Podcast - Sterile pyuria: and now, what?! - Primary Care Guidelines | Lyssna här

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For the non-visible haematuria video:

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My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode, I go through the interpretation and initial management of sterile pyuria, always focusing on what is relevant in Primary Care only. The information is based on based on published medical articles in the British Journal of General Practice as well as the New England Journal of Medicine. The link to them can be found below. Please note that the content on this channel reflects my professional interpretation/summary of the guidance and that I am in no way affiliated with, employed by or funded/sponsored by any of the institutions.

I am not giving medical advice; this video is intended for health care professionals; it is only my summary and my interpretation of the information consulted. You must always use your clinical judgement.

There is a YouTube version of this and other videos that you can access here:

· The Practical GP YouTube Channel:

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

The resources consulted can be found here:

Sterile pyuria: a practical management guide - British Journal of General Practice 2016; 66 (644): e225-e227:

· https://bjgp.org/content/66/644/e225

Sterile Pyuria – Review article NEJM - N Engl J Med 2015; 372:1048-1054:

· https://www.nejm.org/doi/10.1056/NEJMra1410052?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov

The non-visible haematuria video can be found here:

· https://youtu.be/SaizjWg7Fng

The non-visible haematuria podcast can be found here:

· https://youtu.be/bIKhn43o7ZI

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Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I’m Fernando, a GP in the UK. Today we are going to go through the interpretation and initial management of sterile pyuria, always focusing on what is relevant in Primary Care only.

The information is based on two relevant medical publications in the British Journal of General Practice as well as the New England Journal of Medicine. The links to them are in the episode description.

If you want a reminder on how to manage non-visible haematuria, please watch the corresponding episode on this channel. The link is in the episode description too.

Right, so let’s jump into it.

Sterile pyuria is not an uncommon finding in clinical practice. Nine per cent of patients with lower urinary symptoms, and who are suspected of a UTI, are found to have sterile pyuria. It can be higher in specific populations and sterile pyuria is more common among women because of the higher incidence of pelvic infection.

Sterile pyuria continues to pose a diagnostic conundrum because there are no guidelines on its management. Furthermore, no agreed definition for sterile pyuria exists. It is simply the presence of white blood cells in the urine, in the absence of infection. Some authors have defined it as the presence of 10 or more white cells per cubic millimetre of urine, 3 or more white cells per field on microscopy, or a urinary dipstick test that is positive for leucocytes, all of this in the absence of positive urine cultures.

Sterile pyuria can also be associated with haematuria, proteinuria, and casts, complicating the diagnosis.

(Causes)

Looking at the cause, broadly speaking, sterile pyuria may be classified as infectious or non-infectious.

Let’s look at the infectious causes first. Simple bacterial UTIs are extremely common. However, a recently treated UTI, usually within 2 weeks, or even after a single dose of antibiotics, can present as sterile pyuria. Therefore, we should check whether a recent course of antibiotics has been given and, if we are treating a UTI and requesting a urine culture, we should ensure that we advise patients to collect the urine sample before taking the first dose of antibiotics.

When considering UTIs, we also need to take into account that, although colony counts greater than 100,000 colony-forming units per millilitre of urine (CFU/ml) have historically been used to diagnose a UTI, bacterial colony counts as low as 1000 colony-forming units per millilitre (CFU/ml) can be a sign of bacteriuria. So, it is important to consider that lower bacterial counts can still be associated with a urinary tract infection, even though the urine culture may be reported as negative, so repeating the cultures may be necessary.

Sexually transmitted infections should be considered in the younger, sexually active population. Chlamydia is the most common cause, but others are also possible such as, for example, gonorrhoea, mycoplasma, trichomonas, genital herpes and HPV. Therefore, a sexual history should always be sought in young patients presenting with urinary symptoms.

In the older population, prostatitis, cystourethritis, and balanitis may also present as sterile pyuria. Furthermore, common viruses such as adenovirus and parasitic infections such as schistosomiasis can also be a potential cause, so we should enquire about foreign travel.

In patients with chronic sterile pyuria, atypical infection should be considered, in particular renal tuberculosis. We should suspect it in patients coming from endemic regions, the immunocompromised, and those presenting with unintentional weight loss. Genitourinary tuberculosis is the most common form of non-pulmonary tuberculosis after lymphadenopathy.

And finally, fungal infections can also be a cause of sterile pyuria.

Pyuria has also been noted in the absence of infection, so let’s have a look now at the non-infectious causes. Some obvious causes include:

· Pelvic inflammation secondary to, for example, appendicitis.

· Radiotherapy involving the pelvis and urinary tract

· Instrumentation like, for example, a cystoscopy and

· Indwelling catheters and ureteric stents. However, when there is not a clear cause we must consider other causes such as

· Local disease, including malignancy

· Systemic disease, and

· medication. Let’s look at these causes in a little bit more detail:

Sterile pyuria can be found in patients with local disease, from benign conditions like renal stones to malignancy. When presenting with either visible or non-visible haematuria, we should always investigate the cause, referring the patient if appropriate. Possible causes of sterile pyuria with haematuria are:

· Malignancy

· Polycystic kidney disease and

· Renal papillary necrosis, which can be typically seen in patients with diabetes, sickle cell disease, and long-term analgesic use.

Systemic conditions that can cause sterile pyuria include SLE, Kawasaki disease, diabetes, sarcoidosis, and malignant hypertension.

There are also physiological causes such as post-menopausal changes and pregnancy. Therefore, repeated sterile pyuria with negative cultures during antenatal checks could be physiological, although we should always exclude other conditions too.

Finally, medications are also a common cause of sterile pyuria. Olsalazine and mesalazine, used to treat inflammatory bowel disease, and nitrofurantoin have been reported to cause sterile pyuria. Additionally, penicillin-based antibiotics, non-steroidal anti-inflammatory drugs, aspirin, PPIs, and diuretics have also been involved in acute drug reactions, causing tubulointerstitial nephritis with sterile pyuria.

Let’s summarise all this by looking at this algorithm published in the British Journal of general Practice:

So, the common causes include infectious and non-infectious.

Infectious causes include STIs, as well as parasitic and atypical infections

And examples are unresolved UTIs, prostatitis, cystourethritis, balanitis, post antibiotic pyuria, chlamydia, gonorrhoea, schistosomiasis, and adenoviruses.

In the non-infectious causes

If there is unintentional weight loss

We will think of malignancy or renal tract TB.

If there is a history of previous surgical procedures or pelvic radiotherapy

Then, the cause could be indwelling catheters, ureteric stents, cystoscopy and post intrabdominal surgery or pelvic radiation.

If there is haematuria

We will think of renal calculi, malignancy, polycystic kidney disease, renal papillary necrosis and interstitial nephritis.

I we are thinking of systemic conditions,

We will consider SLE, Kawasaki, diabetes, pregnancy, malignant hypertension, post-menopausal changes and interstitial cystitis.

And, finally, if we are thinking of drugs

We will check for the use of NSAIDs, steroids, olsalazine, penicillin, vancomycin, and PPIs.

(MANAGEMENT)

How do we manage sterile pyuria?

First of all, we will start with a detailed clinical history and examination to help us identify a possible cause.

General findings like hypertension, skin rashes, and oedema, can be signs of more serious underlying pathology.

Abdominal and pelvic examination, including a digital rectal examination and vaginal examination in females may be necessary.

Then we will move to carry out some investigations, generally in the form of urine tests, blood tests and imaging of the urinary tract.

As urine tests, urinalysis and urine cultures are the prime investigations for sterile pyuria. Importantly, sterile pyuria is not always sterile, so, as mentioned earlier, repeating urine cultures often yields a positive result on subsequent testing. Contamination, especially with vaginal leucocytes in females, is common, and samples should always be collected as a midstream sample.

If sterile pyuria is detected during routine screening tests sending a urine sample for culture is recommended, with onward review for further investigation.

For sexually active patients, a urine test or, in some cases, swabs for Chlamydia and Gonorrhoea are also recommended.

Other investigations to be considered are routine blood tests including a full blood count, renal, and liver function tests.

Eosinophilia is an important marker of drug-induced interstitial nephritis, but may also be seen in parasitic infections such as schistosomiasis.

Finally, if imaging is required, the type depends on the presentation. A renal tract ultrasound scan or CT is recommended when renal stones, masses, or nephritis are differential diagnoses. Other procedures such as a cystoscopy are recommended if tumours are suspected, although they also have the advantage of diagnosing and treating benign pathologies such as bladder stones.

The NEJM has proposed a flow chart on how to manage patients presenting with sterile pyuria. Let’s have a look at it.

If a patient presents with sterile pyuria, we will review the clinical presentation.

If the symptoms are primarily local, like pelvic pain, urinary or urethral symptoms

Then we will investigate for conditions like, for example, STDs, prostatitis and pelvic inflammatory disease.

And if these are not detected we will consider alternative diagnoses like urinary stones, foreign bodies, interstitial cystitis, bladder tumours and schistosomiasis, particularly if the patient has travelled to a high-risk area such as Africa.

On the other hand, if the symptoms are primarily systemic, like fever, other systemic and urinary symptoms or back, abdominal or pelvic pain

We will reassess for bacterial infection by repeating bacteriological studies and cultures.

And if bacteria are found, then we will treat accordingly.

And if bacteria are not detected

We will consider alternative diagnoses such as tuberculosis or fungal infections, especially if they are immunocompromised or they have been in endemic or high-risk areas.

And if no infection is detected, then appropriate referral will be the next step.

And that is it, a brief review of the causes and initial management of sterile pyuria.

We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.

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