Karl-Gösta Henriksson

EULAR evidence-based recommendations for the management of fibromyalgia syndrome

Objective: To develop evidence-based recommendations for the management of fibromyalgia syndrome. Methods: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords “fibromyalgia”, “treatment or management” and “trial”. Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. Results: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and “other pharmacological” and exercise, cognitive behavioural therapy, education, dietary interventions and “other non-pharmacological”. In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. Conclusions: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

Myosin storage myopathy associated with a heterozygous missense mutation in MYH7

Myosin constitutes the major part of the thick filaments in the contractile apparatus of striated muscle. MYH7 encodes the slow/β‐cardiac myosin heavy chain (MyHC), which is the main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle. It is also the major MyHC isoform of cardiac ventricles. Numerous missense mutations in the globular head of slow/β‐cardiac MyHC are associated with familial hypertrophic cardiomyopathy. We identified a missense mutation, Arg1845Trp, in the rod region of slow/β‐cardiac MyHC in patients with a skeletal myopathy from two different families. The myopathy was characterized by muscle weakness and wasting with onset in childhood and slow progression, but no overt cardiomyopathy. Slow, oxidative, type 1 muscle fibers showed large inclusions consisting of slow/β‐cardiac MyHC. The features were similar to a previously described entity: hyaline body myopathy. Our findings indicate that the mutated residue of slow/β‐cardiac MyHC is essential for the assembly of thick filaments in skeletal muscle. We propose the term myosin storage myopathy for this disease.

Chronic widespread musculoskeletal pain - a comparison of those who meet criteria for fibromyalgia and those who do not.

Fibromyalgia is currently classified as chronic widespread pain with widespread allodynia to pressure pain. There are few data describing pain characteristics, quality of life, consequences for daily living, and psychosocial status in patients who meet the classification criteria for fibromyalgia proposed by the American College of Rheumatology compared with patients with chronic widespread pain but not widespread allodynia.

Skeletal muscle function in primary fibromyalgia. Effect of regional sympathetic blockade with guanethidine

ABSTRACT— Muscle fatigue is the most disabling symptom in primary fibromyalgia (PF), which in addition is characterized by generalised pain and muscle stiffness. In order to assess whether the fatigue is of central and/or peripheral origin, skeletal muscle function was studied by measuring maximum voluntary hand grip strength, and by measuring various contraction characteristics in the adductor pollicis muscle after electrical stimulation of the ulnar nerve. The PF‐patients were also studied after a regional sympathetic blockade of the forearm with guanethidine. A lower hand grip strength was found in the PF‐patients compared to the controls, before as well as during the sympathetic blockade. The developed force, measured during electrical stimulation, did not differ between patients and controls. A lower muscle relaxation rate was found in the PF‐patients. The relaxation rate increased in the PF‐patients during the sympathetic blockade. The results indicate both a central and a peripheral cause of muscle dysfunction. Activity in the muscle sympathetic system may be one link in the chain of events that lead to muscular symptoms in PF.

Prevalence of widespread pain and associations with work status: a population study

BackgroundThis population study based on a representative sample from a Swedish county investigates the prevalence, duration, and determinants of widespread pain (WSP) in the population using two constructs and estimates how WSP affects work status. In addition, this study investigates the prevalence of widespread pain and its relationship to pain intensity, gender, age, income, work status, citizenship, civil status, urban residence, and health care seeking.MethodsA cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, 18–74 years) in a county (Östergötland) in the southern Sweden. The questionnaire was mailed and followed by two postal reminders when necessary.ResultsThe participation rate was 76.7% (n = 7637); the non-participants were on the average younger, earned less money, and male. Women had higher prevalences of pain in 10 different predetermined anatomical regions. WSP was generally chronic (90–94%) and depending on definition of WSP the prevalence varied between 4.8–7.4% in the population. Women had significantly higher prevalence of WSP than men and the age effect appeared to be stronger in women than in men. WSP was a significant negative factor – together with age 50–64 years, low annual income, and non-Nordic citizen – for work status in the community and in the group with chronic pain. Chronic pain but not the spreading of pain was related to health care seeking in the population.ConclusionThis study confirms earlier studies that report high prevalences of widespread pain in the population and especially among females and with increasing age. Widespread pain is associated with prominent effects on work status.

The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls.

Abstract The association of cytochrome c oxidase negative fibres (COX‐negative) and ragged‐red fibres (RR‐fibres) with work related trapezius myalgia has been proposed. Hitherto studies have been small or without control groups. The aim of the present study was to investigate the prevalences of RR‐fibres and COX‐negative fibres in female cleaners with (n=25) and without (n=23) trapezius myalgia and in clinically healthy female teachers (n=21). The cleaners did mainly floor cleaning requiring monotonous loading on the trapezius muscle. A questionnaire covering background data and aspects of pain (prevalence, duration, intensity and influence on daily living) was answered. Biopsies were obtained from the trapezius muscle by an open surgical technique. The three groups did not differ in prevalence of COX‐negative or COX‐superpositive (i.e. type‐I fibres with extremely strong brownish reaction in both the COX and SDH/COX stainings) fibres. The prevalence of COX‐negative fibres was age dependent. Two subgroups of RR‐fibres were present when stained for COX; COX‐negative (73%) and COX‐superpositive (26%) fibres. Forty‐two percent of the COX‐negative fibres were RR‐fibres and 79% of the COX‐superpositive were RR‐fibres. A significantly (P=0.002) higher proportion of the COX‐superpositive fibres in the cleaners were RR‐fibres compared to the teachers. Multivariate regression analysis revealed that age, occupation as cleaner and a tender point in the trapezius were significantly associated with increased prevalences of RR‐fibres; a cleaner with a tender point had a 4.35 higher prevalence of RR‐fibres compared to a teacher without a tender point. No correlations between other pain related variables and prevalence of RR‐fibres were noted. In conclusion, RR‐fibres but not COX‐negative or COX‐superpositive fibres were correlated with cleaning work tasks and with a tender point in the trapezius.

The distribution of intermediate filament protein (skeletin) in normal and diseased human skeletal muscle: An immunohistochemical and electron-microscopic study☆

The presence of intermediate filaments in various mature and immature eukaryotic cells is well documented. By using antibodies against the intermediate (skeletin) filaments of cow heart Purkinje fibres, we have in the present work analyzed the distribution of skeletin in normal and diseased skeletal muscle fibres. Antiskeletin proved to be a useful tool for the identification of regenerating fibres in Duchenne muscular dystrophy. In mature muscle fibres with well-preserved myofibrils, skeletin had an intermyofibrillar localization at the Z-disk level where intermediate filaments were demonstrated. The presence of skeletin was also demonstrated around the rods of muscle fibres in nemaline myopathy biopsies, but the rods themselves did not show any cross-reactivity. This report exemplifies the usefulness of antibodies in muscle pathology.

Fibromyalgia - From syndrome to disease. Overview of pathogenetic mechanisms

According to the classification criteria proposed by the American College of Rheumatology, fibromyalgia is a long-standing multifocal pain condition combined with generalised allodynia/hyperalgesia. It is the generalised allodynia/hyperalgesia that distinguishes fibromyalgia from other conditions with chronic musculoskeletal pain. Central sensitisation of nociceptive neurons in the dorsal horn due to activation of N-methyl-D-aspartic acid receptors and disinhibition of pain due to deficient function of the descending inhibitory system are probable pathogenic factors for allodynia/hyperalgesia. Furthermore, chronic pain is a chronic emotional and physical stressor. Chronic stress and chronic sleep disturbance are not specific for fibromyalgia but could be the causes of symptoms like fatigue, cognitive difficulties and other stress-related symptoms. They may also cause neuroendocrinological and immunological aberrations.

The promise of N-methyl-D-aspartate receptor antagonists in fibromyalgia.

There is strong evidence that intravenous administration of ketamine following a standardized protocol could be used as a diagnostic test for a central sensitization in the central nervous system in patients with FM. The combination of a weak opioid and an NMDA-receptor antagonist with few side effects is presently a promise for treatment of pain in a subgroup of patients with FM. The response to intravenously administered ketamine may help select patients for this treatment modality.

Neuropathy and myopathy in primary Sjögren's syndrome: neurophysiological, immunological and muscle biopsy results

Seventeen consecutive patients with primary Sjögrens syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve‐myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum‐antibodies against PNM; 1 of IgM‐, and 1 of IgA‐isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease.