Cryptococcosis

Introduction to cryptococcosis Cryptococcosis is a subacute or chronic deep mycosis caused by Cryptococcus neoformans in the genus Cryptococcus, which can invade the body's skin, lungs, bones and other organs, but is most common invading the central nervous system. About 80% of cryptococcal infections. The prognosis is serious and the mortality rate is high. In recent years, due to the emergence and spread of AIDS, the incidence of cryptococcal infection has increased significantly. basic knowledge The proportion of sickness: 0.01% - 0.02% Susceptible people: no special people Mode of infection: digestive tract spread Complications: pyelonephritis meningitis cerebral edema cerebral palsy sepsis

Cause of cryptococcosis

[cause]

Cryptococcus neoformans is round or oval in the tissue and has a diameter of 5 to 12 m, which can retain Gram staining. The cells are wrapped in a wide capsule, no hyphae and spores are formed, and the buds are germinated. Cryptococcus neoformans can easily grow on various media at room temperature or 37 ° C. It grows colonies and is milky white. It is mucoid for a long time.

According to the capsular antigenicity, Cryptococcus neoformans has four serotypes, A, B, C and D. Domestically, it is mostly type A, followed by type B and type D, and no type C. The capsular antigen can be dissolved in Cerebrospinal fluid, serum and urine can be detected by specific serum. It is found that the B/C strain is more resistant to 5FC than the A/D strain.

[Pathogenesis]

Cryptococcus present in the soil and pigeon dung can be inhaled into the respiratory tract along with the dust. The dried Cryptococcus is only 1m in diameter and can enter the alveoli. Cryptococcus is not encapsulated in the outer body and forms a capsule soon after entering the body. The cryptococcal capsular bacterium has pathogenicity. Cryptococcus invading the human body does not necessarily cause disease, and cellular immunity plays a major role in preventing cryptococcal infection.

After cryptococcosis invades the lungs, a small number of granulomas are formed and symptoms appear. Cryptococcus can enter the central nervous system through the blood of the lungs. The cause of the bacteria often invading the central nervous system may be: 1 lack of antibodies in the cerebrospinal fluid. 2 lack of complement activation system in cerebrospinal fluid. 3 Dopamine in cerebrospinal fluid is conducive to the growth of cryptococcus.

Cryptococcal meningitis has a significant lesion on the base of the skull, and there is extensive exudate accumulation in the subarachnoid space. It contains mononuclear cells, lymphocytes and cryptococcus, and can also form localized granuloma. The latter is the body. Strong reaction, composed of tissue cells, giant cells, lymphoid cells and fibroblasts; Cryptococcus is less found, mostly in giant cells and tissue cells, pathogens can also invade the brain parenchyma along the perivascular sheath The vasculitis of the brain stem causes ischemia and softening of the brain tissue, and granulomas can also form in the brain parenchyma. Cryptococcus can also proliferate in the perivascular space and form many macroscopic cysts in the gray matter. The cyst is filled with Cryptococcus.

There are two types of skin lesions, granuloma and glial lesions. The latter has less tissue reaction and contains a large amount of cryptococcus.

Cryptococcosis prevention

In patients with unimpaired immunity, if there is only focal lung involvement, the cerebrospinal fluid parameters are normal, cerebrospinal fluid and urine culture are negative, and there are no signs of skin, bone or other extrapulmonary tissue lesions, and no treatment is needed. In the absence of meningitis, localized antifungal treatments are required for localized lesions of the skin, bones and other areas, but the optimal treatment regimen has not been determined from comparative trials. It has been demonstrated in most cases that amphotericin B is effective with flucytosine or amphotericin B alone, but recent reports of successful oral amphotericin B have been reported.

Cryptococcosis complications Complications pyelonephritis meningitis cerebral edema cerebral septicemia

Pyelonephritis with renal papillary necrosis can occur. In addition to skin lesions, bone, abdominal organs or other tissue-constrained lesions have almost no clinical symptoms. Can be complicated by granuloma, cysts, a small number of critically ill patients can be complicated by meningitis, cerebral edema, and even cerebral palsy, sepsis.

Symptomosis symptoms common symptoms cryptococcal capsular polysaccharide accumulation irritability low fever nausea high fever lung infection dyspnea severe headache cellulitis granuloma

Although most cryptococcal infections have a self-limiting, subacute or chronic process, AIDS patients with cryptococcus can present with severe progressive pneumonia with acute dyspnea and pulmonary X-ray signs similar to Pneumocystis infections. . Diffuse skin involvement can occur in any infected person, causing pustular papule-like nodules, or ulceration, sometimes like acne, contagious soft palate or basal cell carcinoma. Disseminated lesions can also occur in subcutaneous nodules, long bone ends, joints, liver, spleen, kidney, prostate, and other tissues. A typical affected tissue contains a capsule-like yeast cyst, which is formed by the accumulation of cryptococcal capsular polysaccharide, but with little or no acute inflammation, especially in the brain.

Primary lung lesions are usually asymptomatic and self-limiting. In patients with normal immune function, clinically typical and single lung lesions can sometimes self-heal without spreading, or even antifungal therapy. Pneumonia usually causes cough and other non-specific respiratory symptoms. In rare cases, pyelonephritis with renal papillary necrosis can occur. In addition to skin lesions, bone, abdominal organs or other tissue-constrained lesions have almost no clinical symptoms.

The symptoms of cryptococcal encephalitis are mostly caused by cerebral edema, usually without specificity, including headache, blurred vision, confusion, depression, irritability and other behavioral changes. In addition to eye or facial paralysis, focal signs appear only at a later stage of the disease. Blindness can be caused by cerebral edema or direct involvement of the visual conduction beam. May have low or no heat. AIDS patients may have mild or asymptomatic symptoms, and the cerebrospinal fluid may be completely normal except for many yeasts. However, increased cerebrospinal fluid protein and mononuclear lymphocyte increase are also common, and neutrophils are also significantly increased. Glucose is often low, and cerebrospinal fluid smear in most cases can be found in the narrow base spores formed by the spore yeast. Cryptococcus capsular polysaccharide antigen can be detected in cerebrospinal fluid and/or serum of more than 90% of meningitis patients.

The site of cryptococcal invasion into the human body is different, and the clinical manifestations are also different.

1. Skin mucosal cryptococcosis 10% to 15% of patients with cryptococcosis have skin lesions, the original hair style is relatively rare, and the subsequent hair style is mostly spread by systemic infection.

(1) Skin damage: manifested as papules, blisters, pustules, contagious soft palate-like papules, acne-like pustules; subcutaneous tissue masses, invasive nodules, abscesses, cellulitis, varicella-like rash, carbuncle-like lesions , purple spot, verrucous proliferation, ulcer, etc., no characteristic, the surface can be covered with a viscous exudative film.

(2) Mucosal damage: often occurs in soft palate, hard palate, tonsil, gingiva, nasal septum or pharynx, maxillary sinus, etc., caused by blood, or from skin expansion, manifested as nodules, granulomas or chronic Ulcers, etc.

2. Central nervous system cryptococcal cryptococcal invasion of the central nervous system is the most common, clinically divided into 4 types.

(1) meningitis type: the most common, can be acute, subacute or chronic process, manifested as meningitis symptoms, signs, more onset, can start with upper respiratory tract infection symptoms, mild headache, low fever, body temperature The fluctuations ranged from 37.5 °C to 38 °C. Afterwards, the headache gradually increased. A few people could start to have severe headache, high fever, nausea, vomiting, and meningeal irritation. The pyramidal tract sign was lighter and appeared later.

(2) meningophage type: in addition to meningeal involvement, there is still brain parenchymal involvement, it is called cryptococcal meningoencephalitis, cryptococcal can invade the brain, cerebellum, bridge brain or cerebral palsy, due to the difference in the brain parenchymal involvement There is a corresponding seizure of brain lesions and signs of seizures.

(3) granuloma type: less common, is an inflammatory granuloma lesion formed by Cryptococcus neoformans invading the brain parenchyma, which occurs in the spinal cord of the brain, cerebellum and brainstem, and is located in the cerebral parenchyma. Can be expressed as symptoms and signs of brain occupying lesions.

(4) Cyst type: caused by cryptococcal stimulating meningeal cysts, arachnoid can be thickened, single or multiple cysts can be formed in the arachnoid cavity, and the cyst is a colorless and transparent liquid, which is manifested as intracranial space. Sexual lesions.

3. Pulmonary cryptococcosis is the portal of cryptococcal invasion. Primary lung infections are generally mild, about one-third of cases are asymptomatic, and there is a tendency to self-healing. The initial symptoms of upper respiratory tract infection often occur. Then manifested as bronchial pneumonia, there may be cough, cough, chest pain, there may be a large number of bacteria in the sputum.

4. Other parts of cryptococcosis include bones and joints as well as prostate, liver, spleen, lymph nodes and other tissues and organs can be involved, but are relatively rare, or often associated with central nervous system cryptococcosis and pulmonary cryptococcosis.

According to the clinical manifestations, mycological examination can be diagnosed. For central nervous system cryptococcal disease, the use of latex agglutination test to check the cryptococcal polysaccharide antigen has great reference significance for early diagnosis.

Cryptococcal disease test

(1) routine examination of cerebrospinal fluid

70% of patients with cerebrospinal fluid pressure increased, generally 1.96 ~ 3.92 kPa (200 ~ 400mmH2O), chronic cases can be in the normal range, the appearance is clear, transparent or slightly mixed, 97% of cases of white blood cell counts light to moderate increase, the average about 180/mm3, a few can exceed 500/mm3, often with lymphocytes predominating, more than 90% of cases have a mild to moderate increase in protein content, individual up to 400mg / dl or more, sugar quantification is mostly reduced, a few cases can be reduced 0, the chloride content is mild to moderately reduced, when AIDS patients with cryptococcal meningitis, cerebrospinal fluid examination can be normal, but the pathogen test is positive.

(two) pathogen examination

1. Smear early meningitis cerebrospinal fluid smear positive rate of more than 85%, take 3 ~ 5ml cerebrospinal fluid, centrifugal sedimentation, sediment plus the same amount of Shanghai ink, microscopic examination, bacterial cell diameter 4 ~ 6m, the outer ring has a thorough Thick wall, thickness is generally 5 ~ 7m, thick film is the hallmark of pathogenic cryptococcus, treated with 10% potassium hydroxide solution or direct smear for microscopic examination, only the bacteria are not seen thick film, often wrong Think of lymphocytes.

2. Culture The specimens are inoculated on glucose peptone agar medium and grown at room temperature (25 ° C) or 37 ° C for 2 to 5 days. Non-pathogenic cryptococcus does not grow at 37 ° C. 3 to 4 weeks, the positive rate of sputum culture was only 20%, and the positive rate of cerebrospinal fluid culture was higher in meningitis patients.

3. Animals are most sensitive to mice. Cerebrospinal fluid or other specimens are injected intraperitoneally, tail vein or intracranially. The mice die within 2 to 8 weeks, and a large number of cryptococcus can be found in the brain.

(3) Immunological test

1. The antibody detects that the thick capsule of Cryptococcus contains a specific antigenic polysaccharide, and the antigen or the corresponding antibody can be detected in the serum or cerebrospinal fluid of about 90% of patients with cryptococcal meningitis.

2. Antigen detection The cryptococcal antibody coated latex can be used to detect antigen. The positive rate of cerebrospinal fluid antigen in meningitis patients is 92%, the positive rate of serum is 75%, and the positive rate of non-meningitis patients is 20%. 50%, if there is rheumatoid factor in the patient, false positives may occur, and a rheumatoid factor positive control shall be established. The cerebrospinal fluid contains antigen and no antibody indicates that the lesion is still active, otherwise the condition is improving, and the cerebrospinal fluid smear is negative. The patient's antigen test can be positive.

X-ray film: suspected pulmonary cryptococcosis should be X examination, pulmonary cryptococcosis X-ray examination is not specific, visible diffuse inflammatory infiltration, peri-bronchial infiltration or similar miliary tuberculosis shadow, few hilar and mediastinum Invaded.

The bones are tired in time, and the X-ray examination shows the osteolytic lesions with clear edges.

Diagnosis and identification of cryptococcosis

Cryptococcus neoformans is easier to find than other pathogenic microorganisms. Ink smears and fungal cultures of cerebrospinal fluid are extremely important, in view of tuberculous meningitis, brain abscess, partial treatment of purulent meningitis, intracranial tumors, and other fungal meningitis. Cerebrospinal fluid changes are similar to cryptococcal meningitis, so it is the focus of differential diagnosis, cryptococcal meningitis and tuberculous meningitis and brain tumors.

Skin cryptococcosis is distinguished from acne, infectious soft palate, skin tuberculosis, sporotrichosis or malignant tumor by pathological and fungal culture.

2. Pulmonary cryptococcosis should be differentiated from pneumococcal disease caused by pneumococcal pneumonia, tuberculosis and pulmonary candidiasis, pulmonary aspergillosis.

3. Other cryptococcosis skin cryptococcosis should be differentiated from sporotrichosis, pigmented germination and various chronic ulcers. Osteochorcococcus should be differentiated from bone tumors. Cryptococcal sepsis should be associated with bacterial sepsis. Identification.

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