This article presents a case of an HIV-infected paediatric patient with an unusual
The patient is a chronically ill 8-year-old boy from Limpopo province in South Africa, living with his adoptive parents. He was born prematurely at 7 months’ gestation, weighing 1.9 kg. There was a history of recent travel to the Kruger National Park, and to India 6 months prior to admission. All his vaccinations were up to date on history, but this was never confirmed. He was markedly underweight for his age (with weight-for-age and height-for-age
The patient was referred to a paediatric gastroenterologist in October 2016. He was acutely ill, severely wasted (17 kg) and pyrexial (39 °C). He was clinically pale with a tachycardia and mild oedema of his lower limbs. Hepatosplenomegaly was detected, although there was no peripheral lymphadenopathy. His abdomen was severely distended, and he had recurrent diarrhoea and vomiting with marked intolerance of all foods.
Abdominal computed tomography (CT) scan and ultrasound revealed massively enlarged intra-abdominal lymph nodes (see
Radiology (computed tomography coronal images of the chest, abdomen and pelvis, a–c). Multiple conglomerate nodal masses are seen along the mesenteric, aorta, iliac and para-aortic nodal chains. There are also enlarged nodes in the porta hepatis. Several of the upper abdominal mesenteric nodes demonstrate low density, compatible with central necrosis. Diffuse hepatomegaly with no discrete lesion is seen.
Laboratory investigations confirmed that the patient was HIV-infected with a CD4 count of 59 cells/μL (7%) and HIV viral load of 453 780 copies/mL (log10 5.66). Further testing revealed mildly elevated liver enzymes. Moderate proteinuria was present and the faecal α-1 antitrypsin result was in keeping with a protein-losing enteropathy. His blood count showed microcytic hypochromic anaemia, with the iron function studies reflecting a pattern of reticuloendothelial iron blockade (see
Laboratory results.
Biochemical/haematological parameter | Patient value |
Reference range | |
---|---|---|---|
October 2016 | March 2017 | ||
ALP | 91 IU/L | 445 IU/L | < 300 IU/L |
GGT | 58 IU/L | 1098 IU/L | < 17 IU/L |
ALT | 44 IU/L | 92 IU/L | < 39 IU/L |
AST | 84 IU/L | 132 IU/L | < 51 IU/L |
Albumin | 20 g/L | - | 38 g/L – 54 g/L |
Globulin fraction | 57 g/L | - | 22 g/L – 36 g/L |
Urine protein:creatinine ratio | 61 mg/mmol | - | < 20 mg/mmol |
Faecal α-1 antitrypsin | 1.72 mg/g | - | 0.43 mg/g – 1.47 mg/g |
Haemoglobin | 8.8 g/dL | - | 11.5 g/dL – 15.5 g/dL |
MCV | 75.6 fL | - | 77.0 fL – 95.0 fL |
MCH | 24.4 pg | - | 25.0 pg – 33.0 pg |
Iron | 6.2 mmol/L | - | 4.8 mmol/L – 17.2 mmol/L |
Transferrin | 1.5 g/L | - | 1.3 g/L – 3.1 g/L |
Percentage saturation | 17% | - | 17% – 42% |
Ferritin | 495 ng/mL | - | 7 ng/mL – 140 ng/mL |
ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin.
The differential diagnosis included tuberculosis or lymphoma. Over a period of 7 months, endoscopically and surgically obtained biopsy material was submitted for histology (see
Histological images of the duodenum and lymphnode. (a) Histology of the duodenal mucosa showing lamina propria expansion by histiocyte sheets (hematoxylin and eosin, 100×). (b) Duodenal villus filled with abundant organism-containing histiocytes (hematoxylin and eosin, 400×). (c) Lymph node replaced by sheets of histiocytes with scattered intervening inflammatory cells (hematoxylin and eosin, 100×). (d) Lymph node histiocytes revealing finely granular to foamy cytoplasm, engorged with bacilli (hematoxylin and eosin, 400×). (e) Ziehl–Neelsen stain demonstrating large numbers of acid-fast bacilli in duodenal histiocytes (400×). (f) Periodic acid-Schiff stain showing granular positivity in the histiocyte intracytoplasmic organisms (400×).
Histology results.
Date | Biopsy material | Histological findings |
---|---|---|
12 October 2016 | Mesenteric lymphnode | Lymphadenitis; acid-fast bacilli (AFB) (short morphology); Periodic Acid Schiff (PAS) positive; poorly formed, focal granulomata |
Duodenum and caecum | Granulomatous duodenitis and colitis; histiocytes packed with acid-fast and PAS positive bacilli (small) | |
08 March 2017 | Duodenum | Duodenitis; weak epithelioid granuloma formation; histiocytes noted again as on previous biopsy material |
Liver and intra-abdominal lymphnode | Liver: granulomatous hepatitis (moderate to well-formed epitheloid granulomata; scattered intracytoplasmic AFB in portal granulomata); intra-abdominal lymphnode: lymphadenitis; histiocytes filled with acid-fast and weakly PAS positive bacilli | |
06 May 2017 | Duodenum | The results were similar to previous biopsies, although the infiltrate of AFB containing histiocytes was less impressive in this specimen |
Further testing of the biopsy specimens included mycobacterial cultures, all of which showed no growth. Acid-fast bacilli (AFB) were noted during the processing of the tissue samples obtained from the intra-abdominal lymph nodes on 12 October 2016, and again in biopsy material obtained on 08 March 2017. Microscopy performed on a stool sample on 26 March 2017 also showed acid-fast organisms with a coccoid appearance. The polymerase chain reaction (PCR) assay for
A cytomegalovirus (CMV) viraemia of 3974 copies/mL (log10 3.60) was measured in March 2017 together with a colon biopsy that was PCR positive for CMV. The Epstein Barr viral load at the time was 9318 copies/mL (log10 3.97).
Anti-mycobacterial treatment was started (rifampicin, isoniazid, ethambutol, pyrazinamide and clarithromycin) followed 4 weeks later with antiretroviral therapy (abacavir, lamivudine and efavirenz). The patient’s HIV viral load was undetectable at 3 months, and his CD4 count at that stage was 101 cells/μL (6%). Clinically and radiologically, however, there was no improvement in his abdominal signs and symptoms. Malabsorption and refeeding syndrome was considered, and all treatment, including ganciclovir, was given intravenously. His antiretroviral medication was temporarily suspended until oral feeding could be tolerated. Immune reconstitution inflammatory syndrome (IRIS) was considered, and methylprednisone was initiated (1 mg/kg/dose) for 4 weeks, after which the dosage was tapered and stopped. The patient was given a period of bowel rest and free drainage, after which he was placed on an elemental diet. There was no clinical improvement and liver dysfunction worsened (see
In May 2017, a diagnosis of
The patient’s response to the new regimen was slow, and initially he was unable to tolerate food. Insertion of a nasogastric tube was required for continuous feeds together with total parenteral nutrition. At the time of writing this article (17 months of treatment completed), his clinical response had improved. He was able to tolerate small regular meals with no nausea, vomiting or diarrhoea. His weight gain had been slow (now up to 20 kg) despite nutritional supplementation. The hepatosplenomegaly and abdominal distension had improved markedly, and his HIV remains virologically suppressed.
Dr R. de Gama obtained consent from the patient’s parents to publish this case report.
The first case of
Human isolates have been recovered from cultures of blood, bone marrow, liver, spleen and other tissues.
Most clinical
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Other diseases that may be associated with
While most patients with
The clinical presentation of cases with
The laboratory diagnosis of
Multidrug therapies that include clarithromycin appear to be more effective than those without clarithromycin.
The documented cases of
Follow-up radiological investigation, especially if CT is used, increases the risks associated with radiation exposure. Some authors suggest an X-ray and high-resolution CT at baseline prior to the commencement of therapy.
A poorly understood pathogen-specific syndrome similar to retractile mesenteritis has been described in patients infected with
The patient described in this case report is illustrative of the difficulties encountered in accurately diagnosing and managing disease caused by non-tuberculous mycobacteria, in this case
This organism is the most common cause of psittacine mycobacteriosis.
The clinical presentation of patients with
Available molecular diagnostic tools are used to obtain a diagnosis.
A three- or four-drug regimen is typically suggested for treatment.
Treatment is prolonged to more than 12–27 months.
The authors wish to thank Prof. Mark Cotton and Prof. Helena Rabie from the University of Stellenbosch and Dr Carlos Perez-Velez from the University of Arizona for their contributions to the management of this case.
The authors have no conflict of interests.
R.D.G. and C.K. contributed to the clinical information. E.H. was the initial pathologist involved in assisting with work-up of the case. P.E. assisted with the trouble shooting of the diagnostic work-up. C.C. managed to get the primers for the mycobacterial 16s rRNA polymerase chain reaction (PCR) and assisted with the running of that PCR. T.S. assisted with the histological work-up of the case. T.M. assisted greatly with integrating the HIV management with that of the Mycobacterium genavense. E.H. assisted with checking all the lab data in the article. P.E. did the literature review. J.v.I. assisted with checking the academic content of the document as an international expert in non-tuberculous mycobacteria. T.M. and C.C. assisted with the editing of the final version. All the authors reviewed the document and were satisfied with the final version.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Data sharing is not applicable to this article as no new data were created or analysed in this study.
The views expressed in the article are those of the authors and not an official position of the institution or funder.