What is Triaditis?
‘Triaditis’ is the term coined many years ago in a lecture by David Twedt in the USA to denote concurrent chronic cholangitis, chronic pancreatitis, and inflammatory bowel disease in cats. It is a frustrating term because in fact, a literature search will show you there are no publications on ‘triaditis’ in cats. There are publications on ‘triaditis’ in humans but they mean something very different - inflammation of the portal triad - i.e., confined to the liver. The term as used for cats could, therefore, lead to confusion, particularly in comparative studies - but it has gained widespread acceptance as a short-hand way of reminding us that these three conditions can occur together in cats.
There is continuing debate about whether these three conditions are really related in cats. The first published report was Weiss and others in 1996 who reported an increased prevalence of inflammatory bowel disease (IBD) and pancreatitis in cats with cholangiohepatitis. More recent studies of cholangiohepatitis seem to support this: for example, in a study of MRI in cats with cholangitis or pancreatitis, 8 out of 10 cats had both histologically confirmed pancreatitis and cholangiohepatitis on laparoscopic biopsies. In another study of ultrasound in 26 cats with cholangitis, 17 had concurrent ultrasonographic abnormalities in the gut wall and 7 had concurrent pancreatic abnormalities.
The evidence does suggest, therefore, that a sub-set of cats has concurrent gut, liver, and pancreas disease. There are also cats which suffer from one or the other but not all three.
Why Does ‘Triaditis’ Occur in Cats?
The short answer is nobody knows. There are a number of possible reasons but more research will be needed to identify which of these are important. Broadly speaking, chronic pancreatitis, chronic cholangitis, and IBD could occur because of an infectious process; an autoimmune process or something physical (such as duct obstruction). An autoimmune disease could also involve food allergy (particularly in the gut) and an infectious cause could also encompass an unusual host reaction to their own microflora. In reality, particularly for chronic pancreatitis and chronic cholangitis, it is likely that cats suffer from several different diseases and not just one disease and that the aetiologies vary. It will be very difficult to define effective treatments until we know the causes and can separate out cats into their different groups.
Many authors simplistically suggest that cholangitis and pancreatitis occur because the pancreatic and bile ducts join before they enter the duodenum. Cats are like humans in this respect, whereas in most dogs the ducts don’t join and enter the duodenum separately. Having a single outflow through the sphincter of Oddi would certainly pre-dispose to pancreatitis and cholangitis (although not explain the concurrent IBD) if both ducts were blocked concurrently. This is unusual in cats - in humans, the commonest reason for this to occur would be gall stones blocking the ducts near the sphincter of Oddi. This is very rare in cats. Cats do sometimes suffer from poorly defined sphincter dysfunction which may cause this syndrome: ‘sphincter of Oddi dysfunction’ has been described in both humans and cats and describes a spasm of the sphincter which can block both pancreatic and bile ducts. It produces a dynamic obstruction which can be very difficult to diagnose without dynamic imaging with stimuli for gall bladder emptying. However, it is diagnosed more often in humans with IBD and it is proposed that inflammation in the intestinal wall around the sphincter predisposes to it. Too few cases have been reported in cats for us to know if there is any association with IBD - but it is likely to be a condition which is under-diagnosed in cats because it will not be found unless you are looking for it.
Some cats may get ascending infection from the gut into both ducts, which potentially could be predisposed by vomiting or overgrowth of bacteria secondary to IBD, but it is not clear how often this happens. Bacteria could also pass across the mucosal barrier and into the portal blood circulation and then enter the liver (Twedt et al. 2014). A second possible reason could be close proximity of the pancreas, bile duct, and small intestine, such that inflammation of infection in one organ has a ‘local’ effect spreading to the others. This could be particularly true with pancreatitis as the bile duct passes through the pancreas so could be blocked during an episode of pancreatic inflammation and the neighbouring small intestinal wall might also be involved. David Twedt and Kenny Simpson have performed fluorescent in situ hybridization (FISH) on liver and pancreas from cats with cholangitis and pancreatitis and shown bacteria within the organs: but it is not clear whether these are a primary cause or secondary phenomenon.
The third possible reason, which seems very plausible in a number of cases, is that all three organs are affected by the same disease process, as can occur in humans. The bile duct, pancreatic duct, and small intestine might all be concurrently affected by autoimmune disease, similar to IgG4+ cholangitis in humans. It is worth considering human biliary tract disease because it helps to understand how relying entirely on histology in cats may be leading us to put several diseases together. We need to develop better methods of imaging and blood tests to help us understand these feline diseases further.
A Summary of Human Diseases with Similar Clinical and Histological Appearances
There are three (or four) diseases of the biliary tract in humans which all have a very similar appearance on histology and yet are clinically very distinct.
- Primary sclerosing cholangitis
- Primary biliary cirrhosis
- IgG4+ cholangitis
- Sphincter of Oddi dysfunction
I will describe these as an example of how relying entirely on histology in cats may be leading us to put several diseases together. We need to develop better methods of imaging and blood tests to help us understand these feline diseases further.
In a recent, multi-centre, unfinished (!) project, we looked at 39 cases of chronic cholangitis to ask the questions: what type of pathology is present? Are any similar to primary sclerosing cholangitis in humans?
Based on the human classification systems, a human pathologist, grading the cats ‘blind,’ categorised nine cases as secondary biliary cirrhosis - suspected chronic extra-hepatic obstruction; seven cases as PSC-like changes; five cases as vanishing bile duct syndrome; one case as PBC-like changes and the rest non-specific ‘cholangiopathy.’ Whatever is going on in these cats with chronic cholangitis, we undoubtedly have several diseases present and we are undoubtedly missing the diagnosis of extra-hepatic biliary tract disease in many cases.