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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Ophthalmology

Uncovering the Cause: Systemic Diseases and Infection

At a Glance

Scleritis may be linked to an autoimmune disease or an infection, and the two can look alike. Doctors use targeted blood, urine, eye-sample, and imaging tests to identify the cause before starting steroids or other immune-suppressing treatment.

While scleritis is an eye condition, it often acts as a “window” into the health of your entire body. For many people, the inflammation in the eye is the first sign of a systemic (body-wide) condition that has not yet been diagnosed. Because of this, a diagnosis of scleritis almost always triggers a thorough medical investigation that goes far beyond the eye itself [1][2].

The Autoimmune Connection

Research shows that between 31% and 46% of adults with scleritis have an underlying systemic autoimmune or immune-mediated disease [3][4]. In these cases, the same overactive immune response attacking the eye may also be affecting joints, skin, or internal organs.

The most common associated conditions include:

  • Rheumatoid Arthritis (RA): This is the most frequent association, found in nearly 40% of scleritis patients who have an underlying immune disease [3].
  • Vasculitis: This is a group of disorders that cause inflammation of the blood vessels. Granulomatosis with Polyangiitis (GPA) is a particularly serious form of vasculitis that frequently involves the eye [5][1].
  • Other Conditions: Scleritis is also linked to Inflammatory Bowel Disease (IBD), Systemic Lupus Erythematosus (SLE), Relapsing Polychondritis (inflammation of the cartilage), and Sjögren’s Syndrome [3][4][6].

Why the Diagnostic Workup Matters

Your doctor will likely order blood and urine tests to evaluate the underlying cause. There is no single screening panel; tests are selected based on your clinical picture [1].

Test Category What It Looks For What It Means
ANCA Tests Vasculitis (e.g., GPA) Identifying PR3/MPO markers helps check for blood vessel inflammation [7].
RF and Anti-CCP Rheumatoid Arthritis Used to identify markers associated with RA [8].
ESR and CRP Systemic Inflammation General blood tests showing high-level inflammation [9].
Kidney Function / Urine Organ involvement Checks for silent kidney impact seen in some autoimmune diseases [10].

A negative autoimmune workup is common and does not invalidate the diagnosis, while systemic symptoms can emerge later and should be reported to your care team.

Assessing for Infection

Before you begin high-dose steroids or immunosuppressants, your medical team will assess whether the inflammation could be caused by an infection [11].

Infectious scleritis can be caused by bacteria (like Pseudomonas), fungi, or viruses (like the shingles virus, VZV) [12][13][14]. It is especially common in people who have had prior eye surgeries, such as cataract or pterygium removal, or previous eye trauma [15].

The Danger of Misdiagnosis

Infectious and autoimmune scleritis can look identical to the naked eye. However, their treatments differ significantly:

  • Autoimmune scleritis is treated by suppressing the immune system with steroids or other agents [1].
  • Infectious scleritis requires the immune system (and targeted antimicrobials) to fight the invader [11].

If a doctor treats an active infection with steroids, the medication suppresses the body’s defenses, which can potentially worsen the infection and lead to severe tissue destruction [16][13].

How Doctors Rule Out Infection

If your doctor suspects an infection—especially if you have a history of eye surgery or the eye is not responding to standard treatment—they may perform:

  • Scleral Scraping or Biopsy: Taking a tiny sample of the tissue to “culture” it (grow it in a lab) and identify any germs [12][17].
  • PCR Testing: A highly sensitive test that looks for viral or microbial DNA in the fluid of the eye [14].
  • Imaging: Looking for abscesses (pockets of infection) within the sclera [15].

By assessing for infection before and during immunosuppression, your care team can safely proceed with the systemic treatments needed to calm your immune system and protect your vision [1][11].

Common questions in this guide

Why can scleritis be a sign of a disease elsewhere in the body?
Scleritis can occur when an overactive immune response affects the eye as well as joints, skin, blood vessels, or internal organs. Conditions associated with it include rheumatoid arthritis, vasculitis, inflammatory bowel disease, lupus, relapsing polychondritis, and Sjögren syndrome.
Which tests may be used to find the cause of scleritis?
There is no single test panel for every person with scleritis. Depending on your symptoms, doctors may order blood tests for vasculitis, rheumatoid arthritis, and inflammation, along with kidney-function tests and urine testing.
Why must infection be ruled out before starting steroids for scleritis?
Infectious and autoimmune scleritis can look similar, but they need opposite treatment approaches. Steroids and other immune-suppressing medicines can weaken the body's defenses and allow an untreated infection to worsen.
How do doctors check whether scleritis is caused by an infection?
If infection is suspected, doctors may culture a small tissue sample obtained by scleral scraping or biopsy, use PCR to look for microbial or viral genetic material, or order imaging to check for an abscess. The approach depends on your examination, history, and response to treatment.
Can previous eye surgery or an eye injury increase concern for infectious scleritis?
Yes. Infectious scleritis is especially associated with prior eye surgery, such as cataract or pterygium removal, and previous eye trauma. Tell your eye doctor about any procedures or injuries, even if they happened some time ago.
What does a negative autoimmune workup mean if I still have scleritis?
A negative initial workup does not rule out scleritis or prove that no immune-related condition will ever appear. Your clinicians may monitor for new symptoms and decide whether repeat testing is appropriate based on your ongoing clinical picture.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Given my scleritis, what specific autoimmune diseases are we screening for, and which lab tests have been ordered?
  2. 2.How are we assessing for a potential infection (bacterial, fungal, or viral) before starting my treatment?
  3. 3.Since my eye inflammation can be related to other parts of my body, should I be seen by a rheumatologist to coordinate my care?
  4. 4.If my initial lab tests are negative, how often will we re-test or screen for 'emerging' autoimmune conditions in the future?
  5. 5.Are there specific symptoms outside of my eyes—like joint pain, sinus issues, or skin rashes—that I should be tracking for you?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    Current Approach for the Diagnosis and Management of Noninfective Scleritis.

    Dutta Majumder P, Agrawal R, McCluskey P, Biswas J

    Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) 2020; (10(2)):212-223 doi:10.1097/APO.0000000000000341.

    PMID: 33290287
  2. 2

    Scleritis and associated systemic diseases: contribution of systemic examination, follow-up, and additional investigations.

    Soubrier M, Vasseneix C, Jacquot R, et al.

    Journal of ophthalmic inflammation and infection 2025; (16(1)):7 doi:10.1186/s12348-025-00566-7.

    PMID: 41447412
  3. 3

    Scleritis and Development of Immune-Mediated Disease: A Retrospective Chart Review.

    Morrison T, Gottman M, Do T, et al.

    The Journal of rheumatology 2024; (51(8)):825-830 doi:10.3899/jrheum.2023-0788.

    PMID: 38302174
  4. 4

    Health system wide "big data" analysis of rheumatologic conditions and scleritis.

    Berkenstock MK, Carey AR

    BMC ophthalmology 2021; (21(1)):14 doi:10.1186/s12886-020-01769-3.

    PMID: 33407267
  5. 5

    Clinical patterns and risk factors in scleritis: a multicentric study in Colombia.

    de-la-Torre A, Cabrera-Pérez M, Durán C, et al.

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2022; (260(12)):3957-3967 doi:10.1007/s00417-022-05754-y.

    PMID: 35796822
  6. 6

    Systemic Disease Associations in a Cohort of Hispanic Patients with Scleritis.

    Arruza C, Requejo Figueroa GA, Colón J, et al.

    Journal of clinical medicine 2023; (12(5)) doi:10.3390/jcm12051969.

    PMID: 36902755
  7. 7

    ANCA-associated scleritis: impact of ANCA on presentation, response to therapy and outcome.

    Perray L, Nguyen Y, Clavel Refregiers G, et al.

    Rheumatology (Oxford, England) 2024; (63(2)):329-337 doi:10.1093/rheumatology/kead252.

    PMID: 37233203
  8. 8

    Clinical Relevance of Autoantibodies and Inflammatory Parameters in Non-infectious Scleritis.

    Vergouwen DPC, Ten Berge JC, Boukhrissi S, et al.

    Ocular immunology and inflammation 2022; (30(7-8)):1859-1865 doi:10.1080/09273948.2021.1966050.

    PMID: 34464233
  9. 9

    Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review.

    Kojima T, Dogru M, Shimizu E, et al.

    Diagnostics (Basel, Switzerland) 2021; (11(4)) doi:10.3390/diagnostics11040680.

    PMID: 33918928
  10. 10

    Refractory Nodular Scleritis as a Presenting Sign of Colorectal Cancer.

    Duran R, Kıran Y, Özdemir Yalçınsoy K, et al.

    Ocular immunology and inflammation 2025; (33(7)):1479-1482 doi:10.1080/09273948.2025.2495069.

    PMID: 40267120
  11. 11

    Scleritis: Differentiating infectious from non-infectious entities.

    Murthy SI, Sabhapandit S, Balamurugan S, et al.

    Indian journal of ophthalmology 2020; (68(9)):1818-1828 doi:10.4103/ijo.IJO_2032_20.

    PMID: 32823398
  12. 12

    Pseudomonas Scleritis following Pterygium Excision.

    Chaidaroon W, Supalaset S

    Case reports in ophthalmology 2017; (8(2)):401-405 doi:10.1159/000478721.

    PMID: 28924436
  13. 13

    Occult Fungal Scleritis.

    Jeang LJ, Davis A, Madow B, et al.

    Ocular oncology and pathology 2017; (3(1)):41-44 doi:10.1159/000449103.

    PMID: 28275602
  14. 14

    Nodular Scleritis Associated with Herpes Zoster Virus: An Infectious and Immune-Mediated Process.

    Loureiro M, Rothwell R, Fonseca S

    Case reports in ophthalmological medicine 2016; (2016()):8519394 doi:10.1155/2016/8519394.

    PMID: 27298747
  15. 15

    Infectious Scleritis: Pathophysiology, Diagnosis, and Management.

    Yu J, Syed ZA, Rapuano CJ

    Eye & contact lens 2021; (47(8)):434-441 doi:10.1097/ICL.0000000000000813.

    PMID: 34224444
  16. 16

    Pseudomonas aeruginosa scleritis initially presenting as idiopathic diffuse anterior scleritis.

    Agarwal S, Majumder PD

    Oman journal of ophthalmology 2020; (13(1)):51-52 doi:10.4103/ojo.OJO_256_2018.

    PMID: 32174745
  17. 17

    Infectious Scleritis: What the ID Clinician Should Know.

    Guerrero-Wooley RL, Peacock JE

    Open forum infectious diseases 2018; (5(6)):ofy140 doi:10.1093/ofid/ofy140.

    PMID: 29977974

This page is for informational purposes only and does not constitute medical advice. Your ophthalmologist and other specialists can interpret your tests and decide whether treatment is safe for your situation.

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