Symptoms and outcomes

(Linked pictures may be disturbing to some people)

These are all things that may happen to you if you have Behcet Disease, but not necessarily. They also often happen at different times, although they can overlap.

Oral Ulcers

The oral aphthae that occur in patients with Behcet disease are indistinguishable from common aphthae (canker sores), although they may be more extensive and may occur more frequently. In addition, Behcet ulcers are characterized by severe pain and chronic progression, beginning as a pin-point-sized flat ulcer, which may evolve into a large ulcer within a day. The lesions are usually shallow or deep (2-30 mm in diameter) with a central yellowish necrotic base but a punched-out clean margin and a surrounding red rim. A white or yellowish pseudomembrane usually covers the surface of the ulcer.

Oral aphthae can appear singly or in crops, and are located anywhere in the oral cavity. The most common sites are the tongue, lips, buccal mucosa and gingiva. The tonsil, palate, uvula, larynx and pharynx are less common sites. The ulcers can persist for one week or longer and subside without leaving scars. However, fusion of several small ulcers may produce a large ulcer that leads to scar formation. The interval between recurrences ranges from days to months.

Oral ulcers can be classified into 3 types:

• Minor ulcer: 1-5 small, moderately painful ulcers, persisting for 4-14 days. 
• Major ulcer: 1-10 very painful ulcers, measuring 10-30 mm in size, persisting up to 6 weeks that can leave a scar on healing.
• Herpetiform ulcer: Recurrent crops of up to 1000 small and painful ulcers.

Oral ulcers are the first symptom in most patients, sometimes preceding other symptoms by years, and occur in over 90% of patients, although in part this may be due to problems with the diagnostic criteria. (see also problems with the diagnostic criteria). In one study of pediatric Behcet disease, the average time interval between the initial oral ulceration and the second manifestation was 8.8 years.

Genital Manifestations

Genital ulcers are recurrent and painful, punched-out lesions. They resemble their oral counterparts but may be deeper, last longer and show greater scarring. These scars are indicators of old disease and may help in diagnosis. Genital ulcers have been found in 56.7-97% of cases, but their appearance is mostly as a secondary symptom accompanying oral ulcers, and they typically occur less frequently. 

• In males, the ulcers usually occur on the scrotum, penis and groin.
• In females, they occur on the vulva, vagina, groin and cervix.

In women, genital ulcers may be related to menstruation, pregnancy and child delivery. However, they can also have asymptomatic ulcers, especially in the vagina.

Ocular Manifestations

The most diagnostically relevant lesion is posterior uveitis (retinal vasculitis). Other lesions include anterior uveitis, iridocyclitis, chorioretinitis, scleritis, keratitis, cataracts, vitreous hemorrhage, optic neuritis, conjunctivitis, retinal vein occlusion and retinal neovascularization.

Hypopyon (Frank pus), which is considered the hallmark of Behcet disease, is now less common. One characteristic feature of the hypopyon in Behcet disease is that it may change position with head movement, and it may form and disappear rapidly without sequelae. Recurrent attacks may result in posterior synechiae, peripheral anterior synechiae, iris atrophy, and secondary glaucoma. Repeated episodes of posterior segment inflammation cause sheathing of retinal vessels, chorioretinal scars, and both retinal and optic nerve atrophy. 

Disc may appear edematous with retinal detachment.  Retinal arterial and venous lesions are prognostic indicators for blindness. Fluorescein angiography can show leaky retinal vessels. Atrophy and fibrosis may be the ultimate outcome. 

The classic fundus finding is retinal vasculitis, which affects both arteries and veins in the posterior pole.

Severe vasculitis may lead to thrombosis of vessels and secondary ischemic retinal changes. Vitreous cellular infiltration almost always is present during the acute phase. Retinal neovascularisation, secondary to either retinal vein occlusion or chronic inflammation, may result in retinal or vitreous hemorrhage. Neovascular glaucoma occurs in some patients and often results in phthisis bulbi(shrinking of the eye).

 

Eye disease can be present from the outset, and can be the first symptom in up to 20% of patients, but may also develop within the first few years. Manifestations can be asymptomatic initially. Complaints may include blurred vision, periorbital pain, eye pain, photophobia,  scleral injection, excessive lacrimation or erythematous conjunctiva. 

Decreased visual acuity is a result of secondary glaucoma, cataracts, vaso-occlusive lesions of the posterior chamber or vitreous hemorrhage. Blindness has been reported to occur within 3-5 years from the onset of ocular symptoms. Retinal vein thrombosis leading to sudden blindness is not rare. Men tend to have more severe eye involvement in most populations. In Japan and Turkey more than 50% of patients can be expected to be legally blind within 4 years of onset, while in the US only 25% of patients will ever reach this stage; no figures are available for Isreal, but it can be assumed that they are somewhere in between the aforementioned.

 

Cutaneous Manifestations

A variety of skin lesions have appeared in patients with Behcet disease (58.6-97%): erythema nodosum-like lesions and pseudofolliculitis are probably most common; other common lesions include papulopustular eruptions, erythema multiforme-like lesions, thrombophlebitis, ulcers, lesions resembling Sweet syndrome, bullous necrotizing vasculitis and pyoderma gangrenosum; pustular, acneiform (acnelike), and comedones lesions appear on the upper parts of the body. Migratory thrombophlebitis also can develop. 

Lesions often occur in combination. Erythema nodosum-like lesions may ulcerate, something that is not common in non- Behcet cases. 

A folliculitis-like rash, resembling acne vulgaris, may appear on the face, neck, chest, back and hairline of patients. Some lesions become more pustular. Acneiform lesions occur in almost 60% of patients, but their presence is of questionable diagnostic usefulness in patients who receive corticosteroid treatment which can induce such lesions. Follicle-based pustules or acne-like lesions are not considered specific lesions of Behcet disease by some physicians, while others note them important for diagnosis. (a view from a Jordanian expert)

Erythema nodosum-like lesions, which occur in more than two thirds of patients with Behcet disease, usually are found on the anterior surface of the legs but also may be seen on the face, neck, arms, and buttocks. These lesions appear as slightly raised, red nodules with subcutaneous induration and tenderness. They tend to involute in 10-14 days and usually do not ulcerate. Lesions may leave a hyperpigmented area on the skin.

A peculiar feature of Behcet disease is cutaneous hypersensitivity, which results in small pustules that form on skin after it has been scratched, shaved, or pricked with a needle. Nonspecific skin inflammatory reactivity to any scratches or intradermal saline injection is a common and specific manifestation of these lesions (pathergy test, see discussion below).

 

Pathergy (Skin Hyperreactivity)

The pathergy phenomenon is considered an outstanding feature of Behcet disease. Following a needle prick or intradermal injection with saline or dilute histamine, the puncture site becomes inflamed and develops a small sterile pustule due to hyperactivity of the skin to any intracutaneous insult. The pustular reaction of the skin is thought to denote increased neutrophil chemotaxis. The presence of pathergy strongly suggests the diagnosis of Behcet disease. 

Higher positivity (84-98%) is found in Mediterranean and Middle Eastern countries as compared to Far Eastern countries (40-70%), with Western countries having significantly lower positivity than either region.

 

Joint Manifestations

Joint symptoms are the most frequently cited minor criterion. Although the prevalence of joint involvement varies among different populations, more than one-half of the patients develop signs or symptoms of synovitis, arthritis and/or arthralgia during the course of the disease. The most frequent minor feature in childhood-onset Behcet disease is arthritis, occurring in one quarter of patients.

Arthritis and arthralgias occure in any pattern in as many as 60% of patients or more. In Behcet disease, arthritis is not deforming, destructive or chronic, and may be the presenting symptom. A predilection exists for the lower extremities, and overall involvment of the large joints is predominant, with many cases being symmetric. Rare manifestations include aseptic necrosis, enthesopathies, and sacroiliitis (in HLA B-27 patients). The latter can cause back pain.

The involvement of multiple joints is common. Clinical features are pain, tenderness, swelling, limitation of joint movement, warmth, redness and morning stiffness. Transient, recurrent, nondestructive, and nonmigratory arthritis commonly affects large joints, although small joints can also be affected.

 

Vascular Involvement

Vasculitis of the small and large vessels can cause a panoply of symptoms. Vascular manifestations have been reported in 7-40% of the patients (more frequently in males) with Behcet disease, and are commonly considered as essential to the pathology of Behcet disease. Histologic findings include thickening of media, splitting of the elastic fiber and perivascular round cell infiltration.

 

The four types of vascular lesion recognized in Behcet disease are arterial and venous occlusions, aneurysms and varices. Venous involvement typically includes superficial thrombophlebitis or deep venous thrombosis. Patients with intracranial venous occlusion may present with headache and visual blurring. Occlusion of major veins may cause bleeding, infarction, organ failure or restriction of arm and leg movement. Rupture of a vascular aneurysm may be fatal. Venous involvement is usually limited to occlusion, with the varices rarely affected. Most affected sites of the venous system are the superior vena cava, inferior vena cava, deep femoral vein and subclavian vein. Up to 20% of patients with occlusive venous disease are anticardiolipin antibody positive. With venous occlusion, collateral circulation may develop.

Arterial complications make up 7% of cases (aneurysm and occlusion most common). Patients with arterial manifestations may present with thrombosis or aneurysm formation, with possible fatal rupture. Aneurysm formation carries a worse prognosis than occlusive disease. The subclavian artery and pulmonary artery are most common arteries occluded. Depending on the site, arterial occlusions can have different clinical presentations. Pulseless disease is due to subclavian artery occlusion. Arteritis may involve the aorta or its branches and lead to aneurysm formation.

Obliterating thrombophlebitis, arterial occlusion and aneurysm may occur in vessels of all sizes. 

 

Deep venous thrombophlebitis has been described in about 10-15% of patients, and superficial thrombophlebitis occurred in 24% of patients in the same study. Symptoms correlate with the vessel involved and may be devastating. For example, Budd-Chiari syndrome is reported in these patients (particularly younger ones), and as many as 32% of the patients with vascular involvement in one series had occlusion of the vena cava. Esophageal varices also have been described.

Hypertension can originate from renal artery stenosis. Avascular necrosis of the femoral head is caused by femoral artery stenosis and intermittent claudication. Pulmonary vasculitis can produce dyspnea, chest pain, cough or hemoptysis.

 

Although less common than occlusion, aneurysm formation accounts for most vascular deaths. Common sites of aneurysms are abdominal aorta, femoral artery and thoracic artery.

 

As vascular involvement of Behcet disease can be significant and prove life threatening, it is vital to find and treat vascular involvement early. 

 

A study focusing on coagulating factors is run by a team of physicians and researchers from the medical centres of Shiba and Rambam, Isreal. (If you are interested in taking part in it, click here and state your purpose.)

 

(For the transcript of a lecture by a specialist on Vasculo-Behcet click here).

 

Gastrointestinal Involvement

The clinical spectrum of the gastrointestinal effects of Behcet disease is enormously varied and occurs in 10-50% of patients or more (with great variations in different populations). Symptoms suggestive of inflammatory bowel disease, Crohn's disease and other inflammatory bowl disorders such as anorexia, vomiting, dyspepsia or flatulence, dysphagia, diarrhea or gastrointestinal bleeding or constipation, ulcerative lesions (described in almost any part of the gastrointestinal tract), melena (abnormally dark tarry stools containing blood), perforation, abdominal distention and abdominal pain may all occur.

Lee et.al., reported results from a survey of 10 cases of intestinal Behcet disease in Korea: the mean age was 34 years and the male-to-female ratio was 6:4. The most common symptom was acute abdominal pain. Preoperative diagnosis included intestinal Behcet disease (30%), perforated appendicitis (20%) and periappendiceal abscess (10%). Peritonitis bleeding, fistula formation and recurrent gastrointestinal symptoms were postoperative complications. However, symptoms vary in kind and severity in different ethnic groups and between studies.

Besides the oral mucosa, ulcerative lesions may occur anywhere in the gastrointestinal tract. Most commonly, ulcers occur in the ileocecal region. Other involved areas include the transverse and ascending colon and esophagus. Anticoagulation is controversial in patients with Behcet because of the risk of bleeding from one of these ulcers.

 

Gastrointestianl involvement of Behcet Disese can be significant and sometimes life threatening, so it is vital to find and treat it urgently. 

 

(For the transcript of a lecture by a specialist on GI Behcet click here).

 

Neurologic Manifestations

The incidence of neurologic involvement in Behcet disease varied from 3.2% up to 49% according to the reports of different populations, with CNS involvement of up to 25% in children. The most severe manifestation of the disease, pathologic changes include vasculitis, perivascular white matter inflammation, and demyelinating lesions.

 

Neurologic involvement may include meningoencephalitis (presents as headache and stiff neck), a multiple sclerosis-like illness, acute myelitis, stroke or pseudotumor cerebri. Focal neurological abnormalities also can be seen. Multiple neurological disorders that involve pyramidal and extrapyramidal tracts (the pathway of messages sent from the brain to the organs to instruct voluntary and involuntary motion, respectively), cerebellum, and the cranial nerves occur in 8-25% of patients who have Behcet disease. Neurological deficits, including hemiparesis (incomplete paralysis of half the body), may be progressive, with up to 30% of patients with neurologic manifestations eventually developing dementia.

Three categories of neurologic involvement are (1) brain stem syndrome, (2) meningomyelitic syndrome and (3) organic confusional syndrome. Complicating the clinical picture is the occurrence of these different types in various combinations.

 

Neurologic involvement is one of the most serious complications; it is thought to indicate a poor prognosis, with severe disability, dementia (at times irreversible) and a high fatality rate. Neurologic manifestations usually occur within 5 years of onset of the disease. Signs may include mental status changes and emotional lability; meningitis or meningoencephalitis (often presenting as headache with stiff neck); brainstem lesions; seizures; clonus; positive Babinski sign; difficulty with speech or swallowing; and acute deafness.

 

The most frequent initial neurologic symptom is severe headache, sometimes accompanied by stiffness in the neck. Other symptoms and signs can be

• unusual spells of confusion
• instability
• hallucinations and personality changes
• spells of inability to focus or double vision
• unusual difficulty in walking or balancing
• incontinence
• unusual dizziness or fainting
• cranial nerve abnormalities (palsy)
• pyramidal tract lesions with spastic paralysis; extrapyramidal, and cerebellar symptoms
• dementia 
• numbness, pins and needles or weakness for no apparent reason.

While most physicians maintain that peripheral nerve involvement is rare, many patients complain about this problem.

          

(For the transcript of a lecture by a specialist on CNS Behcet click here).

 

Pregnancy-Associated Manifestations

As pregnancy is associated with physiologic changes in the body due to alterations in the metabolic and endocrine systems, it has been speculated that these changes may in some way influence the course of Behcet disease. Unfortunately, there is a scarcity of reports in the world literature that address this problem.

 

In a study of 27 pregnant women with Behcet disease, clinical symptoms improved in 9 patients (33.3%) and were exacerbated in 18 patients (66.7%), with exacerbation occurring mostly during the first trimester. All the newborns were healthy but 4 pregnancies were terminated due to worsening of disease.

 

Other studies indicated entirely different findings, although most support a strong possibility of worsening of symptoms either during the pregnancy or soon after birth, and only a few mention problems during birth or to do with the foetus/ newborn's well being. 

Experts seem to agree that the first trimester is more prone to trouble and that neonatal BD can be a result of a pregnant mother in flare (even if she never suffered BD symptoms previous to her pregnancy).

Therefore, close followup is necessary to monitor health of mother and baby.

 

Other Organ Manifestations

Hearing loss, tinnitus, dizziness and balance problems may occur. 

Myocarditis and cardiac vessel disease may occur (including arrhythmias, pericarditis, vasculitis of the coronary arteries, endomyocardial fibrosis, and granulomas in the endocardium). Cardiac valves may grow vegetations with subsequent emboli. Clinically, these lesions are similar to bacterial endocarditis, but cultures are negative and round cell infiltration is most typically observed on histology.

Major hemoptysis can be the result of pulmonary vascular thrombosis, aneurysms (with pulmonary artery–to–bronchus fistula formation) or vasculitis. Wheezing and breathlessness may point at pulmonary involvement. 

Cases with renal involvement such as mild asymptomatic glomerulonephritis have also been reported. However, nephrotic syndrome and kidney amyloidosis have rarely been described. Some patients display recurrent urinary tract infections, although these may be in part due to immunosuppressive therapy. General swelling in all parts of the body (particularly face and limbs) with or without pain is common, but should be distinguished from that brought on as a side-effect of corticosteroidal medications. 

Myositis (inflammation of the muscles) has been described in pediatric Behcet patients.

 

In general, you can expect to experience many more non-Behcet-specific symptoms, that are characteristic of other chronic diseases, such as chronic fatigue, not relieved by any amount of rest or sleep, depression, muscle pain and weakness.

(The above material has been amended by the author and does not necessarily reflect the views of the sources)

Sources

e-medicine - Behcet Disease - Sungnack Lee, M.D. et al (March 2003)   

e-medicine - Behcet Disease - Jeffrey R Lisse, M.D. et al (March 2003)   

e-medicine - Behcet Disease - C Egla Rabinovich, M.D. et al (March 2003)   

-medicine - Behcet Disease - Mounir Bashour, M.D. et al (March 2003)   

Vanderbilt University Medical Center - Allergy/Immunology - Behcet Disease (June 1998)

 Pictures provided courtesy of e-medicine