What is a disease flare in RA? A medical student’s perspective

Introduction: This guest article was written by Anca Smyth, who is currently a fourth year medical student at Queen’s University Belfast. She wrote an essay during her ‘special study component’ three week attachment in Altnagelvin hospital and later submitted it to the Irish Society for Rheumatology. Anca not only won the prestigious Bernard Connor Prize at the 2016 conference, but she was invited to present her paper to the Society. So congratulations to Anca and best wishes for the future! – Philip Gardiner

“When it comes to our health most of us are guilty of thinking that we are invincible. Imagine waking up one morning with excruciating pain, having stiff, swollen joints and weakness which markedly interfere with your ability to carry out the normal activities of daily living. To a rheumatoid arthritis (RA) sufferer such debilitating symptoms may constitute ‘a significant disease flare’, an episodic exacerbation of this chronic, symmetrical, small joint inflammatory condition. Or does it?

Unlike the ACR/EULAR classification criteria for RA [1] which is based on objective measurements of serological parameters, acute phase reactants, numbers and sites of swollen or tender joints and symptom duration, there has been no standard definition of what constitutes a RA flare or how it can be objectively assessed and classified according to severity. Apart from measuring the efficacy and safety of novel pharmacological agents used in the treatment of RA by means of randomised controlled clinical trials, a valid definition and classification of a flare would prove to be an invaluable tool in guiding clinical care and monitoring disease outcome.

When a patient is experiencing a flare, a significant increase in the disease activity so that it requires a change of treatment [2], there is often discrepancy in the interpretation of the severity of signs and symptoms between the doctor and the patient [3]. This may lead to inappropriate treatment, patient dissatisfaction and non-adherence to therapeutic interventions [4, 5]. Such discordance is due to the heterogeneous nature of the patient experience during this acute episode, which not only affects objectively measured clinical parameters but also generates self-reported symptoms such as pain, weakness, sleeplessness or fatigue [6, 7]. From the patient’s perspective the experience of a flare is also about functional impairment, disability and social participation [8, 9] which interfere with the patient’s quality of life and psychological well-being.

There is also variation between RA sufferers regarding what constitutes a significant disease flare. Reasons for this include the fact that patients report the severity of a flare according to their baseline disease activity and previous experiences with the disease [10], thus what seems a severe flare to an early RA patient may be classified as a normal fluctuation of disease activity by someone who has been living with this disease for an extended period of time. Additional factors in defining a significant flare include the level of a patient’s tolerance to worsening of signs and symptoms, health beliefs and coping skills [11, 12].

Current methods of assessing RA patients include measuring the disease activity in 28 joints using the DAS28 score and evaluating physical disability by means of a Health Assessment Questionnaire (HAQ28) and patient’s global health status by employing a 10cm Visual Analogue Scale (VAS).  However, none of these approaches are without flaws. Two of the main determinants of the patient’s global health are pain and fatigue [13], subjective symptoms which cannot be measured accurately and which are influenced by many factors including mental health status and co-morbidities [14]. Considering the ACR/EULAR disease remission criteria of a score of 1 or less on the patient’s global assessment scale of 0-10 such targets may be difficult to achieve accounting for the fact that many RA patients suffer from depression [15] or chronic pain syndrome [16].

The HAQ tool, limited by its ‘ceiling effect’ due to lack of adequate sensitivity in detecting a worsening of disability towards its upper limits or assessing lower limb function [17] does not accurately evaluate the severity of a RA flare. The DAS 28 score, a weighted composite of the number of swollen joints, level of the inflammatory marker ESR (erythrocyte sedimentation rate) and patient global assessment score is currently employed in clinical practice to classify disease activity, guide therapeutic treatment and function as an outcome measure in the treat-to-target approach [18]. Limitations of this approach include a misleadingly low DAS28 score if the flare predominantly affects the patient’s feet, which are not included in the DAS28 joint count, or if it is concentrated on a single joint, causing debilitating pain and rendering the patient unable to work. Conversely, a high DAS28 score based on a large number of swollen joints in the absence of pain or elevated ESR may initiate an unnecessary escalation in therapeutic treatment [19]. Some studies have used the inverse of the improvement criteria based on the DAS28 score to assess the severity of a flare but such a correlation seems inappropriate [20].

Given the complexity of patient experiences and heterogeneity of assessment tools that affect the interpretation of a significant disease flare, there is no ‘one size fits all’ approach to monitoring a flare. In an era of demedicalisation, there is an emphasis on treating the individual in the community, with medical care providers offering evidence based patient education and counselling regarding management of flares or side-effects of medication in the form of leaflets, telephone consultation with various members of the multi-disciplinary team or telecare services for people to report and be advised on their flares [21]. Such a model of care not only promotes self-efficacy and helps achieve an internal locus of control but it also increases accessibility and reduces travelling time for patients in the rural communities.

Since RA is a chronic condition, the patient may be the expert in monitoring their condition and self-management of a flare by means of non-pharmacological (such as exercise, bed rests, applying ice or heat packs or via complementary and alternative therapies) or pharmacological interventions (by increasing the dose of glucocorticoids, analgesics or non steroidal anti-inflammatory medication alongside a fixed-dose of disease modifying anti-rheumatic drugs) seems to be the approach employed by most RA sufferers [22]. There are times, however, when self-management of a flare is ineffective and the patient decides to seek medical help. Although the threshold at which such a decision is made is unknown, the doctor must adopt a holistic approach in assessing the patient and based on shared-decision making determine an appropriate change in treatment.

In conclusion, the concept of a significant disease flare in RA is complex, non-standardised and its interpretation depends on interplay between a patient’s physical and psychological parameters, previous disease experience and health beliefs. Monitoring of this acute episode should occur in the community, with health professionals providing ongoing patient education and counselling and facilitating timely review by the clinician when the patient seeks medical help.”

References

[1]. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burnester GR et al. 2010 Rheumatoid Arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheumatism 2010; 62(9): 2569-2581.

[2]. Alten R, Pohl C, Choy EH, Christensen R, Furst DE, Hewlett SE, Leong A, May JE, Sanderson TC, Strand V, Woodworth TG and Bingham CO. Developing a Construct to Evaluate Flares in Rheumatoid Arthritis: A Conceptual Report of the OMERACT RA Flare Definition Working Group

[3]. Studenic P, Radner H, Smolen JS and Aletaha D. Discrepancies Between Patients and Physicians in Their Perceptions of Rheumatoid Arthritis Disease Activity. Arthritis and Rheumatism 2012; 64(9): 2814-2823.

[4]. Van den Bemt BJF, van den Hoogen FHJ, Benraad B, Hekster YA, van Riel PLC, van Lankveld W. Adherence Rates and Associations with Nonadherence in Patients with Rheumatoid Arthritis Using Disease Modifying Antirheumatic Drugs. The journal of Rheumatology 2009; 36: 2164-2170.

[5]. Matteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Medical Care 2004; 42: 200-209.

[6]. van Tuyl LHD and Boers M. Patient’s Global Assessment of Disease Activity: What Are We Measuring? Arthritis and Rheumatism 2012; 64(9): 2811–2813.

[7]. Kalyoncu U, Dougados M, Daures JP, Gossec L. Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: a systematic literature review. Annals of the Rheumatic Diseases 2009; 68: 183–190.

[8]. Benka J, Nagyova I, Rosenberger J, Marcejova Z, Lazurova I, van der Klink JL, Groothoff JW and van DijkJP. Social participation in early and established rheumatoid arthritis patients. Disability and Rehabilitation 2015; 19: 1-8.
[9]. Sverker A, Ostlund G, Thyberg I, Valtersson E and Bjork M. Dilemmas of participation in everyday life in early rheumatoid arthritis: a qualitative interview study. Disability and Rehabilitation 2015; 37(14): 1251-1259.
[10]. Seror R, Tubach F, Baron G, Guillemin F, Ravaud P. Measure of function in rheumatoid arthritis: individualised or classical scales? Annals of the Rheumatic Diseases. 2010; 69(1): 97–101.

[11]. Rohekar G and Pope J. Test-Retest Reliability of Patient Global Assessment and Physician Global Assessment in Rheumatoid Arthritis. The Journal of Rheumatology 2015; 36(10): 2178-2182.

[12]. Sanderson TC, Hewlett SE, Flurey C, Dures E, Richards P and Kirwan JR. The impact triad (severity, importance, self-management) as a method of enhancing measurement of personal life impact of rheumatoid diseases. The Journal of Rheumatology 2011; 38: 191-194.

[13]. Bartlett SJ, Bykerk VP, Cooksey R, Choy EH, Alten R, Christensen R, Furst DE et al.  Feasibility and Domain Validation of Rheumatoid Arthritis Flare Core Domain Set: Report of the OMERACT 2014 RA Flare Group Plenary. The Journal of Rheumatology 2015; 42(11): 2185-2189.

[14]. Barton JL, Imboden J, Graf J, Glidden D, Yelin EH and Shillinger D. Patient-Physician Discordance in Assessments of Global Disease Severity in Rheumatoid Arthritis. Arthritis Care and Research 2010; 62(6): 857–864.

[15]. Khan NA, Spencer HJ, Abda E, Aggarwal A, Alten R and Ancuta C. Determinants of discordance in patients’ and physicians’ rating of rheumatoid arthritis disease activity. Arthritis Care Research 2012; 64: 206–14.

[16]. Wolfe F, Michaud K. Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia. J Rheumatol 2004; 31: 695–700.

[17]. Gardiner PV, Sykes HR, Hassey GA and Walker DJ. An evaluation of the health assessment questionnaire in long term longitudinal follow-up of disability in Rheumatoid Arthritis. British Journal of Rheumatology 1993; 32: 724-728.
[18]. Ward MM, Guthrie LC and Alba MI. Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials. Annals of the Rheumatic Diseases 2013; 1: 205079.
[19]. Pincus T, Yazici Y and Sokka T. Quantitative measures of rheumatic diseases for clinical research versus standard clinical care: differences, advances and limitations. Best Practice and Research Clinical Rheumatology 2007; 21(4): 601-628.

[20]. Leeb BF, Sautner J, Leeb BA, Fassl C, Rintelen B. Lack of agreement between patients’ and physicians’ perspectives of rheumatoid arthritis disease activity changes. Scandinavian Journal of Rheumatology 2006; 35: 441-446.

[21]. National Institute for Health and Care Excellence. Commissioning for people with rheumatoid arthritis. NICE commissioning guides [CMG51], 2013.

[22]. Hewlett S, Sanderson T, May J, Alten R, Bingham CO, Cross M, March L, Pohl C, Woodworth T and Bartlett SJ. ‘I’m hurting, I want to kill myself’: rheumatoid arthritis flare is more than a joint count- an international patient perspective on flare where medical help is sought. Rheumatology 2012; 51:69-76.

Arth-rit-is-is- not-right

Sometimes we are so busy doing our activity scores we don’t have time to really listen to what our patients are saying. Dorothy Logue is a talented poet who also happens to have rheumatoid arthritis – she has very kindly agreed to share this poem with us…

‘Arth-rit-is-is- not-right’

I am not my usual self, for days I’ve felt unwell.
I’ve lost my mojo, anyone who knows me can tell.
I feel so ill, my back hurts, my arms and legs hurt too,
My neck is so sore, I really don’t know what to do.
I could ring the doctor again, what good would that be?
I could go visit him but there’s nothing new to see.
I cannot drive today, my fingers are so sore.
I can just complain and mope and it is such a bore.
No one knows how I feel, I can’t make them understand,
When you feel as low as this, your thoughts get out of hand.
I’m not a hypocondriac, nor one to complain,
I could whinge all the time but that would be in vain.
Unless you are a sufferer, you wouldn’t believe
The lengths I will go to, to have the pain relieved.
Maybe tomorrow morning when I get out of bed
I will feel much better and love the day ahead.
Days I ask myself questions, there are no answers back,
Days I go out and enjoy myself, life is back on track.
I keep my pain and suffering private so no one will ever know,
They only see the “ME” which I force to “get up and go.”

by Dorothy Logue

Stiffness: the forgotten outcome measure in Rheumatoid arthritis?

The history of measuring disease activity in Rheumatoid Arthritis goes back to the 1950s with the Lansbury Index and the Mallya and Mace Score. The Lansbury Index is incredibly complex to calculate but it was a serious effort at getting an objective handle on how patients were doing. He knew that his Index could also be used to test whether drugs for RA were effective. The Lansbury index incorporated morning stiffness, fatigue, amount of aspirin used, Grip strength, and ESR in a ‘systemic index’ as well as an ‘articular index’ which attempted to estimate the joint surface area. Lansbury was very careful in how he asked patients about their joint stiffness. He recommended that we should ask them what time they get up in the morning and then when they ‘limber up’ or feel less stiff. He published a paper in which he demonstrated that the duration of morning stiffness reduced as patients went into remission [Lansbury J. Quantification of the activity of rheumatoid arthritis. Recession of morning stiffness as patients go into remission. Am J Med Sci 1956; 232: 8-11]. The duration of morning stiffness was also included in the multi-component Mallya and Mace score. This score was validated in that each component was shown to be related to disease activity. I am not aware of any studies that have looked at the intensity of stiffness as a patient reported outcome measure, but it stands to reason that there might be a close relationship between the intensity of stiffness and the degree of disability. If I see a young mother whose stiffness prevents her from dressing herself or her children for an hour after she gets up in the morning I regard this as more suggestive of early RA than someone who complains of stiffness for four hours but without the same intensity.

Joint stiffness was excluded from the EULAR and WHO ‘core set of variables’ to assess disease activity, and so it does not feature in most of the commonly used disease activity scores in recent times. Some have even questioned whether or not the duration of morning stiffness reflects disease activity. It is certainly possible that other conditions such as Parkinson’s disease or oedema could cause a feeling of stiffness, and joint damage can certainly cause a complete loss of mobility. A brief review of past research would tend to support the claim that stiffness is indeed a valid marker of disease activity in RA.

In Hot joints1985 Hazelman and colleagues published a study using infrared thermography to provide a thermal image of the inflamed joints and derive a ‘heat distribution index’ for the larger joints. This technique must still be one of the most ‘direct’ measures of the degree of joint inflammation in someone with RA. Although this did not prove to be a practical test for the clinic, they did show that the heat distribution index correlated well with the duration of morning stiffness and other disease activity measures. The correlation with stiffness was just as strong as the relationship to joint pain. However, it is certainly true that many people do find it difficult to say how long their stiffness lasts for. People with severe disease activity may well have stiffness throughout the day. It is therefore not an accurate guide as to how active the arthritis is in an individual patient.

But what is joint stiffness, anyway? Like pain, it is a subjective phenomenon. It is difficult to define but may be regarded as a perception of difficulty moving a joint. So it is not quite the same as loss of movement. A joint that has been fused will often not feel stiff to the patient. Of course there may also be a loss of movement in a joint, for instance in a knee or elbow that won’t straighten properly. We do know that joints that are swollen and inflamed will often feel stiff to the patient, but we still don’t understand exactly what causes this feeling and why it should be worse in the morning. Is there a biochemical marker that correlates with the symptom of stiffness?

Assuming that stiffness reflects disease activity, could there be a better way to quantify the feeling of stiffness? This is a field where technological advances should begin to help. It is now technically feasible to measure movement accurately and have the data analysed and presented to the patient and/or their health professional in a meaningful way that can help to encourage health behaviour. This sort of technology should be able to provide accurate quantitative information about joint movement, which is clearly a very relevant outcome for people with arthritis. We are doing some research in this area, so hopefully there will be more to say about this in the near future!