Abstract
Ulceration over tophi in patients with gout usually causes a number of clinical problems. The aim of this study was to investigate the risk factors for ulceration of tophi in patients with gout. Patients with gout who had tophi with or without ulceration were prospectively recruited and underwent a comprehensive clinical assessment. Clinical factors independently associated with the presence of ulceration were analysed using logistic regression models. Of the 113 participants, 18 (13·7%) had clinically apparent ulceration over tophi. In univariate analysis, ulceration over tophi correlated with age, tophus duration, size, location and lack of protective sensation. In logistic regression analysis, age, tophus size and lack of protective sensation were associated with ulceration over tophi. These findings indicate that old age, large tophus size and lack of protective sensation were independent risk factors for ulceration over tophi.
Keywords: Gout, Protective sensation, Risk factors, Tophi, Ulceration
Introduction
Gout is the most common inflammatory arthropathy, reported to affect 2·13% of the population of the USA in 2009 1. The tophus represents an organised chronic foreign body granulomatous inflammatory response to monosodium urate (MSU) crystals and is present in approximately 12–35% of patients 2, 3. The presence of tophi impacts many aspects of the patient's life, including pain, restricted joint range of motion, joint deformity and complications such as infection and ulceration 2, 4, 5, 6, 7. Ulcerated tophaceous gouty lesions are susceptible to infection, and the main indication for surgery in patients with tophaceous gout is sepsis or infection of ulcerated tophi 8. Even after adequate surgical debridement and infection control, there remains the challenge to balance these potential advantages against the risks associated with surgery, especially poor wound healing and infection. However, the risk factors for ulceration of tophi in patients with gout are incompletely understood because of the lack of high‐quality evidence. This prospective study was undertaken to investigate the risk factors for ulceration over tophi in patients with gout.
Patients and methods
Participants who underwent surgery for tophaceous gout from July 2013 to July 2015 were prospectively recruited. Patients with gout who had surgery related to gouty tophi were included in the study. Patients with gout who had other surgical procedures were excluded. The following data were recorded: demographic data (age, gender, ethnicity), body mass index (BMI), estimated glomerular filtration rate (eGFR), comorbidities (diabetes, hypertension, heart disease), gout duration, tophus duration, number of tophi, size of tophus [the ulcerative one or the largest one was selected and the longest tophus diameter was measured with Vernier callipers 9], main location of tophus (hand, foot, elbow and knee), serum urate, skin ulceration, long‐term urate‐lowering therapy (at least 3 months after the detection of tophi), serum albumin, protective sensation (the sensation of avoiding friction, such as wearing loose shoes or clothing ) and indications for surgery.
Statistical analyses
Variables are described as mean and standard deviation or proportion. Differences between participants with and without ulceration were analysed using chi‐square analysis or t‐tests. The difference between the main locations was analysed using the Mann–Whitney test. The Spearman rank correlation test was used to assess the strength of the association between ulceration and other variables. Subsequently, binary logistic regression was used to determine the independent clinical variables associated with the presence of ulceration. A P‐value of <0·05 was considered statistically significant. All statistical analyses were performed using SPSS 17 (IBM, Cary, NC).
Results
A total of 131 consecutive patients met the inclusion criteria and were enrolled in this study. The main indication for surgery was mechanical problems (73·3%), such as improving joint function or ease in wearing shoes, followed by ulceration (13·7%), pain control (6·8%), appearance (3·8%) and infection (2·2%). Of the 131 patients, 18 (13·7%) had evidence of ulceration over a tophus. Each patient had one ulceration, mainly on the foot (77·8%), and the average size of the ulceration was 1·35 ± 0·84 cm.
The clinical features of those with and without ulceration are shown in Table 1. Those with ulceration were older, had a longer tophus duration, had large tophus size, had less protective sensation and ulceration more frequently on the foot. In univariate analysis, ulceration over a tophus was correlated with age, tophus duration, size, location and less protective sensation but not with diabetes, hypertension, heart disease, gout duration, BMI, tophi number, albumin, urate, eGFR and urate‐lowering therapy (Table 2). In the logistic regression analysis, age, tophus size and protective sensation, included in the regression model (Table 3), indicated that old age, big tophus size and lack of protective sensation were independently associated with ulceration over tophi.
Table 1.
Clinical features of participants with and without ulceration†
| Variable | All patients (n = 131) | No ulceration (n = 113) | Ulceration (n = 18) | P‐value |
|---|---|---|---|---|
| Male, n (%) | 131 (100) | 113 (100) | 18 (100) | 1 |
| Age, years | 61·7 ± 13·9 | 60·4 ± 13·7 | 70·4 ± 12·0 | 0·04* |
| Diabetes, n (%) | 28 (21·3) | 22 (19·4) | 6 (33·3) | 0·21 |
| Hypertension, n (%) | 40 (30·5) | 34 (30·0) | 6 (33·3) | 0·78 |
| Heart disease, n (%) | 26 (19·8) | 21 (18·5) | 5 (27·7) | 0·35 |
| Gout duration, years | 13·3 ± 8·0 | 13·5 ± 5·4 | 13·3 ± 8·4 | 0·92 |
| Tophi duration, years | 3·7 ± 3·2 | 3·4 ± 3·0 | 5·6 ± 3·5 | <0·01* |
| Tophi size (diameter, cm) | 2·15 ± 0·85 | 1·99 ± 0·75 | 3·17 ± 0·78 | <0·01* |
| Tophi number, n | 3·4 ± 3·0 | 3·5 ± 3·0 | 2·9 ± 2·5 | 0·44 |
| BMI, kg/m2 | 29·2 ± 5·9 | 29·3 ± 6·1 | 28·6 ± 5·6 | 0·77 |
| Albumin, g/l | 34·3 ± 8·3 | 34·3 ± 8·5 | 33·8 ± 7·6 | 0·80 |
| Serum urate, µmol/l | 487 ± 133 | 491 ± 135 | 464 ± 123 | 0·43 |
| eGFR (ml/min/1·73 m2) | 49·2 ± 24·6 | 50·2 ± 24·8 | 43·3 ± 23·1 | 0·27 |
| Urate‐lowering therapy, n (%) | 38 (29·0) | 32 (28·3) | 6 (33·3) | 0·78 |
| Main location, n (%) | 0·02* | |||
| Hand | 61 (46·5) | 58 (51·3) | 3 (16·7) | |
| Foot | 60 (45·8) | 46 (40·7) | 14 (77·8) | |
| Elbow | 6 (4·6) | 5 (4·4) | 1 (5·6) | |
| Knee | 4 (3·0) | 4 (3·5) | 0 (0) | |
| Protective sensation, n (%) | 61 (46·6) | 58 (51·3) | 3 (16·7) | <0·01* |
BMI, body mass index; eGFR, estimated glomerular filtration rate.
Results are expressed as mean ± SD or number (percentage).
P < 0·05.
Table 2.
Correlations between ulceration and clinical features in all participants (n = 131)
| Variable | Correlation coefficient | P‐value |
|---|---|---|
| Age | −0·24 | <0·01* |
| Diabetes | −0·11 | 0·18 |
| Hypertension | −0·02 | 0·78 |
| Heart disease | −0·08 | 0·37 |
| Gout duration | −0·08 | 0·40 |
| Tophi duration | −0·23 | <0·01* |
| Tophi size | −0·45 | <0·01* |
| Tophi number | 0·08 | 0·35 |
| BMI | 0·02 | 0·83 |
| Albumin | 0·02 | 0·85 |
| Serum urate | 0·10 | 0·25 |
| eGFR | 0·09 | 0·32 |
| Urate‐lowering therapy | 0·04 | 0·67 |
| Main location | −2·0 | 0·02* |
| Protective sensation | −0·24 | <0·01* |
BMI, body mass index; eGFR, estimated glomerular filtration rate.
P < 0·05.
Table 3.
Binary logistic regression analysis with ulceration as the dependent variable (R 2 = 0·51)
| Variable | Coefficient | SE | P‐value | 95% CI |
|---|---|---|---|---|
| Age | −0·05 | 0·02 | 0·04 | 0·91; 0·99 |
| Tophi size | −2·04 | 0·50 | <0·01 | 0·05; 0·35 |
| Protection sensation | −2·07 | 0·82 | 0·01 | 0·03; 0·63 |
CI, confidence interval; SE, standard error.
Discussion
Gouty tophi are one manifestation of prolonged, uncontrolled hyperuricemia and result from the deposition of urate crystals in soft tissues, tendon sheaths, bony prominences and joints 1, 2. This causes joint destruction and deformities. The presence of tophi has also been associated with significant morbidity, including poor quality of life and increased use of health care resources 2, 10. Breakdown of tissue overlying the tophus may lead to persistent discharge and chronic ulceration, and these ulcerated tophaceous gouty lesions increase the risk of further tissue breakdown and delay healing 10.
In this study, just 13·7% of participants with tophi had ulceration. Age, tophus size and lack of protective sensation were the major factors independently associated with ulceration over tophi. Although other factors, such as tophus duration and location, were associated with the presence of ulceration in univariate analysis, these factors were not independently associated with ulceration when age, tophus size and lack of protective sensation were included in the regression models. Previous studies have mainly been case reports describing the operative approach to ulceration over tophi and wound healing 11, 12, 13. To the authors' knowledge, the present study is the first to report risk factors associated with ulceration over tophi in patients with gout.
Aged patients often have more comorbidity, such as diabetes, hypertension and heart disease. Although those comorbidities were not included in the regression model, they all have a potential effect on the formation of ulceration. Rome et al. reported a study of the clinical characteristics of foot ulceration in people with chronic gout 14, which showed that those affected were predominantly older men with a long duration of gout and that most wore shoes that were considered poor footwear. The present study also found that lack of protective sensation was independently associated with ulceration over tophi, suggesting that careful monitoring of people with gouty ulceration is warranted. Similar findings have been reported in people with foot ulceration who have rheumatoid arthritis or nephritis 15, 16, 17. The ulceration over tophi is different from that seen in the diabetic foot or as a result of other causes of ulceration because the tophus bulges out over the skin. When it becomes large, the skin overlying the gouty tophus often appears stretched and thin and is therefore susceptible to ulceration. Based on our results, the tophus can become ulcerative more often when it is large and under constant friction.
In this study, most of the patients (77·8%) had ulceration on the foot, including the first metatarsophalangeal joint, the ankle joint and the dorsum of foot, suggesting that foot tophi develop ulceration more easily. The study found that mechanical problems were the main indication for surgery (73·3). This finding differs from that of Kumar and Gow 8, who did a retrospective study to document the indications, results and complications associated with surgery for tophaceous gout. They found that sepsis control in infected or ulcerated tophi was the main indication for surgery (51%), followed by mechanical problems caused by foot, elbow and hand tophi (27%). Based on our experience, infected tophi are rare if the overlying skin is intact. It is difficult to distinguish infected tophi from inflamed tophi without an aetiological diagnosis because their clinical manifestations are nearly the same.
Previous studies have demonstrated that high serum urate concentrations and impaired renal function are key risk factors for the presentation of tophaceous lesions 18, 19. The central strategy for effective treatment of gouty tophi is long‐term urate‐lowering therapy to achieve a serum urate concentration low enough to dissolve MSU crystals 9, 20, 21. In this study, serum urate, eGFR and urate‐lowering therapy were not risk factors for tophi ulceration. The key risk factors for tophus ulceration were age, tophus size and lack of protective sensation. We speculate that friction is the major cause of tophi ulceration. We advise that patients with tophi, especially large foot tophi, be given long‐term urate‐lowering therapy to minimise tophi size and enhance protective sensation to avoid friction in daily life.
Acknowledgement
The authors declare that there are no conflicts of interest.
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