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CASE REPORT
Chylothorax associated with non-endemic Kaposi’s sarcoma
1 Department of Oncology, Princess Marina Hospital, Gaborone, Botswana
2 HIV Care and Support, Botswana-UPenn Partnership, Gaborone, Botswana
3 Department of Pathology, National Health Laboratory, Gaborone, Botswana
4
Department of Oncology, Princess
Marina Hospital, Gaborone, Botswana
Corresponding
author:
K Verma
(kv_erma@yahoo.com)
Chylothorax is a rare cause of pleural
effusion, seen in approximately 2% of cases. In HIV-positive
patients with Kaposi’s sarcoma (KS), the development of
chylothorax presents as a diagnostic challenge with an
aggressive course and poor, often lethal outcome. In this
clinical scenario, the aetiology of chylothorax may include
infections and malignancy, while pleural fluid examination and
computed tomography of the mediastinum may fail to establish a
cause. We present a case of KS-associated non-traumatic
chylothorax resulting in death, and a review of available
literature on this condition.
S Afr J HIV Med 2013;14(3):141-143.
DOI:10.7196/SAJHIVMED.933
In HIV-positive patients with Kaposi’s
sarcoma (KS), chylothorax is a rare complication.
KS
is related to human herpesvirus-8 (HHV- 8),
and striking reductions in incidence and improvements in
survival have been reported after the introduction of highly
active antiretroviral therapy (HAART). 1
With
prolonged survival, the sequelae as well as related
complications of KS pleural effusions are increasingly being
noted. However, in settings of high tuberculosis (TB)
prevalence and limited clinical resources, patients with
pleural effusions are typically treated empirically for TB,
often with little consideration for KS. The limited
availability of diagnostic testing in many settings to
investigate unresolving pleural effusion despite TB treatment
often presents a diagnostic dilemma. Chylous pleural effusion
is an uncommon complication secondary to pathology of the
thoracic duct; however, determining the aetiology of
chylothorax in HIV-positive patients with KS and/or TB is a
significant challenge. The contribution of infectious,
malignant and iatrogenic causes needs to be investigated to
determine the appropriate management strategy.
Case
A 40-year-old man sought medical attention for shortness of breath on mild exertion with dry cough of 1 month’s duration. He had no significant past medical, social or family history. Physical examination revealed dullness to percussion at both bases, but no significant lymphadenopathy. A chest X-ray revealed bilateral pleural effusion without any infiltration. His sputum was negative twice for acid-fast bacilli (AFB). He tested positive for HIV with a CD4+ count of 119 cells/µl (6%). He was started on emtricitabine, tenofovir and efavirenz as a fixed-dose combination, Pneumocystis jerovii prophylaxis, and 6 months of standard treatment for pulmonary TB.
After 2 months of this therapy, he reported with violaceous lesions on both legs and his chest wall. Skin biopsy revealed KS and he completed 6 cycles of chemotherapy with doxorubicin, bleomycin and vincristine.
After 6 months of ART, he was virologically suppressed;
however, he had immunological failure with a CD4+ count
of 41 cells/µl (5%). Shortness of breath responded to this
therapy, but he had radiological persistence of bilateral
pleural effusions (Table 1). Repeated thoracocentesis
revealed straw-coloured fluid with protein >3 g/dl, and inflammatory
cells with a lymphocytic predominance without any atypical
cells. Despite multiple attempts, no bacterial pathogens or
AFB were isolated from the pleural effusion. His skin
lesions decreased in size, but he developed woody oedema of
the left leg that responded to lower-hemibody irradiation of
800 cGy in a single fraction. Table 1 presents a summary of
the major investigations and findings.
Due to persistent
bilateral pleural effusions, the patient received 6 cycles of 150 mg/m2/day etoposide (injection)
from day 1 through day 3 for treatment of pulmonary KS, with
a temporary relief in his cough and shortness of breath. He
still required repeated thoracocentesis to relieve his
episodes of breathlessness. Three months after completion of
chemotherapy, he developed a worsened shortness of breath and
productive cough. The whitish sputum was negative upon
Ziehl-Neelsen smear. Contrast-enhanced computed tomography
(CT) of the chest confirmed bilateral pleural effusions with
consolidation of the right lower zone of the lung, but no
pulmonary nodules, mediastinal or hilar lymphadenopathy
(Fig. 1). The patient underwent bilateral intercostal chest
drainage, revealing thick brownish fluid (Fig. 2).
Sputum and pleural fluid were negative for AFB cultures and
Mycobacterium
tuberculosis polymerase chain reaction
(PCR) (GeneXpert), but bacterial cultures from pleural fluid
grew Staphylococcus aureus. These were identified as
methicillin-resistant S.
areus (MRSA) and the coverage was
narrowed down to vancomycin only. After 5 days of vancomycin
therapy, pleural fluid draining from both sides turned milky
white in colour.
The fluid triglyceride level was 3.1 mmol/l (247 g/dl),
protein was 2.2 g/
dl, cholesterol was
0.1 mmol/l and lactate dehydrogenase (LDH) was 1 344 mol/l. The patient
was diagnosed with bilateral chylothorax and underwent blind
pleural biopsy to rule out other aetiologies of persistent
bilateral pleural effusion aside from KS-induced scarring of
the thoracic duct. Diagnostic bronchoscopy revealed normal
trachea and bronchi. The respiratory mucosa was inflamed and
red, but visibly normal with no evidence of endobronchial
lesions. There
were profuse, whitish secretions in the trachea-bronchial
tree, which were washed out and sent for microscopy, culture
and sensitivity, as well as TB and fungal investigations.
Bilateral thoracoscopy revealed empyema with loculations
with beefy, inflamed, thick-walled visceral and parietal
pleurae. In the presence of low CD4+ counts, this was regarded as a
relapse of pulmonary TB, and anti-tubercular treatment was
started. The patient developed sepsis from extended spectrum
β-lactamase (ESBL)
gram-negative bacteria and died after several days in the
intensive care unit.
Fig. 1. Computed tomography scan of the chest showing bilateral pleural effusions with consolidation of the right lower zone of the lung with thickened pleura and intercostal drainage tube in place. No significant pulmonary nodules or lymphadenopathy are visible.
Fig. 2. Chest X-ray posteroanterior view showing bilateral pleural effusions with intercostal drainage tube in place.
Discussion
This patient was diagnosed with HIV with non-endemic KS and pulmonary TB manifesting as bilateral pleural effusion with S. aureus empyema with bilateral chylothorax. Bilateral pleural effusions persisted even after empirical anti-tubercular treatment for 6 months. The presence of advanced HIV disease, pulmonary TB and disseminated KS synchronously posed a difficult diagnostic scenario, and the aetiology of bilateral chylothorax in this patient was unclear. In the setting of HIV-associated KS, the underlying aetiology for bilateral chylothorax may include primary tumour (KS with involvement of pleura or thoracic nodes), infections (related to immunocompromised status and multi-agent chemotherapy) or an unrelated aetiology. Diagnostic bronchoscopy revealed no evidence of endobronchial lesions and ruled out pleuropulmonary KS as the cause for chylothorax.
Chyle consists of lymph of intestinal origin, which is a milky and opalescent fluid rich in lymphocytes, protein, triglycerides and chylomicrons. Chyle is conducted from intestinal lymphatics to the cisterna chyli, which eventually drains into the left subclavian vein via the thoracic duct through the posterior mediastinum. Disruption of flow in the thoracic duct results in mediastinal collection of chyle, which can leak into the pleural space resulting in chylothorax. This manifests as shortness of breath and chest discomfort due to compression of the lung by the collection of chyle. Drainage of milky-white pleural fluid suggests chylothorax that can be confirmed by pleural fluid examination. A level of pleural fluid triglycerides >110 mg/dl and a pleural fluid/serum cholesterol ratio <1 is diagnostic of chylothorax.2 Normally, the average flow of chyle is about 2 l/day; following meals it may increase to a rate of 4 l/day.3 Continued loss of chyle leads to depletion of protein, fat and lymphocytes. The four main causes of chylothorax include: malignancy; trauma; idiopathic; and miscellaneous causes such as thrombosis of the superior vena cava or subclavian vein, cirrhosis and rarely, pulmonary lymphangiomyomatosis.4
KS is one of the most common causes of pleural effusion in patients with AIDS. The pathological diagnosis of pleural KS requires a characteristic architectural appearance and not a particular neoplastic cell type.5 The sampled fluid (usually serosanguineous or haemorrhagic exudate) is unlikely to contain diagnostic cytological material. Since KS tends to involve only the visceral pleura, closed pleural biopsy is often non-diagnostic and the diagnosis requires thoracoscopy with the characteristic multiple cherry-red to purple appearance of the KS lesions on the visceral pleura.6 In most cases, the clinical picture and the characteristic bronchoscopic appearance of the lesions help to make a presumptive diagnosis and may obviate the need for biopsy.7 A study describing the clinical course and pleural fluid findings in patients with AIDS-associated pleural KS showed that 21/105 (20%) cases had pleuropulmonary KS involvement. Of these, 13 (62%) had pleural effusions and only 2 had chylothorax. Neither cytological examination nor needle biopsy of the parietal pleura was able to establish the diagnosis. At autopsy, patients with pulmonary KS have multiple cherry-red to purple lesions on the visceral, but not on the parietal pleural surface. The reported median survival from KS diagnosis to death was 205 days for patients with pleuropulmonary KS.6 In another series, 29/53 (55%) patients had pleural effusions including 76% bilateral.8
Currently, the exact aetiology of chylothorax in patients affected by advanced HIV with KS is unclear, and few cases have been described in the literature.[8-10] Most cases reported evidence of lymphatic obstruction via KS involvement of the mediastinal nodes and/or prominent pulmonary KS, and the treatment included palliative measures such as pleural drainage, pleural sclerosis, fluid shunting and/or chemotherapy directed at KS. The treatment was largely unsuccessful, and patients in whom the outcome was noted, died within a few weeks to months. Average survival after diagnosis of KS pleural disease is around 4 months. 6 The potential cause of chylothorax in HIV-positive patients also includes TB, but chylothorax appears to be rare in patients with TB, and KS remains the leading concern in the differential diagnosis. 11 Chylothorax is also rare in patients with KS without HIV infection (endemic KS) and only a single case of KS-related chylothorax in an HIV-negative patient was reported in past years.12 The pathogenesis of most effusions due to malignancy has been attributed to blockade of the lymphatic drainage system located in the parietal pleura, but this is unlikely in patients with KS-related pleural effusions, since their parietal pleura is not involved. The KS-related effusion may be due to the elaboration of vascular endothelial growth factor (VEGF). VEGF promotes angiogenesis and microvascular hyper-permeability to produce extravascular fluid that appears bloody.13 In patients with KS, the pleural effusion is a chylothorax in about 2% of cases, which suggests involvement of the thoracic duct by the tumour. KS-related chylothorax is postulated to develop from metastases to the thoracic duct. More recently, however, it was demonstrated by the co-expression of HHV-8, CD34 and D2-40 on lesional cells, that chylothorax may arise due to the development of in situ KS in this region.14
The patient described here had no clinical, radiological or cytological indication of pleuropulmonary KS. There was no mediastinal lymphadenopathy, nor any history of chest trauma. Thus, the aetiopathogenesis of his bilateral chylothorax was not clinically or radiologically evident. In this scenario, the reason for chylothorax appeared to be involvement of the thoracic duct by KS, leading to obstruction and a resultant leakage of chyle from the thoracic duct. The process might have been exacerbated by post-chemotherapy fibrosis of mediastinal nodes and/or lymphatic involvement by mycobacteria. This can be evaluated by radioisotope lymphangiography, magnetic resonance imaging or positron emission tomography; however, these investigations are unfortunately not widely available. Further, thoracoscopy with biopsy of mediastinal nodes and a visceral pleural biopsy may help to differentiate KS from TB as the underlying aetiology.
Patients immunocompromised by HIV infection and chemotherapy
are at high risk for infection-related effusions. A
concomitant infection must be ruled out in patients with
KS-related pleural effusion, as a failure to treat a
concomitant infection carries a high short-term mortality. In
this patient, isolation of MRSA from pleural fluid was
probably related to pleurocentesis-related iatrogenic empyema.
Conclusion
KS-associated chylothorax may present a
diagnostic challenge and carries a poor prognosis. Current
literature is sparse and a congregation of such cases can
provide more insight into the aetiopathogenesis of non-endemic
KS-related chylothorax.
References
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2. Staats BA, Ellefson RD, Budahn LL, et al. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc 1980;55(11):700-704.
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11. Singh S, Girod JP, Ghobrial MW. Chylothorax as a complication of tuberculosis in the setting of the human immunodeficiency virus infection. Arch Intern Med 2001;161(21):2621.
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