What is Cryptococcosis?

Cryptococcus includes 17 species and 18 variants, of which only Cryptococcus neoformans and its variants are pathogenic. Almost all Cryptococcus neoformans infect humans with lung invasion. 90% of the lesions are confined to the lungs, and 10% can spread to other organs through blood transmission. The central nervous system and skin are the most common sites of secondary infections. The susceptibility of the bacteria to the central nervous system may be related to the presence of aspartin and creatinine in the cerebrospinal fluid to help the bacteria grow. The route of transmission of this disease has not been clarified. When the body's immunity decreases, pathogenic bacteria can directly invade and cause bloodstream transmission. Therefore, patients who have been using immunosuppressive agents or glucocorticoids for a long time, AIDS, leukemia and other patients are susceptible to this disease.

Basic Information

English name: cryptococcosis
Visiting department: Department of Infectious Diseases
Multiple groups: Patients with long-term use of immunosuppressants or glucocorticoids, leukemia, and AIDS are susceptible to this disease
Common locations: whole body

Common causes: Cryptococcus neoformans is the only pathogen of this disease
Common symptoms: Clinical manifestations can be divided into pulmonary cryptococcosis, central nervous system cryptococcosis, cutaneous mucosal cryptococcosis, osteo cryptococcosis and visceral cryptococcosis type 5
Contagious: Have
way for spreading: Infecting the human body with lung invasion

Causes of cryptococcosis

Cryptococcus neoformans is generally considered to be the only pathogen of this disease. The bacteria are widely distributed in nature and can be found in human skin, soil, dust, and pigeon droppings. Pigeon droppings on windowsills often become a source of infection in large cities. Cryptococcus includes 17 species and 18 variants, of which only Cryptococcus neoformans and its variants are pathogenic. Cryptococcus neoformans is a round yeast-type fungus with a broad capsule around it, called a thick capsule. There are one or more reflective particles in the bacteria body, which have a nuclear structure. Part of the mycelium showed budding, but no pseudohyphae was formed. Non-pathogenic cryptococcus has no capsule. Cryptococcus neoformans can grow at 25 ° C and 37 ° C on both sand protection medium and blood agar medium, while non-pathogenic Cryptococcus cannot grow at 37 ° C. Yeast-type colonies were formed after several days of culture, and the surface was sticky. It was milky white at first, and then turned orange. This bacteria can distinguish urea from Candida. Both humans and animals can be infected. In recent years, it has been found that other cryptococci can also cause disease, such as Cryptococcus lorentii and Cryptococcus garteri. ^[1-2]

Clinical manifestations of cryptococcosis

Multiple groups

When the body's immunity decreases, pathogenic bacteria can directly invade and cause bloodstream transmission. Therefore, patients who have been using immunosuppressants or glucocorticoids for a long time, leukemia, and AIDS are susceptible to this disease.

2. Symptoms

According to clinical manifestations, the disease can be divided into five types: pulmonary cryptococcosis, central nervous system cryptococcosis, cutaneous mucosal cryptococcosis, osteo cryptococcosis and visceral cryptococcosis.

(1) Cryptococcus neoformans existing in the environment of pulmonary cryptococcosis are less than 10 m in diameter. After inhalation into the human body through the respiratory tract, once it is deposited in the respiratory tract, under the influence of high carbon dioxide concentration, a clear polysaccharide capsule protective layer is formed to Antagonistic host defense mechanisms. Most healthy people have infections that can heal on their own or the disease is limited to the lungs. In patients with impaired immune function, Cryptococcus can progress and can cause severe lung infections and even blood circulation throughout the body. Symptoms include cough, chest pain, fatigue, low fever, weight loss, etc. There is often a small amount of mucus or blood sputum, and pathogenic bacteria can be found in the sputum. X-ray manifestations: The lesions are more common in the bilateral middle and lower lungs, and can also be unilateral or confined to a certain lung lobe. They can be isolated large spherical lesions or several nodular lesions, and there is no obvious reaction around them, similar to tumor ; Or diffuse miliary shadows; or flaky infiltrating shadows. Cavities form in some patients.

(2) Patients with cryptococcosis of the central nervous system often complain of pain in the forehead, double temporal or eyeballs, intermittent episodes, pain gradually worsening, and often accompanied by meningeal irritation such as fever, neck stiffness, and positive neck and leg test. If localized granulomatous lesions occur in the brain and simple space-occupying lesions occur, nausea, vomiting, mental retardation, coma, hemiplegia, blurred vision, dizziness, palsy, nystagmus, diplopia and other symptoms may occur. Mental disorders can be significant. Seizures can also occur. This disease often occurs in AIDS patients and is one of the common causes of death.

(3) Cryptococcosis of the skin and mucous membranes Cryptococcus skin infections are most common in the head and neck, often caused by the spread of primary lesions. The rash manifests as pimples, acne-like pustules, or abscesses and is prone to festering. Molluscum contagiocutaneous lesions will occur in some HIV-infected persons. Primary damage to the skin is rare and manifests as isolated gangrene, which must be diagnosed based on a clear history of implantation and the cultivation of cryptococcus in suspicious implants. Some patients may have nodular, granulomatous, or ulcerative lesions due to mucosal involvement.

(4) Cryptococcosis occurs in the skull and spine, but often does not involve joints. Bone damage is often chronic and multiple scattered destructive lesions, without periosteal hyperplasia, swelling and pain. X-ray has no special performance.

(5) Visceral cryptococcosis Disseminated cryptococcosis can first appear in many organs or systems. It is reported that osteomyelitis, prostatitis, pyelonephritis, and peritonitis can be the first manifestations of cryptococcosis. Gastrointestinal and urogenital infections are similar to tuberculosis. Individual cases can invade the heart and cause endocarditis

Cryptococcus disease test

Etiological examination

(1) The ink staining method is a fast, simple, and reliable method. According to the different damaged parts, take fresh specimens that need to be checked, such as cerebrospinal fluid, sputum, lesion tissue or exudate. Cover with a cover slip and look for Cryptococcus in the dark field of the microscope. You can see round bacteria. The outer axis has a transparent hypertrophic capsule with reflective spores inside, but sterile silk. Repeatedly find a high positive rate, the cerebrospinal fluid should be centrifuged to take a sediment smear.

(2) Fungal culture Take a few specimens and place them in Shaw's medium, and grow at room temperature or 37 ° C for 3 to 4 days.

2. Serological examination

Because there is not much detectable antibody in the patient's serum, the positive rate of detection of the antibody is not high and the specificity is not strong. It is only used for counseling diagnosis. The detection of new Cryptococcus capsular polysaccharide antigen is usually sensitive and specific in a latex agglutination test, and it has the effect of estimating prognosis and efficacy.

3. Pathological examination

Varies depending on the stage of illness and affected organs. There can be no tissue reaction in the brain tissue and only gummy myxedema can be seen. The meninges showed a chronic, non-specific purulent inflammatory response with a large number of lymphocytes and plasma cells infiltration. Tuberculous granulomatous manifestations can be seen in chronic lesions. Visible cells in the tissue. Cryptococcal disease of the skin and mucous membranes has two types of lesions:

(1) The reaction of the colloidal damage tissue is small, and there is a large number of bacteria in the area.

(2) Granulomatous lesions can have obvious tissue reactions, including infiltration of histiocytes, macrophages, lymphocytes and fibroblasts, and there can be necrotic areas.

Cryptococcus disease diagnosis

Early diagnosis of the disease is particularly important for prognosis and reducing or avoiding sequelae. In the early days, it was mainly dependent on the high vigilance of clinicians. Cerebrospinal fluid examination should be performed in time when encephalopathy is suspected, such as direct ink smear to check whether there are thick capsular cells, and cerebrospinal fluid culture.

Differential diagnosis of cryptococcosis

Cryptococcal disease of the central nervous system must be distinguished from tuberculous meningitis, intracranial space-occupying lesions, and other intracranial diseases.

Cryptococcus disease treatment

General treatment

(1) Actively treat the primary disease and remove the cause.

(2) Strictly grasp the indications for antibiotics, glucocorticoids and immunosuppressants.

(3) Strengthen nursing and supportive therapies.

2. Antifungal treatment

Fluconazole, itraconazole, flucytosine, amphotericin B and its liposomes can be used. For severe patients, the standard treatment of oral fluconazole after intravenous administration of amphotericin B is given. In mild patients without AIDS, fluconazole is administered orally and may be effective for 8 to 10 weeks. When other antifungal drugs are not effective, voriconazole has a certain therapeutic effect. Caspofungin has limited effect on this disease. Cryptococcal disease of the skin and mucous membranes should be supplemented with local treatment in addition to systemic administration.

(1) Amphotericin B Amphotericin B is a polyene antibiotic, which combines with sterols on the membrane of fungi, changes the permeability of the membrane, destroys the bacteria and plays a bactericidal effect. It is the drug of choice for the treatment of cryptococcosis, histoplasmosis, and systemic candidiasis. It has a poor effect on aspergillosis.

1) Route of administration A small amount should be used at the beginning of intravenous infusion . If there are no adverse reactions, gradually increase the dose. The course of treatment is 1 to 3 months. Intravenous injection is diluted with 5% glucose solution, the concentration does not exceed 0.05 ~ 0.1mg / ml, slow intravenous infusion, each dose is completed no less than 6 hours. Concentrations that are too high can cause phlebitis, convulsions that occur too quickly, arrhythmias, sudden drop in blood pressure, and even cardiac arrest. Intraspinal injection or intraventricular injection is limited to the treatment of cases with severe conditions of cryptococcal membranes or failure of intravenous drip. If there are side effects, the dosage can be reduced or suspended. Too much medicine in the cerebrospinal fluid can cause arachnoiditis and increase in cerebrospinal fluid cells. Transient radiculitis, loss of sensation, urinary retention, and even paralysis and convulsions can be relieved if they are stopped early. .

2) Side effects: nausea, vomiting, abdominal pain, fever, chills, headache, dizziness, anemia, thrombocytopenia, thrombophlebitis, etc., have certain toxicity to the kidney and hematopoietic system. To reduce side effects, aspirin can be given half an hour before and 3 hours after treatment. In severe cases, hydrocortisone or dexamethasone can be administered intravenously. During the medication period, blood, urine routine, liver and kidney function should be checked every 3 to 7 days. The dose should be reduced when serum creatinine is greater than 2.5 mg / dl, the dose should be discontinued when urea nitrogen is greater than 40 mg / dl, and the medication should be discontinued for 2 to 5 weeks. Return to normal, and then start the drug from a small dose. Thrombus phlebitis is prone to occur at the injection site. The initial infusion site should start from the small veins of the distal limbs.

(2) 5-Fluorocytosine 5-Fluorocytosine is an oral systemic antifungal drug, which can inhibit cryptococcus and candida albicans. Can be combined with amphotericin B to treat systemic cryptococcosis. Reduce infant dose. Good oral absorption, high serum concentration, cerebrospinal fluid concentration can reach 64% to 88% of serum, easy to produce drug resistance, side effects include nausea, vomiting, rash, neutrophil nuclear thrombocytopenia, liver and kidney damage, and amphotericin B When combined, drug resistance can be reduced, the amount can be slightly reduced, toxicity can be reduced, and the course of treatment can be shortened.

(3) Fluconazole bistriazole antifungal drugs, the mechanism of action and antibacterial spectrum is similar to ketoconazole, the antifungal activity in vivo is stronger than ketoconazole, high bioavailability, good oral absorption, and candida and cryptococcus There are inhibitory effects, side effects include gastrointestinal reactions, rashes, and occasionally abnormal liver function.

(4) Monoclonal antibody treatment of Cryptococcus capsules Monoclonal antibodies against Cryptococcus capsules have made some progress in the treatment of cryptococcosis. The first-phase clinical study of rat-derived capsular-specific monoclonal antibodies in 20 cases of cryptococcosis has been completed abroad, and its clinical efficacy needs further study. Thl-type cytokine IFN- has also been used for the treatment of cryptococcosis in the central nervous system, and its efficacy needs to be verified by large-scale clinical experiments. ^[3-5]

References:

[1] Lingegowda BP, Koh TH, Ong HS, TanTT.Primary cutaneous cryptococcosis due to Cryptococcus gatti inSingapore.Singapore Med [J] .2011 Jul; 52 (7): e160-2.

[2] Kulkarni A, Sinha M, Anandh U. primarycutaneous cryptococcosis caused by Cryptococcous laurentii in a renaltransplantation recipient. Saudi J Kidney Dis Transpl [J] .2012 Jan; 23 (1): 102-5.

[3] Zhao Bian. Clinical Dermatology [M]. Nanjing: Jiangsu Science and Technology Press, 2011.577 579.

[4] William D, Timothy G, Dirk M. Andrews' Diseases of the Skin: Clinical Dermatology [M]: WB Philadelphia, Saunders, 10th, ed, 2006: 318-319.

[5] Li Ping, Wen Hai. Progress in diagnosis and treatment of cryptococcosis.Chinese Journal of Mycology [J] .2011 Jul; 6 (3): 186-189.