SPECIAL FEATURE: STERILE PYURIA ASSESSMENT OF STERILE PYURIA IN PRIMARY CARE In the article the authors look at how to investigate patients with the finding of sterile pyuria and when to refer Dr Jonathan Sterile pyuria can be broadly de!ned as the presence of management of non-visible haematuria in primary Rees leucocytes in the urine in the absence of demonstrable care is now well described, 1 but guidance on sterile GP with urinary tract infection. It is a relatively common pyuria is entirely absent. This article aims to provide special interest problem, with a wide range of causes, encountered a framework for assessing patients with sterile pyuria, in Urology, frequently in both primary and secondary care settings, but in the absence of a good evidence base must Backwell although there is no data to suggest the estimated represent basic guidance only, with individualised & Nailsea prevalence in either a community or hospital setting. management decisions required when faced with this Medical Group Indeed, the medical literature, in all its vastness, problem in primary care. contains remarkably little research or guidance How can we define sterile pyuria? Jonathan regarding this problem, leaving many primary care Manley physicians in the dark as to how best to manage their If we take a pragmatic approach, it is easiest to de!ne patients. This results in inconsistent management, sterile pyuria along similar lines to those recommended Specialist ranging from ignoring the !nding completely to over- for non-visible haematuria. Thus, a suggested working Trainee in investigation and possibly unnecessary secondary de!nition for use in primary care is: Urology, care referral. Urine dipstick positive for leucocytes in the absence Gloucestershire There are many overlaps between the !nding of of dipstick haematuria or nitrites, with subsequent Hospitals NHS sterile pyuria and that of asymptomatic non-visible MSU showing no bacterial growth Foundation haematuria – both are fairly common incidental Again, to be consistent with non-visible haematuria Trust. !ndings, both with relatively low risk of signi!cant guidelines, 1 it would appear sensible to consider a underlying pathology, but both with potential causes dipstick showing only a trace of leucocytes to be a that we would not want to miss. The recommended negative result, which can be safely ignored, and to treat “+” or greater as a positive result. There is no BOX 1: CAUSES OF STERILE PYURIA 2 prognostic difference between “+” or “+++” of red Common Uncommon Rare blood cells for patients with non-visible haematuria – it is not known whether the same applies in sterile pyuria, Urinary tract Bladder cancer* Genito-urinary but it would seem to be a reasonable assumption. infection tuberculosis** An MSU is sent to allow urine culture to detect the Sexually transmitted Interstitial cystitis Schistosomiasis** presence of organisms, and not to con!rm the presence infection (especially of leucocytes, which may degrade while in transit to the chlamydia) laboratory, thus creating a false negative result. Post-menopausal Renal disease Sarcoidosis If pyuria is seen on microscopy in the absence atrophic vaginitis / of prior dipstick analysis, it is unclear on the exact trigonitis threshold for clinical signi!cance, although a value of >10 white blood cells per μl of urine may be sensible. Balanitis Lupus Kawasaki disease It is important to ensure that a urine specimen is Prostatitis Ketamine abuse* Cyanotic congenital taken clean-catch and mid-stream to reduce the risk of heart disease contamination. Urine from catheters or urostomies will Appendicitis or almost always contain white cells and cannot therefore diverticulitis be interpreted, except in the context of symptoms, e.g. of suspected infection. Renal calculi Non-urological Causes of sterile pyuria (see Box 1) 2 infections e.g. pneumonia Infectious causes *: usually but not exclusively also with non-visible or visible haematuria The very name, sterile pyuria, is potentially misleading, **: rare causes in a UK population but common causes on a global perspective as the commonest cause for the !nding is undoubtedly 34 | MayJune 2015 | SPECIAL FEATURE: STERILE PYURIA may develop many years after the original infection. If schistosomiasis is considered a possibility, urine There are many microscopy for ova plus sending blood for ELISA overlaps between antigen testing is recommended, but it would be worth discussing with the local microbiology the nding of sterile department prior to testing to ensure appropriate tests pyuria and that of are performed. Non-urological infections can also cause sterile asymptomatic non- pyuria. 5 A small study of 210 patients (adults and visible haematuria children) admitted to hospital with a variety of conditions including pneumonia, intra-abdominal infections and bacterial septicaemia, found pyuria in almost one-third of cases. infection of some sort. This may be a partially treated urinary tract infection (even one dose of antibiotic Non-infectious causes before urine collection), a recently treated UTI (pyuria Non-infectious pathology of the urinary tract may often remains for one-two weeks after clearing cause sterile pyuria – tumours of the kidney or bladder infection), a UTI with fastidious or slow growing can be responsible, although the exact risk associated atypical organisms that fail to grow during standard with isolated asymptomatic sterile pyuria, while laboratory culture, or a sexually transmitted infection, not stated in the medical literature, is likely to be particularly chlamydia in the asymptomatic sexually extremely low. Intersitial cystitis, or painful bladder active person. Patients with typical symptoms of a UTI syndrome, may also be a cause of sterile pyuria, but and sterile pyuria should be treated empirically with will present with the typical symptoms of this condition antibiotics and urine retested after treatment to ensure – suprapubic pain (especially with a full bladder), resolution of the pyuria (i.e. treating for probable UTI dysuria and urinary frequency. This condition should with a fastidious organism). be suspected on clinical grounds and requires further Other, symptomatic infective causes are also urological investigation. possible – urethritis (due to chlamydia or gonorrhoea), In older women, decreased oestrogenisation of prostatitis, balanitis and vulvo-vaginitis can cause the vulva, vagina and bladder can lead to a degree pyuria, but symptoms should make these diagnoses of in$ammation, making sterile pyuria a relatively apparent. Likewise, extrinsic irritation of the ureters common !nding. In this situation, treatment of women or bladder by appendicitis or diverticulitis may with symptomatic atrophic vaginitis with topical cause pyuria. oestrogen therapy can lead to resolution of sterile On a global scale, infection with tuberculosis (TB) pyuria. However, it is dif!cult to justify treatment in the or schistosomiasis are common causes of pyuria, but absence of symptoms, purely to see clearance of white clearly these conditions are rare in a UK population cells from the urine. without other risk factors. Genito-urinary TB is often asymptomatic, but may present with urinary symptoms (especially frequency and urgency), loin pain (from upper tract obstruction), haematuria and non-speci!c On a global scale, symptoms such as fever, weight loss, night sweats and malaise. The diagnosis should be considered in infection with patients with sterile pyuria who have previous contact with active TB, recent arrival from a high risk country, tuberculosis (TB) the immuno-compromised or health care workers in or schistosomiasis settings with high TB prevalence. Testing for TB should be reserved for those considered to be at risk, based are common causes on symptoms and these risk factors – urine should be of pyuria cultured for acid and alcohol fast bacilli (AAFB) using three early morning urine specimens, and upper-tract imaging (e.g. ultrasound) should be performed. Schistosomiasis haematobium infection (a tropical Sterile pyuria is a common !nding in pregnancy – disease also known as bilharzia) may cause sterile usually due to contamination by physiological vaginal pyuria, as well as cystitis like symptoms or haematuria discharge. It is vital, however, to con!dently exclude the and a travel history should be taken for persistent possibility of urinary tract infection, as asymptomatic unexplained pyuria. High risk areas are Africa bacteriuria is such an important preventable cause (especially Lake Malawi) and the Mediterranean part of pre-term labour. If pyuria is found, it is worth of the Middle East, particularly in people who have repeating the urine specimen after cleaning the vulva been swimming in open water. Urinary symptoms and rigorously ensuring a true clean-catch specimen. | May/June 2015 | 35 SPECIAL FEATURE: STERILE PYURIA is 16-34 years). Patients with urinary symptoms with TABLE 1: RENAL CAUSES OF STERILE PYURIA: sterile pyuria and/or haematuria should be strongly Papillary necrosis (e.g. secondary to analgesic nephropathy, encouraged to discontinue ketamine use. diabetic nephropathy, sickle cell disease nephropathy) Tubulo-interstitial diseases (interstitial nephritis, lupus nephritis, Investigating sterile pyuria sarcoidosis) Again it seems reasonable to mirror the guidance from the British Association of Urological Surgeons and the Structural causes (e.g. polycystic kidney disease) Renal Association (www.renal.org) on the assessment of non-visible haematuria