Pandora syndrome: Rethinking our approach to idiopathic cystitis in cats - Veterinary Medicine
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Pandora syndrome: Rethinking our approach to idiopathic cystitis in cats
Cats with idiopathic cystitis often have multisystemic comorbidities, so look outside the urinary tract—as well as in the cat's environment—for diagnostic and therapeutic answers.



The sensitivity of cats to their surroundings and their responses to threatening stimuli have been studied for decades. The term fight-or-flight response resulted from studies of cats conducted during the first two decades of the 20th century by the eminent physiologist Walter B. Cannon.5 Cats are a relatively solitary species,6 often choosing population densities of fewer than 50 cats per square kilometer. Although free-ranging male and female cats occupy overlapping home ranges of about 100 meters in diameter, they often avoid meeting each other by keeping to a schedule. In a study of households with two cats, about 50% of time was spent out of one another's sight, even though they were often within 1 to 3 meters of each other.7 Thus, cats may be unusually susceptible to indoor restriction because of the differences between their behavioral strategies and those of other social species, including most other domestic animals, and people.


Based on a series of studies conducted during the past two decades, various conditions and diseases beyond the urinary tract have been identified in cats with severe, recurrent LUTS.8 Understanding the underlying processes that lead to these abnormalities may be the key in diagnosing and treating affected cats. It is thought that some cats, because of a combination of genetics and early environment, have a more sensitive and overactive sympathetic nervous system,9 and this is thought to be associated with abnormalities in intestinal, behavioral, dermatologic, epithelial, neurologic, endocrine, or immune systems. These comorbidities can occur in any combination, and some of them may precede the development of LUTS. These conditions, as well as environmental stressors, can manifest as what we call sickness behaviors.10

Sickness behaviors refer to a group of nonspecific behavioral and clinical signs including vomiting, diarrhea, anorexia or decreased food and water intake, fever, lethargy, somnolence, enhanced painlike behaviors, and decreased general activity, body-care activities (grooming), and social interactions. Although these behaviors are well-documented responses to infection, they also occur in response to aversive environmental events. Thus, sickness behaviors can result both from peripheral (i.e. afferent) and central (i.e. efferent) pathways.10

The repeated observation that most of these associated problems and sickness behaviors resolve after exposure to an enriched environment provides additional evidence of a central nervous system disorder resulting in a chronic multisystem illness variably affecting the bladder and other organs, as opposed to a peripheral organ-based problem.10-12


Because of the evidence outlined above, I think that some cats with chronic LUTS may have a Pandora syndrome, named for the Pandora myth (see The myth of Pandora's box). The name Pandora syndrome reflects my experience in studying this problem and my optimism that hope for effective treatment remains.8 Pandora syndrome is, thus, analogous to so-called "medically unexplained" chronic functional syndromes in people, such as interstitial cystitis, irritable bowel syndrome, fibromyalgia, and panic disorder (which commonly are comorbidities as well).9

Based on the available evidence, provisional criteria for a diagnosis of Pandora syndrome might include

  • Chronicity: Persistence or recurrence of the condition over months to years
  • Comorbidity: Evidence of problems in other body systems (e.g. behavior, endocrine, gastrointestinal, respiratory, or dermatologic problems), particularly preceding the presenting LUTS
  • Patient history: A history of early adverse experience (orphaned, bottle fed, rescued)
  • Genetics: Evidence of familial involvement (parents or littermates have a similar illness profile).

Owners often do not have information about their cats' early experience and family members, and none of these criteria can be considered pathognomonic for anything. They may serve only to raise an index of suspicion that a more systemic problem may be present.

Before assuming that a cat has an isolated bladder (or other) disease, take the time to obtain a comprehensive review of the cat's history and conduct a thorough physical examination. You may find that some cats have a disease affecting more than just the organ attributed to the presenting signs, which can helpfully guide your diagnostic and therapeutic recommendations.


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