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Posted to Co-Cure Thu, 18 Jan 2001 22:59:46 -0500 by Fred Springfield

Tender Point Injections Are Beneficial in Fibromyalgia Syndrome...

Full Title: Tender Point Injections Are Beneficial in Fibromyalgia Syndrome: A Descriptive, Open Study
Journal: Journal of Musculoskeletal Pain, Vol. 8(4) 2000, pp. 7-18
Authors: Savitha S. Reddy, MD; Muhammad B. Yunus, MD; Fatma Inanici, MD; Jean C. Aldag, PhD
Dr. Reddy, Yunus and Aldag: University of Illinois College of Medicine at Peoria [UICOM-P], Peoria, Illinois, USA
Dr. Inanici: Department of Physical Medicine and Rehabilitation, Hacettepe University Medical School, Ankara, Turkey
Address correspondence to: Dr. Muhammad B. Yunus, Department of Medicine,UICOM-P, One Illini Drive, P.O. Box 1649, Peoria, IL 61656-1649 [E-mail: ]
Submitted: July 8, 1999.
Revision accepted: October 9, 1999

Objective: Efficacy of tender point [TeP] injections in fibromyalgia syndrome [FMS] has not been well described in the literature. The goal of our study was to determine the extent of benefit from such injections in this syndrome in the usual clinical practice setting.

Methods: Tender points at most symptomatic sites of forty-one patients with FMS, 40 females and one male, were injected with a mixture of 1/2 ml 1% lidocaine and 1/4 ml intralesional triamcinolone diacetate suspension, and prospectively followed for a mean period of 66 [range 14-240] weeks. All patients were asked to maintain a diary to record the duration of pain relief from injections. They continued their usual therapies.

Results: On an average, 3.97 injections per visit were performed. Mean duration of pain relief per injection site was 13.1 ± 9.4 weeks, excluding a single outlier patient. Only one patient failed to obtain any relief at any injected site. There were no side-effects with the exception of a brief post-injection flare in one patient. No demographic or clinical variables at initial consultation were associated with duration of pain relief, with the exception of anxiety and depression scores, which were negatively correlated [P < 0.001].

Conclusion: Our prospective but open study demonstrates that TeP injections are a useful and safe adjunct to other forms of therapy in FMS. However, further studies in the future are indicated.

KEYWORDS. Fibromyalgia syndrome, tender point injections


Fibromyalgia syndrome [FMS] is a form of nonarticular rheumatism characterized by chronic pain at widespread location accompanied by tenderpoints [TePs] at multiple sites, fatigue, and poor sleep (1,2). Pathophysiology of FMS is most likely based on neurochemical aberrations (3). Managementof FMS involves a multidisciplinary approach (4,5). Management includes nonpharmacologic therapy, e.g., education, psychological support, and physical therapy, as well as various medications, including simple analgesics, e.g.,acetaminophen and nonsteroidal anti-inflammatory drugs [NSAIDs], and serotonergic/noradrenergic agents, such as amitriptyline and fluoxetine (4). However, treatment is generally unsatisfactory, and it has been suggested that TeP injections are useful in FMS (4-6).

Although several papers have described the efficacy of trigger point [TrP] injections in myofascial pain syndrome [MPS] (7-15), data in FMS are limited. Only one study included a combined group of MPS and FMS in determining the effects of TrP injections (12) with 0.5% Xylocaine. However, only nine patients with FMS [who also had MPS by authors’ definition] were investigated. In this study, TrP injections were carried out only in one site, i.e., the trapezius muscle, which were followed by spray and stretch of this muscle, thus possibly confounding the effect of TrP injection alone. Moreover, outcome measures, including pain intensity, pain threshold, and range of motion were evaluated immediately after injection and only two weeks later. We, therefore, undertook a preliminary prospective, open study to investigate the efficacy of TeP injections in FMS in the usual clinical practice setting with a fairly large sample size and a relatively long period of follow-up.

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© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Wed, 17 Jan 2001 01:18:53 -0500 by Fred Springfield

Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with CFS

Full Title: Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with Chronic Fatigue Syndrome
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(3) 2000, pp. 65-75
Authors: Mary Ann Fletcher, PhD; Kevin Maher, PhD; Roberto Patarca-Montero, MD, PhD; Nancy Klimas, MD
Affiliation: Department of Medicine, University of Miami School of Medicine and the Miami VA Medical Center.
Address correspondence to: Mary Ann Fletcher, E.M. Papper Laboratory of Clinical Immunology - R-42, R.M.S.B. Room 8168, 1600 NW 10th Avenue, Miami, FL 33136 (E-mail:

This work was supported, in part, by a grant from the CFIDS Association of America, by NIH Center Grant 1UDI-Al 45940-02, and by funds from Neoprobe Corporation and Ciratech Corporation.

Blood and lymph node samples were obtained from patients with chronic fatigue syndrome (CFS) who had volunteered to undergo a lymph node biopsy while participating in a phase 1 clinical trial of a novel immunomodulatory therapy. The surface marker phenotypes of the peripheral blood and lymph node samples were examined using four-color flow cytometry and compared to published proportions of cells in peripheral blood and lymph nodes from control individuals. While a greater proportion of T lymphocytes from both lymph nodes and peripheral blood of control subjects are immunologically “naive” (CD45RA+), the proportions of lymphocytes with a “memory” phenotype predominate in lymph nodes and peripheral blood of CFS patients. CFS has been proposed to be a disease of autoimmune etiology and in this respect it is interesting to note that decreased proportions of CD45RA+ T (“naive”) cells are also seen in the peripheral blood of patients with autoimmune diseases.

KEYWORDS. Lymph node, naive T cells, memory T cells, chronic fatigue syndrome, four-color flow cytometry

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue that is not attributable to known clinical conditions, that has lasted for > 6 months, that has reduced the activity level of a previously healthy person by > 50%, and that has been accompanied by flu-like symptoms (e.g., pharyngitis, adenopathy, low-grade fever, myalgia, arthralgia, headache) and neuropsychological manifestations (e.g., difficulty concentrating, exercise intolerance, and sleep disturbances) (1-6). CFS is frequently of sudden onset. Possible precipitating events include infections, psychiatric trauma, and exposure to toxins (7-9). However, studies from our laboratory and many others, suggest a central role of chronic immune dysfunction and immune activation in the pathogenesis of CFS. Dysregulation of soluble mediators expressed by cells of the immune system has been demonstrated, and the impact of these mediators on non-immune tissues postulated (10-13). The role of reactivated or inciting viruses in onset or perpetuation of these immunologic aspects of CFS remains unknown.

We have published evidence in CFS patients of a significant expansion of activated T lymphocytes bearing surface markers HLA-DR, CD26 and CD38 (10,11). As is usually the case in studies of the human condition, the view of lymphocyte surface marker phenotype afforded to immunologists studying CFS is that provided by examination of peripheral blood samples. All previous studies of lymphocyte phenotypes in patients with CFS have been restricted to samples obtained from the peripheral blood. Recently, we had the opportunity to examine simultaneously collected samples of blood and lymph node from 11 patients with clinically diagnosed CFS. Results obtained from multi-color flow cytometric analysis are reported herein and compared to those obtained in similar studies in control individuals.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address:   Website: ]

© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Mon, 15 Jan 2001 23:53:20 -0500 by Fred Springfield

Severe and Very Severe Patients with Chronic Fatigue Syndrome:...

Full Title: Severe and Very Severe Patients with Chronic Fatigue Syndrome: Perceived Outcome Following an Inpatient Programme
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(3) 2000, pp. 33-47
Authors: Diane L. Cox, PhD, MSc, Dip COT; Leslie J. Findley, OLJ, TD, MD, FRCP, FACP
Affiliations: Diane L. Cox, Senior Lecturer in Occupational Therapy, Faculty of Health, South Bank University, Southwark, London SEI 0AA, UK. Dr. Cox was Head Occupational Therapist and Coordinator of the CFS Team at Essex Centre for Neurological Sciences.
Current address of Diane L. Cox: Department of Occupational Therapy Education, St. Martin’s College, Lancaster, LA1 3JD, UK.
Leslie J. Findley is Consultant Neurologist, CFS Diagnostic & Management Service, Essex Centre for Neurological Sciences, Oldchurch Hospital, Romford, Essex, RM7 0BE, UK.
The Chronic Fatigue Syndrome (CFS) Service within the Essex Neuroscience’s Centre has been developing since 1990. The service was established as a comprehensive diagnostic and management service in July 1994. From May 1990 to March 1998, 318 patients with CFS were admitted into the programme and since November 1994, 1189 patients seen as outpatients. A previous survey indicated a positive perceived change in level of ability following the inpatient programme for all levels of CFS from mild to very severe. Of those admitted since 1990, 14% (43/318) were severely affected (extremely restricted mobility) and 9% (29/3 18) very severely affected (totally bedbound).

Most studies on CFS do not include the more severe expressions of the disease; therefore, this descriptive paper aims to show the perceived outcome of these more severely affected patients following the inpatient programme. In particular, the eventual diagnosis, the specific approach to treatment and management and grading of patients will be described and the potential influence of the programme presented. The patients not diagnosed with CFS on discharge appeared to do least well at follow up.

KEYWORDS. Severe Chronic Fatigue Syndrome, very severe CFS, inpatient, management, occupational therapy


A conceptual framework to enable an integrated and comprehensive approach to the study of CFS has been defined (1). Historically, many chronic illnesses have been difficult to define, specific causative agents are often unknown and diagnostic laboratory tests often have poor sensitivity and specificity (2,3).

The Fukuda et al. (1) definition has become the most accepted. The case definition requires considerable morbidity from new fatigue in excess of six months with all other recognised causes of fatigue having been excluded by history, observation and clinical assessment. It suggests three sub divisions: Chronic Fatigue Syndrome, Post Viral Fatigue Syndrome and Idiopathic Chronic Fatigue. To fulfill the definition the person must have a new onset of self-reported persistent or relapsing, debilitating fatigue with no previous history of similar symptoms, that has lasted for 6 months or longer, is disabling and affects physical and mental functioning and is:

a. characterised by fatigue as the principal symptom, b. new or definite onset (has not been lifelong), c. not the result of ongoing exertion, d. not substantially alleviated by rest, and e. results in substantial reduction in previous levels of occupation, educational, social or personal activities.

In addition, all other clinical conditions that may produce similar symptoms, including pre-existing psychiatric diseases, must be excluded by thorough evaluation, based on history, physical examination, and appropriate laboratory findings (1).

However, although the definition states that, “. . . CFS is characterised by severe disabling fatigue . . .,“ and identifies the subgroups discussed previously, it does not discuss the range of disability and reduced functioning seen within the syndrome (1). In addition, most studies on CFS do not include the more severe presentation of the disease (4-8). In addition, health agencies often do not appear to appreciate the differing level of dysfunction seen within the illness and the consequent impact on daily life (9). This descriptive paper therefore aims to illustrate the perceived outcome of these more severely affected patients following the inpatient programme.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address:   Website: ]

© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Sun, 14 Jan 2001 13:46:18 -0500 by Fred Springfield

Defining Chronic Fatigue Syndrome: Methodological Challenges

Full Title: Defining Chronic Fatigue Syndrome: Methodological Challenges
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(3) 2000, pp. 17-32
Authors: Leonard A. Jason, PhD; Caroline P. King, MA; Renee R. Taylor, PhD; Cara Kennedy, BA
Affiliation: DePaul University.
Address correspondence to: Leonard A. Jason, PhD, Department of Psychology, DePaul University, 2219 North Kenmore Avenue, Chicago, IL 60614 (E-mail: ).
Financial support for this study was provided by NIAID Grant Number A136295.

Accurate diagnosis of Chronic Fatigue Syndrome (CFS) is greatly complicated by the vague wording of many of the major diagnostic criteria (i.e., substantial reductions in previous levels of occupational, educational, social, or personal activities) and the absence of guidelines for health care professionals to follow.

The lack of operationally explicit criteria has forced health care professionals to rely heavily on their own clinical judgement, which may be biased by personal and highly idiosyncratic factors. Thus, in the case of CFS, the lack of consensus among clinicians regarding the interpretation and application of the diagnostic criteria has likely produced problems in diagnostic reliability.

Data from a recent community based epidemiologic study are presented to illustrate these problems and provide recommendations for improving criterion reliability.

KEYWORDS. Chronic Fatigue Syndrome, case definition, diagnosis

Chronic Fatigue Syndrome (CFS) is an illness that results in severe, prolonged fatigue as well as neuropsychiatric, rheumatological, and infectious symptoms (1). Despite several years of research, CFS remains a poorly understood and controversial disease (2). Historically, many chronic illnesses have been difficult to define, particularly when the exact causal agents of the illness are not known, physical signs and symptoms are nonspecific or variable, and diagnostic laboratory tests are not applicable, unavailable, or have poor specificity and sensitivity (3).

Some argue that syndromes such as CFS, Fibromyalgia and Irritable Bowel Syndrome may be better understood in terms of a unitary model of functional somatic distress, rather than as separate diagnostic entities (4). A recent study by Taylor, Jason and Schoeny (5) evaluated the diagnostic validity of conditions that have been labeled functional somatic syndromes. Latent variable models of functional somatic distress were estimated from the responses of 213 community members to a medical questionnaire. Results of confirmatory factor analysis supported diagnostic distinctions between five syndromes (fibromyalgia, chronic fatigue syndrome, somatic depression, somatic anxiety, and irritable bowel syndrome). The diagnostic validity of the latent constructs of FMS and CFS emerging from this five-factor model were cross-validated using findings from an independent physician evaluation.

The primary goal of classifying any disease or illness is to group together patients who have an illness that may have many manifestations, but a common underlying pathophysiological pathway (6). Historically, classification of such patients has facilitated research on the etiology and treatment of illnesses and diseases before the underlying pathophysiological pathway was identified by simply classifying these illnesses as syndromes of signs and symptoms (e.g., systemic lupus erythematosus or tuberculosis). It has been suggested that a similar classification process may help facilitate research in the field of CFS (6). At present, a variety of classification methods have been used to classify fatigue. Researchers from the Centers for Disease Control, such as Fukuda and associates (7), have used clinical approaches to the classification of fatigue whereas researchers such as Haley, Kurt, and Horn (8) and Hall, Sanders, and Repologle (9) have used statistical approaches. Methods to confirm the current U.S. CFS case definition have also been established by Komaroff, Fagioli, Geiger et al. (10) and Nisenbaum, Reyes, Mawle, and Reeves (11).

In the absence of laboratory tests or other objective indicators, case identification of CFS depends primarily on information obtained through clinical interviews (12). The reliability of the clinical interview with patients with CFS is therefore crucial. However, one factor that has continued to complicate progress toward understanding CFS is the lack of consensus among health care professionals regarding the interpretation and application of the diagnostic criteria for CFS (13).

Studies examining sources of diagnostic unreliability have shown that subject, occasion, and information variance account for only a small portion of diagnostic reliability (14). However, criterion variance, differences in the formal inclusion and exclusion criteria used by clinicians to classify patients’ data into diagnostic categories, accounts for the largest source of diagnostic unreliability. Therefore, improvement in diagnostic reliability is primarily dependent on reducing criterion variance as a source of unreliability. Criterion variance is most likely to occur when operationally explicit criteria do not exist for diagnostic categories (15).

The current U.S. case definition for CFS (7) is characterized by vaguely worded criteria that lack operational definitions and guidelines to assist health care professionals in their interpretation and application of the diagnostic criteria (13). In addition, because of the lack of objective clinical or laboratory diagnostic markers, the current case definition for CFS is dependent upon subjective factors and patient self-report (7). For example, symptoms of sore throat or lymph node pain can only be infrequently confirmed by a physician, and the other symptomatic criteria are even more difficult to confirm because of their ambiguous nature (e.g., difficulty concentrating) (3). Together, this combination of poorly defined diagnostic criteria and lack of objective clinical diagnostic markers has made the assessment and diagnosis of CFS a complex and difficult process. As a result, health care professionals have been forced to rely on their own clinical judgement, which may be biased by personal and highly idiosyncratic factors. Efforts to develop objective clinical means of distinguishing patients with CFS from those with other illnesses are therefore greatly needed. More specifically, precise criteria for identifying key symptoms of CFS are essential to reduce criterion variance and obtain adequate diagnostic reliability.

An important criterion for the current case definition of CFS (7) involves the need to have a substantial reduction in critical areas of functioning. Therefore, there is a need to assess reductions in activity levels in the realms of social, occupational, and familial functioning. One instrument that provides standardized scales for assessing physical functioning, physical-role functioning, emotional-role functioning, and social functioning is the SF-36 Health Survey (16). The SF-36 Health Survey is a standardized questionnaire comprised of eight multi-item scales measuring eight different aspects of health. Use of these functioning scales with cutoff scores would likely improve clinicians’ ability to accurately identify individuals with limited capacities for functioning and assess reductions in social, occupational, and familial functioning. Research (17) has demonstrated the SF-36 to be a useful and reliable instrument for assessing functional status in patients with CFS and for distinguishing patients with CFS from patients with other fatiguing conditions on the basis of functional status. In Buchwald et al.‘s (17) study, individuals with CFS had mean scores of 40 or less for the following scales: physical functioning, general health, vitality, body pain, physical-role function, and social function. One study (18) found that patients with CFS had mean scores below 40 on the following scales: physical role-function, vitality and general health. A treatment study (19) used the physical functioning scale, and patients with CFS mean baseline scores were below 40.

The current CFS case definition also requires the occurrence of four or more minor symptoms (7). A number of problems with the definitions of the minor criteria (i.e., difficulties with memory and concentration; sore throat; lymph node pain; muscle pain; joint pain; headache; unrefreshing sleep; and post-exertional malaise) have resulted from the lack of operational definitions and the absence of guidelines for clinicians to follow when assessing patients presenting with chronic fatigue. Unfortunately, many of the minor symptoms for CFS are subjective in nature and the assessment of subjective symptoms is inherently problematic as these symptoms often cannot be directly observed or objectively measured. A critical issue concerning the assessment of the minor symptom criteria is the use of binary classification (i.e., occurrence versus nonoccurrence). Many patients with CFS have symptoms for extended periods of time, but because of imprecise wording of the binary symptoms, some individuals with CFS are not scored as having a symptom when they actually have it.

Three of the most commonly used methods to assess symptoms are the visual analog scale (VAS), the verbal rating scale (VRS), and the numerical rating scale (NRS) (20). The primary advantages of using numeric rating scales (NRS) are the following: they are easy to administer and score, they have demonstrated good evidence of construct validity, compliance with the measurement task is high, and the data can be treated as ratio data (20). CFS symptoms could easily be rated on 100 point rating scales rather than binary scales involving occurrence vs. non-occurrence.

Another problem with the minor symptom criteria in terms of diagnostic reliability is the specification that the four or more minor symptoms must not predate the fatigue (7). Clarification is needed as to what exactly “predating” the fatigue means. If a patient had only four minor symptoms and one of the symptoms (e.g., sore throat) began three months before the overwhelming fatigue, the definition suggests that this individual would be excluded from the diagnosis of CFS. Some individuals who develop CFS experience a prodromal phase, in which symptoms begin to appear in the year prior to the onset of fatigue. It is therefore unclear why such symptoms would not be counted as minor symptoms. As a result, some clinicians might allow symptoms from the prodromal phase to count toward fulfilling the diagnostic criteria while others might not. This lack of precision in the definition is likely to lead to problems in interrater reliability, as well as the misdiagnosis of patients who do and do not have CFS.

Given the absence of specific thresholds and scoring rules for the symptomatic criteria of the current U.S. CFS case definition, the probability of criterion variance is greatly increased. More importantly, the absence of specific thresholds and scoring rules has likely compromised the diagnostic reliability of the current U.S. CFS case definition. The present study uses data from a CFS epidemiologic study to consider parameters of scoring rules that might be developed for different criteria specified by the U.S. case definition.

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© 2000 by The Haworth Press, Inc. All rights reserved.

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