Health Topics

Malignant Histiocytosis (Histio)

Histiocyctic Sarcoma (HS)

This was formerly referred to as Malignant Histiosarcoma and referred to as MH or most commonly still spoken about mostly as ‘Histio” in the UK.

The following article is based on that first published in the BMDC of GB Magazine in December 2016

A Brief History

From the very earliest times when we began to believe/realise our breed was generally susceptible to various forms of ‘cancer’, probably around 25 – 28 years ago in the UK, it was accepted that this vulnerability appeared to have something of an hereditary influence, that is to say certain lines appeared to have just a little bit more susceptibility than others. At the same time it was definitely not an identifiable recessive gene type autosomal mode of inheritance but something much vaguer than that.

The amount of ‘cancer’ encountered was realised to have a widespread bad effect on the breed and our low average age at death was much talked about and ‘cancer’ was widely quoted and accepted as the biggest factor in this. The problem was that we were not looking at one kind of cancer. Whilst other breeds would have specific problems to deal with ours seemed to be a general susceptibility to various forms of the disease. At the time cancer treatment in humans was moving on in the public eye and we were being encouraged to think of cancer as not a single disease but a generic term covering hundreds of different diseases each requiring different very specific, and increasingly effective, approaches. In short, the general thinking was that you needed to identify a specific disease in order to properly tackle it.

As explained below, (in “What are the Symptoms?”), looking back with that most effective of teachers, hindsight, I now feel many of these various cancers were being initiated by the, yet to be identified, Malignant Histiocytosis. The real (unknown) enemy was MH and many of the other cancers we were identifying were actually secondary cases. I am the first to admit this is a personal theory which can never be proved, or disproved, but looking back now it just makes so much sense. At the time in the UK we just considered we were prone to a variety of cancers and that was unfortunately the way it was. Due to the non specific threat were at something of a loss as to what to do. Various schemes were tried but these petered out through lack of support as people could not properly engage with any specific cancer threat. Sadly some of this attitude still exists today.

In some other countries, most notably the USA and France, the existence of Histio and it’s threat to the breed was understood much quicker and, more importantly, acknowledged and accepted by the owners and breeders. In these countries the battle against ‘Histio’ was engaged much earlier. Although others have since joined in, these two countries are still the main front line for the breed against this insidious problem and, in my opinion, our breed has much to thank them for.

What is ‘Histio’?

According to the Antagene website, referenced below, it “ … is a major cause of death in the Bernese Mountain Dog. It is a cancer of the histiocytes, cells responsible for immune function, which are present in the lymph nodes and a number of organs. No treatment is effective to date, and the disease is fatal.”

This is a succinct summary of what is an awful disease for our breed which, for most experienced people, is still the most serious health problem we have in the breed as it is far more widespread than DM for example and much more difficult to address.

Whilst not for one minute advocating any complacency about everything else, it is perhaps the case that we have taken our eye off the ball a little bit with ‘Histio’ in recent years. This disease is complex and complicated to even recognise, let alone address, and because of this many people just accept it and still refer to people being ‘unlucky’ when it strikes. Alternatively, due to the lack of accurate diagnosis some choose to ignore and forget it and deny it’s existence. We have to move on from this viewpoint or we will never progress.

Most typically, but not exclusively, Histio affects middle-aged dogs with the average age of onset being 5-7 years but older and, even more tragically, younger dogs can and do develop it. If we choose to carry on doing nothing then it is only logical to expect things to get worse with younger and younger onset age.

What are the symptoms?

As already mentioned, one of the biggest problems with Histio is that it can present with a variety of symptoms making it hard to be sure what you’re dealing with especially at first. HS can even be fatal in just a few days from first noticing symptoms in your beloved pet. If you are definitely dealing with Histiocytic Sarcoma the prognosis for your Bernese family member is, to put it bluntly, extremely poor. The average life span after diagnosis is probably no more than a few weeks. Sometimes there may be a briefly encouraging response to steroid based treatment but this is usually short lived and sadly only delays the inevitable.

The symptoms of Histio are many fold as it can affect many different parts and functions of the body depending on which part of the immune system function or organ any particular case affects the most. Fairly typical, but by no means the only, symptoms are increasing lethargy, tiredness, breathlessness and loss of appetite and a severe anemia will often be noticed by the owner or the vet, (extremely pale gums). After little or no response to speculative treatments with antibiotics or partial or temporary response to steroids, an X ray will often reveal vague shadows on the lungs, so lung cancer is sometimes presumed.

It is not surprising, or any slight on any vet or owner, that the wide variety of symptoms at onset has no doubt led to much misdiagnosis and lack of diagnosis over the years. I feel Histio has been misdiagnosed as various systemic cancers, such as lymphosarcoma and lymphoma, as well as other cancers such as bone cancer or lung cancer or skin cancer when in fact the symptoms being assessed are actually secondary sites of tumours and the root cause has been missed. This is because the root cause is often not visible to any X ray or scan and by the time the owner notices and symptoms the secondary problems are all too well established and appear to be the sole problem. There is usually no visible or obvious tumour to sample.

I also feel this is also why some Bernese have been observed to not respond well to treatments to ‘cancers’ and in some contexts developed a reputationof not putting  up much of a fight against illness compared to other breeds. The well meaning treatment is not addressing the primary cancer but the secondary, more observable, symptom. So, whilst the secondary conditions may initially respond to treatment for a short time, the prime cause carries on in the background pushing the disease to manifest in other areas and hastening the time to the inevitable conclusion leaving owners and families completely devastated with a massive and sudden hole in their lives.

This rapid escalation to the obviously terminal stage is another reason why the disease is sometimes not diagnosed. The dog is rapidly so seriously ill that the end is all too clear and vets and owners do not see the point in spending money on potentially expensive diagnostic procedures or putting the poor dog through even more trauma.

What treatments are available?

To put it realistically, there is no treatment for this disease or at least nothing that will significantly extend your afflicted dog’s life. If the diagnosis is correct then, effectively, any medication can only be viewed as palliative.

What causes it?

As stated earlier, from the very beginning of our breed’s ‘cancer’ problem there was always the feeling of a familial connection to this disease. Population type genetic analysis in the early days could not confirm this in any meaningful way most probably because there were not enough definite cases being confirmed but this loose family susceptibility to ‘cancer’ was accepted by most people.

In France a massive pedigree study of their much larger Bernese population was established. I recall being shown a massive constructed family tree with hundreds of dogs covering dozens of different breeder’s lines on it with connections drawn all across it. Crucially this analysis showed that when you looked at a big enough spread of dogs and linked up the pedigrees then connections definitely started to emerge. This evidence kick-started the fight back that still continues today across the channel. Following on from this, as technology and science developed apace as the new century unfolded, a DNA genetic project was launched both in the States and France and the two have worked together for many years now. Much funding has been poured into these projects and our club has contributed to this in different ways at different times.

Unlike many other diseases however, it has proven extremely difficult to find a reliable genetic marker in affected dogs and the search continues. However, because the project is still ongoing this does not mean that no progress has been made.

In summary, a genetic link associated with this disease has been found but work continues to refine it’s identity even more.

No Treatment, So What Can Be Done?

As already outlined there is no viable treatment for Histiocytic Sarcoma and there is nothing known to be in the pipeline either, it really is that fatal and unstoppably terminal. So, the only logical statement to make is to say that we cannot do anything about it when it occurs so we have to do everything we reasonably can to stop it occurring in the first place which will in turn reduce it’s spread throughout the breed. This obviously falls mostly on the shoulders of breeders and stud dog owners but other groups are also important stakeholders in this process such as puppy purchasers who need to ask the right questions.

Even without utilizing the test, there are sensible and meaningful things that can be done. Look honestly at your breeding bitch and proposed stud dog and consider their relatives and antecedents. Ask questions if you have to. Have many of them died young from often vague not properly diagnosed illnesses, typically referred to as ‘ … probably cancer but it wasn’t worth spending any more money diagnosing them as they were so ill and not responding to treatment anyway ‘’. We have all probably been in and understand that position with our dogs and this comment is not intended as any slight on any owner or vet but, if so, is it just an odd relative or is it several? Is it lots even? Is it several in the same litter? How close are the relatives? Do you think your breeder would even know about such things?

This is not rocket science so I will not explain how to assess the answers except to say this is not about reacting to the odd isolated early death or two in a whole pedigree but just looking for evidence of a more significant problem. Just make sure the questions are asked and act appropriately on the replies. It does not matter how attractive the dog is and what other assets he or she has, the unseen features you are bringing into your litter could have devastating consequences for your puppy buyers. Researching the background of your breeding stock is not a new thing and should always be done anyway but it is so important to try to look a bit wider with this disease. I think I was once told at a seminar that what you physically see with any dog is affected by less than 10% of it’s DNA. What you cannot see therefore is affected by the other 90% and the only way to even begin to gauge the effects of this much more important 90% is to look at the history, along with any guidance you can get from DNA testing.

The ‘Test’

As mentioned previously there is now a test available to help. The test has been developed in France over many years and before it’s commercial release it was tested on French BMDs over several generations. Only when there was sufficient data to validate it’s efficacy was it offered to the breed to help us.

It is available from the French company Antagene and research continues by the team at the University of Rennes who, a few people may remember, presented their latest progress at the 2011 international BMD health seminar held in the UK in the shape of Benoit Hedan. Since the project was launched in France Benoit and/or Catherine Andre have attended the breed’s International Health seminars so I have watched the development of this test over the last 10 years and more. The 2015 presentation in Finland reported much progress and validation of the test with good evidence of it’s efficacy. It is not however a 100% indicator but a guide intended to generally assist the breed to reduce the incidence of the problem within the European Bernese Mountain Dog population. This is why it is referred to as a Pre Test as a guide to assist breeders. Nothing more nothing less.

The test for Histiocytic Sarcoma has three possible results expressed as an index :

Index Explanation
A The individuals tested have four times the chance of NOT developing Histiocytic Sarcoma.
B Neutral index
C The individuals tested have four times the risk of developing Histiocytic Sarcoma. The risk of the markers associated with the disease being transmitted to offspring is greatly increased.

Antagene web site 2016

Obviously the advice is to try to stick to A and B dogs for breeding but Anatgene do not say to remove C dogs from the breeding programme. There is much more detail and sensible advice about this test on the Antagene web site page via the link below and I suggest you read this rather than extend this article repeating even more of it. If you read this page you will realise that Antagene are not overly idealistic and fully accept the need to broaden gene pools and not exclude dogs completely for one single reason.

Summary

HS is such a devastating disease that the breed needs every breeder to join in the fight against it. It will not go away on its own but it WILL be gradually beaten if we all get together and join in with initiatives. So PLEASE support the efforts made to push this disease out of our breed. The only certain thing is that if we do nothing the situation will not improve but get worse and it is only logical to expect that if the advice is ignored then more of the affected litters will die younger than they need to and the age at death will get younger. This destroys the health reputation of the breed even more, makes insurance more expensive, will gradually make puppies harder to sell, makes lots of really good owners leave the breed but of course most seriously of all causes unnecessary suffering in our dogs and corresponding grief in their families.

Isolated cases can always appear but please look backwards and sideways into pedigrees of potential stud dogs and brood bitches and simply look for any repetition of early deaths, whether officially diagnosed as Histio or not, especially if it affects more than one in a litter. Look for vague references to cancer or unknown reasons as a cause of premature deaths. Just pause for a moment to think what it means for your puppies and your lines if these ‘vaguely cancer of some sort’ deaths were caused by the hereditary Histio but also consider what it means for the breed if you still go ahead. Of course no one can say any particular undiagnosed and fatal diseases were Histio related but if there are several present within the lines there is obviously something amiss.

There are many valid reasons Histio is not officially diagnosed in any individual dog but that does not mean it is not responsible for many deaths of Bernese Mountain Dogs. It is easy to say ‘it wasn’t officially diagnosed so I don’t have the problem’ but please accept that the nature of this disease dictates it will not be diagnosed in many cases for all the reasons given above. At least take the viewpoint that something is causing too many early deaths in our breed and we have to get to grips with it. We have to get smarter, more open minded and accept it is out there and only then will we start to effectively do something about it.

The test is still a work in progress but it is a validated process so please use it on your breeding animals. I am not even going to discuss how irrelevant the cost is when spread over the price of all the puppies that an animal could have during it’s lifetime or the stud work that a male could undertake.

If you choose to ignore this kind of information then you cannot be considered simply unlucky if some of your puppies become ill and die premature deaths. I know some may consider this language harsh but people who purport to love the breed and care for it’s future really do need to wake up and address this issue. There are no certainties with this and even ‘doing the right thing’ does not absolutely guarantee anything but, overall, if enough people do the right thing for enough generations then this disease will recede and it’s effect on our breed will weaken and eventually become insignificant. We are a very long way from this point but it is an attainable position but only if breeders act to improve matters. This may mean taking tough decisions for your own lines but by ignoring these factors and just considering it a matter of luck you will only make tragic problems for your puppy purchasers and be failing in your responsibility to improve the breed we all love.
If your Bernese is unfortunate enough to be diagnosed with this exact complaint, remember there are various less severe and similar sounding related conditions, unfortunately you have very few options really. Sometimes massive steroid doses appear to slow things down a little but such respite is usually very short lived. Normally by the time you have noticed symptoms, been to the vet, gone through several days of maybe trying antibiotics, steroids etc before moving onto tests to confirm diagnosis your dog will probably be too ill to leave you with much option. Sometimes one hears of significant remissions but these are usually very short and their rarity leads to questions of the original diagnosis.

Finally, it is perhaps worth saying that it is easy to get caught up in the debate about ‘Histio’ and become paranoid about nay illness in your Bernese or the state of the breed. Whilst Histio is a significant disease for our breed we have to remember that many Bernese do have a full and lasting life and do not develop this condition. The challenge for the breed is make sure the number of dogs living longer gets greater as we move into the future. This will not happen of its own accord but needs everyone to contribute

Steve Green, BMD Breed Health Co-Ordinator