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Int J STD AIDS OnlineFirst, published on August 13, 2014 as doi:10.1177/0956462414546915

Case report

A case of relapsed visceral Kaposi’s sarcoma with bilateral chylothoraces successfully treated with paclitaxel

International Journal of STD & AIDS 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414546915 std.sagepub.com

Pavithra Natarajan and Alastair Miller

Abstract Chylothorax is a rare complication of visceral Kaposi’s sarcoma. We report a case with bilateral chylothoraces secondary to relapsed visceral Kaposi’s sarcoma who was successfully treated with paclitaxel chemotherapy.

Keywords Paclitaxel, chylothorax, human immunodeficiency virus, HIV, Kaposi’s sarcoma Date received: 20 January 2014; accepted: 30 June 2014

Introduction Chylothorax results from disruption of the thoracic duct or its tributaries such that chyle is present in the pleural space. The commonest cause is trauma, followed by malignancies, of which lymphoma is predominant.1 Chylothorax is a rare but recognised complication of visceral Kaposi’s sarcoma (KS). This is the first case in the medical literature of successful treatment with paclitaxel of visceral KS in a patient with chylothorax.

Case report We report the case of a 35-year-old HIV-positive Caucasian man with a CD4 count at diagnosis of 420 cells/mL, HIV viral load (VL) 176,000 copies/mL and wild type virus. One year following diagnosis, he developed skin lesions affecting his palate, back, shins and arms with associated significant axillary, submental and cervical lymphadenopathy. His CD4 count was 400 cells/mL and Atripla was commenced due to clinical suspicion of KS. Histology from a punch biopsy of skin and cervical lymph node biopsy confirmed KS. Due to dyspnoea and episodes of haemoptysis, bronchoscopy was performed. This revealed patchy erythematous lesions, which were confirmed histologically as KS (Figure 1). A diagnosis of cutaneous and visceral KS was made and six cycles of liposomal daunorubicin chemotherapy were completed after which, the KS skin lesions had markedly reduced in size and number.

He presented 1 month later with dyspnoea and peripheral oedema. A chest X-ray showed bilateral pleural effusions. A computerized tomography (CT) scan with contrast confirmed bilateral large pleural effusions, discreet pleural enhancement and small volume adenopathy in the mediastinum and axillae. There was generalised oedema of the soft tissues, a thickened nodular omentum and peritoneum and mild colonic wall thickening. The CT conclusion was of pleural, peritoneal and mesenteric lesions, in keeping with diffuse KS, possibly in combination with primary effusion lymphoma (PEL). A pleural aspirate revealed slightly turbid yellow fluid; with protein count 39 g/L. Gram stain showed scanty leucocytes only, and standard bacterial culture was negative. Histology of pleural fluid showed no malignant cells and appearances in keeping with a reactive effusion. As his disease had progressed within 3 months of treatment, treatment with paclitaxel 100 mg/m2 was commenced without delay, as per the BHIVA guidelines for liposomal-anthracycline refractory KS. He received Paclitaxel 100 mg/m2 every 14 days, administered along with 10 mg dexamethasone iv, ranitidine 50 mg and chlorphenamine 10 mg. Tropical and Infectious Diseases Unit, Royal Liverpool University Hospital, Liverpool, UK Corresponding author: Pavithra Natarajan, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. Email: [email protected]

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Figure 1. Bronchoscopy photos and histology. (a) Bronchoscopy revealing patchy erythematous lesions. (b) Histology from lung biopsy: a proliferation of slit-like vascular spaces (H&E, x10 magnification). (c) Histology from lung biopsy: atypical endothelial cells. Extravasated red blood cells present (H&E, x30 magnification). (d) Irregular vascular spaces highlighted by CD34 immunostaining (x10 magnification).

He had a complicated clinical course as it became difficult to manage his pleural effusions, which were reaccumulating at a rate of 1 L/day and causing significant dyspnoea. He underwent two therapeutic aspirations and three chest drains as well as a failed attempt at talc pleurodesis. At this stage it was noted that the pleural fluid had become cloudy in appearance (Figure 2), so further pleural fluid analysis was performed which showed a fluid cholesterol 1.7 mmol/L and fluid triglycerides 2.9 mmol/L. These figures fit with the British Thoracic Society Guidelines for diagnosis of a chylothorax.2 Samples were sent to Public Health England for quantitative Human Herpesvirus-8 (HHV-8) testing. On the pleural aspirate, HHV-8 was detected by polymerase chain reaction (PCR) at 1300 genomic equivalents/mL, which was reported as compatible with a diagnosis of KS. The HHV-8 copy/cell ratio in pleural fluid was 0.028% which was reported as not compatible with PEL, which would typically have a much higher copy/cell ratio. Our patient’s care was discussed with the local respiratory team and the regional cardio-thoracic centre. He had initial conservative management with nasogastric feeding and a low lipid diet. He went on to require further chest drains for significant fluid reaccumulation despite on-going paclitaxel chemotherapy and found nasogastric feeding and the low lipid diet very difficult to adhere to. He was transferred to

Figure 2. Patient’s chest drain revealing pleural fluid cloudy in appearance. Further testing confirmed this as chyle.

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1963

Jackson and Madoff13 78 yr M

Not HIV

Likely HIV positivea

Likely HIV positivea

HIV positive

HIV positive

HIV positive HIV positive

HIV positive

HIV positive

HIV positive

HIV positive

HIV positive

HIV serostatus

–

–

–

–

–

– –

–

–

35 mm3

156 mm3

294 mm

3

CD4 count

N/a

None

None

None

None

None None

None

None

ART (not specified)

Indinavir/Ritonavir/ Zidovudine/Lamivudine

None

Antiretroviral therapy

Nitrogen mustard, thiotepa, sarcolysin

Actinomycin D and etoposide

Chemotherapy pre-diagnosis

Vincristine, bleomycin, etoposide

Methotrexate, vincristine

No treatment Vinblastine, bleomycin, doxorubicin pre-


No treatment

Vinblastine, bleomycin, doxorubicin

Liposomal daunorubicin

Liposomal doxorubicin

Vincristine, bleomycin planned

Chemotherapy

Closed thoracotomy

Bilateral tetracycline pleurodesis

Bilateral tetracycline pleurodesis

Pleurodesis

Pleurodesis

Thoracocentesis Chest drain

Pleuroperitoneal shunt planned

Thoracocentesis

Chest drain

Chest drains

Interventions

Died

Died

Lived

Died

Died

Died Died

Died

Lived

Died

Lived

Died

Outcome

The two patients labelled ‘Likely HIV positive’ were both homosexual men with opportunistic infections. These case reports were published in 1986 and 1988 when HIV was only just being recognised and routine testing was not available. Although an HIV test result is not stated, the implication is that they were HIV positive.

a

1986

Schulman and Grimes12 36 yr M

25 yr M

1988

41 yr M

Pandya et al.11

1989

O’Brien and Cohn10

35 yr M 29 yr M

48 yr M

36 yr M

1990 1990

Pennington et al.8 Judson and Postic9

32 yr M

46 yr M

(2 patients)

1991

Bogner et al.7

Priest and Weiss

1991

1998

40 yr M

3 yr M

Patient

(STD)

6

Vandenbos et al.5

2003

2002

3

Publication Year

Maradona et al.4

Marais et al.

Author

Table 1. Summary of published cases of Kaposi’s sarcoma (KS) and chylothorax.

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the regional cardiothoracic unit for consideration of total parenteral nutrition and surgical intervention. Ultimately, however, after a further period of observation the chylothoraces stopped reaccumulating, his chest drains were removed and he was allowed home to continue paclitaxel as an outpatient. Our patient completed ten cycles of paclitaxel. He was consented regarding possible side effects of paclitaxel chemotherapy to include alopecia, cytopenias and peripheral neuropathy, but did not experience any side effects attributable to paclitaxel chemotherapy. He did not develop neutropenia and gCSF support was not required. A CT scan was not repeated but plain radiography was performed after eight cycles of paclitaxel, and this showed that the lung fields were cleared. His CD4 count at the end of treatment was 495 cells/mL (and indeed his CD4 count never dropped below 400 cells/mL throughout treatment). His HIV VL was 104 copies/mL. He was feeling well and his cutaneous KS lesions had more or less disappeared. He was tolerating Atripla well and was discharged back to the referring hospital.

HIV-positive patients. The diagnoses can sometimes be difficult to distinguish. Our case serves as a reminder that KS can occur at high CD4 cell counts, and is an indication for anti-retroviral therapy, irrespective of CD4 count. Acknowledgements The authors acknowledge Dr Anu Chawla, Consultant Virologist, Specialist Virology Centre, Royal Liverpool University Hospital, Professor Mark Bower, Consultant in Medical Oncology, Chelsea and Westminster Hospital, and Dr Simon Carne, Clinical Scientist, HHV-8 service, Virus Reference Department, Public Health England.

Conflict of interest The authors declare no conflict of interest.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

Discussion Chyle is lymphatic fluid enriched with fat and its digestive products absorbed by the intestinal epithelium; it is collected and transported by the thoracic duct into the circulation. Damage to the duct leads to leakage of chyle into the pleural space. Among the neoplastic aetiologies for chylothorax, lymphoma accounts for 70% of cases. In visceral KS, chylothorax is thought to be related to infiltration of the thoracic duct. Chylothorax in the context of visceral KS is rare, and carries a poor prognosis. There are a total of 12 cases reported in the literature, 10 of which are case reports.3–13 These are summarised in Table 1. These are mainly in the pre-ART era and the original case13 from 1963 is pre-HIV. Most of these patients were dead by the time of publication, and for a number of these patients, the diagnosis of chylothorax was only made at autopsy. Many patients required repeated aspirations, chest drains and pleurodesis, as did ours. Adjuvant measures included TPN and low lipid diets and medium chain triglyceride nasogastric feeding. Medium chain fatty acids are absorbed directly into the portal circulation bypassing the thoracic duct and therefore help reduce re-accumulation of chyle. A variety of chemotherapeutic agents were tried, as was radiotherapy. Our patient is the first reported case of treatment with paclitaxel for relapsed KS with a successful outcome. Human Herpesvirus-8 is associated with KS as well as PEL, a rare non-Hodgkin’s lymphoma affecting

1. Nair SK, Petko M and Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007; 32: 362–369. 2. Hooper C, Lee YC and Maskell N BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65(Suppl 2): ii4–ii17. 3. Marais BJ, Pienaar J and Gie RP. Kaposi sarcoma with upper airway obstruction and bilateral chylothoraces. Pediatr Infect Dis J 2003; 22: 926–928. 4. Maradona JA, Carton JA, Asensi V, et al. AIDS-related Kaposi’s sarcoma with chylothorax and pericardial involvement satisfactorily treated with liposomal doxorubicin. AIDS 2002; 16: 806. 5. Vandenbos F, Barel R, Abbyad R, et al. Chylothorax as a complication of Kaposi sarcoma. Presse Med 1998; 27: 1218. 6. Priest ER and Weiss R. Chylothorax with Kaposi’s sarcoma. South Med J 1991; 84: 806–807. 7. Bogner JR, Gross M, Zietz C, et al. Chylothorax as fatal complication in fulminating Kaposi’s sarcoma in a patient with AIDS. Klin Wochenschr 1991; 69: 134. 8. Pennington DW, Warnock ML and Stulbarg MS. Chylothorax and respiratory failure in Kaposi’s sarcoma. West J Med 1990; 152: 421–422. 9. Judson MA and Postic B. Chylothorax in a patient with AIDS and Kaposi’s sarcoma. South Med J 1990; 83: 322–324. 10. O’Brien RF and Cohn DL. Serosanguineous pleural effusions in AIDS-associated Kaposi’s sarcoma. Chest 1989; 96: 460–466.

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11. Pandya K, Lal C, Tuchschmidt J, et al. Bilateral chylothorax with pulmonary Kaposi’s sarcoma. Chest 1988; 94: 1316–1317. 12. Schulman LL and Grimes MM. Metastatic Kaposi’s sarcoma and bilateral chylothorax. N Y State J Med 1986; 86: 205–206.

13. Jackson DR and Madoff IM. Kaposi’s sarcoma. Report of a unique case with visceral metastases presenting as an idiopathic chylothorax. BMQ 1963; 14: 57–59.

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