Candidiasis

Introduction to candidiasis Candida species can cause a variety of clinical syndromes, collectively known as candidiasis, which are usually classified according to the affected site. In general, the two most common syndromes are mucosal cutaneous candidiasis (such as oropharyngeal candidiasis or thrush, esophagitis and vaginitis) and invasive or deep organ candidiasis (such as candidemia, Chronic disseminated or hepatic spleen candidiasis, endocarditis and endophthalmitis). In most patients, candidiasis is an opportunistic infection. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: contact infection Complications: pneumonia, renal failure, gastrointestinal bleeding

Cause of candidiasis

(1) Causes of the disease

Among the more than 190 species of Candida species known, C. albicans is the most frequently detected pathogen in humans, and other clinically significant species still have Candida tropicalis (C. Tropicalis), C. parapsilosis, C. glabrata, C. krusei, C. pseudogealis, Rush rosary C. lusitaniae and C. guilliermondii, etc., Candida fungi have bimorphic characteristics: small globular yeast type (4-6 m size) which is propagated by budding and close in the middle A pseudohyphal (faux mycelium) type in which the yeast is chain-extended. In the body fluid or tissue, both the budding yeast cell type and the pseudohyphae fragment are visible, and the microbiology laboratory identification of the genus Candida And species classification (speciation), based on both morphological characteristics and results of metabolic tests, Candida albicans has the ability to produce germ tubes, which can be used as a marker for identification, using Candida CHROM - Agar color-producing medium, which helps to culture specimens from a single species Urine or blood) to identify a variety of different type of yeast Candida albicans can quickly make a non-conclusion.

(two) pathogenesis

Several components of the host defense system have important protective significance against the infection of Candida species. The intact skin and mucosal surface barrier can prevent the invasion of normal resident Candida with adhesion characteristics, due to percutaneous cannulation. Intratracheal indwelling catheters, severe burns or abdominal surgery, etc., leading to normal barrier damage or loss of function, a common cause of Candida infection, especially deep or disseminated candidiasis, polymorphonuclear leukocytes and monocytes For the main cell defense system against Candida species; for the killing of Candida through the oxidant-dependent and - independent effector mechanism, although not fully elucidated, tissue macrophages Lymphocytes and cell-mediated immunity also play a role in the elimination of Candida. Host defense functions include T cell dysfunction, causing mucosal skin lesions (such as oropharyngeal or esophageal candidiasis in HIV-infected individuals) and chronic The cause of mucosal cutaneous candidiasis, which is secondary to candidiasis (secondary candidiasis) Related causes of beademia or invasive candidiasis, histopathology of chronic dermatitis of cutaneous candidiasis, characterized by yeast-type Candida stagnation in the stratum corneum, and conversely, visceral candida Pathological examination of the disease is characterized by microabscess spread in normal tissues. The initial stage of the inflammatory response is neutrophils, followed by tissue cells and giant cells, sometimes granulation can occur very quickly. Swelling, severe immune-impaired patients, the inflammatory response may be mild or absent, and special staining with periodic acid Schiff or Gomori urotropine, the yeast type and pseudohyphal type of Candida, Usually visible.

Candidiasis prevention

On the basis of the increasing incidence and potential severity of candidemia in hospitals, it is important to raise awareness and take targeted preventive measures, and the frequency and duration of use of endovascular catheterization and monitoring devices should be reduced. In particular, attention should be paid to the long-term indwelling catheter pathway for surgical implantation for chemotherapy or other purposes. At the same time, the number of antibiotics used, the duration of the variety and duration of treatment should be reduced, and antifungal drugs are now commonly used in patients with severe diseases who have been hospitalized. In particular, granule cells are reduced to prevent Candida infection. Although the most commonly used fluconazole is more beneficial for patients with bone marrow transplantation than for acute leukemia, it is inconclusive for prolonging survival, and it is extensive or Inadvertent use of oral imidazoles for prevention does not prevent the prevention of naturally-resistant pathogenic fungi (Aspergillus species, Mucor, Mucor, Candida and Grubb The purpose of infection with Candida albicans and the possibility of producing new resistant strains does not meet the price-effectiveness principle.

Candidiasis complications Complications, pneumonia, renal failure, gastrointestinal bleeding

Complications are diverse, the respiratory system can be complicated by pneumonia, the digestive tract can be complicated by intestinal bleeding, and the intestinal perforation urinary system can be complicated by renal failure.

Symptoms of Candidiasis Common Symptoms Candida Albicans Infection Triads Pap rash Herpes Post-sternal Pain Pustular Abscess Nodules Pericarditis

Mucosal cutaneous candidiasis

Thrush or oropharyngeal candidiasis is characterized by a creamy, white, curd-like exudative patch on the surface of the tongue, buccal mucosa, ankle or other oral mucosa. These patches are actually pseudomembranes, which are visible in the mask. Fresh meaty erythema with bleeding and pain, dentition can be the cause of its cause, while erythema can be the only sign of the lesion, acute or chronic horn inflammatory reactive cheilosis and atrophic lesions, both non-oral Common manifestations of candidiasis, candida esophagitis can be caused by the spread of thrush, but about one-third of patients with esophagitis can be without thrush, which is typically swallowing pain, difficulty swallowing, or sternum Post-pain, but bleeding is rare, in the absence of any known incentives, thrush or esophagitis, should be highly suspected of HIV infection, involving the stomach, intestinal mucosa of gastrointestinal candidiasis, cancer Swelling patients are the most common and are the main source of disseminated infections, involving the tempests (intertrigo) caused by Candida infections on the surface of warm and humid skin such as armpits, buttocks, under breast folds, and groin. Different performance, but more marginal erythema exudative patch, peripheral small blisters or small pustules like a satellite, paronychia (paronychia) for the bottom of the nail or along the edge of the pain, swelling, red, swollen The inflammation is caused by Candida species, especially in diabetic patients and workers who are engaged in long-term soaking in water. Although Candida species can cause hyperthyroidism (onychomycosis), this kind of fingering A chronically deformed infection is most common in superficial dermatophytes, such as Trichophtin or Epidermophyton. Vulvovaginitis is the most common Candida in women. It is a mucosal skin infection, especially during pregnancy, oral contraceptives, antibiotics, diabetes and HIV infection. The main pathogens are Candida albicans. The clinical manifestations are thick creamy vaginal discharge, labial erythema and odd Itching is characteristic, male balanitis is often infected by sexual intercourse, usually manifested as superficial small blisters and exudative patches on the head of the turtle, candida cystitis, cystoscopy similar to the oral gooseneck The most common complication of indwelling catheters for the bladder. Chronic mucocutaneous candidiasis is a rare disease usually caused by the infection of Disfiguring Candida, which persists in heterogeneous genomes, involving the skin, mucous membranes, hair and fingers ( A toe, mainly seen in patients with altered T-cell function or endocrine disease (eg, hypoparathyroidism or adrenal insufficiency).

2. Deep organ candidiasis

Serious or deep Candida infection, there are multiple diagnostic classifications or nomenclature, such as candidemia, disseminated candidiasis, systemic candidiasis, invasive candidiasis, visceral candidiasis, and specific organs Involved names, such as liver and spleen candidiasis and candida albicans, this chapter mainly discusses two major categories:

1 candidemia (candidemia), with or without involvement of relevant internal organs;

2 chronic disseminated candidiasis refers to systemic multiple organ candidiasis and includes other subgroups such as visceral, invasive and hepatic spleen candidiasis.

3. Candidaemia

Candidemia is defined as one or more positive blood cultures of Candida species, with or without clinical manifestations (eg, fever or skin lesions), and Candida has first settled in a site other than blood flow. Or infection, in recent years with immunocompromised hosts (such as cancer or burn patients, intensive care unit patients and recipients of organ transplants) using invasive interventions, including empirical application of broad-spectrum antibiotics, cytotoxic chemotherapy, hemodialysis, As well as the most important, the number of patients with venous cannula and other vascular indwelling devices has increased, and the incidence of candidemia has increased significantly. In many hospitals, the blood culture of Candida species has become the most common cause. 1/3 to 1/5 of the pathogen, the duration of "transient candidemia" used to express fungalemia is short (<24h), suggesting that after removal of the infected intravascular catheter Candidaemia can be eliminated, or a benign condition that does not require antifungal therapy. Recent data strongly oppose this view, demonstrating that even if the catheter is removed, even in non-immune-impaired patients, Can prevent the spread of blood-borne metastasis to the internal organs.

Although Candida albicans is the most common species isolated from blood, recent studies have shown that candidemia caused by non-Candida albicans species has increased, especially Candida tropicalis, Candida parapsilosis and Grubb Candida albicans, found in patients who have received antifungal therapy, is more likely to be caused by non-Candida albicans strains, and is often associated with the most widely used imidazole drug fluconazole resistance, The incidence of fungalemia caused by non-Candida albicans strains varies widely among research institutions, some of which may differ from specific measures for empirical antibacterial therapy and antifungal prophylaxis, as well as immunosuppression by cancer and others. The classification caused by the cause is different. For example, Candida tropicalis and Candida krusei infections occur in tumor patients, while Candida albicans infection is apparently more common in non-tumor patients.

Various types of intubation are the most important invasive portals, accounting for more than 50% of candidemia. In order to eliminate candidemia, especially persistent candidaemia, in most cases it is necessary to remove or replace the periphery or center. Sexual intubation, other invasive pathways are the gastrointestinal tract, especially in patients with granulocytopenia and surgical trauma. Although the urinary tract and respiratory tract often have Candida species, they are rarely the source of blood-borne infections. The mortality rate of candidemia caused by various Candida species is high, ranging from 40% to 60%, and the mortality and rapid fatal underlying diseases and persistent candidemia are sensitive to physiology and chronic health. The assessment (acute physiology and chronic health evaluation, APACHE) was significantly higher than the score of II, and the candidiasis associated with intubation was lower than that of other sources.

Candidaemia causes the incidence of localized single organ lesions (eg, candida albicans) or widespread disseminated multi-organ lesions. It is unclear that pre-mortem diagnosis of invasive or disseminated candidiasis must be The tissue invaded by Candida is confirmed by histopathology. The rate of negative blood culture is about 50% in patients with disseminated candidiasis, and there are no other reliable markers such as serological tests. Therefore, such patients may not be suspected of broadcasting. Disseminating candidiasis, therefore, will not carry out the corresponding invasive diagnostic test, serial autopsy data show that disseminated candidiasis involving the kidney, liver, spleen, brain, heart muscle and eyes, mostly found in the original enough Patients with fatal underlying diseases, such as leukemia with concurrent neutropenia; and patients with candidemia in non-neoplastic diseases, especially catheter-associated bacteremia, are unlikely to cause these results, in addition, after treatment Disseminated lesions are less likely to occur in patients with candidemia.

4. The characteristic skin lesions associated with persistent candidiasis in the skin lesions of disseminated candidiasis, papule pustules and large nodules on the erythematous basal, which usually spread throughout the trunk and limbs, hemorrhagic Bullae has also been reported.

5. Candidiasis

Such localized candidiasis can be caused by blood-borne transmission, or by direct vaccination (such as cataract extraction or intraocular lens implantation), any structure of the eye can be infected; Most, can lead to blindness, endophthalmitis with single or multiple white chorionic choroidal chorioretinopathy, and often extended to the vitreous, the above-mentioned lesions are easy to identify otoscopy, so for all patients with known candidaemia, The fundus examination should be repeated.

6. Renal Candidiasis

Kidney infection may be secondary to the ascending spread of the bladder (candida cystitis), leading to nipple necrosis, invasion of the renal pelvis, or formation of fungal balls in the ureter or renal pelvis, renal candidiasis, secondary to confirmed or unproven Blood-borne disseminators in patients with candidemia are more common, manifested as pyelonephritis, with diffuse abscesses of the cortex and medulla, candidaemia, Candida urine and urinary sediment tube type candida triple The levy can be used as a basis for diagnosis of urinary tract infections.

7. Liver and spleen candidiasis

This type of deep organ infection most commonly occurs in patients with malignant hematopathy, especially in the remission of leukemia with long-term chemotherapy leading to neutropenia. Most patients have a source of infection that is complicated by gastrointestinal candidiasis. Portal mycosis usually does not have evidence of confirmed candidaemia or other organ lesions, unexplained fever for persistent causes, tenderness and pain in the right upper quadrant, elevated alkaline phosphatase levels, abdominal ultrasound or CT scan Liver and spleen can be seen in multiple "bulls'eye"-like lesions. Liver biopsy found characteristic histopathological damage and can establish a diagnosis.

8. Lung candidiasis

Severely ill patients who are mechanically ventilated in intensive care units. Pneumonia caused by Candida species is rare, but is parasitic in the tracheobronchial system by yeast type Candida. Therefore, the diagnosis should be invaded by yeast type. Substantial histopathological evidence is based.

9. Cardiac candidiasis

Disseminated candidiasis is often associated with candida myocarditis (>50% of cases), occasionally with pericarditis, Candida is the most common cause of fungal endocarditis, for interventional heart repair, intravenous drug use and long-term central vein Intubation for chemotherapy, high-energy nutrition or hemodynamic monitoring should be suspected of fungal endocarditis, due to the large and fragile heart valve fungal neoplasms, involving the central nervous system (CNS) Larger embolic accidents in the coronary arteries and peripheral arteries occur from time to time.

10. Central nervous system candidiasis

Candida meningitis and small brain abscess or large abscess, combined with disseminated candidiasis, and often belong to complications caused by frequent intravenous drug or ventricular shunt infection, with increased number of cerebrospinal fluid cells (more lymphocytes increased) Mainly), the amount of glucose decreased, protein increased as a typical performance; using cerebrospinal fluid wet film, Gram stain, or culture, can detect less than half of the yeast type Candida.

11. Musculoskeletal candidiasis

In patients with neutropenia, manifested as myositis (abscess), while in injecting drug users, it appears as costal cartilage, arthritis and osteomyelitis (especially in the vertebrae and intervertebral disc), the above complications can be seen in the dissemination Any patient with candidiasis, regardless of the patient's background or source of infection.

Candidiasis examination

Candida can be prepared by scraping or wiping the specimen from the lesion to make a potassium hydroxide wet pile, or smear Gram stain for inspection, see a large number of globular budding yeast type and pseudohyphae, for characteristic discovery, Patients suspected of having candidiasis esophagitis should not only be examined by endoscopic brushing, but also biopsy to further find evidence of Candida invasion of the mucosa from histopathology, caused by herpes simplex virus or cytomegalovirus. Esophagitis, similar to candida esophagitis; in the same patient, infection by more than one pathogenic microorganism is not uncommon, patients suspected of candidemia or disseminated candidiasis should adopt new One of highly sensitive systems, such as lysis centrifugation, biphasic media, or automated non-radiometer method (eg BACTFEC, Bact/Alert, or ESP) for blood Candida cultivation should be carried out for 2 consecutive days, and blood collection should be carried out twice. The accumulated data in the past 10 years indicates that the single culture of Candida species is positive, it should be assumed Clinically, there is obvious candidemia, which is worthy of antifungal treatment, sputum, tracheal suction, wound secretion or urine culture. Seeing the growth of a large number of Candida species, it can increase the possibility of invasive blood flow, but Can not prove that there has been dissemination, because the blood culture negative patients with disseminated rosary disease can be as high as 50%, so the diagnosis must often be based on biopsy tissue histopathological examination and fungal culture results.

Histopathology:

Skin mucosal cutaneous candidiasis

Mainly for the chronic inflammation of the dermis or the formation of cavernous pustules under the cornea. There is a small amount of separation in the shallow part of the horn. The mycelium is about 2 to 4 m in diameter and has 3 to 5 m oval snails. It is in the germination stage and chronic skin mucosa. Candidiasis epidermis shows papillary hyperplasia, there are clusters and scattered hyphae and spores in the horns and angle plugs, chronic inflammatory cell infiltration in the dermis, and papilloma granuloma with obvious papillary hyperplasia and hyperkeratosis. There are inflammatory cells that migrate to the epidermis. Dense lymphoid cells, neutrophils, plasma cells and multinucleated giant cells infiltrate into the dermis and penetrate deep into the skin. Occasionally, hyphae and spores can be found in the dermis.

2. Systemic candidiasis

The fungus is distributed in parenchymal cells and is a multiple abscess. It is usually seen in the liver, gastrointestinal and kidney. It is an acute inflammatory reaction under the microscope. There is a microabscess mainly due to neutrophil infiltration. HE staining can be seen between the pus cells. Light-colored yeast-like cells are scattered. PAS and GMS staining can be seen as thin-walled oval spores, 3-6 m in size, with pseudohyphae. There is no cell reaction in the lesions of patients with leukopenia, and may be associated with hemorrhagic necrosis. There are a few lesions with granuloma reactions, spores containing fungi, and polymorphic giant cells of hyphae.

Diagnosis and identification of candidiasis

diagnosis

Diagnosis of mucosal cutaneous candidiasis, based on clinical manifestations and detection of Candida, Candida can be prepared by scraping or wiping specimens from the lesion to prepare potassium hydroxide wet piles, or smear Gram staining, for inspection See a large number of globular budding yeast type and pseudohyphae. For the characteristic findings, patients suspected of having candida esophagitis should not only perform endoscopic brush specimen examination, but also should perform biopsy to further biopsy. Find evidence that Candida invades the mucosa. Esophagitis caused by herpes simplex virus or cytomegalovirus is similar to candida esophagitis. In the same patient, infection by more than one pathogenic microorganism is not uncommon. Patients with suspected candidemia or disseminated candidiasis should use one of the new highly sensitive systems, such as lysis centrifugation, biphasic media, or automated non-radiometer methods. (Automatic non-radiometer method, such as BACTFEC, Bact/Alert, or ESP) for culture of Candida albicans. It should be taken for 2 consecutive days, and blood is collected twice for the past 10 times. The accumulated data indicates that a single Candida species is positive for blood culture, and it should be assumed that there is obvious clinical candidaemia, which is worthy of antifungal treatment, sputum, tracheal suction, wound secretion, or urine culture. See a large number of Candida species growth, can increase the possibility of invasive blood flow, but can not prove that there has been dissemination, because disseminated rosary patients can be up to 50% negative blood culture, so the diagnosis often requires biopsy The histopathological examination and fungal culture results of the tissue are based on diagnostic measures including head, chest, abdominal CT scan, echocardiography, thoracic puncture, joint cavity puncture, lumbar puncture, and skin, liver, kidney, and myocardium. Multiple methods in various aspects such as bone, muscle or lung biopsy. Although it has been considered that quantitative or semi-quantitative culture of selective tissue specimens can help predict the occurrence of disseminated lesions, it lacks relevant information to support this view. , Candida antigen skin test, helps to assess the host's anergy, but is meaningless for the diagnosis of candidiasis, used to detect serum beads Reliable, simple, sensitive and specific serological tests of antibodies, circulating Candida antigens (eg, cell wall mannan or cytoplasmic enolase) or metabolites, although vigorously developed, but with regard to these serological diagnostic methods The value of the problem is always divided. Because the false positive and false negative results are ubiquitous, the results of the serological test cannot be used as the basis for determining the start of treatment. The genotyping method includes electrophoretic karyotyping. , DNA probes, genomic DNA restriction endonuclease analysis, restriction fragment-to-length polymorphism, and randomly amplified polymorphic DNA, all identifying Candida species Sensitive methods are extremely helpful for epidemiological investigations and the control of pathogens in the hospital for Candida species.

Differential diagnosis

Digestive candidiasis should be differentiated from esophagitis, gastritis, enteritis, candida pneumonia, meningitis, endocarditis should be identified with tuberculosis, bacterial and other fungal infections.

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