"Chronic Lyme disease" as the incorrect diagnosis in patients with fibromyalgia

OBJECTIVE: To evaluate a large number of patients referred with persistent symptoms thought to represent chronic Lyme disease. METHODS: We retrospectively reviewed the charts of nearly 800 patients referred with persisting nonspecific musculoskeletal and/or neurologic symptoms thought to represent chronic Lyme disease. RESULTS: Seventy-seven patients were found to have fibromyalgia, not ongoing Lyme disease, as the explanation of their chronic symptoms. Many had received multiple courses of antibiotic therapy for symptoms of fibromyalgia mistakenly attributed to chronic Lyme disease. No patient reported permanent and/or total resolution of fibromyalgia symptoms following antibiotic therapy. Appropriate therapy for fibromyalgia in those who remained compliant, however, was often effective in improving some if not all of the chronic symptoms. CONCLUSION: Fibromyalgia is a treatable and potentially curable disorder, and should be considered in the evaluation of patients with "refractory Lyme disease."     

Fibromyalgia. A critical review

Fibromyalgia is a chronic pain syndrome, more common in women. Its prevalence is estimated around 2% in the general population, and up to 20% among rheumatology outpatients. Besides musculoskeletal pain, symptoms as fatigue and sleep disturbance are considered characteristic. Research criteria have been set up, but their seemingly preciseness is unable to distinguish clearly between fibromyalgia and other functional somatic syndromes (chronic fatigue syndrome, irritable bowel syndrome) and psychiatric disorders (depression, anxiety), with which a striking comorbidity is documented. The diagnosis of fibromyalgia does not theoretically require the exclusion of muscle, joint, or metabolic diseases, but in clinical practice this problem proves to be of crucial importance. There are numbers of pathophysiological hypothesis for fibromyalgia, but none of them is fully satisfying: muscle is probably innocent; sleep disturbance, although sometimes considered a landmark of the syndrome, is unspecific; stress response studies show subtle anomaly; psychiatric disorders may represent factors of vulnerability and perpetuation rather than causes. We propose to include some of these etiological contributors in vicious circles leading to a "final common pathway" characterized by generalized hyperalgesia. Treatments of fibromyalgia, whether pharmacological (antidepressants) or psychological (cognitive-behavioral therapies) are of little efficacy, and the global prognosis of fibromyalgia is poor. However, the outcome might prove better outside the specialized clinics in which studies of chronic sufferers with severe abnormal illness behaviors are done. The social consequences of the popularization of the diagnosis of fibromyalgia should not be neglected.     

Laboratory diagnosis of Lyme borreliosis

Three stages can be observed in Lyme borreliosis: the acute stage (with dermal and systemic disease), an intermediate stage (with neurological and cardiovascular complaints and myositis), and a chronic stage (with arthritis, low back pain, dermatological and neurological complaints). If no acute stage with erythema chronicum migrans is seen, laboratory tests must provide the diagnosis. In the so-called two-test protocol at least two different tests must be positive for a definite diagnosis. Because culture is difficult, serology (demonstration of specific IgM and IgG antibodies against spirochaetal antigens) is the preferred technique. Cross reactions, antigenic variations and differences in antigenic expression in American and European strains may cause false-negative and false-positive results with the current tests. Moreover, previous use of antibiotics can interfere with the production of specific antibodies, and the effect of therapy is not correlated with height and behaviour of antibody titres. Additional investigation with immunoblot techniques, demonstrating specific antibody patterns may be valuable. An interesting alternative, not yet fully developed, is detection of specific antigens in tissues.     

Becoming familiar with fibromyalgia

Although the term "fibromyalgia" has appeared in the literature for 90 years, the disease may go unrecognized by clinicians. It is a devastating disease, more common than rheumatoid arthritis, yet its cause remains a mystery. There is no cure for fibromyalgia; however, nurses may be able to help improve the quality of life for the patients who live with this disease. This article explores theories of causation, treatment modalities, and the potential role of nurses in their work with these patients.     

Case management study: polyarthritis with fever

In most cases, a thorough initial evaluation will reveal the cause of fever and polyarthritis. However, in some patients the initial diagnosis may be unclear and, as time passes, the characteristic clinical patterns emerge. Recurrent attacks are suggestive of other conditions such as crystal-induced arthritis, Lyme disease, and Mediterranean fever. In rheumatoid arthritis and Reiter's syndrome, the fever resolves and the articular findings predominate with the passage of time. Similarly, Still's disease is initially diagnosed on the basis of clinical criteria, and later confirmed by the evolution of chronic polyarthritis. Diagnostic approaches for the evaluation of patients presenting with acute arthritis have been published and are readily available (2,8,9). The most reliable way to establish the diagnosis for a rheumatic disease is thoughtful and thorough evaluation by an experienced clinician (3,10). Certain discriminating features and confirmatory tests can aid in the diagnosis of polyarthritis with fever (Tables 2 and 3).     

Dyspnea resulting from fibromyalgia

Two patients with chronic, severe, episodic dyspnea underwent prolonged, extensive, and invasive evaluations without a diagnosis being made. Both were subsequently diagnosed with fibromyalgia, and therapy directed at this condition resulted in resolution of their symptoms. Fibromyalgia is rarely included in the differential diagnosis of dyspnea, and timely diagnosis and treatment may be delayed. However, this condition must be considered because it can only be established by seeking the appropriate history and physical findings.     

Attenuation of S-T segment elevation during repetitive coronary occlusions truly reflects the protection of ischemic preconditioning and is not an epiphenomenon

The study, which was part of a cardiovascular screening programme of 40-42 year old women organised by the National Health Screening Service, wanted to assess the prevalence of locomotor complaints in Middle-Norway. Forty-nine percent of the respondents reported the occurrence of musculoskeletal disorders. Low back pain and myalgia was the most and chronic inflammatory joint diseases the least frequent. Between healthy women and some groups of women reporting musculoskeletal disorders, significant differences in sociodemographic background, workload, working ability, and health care utilisation emerged. Among lifestyle factors, smoking was significantly more frequent for women reporting fibromyalgia. Analysing the occurrence of symptoms and diseases in the genital tract revealed that a significantly higher proportion of women reporting musculoskeletal disease answered positively. Differences between healthy women and women reporting pelvic joint syndrome, fibromyalgia, whiplash, or arthritis were significant in bleeding disorders chronic pelvic pain and inflammatory pelvic disease. Patients with rheumatoid arthritis reported oophorectomy significantly more often than healthy women. In conclusion, a high rate of musculoskeletal symptoms and disorders was reported by middle-aged women. A strong association between musculoskeletal disorders and gynecological disease was found.     

Fibromyalgia and the serotonin pathway

Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.     

T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis

Cytokines produced by subsets of CD4+ T helper cells responding to an infection influences the efficiency with which the host is able to mount a protective immune response. In an attempt to elucidate the population of active cells involved in the propagation of Lyme arthritis we have utilized intracellular cytokine staining to analyze the polyclonal immune response at the single cell level. We have determined the Th phenotype in the synovial fluid of patients with a variety of chronic inflammatory arthritides, including patients representative of the spectrum of Lyme arthritis. Th1 cells dominate the immune response in the synovial fluid of patients with Lyme as well as those with rheumatoid or other types of chronic inflammatory arthritis. In addition, the severity of Lyme arthritis directly correlates with the ratio of Th1 to Th2 cells in the synovial fluid, such that the larger the effusion, the higher the ratio (r = 0.67, p < 0.05). These results suggest that Th1 cells play a direct role in the pathogenesis of the inflammatory process seen in Lyme arthritis, and that Th2 cells modulate the pro-inflammatory response generated by Th1 cells in the joint. Finally, we identify Th1 cells specific for outer surface protein A of Borrelia burgdorferi, the agent of Lyme disease. These cells are restricted to patients with Lyme arthritis and are localized to the joint. Furthermore, they persist in patients with prolonged antibiotic treatment-resistant Lyme arthritis, suggesting the possibility of an autoimmune process.     

12-O-tetradecanoylphorbol-13-acetate inhibits aminophospholipid translocase activity and modifies the lateral motions of fluorescent phospholipid analogs in the plasma membrane of bovine aortic endothelial cells

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and fibromyalgia respectively, both disorders share a number of features, including similar demographics, "allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were questioned regarding current symptomatology. A dolorimeter examination was also performed in the three groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder.     

Rheumatic manifestations in Lyme borreliosis: personal experience in patients with oligoarthritis of "unknown" origin

Lyme borreliosis is an infectious illness caused by the spirochete Borrelia burgdorferi and is transmitted by tick vectors. A prospective study was performed from January 1990, to investigate whether Lyme arthritis might have been undetected among patients with (unclassified arthritis) oligoarthritis of "unknown" aetiology. 210 patients were tested for antibodies to Borrelia burgdorferi: 82 patients with oligoarthritis of "unknown" aetiology; 52 patients with Reiter's syndrome; 20 patients with seronegative, B-27 positive oligoarthritis and 56 controls. Serological testing for Borrelia burgdorferi was performed by indirect immunofluorescence assay. The occurrence of positive antibodies (1:80) in 11 (13.4%) patients with arthritis of "unknown" aetiology was significantly different from the combined control group (1.6%) (p < 0.05). Four out of 11 patients remembered a tick bite, two out of 11 patients developed erythema migrans after 3 to 10 days. Six weeks later 2 patients developed oligoarthritis and one patient after a month. In the remaining 8 patients arthritis was the first sign of the disease. Knees were most commonly affected (90%). Radiographic abnormalities (osteoporosis, soft tissue swelling) were noted in 3 patients. The synovial fluid findings were typical for inflammatory arthritides in 6 patients. The diagnosis of Lyme borreliosis was made according to following data: origin from an area endemic for Lyme borreliosis, tick bite, erythema migrans, significant levels of the antibodies to the Borrelia burgdorferi and oligoarthritis. It can be concluded that arthritis may be the main manifestation of Borrelia burgdorferi infection.     

Fullerene lipids: synthesis of dialkyl 1,2-[6,6]-methano-[60]-fullerene dicarboxylate derivatives

OBJECTIVE: To determine the prevalence of chronic arthritis with special reference to rheumatoid arthritis. METHOD: A cross-sectional study was performed during the years 1990 and 1991 in a randomly selected sample of the urban population of Belgrade. RESULTS: Out of 2184 participants, > or = 20 yr old, surveyed by questionnaire, 756 (34.6%) reported peripheral joint complaints. Of those with complaints, 621 (82.1%) agreed to undergo detailed examination. Arthritis was diagnosed in four men (one had rheumatoid arthritis and three had spondylarthropathy with peripheral arthritis) and 11 women (three had rheumatoid arthritis, one had B27-positive polyarthritis and seven had undifferentiated chronic arthritis). The prevalence of chronic arthritis in the adult population was 0.69% (0.35% for men and 1.05% for women). The prevalence for rheumatoid arthritis was 0.18% (0.09% for men and 0.29% for women). Re-examination of 15 individuals with chronic arthritis 3 yr later showed changes in diagnosis only in those patients who at baseline examination had undifferentiated chronic arthritis. CONCLUSION: According to the results obtained, the urban population of Belgrade is among populations with a low prevalence of rheumatoid arthritis.     

Sleep quality in Lyme disease

Complaints of chronic fatigue as well as sleep disturbances are prevalent in Lyme disease. We compared polysomnographic measures of sleep in patients with documented Lyme disease with those of a group of age-matched normal control subjects. Eleven patients meeting Centers for Disease Control criteria for late Lyme disease with serologic confirmation by enzyme-linked immunosorbent assay and Western blot without a history of other medical or psychiatric illness and 10 age-matched control subjects were studied. Lyme disease patients and controls underwent 2 nights of polysomnography. Multiple sleep latency testing (MSLT) was performed in the patients. Sleep was staged by standard criteria, and continuity of sleep was assessed for each stage of frequency analysis of consecutive epochs. All patients studied reported sleep-related complaints, including difficulty initiating sleep (27%), frequent nocturnal awakenings (27%), excessive daytime somnolence (73%) and restless legs/nocturnal leg jerking (9%). Greater sleep latency, decreased sleep efficiency and a greater arousal index were noted in Lyme patients. The median length of uninterrupted occurrences of stage 2 and stage 4 non-rapid eye movement (NREM) sleep was less in Lyme patients (6.3 +/- 3.0 epochs in patients vs. 11.4 +/- 4.4 epochs in controls for stage 2, p < 0.01, and 4.3 +/- 4.4 epochs in patients vs. 11.2 +/- 6.3 epochs in controls for stage 4, p < 0.01), indicating greater sleep fragmentation. Mean sleep onset latency during the MSLT was normal (12.7 +/- 5.6 minutes). Three patients demonstrated alpha-wave intrusion into NREM sleep. These sleep abnormalities may contribute to the fatigue and sleep complaints common in this disease.     

A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia

OBJECTIVE: To study, for the first time, service utilization and costs in fibromyalgia, a prevalent syndrome associated with high levels of pain, functional disability, and emotional distress. METHODS: Five hundred thirty-eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7-year prospective study of fibromyalgia outcome. Patients were assessed every 6 months with validated, mailed questionnaires which included questions regarding fibromyalgia symptoms and severity, utilization of services, and work disability. RESULTS: Fibromyalgia patients averaged almost 10 outpatient medical visits per year, and when nontraditional treatments were considered, this number increased to approximately 1 visit per month. Patients were hospitalized at a rate of 1 hospitalization every 3 years. In each 6-month study period, patients used a mean of 2.7 fibromyalgia-related drugs. Costs increased over the course of the study. The mean yearly per-patient cost in 1996 dollars was $2,274. However, results were skewed by high utilizers, and many patients used few services and had limited costs. Total costs and utilization were independently associated with the number of self-reported comorbid or associated conditions, functional disability, and global disease severity. Compared with patients with other rheumatic disorders, those with fibromyalgia were more likely to have lifetime surgical interventions, including back or neck surgery, appendectomy, carpal tunnel surgery, gynecologic surgery, abdominal surgery, and tonsillectomy, and were more likely than other rheumatic disease patients to report comorbid or associated conditions. Almost 50% of hospitalizations occurring during the study were related to fibromyalgia-associated symptoms. CONCLUSION: The average yearly cost for service utilization among fibromyalgia patients is $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions, and symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.     

Fibromyalgia (generalized tendomyopathy) in expert assessment. Analysis of 158 cases

MEDAS-agencies are medical institutions within the Swiss Disability Insurance, which specialize in assessing the working capacity of candidates who apply for a disability pension. Degenerative and other chronic pain disorders of the musculoskeletal system form the majority of cases that we investigate. Fibromyalgia is one of our most frequent diagnoses (8.6%). We become involved in cases on average 8.5 years after the first onset of painful symptoms and on average 2.5 years after the patients have ceased to work. Our experience, tells us that fibromyalgia is usually associated with psychological disturbances; thus our psychiatrists have found important psychological problems in 86.7% of applicants. They found mainly neurotic and depressive syndromes. Our investigations have shown that psychological disturbances precede the onset of musculoskeletal pain in about 70% of patients. Therefore, we don't consider fibromyalgia syndrome as an entity of its own, but regard it as a pain syndrome in which there are underlying psychological problems in most cases.     

Activation of natural killer cells in arthritis-susceptible but not arthritis-resistant mouse strains following Borrelia burgdorferi infection

Infection of susceptible mouse strains with Borrelia burgdorferi, the agent of Lyme disease, results in the development of arthritis. Components of the innate immune system may be important mediators of this pathology. To investigate the potential role of NK cells in development of experimental Lyme arthritis, we examined their activation in vivo in both resistant and susceptible mouse strains. Following inoculation of B. burgdorferi into the footpad, lymph node NK cells from susceptible C3H/HeJ (C3H) mice produced more gamma interferon than NK cells from resistant DBA/2J mice. Lymph node cells from susceptible C3H and AKR mice also had increased ability to lyse YAC-1 target cells 2 days following infection. Antibody depletion of NK cells from susceptible mice, however, did not alter the development of arthritis following B. burgdorferi challenge. In addition, NK cell depletion had little effect on spirochete burden. Thus, there is a marked activation of NK cells in susceptible mouse strains following infection. Although NK cells are not absolutely required for arthritis, events occurring prior to NK cell activation might be important in mediating pathology in experimental Lyme disease.     

Longitudinal investigation of bacterium-specific synovial lymphocyte proliferation in reactive arthritis and lyme arthritis

BACKGROUND: Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients. METHODS: In this study, the synovial lymphocyte proliferation to Yersinia, Chlamydia, Shigella and Borrelia burgdorferi was investigated sequentially at different time points in 28 patients with reactive arthritis, undifferentiated oligoarthritis or Lyme arthritis responding to one of these bacteria. RESULTS: The same bacterium was always recognized in arthritis triggered by Chlamydia, Shigella or Borrelia, with much variation in the proliferative response. Only the Yersinia-specific responses changed specificity, suggesting that the proliferative response to Yersinia is non-specific in some patients. CONCLUSIONS: Our data support the concept of a local antigen-specific T-cell response in reactive arthritis or Lyme arthritis but not the concept suggested by others that a switch to an autoimmune response takes place in long-standing disease.