Category: Overlapping Illnesses

Cytokine dysregulation in the post-Q-fever fatigue syndrome

Abstract:

The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgia and arthralgia, night sweats, changes in mood and sleep patterns) follows about 20% of laboratory-proven, acute primary Q-fever cases. Cytokine dysregulation resulting from chronic immune stimulation and modulation by persistence of Coxiella burnetii cells or their antigens is hypothesized.

We studied cytokine release patterns of peripheral blood mononuclear cells (PBMC) stimulated with various ligands in short-term culture, from 18 patients with active QFS, and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequent QFS, eight healthy Q-fever vaccinees and eight healthy subjects without Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN gamma by AgEIA, and for IL-1 and TNF alpha/beta by bioassay.

Aberrant cytokine release patterns were observed with PBMC from QFS patients when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly [p = 0.01, non-parametric one-way analysis of variance (ANOVA)] in excess of medians for all four control groups. With IL-2, the number of responders in the active QFS group was decreased relative to control groups (Fisher’s exact test, p = 0.01) whereas the number of IFN gamma responders was increased (Fisher’s exact test, p = 0.0008). Significant correlations were observed between concentrations of IL-6 in CM, total symptom scores, and scores for other key symptoms.

Comment in: Fatigue syndromes. [QJM. 1999]

 

Source: Penttila IA, Harris RJ, Storm P, Haynes D, Worswick DA, Marmion BP. Cytokine dysregulation in the post-Q-fever fatigue syndrome. QJM. 1998 Aug;91(8):549-60. http://qjmed.oxfordjournals.org/content/91/8/549.long (Full article)

 

The non-specific environmental syndromes MCS (Multiple Chemical Sensitivity), IEI (Idiopathic Environmental Intolerance) and SBS (Sick Building Syndrome)

Abstract:

This review starts with a clinical description of the most common unspecific environmental diseases, such as Multiple Chemical Sensitivities (MCS), Idiopathic Environmental Intolerances (IEI) and Sick Building Syndrome (SBS). These syndromes are very controversial discussed between scientific medicine and “clinical ecology”. In addition, they have fundamental similarities to Chronic Fatigue Syndrome (CFS) and Fibromyalgia. Finally the spectrum of therapeutic approaches is discussed.

 

Source: Csef H. The non-specific environmental syndromes MCS (Multiple Chemical Sensitivity), IEI (Idiopathic Environmental Intolerance) and SBS (Sick Building Syndrome). Fortschr Med. 1998 Nov 30;116(33):18-20, 22, 24. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/9889460

 

Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome

Abstract:

The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) from peripheral blood lymphocytes.

Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)-a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively.

We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls.

In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-gamma, and TNF-alpha than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.

 

Source: Zhang Q, Zhou XD, Denny T, Ottenweller JE, Lange G, LaManca JJ, Lavietes MH, Pollet C, Gause WC, Natelson BH. Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome. Clin Diagn Lab Immunol. 1999 Jan;6(1):6-13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC95652/ (Full article)

 

Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity

Abstract:

The purpose of this study was to determine if Gulf War veterans with complaints of severe fatigue and/or chemical sensitivity (n = 72) fulfill case definitions for chronic fatigue syndrome (CFS) and/or multiple chemical sensitivity (MCS) and to compare the characteristics of those veterans who received a diagnosis of CFS (n = 24) to a group of non-veterans diagnosed with CFS (n = 95).

Thirty-three veterans received a diagnosis of CFS with 14 having MCS concurrently; an additional six had MCS but did not fulfill a case definition for CFS. The group of fatigued veterans receiving a diagnosis of CFS was comprised of significantly fewer women and fewer Caucasians than the civilian group, and significantly fewer veterans reported a sudden onset to their illness.

Veterans with CFS had a milder form of the illness than their civilian counterparts based on medical examiner assessment of the severity of the symptoms, reported days of reduced activity, and ability to work. Since CFS in veterans seems less severe than that seen in civilians, the prognosis for recovery of veterans with this disorder may be better.

 

Source: Pollet C, Natelson BH, Lange G, Tiersky L, DeLuca J, Policastro T, Desai P, Ottenweller JE, Korn L, Fiedler N, Kipen H. Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. J Med. 1998;29(3-4):101-13. http://www.ncbi.nlm.nih.gov/pubmed/9865452

 

Autonomic neuropathies

Abstract:

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

 

Source: Low PA. Autonomic neuropathies. Curr Opin Neurol. 1998 Oct;11(5):531-7. http://www.ncbi.nlm.nih.gov/pubmed/9848003

 

Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome

Abstract:

Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with chronic fatigue syndrome (CFS). All values were within normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.

 

Source: Evengard B, Nilsson CG, Lindh G, Lindquist L, Eneroth P, Fredrikson S, Terenius L, Henriksson KG. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. Pain. 1998 Nov;78(2):153-5. http://www.ncbi.nlm.nih.gov/pubmed/9839828

 

Clinical and serologic follow-up in patients with neuroborreliosis

Abstract:

The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.

Comment in: Neuropsychological deficits in neuroborreliosis. [Neurology. 1999]

 

Source: Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology. 1998 Nov;51(5):1489-91. http://www.ncbi.nlm.nih.gov/pubmed/9818893

 

The relationship between temporomandibular disorders and stress-associated syndromes

Abstract:

OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia.

STUDY DESIGN: Of 92 patients who fulfilled the criteria for chronic fatigue syndrome or fibromyalgia (or both), 39 (42%) reported a prior diagnosis of temporomandibular disorder. Further questionnaires were sent to the members of this group, and 30 patients responded.

RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis. Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms before the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints.

CONCLUSIONS: Patients appearing for treatment with chronic facial pain show a high comorbidity with other stress-associated syndromes. The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals. A multidisciplinary clinical approach to temporomandibular disorders would improve diagnosis and treatment outcomes for this group of patients.

 

Source: Korszun A, Papadopoulos E, Demitrack M, Engleberg C, Crofford L. The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Oct;86(4):416-20. http://www.ncbi.nlm.nih.gov/pubmed/9798224

 

Chronic fatigue syndrome and seasonal affective disorder: comorbidity, diagnostic overlap, and implications for treatment

Abstract:

This study aimed to determine symptom patterns in patients with chronic fatigue syndrome (CFS), in summer and winter. Comparison data for patients with seasonal affective disorder (SAD) were used to evaluate seasonal variation in mood and behavior, atypical neurovegetative symptoms characteristic of SAD, and somatic symptoms characteristic of CFS.

Rating scale questionnaires were mailed to patients previously diagnosed with CFS. Instruments included the Personal Inventory for Depression and SAD (PIDS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE), which catalogs the current severity of a wide range of somatic, behavioral, and affective symptoms. Data sets from 110 CFS patients matched across seasons were entered into the analysis. Symptoms that conform with the Centers for Disease Control and Prevention (CDC) case definition of CFS were rated as moderate to very severe during the winter months by varying proportions of patients (from 43% for lymph node pain or enlargement, to 79% for muscle, joint, or bone pain).

Fatigue was reported by 92%. Prominent affective symptoms included irritability (55%), depressed mood (52%), and anxiety (51%). Retrospective monthly ratings of mood, social activity, energy, sleep duration, amount eaten, and weight change showed a coherent pattern of winter worsening.

Of patients with consistent summer and winter ratings (n = 73), 37% showed high global seasonality scores (GSS) > or = 10. About half this group reported symptoms indicative of major depressive disorder, which was strongly associated with high seasonality.

Hierarchical cluster analysis of wintertime symptoms revealed 2 distinct clinical profiles among CFS patients: (a) those with high seasonality, for whom depressed mood clustered with atypical neurovegetative symptoms of hypersomnia and hyperphagia, as is seen in SAD; and (b) those with low seasonality, who showed a primary clustering of classic CFS symptoms (fatigue, aches, cognitive disturbance), with depressed mood most closely associated with irritability, insomnia, and anxiety.

It appears that a subgroup of patients with CFS shows seasonal variation in symptoms resembling those of SAD, with winter exacerbation. Light therapy may provide patients with CFS an effective treatment alternative or adjunct to antidepressant drugs.

 

Source: Terman M, Levine SM, Terman JS, Doherty S. Chronic fatigue syndrome and seasonal affective disorder: comorbidity, diagnostic overlap, and implications for treatment. Am J Med. 1998 Sep 28;105(3A):115S-124S. http://www.ncbi.nlm.nih.gov/pubmed/9790493

 

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia

Abstract:

This article summarizes (1) epidemiologic and clinical data on the symptoms of maladies in association with low-level chemicals in the environment, i.e., environmental chemical intolerance (CI), as it may relate to chronic fatigue syndrome (CFS) and fibromyalgia; and (2) the olfactory-limbic neural sensitization model for CI, a neurobehavioral synthesis of basic and clinical research. Severe CI is a characteristic of 20-47% of individuals with apparent CFS and/or fibromyalgia, all patients with multiple chemical sensitivity (MCS), and approximately 4-6% of the general population.

In the general population, 15-30% report at least minor problems with CI. The levels of chemicals reported to trigger CI would normally be considered nontoxic or subtoxic. However, host factors–e.g., individual differences in susceptibility to neurohormonal sensitization (amplification) of endogenous responses–may contribute to generating a disabling intensity to the resultant multisystem dysfunctions in CI.

One site for this amplification may be the limbic system of the brain, which receives input from the olfactory pathways and sends efferents to the hypothalamus and the mesolimbic dopaminergic [reward] pathway. Chemical, biologic, and psychological stimuli can initiate and elicit sensitization. In turn, subsequent activation of the sensitized limbic and mesolimbic pathways can then facilitate dysregulation of behavioral, autonomic, endocrine, and immune system functions.

Research to date has demonstrated the initiation of neurobehavioral sensitization by volatile organic compounds and pesticides in animals, as well as sensitizability of cardiovascular parameters, beta-endorphin levels, resting EEG alpha-wave activity, and divided-attention task performance in persons with CI. The ability of multiple types of widely divergent stimuli to initiate and elicit sensitization offers a new perspective on the search for mechanisms of illness in CFS and fibromyalgia with CI.

 

Source: Bell IR, Baldwin CM, Schwartz GE. Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia. Am J Med. 1998 Sep 28;105(3A):74S-82S. http://www.ncbi.nlm.nih.gov/pubmed/9790486