Abstract
The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. A young man, suffering from idiopathic dilated cardiomyopathy with a left ventricular ejection fraction of 20%, presented with subacute, painful tender swelling in both legs initially attributed to congestive cardiac failure. No response to diuretics was achieved. Metabolically active lesions in the muscles of both lower limbs suggestive of muscle abscesses were found. A diagnosis of tropical pyomyositis was therefore made, but aspiration surprisingly revealed gram-positive yeast cells, staining of which on India ink and culture confirmed Cryptococcus. A good response to a combination of liposomal amphotericin B and flucytosine was obtained, but nevertheless the patient died from heart failure after induction of antifungal therapy.
Case report
A 25-year-old man, from a low socioeconomic background, reported an insidious onset of pain and swelling in both lower limbs associated with intermittent oozing of fluid from multiple points for the previous month. The most prominent site of swelling was around the left calf muscle. He also reported occasional fever and fatigue.
He was known to have idiopathic dilated cardiomyopathy with severe left ventricular dysfunction (ejection fraction of 20%) and taking medication for heart failure. There was a history of trauma to the legs six months before the onset of his symptoms.
Two months previously, he was admitted with acutely decompensated heart failure, requiring ventilatory support. He then developed ventilator-associated pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and was also found to have Acinetobacter baumanii bacteraemia. Through prolonged treatment with colistin, he subsequently improved. There was no significant travel history, exposure to pets or contact with pigeons, nor consumption of alcohol, tobacco or illicit drugs.
The leg swelling was initially attributed to known congestive cardiac failure and diuretics were given without effect.
Considering his previous condition, he appeared well and vital signs were within normal limits. He had markedly swollen and severely tender lower limbs with multiple sites of pustular discharge.
Complete blood count, renal and liver function tests were within normal limits. Ultrasonography of the lower limbs revealed multiple subcutaneous collections. Whole-body positron emission tomography–computed tomography scan with 18-fluorodeoxyglucose and intravenous contrast revealed metabolically active, heterogeneously enhancing multiple nodular lesions in multiple muscles of both lower limbs with involvement of intermuscular planes (Figure 1). The largest lesion in the left leg measured 9.0 × 6.7 cm. Subcutaneous oedema was noted in bilateral lower limbs
Positron emission tomography–computed tomography demonstrating metabolically active, heterogeneously enhancing multiple nodular lesions in multiple muscles of both lower limbs.
Testing for human immunodeficiency virus (HIV) and diabetes mellitus was negative. Our aim was later to evaluate for a primary immune deficiency following stabilisation of the patient’s clinical condition after induction of antifungal therapy.
The major differential diagnosis entertained was multifocal pyomyositis due to Staphylococcus aureus (or other bacteria) or tubercular pyomyositis.
Aspiration of the collection over the left calf muscle showed spherical, budding, gram-positive yeast cells (Figure 2). A rapid, urease test showed a bright-pink colour indicating a possible identification of Cryptococcus. India ink staining was consistent with round, encapsulated yeast organisms consistent with Cryptococcus (Figure 3). Culture on blood agar showed cream-coloured, mucoid colonies confirming cryptococcosis (Figure 4). Speciation on matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) determined the organism to be Cryptococcus neoformans.
Gram stain. Spherical, gram-positive budding yeast cells. Staining with India ink. Round, encapsulated yeasts are seen with a halo around the cell. Culture on blood agar demonstrating cream-coloured, mucoid colonies.
Liposomal amphotericin B (4 mg/kg/day) and oral flucytosine (100 mg/kg/day in four divided doses) were started, with good therapeutic response. However, worsening cardiac dysfunction ensued, with death from congestive heart failure two weeks after the initiation of his antifungal treatment.
Discussion
The possible aetiology of dilated cardiomyopathy includes myocarditis, ischemic heart disease, infiltrative myocardial disease, hypertension, HIV infection, connective-tissue disease and substance abuse. 1 Anti-heart autoantibodies have been detected in 25% of patients with idiopathic dilated cardiomyopathy 2 and 20% of their asymptomatic relatives. 3 Therefore, an autoimmune process may explain the pathogenesis of ‘idiopathic’ cardiomyopathy. In the above-mentioned clinical case, we ruled out the known causes of a dilated cardiomyopathy. However, we were unable to identify the exact aetiology. On screening of first-degree relatives, no cardiac abnormalities were detected. We did not test for anti-heart antibodies.
Cryptococcus, a genus of basidiomycetous, encapsulated, yeast-like fungi, is the cause of cryptococcosis. The two varieties of C. neoformans-grubii and neoformans correlate with serotypes A and D, respectively. 4 C. gatti, although not divided into varieties, is also antigenically diverse, encompassing serotypes B and C. 5
Our patient reported a history of trivial trauma, but it is difficult to ascertain whether this was significant in the causation of disease. C. neoformans-grubii and neoformans have been found in soil samples in areas frequented by pigeons, 6 though our patient had no known risk factors for Cryptococcal disease. However, organ failure syndromes have been reported to constitute a risk for cryptococcosis among non-HIV, non-transplant populations. 7 These represent subclinical primary immunodeficiency syndromes. 7 The patient’s death prevented us from fully evaluating for primary immunodeficiency.
Serologic evidence of cryptococcosis is common among immunocompetent individuals, and cryptococcal disease is relatively rare in the absence of impaired immunity. Risk factors include known causes including advanced liver disease and sarcoidosis.8,9
The spectrum of disease caused by Cryptococcus species consists predominantly of meningoencephalitis and pneumonia, but skin and soft tissue disease is also known. Skin lesions actually occur in 15% of patients with disseminated infection and are highly variable in nature as papules, plaques, purpura, vesicles, tumour-like lesions, abscesses and sinus tracts.10,11 Primary cutaneous cryptococcosis may occur by direct inoculation. 12
The treatment of choice for extrapulmonary cryptococcosis without central nervous system involvement limited to a single site is Fluconazole 400 mg/day for six months. Patients with disseminated disease (involvement of at least two non-contiguous sites or cryptococcal antigen titre ≥1:512) should be treated with liposomal amphotericin B (3–4 mg/kg intravenously daily) plus flucytosine 100 mg/kg/day orally in four divided doses for at least two weeks. This is followed by a consolidation phase with fluconazole 12 mg/kg/day for eight weeks. Maintenance therapy consists of fluconazole at 400 mg/day for at least one year (longer in patients on immunosuppressants). 13 An all-oral regimen consisting of fluconazole and flucytosine has also been used successfully. 14
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
