What Autoimmune Diseases Cause Scleritis?

Roughly half of all scleritis cases are tied to a systemic autoimmune or inflammatory condition, with rheumatoid arthritis and granulomatosis with polyangiitis topping the list. The full roster of linked diseases is longer than most people expect, stretching from common conditions like inflammatory bowel disease to rarer ones like IgG4-related disease and relapsing polychondritis. Understanding which autoimmune diseases drive scleritis matters because the eye inflammation is sometimes the first visible sign that something broader is going wrong in the body.

How Often Is Scleritis Autoimmune?

Scleritis can occur on its own, triggered by infection or without any identifiable cause, but an autoimmune connection is found in a substantial share of patients. One large analysis of over five million patients in a U.S. health system found that about 31% of people diagnosed with scleritis had an associated autoimmune condition.¹ Other estimates put the figure closer to half. A widely cited review noted that in up to 50% of affected individuals, scleritis occurs alongside an immune-mediated systemic inflammatory disease.² The spread in those numbers comes down to how “associated autoimmune condition” is defined and how aggressively clinicians investigate, but the takeaway is the same: if you have scleritis, there is a meaningful chance an autoimmune disease is involved.

A population-based study covering 11 million patients in the United Kingdom reinforced this picture. Compared with matched controls, scleritis patients had roughly double the risk of carrying a prior autoimmune diagnosis, and they also faced a significantly increased risk of being diagnosed with one afterward.³ That second finding is clinically important: scleritis does not just accompany known autoimmune disease; it can announce one that has not yet been caught.

Rheumatoid Arthritis

Rheumatoid arthritis is the single most common autoimmune disease found in scleritis patients, representing the largest share of associated autoimmune diagnoses in the big-data analysis mentioned above.¹ The connection makes sense biologically: rheumatoid arthritis is a systemic condition, and the sclera is made largely of collagen, one of the very tissues the disease attacks elsewhere in the body.

The most alarming form of scleritis in rheumatoid arthritis patients is necrotizing scleritis, where the scleral tissue actually breaks down. Older research showed that necrotizing scleritis in the setting of rheumatoid arthritis can serve as a red flag for potentially lethal hidden vasculitis elsewhere in the body.⁴ In other words, the eye may be shouting about a problem the rest of the body is hiding.

At the far end of the spectrum sits scleromalacia perforans, a rare and painless but destructive variant seen almost exclusively in people with longstanding rheumatoid arthritis. The scleral tissue thins so severely that the dark underlying layer of the eye becomes visible through it.⁵ What makes scleromalacia perforans unusual is that the thinning happens quietly, without much overt redness or pain, so patients and clinicians can miss it until the damage is advanced.⁶ It tends to appear late in the course of the disease, often in patients who already have obvious joint deformities.

Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA, formerly called Wegener’s granulomatosis) has the strongest per-patient association with scleritis of any autoimmune disease. While rheumatoid arthritis contributes more total cases because rheumatoid arthritis itself is so much more common, a higher percentage of GPA patients develop scleritis than patients with any other autoimmune condition.¹ The UK population study likewise identified GPA as one of the conditions most strongly linked to scleritis.³

GPA is a form of ANCA-associated vasculitis, meaning the immune system produces antibodies against components of white blood cells, leading to widespread blood-vessel inflammation. Ocular and orbital involvement is common in GPA, and the inflammation can be severe enough to cause tissue necrosis. Case series have documented both necrotizing and non-necrotizing anterior scleritis in GPA patients, and the scleritis can be the very first sign that brings someone to medical attention.⁷ In one reported case, a patient’s scleritis prompted evaluation that revealed ANCA positivity, with granulomas found in scleral tissue and vasculitis confirmed on nerve biopsy.⁸

The seriousness of GPA makes this association especially high-stakes. A case documented in a rheumatology journal described a patient who presented with scleritis as the initial feature of ANCA-associated vasculitis and within days developed systemic symptoms including life-threatening pulmonary hemorrhage.⁹ This is exactly why ophthalmologists take scleritis so seriously and often order blood work even when the eye problem seems straightforward.

Behçet’s Disease

Behçet’s disease was identified in the UK population study as one of the autoimmune conditions most strongly associated with scleritis, alongside GPA and Sjögren’s syndrome.³ Behçet’s is a systemic vasculitis that causes recurrent mouth ulcers, genital ulcers, and eye inflammation. The eye involvement is more commonly uveitis, so when scleritis does appear, it can catch clinicians off guard.

Both necrotizing scleritis and nodular scleritis have been documented as complications of Behçet’s disease. Because vasculitis is the underlying pathology of Behçet’s, the sclera’s dense vascular network makes it a plausible target, though the precise inflammatory pathway from Behçet’s to scleral damage remains unclear.¹⁰ Nodular scleritis, where a distinct raised bump forms on the sclera, has been specifically described as an eye manifestation of Behçet’s syndrome.¹¹

Sjögren’s Syndrome, Lupus, and Relapsing Polychondritis

Several other connective-tissue diseases round out the list of conditions frequently linked to scleritis. Sjögren’s syndrome, best known for causing dry eyes and dry mouth, accounted for about 4.5% of scleritis cases in the large U.S. health-system study and appeared as one of the three most strongly associated conditions in the UK population data.¹ Systemic lupus erythematosus (lupus) is another well-recognized companion. Both diseases involve widespread immune dysfunction that can attack collagen-rich tissues, including the sclera.

Relapsing polychondritis is rarer but particularly notable. This autoimmune disease targets cartilage throughout the body, most visibly in the ears and nose. Scleritis is actually one of its most common manifestations.¹² Polychondritis also appeared in a clinicopathologic study of surgically removed scleritis tissue, alongside Goodpasture syndrome and other systemic autoimmune diseases.¹³ While the cartilage connection might not seem obvious for an eye condition, the sclera shares structural proteins with cartilage, making it a target when the immune system goes after those proteins.

Inflammatory Bowel Disease

Crohn’s disease and ulcerative colitis both carry extra-intestinal manifestations, and the eyes are one of the most commonly affected sites. Episcleritis, uveitis, and scleritis are all documented complications.¹⁴ In one cohort of 500 scleritis patients, about 2% had inflammatory bowel disease, with Crohn’s disease outnumbering ulcerative colitis. Every one of those patients also had arthritis, and all experienced recurrent episodes of scleritis rather than a single flare.¹⁵

Two percent may sound small, but inflammatory bowel disease is common enough that it still accounts for a meaningful number of scleritis cases overall. The recurrent nature of the scleritis in these patients is worth noting: flares of eye inflammation often track with flares of gut inflammation, so managing the underlying bowel disease can help control the eye problem.

Ankylosing Spondylitis

Ankylosing spondylitis is more famously associated with uveitis (inflammation inside the eye), but recent genetic evidence supports a causal link with scleritis as well. A Mendelian randomization study found that the genetic variants predisposing someone to ankylosing spondylitis are associated with a roughly 70% increased risk of scleritis.¹⁶ Mendelian randomization is useful here because it can suggest a causal direction, not just a coincidence. The same analysis found even stronger links between ankylosing spondylitis and uveitis, confirming that the spondyloarthropathies as a group are eye-inflammation conditions as much as they are spine-and-joint conditions.

IgG4-Related Disease

IgG4-related disease is a relatively recently recognized condition in which an overabundance of a specific antibody subtype drives fibrosis and inflammation in multiple organs, commonly the pancreas, salivary glands, and tissue around the eyes. Scleritis has been documented as both an early and an isolated manifestation of this disease. One case involved a young woman whose nodular scleritis turned out to be the only presenting feature of IgG4-related disease.¹⁷ In another, scleritis and inflammation of the vitreous (the gel inside the eye) were the first signs, with the disease later progressing to involve both orbits.¹⁸

IgG4-related disease is worth knowing about because it can mimic other conditions, including cancer and infections. In one pediatric case, posterior scleritis was the initial presentation of IgG4-related ophthalmic disease, which is particularly unusual in children.¹⁹ Diagnosis typically requires a tissue biopsy showing the characteristic pattern of IgG4-positive cells, since blood levels alone are not always reliable.

When Scleritis Shows Up Before the Autoimmune Diagnosis

One of the most clinically significant aspects of scleritis is that it can be the first clue to a systemic autoimmune disease, especially vasculitis.²⁰ In a study that evaluated 107 scleritis patients who turned out to have an underlying systemic disease, about 78% already had a known diagnosis. But roughly 14% were diagnosed as a direct result of the workup prompted by their scleritis, and another 8% developed a recognizable systemic disease during follow-up.²¹ That means about one in five scleritis patients with an underlying autoimmune disease did not know they had one when their eye symptoms appeared.

This is why a thorough systemic evaluation is standard practice after a scleritis diagnosis. The basic workup typically includes blood tests looking at inflammatory markers, rheumatoid factor, antibodies associated with vasculitis (ANCA), and other autoimmune markers. The eye findings can guide which direction to investigate: necrotizing scleritis, for instance, raises particular suspicion for GPA or rheumatoid vasculitis, while posterior scleritis may prompt investigation of lupus or IgG4-related disease.

Telling Autoimmune Scleritis from Infectious Scleritis

Not all scleritis is autoimmune. Infections, particularly with herpes viruses, fungi, and certain bacteria, can produce scleritis that looks clinically similar. Distinguishing the two matters enormously because the treatments are nearly opposite: autoimmune scleritis calls for immune suppression, while infectious scleritis requires antimicrobial therapy. Starting steroids on a patient who actually has an infection can make the infection spread and worsen outcomes.²²

Clues that point toward infection include a history of eye surgery or trauma at the site, a single affected eye, and a more acute onset. Autoimmune scleritis is more likely to be bilateral, to recur, and to come with systemic symptoms like joint pain, skin rashes, or unexplained weight loss. When the picture is ambiguous, tissue biopsy can help. Histopathological examination can distinguish autoimmune scleritis, which shows patterns of palisading granulomas, necrosis, and vasculitis, from infectious scleritis, which features acute inflammation and necrosis of a different character, and from idiopathic scleritis, which shows chronic nonspecific inflammation with fibrosis.²³

What Drives the Tissue Damage

Regardless of which autoimmune disease is doing the driving, the destructive process in the sclera follows a shared pathway. Inflammatory cells, including macrophages and T cells, infiltrate the scleral tissue and produce enzymes called matrix metalloproteinases that digest the collagen and other structural proteins making up the sclera. Normally, the body keeps these enzymes in check with natural inhibitors. In scleritis, the balance tips: the enzymes outpace the inhibitors, and scleral tissue gets broken down.²⁴ This enzyme-inhibitor imbalance is what makes necrotizing scleritis so destructive and why aggressive immune suppression is needed to halt it.

Drug-Induced Scleritis

An emerging category worth knowing about is scleritis triggered by medications, particularly immune checkpoint inhibitors used in cancer treatment. These drugs work by releasing the brakes on the immune system so it can attack tumors, but that unleashed immune activity can also target healthy tissues, including the sclera. One case involved a 20-year-old woman who developed nodular posterior scleritis after starting pembrolizumab for a brain tumor. The scleritis resolved when the drug was stopped and steroids were given.²⁵

Data from the World Health Organization’s pharmacovigilance database show that immune checkpoint inhibitors and protein kinase inhibitors are among the most recently emerging drug classes linked to inflammatory eye disease. Severe visual loss was reported in about 12% of drug-induced eye inflammation cases overall.²⁶ As these drugs become more widely used in oncology, clinicians expect to see more cases. If you develop deep eye pain while on a checkpoint inhibitor, it should be evaluated urgently.

Scleritis in Children

Scleritis is uncommon in children, but when it does occur, an autoimmune connection should still be investigated. Juvenile idiopathic arthritis (JIA) is the main culprit in pediatric cases, appearing in about 0.3% of scleritis patients in the large U.S. analysis.¹ JIA is far better known for causing uveitis in children, so scleritis can be overlooked as a possible manifestation.

An unusual but instructive case involved a child with JIA who developed necrotizing scleritis after eye surgery. The combination of an underlying autoimmune condition, prior surgery, and the suture material used was thought to have provoked a severe immune response in the sclera.²⁷ IgG4-related disease presenting as posterior scleritis has also been reported in a pediatric patient, reinforcing the idea that even rare autoimmune conditions should stay on the differential in children with unexplained scleral inflammation.¹⁹