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]

  Case presentation: A 25-years old pregnant woman presented with fever without lymphadenopathy or cutaneous manifestations or manifestations pertaining to any other organ system. She was investigated to detect the cause of fever. [scopemed.org]

• 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]

  Case Report A 44 years old non-diabetic female from rural West Bengal was suffering from low grade intermittent fever, dry cough, fatigue and weight loss for one and half year. [omicsonline.org]

  Case report A 31-year-old man initially presented in early February 2013 with complaints of fatigue and was subsequently diagnosed with primary B-lineage acute lymphoblastic leukemia. [nature.com]

• 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]

  […] patients with CNS cryptococcal infection when administered for a median of 13 days. [52] In a randomized open-label trial from Burundi, the use of intralipid Amp B was associated with significantly lower chance of infusion related toxicity (fever and chills [jpgmonline.com]

• 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]

  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]

  […] 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]

• Anemia

  The patient developed evidence of microangiopathic hemolytic anemia, leading to a diagnosis of atypical hemolytic uremic syndrome, and was started on eculizumab. [ncbi.nlm.nih.gov]

  Complete blood count readings showed mild anemia (hemoglobin 105 g/L), normal white blood cell count (7.8 × 10 9 /L) with severe lymphopenia (0.15 × 10 9 /L), and severe thrombocytopenia (41 × 10 9 /L), which prompted a bone marrow (BM) aspiration. [bloodjournal.org]

  Peripheral smear examination revealed leukocytosis (Total leukocyte count, 50.2 × 10 3 /L) with eosinophilia (66% eosinophils, 18% neutrophils, 15% lymphocytes and 1% monocytes) without anemia or thrombo-cytopenia. [indianpediatrics.net]

• Tachypnea

  The patient was conscious, oriented to time, place and person, had tachypnea, tachycardia, pallor, and edema. The past history was significant for smoking and alcoholism. [jlponline.org]

• 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]

  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]

  Addition of FC causes side effects like diarrhea, hepatitis, and bone marrow suppression [36] usually in the first 2 weeks in a third of patients. [jpgmonline.com]

• Morning Stiffness

  Several metacarpophalangeal joints and wrist joints were swollen, with tenderness and stiffness in the morning for over 3 h. Her serum rheumatoid factor was high. [karger.com]

• Cutaneous Manifestation

  Case presentation: A 25-years old pregnant woman presented with fever without lymphadenopathy or cutaneous manifestations or manifestations pertaining to any other organ system. She was investigated to detect the cause of fever. [scopemed.org]

  Cutaneous manifestations can take various forms such as ulcers, papules, pustules, abscesses, purpura, nodules, subcutaneous swellings, and so on. [karger.com]

  Cutaneous manifestations of disseminated cryptococcosis. J Am Acad Dermatol. 1995;32(5 Pt 2):844–50. View Article PubMed Google Scholar Tanner DC, Weinstein MP, Fedorciw B, Joho KL, Thorpe JJ, Reller LB. [bmcinfectdis.biomedcentral.com]

• 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]

• Confusion

  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]

  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]

  Because most symptoms of cryptococcal meningitis result from cerebral edema, they are usually nonspecific (eg, headache, blurred vision, confusion, depression, agitation, other behavioral changes). [merckmanuals.com]

  […] laboratory accident cryptococci can be injected directly into the soft tissue causing localized infection, the vast majority are due to dissemination from the lung. [23] Ocular involvement is seen as choroidal infection and endophthalmitis [24] and can be confused [jpgmonline.com]

• Lethargy

  She reached a stringent complete response and presented with lethargy and seizure. Laboratory findings revealed severe CD4 lymphopenia, and Cryptococcus neoformans was detected in her cerebrospinal fluid and blood culture. [ncbi.nlm.nih.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]

  Instead they could present with lethargy, obtundation, stupor, coma, or even dementia. [18] Clinical signs lack precision or accuracy in predicting the aetiology in meningitis. [jpgmonline.com]

• Neck Stiffness

  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]

  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]

  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]

• Myoclonus

  Background: Opsoclonus-myoclonus-ataxia syndrome (OMA) is a rare neurological syndrome,characterized by a rapid onset of generalized myoclonus with multidirectional chaotic eye movements,and less frequently cerebellar ataxia.While the association of OMA [mdsabstracts.org]

  Dementia and myoclonus in a case of cryptococcal encephalitis. Arch Neurol 1984;41:216-7. [ PUBMED ] 19. Baker RD. The primary pulmonary lymph node complex of cryptococcosis. Am J Clin Pathol 1976;65:83-92. [ PUBMED ] 20. [jpgmonline.com]

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].

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]

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]

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]

Moreover, the etiological and clinical aspects and the histologic and electron microscopic features of biopsy samples are reported. [books.google.com]

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]

Epidemiologic differences between the two varieties of Cryptococcus neoformans. American Journal of Epidemiology 1984, 120: 123–130. Google Scholar Copyright information © Friedr. [springerlink.com]

The unique problems of developing countries, the epidemiological and immunological aspects, the risks for immunodeficient travellers and the reservoirs and ways of transmission from animal to man are all equally considered, as are the diagnostic advances [books.google.com]

Clin Infect 50: 1559–67 CrossRef Google Scholar Petrikkos G, SkiadaA, Lortholary O, et al. (2012) Epidemiology and clinical manifestations of mucormycosis. [link.springer.com]

Retrospective study of the epidemiology and clinical manifestations of Cryptococcus gattii infections in Colombia from 1997-2011. PLoS Negl Trop Dis 2014;8:e3272. https://doi.org/10.1371/journal.pntd.0003272. [medicinaylaboratorio.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]

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]

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]

Oral fluconazole can be used in less severe infections and is used for life-long treatment to prevent relapses. See smartphone apps to check your skin. [Sponsored content] Related information References Book: Textbook of Dermatology. [dermnetnz.org]

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.