Interstitial Cystitis vs. UTI: What Is the Difference?

One of the most prominent examples of urinary conditions that share symptoms are urinary tract infections and interstitial cystitis/bladder pain syndrome (IC/BPS). Despite this, there are important differences between the two, and diagnostic testing plays an important role in getting an accurate diagnosis.

What is a UTI?

When most people discuss UTIs, they are usually referring to infections of the lower urinary tract, which includes the urethra and the bladder. When a UTI ascends to the upper urinary tract, it is typically referred to as pyelonephritis, or a kidney infection.

UTIs may be caused by bacterial or fungal pathogens. Most often they reach the urinary tract from the genitoanal region, which is why many of the pathogens that cause UTIs are often found in the human gastrointestinal tract as well. In other cases, bacteria or fungi may be introduced into the urinary tract from a contaminated external source.

When the bacteria or fungi are in the urinary tract, they multiply and disrupt the natural composition of the urobiome – the community of microbes that live inside the urinary tract. When they multiply, they can cause disruption to the lining of the urethra and bladder, trigger an immune response, and alter the urine itself, which affects the nerves found in the bladder wall.

What is Interstitial Cystitis/Bladder Pain Syndrome?

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition of the urinary tract that causes symptoms similar to UTIs. For some patients, these symptoms may be persistent, whereas for others, the symptoms may come and go over time. Unlike UTIs, IC/BPS is not thought to be caused by an acute infection. In fact, there is still much debate about what causes IC/BPS.

Interstitial Cystitis/Bladder Pain Syndrome Phenotypes

Those who are diagnosed with interstitial cystitis may experience dramatically different symptoms as compared to other people living with IC/BPS. As our understanding of interstitial cystitis has progressed, researchers and clinicians have worked to categorize different patients based on the symptoms they present with. Some of the proposed IC subtypes or phenotypes are included here.

Hunner-lesion vs. Non-Hunner-lesion IC/BPS

The oldest and most widely used split divides IC/BPS according to whether Hunner lesions are present. Hunner lesions (historically called Hunner’s ulcers, though they are not true ulcers), are painful, red, fragile areas of inflammation found on the bladder wall. The exact cause of these lesions is unknown, and researchers have hypothesized long-term bladder inflammation, autoimmune or immune system responses, chronic viral infections, and others. Patients with Hunner lesions were traditionally described as having ulcerative IC, and those without as non-ulcerative IC – terms you may still encounter, though current urologic practice favors the Hunner-lesion labels.

How common are Hunner lesions? Reported figures vary widely: one review notes that “the prevalence of Hunner lesion has been reported to be 5-57%”¹, and in one large research cohort, 12.5% of participants who underwent cystoscopy had them². The range is wide largely because a Hunner lesion cannot be found without looking for it, and cystoscopy rates differ between practices.

Importantly, this is no longer understood as a tidy split within one condition. Research comparing the two groups has found meaningful differences in symptoms, urinary inflammatory markers, and treatment response, concluding that “Hunner lesion is a distinct phenotype from non-Hunner lesion”². Even so, this classification fails to account for the diversity of symptom presentation experienced by patients diagnosed with IC. Other subtyping systems have been proposed that function to provide a clearer treatment direction for providers.

Nine Phenotypes of IC/BPS

In 2022, Dr. Curtis Nickel, a Canadian doctor who spent much of his career researching interstitial cystitis/bladder pain syndrome, proposed nine phenotypes to describe different symptom patterns among IC/BPS³. Importantly, these phenotypes were proposed to help providers determine potential treatment options based on the suspected root cause of a patient’s symptoms. People diagnosed with IC/BPS may fit into multiple phenotypes, making matters even more complicated. The nine phenotypes include:

• Inflammatory: Defined by bladder wall inflammation and the presence of Hunner lesions as confirmed by cystoscopy
• Infection-mediated: Patients who experience or have experienced recurrent urinary tract infections
• Neurogenic hypersensitivity: Describes patients who experience pain due to the nerves in the bladder wall becoming more sensitive
• Multiple allergies: Suggests that a patient’s IC/BPS symptoms are caused by an allergic reaction to things in their environment or diet
• Pelvic floor pain: Considers the muscle or myofascial pain that can be caused from increased pelvic floor tone or spasm
• Primary storage symptom syndrome: Describes patients whose primary symptoms pertain to urinary urgency and frequency associated with bladder pain
• Urethral pain syndrome: Patients who experience pain in the urethra
• Associated sexual pain: After sexual intercourse, the person experiences bladder, pelvic floor, vaginal, and/or vulvar pain
• IC flares: A sudden worsening of bladder urination and pain symptoms

People who have been diagnosed with IC/BPS may find value in these phenotypes, which is why we are sharing them here. However, this nine-phenotype framework is one clinician’s proposal, and it is not the categorization used by the American Urological Association (AUA), the body of clinicians and researchers that sets clinical guidelines for healthcare providers managing patients with urological issues.

AUA Subtypes of IC/BPS

In the same year Dr. Curtis Nickel described the nine phenotypes of IC/BPS, the American Urological Association released updated clinical guidelines for healthcare providers managing patients with interstitial cystitis/bladder pain syndrome. In these new guidelines, the AUA offered three different subtypes of IC/BPS⁴.

Bladder-centric IC/BPS

Bladder-centric IC/BPS refers to patients whose problem appears to originate in the bladder itself, characterized by findings such as Hunner lesions, reduced bladder capacity, and pain that improves with anesthetic instilled directly into the bladder⁴. There are a number of different theories as to what causes bladder-centric IC/BPS, the most common being a compromised bladder lining and nerve sensitivity.

The bladder is made up of several layers of tissue. The mucosal layer of the bladder is the layer that contains the urothelium, or the cells that are directly exposed to urine. The urothelium is protected by a thin coating called the glycosaminoglycan (GAG) layer. This mucus-like layer protects the rest of the bladder wall from infection, toxins, and harsh chemicals that are naturally formed as a byproduct of creating urine. One leading hypothesis holds that if this layer is compromised in some manner, it may allow bacteria, toxins, and harsh chemicals found in the bladder to reach nerves in the bladder wall, causing urinary symptoms⁵. This is an influential idea with a substantial body of work behind it, but it remains a hypothesis rather than established mechanism.

On the other hand, rather than the protective layer being compromised, the nerves located in the bladder wall may be hypersensitive, meaning that it takes very little input to have them send the signals that produce urinary symptoms. Even in individuals without IC/BPS, the GAG layer does not keep out bacteria, toxins, and harsh chemicals entirely. When nerve sensitivity is thought to be the cause, even small amounts that reach the nerves may be enough to cause symptoms. Nerve sensitivity itself can be caused by a number of things, including urinary tract infections, nervous system disorders, certain foods/medications, and damage to the tissues in the bladder.

Pelvic floor-centric IC/BPS

Pelvic floor-centric IC/BPS describes patients who experience pelvic floor pain, caused by heightened muscle tone or spasms of the pelvic floor muscles or following sexual activity. The pelvic floor is a layer of muscles and tissue that supports the internal organs, helps control the bladder and bowels, and assists with sexual function. When the resting state of the pelvic floor is tighter than the average person’s, the muscles and tissues may apply pressure to the urinary tract, producing symptoms such as urinary urgency or frequency and pelvic pain. There are a number of reasons why a person’s pelvic floor may have heightened muscle tone. Pelvic floor therapy may help patients with pelvic floor-centric IC/BPS.

Widespread pain IC/BPS

Perhaps the most misunderstood subtype is widespread pain IC/BPS. This subtype of IC/BPS is characterized by “widespread pain” due to chronic overlapping pain conditions (COPCs) that can cause or heighten pain both within and outside the urinary tract, such as irritable bowel syndrome, fibromyalgia, and others². Because of the number and diversity of conditions that can cause chronic pain, it has proved challenging for researchers to characterize how each contributes to IC/BPS symptoms.

What symptoms do UTIs and IC/BPS share?

UTIs and IC/BPS have a number of symptoms in common, whereas others are more specific to each condition. The table below outlines which symptoms UTI and IC/BPS share, as well as symptoms that are more commonly tied to one of the two.

UTI and IC/BPS symptoms

*Cloudy and strong-smelling urine are poor discriminators – both are common with dehydration, diet, and certain medications. Visible blood in the urine should always be evaluated by a clinician regardless of which condition is suspected.

While the table above is a useful reference, a few patterns are worth spelling out, because they are often what sends someone searching for answers in the first place. UTIs tend to come on suddenly and escalate quickly, and they frequently bring signs that point clearly to infection: cloudy or strong-smelling urine, and in more serious cases, fever or chills. IC/BPS, by contrast, tends to be persistent rather than sudden, lasting weeks or months, and for some patients, it carries two features that a UTI usually does not: pain during sexual activity and bladder pain that builds as the bladder fills and eases after urinating. The most telling difference, though, is based on diagnostic test results – not symptoms.

How is a UTI diagnosed?

A healthcare provider will take into account a patient’s current symptoms, their medical history, and laboratory test results to diagnose them with a urinary tract infection. The current standard of care for laboratory testing includes two types of tests: urinalysis and standard urine culture. Urinalysis typically looks at different physical and chemical properties of a patient’s urine sample. These physical and chemical properties indicate the presence of infection – they do not necessarily tell the healthcare provider what pathogen is present. That is what standard urine culture is for.

Standard urine culture works by attempting to grow any pathogens that may be present in a urine sample on a petri dish in a lab. After putting urine into the petri dish and waiting for a few days, a laboratory technician will look at what has grown. While widely available and considered the standard of care, there are a number of limitations that both patients and their providers should be made aware of.

A significant proportion of urine cultures fail to identify the pathogen that is causing a patient’s symptoms. This is referred to as a culture-negative UTI, which can happen when the pathogen causing the UTI cannot grow in the laboratory, grows too slowly to be found by the person looking at the plate, or is below the threshold required for reporting the sample as a positive. Sometimes, laboratories may report urine culture results as contaminated when multiple pathogens are found, despite the fact that some UTIs can be caused by multiple pathogens at once. One study comparing standard urine culture against an enhanced protocol in women with UTI-like symptoms found that standard culture missed 67% of uropathogens overall, and that among participants whose pathogen was missed, 36% reported no symptom resolution after being treated based on their standard culture result⁶.

More advanced diagnostic testing options for UTI symptoms exist. Called molecular diagnostics, these types of tests look for pathogen DNA present in urine samples rather than trying to grow them in a lab. Biotia specializes in clinical metagenomics, a specific type of molecular diagnostic that outperforms standard urine culture for UTI diagnosis⁷.

How is Interstitial Cystitis/Bladder Pain Syndrome diagnosed?

Interstitial Cystitis or Bladder Pain Syndrome does not have a specific diagnostic test. It is diagnosed by exclusion of other potential causes, including urinary tract infections⁴. Generally, patients must meet the following three baseline criteria to be considered for an IC/BPS diagnosis:

• No identifiable infection: The AUA definition requires that symptoms occur “in the absence of infection or other identifiable causes”⁴. In practice, this is established through urinalysis and urine culture – a point we return to below
• Chronicity: Urinary symptoms must be present for more than six weeks⁴
• Specific sensation: Experiencing an unpleasant bladder sensation (such as pain, pressure, or discomfort) that worsens as the bladder fills and temporarily improves after emptying⁴

For patients experiencing chronic or persistent urinary symptoms who have already tested negative for UTI by urinalysis and urine culture, a number of other exams, tests, or procedures may be performed to provide additional information to help arrive at an IC/BPS diagnosis. These can include:

• Pelvic examination: The clinician will thoroughly examine the pelvic region to map pain and rule out other potential conditions, such as endometriosis in women, prostatitis in men, or pelvic floor dysfunction
• Laboratory testing: Urine cytology may be performed to look for abnormal cells that may indicate the presence of a cancer affecting the urinary tract
• Cystoscopy: A procedure in which a clinician inserts a small camera into the urinary tract to examine the bladder lining, particularly recommended when Hunner lesions are suspected
• Bladder biopsy: During cystoscopy, the clinician may take a small tissue sample of the bladder lining, especially if any unusual tissue masses or lesions are present

After thorough evaluation and other potential conditions ruled out, the clinician may settle on an IC/BPS diagnosis. While receiving a diagnosis for a chronic condition can feel disheartening, there are a number of evidence-based symptom management strategies, patient support groups, and other resources to help patients living with IC/BPS. For more information, you can visit the Interstitial Cystitis Association.

When an IC/BPS diagnosis is really a missed UTI

As one of the diagnostic criteria for IC/BPS is the absence of infection – established in practice through negative urine culture results – what does this mean when standard urine culture is known to produce a significant number of false-negative test results? What if the patient’s symptoms were being caused by a pathogen that simply could not grow in urine culture? These questions have real implications for both patients and their providers, and they are questions Biotia is working to answer.

They are not hypothetical questions, either. In a case-control study of 314 women with recent-onset IC/PBS symptoms, with medical records reviewed for 98% of participants, investigators found evidence of a urinary tract infection at the onset of IC/PBS in 18% to 36% of women, depending on the diagnostic method applied⁸. The authors are careful about what this shows, concluding that “a proportion, probably a minority, of women at IC/PBS onset had evidence of UTI or inflammation”⁸. A minority is not nothing: if somewhere between one in five and one in three women had evidence of infection when their symptoms began, then how confidently infection was excluded is worth asking about – particularly for a diagnosis defined by that exclusion.

When patients and providers receive “normal”, “no growth”, “negative”, or “contaminated” urine culture results in the face of persistent urinary symptoms, it is worth pausing to consider whether there may be more to the story. Rather than settling on an IC/BPS diagnosis, it may be worth considering advanced infectious disease testing, such as clinical metagenomic-based diagnostic tests, to more confidently rule out other factors that could be influencing the symptoms.

If a person’s symptoms are due to a UTI that was missed by urine culture, advanced infectious disease testing allows the patient to receive proper treatment faster. Alternatively, if the test is negative, the patient can get any necessary treatments or support for IC/BPS with more confidence in the diagnosis. It is also worth noting the psychological benefits of eliminating doubts that may surround a sensitive health condition.

When a UTI diagnosis is really IC/BPS

The confusion runs in both directions. In many instances, Interstitial Cystitis/Bladder Pain Syndrome may be misdiagnosed as a UTI. When patients visit their provider after the onset of urinary symptoms, the provider may not always order a urine culture. They may instead rely on their knowledge of their patient’s medical history and prescribe antibiotic medication empirically. In other cases, the provider may have ordered a urine culture that came back “normal”, “no growth”, “negative”, or “contaminated” and given the patient an antibiotic medication anyway, assuming that the urine culture failed.

IC/BPS is not an infection, so antibiotics do not address what is causing the symptoms. A patient who has completed course after course of antibiotics without lasting improvement – especially alongside repeatedly negative cultures – is a patient whose diagnosis deserves another look.

It is tempting to treat the response to antibiotics as a diagnostic test in itself, but it is not a reliable one. Uncomplicated UTIs can resolve on their own, IC/BPS flares remit spontaneously by definition, and placebo response in bladder pain is substantial. Improvement on antibiotics is suggestive of infection, but it does not confirm one – and it is not evidence that the next course will work either. Repeated antibiotic courses without a confirmed pathogen are a reason to test rather than a reason to keep treating.

Advanced infectious disease testing is warranted in this direction too. Clinical metagenomic-based diagnostic tests, a type of next-generation sequencing, offer broader pathogen coverage to more confidently rule out UTI, which supports moving forward with IC/BPS management. And in the cases where a UTI-causing pathogen that was missed by urine culture is found, these tests can also provide insights into antimicrobial resistance. This enables providers to select the optimal antibiotic or antifungal medication to treat your symptoms rather than prescribing empirically.

Can you have UTI and IC/BPS at the same time?

Yes, a patient can have both a UTI and IC/BPS at the same time. This is one of the most important – and most overlooked – points for anyone living with bladder symptoms: interstitial cystitis and UTI are not mutually exclusive.

A subset of people with IC/BPS experience recurrent urinary tract infections associated with symptom flares⁹. Many describe their baseline urgency, frequency, and pelvic pain intensifying well beyond their normal day-to-day symptoms when an infection develops. Having IC/BPS does not protect against infection, and a new infection on an already irritated bladder can be considerably more uncomfortable than either problem alone.

What happens when the infection is treated is more interesting than it may seem. In a small secondary analysis of 16 women with both recurrent UTI and IC/BPS symptoms, reducing infection episodes was associated not only with fewer UTIs but with improvement in long-standing bladder symptoms – 8 of the 16 reported “significant or almost complete resolution” of their long-term bladder discomfort and urinary symptoms⁹. The authors propose that some cases of IC/BPS may be driven by a hypersensitivity response to bacteria in the urinary tract⁹. This was an uncontrolled, hypothesis-generating study and should be read as a signal rather than a conclusion, but it suggests the relationship between infection and IC/BPS symptoms is not always a matter of two separate problems sitting side by side.

The practical implication for patients is this: in some people, treating an infection improves the bladder symptoms substantially, potentially because infection was driving them. In others it will not, because the symptoms were never infectious to begin with. Symptoms alone cannot tell you which group you are in, which is a large part of why establishing whether infection is present matters so much.

IC/BPS vs. UTI: Getting the right diagnosis

Given the overlap in symptoms between IC/BPS and UTI, the limitations of standard urine culture to accurately diagnose UTIs, and the risks of misdiagnosis, it is clear that differentiating between the two can be difficult. Accurate and timely diagnosis is important whether it be a UTI or IC/BPS, particularly given the evidence that a meaningful minority of patients have signs of infection at the time their IC/BPS symptoms begin. Advanced infectious disease testing, such as next-generation sequencing, may be able to help ease anxiety surrounding diagnosis – especially in cases where standard urine culture results were negative, giving patients and providers clear next steps to getting urinary symptoms under control.