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Mycobacterium kansasii tenosynovitis in a rheumatoid arthritis patient with long-term therapeutic immunosuppression.

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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 59, No. 6, June 15, 2008, pp 900 –903
DOI 10.1002/art.23717
© 2008, American College of Rheumatology
Mycobacterium kansasii Tenosynovitis in a
Rheumatoid Arthritis Patient With Long-Term
Therapeutic Immunosuppression
Atypical or nontuberculous mycobacteria are normal commensals of water, soil, dust, and cattle milk. Human infections are relatively uncommon, but an increasing number
of cases have been reported in the context of human immunodeficiency virus (HIV) or therapeutic immunosuppression (1). Mycobacterium avium complex and Mycobacterium kansasii account for most episodes of
nontuberculous systemic diseases. Besides many reports
of patients with HIV, there are only rare published examples of patients with chronic inflammatory arthritides under immunosuppression therapy. Most of these reports
describe Mycobacterium marinum infections (2– 4). In the
last 7 years, there have been only a few reports of M
kansasii infections in patients with chronic inflammatory
rheumatic diseases (5–11). Nakamura et al (8) collected
references on 11 patients from the literature since 1963.
Bernard et al (9) described a French retrospective study of
26 patients from their own clinic and the literature who
had M kansasii septic arthritis and no underlying disease.
This indicates that, overall, this infectious complication is
very rare. However, the incidence might increase as we
tend to use more aggressive immunosuppressants (especially tumor necrosis factor ␣ inhibitors) with a more rel1
Hanns-Martin Lorenz, MD: University Hospital Heidelberg, Heidelberg, and Center for Rheumatic Diseases, Baden-Baden, Germany; 2Alexander H. Dalpke, MD, Anthony
D. Ho, MD, Axel Greiner, MD, Martin Jung, MD: University
Hospital Heidelberg, Heidelberg, Germany; 3Axel Deboben,
PhD: Vesalius Klinik, Bad Rappenau, Germany; 4Christoph
Fiehn, MD: Center for Rheumatic Diseases, Baden-Baden,
Dr. Lorenz has received consultant fees, speaking fees,
and honoraria (less than $10,000 each) from Abbott, MSD,
Essex, Wyeth, Bristol-Myers Squibb, Pfizer, and Novartis.
Dr. Deboben has received consultant fees (less than $10,000)
from Pfizer pain academy.
Address correspondence to Hanns-Martin Lorenz, MD,
Department of Medicine, Division of Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410,
69120 Heidelberg, Germany. E-mail: Hannes.Lorenz@med.
Submitted for publication October 9, 2007; accepted in
revised form January 4, 2008.
evant impact on the immune system. Moreover, with better diagnostic possibilities and better awareness of the
necessity of an aggressive treatment, immunosuppression
therapy will start much earlier.
We report a patient with long-lasting seronegative rheumatoid arthritis and a more recent local tenosynovitis. We identified a local M kansasii infection as the cause for the tenosynovitis on the basis of a positive bacterial culture result.
Although M kansasii is second only to M avium complex
as the causative agent of nontuberculous lung disease,
which often involves the upper lobe, it is rarely identified
as a cause of extrapulmonary infection, especially arthritis
or tenosynovitis. The infection primarily infects the lungs
with rare precipitation in joints, tendons, or bone (9,12).
When affecting the joints, monarthritis is usually erosive
(11,13). Infections with M kansasii are environmentally
acquired. It has been isolated from tap water in the warm
southern US states (Texas), where it can survive for up to
12 months (14,15).
Case Report
A 48-year-old female farmer (including dairy farming) was
diagnosed with seronegative nonerosive rheumatoid arthritis on the basis of symmetric polyarthritis of the metacarpophalangeal (MCP) joints and wrists when she was 35
years old. She was first treated with corticosteroids alone,
then later a combination of disease-modifying antirheumatic drug therapy with chloroquine and methotrexate
was necessary to optimally control the disease. This was
continued for 10 years without symptoms; corticosteroids
were tapered and stopped. The patient had no other underlying illnesses.
In 2003, she developed a primarily soft (later scar-forming) tenosynovitis of her second flexor tendon in her right
hand, which later spread to the third finger and then
affected the wrist on her palmar side. The swelling increased in size over a period of weeks. She did not report
night sweats or fever. The tumor was surgically removed,
and the histology showed unspecific inflammation. With
the possibility of chronic rheumatic tenosynovitis, chloroquine was stopped and leflunomide was added to the
continued methotrexate therapy. However, after 2–3
months the swelling recurred, which hindered the pa-
Tenosynovitis in a Rheumatoid Arthritis Patient
Figure 1. Tenosynovitis at the first visit in our hospital.
tient’s daily activities. For that reason, she again underwent tenosynovectomy in 2004; however, the swelling
recurred some months after surgery. Short-term corticosteroid therapy did not reduce the scar tissue. Therefore, a
third surgery was necessary in 2005, methotrexate was
increased to 20 mg/week, leflunomide was replaced by
sulfasalazine, and corticosteroid treatment was initiated
postsurgery. Again, this did not affect the recurrence of
swelling that occurred some weeks after the third surgery.
Microbiologic tests of the resected tissue were not performed prior to that time.
At that time the patient was referred to our clinic (Figure
1). Her laboratory results including autoimmune parameters, blood count, C-reactive protein level, and routine
serology were not indicative of any diagnosis. Radiographs
of the hands were normal, excluding erosive arthritis and
any affection of the bones in her right wrist or MCP joints
(Figure 2). The images, however, visualized the significant
noncalcareous swelling of her palm and her wrist. Based
on the patient’s history, her profession as a dairy farmer,
and the inefficacy of the antiinflammatory therapy, we
suspected an infectious cause including atypical mycobacterial tenosynovitis as a possible reason for the recurrent
Because culture of affected tissue is the most sensitive
way of diagnosing an infection with atypical mycobacteria, we again sent the patient to surgery. The histologic
picture showing a nonspecific “young” granuloma with
central necrosis surrounded by cell layers but no giant
cells is presented in Figure 3. This young granuloma was
seen only in a few histologic sections; the other specimens
only showed nonspecific inflammation. A Gram stain from
the excised material was negative; similarly, an auramine
and Tan-Thiam-Hok stain did not indicate acid-fast bacilli.
A 16S ribosomal RNA polymerase chain reaction (16S
rRNA PCR) using universal, degenerate primer did not
produce a PCR product. However, culture of the material
using the BACTEC MGIT system (Becton Dickinson,
Mountain View, CA) resulted in growth of acid-fast bacilli
after 3 weeks. Subcultivating revealed a photochromogenic species. For further differentiation, a 16S rRNA PCR
was performed, which revealed a weak band that was
subsequently used for sequencing. This allowed for the
identification (457/458 bp ⫽ 99% identity with type
strain) of M kansasii. Due to the photochromogenic
growth, the isolate could be differentiated from the phylogenetically closely related Mycobacterium gastri.
With the exception of low-dose corticosteroid treatment,
all immunosuppressants were stopped. After review of the
literature, we decided to start an antibiotic regimen with
rifampin (600 mg/day), clarithromycin (2 ⫻ 500 mg/day),
and ethambutol (25 mg/kg/day for the first 2 months, then
15 mg/kg/day). After 2 months, the tenosynovitis was significantly improved with further improvement observed
after 6 months (data not shown).
Under this regimen, the arthralgias recurred after a few
weeks for a short time only, with no necessity to reinitiate
a more stringent antiinflammatory treatment.
Atypical mycobacterial infection is normally localized to
the lungs and occurs in immunocompromised hosts such
as patients with HIV or patients with long-term immunosuppression, after chemotherapy or with aggressive tumors. Deeper infections such as tenosynovitis, septic (then
usually erosive) arthritis, and osteomyelitis spread by
means of the lymphatics.
Among the nontuberculous mycobacteria, M kansasii is
the most common cause of monarthritis, usually exhibiting erosive changes (11,13). The duration from first symp-
Lorenz et al
Figure 2. Radiograph of the affected right hand and wrist.
toms to final diagnosis is long (1– 60 months in the literature [9], 36 months in our case). In the literature, as in our
case, tests for acid-fast bacteria in synovial fluid or tissue
are often negative; from this perspective, the culture of the
bacteria is the most sensitive diagnostic method, even
exceeding a 16S rRNA PCR.
Overall, only 50 cases of M kansasii arthritis or tenosyn-
ovitis have been described during the past 40 years; these
were reviewed by Bernard et al in 1999 (9). Since that time,
only a few cases could be added in the literature. Among
these 50 cases, approximately half had an underlying disorder (HIV, inflammatory rheumatic diseases), but for some,
previous joint puncture or trauma was suspected as the route
and cause of entry (16). Trauma might be the cause in our
Figure 3. Histology of the inflamed tissue: central necrosis and surrounding cell layers
without giant cells (hematoxylin and eosin stained; original magnification ⫻ 200).
Tenosynovitis in a Rheumatoid Arthritis Patient
patient because she works as a farmer and frequently has
open wounds. Regularly, these patients do not report night
sweats or fever (9). In the chest radiograph, we did not see
signs of pulmonary infection; this seems to be the rule for
patients with localized M kansasii infection (9).
In patients with M kansasii arthritis or tenosynovitis, routine laboratory investigations are not helpful and a purified
protein derivative test is usually negative or weakly positive.
Diagnosis requires the culture of synovial fluid or biopsy
sample of the synovium or affected tissue. Even though PCR
and DNA hybridization tests are recommended to instantly
identify the infectious microorganism (17), negative results do not exclude an infection of atypical mycobacteria.
The value of culturing articular tissue to diagnose an atypical mycobacterial infection is again emphasized by our case.
It is unclear whether in our case the infection resulted
from inhalation of contaminated water or infection from
the milk of the patient’s cattle, or directly from a wound
that may have allowed entry of the bacteria through contaminated water in her right palm. There was neither a family
history of mycobacterial infection nor mycobacterial pulmonary lesions on the patient’s chest radiograph (a computed
tomography scan of the chest was not performed).
Optimal therapy for M kansasii arthritis has not been
established in a controlled trial. It is accepted that immunocompetent patients respond better to combined synovectomy and antibiotic therapy than do immunodeficient
patients (18,19). Generally, treatment with 3 or 4 antibiotic
drugs in combination for 18 –24 months has been recommended at least for a pulmonary infection. Unfortunately,
in vitro susceptibility tests do not always correlate with
clinical response; however, a combination of isoniazid,
rifampin, and ethambutol or of clarithromycin, rifampin,
and ethambutol are the most frequently used combinations
(10). We treated our patient with the latter combination,
which led to a significant reduction of the tenosynovitis
with improved mobility of the fingers and reduced pain.
We will continue this regimen for another 12 months to
completely eradicate the M kansasii infection.
In conclusion, our case again highlights the importance
of considering alternative explanations for atypical inflammatory signs such as monarthritis or localized tenosynovitis in patients with chronic inflammatory rheumatic diseases and concomitant immunosuppression. This is
especially important and should be considered if patients
report risk factors such as contact with milk cows or fish
farming, which may predispose patients to an infection
with an atypical mycobacterium. The importance of a culture of the biopsy tissue for the diagnosis of atypical mycobacteriosis as the most sensitive diagnostic tool has been
confirmed in our case and cannot be emphasized enough.
In contrast, 16S rRNA PCR of infected tissue was not
sensitive enough to detect the infectious agent in this case.
With the appropriate diagnosis, eradication of the infection is possible.
Dr. Lorenz had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study design. Lorenz.
Acquisition of data. Lorenz, Dalpke, Deboben, Ho, Greiner, Jung,
Analysis and interpretation of data. Lorenz, Dalpke, Deboben,
Ho, Greiner.
Manuscript preparation. Lorenz, Fiehn.
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terms, patients, long, therapeutic, mycobacterium, immunosuppressive, arthritis, tenosynovitis, rheumatoid, kansasii
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