Nanna Skaarup Andersen

Prognostic factors associated with mortality in patients with septic arthritis: a descriptive cohort study

Objectives: To evaluate the 30-day mortality rate of septic arthritis (SA) in adults in Funen, central Denmark, and to explore whether, at the time of SA presentation, risk factors for the 30-day mortality rate could be revealed. Our secondary objective was to describe the microbiological aetiologies, systemic signs of inflammation, and co-morbidity. Method: A descriptive study identifying patients with SA from central Denmark, during the period 2006–2013, by the use of joint fluid culture data retrieved from the electronic database at the Department of Clinical Microbiology, Odense University Hospital. Patients with a positive joint fluid culture were considered eligible and their medical records were examined. Results: We identified 215 patients with SA, mean age 64.8 years. At presentation, mean C-reactive protein (CRP) was 204 mg/L, mean white blood cell count (WBC) 11.9 × 109/L, and mean body temperature 37.6°C. A total of 101 patients (47%) had a prosthetic joint, 46 (21%) had an inflammatory joint disease, and 24 (11%) had diabetes mellitus (DM). Staphylococcus aureus was the most common pathogen (104 patients, 48.4%). The 30-day mortality rate was 9.3% and the significant risk factor for death was liver disease at time of presentation [odds ratio (OR) 40.40, 95% confidence interval (CI) 5.38–303]. The other factors tested such as age > 65 years, elevated temperature, rheumatoid arthritis (RA), prostheses, and diabetes mellitus (DM) did not reach statistical significance. Conclusions: In our sample of patients with SA, we found a 30-day mortality rate in almost one in 10 adults. Among possible explanations, our study indicates that liver disease is a clinically relevant risk factor.

Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995–2014: A Retrospective Cohort Study in Denmark

Background Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the symptomatology and epidemiology of LNB. Methods We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014. Results The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment. Conclusions The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.

Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry

Background Large health care databases are a valuable source of infectious disease epidemiology if diagnoses are valid. The aim of this study was to investigate the accuracy of the recorded diagnosis coding of herpes simplex encephalitis (HSE) in the Danish National Patient Registry (DNPR). Methods The DNPR was used to identify all hospitalized patients, aged ≥15 years, with a first-time diagnosis of HSE according to the International Classification of Diseases, tenth revision (ICD-10), from 2004 to 2014. To validate the coding of HSE, we collected data from the Danish Microbiology Database, from departments of clinical microbiology, and from patient medical records. Cases were classified as confirmed, probable, or no evidence of HSE. We estimated the positive predictive value (PPV) of the HSE diagnosis coding stratified by diagnosis type, study period, and department type. Furthermore, we estimated the proportion of HSE cases coded with nonspecific ICD-10 codes of viral encephalitis and also the sensitivity of the HSE diagnosis coding. Results We were able to validate 398 (94.3%) of the 422 HSE diagnoses identified via the DNPR. Hereof, 202 (50.8%) were classified as confirmed cases and 29 (7.3%) as probable cases providing an overall PPV of 58.0% (95% confidence interval [CI]: 53.0–62.9). For “Encephalitis due to herpes simplex virus” (ICD-10 code B00.4), the PPV was 56.6% (95% CI: 51.1–62.0). Similarly, the PPV for “Meningoencephalitis due to herpes simplex virus” (ICD-10 code B00.4A) was 56.8% (95% CI: 39.5–72.9). “Herpes viral encephalitis” (ICD-10 code G05.1E) had a PPV of 75.9% (95% CI: 56.5–89.7), thereby representing the highest PPV. The estimated sensitivity was 95.5%. Conclusion The PPVs of the ICD-10 diagnosis coding for adult HSE in the DNPR were relatively low. Hence, the DNPR should be used with caution when studying patients with encephalitis caused by herpes simplex virus.

Septic arthritis and subsequent fatal septic shock caused by Vibrio vulnificus infection

Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case reports; however, it has not been previously noted in Denmark. The authors report a case of septic arthritis caused by V. vulnificus in an immunocompromised patient. The disease progressed to severe sepsis and subsequent death within 10 h of admission.

Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study

Abstract Objective To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population. Design Nationwide population based cohort study using national registers. Setting Denmark. Participants All Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive Borrelia burgdorferi intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20 670). Main outcome measures Mortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes. Results Mortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference −0.22, 95% confidence interval −0.45 to 0.02, in-hospital days/year; 0.37, −0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, −2.1% to 5.1%), income (difference −1000, −20 000 to 18 000, Danish kroner), days of sick leave (difference −0.3, −3.5 to 3.0, per year), rates of receipt of a disability pension (difference −0.9%, −3.2% to 1.3%), and number of children (difference –0.10, −0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%). Conclusion A verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.

Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer

Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe.

Continued expansion of tick-borne pathogens: Tick-borne encephalitis virus complex and Anaplasma phagocytophilum in Denmark

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus within the tick-borne encephalitis (TBE) complex. The TBE complex is represented by both TBEV and louping ill virus (LIV) in Denmark. Anaplasma phagocytophilum is also transmitted by ticks and is believed to play an essential role in facilitating and aggravating LIV infection in sheep. This study aimed to describe the distribution of TBE complex viruses in Denmark, to establish the possible emergence of new foci and their association with the distribution of A. phagocytophilum. We performed a nationwide seroprevalence study of TBE complex viruses using roe deer (Capreolus capreolus) as sentinels and determined the prevalence of A. phagocytophilum in roe deer. Danish hunters obtained blood samples from roe deer during the hunting season of 2013-14. The samples were examined for TBEV-specific antibodies by virus neutralization tests (NT). A. phagocytophilum infection was assessed by specific real-time-PCR. The overall seroprevalence of the TBE complex viruses in roe deer was 6.9% (51/736). The positive samples were primarily obtained from a known TBE endemic foci and risk areas identified in previous sentinel studies. However, new TBE complex risk areas were also identified. The overall prevalence of A. phagocytophilum was 94.0% (173 PCR-positive of 184 roe deer), which is twice the rate observed ten years ago. These results point to an expansion of these tick-borne diseases geographically and within reservoir populations and, therefore, rationalize the use of sentinel models to monitor changes in transmission of tick-borne diseases and development of new risk areas. We found no association between TBE complex-positive roe deer and the prevalence of A. phagocytophilum, as almost all roe deer were infected. Based on our findings we encourage health care providers to be attentive to tick-borne illnesses such as TBE when treating patients with compatible symptoms.

Authors’ reply: Prognostic factors associated with mortality in patients with septic arthritis: a descriptive cohort study

change on leucocyte esterase test strip; (iii) elevated synovial fluid polymorphonuclear neutrophil (PMN) percentage; (iv) a single positive periprosthetic culture; and (v) positive histological analysis of periprosthetic tissue (2). There are different types of PJIs. Acute postoperative infections are defined as infections of the prosthesis that occur within 90 days after surgery (2). Infections diagnosed later than 90 days after surgery are defined as chronic PJIs (2). Each type has its own treatment modality. In acute PJIs, usual care means debridement, antibiotics, and implant retention (2, 5). Chronic PJIs are treated with implant revision surgery (2, 5). In general, antibiotics are administered for a minimum of 3 months in both acute and chronic PJIs (2, 5). This is due to biofilm formation that occurs on the prosthesis, which functions as a foreign body (2, 5). Therefore, antibiotics that penetrate biofilms are recommended (2, 5). Treatment of native SA generally consists of 6 weeks of antibiotics with needle aspiration or arthroscopy of the joint (6). Furthermore, there are other factors that may influence the primary outcomes of this study. The characteristics of patients with a TJA in the general population may be different from those of the native joint group. The threshold for operating on vulnerable patients with chronic diseases has decreased (7). So, within the population of patients who receive TJAs, comorbidities may be more often present and they generally have a higher age (7). The conclusion of the authors that the 30 day mortality rate in their study could not be explained by comorbidities or old age in native SA may have to be reconsidered after eliminating these factors. Concerning their secondary outcomes, there also are some points of discussion that may be important in interpreting the results of this study. Systemic signs are less common in chronic PJIs (2). Therefore, the secondary objective, to describe systemic signs of inflammation, could be biased in case a significant number of the included patients had chronic PJIs. Furthermore, the authors have given averages for several microorganisms for the WBC count in synovial fluid, but it is not known whether they were aware that the cut-offs for WBC and PMNs in synovial fluid are different between acute and chronic PJIs (2). The cutoffs presented in this study may also be biased because of this phenomenon. In conclusion, this study could be a valuable addition to the current literature in determining prognostic factors associated with mortality in patients with SA in native joints and in PJIs. A recommendation would be to split these different pathologies into separate groups. For the group of PJIs it is recommended also to differentiate between acute and chronic joint infections.

THU0300 Septic Arthritis in the Central Part of Denmark

Background Septic arthritis (SA) is a serious condition which can lead to rapid cartilage destruction and irreversible joint damage and is asociated with a significant mortality. SA is an uncommon condition with an incidence of 4-10/100.000/year. Risk factors for SA are age >60 years, recent bacteremia, diabetes mellitus, rheumatoid arthritis, gout, recent joint surgery, degenerative joint disease and joint prosthesis [1]. An accurate diagnosis can be difficult to state for patients with an underlying inflammatory joint disease. Intra-articular corticosteroid injections are widely used in aseptic arthritis and reduce the manifestations of inflammation. However, iatrogenic infection can be a complication to joint puncture, of which septic arthritis (SA) is the most serious[2] Objectives The aim of this study is to describe the microbiological etiology and co-morbidity in patients with SA and to register how many who had received an intra-articular steroid injection prior to the diagnosis Methods In this descriptive cross-sectional study all patients older >18 years diagnosed with SA at all hospitals in the central part of Denmark in the period January 2006 through December 2013 were registered. SA was defined as clinically inflamed joint and positive synovial fluid culture. The department of microbiology at Odense University Hospital identified the microbiological agents. Patients who had received an intra-articular steroid injection in a period of up to one month earlier they were diagnosed with SA and co-morbidities were registered Results We identified 215 patients diagnosed with SA (male:142, female: 73) given an average incidence at 6,9 cases/100.000 inhibitants [3]. Mean age was 64,8 years (21-94) 97% were monoarticular and 3% were polyarticular. Mean C-reactive protein 204 mg/l (2-523), mean leuc 11,9*109/L (0,7-30,6). Nearly half of the patients had a prosthetic joint (47%) followed in frequency by pre-existing inflammatory joint or connective tissue disease (21%), 11% had diabetes mellitus and 5,6% (n=12) had an intra-articular steroid injection prior to the diagnosis. The average time from injection to diagnosis was 9 days.Twenty patients died within four weeks after SA was diagnosed, corresponding to a mortality of 9,3%. Bacterial agents: Staphylococcus aureus (n=104) 48% Coagulase negative staphylococcus (n=25) 12% Streptococcus pyogenes group (n=24) 11% Streptococcus mitis group (n=19) 9% Gram-negative rod shape bacteria (n=23) 11% other less common bacteria (n=20) 9% Conclusions In accordense with earlier studies we found staphylococcus aureus to be the most common bacterial microorganism in patients with SA. The highest isolated risk factor was joint prosthesis followed by inflammatory joint and connective tissue diseases. We did not find an increasing incidence of SA even though the numbers of therapeutic steroid injections had markedly increased in recent years. Despite the rarity of SA following intra-articular injections, patients should be informed of the risk of septic arthritis and the possible consequences A strict aseptic technique is important. References Shirtliff M.E. and Mader J. Acute Septic Arthritis, Clinical Microbiology Reviews, Oct 2002, 527-544 Geirsson Ά.J. et al, Septic arthritis in Iceland 1990-2002: increasing incidence due to iatrogenic infections, Ann Rheum Dis 2008; 67: 638-643 Denmark statistical demographic data (http://statistikbanken.dk) Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3263