Autoimmune Rheumatic Disease

As optometrists, we are trained to recognize when our patients’ eyes may be telling a deeper story regarding their overall health. Take, for example, a case of optic neuritis. The need for a systemic workup is obvious because we know this can be an ocular manifestation of a serious underlying systemic condition (multiple sclerosis). But when might the more subtle ocular signs, such as dry eye disease (DED), warrant a systemic workup—specifically, when does DED clue us in to the diagnosis of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Sjögren syndrome (SS) (Figures 1 and 2)? (Though thyroid eye disease is widely known, rheumatic diseases are actually the leading cause of autoimmune-related DED.) What’s more, how can we distinguish among these autoimmune rheumatic conditions when the most common ocular finding is DED, with reportedly 38% to 47% of RA, 13.4% to 39.5% of SLE, and up to 95% of SS patients presenting as such?^1-3

CLUE 1: NO TREATMENT RESPONSE

A major red flag for an underlying autoimmune rheumatic disease is when a patient appears unresponsive to DED treatments. This is due to the fact that in patients who have RA, SLE, or SS, ocular surface health is notoriously difficult to maintain because it is under constant autoimmune attack.

RA, though generally considered a joint disorder, can also cause extra-articular inflammation. While still under investigation, it is suspected that the rheumatoid factor autoantibodies in RA instigate pannus-induced meibomian gland inflammation. This assault results in evaporative DED through meibomian gland dysfunction (MGD).^4,5

Similar to RA, the exact mechanism of SLE-induced DED is still under investigation. That said, it is suspected that the corneal Langerhans cells in SLE are depleted and the function of accessory glands is also compromised, leading to both evaporative and aqueous-deficient DED.⁴

In SS, the immune system targets exocrine glands throughout the body—including the lacrimal glands. The direct destruction of the lacrimal gland morphology causes subsequent aqueous-deficient DED. This can be more specifically designated as “sicca syndrome,” meaning there is both oral and ocular dryness in the presence of confirmed SS.^2,4

Of note: Those who have RA and SLE also have an increased incidence of developing secondary SS, thereby compounding their aqueous-deficient and evaporate DED symptoms.²

CLUE 2: RELATED SYMPTOMATIC HISTORY

If a DED patient is unresponsive to standard treatment, perform a careful history and ask whether they have experienced any of the nonocular symptoms related to autoimmune rheumatic disease, including:

• RA: multiple joint pain and swelling (usually in the hands—look for the “swan neck sign”), morning stiffness, and pressure point nodules.⁶
• SLE: mucocutaneous changes (look for the classic facial malar or “butterfly” rash), general malaise, weight loss or anorexia, and joint pain.⁷
• SS: dry mouth (xerostomia—look for a smooth, cracked tongue), difficulty swallowing, need for frequent drinks, and parotid gland enlargement.⁸

CLUE 3: PATIENT DEMOGRAPHICs

It is also important to take the patient’s biological sex into consideration. The prevalence of autoimmune rheumatic disease is nearly 9:1 in female patients versus male patients.⁹ Why is this? The discrepancy is attributed to the role that sex-linked genes, found on the sex chromosomes X and Y, play in immune pathway regulation. The X chromosome carries 11-times the amount of immune-regulating genes compared with the Y chromosome, resulting in more robust innate and adaptive immune responses in females. Though this heightened immunity is beneficial against extrinsic pathogens, it also increases the risk of autoimmunity.

In the innate branch, immunity is achieved through non-specific defenses (physical barriers, innate immune cells, and chemical mediators), which, in turn, activate proinflammatory pathways. In females, this system is heightened and can lead to an overactivation of cytokine production. In the adaptive branch, T and B lymphocytes provide immunity through a “learned” response. This pathway can become dysregulated in females compared with males due to the effect of estrogen on lymphocytic maturation and activity. Data support that the female predominance in autoimmune risk is likely due to the role sex hormones play as key modulators.¹⁰

TESTING AND TREATMENT

Because the ocular surface in patients who have autoimmune rheumatic diseases can be nonresponsive to standard therapies, the early introduction of steroids (monitoring IOP, of course) or immunomodulators can be beneficial in these patients. More severe autoimmune-related DED patients may also require more specialized treatment, such as blood-serum tears, amniotic membranes, and neurotrophic considerations.

As an example, a 72-year-old White female diagnosed with SS who had previously failed numerous therapies to control her DED, including immunomodulators, blood-serum tears, and scleral lens wear, experienced significant improvement in her DED symptoms when an amniotic membrane was placed to facilitate ocular surface healing.

We should also consider nonmedical therapies when managing patients who have autoimmune rheumatic disease-related DED. As these conditions show a mixed mechanism of pathogenesis, in-office procedures, such as meibomian gland expression and intense pulsed light therapy, can be used to help improve MGD. Further, scleral contact lens wear can be helpful for those patients whose visual symptoms make performing daily activities difficult.

In cases in which we suspect an autoimmune rheumatic disease may be contributing to a patient’s DED, bloodwork should be ordered by us or the patient’s primary care physician to confirm (or contradict) our hunch. These tests include the following: rheumatoid factor, antinuclear antibody, anti-SS-A (Ro) and antibody, anti-SS-B (La) and antibody, and a lacrimal gland biopsy.

Our diagnostic radar

In today’s world, where we see DED in many (if not all) our patients, we must keep autoimmune rheumatic disease on our diagnostic radars. After all, in RA, SS, and SLE, DED is the most common presenting ocular sign. So, if a DED patient presents unresponsive to treatment, reports nonocular symptoms associated with autoimmune rheumatic disease, or is female, we must consider running additional tests. Should these tests reveal positive results, we should pivot to prescribing DED treatments that have proven most effective in providing relief to these patients.