Disease collectors
Many patients with autoimmune diseases report developing symptoms of another disease a few years after their initial diagnosis of a distinct disease, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or multiple sclerosis (MS). When a secondary disease develops alongside the primary disease, the patient’s condition is referred to as a comorbidity. For patients, this often feels like betrayal layered upon betrayal.
Comorbidity is defined as the presence of two or more medical conditions coexisting at the same time, typically another chronic illness or disease. Usually, a secondary disease follows a few years after the initial diagnosis, or the primary diagnosis. Once diseases coexist, the life of an autoimmune patient becomes significantly more complex.
Approximately 25% of patients with autoimmune diseases will develop another disease at some point. This overlap is not coincidental. Once diagnosed with the primary autoimmune disease, the risk of comorbidities increases significantly, as autoimmune diseases are commonly known to be comorbid. Patients diagnosed with RA, MS, SLE, or other autoimmune conditions are at higher risk of developing secondary diseases, specifically, other autoimmune diseases, such as thyroiditis, celiac disease, and psoriasis, among others. When a patient develops more than three distinct autoimmune diseases, this is known as multiple autoimmune syndrome, or MAS, a rare condition. The real question is not whether autoimmune diseases cluster together, but why.
Bad genes, mechanical dysfunction, and poor environments
To understand why patients with autoimmune diseases are at high risk of developing secondary, even tertiary, diseases, it is essential to grasp the concept of shared susceptibility. Shared susceptibility is the phenomenon in which specific gene variants, biological mechanisms, or environmental factors increase an individual’s risk of developing multiple, distinct diseases and conditions.
In patients with autoimmune diseases, there is a higher risk of developing a second autoimmune disease because many autoimmune diseases share genetic material, particularly genes that regulate disease risk or autoimmunity. Once you have one autoimmune disease, you are more genetically likely to develop a second since many autoimmune diseases share the same genetic dysfunctions that allow their existence in the body.
But shared DNA is only part of the puzzle. Another piece of shared susceptibility is immune dysfunction, a key biological mechanism. Patients with autoimmune diseases are already immunocompromised, meaning their immune systems are weakened by the primary disease and its self-inflicted attacks. This leaves room for a secondary disease to be triggered. When immune regulation falters, whether by intrinsic dysfunction or medication-induced suppression, self-reactive immune cells can target new tissues, expanding into a new disease.
Even after genetic predispositions and immune dysfunction, disease often requires an environmental trigger. These triggers, such as viral exposure or infection, stress, toxins, or poor lifestyle choices (e.g., smoking and poor diet), can cause a short circuit in the immune system, leading to the initiation of another disease.
These shared mechanisms do not operate in an abstract way. They manifest in real, recognizable patterns.
Two’s company, three’s a crowd
Some comorbidities are more commonly linked to certain primary diseases than others. For example, many studies and observations have revealed that the following primary autoimmune diseases are more commonly linked to their respective secondary diseases than others:
Autoimmune thyroiditis is most commonly linked to → RA, celiac disease, or pernicious anemia
RA is most commonly linked to → Sjögren’s Syndrome
Type 1 Diabetes (T1D) is most commonly linked to → autoimmune thyroiditis, RA, gastrointestinal diseases
But the immune system’s ripple effects extend beyond autoimmunity.
Although autoimmune patients are at high risk of developing another autoimmune disease, specifically, they are also at risk of developing other diseases or chronic illnesses that are non-autoimmune. Similar to shared susceptibility, non-autoimmune comorbid conditions can share genetic material, but can also appear as a result of chronic inflammation or medication side effects. Common non-autoimmune comorbidities can include cardiovascular disease (CVD), diabetes, chronic infections, and even mental health conditions.
Much like the commonly linked primary-to-secondary autoimmune comorbidities, certain autoimmune diseases have a higher risk for certain non-autoimmune conditions. For example, RA patients have a 1.5 times higher risk of developing cardiovascular disease, or conditions such as heart failure, stroke, and heart attacks, than the general population.
Because autoimmune patients often experience chronic inflammation, they are at increased risk of non-autoimmune inflammation-related comorbidities, such as insulin resistance, obesity, and diabetes. But comorbidities are not just limited to organs below the neck. The brain can also develop a comorbidity as a result of chronic inflammation, such as depression, anxiety, bipolar disorder, or schizophrenia.
Often, patients with autoimmune diseases are monitored closely, depending on the medications they are taking, such as immunosuppressants and corticosteroids, due to the increased risk of comorbidities developing from medication side effects or long-term use. Patients are more prone to infections due to immunosuppressant drugs, and in some cases, are more prone to osteoporosis due to long-term corticosteroid use.
In some cases, the consequences of chronic immune disruption become even more serious. Certain immunosuppressants taken by patients with autoimmune diseases also carry the risk of creating a pro-tumor environment, leading to the development of certain cancers. Due to long-standing chronic inflammation and suppressed immune function, malignancies or abnormal cell growth have room to multiply and develop into various lymphomas.
Understanding these risks is only part of the equation. Managing them is another challenge entirely.
Proceed with treatment caution
Treatment becomes more complicated once a second or third disease coexists with the primary disease. Many factors of the second or third disease must also be considered alongside those of the primary disease and the current treatment being administered. In some cases, the primary disease treatment may worsen the secondary disease, and a patient may need to switch medications entirely. There are medications that can be used to treat multiple diseases, but risk assessment is necessary. Monitoring and safety are of the utmost importance to make sure new immune disorders aren’t triggered, or medications do not worsen pre-existing conditions
When it comes to cancer as a comorbidity, there is a treatment paradox, where an immunotherapy meant to boost the immune system will conflict with an immunosuppressant for an autoimmune disease, and vice versa. If a patient is taking an immunosuppressant, the cancer can grow and worsen. If a patient is receiving immunotherapy to enhance immune function, their autoimmune disease may worsen.
While medication and treatment plans are central to the management of comorbidities, they are not the only strategies. Certain lifestyle changes can be implemented to manage the presence and severity of comorbidities in patients with autoimmune diseases. Engaging in low-impact exercise, such as yoga, adopting an anti-inflammatory diet, and reducing environmental exposure to toxins can help manage symptoms and inflammation associated with comorbid diseases and reduce their burdens over time.