68 J Clin Pathol 1999;52:68–71

Infection by equi in a patient with J Clin Pathol: first published as 10.1136/jcp.52.1.68 on 1 January 1999. Downloaded from AIDS: histological appearance mimicking Whipple’s disease and avium-intracellulare

David Hamrock, Farrukh H Azmi, Edward O’Donnell, William T Gunning, Edwin R Philips, Aiman Zaher

Abstract Case report Rhodococcus equi with sys- A 46 year old HIV positive white male was temic dissemination is being reported admitted to the Medical College of Ohio increasingly in immunocompromised pa- hospital in late October 1996, complaining of tients. This is the first case report of fever, night sweats, dry cough, and weight loss. disseminated R equi infection with biopsy Previously, the patient underwent a bronchos- documented involvement of the large copy in May 1996 in response to a mass in the intestine. The patient was a 46 year old left lower lobe discovered on routine chest x male with AIDS who was diagnosed with ray. A culture at the time of bronchoscopy grew cavitating pneumonia involving the left R equi, which was sensitive to penicillin, eryth- lower lobe. R equi was isolated in culture romycin, trimethoprim-sulphamethoxazole from the blood and lung biopsies. Subse- (TMP-SMX), rifampicin, and vancomycin. It quently, the patient developed anaemia, was resistant to clindamycin. His clinical diarrhoea, and occult blood in the stool. condition improved moderately but not fully, Colonoscopy revealed several colonic pol- after taking TMP-SMX, rifampicin, and clari- yps. Histological examination of the colon thromycin daily for several months. biopsies showed extensive submucosal Biopsies from a subsequent bronchoscopy in histiocytic infiltration with numerous September 1996 showed a severe active, Gram positive coccobacilli and PAS posi- chronic pneumonitis with Gram positive coc- tive material in the histiocytes. Electron cobacilli within foamy histiocytes. R equi grew microscopy showed variably shaped intra- from cultures of these transbronchial biopsies histiocytic organisms which were mor- as well as from bronchial washings. Three blood cultures drawn at the same time also phologically consistent with R equi in the http://jcp.bmj.com/ specimen. Disseminated R equi infection grew R equi. All of these bacterial isolates from may involve the lower gastrointestinal both the lung and blood cultures were sensitive tract and produce inflammatory polyps to the same antibiotics as in May 1996, except with foamy which histologi- that all isolates were now uniformly resistant to cally resemble those seen in Whipple’s penicillin. disease and Mycobacterium avium- Because the lung lesion had not completely intracellulare infection. resolved and the patient was still having cough (J Clin Pathol 1999;52:68–71) and fever despite taking the antibiotics men- on September 28, 2021 by guest. Protected copyright. tioned, it was agreed to resect the aVected lobe. Keywords: Rhodococcus equi; AIDS; colonic disease A presurgical evaluation showed mild anaemia and occult blood present in the stool. The patient also complained of chronic diarrhoea Rhodococcus equi, previously known as Co- which began in September 1996 at the time rynebacterium equi, is an aerobic, Gram posi- when blood cultures were positive for R equi. tive, mildly acid-fast coccobacillus.1 Originally Colonoscopy in early November 1996 showed isolated from foals with pneumonia in 1923, several “colonic polyps” approximately 10 mm this organism is well known today by veterinar- in size which were excised. Histological exam- ians to be a cause of pulmonary abscesses and ination showed inflammatory polyps with Department of lymphadenitis in several animal species.12 Gram positive coccobacilli. Two days later, the Pathology, Medical College of Ohio, 3000 Since the first reported case of Rhodococcus equi patient underwent an operation to resect the Arlington Avenue, in in 1967, there have been several pathological left lower lobe. A culture of this Toledo, OH 43614, USA additional reports of pneumonia caused by this tissue grew R equi which again was sensitive to D Hamrock organism.134 However, only a small minority TMP-SMX, erythromycin, rifampicin, and F H Azmi of these case reports demonstrating pneumonia vancomycin. It was resistant to penicillin and E O’Donnell also showed pathology in organs outside of the clindamycin. After an uncomplicated postop- W T Gunning 3 5–8 E R Philips respiratory system. Furthermore, only one erative course, the patient’s pulmonary func- A Zaher case of probable gastrointestinal involvement tion improved markedly. by R equi has been reported previously.8 As far While in the hospital, the patient slowly Correspondence to: as we know, this is the first case which began losing his short term memory. Magnetic Dr Aiman Zaher. histologically showed the presence of R equi resonance imaging of the brain showed several Accepted for publication within histiocytes densely infiltrating the sub- enhancing lesions in both hemispheres. In 25 August 1998 mucosa of the large intestine. addition to his current three-antibiotic regi- Infection by Rhodococcus equi in a patient with AIDS 69 J Clin Pathol: first published as 10.1136/jcp.52.1.68 on 1 January 1999. Downloaded from

Figure 1 Endoscopic colon biopsy showing extensive infiltration of foamy histiocytes with abundant eosinophilic PAS positive cytoplasm, Left, H&E stain low power; middle, H&E stain high power; right, PAS stain. men, pyrimethamine was added to cover for otics were discontinued except for vancomycin possible infection by Toxoplasma gondii.In and rifampicin. After two months of this treat- December 1996, computed tomography (CT) ment, his neurological symptoms had resolved of the brain was performed because of the and another CT scan of the brain showed that onset of seizure activity. This scan showed sev- nearly all the brain lesions had cleared. There eral additional ring enhancing lesions. Vanco- was also no recurrence of pneumonia. mycin and clindamycin were added for addi- tional R equi and Toxoplasma gondii coverage, Pathological findings respectively. At a subsequent hospital admis- All three biopsies taken from the caecum, sion in February 1997, multiple biopsies were ascending colon, and transverse colon showed obtained from several of the brain lesions to massive infiltration of histiocytes within the determine their cause. These samples showed submucosa (fig 1). These histiocytes had an inflammatory microangiopathy on routine abundant eosinophilic cytoplasm which haematoxylin and eosin stains. A Gram stain stained strongly with periodic acid SchiV (PAS) revealed scant Gram positive rod shaped stain. A Gram stain revealed many intracyto- microorganisms consistent with R equi.No plasmic Gram positive coccobacilli. A silver Toxoplasma gondii organisms were seen. A stain for fungal organisms was negative, and an

repeat CT scan of the brain showed that the acid-fast stain was unremarkable in that only a http://jcp.bmj.com/ lesions were resolving after approximately one few organisms stained faintly positive. Electron month of vancomycin. Subsequently, all antibi- microscopy studies revealed oval shaped bacte- on September 28, 2021 by guest. Protected copyright.

Figure 2 Transmission electron microscopy of colon biopsy (right) and lung biopsy (left), showing intracytoplasmic coccobacilli with thick cell walls and lipid vacuoles (×59 325). 70 Hamrock, Azmi, O’Donnell, et al J Clin Pathol: first published as 10.1136/jcp.52.1.68 on 1 January 1999. Downloaded from

Figure 3 Transbronchial lung biopsy showing obliteration of lung parenchyma by extensive infiltration of foamy histiocytes with abundant eosinophilic cytoplasm. Left, H&E stain low power; right, H&E stain high power. ria with a thick cell wall and multiple lipid reported in patients with functioning immune vacuoles, very similar to the morphology of systems.3 R equi is usually transmitted by inha- mycobacteria (fig 2). There were no aggregates lation and commonly produces a cavitating of membranous material to suggest that the pneumonia.1 So far as we know, this is the first organisms were Whipple’s bacilli. report describing a case of disseminated R equi The left lower lobe of the lung measured infection with histologically documented in- 13.0 × 11.0 × 6.0 cm. and weighed 630 g. The volvement of the gastrointestinal tract. pleural surface had many fine adhesions and a When there is intense infiltration of foamy 5.0 × 4.5 cm. area of subpleural haemorrhage eosinophilic histiocytes within the wall of the http://jcp.bmj.com/ was also present. The entire lobe was consoli- intestine, Whipple’s disease and infection by dated by a soft, creamy, yellowish-tan pasty Mycobacterium avium-intracellulare are two material. Architecturally, the lobe resembled a main which should be considered in liver with macronodular cirrhosis. Microscopi- the diVerential diagnosis.910With this case, we cally, there was obliteration of the normal lung show that the inflammatory response elicited parenchyma with dense infiltration of histio- by R equi in the intestine produces a near iden- cytes. The outline of alveoli was observed only tical histological picture to Mycobacterium on September 28, 2021 by guest. Protected copyright. occasionally, and when they were seen, they avium-intracellulare infection and Whipple’s were nearly filled with histiocytes. Similar to disease. Culture of the colon biopsies were not those in the intestinal wall, these histiocytes ordered. However, the morphological appear- had abundant, eosinophilic, globular cyto- ance of the organisms by light and electron plasm (fig 3). A Gram stain showed the microscopy was identical to those seen in lung presence of Gram positive coccobacilli within biopsies which grew R equi. Furthermore, the the cytoplasm of the histiocytes. The organisms documentation of systemic spread was con- did not stain definitively with an acid-fast stain, firmed by positive blood cultures. Indeed, an and a silver stain for fungal organisms was acid-fast stain, which would be expected to be negative. These histiocytes were likewise strongly positive in Mycobacterium avium- strongly PAS positive. Electron microscopy of a intracellulare infection, was weakly positive in portion of the lung tissue showed many focal areas only, consistent with R equi. intracytoplasmic coccobacilli with thick cell Although the histiocytes were strongly PAS walls and intracytoplasmic lipid vacuoles (fig positive, electron microscopy failed to reveal 2). No Michaelis-Gutmann bodies were identi- the characteristic Tropheryma whippelii bacilli fied to suggest malakoplakia. As mentioned seen in Whipple’s disease. In addition, Whip- cultures from this tissue grew R equi. ple’s disease involving the gastrointestinal tract more often aVects the small rather than the Discussion large intestine.11 Also, Gram staining showed infection with R equi is now increas- numerous intracytoplasmic Gram positive coc- ingly being reported in immunocompromised cobacilli whereas T whippelii is Gram negative.9 patients as a result of HIV infection, haemato- In conclusion, R equi infection should be logical malignancies, and immunosuppression included in the diVerential diagnosis along with for transplantation.36Rare cases have also been Whipple’s disease and Mycobacterium avium- Infection by Rhodococcus equi in a patient with AIDS 71

intracellulare whenever foamy eosinophilic his- 6 Harvey RL, Sunstrum JC. Rhodococcus equi infections in

patients with and without human immunodeficiency virus J Clin Pathol: first published as 10.1136/jcp.52.1.68 on 1 January 1999. Downloaded from tiocytes are seen in colon biopsies from an infection. Rev Infect Dis 1991;13:137–45. immunocompromised patient. 7 Franklin DB, Jackson YJ, Hawkins SS. equi peritonitis in a patient receiving peritoneal dialysis. South Med J 1989;82:1046–7. 1 Prescott JF. Rhodococcus equi: an animal and human 8 Fierer J. Non-pulmonary Rhodococcus equi infections in pathogen. Clin Microbiol Rev 1991;4:20–34. patients with acquired immune deficiency syndrome 2 Prescott JF. Epidemiology of Rhodococcus equi infection in (AIDS). J Clin Pathol 1987;40:556–8. horses. Vet Microbiol 1987;14:211–14. 3 Scott M, Graham BS, Verrall R, et al. Rhodococcus 9 von Herbay A, Maiwald M, Ditton HF, et al. Histology of equi—an increasingly recognized opportunistic pathogen. intestinal Whipple’s disease revisited. Virchows Arch 1996; Am J Clin Pathol 1995;103:649–55. 429:335–43. 4 Frame BC, Pektus AF. Rhodococcus equi pneumonia: case 10 Poorman JC, Katon RM. Small bowel involvement by report and literature review. Ann Pharmacother 1993;27: Mycobacterium avium complex in a patient with AIDS: 1340–2. endoscopic, histologic, and radiographic similarities to 5 Antinori S, Esposito R, Cernuschi M, et al. Disseminated Whipple’s disease. Gastrointest Endosc 1994;40:753–9. Rhodococcus-equi-infection initially presenting as foot 11 Marth T, Strober W. Whipple’s disease. Semin Gastrointest mycetoma in an HIV-positive patient. AIDS 1992;6:740–2. Dis 1996;7:41–8.

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