This study's subtitle is absolutely incendiary.
"Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist"
I consider the subtitle of the study above to be a gauntlet, thrown down by the authors, at the feet of obstructionist medical language. I love it. If you are someone like me, and you’ve searched exhaustively for high-quality studies on secondary Sjogren’s syndrome, then you know that such studies are hard to find. Why? Because it’s difficult to conduct a study on patients with two or more autoimmune disorders, and be able to isolate what is applicable to Sjogren’s syndrome alone.
But, let me back up a bit. An autoimmune disorder is considered “primary” when it is the only autoimmune disorder the person has. A “secondary” autoimmune disorder co-occurs with a pre-existing autoimmune disorder. There are many autoimmune disorders that are not commonly characterized as primary or secondary. The fact that Sjogren’s syndrome, and some others, are divided up into primary and secondary classifications is an indication of how common it is for Sjogren’s syndrome to occur in the presence of other autoimmune disorders. If you are someone who has been diagnosed with an autoimmune disorder that is commonly broken up into the primary and secondary subtypes, this is an important verbal clue for you. It’s likely to mean that polyautoimmunity is built in to the fundamentals of the disease process. The authors of this study would prefer to eliminate these sub-types altogether, to remove any barriers to polyautoimmunity being more accurately studied and described.
Review
Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist is a 2011 observational study that combines a cross-sectional study and a systematic literature review covering the period from 2006-2011. In my last post I explained the study types commonly used for medical research. A cross-sectional study is a sub-type of an observational study, and it is considered the weakest sub-type of observational studies. By weak, I mean the most prone to hidden bias, with results that should be taken seriously, but given less weight than a retrospective or prospective study. Unfortunately, cross-sectional studies are often the easiest and least expensive to accomplish, and are the least likely to involve problematic ethical concerns. In other words, we have to work with what we’ve got.
Why am I reviewing a study on polyautoimmunity when my literature review was for “Multiple Autoimmune Syndrome?” The researchers sum this up for me by expressing a preference for the term polyautoimmunity instead of multiple autoimmune syndrome (MAS)
Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases…Polyautoimmunity is a term that can group all the taxonomy terms referring to coexistence of well-defined ADs in a single individual because some of the terms previously used are confusing and exclude various associations. Polyau- toimmunity was used by Sheenan and Stanton-King [30] for the first time {in 1993} while describing a patient with ITP, PA, AITD, SSc, pancreatic exocrine insufficiency, and CD before dying from vasculitic complications. The case they depicted corresponds to a typical MAS, which is already included in the term polyautoimmunity.”
I’ll be curious to see if the other studies I review favor the term polyautoimmunity over multiple autoimmune syndrome. It appears that this is the trend in the research, and I may need to revise my List of Autoimmune Disorders to reflect the evolution away from Multiple Autoimmune Syndrome.
In their introduction, the study authors review the history of classification of multiple autoimmune syndrome, and even though this quote is based on the authors review of other’s work, and not the authors original work, the way that they characterize multiple autoimmune syndrome by chaperone disease was so interesting that I had to include it here.
Three basic, large clusters were found. Each of them had a predominant disease that was named the “chaperones” of autoimmunity, namely, autoimmune thyroid disease (AITD), Sjo ̈gren’s syndrome (SS), and systemic lupus erythematosus (SLE).
This is the author’s recap of studies and literature to date on multiple autoimmune syndrome, which showed three basic, large clusters of multiple autoimmune syndrome, headed by Autoimmune thyroid disease over one cluster type, Sjogren’s syndrome over another cluster type, and Systemic Lupus Erythematosus over the third cluster type.
Cross-sectional study results
1,083 individuals, who each have one of four index autoimmune diseases, meeting standard diagnostic criteria, were included in this study. The index autoimmune diseases were Systemic Sclerosis (290 participants), Systemic Lupus Erythematosus (335 participants), Rheumatoid Arthritis (304 participants) and Multiple Sclerosis (154 participants). There was a strong association between these four autoimmune diseases and polyautoimmunity. I have listed them from most associated to polyautoimmunity to least associated. In all four index autoimmune diseases, Autoimmune Thyroid Disease and Sjogren’s Syndrome were the most prevalent co-occuring disease processes.
Systemic Sclerosis
40.7% had polyautoimmunity
23.1% had Autoimmune Thyroid Disease
14.8% had Sjogren’s Syndrome
Systemic Lupus Erythematosus
40.6% had polyautoimmunity
17.9% had Autoimmune Thyroid Disease
14% had Sjogren’s Syndrome
Rheumatoid Arthritis
32.2% had polyautoimmunity
21.1% had Autoimmune Thyroid Disease
11.8% had Sjogren’s Syndrome
Multiple Sclerosis
13.6% had polyautoimmunity
9.1% had Autoimmune Thyroid Disease
2.6% had Sjogren’s Syndrome
The study also looked at factors associated with polyautoimmunity. Not surprisingly, being female was associated with polyautoimmunity in all four index autoimmune diseases. Familial autoimmunity was associated with polyautoimmunity in Systemic sclerosis and Systemic Lupus Erythematosus.
Systematic Literature Review
Out of more than 20,000 articles on Pubmed, using comprehensive search terms, which the authors outline in detail, “A total of 142 articles corresponding to 226 cases of MAS were included.” The authors characterize their results using a dendogram, which they summarize this way: “According to the dendogram (Figure 2), the most hierarchical AD in the MAS cases is represented by AITD followed by SLE and SS.”
Discussion
In both the cross-sectional study and the systematic literature review, Autoimmune Thyroid Disease, Sjogren’s Syndrome and Systemic Lupus Erythematosus feature prominently in polyautoimmunity. This is critical information for anyone diagnosed with these autoimmune disorders. The study authors note
In real-life conditions, searching for the specific phenotypes (antibodies and clinical) over the course of disease and constantly looking for associated ADs, including organ specific and systemic, are more useful for developing an exact description of polyautoimmunity than taxonomic discussions.
Phenotypes are the characteristics of a disease that can be observed by a clinician. Test results (antibodies) and clinical signs (rash, swollen joints, white skin patches), as the authors note, are phenotypes. The researchers recommend a level of vigilance in autoimmune disease monitoring that I have never observed in clinical practice.
In conclusion, we suggest searching for well-defined phenotypes by looking for clusters of ADs in the same individual. It is our contention that the term “secondary diseases” should not longer be used because it detracts from the reality that these patients have two or more well- established ADs sharing the same etiopathogenesis [64]. Our results indicate that coexistence of ADs is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases.
AD: autoimmune disease. Etiopathogenesis: the original cause of the disease process.
Reference
Rojas-Villarraga A, Amaya-Amaya J, Rodriguez-Rodriguez A, Mantilla RD, Anaya JM. Introducing polyautoimmunity: secondary autoimmune diseases no longer exist. Autoimmune Dis. 2012;2012:254319. doi: 10.1155/2012/254319. Epub 2012 Feb 20. PMID: 22454759; PMCID: PMC3290803.