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Disseminated Cryptococcosis

Disseminated cryptococcosis is considered to be the most severe form of infection caused by two fungal species - Cryptococcus neoformans and less commonly Cryptococcus gattii. The majority of patients who develop this ailment suffer from immunodeficiency, primarily caused by human immunodeficiency virus (HIV) infection. Virtually every organ can be affected, but the lungs, the central nervous system (CNS), and the skin are main sites where disseminated cryptococcosis exerts symptoms. Clinical suspicion is confirmed by microbiological studies.


Presentation

Cryptococcus neoformans, a ubiquitously distributed (found in soil and bird feces) fungal pathogen, and Cryptococcus gattii (an increasingly prevalent microorganism) are the two species that may cause an infection of virtually every organ termed cryptococcosis [1] [2]. C. neoformans is associated with the incidence of disease in immunocompromised hosts, such as those suffering from HIV infection, organ transplant recipients, and in individuals who are receiving immunosuppressants or cytotoxic drugs; thus it is often described as an opportunistic pathogen [1] [3]. In fact, cryptococcosis is the leading cause of acquired immunodeficiency syndrome (AIDS)-related death from fungi [2]. However, an increasing number of reports show cryptococcosis in immunocompetent individuals, particularly with C. gattii as the underlying cause [4] [5] [6]. The pathogenesis stems from inhalation of spores that should be normally broken down by the macrophages residing in the respiratory epithelium, but impaired immune function can lead to involvement of any organ, such as the skin, the liver, spleen, kidneys, but most importantly, the lungs and the CNS [2]. Disseminated cryptococcosis (DC), however, is a systemic and most severe form of disorder caused by these fungi, primarily because mortality rates rise rapidly in the absence of early recognition and proper therapy [1] [2]. Some authors consider that the cutaneous signs appear first and precede the onset of DC by a few weeks [2]. Lesions range from centrally-ulcerated small papules or macules to marked inflammatory changes (cellulitis or abscess formation), which may often be misdiagnosed as bacterial infections of the skin [1] [2]. In addition to cervical lymphadenitis, manifestations of DC include fever, CNS symptoms such as headaches, cranial nerve palsies, and altered consciousness (hallmarks of cryptococcal meningitis), as well as severe cavitations and effusions of the lungs [1] [2].

Fever
  • We report a case of a 49-y-old leukemic patient with disseminated cryptococcosis who presented with fever, headache, normal cerebrospinal fluid profile and multiple skin lesions mimicking molluscum contagiosum.[ncbi.nlm.nih.gov]
  • A young, unmarried, immunocompetent female presented with complaints of fever and altered sensorium, along with lesions over the face and trunk. A provisional diagnosis of disseminated herpes simplex with giant molluscum contagiosum was made.[ncbi.nlm.nih.gov]
  • Experience from this case suggests that cryptococcal infection should be considered in the differential diagnosis of pregnant women presenting with vague systemic symptoms such as fever, abdominal pain, and generalized lymphadenopathy.[ncbi.nlm.nih.gov]
  • She presented with a cough and a week-long fever. A computed tomography scan showed multiple pulmonary nodules randomly distributed. Eosinophils were observed to have increased in number in both her peripheral blood and bronchoalveolar lavage fluid.[ncbi.nlm.nih.gov]
  • The patient presented with a past history of postmenopausal bleeding with loss of consciousness, altered mental status, few seizures and a low grade fever.[ncbi.nlm.nih.gov]
Malaise
  • Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation.[ncbi.nlm.nih.gov]
  • […] neoformans is the most common fungal infection in HIV patients, and a concurrent rise has also been seen in the number of HIV patients suffering from pandemic influenza A virus. [3] Apart from protean manifestations of upper respiratory tract symptoms and malaise[jlponline.org]
Chills
  • CASE REPORT A 23-year-old Asian man with chronic renal allograft dysfunction was admitted to our hospital in May 2001 with a 10-day history of fever, intermittent chills, dry cough and progressive dyspnea.[e-sciencecentral.org]
  • Most patients treated with amphotericin B had good tolerance, except for 3 patients who had high fever and chills, and 2 who had elevated aminotransferase and neutropenia, respectively.[bmcinfectdis.biomedcentral.com]
Fatigue
  • The common symptom is fatigue, but it is often asymptomatic, and the articular manifestations may occur as arthralgia and non-erosive arthritis on the small joints [ 4, 6 ].[karger.com]
Turkish
  • Disseminated infection in HIV-negative individuals is occasionally seen: a 57-year-old HIV-negative Turkish female initially presented with enlarged mediastinal lymph nodes and a large pulmonary parenchymal nodule, eventually diagnosed with disseminated[ncbi.nlm.nih.gov]
Diarrhea
  • Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation.[ncbi.nlm.nih.gov]
  • A 64-year-old woman with Crohn's disease (CD) was referred to Siriraj Hospital due to worsening of abdominal pain and watery diarrhea for 2 weeks. The dose of immunosuppressive agents was increased for presumed exacerbation of CD.[ncbi.nlm.nih.gov]
  • The patient was a twenty-three-year-old man, with a history of daily fever during one month associated with diarrhea, weight loss, headache, vomiting and generalized seizures.[ncbi.nlm.nih.gov]
  • In addition, 2 patients presented with facial paralysis, 2 with loss of consciousness, and 1 with diarrhea and blindness. Hospitalization time ranged from 2 days to 109 days, with an average of 42.4 27.2 days.[bmcinfectdis.biomedcentral.com]
Excoriation
  • The eruption was characterized by excoriated papules of the upper body and was initially diagnosed as folliculitis. A pseudofollicular eruption is a rare presentation for disseminated cryptococcosis.[ncbi.nlm.nih.gov]
Headache
  • We report a case of a 49-y-old leukemic patient with disseminated cryptococcosis who presented with fever, headache, normal cerebrospinal fluid profile and multiple skin lesions mimicking molluscum contagiosum.[ncbi.nlm.nih.gov]
  • Abstract A 36-year-old homosexual Mexican man was admitted to our hospital, with a 30-day history of fever and headache.[ncbi.nlm.nih.gov]
  • Subsequently patient had developed headache. Radiological evaluation showed presence of ring enhancing lesion in the occipital region. On evaluation with Fibre-optic bronchoscopy, there was no evidence of malignancy or tuberculosis.[ncbi.nlm.nih.gov]
  • However, headache was more common in patients with central nervous system (CNS) invasion than in patients with non-CNS invasion (P CONCLUSIONS: Disseminated cryptococcosis can occur in previously healthy or immunocompetent children in China.[ncbi.nlm.nih.gov]
  • The most frequent signs and symptoms were headache (53.4%) and fever (51.7%). The most widely used medication was the amphotericin B (43 patients). The mortality rate was 45%.[ncbi.nlm.nih.gov]
Neck Stiffness
  • Once she became asymptomatic following treatment with fluconazole and neutropenia was recovered with lenograstim, she had neck stiffness and admitted soon. Cerebro-spinal fluid (CSF) culture was positive for Cryptococcus neoformans.[ncbi.nlm.nih.gov]
  • He was otherwise asymptomatic and, in particular, did not present with fever, a decline in general health, or neurologic signs such as headaches, altered mental status, or neck stiffness.[nejm.org]
  • The patient had a moon face, truncal obesity and neck stiffness. On oscultation of the lungs, there were fine crackles in the left lower lung field. An abdominal examination revealed no remarkable findings.[kjim.org]
Confusion
  • Patients complain mainly of headaches, fever and confusion or clouding of consciousness which progresses rapidly over a few days.[hivbook.com]
  • Other symptoms can include seizures, confusion, dementia, and bizarre behavior. Cerebral edema leading to elevated intracranial pressure can cause blurred vision, diplopia, confusion, hearing loss, and severe headaches [ 8 ].[link.springer.com]
Generalized Seizure
  • The patient was a twenty-three-year-old man, with a history of daily fever during one month associated with diarrhea, weight loss, headache, vomiting and generalized seizures.[ncbi.nlm.nih.gov]

Workup

The diagnosis of disseminated cryptococcosis needs to be made as soon as possible. The physician must first obtain a detailed patient history, during which the assessment of risk factors and previous illnesses could be crucial, particularly if HIV is identified. After an extensive physical examination, microbiological studies should be employed immediately. Several methods have been described in the literature when it comes to detecting cryptococcal species [3] [5] [6]. Identification of cryptococcal antigen through serological methods - latex agglutination and enzyme immunoassays (EIAs) is most frequently utilized due to their very high sensitivity and specificity rates, together with a very short turnaround time [4] [5]. The cerebrospinal fluid (CSF) is usually the sample tested by these methods [2] [5]. Cultivation of cryptococcus from CSF, sputum (specifically the bronchioalveolar lavage), urine, or scrapings from the skin, however, serves as a definite diagnostic measure, with positive results issued within 2-5 days [1] [5] [6]. Some authors advocate the need for a fine-needle aspiration cytology (FNAC) as the optimal technique for obtaining a viable sample of the lymph node aspirate for cultivation [1]. Most recent studies promote the use of newly synthesized lateral flow assay (LFA), a non-invasive, cost-effective, and simple method that can yield positive results on the same day, with the benefit of detecting C. gattii infections that are otherwise unrecognized by standard serology tests [2].

Bilateral Pulmonary Infiltrate
  • Chest X-ray scanning and computed tomography demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was detected in blood, skin, and sputum cultures.[ncbi.nlm.nih.gov]
Ground Glass Appearance
  • Chest computerized tomography revealed diffuse reticulonodular infiltration and a ground-glass appearance in both perihilar regions, suggestive of either Pneumocystis carinii pneumonia or cryptococcal pneumonia.[ncbi.nlm.nih.gov]
Left Pleural Effusion
  • CASE PRESENTATION: We describe a 63-year-old male renal transplant recipient on an immunosuppressive regimen who was admitted for left pleural effusion and fever. Cytological examinations and pleural fluid culture were nonspecific and negative.[ncbi.nlm.nih.gov]
Pyuria
  • Urinary analysis revealed proteinuria (75%), pyuria (31%), and budding yeast (13%). Nine (56%) patients received antifungal therapy. Other patients were misdiagnosed or died before treatment. The mortality rate was 64%.[ncbi.nlm.nih.gov]
Liver Biopsy
  • A liver biopsy performed 22 days after admission revealed numerous yeast-like organisms in hepatic sinusoids consistent with C. neoformans. Despite treatment, the patient died 55 days after admission and 66 days after transplantation.[ncbi.nlm.nih.gov]

Treatment

  • Treatment included reduction in immunosuppression regimen and targeted treatment for cryptococcal disease with liposomal amphotericin B and flucytosine followed by fluconazole consolidation and maintenance therapy.[ncbi.nlm.nih.gov]
  • Conservative treatment alone or treatment with a combination of the medical and surgical curettage is successful in most cases.[ncbi.nlm.nih.gov]
  • Despite treatment with amphotericin B and flucytosine, the patient developed both marked cholestasis and transaminase elevation.[ncbi.nlm.nih.gov]
  • Treatment with amphotericin B(AMPH-B) and flucytosine(5-FC) was initiated as diagnosis of cryptococcus meningitis. Lenograstim was administrated for 9 months, and amount of dose was 9,750 μg.[ncbi.nlm.nih.gov]
  • The diagnosis of disseminated cryptococcosis was confirmed and treatment was established. The patient showed improvement.[ncbi.nlm.nih.gov]

Prognosis

  • Data on clinical manifestations, laboratory tests, treatment, and prognosis were evaluated. RESULTS: A total of 52 pediatric patients with no underlying disease were enrolled, including 38 boys and 14 girls.[ncbi.nlm.nih.gov]
  • Depressed levels of consciousness, high CSF cryptococcal antigen titer, and cryptococcemia are associated with a poor prognosis [ 9 ].[link.springer.com]
  • Treatment and prognosis antifungals such as oral fluconazole or intravenous amphotericin B Promoted articles (advertising)[radiopaedia.org]
  • Information on the prognosis of pediatric patients was collected using telephone follow-up.[bmcinfectdis.biomedcentral.com]
  • Prognosis has much improved over the last years.[hivbook.com]

Etiology

  • A case report of fatal disseminated cryptococcosis in a patient treated with eculizumab is presented along with a review of literature suggesting a possible etiologic mechanism.[ncbi.nlm.nih.gov]
  • Practice Points Uncontrolled diabetes mellitus can be an important etiological factor for disseminated cryptococcosis.[mdedge.com]
  • (CT) of chest and abdomen showed small focal areas of consolidation and patchy ground glass opacities in posterior basal segments of lower lobes, along with multiple centrilobular and peribronchial tiny nodules in both lungs suggestive of infective etiology[indianpediatrics.net]
  • Regardless of etiology, all cases of endogenous Cushing’s syndrome are due to an increased production of cortisol by the adrenal gland.[kjim.org]
  • Discussion AIH is a chronic necroinflammatory liver disorder of unknown etiology.[karger.com]

Epidemiology

  • Epidemiologic differences between the two varieties of Cryptococcus neoformans. American Journal of Epidemiology 1984, 120: 123–130. Google Scholar Copyright information Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1998 Authors and Affiliations G.[springerlink.com]
  • Epidemiology: Cryptococcus neoformans classically is associated with desiccated pigeon feces, although the organism can be found in the feces of other birds including turkeys and starlings as well as in bat feces(4).[path.upmc.edu]
  • Nationwide population-based epidemiologic study of cryptococcal meningitis in Taiwan. Neuroepidemiology. 2011;36:79–84. View Article PubMed Google Scholar Huang KY, Huang YC, Hung IJ, Lin TY.[bmcinfectdis.biomedcentral.com]
  • We conducted a retrospective evaluation to determine the epidemiological, microbiological, immunological and clinical characteristics of disseminated cryptococcosis in 51 hospitalised HIV seropositive patients.[bases.bireme.br]
  • Cryptococcal infections: changing epidemiology and implications for therapy. Drugs. 2013; 73 (6): 495-504[ DOI ][ PubMed ] 4. Giri PP, Pal P, Gouda BR, Sinha R. Disseminated Cryptococcosis in a Patient With Nephrotic Syndrome.[archcid.com]
Sex distribution
Age distribution

Prevention

  • X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of patients to disseminated cryptococcal infections primarily due to CD40L deficiency that causes defective cross talk between T- and B-cells, thus preventing class switching[ncbi.nlm.nih.gov]
  • Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.[ncbi.nlm.nih.gov]
  • Treat your inpatient and ambulatory patients more effectively with the absolute latest on new topics such as quality improvement and patient care safety *school violence and bullying * preventive measures * vitamin deficiencies * adolescent rape * effect[books.google.com]
  • He was diagnosed with pandemic influenza A H1N1 by real-time polymerase chain reaction as per Centers for Disease Control and Prevention guidelines.[jlponline.org]
  • Combination prevents resistance and allows reduction of acute therapy to 4-6 weeks. The choice of combination is not clearly defined.[hivbook.com]

References

Article

  1. Seto H, Nishimura M, Minamiji K, et al. Disseminated Cryptococcosis in a 63-year-old Patient with Multiple Sclerosis Treated with Fingolimod. Intern Med. 2016;55(22):3383-3386.
  2. Lazzara M, Joshi A. Disseminated cryptococcosis involving the head and neck. BMJ Case Rep.. 2014;2014:bcr2013202306.
  3. Philip KJ, Kaur R, Sangeetha M, Masih K, Singh N, Mani A. Disseminated cryptococcosis presenting with generalized lymphadenopathy. J Cytol. 2012;29(3):200-202.
  4. Sacht GL, de Lima AM, Perdomo YC, Boigues RS, Takita LC, Hans Filho G. Disseminated cryptococcosis with cutaneous involvement in an immunocompetent patient. An Bras Dermatol. 2016;91(6):832-834.
  5. Perfect JR, Bicanic T. Cryptococcosis Diagnosis and Treatment: What Do We Know Now. Fungal Genet Biol. 2015;78:49-54.
  6. Bothra M, Selvaperumal P, Kabra M, Joshi P. Disseminated cryptococcosis. Indian Pediatr. 2014;51(3):225-226.

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Last updated: 2019-07-11 20:22