Idiopathic cystitis (Proceedings)

Feline lower urinary tract diseases are characterized by hematuria, pollakiuria, and dysuria, and are common problems encountered in feline practice. It is estimated that they affect over one half million cats in the United States annually. Although there are numerous recognized causes of these signs, the exact cause is never identified in the majority of cases. These cases are classified as feline idiopathic cystitis (FIC) and may represent up to 64-68% of non-obstructive lower urinary tract diseases. The biologic behavior of FIC is variable and may be complicated by urinary obstruction due to urethral plugs. Clinical signs in non-obstructed cats often resolve in 2-3 days without therapy, although in about 40% of cats, signs may be frequently recurrent or may persist for longer than 3 weeks. Cats with persistent signs or frequent recurrence of signs are classified as having chronic FIC.

There are numerous theories regarding the etiopathogenesis of FIC. These theories include roles for external factors (i.e. crystalluria, uropathogens such as viruses, urine toxins...), intrinsic bladder factors (i.e. autoimmunity, increased uroepithelial permeability, alteration of the mucosal glycosaminoglycan layer, mast cell infiltration, neurogenic inflammation...), or more internal/systemic problems (i.e. developmental abnormalities, abnormal neurologic or hormonal stress responses...). Unfortunately, identifying basic pathologic processes has been hindered by lack of comprehensive histopathologic descriptions of tissue samples (including urinary bladder and other organ systems) and the challenge of clearly establishing a progression or link between cystitis and con-morbid abnormalities in other systems.

Clinical features of FIC are similar to those observed in an idiopathic lower urinary tract disease of humans referred to as interstitial cystitis. Interstitial cystitis in humans is a chronic, persistent, and debilitating disorder characterized by pollakiuria, dysuria, lower abdominal pain, normal urinalysis results and distinctive cystoscopic lesions called glomerulations. Similarities between the clinical features of idiopathic cystitis in cats and interstitial cystitis in humans have prompted speculation that these two conditions are analogous to one another. These similarities also seem to extend to underlying pathophysiologic disturbances and histopathologic lesions. For this reason, several studies have been performed in cats to try to identify beneficial effects for treatments that have shown promise in human medicine.

One of the primary difficulties in any clinical trial for this condition is identifying when a medication has a truly beneficial effect since the majority of cats will recover from their symptoms within 5-7 days without (or despite) therapy. Thus, it is exceptionally important to determine whether there was adequate placebo control and appropriate masking of investigators and clients when evaluating these studies.

Diagnosis

First of all, in order to diagnose this condition, all other reasonable potential causes of lower urinary tract disease must be ruled out. This usually requires numerous diagnostic tests including a complete medical history and physical examination, minimum data base (Chemistry, CBC, UA), urine culture, imaging (radiographs, ultrasound, contrast studies, cystoscopy), and potentially others (viral testing, histopathology, etc...).

Most of the time in practice the diagnosis is presumptive based upon the cat's clinical symptoms and some of the tests listed here. This is reasonable. However, if the cat is not improving after a week, further evaluation might be indicated to look for an identifiable cause of signs.

Recent evidence has also been presented which suggests that a thorough evaluation of these patients to identify abnormalities in other systems (e.g. chronic gastrointestinal, behavioral, endocrine, or cardiovascular disorders) is warranted.

Treatment options

At this time, because the underlying cause of FIC remains a mystery, current options for treatment are primarily based upon symptomatic relief, practice experience, and theoretical benefits. As we learn more about the disease, there may be more information available to allow identification of better options. Currently we do not expect that any treatment option will "cure" a cat of this condition. Many cats may not have more than one episode, and no treatment is recommended for these individuals. For those cats that have chronic symptoms or frequently recurrent episodes, some of the potential treatment options are listed below. The goal of therapy is to reduce the severity of the symptoms and/or increase the time between episodes.

Interestingly, there is even some evidence that simply taking extra time to explain this disease and convey a sense of understanding and empathy for the client's frustrations may help improve the perceived clinical outcome.

Diet and water intake

The primary consideration here is to increase the overall water intake of the cat and by extension decrease the concentration of the urine. The primary means of accomplishing this in most cases is by using the canned food formulation of the cat's normal diet. Any change of diet formulation should not be made suddenly, but rather gradually so that there is no added stress associated with the transition.

In addition to the increase water content of canned food, owners should be encouraged to try to increase their cat's water intake in other ways. Consider follow up examinations to monitor the urine specific gravity to help determine if the clients are successful in improving water intake.

There does not appear to be any significant benefit to acidifying the urine or attempting to reduce struvite crystalluria in cats with FIC.

Multimodal environmental enrichment

There is some evidence that stress may play a role in the pathogenesis of FIC. Some cats seem to demonstrate improvement when the owners focus on maintaining a minimally stressful and enriched environment. Primary areas of focus include attention to litter box management, access to and location of food and water resources, social interactions (other pets and owners), toys and other enrichments, and awareness of anything else that seems to impact the cat's overall stress level.

One good source of information about environmental enrichment for cats is the website for the indoor pet initiative at http://indoorpet.osu.edu/. This site has information for veterinarians and pet owners.

There is another talk and a separate proceeding document being given to the technicians at this conference with a bit more focus on different aspects of environmental enrichment.

Feline pheromone (Feliway®)

There is no available data about the efficacy of this product in cases of FIC, but it is used by some in an attempt to help minimize environmental stresses.

Tricyclic antidepressants (amitriptyline, clomipramine) and other antidepressants/anxiolytics (buspirone, fluoxetine)

There are conflicting reports about the efficacy of TCAs, and amitriptyline in particular, for cats with FIC. There are several potential benefits including analgesia, anxiety reduction, mast cell stabilization, and antagonism of glutamate receptors and sodium channels. Even the proponents of TCA use do not recommend it for acute treatment, but rather for those cases that are severe and persistent or frequently recurrent and for which environmental enrichment, increased water intake and pheromones have not helped. Furthermore, if TCA are discontinued it must be done slowly as a taper over 2-3 weeks to avoid rebound withdrawal symptoms. Lastly, although there are no studies implicating specific drug interactions in cats, TCAs are metabolized by the cytochrome P450 system so caution is recommended when using them in conjunction with other medications.

Other antidepressants have also been recommended by some for cats with FIC, but there is even less evidence to support their use. This doesn't mean that they would be ineffective, just that further study is needed.

GAGs (pentosan polysulfate, Cosequin)

There is some evidence in cats and humans that there are alterations in the GAGs in the urinary bladder. Because of this, GAG replacement therapy has been attempted in humans and a subset of patients did demonstrate some short term benefit. There appear to be numerous potential reasons for this improvement, but the exact mechanism remains unknown.

There is no published evidence to support the use of GAGs in cats with FIC. There are also very real questions about the appropriate delivery method. However, many people feel that side effects are likely to be limited and minor, and therefore will recommend trying GAGs in refractory/severe FIC cases.

Analgesics

There are no controlled studies of specifically analgesic medications in cats with FIC. It does appear that the condition is very uncomfortable and humans with interstitial cystitis report significant pain during symptomatic episodes. Therefore it has been suggested that although these medications probably do not have an effect on the underlying pathology (still controversial and unproven), they may still be warranted as symptomatic therapy. There are multiple choices and no evidence to support on over the other, so it is probably best to use a medication that can be administered in a minimally stressful manner and will not adversely affect the cat's quality of life at home (e.g. overly sedative).

Anti-inflammatory medications

There is no evidence at this time to support or refute the potential benefit of steroids or NSAIDS in cases of FIC. No benefit has been identified in cases of interstitial cystitis in humans, however, so they are not generally recommended for cats.

Antibiotics

There is almost no evidence to support the administration of antibiotics for FIC, but they are listed here because they are probably the most frequently administered medication for this condition (usually based upon a false assumption of urinary tract infection). It is hard to overstate the importance of performing urine cultures when a UTI is really suspected. Cats actually have a very low incidence of infection (<1-5% of all lower urinary tract disease). However, because the cats typically get better in 2-3 days, it may appear that an antibiotic (or any other medication) is having a beneficial effect.