Infection can affect virtually any part of the body in Cryptococcosis, including the skin, eyes, genitourinary and gastrointestinal tract [6], but the two most common sites are the lungs and the central nervous system. The signs and symptoms depend on the affected organ [7].

Pulmonary cryptococcosis can manifests in various stages, ranging from asymptomatic disease to possibly life-threatening pneumonia. Usually, a pneumonia-like disease, including symptoms such as a cough, dyspnea, chest pain, and fever, can be observed. Other symptoms, such as fatigue, are also reported.

Cryptococcosis of the central nervous system (primarily causing meningitis, and possibly meningoencephalitis), occurs after hematogenous dissemination of fungi from the respiratory tract, and includes symptoms such as a headache, fever, neck stiffness, nausea, vomiting, and altered mental state and consciousness [8]. Severe cases may present with memory loss, seizures, and coma.

It is important to note that cryptococcosis may affect more than one organ, and patients may present with symptoms that indicate both pulmonary and central nervous system infection.

Presentations which may indicate an involvement of other organs include rash, arthritis, endocarditis, hepatitis, peritonitis, lymphadenopathy, and other organ-related manifestations.

• Pain

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. [ncbi.nlm.nih.gov]

  […] in nearby areas, skin rash, pinpoint red spots (petechiae), bleeding into the skin, bruises, unintentional weight loss, appetite loss, abdominal bloating, abdominal pain, abdominal swelling, weakness, bone pain, and numbness and/or tingling. [rarediseases.org]

• Malaise

  This is associated with cough, pleurisy, malaise and fever. Free organisms are seen in mucopurulent exudate with little or no inflammatory infiltrate. [histopathology-india.net]

  Clinical Presentation: Most patients present with symptoms or signs of subacute meningitis or meningoencephalitis, with fever, malaise, nausea, vomiting, lethargy, and altered mental status. [ajnr.org]

  A large number of pulmonary infections due to cryptococcosis may go unreported; its symptoms include fever, malaise, and a dry cough. [britannica.com]

  Other symptoms include fever, weight loss, malaise and coughing up blood or hemoptysis. On rare occasions, pleural effusion occurs. Severe pulmonary diseases and respiratory syndromes are more likely to occur in those with weakened immune systems. [news-medical.net]

  Immunosuppressed patients may present with mild-to-moderate symptoms, including fever, malaise, dry cough, chest pain. Severe infection may lead to pneumonia or adult respiratory distress syndrome. [dermnetnz.org]

• Weight Loss

  loss People with a healthy immune system may have no symptoms at all. [nlm.nih.gov]

  Remember that HIV-infected patients may be asymptomatic or present with nonspecific symptoms, eg lethargy, weight loss. [patient.info]

  Other symptoms include fever, weight loss, malaise and coughing up blood or hemoptysis. On rare occasions, pleural effusion occurs. Severe pulmonary diseases and respiratory syndromes are more likely to occur in those with weakened immune systems. [news-medical.net]

  In some cases, there may also be weight loss, swollen lymph glands (lymphadenopathy), rapid breathing (tachypnea), and audible crackles in the lung (rales). [verywellhealth.com]

• Fatigue

  A 73-year-old man presented with fatigue and anorexia and underwent FDG PET/CT scan to evaluate a right lung nodule revealed by a chest CT. [ncbi.nlm.nih.gov]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  Types localized cryptococcosis wound cryptococcosis or cutaneous cryptococcosis pulmonary cryptococcosis menigeal cryptococcosis (cryptococcal meningitis) cryptococcal meningoencephalitis systemic cryptococcosis Clinical synopsis Symptoms include fever, fatigue [humpath.com]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions Sweating -- unusual, excessive [mountsinai.org]

• Hodgkin Lymphoma

  Other conditions which pose an increased risk include certain lymphomas (e.g. Hodgkin’s lymphoma), sarcoidosis, and patients on long-term corticosteroid therapy. Distribution is worldwide. [humpath.com]

  Twelve patients (36.4%) had confirmed hematological malignancies, including non-Hodgkin’s lymphoma (NHL), Waldenstrom’s macroglobulinemia (WM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin’s lymphoma (HL), multiple myeloma [bmcinfectdis.biomedcentral.com]

  Other conditions that pose an increased risk include certain lymphomas (e.g., Hodgkin's lymphoma), sarcoidosis, liver cirrhosis, and patients on long-term corticosteroid therapy. [en.wikipedia.org]

  Fludarabine, which causes substantial T cell dysfunction [13], was administered to 5 (36%) of 14 patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia. [academic.oup.com]

  AIDS was the major immunosuppressive disorder with 75% (n = 4314 deaths), followed by other immunodeficiency conditions or risk factors with 5.5% (n = 320) of deaths: non-Hodgkin lymphoma (27), unspecified immunodeficiency (17), lymphoid leukemia (13) [journals.plos.org]

• Cough

  The first patient was a 17-year-old female, had fever, cough, headache and intractable vomiting as well as itchy water bumps on her skin and upper limbs. The cutaneous eruption prompted the accurate diagnosis. [ncbi.nlm.nih.gov]

  People may have no symptoms or may have headache and confusion, a cough and an achy chest, or a rash, depending on where the infection is. The diagnosis is based on culture and examination of tissue and fluid samples. [msdmanuals.com]

  In the minority of cases where symptoms do develop, signs may vary from a non-specific cough to more severe symptoms such as shortness of breath (dyspnea) or pleuritic chest pain. [news-medical.net]

• Sputum

  CSF, sputum, and urine yield organisms most often, and blood cultures may be positive, particularly in patients with AIDS. [msdmanuals.com]

  Sputum cytology for malignant cells and acid-fast stain for acid-fast bacilli was negative. HIV antibody test was negative and CD4 count - 502 cells/microliter. [ccij-online.org]

  Abstract Cryptococcus neoformans was cultured from the sputum, bronchial washings, or pleural fluid of 17 patients, 9 of whom were thought to have cryptococcal pulmonary disease. [annals.org]

  The physical exam may reveal: Abnormal breath sounds Fast heart rate Fever Mental status changes Stiff neck Tests that may be done include: Blood culture to differentiate between the two fungi CT scan of the head Sputum culture and stain Lung biopsy Bronchoscopy [nlm.nih.gov]

• Pleural Effusion

  Routine chest X-ray film showed pleural effusion, and his retropositive status was detected for the first time. [hoajonline.com]

  A new infiltrate in the right lung and pleural effusion associated with fever developed on August 15, 2004. Cultures of the pleural effusion drawn on August 19 yielded Cryptococcus neoformans (isolate A). [nejm.org]

  Masses ( n = 2), lymphadenopathy ( n = 2), areas of consolidation ( n = 2), areas of hazy increased attenuation ( n = 1), pleural effusion ( n = 1), and areas of cavitation ( n = 1) were uncommon. [pubs.rsna.org]

  effusion may also be present. [radiopaedia.org]

  Miliary disease, cavitation, pleural effusions, and lymphadenopathy are also recognized features, but are seen more commonly in immunocompromised patients [ 5 - 7, 9 ]. [ajronline.org]

• Respiratory Distress

  The presentation of pulmonary cryptococcosis can range from asymptomatic nodular disease to severe acute respiratory distress syndrome (ARDS) 3 : most often, causes several lung nodules or masses +/- cavitation, chiefly in immunocompromised patients additionally [radiopaedia.org]

  […] failure or acute respiratory distress syndrome may also be seen Other manifestations include skin (eg papules, pustules, nodules, etc.), osteomyelitis, eye ( chorioretinitis ), hepatitis and myocarditis. [patient.info]

  Symptoms of pulmonary cryptococcosis include: Coughing Difficulty breathing Chest pain Development of pulmonary nodules (small, round masses in the lungs) Severe cases of pulmonary cryptococcosis can develop into acute respiratory distress syndrome (ARDS [study.com]

  Severe infection may lead to pneumonia or adult respiratory distress syndrome. Central nervous system (CNS) Meningitis is the most common presentation. [dermnetnz.org]

• Hemoptysis

  Five weeks after admission, pulmonary consultation was requested to evaluate fever, worsening dyspnea, wheezing, and moderate hemoptysis. [journals.lww.com]

  Other symptoms include fever, weight loss, malaise and coughing up blood or hemoptysis. On rare occasions, pleural effusion occurs. Severe pulmonary diseases and respiratory syndromes are more likely to occur in those with weakened immune systems. [news-medical.net]

  No patient had hemoptysis. [academic.oup.com]

  A patient with pulmonary cryptococcosis may present with mild-to-moderate symptoms, including fever, malaise, cough with scant sputum, pleuritic pain, and hemoptysis (rare). Unusual findings include rales or pleural rub. [emedicine.medscape.com]

  Some patients may also have hemoptysis and hypoxemia. In HIV-infected patients, pulmonary cryptococcosis is more severe and has a more acute onset than that in other hosts. [aidsrestherapy.biomedcentral.com]

• Failure to Thrive

  Surgery should be considered if there is compression of vital structures or failure to thrive, or if four weeks of therapy does not reduce the size of the cryptococcoma. [aafp.org]

• Tachycardia

  CASE REPORT A 72-year-old man was hospitalized after a syncopal episode related to sustained ventricular tachycardia. Coronary angiography disclosed global myocardial dysfunction, an ejection fraction of 20%, and normal coronary arteries. [journals.lww.com]

• Bone Pain

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions Sweating -- unusual, excessive [mountsinai.org]

  […] in nearby areas, skin rash, pinpoint red spots (petechiae), bleeding into the skin, bruises, unintentional weight loss, appetite loss, abdominal bloating, abdominal pain, abdominal swelling, weakness, bone pain, and numbness and/or tingling. [rarediseases.org]

• Blurred Vision

  Symptoms of brain infection may include: Fever and headache Neck stiffness Nausea and vomiting Blurred vision or double vision Confusion The infection can also affect the lungs and other organs. [nlm.nih.gov]

  The principal symptoms of the meningitis are headache, blurred vision, and confusion, lethargy, or personality change. The Cryptococcus fungus can also spread to and cause lesions in the skin, bones, and visceral organs. [britannica.com]

  Headache, nausea, confusion, blurred vision, and abnormal gait may be presenting symptoms. Papilledema, cranial nerve palsies, mild fever, and mild meningismus may be present in some patients. [visualdx.com]

  Larry developed a fever, blurred vision, and he had a difficult time breathing. Additionally, he noticed small sores had began to show up on his legs and arms. Due to these recent symptoms, Larry decided to go to the ER. [study.com]

  Other symptoms vary depending on where the infection is: Lung infection: No symptoms in some people, a cough or an aching chest in others, and, if the infection is severe, difficulty breathing Meningitis: Headache, blurred vision, depression, agitation [msdmanuals.com]

• Diplopia

  Meningitis and meningoencephalitis Headache Confusion Altered mental status Coma Seizures Neurological signs include diplopia, ataxia and aphasia Pulmonary cryptococcosis This is underdiagnosed Seen in between 25-55% of patients with AIDS who have cryptococcal [patient.info]

  A 19-year-old nonaddict boy presented with the chief complaints of the neck pain, headache, vomiting, fever, diplopia, and cough for the past 4 weeks. There was no significant past, personal, and family history. [lungindia.com]

  Symptoms such as blurred vision, photophobia, and diplopia may result from arachnoiditis, papilledema, optic nerve neuritis, or chorioretinitis. Other findings include hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements. [emedicine.medscape.com]

  Headache, high fever, nuchal pain and stiffness, photophobia, confusion, nausea, vomiting and diplopia are the common presenting symptoms of cryptococcal meningitis (CM). [sajhivmed.org.za]

• Visual Impairment

  The factors associated with neurological complications or death were headache (P = 0.008), seizures (P = 0.006), visual impairment (P = 0.011), neck stiffness (P = 0.008), low erythrocyte sedimentation rate (ESR) (P = 0.024), and a cerebral spinal fluid [ncbi.nlm.nih.gov]

  […] consciousness, motor signs, nausea, vomiting, or visual impairment. [emedicine.medscape.com]

  VEP abnormalities were detected in visually impaired patients (68.9% of right eyes and 67.6% of left eyes), and in visually normal patients (56.5% of all eyes). [sajhivmed.org.za]

  Placement of a ventriculoperitoneal shunt was eventually required to control her persistently increased intracranial pressure, but at the most recent medical review, the patient was found to have had severe bilateral visual impairment, which is likely [doi.org]

  Visual impairment may result from either direct invasion of the optic nerve by cryptococci or from the increased intracranial pressure. [40] In the present series of cryptococcal meningitis among immunodeficient individuals, autopsy was done in 57 cases [neurologyindia.com]

• Ulcer

  In this case, it is suggested that a large deep skin ulcer can be an initial manifestation of systemic cryptococcosis, as, in some cases, pulmonary cryptococcosis may be asymptomatic. [ncbi.nlm.nih.gov]

  A well-defined, tender, indurated, ulcerated plaque measuring 3×4 cm on the left side of the neck. Figure 2. An erythematous 1×1-cm nodule with a central ulcerated core on the right shoulder. Figure 3. [mdedge.com]

• Skin Lesion

  Primary cutaneous cryptococcosis (PCC) is a more rare clinical identity that is characterized by skin lesions confined to 1 body region, often presenting as a whitlow or phlegmon with positive culture for C neoformans and no evidence of simultaneous dissemination [ncbi.nlm.nih.gov]

  These are cryptococcus skin lesions. Cryptococcus is a yeast (type of fungus) that seldom causes infection, but is considered opportunistic (it affects people with weakened immune systems). [mountsinai.org]

  In HIV AIDS, cryptococcosis is suspected when papulonodular necrotizing skin lesions like MC are seen with neurological or pulmonary disease. [odermatol.com]

• Skin Rash

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions Sweating -- unusual, excessive [mountsinai.org]

  rash, pinpoint red spots (petechiae), bleeding into the skin, bruises, unintentional weight loss, appetite loss, abdominal bloating, abdominal pain, abdominal swelling, weakness, bone pain, and numbness and/or tingling. [rarediseases.org]

• Petechiae

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  Symptoms of cutaneous cryptococcosis include: Rashes Ulcers Petechiae: small red dots that form on the skin that are caused by blood leaking out of broken blood vessels Cellulitis: a bacterial infection of the skin that causes the skin to become swollen [study.com]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions Sweating -- unusual, excessive [mountsinai.org]

• Sweating

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots ( petechiae ), ulcers, or other skin lesions Sweating -- unusual, [nlm.nih.gov]

  Lung symptoms may include: Difficulty in breathing Cough Chest pain Other symptoms may include: Bone pain or tenderness of the breastbone Fatigue Skin rash, including pinpoint red spots (petechiae), ulcers, or other skin lesions Sweating -- unusual, excessive [mountsinai.org]

  In general, symptoms of various forms of cryptococcosis may include: chest pain, dry cough, headache, nausea, confusion, blurred or double vision, fatigue, fever, unusual and excessive sweating at night, swollen glands without the appearance of infection [rarediseases.org]

• Headache

  Fever, headache, and vomiting were the most common symptoms. The most common sites were the central nervous system (CNS), followed by the lungs. [ncbi.nlm.nih.gov]

• Neck Stiffness

  The factors associated with neurological complications or death were headache (P = 0.008), seizures (P = 0.006), visual impairment (P = 0.011), neck stiffness (P = 0.008), low erythrocyte sedimentation rate (ESR) (P = 0.024), and a cerebral spinal fluid [ncbi.nlm.nih.gov]

  stiffness often absent, fever often late other sites involved in AIDS: lungs, bone marrow, skin (often resembles molluscum contagiosum), and genitourinary tract C. gattii predominantly causes pneumonia Investigations blood culture biopsy lesions CXR [lifeinthefastlane.com]

  Symptoms of brain infection may include: Fever and headache Neck stiffness Nausea and vomiting Blurred vision or double vision Confusion The infection can also affect the lungs and other organs. [nlm.nih.gov]

  Headache was the most common symptom followed by neck stiffness and fever. [acmicrob.com]

• Altered Mental Status

  Clinical Presentation: Most patients present with symptoms or signs of subacute meningitis or meningoencephalitis, with fever, malaise, nausea, vomiting, lethargy, and altered mental status. [ajnr.org]

  Meningitis and meningoencephalitis Headache Confusion Altered mental status Coma Seizures Neurological signs include diplopia, ataxia and aphasia Pulmonary cryptococcosis This is underdiagnosed Seen in between 25-55% of patients with AIDS who have cryptococcal [patient.info]

  Lungs: shortness of breath, cough, chest pain fever Brain: Headache, neck pain, nausea, vomiting, sensitivity to light, altered mental status, fever Symptoms can develop between two to thirteen months after inhalation of the fungus. [health.hawaii.gov]

  Signs and symptoms include headache, altered mental status, confusion, lethargy, nausea and vomiting, blurred vision or double vision, seizures and coma. This form of infection is fatal without appropriate therapy. [dermnetnz.org]

  In patients with AIDS, cryptococcal meningitis may cause minimal or no symptoms, but headache frequently occurs and sometimes slowly progressively altered mental status. [msdmanuals.com]

• Asthenia

  We studied the case of a 21 years old male patient, admitted for asthenia, fever, cough, dyspnea… CONTINUE READING Figures and Topics from this paper. References Publications referenced by this paper. [semanticscholar.org]

  Patients suffering meningoencephalitis presented incomplete meningeal syndrome, vomiting, photophobia, visual alterations, blindness,25 diarrhea, anorexia and asthenia. Seizures and focal signs were much less frequent. [elsevier.es]

• Neurologic Manifestation

  Neuroophthalmological disorders in HIV infected subjects with neurological manifestations. Br J Ophthalmol. 2004;88:1455-9. 11) Tilak R, Prakash P, Nigam C, Tilak V, Gambhir IS, A K Gulati AK. [turkjpath.org]

  Levy RM, Bredesen DE, Rosenblum ML (1985) Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of literature. J Neurosurg 62: 475-495. Casadevall A, Perfect JR (1998) Cryptococcus neoformans. [omicsonline.org]

The combination of clinical findings, as well as patient history, can provide sufficient evidence to investigate Cryptococcosis as a possible illness. Patient history may reveal an underlying disease or risk factors, such as HIV infection, or immunosuppressive therapy, which may predispose the patient to cryptococcal infection.

Workup involves radiographic and laboratory procedures. In a case of respiratory complaints, plain chest X-ray should be performed, and it can reveal single or multiple nodules in the parenchyma, which can mimic malignant tumors because of its shape and appearance. Other findings, such as hilar lymphadenopathy, pleural effusion, and lobar or diffuse infiltrates are also observed.

If there are symptoms indicating a CNS infection, computed tomography (CT) or magnetic resonance imaging (MRI) of the endocranium should be performed, and they can reveal hydrocephalus or such findings as the presence of one or more cryptococcomas. The severity of the disease has been established to be in correlation with the severity of findings in neuroimaging studies, particularly for HIV-positive patients [9].

Because numerous pathogens may cause similar symptoms and signs of pulmonary and central nervous system involvement, several diagnostic procedures are performed to exclude other pathogens as causative agents, but also to confirm Cryptococcosis. Lumbar puncture may show very high opening pressure, as well as abnormal protein and glucose content. In addition to biochemical investigations, a CSF sample is obtained for microbiological investigation, principally for antigen detection and culture. Antigen detection in CSF is both very sensitive and specific, and detects the presence of Cryptococcus neoformans rapidly. A definite confirmation can be given by cultivation of the obtained CSF or blood, and microscopy examination, with both standard as well as India ink stainings, which can clearly visualize budding yeasts and provide results within several days. Biopsy and tissue samples are also possible diagnostic tools, but antigen detection, culture, and microscopic examination are sufficient to obtain a diagnosis in virtually all cases.

Laboratory tests should also include the evaluation of the immune system, including leukocyte count, which may show leukopenia, with either neutropenia, lymphopenia, or both. Additionally, if patients are HIV positive, CD4+ T cell counts should be performed.

• Pulmonary Infiltrate

  We made a provisional diagnosis of pulmonary infiltrates with eosinophilia syndrome with eosinophilic meningitis. [lungindia.com]

  Fluconazole (400 mg [6 mg per kg] per day) should be used for six to 12 months in patients with mild to moderate symptoms without diffuse pulmonary infiltrates. [aafp.org]

  A 46-year-old woman with extensive pulmonary infiltrates. N Engl J Med 2002; 347:517-524 [Google Scholar] 15. Lam CL, Lam WK, Wong Y, et al. Pulmonary cryptococcosis: a case report and review of the Asian-Pacific experience. [ajronline.org]

  For mild-to-moderate symptoms and focal pulmonary infiltrates, treatment with fluconazole (400 mg daily for 12 months) combined with effective ART is appropriate (BIII). [aidsinfo.nih.gov]

  Symptoms of acute pneumonia with cough, fever, and lobar pulmonary infiltrates affecting alveoli or a diffuse interstitial pattern, indistinguishable from P. jiroveci infection occurs in patients with AIDS.[16] Very rarely, it can present as an acute [jpgmonline.com]

• Multiple Pulmonary Nodules

  multiple pulmonary nodules or masses, which mimics primary or metastatic malignancy. [5], [9], [10] A large solitary cryptococcoma replacing the majority of a lobe, as seen in our case, is highly unusual. [ccij-online.org]

  The most common radiographic manifestations of pulmonary cryptococcosis consist of single or multiple pulmonary nodules, segmental or lobar consolidation, or a reticulonodular pattern of opacities [ 3, 5 - 7 ]. [ajronline.org]

• Cryptococcus Antigen

  Cryptococcal capsular polysaccharide antigen test of the CSF or serum was conducted using the latex-Cryptococcus antigen detection system (Immuno-Mycologics, Inc., USA). A result of at least 1:10 was considered positive [12, 13]. [bmcinfectdis.biomedcentral.com]

  Semiquantitative CRAG latex titers ( Cryptococcus Antigen Latex Agglutination Test System; Immy, Inc.) were measured by 2-fold serial dilution on cryopreserved (−80°C) samples in Minnesota. [doi.org]

• Pleural Effusion

  Routine chest X-ray film showed pleural effusion, and his retropositive status was detected for the first time. [hoajonline.com]

  A new infiltrate in the right lung and pleural effusion associated with fever developed on August 15, 2004. Cultures of the pleural effusion drawn on August 19 yielded Cryptococcus neoformans (isolate A). [nejm.org]

  Masses ( n = 2), lymphadenopathy ( n = 2), areas of consolidation ( n = 2), areas of hazy increased attenuation ( n = 1), pleural effusion ( n = 1), and areas of cavitation ( n = 1) were uncommon. [pubs.rsna.org]

  effusion may also be present. [radiopaedia.org]

  Miliary disease, cavitation, pleural effusions, and lymphadenopathy are also recognized features, but are seen more commonly in immunocompromised patients [ 5 - 7, 9 ]. [ajronline.org]

Treatment of Cryptococcosis depends on the severity of disease and the site of infection. Patients who have asymptomatic colonization may not require therapy, and those with mild pulmonary involvement, without evidence of extrapulmonary infection, may receive oral fluconazole 200-400mg PO q24h for a prolonged period of time.

However, patients with serious disease require intravenous administration of antifungals, such as those with symptomatic pulmonary, central nervous system or disseminated infections, and primary choice is amphotericin B in doses of 0.5 to 1.0 mg/kg IV q24h, usually combined with flucytosine 25mg/kg q6h for al least 14 days or longer [10]. The primary parameter of a duration of treatment is the presence of sterile cultures of CSF or blood. Additional treatment options include liposomal amphotericin B 4 mg/kg IV q24h, combined with fluconazole 400mg either PO or IV q24h, or a combination of fluconazole and flucytosine for 4-6 weeks [11]. In addition to antifungal therapy, appropriate symptomatic therapy is necessary, such as antiedematous therapy in the setting of increased cerebrospinal fluid pressure and brain edema.

Once the infection is resolved with therapy, consolidation therapy is necessary to prevent recurrent infections, and it consists of oral administration of fluconazole 400-800mg once daily, for about 10 weeks [12]. Once this course of therapy is finished, the third and last course of therapy includes suppression therapy, which is important to patients who were severely immunocompromised at the time of infection, and consists of administration of fluconazole per os 200mg once daily, for 6-12 months. Patients who improve CD4+ T cell counts (> 200/mm3) may stop this regimen.

Patients with HIV infection, particularly those who are severely immunocompromised, should not be started on immediate antiretroviral therapy, as it has been established that deferral of therapy for several weeks drastically improved survival outcomes [13].

An early diagnosis is essential for a good prognosis because Cryptococcosis can be successfully treatable with systemic antifungal therapy.

However, an important factor is the general condition of the patient. Despite available therapy, Cryptococcosis can still be a fatal disease.

This fungal infection is principally caused by Cryptococcus neoformans, and in a small number of cases, Cryptococcus gattii. Since initial discovery in 1895 [2], the fungal genus Cryptococcus have been extensively researched. These fungi are oval, yeastlike organisms, with the diameter ranging from 2-20 µm. Cryptococcus species are encapsulated, and their polysaccharide capsule is the principal virulence factor. They are classified into different serotypes according to the composition of the polysaccharide capsule.

This fungus replicates through asexual reproduction, specifically by budding, and the replication process is rather slow, which accounts for a slowly developing infectious process, and initial asymptomatic course of the disease.

Fungal genus Cryptococcus has a worldwide distribution, which is particularly true for Cryptococcus neoformans. It is a ubiquitous microorganism that is found in soil which contains bird droppings [3]. It is established that the replication cycle starts in birds, primarily pigeons, who do not develop an infection (presumably because of high body temperatures ) but shed the fungus in feces, which ends up in soil. Inhalation of contaminated aerosols is the principal route of acquisition of the disease. A somewhat different cycle is proposed for Cryptococcus gattii, which was initially restricted to tropical and subtropical regions, and associated with Eucalyptus trees. Outbreaks in the northwestern Pacific have questioned these theories.

Cryptococcosis can be divided by the affected population. Namely, Cryptococcus neoformans causes infection primarily in immunocompromised individuals, which may include patients suffering from various diseases, or receiving specific forms of therapy:

• Patients with HIV infection and Acquired Immunodeficiency Syndrome (AIDS); importantly Cryptococcosis is classified as an AIDS-defining illness [4]
• Organ transplant recipients
• Dialysis patients
• Patients with autoimmune disorders (such as Systemic Lupus Erythematosus)
• Diabetes mellitus patients
• Patients receiving corticosteroids

On the other hand, Cryptococcus gattii infection is primarily reported in immunocompetent individuals.

Cryptococcosis starts with inhalation of aerosols contaminated with the fungus, and the initial site of replication is the respiratory tract [5]. Under physiological circumstances, when the fungi reach the lower respiratory tract, alveolar macrophages are recruited, and together with migrating leukocytes are involved in an inflammatory response, which results in the fungus elimination. However, in cases of immunosuppression, the fungus is able to proliferate and spreads to other sites through blood, and can establish either focal or disseminated infection. Cryptococcosis also may remain dormant in the lungs.

The primary virulence factor of Cryptococcus is the polysaccharide capsule, which prevents binding of complement, prevents phagocytosis, interferes with a secretion of proinflammatory cytokines, and allows the fungi to replicate inside the human host.

Prevention of cryptococcosis can rarely be achieved through avoiding exposure because the organism can be found all over the world in soil, and in locations habituated by pigeons, so the principal preventive measure is managing of possible underlying diseases that can predispose individuals to this infection, and regular follow-ups of patients who are at risk.

Cryptococcosis is caused by Cryptococcus neoformans, a ubiquitous fungal pathogen, while Cryptococcus gattii is responsible for a small percentage of cases [1]. Inhalation of contaminated aerosol which contains avian fecal material is the mode of acquisition of Cryptococcus neoformans infection, while Cryptococcus gattii infection has been associated with contaminated eucalyptus trees, and has been primarily linked to habitation in the tropical and subtropical regions. However, recent outbreaks in the northwestern Pacific suggest other modes are involved in its transmission. Human-to-human transmission has not been documented yet for either species. Once the fungus reaches the respiratory tract, several factors play a role in establishing an infection, including the virulence of the strain, a size of inoculum, and most importantly, host defenses. The majority of patients who develop infection by Cryptococcus neoformans are immunocompromised, most commonly due to human immunodeficiency virus (HIV) infection, with CD4+ T-cell counts of < 200/mm3, while patients with malignant diseases, transplant recipients, or those receiving chemotherapy, are also particularly susceptible to this infection. On the other hand, Cryptococcus gattii infection is more frequently observed in immunocompetent individuals. Cryptococcus species primarily infects the respiratory system, which results in pneumonia-like disease. Patients may be asymptomatic, present with mild respiratory complaints, or have severe bilateral infiltrates with significant consequences on lung function. In addition to pneumonia-like disease, infection of the central nervous system as a result of hematogenous spread from the lungs, poses a greater threat to the patient, and can manifest as meningitis or meningoencephalitis. The diagnosis is made by culture of cerebrospinal fluid (CSF) or blood, or other material, depending on the site of infection. A particular staining, India ink, as well as standard Gram staining is used for identification of cultured fungi, but rapid and reliable confirmation can be obtained through direct identification of cryptococcal antigen in blood or CSF through serological testing. Treatment comprises administration of systemic antifungals, such as amphotericin B, flucytosine, and fluconazole. Prevention of cryptococcosis primarily involves improving the immune status.

in serious casesCryptococcosis is an infection caused by two fungi, Cryptococcus neoformans and Cryptococcus gattii. Cryptococcus neoformans is present in bird feces. Human infection occurs by inhalation of particles from soil that contain this fungus. Humans can inhale the contaminated soil, but they may not develop an infection, and a substantial number of individuals have an asymptomatic infection by this fungus, as their immune system is able to fight off the fungus. However, when patients are immunocompromised, such as patients with HIV or those receiving immunosuppressive therapy and chemotherapy, they are at risk of developing this infection. On the other hand, Cryptococcus gattii, which is not transmitted through bird feces, but instead has been associated with an acquisition from eucalyptus trees, causes infection in immunocompetent and otherwise healthy individuals, although this organism is much rarely observed as a cause of Cryptococcosis.

The most common type of infection in Cryptococcosis is pulmonary, with manifestations such as cough, chest pain, fever, increased breathing rate, and sputum production. Infection of the central nervous system manifests with fever, headache, vomiting, and in severe cases, altered consciousness, seizures, and even coma. Cryptococcosis may also target the eyes, skin, kidneys, liver, prostate, breasts, and other organs, and sometimes more than one organ can be affected.

Cryptococcosis may be life-threatening, and it is one of the most common life-threatening fungal infections in patients with HIV infection and AIDS, which is why prompt diagnosis and treatment is necessary for achieving a good result. The diagnosis is made by identification of fungi through different tests, most common being detection of the fungi from cerebrospinal fluid. In addition to microbiological confirmation, imaging studies, such as chest X-rays, CT and MRI of the head, as well as other accompanying blood tests, should be performed to assess the focus, as well as the severity of the infection.

Treatment includes intravenous and oral administration of antifungals, such as amphotericin B, flucytosine or fluconazole. Once the infection has resolved, antifungal therapy may be continued for up to a year through oral intake of fluconazole, to prevent recurrent infection. In addition to antifungal therapy, symptomatic and supportive therapy are necessary to support the patient during administration of antifungal therapy. If this infection is treated promptly, and properly, a good outcome can be expected. Despite well-defined guidelines, it is still a life-threatening infection in serious cases.

Prevention in high-risk patients can be achieved through proper management of the underlying disease, since avoiding exposure to areas contaminated with this fungus, is highly unlikely.

1. Lin X, Heitman J. The biology of the Cryptococcus neoformans species complex. Annu Rev Microbiol. 2006;60:69-105.
2. Buschke A. Ueber eine durch Coccidien Hervergerufene Krankheit des menschen. Deutsche Med. Wochenschr. 1895;21(3):14.
3. Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am. 2002;16:837-874.
4. Dromer F, Mathoulin-Pelissier S, Fontanet A, et al. Epidemiology of HIV-associate cryptococcosis in France (1985-2001): comparison of the pre-and post-HAART eras. AIDS. 2004;18:555-562.
5. Chang WC, Tzao C, Hsu HH, et al. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest. 2006;129(2):333-340.
6. Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006;20:507-544.
7. Sabiiti W, May RC. Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans. Future microbiol. 2012;7(11):1297-1313.
8. Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141-150.
9. Charlier C, Dromer F, Leveque C, et al. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIV-positive patients in the HAART era. PLoS One. 2008;3:e1950.
10. Jarvis JN, Dromer F, Harrison TS, et al. Managing cryptococcosis in the immunocompromised host. Curr Opin Infect Dis. 2008;21:596-603.
11. Perfect JR, et al. Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(3):291-322.
12. Limper AH, Knox KS, Sarosi GA, et al; American Thoracic Society. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183:96-128.
13. Boulware DR, Meya DB, Muzoora C, et al.Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis. N Engl J Med. 2014;370:2487-2498.