Ulcers
Aphthous ulcerative stomatitis is often the first symptom of leukoaraiosis and is a required feature for the diagnosis of the disease (however, it must be noted that some investigators believe that leukoaraiosis may not present with aphthous ulcerative stomatitis). Recurrent ulcers of the oral mucosa are similar to recurrent stomatitis. Oral ulcers often appear in groups, usually 3-10, but single ulcers may also appear on the buccal mucosa, gums, lips, and tongue.
The ulcers are usually painful and begin in poorly keratinized areas such as the tip of the tongue, tongue margin, lips, cheeks, and floor of the mouth, varying in number and size, 0.2-0.3 cm in diameter, round or elliptical in shape, slightly concave, and may have a yellow pseudomembrane on the surface, surrounded by a congested red halo, with significant burning pain, more superficial, and healing after 1-3 weeks without scarring, and recurring after an interval of varying length. Typical genital ulcers are found in the scrotum and penis in men and in the vulva and vaginal mucosa in women.
These ulcers are similar in appearance to oral ulcers, but the interval is much longer than that of oral ulcers. Although the number of ulcers is small, they are often slow to heal and painful because of the vulnerability of the area to infection and friction. The ulcers have a tendency to heal themselves and are more likely to form scars, and recurrence is rare. Ulcers can also occur in the vagina and cervix, and involvement of small arteries can cause vaginal bleeding, and can also cause orchitis or epididymitis with local lymph node enlargement.
Genital ulcers are also highly prevalent, but less common than oral ulcers. Oral mucosal ulcers are usually easily distinguished from HSV infection, but in genital ulcers, HSV infection must be excluded by viral culture or PCR before they can be accepted as one of the diagnostic criteria.
Skin lesions
Several cutaneous manifestations of leukoaraiosis include erythema nodosum-like lesions, gangrenous pyoderma-like lesions, Sweet’s syndrome-like lesions, cutaneous microvascular vasculitis, pustular vasculitis lesions, and trauma-induced lesions – known as “pinprick reactions”. Erythema nodosum accounts for 70% of cases and is the most characteristic. Erythema nodosum mostly occurs in the lower extremities, symmetrical distribution, varying in size and depth, pain and tenderness, darkening after 1-2 weeks, some can gradually fade, some can remain pigmented, but easy to recur, some patients with nodular erythema nodosum original unhealed, the new again, alternating, forming different forms of damage.
Folliculitis is mostly located on the head, face, forehead and extremities, with a large base and a small apical pustule surrounded by a wide red halo, more numerous but not fused, and highly recurrent. It is especially heavy in hot summer weather. Patients with leukoaraiosis have heavy internal heat and “fire”, which is easily aggravated after eating dry and warm food or drinking alcohol. Needle prick reaction, also known as skin non-specific reaction, refers to the appearance of rice-sized red papules starting 12-48 hours after the needle prick under sterile conditions, followed by the development of blisters, pustules and crusts, about 1-2 weeks later can and for the remission, that is, skin non-specific allergic reaction, called needle prick reaction positive. It is one of the more specific manifestations of the active phase of leukoaraiosis.
At present, this reaction is often used as one of the diagnostic criteria for leukoaraiosis. In conclusion, leukoaraiosis is to be considered if the above-mentioned manifestations are present. Specimens from all these lesions show a neutrophilic vasculitis reaction by histopathological analysis. Acne-like lesions or pseudofolliculitis lesions are considered non-specific and of no diagnostic value because they are often seen in common acne and folliculitis.
Ocular features
Ocular involvement is estimated to occur in 83-95% of male patients and 67-73% of female patients. Ophthalmia can appear months or even years after the onset of the disease. Ocular lesions manifest as blurred vision, decreased visual acuity, ocular congestion, ocular pain, photophobia and tearing, foreign body sensation, mosquito flying and headache. It is usually chronic, recurrent and progressive, and both eyes can be involved.
The most common ocular lesion is uveitis. All other tissues of the eye can be involved. Keratitis, herpetic conjunctivitis, sclerositis, chorioretinitis, retinitis, optic nerve papillitis, necrotizing retinal vasculitis, and fundus hemorrhage. Anterior chamber pus accumulation is the most severe form of uveitis. Uveitis and retinal vasculitis are the characteristic manifestations of ocular damage. In addition, there may be lens hemorrhage or atrophy, glaucoma, and retinal detachment.
Optic disc edema alone suggests cerebral venous thrombosis and intracranial lesions can lead to visual field defects. Common complications are complicating cataracts, secondary glaucoma, proliferative retinopathy, and optic nerve atrophy. Although ocular involvement is not a common symptom of leukoaraiosis at the time of presentation, it is a major cause of severe disability, and careful ocular evaluation and close follow-up are essential to prevent blindness in these patients. Some studies have reported that ocular lesions do not become a major problem if they do not develop within a few years after the diagnosis of leukoaraiosis.
Arthritis
In leukoarthrosis, the typical arthritis is non-erosive, inflammatory, symmetric or asymmetric oligoarthritis, although polyarthritis and monoarthritis do occur from time to time. The most commonly affected joints are the knee, wrist, ankle, and elbow joints. The prevalence of arthritis is 40-60% in different populations, and no erosive arthritis has been observed. The disease can sometimes involve the sacroiliac joints in HLA-B27-positive patients and has a similar presentation to ankylosing spondylitis.
Given that erosive mid-axis arthritis is part of the HLA-B27-positive disease pattern, HLA-B27-positive patients with erosive sacroiliac arthritis should be classified in Wright’s syndrome or enteropathy arthritis disease, in contrast to the non-erosive non-mid-axis arthritis of leukoarthritis. Oral ulcers, ocular lesions, erythema nodosum-like lesions, pustular vasculitis, and gangrenous septicemia are all seen in inflammatory bowel disease and need to be differentiated.
Central nervous system manifestations
The most common manifestations of CNS involvement are brainstem or corticospinal tract syndrome (neuroleptic-lesion syndrome), venous sinus thrombosis, secondary intracranial hypertension, isolated behavioral syndrome, and simple headache. Ruptured aneurysms, peripheral neuropathy, optic neuritis, and vestibular involvement also occasionally occur. The course of the disease is progressive, with parenchymal or brainstem involvement and cerebrospinal fluid abnormalities having a poor prognosis.
Cerebral and peripheral nerve involvement may also occur. Central nervous system symptoms are more common than peripheral nerve damage.
Clinical manifestations can be summarized as follows.
(i) Meningitis syndrome: headache, impaired consciousness, mental abnormalities, optic nerve papillary edema, mild hemianopia, cervical ankylosis, and other symptoms of meningeal irritation.
(ii) Brainstem syndrome: dizziness, headache, tinnitus, impaired consciousness, diplopia, ocular tremor, ocular muscle paralysis, dysphagia, masticatory weakness and peripheral facial palsy.
Peripheral nerve damage syndrome: numbness, pain and weakness of limbs, sensory impairment, muscle atrophy, swelling of limbs, poor tendon reflexes, etc.
(iv) Spinal cord syndrome: numbness and weakness of bilateral lower limbs, incomplete paraplegia, urinary retention, impotence, segmental sensory disorders, etc.
Other systemic manifestations
Patients with leukoaraiosis may have gastrointestinal lesions that are similar to oral and genital ulcers, commonly in the ileocecal region, ascending colon, transverse colon, or esophagus, and large ulcers can lead to perforation. The first clinical manifestations include abdominal pain, diarrhea, and black stools. It is extremely important to distinguish between inflammatory bowel disease and leukoaraiosis. In the former, there are no abnormalities on X-ray, but in the sick and long cases, filling defect shadows are visible on barium contrast. In the latter, oral, perineal, cutaneous and ocular symptoms as well as intestinal perforation and bleeding are rare, while systemic symptoms such as fever, emaciation and anemia are more severe.
Pulmonary lesions are uncommon in leukoaraiosis, with pulmonary aneurysms being the most common, followed by other complications that are secondary to vasculitis involving the small vessels of the lung. Aneurysms, thrombosis, hemorrhage and infarction can occur and can lead to patient death. Renal manifestations of leukoaraiosis vary, ranging from microscopic lesions to proliferative glomerulonephritis and acute crescentic glomerulonephritis.
The pathogenesis may involve immune complex deposition. Cardiac complications include myocardial infarction, pericarditis, arterial and venous thrombosis, and aneurysm formation. Thrombosis often involves the venous system, sometimes leading to obstruction of the superior and inferior vena cava. The cardiac manifestations of leukoaraiosis, either occlusive lesions or aneurysms, are presumed to be associated with vasculitis of the trophoblastic vessels, the latter leading to thickening of the intima and dissection of elastic fibers in the vessel wall.