We compared the demographic, clinical and laboratory characteristics of brucellosis patients with or without complications in order to provide practical reference index for clinicians in early diagnosis and patient management. Over half brucellosis patients suffered complication. Long delay in diagnosis, underlying disease, arthralgia, myalgia bulging pain, CRP > 10 mg/L, ESR elevation were warning factors of complications.
The complication rates of between 27.7% and 90% have been reported in large-scale epidemiological studies[11, 14]. Osteoarticular, hematologic, and genitourinary systems were the main affected anatomical sites, the range of incidence was 2%-77%, 2–53%, 2%-20%, respectively[15]. Consistent with previous studies, complications occurred in 54.8% of the brucellosis cases in this study, and it can involve any organ and tissue, most common in osteoarticular involvement. And therefore, brucellosis should be taken into account in the differential diagnosis of osteoarthropathy, orchitis and other rehabilitation department physiotherapy disease, especially in endemic regions. The spectrum of clinical symptoms and the distribution of focal involvement were different in the previous studies[16–18]. In our study, the incidence of arthralgia, inappetence, nausea, orchialgia, and bulging pain was significantly higher in the complicated group, and fatigue was significantly less frequent, compared with that in the uncomplicated group. These differences may be related to the different definition of complications, diagnostic methods and instruments, epidemiological research methods, and the characteristics of the study subjects. The subjects of this research may be a presentative sample of brucellosis patients in China due to the proper design, and therefore the study findings could provide a sound profile of the clinical spectrum of complicated-brucellosis in China.
In our study, arthralgia, loss of myalgia, and bulging pain were statistically significant warning factors for complicated patients and osteoarticular complications mainly involve large joints such as the spine. In agreement with our results, in similar studies, absence of myalgias and low back pain were associated factors for complications[19–21]. Bulging pain is not common in brucellosis patients and should be paid attention to in the course of diagnosis and treatment.
Delayed diagnosis has been shown to increase the rate of complications, some previous studies were consistent with our findings [19, 22, 23]. The longer brucellosis symptoms persist, the higher the risk of complications. This may be related to the length of time the bacteria exist in the body. Therefore, early diagnosis is important to prevent complication and poor clinical outcome. However, delayed diagnosis occurs quite often, and major reason from the medical practitioners’ perspective lied in its various but non-typical clinical manifestation and mimic other diseases[24]. In addition, prompt and proper confirmation of complication is also important, as longer therapy and extra antibiotics other than first-line drugs is essential for complete eliminating the Brucella for patients with focal brucellosis[9]. Insufficient and inappropriate treatment could easily lead to chronicity[25], which not only cause great harm to patients, but also heavy economic burden to their families and the whole society. And therefore, it is necessary to combine biomarkers to explore comprehensive diagnostic indicators for complicated-brucellosis.
This study found that CRP and ESR were warning signs of focal involvement in brucellosis. The cutoff values were 5.4 mg/L for CRP and 25 mm/h for ESR. Similarly, other studies also shown that CRP and ESR were higher in patients with complications [19]. Betul et al.[21] found that ESR > 30 mm/h as a predictor of brucellosis complications. Besides, Colmenero et al.[22] pointed out that organ involvement is about twofold higher in cases of brucellosis diagnosed 30 days later with an ESR > 40 mm/h. In addition, the titer level of IgG, IgM and neutrophil–lymphocyte ratio in the serum were also reported to be associated with complications[12, 26, 27].
Blood culture is controversial in early identification of brucellosis complications. There are few studies and the results are mixed. Nannan Xu et al.[12] found that blood culture positivity was indicator of complicated brucellosis while Bircan et al. [19] reported that blood culture negativity was statistically significant relevant factors for complicated patients. In the other studies[20–22], blood culture and SAT positivity rates were similar in the groups with and without focal involvement. The condition and technique of blood culture had great influence on the results[7]. In our study, negative blood cultures and low SAT titers were associated with brucellosis complications. It may be related to factors such as taking antibiotics and laboratory conditions.
This study had some limitation. Firstly, due to financial limitation, this study failed to involve some biomarkers in relation to immunity, such as CD4+ T lymphocyte, CD8+ T lymphocyte, IL2, IL6. Secondly, conventional indicators such as inflammatory markers may not be appropriate because they can be affected by autoimmune conditions, immunodeficiency diseases, and so on. In addition, metabolomics, proteomics, and immunomics should be used to detect serum, interstitial fluid, etc., so as to obtain biomarkers of brucellosis complications, such expanded research is needed in the future.
In conclusion, complication is quite common among brucellosis patients; patients with long delayed diagnosis, underlying disease, large arthralgia, bulging pain and high CRP or ESR should be followed up closely at the first visit, and the occurrence of complications should be vigilant during early treatment.