Identifying and treating Pandora syndrome

By Lisa Restine, DVM, DABVP (Feline)

The term Pandora syndrome is being used more frequently in veterinary medicine. Yet, what exactly does it encompass? Why have we changed the name for feline lower urinary tract disease (again) and why is it important?

Pandora syndrome is applied primarily to cats with chronic lower urinary tract disease symptoms.¹ Historically, the terms feline interstitial cystitis (FIC), feline lower urinary tract disease (FLUTD), and feline urologic syndrome (FUS) have all been used to describe this disorder.² These cats exhibit acute, intermittent, or chronic signs of hematuria, stranguria, pollakiuria, and/or periuria. They do not have urinary tract infections, crystalluria, or uroliths—hence the previous use of the term "idiopathic cystitis."³ These cats often have repeated clinical events in addition to other underlying health issues.^1,4

Humans also experience a disease process known as interstitial cystitis (IC)/painful bladder syndrome (PBS), which appears to be similar to Pandora syndrome in cats.^3,5 This disease process is recognized as a systemic disorder that affects the bladder as well as other organ systems.⁶ Patients often have comorbidities such as irritable bowel syndrome (IBS), fibromyalgia, and chronic fatigue.

There are numerous theories about the pathophysiology of IC/PBS, with an alteration in stress function activity being a widely accepted causal link.⁷ This has been shown to occur in cats with Pandora syndrome as well.⁸

Stress and Pandora syndrome

To fully understand what occurs with Pandora syndrome, one needs to understand stress and its effect on the cat. Stressors are events that occur both inside and outside the body that result in an activation of the central threat response system (CTRS, also called the central stress response system or CSRS).^9,11

Stressors can be acute or chronic, positive or negative, and range from mild to severe. Mild stressors are considered a normal part of the environment and can aid in the development of coping mechanisms. Moderate stressors can be things like illness, injury, or exposure to a sudden environmental change. As long as the animal resides in a safe environment, they should be able to cope and recover from moderate stressors. Severe stressors can occur frequently or continuously over a prolonged period of time. They include things such as abuse, chronic disease, or adverse early life occurrences (starvation, maternal separation, etc.).⁹

Pandora syndrome occurs due to prolonged activation of the CTRS.¹⁰ When the CTRS becomes sensitized, changes occur within the endocrine, autonomic nervous, and immune systems, resulting in pathology developing in any one or combination of organ systems.^9,10 It is even shown that fetal development can be affected when a mother experiences severe stressors during pregnancy.¹¹ As such, severe or prolonged pre-birth or early life stressors can cause changes that will predispose the cat to Pandora syndrome later in life.^9,10

Effects

As of right now, we are only scratching the surface of the effects Pandora syndrome has on the cat's body. However, the list of pathologies that can indicate Pandora syndrome in the cat is already quite extensive—and may include some surprises.

While we are most familiar with the signs that an activated CTRS has on the urinary system (cystitis, periuria, crystalluria/uroliths etc.), the effects on other body systems can be just as profound. We can see chronic signs or intermittent flare ups of upper respiratory diseases¹⁰—most commonly feline herpesvirus (FHV-1).¹² Stress related behavioral changes can be seen; these cats may hide, exhibit signs of inter-cat or human-directed aggression, overgrooming, urinating or defecating in inappropriate locations, or other undesirable behaviors. Changes in eating resulting in obesity or picky eating behaviors may also occur.

Gastrointestinal diseases causing vomiting, diarrhea, regurgitation, and hairballs can indicate the presence of Pandora syndrome.¹⁰ Diabetes mellitus, hypertrophic cardiomyopathy, feline acne, and asthma can also be a sign of Pandora syndrome.^4,10 However, these diseases and symptoms do not always indicate Pandora syndrome. Nevertheless, it should be included as a differential diagnosis when working up a cat with signs/symptoms of these disorders.¹⁰

Diagnosis

As the list of possible presentations of Pandora syndrome is quite extensive, the most important part of determining a possible diagnosis of Pandora syndrome is a thorough history. Cats with Pandora syndrome tend to have flare ups of clinical signs during or following an environmental stressor (change of routine, decrease of human interactions, or other stressors).^3,10 It is important to obtain a complete history for the patient as well as other animals in the home as they may have problems that can contribute the patient's issues.¹⁰

Please refer to Table 1 for examples of the type of history questions to ask regarding a patient with potential Pandora syndrome.¹⁴ It is important to recognize that this list does not represent a full and complete history—it is meant to be used as a reference for the type of questions necessary to fully understand the cat, the home environment, and the cat's routines.

A complete history can help to rule in or rule out the possibility of Pandora syndrome, but it is not the only part of the diagnosis. A physical exam and traditional tests (radiographs, blood work, urinalysis/culture, ultrasound, etc.) are all an important part of the complete picture. But evidence of chronic stress, waxing and waning signs, and/or a history of a traumatic or stressful event, should be recognized as potential triggers of Pandora syndrome.¹⁰ Some cats may also display multiple presentations occurring simultaneously or intermittently,¹³ i.e. a cat that experiences chronic diarrhea but also overgrooms.

In some cases of Pandora syndrome, clinical signs may seem disproportionately severe in relation to the disease process.¹⁰ One of the best ways to attempt to diagnose Pandora syndrome is to institute multimodal environmental modification (MEMO) and seeing a partial or complete resolution of the patient's clinical signs.^10,15,16

Instituting MEMO

In short, there is no one treatment that will work for all cats. However, eliminating stressors in the environment through MEMO is the most effective and consistent way to alleviate clinical signs. MEMO can be instituted both at the hospital if the cat needs intensive care and at home to prevent further recurrence of disease.^10,15

In the hospital
Instituting MEMO in the home environment is arguably just as, if not more, important than when the cat is hospitalized. This can be more difficult as it requires effective and empathic communication with the pet parent.¹⁹

The same concepts that are used in the hospital can be used on a larger scale at home. Patients need ample space (especially in multi-cat households) with areas to hide and climb. There should be fresh food, multiple areas for fresh water, and the litterbox should be cleaned daily. Most cats tend to prefer a clumping, unscented litter in an open box¹⁴—which is not what most cat owners prefer.¹⁹

Toys and other enrichment items like scratching posts, cat trees, and cat safe plants (like catnip) should be readily available. Window perches or "birdwatching" videos on streaming platforms are also great options to provide entertainment.¹⁹ Feeding, grooming, play, and attention giving routines from the pet parent should be consistent and catered to the individual cat's personality. Inter-cat conflict should be avoided as much as possible by providing adequate space and ample resources.¹⁰

Managing food and diet

Feeding routines and diet are key factors to treating Pandora syndrome—especially in cats with recurrent urinary signs. The cat should be fed in a quiet, safe area.¹⁰ There should be enough feeding stations to eliminate any perceived (or real) competition between the cat and other housemates. Cats have strong flavour, texture, and odour preferences when it comes to food,²⁰ so be sure the preferred type or types of food are available.

In a cat with recurrent urinary symptoms, feeding a diet designed to eliminate substances that can cause irritation to the bladder mucosa and increase water consumption has been shown to decrease the incidence of recurrent cystitis episodes.^21,22,23 This often means a transition to a canned diet if the cat is amenable to that type of food. It has also been shown that feeding a therapeutic urinary stress food significantly decreases cystitis episode recurrence when compared to cats being fed other commercial diets.²⁴

Pharmaceutical treatment

Pharmaceuticals have often been recommended to treat cats with FIC,²⁵ but the effectiveness of medications in cats with Pandora syndrome has not been established.¹⁰ Medications come with a potential for adverse effects—both metabolic and environmental.

Anyone that has owned or treated a cat knows that giving a cat oral medication can be quite challenging. In fact, administering a medication intended to treat anxiety can often cause more anxiety than it alleviates due to the cat's aversion of receiving medication.¹⁰ This is not to say that behavior-modification drugs are not useful in cats, but they should not be the first or only method used when developing a treatment plan for cats with anxiety or anxiety related disorders such as Pandora syndrome.

Conclusion

There is still much to be learned about Pandora syndrome in cats. We do know that environmental modification and decreasing stressors are key factors in treating and preventing this disease. Historically, cats presenting with lower urinary tract signs were treated for infections or given medications to help with stress—but no environmental changes were recommended.

It is our job as veterinarians to educate pet parents about what is optimal for their cat. We need to work with owners to develop a therapeutic plan that involves MEMO, diet, and (if indicated) medications in order to create as optimal an environment as possible for our patients.

Lisa Restine, DVM, DABVP (Feline) is currently the feline specialist employed by Hill's Pet Nutrition. She had previously worked in feline medicine for nine years before transitioning to industry. Dr. Restine achieved board certification in feline medicine with the American Board of Veterinary Practitioners in 2020.

References

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