Laboratory Testing of the Patient with Multiple Chemical Sensitivity

Howard R. Kehrl

U.S. Environmental Protection Agency, Research Triangle Park, North Carolina and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Key words: immune system, laboratory tests, multiple chemical sensitivity

This paper is based on a presentation at the Conference on Experimental Approaches to Chemical Sensitivity held 20-22 September 1995 in Princeton, New Jersey. Manuscript received at EHP 6 March 1996; manuscript accepted 22 March 1996.

Abbreviations used: MCS, multiple chemical sensitivity; VOCs, volatile organic compounds.

These considerations provide a basis for discussing certain aspects of the role of laboratory testing of the multiple chemical sensitivity (MCS) patient as put forth in the papers of Ross (1) and Ziem (2) about their perceptions of the clinical profile of the MCS patient. It is clear from their presentations that their view is one of MCS advocacy. Although Ross utilized a case presentation and Ziem reported upon a case series of MCS patients in her clinical practice, both researchers were effective in highlighting many of the controversies surrounding the clinical condition known as multiple chemical sensitivity. These controversies provide much of the basis for this workshop. Ross and Ziem touched on case definition, presumed etiology, diagnosis, and treatment, as well as invoked a number of the hypothetical constructs that have been devised to explain the MCS phenomenology. Both authors presented results from clinical laboratory testing that can also be considered controversial. Ross described a case study of a patient who developed asthma and the symptoms of MCS shortly after moving into a new home that was still in the process of being completed. Concomitantly with moving into the new home the patient underwent thoracic surgery that was complicated by a postoperative mediastinal hematoma. She was described as subsequently having repeated episodes of stridor and bronchospasm as well as other symptoms in response to multiple chemical exposures and medications. Her medical history and the report of stridor certainly raises the question of either mechanical or functional upper airway obstruction that should be further evaluated with appropriate pulmonary function testing and endoscopic examination of her upper airway. These tests either were not considered or not presented, yet measures of blood volatile organic compounds (VOCs) were included in her evaluation as indicators of xenobiotic contamination. However, measures of blood VOC levels in ambient exposure situations do not have any known relationship to disease. Furthermore, accurately measuring blood VOC levels is technically very difficult and requires special care both in obtaining and handling the specimen to prevent contamination with nonbody sources. In addition, the pharmacokinetics of VOCs makes blood levels a biomarker of acute exposure and would not, even if accurately measured, reflect xenobiotic contamination. Such measures of VOC levels in patients who report to a physician months to years after the exposure have minimal prognostic or diagnostic value for MCS patients.

In the report of her case series of MCS patients, Ziem presented the results of immune panels from two different clinical laboratories as evidence of the potential involvement of the immune system in the pathobiology of MCS; these assays included lymphocyte markers, autoantibodies, chemical antibodies, and various other markers of immune function. There are both technical and clinical problems with these sets of data. For many of these assays, the technical aspects are not well standardized and their clinical significance is either very specialized or undefined. Indeed, the change to the second laboratory was prompted because of documented concerns about the test reproducibility of the first laboratory. In addition, the large number of parameters tested increases the likelihood of a spurious or false positive result; chances are that for every 20 tests, 1 will be positive. The observation that many of the tests reported as positive were borderline supports the contention that many were falsely positive. Further complicating the interpretation of these test results is the realization that the assays were performed on an exploratory basis without an a priori hypothesis other than the suspicion that the immune system might be involved. Similarly, there was no clear attempt to relate a particular set of symptoms and/or exposures to any specific alteration in function. For this type of testing to be of value requires that the test be shown to have some degree of sensitivity and specificity in identifying the parameter of interest. This would require carefully designed clinical epidemiology studies with a well defined patient population and appropriate control group.

Probably of more significance and controversy is the contention that the biologic plausibility of immune system involvement in the pathogenesis of MCS is suspect. The lack of consistent physical findings or laboratory evidence of systemic inflammation argues against an autoimmune basis for MCS. Moreover, a principal characteristic of the immune system is its specificity, and therefore immune system dysfunction is unlikely to account for the spreading phenomenon described by MCS patients. There also is little evidence of immune system dysfunction in terms of an MCS association with autoimmune disease, increase in opportunistic infections, increase in cancer risk, or even relationship to atopy. At best, some of these immune markers may be identified as biomarkers of exposure and this would also require carefully designed studies with rigorous attention to laboratory methods and exposure assessment. Unfortunately, by focusing interest on the immune system, this and similar reports have overlooked other components of host defense such as direct irritant responses and neurogenic inflammation even though they provide a potential biologic basis for components of the MCS symptomatology.

References
1. Ross GH. Clinical characteristics of chemical sensitivity: an illustrative case history of asthma and MCS. Environ Health Perspect 105(Suppl 2):437-441 (1997).

2. Ziem G, McTamney J. Profile of patients with chemical injury and sensitivity. Environ Health Perspect 105(Suppl 2):417-436 (1997).