Table 3.
Summary of 38 cryptococcosis cases since 2000
| Case | Location | Age | Sex | Medical or surgical history | Clinical manifestations; duration | Treatment course | Outcome |
|---|---|---|---|---|---|---|---|
| [23] | UK | 49 | M | HIV infection | Fever, ulcerated lesion over left loin, dry mucous membranes, headache, vomiting; 14 days | Intravenous AmB (1 mg/kg per day) and flucytosine (100 mg/kg per day) for 2 weeks; fluconazole (400 mg/day) for 10 weeks | No neurological complications and no further episodes of opportunistic infections at 12-month follow-up |
| [24] | USA | 25 | M | HIV-infection (CD4 count less than 20 cells/µl), intermittent asthma, migraines | Altered mental state, weight loss, neck pain, cough, fever, nausea, vomiting, photophobia; 7 days | AmB and flucytosine; placement of a lumbar drain | Clinical improvement and was discharged on oral fluconazole |
| [25] | Australia | 59 | M | Autosomal dominant polycystic kidney disease, renal transplant, direct contact with cockatiel bird | Pruritic and painless rash; 1 month | LAmB and flucytosine 6 weeks; then oral fluconazole consolidation | Improvement in lower leg cellulitis, renal allograft function is stable |
| [26] | China | 63 | M | Uremia, kidney transplant | Headache, dizziness, vomiting, dyspnea, fever; 2 days | ABLC, flucytosine and voriconazole for the first 11 days; ABLC and flucytosine for 8 weeks; fluconazole for maintenance | Asymptomatic at 3-week follow-up |
| [27] | Iran | 39 | F | Relapsing remitting multiple sclerosis, two times | Headache, fever, weakness, and progressive loss of consciousness, neck stiffness with Kernig and Brudzinski signs, bilateral pupil mydriasis and papilledema | LAmB 300 mg/day and fluconazole 800 mg/day for 2 weeks; LAmB 300 mg/day and fluconazole 400 mg/day for 4 weeks; fluconazole 200 mg/day | Discharge without any major complaints after 6-week hospitalization |
| [28] | Spain | 42 | M | Diabetes, worked in public works water and sewer maintenance | 5 kg weight loss and 24 h fever, 6-month history of mechanical lumbar pain | Single dose of LAmB (10 mg/kg, 870 mg) infused over 3 h, oral fluconazole (800 mg/day); fluconazole (800 mg/day for 14 days, then 400 mg/day for 1 year | No symptoms at 12-month follow-up |
| [29] | Cameroon | 41 | F | HIV-infection, gastric Kaposi’s sarcoma | Subacute occipital headaches associated with photophobia, blurred vision, phonophobia, projectile vomiting; 4 weeks | Fluconazole 1200 mg/day and flucytosine 1500 mg × 4/day | Died on day 6 of this treatment |
| [30] | USA | 69 | M | Renal transplantation recipient, diabetes, coronary artery disease, hypertension, and hyperlipidemia | Dizziness, generalized weakness, hypotension; 28 days | AmB and flucytosine for 4 days LAmB and fluconazole for 2 weeks; then oral fluconazole 400 mg/day for 8 weeks | Admitted for delirium 7 weeks after discharge and died at a 3-week hospital course due to sepsis |
| [22] | Vietnam | 39 | M | Myasthenia gravis, thymus gland removal, diabetes, HCV hepatitis, TB pneumonia, had been breeding birds | Recurrent and progressive skin lesions, mild fever, painful and persistent skin lesions with painful and swollen left knee, headache | AmB 1 mg/kg per day and fluconazole 800 mg/day for 4 weeks; fluconazole (1000 mg) for 12 months | Ulcer regression over 11 days with no exudates; discharged on day 32 |
| [31] | Côte d’Ivoire | 41 | M | HIV infection | Confused, incoherent, vomiting, headache | Patient received high oral dose of fluconazole (1200 mg/day) | Died 17 days after treatment initiation |
| [32] | Japan | 51 | M | Renal transplantation recipient | Pain, high fever, erythema, ecchymosis, vesicle formation, and erosion | Lipid AmB and flucytosine | Suffered from immune reconstruction inflammatory syndrome and died |
| [33] | Sri Lanka | 21 | M | Renal transplantation recipient | Headache, low grade fever, alert, neck stiffness, bilateral symmetrical near complete ophthalmoplegia | Intravenous AmB 1 mg/kg per day for 6 weeks; then oral fluconazole 400 mg for 10 weeks | Regained full range of eye movements after 6 weeks |
| [34] | Saudi Arabia | 67 | M | Liver transplantation, cirrhosis developed severe hyponatremia, diabetes | Dizziness, confusion, ataxia, abnormal muscle movements, and leg pain, fever, drowsy, unable to follow commands | AmB for 6 weeks; then fluconazole for 1 year | Serum sodium level returned to normal baseline 3 weeks after starting AmB treatment |
| [35] | Japan | 72 | M | Ischemic heart disease 4 years prior, ICD implantation, diabetes, chronic hepatitis B | Non-productive cough and respiratory discomfort | LAmB 250 mg/day, oral flucytosine 6000 mg/day, and daptomycin 350 mg/day for 25 days | Died 54 days after initial hospital admission, an autopsy was declined by his family |
| [36] | China | 34 | M | Nephrotic syndrome | Massive shallow ulcers of both lower extremities, fever of 39 °C, severe pain | Intravenous fluconazole (400 mg/day) for 8 days; intravenous antibiotic therapy | Died 8 days after initial hospital admission |
| [37] | Germany | 81 | F | Rheumatoid arthritis | Skin ulceration, swelling, erythema and severe pain | Intravenous fluconazole (400 mg/day) for 10 days; then fluconazole (400 mg/day) for 4 weeks | The skin defect was successfully closed with a mesh graft |
| [38] | USA | 51 | M | Cardiac transplantation with mild rejection | Fever, back pain, severe left lower extremity pain | Oral fluconazole and intravenous AmB; Due to fluconazole resistance, switched to oral voriconazole and intravenous AmB | There were no fungal organisms present after treatment |
| [39] | China | 68 | M | No significant past medical history; no noted exposure to bird droppings | Progressive multiple abscesses, fever, lower extremity weakness, urinary retention; 7 months | LAmB, itraconazole, flucytosine, and fluconazole for 4 months | Afebrile, with no new-onset abscess, could walk slowly at 18-month follow-up |
| [40] | Thailand | 70 | M | With a 5-year history of primary myelofibrosis, hypertension, asthma, and osteoporosis presented | Erythematous swollen left leg for 7 days; fever, dyspnea on exertion, and orthopnea for 6 days; multiple ulcers on right foot for 10 days | AmB 50 mg/day and oral fluconazole 800 mg/day; switched to LAmB 180 mg/day and fluconazole 800 mg/day for 28 days; then oral fluconazole 400 mg/day | Developed septic shock and died 48 days after hospital admission |
| [41] | Japan | 56 | M | Hepatitis type B virus infection, hepatic failure, hypertension | Headache, vomiting, gait disturbance; 1 month | LAmB and fluconazole | Developed renal failure and ultimately died 25 days after admission |
| [42] | China | 42 | M | Hepatitis type B virus infection | Aphasia and left hemiparesis; 3 days | Intravenous fluconazole 400 mg/day; switched to intravenous AmB (0.6 mg/kg per day) and voriconazole (400 mg/kg per day) and oral flucytosine (100 mg/kg per day, 4 equal parts) for 2 weeks; then oral voriconazole for 11 months | Neurological recovery was complete and no recurrence was recorded at 6-month follow-up |
| [43] | Canada | 56 | F | Diabetes, seizure disorder with remote left temporal lobectomy | Fever up to 38.4 °C | Posaconazole 300 mg/day for 12 months | Antigen titers were negative at 1-year follow-up |
| [44] | Argentina | 59 | F | Smoking, arterial hypertension, breast cancer, nephroangiosclerosis, kidney graft | Fever, headache episodes, weight loss | Intravenous AmB and oral fluconazole | Infection resolved after antifungal treatment |
| [45] | Norway | 54 | M | Hypertension, migraine | Influenza-like symptoms, palpitations, activity-related presyncope | Intravenous fluconazole (800 mg); switched to AmB (200 mg/day) and flucytosine (1500 mg/ day) twice daily for 1 month; then flucytosine (1500 mg × 2) and fluconazole (400–800 mg/day) for 1 month; then fluconazole (400 mg/day) for 11 months | There was no evidence of infection recurrence during 2 years of follow-up |
| [46] | Brazil | 45 | M | Pulmonary tuberculosis, HIV infection | Difficulty performing basic daily life activities, anorexia, fever, profuse sweating, vomiting episodes preceded by nausea | AmB (1 mg/kg per day) and intravenous fluconazole (800 mg/day) for 7 days; then fluconazole (1200 mg/day) for 7 days; fluconazole (800 mg/day) for 8 weeks | CSF cultures for fungi were negative at 1 and 2 weeks following treatment initiation |
| [47] | Netherlands | 60 | M | HIV-negative patient with low MBL and low naïve CD4 count, chronic relapsing meningoencephali-tis with relatively mild symptoms for approximately 2 years | Relapsing diffuse headaches lasting several days; 3.5 months | LAmB (3 mg/kg per day) and flucytosine (100 mg/kg per day) for 2 weeks; fluconazole (400–800 mg/day) for 8 weeks; then fluconazole maintenance therapy for 12 weeks | Mild headaches |
| [48] | USA | 75 | M | Renal transplantation, diabetes | General weakness, altered mental status, hypoxemia, mild hyponatremia, hypochloremia | AmB and flucytosine | After an initial improvement, the patient became suddenly hypotensive, and died soon after |
| [49] | China | 40 | M | Unremarkable | Apathetic, uncommunicative and slow to move, unresponsive and bed ridden, consciousness level continued to decline during admission | Intravenous AmB 25 mg/day was given initially and then gradually increased to 50 mg/day, with oral flucytosine 6 g/day | Coma began 1 week after treatment onset; treatment was stopped according to the circumstances, and the patient died |
| [50] | Germany | 49 | F | Relapse remitting multiple sclerosis, owned a birdhouse | Cephalgia, fever, confusion, coughing and generalized weakness | Intravenous LAmB and oral fluconazole, replaced by flucytosine | Remained clinically stable |
| [51] | China | 72 | M | Chronic hepatitis B | Dry cough; more than 6 months | Fluconazole 400 mg/day for 6 months | Two pulmonary cryptococcal nodules disappeared |
| [52] | – | 41 | M | HIV-negative; alcoholic liver cirrhosis | Fever, seizure | Flucytosine | Multi-system organ failure leading to death |
| [53] | China | 50 | M | HIV infection | Multiple skin lesions, intermittent headache | AmB and fluconazole | Died 3 days after adding fluconazole |
| [53] | China | 64 | F | HIV infection, diabetes | Mild fever, productive cough, dyspnea on exertion, swelling in both lower limbs | Oral fluconazole 100 mg for 3 days; then AmB (1 mg/kg per day) for 3 days followed by fluconazole 400 mg/day | Became afebrile after 72 h of treatment with considerable improvement of other comorbidities; discharged with continuing oral antifungal therapy |
| [54] | China | 77 | M | Advanced stage non-small cell lung cancer, smoking, severe underlying chronic obstructive pulmonary disease | Non-anginal anterior chest pain, progressive dyspnea | Fluconazole 400 mg/day | Progressive clinical improvements at 10 month follow-up, the patient passed away from malignancy |
| [55] | China | 48 | F | With a 2-month history of elevated serum CA19-9 levels (50.05 IU/ml) | No symptoms | Fluconazole 400 mg/day for 3 months; fluconazole 200 mg/day for 3 months | After 6 months of treatment, serum CA19-9 levels regressed to the normal range |
AmB Amphotericin B; LAmB Liposome bilayer-coated amphotericin B; ABLC Amphotericin B lipid complex; HCV Hepatitis C virus; TB Tuberculosis; ICD implantable cardioverter-defibrillator; CSF Cerebrospinal fluid; CA19-9 Carbohydrate antigen 19-9