Orthopedics

Coexistent Mycobacterium Intracellulare Gonarthritis and Patellar Osteomyelitis in a Patient with Pulmonary Sarcoidosis: A Case Report and Literature Review

Thomas C Namey, MD, FACP; Anthony D Frogameni, MD

Abstract

ABSTRACT: We present a 48-year-old man with known pulmonary sarcoidosis who developed septic arthritis of the left knee with concomitant patellar osteomyelitis due to Mycobacterium intracellulare. The patient underwent synovectomy and was started on appropriate combination chemotherapy, but clinical improvement did not occur until patellectomy was performed. Both bone and radiogallium scans were important in the medical and surgical management of this patient.

Abstract

ABSTRACT: We present a 48-year-old man with known pulmonary sarcoidosis who developed septic arthritis of the left knee with concomitant patellar osteomyelitis due to Mycobacterium intracellulare. The patient underwent synovectomy and was started on appropriate combination chemotherapy, but clinical improvement did not occur until patellectomy was performed. Both bone and radiogallium scans were important in the medical and surgical management of this patient.

Introduction

Atypical mycobacteria are found with increasing frequency to be the pathogens in resistant infections of skin, lung, bone and joints. These organisms may cause diseases which are virtually clinically indistinguishable from those caused by Mycobacterium tuberculosis, but are notorious for in vitro resistance to standard antituberculous chemotherapy.1

Mycobacterium intracellulare, a group III (nonchromogenic) organism in the Timpe-Runyon classification, rarely produces infection in humans, except for the compromised individual.2,3 M. intracellulare joint infections are particularly rare, but present serious management problems in affected patients.

We present a case of M. intracellulare septic arthritis with concomitant patellar osteomyelitis involving the left knee in a patient with previously diagnosed pulmonary sarcoidosis. Although there have been at least six cases of group III mycobacterial septic arthritis described in the English literature, only two of the six cases were due to M. intracellulare.1,3-7 To the best of our knowledge, we are reporting the first case of atypical mycobacterial septic arthritis with concomitant patellar osteomyelitis. Our report includes complete radiographic and scintigraphic evaluation, which proved invaluable in the clinical management of our patient. The technetium-99m-phosphate bone scan confirmed the diagnosis of patellar osteomyelitis, and the radiogallium scan provided presurgical evidence for distal quadriceps involvement. The coexistence of patellar disease mandated surgical patellectomy before clinical resolution occurred, despite prior management with synovectomy and appropriate chemotherapy.

Case Report

A 48-year-old white male with previously diagnosed pulmonary sarcoidosis was referred to the Medical College of Ohio Hospital on March 20, 1983 with a three-month history of painful, swollen left knee. Two months earlier, me patient was treated for prepatellar bursitis with intra-articular steroids by his physician, without benefit.

The patient was formerly employed as a carpet installer and spent much of the day crawling on his hands and knees. He retired two years prior to admission. The patient denied any previous history for arthritis, although he specified that his "knees gave out" during childhood. He denied symptoms of urethritis, uveitis, dermatitis, or direct joint trauma.

The diagnosis of sarcoidosis was established after thoracotomy in 1979 for persistent infiltrates and adenopathy. The biopsy was negative for bacteria or acid-fast bacilli (AFB) but revealed non-caseating granulomas. The patient then received oral prednisone for symptoms of dyspnea with impaired pulmonary function studies.

On physical exam, the patient appeared chronically ill. Although he was afebrile, the left knee was warm, erythematous, swollen and tender. Arthrocentesis revealed a white cell count of 3,020 (50% neutrophils and 50% lymphocytes), red cell count of 150 and glucose 94 (serum glucose 99). Gram stain and bacterial cultures were negative, but Ziehl-Nielson stain for acid-fast bacilli was positive. Admission labs included: WBC 9.1, hemoglobin 11.9, platelets 485,000, erythrocyte sedimentation rate (ESR) 58 mm/hr and C-reactive protein (CRP) positive at 1:256.

Both serum immunoglobulins and angiotensin-converting enzyme were within normal limits. Initial chest x-rays revealed moderate bilateral hilar adenopathy consistent with the diagnosis of sarcoidosis. Also seen was a 3 cm calcification in the spleen which may have represented a large granuloma (Fig. 1). Roentgenograms of the left knee demonstrated patchy lytic changes within the patella and mild subchondral sclerosis in the nonweight bearing surfaces of the joint. No juxta-articular osteoporosis or evidence of chondrolysis was seen (Fig. 2). A joint scan was performed and suggested monoarticular arthropathy involving the left knee with significant patellar uptake, raising the suspicion of concomitant patellar osteomyelitis (Fig. 3). A radiogallium scan demonstrated florid uptake in the left knee with extension into the distal quadriceps muscle. There was no increased uptake in any other musculoskeletal tissues, nor was hilar accretion identified (Fig. 4).

Fig. 1: Radiograph of the chest, AP view. There is evidence of bilateral hilar adenopathy, especially on the right. Also seen is a 3 cm calcification in the left upper abdomen, which may represent a splenic granuloma.

Fig. 1: Radiograph of the chest, AP view. There is evidence of bilateral hilar adenopathy, especially on the right. Also seen is a 3 cm calcification in the left upper abdomen, which may represent a splenic granuloma.

Fig. 2: Radiograph of the left knee (lateral view) taken from admission. A mixture of sclerosis and bony resorption is seen in the central portion of the patella. The joint space is not particularly narrowed.

Fig. 2: Radiograph of the left knee (lateral view) taken from admission. A mixture of sclerosis and bony resorption is seen in the central portion of the patella. The joint space is not particularly narrowed.

Fig. 3A, B: Technetium-99m-phosphate joint scan taken at the time of admission. There is marked patellar uptake with accretion in the left knee, suggesting a septic process.

Fig. 3A, B: Technetium-99m-phosphate joint scan taken at the time of admission. There is marked patellar uptake with accretion in the left knee, suggesting a septic process.

Fig. 4: Transmission radiogallium scan demonstrates abnormal accumulation of radionuclide ia the left knee with extension into the distal quadriceps muscle and suprapatellar bursa. There is no evidence of hilar accretion.

Fig. 4: Transmission radiogallium scan demonstrates abnormal accumulation of radionuclide ia the left knee with extension into the distal quadriceps muscle and suprapatellar bursa. There is no evidence of hilar accretion.

Five days after admission, we performed a closed synovial biopsy of the left knee using a Parker-Pearson needle. Results were negative by gram stain but AFB were seen on direct smear. Cultures were obtained and the patient was started on triple antituberculous therapy: INH 300 mg per day, Rifampin 600 mg per day and Ethambutol 800 mg per day. Prednisone was discontinued at this time. The synovial cultures later grew M. intracellulare, sensitive to Ethambutol and Cycloserine or combination chemotherapy with INH, Rifampin and Ethambutol.*

An open synovectomy with patellar biopsy was performed on March 29, 1985, revealing non-caseating granuloma of the synovium and distal quadriceps muscle, with chronic inflammatory changes seen in the left patella. Necrotic tissue was resected from the distal quadriceps site. No bacteria or AFB were present on smear.

On April 21, 1983, a second aspiration was performed because of a persistently painful, swollen left knee. No bacteria or AFB were seen. A joint scan was again consistent with septic arthritis and patellar osteomyelitis of the left knee. The patient gradually improved and was discharged on triple chemotherapy regimen. (Once sensitivities became available the regimen was reduced to Ethambutol 800 mg per day.)*

The patient's knee again became swollen and painful and an arthrocentesis was performed in the outpatient clinic on May 12, 1983. Fluid was positive for AFB and cultures subsequently grew M. intracellulare. At this time, the ESR was 28 mm/hr and Creactive protein was positive at 1:256.

A draining sinus tract developed at the incision site three months later and the patient was readmitted. The left knee was warm and tender. A sinogram showed no communication with the joint space. Admission labs are summarized: WBC 3.8, hemoglobin 15.2, ESR U and CRP 1:256. Of note was the increase in the angiotensin-converting enzyme to almost twice normal value. Arthrocentesis revealed a white cell count of 4,200 (83% neutrophils and 17% lymphocytes); AFB were again visualized on direct smear. A repeat joint scan was consistent with a septic process in the left knee and demonstrated florid uptake in the patella (Fig. 5). A radiogallium scan revealed increased uptake into the left knee, but extension into the distal quadriceps was not seen (Fig. 6). Twelve days after admission, the patient was discharged on four-drug chemotherapy: INH 300 mg per day, Rifampin 600 mg per day, Ethambutol 400 mg per day and Ethionamide 500 mg per day.

Fig. 5: A comparison view taken 5 months later reveals residual activity within the left knee and patella. Mild resolution is seen.

Fig. 5: A comparison view taken 5 months later reveals residual activity within the left knee and patella. Mild resolution is seen.

On January 16, 1984 the patient was admitted to our hospital for persistent drainage from a sinus tract in the line of previous surgical closure. At the time of admission, the ESR was 10 and CRP positive at 1:128. Radiographs of the left knee showed preservation of the joint space with mild subchondral sclerosis, but severe osteolysis and periosteal disruption was present in the patella (Fig. 7). The following day, surgical debridement of necrotic tissue was performed along with a left patellectomy. Two weeks later, the ESR rose to 33 mm/hr, but decreased to 3 mm/hr and the patient was discharged on March 2, 1984. Discharge chemotherapy consisted of the standard triple regimen mentioned previously.

Fig. 6: Comparison radiogallium scan 5 months later reveals increased activity in the !eft knee, but extension of activity into the distal quadriceps is not seen.

Fig. 6: Comparison radiogallium scan 5 months later reveals increased activity in the !eft knee, but extension of activity into the distal quadriceps is not seen.

Subsequent follow up visits to the outpatient clinic in April, Jury and November of 1984 failed to demonstrate any inflammation, tenderness or evidence of active disease in the left knee. ESR values remained below 4 mm/hr. CRP values decreased steadily to a low value of 1:16 on November 8, 1984. Ethambutol was discontinued and the patient continued on dual therapy (INH, Rifampin).

Eighteen months later, the patient was seen for final follow up. There was no evidence of active disease in the left knee, either clinically or radiographically. A joint scan revealed evidence for osteoatthritic changes, but there were no abnormalities consistent with persistent infection of either bone or joint. AU medications were discontinued.

Discussion

Our patient represents the sixth case of group G? mycobacterial septic arthritis documented in the English literature. To the best of our knowledge, we are reporting the first case of septic arthritis of the knees and coexistent patellar osteomyelitis due to atypical mycobacteria.

The "atypical" mycobacteria, ie mycobacteria other than M. tuberculosis and Mycobacterium leprae, were described shortly after Koch's identification of the tubercle bacillus in 1882.4·7 Timpe and Runyon classified these organisms into four groups based on their rate of growth and pigment production.4 M. intracellulare, a member of the atypical family, does not produce pigment and grows very slowly; this organism is a group III, or nonchromogenic mycobacterium. Because M. intracellulare shares similar laboratory characteristics with both M. avium and M. scrqfulaceum, these group ?? mycobacteria are known as the MAIS (M. avium-intracellulare-scrqfulaceum) complex.7

While group III mycobacteria are usually associated with pulmonary manifestations resembling M. tuberculosis infection, many cases and sites for extrapulmonary disease have been documented.4,8,9 According to Rosenzweig, most extrapulmonary or disseminated forms of group III infections are quite rare in the uncompromised host.2 Chapman noted that middle-aged males from the rural Southeast are particularly predisposed to infection from group III mycobacteria.5 Our patient, a middleaged man, resided in the Midwest, but pre-existing sarcoidosis presented an increased risk for atypical mycobacterial disease. Bretza and Mayfield contend that there may be a causal relationship between sarcoidosis and atypical mycobacterium."1 Mankiewicz' theory that sarcoidosis is actually an altered manifestation of mycobacteriosis is strongly supported by Chapman, who documented mat patients with sarcoidosis fail to produce antibodies against Mycobacterium phages.5 The risk for atypical mycobacterial infection due to depressed immunologic response may have been further amplified in our patient, who had been taking oral corticosteroids.

Fig. 7: A comparison view taken 10 months later, just prior to patellectomy. The lytic lesions seen in Figure 2 are much more pronounced, suggesting progressive disease.

Fig. 7: A comparison view taken 10 months later, just prior to patellectomy. The lytic lesions seen in Figure 2 are much more pronounced, suggesting progressive disease.

Though extrapulmonary atypical mycobacteriosis is rare, cases involving the musculoskeletal system are even less frequent and poorly understood. Halleran states, "osseous and joint infection attributable to M. intracellulare are uncommon and may or may not be associated with concurrent pulmonary or systemic infections by this organism."7 What remains uncertain in most cases of mycobacterial septic arthritis is the portal of entry. The observation that these organisms are found in soil, dairy products and animal excreta suggests that the gastrointestinal tract may be a frequent site.4,7,12 Bemey et al suggest that microtrauma to joints or repeated intraarticular steroid injections may also explain the apparent predisposition of the knees to mycobacterial infection.13 Our patient, a former carpet installer, constantly subjected his knees to trauma.

We had the unique opportunity for complete radiographic and scintigraphic study of the patient and his affected knee. Upon initial admission, the plain radiographs, technetium-99m-phosphate bone and joint scans, and the radiogallium scans together strongly suggested a mycobacterial or fungal arthritis with patellar osteomyelitis. The plain radiographs described in Figure 2A initially suggested a septic process in the left knee and patella. We suspected a mycobacterial or fungal etiology because the changes described were consistent with infection by indolent organisms which do not cause rapid development of juxta-articular osteoporosis, joint space narrowing (secondary to chondrolysis), and subchondral erosions seen in a pyogenic arthritis.14 According to Halleran, preservation of die central joint spaces with sclerotic borders seem characteristic of atypical mycobacterial joint infections. 14 Patchy lytic lesions and sites of periosteal elevation in me patella suggested that osteomyelitis was also present. Both the joint scan and radiogallium scan corroborated the presence of a unifocal septic arthritis in the left knee with high-grade patellar involvement as well. The radiogallium scan also demonstrated contiguous extension into the distal quadriceps muscle. At that point, we realized that surgical debridement of involved tissues was necessary, as demonstrated by Hoffman et al , in their review of 19 cases of atypical mycobacterial septic arthritis.1 However, since surgical pateiiectomy would result in severe functional morbidity, a synovectomy with debridement of soft tissue (including involved muscle) was performed. The patient was then started on appropriate combination chemotherapy, even though species identification and sensitivities were not yet available.

Since repeated aspirations grew M. intracellulare in culture, we again obtained repeat bone and radiogallium scans to define the extent of involvement (Fig. 3B, 4B). Although the radiogallium scan revealed no increased uptake in the quadriceps muscle (following earlier resection of necrotic tissue), florid uptake was noted in the patella on the bone scan. Plain radiographs taken 10 months after synovectomy with debridement and combination chemotherapy revealed further osteolysis and periosteal changes in the patella suggestive of progressive infection (Fig. 2B). Consistent with these findings, only mild clinical resolution occurred, and cultures remained positive for M. intracellulare, so patellectomy was performed. Following patellectomy, the patient's knee showed marked improvement clinically and bom acid-fast stains and cultures became and remained negative for mycobacteria.

It is interesting to note that neither radiogallium study demonstrated abnormal hilar or pulmonary uptake consistent with active pulmonary sarcoidosis. This was an unexpected finding in our patient, since areas of active sarcoidosis usually concentrate radiogallium.15 While these results may be explained on the basis of resolved sarcoidosis or response to corticosteroids, this is questionable since the patient had stopped taking corticosteroids at the time of the scan and his serum angiotensinconverting enzyme was significantly elevated.

We have found six cases of septic arthritis due to group III atypical mycobacteria reported in the English literature.1,3-7 Of these, only two were caused by M. intracellulare.4,7 Cheatum et al described a case involving M. intracellulare septic arthritis of the knee and sacroiliac joint with involvement of the carpal tunnel.4 The patient underwent wrist synovectomy and was treated with antituberculous chemotherapy. Active arthritis was not clinically apparent at 17 months' follow up. In the second patient, septic arthritis of the wrists with concomitant osteomyelitis of the carpus developed and the patient was started on appropriate chemotherapy after refusing surgical debridement and synovectomy. The organism could not be eradicated from me involved sites despite intensive, prolonged chemotherapy (51 months).

Both of these cases, as well as our own, demonstrate the imperative for combined surgical and chemotherapeutic management in patients with atypical mycobacterial septic arthritis, whether or not coexistent osteomyelitis is present. Surgical drainage with debridement of infected synovium and bone is essential to eradicate these organisms.7 Our patient did not show clinical or radiographic improvement until patellectomy was performed, despite prior synovectomy and 10 months of appropriate chemotherapy. We speculate that the patient's patella was the initial focus of infection and continued to seed the knee joint with mycobacteria from pockets of nonvascularized bone. This argument is substantiated by the failure to identify AFB by stain or culture following patellectomy in our patient despite the continuation of the same chemotherapy. The patella may have also provided a pathway for extension via the patellar tendon to the sites of infected muscles. Therefore, patellectomy proved necessary for eradication of infection.

We must emphasize the importance of scintigraphic studies in the management of our patient. The initial radiogallium scan was invaluable in demonstrating the extent of soft tissue infection so surgical resection of involved muscle could be completed. Persistent patellar activity despite chemotherapy and soft-tissue resection confirmed the need for subsequent patellectomy.

Although atypical mycobacterial pulmonary infection shows a predilection for compromised hosts, only one of the six patients with documented group ?? septic arthritis had an underlying disease.1 Our patient had a depressed immune response due to pre-existing sarcoidosis and had been taking oral corticosteroids, both of which would have depressed his cell-mediated immunity.

In summary, we have presented a 48-year-old man who developed septic arthritis of the left knee with patellar osteomyelitis due to M. intracellulare. The patient underwent synovectomy and was started on appropriate combination chemotherapy, but clinical improvement did not occur until patellectomy was performed. Both bone and radiogallium scans were important in the medical and surgical treatment of this patient.

References

1. Hoffman GS. Myers RL, Stark FR, et al: Septic arthritis associated with Mycobacterium avium: A case report and literature review. J Rheum 1978; 5:199-209.

2. Rosenzweig D: Emerging importance of infections due to the Mycobacterium avium-intracellulare complex. NY State J Med 1984; 6:290.

3. Dechairo DC, Kittredge D, Myers A, et al: Septic arthritis due to Mycobacterium triviale. Am Rev Respir Dis 1973; 108:1224-1226.

4. Cheatue DE, Hudman V, Jones SR: Chronic arthritis due to Mycobacterium intracellulare. Sacroiliac, knee and carpal tunnel involvement in a young man and response to chemotherapy. Arthritis Rheum 1976; 19:777-781.

5. Chapman JS: Atypical mycobacterial infections. Med Clin North Am 1967, 51:503-517.

6. Mokray J, Connolly K: Knee arthropathy secondary to Mycobacterium scrofulaceum. Ann Rheum Dis 1973; 32:69-71.

7. Halleran W, Martin N: Nontuberculous mycobacterial arthritis. J Kans Med Soc 1982; 83(6):284-286.

8. Koenig MG, Collins RD, Heyssel RM: Disseminated mycobacteriosis caused by Battey type Mycobacterium (Addendum), Ann Intern Med 1966; 64:145-154.

9. Sanderson TL, Moskowitz L, Hensley GT, et al: Disseminated Mycobacterium avium-intracellulare infection appearing as a panniculitis. Arch Pathol Lab Med 1982; 106(3):112-114.

10. Bretza J, Mayfield JD: Mycobacterium intracellulare presenting as a sarcoid-like illness. South Med J 1978: 71(7):872-874.

11. Mankiewicz E: Relationship of sarcoidosis to anonymous bacteria. Acta Med Stand 1970; 176(suppl):68-70.

12. Fogan L: Atypical mycobacteria. Medicine 1970; 49:243-255.

13. Bemey S, Goldstern M, Bishko F: Clinical and diagnostic features of tuberculous arthritis. Am J Med 1972; 53:36-42.

14. Namey TC, Halla JT; Radiographic and nucleography techniques in the diagnosis and management of septic arthritis and osteomyelitis. Clin Rheum Dis 1978; 4(1):95-133.

15. Namey TC: Nuclear medicine and special radiologic imaging and technique in the diagnosis of rheumatic disorders, in Kelley WN, Harris ED, Ruddy S, et al (eds): Textbook of Rheumatology, ed 2. Philadelphia, WB Saunders Co 1985.

10.3928/0147-7447-19860301-17

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