"Behcet Disease is a multisystem disorder of unknown etiology. It is one of the most interesting and challenging diseases in nature, and attracts the attention of researchers and physicians of different disciplines.
The increase in Number of registered cases, chronicity of the disease, ethnic polymorphism, sex dimorphism and heterogenicity of the disease manifestations, and unsatisfactory results of treatment of some cases makes the problem of Behcet's Disease one of the most actual problems in medicine.
And as you already know now there is a speculation that this disease was known already in 500BC from the description of Hyppocrates. He described the same disease picture like we have in Behcet's disease. But the classical triad of oral and genital ulcerations and inflammatory eye disease was described in 1937 by the Turkish dermatologist Hulusi Behcet and bears his name. The fourth manifestation of the disease, skin involvement, was added later.
We know that Behcet's Disease has a worldwide distribution, and as Prof. Ohno noticed in 1986, it occurs most frequently between latitudes 30 and 45 in North and Asian and EuroAsian population, and that's why he called it the Silk-Road disease.
When we look at the prevalence and the sex ratio of the disease, we notice also that the disease most frequently has higher incidence in places like Turkey, where the incidence or prevalence of the disease is 19 patients per population of 5000, in Saudi-Arabia it is 2 per 10000 of the population as in Egypt, and in these areas also the male to female ratio is higher than in other parts of the world, it's around 3:1 and 5:1 and 2:1, while in other areas, like Japan and Korea, when we move to the east, we notice that there is a higher frequency of female to male ratio, and in the UK it is also the same.
The classification of the disease in the wider spectrum of medicine produced two views, that it might be classified as vasculitis or as seronegative spondylo arthropathies, because these two categories have the same systems to be involved, the mucous membranes, the skin, eyes, gastro-intestinal tract, genital-urinary tract and joints. But later, when BD was found to be associated with HLA-B5 or 51, and we know that the seronegative spondylo arthropathies are associated with HLA B-27, this idea was a little bit changed. We know now that there are different lesions in these two groups, both clinical and histo-pathological findings of arterial and venous vasculitis, we are more having a tendency to classify BD in the vasculitis.
Any age group can be affected with the disease but the higher incidence of the disease are in the age group between 20-29, about 45% of Behcet's are in this age group.
I am going to speak about the disease on the example of Jordan, on the analysis of 150 patients. I think this result is the same as other studies also, that the disease is higher in the third decade of life, in the age of 20-29. But children also might be affected and people at a higher age, but this is rare. When we see the mean-age of the disease onset, the mean-age of the disease onset in our patients was 25, in males it was 24 years and in females it was 27 years, and this is to show us that females might get the disease at an older age.
The onset of the disease might be in different ways. In about 50% of the patients they will have the oral ulcers and other features, the full blown picture, so it is easy to diagnose patients at this stage and there will be no delay. But the presentation might be in different ways in other patients, and we have 40% of patients having recurrent oral ulcers before the onset of other disease manifestations from one year to ten years, and in three patients we had the onset with uveitis only, inflammation of the eye without other symptoms, and that's why the treatment and diagnosis were delayed until the other features became manifested. Two patients had epididymitis as the first manifestation, and other patients had deep venous thrombosis, while in one patient - he observed genital ulcers for a start.
The Disease manifestations are divided in two groups, the major criteria and the minor criteria, according to their prevalence. The major criteria include recurrent oral ulcers, genital ulcers, skin lesions, eye involvement and pathergy test. According to the international study group for BD, a diagnosis of BD can be made if the patient has ROU plus two of these other criteria, which is the genital ulcers or the skin or the eye or the pathergy test.
And so in our patients in Jordan genital ulcers were present in about 84%, and I think this is similar to other countries. The skin lesion was present in 90%, eye disease was in about 46%, and pathergy test in 54%.
The oral ulcer might be present in its three forms, the major ulcers, the minor ulcers and the herpetiform lesions. They are usually painful.
Skin lesions are present in different ways, and the erythema nodosum being present in about 50-60% of patients is very characteristic of BD. The second important skin lesion is the acneiform lesions which is also very frequent in patients, and is considered as specific for BD if the patient is not in puberty or is not taking corticosteroid therapy. Another lesion characteristic for Behcet's also is the inflammation in skin due to phlebitis, and these lesions might turn sometimes into huge ulcers in the legs.
The pathergy test, which is the formation of a sterile pustule at the sight of a needle-prick, is seen frequently in many patients with the severe disease in eastern countries. I think in western countries it is not observed as in our countries. In Japan also.
The frequency of major criteria and minor criteria is recorded here. Among them the superficial thrombophlebitis is noticed in lower numbers of patients, DVT (deep vein thrombosis) in about 30% of patients, arterial lesions in 40%, arthralgia/arthritis in 30%, gastro-intestinal involvement about 19% - it is higher in other countries, like Japan and European countries, central-nervous-system is noticed in about 41% of patients, pulmonary lesions in about 8% rate, and epididimoorchitis in 28%.
If you look at the localisation of the arterial involvements in our patients, we found that radial arteries which are on the hands- arms and forearms- is present in two patients, the coronary arteries- supplying blood to the heart- in two patients, and the mesenteric abdominal arteries- supplying blood to the intestines- in one patient, and in one another femoral aneurysm- gives blood to the hip and leg, and popliteal artery- on the leg- was involved in one patient.
And this is the femoral aneurysm in the patient. He developed this aneurysm at the site of a needle-prick to his femoral artery. They tested his blood gases and at this site he developed a big, huge sack of blood, which is called aneurysm. And then when we looked at the deep venous thrombosis we found also that the veins of the lower extremities were involved mostly in patients 27% and 81% but we also had patients who are having involvement of the major venous system, the vena cava superior and inferior vena cava, also they might be involved. In seven patients we had subclevian involvement, and subclevian is the vein connecting the arm to the chest. And this number was higher in lower legs because among them was too much females - females only had in the lower legs. But these patients were all males. And this is the subclevian vein which is blocked in this patient. This is the arm and this is the chest. The vein is closed up in here. Here is the aneurysm. It is closed here. And when this vein is closed here, the whole arm of this patient will be swollen. Like the legs when they have thrombosis in the legs.
We said that about 30% of the patients had arthritis, and arthritis means the inflammation of joints. When we analysed this we found that 54% of the patients had involvement of one joint only. One Arthritis. While 40% of patients have involvement which we call oligoarticular, when there is 3-5 joints involved in the same patient. And in 4% there are more than 5 joints involved. The most frequently involved joints were knees, in about 60% of patients, followed by the ankles, in about 50% of patients. In all cases the arthritis was not destructive and had benign force.
Central nervous system manifestation, as we said, was noticed in 62%. I will not comment too much about this, because my colleague who is speaking next will comment about this, but I would like to stress on headache - it might be a very important sign in patients with Behcet's disease and may be an indication for CNS in the future. This is one of the magnetic resonance imaging pictures of one of our patients... The changes are sometimes very much like Multiple Sclerosis lesions, like in this patient. These lesions produce the worst prognosis with the development of weakness and disability in the future. The other types of CNS involvement are the nonparynchimal types due to subdural thrombosis. They have a better thrombosis.
In our studies the gastro intestinal tract involvement was very rare, and it was limited to pains and diarrhea and such complaints. And this is one Gastro Intestinal ulcer of one Pakistani patient from central Asia.
Other systems than these which we mentioned might be important in patients with BD - among these is the kidneys, and the kidneys might be important not only in Jordan but in other countries in the world, and the heart with its pericardiomite also might be involved- pericarditis was noticed in one patient of our study, but in other studies we noticed also the development of intracardial thrombosis.
We tried to see also if patients with BD have relatives with another disease that affects Jordanians, Arabs and Turks and other peoples in the region, which is called the Familial Mediterranean Fever, but we could find very weak association. 4% of the relatives of BD had FMF. So there is not much in common between them.
And as I mentioned in the introduction there is problems with the sex dimorphism in BD, and when we analysed the patients according to sex, we could find that female patients with BD had a higher frequency of erythema nodosum, 67%. There is 32% in males. And male patients had higher frequency of CNS involvement, which indicates a more severe disease in the males in our country, like other countries also, 50% and 20%.
This tendency is proved also when we analyse the detailed eye involvement in these patients. We could find that male patients had higher frequency of posterior uveitis, vitriitis and retinitis, which indicates severe eye disease, and we found that patients who lost vision in both eyes were all males.
I would like to speak about the treatment. You all know that we have local and systemic treatment. The local includes ointments to the oral and genital ulcers and eye-drops. The systemic includes colchicin, corticosteroids, immunosuppressant drugs, cyclosporine, alpha-interferon, thalidomide and pentoxifylline (trental) and of course the newest things that Prof. Ohno mentioned today is the Anti tumor necrosis factor. Of course there is place for surgery sometimes in complicated cases either for cataract also in the eye, or for vessels also when we have some blocked vessels, or for the intestines, when we have too much lesions in the intestine, which do not respond to treatment we go to colectomy or what the patient needs." (Dr. Madanat, May 2000)