Early Symptoms of Autoimmune Arthritis

157 Pages·2015·4.04 MB·English

EARLY
Detection + Early Referrals + Early Diagnosis + Early
Treatment = Better Chance to Combat Unnecessary,
Irreversible Damage and Elevate the Chances for
Remission in Autoimmune Arthritis
SYMPTOMS OF
International Foundation for Autoimmune Arthritis

AUTOIMMUNE
ARTHRITIS
Investigation into patient-reported symptoms of early
disease and onset experiences.
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Contents
Foreword .............................................................................................................................................................................. i
About the Study .................................................................................................................................................................. ii
Abbreviations ..................................................................................................................................................................... iii
Summary ............................................................................................................................................................................ iv
Background ........................................................................................................................................................................ iv
Objective ............................................................................................................................................................................ iv
Methods ............................................................................................................................................................................. iv
Results ................................................................................................................................................................................. v
Conclusion ........................................................................................................................................................................... v
Autoimmune Arthritis Patient-Centered Research Study ....................................................................................................... 1
Background ......................................................................................................................................................................... 1
Objectives............................................................................................................................................................................ 2
Methods .............................................................................................................................................................................. 2
Study Design .................................................................................................................................................................... 3
Data Collection ................................................................................................................................................................ 5
Data Analysis ................................................................................................................................................................... 5
Results ................................................................................................................................................................................. 7
Part One: Descriptive Data ...................................................................................................................................................... 7
Demographics ................................................................................................................................................................. 7
Referral and Diagnosis Time ........................................................................................................................................... 8
Additional Autoimmune Disease Diagnoses ................................................................................................................. 12
Onset Triggers ............................................................................................................................................................... 13
Part Two: Early Symptoms Study (ESS) Analysis ................................................................................................................... 15
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Section 1: Hands, Fingers, Wrists, Elbows .................................................................................................................... 16
Section 2: Ankles, Knees, Feet, Toes ............................................................................................................................. 24
Section 3: Jaw, Neck, Back, Sacroiliac, Rib/Spine Junction, Shoulder Blades .............................................................. 32
Section 4: Pelvis, Thighs, Hip ......................................................................................................................................... 42
Section 5: Chest ............................................................................................................................................................. 45
Section 6: Joint Mobility, Swelling, Warmth, Duration, Rigidity ................................................................................... 48
Section 8: Skin ............................................................................................................................................................... 53
Section 9: Eye ................................................................................................................................................................ 56
Section 10: Throat, Nose, Mouth .................................................................................................................................. 60
Section 11: Gastrointestinal .......................................................................................................................................... 63
Section 13: Additional Autoimmune Features .............................................................................................................. 67
Section 14: Other (Raynaud’s, Numbness, Anemia) ..................................................................................................... 70
Part Three: Disease Specific Analysis .................................................................................................................................... 72
Rheumatoid Arthritis ........................................................................................................................................................ 73
Psoriatic Arthritis .............................................................................................................................................................. 82
Sjögren's Syndrome .......................................................................................................................................................... 89
Ankylosing Spondylitis ...................................................................................................................................................... 98
Systemic Lupus Erythematosus ....................................................................................................................................... 106
Conclusion ....................................................................................................................................................................... 118
Part 4: Patient Stories ......................................................................................................................................................... 123
Appendices .......................................................................................................................................................................... 134
Appendix A: Rheumatoid Arthritis CPML ........................................................................................................................ 134
Appendix B: Psoriatic Arthritis CPML .............................................................................................................................. 136
Appendix C: Sjögren’s Syndrome CPML .......................................................................................................................... 138
Appendix D: Ankylosing Spondylitis CPML ...................................................................................................................... 140
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Appendix E: Systemic Lupus Erythematosis CPML ......................................................................................................... 142
Appendix F: Adult Onset Still’s Disease CPML ................................................................................................................ 144
References ...................................................................................................................................................................... 146
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Foreword
“Why won’t they diagnose me?”
Prior to 2009, patients typically only communicated with one another via local
support groups. Discussions often expressed frustrations about medical care,
physical limitations and coping with chronic disease. Not typically disease-
specific, topics were broad and did not focus on symptoms that were unusual
or non-conventional. Then in 2009 something happened - social media
exploded. For the first time patients were discussing their disease with
hundreds of other patients from all over the world. Inquiries about experiences
were asked, non-conventional symptoms were being questioned, and symptomatic
dots were being connected simply by patient to patient communication.
One of the most common questions asked among autoimmune patients with arthritis involvement (“autoimmune
arthritis patients”) was, “Why won’t they diagnose me?” This question surfaced partly due to patient sharing of
experiences, as similar symptoms and laboratory tests had led to diagnosis for some, while others remained
undiagnosed or told they had an ‘undifferentiated’ disease. Many patients were frustrated that they were denied a
diagnosis that could lead to effective treatment.
Over the last few years several patient advocates have surfaced, creating online support groups and blogs, allowing the
patient to connect at a rapid pace and extensive manner with others like themselves. Ten years ago a patient may know
another with a similar diagnosis, now that person knows thousands of others and can access those ‘friends’ at any time,
day or night, to communicate about their daily experiences and find answers, not from their doctors, but from their
fellow patient community. Through these conversations questions have been raised, challenging current detection and
diagnostic standards as well as the real possibility of dual, even triple diagnosis of autoimmune or related conditions.
In 2010, a group of former and current business executives and educators decided it was time to form a nonprofit
organization whose sole purpose was to identify these missing links in the patient community, primarily through
communication with the patient themselves. They would then utilize their professional skills, in conjunction with others
who would volunteer their talents and time, and find solutions to these pressing issues. The unique twist? These
professionals were not only versed in business and higher education, they were also patients themselves, as were the
dozens who offered to volunteer their time and efforts to address and fix the community gaps. This organization, the
International Foundation for Autoimmune Arthritis (IFAA), is now a multi-award winning global nonprofit, who analyzes
the community, through internal investigations and patient to patient communications, to determine the most pressing
issues patients face today and then develops and implements solutions to the problems.
IFAA analyzed four years of patient communications, and the most pressing question was, “Why won’t they diagnose
me?” This qualitative data was then used to create, launch, and analyze a full investigation into the earliest patient-
reported symptoms of Autoimmune Arthritis. The investigation was developed using published symptoms listed by the
most current and credible resources. The patients were then asked to record the early disease symptoms they
experienced. Results of the patient-reported symptoms were compared to the existing publications and the results are
charted in this document.
The results provide both answers, and additional questions, that the IFAA hopes will lead to future investigations and
research. Additionally, these findings will be used to establish a more complete and cohesive Early Symptom Patient
Model (ESPM), per disease and as a group, to promote earlier detection, referrals, diagnosis, and treatment of these
disease.
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About the Study
This investigation is developed as a ‘Phase One’ preliminary investigation led by IFAA, and assisted by four other
Nonprofit Expert Organizations (NEO) and mentored by a respected senior research fellow. Those from IFAA who
participated in information collection, survey design, and analysis are skilled in a variety of aspects related to the
research process (including development, training and evaluation), in addition to being patients themselves.
The NEO participants included the Spondylitis Association of America (SAA) who reviewed both Ankylosing Spondylitis
(AS) and Psoriatic Arthritis (PsA), Lupus UK (LUK) who reviewed Systemic Lupus Erythematosus (SLE), Sjögren’s
Syndrome Foundation (SSF) reviewers of the Sjögren’s Syndrome (SS) module, and the International Still’s Disease
Foundation (ISDF) who reviewed Adult-Onset Still’s Disease (AOSD). IFAA was the NEO which reviewed the Rheumatoid
Arthritis (RA) module.
The diseases selected for investigation were those autoimmune diseases that most often present with similar symptoms
and are treated with similar methods of therapy. The similarity if symptoms was determined by patient communications
observed by IFAA via social media, email, and personal conversations. Although SS has excessive dryness as early
symptom, which is not considered typical of the other diseases, it appears to cross-over in many of the selected diseases
and is often a dual diagnosis. It was included to determine how prevalent it may be early in onset, regardless of
diagnosis. It should be noted that the intent of this investigation was not for patients to act as researchers, but rather to
collect information from a different perspective which can then be used to determine if there is a need for future
research by universities, doctors, and the scientific community. This “pre-research” is one of IFAA’s solutions to include
the patient when determining the best use of research dollars for a patient population. It is also aimed to serve as a
potential tool to better understand disease onset progression and which diseases were diagnosed based on those
presentations.
A ‘Phase Two’ follow up to this investigation will further explore the results and examine existing research, if any, to
determine true disease specific symptoms as well as symptoms presenting as related conditions. This will assist
practitioners and patients to recognize these diseases as early as possible, leading to quicker referrals, diagnosis, and
treatment. The next phase would also use these findings to create early symptom detection models to be used both by
practitioners and the patient community and address symptoms that overlap or could cause an undifferentiated
diagnosis.
This project was made possible with funds provided by Janssen Pharmaceutical Companies, Inc. with additional funding
supplied by the International Foundation for Autoimmune Arthritis (IFAA). Additionally over 3,500 hours of time were
donated by IFAA representatives to complete this investigation.

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Abbreviations
AIA Autoimmune Arthritis
AIA-EPSM Autoimmune Arthritis Early Patient Symptom Model
AOSD Adult Onset Still’s Disease
AS Ankylosing Spondylitis
CMPL Current Master Publications List
DIP Distal Interphalangeal Joints
DMARDS Disease-Modifying Anti-rheumatic Drugs (synthetic, such as methotrexate, sulfasalazine,
leflunomide, hydroxychloroquine)
ED Early Disease
ESPM Early Symptoms Patient Model
ESS Early Symptom Study
FS First Symptom (0 ≤ 6 months)
IFAA International Foundation for Autoimmune Arthritis
ISDF International Still’s Disease Foundation
IDR I Do Not Remember
IO Initial Onset
LUK Lupus UK
MCP Metacarpophalangeal Joints
NSAIDs Nonsteroidal Anti-Inflammatory Drug
NEO Nonprofit Expert Organizations
PsA Psoriatic Arthritis
PIP Proximal Interphalangeal Joints
RA Rheumatoid Arthritis
SLE Systemic Lupus Erythematosus
SAA Spondylitis Association of America
SRS Symptom Rating Scale
SS Sjögren’s Syndrome
SSF Sjögren’s Syndrome Foundation
UCTD Undifferentiated Connective Tissue Disease
USpA Undifferentiated Spondyloarthropathy

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Summary
Background
Delays in detection, referrals, diagnosis, and treatment of Autoimmune Arthritis diseases (AIA) can lead to greater
physical limitations, disability, poorer long-term outcomes, and higher costs for care than when the diseases are
diagnosed and treated within recommended timeframes. While the American College of Rheumatology (ACR) and
European League Against Rheumatism (EULAR) recommend treatments begin within a maximum timeframe of six
months of symptom onset to ensure the best chance of limiting disease progression; early referral and treatment is
difficult to achieve. Inaccurate symptom interpretation, lack of clinical markers and diagnostic confusion have been
found to reduce the chance of a referral and diagnosis of several months to several years.
Objective
Detection + Early Referrals + Early Diagnosis + Early Treatment = Better Chance to Combat Unnecessary, Irreversible
Damage and Elevate the Chances for Remission in Autoimmune Arthritis
Criteria for identification do not reflect the entire patient experience of early onset of symptoms. Moreover, AIA
diseases have specific symptom identifiers that assist in diagnosis that the patient may not experience in early disease or
they may experience identifiers of several diseases, creating diagnostic confusion that delays definitive diagnosis. This
study was developed as a preliminary investigation to identify patient-reported early symptoms of six AIA diseases
(Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), Sjögren’s Syndrome (SS), Systemic Lupus
Erythematosus (SLE), and Adult Onset Still’s Disease (AOSD)) and to compare these with published disease symptoms in
order to determine which symptoms, if any, overlap in early disease (including Undifferentiated Connective Tissue
Disease (UCTD) and Undifferentiated Spondyloarthropathy (USpA)) and which differentiate each disease early on.
In addition to these core objectives, a secondary focus was to evaluate the pervasiveness of Undifferentiated Connective
Tissue Disease (UCTD) and Undifferentiated Spondyloarthropathy (USpA) diagnoses, or delay in diagnosis of more than
one year from onset in patients which later progress to a confirmed diagnosis of an AIA disease.
By determining if there is a higher frequency in patient-reported symptoms that are not currently published as
associated with an AIA disease, the new information could help broaden the disease scope for those detecting early
disease and referring to specialists for diagnosis and treatment.
Methods
The study consisted of a retrospective, quantitative, online survey with a qualitative component that allowed
respondents to report any additional new symptoms not included in the study, but that they experienced for the first
time sometime between onset and 24 months. Participants were asked to describe, locate and report timing of
symptoms. They were also asked to establish which symptoms they considered the first symptoms of the disease
(occurring in the first 6 months of onset).
Participants were recruited through non-profit patient groups and postcards to a randomly selected list of 1,000
certified rheumatologists practicing in the United States for distribution to interested patients. In all 561 participants
from the US participated in this study. A further 151 SLE patients from the United Kingdom were recruited to provide
comparison with the US study.
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The survey was tested by NEOs and then administered via the internet using FluidSurveys from May 20th, 2014 and
closed on August 31st, 2014. Data was analyzed in Statwing and associations between symptoms and diseases were
expressed in terms of Cramér’s V and ranked in a symptoms rating scale.
Results
Participants reported more symptoms beginning in the first 12 months of disease onset compared with the second 12
months of onset suggesting are more acute, rather than insidious onset of disease. Regardless of diagnosis, several
symptoms were prominent in all disease categories. Participants commonly reported symptoms that were not recorded
in the CPML documents used for symptom comparisons. These included fatigue (reported by more than two-thirds of
participants in the first 12 months of onset), stiffness after significant rest, myalgia, mental cloudiness/”brain fog”, flu-
like symptoms, Raynaud’s Phenomenon (reported by one in three participants within 12 months of onset), and redness
and warmth around joints. Moreover, one in three participants also reported swelling, fever, rash, anemia, numbness
and tingling in the extremities. Gastrointestinal issues had low incidence in early disease, but at least one in four of all
patients reported these symptoms starting prior to any disease onset.
Published symptoms were not consistent with the patient experience of AIA onset. In every disease category significant
patient-reported symptoms were not included in their publications. While there are symptoms that differentiate one
disease from the other, our findings suggest these symptoms crossover to other AIA diseases. Furthermore, while
specific cause of tenderness was not investigated (joint versus enthesitis, i.e.), similar onset location occurred frequently
in early disease, regardless of diagnosis. These areas included the neck and hips (> 50%), low and upper back, shoulders,
shoulder blades, knees, chest, feet (> 30%), with hands (RA and PsA > 75%, SS and SLE > 50%, AS > 40%) and wrists (RA >
75%, PsA, SS, SLE > 50%, AS > 30%) fluctuating. Differentiating factors included sacroiliitis, rib/spine tenderness, all
back/neck area, and lowest incidence of fevers, and low incidence of dry mouth/dry eye/SS onset in spondylitis patients
(AS, PsA); canker sores in the mouth, lymph node inflammation, and shortness of breath (SS, SLE); nail pitting (PsA, SLE).
This study also found that only 50 percent patients with of RA and AOSD met the ACR/EULAR diagnosis time frame and
only a quarter of AS patients were referred to an appropriate specialist early in disease progression. Furthermore, a
significant number of patients with PsA, SS, AS, and SLE reported waiting longer than two years to be seen by a
rheumatologist or immunologist.
Conclusion
AIA diseases are complex and onset through early disease progression can present with symptoms that overlap with
other similar diseases. However, early diagnosis is essential to ensure the patient has the best chance for remission.
More complete, cohesive patient symptom models should be established, in conjunction with education about these
symptoms, so that earlier detection and referrals can occur. Undifferentiated disease, and progression to full diagnosis,
is more common that currently suggested. Establishing a more complete and cohesive model for ‘undifferentiated’
autoimmune arthritis, including a treatment plan to slow down progression at an earlier disease stage, should be
considered. Earlier public and professional education in AIA symptoms and testing for SS may be warranted.
v
Autoimmune Arthritis Patient-Centered
Research Study
An investigation into early experiences of patients diagnosed with Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA),
Ankylosing Spondylitis (AS), Sjögren’s Syndrome (SS), Systemic Lupus Erythematosus (SLE), and/or Adult Onset Still’s
Disease (AOSD) to determine gaps in symptom detection and referral and diagnosis times.
Overview prepared by Tiffany Westrich-Robertson, CEO of the International Foundation for Autoimmune Arthritis (IFAA)
and Study Project Manager, and primarily reviewed by Tami Caskey Brown and Kelly Conway, IFAA co-founders.
Background
Delays in detection, referrals, diagnosis, and treatment of Autoimmune Arthritis diseases (AIA) can lead to greater
physical limitations, disability, poorer long-term outcomes, and higher costs for care than when the diseases are
diagnosed and treated within recommended timeframes. While the American College of Rheumatology (ACR) and
European League Against Rheumatism (EULAR) suggest treatments begin within six months of symptom onset to ensure
the best chance of limited progression, irreversible damage, and remission[1], currently the average time to detect,
refer, diagnose, and treat often exceed this recommendation. A lack of clinical markers and/or symptoms that do not
present as classic diagnostic criteria can reduce the chance of a definitive diagnosis[2] and lead to diagnosis delays of
several months to several years[3]. This is a critical issue as treatment delays lead to greater physical disability and
poorer long-term outcomes that potentially affect the ability of patients to lead fully-functional lives [4-8].
Present methods for identifying early symptoms of these diseases rely on clinical diagnostic criteria and scientific
publications. Patient organizations consider these criteria do not reflect the entire patient experience of early onset of
symptoms that may occur before diagnosis is established. Furthermore, each disease is thought to have specific
symptom identifiers that assist in diagnosis; and could in fact cross over multiple diseases, thus lending to confusion and
delay in proper diagnosis. These factors may result in missed opportunities for detection, referral, or diagnosis, as the
patient-reported symptoms may be dismissed as irrelevant or inconsistent with the established, clinically accepted
progression of the disease. By determining if there is a higher frequency in patient-reported symptoms that are not
currently published as associated with an AIA disease, the new information could help broaden the disease scope for
those detecting early disease and referring to specialists for diagnosis and treatment.
Referral guidelines strongly convey the message that if an AIA disease is suspected that the patient should be referred to
a rheumatologist even if symptoms are mild or undifferentiated. However, in practice it is clearly recognized that as
while the type of disease may be difficult to detect, it is also difficult to differentiate from other causes of pain. Patients
presenting with a variety of symptoms and at different stages of the disease progression provide diagnostic challenges
for even the most experienced practitioners [9].
There is compelling evidence that damage can occur early in the course of these diseases and early treatment can
substantially decrease disability and improve long-term health status[6]. For example, in treating RA, delays of as little
as three months are associated with poorer outcomes in terms of disease progression and radiologic discernible damage
[10, 11]. The evidence for early treatment of AIA diseases has continued to accumulate and treatment guidelines have
consolidated into recommendations for referral in shorter timeframes. Patient groups, like IFAA, contend that the
collection of patient-reported early symptoms, and cross-referencing those with existing criteria, can produce a more
complete detection standard.
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