Diagnostic role of inflammatory markers in pediatric Brucella arthritis

Brucellosis, the most common bacterial zoonosis in the world, is still endemic in many developing countries. The clinical presentation of brucellosis is non-specific and the course and the severity of infection is variable; in humans, it presents as a multisystem disease involving many organs and tissues [1]. Fever and arthritis are the most common signs. Osteoarticular involvement is one of the most frequent complications of brucellosis. Although in adults with osteoarticular brucellosis due to Brucella abortus from Northwestern Spain sacroiliitis and spondylitis were more common than peripheral arthritis [2], monoarthritis is now considered as the predominant musculoskeletal manifestation of brucellosis [3, 4]. The most commonly affected joints are the hip and the knee. Unlike in adults, the sacroiliac joint and the axial skeleton are rarely affected. Monoarthritis is more common than polyarthritis. This may lead to confusion with pyogenic arthritis in children; therefore, in a community where brucella is common, awareness about this entity should prompt the investigation of this disease, and physicians should have a high index of suspicion for brucella arthritis (BA) [5].

Laboratory findings may be normal in some pediatric cases of brucella arthritis; however, it is not possible to take synovial fluid from all of these patients. Therefore, new inflammatory markers are required in diagnosis of pediatric BA patients. There are few previous studies on the parameters indicating new inflammatory markers in pediatric brucella arthritis. The present study aimed to investigate the levels of MPV, PDW, RDW, NLR and PLR as possible indirect inflammatory markers in children with brucella arthritis.

The mean age of the patients was 92.3 ± 41.2 months and 53.1 % (n = 34) of the patients were male. The mean age of the control group was 98.5 ± 44.0 months and 53 % (n = 35) were male. There were no significant differences in the mean age and gender distribution between the study and the control groups (p > 0.05).

The median duration of hospitalization was 6 (2–76) days in patients with BA. Five (7.8 %) patients had hepatomegaly, 15 (23.4 %) had splenomegaly and five (7.8 %) had hepatosplenomegaly. The most common symptoms at admission were arthralgia, joint pain and fever. The most commonly affected joint was ankle (n = 34, 53.1 %). Most of the patients (n = 37, 57.8 %) were treated with a combination of rifampicin plus sulfamethoxazole/trimethoprim and gentamicin. Synovial fluid puncture was performed in 24 (37.5 %) patients and brucella agglutination test was found positive in 22 (34.3 %) patients. Puncture culture was positive in nine (14 %) patients. The average ESR was 40.9 ± 20.4 mm/h and the mean CRP level was 28.1 ± 22.4 mg/L in patients with BA (Table 1).

Median WBC was 10.0 ± 4.2 × 10³/ml, PDW was ± 3.0, RDW was 16.2 ± 1.4, MPV value was 8.2 fL (6.3–11), NLR was 4.1 (1–13) and PLR was 154 (9.3–497) in the patient group. The patient group had significantly higher WBC, neutrophil count, PDW, RDW, MPV, NLR, PLR and lower lymphocyte and platelet counts at admission, compared to the control group (p < 0.05) (Table 2). There was a positive correlation between MPV and NLR (R ² = 0.192, p < 0.001) (Fig. 1). No correlation was found between MPV, ESR and CRP values.

Although hematological changes are common in brucella arthritis, they are not diagnostic and usually do not require treatment. In childhood brucella arthritis, hematological disorders may occur as leukocytosis, anemia, relative lymphocytosis along with leukopenia, thrombocytopenia and pancytopenia [6]. The study by El-Koumi et al. found anemia in 43 %, leukopenia in 38 %, leukocytosis in 20 % and pancytopenia in 18 % of the cases [7]. Similar to the previous studies, the present study found anemia in 45.3 %, thrombocytopenia in 21.8 %, leukopenia in 10.9 %, leukocytosis in 9.3 % and pancytopenia in 7.8 % of the patients. Significantly higher leukocyte and neutrophil counts were found in brucellosis patients compared to the control group, whereas the lymphocyte and thrombocyte counts were lower.

The present study aimed to investigate the predictive contribution value of NLR, PLR and MPV in the diagnosis of BA. Our findings showed that NLR, PLR and MPV were higher in patients with BA compared to the control group.

NLR can be determined from routine blood differentials at no additional cost. Changes in the relative abundance of leukocyte subgroups occur in parallel with the increase in overall leukocyte count. Lymphocyte count decreases when neutrophil count increases. NLR increases in inflammatory conditions and this increase is considered as an indicator of systemic inflammation [8]. Studies showed that platelets also play an active role in inflammation, while having regulatory effects on the immune system [9]. The study by Günes et al. [10] was conducted on patients with juvenil rheumatoid arthritis (JRA) and demonstrated that NLR was higher in patients with juvenile idiopathic arthritis compared with the control group. In another study, significantly higher NLR values were found in patients with ankylosing spondylitis [11]. In the study by Türkmen et al., the PLR ratio showed better performance than the NLR ratio in the prediction of inflammation in patients with end-stage renal disease [12]. As a result of changes caused by the inflammation in neutrophils, platelets and lymphocytes, NLR and PLR have turned into inflammatory markers. Based on the results of the present study and other similar studies, we suggest that the NLR and PLR ratios may be inflammatory markers that can be used in the diagnosis and follow-up of the disease in children with brucella arthritis.

Hematologic abnormalities are observed in brucellosis. One of these abnormalities is thrombocytopenia. Over release of proinflammatory cytokines and acute-phase reactants can suppress the size of platelets [8, 9]. The study by Okan et al. found that MPV was statistically significantly lower in brucellosis cases compared to control group [9]. Küçükbayrak et al. and Bozkurt et al. conducted studies on adult patients and established that MPV was increased statistically after treatment in brucellosis cases [13, 14]. The literature contains many studies regarding several diseases related to MPV, PDW and RDW, and a part of such studies demonstrated increased MPV in acute coronary syndrome, diabetes mellitus, cerebrovascular conditions, preeclampsia, renal artery stenosis, hypercholesterolemia, smoking and sepsis [15‐17]. However, there are few studies on brucellosis cases. The present study found higher MPV, PDW and RDW in brucella arthritis patients than control group.

Increased CRP and ESR have been reported to be involved in active inflammation and are often considered as useful criteria for the diagnosis and follow-up effectiveness of treatment in brucella and other inflammatory conditions [1, 17, 18]. The studies evaluating the correlation between MPV and CRP, ESR and SAT reported different results. Kader et al. [19] found a significant negative correlation between MPV and SAT. Öztürk et al. [20] found a negative correlation between MPV and CRP, while two studies found positive correlation between MPV and CRP [21, 22]. The present study found a significant positive correlation between NLR and MPV, whereas there was no significant correlation between MPV, SAT, ESR and CRP.

Our study has several limitations. Firstly, it is a retrospective study with a relatively small sample size and synovial fluid was not taken from all patients. It would be very useful if we can compare the markers between patients with brucella arthritis, septic arthritis and reactive arthritis. The studies with a larger number of patients and more comprehensive analyses can provide further data on these variables.

MPV, PDW, RDW, NLR and PLR values can be useful complementary indirect markers for diagnosis of BA in children. We believe that these variables can be taken into account as quick, cheap and easily measurable new inflammatory markers in patients with BA. Further prospective studies are required to externally cross-validate our findings in larger cohorts of BA patients.