Patients with Fibromyalgia Benefit from Aerobic Endurance Exercise

Fibromyalgia (FM) is a disorder characterised by diffuse widespread musculoskeletal aching and stiffness and multiple tender points [1]. Its pathophysiology is poorly understood. The influence of aerobic endurance exercise on pain in patients with FM was investigated. Twenty-seven patients (25 female, 2 male) participated in a controlled clinical study and performed 12 weeks of jogging, walking, cycling or swimming following a given schedule. Twelve sedentary FM patients (11 female, 1 male) served as controls. Before and after training both the study and the control groups were evaluated spiroergometrically. Tender point pain was quantified by dolorimetry. The painful body surface was estimated by a pain body diagram, and its intensity by a visual analogue scale and a ranking scale. Patients trained for an average of 25 min two to three times a week, with an average intensity of 50% of maximal oxygen uptake (VO_2max). Unlike the control group, the training group exhibited a decrease in heart rate and VO₂ and an increase in respiratory quotient during submaximal workload. Maximal performance capacity and VO_2max remained unchanged, whereas the wattpulse (watt/heart rate) improved at maximal workload. Pain parameters remained unchanged in the control group, but in the training group the mean number of positive tender points (15.4/12.7), the mean pain threshold of the gluteal tender point (2.89 kp/3.50 kp) and the painful body surface (18%/15% body surface) decreased significantly. Subjective general pain condition deteriorated in two patients but improved in 17. Our results suggest a positive effect of aerobic endurance exercise on fitness and well-being in patients with FM. Received: 24 February 1999 / Accepted: 23 September 1999     

The Effect of Melatonin in Patients with Fibromyalgia: A Pilot Study

The aim of the study was to determine the possible effect of melatonin treatment on disturbed sleep, fatigue and pain symptoms observed in fibromyalgia (FM) patients. Twenty-one consecutive patients with FM were included in an open 4-week-duration pilot study. Before and after treatment with melatonin 3 mg at bedtime, patients were evaluated using tender point count by palpation of 18 classic anatomical regions, pain score in four predesignated areas, pain severity on a 10 cm visual analogue scale (VAS), sleep disturbances, fatigue, depression, anxiety, and patient and physician global assessments, also by a VAS. Urine 6-sulphatoxymelatonin levels (aMT-6S) were measured in the patients and 20 age- and sex-matched controls. Nineteen patients completed the study. One patient withdrew because of migraine and another was lost to follow-up. At day 30, median values for the tender point count and severity of pain at selected points, patient and physician global assessments and VAS for sleep significantly improved with melatonin treatment. Other variables improved but did not reach statistical significance. Adverse events were mild and transient. Lower levels of aMT-6S were found in FM patients compared with normal median controls (±SD, 9.16 ± 7.9 μg/24 h vs 16.8 ± 12.8 μg/24 h) (p= 0.06). Although this is an open study, our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM. Double-blind placebo controlled studies are needed. Received: 14 September 1998 / Accepted: 14 May 1999     

Relationship between Chest Expansion and Respiratory Muscle Strength in Patients with Primary Fibromyalgia

In this paper the assessment of the relationship between chest expansion with maximal inspiratory (MIP) and expiratory pressures (MEP) in primary fibromyalgia (FM) syndrome is discussed. Chest expansion (CE) measurements, spirometric values, and MIP and MEP values in 30 female patients with primary FM are compared with 29 healthy age-matched female controls. Patients with FM had lower CE, MEP and MIP values than controls. CE correlated significantly with MIP and MEP values. There was no significant difference between groups in spirometric values. Our results indicate that patients with FM have impaired respiratory muscle strength, and measurement of CE may be a useful clinical parameter. Despite its limitations CE may reflect respiratory muscle strength. It is worth following up these data in a wider and controlled series, with ancillary tests in addition to the MIP and MEP. Received: 24 January 2001 / Accepted: 13 July 2001     

Fibromyalgia Developed after Administration of Gonadotrophin- Releasing Hormone Analogue

We report the case of a woman treated with a gonadotrophin-releasing hormone analogue for endometriosis who developed typical clinical features of fibromyalgia, with widespread musculoskeletal pain, sleep difficulties, neuropsychological complaints and tender points on clininal examination. The gonadotrophin-releasing hormone analogue treatment probably induced disturbances in the neuroendocrine system and the secretion of neurotransmitters, and may be suspected to be the cause of this case of fibromyalgia. Received: 3 May 2000 / Accepted: 25 October 2000     

Prediabetes and mild hepatosteatosis are associated with blunted cortisol response to glucagon but not to growth hormone

BackgroundAlthough there is a close relationship between cortisol and growth hormone (GH) levels, glucose intolerance and hepatosteatosis, changes in GH and the hypothalamo-pituitary-adrenal (HPA) axis were not previously studied in prediabetes. The main purpose of the present study was to assess changes in GH and HPA axis and their relationship with hepatosteatosis in prediabetic patients.MethodsForty prediabetic patients, with body-mass index (BMI) 25–35 kg/m², and 23 healthy individuals, with normal glucose tolerance and similar age and BMI, were included. The 75 g oral glucose tolerance test and glucagon stimulation test (GST) were used.ResultsNo significant differences were detected between prediabetic patients and healthy individuals in terms of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), IGF-1/IGFBP3 ratio or adrenocorticotropic hormone (ACTH). GH responses to GST did not differ between groups. On the other hand, peak cortisol and area under the curve (AUC) _(cortisol) response on GST were significantly lower in prediabetic patients. Both peak GH and AUC _(GH) response on GST correlated negatively with waist circumference and body weight. The degree of hepatosteatosis correlated negatively with peak cortisol, GH, AUC (cortisol) and AUC (GH) response on GST.ConclusionCortisol response to GST is decreased in prediabetic patients, with relatively well conserved GH response. This suggests altered HPA axis responsiveness in prediabetes, as is known in diabetes. Thus, HPA axis changes in patients with diabetes probably start before the development of diabetes as such.     

High Frequency of Hysterectomies and Appendectomies in Fibromyalgia Compared with Rheumatoid Arthritis: A Pilot Study

We investigated, in retrospect, if there were differences in the frequency and types of abdominal surgery between newly diagnosed female fibromyalgia (n= 80) and rheumatoid arthritis (n= 47) patients performed before the formal diagnosis. There was no difference in the total number of abdominal operations between both groups. In the rheumatoid arthritis group more cholecystectomies (p= 0.01) were performed, probably due to the older age of these patients (58.5 vs 48.5 years). However, in the fibromyalgia group there were more hysterectomies (p= 0.04) and appendectomies (p= 0.05) than in the rheumatoid arthritis group. Received: 10 October 1997 / Accepted: 19 June 1998     

Treatment of Fibromyalgia with Tropisetron, a 5HT3 Serotonin Antagonist: A Pilot Study

In this pilot study we investigated 10 women suffering from primary fibromyalgia. All patients received 5 mg of tropisetron in the evening, for a period of 4 weeks. Clinical disease variables included the measurement of a pain score, fatigue, sleep disturbances and measurement of the number of tender points. Five of our patients (50%) showed a statistical clinical improvement of all the above parameters starting after the first week of treatment. Two patients did not respond to the therapy and three discontinued the study because of side-effects. We conclude that administration of tropisetron in fibromyalgia patients could be useful in the management of this difficult and incurable syndrome. Received: 22 January 1999 / Accepted: 20 May 1999     

A Preliminary Study of Circadian Serum Cortisol Concentrations in Response to a 72-hour Fast in Rheumatoid Arthritis Patients not Previously Treated with Corticosteroids

The aim of the study was to investigate the effects a 72-h fast upon serum total and free cortisol concentrations in RA patients not previously treated with glucocorticoids. Total serum cortisol and transcortin concentrations were measured in four RA patients with active disease at 4-h intervals during two 24-h periods (1200 h–1200 h), the first while eating a normal diet (fed state) and the second during the last 24 h of a 72-h water fast. Free cortisol concentrations were calculated from the total cortisol and transcortin values. The 3-day fast increased overall 24-h free and total cortisol concentrations by 50% and 35%, respectively. This was due largely to a marked increase in nocturnal serum cortisol concentrations during fasting, particularly at 0400 h, when mean total and free cortisol levels were increased by 170% and 260% compared to the fed state. Between 2000 and 0800 h overall total- and free cortisol concentrations were increased by 72% and 99%, respectively. These results suggest that an increase in nocturnal concentrations of cortisol occurs in response to fasting in RA patients not previously treated with glucocorticoids. These increases may mediate the beneficial clinical response previously found in studies of longer fasting periods in RA patients. Received: 25 January 2000 / Accepted: 3 August 2000     

A 5.5 Year Prospective Study of Self-Reported Musculoskeletal Pain and of Fibromyalgia in a Female Population: Significance and Natural History

In order to investigate the significance and outcome of self-reported pain and fibromyalgia (FM) in a female population, 214 women with initially self-reported pain were interviewed and examined in 1990 and 1995. In 1990 the sample was categorised into four pain status groups: 46 individuals (21%) with non-chronic (recurrent) pain, 69 (32%) with chronic regional pain 42 (20%) with chronic multifocal pain and 57 with chronic widespread pain (CWP). The last group comprised 39 (18%) women with FM, fulfilling the American College of Rheumatology 1990 criteria. The frequency of tender points, associated symptoms called historical variables and individuals with low education increased statistically significantly with increasing pain status. In 1995, 48 women had non-chronic pain (23%), 46 (21%) chronic regional pain, 39 (18%) chronic multifocal pain and 81 (38%) CWP; of these, 71 (33%) had FM. Eleven of the 39 women initially with FM no longer fulfilled the criteria. The risk of developing CWP among the 157 individuals with initially a lower pain status was statistically higher in women with chronic multifocal pain than in women with less pain extension. Self-reported pain constitutes a continuum of pain severity and thus of clinical and social significance. The overall outcome was poor with an increase of individuals with CWP and FM. The prognosis of chronic multifocal pain, CWP and FM was especially poor. About half of the women with non-chronic pain or chronic regional pain did not deteriorate. However, because the process of developing FM started with localised pain in most cases, self-reported pain of any severity confers a risk for developing FM. Identifying possible risk factors for FM are at present under study and will be presented separately in another report. Received: 27 April 1998 / Accepted: 10 August 1998     

ACTH,cortisol and prolactin in active rheumatoid arthritis

Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1β and TNF-α circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1β and TNF-α levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1β and TNF-α reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients. Received: 26 February 2001 / Accepted: 28 January 2002     

Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients

The serotonin transporter (5-HTT) gene is considered to be a promising candidate for genetic involvement in some mood disorders owing to its role in the regulation of serotoninergic neurotransmission. In this study, we aimed to assess the significance of the 5-HTT gene in fibromyalgia syndrome (FS) as well as to find out whether the 5-HTT gene polymorphism is associated with this disease. Fifty-three mentally healthy fibromyalgia patients and 60 unrelated healthy volunteer controls were included in the study. Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), and State and Trait Anxiety Inventory tests (STAI-I and II) were applied to both patients and controls. A PCR analysis of 5-HTT gene polymorphism was performed, and the results of the patients with FS and healthy controls were compared. In both FS patients and healthy controls the S/S, S/L and L/L alleles of the 5-HTTLPR genotype were represented in 24.5 % and 33%, 56.6% and 38.3%, and 18.9% and 28.3%, respectively. Additionally, in FS patients and healthy controls the 10/10, 10/12 and 12/12 alleles of the VNTR variant were represented in 5.9% and 11.7, 51% and 36.7%, and 43.1% and 51.7%, respectively. The 5-HTTLPR and VNTR results of the patients and controls were not significantly different (P>0.05). We concluded that neither 5-HTT nor its polymorphism is associated with FS. Our results also address the frequencies of 5-HTT gene alleles in our population. Further studies are required to better understand the genetic basis of FS. Received: 2 July 2001 / Accepted: 3 October 2001     

Suppressed Levels of Serum Cortisol Following High-Dose Oral Dexamethasone Administration Differ between Healthy Postmenopausal Females and Patients with Established Primary Vertebral Osteoporosis

Hypercortisolism and glucocorticoid treatment, even in a low dose or administered topically, may influence bone metabolism. It was the aim of this study to investigate whether there might be differences in the regulation of endogenous cortisol secretion between patients with established primary vertebral osteoporosis and healthy controls. Suppressed morning serum cortisol concentrations in a 3 mg dexamethasone overnight suppression test were compared in well-defined healthy postmenopausal women (n = 149) and osteoporotic patients classified as having established primary vertebral osteoporosis with no clinical features of hypercortisolism (n = 78). Suppressed cortisol in the healthy controls was 1.08 +/- 0.44 microg/dl and in the primary osteoporotics 1.58 +/- 1.42 microg/dl (p < 0.0001). Of the investigated primary osteoporotics 15.4% (n = 12) had suppressed cortisol levels above the 97.5th percentile (1.96 microg/dl) of the healthy controls. Subgroup analysis regarding the influence of gonadal steroid hormone replacement in both groups and gender in the osteoporotic group did not change the results. Four of the 12 patients with incomplete suppressive cortisol underwent adrenal endosonography, unilateral adrenal nodular hyperplasia being detected in three cases. In two patients the diagnosis was confirmed by histology and normalisation of a dexamethasone suppression test following endoscopic adrenalectomy. These data yield evidence for a difference in the regulation of cortisol secretion following high-dose dexamethasone administration between healthy subjects and a subgroup of patients with primary osteoporosis. This might be due to a relevant amount of autonomous cortisol secretion in some of these patients; however, even cortisol resistance has to be taken into account.     

The Characteristics of Bronchoalveolar Lavage from a Patient with Antiphospholipid Syndrome who Developed Acute Respiratory Distress Syndrome

The purpose of this study was to investigate the biochemical characteristics as well as the occurrence and specificity of antiphospholipid antibodies in the bronchoalveolar lavage (BAL) fluid from a patient with both antiphospholipid antibodies syndrome (APS) and acute respiratory distress syndrome (ARDS). Proteins, lipids, cells and autoantibodies were determined. Immunoglobulins were purified with affinity chromatography. Autoantibody identification was assessed with enzyme-linked immunosorbent assay (ELISA) and with electrophoresis, followed by immunoblotting and revelation with antihuman IgG–peroxidase conjugate. Antiphospholipid antibodies were found to be present in the BAL fluid as well as in the serum from a patient with APS. Specifically, antiphosphatidylserine and antiphosphatidic acid IgG antibodies in the BAL fluid and antiphosphatidylcholine and anticardiolipin IgG antibodies in the serum were detected at high levels. BAL fluid protein and the percentage of neutrophils were found to be increased. A quantitative as well as qualitative deficiency of surfactant phospholipids was also observed. Antibodies directed against surfactant phospholipids could cause surfactant abnormalities and an inflammatory reaction. These disorders may be one of the causes of the ARDS or a factor in the perpetuation of the inflammation. Received: 16 February 2000 / Accepted: 6 September 2000     

Hormonal Profiles and Immunological Studies of Male Lupus in Taiwan

The aims of this study were to describe hormonal profiles, cytokine production and Fc-gamma receptor (FcγR) distribution in male lupus patients in Taiwan, and to look for any differences between our patients and normal individuals. Sixteen newly diagnosed and untreated male lupus patients were studied. Hormonal profiles were determined by radioimmunoassay. Interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) production from both monocytes and neutrophils was determined by ELISA and murine thymocyte profileration assay. The FcγR distribution on both monocytes and neutrophils was detected by flow cytometer. There were no significant differences in FSH, LH, testosterone, oestradiol, and β-HCG blood levels in male lupus patients compared with normal individuals; however, the prolactin level in lupus patients was significantly higher than in normal individuals. Furthermore, there was no difference in IL-1 and IL-1ra production from both monocytes and neutrophils among male and female lupus patients, and normal individuals. Male lupus patients have a significantly lower FcγRII distribution on both monocytes and neutrophils when compared with female lupus patients and normal individuals. It was concluded that the high prolactin level and low FcγR distribution may play a role in the pathogenesis and prognosis of male lupus. Received: 3 July 1998 / Accepted: 23 November 1998     

Acquired C1 Inhibitor Deficiency Associated with Systemic Lupus Erythematosus, Secondary Antiphospholipid Syndrome and IgM Monoclonal Paraproteinaemia

In this case report, a woman is described who developed systemic lupus erythematosus at the age of 36 years affecting the central nervous system and kidneys, showing the serological evidence of an acquired C1 inhibitor deficiency, but also developing an antiphospholipid syndrome and IgM lambda type paraproteinemia. During the 25 years follow-up she did not show any signs of angioedema. Although the immunological abnormalities are still constantly present, the disease has been quiescent since the past three years. The possible pathophysiology of clinical and laboratory features are discussed. Received: 5 January 1998 / Accepted: 9 June 1998     

Modulation of Glucose and Growth Hormone Responses to Meals and Exercise in Type 1 Diabetes by Cholinergic Muscarinic Blockade

Anticholinergic drugs suppress nocturnal and exercise-related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two-thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (δ peak/_{90 min}) was 2.6 ± 0.5 (mean ±SEM mmol l^?1 (pirenzepine) vs 4.5 ± 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (δ gluc_{90–240 min}) was 6.4 ± 1.9 (pirenzepine) vs 2.0 ± 1.3 (placebo), p < 0.005. The exercise-related peak rise in GH was 12.6 ± 3.3 (pirenzepine) vs 28.5 ± 6.0 mU l^?1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise-related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = ?0.75, p = 0.008). In conclusion suppression of exercise-related GH secretion by pirenzepine is associated with a subsequent lowering of plasma glucose levels. The smaller post-prandial glucose rise pre-exercise implies also a direct effect of pirenzepine on meal-related glucose tolerance in Type 1 diabetes.     

Clinical Manifestation of POEMS Syndrome with Features of Connective Tissue Disease

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare plasma cell disease with multiorgan involvement and varying clinical manifestations. We report a 38-year-old man who presented with scleroderma-like skin changes of the hands and feet, sicca and Raynaud’s syndrome, pleural effusions, glomerulopathy, polyneuropathy, hepatosplenomegaly and lymphadenopathy. Steroid treatment was started on the assumption of a connective tissue disease and led to a temporary improvement. During the further course of the disease, hypothyreosis, monoclonal gammopathy and osteosclerotic bone lesions were detected, leading to the diagnosis of POEMS syndrome. This case emphasises the need to consider POEMS syndrome as a differential diagnosis in patients with signs of connective tissue disease and polyneuropathy. Received: 21 February 2000 / Accepted: 6 September 2000     

Rheumatoid Syndrome Associated with Lung Interstitial Disorder in a Dental Technician Exposed to Ceramic Silica Dust. A Case Report and Critical Literature Review

Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler–Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler–Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk. Received: 6 March 2001 / Accepted: 6 August 2001     

Prophylactic Antibiotics in Recurrent Parotitis in a Patient with Sjogren’s Syndrome

We describe a 41-year-old patient with primary Sjogren’s syndrome with a 16-year history of recurrent parotitis. The institution of prophylactic antibiotic coverage has succeeded, to date, in maintaining her in remission for 4 years. Received: 16 December 1997 / Accepted: 23 September 1998     

The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up

The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sj?gren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.