Try colchicine..

Thank you Velma.Do you have a personal experience with colchicine in treating patients with oral ulcers.

Yes. One 8 years old boy, suffering with terrible oral ulcers... All other specialist gave up of treating him (all profiles of dentists, then gastroenterologist /excluded Crohn/, esc.) It was terribel : most of the time he had ulcers..Several times he lost 4 kg/per week since he could not eat.

Small dose of colchicine - 0,350 mg, was sufficient to control disease, let's say 80%-90%....

p.s.he had no other symptoms or problems....Colchicine - is almost no toxic, well tolerated....

Good luck

Nystatin sublingual tablets

well, the pathogenesis of aphtous ulcers involves TNF alpha. This is the rationale for the success of anti TNF agents eg locally active steroids eg in the form of oral base or by simply applying a paste made out of a "wetted" prednisolone tablet (donot use prednisone as it is not active locally and ask the patient not to swallow the steroids).

The other approach is using pentoxyphylline tablets.

Thanks Velma for your suggestion. Mohamed, I gave up using topical stroids because there were not effective for my patient. Regarding pentoxyphylline, what is the rationale behind using it, and do you have a personal experience with it?

we have tried using low level laser therapy for ididopathic ulcers and found it to be effective

i am using combination of 4 drugs to treatment of idiopathic oral ulcer. these drugs are elixir of diphenhydramine(60cc), suspension of ALMG(150cc), powder of tetracycline(1gr) and injection form of betamethasone(16mg). this combination is effective in controlling of disease during 2-3 days.

after trying colchicine and local corticosteroids, thalidomide is an option because of anti TNF effect. In patients with full-blown Behcet azathioprine or TNF inhibitors sometimes work well for ulcers

Thanks all for your suggestions. Arturo you suggested thalidomide and azathioprine, what is the dosing regime you use for a healthy male in his twenties?

First try to find out the reason for recurrent apthous stomatitis. If its because of some nutritional deficiency, them give that supplements. Otherwise proper oral hygiene with topical application of Amxelanox gives very nice and good results. Try it. You will be surprised.

Thank you Deepak. Topical treatment is always preferrable to systemic treatment. Also we have done all the necessary investigations to rule out any systemic disease. It is interesting that this patient does not have any underlying problem not even Behcet's disease.

Ok Dr. Najla Dar-Odeh. Kindly check whether these ulceration are due to erosive lichen planus or pemphgus. If none of these are the reasons, then go for amxelanox. It will definitely help. You can very easily differentiate the ulcerations occuring because of lichen planus or pemphigus with that of recurrent apthous stomatitis.

Amxelanox ia a newer drug used in topical form. It is greatly effective. Trials are going on for Lichenoid reactions as well as lp too

My patient's ulcers can be described as major aphthous ulcers. They definitely don't belong to OLP or bullous disease. I have to check whether Amlexanox is available in Jordan. It is definitely worth a try before starting the patient on another oral immunosuppressant.

Aphtous oral ulcers are very common in the Middle East (Arab, Armenian and Turkish descent), with or without other signs of Behçet's disease. I can understand your looking for a safe treatment, since the patient presents no other signs of Behçet's. Topical triamcinolone in an oral base can help. If the response is sub-optimal, oral colchicine 1mg daily can be added. Of course, immunosupressors or thalidomide are helpful, but they are not safe enough for a localized problem, unless the ulcers are so extensive that they interfere with eating.

Yes indeed, the ulcers are so deep that healing is always associated with scarring and the end result is a fibrosed lip and limited mouth opening. This caused not only eating problem but also problems in speech.

Another photo of this unfortunate young chap

Thank you for the informative pictures. An immuno-suppressor is certainly needed here. I would nonetheless give topical triamcinolone and oral Colchicine as a mainstay and add Azathioprine as probably one of the safest immuno-suppressors, since it is expected that this patient might need one for years to come. A short shuttle course of oral steroids for no more than a month would give quick relief. As early as 1990, Yazici et al noticed that treating Behçet's disease with Azathioprine for prevention of eye disease led to less frequent oral ulcers, genital ulcers, and arthritis (N Engl J Med. 1990 Feb 1;322(5):281-5.)

Thanks Majda for the informative treatment plan. The patient is currently on 45 mg daily prednisolone. He started to gain weight and have acne. Replacement with another immunosuppressant , as the ones you suggested, seem to be inevitable in the near future.

Hi Najla, can you please give info regarding the effect of prednisolone 45mg which you are giving, on the ulcerations seen. What is the frequency of the ulcers.

to my knowledge Amlexanox has been studied for its effect in RAS where it reduces the severity and duration of the disease. It is also advised to be applied topically from the prodromal stage.

And also if this disease is recurrent and heals by fibrosis; there must be other areas of fibrosis in the mouth (if site is variable).

Does the patient have any habit of chewing on betelnut (?), or anything which can cause progressive fibrosis & ulcerations in oral mucosa.

We had a case of apthous major over soft palate which responded to topical steroids.

I can say that it has a moderate effect on the ulccers because not all ulcers healed well. On the first episode of treatment (few months ago), all ulcers healed at this dose. Once the patient started to reduce the dose, he got ulcers again. Now I am collaborating with his physiciian to modify the treatment, the latter being reluctant to increase the dose or start the patient on medications to prevent osteoporosis. That is why I am keen to replace his current medication.

Actually Saurabh we don't have the habit of betel nut in Jordan. The tobacco use habits that are popular in Jordan are cigarettes and , more recently, narghile. The most common place of ulcers in this patient is the labial mucosa.

Hello Najla...

I just checked the photographs of the patient which you have posted. And the clinical signs which you are telling cannot be classifies under RAS.

The photographs show blanching of the mucosa.. Further lips are also involved. On top of it you are saying that the ulcers are deep and the heal by scar formation and lead to fibrosis.

SO clearly it has nothing to do with RAS.

Further you clarified that the patient was not a tobacco chewer and he also didnot presented any significant history for the same.

So can you please describe the case in detail so that I could be of some help to you.

Further I must say that histopathology is required in case you are not able to diagnose. Do take a biopsy sample and send for the histopathological examination. Further do get the immunofluorescence tests done if possible.

It will help you a lot.

Further you said that the systemic prednisolone is not working that efficiently. This means that the disease is not basically inflammatory in type though it is presenting with ulcers.

There a certain group of diseases which leads to ulceration as well as fibrosis. For example Kimura's Disease. It has got similar presentation which you have elaborated so far.

The tragedy with such lesions is that the diagnosis is very important. Because the lesions of Kimura's disease are similar but treatment is totally different. Intralesional or oral steroids can shrink the nodules but seldom result in cure. Cyclosporine has been reported to induce remission in patients with Kimura Disease. However, recurrence of the lesions have been observed once this therapy is stopped.

Cetirizine is an effective agent in treating the symptoms of Kimura's disease.

So my suggestion is.. Go for biopsy.. Further find out whether any similar lesions are there on other body parts or skin anywhere.

Henceforth you please tell us about your case completely with all the remedies done so far and to what extent those remedies helped.

Waiting for your response.

Kind regards,

Dr. Deepak Gupta,

Dept. of Oral Medicine and Radiology,

MMCDSR, Mullana, INDIA.

And yes Amxelanox will help in such cases also because its effect is basically wide and is antiallergic too..It will definitely be avialable there. Otherwise I can send it if you want. Let me know..

Further one more thing... The photographs shows whitish areas... If the are not scrapable.. That doesnot rule out candidiasis. If the patient's had candidiasis and presented with oral ulcers... Definitely because of pain the mouth opening will reduce.. On top of it ..if you started with systemic cortisteroids.. As they are immunosuppressants..it will lead to flare up of candidiasis apart of resolution. So check for it too. Again biopsy will help.

So my suggestion: If you have not tried antifungals till now... Do biopsy.. If there are fungal predominant elements.. Stop steriods and start with antifungals... It may be hypertrophic candidiasis...

Check the patient systimically...

Check his taste perception too...

Dear Deepak, thank you for all your comments. The patient is about 27 years. He started to get the oral ulcers about 4 years ago.Ulcers are limited only to mouth specifically the upper and lower labial mucosa. The ulcers are so deep so they heal with a scar (the white color you saw is scar tissue not thrush) . When I first saw him about 6 months ago, the ulcers were oozing pus and this turned out to be a superinfection with pyogenic bacteria and not pyostomatitis vegetans. He had all necessary blood tests to uncover any underlying systemic problem. The biopsy showed non-specific inflammatory changes. I think that based on the idiopathic nature and shape and history of ulcers , those ulcers qualify for major aphthous ulcers, and I don't think that immunofluorescence will yield a positive result. Perhaps the patient will develop Behcet's disease

I agree with you, Najla. These do look like bona fide aphtous ulcers, of the severe kind. Usually, when the ulcers are that severe, they also have genital ulcers, that they may not disclose, unless asked.

Kimura's disease rarely involves the oral cavity, and, when it does, it gives painless lumps, in addition to the other signs of lymphadenopathies in close or remote areas, and striking eosinophilia.

All the time, we see, in our geographic area, people with aphtous lesions, who may or may not develop Behçet's disease later on. Sometimes, one of their relatives has Behçet's disease .

Always great to follow your comments Majda. If this was your patient, what tests would you like to request?

Thank you, Najla.

Behçet’s disease is a clinical diagnosis. Consultation with a rheumatologist is among the guidelines for this disease. You already did all necessary blood tests to uncover any underlying systemic problem. I would worry about the possibility of vasculitis (venous and/or arterial) and CNS involvement. I would request anticardiolipin antibodies which occur in up to 30 % of patients and are a contributory factor to thromboses, although these do occur in the absence of such antibodies. Since these can occur in odd places (vena cava, intra-cranial veins...), the patient must be instructed to report any odd symptom or sign anywhere in his body. Ocular involvement in this disease is symptomatic, so even when routine screening is not done, there usually is no delay in its diagnosis. HLA typing is not useful in individual cases, it is reserved for epidemiologic studies.

You can use "smile" mouth ulcer gel - a herbal gel from India. This is mainly due to vit. B12 deficiency. You should have the soft pulp of tender coconut which works best in this case. Take curd with rice and less spicy dishes till it heals. Eat ripe mangoes.

if this all is the case them i would say Majda is giving good opinion...

Still you can try Amxelanox... It has given very good results in certain idiopathic apthae cases of mine....

The treatment plan that my colleagues and I are inclined to do for this patient is to continue on the current course of prednisolone. Once the ulcers are controlled, the dose will be tapered and eventually replaced with thalidomide since the patient had poor response to colchicine in the past. Azathioprine may also be added. As for Amlexanox, I am afraid that it is not available locally so I will see if we can make an order for it.

If I may, I would like to add this:

1. It would be good to start the additional drug (be it Thalidomide or Azathioprine) right away along with the current steroid dose, because these are slow drugs: no effect is to be expected before a month. This would allow to taper the steroid without a rebound flare that would take us back to square one.

2. I would worry about an important POTENTIALLY IRREVERSIBLE side effect of thalidomide, namely Peripheral Neuropathy .

3. Even males taking thalidomide must practice contraception

Thalidomide as it is a reserve drug, and to be used in dentistry it is also far flung option keeping in mind the serious side effects as Majda pointed out, clinician has to keep the risk-benefit ratio in mind.

I wish you the very best Najla in managing this case and pls keep this case updated.

This will really help the people out here on this forum a lot.

So Majda, do you suggest using azathioprine as a safer drug, or going back to colchicine? since it may produce an effect when combined with prednisolone?

I will do my best Saurabh to follow up the patient closely taking into consideration the valuable advice you guys are giving me. Taking into consideration that I am origionally a dentist and not medically qualified, it is essential for me to take the advice of the experienced doctors who were generous enough to share their opinions

I would give colchicine as a baseline drug for someone with aphtous ulcerations regardless of the presence of other signs of Behçet, because it dampens most manifestations, and gives us time to move. It can be kept with azathioprine.

I would opt for azathioprine as a safer drug than thalidomide. We treat many other rheumatic conditions with this drug, and patients can stay with it safely for years.

The role of steroids is just to control symptoms/signs rapidly for a better quality of life until the main drug (ie azathioprine) takes effect. Steroid must be tapered off as soon as possible: as short as 3 months of steroid is enough to give osteoporosis at any point in time. It is not a drug one can stay with for a long time, without a heavy toll.

So Majda do you suggest starting the patient on 0.5 mg colchicine and taper prednisolone over a period of one month til the dose of 5 mg is reached?

Perhaps 1 mg colchicine daily. I would give it for life.

Tapering steroid would be started 2-3 weeks after institution of azathioprine (to get some clinical effect, not the full effect). Decrements of 5mg prednisolone of the daily dose every week is conservative, to avoid flares. The aim is to get to 5mg daily followed by 5 mg every other day then stopping. Since your patient is on 45 mg daily, his weaning would take about 3 months.

Azathioprine can be given 2 mg/kg/day (2.5 mg is allowed). Later on, after many weeks, if the patient improves significantly, it can be lowered to 1mg/kg/day, no less than that , and kept as long as necessary. We are talking about years.

I think it is very important to determine why the oral ulcers are recurrent. Treatment of the underlying cause is recommended in order to stop the recurrence. The answers given are very good.

Proper oral hygeine, Vitamin supplement and also anxiolytic.

Steriod can also be tried. along with above two meassures.

Thank you all. I will start the patient on the drug regime suggested by Majda as above and I will keep you updated of the result.

Dear Majda, do I need to request LFT before starting treatment?

Yes, Dear Najla. As a minimum, baseline laboratory tests are: Complete blood count with platelets, Liver function tests, serum creatinine, urine analysis. These must be repeated after a month, then every 2 months. One must also know if there is a history of hepatitis, and do a tuberculin test. In doubt, do get the full battery of viral tests for hepatitis B & C. Good luck. Usually azathioprine is very well tolerated if there are no infections.

Thanks a million Majda :))

An update on the patient's condition: The patient was controlled by 50 mg prednisolone daily for 2 months, tapered to 15 mg daily. The ulcers are currently improved in frequency and severity. He gets minor ulcers every now and then but the main problem is in the scarring of oral mucosa that has led eventually to limited mouth opening.

Dear all

Does high dose corticosteroid is necessary and two months why not one month? why not moderate ? what is the evidence

colchicine sometimes works

I'm rheumatologist from Amman Jordan 

Dear Dr Basem, I explained earlier that the patient has severe oral ulcers of idiopathic type because we could not identify any causative factor. I mean by "we" the oral medicine specialist and the physician. Colchicine is an option, but for this patient we used prednisolone which was continued for as long as the patient needed. Stopping the medication meant recurrence of ulcers. That is why treatment usually continues for months. 

Dear Dr Najla

koul am wantoum bekheir

My question is :What is the best starting dose of corticosteroids?Is there any controlled studies?

thanks

Happy Eid to you too Dr Basem. The recommended initial dose of prednisolone is 1mg/kg/day as a single morning dose. This is tapered after one to two weeks. However, for severe cases that don't respond we may need to continue the initial dose until all lesions have healed.

topical tacrolimus

in one study , the use of doxycycline cap 100 one daily for 3 months can reduce the recurrence and severity of aphthous ulcer.