Feline idiopathic cystitis (FIC) is the most common pathology under the umbrella term of feline lower urinary tract disease (FLUTD), affecting 55–65% of all patients with FLUTD (Sparkes, 2018).
FIC has a range of clinical signs including dysuria, stranguria, pollakiuria, periuria, haematuria, urethral blockage and pain (Buffington, 2011), with these being shown most commonly by spraying, overgrooming, vocalising, straining, anorexia, nervousness and aggression (Figure 1) (Sparkes, 2018). Identifying the most appropriate treatment for FIC can help prevent reoccurrence, improving the patient's quality of life and reducing risk of rehoming or euthanasia.
Pathogenesis
Because of the wide range of symptoms and presentations it is likely that FIC has multiple causes (Forrester and Towell, 2015).
Stress has been suggested as being integrally involved in FIC (Ikeda et al, 2009). In these patients, the sympathoneural outflow increases without activating the adrenal cortex, and the adrenocorticotropic hormone (ACTH) stimulation is reduced, reducing the cat's ability to cope with stress (Buffington, 2011). Studies completed on this hypothesis are mixed, with one exposing cats to stressful stimuli with no affect (Stella et al, 2011) and others identifying the following distinct neurohormonal abnormalities:
- Increased plasma norepinephrine without a concurrent increase in cortisol or adrenocorticotropic hormone (Westropp et al, 2006)
- Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus, causing increased sympathetic activity (Reche and Buffington, 1998)
- Reduced response to the existing adrenocorticotropic hormone and a reduced volume of adrenal gland, compared with cats without FIC (Westropp et al, 2003).
Bladder abnormalities are also apparent in cats with FIC, that indicate neurohormonal changes are not a single risk factor:
- The glycosaminoglycan (GAG) layer may be abnormal, either decreased or there may be variations in the quality (Buffington, 2011), allowing urinary solutes to cause tissue injury (Forrester and Towell, 2015). Factors such as an altered pH, electrolyte imbalance and infection can weaken the function of the GAG layer and cause damage (Buffington, 2011).
- Dorsal root ganglion cell bodies were found to be 30% larger, and to be desensitising (Buffington, 2011), potentially causing the patient to not express their bladder as frequently as normal. Impaired mobility, confinement, litter tray availability and cleanliness, inter-cat aggression and anxiety (Forrester and Towell, 2015) can also cause a decrease in urination.
- Abnormalities in the urothelium, detrusor and submucosa after a period of stress have been identified in a study on mice (Veranic and Jezernik, 2000), however it is not known if this study is comparable to feline anatomy, and if the damage found in the urothelium is a cause or effect of FIC.
- Mast cells have been identified in the submucosa in biopsy specimens of 20% of cats with idiopathic cystitis, potentially as a by-product of the stress concurrent with FIC, or related to the cause (Buffington et al, 1997). The relatively small percentage indicates that if this is the cause, it is not the only one.
Although these studies have not been able to confirm any particular causative factor, they have identified that bladder abnormalities and neurohormonal changes have occurred in cats with FIC and may be part of the pathogenesis.
Epidemiology
FIC is seen across all breeds and ages ranges, with 5–6-year-old cats being commonly affected (Dorsch et al, 2016). Research in Europe (Saevik et al, 2011) and America (Lekcharoensuk et al, 2001) has found a higher number of males being affected, however the risk of urethral obstruction (Gerber et al, 2005) could increase numbers seeking veterinary attention compared with female cat's, leading to unintentional bias. Risk factors are varied, with a Scottish study identifying overweight males in conflict-filled house-olds to be more at risk (Cameron et al, 2004), and a Belgian and Norwegian study identifying that the household environment was not a factor, and body condition score and disposition were more important (Defauw et al, 2011).
Treatment options
Nutraceuticals
GAG supplements available are N-acetyl, D-glucosamine (precursors of glycosaminoglycan) and hyaluronic acid (main component of the GAG layer). Overall studies to test the benefits of GAG supplements in 40 cats suffering from FIC for 6 months have returned results with no significant difference between the placebo and the supplement (Gunn-Moore and Shenoy, 2004).
Alpha-casozepine is a product derived from a protein in the milk molecule casein. Alpha-casozepine acts directly on the brain through the same neuro transmitter (gamma aminobutyric acid) that benzodiazepines act on, producing a calming effect (Debe, 2013). This product is designed to reduce stress and anxiety in patients and has been used to reduce the stress element of FIC and reduce the likelihood of developing FIC (Buffington and Pacak, 2001). Studies on anxious cats have shown that after a 56-day trial all participants showed signs of improvement for a range of social phobias including aggression, fears and autonomic disorders (Beata et al, 2007).
L-tryptophan is a precursor to serotonin synthesis, which regulates anxiety and mood. An increase in serotonin can act as an anxiolytic (Forrester and Towell, 2015). This supplement is combined with either a GAG supplement or milk proteins such as alpha casozepine, so it is difficult to assess the effectiveness of its use alone. A 2-month study identified that supplementation with L-tryptophan significantly changed the frequency of stress-related behaviours, decreasing signs of anxiety, however this was not applied directly to FIC (Pereira et al, 2010).
Pheromones
The F3 feline facial pheromone (FFP) is spread via the cat's cheeks, pads and body, providing comfort and reassurance (Feliway, 2017).
A study completed by Gunn-Moore and Cameron (2004) tested the wellbeing and FIC signs of nine cats that were exposed to FFP or a placebo in the environment for 2 months. Visual signs were recorded by the owners and compared against a scale to assess clinical and behavioural changes. At the end of the study five of the owners had reported overall improvements. However, on examination of the results it was shown that when the cats were exposed to FFP the periods of cystitis were reduced and the days spent with clinical signs were also reduced (Gunn-Moore and Cameron, 2004). This shows a positive outcome for the use of FFP in the treatment of FIC.
The cat appeasing pheromone (CAP) is derived from the pheromone that queens produce from their mammary glands. This has a soothing effect on the kittens and can keep cohesion between them (Cozzi et al, 2010). If FIC is triggered by stress from other cats within the environment, then using cat appeasing pheromones to alleviate tension, will help to alleviate symptoms of FIC. A study to test the effects of CAP was completed in 2010 by Cozzi et al (2010) which compared the reactions of 16 cats, in pairs, when confronted with a potentially conflicting situation. Those exposed to CAP showed a slight increase in the duration of harmonious exchanges and spent a longer time in proximity to other cats in comparison to the placebo group (Cozzi et al, 2010). Although this study was not related to cats with FIC, an improvement in agreeable cat–cat relations can reduce stress and reduce the severity and length of symptoms.
Nutrition
Nutrition, specifically feeding a wet food diet with more than 60% moisture, is the only treatment that is associated with a significant reduction of clinical signs (Forrester and Roudebush, 2007). Increasing the patient's water intake results in urine that is more dilute and causes less neurogenic bladder inflammation (Figure 2) (Taylor, 2013). The easiest way of increasing water intake is to introduce a wet diet. In a year-long study involving 46 cats being fed a dry urinary diet (n=28) or a wet version of the same diet (n=18), the clinical signs of FIC occurred less frequently in those fed the wet diet, with 16/18 (88%) not developing any signs, compared with 17/28 (60%) (p<0.05) (Markwell et al, 1999).
Environmental enrichment
Anxiety related to the environment can add further strain onto any stress-related abnormalities in the neuroendocrine system, causing a decreased frequency of urination (Forrester and Towell, 2015). The environment is a large part of the cat's life, and is often uncontrollable, especially if the cat goes outside.
The hypothesis that environmental stressors can exacerbate either symptoms or occurrence of FIC originally came from Kirk (1925) who suggested that confinement to the house would contribute to FIC. Following an earthquake in California, Caston (1973) identified an increase in cats suffering from FIC and suggested a treatment of ‘determine the stress and where possible, remove it’.
Environmental modification enhances the environment in line with the cat's behavioural biology. Providing the cat with options and allowing choice encourages appropriate behaviours and can help prevent inter-cat aggression. This includes providing enough necessary resources which contain outlets for the feline's normal behaviours (scratching, hunting, playing, resting, eliminating, chewing and hiding (Forrester and Towell, 2015) for all cats in the household. A general rule is to provide one of every resource per cat, plus one additional (Harvey and Tasker, 2013).
Creating predictable routines between the owner and the cat can also help reduce any stress. This allows the cat to foresee any potential stressors and avoid them, therefore decreasing the central noradrenergic drive (Forrester and Towell, 2015).
Environmental modification is a difficult treatment to analyse and evaluate. A study in a controlled laboratory setting measured catecholamine concentrations and urinary bladder permeability after FIC cats were exposed to stressful and enriched environments. It showed that those exposed to the enriched environment had reduced catecholamine concentrations and bladder permeability, thus having a beneficial effect for FIC (Forrester and Towell, 2015). A prospective study was completed by Buffington et al (2006) which evaluated 46 FIC cats under environmental modification, either alone, or in addition to drug therapy. For 10 months no signs of FIC were identified in 70–75% of the cats, and of those that did show signs, they resolved without further intervention. General fearfulness, nervousness, respiratory signs and gastro-intestinal signs were also reduced. This study showed that the addition of environmental modification reduced the output of the stress response system, thus improving FIC. Despite the prospective study showing positive results, Buffington (2006) identified that individual responses to changes in the environment depend on the cat's history, and what works for one, may not work for others, making it difficult to prove efficacy (Figure 3).
Drug therapy
In randomised clinical trials of the efficacy of treatment for the management of FIC, no drug therapy has been shown to be effective (Sparkes, 2018), and the additional stress of giving medication may contribute to reoccurrence of clinical signs (Buffington, 2011). Recommended drug therapy can differ depending on the patient's clinical signs; however, the administration of analgesia is recommended at all times to alleviate pain and discomfort (Sparkes, 2018).
Non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to improve pain in cats post urethral obstruction, however in a study on 37 cats receiving either meloxicam (n=18) orally or a placebo (n=19) for 5 days post obstruction it was identified that meloxicam did not have a significant benefit. Four (22%) of the meloxicam patients developed repeat obstruction over a period of 3 months compared with five (26%) of the placebo patients (Dorsch et al, 2016). However, this study was using meloxicam as a short-term measure, and the use of meloxicam to relieve symptoms of FIC as they occur may be of benefit to help prevent urethral obstruction.
In the treatment of FIC, a study of 12 cats looking at the efficacy of prednisolone showed that it was no more effective than the offered placebo at reducing the severity or duration of clinical signs (Osborne et al, 1996). This study was only completed over a period of 4 weeks, and the cats were hospitalised during this time for observation, which could have counteracted any benefit of the medication due to the stress of being hospitalised. Dysuria resolved in the cats receiving both the prednisolone and the placebo after 1.5 days, however this was put down to the self-limiting nature of FIC.
Amitriptyline is a tricycle antidepressant with analgesic and anti-inflammatory properties. An uncontrolled study of 15 cats, showed that administration of amitriptyline for 12 months decreased FIC signs for 9/15 (60%) of patients in the last 6 months (Chew et al, 1998). Haematuria and proteinuria were decreased in all cats at the 12-month mark, however abnormalities were evident on cystoscopy at 6 and 12 months post treatment (Chew et al, 1998). When used short term for 7 days in a study involving 31 cats, there was no difference in the rate of recovery from pollakiuria or haematuria, however those treated with the amitriptyline had faster rates of reoccurrence and suffered more frequently than those treated with the placebo (Kruger et al, 2003). These studies indicate that longer use of amitriptyline may help reduce reoccurrence of FIC, potentially by reducing the stress response.
Antimicrobials are a common treatment despite being rarely indicated. This may be due to suspected infection or as antimicrobials are often associated with a resolution due to the self-limiting nature of FIC. However, a study with chloramphenicol showed no real difference in resolution of clinical signs when compared with placebo (Barsanti et al, 1982). A study in Norway showed that 33% of cats with urinary tract signs had bacteriuria (Lund et al, 2015) so it is possible that the cats in the afore mentioned study did not have a positive culture or required differing antibiotics. Due to risk of antimicrobial resistance within companion animals, treatment should be based on urine culture and sensitivity results.
A small study of 47 cats with urinary obstruction, compared prazosin vs a placebo when administered for 1 month following obstruction. Cats were monitored for 6 months for repeat urethral obstruction. It was identified that there was no difference between the rate of reoccurrence or the severity of signs throughout the time frame (Reineke et al, 2017). Prazosin was only administered for 1 month, so it is possible that longer-term treatment could have had some benefit.
Conclusion
Forrester and Towell (2015) identified that stress can be the biggest cause of FIC due to the trigger effect on the body (Buffington et al, 1997), alterations in the urothelium (Buffington, 2011) and behavioural changes which affect toileting habits. Causes of stress can be traced to the cat's environment. Evidence for the treatment of FIC with medication or environmental modification is not strong, however it shows that long-term use of amitriptyline, use of pheromones and environmental modification can help reduce stress and thus reoccurrences of FIC. Veterinary nurses can be more in-volved in the ongoing treatment for these cases, with the setup of behaviour clinics, environmental assessments, and branching out to home visits and district veterinary nursing (Figure 4). This could also help with improving the general care and husbandry of cats across the UK.
KEY POINTS
- Feline idiopathic cystitis (FIC) is seen across all breeds and age ranges, with 5–6-year olds being commonly affected.
- Stress can be the biggest cause of FIC, stimulating changes in the urothelium and behavioural alterations, leading to a reduction in urination.
- Introducing a wet food is the only treatment that is associated with a significant reduction in clinical signs of FIC.
- Further research is required into the true cause of FIC to identify further treatment options.
- Reduction of stress can be implemented by the owner through veterinary nursing consultations; including behaviour clinics and environmental assessment through home visits and the utilisation of district nursing.