Fibromyalgia and the Difficult Synthesis

The pathophysiological uncertainties in fibromyalgia (FM) mean that its diagnosis, to this day, remains a strictly clinical exercise. The physician’s evaluation of symptoms is therefore of fundamental importance both for the correct diagnostic framing of the patient and also for guiding a personalized therapeutic approach.¹

However, the symptomatic diagnostic framing is not at all simple. Fifty-three percent of physicians describe difficulties in diagnosing FM, 38% report low confidence in recognizing symptoms, and 48% feel unsure about differentiating FM from similar conditions. These difficulties are reported not only by general practitioners but also by specialists such as rheumatologists, who are accustomed to diagnosing conditions of chronic musculoskeletal pain.²

The identification of symptomatic domains in patients with FM has been the focus of various studies. A 2008 study, based on a Delphi exercise, started with 104 domains and arrived at 15 through various rounds. The 3 most impactful domains for patients were identified as pain or physical discomfort, joints aching or pain, and lack of energy or fatigue.³ Other studies have performed cluster analyses of symptomatic items using the revised Fibromyalgia Impact Questionnaire.⁴

In this issue of The Journal of Rheumatology, Weinstein and colleagues, using a large sample size from the Fibromyalgia Association registry, studied the importance of various symptoms in FM through direct patient input. Through semistructured qualitative interviews conducted on 15 patients, the authors identified 149 important symptoms belonging to 14 symptomatic domains: fatigue, sleep quality, pain, emotional issues, cognitive difficulties, functional limitation, gastrointestinal problems, limitations in walking and mobility, social limitations, problems with shoulders and arms, headaches, muscle tenderness, paresthesia, and auditory problems. Then, through an international survey, 1044 patients responded to more than 172,000 questions regarding symptoms. Indeed, pain, muscle tenderness, and fatigue were the symptomatic domains described in most patients (in 99.8% of participants for pain and muscle tenderness, and 99.3% for fatigue), and more than 98% of patients described symptoms in at least 5 of the 14 symptomatic domains.⁵

There is nothing seemingly revolutionary from the published results. However, this study confirms the plethora of symptoms that patients with FM can potentially report, and likely explains many of the above-mentioned difficulties that physicians encounter in symptom framing and diagnosis.

Further proof of the complexity in the correct symptomatic interpretation (and thus diagnosis) of FM is the evolution of diagnostic criteria proposed over the last decades. The 1990 American College of Rheumatology (ACR) classification criteria were based on the count of tender points upon palpation in individuals with a history of widespread pain.⁶ The main criticisms of these criteria were that, despite providing an objective criterion for diagnosis corroborated by physical examination, the tender point count was challenging for nonrheumatologists to perform, judging their presence was thus arbitrary, and importantly, they did not inform about nonpainful symptoms.⁷ In 2010, preliminary diagnostic criteria were developed by the ACR, which, through subsequent revisions, resulted in the ACR 2016 FM diagnostic criteria.^8,9 Currently, these criteria, widely known by those dealing with FM, are the diagnostic reference used in research contexts. Complicating matters further, other North American scientific societies, specifically the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION), in partnership with the US Food and Drug Administration and the American Pain Society (APS), under the name ACTTION-APS Pain Taxonomy (AAPT), proposed in 2019 a new diagnostic system for FM that was completely different from the Polysymptomatic Distress Scale of the ACR 2016 criteria.¹⁰ These AAPT 2019 criteria appear to have expanded the cohort of individuals with FM by 73%, allowing diagnosis with less severe symptoms and fewer painful body sites.¹¹

Further, challenges have emerged with the 11th version of the International Statistical Classification of Diseases and Related Health Problems (ICD) codes by the World Health Organization, wherein FM is no longer categorized under musculoskeletal system conditions, as it is still considered by the majority of scientific contributions, but is classified under the definition of primary chronic pain.¹² This classification, which defines primary chronic pain as occurring when “the symptoms are not better accounted for by another diagnosis,”¹² is regarded by some healthcare providers as a regression compared to the advancements in the field that have been made in recent years.¹²

The complexity is such that the UK Royal College of Physicians recently felt the need to publish a paper to provide clinicians with “digestible” information to aid them in the diagnostic pathway of FM.¹³

Delineating the boundaries of what constitutes centralized nociplastic pain (and thus FM) from what does not is crucial for several reasons. The first reason is of a rheumatological nature. FM often goes hand in hand with chronic arthritides, having the capacity to significantly inflate the patient-reported components of clinimetric disease activity indices. This could potentially lead to overtreatment with drugs that are unnecessary, harmful, and very costly.^14,15 The second reason is of a more general medical nature. The diagnostic difficulties of FM also translate into diagnostic delays, a higher number of physicians consulted, and an increased risk of undergoing surgical procedures that, in patients with FM, are often not resolutive. Conversely, an early diagnosis reduces the number of procedures, procedures are accompanied by greater success, and overall healthcare spending is reduced.¹⁶

The third reason is somewhat of a social nature. Recognizing a patient with FM means relating to a vulnerable person who may be at a higher risk of taking extreme actions. A recent metaanalysis showed that, in patients with FM compared to the general population, the risk of death by suicide is significantly increased, with a standardized mortality ratio of 3.37.¹⁷

Data from FM registries also deserve a comment. In a world so heterogeneous in terms of diagnosis, clinimetry, and treatment, having data collected uniformly on large sample sizes is more important than ever, as is talking about precision medicine in this field.^18,19

What can be gleaned from what has been stated so far? It is probably safe to say that in dealing with FM, a multilevel synthesis is required. The first is at the level of the individual patient. At this level, it is necessary that the patient with a history of widespread chronic pain and other (often numerous) disorders be framed and possibly be diagnosed by specialist physicians who deal with this pathology. Although it is a highly prevalent condition in the general population, the importance of early diagnosis is increasingly clear, not so much because it has been shown to improve outcomes but in order to at least reduce iatrogenic harm from unnecessary therapies and costs. However, reasoning from a more upstream perspective, a synthesis should also be conducted at a supranational level among scientific societies to establish diagnostic and/or classificatory reference standards that maintain a certain temporal stability. These considerations do not intend to appear overly reductionist, but when addressing FM, as with all complex issues, it is increasingly necessary to proceed methodically.

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