction:
Cryptococcal meningoencephalitis is a life-threatening disease affecting mainly immunocompromised hosts.
Case report:
We present a case of a 64-year-old immunocompetent patient, who initially developed a traumatic scalp skin infection due to Cryptococcus neoformans. The patient received oral fluconazole and subsequently liposomal a...
Cryptococcal meningitis is a common opportunistic infection in HIV-infected patients and other immunocompromised people. Pregnancy, which is a state of relative immunosuppression, can also be a risk factor for the development of cryptococcal meningitis. We report a clinical case of a 41-year-old woman who developed a severe meningeal syndrome after...
We describe a case of Cryptococcal choroiditis in a person with advanced HIV/AIDS. A 29-year-old male with AIDS presented with fever, photophobia, and ataxia secondary to cryptococcal and toxoplasma meningoencephalitis. Dilated fundoscopic examination revealed bilateral and multifocal posterior infiltrates consistent with cryptococcal choroiditis....
Cryptococcal meningitis is being increasingly described in immunocompetent adults. We describe here a young immuncompetent adult of Indian origin from Ghana, West Africa with cryptococcal meningitis who had several ups and downs during his treatment. First he developed neurologic worsening due to premature transition from intensive to consolidation...
Citations
... The molecularly defined IEI associated with severe or disseminated cryptococcosis strikingly overlap with those that predispose one to infection with TDEF, namely, MSMD [253][254][255], GATA2 [174,176], CD40L deficiency [163,[256][257][258][259][260][261][262][263], STAT1 GOF [47,264,265], and DN-STAT3 [266,267]; these IEI have been detailed above. This overlap most likely reflects a comparable, if not homologous, immunopathophysiology ( Figure 2). ...
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases.
... Clinically, CD40 deficiency is similar to CD40L deficiency, especially with regards to pathogen susceptibility [25]. The main clinical features of CD40L defect are early onset of infectious complications, recurrent sinopulmonary infections, mainly due to encapsulated bacteria, and susceptibility to opportunistic infections caused by Pneumocystis, Cryptosporidium, Mycobacteria, Cytomegalovirus (CMV), Toxoplasma and Cryptococcus [25][26][27][28][29][30][31][32][33][34]. Cryptosporidium parvum-related biliary disease can be fatal, resulting in sclerosing cholangitis or cholangiocarcinoma [25]. ...
B cells and antibodies are indispensable for host immunity. Our understanding of the mechanistic processes that underpin how B cells operate has left an indelible mark on the field of clinical pathology, and recently has also dramatically reshaped the therapeutic landscape of diseases that were once considered incurable. Evaluating patients with primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) that primarily affect B cells, offers us an opportunity to further our understanding of how B cells develop, mature, function and, in certain instances, cause further disease. In this review we provide a brief compendium of IEI that principally affect B cells at defined stages of their developmental pathway, and also attempt to offer some educated viewpoints on how the management of these disorders could evolve over the years.
... Cryptococcal meningoencephalitis (CM) can cause significant morbidity and mortality in previously healthy, non-HIV-infected patients, with all-cause mortality as high as 29% at 1 year (22). Today, a few cases of CM in CD40 deficiency patients are reported in the literature (6)(7)(8)(9). ...
The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.
... To the best of our knowledge, this is the first reported case of cryptococcal meningitis in a patient with HIGM due to CD 40 deficiency. One other case has previously been reported in a patient with HIGM due to CD40 L deficiency (Malheiro et al., 2014). ...
... With these immunological abnormalities, patients with CD40 deficiency will be more susceptible to fungal infection since there isaltered generation of TH1 cells that are normally responsible for stimulating phagocytic activity towards fungal infections. As a consequence, the immune reaction will be less severe, with reduced immune activation and migration and fewer symptoms that are typically associated with meningeal inflammation (Malheiro et al., 2014) Current guidelines for cryptococcal treatment recommendstarting Amphotericin B and Flucytosine. In our case, these were effective therapies against Cryptococcus neoformans evidenced by the clinical improvement and the negative LP after completion of treatment (Perfect et al., 2010). ...
... Although this treatment was effective, there is no consensus on the appropriate duration for maintenance therapy. The previously reported HIGM patients with this infection were treated similar to HIV patients with cryptococcal infection (Lee et al., 2001;Jo et al., 2002;Malheiro et al., 2014). In the HIV setting, there is evidence that maintenance therapy should be kept until an immunologic improvement, characterized by CD4+ T-cells > 100/µL for more than 3 months, is achieved (Levy et al., 1997). ...
Hyper-IgM syndrome (HIGM) due to CD40 deficiency is a very rare form of combined immunodeficiency with increased susceptibility to opportunistic infections. Cryptococcus is an opportunistic infection usually affecting immunocompromised individuals. This is the first report to describe a patient with HIGM due to CD40 deficiency presenting with meningoencephalitis secondary to Cryptococcus infection. © 2019 Maram Al-Banyan, Abdulhadi Alqahtani, Farrukh Sheikh, Agha M. Rehan Khaliq, Hasan Al Rayes, Ashraf Al-Tarifi, Bandar Al-Saud and Rand K. Arnaout.
... C. neoformans and C. gattii are the two species pathogenic for humans. Cryptococcosis has further been reported in patients with idiopathic CD4 T cell lymphopenia, XL HIGM syndrome, AD HIES, and GATA2 deficiency [50,63,78,[95][96][97][98][99][100][101][102][103]. In some of these patients, the infection only manifested as lymph node infiltrate, but mostly it affected the CNS as meningoencephalitis. ...
Purpose of Review
In this review, we focus on the inborn errors of immunity known to render the host susceptible to fungal infections, including candidias, aspergillosis, dermatophytosis, phaeohyphomycosis, pneumocystosis, fusariosis, cryptococcosis, and endemic mycoses.
Recent Findings
Classically, the burden of fungal disease in humans is believed to be carried by patients with a secondary immunodeficiency, either due to malignancy, to chemotherapy, to an immunocompromised state post hematopoietic stem cell transplantation, or to treatment with anti-cytokine therapies. However, in the last decade, the study of patients affected by fungal infections without any overt risk factors has led to the unraveling of several monogenic defects of human immunity to fungi. The study of these inborn errors of immunity has added vastly to our comprehension of antifungal immunity. For example, the role of IL-17 immunity in human defense against mucocutaneous candidiasis has been extensively characterized through the analysis of IL-17F, IL-17RA, IL-17Rc, ACT1, RORγT and, indirectly, CARD9 deficiency.
Summary
Many monogenic causes of susceptibility to superficial and/or invasive fungal infections have been recently unraveled. Most of these inborn errors of immunity associate with a specific type of fungal infection, and such a defect should always be suspected and sought in patients affected by fungal infection in the absence of predisposing factors.
... Here, experiments using cryptococcal polysaccharide to stimulate white cells were also performed to refute Cryptococcus as the cause of these autoimmune phenomena [9]. Recently, a case of cryptococcosis was also reported in the setting of HyperIgM syndrome [9,12] and in a patient with a known "Jak3" gene mutation with severe combined immunodeficiency [13], raising an alert for physicians managing patients with primary immunodeficiencies. ...
Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, and identified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogen has now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized as an opportunistic infection and was first noted to be associated with reticuloendothelial cancers in the 1950s. Since then, advances in transplant immunology, medical science and surgical techniques have led to increasing numbers of solid organ transplantations (SOT) and hematological stem cell transplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally, however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease, environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis.
X-linked hyper IgM (X-HIGM) syndrome is a combined immunodeficiency disease caused by mutations in the CD40LG gene, leading to a defect in immunoglobulin (Ig) class switching recombination and effector T-cell responses. X-HIGM patients usually present in early life with pyogenic bacterial and opportunistic infections. Herein, we report a previously healthy 13-year-old Thai boy who first presented with cutaneous and meningoencephalitis cryptococcosis. Whole-exome sequencing revealed that he was hemizygous for a missense c.514T>C (p.Tyr172His) in CD40LG, confirming a diagnosis of X-HIGM. This report demonstrates that X-HIGM could have an age of onset in teens and systemic cryptococcosis could be its presenting symptoms.
Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.
We report a case of cutaneous cryptococcosis due to Cryptococcus neoformans in a pediatric patient with hyper IgM syndrome with scalp lesions that resembled tinea capitis on gross examination and mimicked juvenile xanthogranuloma on histologic examination. This case highlights the importance of considering cutaneous cryptococcosis in patients with hyper IgM syndrome.
IFIs are important causes of morbidity and mortality in patients with either primary or acquired immunodeficiency. A wide spectrum of invasive mold and yeast infections are variably implicated depending on the type of immune deficit. A high index of suspicion is needed as prompt diagnosis of IFIs remains a challenge. Establishment of diagnosis is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic methods (e.g. serum biomarkers such as 1,3-β-D-glucan or galactomannan) and high-resolution radiological imaging has improved our diagnostic evaluation. The antifungal armamentarium has expanded rapidly in the past few decades.
