Category: Overlapping Illnesses

Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins

Abstract:

This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients’ sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40.

In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2.

Inhibition analysis with antigens, CTX, CFS “Acute Phase Lipids”, commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients’ serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria.

We designate this “Acute Phase Lipid” comparable to “Acute Phase Proteins” (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.

(Copyright ) 2008 Wiley-Liss, Inc.

 

Source: Hokama Y, Empey-Campora C, Hara C, Higa N, Siu N, Lau R, Kuribayashi T, Yabusaki K. Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. J Clin Lab Anal. 2008;22(2):99-105. doi: 10.1002/jcla.20217. https://www.ncbi.nlm.nih.gov/pubmed/18348309

 

Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study

Abstract:

BACKGROUND: The aim was to determine the prevalence of chronic fatigue syndrome (CFS), chronic fatigue and fibromyalgia in UK military personnel after the Gulf War 1990-1991.

METHOD: A two-phase cohort study was used. Three randomly selected subsamples identified from a population-based cross-sectional postal survey of over 10,000 current and ex-service UK military personnel (Gulf veterans were those deployed to the Gulf War 1990-1991; non-Gulf veterans were Bosnia peacekeepers 1992-1997 and those on active duty during the Gulf War 1990-1991 but not deployed) were recruited. Their disability status was assessed using the Short Form 36 physical functioning scale; Gulf veterans who reported physical disability (n=111) were compared with non-Gulf (n=133) veterans who reported similar levels of physical disability. Screening for known medical and psychiatric conditions was conducted to exclude medical explanations for disability and symptomatic distress. Standardised criteria for CFS, chronic fatigue and fibromyalgia were used.

RESULTS: Disabled Gulf veterans were more likely to be overweight, have elevated gamma-glutamyl transferase levels and screen positive for hypertension. There were no other clinically significant differences in clinical markers for medically explainable conditions. Disabled Gulf veterans were more likely than similarly disabled Bosnia and Era veterans (adjusted odds ratio 7.8, 95% confidence interval 2.5-24.5) to meet the criteria for CFS. Rates for other medically unexplained conditions were not significantly increased.

CONCLUSIONS: Symptoms in keeping with CFS account for a significant part of the symptomatic distress in Gulf veterans.

Comment in: Chronic fatigue in Gulf War veterans: should it be treated as chronic fatigue syndrome? [Psychol Med. 2009]

 

Source: Ismail K, Kent K, Sherwood R, Hull L, Seed P, David AS, Wessely S. Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study. Psychol Med. 2008 Jul;38(7):953-61. Epub 2007 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/17892626

 

Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome

Abstract:

OBJECTIVE: We reviewed previous studies that have described an association between abnormal functioning of the hypothalamic-pituitary-adrenal axis and depression. In addition to melancholic depression, a spectrum of conditions may be associated with increased and prolonged activation of the hypothalamic-pituitary-adrenal axis. In contrast another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of corticotropin releasing factor may result in pathological hypoarousal and an enhanced hypothalamic-pituitary-adrenal negative feedback. Patients with atypical depression, seasonal affective disorder and chronic fatigue syndrome fall in this category.

METHOD: The literature data on the overlap between the key-words were reviewed, summarized and discussed.

RESULTS: Many studies suggest that these conditions themselves overlap biologically, showing hypofunction of central corticotropin releasing factor neuronal systems.

CONCLUSIONS: Therefore, in the real world of clinical practice, patients often present in a grey area between classical idiopathic fatigue and early chronic atypical depression and/or seasonal depression. This underscores the potential common biological links underpinning common symptom clusters not only between depression (atypical and seasonal) and chronic fatigue syndrome, but also other conditions characterized by the hypothalamic-pituitary-adrenal axis mainly diminished the corticotropin releasing factor activity.

 

Source: Juruena MF, Cleare AJ. Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome. Rev Bras Psiquiatr. 2007 May;29 Suppl 1:S19-26. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462007000500005&lng=en&nrm=iso&tlng=en (Full article)

 

Chronic fatigue syndrome after Q fever

Abstract:

BACKGROUND: Q fever is a common and acute but rare chronic zoonosis caused by Coxiella burnetii. Its acute form manifests as atypical pneumonia, flu-like syndrome, or hepatitis. Some authors observed symptoms of chronic fatigue in a small number of patients after the acute phase of Q fever; in many cases serological assay confirmed the activity of Coxiella burnetii infection. The effect of antibiotic therapy on post-Q-fever fatigue syndrome has not been studied in south-east Europe thus far.

CASE REPORTS: Three patients are presented with post-Q-fever fatigue syndrome. All fulfilled the CDC criteria for chronic fatigue syndrome. IgA antibodies to phase I of the growth cycle of Coxiella burnetii were positive in two patients and negative in one. Two patients were treated with doxycycline for two weeks in the acute phase of illness and one with a combination of erythromycin and gentamycin. After 4-12 months they developed post-Q-fever fatigue syndrome and were treated with intracellular active antibiotics (fluoroquinolones and tetracycline) for 3-12 months. Efficacy of the treatment was observed in two patients, but in one patient the results were not encouraging.

CONCLUSIONS: These results suggest the possibility of the involvement of Coxiella burnetii infection in the evolution of chronic fatigue syndrome. This is the first report on post-Q-fever fatigue syndrome in Mediterranean countries. Evidence of IgA antibodies to phase I of the growth cycle of Coxiella burnetii is not a prerequisite for establishing a diagnosis of CFS. The recommendation of antibiotic treatment in post-Q-fever fatigue syndrome requires further investigation.

 

Source: Ledina D, Bradarić N, Milas I, Ivić I, Brncić N, Kuzmicić N. Chronic fatigue syndrome after Q fever. Med Sci Monit. 2007 Jul;13(7):CS88-92. https://www.ncbi.nlm.nih.gov/pubmed/17599032

 

The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study

Abstract:

Cancer-related fatigue (CRF) is a common and disabling symptom complex reported by survivors. This study aimed to better understand the manifestations of CRF in women treated for breast cancer, and to compare them with those of women diagnosed with chronic fatigue syndrome (CFS).

Women with CRF persisting 6 months after treatment for early stage breast cancer, and women with CFS participated in separate, audiotaped focus groups. Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted using grounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from both groups revealed a similar core set of symptoms, featuring fatigue, neurocognitive difficulties, and mood disturbances.

Women with CFS reported additional symptoms including musculoskeletal pain and influenza-like manifestations. Both groups suffered disabling behavioral consequences of the symptom complex. Qualitatively, CRF appears closely related to CFS. These findings raise the emergent hypothesis of a conserved neurobehavioral symptom complex, which results from diverse triggering insults.

 

Source: Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A. The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study. J Pain Symptom Manage. 2007 Aug;34(2):126-35. Epub 2007 Jun 4. https://www.ncbi.nlm.nih.gov/pubmed/17544246

 

Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring multiple chemical sensitivity and fibromyalgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS), multiple chemical sensitivity (MCS), and fibromyalgia (FM) commonly co-occur. Some propose that CFS, MCS, and FM are manifestations of the same illness based on high rates of co-occurrence and overlapping diagnostic criteria. This study seeks to differentiate these diagnoses by comparing individuals with one or more illness on functioning, psychiatric comorbidity, coping style, and in vivo physical measures.

METHODS: Participants included 114 men and women who met criteria for CFS. FM was diagnosed during a physical examination, and MCS was assessed using a questionnaire. Participants were divided into four groups: CFS alone, CFS-MCS, CFS-FM, and CFS-MCS-FM. Self-report measures, a psychiatric interview, and in vivo physical measures were given.

RESULTS: 43.9% met criteria for CFS alone, 23.7% met criteria for CFS-MCS, 15.8% met criteria for CFS-FM, and 16.7% met criteria for CFS-MCS-FM. The CFS-MCS-FM group was more disabled than the CFS alone group on measures of physical functioning, general health, and bodily pain. In vivo measures did not differ, but the CFS-MCS-FM group rated exertion higher than the CFS alone group.

CONCLUSION: Individuals with CFS alone were the highest functioning group across several domains, such as disability, depression, and severity of symptoms. Participants with three diagnoses experienced the greatest amount of disability. While substantial co-occurrence of these illnesses was found, this study provides evidence that having more than one illness exacerbates one’s disability beyond CFS alone.

 

Source: Brown MM, Jason LA. Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring multiple chemical sensitivity and fibromyalgia. Dyn Med. 2007 May 31;6:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1890280/ (Full article)

Multiple chemical sensitivity in sick-building syndrome

Abstract:

The sick building syndrome includes irritation of the eyes and the respiratory tract neurotoxicity affectation and skin problems, which can occur in individuals under improperly ventilated buildings. Poor air quality, as shown in CO2 atmospheric levels of more than 1,000 ppm, results in a pathological exposure to biological and chemical products. We present a work-related case of multiple chemical hypersensitivity from a dialysis unit that had no air renewal. This person, who was summitted to continuous exposure despite having taken corrective measures in the ventilation, developed chronic fatigue syndrome. An acoustic voice observation alerted of the case which led to the analysis of the environmental conditions which confirmed the relationship between multiple chemical hypersensitivity and chronic fatigue syndrome. This case stresses the neglected fact that all health service centres pose a high risk of chemical exposure and that there exists a lack of rigoroursness in putting in practice scientific medical knowledge.

 

Source: Arnold Llamosas PA, Arrizabalaga Clemente P, Bonet Agusti M, de la Fuente Brull X. Multiple chemical sensitivity in sick-building syndrome. Med Clin (Barc). 2006 May 27;126(20):774-8. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/16883665

 

Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis

Abstract:

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity.

Adenylate cyclase-activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their receptors are potentially immunogenic.

VNs are widely distributed in the body particularly in the central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells, reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-respiratory function, thermoregulation, memory, concentration and executive functions such as emotional responses including social cues and appropriate behaviour. They are co-transmitters for a number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system against toxic assault as well as being important in the maintenance of homeostasis.

This paper describes a biologically plausible mechanism for the development of certain fatigue-related syndromes based on loss of immunological tolerance to these VNs or their receptors following infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG fragments and heat shock (stress) proteins. These conditions extend the public health context of autoimmunity and VN dysregulation and have implications for military medicine where radiological, biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention options are considered.

 

Source: Staines DR. Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis. Clin Dev Immunol. 2006 Mar;13(1):25-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270748/ (Full article)

 

Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection

Abstract:

OBJECTIVE: To examine whether Coxiella burnetii (C. burnetii) is involved in chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to subjects with CFS, and followed changes in clinical symptoms, PCR findings, and C. burnetii antibody titers.

PATIENTS AND METHODS: The subjects were 8 patients with CFS and 213 with nonspecific complaints such as chronic fatigue and low-grade fever for several months or longer but not meeting the diagnostic criteria for CFS. All were examined for C. burnetii infection by nested PCR and the indirect immunofluorescence test (IF).

RESULTS: Four CFS patients (the CFS group) and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C. burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3 months. After treatment, all 58 patients tested negative for C. burnetii infection. In the CFS group, no significant difference was noted between the mean pre- and post-treatment temperatures or headache scores. Similarly, there was no significant improvement in performance status (PS) scores. In the QFS group, however, mean temperatures and headache scores were significantly decreased after treatment (p<0.001). PS scores were also improved.

CONCLUSION: These results suggest the possibility of direct involvement of C. burnetii in the pathological state of CFS to be low, despite the C. burnetii infection rate being high in CFS patients. This is a pilot study and further larger investigations are necessary to confirm our preliminary results.

 

Source: Iwakami E1, Arashima Y, Kato K, Komiya T, Matsukawa Y, Ikeda T, Arakawa Y, Oshida S. Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection. Intern Med. 2005 Dec;44(12):1258-63. https://www.ncbi.nlm.nih.gov/pubmed/16415546

 

Chronic fatigue syndrome, exercise, cortisol and lymphadenopathy

Dear Sir,

As in the past [1], the effects of exercise in the treatment of chronic fatigue syndrome (CFS) are conflicting. Indeed, while Powell et al. [2], in 2004, reported that graded exercise was beneficial to CFS patients, Black et al. [3] have lately written that ‘overall mood, muscle pain intensity, and time spent each day with fatigue worsened following increased activity’ [3] in CFS patients, despite the fact that their increase in daily physical activity was rather moderate (28%) [3]. The virtually opposite effects of exercise in different groups of CFS patients [1–3] may reflect their different cortisol levels [1], which, just as occurred some years ago [1], continue to be contradictory. For example, Inder et al. [4], in March 2005, reported that cortisol levels were normal in their patients with CFS, whereas Segal et al. [5], in the same month, reported that their subjects with CFS had hypocortisolism.

Considering that most features of CFS, such as ‘debilitating fatigue, an abrupt onset precipitated by a stressor, feverishness, arthralgias, myalgias, adenopathy, postexertional fatigue, exacerbation of allergic responses, and disturbances in mood and sleep are all characteristic of glucocorticoid insufficiency’ [6], it is not surprising that hypocortisolism has been convincingly shown to be implicated in the pathophysiology of CFS [7]. Therefore, especially the postexertional fatigue caused by glucocorticoid insufficiency [6] strongly suggests that exercise could be of benefit to CFS patients with high [1] or normal cortisol levels [4], whereas it could be harmful to CFS patients with hypocortisolism [1, 5, 6]. Unfortunately, because of the misleading coexistence of quite different diagnostic criteria for CFS [1], it is difficult to predict the patients with CFS who are more likely to have hypocortisolism and which would worsen with exercise. However, it is arguable that the presence or absence of lymphadenopathy [8], which is a sign of hypocortisolism [6, 9] and is one of the 43 clinical features that CFS shares with Addison’s disease [10–12], could reliably discriminate CFS patients who may worsen with exercise from those who may improve with it. Indeed, lymphadenopathy, unlike other symptoms of CFS [11, 12], many of which are non-specific and can also be found in depression and other affective disorders [11, 12], is far from being common in physical diseases and is absent in psychiatric conditions.

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01526.x/full

 

Source: Baschetti R. Chronic fatigue syndrome, exercise, cortisol and lymphadenopathy. J Intern Med. 2005 Sep;258(3):291-2. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01526.x/full (Full article)