Our body’s immune system is capable of combating external threats such as pathogens and infections while sparing the host tissues. Sometimes this delicate balance between ‘self’ and ‘non-self’ entities is disrupted, leading to autoimmune diseases. In autoimmune disease, the body’s immune system starts attacking itself. Autoimmune thyroid eye disease (TED) is an autoimmune condition where the immune system attacks tissues around the eyes, causing inflammation, swelling, and potential vision loss. TED is most commonly seen in patients with Graves’ disease or Hashimoto’s thyroiditis. But it frequently coexists with other autoimmune conditions and this phenomenon known as polyautoimmunity.
What Is Autoimmune Thyroid Eye Disease?
TED is a complex inflammatory disorder of the orbit (eye sockets in the skull). It can present as either a unilateral dry-eye disease affecting only one eye or with bilateral sight-threatening complications. It is also the most common cause of unilateral and bilateral proptosis (protruding or bulging eyes) in adults. Ocular discomfort is the most common presentation in thyroid eye disease patients. Other common symptoms include:
- Double vision (diplopia)
- Eye discomfort, pain, or pressure
- Eyelid retraction and puffiness
- Dryness, redness, or irritation
TED is usually associated with Graves’ disease (an autoimmune thyroid disorder causing hyperthyroidism or an overactive thyroid gland), but it can also occur in euthyroid (normal thyroid function) or hypothyroid (under-functioning thyroid gland) autoimmune contexts.
Prevalence of Other Autoimmune Diseases Among TED Patients
As mentioned above, due to the phenomenon of polyautoimmunity, there is often a high frequency of coexisting autoimmune disorders in patients with TED. Several systematic studies and reviews have established a strong correlation between TED and other autoimmune diseases and some of the key summaries from these studies are:
- Approximately 13.9% of patients with TED had at least one other autoimmune disease.
- The most common non-thyroid autoimmune disorders were rheumatoid arthritis, vitiligo, and psoriasis, each seen in about 3% of patients.
- Of those with other autoimmune conditions, around 43% had been on immunosuppressive therapy before the onset of their TED symptoms.
So while autoimmune TED primarily affects the eyes and thyroid, a sizeable minority (around 1 in 7) of TED patients also have other autoimmune disorders.
How Coexisting Autoimmune Disorders Affect TED
One of the most important questions is how the presence of another autoimmune disease affects TED. Does it worsen TED or make it harder to manage? A summary of the systematic studies shows:
Higher Clinical Activity at Presentation
Patients with TED harboring another autoimmune disease and who had not been on immunosuppressive therapy prior to TED onset presented with significantly higher clinical activity scores (CAS) than those with TED alone or those with other autoimmune diseases but previously on immunosuppression. The CAS were determined based on disease severity parameters as per the European Group on Graves’ Orbitopathy (EUGOGO) criteria. This suggests that polyautoimmunity may correlate with a more active or aggressive phase of TED at first diagnosis.
Severity & Likelihood of Treatment to Succeed
Studies also suggest that patients with other autoimmune disorders may need more aggressive or earlier therapy.
Effect of Immunosuppression Before TED Diagnosis or Occurrence
Interestingly, patients who had received prior immunosuppressive therapy before TED onset tended to have less active TED at presentation. This is compared to those who have other autoimmune diseases but without immunosuppression. This may be because immunosuppression for other conditions might modulate immune responses more broadly and provide some protective effect or mitigate TED’s severity.
Which Autoimmune Diseases Most Commonly Coexist with TED
Review of related literature shows that the following autoimmune disorders are among the most frequently associated with TED:
- Rheumatoid arthritis (RA): chronic joint inflammation, often systemic and present in 3.7% of patients with TED
- Vitiligo: an autoimmune attack on pigment-producing cells and is seen to coexist with ~3.0% of TED patients
- Psoriasis: a skin disease involving immune-mediated hyperproliferation, seen at similar rates as vitiligo.
Other autoimmune conditions that commonly overlap with thyroid autoimmunity (though not always specifically with TED) include Hashimoto’s thyroiditis, systemic lupus erythematosus (SLE), Sjögren’s syndrome, celiac disease, type 1 diabetes, etc.
Possible Mechanisms of Interaction
Some of the reasons for which TED behaves differently or more severely in people with other autoimmune diseases include:
- Shared genetic risk: Many autoimmune diseases share susceptibility genes or encourage immune system dysregulation. For example, genes that influence immune checkpoint regulation, HLA genes, etc.
- Immune priming: If your immune system is already “primed” towards an autoimmune response (due to an existing autoimmune condition), adding another one (like TED) may provoke a more widespread and aggressive response.
- Cross-reactivity and immune spillover: Autoantibodies or immune cells in one disease might escalate activity in another; for instance, B cells producing antibodies may become more reactive overall.
- Inflammatory environment: Autoimmune diseases always show systemic inflammation and in such individuals, the use (or discontinuation) of immunosuppressive therapy may influence the inflammatory phase of TED.
Implications for Diagnosis & Treatment
The fact that TED often interacts with other autoimmune disorders has several practical implications:
Screening and Patient History
Clinicians evaluating patients with TED should inquire about other autoimmune diseases (past or current) and past immunosuppressive therapy in their medical history.
Monitoring for Severity
Patients with comorbid autoimmune disorders might be at higher risk for more active disease and warrant earlier or more aggressive treatment, especially if TED is appearing to escalate.
Therapeutic Approach
Immunosuppressive treatments used for other autoimmune diseases could influence TED, either beneficially (by reducing immune activation) or harmfully (with possible side effects).
A coordinated team of specialists are important (endocrinologists, ophthalmologists, rheumatologists, etc.) to manage all autoimmune issues in a balanced way.
Patient Counseling
Patients with autoimmune TED and concurrent autoimmune disorders should be made aware that their disease might present differently (more active with more inflammation) and the prognosis should be discussed in light of their overall autoimmune burden.
Gaps in our Understanding of the Correlation Between TED and Other Autoimmune Diseases
While the coexistence of TED with other autoimmune diseases is an established fact, the exact mechanisms by which other autoimmune diseases increase TED activity are not fully understood. It is also not clear whether treating the other autoimmune disorder (and with what therapy) will reduce the risk or severity of TED. More large-scale, prospective studies are needed to confirm findings and guide precise treatment protocols.
Address Your TED Symptoms with Professional Guidance
Autoimmune thyroid eye disease often does coexist with other autoimmune disorders: in the studied cohort, about 14% of TED patients had at least one non-thyroid autoimmune disease. If you are suffering from symptoms of TED and are concerned about treatment options, do not hesitate to schedule an appointment with Dr. Raymond Douglas.
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