Associations between autoimmune diseases and amyotrophic lateral sclerosis: a register-based study

Abstract

Objective: To assess the associations of 43 autoimmune diseases with the subsequent risk of ALS and further evaluate the contribution of familial confounding to these associations. Methods: We conducted a nationwide register-based nested case-control study including 3561 ALS patients diagnosed during 1990-2013 in Sweden and 35,610 controls that were randomly selected from the general population and individually matched to the cases on age, sex, and county of birth. To evaluate the contribution of familial factors on the studied association, we additionally studied the first-degree relatives (siblings and children) of ALS patients and their controls. Results: Patients with ALS had a 47% higher risk of being previously diagnosed with autoimmune disease (OR 1.47, 95% confidence interval [CI] 1.31-1.64), compared with controls. A positive association was noted for several autoimmune diseases, including myasthenia gravis, polymyositis or dermatomyositis, Guillain-Barre syndrome, type 1 diabetes diagnosed younger than 30 years, multiple sclerosis, and hypothyreosis. The increased risk of any autoimmune disease was greatest during the year before ALS diagnosis, likely due to misdiagnosis. A statistically significantly increased risk was also noted during 2-5 years, but not earlier, before ALS diagnosis. First-degree relatives of ALS patients had however no increased risk of autoimmune diseases compared with first-degree relatives of controls. Conclusions: Although it is difficult to completely remove the potential effects of misdiagnosis, there is likely a positive association between autoimmune disease (such as type 1 diabetes and multiple sclerosis) and ALS, which is not fully explained by shared familial confounding factors.

ALS patients with concurrent neuroinflammatory disorders; a nationwide clinical records study

“…The concurrence between ALS and MG has also been reported (3,(7)(8)(9)(10)(11)(12)(13)(14). The cohort study that examined the risk of ALS in people with MS, found that MG and polymyositis were also associated with later ALS risk (4).…”

“…The association of dermatomyositis and polymyositis with ALS was later confirmed in other populations (3,15). In contrast, the overlap between ALS and IP such as Guillain-Barr e syndrome (GBS) has been reported only in the Swedish population (3).…”

“…Although early symptoms of amyotrophic lateral sclerosis (ALS) may mimic multiple sclerosis (MS), myasthenia gravis (MG), inflammatory polyneuropathies (IP), or dermatopolymyositis (DMPM) (1), biological overlap among these diseases may also exist (2,3). Such biological overlap may be due to shared etiologies, but also a causal relationship between the inflammation around the motor unit associated with MS/MG/IP/DMPM and neurodegeneration.…”

“…A study from the United Kingdom investigated five concurrent ALS/MS patients and proposed that MS-associated neuroinflammation could affect penetrance of the C9ORF72 expansion (2). Larger epidemiological studies have confirmed the association between MS and ALS (3,4) and found an increased risk for MS among children of ALS patients (5,6).…”

“…The cohort study that examined the risk of ALS in people with MS, found that MG and polymyositis were also associated with later ALS risk (4). The association of dermatomyositis and polymyositis with ALS was later confirmed in other populations (3,15). In contrast, the overlap between ALS and IP such as Guillain-Barr e syndrome (GBS) has been reported only in the Swedish population (3).…”