Concomitant septic and gouty arthritis—an analysis of 30 cases

K. H. Yu, S. F. Luo, L. B. Liou, Y.-J. J. Wu, W. P. Tsai, J. Y. Chen and H. H. Ho

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China


    Abstract
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 Abstract
 Introduction
 Methods and patients
 Results
 Discussion
 References
 
Objectives. To analyse the clinical features and outcomes of gouty patients with concomitant septic arthritis in a medical centre.

Methods. From the hospital database, we collected 30 hospitalized cases with concomitant septic arthritis and gouty arthritis from 1987 to 2001. All patients had positive bacterial culture and monosodium urate crystals in the affected joints. Medical records of the patients were analysed in detail.

Results. The mean age of patients was 52.8±12.5 yr. One-third of patients were afebrile at presentation, 30% had a normal blood leucocyte count and 10% had a synovial fluid leucocyte count less than 6000/mm3. The knee joint was the most common site of involvement, followed by the ankle, shoulder and wrist joints. Most patients had long-standing disease and subcutaneous tophi. Subcutaneous tophi rupture with secondary wound infection is the most common route of infection. Causative micro-organisms were Staphylococcus aureus (16 cases, 7 of whom were oxacillin-resistant), Streptococcus sp. (5 cases), Pediococcus sp. (1 case), and Gram-negative bacilli (9 cases). Fourteen patients received surgical debridement, among them two patients had an arthrodesis owing to severe joint destruction and one received above-knee amputation. Two patients died. One died of septic complications and the other died of acute myocardial infarction.

Conclusions. Septic arthritis coexistent with gout presented a diagnostic difficulty. An early diagnosis requires a high level of suspicion. Prompt aspiration and analysis of the synovial fluid is imperative, regardless of the absence of fever or leucocytosis. Culture of the aspirated synovial fluid is warranted in gouty attack, even when it has a low white cell count or the Gram stain reveals no organisms.

KEY WORDS: Gout, Septic, Arthritis, Infection, Tophi, Surgery.


    Introduction
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 Abstract
 Introduction
 Methods and patients
 Results
 Discussion
 References
 
Septic arthritis is a rare but serious complication of gout and presents a diagnostic difficulty [1]. Since both conditions may cause inflammation of the affected joint with redness and swelling, it is difficult to distinguish them from one another [2]. Delay in diagnosis may cause destruction of the affected joint. It is thus important to diagnose these acute arthritides accurately in the initial management [3]. Literature reports about concomitant septic and gouty arthritis are rare [416]. We herein analyse 30 cases encountered at Chang Gung Memorial Hospital from 1987 to 2001.


    Methods and patients
 Top
 Abstract
 Introduction
 Methods and patients
 Results
 Discussion
 References
 
From the database of our hospital, we searched for patients with both bacteriologically proved septic arthritis and gouty arthritis between 1987 and 2001. Thirty patients were identified. They had concomitant positive bacterial culture and monosodium urate crystals or tophi in the affected joints. All patients had previously fulfilled the 1977 American Rheumatism Association criteria for acute gout [17]. However, patients with septic arthritis and only a past history of gout, but without intra-articular monosodium urate or tophi in the same joints, were not included. Bacteriological diagnosis was established on the basis of synovial fluid cultures aspirated by arthrocentesis or during surgical debridement.

Clinical data including gout duration, tophi, affected joints, concomitant diseases, presence of fever (defined as an oral temperature over 37.8°C), the duration of symptoms before the visit to our hospital, white blood cell count (WBC), synovial fluid white cell count, blood culture, synovial fluid culture, presumed source of infection, surgical debridement and patient outcome were analysed. The literature from 1976 to 2001 was searched with Medline. Key words used for the search were gout and infectious arthritis (or septic arthritis).


    Results
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 Abstract
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 Methods and patients
 Results
 Discussion
 References
 
Patient's demography
Thirty gout patients in whom bacteria were cultured from synovial fluid were identified (Table 1Go). Nineteen patients had intracellular monosodium urate (cases 1–18 and 30) and 11 patients had intra-articular tophi in the infected joints at surgical debridement (case 19–29). The mean age was 52.8±12.5 yr (range 30–83) and the mean duration of gout was 10.8±6.9 yr (range 2–30). Four patients were female. All except five patients had subcutaneous tophi. This incidence (83.3%) is much higher than that of our previous study (16.8%) from the years 1993 to 2000 [18]. The knee joint is the commonest site of involvement (24 cases), followed by the ankle (6 cases), shoulder (1 case) and wrist joint (1 case). Twenty-seven patients (90%) had monoarticular joint involvement. There were three patients who had two joints infected, two of whom had knee and ankle joint involvement and one had bilateral knee joint involvement.


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TABLE 1. Clinical and laboratory data of 30 patients with concomitant crystal and septic arthritis

 

Concomitant diseases
Several coexistent medical conditions were identified, including iatrogenic Cushing's syndrome as a result of glucocorticoid abuse for no specific underlying diseases in seven patients, diabetes mellitus in five, liver cirrhosis in two and haemodialysis in one. Two patients had knee replacement owing to degenerative joint disease. Local causes of infection were identified in 13 patients, 11 with a ruptured tophaceous wound and two after total knee replacement surgery. The other patients had no obvious route of joint infection.

Symptoms and laboratory data at presentation
Fever was described in only 20 (66.7%) patients at presentation. The median time from onset of joint pain to hospital visit was 6.5 days. The mean white blood cell count was 18 290±11 059 (109/l) (range 2250–38 500), and in nine (30%) patients within the normal range. The mean synovial white cell count was 59 470±55 330/mm3 (range 3200–154 500), with a mean of 95.7% neutrophils on differential count. However, three patients (cases 3, 8 and 16) had a synovial white cell count less than 6000/mm3. Eleven patients had positive blood cultures. Seven out of 21 (33.3%) patients in the leucocytosis group had positive blood cultures, in contrast to four out of nine (44.4%) patients in the normal white blood count group.

Bacteriological investigation and antibiotic treatment
Gram-positive cocci comprised 73.3% (22 cases) of infections. Staphylococcus aureus was the commonest pathogen found in 16 cases, with seven isolates being oxacillin-resistant Staph. aureus (ORSA). Streptococcus infections were found in five patients and one patient had a Pediococcus infection. Gram-negative bacteria were found in nine cases (three Pseudomonus aeruginosa, two Escherichia coli, two Salmonella sp., one Proteus vulgaris, one Enterococcus sp.), including one patient with concomitant P. aeruginosa and ORSA infection (case 24). Two patients developed septic arthritis in the replaced knee joint. The time from joint replacement to the development of septic arthritis was 6 and 56 days, respectively, and both were caused by ORSA. In this study, there were no infections with Haemophilus influenzae, gonococci or anaerobes.

According to the results of drug sensitivity, initial empirical antibiotic treatment with oxacillin and gentamicin covered the infectious micro-organisms in only 63.3% (19 out of 30) of cases. Two Gram-negative bacilli infections were resistant to gentamicin but sensitive to amikacin. Seven ORSA-infected patients were shifted to vancomycin treatment and one Pediococcus-infected patient was treated with clindamycin. One patient had concomitant necrotizing fasciitis (case 19) and was treated with vancomycin and metronidazole. The mean duration of antibiotic therapy in our patients was 35.2±16.6 days (range 15–55). The mean delay in appropriate antibiotic treatment before the available bacterial drug sensitivity test in 12 patients was 4.8 days. Among them, seven patients received medical treatment and five patients received surgical debridement.

Surgical treatment and outcome
Fourteen patients underwent surgical debridement. The median time from admission to surgical debridement was 7 days (mean 11.9 days, range 1–66). Five of them received surgical debridement within 2 days. Nine patients received surgical drainage after medical treatment failure. In the latter group, three were within 1 week and an additional five cases were within 1 month. The other patient (case 1) received one-stage arthrodesis at 66 days of hospitalization owing to severe joint destruction. In the two patients with prosthetic joint infection, one (case 27) also had an arthrodesis owing to severe joint destruction and the other patient only received medical treatment. One patient (case 19) had an amputation on day 7 owing to uncontrolled necrotizing fasciitis and septic arthritis. Two patients died. One (case 11) died of sepsis as a consequence of infection and the other, a 83-yr-old female patient (case 6), died of acute myocardial infarction on day 6 of hospitalization.


    Discussion
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 Abstract
 Introduction
 Methods and patients
 Results
 Discussion
 References
 
The association between pyarthrosis and pre-existing rheumatoid arthritis has been well documented [19, 20]; in contrast, the association of pyarthrosis and gouty arthritis has rarely been reported. In a recent study from Taiwan [21], a high proportion (43.5%) of patients with a septic ankle had concomitant gouty arthritis but none had concomitant rheumatoid arthritis, suggesting the possibility of a racial difference or that the association of septic and gouty arthritis has previously been under-reported. The differential diagnosis of gouty arthritis and septic arthritis is usually easy, however it may be difficult and often overlooked when these two diseases are concomitant. Since patients with gout and septic arthritis can present with fever, joint swelling, pain and redness, prompt aspiration of the synovial fluid for analysis is imperative to reach an accurate diagnosis.

As the present study illustrates, one-third of the patients were afebrile at presentation. The diagnosis of septic arthritis in gout patients rests on a high index of suspicion. An acutely inflamed joint in gout should also be worked up for septic arthritis. Synovial fluid white cell counts generally exceed 50 000/mm3 with more than 90% polymorphonuclear cells (PMNs) in septic arthritis [22]. However, such high cell counts and predominance of PMN may also occur in rheumatoid arthritis, crystal-induced arthritis and seronegative spondylarthropathy [2325]. The wide range and a substantial overlap of values make these laboratory values less helpful as diagnostic aids. Hence, they should not be used as the primary parameters for diagnosis, but rather as a supplement to clinical information [2]. In this series, 30% of patients initially had a peripheral blood leucocyte count of less than 10 000/mm3 and 10% of patients had a synovial leucocyte count less than 6000/mm3. Thus, culture is warranted in gouty attack even though the synovial fluid has a low white cell count or the Gram stain reveals no organisms. This is especially important for the immunocompromised patients with diabetes mellitus, liver cirrhosis, on haemodialysis or using steroids. In addition, breakdown of the skin overlying tophi carries an increased risk of infection.

Both gout and infection can affect any joint of the body [26, 27]. While infection most often occurs in the knee, this joint is also commonly affected with pseudogout and gout [28]. We had one patient (case 9) with concomitant pseudogout, gout and septic arthritis, which has also been reported by others [10, 11, 14, 16]. Since crystal synovitis may cause severe synovial fluid leucocytosis and clinically simulate or coexist with a joint infection, a careful search for concomitant monosodium urate or calcium pyrophosphate dihydrate crystals should be routinely performed in septic arthritis. Besides, joint infection can complicate any synovitis and the septic process may promote the release of crystals from cartilage or synovial membrane, the so-called crystal shedding and strip mining [29, 30]. Thus the demonstration of crystals does not rule out concomitant bacterial arthritis. Micro-organism study should also be performed in crystal arthritis.

There was a wide range of organisms involved. Staph. aureus is the most common causative organism and Gram-negative bacilli were found in 30% of cases. It is worthwhile to note that ORSA comprised 23% of the infectious organisms in this study, which explained the decreased response rate to initial oxacillin and gentamicin treatment. ORSA has not previously been a common pathogen in septic arthritis, but seven cases in this study highlight the increasing ORSA infections. This is in accordance with the trend of increased frequency of ORSA joint infection noted in other centres in the past decade [31].

The case fatality rate for bacterial arthritis has not changed substantially in the past 25 yr and ranges from 5 to 15% [32]. The mortality rate was 6.7% in our gout patients with concomitant septic arthritis. This is in contrast to septic arthritis in patients with rheumatoid arthritis (RA), a group with less gratifying results of treatment. Gardner and Weisman [33] reviewed the literature and noted that 22% of patients with pyarthrosis and RA died as a consequence of infection. This may be due to the use of more immunosuppressive agents and steroids in RA patients.

This study highlights the previously under-recognized problem of concomitant septic and gouty arthritis. Diagnosis of these two concomitant diseases rests on a high index of suspicion. The acute inflamed joint in gout should also be worked up for septic arthritis, especially in those who have ruptured subcutaneous tophi or have concomitant medical diseases. Prompt aspiration and analysis of the synovial fluid is imperative and culture is warranted. Initial combination treatment of vancomycin and gentamicin is recommended in areas with a high percentage of oxacillin resistance of Staph. aureus.


    Notes
 
Correspondence to: Dr. H. H. Ho, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, 5 Fu-Shin St., Kuei-Shan, Tao-Yuan, Taiwan, Republic of China. E-mail: gout{at}adm.cgmh.org.tw Back


    References
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 Abstract
 Introduction
 Methods and patients
 Results
 Discussion
 References
 

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Submitted 14 November 2002; Accepted 5 February 2003