Feline Chronic Gingivitis Stomatitis Complex

RE: Feline Chronic Gingivitis Stomatitis Complex

Kara Gibson — Thu, 16 Sep 2021 02:28:28 GMT

[quote userid="2161" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232971#232971"]Just another thought Kara- I know you said you knew you got all the roots, but I'm assuming you have radiographic proof? I've heard that statement said many times before...[/quote]

Sorry for the late reply, it's been a busy week!

Yes radiographic proof. Also I checked this case this morning and can see a marked reduction in inflammation and swelling versus 10 days ago so will continue with current regime and recheck in 2 weeks.

RE: Feline Chronic Gingivitis Stomatitis Complex

Alexander Geddes — Sat, 11 Sep 2021 22:13:12 GMT

Great thread all - I enjoyed following this week.

I don't have anything to add on preferences for treatment and experiences that isn't anecdotal and already been provided by colleagues.

There is one thing I thought worth mentioning. Please direct me if I have missed something, but I believe there is only one paper that has looked at what an appropriate sub-antimicrobial dose of doxycycline might be, and it is in dogs: Kim et al 2013 Am J Vet Res

https://pubmed.ncbi.nlm.nih.gov/23270357/

I would also argue that whilst this paper provides us with a single piece of evidence to what serum dose may be appropriate in dogs - it does not provide us with what may be going on in the crevicular fluid. We know from the human literature that antibiotic excretion is not always equal between serum and crevicular fluid. I think this is particularly important when considering the consequences of whether one is providing an antimicrobial or sub-antimicrobial dose.

So to Rachel's point - whilst I agree we need to develop evidence - I don't plan on introducing "sub-antimicrobial" doxycycline into my protocols until we have better basic science on how its working and what its dosing might be in both canine and feline patients.

RE: Feline Chronic Gingivitis Stomatitis Complex

Evelyn Barbour-Hill — Sat, 11 Sep 2021 21:16:02 GMT

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232995#232995"]In my personal opinion I believe those that respond to antibiotic therapy are likely patients suffering from chronic periodontal disease (possibly with an element of osteomyeltitis) and severe inflammation associated with this rather than true FCGS, the problem is differentiating between them at initial presentation.[/quote]

Indeed so.

The thing is, the two diseases at times are impossible to tell apart (but when there is inflammation advancing across the mucosa toward the pharynx, that is FCGS), but their respective appropriate treatments have little in common after the basic essentials of extractions and oral hygiene.

Personally – personally – I don't treat chronic periodontal disease with an antibiotic, unless I have a strong suspicion of a secondary osteomyelitis, which is rare.

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232995#232995"]Reiter (Characterization of Oral Microbiota in Cats: Novel Insights on the Potential Role of Fungi in Feline Chronic Gingivostomatitis, Pathogens 2021, doi.org/10.3390/pathogens10070904) which shows cats with FCGS tend to have higher number of fungal species present than the general population - maybe we should be exploring the use of anti-fungals?[/quote]

Hmm....worth looking into... or maybe the state of the inflamed mucosa renders it more favourable to incidental fungal growth?

Even then, can one be sure it's a purulent exudate rather than a thick accumulation of mature plaque?

RE: Feline Chronic Gingivitis Stomatitis Complex

Martin Hamilton — Sat, 11 Sep 2021 02:44:27 GMT

[quote userid="2131" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232994#232994"]Not knowing the cause of a condition is not really an indication for the administration of an antibiotic drug in any other branch of medicine that I can think of; and the days of "give it some antibiotic as well,just to be sure, can't do any harm" are past. We know now that indiscriminate use most certainly does do harm.[/quote]

In 99% of cases I would agree (as a new grad I was the sole outlier at our practice who wouldn't dispense flagyl as a first line response to diarrhoea, and I took some flack for it), but with FCGS my opinions differ. If a 14 day course of metronidazole or clindamycin prevents a cat from receiving a lifetime of prednisolone or cyclosporine (which may have further reaching consequences for antibiotic resistance later in life) then it's worth trying, especially in those cases with a purulent exudate overlying proliferative tissue. And although it's anecdotal I can attest to at least a couple of cases that looked like horrible FCGS cases (had already had full mouth extractions) and a course of one or both clinda and metro in conjunction with meloxicam resolved the inflammation (not just in the short term, but also long term, up to at least 12 months post-antibiotic course). The fact we haven't consigned any cats to long term pred use is a win in my book (though one will surely come along soon enough, especially since I'm only 2 years into dentistry-only practice).

I know anecdotal evidence is the lowest form of evidence we have, but unfortunately most of FCGS management is based on just that. Dr Anderson (Dip AVDC and Dip ACVIM) has done a lot of work on CCUS and has found metronidazole & cyclosporine to be an effective tool in managing these cases and, although not the same, both diseases present similarly (I don't think her study has been published yet).

I could brandish interferon with the same stick as antibiotics in the absence of us understanding the underlying aetiology of FCGS. There's a new paper published in conjunction with Reiter (Characterization of Oral Microbiota in Cats: Novel Insights on the Potential Role of Fungi in Feline Chronic Gingivostomatitis, Pathogens 2021, doi.org/10.3390/pathogens10070904) which shows cats with FCGS tend to have higher number of fungal species present than the general population - maybe we should be exploring the use of anti-fungals?

In my personal opinion I believe those that respond to antibiotic therapy are likely patients suffering from chronic periodontal disease (possibly with an element of osteomyeltitis) and severe inflammation associated with this rather than true FCGS, the problem is differentiating between them at initial presentation.

I just hope that we make some progress with this condition and can develop targetted therapies - I'm sure that is something we can all agree upon.

And no criticism taken Evelyn - I'm always open to learning more and finding ways to progress my knowledge and medicine!

RE: Feline Chronic Gingivitis Stomatitis Complex

Evelyn Barbour-Hill — Sat, 11 Sep 2021 00:21:10 GMT

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232992#232992"]

Evelyn Barbour-Hill said:
As a matter for discussion, what's the rationale for antibiotic or other antibacterial systemic treatment in this condition?

Our rationale is that we dont know what causes the condition, there are areas of ulcerated tissue, and anecdotally as per my mentor (AVDC Dip) there have been cases where oral inflammation has improved following a course.

Clindamycin is our first choice antibiotic and metronidazole used for action against pasteurella sp and it's immunomodulatory effects.

[/quote]

This forum being what it is, I want to point out that I've no axe to grind, I've full respect for all the experts participating here, I am not criticising or trying to stir up contention, I'm trying to get people to think and have a civilised discussion.

To be honest, it seems to me that all three reasons are a bit thin.

Not knowing the cause of a condition is not really an indication for the administration of an antibiotic drug in any other branch of medicine that I can think of; and the days of "give it some antibiotic as well,just to be sure, can't do any harm" are past. We know now that indiscriminate use most certainly does do harm.

Anecdotes from a mentor surely are a very poor reason, especially if it's on the basis of post hoc ergo propter hoc which we are very ready to condemn when quack remedies are being promoted.

So we are left with areas of ulcerated tissue. Is that an indication for administration of systemic antibiotic? I'm not so sure. I can't quite follow the logic through to certainty. What – precisely – is the systemic antibiotic intended to do?

Furthermore, those ulcerated areas are full of granulation tissue and heaving with plasma cells and neutrophils and all sorts of immune mechanism reactions. Are bacteria invading through them into the circulation?

RE: Feline Chronic Gingivitis Stomatitis Complex

Beats — Fri, 10 Sep 2021 23:24:32 GMT

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232992#232992"]Clindamycin is our first choice antibiotic and metronidazole used for action against pasteurella sp and it's immunomodulatory effects.[/quote]

I use amoxicillin first-line in cats. Amoxibactin tablets are surprisingly tasty and the oral suspension seems ok too. I think antibiotics do help. I'm no expert.

RE: Feline Chronic Gingivitis Stomatitis Complex

Martin Hamilton — Fri, 10 Sep 2021 22:17:35 GMT

[quote userid="2131" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232955#232955"]As a matter for discussion, what's the rationale for antibiotic or other antibacterial systemic treatment in this condition?[/quote]

RE: Feline Chronic Gingivitis Stomatitis Complex

Mike Dale — Fri, 10 Sep 2021 13:52:46 GMT

I so agree with everything Evelyn says. As for post molar and premolar extraction antibiosis I had so amy patients that could not be medicated at home that I gave up prescribing antibiotics. I don't think any of them failed to achieve full healing and I never resorted to ciclosporin. Thorough, complete extraction is essential. I'm retired now with no access to library but there was a superb article on technique in the Feline (formerly FAB) journal some years ago that I followed that was just doable under the aforesaid "line manager" scrutiny without causing any fidgetting.

RE: Feline Chronic Gingivitis Stomatitis Complex

Julian Earl — Fri, 10 Sep 2021 11:13:00 GMT

[quote userid="2161" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232970#232970"]t's worth remembering that steroids are not analgesics however.[/quote]

Thanks Rachel, I did not mean to suggest that they are primarily analgesics but are indirectly because the cats are clearly in a lot less pain when the inflammation is reduced by whatever means? My only concern then is if they permit any viral component, calici- or other to multiply? On this general topic, I do not think that NSAIDS are very potent ant-inflammatories for that matter?

RE: Feline Chronic Gingivitis Stomatitis Complex

Rachel Perry — Fri, 10 Sep 2021 08:20:37 GMT

Just another thought Kara- I know you said you knew you got all the roots, but I'm assuming you have radiographic proof? I've heard that statement said many times before...

RE: Feline Chronic Gingivitis Stomatitis Complex

Rachel Perry — Fri, 10 Sep 2021 08:16:51 GMT

absolutely. Any oral inflammation is excruciatingly painful- think of the last time you had an ulcer then looked in the mirror to see how tiny it is. it's unbelievable that these cats can cope/get any food at all when you see their mouths. So, yes definitely NSAIDs- potentially robenacoxib if meloxicam not tolerated, plus transmucosal buprenorphine, plus gabapentin. Peri-operative for extractions then pure mu opioids (methadone/fentanyl CRI), ketamine, alpha 2 agonists, local nerve blocks etc. I've also used maropitant in the hope this also imparts some analgesic effect.

It's worth remembering that steroids are not analgesics however.

RE: Feline Chronic Gingivitis Stomatitis Complex

Julian Earl — Fri, 10 Sep 2021 07:50:13 GMT

One aspect not specificallymentioned so far is tgat of analgesia. These mouths seem excrutiatingly painful as one might expect. Hence i think either NSAIDs or else steroids are essential?

Thanks...

RE: Feline Chronic Gingivitis Stomatitis Complex

Kara Gibson — Fri, 10 Sep 2021 01:17:25 GMT

[quote userid="3341" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232965#232965"]There is the old adage - that where there are multiple therapies advocated - there may well be a multifactorial disease (or diseases!)[/quote]

I said this almost verbatim to the owner at the last consult!

Thank you for all the advice. I luckily do have a dedicated owner but perhaps because of this she is a bit unwilling to give him a bit more time to see how things settle down post dental!

RE: Feline Chronic Gingivitis Stomatitis Complex

Bob Partridge — Thu, 09 Sep 2021 22:12:25 GMT

FCGS really highlights the paucity of good research in vet dentistry (the review paper by Verstraete makes that clear)

As Martin states - every dentist will have their own protocol (often based on anecdotal experience). Geography also plays a role - a survey in a lecture at EVDS showed that the preference in North America was for full mouth clearance, whereas in Europe caudal clearance was the preferred 1st option.

Personally - I have found similar levels of success with oral interferon & atopica. If one fails - I will try the other. Have had a few cases where used both as last resort & had good result in some. Generally I understand that s'cut Interferon is less effective (although easier & more fun for the accountants!) than topical. So have not used.

Once you get re-epithelialization you are onto a winner. Some never get there. If level of inflamm is reduced and QoL is OK then this can be an acceptable (if not ideal) endo-point. There are some cases that PTS is required (financial or other reasons) - this is not a failure if it prevents suffering (albeit not ideal!). Granulation extending into the esophagus would suggest a poorer prognosis.

Pain relief is of key importance IMHO.

Lactoferin can be of benefit, interesting research on mesenchymal stem cells may be the way forwards.

There is the old adage - that where there are multiple therapies advocated - there may well be a multifactorial disease (or diseases!)

RE: Feline Chronic Gingivitis Stomatitis Complex

Norman Johnston — Thu, 09 Sep 2021 19:40:12 GMT

The Matsumoto paper uses eight sc injections of interferon, which is similar to Virbacs own advised use. For an average weight cat that is four 10mu vials. I’m not sure of the current price but maybe £600?

The Hennet intraoral regime uses only one vial but probably less successful over time. Having said that it helped a lot of cats!

RE: Feline Chronic Gingivitis Stomatitis Complex

Rachel Perry — Thu, 09 Sep 2021 19:07:51 GMT

I think Martin has covered everything really well. There's still so much we don't know about this disease even though we have more and more research looking at it and trying to elucidate it.

I have thought about using doxycycline for these patients as we know that sub-antimicrobial doses are actually immunomodulatory, reuducing matrix metalloproteinase activity and reducing collagenase activity. It has been used in the treatment of periodontitis in people for that reason, and there are also reports of use for dermatological problems. However no convincing evidence for it's use for this condition in cats, so if we do follow an evidence-based approach then we should reach for cyclosporine or interferon or preds. But then if we never use doxy, we'll never gather evidence as to whether it is helpful or not. I do use it for medical therapy of CCUS cases and have had some success with it. Interestingly though, a cochrane review on the use of doxycycline for the treatment of recurrent aphthous ulcers in people shows no evidence for any benefit- though it is suggested to be used as a mouthwash.

I've never used interferon much, have always reached for cyclo as I felt the evidwnce- base was better, but this paper is interesting, and opens a whole can of worms, as it suggests it's helpful by reducing calicivirus' ability to replicate, which is opposite to Norman's findings.

Matsumoto H, Teshima T, et al. (2018) ‘Evaluation of the efficacy of the subcutaneous low recombinant feline interferon-omega administration protocol for feline chronic gingivitis-stomatitis in feline calicivirus-positive cats’, Research in Veterinary Science, 121, 53-58 https://doi.org/10.1016/j.rvsc.2018.10.003

Preds are a potent anti-inflammatory rather than immuno-modulatory drug and you have to accept significant side effects with their use, ands steroid tachyphylaxis especially if using injectable forms. I tend to reserve oral preds for patients as a last resort, or where costs prohibit cyclo or interferon. Then taper to lowest effective dose.

It's worth remembering you might not get all oral inflammation to disappear- but you want a patient that can eat comfortably and maintain body weight. I use a client's quality of life score when assessing response to treatment.

Oesophagitis- really interested by this- how many of these do we scope to check? I suspect not many, but I've definitely seen follicular inflammation extending into oropharynx as far as laryngeal area. Should we be treating for it? Maybe... We don't use a antacid, but will often add in maropitant- hopefully adding some analgesia as well.

It can take a while as well for the inflammation to settle, so might just need more time. I have used robenacoxib successfully in cats that can't tolerate meloxicam, so worth considering another time.

Evelyn raises an interesting point about antibiotic use in these patients.....we advise not to use it for most dental problems, but this is one disease where we seem to reach for them. My justification has usually been where there is mucosal/epithlial ulceration then it would be helpful/necessary, however most ulcerative human oral diseases are treated by topical management. Metronidazole is also an interesting choice- and perhaps is helping more for its immunomodulatory effects than antimicrobial per se. I always struggle getting metronidazole into cats however.

And lastly, good luck administering cyclosporine to a cat.. it's horrible- you need a competent owner and compliant cat!

RE: Feline Chronic Gingivitis Stomatitis Complex

Rachel Perry — Thu, 09 Sep 2021 18:42:43 GMT

Lurking? I take that as a compliment !

RE: Feline Chronic Gingivitis Stomatitis Complex

Norman Johnston — Thu, 09 Sep 2021 18:14:20 GMT

Also - Boaz Arzi from UC Davis did two great talks at BSAVA this year. They are both still in the on line library if you are a member

RE: Feline Chronic Gingivitis Stomatitis Complex

Norman Johnston — Thu, 09 Sep 2021 18:09:46 GMT

I often think that the use of cyclosporin is often geographical. In North America, where feline recombinant interferon is hard to come by, cyclosporin is used as an alternative. The Lommer paper is pretty well the only one out there but even the author admits that the study was short on numbers and follow up. The Hennet paper compared interferon with pred and also did not rule interferon out but concluded the results were no better.
Interferon has the advantage of having minimal side effects. Cyclosporin needs proactive follow up to ensure proper trough levels and major organ health. Pred, is used, needs to be at immunosuppressive doses.

At Dentalvets we ran an interferon study on all FCVS cases from 2007. The success rate in FCV negative cats was very high. If the patient is FCV positive, the results are less good. Using PCR testing we were also able to determine the virus load in these cats.

Now that the teeth are out your tools are all medical. My personal view is that interferon is not the silver bullet by any means but better than cyclosporin for the reasons above. Pred is often used as rescue therapy and has the advantage of being inexpensive and well tolerated. Analgesia and nutritional support are vital. This guide might help you.

https://weu-az-web-cdnep.azureedge.net/mediacontainer/medialibraries/dentalvets/documents/fcgs-nov_2015.pdf

This will be tough case by the sounds of it. The owners have to be patient and deep pockets also help. Best of luck!

RE: Feline Chronic Gingivitis Stomatitis Complex

Martin Hamilton — Thu, 09 Sep 2021 17:52:58 GMT

[quote userid="2131" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232955#232955"]I hope Rachel Perry is lurking and may chip in here.[/quote]

As far as I'm aware there are no papers demonstrating the subantimicrobial dose in cats? Dr Reiter at U Penn uses 1mg/kg BID in cats I believe, but I'd have to double check.

RE: Feline Chronic Gingivitis Stomatitis Complex

Evelyn Barbour-Hill — Thu, 09 Sep 2021 17:37:54 GMT

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232937#232937"] It's important the client knows that these cases can be a journey rather than a quick "one and done" approach. [/quote]

Oh, how true.

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232937#232937"]I'd say approx half our cases respond to this and it's questionable as to whether these are true FCGS cases, especially in younger patients).[/quote]

Indeed, it's hard sometimes to discriminate between "true FCGS" and other severe periodontal diseases.

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232937#232937"]We tend to perform selective extractions, particular the premolars and molars as you have already done[/quote]

I think most would agree that total extraction of the cheek teeth is a sine qua non even though it may not in itself be curative.

[quote userid="3094" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232953#232953"]radical dental extractions which is extremely tough when the roots are not purulentetc, then when the cavities are healed, using corticosteroids.[/quote]

Oddly, I never found corticosteroid administration terribly helpful. It can be a quick temporary fix and relieved things enough for the cat to eat well, but has rarely achieved anything resembling a cure, in my hands. It is odd how experiences differ from one clinician to another.

I've also abandoned excision of tissue, except maybe very selectively here and there; but in the older cat any very florid tissue must have a deep biopsy in case there's a squame cell carcinoma under it.

I've also abandoned interferon as expensive and useless.

But I would say that extraction, with good instruments and technique and above all patience, should not be so tough. Of course if you've got the boss or your "line manager" breathing down your neck and muttering about margins and targets and KPIs, you might do better not to attempt it.

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232937#232937"]In the immediate post-op period we generally give 14 days of clindamycin (5.5mg/kg BID) with Metacam 0.05mg/kg SID. After two weeks clinda, we then switch to metronidazole 10mg/kg BID for 14 days [/quote]

As a matter for discussion, what's the rationale for antibiotic or other antibacterial systemic treatment in this condition?

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232939#232939"]I have also heard of some using doxycycline at a subantimicrobial dose, but haven't tried it.[/quote]

I hope Rachel Perry is lurking and may chip in here.

RE: Feline Chronic Gingivitis Stomatitis Complex

Julian Earl — Thu, 09 Sep 2021 16:22:59 GMT

I will be interested to see people's approach to these! Inever had any success except with radical dental extractions which is extremely tough when the roots are not purulentetc, then when the cavities are healed, using corticosteroids.They are so effective at reducing/removing the painful inflammation other meds tend to be much easier. No?? No antibiosis made a difference as I recall, certainly not metronidazole?

TIA.

RE: Feline Chronic Gingivitis Stomatitis Complex

Anthony Todd — Thu, 09 Sep 2021 15:55:56 GMT

My son's cat had extensive lesions and grotty teeth and the usual gums.

The affected teeth were [easily!] removed, [not me] a short course of ABs, chlam I think, and no problems since.

Photos hopefully will follow [before end of this week]

My experience agrees with this approach but I'll get him to take a current picture. [cat permitting!!]

RE: Feline Chronic Gingivitis Stomatitis Complex

Martin Hamilton — Thu, 09 Sep 2021 03:00:21 GMT

[quote userid="11285" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232938#232938"]

Couple of questions:

1) How do your owners get on tableting these cats for antibiotics? My patient is really sweet and will take liquid meds but I suspect his owners will struggle with tablets.

[/quote]

We use liquid clindamycin (antirobe) and a compounded metronidazole (the benefits of a less stringent cascade system here in Canada). We also stock capsules of both which can be opened and sprinkled on wet food. Liquids realy do help.

[quote userid="11285" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232938#232938"]2) Are you checking for Toxoplasma before starting cyclosporin in these cases?[/quote]

Unless the cat is outdoors, or FeLV/FIV positive, then no. We do warn about it, however. Yet to have any problems. Indoor cats are much more commonplace here.

[quote userid="11285" url="~/001/veterinary-clinical/small-animal/dentistry/f/discussions/29988/feline-chronic-gingivitis-stomatitis-complex/232938#232938"]3) Are you recognizing oesophagitis as a potentially complicating factor in any of your cases?[/quote]

Can't say we've noticed any.

I'm looking forward to hearing the opinions and experiences from the experts and specialists on here too! Because protocols are so variable, you never know what little gem of info you'll come across. I have also heard of some using doxycycline at a subantimicrobial dose, but haven't tried it.

RE: Feline Chronic Gingivitis Stomatitis Complex

Kara Gibson — Thu, 09 Sep 2021 02:51:39 GMT

Thank you for your wonderfully detailed reply!

Couple of questions:

1) How do your owners get on tableting these cats for antibiotics? My patient is really sweet and will take liquid meds but I suspect his owners will struggle with tablets.

2) Are you checking for Toxoplasma before starting cyclosporin in these cases?

3) Are you recognizing oesophagitis as a potentially complicating factor in any of your cases?