Complex Patient Presents With….

Diagnosing Still’s disease

by: Shalla Newton MSN, RN, NE-BC and David Maher

Let’s recap

Still’s is a rare systemic autoinflammatory disease with complex and aggressive complications. Still’s and its respective complications can be variable and capricious in presentation making a definitive diagnosis difficult. Diagnostic errors and delays to treatment are compounded by both limited physician knowledge regarding autoinflammation as well as patient knowledge regarding their own disease.

Historically, the Still’s Triad of fever, rash and arthritis was used to diagnose Still’s disease. However, as we explored in our discussion of Adult Onset Still’s disease (AOSD) this is not an effective way to diagnose Still’s as many patients present with much more complex and systemic complications. Patient presentations are highly variable, and the element of variance in disease presentations makes it impossible to build an accurate picture of the disease by focusing on the symptoms. 

What the heck is happening to me?

The Still’s disease journey often begins with years of unknown diagnosis, misdiagnosis, and lots of detours to satisfy the exclusionary diagnostic criteria.

Rather than jump right into those diagnostic criteria, we are starting where patients do. We bring our readers to a land where something, potentially very serious, is wrong, but no one seems to know what that is and why it is wrong. 

Lack of up to date and accurate diagnostic screening, including patients that present with normal laboratory values but odd and complicated systemic symptoms, often leads to a very long and exhausting diagnostic odyssey for patients and their caregivers.

You want me to go where and see which specialist?

Where the diagnostic odyssey begins is mainly a reflection of the primary symptoms a patient experiences. For instance, patients with high fevers and other systemic problems (particularly respiratory and cardiovascular) often initially present to emergency departments. Patients with prominent arthritis typically start their journey with general practitioners and rheumatologists. 

Often infectious disease specialists are called in to consult with suspected infectious disease symptoms (fevers, rashes, fatigue). Elevated Epstein Barr viral loads from latent Mono virus episodes will often be present, providing an easy scapegoat for symptoms. The exhaustion and pain from the hidden inflammatory process often get diagnosed as Chronic Fatigue Syndrome or Fibromyalgia and dismissed by providers.

A pile of question marks. Highly unsatisfying. Source

Unless they are lucky enough to be treated by the few physicians with autoinflammatory expertise, patients are typically left with a pile of questions for years after they start to experience symptoms. Most patients are misdiagnosed and many are told their symptoms are in their head or will clear with time if laboratory values do not indicate an unambiguous problem. 

Patients begin to distrust their own bodies, minds and their providers and enter a hamster wheel spiral of cognitive destruction. A spiral many never come out of to find a true diagnosis. 

Our personal journeys and message to providers

Our personal diagnostic odysseys are reflected in our stories. Suffice it to say our journeys have left a permanent imprint of feeling punted among many specialists. Both of us have experienced many providers unable to figure out our diagnosis and wanting to transfer care. We have both experienced providers of all kinds refusing care, and in one of our case’s, a rheumatologist actually abandoned care due to complexity. 

Complexity spooks even the best of providers, but that does not make it acceptable to drop patients. We as patients know that providers are human too and feel anxious and isolated by complex cases. We know that unless providers have built in metacognition like that of academic centers, providers might be at a loss for resources to treat complex rare cases. As frustrating as that is, it hopefully gives some guidance on the kind of education and intervention needed at the medical practitioner level to address this shortfall.

AOSD Diagnosis: Yamaguchi Criteria

Diagnosis of Still’s disease in the adult population (AOSD) is generally defined as being over the age of 16. AOSD is primarily diagnosed via the Yamaguchi criteria. Yamaguchi criteria was originally published in 1992. The image below shows the Yamaguchi criteria. There are other criteria sets but Yamaguchi has remained the most popular because it is the easiest to use in the clinic. 

Source

SJIA Diagnosis: 2001 ILAR Criteria

Diagnosis of Still’s disease in the pediatric population under the age of 16 is called Systemic Juvenile Idiopathic Arthritis (SJIA). SJIA criteria is made via the 2001 International League Against Rheumatism (ILAR) criteria. The same committee laid out the diagnostic criteria for the other forms of Juvenile Idiopathic Arthritis (JIA).

Source

Inclusion among other diseases that are primarily arthritic gives the mistaken impression that SJIA is somehow related. One study of SJIA patients in Germany found that up to 50% of patients did not meet the ILAR guidelines, primarily due to a lack of arthritis despite arthritis being a defining feature of the diagnosis criteria. This discrepancy has prompted the use of the Yamaguchi criteria in some pediatric cases.

Both cluster studies and genetic association studies have found that SJIA is fully distinct from the other JIA diseases. Evidence simultaneously shows that SJIA and AOSD are, as we have said before and will say again here resolutely, the pediatric and adult continuum of Still’s disease. One disease continuum, One name, Still’s Disease. 

Clinical Trial Hope…Interleukin-18

Current evidence points to an intercellular messenger called Interleukin-18 (IL-18) as a possible diagnostic factor and likely treatment target in both Still’s disease and MAS. Studies of IL-18 in SJIA patients have consistently shown elevated and irregular levels, as have studies in AOSD. 

There are two hurdles to IL-18 as a diagnostic factor. First, IL-18 testing is not widely available around the world. Presently it is only available at select medical centers. Second, in order to declare IL-18 as a diagnostic measurement, we need the kind of data that can only come from a large-scale multicenter study. We strongly believe that any large scale study must include the full continuum of Still’s patients, both pediatric and adult, to provide an accurate patient sample population.

Interest in IL-18 has prompted trials of anti-IL-18 agents as Still’s disease treatments. Furthest along in trials is tadeking alfa from AB2 Bio which is currently awaiting a phase III trial after a successful phase II trial. Phase III trials for MAS and HLH are ongoing with anti-IL-18 agents as well. A handful of compassionate use or expanded access cases have reported excellent results.

It appears IL-18 might drive a number of inflammatory processes in Still’s disease. Thus, IL-18 could be a strong diagnostic factor that currently eludes the limited and crude tools we have to measure inflammation. 

Nothing Fits!…Think Autoinflammation!

Autoinflammatory diseases in general, but Still’s disease in particular, are difficult and scary for both patients and providers. They are rare, systemic, and extremely complex in presentation. By the time autoinflammatory diseases are recognized and have changed their status to it’s complicated, permanent organ damage, blood clots, and all their other horrible buddies have moved in and are sleeping on the couch.

The current tools used in diagnosis of Still’s disease are flawed and antiquated. They do not account for the variance in presentation, to say nothing of the frustration and misunderstandings inherent in a diagnosis of exclusion. Furthermore, most patients with Still’s do not present with the typical triad of fevers, joint pain and salmon colored rashes. Those who do are the easier patients to diagnose and treat, but appear to represent a minority of cases.

The scientific understanding of autoinflammation is much younger than that of its autoimmune brother. Many of the most valuable insights about autoinflammation have not yet made it into clinical practice or even into the general medical consciousness. It is our role as patients to continue to push for wider awareness and recognition.

Our scientific tools and understanding of Still’s disease have evolved enormously since the diagnostic criteria were authored. Is it not time our diagnosis evolved to include all that information too?

5 thoughts on “Complex Patient Presents With….

  1. Thank you again for yet another informative article and your continued dedication to finding answers to this disease.

    Like

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