Mycobacterial disease causing chylous effusions in two patients living with uncontrolled HIV

Case 1

A man in his 40s was diagnosed with HIV with a CD4 of 2 cells/µL and a viral load (VL) of 467 735 of copies/mL. He was given raltegravir and tenofovir disoprixil fumarate/emtricitabine. MG was cultured from a biopsy of a coalesced retroperitoneal lymph node mass, found on abdominal CT (figure 1). Antimycobacterial treatment with ethambutol, rifabutin and azithromycin was given. Azithromycin was subsequently switched to levofloxacin due to gastrointestinal intolerance. Eight months later, he presented with shortness of breath and abdominal swelling. A CT of the chest/abdomen/pelvis (CT CAP) revealed bilateral pleural effusions and large volume intra-abdominal ascites. The intra-abdominal lymph node mass had not changed in size. HIV VL was less than 20 copies/mL, and CD4 count was 50 cells/µL.

Figure 1

Coronal CT image of mesenteric nodal mass of case 1.

Pleural and ascitic drain fluid was chylous, confirmed by triglyceride level in the fluid of 130 mg/dL. Repeat biopsy of the abdominal lymph nodes demonstrated persistent mycobacteria and fibrosis. Mycobacterial culture of the tissue sample was negative after extended incubation. A lymphangiogram suggested the cause of the chylous effusion to be nodal involvement and lymphatic obstruction within the proximal small bowel mesentery. After extensive investigation, other non-traumatic causes of chylothorax were excluded, and a diagnosis of sclerosing mesenteritis was made.

He was given prednisolone 1.5 mg/kg to reduce inflammation driven by immune reconstitution and minimise the progression of fibrosis. Repeat ascitic drains were required due to persistent reaccumulation of chylous fluid. Octreotide 100 µg two times per day was given subcutaneously, and tamoxifen 20 mg once daily orally was added to the treatment regimen together with a low-fat diet. Over a 4-week admission, the chylous output reduced sufficiently for the patient to be discharged. He was weaned off steroids over the course of 4 months but required intermittent abdominal paracentesis.

Six weeks after weaning steroids completely, he was readmitted due to increasing reaccumulation of ascites. The octreotide dose was increased to 200 µg three times per day, thalidomide 100 mg once daily was added and prednisolone 60 mg was restarted. The patient was again discharged. Two weeks later, he was admitted a third time with increased chylous ascites (draining~1 L/day). Over the course of a 3-month admission, total parenteral nutrition (TPN) was started with fast and significant reduction of the chylous effusion. Ocreotide and thalidomide were stopped, and the patient was successfully discharged on TPN and fat-free only oral diet, without reaccumulation of chylous effusion for the past 6 months. Steroids were weaned slowly (over the course of 6 months). He continues to fail to immune-reconstitute (latest CD4+25, 7%; VL <20 copies/mL) and remains on antimycobacterials (22 months of treatment), aiming to complete 24 months of treatment.

Case 2

A man in his early 30s was diagnosed with HIV and disseminated M. avium complex (DMAC) via laparoscopic retroperitoneal lymph-node biopsy. His CD4 count at diagnosis was 15 cells/µL, and his HIV VL 10 million copies/mL. He was given antiviral therapy with raltegravir+tenofovir DF/emtricitabine together with rifabutin, ethambutol and azithromycin for DMAC. Two months into treatment, he suffered virological failure with development of M184V in the reverse transcriptase gene and 155NH in the integrase gene.

Resistance sequencing on his original VL had not demonstrated any previous resistance, so non-adherence to his antiretroviral treatment (ART) was suspected. The importance of adherence was emphasised, and a direct observation of treatment strategy (DOTS) was instituted to improve adherence to the patient’s DMAC medications. His antiretrovirals were switched to doravirine 100 mg two times per day, dolutegravir 50 mg two times per day and tenofovir DF/emtricitabine, with subsequent VL suppression. The VL suppression and good engagement with DOTS suggested improved adherence.

Over the following 12 months, the patient had multiple admissions with abdominal pain and enlargement and necrosis of mesenteric and retroperitoneal lymph nodes, thought to be secondary to IRIS, managed with high-dose steroids.

Five months after starting DMAC treatment, further mycobacterial blood cultures were positive and resistant to clarithromycin. His antimycobacterial regimen was optimised to rifabutin, linezolid and ethambutol.

Twelve months after treatment optimisation, he was admitted with shortness of breath and abdominal swelling. CT CAP showed bilateral pleural effusions, significant ascites and an unchanged appearance of the mesenteric and retroperitoneal lymph-nodal mass. Drains in the peritoneum and chest drained high volumes of chylous fluid daily (303.8 mg/dL), with an output of up to 5 L/day from the chest. A lymphangiogram showed no lymphatic focal obstruction but evidenced extremely slow progression of the dye above the diaphragm. Repeat mycobacterial blood cultures were negative, and extensive investigation for non-traumatic causes of chylous effusions was negative (see differential section).

On the basis of radiological features and clinical picture, he was diagnosed with IRIS and sclerosing mesenteritis. High dose oral steroids (1.25 mg/kg of prednisone) were given, and octreotide 100 mg two times per day and tamoxifen 100 mg once daily were added into his treatment regimen. A medium-chain triglyceride diet was given.

In spite of this, he continued to output high volumes of chyle from his chest drain. TPN was trialled. Chylous output reduced drastically to a few millilitres a day, and the chest drain was removed. A low-fat oral diet was gradually introduced with minimal reaccumulation, and the patient was subsequently able to be discharged (CD4 22 cells/µL, 7%; VL <20 copies/mL). Ocreotide was stopped, and steroids were gradually weaned over 3 months. Four months later, he was readmitted for recurrence of pleural and ascitic chylous effusions. A repeat CT of the abdomen showed increase in size in the known intra-abdominal mass; this was biopsied with evidence of granulomatous inflammation and acid fast bacilli seen. Mycobacterial cultures failed to grow. Chest and abdominal drains were inserted, and steroid treatment was restarted (1.5 mg/kg prednisolone). High chylous ascites production continued (1–2 L/day) despite a fat-free diet, so an intra-abdominal pleurex drain was inserted to facilitate discharge from hospital. Ascitic production reduced gradually over the following 3 months and the drain was removed.

Steroids were weaned gradually over the course of 5 months. Investigations at 12 months show evidence of some immune-restoration (CD4 143 cells/µL, 12%; VL <20) and reduction in the size of intra-abdominal lymph nodal mass, with no new ascites nor pleural effusion.