Chylous ascites: a late complication of intra-abdominal Mycobacterium avium complex immune reconstitution syndrome in HIV-infected patients

Abstract

Chylous ascites related to Mycobacterium avium complex (MAC) in HIV-infected patients is rare, with only six cases reported in the English literature. We report a series of six cases from a single institution. During the past six years, chylous ascites was diagnosed in six (35%) of 17 AIDS patients, all of whom had previously been diagnosed with intra-abdominal MAC immune reconstitution syndrome (MAC-IRS). A review of medical records identified no other cases of chylous ascites among HIV-positive patients over the past 13 years (1994–2007), and the incidence was estimated at one in 2248 HIV-positive admissions. The ascitic fluid had a milky appearance and a median triglyceride level of 4.07 mmol/L (range 3.19–29.6 mmol/L) (360 mg/dL, range 282–2620 mg/dL). After a median follow-up of 20 months, five (83%) of six patients survived. Chylous ascites is a late complication of intra-abdominal MAC-IRS, and is usually associated with a favourable prognosis.

Keywords

chylous ascites immune reconstitution syndrome HIV AIDS

INTRODUCTION

Chylous ascites refers to the accumulation of milky appearing fluid in the peritoneal cavity, which has a high content of triglycerides (defined as >200 mg/dL) due to the accumulation of intestinal or thoracic lymph. A wide variety of congenital and acquired aetiologies have been described. Acquired lesions of the lymphatic system causing chylous ascites may be related to neoplasm, trauma, surgery, cirrhosis, right-sided heart failure and inflammatory conditions such as radiation, pericarditis, pancreatitis, tuberculosis, filariasis, sarcoidosis and Whipple's disease.^1–3 Among HIV-positive patients, chylous ascites has rarely been reported in association with Mycobacterium tuberculosis, Mycobacterium avium complex (MAC), lymphoma and Kaposi's sarcoma.^4–8

We identified only six reported cases of MAC-related chylous ascites in AIDS,^4–8 two of whom we reported in a case series of non-tuberculous mycobacterial immune reconstitution syndrome (NTM-IRS).⁴

METHODS

Cases of NTM-IRS were defined as previously outlined.⁴ Chylous ascites was defined as an ascitic fluid with a triglyceride level of >200 mg/dL (2.26 mmol/L).² Statistical analyses were performed using SAS software version 9.1.3 Service Pack 3 (SAS, Cary, NC, USA). Categorical variables were analysed using Fisher's exact test.⁹

RESULTS

Between January 1993 and May 2007, we identified 17 cases of intra-abdominal MAC-IRS: 11 had been previously reported.⁴ Six (35%) of the 17 intra-abdominal cases (11% of all the MAC-IRS cases) developed chylous ascites, and have been followed up for a median of 20 months (range 4–75 months). A medical records search of all cases of chylous ascites admitted to St Paul's Hospital between 1 April 1994 and 23 March 2007 identified only the six cases related to MAC-IRS reported here, among 4144 known HIV-positive patients who had a total of 13,485 admissions. The incidence of chylous ascites among HIV-positive patients was therefore estimated at one in 2248 admissions for the 13-year interval. However, during the earlier time period (1 April 1994 to 31 March 2001), there were no cases of chylous ascites among the 7688 HIV-positive admissions, in comparison with the later period (1 April 2001 to 23 March 2007), during which there were six cases among the 5797 HIV-positive admissions (P value: 0.0063). The incidence of chylous ascites in the latter period was estimated at one case per 966 HIV-positive admissions.

Clinical presentations with chylous ascites included abdominal pain (83%), distension (100%) and gross ascites (83%), but none had fevers. Table 1 includes the clinical and laboratory findings for the six cases. The median CD4 counts before the initiation of highly active antiretroviral therapy (HAART), at the time of initial diagnosis with MAC-IRS and at the time of documentation of chylous ascites were 10, 75 and 130 cells/mL, respectively. Compared with the baseline before the initiation of HAART, the median reduction in HIV RNA in log₁₀ copies/mL was 3.3 at the time when chylous ascites was documented. Macrolide-resistant MAC (clarithromycin MIC >64 µg/mL) was documented from various body sites in four (66%) of the cases.

Table 1

Sites of disease and laboratory findings for six cases of chylous ascites associated with M. avium complex immune reconstitution syndrome

Case	Age/sex HIV risk	Sites of previous or concurrent MAC disease	CD4 at time of			HIV RNA log₁₀ decrease^† at		Intervals (months)^‡		Chylous ascites fluid analysis
Case	Age/sex HIV risk	Sites of previous or concurrent MAC disease	Baseline*	MAC-IRS Dx	Ascites Dx	MAC-IRS Dx	Ascites Dx	HAART to MAC-IRS Dx	MAC-IRS to ascites Dx	TG^§	WBC**	AFB smear	AFB culture^††	Comments and outcome
1	38/M IDU	Blood, abdom. node	40	90	210	3.3	5	7	4	6.7	118	−	+	Clinically well at F/U; no recurrence for 57 mo.
2	40/M hetero	Blood, abdom. node, duodenal bx, liver bx	100	60	150	2.6	2.1	1.5	16	3.9	87	+	+	Refractory ascites and MAC bacteremia, despite CD4 up to 350 (18%); died 9 mo. later
3	43/M MSM	Blood, abdom. node, duodenal bx, medastinal bx, psoas abscess	10	130	150	3.3	5	8	24	3.2	220	−	−	Refractory ascites and wasting; improved on long-term TPN^‡‡
4	42/M MSM	Blood, duodenal bx, supraclav. node	<10	<10	60	1.9	3.5	24^§§	37^§§	29.6	420	−	−	Clinically well at last F/U; no recurrence for 50 mo.
5	34/M MSM	Blood, abdom. node	<10	20	30	5	5	1***	8***	4.2	265	−	−	Clinically well at last F/U; no recurrence for 16 mo.
6	23/M MSM	Blood, abdom. node, duodenal bx, supraclav. node	<10	220	110	3.3	0^†††	2	23	3.5	NA	−	−	Recurrent abdominal pain off all medications 3 mo later

abdom. = abdominal; AFB = acid-fast bacilli; AZM = azithromycin; bx = biopsy; CLA = clarithromycin; Dx = diagnosis; EMB = ethambutol; F/U = follow-up; hetero = heterosexual contact; HAART= highly active antiretroviral therapy; IDU = injection drug use; MAC = Mycobacterium avium complex; MAC-IRS Dx = M. avium complex immune reconstitution syndrome diagnosis; MSM = men who have sex with men; NA = not available; supraclav. = supraclavicular; TG = triglycerides; WBC = white blood cells

*Baseline: CD4 at baseline before initiation of antiretroviral therapy

^†HIV RNA log₁₀ decrease: reduction in HIV RNA log₁₀ at time of MAC-IRS diagnosis, and chylous ascites diagnosis compared with baseline before initiation of antiretroviral therapy

^‡Intervals: from the time of initiation of HAART to the diagnosis of abdominal MAC-IRS, and from the date of diagnosis of abdominal MAC-IRS to the time of diagnosis of chylous ascites

^§TG: triglycerides (mmol/L)

**WBC: ascitic fluid white blood cell count (m/L)

^††AFB culture: mycobacterial (acid-fast bacilli) culture of ascitic fluid, positive (+) or negative (−) for M. avium complex

^‡‡Non-chylous ascites was present seven months before the diagnosis of chylous ascites and was associated with an episode of septic portal vein thrombophlebitis (bacteremic with Bacteroides gracilis and Prevotella melaninogenica). In total, chylous ascites persisted for eight months until TPN initiated. Mild–moderate non-chylous ascites and residual partial thrombosis of the portal vein have persisted since starting TPN and anticoagulation

^§§Abdominal MAC-IRS was suspected 24 months after starting HAART when abdominal lymphadenopathy was present; however, a needle aspirate was non-diagnostic. Abdominal lymphadenopathy was not present when chylous ascites was diagnosed. Supraclavicular lymphadenitis due to MAC-IRS had been confirmed three months after starting HAART

***Abdominal MAC-IRS was suspected one month after starting HAART, but was not confirmed by abdominal lymph node needle aspirate until seven months after starting HAART. The interval from suspected abdominal MAC-IRS to the diagnosis of chylous ascites was eight months

^†††Patient had stopped antiretroviral therapy, AZM and EMB two months before chylous ascites diagnosis

All patients had chylous peritoneal fluid with a milky appearance and a median peritoneal fluid triglyceride level of 4.07 mmol/L (range 3.19–29.6 mmol/L). The median peritoneal fluid white blood cell count was 220 M/L, with a mononuclear cell predominance (median 82%). An alternate possible aetiology of chylous ascites was only identified in Case 3, who had developed septic thrombophlebitis of the portal vein eight months before.

Therapeutic interventions included large volume paracentesis (n = 5 patients), low-fat diet with medium chain triglyceride oil supplement (n = 2), tube feeding with elemental diet (n = 2) and total parenteral nutrition (n = 2). The median duration of chylous ascites was nine months, and assessment of the effect of the above treatments was often confounded by simultaneous interventions.

DISCUSSION

Our chylous ascites incidence of one per 2248 HIV-positive hospital admissions is approximately five-fold higher than the highest reported incidence of one per 11,589 admissions in the general population during the era before the HIV epidemic.¹ It is noteworthy that all six cases of chylous ascites occurred in association with a prior diagnosis of intra-abdominal MAC-IRS, supporting a causal relationship. Following the initiation of antiretroviral therapy in patients with previously documented AIDS-related MAC infection, approximately 31% will subsequently develop MAC-IRS.¹⁰ Among 17 cases of intra-abdominal MAC-IRS in our institution, six (35%) developed chylous ascites at a median of 19.5 months later.

In contrast to HIV-related MAC infection without immune reconstitution, abdominal MAC-IRS is associated with histologically well-formed granulomas,¹¹ suggesting that the pathogenesis of chylous ascites may be related to granulomatous lymphadenitis causing lymphatic obstruction at the base of the mesentery or the cisterna chili, analogous to cases associated with neoplastic infiltration and fibrosis.²

In conclusion, chylous ascites has developed as a significant late complication in 35% of our patients with intra-abdominal MAC-IRS. This appears to be associated with a generally favourable prognosis, with the use of specific HIV and MAC therapy, even in the presence of macrolide-resistant MAC.

Footnotes

ACKNOWLEDGEMENTS

We thank Kelly Hsu, who helped prepare this manuscript.

CONFLICTS OF INTEREST

There was no financial support for this study.

PP has received research funding from, has been a consultant for and is a member of the speakers' bureau for Pfizer, Merck Frosst Canada, Hoffmann-La Roche and Schering-Plough Pharmaceuticals. EY has received unrestricted research grants from Gilead Sciences and Pfizer-Canada. JM has received recent research funding from, has been a consultant for, and is a member of the speakers' bureau for Abbott, Argos Therapeutics, Bioject Inc., Boehringer Ingelheim, Brisol Myers-Squibb, Gilead Sciences, GlaxoSmithKline, Hoffman-La Roche, Janssen-Ortho, Merck Frosst, Panacos, Pfizer, Schering, Serono Inc., TheraTechnologies, Tibotec (Johnson &Johnson) and Trimeris.

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