Importance of Candida related Histamine release
High levels of histamine are not healthy, one reason for this is because it opens the blood brain barrier. This can allow Candida, or at least the toxins it produces, into the brain. Although the causes behind it aren't clear, Candida can cause meningitis, something that is recognized by the Meningitis Research Foundation (
http://www.meningitis.org/disease-info/types-causes/fungal). Due to the link between Candida overgrowth and Histamine intolerance, and the interaction between them just worsens symptoms until a diet that doesn't feed Candida is adopted.
Overview of Fungal Meningitis (Gottfredsson, Magn?s, and John Perfect. "Fungal Meningitis.")
"Fungal infections have increased in incidence. This increase is attributed to an enlarging population of high-risk immunosuppressed patients, which is due in part to more successful pharmacological immunosuppression and chemotherapies and the frequent use of antibacterial and antiviral therapies. In addition, large numbers of patients living with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) develop life-threatening fungal infections during the course of their illness. As a result of these trends, central nervous system (CNS) infections caused by opportunistic fungal pathogens are becoming increasingly relevant. In addition, seemingly immunocompetent individuals can acquire these CNS infections with fungi.
In the majority of cases the fungus appears to seed the CNS hematogeneously, usually from a pulmonary focus of infection but occasionally from extracranial sites such as infective endocarditis. Direct extension of fungal infections involving the cranial bones or sinuses into the subarachnoid space has also been described, usually causing basal meningitis or mass lesions. For clinicians, the varied clinical presentations of fungal meningitis and its possible concomitant brain parenchymal involvement constitute a major diagnostic challenge, because the yield of traditional diagnostic methods, such as culture, may not routinely be positive. Moreover, as more potential treatment options for these CNS infections become available, a timely and accurate diagnosis is crucial to improve prognosis for these seriously ill patients. In this review, we examine the topic of fungal infections of the meninges in both a general and a fungus-specific format...
The brain and the subarachnoid space are considered immunologically sequestered sites. The subarachnoid space has anatomic and functional barriers that exclude or modify immune responses. Except for the apparent neurotropism of C. neoformans, it remains unclear why this fungus uniquely invades this privileged sanctuary and what factors possessed by the fungus allow it to do so. On the other hand, although some patients with fungal meningitis have no overt immune defect or underlying disease, most patients with this infection have some predisposing factors or immune abnormalities that allow invasion by these low-virulent pathogens.
Certain clinical conditions have been identified that lead to failure of these host defenses. For example, direct inoculation of fungi into the brain following head injuries or neurosurgical procedures is an easily defined pathological mechanism. However, there can be subtle local immune cell dysregulation that allows establishment of meningitis; for instance, development of suppressor T cells in cerebrospinal fluid (CSF) has been observed in a case of Histoplasma meningitis. Even potent antibacterial regimens may be a contributing factor to Candida meningitis. Corticosteroid treatment is a risk factor for fungal meningitis, and C. neoformans is the most prominent fungus complicating corticosteroid use. The host immune responses and underlying disease are not only the major factors in the pathogenesis of these infections but also the most significant determinants of outcome in the patients.
All types of invasive infections with C. albicans and other Candida species are increasing in prevalence. The clinical symptoms of Candida meningitis are highly variable and can range from acute to chronic in nature, with headache and fever the most common clinical manifestations. In patients with Candida meningitis without concomitant HIV infection, [neck] rigidity is also commonly detected. Almost all of these patients have also received broad-spectrum antibacterial agents and in some reports have had an antecedent bacterial meningitis. In rare circumstances, Candida species can invade the subarachnoid spaces from the sinuses and the adjacent bone. This is generally associated with an anatomic defect. Intracranial extension of the Candida infection can lead to arteritis within the CNS and subarachnoidal hemorrhage.
All Candida meningitis cases should be aggressively treated. The mortality for Candida meningitis with treatment has been reduced to 10 to 20%. The combination of amphotericin B and flucytosine is attractive as the regimen of choice because this combination has synergistic activity against Candida in vitro and flucytosine immediately reaches high concentrations in the CSF. Clinical experience suggests that this combination provides an excellent cure rate."
Pathology of fungal meningitis (S?nchez?Portocarrero, Jorge, et al. "The Central Nervous System and Infection by Candida Species.")
"When the CNS is involved in patients with systemic candidiasis, several clinical manifestations can be overlooked due to the severity of the patient?s situation. The decrease in the level of consciousness is the most frequent manifestation of CNS candidiasis. Often, not much attention is given to this manifestation when we come across septic patients suffering from severe illnesses in intensive care units, patients undergoing invasive procedures or sedated on drugs. Studies of the brain of patients who died from systemic candidiasis have concluded that up to 50% had CNS invasion by Candida species. However, these patients were rarely diagnosed when alive because of the lack of clinical manifestations.
Recently, Candida species have been considered to be responsible for other neurologic clinical manifestations besides decreasing the level of consciousness. We therefore think that it is necessary to review the full and constantly changing spectrum of neurologic pathology caused by this microorganism. The physiopathology of Candida CNS involvement varies according to the clinical setting. When systemic candidiasis is prolonged, it can affect the CNS and induce diffuse encephalopathy with diminished consciousness in which the predominant lesions are microabscesses. These have been reproduced experimentally by introducing C. albicans into the internal carotid of rats, thus simulating candidemia.
Pathologic findings are many. Microabscesses are usually found in the joint between the gray and white matters and they are widely spread in the CNS, being the basal ganglia and the cerebellum the sites more frequently involved. Other findings are macroabscesses and lesions of vascular origin such as cerebral infarcts by vasculitis or mycotic aneurysms. Up to 23% of patients with CNS candidiasis in necropsy studies may have evidence of vascular invasion, either in the vascular wall itself or with invasion of the arterial lumen. When cerebral ischemic damage exists, the infarcts are usually found in the basal ganglia. Old vascular lesions such as operated subdural hematoma can be infected by Candida species (Lipton et al., 1984). In general, these vascular complications seem to have a less important clinical role, although invasion of the arteries at the base of the brain by the fungus can produce transitory or permanent neurologic deficits. Microabscesses cannot generally be seen on the cranial CT scan. They can be observed using magnetic resonance (MR) imaging, where they are seen as small enhanced ring lesions with a hemorrhagic component and widely spread in the brain."
