by: Shalla Newton MSN, RN, NE-BC and David Maher
In our previous posts about Still’s disease, we have thoroughly reviewed the science behind the disease. As readers, you might have noticed we have been quite deliberate about not referring or comparing Still’s to any form of arthritis. We have focused the discussion on the severe complications of Still’s, including cytokine storms/MAS, blood clots, and primary immune deficiency disorders (PIDD). The severity of Still’s complications are not mirrored in any arthritis diagnosis.
To all providers out there and patients, we would like to retrain your mental models of Still’s vs RA and start this article with a few key thoughts:
- Autoinflammatory & Systemic*
- Innate Immune System
- Cytokine Storms
- Disease Classification: NOT Inflammatory Arthritis (symptom ONLY)
- Does NOT have defined diagnostic serology (diagnosis of exclusion)
*Still’s can lead to autoimmune conditions & has autoimmune similarities
- Adaptive (humoral) Immune System
- Disease Classification: IS Inflammatory Arthritis
- HAS defined diagnostic serology: RA Factor, CCP
All roads do not lead to arthritis
You say the word arthritis and there would be few people globally who would not recognize the disease. The global disease education, research, and treatment for arthritis is astronomical. Monetary support for arthritis goes back decades, including generous foundational support behind fundraising events like galas, telethons, marathons, etc. Arthritis research and funding generated some of the first modern biologic treatments still utilized today.
Newer generations of therapeutics developed for arthritis are often used for more rare diseases like Still’s. However, when arthritis medications are used for Still’s, the underlying treatment modalities are generally not therapeutic for the root cause of the inflammation behind Still’s, such as IL-1 and IL-6 cytokine inflammation. Arthritis therapies will target the arthritis/joint pain only. Arthritis is a symptom of Still’s but not the disease classification.
Several stakeholders and shareholders within arthritis organizations benefit from the disease classification of Still’s under the inflammatory arthritis umbrella. Let’s unpack this deceptive narrative a bit more.
Lack of evidence- based context for including Still’s disease under RA umbrella
Still’s disease (SJIA/AOSD) is a systemic autoinflammatory disease derived from innate immune dysregulation. Erroneously classifying Still’s as an inflammatory arthritis like RA is an attempt at pigeonholing the disease into a simplified designation that reflects an immature understanding of its complexity. While convenient for some, mis-classifying Still’s medically constitutes an erasure of the autoinflammatory and innate immune experience that is neither captured nor conveyed by arthritis (RA).
Arthritis is a symptom NOT a disease Classification of Still’s
Arthritis is a common symptom of Still’s disease. Overall it appears more common in adult populations with up to 50% of patients in the pediatric population not exhibiting any arthritis. However, arthritis is NOT a disease classification for Still’s and does a great disservice to the systemic aggressiveness it displays.
Still’s includes a number of hallmark complications that are not shared with RA, including those that are potentially life-threatening, such as: cytokine storms/MAS leading to sepsis and organ failure, chronic systemic inflammation with increased heart and respiratory comorbidities, severe innate immune dysregulations (leading to primary immunodeficiencies), HLH and other blood disorders (including blood clots).
I wish people would stop telling me I just have arthritis and I have to always correct them that arthritis is a symptom but is not what will kill me from Still’s32 year old Still’s patient
Arthritis Stakeholder/Shareholder Financial Incentive
Organizations like the Arthritis Foundation and biopharma companies, who are stakeholders and shareholders on arthritis dissemination (specifically usually RA), serve to benefit financially and publicly from the “inflammatory arthritis” classification of Still’s. Arthritis is one of the most common, visible and profitable diseases globally, and certainly of rheumatic and chronic/pain origin. As an example, the frontline biologics to treat RA are TNFa inhibitors (Enbrel, Humira, Remicaid etc.) are over a $40 billion dollar industry.
As a rare disease that has arthritis as a symptom, Still’s offers magnified visibility for organizations dedicated to arthritis. Organizations that can claim a rare disease with an arthritis component are able to profit from the rare and orphan disease designation. Lobbying for rare disease certainly creates research, treatment and policy opportunities, but is also monetarily opportunistic for said companies as well as tax benefits. For many reasons, the pediatric Still’s population (SJIA) has certainly partnered well with researchers and pharmaceutical companies allowing for procurement of further treatment modalities. However, often when a company or researcher focuses on the arthritis component of a rare systemic disease like Still’s, the root cause analysis treatment is lost in the translation of the arthritis myopic vision.
When providers are trained early on in medical school and residencies by invested stakeholders in arthritis that Still’s is an inflammatory arthritis, providers end up disseminating that erroneous arthritis classification to their patients and fail to recognize how distinct Still’s is in treatment and disease course. Subsequently, even in the absence of positive serological findings for autoimmune diseases (e.g. lupus or RA), providers often use these diagnoses as defaults because they were trained by a system that does not fully distinguish diseases under the umbrella of arthritis as the shared symptom.
Accordingly, patients end up being misdiagnosed with an autoimmune diagnosis that is mutually accepted by the provider and patient. Patients on a rare disease journey are often so fatigued by their own diagnostic searching, that they become willing participants in their own erroneous diagnosis loop. As we covered in our post on diagnosing Still’s disease this can lead to significant delays to diagnosis and, subsequently, appropriate treatment.
To make things worse, Still’s disease is medically coded under RA. The M06 heading is the category for RA with Still’s is listed as M06.1. Still’s diagnostic coding is listed in the middle of RA coding and its associated syndromes. Is it any wonder why so many providers think RA and Still’s are practically the same thing?!
The frustrating part is that medical associations have led the way with providers and patients following suit. Arthritis is a HUGE financial industry as discussed above, both for nonprofit and for-profit organizations. Lobbying to place Still’s under RA has been a proactive policy, research, treatment, and advocacy strategy for years, but not one backed by evidence. For us, evidence is the paramount guide.
Medical Literature: Defining Still’s vs. RA
International research further contributes to the confusion. Some research communities befuddle the comparison of Still’s and RA and other subtypes of the diseases, lending to some further deception and acceptance, particularly by the adult rheumatology community. There are currently two naming systems used for Still’s disease phenotypes (subtypes). One of which really confuses the idea that Still’s is separate from RA:
|General Phenotype Description||RA Focused||Descriptive Classification|
|Chronic, rash, fever (generally <103.5), sore throat, arthritis||RA-typeseropositive||Articular or Chronic-Articular|
|Relapsing-remitting, rash, fever, (generally ≧103.5), sore throat, arthritis||non-RA-typeseronegative||Systemic|
Not only is the RA focused naming scheme a bit unwieldy, it misses the biggest differences between the two phenotypes. Admittedly, the authors do not explicitly say Still’s is RA, but instead talk about one subtype as “RA-type.” In today’s healthcare system, quality of medical care is even more crucial with overt viral threats to underlying conditions. Thus, science must be the backbone to the questions asked, or fail to ask, and the respective answers by providers. So to further illustrate the differences between Still’s and RA, we are going to conclude with some FAQs we think show the dis-similarities in the two diseases.
Teaching Patients and Providers: FAQs
- How much do the symptoms of RA overlap with the symptoms of Chronic-Articular Still’s?
The primary overlap is that both CA-Still’s and RA show chronic, bilateral arthritis. However, CA-Still’s often does not stick to the classic small joint pattern of RA and is instead described as “peripatetic” or “traveling,” meaning that it tends to move from joint to joint. Furthermore, CA-Still’s appears less erosive than RA in general, and most commonly strikes the hips when it is erosive. The widespread use of high dose corticosteroids in CA-Still’s complicates the idea that hips are uniquely at risk in the adult spectrum of Still’s, or AOSD.
- Do Still’s and RA share any apparent causative mechanisms?
No. RA is the quintessential autoimmune disease. While the full picture of what causes RA remains to be determined (as does the cause of Still’s), what we know points definitively to autoimmunity (including HLA associations, and autoantigens RF and CCP), or a defect in the adaptive immune system. RA can cause inflammation and thus is deemed an inflammatory arthritis.
While it is true that inflammation and arthritis ARE symptoms of Still’s, it is apparent that Still’s shares a very different causative mechanism based in autoinflammation, or a dysfunction of the innate immune system. Still’s shares features with some autoimmune diseases, and can likely ignite the inflammatory response potentially leading to autoimmune complications. However, Still’s has a radically different causation and outcomes.
- Specifically, how do Still’s and RA differ?
Still’s is a systemic autoinflammatory disease and innate immune dysfunction that has the potential for severe complications, with the predisposition for non- or minimally- erosive arthritis. The incidence rates of Still’s is roughly proportional in males and females. Inflammation and arthritis are symptoms, NOT the disease classification of inflammatory arthritis.
RA is an autoimmune inflammatory arthritis featuring prominent joint erosion, a strong female predominance, and age-based diseases-onset incidence rates in the late 20’s to 30’s.
- What are some proposed strategic solutions to differentiate Still’s from RA?
To put it simply, solutions and strategic planning must include widespread training, particularly for adult rheumatologists and immunologists. Collaborative care (metacognition) will yield earlier awareness of an autoinflammatory disease versus autoimmune, distinguishing the zebra from the hoof beats of horses. Increased provider and patient education will also augment diagnostic errors, circumnavigate unnecessary tertiary referrals and curate a more local registry of providers educated in autoinflammation who will share their knowledge with their peers. How do we accomplish this? Let’s start with the following:
- Training beginning in medical schools and residencies on autoinflammatory disorders
- Autoinflammatory organizations (nonprofit and for-profit) directing their fundamental resources and efforts into earlier education like the already saturated arthritis market
- Incorporation of modern revelations on disease pathology into existing diagnostic sets
- Evidenced based teaching / scientific conferences
- i.e. NIH annual autoinflammatory meeting more readily addressing this topic and inviting more adult rheumatology and immunology peers
- Virtual training (fellowship) in autoinflammation vs brick and mortar
- i.e. Project Echo uses a hub/spoke model that is a natural fit to take knowledge from the few experts and train providers around the country on autoinflammation virtually, and with weekly CEU’s built in!
We have more content coming your way!
- Check out our series on Still’s disease Complications, next up we will be tackling autoimmune complications.
- We have also been hard at work on creating our video series discussing the challenges of navigating the U.S. healthcare system as complex care patients and further diving into the insurance and procurement of specialty therapeutics for our diseases!