A 64 year old Caucasian man presented to the Emergency Room in 2016 with approximately 2 months of generalized malaise, weight loss (7 kg), anorexia and vesperal temperatures of around 37.5  C. He also noticed epigastric abdominal pain, liquid stools (once a day, without blood or mucous) and night sweats in the two previous weeks. He denied increased ganglia, increased abdominal volume, vomits or respiratory symptoms.
The patient was born in Angola (Sub-saharan Africa), but was living in Portugal since 1975 and denied any trip abroad since then. His past medical history was not remarkable.
On clinical presentation, he was underweight and febrile (temperature of 38.1  C). Skin was colored and hydrated. Cardiopulmonary auscultation was normal. Abdominal palpation was slightly painful in the epigastric region. Hepatosplenomegaly or peripheric adenopathy were not found. The fundoscopy was normal. No additional clinical findings were noticed.
The laboratory study revealed mild thrombocytopenia and slightly elevated C-Reactive Protein. The HIV screening was positive with ELISA and Western blot for infection with HIV-1. The patient was unaware of this condition. Immunologically the patient presented with CD4 + T-cel count of 64.8/uL (6,4 %) and HIV-1 viral load of 61,249 copies/mL.
The abdominal ultrasound revealed multiple ganglia in the emergence of the celiac trunk (the largest one with approximately 20 mm). The CT scan confirmed the presence of this multiple adenopathy, sometimes necrotic and coalescent, diffusely distributed in the mesenterium, the largest with 2 cm in diameter (Fig. 1). There were also multiple adenopathy around the mesenteric vessels and around the aorta and inferior vena cava, predominantly in the emergence of the renal vessels and in the retrocural region.
As imagiological findings suggested lymphoproliferative disease, a bone marrow aspiration was performed. It failed to detect abnormal lymphoid populations, showing a normal ratio of the myeloid/erythroid lineage and the molecular study using RT-PCR for nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis (MTB) was negative. Bone marrow mycobacterial culture was ensued yielding the growth of Mycobacterium genavense six weeks later.
The patient was also submitted to laparoscopic mesenteric ganglia biopsy. Molecular biological analysis using RT-PCR was positive for NTM and negative for MTB; mycobacterial cultures were negative. The histopathological examination showed an alteration of the ganglia architecture, filled with histiocytes and numerous Ziehl-Neelsen+, PAS- microorganisms (Fig. 2), which was compatible with an atypical mycobacteriosis. Upper endoscopy revealed focal hyperemia and loss of the vascular appearance in the duodenum; the stomach antrum was atrophic with reduction of the vascular supply. Histopathological examination of the duodenum mucosa showed infiltration by histiocytes (CD68+, S100-, PAS-), filled with numerous mycobacteria (Ziehl Neelsen and FITE+) (Fig. 3). The diagnosis of a disseminated mycobacteriosis by Mycobacterium genavense was then confirmed.
As the HLAB5701 was not present and the HIV drug resistance test was negative, antiretroviral therapy was initiated with a single tablet regimen containing abacavir, lamivudine and dolutegravir with good tolerance and adherence. Due to severe immunosuppression trimethoprim/sulfamethoxazole prophylaxis was also initiated. Antimycobacterial treatment was started empirically with rifabutin, ethambutol and clarithromycin.
After 4 months under the antimycobacterial treatment, the patient, although clinically stable and with no signs of immune reconstitution inflammatory syndrome (CD4 + T-cel count of 94/uL and HIV viral load of 0 copies/mL), showed imagiological deterioration of the adenopathy, with presence of the "sandwich sign" (Fig. 4), meaning the mesenteric ganglia compressing the superior mesenteric vein. After 6 months of treatment, we had access to the drug susceptibility testing, which showed resistance to all first and second lines antibacillary drugs (ethambutol, linezolide, amikacin, rifampicin, rifabutin, ofloxacin, olarithromycin, Isoniazid, ciprofloxacin). At the time, the patient was kept under the antymicobacterial treatment described before as the drug susceptibility testing is not clearly validated for this microorganism.
After 9 months of treatment, the patient still complained about abdominal pain and presented with CD4 + T cel count of 204/uL and indetectable HIV viral load. Another abdominal CT scan was performed, presenting similar findings as the ones previously described and thrombosis of the inferior mesenteric vena (Fig. 5).
To exclude the presence of another HIV-associated infection or lymphoproliferative disease, a second mesenteric ganglia biopsy was performed, which revealed persistence of the atypical mycobacteriosis on the histopathological examination. Bone marrow aspiration was also repeated. Both products were negative for culture and RT-PCR of NTB and MTB.
Because of the imagiological deterioration and antibacterial resistance pattern, it was considered the possibility of non-response and treatment was revised at that time for amikacin, rifampicin, moxifloxacin and clarithromycin and enoxaparin. Due to drug interactions, dolutegravir was changed to efavirenz with good tolerance. The patient was kept under this antimycobacterial treatment for 3 months, but due to intolerance to the amikacin (local injection site pain), this drug was discontinued. After more than 3 years, the patient is currently alive, clinically stable, with no imagiological deterioration, although he is still on antimycobacterial treatment with rifampicin, moxifloxacin and clarithromycin.