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An investigation about chronic prostatitis in ankylosing spondylitis

An investigation about chronic prostatitis in ankylosing spondylitis Background: Chronic prostatitis has been a common disease reported with high frequency in ankylosing spondylitis (AS) even from decades ago. Infectious (Chlamydia trachomatis) or non-infectious (uric acid) prostatitis can hypothetically trigger vertebral inflammation in AS. This study aimed to assess the features of chronic prostatitis in patients with AS compared to healthy controls. Methods: A cross-sectional study including male patients with AS and healthy controls who agreed to undergo a prostate examination was conducted. Structured clinical interviews, prostate physical examinations, and cytological, biochemical, and microbiological tests on urinary samples collected before and after standardized prostatic massage (pre- and post-massage test) were performed. Results: Ninety participants (45 AS patients, mean age: 52.5 ± 10.0 years, with longstanding disease, 12.4 ± 6.9 years, and 45 controls, mean age: 52.8 ± 12.1 years) were included. National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores were similar in the AS and control groups (4.0 [1.0–12.0] vs. 5.0 [1.0–8.5], p = 0.994). The frequencies of symptoms of chronic prostatitis (NIH-CPSI Pain Domain ≥4) were also similar in both groups (23.3% vs. 22.7%, p = 0.953). Results of polymerase chain reaction tests for Chlamydia trachomatis were negative in all tested urinary samples, and uric acid concentrations and leukocyte counts were similar in all pre- and post-massage urinary samples. Conclusions: In this study, chronic prostatitis occurred in male patients with AS, but its frequency and characteristics did not differ from those found in the healthy male population of similar age. Keywords: Ankylosing spondylitis, Pelvic pain, Prostatitis, Chlamydia trachomatis, Uric acid Background In 1958, Mason et al. described a strikingly high fre- Ankylosing spondylitis (AS) is the most common form of quency (83%) of prostatitis in men with AS based on the spondyloarthritis, mainly affecting the sacroiliac joints and cytological analysis of urethral fluids obtained after pros- spine. In severe cases, it can even cause progressive calcifi- tatic massage [2]. However, these results have never cation and ankylosis, often in an ascending nature through been reproduced since then. More recently, an Icelandic its longitudinal ligaments. In addition, extra-articular survey identified prostatitis in 27% of male patients with manifestations may also occur, such as uveitis [1]. AS based on medical record reviews, and the authors suggested that prostatitis was the second most frequent extra-articular manifestation of AS [3]. * Correspondence: fabricio.souza.neves@ufsc.br Graduate Program in Medical Sciences (PPGCM), Health Sciences Center Chronic prostatitis could not only be a consequence of (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil AS, but also a cause of the disease. It is hypothesized that Internal Medicine Department, Health Sciences Center (CCS), Federal the spread of pathogen-associated molecular patterns University of Santa Catarina (UFSC), Florianópolis, Brazil Full list of author information is available at the end of the article (PAMPs) or damage-associated molecular patterns © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Deves et al. Advances in Rheumatology (2021) 61:23 Page 2 of 5 (DAMPs) through the pelvic and vertebral lymphatic ves- the Bath Ankylosing Spondylitis Disease Activity Index sels from chronic prostate inflammation caused by an in- (BASDAI) [11], with further calculation of Ankylosing fectious (Chlamydia trachomatis) or non-infectious agent Spondylitis Disease Activity Score (ASDAS) [12] based on (uric acid) could induce vertebral inflammation [4]. serum C-reactive protein (CRP) levels (nephelometry). To the best of our knowledge, the characteristics of Erythrocyte sedimentation rate (ESR) (Westergren) and prostatitis in AS patients have yet to be investigated and serum prostate-specific antigen (PSA) were also measured compared to a healthy control group using current stan- (chemiluminescence) prior to prostate palpation. Partici- dardized clinical and laboratory procedures to specific- pants were defined as having prostatitis symptoms if they ally assess these hypotheses. expressed concern of perineal pain or discomfort, and The current classifications of chronic prostatitis were their NIH-CPSI pain domain score (ranging from 0 to 21) established in 1999 by the US National Institutes of was ≥4[13]. These cases were also defined as having mod- Health (NIH) as the following: chronic bacterial prosta- erate to severe prostatitis symptoms if their NIH-CPSI titis (CBP, NIH category II), inflammatory chronic pros- pain domain scores were ≥8[14]. tatitis/chronic pelvic pain syndrome (CP/CPPS, NIH The prostate physical examination was performed in category IIIa), and non-inflammatory CP/CPPS (NIH all participants by an experienced urologist (ED or CN), category IIIb) [5]. The Meares-Stamey 4-glass test [6]or with a 30-s standardized prostatic massage procedure. its simplified version by the Nickel’s 2-glass test [7], also Midstream urine samples were collected immediately be- known as the pre- and post-massage test (PPMT), are fore and after the prostatic massage. Leukocyte counts the standard criteria for diagnosis using urinary samples were performed in Neubauer chambers, cultures were collected after prostatic massage, in which NIH category performed with the seeding of urine samples in the II is confirmed with positive bacteriological culture re- growth medium ChromID CPS® (Biomerieux, France), sults and NIH category IIIa with positive leukocyte and uric acid urinary concentrations were measured by counts. However, most men with chronic prostatitis uricase reaction. Polymerase chain reaction (PCR) assays symptoms are classified as NIH IIIb, with negative cul- for Chlamydia trachomatis were also performed in post- tures and normal leukocyte counts at PPMT given the massage urinary samples of AS patients using GeneXpert lack of biomarkers for this condition. CT/NG (Xpert)® (Cepheid, USA) assay. Clinical and la- In this study, we first aimed to assess whether chronic boratory data of participants with positive microbio- prostatitis symptoms were more frequent or more se- logical test results (cultures or PCR) were then analyzed vere, and whether urinary leukocyte counts at PPMT separately from the whole group. were higher in patients with AS than in healthy controls. This study was approved by the National Committee Second, we also aimed to evaluate uric acid concentra- on Ethics in Research (44,333,115.0.0000.0121), and a tions, bacterial growth, and presence of Chlamydia tra- written informed consent was obtained from all patients. chomatis in urinary samples obtained after prostatic The sample size was estimated as 41 participants in each massage in order to investigate possible causes of group in order to verify a difference of two points in the chronic prostatitis in this group. median NIH-CPSI score (from 4 to 6) with a 95% confi- dence level and 80% statistical power. Statistical analysis Methods was performed using IBM SPSS® v20.0. Normality of We conducted a cross-sectional study including all male data distribution was tested using the Kolmogorov- patients with AS attending an outpatient rheumatology Smirnov test, and the normally distributed data are pre- public service who agreed to undergo prostate examin- sented as mean ± standard deviation, in which differ- ation between 2015 and 2019. To be included in this ences between means were tested by Student’s t-test. study, these patients needed to fulfill the 1984 New York Non-parametric data are presented as median interquar- modified criteria for AS [8]. Exclusion criteria included tile ranges, and the differences between medians were the acute presence of urinary symptoms, use of antibi- evaluated by Mann-Whitney U test. Additionally, differ- otics in the last 30 days, use of uric acid-lowering ther- ences between proportions were tested using the chi- apy, use of diuretics, and any previous diagnosis of square test. prostatic disease. The control group comprised volun- teers who attended the outpatient urology service, pre- Results senting without any current disease for prostate cancer Ninety men were included, including 45 patients with screening. AS and 45 controls. Regarding microbiological examin- All participants were interviewed using the validated ation, all tested urinary samples (post-massage urine in versions of the National Institutes of Health - Chronic the AS group) showed negative results for C. trachoma- Prostatitis Symptom Index (NIH-CPSI) [9], International tis. The cultures showed positive results with more than Prostate Symptom Score (IPSS) [10] and, in the AS group, 10 colony-forming units (CFU)/mL in both pre- and Deves et al. Advances in Rheumatology (2021) 61:23 Page 3 of 5 post-massage samples (suggesting bacterial cystitis) in Iceland [3]; however, chronic prostatitis symptoms were two participants - one AS patient with Escherichia coli equally frequent in the control group (22.7%) of our and one control with Enterococcus faecalis. The culture study. The frequencies of moderate to severe prostatitis result was positive in the post-massage sample and nega- symptoms (NIH-CPSI pain scores ≥8) were also similar tive in the pre-massage sample (suggesting bacterial between the AS (14.0%) and control groups (11.4%), prostatitis) in one AS patient with Enterococcus faecalis. which resembled the overall prevalence of chronic pros- These patients were treated as indicated and excluded tatitis in the general male population, estimated to be from further analysis. The clinical and blood laboratory 8.2% [15]. The median values of the NIH-CPSI and IPSS data of the participants included in the study are pre- scores were also compared between the AS and control sented in Table 1. All AS patients underwent regular groups. In our study, post-massage urinary leukocyte treatment, and those who were not under treatment counts were not elevated in chronic prostatitis cases in with anti-tumor necrosis factor (TNF) agents were using the AS group, which meant that all of them could be different combinations of non-steroidal anti- classified as non-inflammatory chronic prostatitis (NIH- inflammatory drugs (NSAIDs) and non-biological IIIb classification). This was the most frequent form of disease-modifying antirheumatic drugs (DMARDs). chronic prostatitis and was recently conducted to the The urinary data comparison between the groups is broader definition of “chronic pelvic pain syndrome” presented in Table 2. All cases with symptoms of prosta- (CPPS) for this entity [16]. Thus, the characteristics of titis in the AS group had leukocyte counts in post- the chronic prostatitis cases in AS patients described in massage samples lower than 20,000/mm and were clas- our study were quite similar to those expected in the sified as non-inflammatory chronic prostatitis/chronic general adult male population. Our results suggested pelvic pain syndrome (CP/CPPS, NIH-IIIb). that chronic prostatitis was a frequent finding in the adult male population, irrespective of the presence of Discussion AS. In our study, 23.3% of patients with AS had symptoms Our findings did not support the pioneering study by of chronic prostatitis (NIH-CPSI pain scores ≥4), which Mason et al., which described an impressive frequency resembled the frequency of chronic prostatitis (27%) de- of 83% of chronic prostatitis, defined by the presence of scribed in the 2010 epidemiological study conducted in ≥10 polymorphonuclear leukocytes per high-power mi- croscopy field in post-massage prostatic fluids [2]. Table 1 Clinical characteristics and blood laboratory tests of AS Leukocyte counts in the post-massage samples were patients and controls (excluding participants with positive similar in the AS and control groups in our study. How- urinary cultures - two in the AS group and one in the control ever, we may consider that current treatment of AS with group) anti-TNF agents may also be a therapy for chronic pros- AS (n = 43) Controls (n = 44) p tatitis, and they could have influenced our results, redu- Age (years) 52.5 ± 10.0 52.8 ± 12.1 0.882 cing the severity of prostatitis in the AS group (86.0% of Disease duration (years) 12.4 ± 6.9 AS patients were using anti-TNF agents) [17]. Another Anti-TNF treatment 35 (86.0%) possible confounding factor in our study was the fact BASDAI 4.9 ± 1.7 that our control group was composed of healthy men who were interested in the prostatic cancer screening. ASDAS 2.7 ± 0.6 This could have led to a bias in our control group to- NIH-CPSI 4.0 [1.0–12.0] 5.0 [1.0–8.5] 0.944 ward a higher severity of prostatitis symptoms. Before NIH-CPSI (Pain Domain) ≥ 4 10 (23.3%) 10 (22.7%) 0.953 making any definitive conclusions, we believe that our NIH-CPSI (Pain Domain) ≥ 8 6 (14.0%) 5 (11.4%) 0.716 findings need to be reassessed by other investigators. IPSS 6 [2.5–13.5] 2.5 [0.0–12.0] 0.105 Our study did not identify the etiologic factors that we IPSS > 8 14 (32.6%) 13 (29.5%) 0.499 tested as causative agents of prostatitis in patients with AS. All post-massage urinary samples showed negative PSA (ng/mL) 1.2 ± 1.1 1.8 ± 2.0 0.324 results for C. trachomatis in a highly sensitive PCR CRP (mg/L) 3.2 [2.8–3.3] 2.3 [1.0–2.6] 0.011* assay, and uric acid concentrations did not differ be- ESR (mm/h) 4 [3–5] 3 [2–5] 0.857 tween pre- and post-massage urine samples. Thus, our Uric acid (mg/dL) 5.8 ± 1.3 5.5 ± 1.2 0.624 results did not support the hypothesis that spreading of ASDAS Ankylosing spondylitis disease activity score, AS Ankylosing spondylitis, PAMPs or DAMPs from the prostate contributes to the BASDAI Bath ankylosing spondylitis disease activity index, NIH-CPSI National pathogenesis of AS [4]. However, the long duration of Institutes of Health - Chronic Prostatitis Symptom Index, IPSS International Prostate Symptom Score, PSA Prostate-specific antigen, TNF Tumor necrosis disease in our study group may have diminished urinary factor, CRP C-reactive protein, ESR Erythrocyte sedimentation rate. Data are findings that could have been present in the early course presented as mean ± standard deviation (for normally distributed data), median [interquartile range] for non-parametric data of untreated disease. Prostate assessment in the early Deves et al. Advances in Rheumatology (2021) 61:23 Page 4 of 5 Table 2 Comparison of pre- and post-massage urinary tests between AS patients and healthy controls (excluding participants with positive urinary cultures) pre-massage post-massage AS control p AS control p Leukocyte count (/mm ) 2000 [1000-6000] 2000 [1000-5250] 0.603 3000 [2000-5000] 3000 [1000-11,475] 0.704 Uric acid (mg/dL) 53.3 ± 29.4 54.9 ± 24.8 0.782 55.3 ± 24.9 51.2 ± 28.9 0.480 AS Ankylosing spondylitis; Data are presented as mean ± standard deviation (for normally distributed data) or median [interquartile range] for non-parametric data and untreated AS or undifferentiated spondyloarthtitis Author details Urology Service, University Hospital Prof. Polydoro Ernani de São Thiago could be a field for further research. HU/EBSERH, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. Graduate Program in Medical Sciences (PPGCM), Health Sciences Center (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. Conclusions Laboratory of Molecular Biology, Microbiology and Serology, Health In the present study, chronic prostatitis/chronic pelvic Sciences Center (CCS), Federal University of Santa Catarina (UFSC), pain syndrome (CP/CPPS) occurred in male patients Florianópolis, Brazil. Rheumatology Unit, University Hospital Prof. Polydoro Ernani de São Thiago HU/EBSERH, Federal University of Santa Catarina with longstanding ankylosing spondylitis (AS) under (UFSC), Florianópolis, Brazil. Internal Medicine Department, Health Sciences standard treatment (mainly based on anti-TNF agents); Center (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. however, in this population, the frequency and charac- Departamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, 3° andar, Rua Profa. Maria Flora Pausewang, teristics of prostatic disease did not differ from those Florianópolis, SC 88036-800, Brazil. found in healthy controls of similar age. Received: 23 November 2020 Accepted: 12 April 2021 Abbreviations AS: Ankylosing spondylitis; ASDAS: Ankylosing Spondylitis Disease Activity Score; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CP/ CPPS: Chronic prostatitis / Chronic pelvic pain syndrome; CPSI: Chronic References Prostatitis Symptom Index; DAMP: Damage-associated molecular pattern; 1. Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial IPSS: International Prostate Symptom Score; NIH: National Institutes of Health; Spondyloarthritis. N Engl J Med. 2016;374:2563–74. PAMP: Pathogen-associated molecular pattern; PPMT: Pre- and post-massage 2. Mason RM, Murray RS, Oates JK, Young AC. Prostatitis and ankylosing test spondylitis. Br Med J. 1958;1(5073):748–51. https://doi.org/10.1136/bmj.1. 5073.748. Acknowledgements 3. Geirsson AJ, Eyjolfsdottir H, Bjornsdottir G, Kristjansson K, Gudbjornsson B. Hospital Universitário Prof. Polydoro Ernani de São Thiago / Universidade Prevalence and clinical characteristics of ankylosing spondylitis in Iceland - a Federal de Santa Catarina / Empresa Brasileira de Serviços Hospitalares (HU/ nationwide study. Clin Exp Rheumatol. 2010;28(3):333–40. UFSC/EBSERH). 4. Pöllänen R, Sillat T, Pajarinen J, Levón J, Kaivosoja E, Konttinen YT. Microbial antigens mediate HLA-B27 diseases via TLRs. J Autoimmun. 2009;32(3-4): Authors’ contributions 172–7. https://doi.org/10.1016/j.jaut.2009.02.010. ED, RN, MCS, AFZ, IAP, MLB, FSN contributed to study design. ED, RN, MLB, 5. Krieger JN, Nyberg LJ, Nickel JC. NIH consensus definition and classification of AFZ, IAP, FSN performed clinical procedures and contributed to data prostatitis. JAMA. 1999;282(3):236–7. https://doi.org/10.1001/jama.282.3.236. collection. FHB, MCS, LKP performed laboratorial procedures and contributed 6. Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial to data collection. ED and FSN analyzed data and wrote the main prostatitis and urethritis. Investig Urol. 1968;5(5):492–518. manuscript. All authors reviewed and contributed to the final text. The 7. Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler JE, Zeitlin S, et al. How author(s) read and approved the final manuscript. does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? J Urol. 2006;176(1):119–24. https://doi.org/10.1016/S0022- Funding 5347(06)00498-8. There is no funding to be reported. 8. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York Availability of data and materials criteria. Arthritis Rheum. 1984;27(4):361–8. https://doi.org/10.1002/art.17802 The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. 9. Novotny C, Deves E, Novotny R, Rodrigues IK, Neves FS. Cultural adaptation of the National Institutes of Health--chronic prostatitis symptom index (NIH- Declarations CPSI)--to Brazilian spoken Portuguese: NIH-CPSI (Braz). Int Braz J Urol. 2013; 39(5):683–91. https://doi.org/10.1590/S1677-5538.IBJU.2013.05.11. Ethics approval and consent to participate 10. Rodrigues Netto N Jr, de Lima ML, de Andrade EF, et al. Latin American The study was approved by the National Committee for Research Ethics study on patient acceptance of the international prostate symptom score (number 44333115.0.0000.0121). Written informed consent was obtained (IPSS) in the evaluation of symptomatic benign prostatic hyperplasia. from all patients. Urology. 1997;49(1):46–9. https://doi.org/10.1016/S0090-4295(96)00372-X. 11. Shinjo SK, Gonçalves R, Gonçalves CR. Measures of clinical assessment in Consent for publication patients with Ankylosing spondylitis: review of literature. Rev Bras Reumatol. All authors read and approved the final manuscript and gave their consent 2006;46(5):340–6. https://doi.org/10.1590/S0482-50042006000500007. for publication. 12. Machado P, Landewé R, Lie E, et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and Competing interests improvement scores. Ann Rheum Dis. 2011;70(1):47–53. https://doi.org/1 The authors declare no conflict of interest. 0.1136/ard.2010.138594. Deves et al. Advances in Rheumatology (2021) 61:23 Page 5 of 5 13. Nickel JC, Downey J, Hunter D, Clark J. Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index. J Urol. 2001;165(3):842–5. https:// doi.org/10.1016/S0022-5347(05)66541-X. 14. Kunishima Y, Mori M, Kitamura H, Satoh H, Tsukamoto T. Prevalence of prostatitis-like symptoms in Japanese men: population-based study in a town in Hokkaido. Int J Urol. 2006;13(10):1286–9. https://doi.org/10.1111/ j.1442-2042.2004.01556.x. 15. Krieger JN, Lee SWH, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents. 2008;31(Suppl 1):S85–90. 16. Magistro G, Wagenlehner FM, Grabe M, Weidner W, Stief CG, Nickel JC. Contemporary Management of Chronic Prostatitis/chronic pelvic pain syndrome. Eur Urol. 2016;69(2):286–97. https://doi.org/10.1016/j.eururo.2015. 08.061. 17. Drannik GN, Gorpinchenko II, Kurchenko AI, Gusev SN. Efficacy study of new drug Mercureid (MSC-428) in anti-TNFα therapy for chronic prostatitis. Acta Sci Cancer Biol. 2019;3:9–16. 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An investigation about chronic prostatitis in ankylosing spondylitis

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Abstract

Background: Chronic prostatitis has been a common disease reported with high frequency in ankylosing spondylitis (AS) even from decades ago. Infectious (Chlamydia trachomatis) or non-infectious (uric acid) prostatitis can hypothetically trigger vertebral inflammation in AS. This study aimed to assess the features of chronic prostatitis in patients with AS compared to healthy controls. Methods: A cross-sectional study including male patients with AS and healthy controls who agreed to undergo a prostate examination was conducted. Structured clinical interviews, prostate physical examinations, and cytological, biochemical, and microbiological tests on urinary samples collected before and after standardized prostatic massage (pre- and post-massage test) were performed. Results: Ninety participants (45 AS patients, mean age: 52.5 ± 10.0 years, with longstanding disease, 12.4 ± 6.9 years, and 45 controls, mean age: 52.8 ± 12.1 years) were included. National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores were similar in the AS and control groups (4.0 [1.0–12.0] vs. 5.0 [1.0–8.5], p = 0.994). The frequencies of symptoms of chronic prostatitis (NIH-CPSI Pain Domain ≥4) were also similar in both groups (23.3% vs. 22.7%, p = 0.953). Results of polymerase chain reaction tests for Chlamydia trachomatis were negative in all tested urinary samples, and uric acid concentrations and leukocyte counts were similar in all pre- and post-massage urinary samples. Conclusions: In this study, chronic prostatitis occurred in male patients with AS, but its frequency and characteristics did not differ from those found in the healthy male population of similar age. Keywords: Ankylosing spondylitis, Pelvic pain, Prostatitis, Chlamydia trachomatis, Uric acid Background In 1958, Mason et al. described a strikingly high fre- Ankylosing spondylitis (AS) is the most common form of quency (83%) of prostatitis in men with AS based on the spondyloarthritis, mainly affecting the sacroiliac joints and cytological analysis of urethral fluids obtained after pros- spine. In severe cases, it can even cause progressive calcifi- tatic massage [2]. However, these results have never cation and ankylosis, often in an ascending nature through been reproduced since then. More recently, an Icelandic its longitudinal ligaments. In addition, extra-articular survey identified prostatitis in 27% of male patients with manifestations may also occur, such as uveitis [1]. AS based on medical record reviews, and the authors suggested that prostatitis was the second most frequent extra-articular manifestation of AS [3]. * Correspondence: fabricio.souza.neves@ufsc.br Graduate Program in Medical Sciences (PPGCM), Health Sciences Center Chronic prostatitis could not only be a consequence of (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil AS, but also a cause of the disease. It is hypothesized that Internal Medicine Department, Health Sciences Center (CCS), Federal the spread of pathogen-associated molecular patterns University of Santa Catarina (UFSC), Florianópolis, Brazil Full list of author information is available at the end of the article (PAMPs) or damage-associated molecular patterns © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Deves et al. Advances in Rheumatology (2021) 61:23 Page 2 of 5 (DAMPs) through the pelvic and vertebral lymphatic ves- the Bath Ankylosing Spondylitis Disease Activity Index sels from chronic prostate inflammation caused by an in- (BASDAI) [11], with further calculation of Ankylosing fectious (Chlamydia trachomatis) or non-infectious agent Spondylitis Disease Activity Score (ASDAS) [12] based on (uric acid) could induce vertebral inflammation [4]. serum C-reactive protein (CRP) levels (nephelometry). To the best of our knowledge, the characteristics of Erythrocyte sedimentation rate (ESR) (Westergren) and prostatitis in AS patients have yet to be investigated and serum prostate-specific antigen (PSA) were also measured compared to a healthy control group using current stan- (chemiluminescence) prior to prostate palpation. Partici- dardized clinical and laboratory procedures to specific- pants were defined as having prostatitis symptoms if they ally assess these hypotheses. expressed concern of perineal pain or discomfort, and The current classifications of chronic prostatitis were their NIH-CPSI pain domain score (ranging from 0 to 21) established in 1999 by the US National Institutes of was ≥4[13]. These cases were also defined as having mod- Health (NIH) as the following: chronic bacterial prosta- erate to severe prostatitis symptoms if their NIH-CPSI titis (CBP, NIH category II), inflammatory chronic pros- pain domain scores were ≥8[14]. tatitis/chronic pelvic pain syndrome (CP/CPPS, NIH The prostate physical examination was performed in category IIIa), and non-inflammatory CP/CPPS (NIH all participants by an experienced urologist (ED or CN), category IIIb) [5]. The Meares-Stamey 4-glass test [6]or with a 30-s standardized prostatic massage procedure. its simplified version by the Nickel’s 2-glass test [7], also Midstream urine samples were collected immediately be- known as the pre- and post-massage test (PPMT), are fore and after the prostatic massage. Leukocyte counts the standard criteria for diagnosis using urinary samples were performed in Neubauer chambers, cultures were collected after prostatic massage, in which NIH category performed with the seeding of urine samples in the II is confirmed with positive bacteriological culture re- growth medium ChromID CPS® (Biomerieux, France), sults and NIH category IIIa with positive leukocyte and uric acid urinary concentrations were measured by counts. However, most men with chronic prostatitis uricase reaction. Polymerase chain reaction (PCR) assays symptoms are classified as NIH IIIb, with negative cul- for Chlamydia trachomatis were also performed in post- tures and normal leukocyte counts at PPMT given the massage urinary samples of AS patients using GeneXpert lack of biomarkers for this condition. CT/NG (Xpert)® (Cepheid, USA) assay. Clinical and la- In this study, we first aimed to assess whether chronic boratory data of participants with positive microbio- prostatitis symptoms were more frequent or more se- logical test results (cultures or PCR) were then analyzed vere, and whether urinary leukocyte counts at PPMT separately from the whole group. were higher in patients with AS than in healthy controls. This study was approved by the National Committee Second, we also aimed to evaluate uric acid concentra- on Ethics in Research (44,333,115.0.0000.0121), and a tions, bacterial growth, and presence of Chlamydia tra- written informed consent was obtained from all patients. chomatis in urinary samples obtained after prostatic The sample size was estimated as 41 participants in each massage in order to investigate possible causes of group in order to verify a difference of two points in the chronic prostatitis in this group. median NIH-CPSI score (from 4 to 6) with a 95% confi- dence level and 80% statistical power. Statistical analysis Methods was performed using IBM SPSS® v20.0. Normality of We conducted a cross-sectional study including all male data distribution was tested using the Kolmogorov- patients with AS attending an outpatient rheumatology Smirnov test, and the normally distributed data are pre- public service who agreed to undergo prostate examin- sented as mean ± standard deviation, in which differ- ation between 2015 and 2019. To be included in this ences between means were tested by Student’s t-test. study, these patients needed to fulfill the 1984 New York Non-parametric data are presented as median interquar- modified criteria for AS [8]. Exclusion criteria included tile ranges, and the differences between medians were the acute presence of urinary symptoms, use of antibi- evaluated by Mann-Whitney U test. Additionally, differ- otics in the last 30 days, use of uric acid-lowering ther- ences between proportions were tested using the chi- apy, use of diuretics, and any previous diagnosis of square test. prostatic disease. The control group comprised volun- teers who attended the outpatient urology service, pre- Results senting without any current disease for prostate cancer Ninety men were included, including 45 patients with screening. AS and 45 controls. Regarding microbiological examin- All participants were interviewed using the validated ation, all tested urinary samples (post-massage urine in versions of the National Institutes of Health - Chronic the AS group) showed negative results for C. trachoma- Prostatitis Symptom Index (NIH-CPSI) [9], International tis. The cultures showed positive results with more than Prostate Symptom Score (IPSS) [10] and, in the AS group, 10 colony-forming units (CFU)/mL in both pre- and Deves et al. Advances in Rheumatology (2021) 61:23 Page 3 of 5 post-massage samples (suggesting bacterial cystitis) in Iceland [3]; however, chronic prostatitis symptoms were two participants - one AS patient with Escherichia coli equally frequent in the control group (22.7%) of our and one control with Enterococcus faecalis. The culture study. The frequencies of moderate to severe prostatitis result was positive in the post-massage sample and nega- symptoms (NIH-CPSI pain scores ≥8) were also similar tive in the pre-massage sample (suggesting bacterial between the AS (14.0%) and control groups (11.4%), prostatitis) in one AS patient with Enterococcus faecalis. which resembled the overall prevalence of chronic pros- These patients were treated as indicated and excluded tatitis in the general male population, estimated to be from further analysis. The clinical and blood laboratory 8.2% [15]. The median values of the NIH-CPSI and IPSS data of the participants included in the study are pre- scores were also compared between the AS and control sented in Table 1. All AS patients underwent regular groups. In our study, post-massage urinary leukocyte treatment, and those who were not under treatment counts were not elevated in chronic prostatitis cases in with anti-tumor necrosis factor (TNF) agents were using the AS group, which meant that all of them could be different combinations of non-steroidal anti- classified as non-inflammatory chronic prostatitis (NIH- inflammatory drugs (NSAIDs) and non-biological IIIb classification). This was the most frequent form of disease-modifying antirheumatic drugs (DMARDs). chronic prostatitis and was recently conducted to the The urinary data comparison between the groups is broader definition of “chronic pelvic pain syndrome” presented in Table 2. All cases with symptoms of prosta- (CPPS) for this entity [16]. Thus, the characteristics of titis in the AS group had leukocyte counts in post- the chronic prostatitis cases in AS patients described in massage samples lower than 20,000/mm and were clas- our study were quite similar to those expected in the sified as non-inflammatory chronic prostatitis/chronic general adult male population. Our results suggested pelvic pain syndrome (CP/CPPS, NIH-IIIb). that chronic prostatitis was a frequent finding in the adult male population, irrespective of the presence of Discussion AS. In our study, 23.3% of patients with AS had symptoms Our findings did not support the pioneering study by of chronic prostatitis (NIH-CPSI pain scores ≥4), which Mason et al., which described an impressive frequency resembled the frequency of chronic prostatitis (27%) de- of 83% of chronic prostatitis, defined by the presence of scribed in the 2010 epidemiological study conducted in ≥10 polymorphonuclear leukocytes per high-power mi- croscopy field in post-massage prostatic fluids [2]. Table 1 Clinical characteristics and blood laboratory tests of AS Leukocyte counts in the post-massage samples were patients and controls (excluding participants with positive similar in the AS and control groups in our study. How- urinary cultures - two in the AS group and one in the control ever, we may consider that current treatment of AS with group) anti-TNF agents may also be a therapy for chronic pros- AS (n = 43) Controls (n = 44) p tatitis, and they could have influenced our results, redu- Age (years) 52.5 ± 10.0 52.8 ± 12.1 0.882 cing the severity of prostatitis in the AS group (86.0% of Disease duration (years) 12.4 ± 6.9 AS patients were using anti-TNF agents) [17]. Another Anti-TNF treatment 35 (86.0%) possible confounding factor in our study was the fact BASDAI 4.9 ± 1.7 that our control group was composed of healthy men who were interested in the prostatic cancer screening. ASDAS 2.7 ± 0.6 This could have led to a bias in our control group to- NIH-CPSI 4.0 [1.0–12.0] 5.0 [1.0–8.5] 0.944 ward a higher severity of prostatitis symptoms. Before NIH-CPSI (Pain Domain) ≥ 4 10 (23.3%) 10 (22.7%) 0.953 making any definitive conclusions, we believe that our NIH-CPSI (Pain Domain) ≥ 8 6 (14.0%) 5 (11.4%) 0.716 findings need to be reassessed by other investigators. IPSS 6 [2.5–13.5] 2.5 [0.0–12.0] 0.105 Our study did not identify the etiologic factors that we IPSS > 8 14 (32.6%) 13 (29.5%) 0.499 tested as causative agents of prostatitis in patients with AS. All post-massage urinary samples showed negative PSA (ng/mL) 1.2 ± 1.1 1.8 ± 2.0 0.324 results for C. trachomatis in a highly sensitive PCR CRP (mg/L) 3.2 [2.8–3.3] 2.3 [1.0–2.6] 0.011* assay, and uric acid concentrations did not differ be- ESR (mm/h) 4 [3–5] 3 [2–5] 0.857 tween pre- and post-massage urine samples. Thus, our Uric acid (mg/dL) 5.8 ± 1.3 5.5 ± 1.2 0.624 results did not support the hypothesis that spreading of ASDAS Ankylosing spondylitis disease activity score, AS Ankylosing spondylitis, PAMPs or DAMPs from the prostate contributes to the BASDAI Bath ankylosing spondylitis disease activity index, NIH-CPSI National pathogenesis of AS [4]. However, the long duration of Institutes of Health - Chronic Prostatitis Symptom Index, IPSS International Prostate Symptom Score, PSA Prostate-specific antigen, TNF Tumor necrosis disease in our study group may have diminished urinary factor, CRP C-reactive protein, ESR Erythrocyte sedimentation rate. Data are findings that could have been present in the early course presented as mean ± standard deviation (for normally distributed data), median [interquartile range] for non-parametric data of untreated disease. Prostate assessment in the early Deves et al. Advances in Rheumatology (2021) 61:23 Page 4 of 5 Table 2 Comparison of pre- and post-massage urinary tests between AS patients and healthy controls (excluding participants with positive urinary cultures) pre-massage post-massage AS control p AS control p Leukocyte count (/mm ) 2000 [1000-6000] 2000 [1000-5250] 0.603 3000 [2000-5000] 3000 [1000-11,475] 0.704 Uric acid (mg/dL) 53.3 ± 29.4 54.9 ± 24.8 0.782 55.3 ± 24.9 51.2 ± 28.9 0.480 AS Ankylosing spondylitis; Data are presented as mean ± standard deviation (for normally distributed data) or median [interquartile range] for non-parametric data and untreated AS or undifferentiated spondyloarthtitis Author details Urology Service, University Hospital Prof. Polydoro Ernani de São Thiago could be a field for further research. HU/EBSERH, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. Graduate Program in Medical Sciences (PPGCM), Health Sciences Center (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. Conclusions Laboratory of Molecular Biology, Microbiology and Serology, Health In the present study, chronic prostatitis/chronic pelvic Sciences Center (CCS), Federal University of Santa Catarina (UFSC), pain syndrome (CP/CPPS) occurred in male patients Florianópolis, Brazil. Rheumatology Unit, University Hospital Prof. Polydoro Ernani de São Thiago HU/EBSERH, Federal University of Santa Catarina with longstanding ankylosing spondylitis (AS) under (UFSC), Florianópolis, Brazil. Internal Medicine Department, Health Sciences standard treatment (mainly based on anti-TNF agents); Center (CCS), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. however, in this population, the frequency and charac- Departamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, 3° andar, Rua Profa. Maria Flora Pausewang, teristics of prostatic disease did not differ from those Florianópolis, SC 88036-800, Brazil. found in healthy controls of similar age. Received: 23 November 2020 Accepted: 12 April 2021 Abbreviations AS: Ankylosing spondylitis; ASDAS: Ankylosing Spondylitis Disease Activity Score; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CP/ CPPS: Chronic prostatitis / Chronic pelvic pain syndrome; CPSI: Chronic References Prostatitis Symptom Index; DAMP: Damage-associated molecular pattern; 1. Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial IPSS: International Prostate Symptom Score; NIH: National Institutes of Health; Spondyloarthritis. N Engl J Med. 2016;374:2563–74. PAMP: Pathogen-associated molecular pattern; PPMT: Pre- and post-massage 2. Mason RM, Murray RS, Oates JK, Young AC. Prostatitis and ankylosing test spondylitis. Br Med J. 1958;1(5073):748–51. https://doi.org/10.1136/bmj.1. 5073.748. Acknowledgements 3. Geirsson AJ, Eyjolfsdottir H, Bjornsdottir G, Kristjansson K, Gudbjornsson B. Hospital Universitário Prof. Polydoro Ernani de São Thiago / Universidade Prevalence and clinical characteristics of ankylosing spondylitis in Iceland - a Federal de Santa Catarina / Empresa Brasileira de Serviços Hospitalares (HU/ nationwide study. Clin Exp Rheumatol. 2010;28(3):333–40. UFSC/EBSERH). 4. Pöllänen R, Sillat T, Pajarinen J, Levón J, Kaivosoja E, Konttinen YT. Microbial antigens mediate HLA-B27 diseases via TLRs. J Autoimmun. 2009;32(3-4): Authors’ contributions 172–7. https://doi.org/10.1016/j.jaut.2009.02.010. ED, RN, MCS, AFZ, IAP, MLB, FSN contributed to study design. ED, RN, MLB, 5. Krieger JN, Nyberg LJ, Nickel JC. NIH consensus definition and classification of AFZ, IAP, FSN performed clinical procedures and contributed to data prostatitis. JAMA. 1999;282(3):236–7. https://doi.org/10.1001/jama.282.3.236. collection. FHB, MCS, LKP performed laboratorial procedures and contributed 6. Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial to data collection. ED and FSN analyzed data and wrote the main prostatitis and urethritis. Investig Urol. 1968;5(5):492–518. manuscript. All authors reviewed and contributed to the final text. The 7. Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler JE, Zeitlin S, et al. How author(s) read and approved the final manuscript. does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? J Urol. 2006;176(1):119–24. https://doi.org/10.1016/S0022- Funding 5347(06)00498-8. There is no funding to be reported. 8. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York Availability of data and materials criteria. Arthritis Rheum. 1984;27(4):361–8. https://doi.org/10.1002/art.17802 The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. 9. Novotny C, Deves E, Novotny R, Rodrigues IK, Neves FS. Cultural adaptation of the National Institutes of Health--chronic prostatitis symptom index (NIH- Declarations CPSI)--to Brazilian spoken Portuguese: NIH-CPSI (Braz). Int Braz J Urol. 2013; 39(5):683–91. https://doi.org/10.1590/S1677-5538.IBJU.2013.05.11. Ethics approval and consent to participate 10. Rodrigues Netto N Jr, de Lima ML, de Andrade EF, et al. Latin American The study was approved by the National Committee for Research Ethics study on patient acceptance of the international prostate symptom score (number 44333115.0.0000.0121). Written informed consent was obtained (IPSS) in the evaluation of symptomatic benign prostatic hyperplasia. from all patients. Urology. 1997;49(1):46–9. https://doi.org/10.1016/S0090-4295(96)00372-X. 11. Shinjo SK, Gonçalves R, Gonçalves CR. Measures of clinical assessment in Consent for publication patients with Ankylosing spondylitis: review of literature. Rev Bras Reumatol. All authors read and approved the final manuscript and gave their consent 2006;46(5):340–6. https://doi.org/10.1590/S0482-50042006000500007. for publication. 12. Machado P, Landewé R, Lie E, et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and Competing interests improvement scores. Ann Rheum Dis. 2011;70(1):47–53. https://doi.org/1 The authors declare no conflict of interest. 0.1136/ard.2010.138594. Deves et al. Advances in Rheumatology (2021) 61:23 Page 5 of 5 13. Nickel JC, Downey J, Hunter D, Clark J. Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index. J Urol. 2001;165(3):842–5. https:// doi.org/10.1016/S0022-5347(05)66541-X. 14. Kunishima Y, Mori M, Kitamura H, Satoh H, Tsukamoto T. Prevalence of prostatitis-like symptoms in Japanese men: population-based study in a town in Hokkaido. Int J Urol. 2006;13(10):1286–9. https://doi.org/10.1111/ j.1442-2042.2004.01556.x. 15. Krieger JN, Lee SWH, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents. 2008;31(Suppl 1):S85–90. 16. Magistro G, Wagenlehner FM, Grabe M, Weidner W, Stief CG, Nickel JC. Contemporary Management of Chronic Prostatitis/chronic pelvic pain syndrome. Eur Urol. 2016;69(2):286–97. https://doi.org/10.1016/j.eururo.2015. 08.061. 17. Drannik GN, Gorpinchenko II, Kurchenko AI, Gusev SN. Efficacy study of new drug Mercureid (MSC-428) in anti-TNFα therapy for chronic prostatitis. Acta Sci Cancer Biol. 2019;3:9–16. 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