Pulmonary cryptococcosis presenting as acute severe respiratory distress in a newly diagnosed HIV patient in Tanzania: a case report.

Pulmonary cryptococcosis is a common condition in HIV-infected patients which is frequently missed or misdiagnosed in resource-limited countries. We report a case of HIV/AIDS patient who was misdiagnosed with a fatal outcome. There is a need to implement screening tools to be used where the diagnosis may not be confirmed.

Introduction

Pulmonary cryptococcosis (PCr) is a common condition in HIV/AIDS patients with acute respiratory symptoms, second to pulmonary tuberculosis (PTB) 1,2. Cryptococcosis is caused by the fungi Cryptococcus neoformans and Cryptococcus gattii which are widely distributed in nature 3. The organism is usually acquired through inhalation of spores or dried yeast cells from the environment and is usually deposited in the alveoli where it may be contained. In patients who are immune-compromised, a localized infection may occur and progress into a life-threatening pneumonia with acute respiratory failure 4,5 or else it enters the blood stream to cause a more disseminated form of infection which commonly presents as cryptococcal meningitis (CM) 6.

Manifestations of PCr in immune-compromised hosts are quite variable; seldom subclinical, to severe condition with substantial mortality 7. In symptomatic patients, the clinical features are nonspecific and can simulate a wide range of other respiratory distress diseases 8,9 hence frequently misdiagnosed as pulmonary tuberculosis, Pneumocystis carinii Pneumonia (PCP), or severe bacterial pneumonia in the background of immune suppression 10,11. The commonly presenting features of PCr include fever, cough, dyspnea, pleuritic chest pain, hemoptysis, tachypnea, hypoxia, crepitations on auscultation, and diffuse interstitial infiltrates on chest radiography 2,3,7,12,13.

A definitive diagnosis of PCr requires identification of the organism by culture or India ink staining of samples obtained by bronchoalveolar lavage (BAL) or tissue biopsy 3,8,9,14. Tanzania like most of other resource-limited countries face a diagnostic limitation for this condition and most of these cases are presumed to be frequently missed or misdiagnosed. We report a case of a newly diagnosed HIV/AIDS middle aged male who presented with acute respiratory distress secondary to PCr which was initially misdiagnosed as PCP with fatal outcome.

Case Presentation

A 33-year-old male presented with a 1-week history of acute onset of difficulty in breathing, right-sided pleuritic chest pain with intermittent low-grade fever. Physical examination revealed an obese middle-aged man in severe respiratory distress using accessory muscles of respiration, tachypnoeic (RR 38 bpm), and severely hypoxic with SPO2 of 78% in room air. He was not cyanosed. His respiratory examination was significant for presence of diffuse course crackles bilaterally. He had a BP of 110/70 mmHg and PR 110 beats/min. The rest of physical examination was unremarkable. His chest X-ray showed diffuse alveolar and interstitial infiltrates bilaterally and the initial laboratory investigations were significant for Positive HIV antibodies. A provisional diagnosis of severe pneumonia due to Pneumocystis carinii infection was entertained with differential diagnoses of severe bacterial pneumonia and pulmonary tuberculosis. On the emergency basis, he was managed as per our standard treatment protocols in the ICU 15 with 10 L of Oxygen, cotrimoxazole 1920 mg per oral q8hourly along with prednisolone 40 mgs per oral q12 hourly for probable PCP infection. He was also given intravenous ceftriaxone 1 g q 12hourly in combination with azithromycin 500 mg per oral q 12hourly for coverage of both typical and atypical bacteria. The patient rapidly deteriorated that and in spite of all the efforts he died just 10 h after admission. A consent was obtained for autopsy which was only limited to the chest. The gross histopathologic examination of the lungs revealed heavily congested lungs oozing blood-stained fluid with hyperemic and frothy small airways (Fig.1). On microscopic examination of the tissue sections, interstitial edema which was mixed with hemorrhage with few lymphocytic infiltrates was seen. There was also presence of desquamated cells in the alveoli. Several round organisms with a thick capsule in the interstitial and alveoli together with foreign body giant cells were seen in some areas (Fig.2). Periodic acid Schiff (PAS) staining was positive, and very thick capsulated organisms were highlighted (Fig.3). According to our pathologist, these findings are consistent with pulmonary cryptococcosis. However, we did not see any hyaline membrane or foamy amorphous material-containing cell debris which is typical for PCP infection. The silver stain was not available in our settings. No acid-fast bacilli (AFB) which were detected on the Ziehl– Nielsen stain. A serum result which was traced later was positive for cryptococcal antigen.

Figure 1

Gross appearance of the lungs after dissection of the chest. (A) Dark reddish lungs with loss of normal color of the lungs. (B) Hemorrhagic congested lungs on cut surface.

Figure 2

H&E histological stain showing (A) interstitial edema, desquamated cells in alveoli and round fungal organism with a thick capsule. (B) Giant cells, few lymphocytes and fungal organism in the interstitial.

Figure 3

Periodic acid Schiff-stained histological section showing a well pink-stained capsule.

Discussion

Pulmonary Cryptococcus in HIV/AIDS population is common in sub-Saharan Africa countries with high mortality 2,16. In Tanzania, the magnitude of PCr is unknown. Cryptococcal meningitis (CM), which on clinical grounds is a late stage of the disease has been extensively studied and documented with a significant high prevalence and mortality in the country 17,18.

Prior to the presentation of meningeal symptoms, the majority of the patients with CM usually present with unspecific features of respiratory distress 26 which is usually misdiagnosed and mistreated. Autopsy studies in Uganda and South Africa has shown a very high rate of PCr misdiagnosis. More than 95% of the patients with PCr were misdiagnosed 2 16 and among them more than 50% were treated for PTB. Comparable to these studies, our patient presented with acute onset of severe respiratory distress symptoms and was misdiagnosed as PCP, and we as well did not suspect PCr before autopsy. In this outlook, therefore a timely diagnosis and treatment of these patients at a primary lung involvement would likely improve their outcome 23,24 as the capability to optimally execute the complicated management of CM which is also inadequate in a resource-limited setting like ours 6,19–22.

Bronchoalveolar lavage (BAL) and tissue biopsy which are the gold standard diagnostic investigations are usually not routinely available in most of the resource-limited settings like ours, and clinical-radiological presentation of PCr is very unspecific which poses a big diagnostic challenge. In light of this information, we assume that many cases of PCr are missed in Tanzania and therefore not reported. Consequently, serum cryptococcal antigen (SCrAg) test, though nonspecific, may assist in the diagnosis of PCr. Majority of HIV/AIDS patients, who presents with respiratory symptoms and positive SCrAg, has also been found to have PCr 1,25. It is therefore important to perform SCrAg in HIV-infected patients presenting with respiratory.

Fluconazole remains the mainstay of treatment of PCr in a capacity where Amphotericin B is either not available or cannot be used safely. According to the available guidelines, severe PCr should be treated with a high dose of fluconazole 1200 mg once daily orally or intravenously for 14 days (induction phase), then 600–800 mg once daily orally for 8 weeks (consolidation phase) then 200 mg orally once daily for 6–12 weeks as a maintenance phase 27,28. In milder cases, a lower dose of Fluconazole 400 mg once daily orally 6–12 months is recommended. Lumber puncture should be performed before commencement of the treatment to exclude meningeal involvement as may additionally require intracranial pressure management. An effective treatment is usually marked by resolution of PCr clinical symptoms, radiological normalization and negative test for Cryptococcal organisms 27. From these recommendations, it is clear that our patient would benefit from antifungals (fluconazole), which is widely available in our facility only if the diagnosis was timely made.

Conclusion and Recommendation

This case emphasizes the need to increase index of suspicion of PCr in all HIV/AIDS patients who present with respiratory symptoms among the clinicians. Obtaining a tissue or BAL for fungal culture is difficult in a resource-limited setting like ours, so empirical treatment to suspected cases should be provided to improve the outcome. Serum cryptococcal antigen (SCrAg) test should be available in all health facilities and advocated to the suspected cases to increase the window of confidence in areas where the microbiological tests cannot be performed. SCrAg is usually positive in essentially all patients with PCr 13. Further studies are recommended to establish the magnitude and associated factors of this condition in Tanzania.