Category: Overlapping Illnesses

Potential mechanisms in chemical intolerance and related conditions

Abstract:

The symptom of chemical intolerance may occur in isolation, but often occurs in conjunction with other chronic symptoms such as pain, fatigue, memory disturbances, etc. This frequent clustering of symptoms in individuals has led to the definition of several chronic multisymptom syndromes, such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and Gulf War illnesses. The aggregate research into these syndromes has suggested some unifying mechanisms that contribute to symptomatology. Multiple lines of evidence suggest that there is aberrant function of numerous efferent neural pathways, such as the autonomic nervous system and hypothalamic-pituitary axes, in subsets of individuals with these conditions.

There is perhaps the greatest evidence for abnormal sensory processing in these syndromes, with a low “unpleasantness threshold” for multiple types of sensory stimuli. Psychological and behavioral factors are known to play a significant role in initiating or perpetuating symptoms in some persons with these illnesses. In the field of pain research, the interrelationship between physiologic and psychologic factors in symptom expression has been well studied. Using both established and novel methodologies, studies have suggested that psychologic factors such as hypervigilance and expectancy are playing a relatively minor role in most individuals with fibromyalgia and that clear evidence exists of physiologic amplification of sensory stimuli.

These studies need to be extended to more sensory tasks and to larger numbers of subjects with related conditions. It is of note, though, that existing data on this spectrum of illnesses would suggest that there may be greater psychologic contributions to symptomatology if an illness is defined in part by behavior (e.g., avoidance of chemical exposures) rather than on the basis of symptoms alone.

 

Source: Clauw DJ. Potential mechanisms in chemical intolerance and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:235-53. http://www.ncbi.nlm.nih.gov/pubmed/12000024

 

Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set

Abstract:

OBJECTIVE: The definition of chronic fatigue syndrome (CFS) is still disputed and no validated classification criteria have been published. Artificial neural networks (ANN) are computer-based models that can help to evaluate complex correlations. We examined the utility of ANN and other conventional methods in generating classification criteria for CFS compared to other diseases with prominent fatigue, systemic lupus erythematosus (SLE) and fibromyalgia syndrome (FMA).

PATIENTS AND METHODS: Ninety-nine case patients with CFS, 41 patients with SLE and 58 with FMA were recruited from a generalist outpatient population. Clinical symptoms were documented with help of a predefined questionnaire. The patients were randomly divided into two groups. One group (n = 158) served to derive classification criteria sets by two-fold cross-validation, using a) unweighted application of criteria, b) regression coefficients, c) regression tree analysis, and d) artificial neural networks in parallel. These criteria were validated with the second group (n = 40).

RESULTS: Classification criteria developed by ANN were found to have a sensitivity of 95% and a specificity of 85%. ANN achieved a higher accuracy than any of the other methods.

CONCLUSION: We present validated criteria for the classification of CFS versus SLE and FMA, comparing different classification approaches. The most accurate criteria were derived with the help of ANN. We therefore recommend the use of ANN for the classification of syndromes with complex interrelated symptoms like CFS.

 

Sour ce: Linder R, Dinser R, Wagner M, Krueger GR, Hoffmann A. Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set. In Vivo. 2002 Jan-Feb;16(1):37-43. http://www.ncbi.nlm.nih.gov/pubmed/11980359

 

Dry eyes and mouth syndrome–a subgroup of patients presenting with sicca symptoms

Abstract:

OBJECTIVE: To evaluate the characteristics of patients presenting with symptoms suggestive of Sjögren’s syndrome (SS) but failing to satisfy diagnostic criteria.

METHODS: Clinical, serological and histological data were collected on 34 patients presenting with dry eyes and/or mouth who did not satisfy the Vitali criteria for the diagnosis of SS. They were compared with 136 patients with primary SS, 38 patients with secondary SS, and 13 patients without SS. Questionnaires on symptoms from each group were compared with 43 healthy controls.

RESULTS: The 34 patients who did not satisfy the diagnostic criteria for SS or any other connective tissue disease were designated dry eyes and mouth syndrome (DEMS). Their demography including age was similar to that of a primary SS group and there was no more atrophy seen on their biopsies compared with SS and non-SS controls. They scored highly on visual analogue scales of symptoms but had few objective signs. All were negative for anti-Ro and anti-La although the prevalence of antinuclear antibodies (19%) was increased compared with a normal population. There was no excess of SS-associated tissue types.

CONCLUSION: There was no evidence that age, salivary gland atrophy or subclinical SS accounted for the symptoms in DEMS. Most of the patients fitted into a spectrum of disease which tended more towards fibromyalgia and/or chronic fatigue syndrome.

Comment in: Dry eyes and mouth syndrome or sicca, asthenia and polyalgia syndrome? [Rheumatology (Oxford). 2003]

 

Source: Price EJ, Venables PJ. Dry eyes and mouth syndrome–a subgroup of patients presenting with sicca symptoms. Rheumatology (Oxford). 2002 Apr;41(4):416-22. http://rheumatology.oxfordjournals.org/content/41/4/416.long (Full article)

 

 

 

Brainstem conundrum: the Chiari I malformation

Abstract:

PURPOSE: To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider.

DATA SOURCES: Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies.

CONCLUSIONS: The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa.

IMPLICATIONS FOR PRACTICE: Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

 

Source: Mueller D. Brainstem conundrum: the Chiari I malformation. J Am Acad Nurse Pract. 2001 Apr;13(4):154-9. http://www.ncbi.nlm.nih.gov/pubmed/11930527

 

Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses

Abstract:

Gulf War unexplained illnesses (GWUI) are a heterogeneous collection of symptoms of unknown origin known to be more common among veterans of the Gulf War than among nonveterans. In the present study we focused on one of these unexplained illnesses.

We tested the hypothesis that in a sample of Persian Gulf War veterans chronic fatigue syndrome (CFS) was associated with cognitive deficits on computerized cognitive testing after controlling for the effects of premorbid cognitive differences. We obtained Armed Forces Qualification Test (AFQT) data acquired around the date of induction into the military on 94 veterans of the Gulf War, 32 with CFS and 62 healthy controls. Controls performed better than participants diagnosed with CFS on the AFQT. Cognitive deficits were associated with CFS on 3 of 8 variables after the effect of premorbid AFQT scores was removed with ANCOVA.

 

Source: Binder LM, Storzbach D, Campbell KA, Rohlman DS, Anger WK; Members of the Portland Environmental Hazards Research Center. Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses. J Int Neuropsychol Soc. 2001 Nov;7(7):835-9. http://www.ncbi.nlm.nih.gov/pubmed/11771626

 

A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction

Abstract:

This study investigated the biological basis of visual processing disabilities in adults with Chronic Fatigue Syndrome. The study involved 61 adults with symptoms of Chronic Fatigue Syndrome who were screened for visual processing problems (Irlen Syndrome) and divided into two groups according to the severity of symptoms of Irlen Syndrome.

Significant variations were identified in blood lipids and urine amino and organic acids of the two groups, which may be indicative of activation of the immune system due to some infective agent. It was suggested that metabolic profiling may help the development of more valid diagnostic categories and allow more investigation of immune system dysfunction as a possible causal factor in a range of learning and behaviour disorders.

 

Source: Robinson GL, McGregor NR, Roberts TK, Dunstan RH, Butt H. A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction. Percept Mot Skills. 2001 Oct;93(2):486-504. http://www.ncbi.nlm.nih.gov/pubmed/11769907

 

Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness

Abstract:

Few epidemiological studies have been conducted that have incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls.

The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of the veterans with unexplained musculoskeletal pain met the criteria for fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others.

 

Source: Bourdette DN, McCauley LA, Barkhuizen A, Johnston W, Wynn M, Joos SK, Storzbach D, Shuell T, Sticker D. Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness. J Occup Environ Med. 2001 Dec;43(12):1026-40. http://www.ncbi.nlm.nih.gov/pubmed/11765674

 

Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension

Abstract:

Corticosteroid-binding globulin is a 383-amino acid glycoprotein that serves a hormone transport role and may have functions related to the stress response and inflammation. We describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. A second, previously described, mutation (Lyon) segregated independently in the same kindred. The novel exon 2 mutation led to a premature termination codon corresponding to residue -12 of the procorticosteroid-binding globulin molecule (c.121G–>A).

Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without corticosteroid-binding globulin mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean corticosteroid-binding globulin levels were reduced by approximately 50% at 18.7 +/- 1.3 microg/ml (reference range, 30-52 microg/ml) in null heterozygotes. Morning total plasma cortisol levels were less than 1.8 microg/dl in homozygotes and were positively correlated to the plasma corticosteroid-binding globulin level in heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue.

Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 +/- 3.5; 11 of 19 subjects (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 +/- 3.4; 8 of 19 subjects (42%) had a diastolic blood pressure z-score below 10.

Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaires revealed scores of 25.1 +/- 2.5 in 18 adults with the mutation vs. 4.2 +/- 1.5 in 23 healthy controls (P < 0.0001).

Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. Abnormal corticosteroid-binding globulin concentrations or binding affinity may lead to the misdiagnosis of isolated ACTH deficiency. The mechanism of the association between fatigue and relative hypotension is not established by these studies. As idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of corticosteroid-binding globulin may be pathogenic.

 

Source: Torpy DJ, Bachmann AW, Grice JE, Fitzgerald SP, Phillips PJ, Whitworth JA, Jackson RV. Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. J Clin Endocrinol Metab. 2001 Aug;86(8):3692-700. http://www.ncbi.nlm.nih.gov/pubmed/11502797

 

A review of the evidence for overlap among unexplained clinical conditions

Abstract:

PURPOSE: Unexplained clinical conditions share features, including symptoms (fatigue, pain), disability out of proportion to physical examination findings, inconsistent demonstration of laboratory abnormalities, and an association with “stress” and psychosocial factors. This literature review examines the nature and extent of the overlap among these unexplained clinical conditions and the limitations of previous research.

DATA SOURCES: English-language articles were identified by a search of the MEDLINE database from 1966 to January 2001 by using individual syndromes and their hallmark symptoms as search terms.

STUDY SELECTION: Studies that assessed patients with at least one unexplained clinical condition and that included information on symptoms, overlap with other unexplained clinical conditions, or physiologic markers. Conditions examined were the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome, multiple chemical sensitivity, temporomandibular disorder, tension headache, interstitial cystitis, and the postconcussion syndrome.

DATA EXTRACTION: Information on authorship, patient and control groups, eligibility criteria, case definitions, study methods, and major findings.

DATA SYNTHESIS: Many similarities were apparent in case definition and symptoms, and the proportion of patients with one unexplained clinical condition meeting criteria for a second unexplained condition was striking. Tender points on physical examination and decreased pain threshold and tolerance were the most frequent and consistent objective findings. A major shortcoming of all proposed explanatory models is their inability to account for the occurrence of unexplained clinical conditions in many affected patients.

CONCLUSIONS: Overlap between unexplained clinical conditions is substantial. Most studies are limited by methodologic problems, such as case definition and the selection and recruitment of case-patients and controls.

 

Source: Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med. 2001 May 1;134(9 Pt 2):868-81. http://www.ncbi.nlm.nih.gov/pubmed/11346323

 

High prevalence of serum markers of coeliac disease in patients with chronic fatigue syndrome

There has been recent interest in the possibility that undiagnosed coeliac disease (CD) might be the cause of diverse clinical symptoms, most particularly “tired all the time”.1 A recent study reported a prevalence of three in 100 cases in a primary care environment in which samples were taken from patients with a range of symptoms and signs.2 The second most frequent symptom reported by the endomysial antibody (EMA) positive patients was “being tired all the time”. We decided to examine the prevalence of EMA in patients attending our tertiary referral centre with the diagnosis of chronic fatigue syndrome (CFS).

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1731400/pdf/v054p00335a.pdf

 

Source: Skowera A, Peakman M, Cleare A, Davies E, Deale A, Wessely S. High prevalence of serum markers of coeliac disease in patients with chronic fatigue syndrome. J Clin Pathol. 2001 Apr;54(4):335-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1731400/ (Full article)