An unusual presentation of pulmonary cryptococcosis with co-existing disseminated tuberculosis in an AIDS patient

Case history

A 36-year-old man was admitted to hospital with a two-month history of moderate grade, intermittent fever, cough with minimal expectoration, weight loss and generalized weakness. He had recently been diagnosed as being HIV seropositive but was not receiving therapy. On examination he was seen to have severe pallor with multiple small bilateral cervical lymph nodes. Oral thrush was also noted. A chest examination revealed crepitations in the right infrascapular region and an abdominal examination showed mild hepatosplenomegaly. Clinically, no features of a meningoencephalitis were present. Blood investigations showed: haemoglobin 4.2 g/dL; white blood cell count of 11400/mm³; a high erythrocyte sedimentation rate of 79 mm/h with features of iron deficiency anaemia on a peripheral smear; but the remaining blood tests were normal. Sputum for acid-fast bacilli (AFB) was negative, as was the culture. Blood cultures were negative. A chest X-ray (CXR) showed consolidation in the right lower zone (Figure 1a). An ultrasound of the abdomen showed mild hepatosplenomegaly with ascites. A clinical diagnosis of disseminated tuberculosis (TB) was made and the patient was commenced on isoniazid, rifampicin, ethambutol and pyrazinamide. A repeat CXR after two months showed an increase in the right lower zone consolidation. Therefore, we considered whether it was an immune reconstitution as a result of the TB therapy. A computed tomography (CT) of the chest confirmed a dense consolidation in the posterior and lateral segments of the right lower lobe (Figure 1b). A fibre optic bronchoscopy was performed in order to look for AFB, fungus or other possible aetiologies for the persisting abnormality. Subsequently, the tests from bronchoscopy, including the AFB and fungal cultures, came back negative. The anti-TB therapy (ATT) drugs were continued as he had gained weight and remained afebrile. We documented it as a peripheral pleural based consolidation and the aetiology remained unclear. A CT-guided fine needle aspiration cytology of the lesion was performed with concomitant microbiological studies. This yielded scant material, as the lesion was solid and a biopsy showed yeasts of varying sizes in the macrophages – some showed budding and some a mucicarmine positive capsule. Melanin pigmentation was also prominent on the biopsy (Figure 1c). This was consistent with a cryptococcal pneumonia which is rarely present in this fashion in AIDS. The patient was started on oral fluconazole (400 mg once daily) as he was relatively stable. After eight weeks of antifungal therapy, a repeat CXR revealed a persisting opacity in the right lower zone. The absolute CD4 count was 50 cells/mm³. Antiretroviral drugs were initiated at this stage, which he tolerated without incident. Follow-up showed a definite decrease in the size of the density in his CXR and he was asymptomatic.

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Figure 1

CXR showing right lower zone consolidation (a). CT of the chest showing consolidation in the posterior and lateral segments of the right lower lobe (b). Haematoxylin and eosin stain of lung biopsy showing yeasts of varying sizes in the macrophages, some of which show budding. The section also shows prominent melanin pigmentation (c)

Discussion

Pulmonary disease frequently develops in HIV patients and involves Cryptococcus neoformans in 2–11%. This pathogen enters the host primarily through the lungs and can remain dormant or spread to other organ systems, with a particular predisposition for the central nervous system. It mimics pulmonary TB both clinically and radiologically. Concomitant opportunistic infections such as TB, nocardiosis and histoplasmosis are frequently seen in AIDS patients with cyptococcosis. ¹ The possibility of a dual presentation of these diseases should always be borne in mind. The dual pathology is known to increase mortality in patients with HIV. ²

The pulmonary manifestations of cryptococcosis in the immunocompromised hosts are quite variable. Common presenting symptoms include: fever; cough; dyspnoea; weight loss; and pleuritic chest pain. ^3–5 Most symptomatic cases occur in patients with CD4 counts of <100 cells/µL. ²

A chest radiograph of pulmonary cryptococcosis can show various features, including: focal or diffuse interstitial and alveolar infiltrates; lymphadenopathy; nodules; and pleural effusions. ^3,5,6 The most common radiographic findings are a solitary or few well-defined calcified nodules.

Detection of cryptococcal antigen by latex agglutination testing, which is very useful for cryptococcal meningitis, is of little value for the diagnoses of pulmonary disease.

Both biopsy and cytology of tissue specimens can be extremely helpful in the diagnosis of pulmonary cryptococcosis. C. neoformans is distinguished from other fungi by a mucinous capsule, which is best defined by mucin stains such as mucicarmine. ⁶ In this case, the presence of a capsule, and the fact that some of the yeasts were fairly large, argued against the fungus being histoplasma.

Fluconazole (400 mg/day) is considered to be the standard therapy for mild to moderate pulmonary cryptococcosis in the absence of diffuse pulmonary infiltrates or disseminated infection and is recommended for 6–12 months in immunocompromised patients. If fluconazole is contraindicated, acceptable alternatives include itraconazole (200 mg twice/day orally) and voriconazole (200 mg twice/day orally). HIV infected patients should be continued on chronic suppressive therapy with 200 mg/day of fluconazole. In those with HIV, who are receiving HAART and who have a CD4 count of >100 cells/µL, it may be reasonable to discontinue maintenance fluconazole after a year of treatment. ⁴

Conclusion

In our patient, the initial fever, weight loss and other symptoms had cleared with the ATT suggesting that he had both diseases. Co-infection of the lungs by C. neoformans and Mycobacterium tuberculosis can hinder the diagnosis of cyptococcosis on clinical and radiological grounds. For a patient with a lung lesion due to possible pulmonary TB in whom there is no improvement after ATT, the possibility of cryptococcosis should be considered. Clinicians should be aware of this entity in immunocompromised patients with respiratory infections who fail to respond to ATT.

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Conflicts of interest: None declared.