A 71-year-old French man suffered Behçet's disease since he was a teenager. A punched-out ulcer of the ileo-colonic valve, microscopically non-specific, was discovered fortuitously by colonoscopy. The occurrence of atrial fibrillation led to the prescription of anticoagulation together with amiodarone.
Oral ulcers disappeared within a week, although they had been continuous for 55 years. Colonoscopy performed within a month disclosed healing of ulceration on the valve. Ulcers failed to recur after stopping anticoagulation one year later.
The benefit of amiodarone on the ileo-caecal ulceration was effective for at least 7 years, until last colonoscopy in July 2007. The mouth ulcers failed to recur until December 2008.
Behçet's disease is a multisystemic vasculitis of unknown origin, with a genetic predisposition and inflammation deregulation concerning cytokines and tyrosinekinases . Behçet's is especially frequent among Japanese and Turks, with different locations in these ethnic groups. Low prevalence Caucasian populations pose different diagnostic and possibly therapeutic problems.
The most frequent, almost constant, lesions are mouth ulcers. More specific are genital aphtous ulcers . The other systems involved are eyes as uveitis, skin, central and peripheral nervous system, blood vessels, joints and digestive tract [1,2].
Digestive locations can be isolated especially frequent in Japan where it has been described as "enterobehcet" . Ileo-caecal location as discrete, punched out ulcers is the most frequent and the most classical [2,4].
Diagnostic criteria vary, and don't take the place of a good clinical analysis of each individual case .
The efficiency of amiodarone has been discovered fortuitously in the present case.
A 71-year-old male of French origin suffered gastroesophageal reflux. He consulted first in February 1994. He suffered during the 1950's from chronic skin lesions diagnosed as furunculosis. A severe and continuous oral aphthosis had been developing since he was a teenager. Genital aphthosis in 1990 made the diagnosis of Behçet's.
A treatment with colchicine, then thalidomide, failed to develop any clear-cut effect. Nevertheless, genital ulcers did not recur later.
Confluent erosive esophagitis was associated with reflux. Two days after beginning omeprazole 20 mg o.d. he developed a severe, acute necrotizing pancreatitis. A less severe bout occurred in July 1999 without taking any medication. He failed to develop later any sign of chronic pancreatitis.
In August 1995, because of vague abdominal discomfort paralleling burst of oral apthous ulcers, he underwent colonoscopy (Fuji 200, St Quentin en Yvelines F78185 France). This revealed a single, punched out ulcer of the upper lip of ileo-caecal valve, very hard under the forceps. Many biopsies of ulceration and around elicited only non-specific inflammation. The valve was gaping. The remainder of the colon and the last 30 cm of ileum were normal macro- and microscopically. As it was far from certain that the ulcer was responsible for the pain and because of the lack of any efficient medication, a simple follow-up was selected.
A further treatment with colchicine lessened transiently the oral aphtous ulcers but the colonic ulceration got wider and wider and progressively destroyed the valve (Fig 1).
Figure 1 April 1998 - Large ulceration with gaping valvula.
In August 1999 atrial fibrillation led to the prescription of fluindione and amiodarone 400 mg daily. Within a couple of days the oral aphthous ulcers, which were almost permanent, disappeared. A follow-up colonoscopy was performed within a month: the ulceration at the valve was completely healed with only scar distortion (Fig 2).
Figure 2 October 1999 - Cicatrization 1 month after starting amiodarone and fluindione.
After long-lasting normalization of cardiac rhythm at 1g amiodarone per week, anticoagulation was stopped in July 2000. Oral and colonic ulcers did not recur.
In May 2001, without any obvious reason, a moderately severe oral aphtous burst occurred; the patient denied poor compliance with the amiodarone.
Colonoscopy, performed quickly thereafter, disclosed the recurrence of a small ulcer on the valve on the opposite lip (Fig 3). It healed again together with the oral ulcers, within a few weeks. Repeat colonoscopy failed to disclose any recurrence since that time and until December 2008. It was not conceivable, on cardiologic grounds, to stop amiodarone, as a test.
Figure 3 April 2001 - Transitory recurrence of ulceration paralleling buccal ulcers burst.
A cutaneous prick test was negative during amiodarone therapy. Ocular examination remained normal.
Behçet's disease seems very probable in the present case as 3 major criteria (oral and genital aphthous ulcers associated with skin lesions) and 2 minor criteria (digestive and cardiac lesions) are present. The absence of ocular lesions seems to be more frequent in case of colonic lesions.
Isolated punched out lesions are classical for colonic Behçet's disease . Non-specific microscopic inflammation is usual, as underlying vasculitis is rarely evidenced on biopsies. Normality of ileum and colon otherwise did not favour atypical Crohn's disease.
The earlier lack of efficiency of thalidomide and its poor tolerance did not favour this medication. Surgery seemed to be inappropriate taking into account the lack of clear-cut clinical manifestation. Moreover, it was far from certain that resection of the ulcerated region would prevent recurrence of ulcers after surgery. The patient was informed that perforation could occur [2,4].
It is possible that the present type of lesion, moderately deep with smooth margins, could lead to less complications than the "volcano type" - moderately large, deep, with nodular margins .
Pancreatitis could be due to Behçet's as previously described [2,6]. However, this complication is rare. Omeprazole is, most probably not the cause despite the close temporal relationship, as pancreatitis is no more frequent with this medication than with placebo, and because of recurrence without taking any medication.
Amiodarone could be the cause of the negative pathergy test. However, it is positive in only 50% of cases among high prevalence populations , and this positivity is even more unusual among low prevalence, occidental patients.
Medical treatment of Behçet's disease is difficult. Colchicine is well tolerated and has been used with some success, as is thalidomide, but the latter is sedative and leads to long-term polyneuropathy . Corticotherapy could also be useful for short-term use but could increase the risk of perforation. Various immunomodulating medications like mesalazine, cyclosporine and azathioprine, interferon , pentoxyphilline and a Chinese plant On Chung Eum have been used. They act probably through a reduction of TNF alpha secretion or effect .
Recently, anti-TNF alpha medications: infliximab and etanercept, mycophenolate mofetil: an inducer of caspase-independed, lymphocytes activated apoptosis, and anakinra: an IL1R antagonist, have been also used with success. Hypersecretion of various cytokines, especially TNF alpha, seems to play a central role in Behçet's disease. Thalidomide also acts on TNF alpha.
Amiodarone led to a dramatic healing of both oral and colonic ulcers. This effect lasted at least 7 years for colon and 9 years for the mouth. This improvement is most probably not fortuitous though it has not yet been described before.
Amiodarone decreases TNF alpha and Il 6 secretion (9) and has also anti-inflammatory and anti-oxydative properties . These properties could explain its benefit for the present patient. However, amiodarone can, very rarely, induce leucocytoclastic vasculitis.
In conclusion, in this patient suffering of Behçet's disease, amiodarone led to a dramatic and long lasting remission of oral and colonic ulcers. This effect could have occurred through the actions of this medication on inflammation and cytokine secretion.
This article was first published on GastroHep.com on 7 July 2009.
Corresponding authorBernard Maroy
Maison Médicale de Lunesse. 24 rue Chabernaud
F16340 L'Isle d'Espagnac France
Fax: +33(0)545 942 500
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