Is fibromyalgia a discrete entity?

doi:10.1016/j.autrev.2011.10.018

Autoimmunity Reviews

Volume 11, Issue 8, June 2012, Pages 585-588

https://doi.org/10.1016/j.autrev.2011.10.018 Get rights and content

Abstract

Fibromyalgia (FM) is defined as chronic widespread pain (CWP) with allodynia or hyperalgesia to pressure pain, and is classified as one of the largest group of soft tissue pain syndromes. Its pathogenesis is not entirely understood, although it is currently believed to be the result of a central nervous system (CNS) malfunction that increases pain transmission and perception. There are no instrumental tests to confirm the diagnosis, but many of the differential diagnoses can be excluded by means of an extensive clinical examination and patient history. Although fibromyalgia is a recognisable clinical entity, it would seem appropriate to consider the entire range of tenderness and distress in clinic patients in order to tailor treatment on an individual basis.

Introduction

Musculoskeletal pain conditions, which can be found in all age groups of men and women, are different in terms of pathophysiology but linked anatomically and by their association with pain and impaired physical function. They include inflammatory diseases such as rheumatoid arthritis or gout; age-related conditions such as osteoporosis and osteoarthritis; common conditions of uncertain aetiology such as back pain and fibromyalgia (FM); and conditions related to physical activity or injuries such as occupational musculoskeletal disorders, sports injuries or the consequences of falls.

FM is characterised by a considerably abnormal and reduced pain threshold, and a series of clinical distress variables that include pain, fatigue, sleep disturbance, anxiety and depression. According to the American College of Rheumatology (ACR) criteria, a diagnosis of FM can be made if a patient has 11 or more tender points together with widespread pain, although epidemiological studies suggest that FM may simply be the end of a continuum of distress. Epidemiologically defined disease may be different from clinically defined disease, and it is still debated whether FM is a discrete clinical entity. This is an important question because, if the disease is also a clinical continuum, there may be patients with FM who remain unidentified because they have fewer tender points and their symptoms of distress are overlooked. Finally, basic and clinical research may be inappropriately concentrating on a limited area of what is actually a pain–distress continuum.

Section snippets

Fibromyalgia as a clinical entity

The FM syndrome has gradually crystallised as the paradigmatic central sensitisation syndrome [1]. It was originally considered to be a form of “soft tissue rheumatism” or a disorder related to an ill-defined connective tissue disease but, over the last twenty or thirty years, it has become increasingly clear that it is characterised by increased processing of pain in the central nervous system. This has been objectively documented by means of the evolving techniques of functional brain imaging

Fibromyalgia: A multi-symptom disorder based on stress system dysregulation

We argue that FM can be best understood as a disorder of the stress system following a prolonged period of physical and/or mental overburdening. This view not only provides a heuristic theoretical framework, but can also inform clinical practice.

Although firstly a chronic disorder, FM is also characterised by a number of symptoms, including increased sensory and stress sensitivity, physical and mental fatigue and effort intolerance, neuropsychological deficits such as concentration and memory

The key-role of life stress in the aetiology of fibromyalgia

Many FM patients report a long history of accumulating psychosocial and/or physical stressors. In this respect, there is evidence to suggest that childhood trauma or victimisation experiences may lead to a predisposition for the condition [21]. It has also been suggested that over-commitment to work, compulsive care-giving and a tendency to physical or mental over-exertion (which may be associated with personality traits such as maladaptive perfectionism) may be predisposing factors [22].

The pathophysiology of fibromyalgia: An interplay of neural, neuro-hormonal and immunological mechanisms

The pathophysiology of FM most probably involves reciprocal interactions between impaired descending pain inhibition, high basal sympathetic outflow, hypothalamic pituitary adrenal (HPA) axis hyporeactivity, and abnormal inflammation. These may persist over the long term and underlie both central sensitisation and the inability to adapt adequately to various stressors [28], [29].

Against this background, the core symptoms of FM may at least partially be considered manifestations of an abnormal

Relevance of the stress concept in the treatment of fibromyalgia

In order to counteract the fear of FM patients that their illness will not be taken seriously or be viewed as ‘purely psychological’, clinicians could explain to patients that ‘their stress mechanisms have become exhausted and hypersensitive as a result of prolonged overload’. Moreover, this plausible and non-stigmatising illness theory may be used as a starting point for realistic and pragmatic therapeutic help because many of the ongoing stressors that influence symptoms and disability can be

Conclusions

One of the conflicting problems with diagnosing of fibromyalgia is where to locate the underlying pathogenetic mechanism [[32], [33], [34]]. Not everyone is yet convinced that FM is a discrete entity and, depending on their specialty or knowledge, they may consider patients as being psychosomatic, masked depressive, abnormal pain processors or distressed. However, whatever the pathogenetic mechanism(s), patients can still be found every morning in our outpatient clinics seeking help and

Take-home messages

•
Fibromyalgia is defined as chronic widespread pain (CWP) with allodynia or hyperalgesia to pressure pain.
•
The pathogenesis of FM is not entirely understood.
•
FM is a disease with multi-symptoms, considered a stress-related disorder overlapping other ‘functional somatic’ syndromes.
•
FM treatment requires an individualised, multimodal and multidisciplinary approach.

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Fibromyalgia represents one of the most enigmatic and likely least autoimmune diseases in rheumatology practice, being a chronic condition of unknown etiology and functional features. The disease is characterised by widespread pain with allodynia or hyperalgesia to pressure pain, combined with profound fatigue [101–104]. Additional non-specific symptoms include sleep disturbances, mood disorders, and neurocognitive impairment [105–110].
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It is a highly debilitating condition that most often affects women (Jason et al., 1999) and that is associated with high psychosocial and economic costs (Collin et al., 2011). A considerable proportion of CFS patients also suffers from chronic pain symptoms, and studies increasingly suggest that CFS may be part of a broader spectrum of chronic pain and fatigue disorders (Kanaan et al., 2007; Van Houdenhove et al., 2010; Ablin et al., 2012). There is accumulating evidence that impairments in stress regulation may play a key role in the development and perpetuation of CFS (Silverman et al., 2010; Luyten et al., 2011; Nater et al., 2011).
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Perhaps examining multiple areas, especially the painful spots longitudinally, may be more informative. Other factors such as polymorphisms in genes associated with pain may also play a role [21]. A possible factor that might be perceived as weakness in our study is the examination only of a distal leg with a single skin biopsy and not concurrently with a second biopsy from the proximal thigh, as done by others [9,11,12].
Fibromyalgia (FM) is one of the most common chronic pain syndromes. Various pathogenetic mechanisms have been implicated but none is proven. Our scope was to determine if Intraepidermal Nerve Fiber Density (IENFD) is reduced in the skin of FM patients, as observed in patients with painful small fiber sensory neuropathy (SFSN).
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15 of 46 (32.6%) FM patients had reduced IENFD [range: 0.6–12.5 fibers/mm (mean: 4.83 SD: 2.5)], compared to healthy controls [2.8–11.5 fibers/mm (mean: 7.35, SD: 1.85)] (p < 0.0001). No significant correlation was noticed between NPSI scores and IENFD. No difference in the Langerhans cells, the major Antigen Presenting Cells (APCs) in the epidermis, or in IL-6 staining, was noted between FM and controls. IENFD was equally reduced in a subset of FM patients who also had another autoimmune disease.
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The prevalence and impact of early childhood trauma in Chronic Fatigue Syndrome
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It is a highly debilitating condition that is mainly characterized by medically unexplained fatigue and post-exertional malaise (Carruthers et al., 2011; Fukuda et al., 1994). Studies have found a high degree of comorbidity between CFS and other functional somatic syndromes such as Fibromyalgia (FM) and Irritable Bowel Syndrome (IBS), indicating that similar factors may be involved in the causation of these disorders (Ablin et al., 2012; Van Houdenhove, Kempke, and Luyten, 2010; Van Houdenhove and Luyten, 2009). A growing body of research suggests that early life stress may be implicated in the development of CFS and related conditions (Van Houdenhove, Egle, and Luyten, 2005; Van Houdenhove and Egle, 2004; Van Houdenhove et al., 2010; Van Houdenhove, Luyten, and Egle, 2009).
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View full text

ReviewIs fibromyalgia a discrete entity?

Abstract

Introduction

Section snippets

Fibromyalgia as a clinical entity

Fibromyalgia: A multi-symptom disorder based on stress system dysregulation

The key-role of life stress in the aetiology of fibromyalgia

The pathophysiology of fibromyalgia: An interplay of neural, neuro-hormonal and immunological mechanisms

Relevance of the stress concept in the treatment of fibromyalgia

Conclusions

Take-home messages

Semin Arthritis Rheum

Pain

Pain.

J Pain

FibroCollaborative. Mayo Clin Proc.

Metabolism

Biol Psychol

Autoimmun Rev

Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia

Arthritis Rheum

Pain is real; fibromyalgia isn't

J Rheumatol

Somatization and fashionable diagnoses: illness as a way of life

Scand J Work Environ Health

Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome

Arthritis Rheum

Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia

J Rheumatol

Elevated insular glutamate in fibromyalgia is associated with experimental pain

Arthritis Rheum

Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: a magnetic resonance spectroscopy study

Arthritis Rheum

Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury

Arthritis Rheum

Holocaust survivors: the pain behind the agony. Increased prevalence of fibromyalgia among Holocaust survivors

Clin Exp Rheumatol

Review
Is fibromyalgia a discrete entity?