Journal of the Louisiana State Medical Society

182 J La State Med Soc VOL 166 July/August 2014

A 44-Year-Old HIV-Infected Man With Right-Shoulder Swelling

CliniCal Case of the Month

Carl Mickman, MS; Carrie Caruthers, MD; Jaclyn Spiegel, MD; Ron Schiro, BS; Joanne Maffei, MD; Charles V. Sanders, MD; Fred A. Lopez, MD

Immunocompromised patients are susceptible to various joint infections with less-common pathogens, such as mycobacterium. Physicians should have a low threshold to investigate the cause of an arthropathy further. An aspiration of the effusion is usually warranted to identify the possible pathogen and target treatment. We report an unusual presentation of a human immunodeficiency virus-infected patient with a chronic effusion arthropathy of his right shoulder due to Mycobacterium kansasii. We review the risk factors, transmission, clinical manifestations, and management of Mycobacterium kansasii.

CASE PRESENTATION

A 44-year-old man with a past medical history of hu-man immunodeficiency virus (HIV) and hepatitis C infec-tions presented for a therapeutic paracentesis secondary to acute liver failure. His past medical history also included non-adherence to combination antiretroviral therapy, a his-tory of Pneumocystis jirovecii pneumonia, and a resection of a squamous cell cancer of the tongue. At this presentation, the patient was also evaluated for a longstanding effusion arthropathy of the right shoulder. He had first noticed swell-ing in the area two years earlier and denied any trauma, associated pain, or limitation of his daily activities. Three weeks prior to presentation, his CD4 count was 40/mm3 with a CD4 percentage of 8.3% and a viral load of 49,504 copies/mL. His tuberculous interferon-gamma release as-say test was negative, he denied any respiratory symptoms, and his chest X-ray was within normal limits. He admitted to prior intravenous drug use, and his last use was more than one year prior to presentation. He had been monoga-mous for the past two years with one partner who was also HIV-infected. At the time of presentation, the patient had recently been prescribed a new regimen of combination antiretroviral therapy; however, he had been non-adherent due to medication side effects.

On examination, the patient’s right shoulder mani-fested a marked effusion anterior to the deltoid muscle that extended to the subdeltoid region (see Figures A, B). The area was non-tender, non-erythematous, and cool to the touch; and a transillumination test was positive. There

were no associated skin lesions. He had nearly full active range of motion, and his strength was only mildly decreased compared to the contralateral side. The patient developed minimal discomfort with medial humeral rotation; however, he had no point tenderness or pain with use of rotator-cuff muscles.

An X-ray revealed degenerative changes of the humeral head, including subchondral cysts and narrowing of the joint space. Swelling caused displacement of the deltoid muscle laterally. Magnetic resonance imaging (MRI), with and without gadolinium contrast, revealed a large simple subacromial-subdeltoid bursa fluid collection with no septations or irregularity of the wall (see Figure C). The fluid collection involved the majority of the entire under-surface of the deltoid muscle. It measured approximately 11 cm anteroposteriorly, 8 cm craniocaudally, and 2 cm in thickness. There was no communication between the subacromial-subdeltoid bursa and the glenohumeral joint space. Extensive diffuse synovial thickening with pannus formation and periarticular erosions was present in the glenohumeral joint.

The patient underwent a diagnostic arthrocentesis of the bursa. Approximately 10 ml of a thick, reddish, myxoid fluid with fatty material were aspirated. Drainage was limited in quantity by the viscosity of the fluid. A Gram stain noted moderate white blood cells (WBC) and no organisms. No crystals were noted, and the cytology for malignant cells was negative. Smears for fungal and mycobacterial organisms were also negative (including acid-fast bacilli smears), and cultures for aerobic and anaerobic organisms were negative

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after five days. The patient was discharged home

with symptomatic treatment for his as-cites. He was restarted on combination antiretroviral therapy and scheduled for close follow-up with his infectious diseases primary care provider. Two weeks after discharge, cultures of the shoulder aspirate grew Mycobacte-rium kansasii (see Figures D, E). The speciation of the mycobacteria was first determined by high-performance liquid chromatography, which gave the isolate a similarity index of 0.887 for Mycobacterium kansasii and 0.573 for Mycobacterium szulgai (see Figure F). The isolate was later confirmed as My-cobacterium kansasii with a DNA probe for RNA target (GEN-PROBE). Blood cultures were consistently negative for acid-fast bacilli, indicating that his infection was likely not disseminated.

Due to marked serum transami-nase elevations, thought to be hepatic disease, the patient was not able to receive treatment for his mycobacterial infection. His combination antiretro-viral therapy was halted as well. The patient expired approximately three months later due to progressively worsening liver failure.

INTRODUCTION

Mycobacterium kansasii is an atypi-cal, slow-growing mycobacterium that causes pulmonary infections in the immunocompromised host. It is the second-most common opportu-nistic atypical mycobacterial pathogen after Mycobacterium Avium Complex (MAC).3 M. kansasii is commonly dif-ferentiated by its characteristic yellow pigmentation. It has been isolated almost exclusively from municipal water sources, and the majority of reported cases have presented in the southern United States.1 M. kansasii is not considered a public-health threat, as there is no evidence of person-to-person transmission. The primary method of colonization is thought to be pulmonary. Pulmonary-disease presentation is similar to that of Mycobacterium tuberculosis, though symptoms are typically milder.2 Pulmonary M. kansasii occurs in both

Figure A: Gross anterior image of chest and bilateral shoulders. The degree of anterior and lateral swelling of the right shoulder can be appreciated in comparison to the patient’s left shoulder.

Figure B: Anterolateral view of the patient’s right shoulder, status post-removal of fluid sample from bursa.

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184 J La State Med Soc VOL 166 July/August 2014

immunocompetent and immunocompromised patients, but it is much more common in immunocompromised hosts, including HIV-infected patients.3-4 Louisiana, in particular, has a high incidence of both HIV and M. kansasii and has recorded more co-infections than any other state.4

RISK FACTORS

HIV-infected patients, particularly those with CD4 counts below 100/mm3, represent the largest percentage of those with articular mycobacterial infections.3 Individuals receiving immunosuppressive therapy for inflammatory diseases that affect the joints are also at high risk, such as those with rheumatoid arthritis, psoriatic arthritis, dermato-myositis, lupus, gout, or those receiving intrarticular steroid injections.3 Previous articular pathologies are thought to promote the colonization of injured tissue and predispose affected individuals to hematogenous spread.3 Researchers have also described cases of acute-onset articular manifes-tations secondary to immune reconstitution inflammatory syndrome (IRIS).5

TRANSMISSION

Mycobacterial articular infections typically occur through one of two methods: direct inocu-lation or disseminated infection. Joint infection with M. kansasii via direct inoculation has been documented in both immunocompromised and immunocompetent patients.3 Patients usually present with monoarticular disease and a history of trauma, though recent steroid injection is also a significant risk factor.6 Patients rarely present with systemic symptoms such as fever or malaise and usually complain of only localized pain and swelling.

Disseminated infection leading to joint colo-nization with M. kansasii has almost exclusively been documented in immunocompromised patients, and case reports reveal presentations of both monoarticular and polyarticular disease. Patients can present with systemic symptoms, though subacute presentation with only mild articular complaints is more common.3 Pulmo-nary infections have been reported to lead to disseminated infections in 35% of those infected with HIV.4 Joint colonization in the presence of disseminated disease is well documented; how-ever, no study has looked at the likelihood of dis-semination leading to articular manifestations.

DIAGNOSIS

Healthcare providers should consider myco-bacterial infection when evaluating immunocom-promised patients who present with subacute joint pathology. Aspirates of the infected area

should be sent for histopathologic analysis and cultured for aerobic, anaerobic, fungal, and mycobacterial organisms. A histopathologic analysis should be performed using the fluorochrome technique for optimal sensitivity. Smear analysis is often negative; however, a negative smear does not rule out infection.3

CLINICAL MANIFESTATIONS

Articular manifestations of M. kansasii infections, and particularly infections of the bursae, are extremely rare. In 1999, only 50 cases of Mycobacterium kansasii septic arthritis were described,3 and another review in 2012 discussed four cases of M. kansasii bursitis.7 Of the four cases reported, one presented with monoarticular disease while the three others presented with polyarticular disease.7,8

M. kansasii is seldom reported to infect via direct in-oculation while organisms such as Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium marinum are well-known causes of localized trauma-associated infec-tions.9 The most common bursal infections associated with these organisms are the olecranon and prepatellar bursae, as

Figure C: Magnetic resonance imaging of right shoulder with contrast agent shows large subacromial subdeltoid fluid collection with extensive synovial thickening and periarticular erosions in the glenohumeral joint, consistent with hypertrophic HIV arthoropathy. No communication between subacromial subdeltoid bursa and glenohumeral joint space is observed.

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they are superficial and most frequently exposed to trauma.10 This presentation is in contrast to that of M. tuberculosis, which, due to its propensity for hematogenous spread, does not show preference for particular bursae.10 One patient, described by Barham and Hargreaves, presented with monoarticular M. kansasii bursitis contracted through local trauma and direct inoculation.8

In contrast, three cases of polyarticular M. kansasii bursitis described by Mathew et al. were thought to result from hematogenous spread. Interestingly, all three patients were immunocompromised secondary to immunosuppres-sive therapies. The only patient described with M. kansasii subacromial bursitis was predisposed to infection second-ary to articular manifestations of dermatomyositis. The patient initially presented with cutaneous nodules on his forearms that later spread to the subacromial bursa, a result of hematogenous dissemination.7 M. tuberculosis is the only other mycobacteria that has been demonstrated to infect this particular bursa, though neither of the two cases described were in HIV-infected patients.11 All of these infections oc-curred in the absence of trauma.7, 11

MANAGEMENT

Guidelines for the treatment of M. kansasii joint infec-tions currently do not exist due to the uncommon nature of this condition, and guidelines regarding disseminated nontuberculous mycobacterial infections are similar to those for pulmonary infections. Clinical experience has shown that with other infectious causes of bursitis, antibiotic treatment

alone is often inadequate, and needle or surgical drainage is recommended. Pulmonary infections with rifampin-susceptible M. kansasii isolates have been shown to respond well to a prolonged regimen of isoniazid (300 mg/d), rifampin (600 mg/d), ethambutol (15 mg/kg/d), and pyridox-ine (50 mg/d) for at least 12 to 18 months.13 As in HIV-associated MAC infections, the duration of therapy should also be dictated by the immune status of the patient. Clinical recovery should be monitored closely as resistance to rifampin can lead to failure of treatment and resistance to other drugs.13 If failure of the initial regimen does occur, a new three-drug regimen based on susceptibilities should include clarithromycin or azithromycin, moxifloxacin, ethambutol, sulfa-methoxazole, or streptomycin.13

For patients who are co-infected with HIV, additional information must be considered. Combination antiretroviral therapy and the agents used for the treatment of M. kansasii have associated side effects and may also inter-act with each other when used concomitantly. Importantly, rifabutin is known to interact less with combination antiretroviral therapy than rifampin.14 The interplay of preexisting comor-bidities must also be taken into account. Since

isoniazid is a known hepatotoxic drug, liver enzymes should be closely monitored, and patients must be educated to strictly avoid alcohol.

Since the majority of HIV patients with disseminated M. kansasii infections present with very low CD4 counts, the possibility of IRIS must be considered as well. Currently, no guidelines exist recommending when to discontinue combination antiretroviral therapy, and clinical judgment must be used in these situations. Steroids should be used to treat any inflammatory symptoms that appear. Combination antiretroviral therapy should only be discontinued in the presence of life-threatening inflammatory conditions that do not respond to steroids.15

DISCUSSION OF CASE

Our patient’s case is significant for multiple reasons. First, his presentation was more indolent than the cases described in the available literature. His lack of pain or inhibition of his daily activities contrasts with the other cases, in which patients directly sought medical attention for their joint complaints. In addition, the patient’s physical exam showed no signs of acute inflammation such as pain, warmth, or erythema – all of which were present in the other cases of M. kansasii joint infections, even those with deficient immune status.3 Immunocompromised patients are susceptible to less-common pathogens and often pres-ent with unusual symptoms and findings. It is imperative that physicians have a low threshold to further investigate the cause of an arthropathy, whether it be monoarticular or

Figure D: A thin-pour agar plate (Hardy Diagnostics) with a Myobacterium kansasii sample grown from a broth culture of the aspirate of myxoid-appearing fluid drawn from right subacromial-subdeltoid bursa. Heterogeneously yellow hue is indicative of a photochromogen. Identification of organism as Mycobacterium kansasii was confirmed by DNA probe of RNA target (GEN-PROBE).

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186 J La State Med Soc VOL 166 July/August 2014

Figure E: Mycobacterium kansasii with TB Carbolfuchsin KF stain (Becton-Dickinson) from 7H11 plate that was inoculated with an aspirate from the right subacromial-subdeltoid bursa, viewed at 1,000x with oil-immersion lens.

Figure F: High-performance liquid chromatography (MIDI, Inc.) results identified a similarity index for Mycobacterium kansasii (0.887) and Mycobacterium szulgai (0.573).

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polyarticular. It is often essential to sample fluid from the joint space or bursa in order to identify any pathogen and tailor treatment.

Another noteworthy aspect of our case is the pres-ence of articular pathology, including subchondral cysts, diffuse synovial thickening with pannus formation, and periarticular erosions. The pathology could be explained as a primary bone or joint infection that later spread to the bursa or repetitive mechanical friction between bone and skin leading to chronic bursitis.12 A differential diagnosis of these changes could include common joint pathology, such as rheumatoid or psoriatic arthritis or, more rarely, HIV arthropathy; however, an indolent infectious process should also be included. The mechanism of infection in our patient remains unclear as he had no evidence of lung pathology, no other manifestations of disseminated M. kansasii, and no history of trauma to the area.

Our patient’s case presentation and diagnosis stress the importance of further investigating unusual presenta-tions of uncommon infections in the immunocompromised patient population.

CITATIONS

1. Bailey RK, Wyles S, Dingley M, Hesse F, Kent GW. The isolation of high catalase Mycobacterium kansasii from tap water. Clin Am Rev Respir Dis 1970;101:430-1.

2. Mazor Y, Sprecher H, Braun E. Mycobacteria kansasii disseminated disease. Israel Med Assoc J 2010;12:121-2.

3. Bernard L, Vincent V, Lortholary O, et al. Mycobacterium kansasii septic arthritis: French retrospective study of 5 years and review. Clin Infect Dis 1999 Dec;26(6):1455-60.

4. Witzig RS, Fazal BA, Mera RM, et al. Clinical manifestations and implications of coinfection with Mycobacterium kansasii and human immunodeficiency virus type 1. Clin Infect Dis 1995;21:77-85.

5. Ito M, Komatsu Y, Ushiki A, et al. An AIDS patient with immune reconstitution inflammatory syndrome due to pulmonary Mycobacterium kansasii infection during antiretroviral therapy. J Infect Chemother 2009 Oct;15(5):331-4.

6. Leader M, Revell P, Clarke G. Synovial infection with Mycobacterium kansasii. Ann Rheum Dis 1984;43:80–2.

7. Mathew SD, Tully CC, Borra H, et al. Septic subacromial bursitis caused by Mycobacterium kansasii in an immunocompromised host. Mil Med 2012 May;177(5):617-20.

8. Barham GS, Hargreaves DG. Mycobacterium kansasii olecranon bursitis. J Med Microbiol 2006;55:1745-6.

9. Woods G, Washington J. Mycobacteria other than Mycobacterium tuberculosis: Review of microbiologic and clinical aspects. Rev Infect Dis 1987;9:275-94.

10. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979;119:107-59.

11. Kenin A. Tuberculosis of the subdeltoid bursa. Bull Hosp Jt Dis 1950;11:128-33.

12. Norden C, Gillespie W, Nade S. Mycobacterial infections of the musculoskeletal system. In: Norden C, Gillespie W, Nade S (editors). Infections in bones and joints. Boston: Blackwell Scientific, 1994:211-30.

13. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med

2007;175:367-416.14. Spradling P, Drociuk D, McLaughlin S, et al. Drug-drug

interactions in inmates treated for human immunodeficiency virus and Mycobacterium tuberculosis infection or disease: An institutional tuberculosis outbreak. Clin Infect Dis 2002 Nov 1;35(9):1106-12.

15. Puthanakit T, Oberdorfer P, Ukarapol N, et al. Immune reconstitution syndrome from nontuberculous mycobacterial infection after initiation of antiretroviral therapy in children with HIV infection. Pediatr Infect Dis 2006 Jul;25(7):645-8.

Mr. Mickman is a Medical Student at the Louisiana State University School of Medicine in New Orleans. Dr. Caruthers is a Chief Resident in the Department of Medicine at the LSU Health Sciences Center in New Orleans. Dr. Spiegel is a Resident in the Department of Medicine at the LSUHSC-New Orleans. Mr. Schiro is a Medical Laboratory Technician in the Microbiology Department at the Interim LSU Hospital in New Orleans. Dr. Maffei is an Associate Professor of Clinical Medicine in the Department of Medicine, Section of Infectious Diseases/HIV, at the LSUHSC-New Orleans and the Medical Director of the Infection Control Department at the Interim LSU Hospital in New Orleans. Dr. Sanders is the Chairman of the Department of Medicine, the Edgar Hull Professor of Medicine, and a Professor of Microbiology, Immunology, and Parasitology at the LSUHSC-New Orleans. Dr. Lopez is the Vice Chair of Education in the Department of Medicine, the Richard Vial Professor of Medicine, and Assistant Dean of Student Affairs in the School of Medicine at the LSUHSC-New Orleans.