Abstract
Purpose
Despite several reports on risk factors for septic arthritis (SA) in adults, the outcomes on quality of life and joint function are sparsely reported. This study aimed to investigate the quality of life and joint function in adult patients treated for SA.
Methods
This prospective observational study enrolled clinically diagnosed adult SA patients and estimated Euroqol 5-dimension 5 levels (EQ-5D-5L) questionnaire, Euroqol Visual Analog Scale (EQ-VAS) and a validated tool for joint function at 1, 3, 6 and 12 months after debridement.
Results
Twenty seven patients (20 males/7 females) with 21 knees, four shoulders, and two elbows were evaluated. The mean age of the cases was 51(± 13.00) years. Three cases sustained mortality. EQ-5D-5L (P < 0.01) and EQ-VAS (P < 0.01) scores improved significantly between all time frames. Mean Knee society (P < 0.01), Shoulder QuickDASH, and Mayo elbow scores improved at all time frames. There was no difference in primary outcomes between early (< 14 days) and late (14 days or more) presentation. There was no difference in primary outcome measures between confirmed and suspected SA. Fifteen patients could ambulate without support, while 6 needed some support for walking at 1 year.
Conclusion
Improved outcomes can be expected in quality of life and joint function in adults' septic arthritis at the end of 1 year after surgical treatment; however, the effects of delay in presentation need to be investigated further. Isolation of the microorganism from an infected joint has no bearing on the outcome measures.
Keywords: Quality of life, Mortality, Morbidity, Septic arthritis, Knee society score, Prognosis, C-reactive protein, Functional outcome, Risk factors, EuroQol
Introduction
Incidence of septic arthritis in adults is rising due to the evolution of the diagnosis, opportunistic infections, methicillin-resistant staphylococcus (MRSA), and patient longevity [1]. Clinical and laboratory profiles are the described outcomes for septic arthritis (SA) in adults [2–4]. The reports on clinical outcomes confine to the evaluation of mortality and morbidity of SA in adults [5, 6]. Joint function and quality of life in adults following SA are compounded by underlying joint disease and comorbidities.
Recent reports of outcomes following SA in adults are dominated by infection following prosthetic joint infections (PJI) [7]. The effects studied in these reports are osteomyelitis, functional deterioration, joint stiffness, fibrous and bony ankylosis, joint sacrifice, joint replacement, osteosynthesis, limb shortening, and amputation [7, 8]. However, very few studies assessed joint function after native SA in adults [9–12]. Historically the joint function is reported in the published literature on composite functional scales exclusive to the knee joint given by Bussière and Beaufils and Larson's) [11–14]. Another study reported joint function as excellent, good, fair, and poor in SA. The joint function fails to restore after adult SA [8]. The critical questions on the quality of life and joint function after lavage in these patients remain unanswered. This study's primary objective was to report serial global health status (quality of life) and joint function in adult SA patients following operative treatment.
Patients and methods
This Prospective observational cohort study was conducted at a tertiary referral center to treat bone and joint disorders from January 2018 to July 2019. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. We obtained Informed consent from all patients included in the study. The institute's review board approved the study (JIP/IEC/2017/47). We used a consecutive sampling method for recruiting the patients into the study. Adult patients who had undergone arthrotomy for clinically suspected SA were included in the study. Patients with polyarticular involvement were included in the study, and the most affected joint was selected for assessment. PJI, SA of the axial skeleton were excluded from the study.
According to Newman's criteria, the cases were classified into two groups based on the synovial fluid (SF) analysis findings [15]. Group, I named Newman A (Confirmed) subjects had isolated microorganisms from an affected joint. Group II named Newman B&C (Suspected) patients had isolation of an organism from elsewhere and no organism isolated but histologic or radiologic evidence consistent with infection or turbid fluid aspirated from the joint. Cases were managed by open joint arthrotomy and lavage. They received broad-spectrum intravenous antibiotics (Cloxacillin 1gm Q6H and Gentamycin 80 mg Q8H), as per the hospital's antibiotic policy, which was changed according to the antibiotic sensitivity of cultured microorganisms from SF. The samples obtained from the joint and elsewhere were inoculated on blood, MacConkey and Chocolate agar for aerobic bacteria and Robertson’s cooked meat medium for anaerobic bacteria. The culture-negative samples after 48 h were subjected to extended cultures as per the institute’s policy. Antibiotic sensitivity of microorganisms cultured from blood or wound exudate was used for management in the SF culture, sterile patients. The intravenous antibiotics were administered for 2 weeks, followed by oral antibiotics for 4 weeks. The antibiotic protocol was modified, and the dose titrated in patients with diabetes mellitus and chronic kidney disease. A vacuum suction drain was used in all the cases and discontinued on less than 40 ml collection in 24 h. A suitable splint immobilized the operated joint. The severity of pain guided joint immobilization in the postoperative period. All patients were observed up to discharge from the hospital. The primary outcome variables were EuroQol 5-dimension 5 level (EQ-5D-5L) for clinical and global health and EuroQol Visual Analogue Scale (EQ-VAS) for best health, and joint function which was assessed at 1,3,6 and 12 months after the operation [16]. The EQ-5D-5L and EQ-VAS at six months were evaluated by the telephonic interview. A validated joint function tool depending on the infected joint (Knee Society Score (KSS), Mayo Elbow Score, and QuickDASH score) was used to serially assess the peripheral joints at 1, 3, and 12 months. EuroQol group permitted the use of the EQ-5D-5L questionnaire. EQ-5D-5L questionnaire is a standardized measure of health status developed by EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels: no problems 1, slight problems 2, moderate problems 3, severe problems 4, unable to /extreme problems 5.
Being part of a larger ongoing study where the estimation of morbidity due to septic arthritis is being explored, we recruited 47 patients. The proportion of morbidity among septic arthritis in adults being 30%, the sample size estimated was 81, with 10% absolute precision, 80% power and 5% alpha error using nMaster software [6]. The data obtained from the study were analyzed with the Statistical Package for Social Sciences [SPSS] for Windows, Version 19.0. (Released 2013. Armonk, New York IBM Corporation). The descriptive statistics for continuous variables were expressed in mean (± SD) or median (IQR) depending on the variable's distribution. Categorical variables were described using frequencies and percentages. Comparison between median scores of each dimension of EQ-5D-5L, mean EQ-VAS score, and mean joint function scores for the individual joints at different time frames was done using Friedman's Greenhouse–Geisser test. Comparison of global health (EQ-5D-5L and EQ-VAS) and joint function measures between group I and group II cases was done by Mann–Whitney test. The statistical significance was set at 5% (P < 0.05).
Results
Forty-seven patients were recruited to the study from January 2018 to July 2019; however, 24 patients reported evaluating outcomes at 1 year. Twenty patients did not report for follow-up; however, there was no difference in demography, clinical, and laboratory parameters between them and patients reported at 1 year (Fig. 1). The patients' mean age in the study was 51.6 ± 13.00 years (range 30–73 years) with 20 males and 7 Females. The mean time to presentation was 13 ± 8 days (range 2–30 days). Fifteen patients presented within 13 days of onset of symptoms, while 12 patients presented 14 days or later. The average length of hospital stay was 27 days (range 7–45 days). Six patients required ICU admission. Pain joint swelling, local warmth, and restriction of range of motion of affected joint were recorded in all patients. However, fever (> 38.5 degree Celsius) was recorded in all except three (11%) patients. A summary of demographic outcomes, risk factors, clinical and laboratory parameters is presented in Table 1. There was a significant improvement in median EQ-5D-5L (P < 0.01), mean EQ-VAS (P < 0.01) and mean KSS scores (n = 21) (function P < 0.01 and objective P < 0.01) over a period of 1 year (Table 2). The mean QuickDASH scores (n = 4) improved from 55.80 ± 4.71 at one month to 21.05 ± 5.01 at 12 months, though it failed to reach statistical significance. The Mayo elbow scores (n = 2) improved for one patient from 55 to 90 between one and 12 months, and the other patient died in follow up her score improved from 55 to 75 between one and three months. There was no difference in EQ-5D-5L (0.881, 1.0, 0.417, 0.717, 0.574 Mann–Whitney test), EQ-VAS (0.543 Mann–Whitney test), and joint function (0.160, 0.824 Mann–Whitney test) scores between Newman group I and II patients. There was no difference in quality-of-life measures and joint function described above between early (< 14 days) versus late (> 14 days) presentation (Mann–Whitney test). There was an overall improvement of mean EQ-VAS scores in monoarticular and polyarticular patients over time (1,3 6, and 12 months). The difference between them failed to reach statistical significance (P = 0.17, 0.14, 0.52, 0.64 Mann–Whitney test). In the subgroup of 21 knee SA cases, 15 patients could ambulate without support, while six needed some support for walking at 1 year.
Fig. 1.
Flow diagram of patients recruited in the study
Table 1.
Demographic factors, risk factors and laboratory parameters of patients
| Parameter/outcome | Value |
|---|---|
| Joint infected (n) | |
| Knee | 21 |
| Shoulder | 4 |
| Elbow | 2 |
| Monoarticular | 23 |
| Polyarticular | 4 |
| Risk factors (n) | |
| Diabetes mellitus | 9 |
| Chronic kidney disease | 7 |
| Underlying joint disease | 4 |
| Alcoholic liver disease | 2 |
| Distant site infection | 3 |
| More than 1 risk factor | 7 |
| Laboratory outcomes | |
| ESR mm at 1 h (mean) | 77.3 (± 17.95) |
| CRP (> 3.2 mg/L) (n) | 24 |
| WBC count (4000–11,000) | |
| Normal (n) | 19 |
| Elevated (n) | 8 |
| Creatinine clearance (less than 15) | 3 |
Table 2.
Demonstrating comparative summary of Euroqol 5-dimension-5 level questionnaire and EQ-(VAS) best health score in the patients at 1, 3, 6 and 12 months
| EQ-5D-5LDimension | 1 month | 3 month | 6 months | 12 months | P value |
|---|---|---|---|---|---|
| Mobility (Median) | 4 (IQR-1) | 3 (IQR-1) | 2( IQR-1) | 1 (IQR-0) | < 0.01a |
| Self-care (Median) | 4 (IQR-1.25) | 2(IQR-1) | 1(IQR-1) | 1(IQR-0) | < 0.01 |
| Usual activities (Median) | 4 (IQR -2) | 3 (IQR-1) | 2 (IQR-1) | 1 (IQR-0) | < 0.01 |
| Pain/Discomfort (Median) | 4( IQR-1) | 3 (IQR-1) | 1(IQR-1) | 1 (IQR-1) | < 0.01 |
| Anxiety/Depression (Median) | 3 (IQR-1) | 1 (IQR-2) | 1 (IQR-0.5) | 1 (IQR*0) | < 0.01 |
| EQ-VAS (best health scores) (Mean) | 40.60 | 63.60 | 80.16 | 92.40 | < 0.001 |
| Mean KSS Objective (Maximum score 100) | 33.43 | 58.62 | 74.38 | < 0.01b | |
| Function (Maximum score 100) | 14.25 | 55.50 | 72.75 | < 0.01b |
EQ-5D-5L Euroqol 5 Dimension 5 Level Questionnaire, EQ-VAS Euroqol Visual Analog Scale, KSS Knee society score
aComparison of median scores at all time frames was done with Friedman’s test
bComparison of mean scores at all time frames was done with Greenhouse–Geisser test
Three patients died during the study period and were included in the mortality. One patient died due to septicaemia in the hospital, while the other two patients succumbed in follow-up due to Chronic kidney disease. Six patients required a repeat operation during the study period. Five patients had joint debridement more than once during their hospital stay, and another patient had joint debridement after discharge from the hospital in the follow-up period of 1 year. The description of organisms cultured in 19 Newman A cases is presented in Fig. 1.
Discussion
This prospective observational study found significant improvement in clinical outcomes and quality of life after treatment in adult SA patients at 1 year. The best health scores (EQ-VAS) also improved at different time frames. The outcomes improved irrespective of the number of joints affected and the organism isolated. Significant differences in joint outcome measures were expected in most patients because of lavage and early presentation. However, we find considerable variation in the delay to presentation in adult SA [2, 3, 6, 13, 17, 18]. A delay to presentation ranging from 4 to 22 days has been reported [2, 3, 6, 13, 17, 18]. There is a paucity of data on cut-off time to presentation beyond which permanent damage to the affected joint sets in. A study found no difference in outcomes between early (within 5) and late (up to 10 days) presentation of SA in adults [13]. However, septic arthritis in children causes impaired function in a significant proportion of SA cases with a mean time to the presentation of 4 days [19]. The same does not translate in adults. It is because the joint damage is dependent on the type and the virulence of the infecting microorganism. It is also dependent on the host immune mechanisms and antibiotic administration before the presentation. We had no difference in the primary outcomes between early and late presentation.
Functional outcomes following treatment are inadequately reported. The published reports on SA in adults are limited by the study design, the outcomes assessed, and the joints studied [9, 11, 13, 14]. Yanmış and colleagues determined the relationship between Gachter criteria and functional evaluation scale by Bussiere in SA; however, their study was limited to the knee joint [11]. Two studies reported outcomes following open and arthroscopic debridement of the knee in SA on Larson's criteria or its modifications [13, 14]. Sreenivas et al. retrospectively compared KSS between normal and infected knee joints in adult SA patients and reported low scores with advancing age and infection [9]. However, they did not report global health status and ability to ambulate in the cohort studied. We note that none of the studies compared outcomes in confirmed and suspected SA or report effects on individual joint function measures and quality of life. However, the correlation between locomotion and functional joint scores in total knee arthroplasty has been investigated [20].
Similarly, the relationship between knee society pain and function scores, range of motion, and individual functional force measures in total knee arthroplasty is also reported [21]. However, a correlation between function and pain scores has been reported, but objective outcome measures or range of motion after the operation are missing. The influence of pain and function of the non-operated limb on walking and KSS postoperatively has been studied [20, 21]. We excluded patients with prosthetic joint infections and, therefore, did not encounter complications of arthrodesis, revision arthroplasty, and amputation in the patients studied. We assessed global health status as well as the joint function outcomes in this study. We report the number of patients that could walk with or without support at the end of 1 year not reported before.
The global health measures improved with time in the patients studied. However, we noted that the dimensions for self-care and usual activities improved more than mobility, pain, and discomfort over time in the EQ-5D-5L questionnaire reflecting delayed ambulation in patients with the lower extremity SA. We measured quality of life outcomes in adult SA patients because it is vital to know the patients' perception of their disease outcomes. Besides, the quality-of-life outcome scores are an indirect measure of patient mobility and independence in executing household tasks. Jansson et al. investigated the quality of life outcomes through EQ-5D data in 2444 patients with musculoskeletal disorders before and after the operation [22]. The investigators reported substantial improvements in EQ-5D scores in the knee and hip arthroplasty, trauma-related procedures, operations related to previous surgery, and rheumatoid arthritis. The authors noted that though the scores improved over time but did not reach the level reported for age and sex-matched population sample.
It would be unwise to comment on mortality based on this study's results because we had three patients that sustained early and late deaths during the study period. However, the 30-day case fatality rate in adult SA is 12.2% [5]. Patients with infection of the large peripheral joints, age greater than 65, Rheumatoid arthritis, liver disease, and isolation of methicillin-resistant staphylococcus aureus (MRSA) from synovial fluid sustain significant mortality [5, 6]. The patients that sustained mortality in this study died from the causes reported by the studies cited above. Based on the time of death after disease onset, the mortality manifests either early (less than 30 days) or late in adult SA patients [5, 6]. While joint infection and septic shock resulting in multiple organ failure cause the former, the latter is due to associated comorbidities ( kidney failure, chronic liver disease, and inflammatory arthropathies) [5, 6]. The morbidity from the damaged articular cartilage of an infected joint is dependent on the time to presentation, recurrence, prior antibiotic administration, and virulence of microorganisms. The joint function and EQ-5D-5L scores of one patient each of recurrent knee SA and necrotizing fasciitis were inferior compared to others in the knee SA subgroup. The soft tissue infection of the latter patient healed on antibiotic treatment.
We could not assess outcomes in 20 patients who did not report due to various reasons in the follow-up. The outcomes of global health and joint function in these patients could have significantly influenced our results. However, we compared the demographic outcomes of the patients who were lost to follow-up during the study and noted that they were not different from the patients evaluated. We cannot draw logical conclusions on the effects of delay in the presentation and outcomes of SA in other large joints from this study due to a smaller number of patients studied. We cannot comment on the difference in joint functions between patients with and without underlying joint disease because only two such patients were available at 12 months for evaluation. The effects of delay in presentation adults SA warrants further investigation because we had no difference in primary outcomes between early and late presentation.
Conclusions
Improved outcomes can be expected in quality of life and joint function in adults' septic arthritis at the end of 1 year after surgical treatment; however, the effects of delay in presentation need to be investigated further. Isolation of the microorganism from an infected joint has no bearing on the outcome measures.
Author Contributions
RM: Data acquisition and collection, manuscript preparation editing and review. SKN: Study conception and design, manuscript preparation editing and review, overall Guarantor and correspondence. GB: Manuscript Preparation and review. PM: Manuscript review and statistical analysis. PP: Manuscript editing and review. SG: Manuscript editing and review.
Availability of Data and Material
The supporting data management forms will be available at the appropriate repository (Mendley).
Declarations
Conflict of Interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Ethical Approval
Institute’s ethics committee approved the study.
Informed Consent
The patients consented for participation in the study.
Consent for Publication
Due consent was obtained from the participants for publication of results keeping their identity and personal data secure.
Footnotes
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Data Availability Statement
The supporting data management forms will be available at the appropriate repository (Mendley).