There are many types of rheumatic diseases, and some rheumatic diseases often have multi-system or multi-organ damage, including ocular manifestations. In clinical practice, we see many patients who first go to the ophthalmology department, resulting in misdiagnosis and mistreatment. It should be clear that some eye diseases happen to be caused by rheumatic diseases, and ocular manifestations may suggest certain rheumatic diseases, and some of them have certain specificity, which is important for the diagnosis and estimation of prognosis of rheumatic diseases. For this reason, it is necessary to understand the relationship between rheumatic diseases and ocular manifestations in order to make accurate diagnosis and treatment. Gao Jianxin, Department of Immunology, Baotou Central Hospital
I Rheumatoid arthritis (RA)
The joints and eyes of RA patients have the same pathological process. The inflammatory changes of conjunctiva and sclera are similar to those of synovium and cartilage, and the inflammation mediated by immune factors causes damage to various organs, including the eyes. The most common ocular manifestations are sclerenchymal and keratitis, and outer scleral inflammation. The most common is secondary dry syndrome, with 10% to 35% of patients having ocular lesions [1][2][3].
(i) Sclerositis The presence of sclerositis in RA patients indicates extensive RA lesion invasion and is a sign of involvement of other vital organs [4]. The prominent symptom of patients with sclerositis is ocular pain, most often with severe eye pain. The ⒈ anterior sclerositis is divided into diffuse, nodular and necrotic types, while the necrotic type has a more severe inflammatory response, extensive damage and an extremely poor prognosis. Anterior sclerositis is congested with a deep purple-red color, and the congestion does not subside after drops of vasoconstrictors (such as epinephrine), suggesting scleral congestion, which is an important sign of sclerositis. If sclerositis persists, the sclera of the focal area becomes thin and blue with no blood vessels on the surface, which is a sign of scleral necrosis due to vascular occlusion. The thin sclera can hardly withstand the normal intraocular pressure, resulting in local expansion of the sclera, called scleral chylomicron, and in severe cases, the sclera can be perforated. Posterior sclerositis is often combined with diffuse anterior sclerositis or can exist alone, and its clinical manifestations include uveal leakage, retinal detachment and optic papillary edema, as well as invasion of the orbital tissues and extraocular myositis, resulting in protrusion of the eye or limited eye movement [4]. Scleral inflammation is less common than outer scleral inflammation, but is more commonly associated with vasculitis and long-term active arthritis, which can progress to scleral softening if left untreated. RA treatment is not effective for scleral ophthalmopathy due to the lack of vascularity in the sclera [1].
(ii) Scleral outer layer inflammation Mostly indicative of disease activity, divided into simple and nodular types, with common features of superficial scleral congestion and tissue edema without involvement of the deeper layers of the sclera. The congestion is purplish red, the inflammation is limited or diffuse, there is pressure pain at the site of inflammation, and the course of the disease is mostly self-limiting. It should be noted that patients with nodular outer sclerositis often have nodules under the bulbar conjunctiva that are mobile and have histopathological changes similar to those of RA subcutaneous nodules [4].
(iii) Keratoconjunctival lesions The keratoconjunctival lesions caused by RA are consequential and often neglected, and it can be accompanied by sclerositis or occur alone. One type is a peripheral or marginal corneal ulcer, which can lead to corneal perforation if it spreads gradually [2].
(iv) The ocular manifestations of juvenile RA differ markedly from those of adults, as adult RA mainly affects the sclera in the posterior five-sixths of the outer layer of the eye wall causing sclerositis, while juvenile RA (oligoarticular type) mostly invades the middle layer and presents with uveitis, with a prevalence of about 10% and sclerositis is rare. In severe cases, it manifests as ocular redness, pain, photophobia, tearing, and also subepithelial calcium deposits in the conjunctiva, causing band keratopathy, which can lead to cataract and secondary glaucoma, and severe iritis can cause blindness, and topical and systemic treatment with glucocorticoids can also cause cataract and glaucoma [2].
In addition, the incidence of uveitis in patients with Still disease is 2% to 21%, with patients with joint involvement being the most susceptible to uveitis, which can be divided into acute and chronic anterior uveitis according to their condition [4].
II Nodular disease
Subacute or chronic iridocyclitis is more common, with posterior uveitis, chorioretinitis and retinitis less common [5].Ocular complications can occur in 25% to 50% of patients with nodular disease, with a variety of presentations, the most common being uveitis, which often presents as acute or chronic non-granulomatous iridocyclitis. Small yellowish-white nodules on the retina and choroid may also be seen, with “candle tear”-like or perivasculature-like white sheaths along the venous side of the retinal veins. In addition, nodules may occur in the eyelid skin and orbit, and small nodules may be present in the lid conjunctiva and bulbar conjunctiva with lacrimal gland enlargement and dry keratitis due to lacrimal gland infiltration [6].
III Seronegative spondyloarthropathies
(i) Ankylosing spondylitis (AS)
Iridocyclitis (anterior uveitis) is more common in AS with an incidence of 4% to 33%, while AS is combined in 40% of patients with acute anterior uveitis and the presence of positive HLA-B27 is also above 40%. In some cases, iritis appears 1 to 2 years before the joint lesion, or it may occur during the resting phase of the disease, with unilateral, bilateral or alternating bilateral onset, and symptoms of pain, lacrimation and photophobia. Physical examination reveals pericorneal congestion and iris edema. Slit lamp examination reveals a large amount of exudate and posterior corneal deposits in the anterior chamber and floating cells in the vitreous, which are often prone to recurrence and some AS can be disabling [1] [2]. Lou Y. Inscription also suggested that acute anterior uveitis combined with AS has an acute onset, heavy symptoms, significant ocular pain, marked congestion, large amounts of grayish dusty posterior corneal deposits, increased protein content in the anterior chamber water, severe protein coagulation like jelly, low intraocular pressure, marked ocular pressure pain, and a self-limiting course of about 8-10 weeks, responding well to topical hormone therapy and occasionally prone to recurrence [4]. Iritis is an ocular manifestation of several systemic diseases, and young male patients who present to the ophthalmology department with this condition should be alerted to the possibility of AS.
(ii) Wright’s syndrome (RS)
The typical triad of RS includes non-gonococcal uveitis, arthritis, and conjunctivitis. 63% of patients present with ocular signs that manifest as conjunctivitis, iritis, and corneal ulcers. conjunctivitis is mostly mild, painless redness with increased discharge, unilateral or bilateral involvement, and resolves in 2 to 7 days, with a few cases of more severe inflammation lasting several weeks. 5% of patients present with iritis, which is more common unilaterally or can alternate bilaterally, lasting 1 ～Uveitis is present in 8% to 40% of patients and is likely to occur with recurrent disease. Other ocular signs are superficial punctate keratitis, corneal ulcers, superficial sclerositis, optic nerve and retrobulbar neuritis, and complete destruction of the eye due to total uveitis [1] [7].
(iii) Enteropathic arthritis
It refers to polyarthritis caused by ulcerative colitis and limited enteritis, uveitis involvement causing iridocyclitis and occasionally scleral inflammation. 3% to 11% of patients with acute inflammatory bowel disease may have anterior uveitis, mostly unilateral and transient, but prone to recurrence,uveitis and mid-axis joint involvement are associated with HLA- B27 [1][3].
(iv) Psoriatic arthritis (PsA)
In addition to joint lesions, PsA presents with ophthalmia in approximately 30% of patients, conjunctivitis in 20%, and iritis in 7% [7].
(v) Reactive arthritis
Conjunctivitis and iritis may also be present [1].
(iv) Systemic lupus erythematosus (SLE)
Any part of the eye can be involved, but inner layer involvement is less common than RA and outer layer involvement is less common than seronegative spondyloarthropathy, which is meaningful for clinical differentiation. if a patient has sclerositis along with uveitis, SLE is more likely. SLE is most common in women aged 20 to 45 years, with sclerositis, conjunctivitis and dry keratitis being the most common. external eye damage is mainly erythema and puffiness of the eyelids. Uveitis is uncommon, and the most important change in the fundus is that the posterior pole retina can have many absorbent cotton spots in the acute phase, but they can disappear in remission. Retinal vasculitis, retinal artery or vein obstruction, deep and superficial retinal hemorrhage, optic papillary edema, secondary optic nerve atrophy and diplopia and nystagmus due to neurological damage are sometimes seen [6].
V Wegener’s granulomatosis (WG)
In 50% ~ 60% of patients with WG, the eye and surrounding tissues are involved and the lesions have two causes: septic sinusitis can extend directly into the orbit and cause ptosis, lacrimal sacitis, protrusion of the eye, cavernous sinus embolism and impaired vision, and ocular vasculitis itself leads to conjunctivitis, sclerositis, episclerositis, corneoscleral ulceration, optic nerve vasculitis, but also uveitis and retinal vasculitis and in a few cases may have central retinal artery infarction and central retinal vein thrombosis [1] [10].
VI Behçet’s syndrome (BD)
The average incidence of ocular involvement is 66%, and the common ocular lesions are uveitis and retinal vasculitis, optic nerve atrophy vitreous inflammation and fundus hemorrhage. The main manifestations are blurred vision, decreased visual acuity, ocular congestion, ocular pain, photophobia and tearing, foreign body sensation and flying mosquitoes. Recurrent episodes of anterior uveitis (iridocyclitis), with or without pus accumulation in the anterior chamber, and posterior uveitis and retinal vasculitis are the main causes of visual impairment. Recurrent episodes of uveitis can lead to severe visual impairment or even blindness, with a blinding rate of 33% to 44% [1] [2]. Anterior chamber pus-forming iridocyclitis and retinal lesions are often important components of BD and are specific for diagnosis [4]. Our department admitted a 35-year-old male patient with BD in July 2000, who had been blind in his left eye for 2 years.
VII Aortitis
Pulseless fundus is a specific change of this disease, with an incidence of 8%-12%, and can be divided into three stages, each with different manifestations. Phase I (vasodilatation phase): reddening of the optic nerve papillae, dilation and bruising of the arterioles, uneven venous lumen, and capillary neovascularization. Small hemorrhages, small hemangiomas, iris and vitreous are normal. In the second stage (anastomosis phase), pupil dilatation, loss of reaction, iris atrophy, formation of retinal arteriovenous anastomosis, and loss of peripheral vessels. In the third stage (complication stage), cataract, retinal hemorrhage and detachment are manifested [1]. Our department admitted a 42-year-old female patient with polyarteritis major combined with proptosis hyperthyroidism in June 2000, who also presented with left eyelid ptosis.
VIII Dry syndrome (SS)
Patients with SS have dry keratoconjunctivitis due to decreased tear production, causing dryness, pain, photophobia, foreign body sensation, gritty or burning sensation in the eye. Early symptoms may include excessive tearing, difficulty opening the eyes after morning rising, and excessive visceral mucous secretions. Examination reveals dilated and dilated bulbar conjunctival vessels, drooping eyelids, mild pericorneal infection, clouding of the conjunctiva, formation of vascular opacities in some patients, causing conjunctival crinkling, corneal ulceration, perforation, uveal ulceration, cataract, glaucoma, and enlarged lacrimal glands. Poor response to chemical or emotional stimuli [8].
IX Polyarteritis nodosa (PAN)
A variety of ocular manifestations can occur involving small and medium-sized arteries, commonly including scleral keratitis, similar to RA but with severe pain and ulceration of the corneal rim extending into a ring that progresses centrally across much of the cornea causing scarring, vascularization, and perforation [2]. Uveitis may also be present. Central retinal arteritis presents with yellow and grayish white exudate spots in the retina and obstruction of the central retinal artery. Posterior ciliary arteritis can cause ischemic optic neuropathy. The fundus of the eye may also be seen at different stages of nephritis, and visual acuity, visual field disturbances and diplopia may occur in eyes with cerebral artery involvement [10].
X Recurrent polychondritis (RP)
RP ocular inflammatory lesions occur in 55% of the eyes and mainly present as adnexal lesions of the eye, which can be unilateral or symmetrical. The most common are sclerositis, episclerositis, and non-granulomatous uveitis. The severity of the above parallels inflammation elsewhere. There are also manifestations of inflammatory corneal infiltrates, swelling and pericorneal thinning, others such as ocular protrusion, bulbar conjunctival edema, eyelid edema, ocular muscle paralysis, conjunctivitis, scleral conjunctivitis, ocular dryness, cataracts and visual loss. Retinal lesions also occur frequently and the retina may have microaneurysms, hemorrhages and exudates, retinal vein occlusion, arterial embolism, retinal detachment, and optic neuritis [1].
Eleven polymyositis/dermatomyositis (PM/DM)