1.Mouth ulceration
Almost all patients have recurrent, painful oral ulcers (Aphthous ulceration, Aphthous ulcer) and often this is the first symptom. The ulcers can occur anywhere in the mouth, mostly on the edge of the tongue, cheeks, lips, soft palate, pharynx, tonsils, etc.. They can occur singly or in batches, isolated and scattered, in the size of a grain of rice or a soybean, round or oval, with clear edges and varying depths, with a yellow covering at the bottom and surrounded by a red halo with clear edges, fading on their own after about 1 to 2 weeks without leaving scars, and continuing to recur in some patients. In severe cases, the ulcers are deep and slow to heal and may occasionally leave scars. Recurrent oral ulcers are the most basic necessary symptom for the diagnosis of this disease.
2. Genital ulcers
About 75% of patients have genital ulcers, and the lesions are basically similar to oral ulcers. However, the number of occurrences is less. The ulcers are deep and large, with severe pain and slow healing. The affected areas are the vulva, vagina, perineum, cervix, scrotum, and penis. Vaginal ulcers may be painless with only increased discharge. In some cases, the ulcers may be deep enough to cause hemorrhage or rupture of the scrotal vein wall due to necrosis.
3. Ophthalmia
About 50% of patients are affected, and both eyes can be involved. Ocular lesions can appear months or even years after the onset of the disease, which manifests as blurred vision, decreased visual acuity, ocular congestion, ocular pain, photophobia and tearing, foreign body sensation, flying mosquitoes and headache. The disease usually has a chronic, recurrent, progressive course. Ocular involvement can cause blindness in up to 25% of cases and is the leading cause of disability in this disease. The most common and severe ocular lesion is uveitis. Anterior uveitis, or iridocyclitis, combined with pus accumulation in the anterior chamber is a typical specific sign of leukoaraiosis, and posterior uveitis and retinal vasculitis are the main causes of blindness. Other manifestations of ocular involvement include keratitis, herpetic conjunctivitis, scleritis, chorioretinitis, retinitis, optic nerve papillitis, and fundus hemorrhage. In addition there may be lens hemorrhage or atrophy, glaucoma, and retinal detachment. Optic disc edema alone suggests cerebral venous thrombosis, and intracranial vascular lesions caused by leukoaraiosis can lead to visual field defects.
4.Dermal lesions
The incidence of skin lesions is high, up to 80%-98%, with various manifestations, including erythema nodosum, herpes, papules, acne-like rash, erythema multiforme, erythema annulare, necrotizing tuberculosis rash-like damage, herpetic necrotizing vasculitis, Sweet’s disease-like lesions, and pyoderma. A patient may have one or more of these lesions. The skin signs of particular diagnostic value are erythema nodosum-like lesions and inflammatory reactions to minor trauma (pinpricks).
5. Joint damage
Joint symptoms are present in 25% to 60% of patients. The manifestations are relatively mild, limited, asymmetric arthritis. HLA-B27 positive patients may have sacroiliac joint involvement, similar to ankylosing spondylitis.
6.Nervous system damage
Also known as neuroleukopenia, the incidence is about 5% to 50%. It often appears several months to years after the disease, and a few (5%) may be the first symptoms. Clinical manifestations vary depending on the site of involvement. Central nervous system involvement is more common and may include headache, dizziness, Horner syndrome, pseudobulbar palsy, respiratory disorders, epilepsy, ataxia, aseptic meningitis, optic papilledema, hemiplegia, aphasia, paraplegia of varying degrees, urinary incontinence, bilateral lower extremity weakness, sensory disturbances, impaired consciousness, and mental abnormalities. Peripheral nerve involvement is less common, manifesting as numbness and weakness of the extremities and peripheral-type sensory impairment.
Most patients have a poor prognosis, especially brainstem and spinal cord lesions, which are one of the main causes of disability and death.
7.Digestive tract damage
Also known as intestinal leukoplakia. The incidence is 10% to 50%. The ulcers can be single or multiple, varying in depth, and can be found in the lower esophagus, stomach, distal ileum, ileocecal region, ascending colon, but the ileocecal region is more common. Clinical manifestations may include epigastric fullness, belching, dysphagia, middle and lower abdominal fullness, vague pain, paroxysmal colic, diarrhea, black stool, and constipation. In severe cases, there may be ulcer perforation and even death due to complications such as hemorrhage. Intestinal leukodystrophy should be distinguished from inflammatory bowel disease and mucosal lesions caused by non-steroidal anti-inflammatory drugs. Pain in the right lower abdomen should be distinguished from appendicitis, and there are often clinical cases of non-healing postoperative wounds.
8.Vascular damage
The basic lesion of this disease is vasculitis, the whole body can be involved in large and small vessels, about 10%-20% of patients combined with large and medium vasculitis, is the main cause of death and disability. When the arterial system is involved, the elastic fibers of the arterial wall are destroyed and the intima fibers of the arterial wall are proliferated, resulting in arterial stenosis, dilatation or aneurysm, with corresponding clinical manifestations, including dizziness, headache, syncope and pulselessness. Aneurysms on the aortic arch and its branches are at risk of rupture. The venous system is more commonly involved than the arterial system, and superficial or deep migratory thrombophlebitis and venous thrombosis, resulting in stenosis and embolism, occur in about 25% of patients. Inferior vena cava and lower limb veins are more frequently involved and may present with Budd-Chiari syndrome, ascites, and swelling of the lower limbs. Superior vena cava obstruction may have swelling of the jaw and neck and increased venous pressure in the upper extremities.
9.Pulmonary damage
The incidence of pulmonary damage is low, about 5-10%, but most of the disease is serious. Pulmonary aneurysm can be formed when pulmonary vessels are involved, and pulmonary vascular-bronchial fistula can be formed when the aneurysm ruptures, resulting in intrapulmonary hemorrhage; pulmonary venous thrombosis can lead to pulmonary infarction; alveolar pericapillaritis can cause endothelial proliferation and fibrosis, affecting the function of gas exchange. Patients have cough, hemoptysis, chest pain, and dyspnea when the lungs are involved. Massive hemoptysis can lead to death.
10.Other
Renal damage is rare and may include intermittent or persistent proteinuria or hematuria, renal hypertension, and IgA glomerular proliferative lesions or amyloidosis on renal pathology.
Cardiac involvement is less common and may include myocardial infarction, valvular lesions, conduction system involvement, and pericarditis. There may be epicardial thrombosis in the heart cavity, and a few patients have dilatation-like changes and constrictive pericarditis-like manifestations in the heart, with cardiac lesions associated with local vasculitis.
The incidence of epicarditis is about 4% to 10% and is more specific. It starts acutely and manifests as painful swelling and pressure of unilateral or bilateral epididymis, which can be relieved in 1~2 weeks and is prone to recurrence.
Pregnancy can aggravate the disease in most patients, and remission of uveitis has also been reported. There may be intrauterine fetal growth retardation, and the condition mostly worsens after delivery. Nearly 10% of patients present with fibromyalgia syndrome-like manifestations, which are more common in women.