A 29-year-old man was admitted in August, 2019 for a 10-month history of refractory diarrhea and fever. In September 2015, he was diagnosed with HIV infection and AIDS following the onset of esophageal candidiasis, cytomegalovirus (CMV) enteritis, and Pneumocystis jirovecii pneumonia, which prompted the initiation of antiretroviral therapy (ART) with dolutegravir (DTG), abacavir, and lamivudine. However, viral replication persisted due to poor adherence to medications. In May 2017, the patient was admitted for fever with associated cervical and mediastinal lymphadenopathy with elevated viral load (VL) of > 10 million copies/mL. Moreover, his CD4-positive T-lymphocyte count was low (17 cells/µL) (Fig. 1) and lymph node biopsy revealed M. avium. Findings were consistent with a diagnosis of DMAC infection and despite receiving-mycobacterial therapy, such as clarithromycin, ethambutol, and rifabutin, it did not improve his fever and lymphadenopathy. This prompted the initiation of prednisolone for immune reconstitution inflammatory syndrome. In July 2018, his VL remained uncontrolled due to poor adherence to medications. As a result, the ART was modified to tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), darunavir (DRV), and cobicistat (c).
In October 2018, he presented with watery diarrhea; however, colonoscopy revealed no abnormalities in the lower gastrointestinal tract. In March 2019, the patient also developed optic neuritis due to ethambutol. Because antimicrobial blood cultures remained positive for M. avium, treatment for DMAC infection was continued following the replacement of ethambutol with levofloxacin. However, the patient’s fever and watery diarrhea worsened, and blood cultures remained positive for M. avium despite treatment. In May 2019, intravenous amikacin was started and later discontinued as the patient had symptoms of vomiting, sensorineural hearing loss, and progressive hypoalbuminemia. A colonoscopy showed an ulcer in the ileocecal region and histopathologic analysis of the biopsy sample confirmed the diagnosis of CMV enteritis. Treatment with intravenous ganciclovir followed by oral maintenance therapy with valganciclovir did not helped with his fever, watery diarrhea, and elevated VL. The HIV drug resistance test detected M184V mutation, which led to further modification of the ART to TDF, FTC, DTG, DRV/c in July 2019. However, VL remained elevated.
In August 2019, the patient was admitted for monitoring of his refractory diarrhea, and a colonoscopy revealed improvement of the ulcers due to CMV enteritis. A 99mTc human serum albumin scintigraphy showed a faint accumulation in the center of the left upper quadrant at the third hour, followed by migration at the sixth hour. These findings were consistent with a diagnosis of PLE.
Capsule endoscopy revealed scattered yellowish-white nodules from the horizontal part of the duodenum to the upper jejunum while upper gastrointestinal endoscopy (Fig. 2) showed multiple yellowish-white granular nodules and lymphatic dilatation from the upper duodenal angle to the horizontal part of the duodenum, suggesting that the PLE was due to intestinal lymphangiectasia (IL). Histopathologic analysis showed dense histiocytic infiltration in the mucosal lamina propria, while the Ziehl-Neelsen staining showed numerous acid-fast bacteria. Polymerase chain reaction (PCR) identified the bacteria as M. avium, which implicates that DMAC infection is an etiology of IL.
During hospitalization, the blood levels of DTG and DRV were below the detection limits, indicating that the patient did not absorb any of his oral medications due to PLE. As a result, azithromycin, levofloxacin, ganciclovir, and pledonisolone were administered intravenously, and the ART (TDF, FTC, DRV/c) were administered orally. In addition, symptomatic therapy for splenomegaly and vomiting was also received by the patient.
In February, 2020, he was admitted for worsening pain and hypotension, and as per the request of the patient and his family, cardiopulmonary resuscitation did not occur. He died due to sepsis on the third day after admission.
An autopsy was performed (Fig. 3) and revealed gross pathological findings as follows: (1) diffuse white granular esophageal and duodenojejunal lesions, (2) generalized intestinal edema, (3) enlarged and nodular peritoneal lymph nodes, and (4) enlarged spleen (818g weight) with similar white granular lesions. Histopathological examination showed acid-fast bacilli in various organs of the body, which includes the esophagus, stomach, duodenum, jejunum, ileum, colon, liver, spleen, lymph nodes (e.g., intestinal, periaortic, mediastinum), lung, adrenal gland, thyroid gland, bone marrow, and renal vessels. In particular, the small intestine had diffuse lesions and showed positive for M. avium complex in PCR. Furthermore, a CMV infection was observed in the colon, lung, and adrenal glands, but the number of infected cells was small. Methicillin-susceptible Staphylococcus aureus was detected in the blood culture and masses in the right lung and bladder mucosa.