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Double-blind non-controlled chemical challenge with environmental toxicological assessment in a Multiple Chemical Sensitivity case
Journal of the Neurological Sciences 306 (2011) 154–156
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Double-blind non-controlled chemical challenge with environmental toxicological assessment in a Multiple Chemical Sensitivity case Baden Ralph a, Ott Martine b, Reis Jacques c,⁎ a b c
Ministry of Health, Department of Occupational Health, Luxembourg Pôle de Pathologie Thoracique, University Hospital of Strasbourg, France University of Strasbourg, Faculty of Medicine, Club de Neurologie de l'Environnement, France
a r t i c l e
i n f o
Article history: Received 3 May 2010 Received in revised form 23 March 2011 Accepted 28 March 2011 Available online 14 April 2011
a b s t r a c t The report of a Multiple Chemical Sensitivity case highlights two original points. First, even if non-controlled, the reappearance of MCS symptoms after an accidental re-exposure to one scentless semi-volatile chemical (permethrin) of the initial toxic cocktail exposure can be considered as a double blind re-exposure study in situ. Second, environmental toxicology investigations were warrant for a correct treatment and prevention measures. © 2011 Elsevier B.V. All rights reserved.
Keywords: Multiple Chemical exposure MCS Recurrent atypical ophthalmic migraines Indoor air pollution
1. Introduction MCS diagnosis is based on a criteria set of more or less unspecific clinical symptoms involving the respiratory and cardio-vascular system, the eye-ear-nose-throat-tract, the gastro-intestinal tract, the nervous system (headache, attention and memory), associated with fatigue, depression and irritability. MCS is induced by different chemicals such as pesticides, cleaning products, perfumes, environmental tobacco smoke, formaldehyde, paintings, glues, wall papers, printers or newspapers [1–3]. The main difficulty in MCS diagnosis is to assess the causality relation between exposure and symptoms. That is why MCS is not recognized as an organic, chemical-caused illness by most of the Medical Associations. A psychosomatic condition has been suggested [3,4]. We had the opportunity to examine and follow up a patient since the diagnosis was set up. We documented the changes in MCS symptoms depending on and related with chemical indoor changing exposure, under double-blind conditions. 2. Case report A 29-year-old woman, S.W, contacted M.O. (Medical Indoor Environment Counselor) in August 2007. She is a social worker (occupational exposure not likely), married, with no previous medical ⁎ Corresponding author at: University of Strasbourg, Faculty of Medicine, Institut de Médecine légale, 11 rue HUMAN 67070 Strasbourg, France. Tel.: +33 3 68 85 33 43; fax: +33 3 68 85 33 62. E-mail address: [email protected] (R. Jacques). 0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2011.03.044
history. Since 2004, she was developing puzzling symptoms leading to many medical investigations (including EEG, MRI) and often to the emergency room without any diagnosis. She suffered from severe headache attacks with visual troubles, lasting several hours, diagnosed as “recurrent atypical ophthalmic migraines” by her GP. These attacks, at least 5 in number, occurred each time 24 to 48 h after having restored furniture during the week end. For precautionary reasons in relation with the use of painting products, she worked outside and wore gloves, but never felt uncomfortable with smells. In January 2005, the couple moved into a new apartment which was then furnished by her refurbished furniture. The headaches worsened. In March she suffered from a severe migraine crisis with a half hour partial visual lost, blurring and illusion. The following weeks, the troubles became chronic: ongoing fatigue, daily nausea, vertigo, tinnitus, visual illusions. New medical investigations failed. Nevertheless she recovered partially. Meanwhile she went on restoring other furniture using the same products again. By the end of 2005, she became pregnant and so stopped furniture restoring. She stayed in bed most of the last trimester, because of fatigue, vertigo, nausea, visual complains, which she assumed to be normal pregnancy symptoms. She gave birth to twins in September 2006. In January 2007, the couple started refurbishing furniture again using the same painting products with the same health consequences. During summer 2007, her apartment was investigated for indoor air pollutants (MO and RB). Samples of dust (sleeping room, living room and kitchen) and material (living room wooden door and painting products) revealed contaminations by different organic compounds. Although she was still complaining about dysesthesia circumoral, burning hands and legs feelings, visual disturbance, nausea and vomiting, severe fatigue, sleep disorders (awaking with balance trouble,
B. Ralph et al. / Journal of the Neurological Sciences 306 (2011) 154–156
vasomotor flush, sweating and shivering) her neurological examination (JR) was normal in fall 2007. She was worried because of the possible intrauterine exposure of her children during pregnancy and after and became stressed and anxious. Because of a professional promotion of her husband, the family had to move out. They got rid of the refurbished furniture and cleaned and washed thoroughly what would be kept. S.W. resigned and moved to her parent's house since the new home was not ready. Surprisingly, she noted that her health condition improved during her stay in her parent's house but the symptoms reappeared regularly at the new home during night in the bedroom. We must underline again that, at that time, nobody used painting products or solvents and that nobody was disturbed by any odour. As the link between the appearance of symptoms and the bedroom appeared clearly, the foam of the bed mattress was analyzed revealing a contamination of the foam by permethrin (scentless). The patient recovered slowly after the exchange and replacement of the contaminated (permethrin) bed mattress by a non contaminated one (that was also analyzed). After clinical improvement, neurophysiological investigations (electromyography and nerve conduction studies) were normal by the beginning of 2008. Neuropsychological testing still revealed attention impairment at the PASAT test but executive function, motor abilities, learning and short-term memory, verbal fluency, visuospatial skills were preserved. At that time, Misses S.W refused any supplementary investigations (e.g. SPECT scanning, LAT or LTT). Since the moving into her new home, S.W. still has clinical symptoms but these are drastically reduced both in frequency and in intensity, meaning that she still has headaches from time to time but less severe and more seldom. S.W. describes these headaches as “normal” headaches not comparable to the severe headache attacks she used to have while being exposed to permethrin, solvents and flame retardants.
3. Investigations on indoor air quality Though, seven-days-old-dust-samples were taken in different pieces including the sleeping and living room and the kitchen through a classic vacuum cleaner by the patient and sent to Luxembourg to be analyzed for biocides, pyrethroids and organophosphorous esters. The analyses, including three dust samples and two material samples were performed by the National Laboratory for Health according the SOP-B-29 method, extraction, derivatisation, identification and quantification by gas chromatography and mass spectrometry including 17 different biocides,1 8 pyrethroids2 and 8 different organo-phosphorous esters.3 After the accidental re-exposure, a supplementary sample was taken from the foam of the bed mattress. This sample was analyzed following the same procedure described before. Secondary contaminations during transport could be excluded. The results of the dust samples revealed the presence of different organic semi-volatile compounds in the kitchen (Permethrin 4.1 mg/kg dust, Propiconazol 2,5 mg/kg, TBEP 27 mg/kg and TCPP 29 mg/kg), the living room (Permethrin 5,5 mg/kg, Propiconazol 1,1 mg/kg and PCP 1,6 mg/kg) as well as in the bedroom (Permethrin 10 mg/kg). Whereas Propiconazol, Pentachlorphenol and Permethrin are commonly used as biocides against insects or moulds, TBEP and TCPP belong to the group of organo-phosphorous esters commonly used as flame retardants. The painting product contained, according to the analyses, different volatile
1 Azaconazole, chlorothalonil, chlorpyrifos, 4,4′-DDE, 4,4′-DDT, dichlofluanid, dieldrin, endosulfan, Eulan, lindan, methoxychlor, pentachlorophenol, propiconazol, tetrachlorvinphos, tolyfluanid and tribromophenol, tebuconazol. 2 Permethrin, cyfluthrin, cypermethrin, deltamethrin, fenvalerate, phenothrin, tetramethrin and piperonyl butoxid. 3 2-ethylhexyl-diphenyl-phosphate EHDPP, tributyl-phosphate TBP, triphenyl-phosphate TPP, tris(2-butoxyethyl)-phosphate TBEP, tris(2-chloroethyl)-phosphate TCEP, tris(3chloropropyl)-phosphate TCPP; tris(1,3-dichloro-2-propyl)-phosphate TDCP or TDCPP and tris(2-ethylhexyl)-phosphate TEHP.
155
organic compounds: xylenes, ethylbenzene, probylbenzene, trimethylbenzenes and butoxyethanol. Finally the bed mattress was heavily contaminated with permethrin (30 mg/kg foam). 4. Discussion Many investigators looked for laboratory testing to confirm the diagnosis, or at least a relation between symptoms and chemical exposure [5–7]. Provocation test and odor perception differences were also proposed to discriminate MCS patients from controls [8–10]. Seldom environmental toxicological investigations in situ, for example, personal sampling [11] or air sampling [12] were used to assess the exposure. The originality of our case is the accidental re-exposure to a scentless chemical (permethrin). The contaminated mattress was contributing to a regular long time exposure by inhalation and by dermal pathways (permethrin is highly lipid-soluble). We consider this accidental reexposure as a double blind non-controlled re-exposure study. We have found no other reports or studies of this type. As known, re-exposure is the highest value criterion to prove a causal link and to assess causality of pharmacological treatments side-effects [13,14]. The imputation criterion between the symptoms and the toxic cocktail is fulfilled. Considering the diagnosis criteria for MCS of the 1999 consensus [15], our case fits well and the diagnosis is obvious. The first attacks were diagnosed as “recurrent atypical ophthalmic migraines”. Following the International classification of headaches disorders [16] only a few chemicals are known to trigger headaches. Migraineurs as well as MCS patients show a sensitization to environmental triggers and chronic anxiety with panic disorders [17–19]. The severity of the first attacks in MCS may trigger a “posttraumatic stress disorder” [20]. Neuropsychological examination showed in the SW case, even during the improvement phase, persistence of attention troubles [21–23]. These cognitive disorders (attention and memory) could be related to impairment of the hippocampus area (as shown by brain SPECT hypoactivity) [23]. The reappearance of symptoms after re-exposure to permethrin excludes a solvent syndrome or an olfactive syndrome, since permethrin is not a solvent and absolutely odorless. The neuropsychological profile and clinical facts contribute also to exclude a solvent syndrome [24]. In the dust samples of the indoor environment, five different chemicals belonging to the groups of biocides, pyrethroids and organophosphorous esters were identified and quantified. All five pollutants are soluble in fat and thus accumulate in fatty tissues within the human organism. They are absorbed through ingestion, inhalation and dermal pathways. This last pathway is especially important in the case of the contaminated bed mattress because of the supplementary dermal exposure by permethrin. The biological mechanism of permethrin consists in the extension of transmembranous flux of sodium into the cell during the excitation phase inducing repetitious excitations of nerves and enhancing the affinity of sensory receptors [25]. In animal testing, Type I-pyrethroids like permethrin induce the so called “T-syndrome” characterized by an increase of tremor and ataxia as well as an increase of sensibility and sensitivity to external excitations. We do not know the exact role of these biological mechanisms in the pathogenesis of our case. Our report highlights two original points. First, in our case the reappearance of MCS symptoms after an accidental re-exposure to one scentless semi-volatile chemical (permethrin), can be considered as a double blind-re-exposure study in situ. Second, environmental toxicology investigations were warrant for a correct treatment and prevention measures. Acknowledgements Gilbert Hansen and Marc Fischer, Laboratoire d'Hygiène du Milieu et de Surveillance Biologique, National Laboratory for Health Luxembourg.
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B. Ralph et al. / Journal of the Neurological Sciences 306 (2011) 154–156
References [1] Weiss B. Neurobehavioral properties of chemical sensitivity syndromes. Neurotoxicology 1998;19(2):259–68. [2] Seidel HJ. Praxis der Umweltmedizin: Grundlagen, Fakten und Informationen für einen verantwortungsvollen Umgang mit Umwelt und menschlicher Gesundheit. Thieme-Verlag; 1998. p. 432–5. [3] Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Letters 2002;128: 85–97. [4] McKeown-Eyssen GE, Baines CJ, Marshall LM, Jazmaji V, Sokoloff ER. Multiple chemical sensitivity: discriminant validity of case definitions. Arch Environ Health 2001;56:406–12. [5] Kehrl HR. Laboratory testing of the patient with multiple chemical sensitivity. Environ Health Perspect 1997;105(Suppl2):443–4. [6] Hoover DR, Donnay A, Mitchell CS, Ziem G, Rose NR, Sabath DE, et al. Reproducibility of immunological tests used to assess multiple chemical sensitivity syndrome. Clin Diagn Lab Immunol 2003 Nov;10(6):1029–36. [7] Baines CJ, McKeown-Eyssen GE, Riley N, Cole DEC, Marshall L, Loescher B, et al. Case-control study of multiple chemical sensitivity, comparing haematology, biochemistry, vitamins and serum volatile organic compound measures. Occup Med (Lond) 2004 Sep;54(6):408–18. [8] Eissenberg T, Griffiths RR. Human drug discrimination and multiple chemical sensitivity: caffeine exposure as an experimental model. Environ Health Perspect 1997;105(Suppl 2):509–13. [9] Ojima M, Tonori H, Sato T, Sakabe K, Miyata M, Ishikawa S, et al. Odor perception in patients with multiple chemical sensitivity. Tohoku J Exp Med 2002 Nov;198(3): 163–73. [10] Papo D, Eberlein-König B, Berresheim HW, Huss-Marp J, Grimm V, Ring J, et al. Chemosensory function and psychological profile in patients with multiple chemical sensitivity: comparison with odor-sensitive and asymptomatic controls. J Psychosom Res Feb, 2006;60(2):199–209. [11] Shinohara N, Mizukoshi A, Yanagisawa Y. Identification of responsible volatile chemicals that induce hypersensitive reactions to multiple chemical sensitivity patients. J Expo Anal Environ Epidemiol Jan, 2004;14(1):84–91. [12] Miller CS, Gammage RB, Jankovic JT. Exacerbation of chemical sensitivity: a case study. Toxicol Ind Health 1999;15:398–402.
[13] Begaud B. Critères d'imputabilité des effets secondaires des traitements. Rev Prat 2000;50:1803–6. [14] Begaud B, Evreux JC, Jouglard J, Lagier G. Unexpected or toxic drug reaction assessment (imputation). Actualization of the method used in France. Therapie 1985;40:111–8. [15] Bartha L, Baumzweiger W, Buscher DS, Callender T, Dahl KA. Multiple chemical sensitivity: a consensus. Arch Environ Health 1999;54(3):147–9. [16] Headache Classification Subcommittee of the International Headache Society, 2nd edition, 24 Suppl 1. Cephalalgia: The International Classification of Headache Disorders; 2004. p. 9–160. [17] Demarquay G, Royet JP, Giraud P, Chazot G, Valade D, Ryvlin P. Rating of olfactory judgments in migraine patients. Cephalalgia 2006;26(9):1123–30. [18] Radat F, Mekies C, Geraud G, Valade D, Vives E, Lucas C, et al. Anxiety, stress and coping behaviours in primary care migraine patients: results of the SMILE study. Cephalalgia 2008;28:1115–25. [19] Tarlo SM, Poonai N, Binkley K, Antony MM, Swinson RP. Responses to panic induction procedures in subjects with multiple chemical sensitivity/idiopathic environmental intolerance: understanding the relationship with panic disorder. Environ Health Perspect 2002;110(suppl 4):669–71. [20] Feldman RG. Occupational & Environmental Neurotoxicology. Philadelphia: Lippincott-Raven; 1999. p. 15–6. [21] Bolla KI. Neurobehavioral performance in multiple chemical sensitivities. Regul Toxicol Pharmacol Aug, 1996;24(1 Pt 2):52–4. [22] Osterberg K, Ørbaek P, Karlson B. Neuropsychological test performance of Swedish multiple chemical sensitivity patients – an exploratory study. Appl Neuropsychol 2002;9(3):139–47. [23] Orriols R, Costa R, Cuberas G, Jacas C, Castell J, Sunyer J. Brain dysfunction in multiple chemical sensitivity. J Neurol Sci 2009;287(1–2):72–8. [24] Geens T, Vermeir G, Godderis L, Van Damme J, Viaene MK. L'encéphalopathie toxique chronique provoquée par l'utilisation de solvants: dix ans d'expérience autour d'un diagnostic difficile. Archives des maladies professionnelles et de l'Environnement 2009;70:494–501. [25] Marquardt H, Schaefer SG. Lehrbuch der Toxikologie. Spektrum Akademischer Verlag Heidelberg; 1997. p. 475–80.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Double-blind non-controlled chemical challenge with environmental toxicological assessment in a Multiple Chemical Sensitivity case Baden Ralph a, Ott Martine b, Reis Jacques c,⁎ a b c
Ministry of Health, Department of Occupational Health, Luxembourg Pôle de Pathologie Thoracique, University Hospital of Strasbourg, France University of Strasbourg, Faculty of Medicine, Club de Neurologie de l'Environnement, France
a r t i c l e
i n f o
Article history: Received 3 May 2010 Received in revised form 23 March 2011 Accepted 28 March 2011 Available online 14 April 2011
a b s t r a c t The report of a Multiple Chemical Sensitivity case highlights two original points. First, even if non-controlled, the reappearance of MCS symptoms after an accidental re-exposure to one scentless semi-volatile chemical (permethrin) of the initial toxic cocktail exposure can be considered as a double blind re-exposure study in situ. Second, environmental toxicology investigations were warrant for a correct treatment and prevention measures. © 2011 Elsevier B.V. All rights reserved.
Keywords: Multiple Chemical exposure MCS Recurrent atypical ophthalmic migraines Indoor air pollution
1. Introduction MCS diagnosis is based on a criteria set of more or less unspecific clinical symptoms involving the respiratory and cardio-vascular system, the eye-ear-nose-throat-tract, the gastro-intestinal tract, the nervous system (headache, attention and memory), associated with fatigue, depression and irritability. MCS is induced by different chemicals such as pesticides, cleaning products, perfumes, environmental tobacco smoke, formaldehyde, paintings, glues, wall papers, printers or newspapers [1–3]. The main difficulty in MCS diagnosis is to assess the causality relation between exposure and symptoms. That is why MCS is not recognized as an organic, chemical-caused illness by most of the Medical Associations. A psychosomatic condition has been suggested [3,4]. We had the opportunity to examine and follow up a patient since the diagnosis was set up. We documented the changes in MCS symptoms depending on and related with chemical indoor changing exposure, under double-blind conditions. 2. Case report A 29-year-old woman, S.W, contacted M.O. (Medical Indoor Environment Counselor) in August 2007. She is a social worker (occupational exposure not likely), married, with no previous medical ⁎ Corresponding author at: University of Strasbourg, Faculty of Medicine, Institut de Médecine légale, 11 rue HUMAN 67070 Strasbourg, France. Tel.: +33 3 68 85 33 43; fax: +33 3 68 85 33 62. E-mail address: [email protected] (R. Jacques). 0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2011.03.044
history. Since 2004, she was developing puzzling symptoms leading to many medical investigations (including EEG, MRI) and often to the emergency room without any diagnosis. She suffered from severe headache attacks with visual troubles, lasting several hours, diagnosed as “recurrent atypical ophthalmic migraines” by her GP. These attacks, at least 5 in number, occurred each time 24 to 48 h after having restored furniture during the week end. For precautionary reasons in relation with the use of painting products, she worked outside and wore gloves, but never felt uncomfortable with smells. In January 2005, the couple moved into a new apartment which was then furnished by her refurbished furniture. The headaches worsened. In March she suffered from a severe migraine crisis with a half hour partial visual lost, blurring and illusion. The following weeks, the troubles became chronic: ongoing fatigue, daily nausea, vertigo, tinnitus, visual illusions. New medical investigations failed. Nevertheless she recovered partially. Meanwhile she went on restoring other furniture using the same products again. By the end of 2005, she became pregnant and so stopped furniture restoring. She stayed in bed most of the last trimester, because of fatigue, vertigo, nausea, visual complains, which she assumed to be normal pregnancy symptoms. She gave birth to twins in September 2006. In January 2007, the couple started refurbishing furniture again using the same painting products with the same health consequences. During summer 2007, her apartment was investigated for indoor air pollutants (MO and RB). Samples of dust (sleeping room, living room and kitchen) and material (living room wooden door and painting products) revealed contaminations by different organic compounds. Although she was still complaining about dysesthesia circumoral, burning hands and legs feelings, visual disturbance, nausea and vomiting, severe fatigue, sleep disorders (awaking with balance trouble,
B. Ralph et al. / Journal of the Neurological Sciences 306 (2011) 154–156
vasomotor flush, sweating and shivering) her neurological examination (JR) was normal in fall 2007. She was worried because of the possible intrauterine exposure of her children during pregnancy and after and became stressed and anxious. Because of a professional promotion of her husband, the family had to move out. They got rid of the refurbished furniture and cleaned and washed thoroughly what would be kept. S.W. resigned and moved to her parent's house since the new home was not ready. Surprisingly, she noted that her health condition improved during her stay in her parent's house but the symptoms reappeared regularly at the new home during night in the bedroom. We must underline again that, at that time, nobody used painting products or solvents and that nobody was disturbed by any odour. As the link between the appearance of symptoms and the bedroom appeared clearly, the foam of the bed mattress was analyzed revealing a contamination of the foam by permethrin (scentless). The patient recovered slowly after the exchange and replacement of the contaminated (permethrin) bed mattress by a non contaminated one (that was also analyzed). After clinical improvement, neurophysiological investigations (electromyography and nerve conduction studies) were normal by the beginning of 2008. Neuropsychological testing still revealed attention impairment at the PASAT test but executive function, motor abilities, learning and short-term memory, verbal fluency, visuospatial skills were preserved. At that time, Misses S.W refused any supplementary investigations (e.g. SPECT scanning, LAT or LTT). Since the moving into her new home, S.W. still has clinical symptoms but these are drastically reduced both in frequency and in intensity, meaning that she still has headaches from time to time but less severe and more seldom. S.W. describes these headaches as “normal” headaches not comparable to the severe headache attacks she used to have while being exposed to permethrin, solvents and flame retardants.
3. Investigations on indoor air quality Though, seven-days-old-dust-samples were taken in different pieces including the sleeping and living room and the kitchen through a classic vacuum cleaner by the patient and sent to Luxembourg to be analyzed for biocides, pyrethroids and organophosphorous esters. The analyses, including three dust samples and two material samples were performed by the National Laboratory for Health according the SOP-B-29 method, extraction, derivatisation, identification and quantification by gas chromatography and mass spectrometry including 17 different biocides,1 8 pyrethroids2 and 8 different organo-phosphorous esters.3 After the accidental re-exposure, a supplementary sample was taken from the foam of the bed mattress. This sample was analyzed following the same procedure described before. Secondary contaminations during transport could be excluded. The results of the dust samples revealed the presence of different organic semi-volatile compounds in the kitchen (Permethrin 4.1 mg/kg dust, Propiconazol 2,5 mg/kg, TBEP 27 mg/kg and TCPP 29 mg/kg), the living room (Permethrin 5,5 mg/kg, Propiconazol 1,1 mg/kg and PCP 1,6 mg/kg) as well as in the bedroom (Permethrin 10 mg/kg). Whereas Propiconazol, Pentachlorphenol and Permethrin are commonly used as biocides against insects or moulds, TBEP and TCPP belong to the group of organo-phosphorous esters commonly used as flame retardants. The painting product contained, according to the analyses, different volatile
1 Azaconazole, chlorothalonil, chlorpyrifos, 4,4′-DDE, 4,4′-DDT, dichlofluanid, dieldrin, endosulfan, Eulan, lindan, methoxychlor, pentachlorophenol, propiconazol, tetrachlorvinphos, tolyfluanid and tribromophenol, tebuconazol. 2 Permethrin, cyfluthrin, cypermethrin, deltamethrin, fenvalerate, phenothrin, tetramethrin and piperonyl butoxid. 3 2-ethylhexyl-diphenyl-phosphate EHDPP, tributyl-phosphate TBP, triphenyl-phosphate TPP, tris(2-butoxyethyl)-phosphate TBEP, tris(2-chloroethyl)-phosphate TCEP, tris(3chloropropyl)-phosphate TCPP; tris(1,3-dichloro-2-propyl)-phosphate TDCP or TDCPP and tris(2-ethylhexyl)-phosphate TEHP.
155
organic compounds: xylenes, ethylbenzene, probylbenzene, trimethylbenzenes and butoxyethanol. Finally the bed mattress was heavily contaminated with permethrin (30 mg/kg foam). 4. Discussion Many investigators looked for laboratory testing to confirm the diagnosis, or at least a relation between symptoms and chemical exposure [5–7]. Provocation test and odor perception differences were also proposed to discriminate MCS patients from controls [8–10]. Seldom environmental toxicological investigations in situ, for example, personal sampling [11] or air sampling [12] were used to assess the exposure. The originality of our case is the accidental re-exposure to a scentless chemical (permethrin). The contaminated mattress was contributing to a regular long time exposure by inhalation and by dermal pathways (permethrin is highly lipid-soluble). We consider this accidental reexposure as a double blind non-controlled re-exposure study. We have found no other reports or studies of this type. As known, re-exposure is the highest value criterion to prove a causal link and to assess causality of pharmacological treatments side-effects [13,14]. The imputation criterion between the symptoms and the toxic cocktail is fulfilled. Considering the diagnosis criteria for MCS of the 1999 consensus [15], our case fits well and the diagnosis is obvious. The first attacks were diagnosed as “recurrent atypical ophthalmic migraines”. Following the International classification of headaches disorders [16] only a few chemicals are known to trigger headaches. Migraineurs as well as MCS patients show a sensitization to environmental triggers and chronic anxiety with panic disorders [17–19]. The severity of the first attacks in MCS may trigger a “posttraumatic stress disorder” [20]. Neuropsychological examination showed in the SW case, even during the improvement phase, persistence of attention troubles [21–23]. These cognitive disorders (attention and memory) could be related to impairment of the hippocampus area (as shown by brain SPECT hypoactivity) [23]. The reappearance of symptoms after re-exposure to permethrin excludes a solvent syndrome or an olfactive syndrome, since permethrin is not a solvent and absolutely odorless. The neuropsychological profile and clinical facts contribute also to exclude a solvent syndrome [24]. In the dust samples of the indoor environment, five different chemicals belonging to the groups of biocides, pyrethroids and organophosphorous esters were identified and quantified. All five pollutants are soluble in fat and thus accumulate in fatty tissues within the human organism. They are absorbed through ingestion, inhalation and dermal pathways. This last pathway is especially important in the case of the contaminated bed mattress because of the supplementary dermal exposure by permethrin. The biological mechanism of permethrin consists in the extension of transmembranous flux of sodium into the cell during the excitation phase inducing repetitious excitations of nerves and enhancing the affinity of sensory receptors [25]. In animal testing, Type I-pyrethroids like permethrin induce the so called “T-syndrome” characterized by an increase of tremor and ataxia as well as an increase of sensibility and sensitivity to external excitations. We do not know the exact role of these biological mechanisms in the pathogenesis of our case. Our report highlights two original points. First, in our case the reappearance of MCS symptoms after an accidental re-exposure to one scentless semi-volatile chemical (permethrin), can be considered as a double blind-re-exposure study in situ. Second, environmental toxicology investigations were warrant for a correct treatment and prevention measures. Acknowledgements Gilbert Hansen and Marc Fischer, Laboratoire d'Hygiène du Milieu et de Surveillance Biologique, National Laboratory for Health Luxembourg.
156
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References [1] Weiss B. Neurobehavioral properties of chemical sensitivity syndromes. Neurotoxicology 1998;19(2):259–68. [2] Seidel HJ. Praxis der Umweltmedizin: Grundlagen, Fakten und Informationen für einen verantwortungsvollen Umgang mit Umwelt und menschlicher Gesundheit. Thieme-Verlag; 1998. p. 432–5. [3] Winder C. Mechanisms of multiple chemical sensitivity. Toxicol Letters 2002;128: 85–97. [4] McKeown-Eyssen GE, Baines CJ, Marshall LM, Jazmaji V, Sokoloff ER. Multiple chemical sensitivity: discriminant validity of case definitions. Arch Environ Health 2001;56:406–12. [5] Kehrl HR. Laboratory testing of the patient with multiple chemical sensitivity. Environ Health Perspect 1997;105(Suppl2):443–4. [6] Hoover DR, Donnay A, Mitchell CS, Ziem G, Rose NR, Sabath DE, et al. Reproducibility of immunological tests used to assess multiple chemical sensitivity syndrome. Clin Diagn Lab Immunol 2003 Nov;10(6):1029–36. [7] Baines CJ, McKeown-Eyssen GE, Riley N, Cole DEC, Marshall L, Loescher B, et al. Case-control study of multiple chemical sensitivity, comparing haematology, biochemistry, vitamins and serum volatile organic compound measures. Occup Med (Lond) 2004 Sep;54(6):408–18. [8] Eissenberg T, Griffiths RR. Human drug discrimination and multiple chemical sensitivity: caffeine exposure as an experimental model. Environ Health Perspect 1997;105(Suppl 2):509–13. [9] Ojima M, Tonori H, Sato T, Sakabe K, Miyata M, Ishikawa S, et al. Odor perception in patients with multiple chemical sensitivity. Tohoku J Exp Med 2002 Nov;198(3): 163–73. [10] Papo D, Eberlein-König B, Berresheim HW, Huss-Marp J, Grimm V, Ring J, et al. Chemosensory function and psychological profile in patients with multiple chemical sensitivity: comparison with odor-sensitive and asymptomatic controls. J Psychosom Res Feb, 2006;60(2):199–209. [11] Shinohara N, Mizukoshi A, Yanagisawa Y. Identification of responsible volatile chemicals that induce hypersensitive reactions to multiple chemical sensitivity patients. J Expo Anal Environ Epidemiol Jan, 2004;14(1):84–91. [12] Miller CS, Gammage RB, Jankovic JT. Exacerbation of chemical sensitivity: a case study. Toxicol Ind Health 1999;15:398–402.
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