The Link Between Scleritis and Autoimmune Diseases

Scleritis: A Comprehensive Guide for Medical Professionals

Introduction

Scleritis is a serious inflammatory disease affecting the sclera, the white outer layer of the eye. Often associated with autoimmune conditions, scleritis can lead to severe pain, redness, and vision-threatening complications if left untreated. Unlike the more common episcleritis, scleritis is a deeper, more intense inflammation that requires careful diagnosis and targeted therapy. Understanding the pathology, clinical presentation, diagnostic criteria, and management options for scleritis is essential for healthcare providers to effectively treat and manage this complex condition.

In this article, we provide a detailed exploration of scleritis, offering a thorough understanding of its types, underlying causes, diagnostic workup, and the latest treatment strategies. This guide is designed for medical professionals, helping doctors and medical students alike to gain a comprehensive insight into scleritis management.

What is Scleritis?

Scleritis is a rare, often painful inflammatory condition of the sclera, the thick, fibrous layer that forms the white part of the eye. Scleritis can be vision-threatening and is often associated with systemic autoimmune diseases, including rheumatoid arthritis, granulomatosis with polyangiitis (GPA), and lupus. The inflammation can extend to adjacent structures, such as the cornea, episclera, and even the retina, leading to serious ocular complications.

Epidemiology

Scleritis is relatively uncommon, with an incidence of approximately 3–4 cases per 100,000 people annually. It primarily affects adults, particularly those between 30 and 60 years of age, and has a slight female predominance due to its association with autoimmune diseases. The condition can be classified into different types, each with distinct clinical features and prognoses.

For more on the epidemiology of scleritis, refer to the American Academy of Ophthalmology at https://www.aao.org/.

Types of Scleritis

Scleritis is classified into two main types based on the anatomical location of inflammation: anterior scleritis and posterior scleritis. Anterior scleritis is further subdivided based on clinical appearance.

1. Anterior Scleritis

Anterior scleritis is the most common form, accounting for over 90% of cases. It involves inflammation at the front of the sclera and can be subclassified into:

• Diffuse Anterior Scleritis: The most common type, presenting as widespread redness and inflammation across the sclera without focal nodules.
• Nodular Anterior Scleritis: Characterized by one or more inflamed, tender nodules on the sclera. It is associated with more severe and persistent pain.
• Necrotizing Anterior Scleritis: This is the most severe form of scleritis, characterized by intense pain and potential scleral necrosis. Necrotizing scleritis can result in vision loss and is often associated with systemic autoimmune diseases. It can be further divided into:
  • With Inflammation: Severe and destructive, often leading to scleral thinning and risk of perforation.
  • Without Inflammation (Scleromalacia Perforans): Rare and seen primarily in patients with longstanding rheumatoid arthritis, characterized by scleral thinning without significant pain or redness.

2. Posterior Scleritis

Posterior scleritis involves the sclera at the back of the eye and is less common than anterior scleritis. Due to its location, it may lack visible redness, making it more challenging to diagnose. Posterior scleritis can cause vision disturbances, including pain with eye movement, blurred vision, and even double vision due to orbital inflammation.

Pathophysiology of Scleritis

The pathogenesis of scleritis involves an immune-mediated inflammatory response, often triggered by an underlying systemic autoimmune disease. Inflammatory cells, including lymphocytes and neutrophils, infiltrate the scleral tissue, releasing cytokines and proteases that damage scleral fibroblasts and extracellular matrix components. In severe cases, this inflammatory cascade leads to necrosis, thinning, and even perforation of the scleral tissue.

1. Autoimmune Mechanisms

Autoimmune diseases are implicated in the majority of scleritis cases, especially rheumatoid arthritis and granulomatosis with polyangiitis. In autoimmune scleritis, the immune system mistakenly targets scleral tissues, leading to chronic inflammation and tissue destruction.

2. Infectious Etiologies

Though rare, infections such as herpes zoster, tuberculosis, and syphilis can also lead to scleritis. Infectious scleritis is more common in immunocompromised individuals and requires targeted antimicrobial therapy in addition to anti-inflammatory treatment.

3. Environmental Triggers

Environmental triggers, such as trauma or surgical procedures, can occasionally precipitate scleritis in predisposed individuals. Additionally, smoking has been associated with an increased risk of autoimmune diseases and may exacerbate scleritis.

For more on scleritis pathophysiology, visit the National Eye Institute at https://nei.nih.gov/.

Clinical Presentation of Scleritis

Scleritis is characterized by a range of symptoms, primarily marked by severe, persistent eye pain and redness. The pain often radiates to adjacent areas, including the temple, jaw, or sinuses, and can be exacerbated by eye movement. Other symptoms depend on the type and severity of scleritis.

1. Pain

• Intensity: Scleritis pain is often described as deep, boring, and severe, distinguishing it from the milder discomfort of episcleritis.
• Radiation: Pain can radiate to surrounding facial structures and is typically unresponsive to over-the-counter pain relief.

2. Redness and Swelling

• Diffuse or Nodular Redness: The affected sclera appears red or purple, and in nodular scleritis, tender nodules may be visible.
• Edema and Tearing: Swelling of the scleral and conjunctival tissues is common, and tearing or photophobia may also be present.

3. Visual Disturbances

• Blurry Vision: Blurred vision may occur due to corneal involvement, elevated intraocular pressure, or posterior scleritis.
• Double Vision: Diplopia (double vision) can result from posterior scleritis affecting the extraocular muscles or optic nerve.

For more details on the clinical presentation of scleritis, see the American College of Rheumatology at https://www.rheumatology.org/.

Diagnosis of Scleritis

The diagnosis of scleritis is based on clinical examination, imaging studies, and laboratory tests to identify any underlying systemic conditions.

1. Clinical Examination

A thorough eye examination, including slit-lamp biomicroscopy, is essential. The following signs help differentiate scleritis from other inflammatory eye conditions:

• Scleral Redness and Tenderness: Scleritis is characterized by deep, bluish-red coloration and marked tenderness on palpation.
• Vascular Congestion: In scleritis, the inflammation affects deeper vessels, resulting in a “violaceous” hue that does not blanch with topical vasoconstrictors (a finding useful to distinguish from episcleritis).

2. Imaging Studies

• Ultrasonography: B-scan ultrasound is useful for detecting posterior scleritis, particularly when examining the posterior sclera is difficult.
• Optical Coherence Tomography (OCT): OCT can help assess scleral and retinal thickness and rule out other conditions.
• MRI or CT Scan: These modalities are helpful in detecting orbital extension of inflammation or in cases with suspected infectious or neoplastic processes.

3. Laboratory Tests

Since scleritis is often associated with autoimmune diseases, laboratory testing is recommended to identify underlying systemic conditions:

• Antinuclear Antibody (ANA) Test: ANA is useful in screening for connective tissue diseases, such as lupus.
• Rheumatoid Factor (RF) and Anti-CCP: These are particularly relevant for patients with suspected rheumatoid arthritis.
• Antineutrophil Cytoplasmic Antibodies (ANCA): This test is essential in patients with suspected granulomatosis with polyangiitis.

For diagnostic guidelines, refer to the American Society of Ophthalmology at https://www.aao.org/.

Differential Diagnosis of Scleritis

Several conditions can mimic scleritis, necessitating a careful differential diagnosis to guide effective treatment.

1. Episcleritis: This is a milder inflammation of the episclera, presenting with less severe pain, redness, and often resolves without treatment.
2. Uveitis: Uveitis may involve the sclera but typically presents with photophobia, reduced vision, and flare in the anterior chamber.
3. Keratitis: Corneal inflammation can cause similar symptoms but affects the cornea rather than the sclera.
4. Orbital Cellulitis: This condition involves infection of the orbit and can cause eye pain and redness, often with fever and proptosis.

Complications of Scleritis

The complications of scleritis are primarily related to its potential to damage ocular structures, especially in cases of necrotizing scleritis.

1. Scleral Thinning and Perforation

Severe or necrotizing scleritis can lead to scleral thinning, which increases the risk of perforation and requires urgent surgical intervention.

2. Vision Loss

Uncontrolled inflammation may spread to the cornea, retina, or optic nerve, resulting in significant vision loss.

3. Glaucoma

Chronic scleritis can lead to elevated intraocular pressure and secondary glaucoma, requiring management to prevent optic nerve damage.

4. Retinal Detachment

In posterior scleritis, inflammation can lead to retinal detachment, which presents as sudden loss of vision and requires prompt surgical intervention.

Treatment of Scleritis

The treatment of scleritis involves a combination of local and systemic anti-inflammatory medications, with the approach depending on severity and underlying etiology.

1. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs are often effective for mild cases of diffuse anterior scleritis. Examples include ibuprofen and indomethacin.

2. Corticosteroids

• Oral Corticosteroids: Oral prednisone is the mainstay for more severe scleritis, particularly nodular and posterior scleritis.
• Topical Steroids: Topical steroids alone are generally insufficient but can be used as adjunct therapy.
• Intravenous Steroids: In severe necrotizing scleritis, intravenous methylprednisolone may be required.

3. Immunosuppressive Agents

In cases resistant to corticosteroids or associated with systemic autoimmune disease, immunosuppressive agents like methotrexate, azathioprine, or mycophenolate mofetil are used. For particularly refractory cases, biologic agents, including TNF inhibitors, have shown efficacy.

For treatment guidelines, see the American Society of Ophthalmic Immunology at https://www.asoi.org/.

Long-Term Management and Prognosis

The prognosis of scleritis varies widely based on the type and severity of the disease and the presence of underlying autoimmune conditions. With appropriate treatment, many cases achieve remission, although lifelong monitoring may be required. Preventing complications, ensuring patient compliance with immunosuppressive therapy, and regular eye examinations are essential for optimal outcomes.

Conclusion

Scleritis is a rare but serious inflammatory eye disease that can lead to vision-threatening complications if left untreated. By understanding its clinical features, associated systemic diseases, and treatment strategies, healthcare providers can offer effective management to patients with this complex condition. Early diagnosis, a multidisciplinary approach, and targeted therapy are critical for preventing complications and preserving vision.