Cited by 31

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Mast cell activation may explain many cases of chemical intolerance

Miller, Claudia S., Palmer, Raymond F., Dempsey, Tania T., Ashford, Nicholas A., Afrin, Lawrence B.·2021·Environmental Sciences Europe

Abstract

Background: This paper explores the relationship between chemical intolerance (CI) and mast cell activation syndrome (MCAS). Worldwide observations provide evidence for a two-stage disease process called toxicant-induced loss of tolerance (TILT) as a mechanism for CI. TILT is initiated by a major exposure event or a series of lower-level exposures. Subsequently, affected individuals report that common chemical inhalants, foods, and drugs (i.e., various xenobiotics) trigger multi-system symptoms. Purpose: To determine whether MCAS provides a plausible biological mechanism for CI/TILT. Methods: Using the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with MCAS (n = 147) to individuals who reported chemical intolerances (CI/TILT) following various exposures (n = 345) and to healthy controls (n = 76). Using ANOVA, we compared QEESI scores across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results: More than half (59%) of the MCAS group met criteria for CI. A logistic regression model illustrates that as the likelihood of patients having MCAS increased, their likelihood of having CI/TILT similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom and intolerance patterns were nearly identical for the CI and MCAS groups. Discussion: We present data suggesting that xenobiotic activation of mast cells may underlie CI/TILT. The strikingly similar symptom and intolerance patterns for MCAS and TILT suggest that xenobiotics disrupt mast cells, leading to either or both of these challenging conditions. Faced with patients suffering from complex illness affecting multiple organ systems and fluctuating inflammatory, allergic, and dystrophic symptoms, clinicians can now ask themselves two questions: (1) Could MCAS be at the root of these problems? (2) Could environmental exposures be driving MC activation and mediator release? Increasing our understanding of the connection between TILT and MCs has the potential to expose a new link between environmental exposures and illness, offering new opportunities for improving individual and public health. Conclusion: The close correspondence between QEESI scores and symptom patterns for MCAS and TILT patients supports xenobiotic-driven mast cell activation and mediator release (i.e., MCAS) as a plausible unifying biological mechanism for CI/TILT, with profound implications for medicine, public health, and regulatory toxicology.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12302-021-00570-3

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Figures

Image 1
CC-BY · From the PDF
Image 2
CC-BY · From the PDF
Image 3
CC-BY · From the PDF
Image 4
CC-BY · From the PDF
Image 5
CC-BY · From the PDF
Image 6
CC-BY · From the PDF
Image 7
CC-BY · From the PDF

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 74

  1. Steinemann A (2018) National prevalence and effects of multiple chemical sensitivities. J Occup Environ Med 60(3):e152–e156. https://doi.org/10.1097/JOM.0000000000001272 · DOI
  2. Hojo S, Mizukoshi A, Azuma K, Okumura J, Ishikawa S, Miyata M, Mizuki M, Ogura H, Sakabe K (2018) Survey on changes in subjective symptoms, onset/trigger factors, allergic diseases, and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity. Int J Hyg Environ Health 221(8):1085–1096. https://doi.org/10.1016/j.ijheh.2018.08.001 · DOI
  3. Macy E (2018) Chapter 16—Multiple drug intolerance syndrome. In: Khan DA, Banerji A (eds) Drug allergy testing. Elsevier, Amsterdam, pp 165–168, ISBN 9780323485517, · DOI
  4. Young E, Stoneham MD, Petruckevitch A, Barton J, Rona R (1994) A population study of food intolerance. Lancet 343(8906):1127–1130. https://doi.org/10.1016/S0140-6736(94)90234-8 · DOI
  5. Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, Sigurdardottir ST, Lindner T, Goldhahn K, Dahlstrom J, McBride D, Madsen C (2007) The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 120(3):638–646. https://doi.org/10.1016/j.jaci.2007.05.026 · DOI
  6. Ashford N, Miller C (1998) Chemical exposures: low levels and high stakes. Van Nostrand Reinhold, New York
  7. Masri S, Miller CS, Palmer RF, Ashford N (2021) Toxicant-induced loss of tolerance for chemicals, foods, and drugs: assessing patterns of exposure behind a global phenomenon. Environ Sci Eur 33:65. https://doi.org/10.1186/s12302-021-00504-z · DOI
  8. Moon TC, Befus AD, Kulka M (2014) Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol 5:569. https://doi.org/10.3389/fimmu.2014.00569 · DOI
  9. Miller CS (1996) Chemical sensitivity: symptom, syndrome or mechanism for disease? Toxicology 111:69–86. https://doi.org/10.1016/0300-483x(96)03393-8 · DOI
  10. Rossi S, Pitidis A (2018) Multiple chemical sensitivity: review of the state of the art in epidemiology, diagnosis, and future perspectives. J Occup Environ Med 60(2):138–146. https://doi.org/10.1097/JOM.0000000000001215 · DOI
  11. Dantoft TM, Andersson L, Nordin S, Skovbjerg S (2015) Chemical intolerance. Curr Rheumatol Rev 11(2):167–184. https://doi.org/10.2174/157339711102150702111101 · DOI
  12. Clauw DJ (2001) Potential mechanisms in chemical intolerance and related conditions. Ann N Y Acad Sci 933:235–253. https://doi.org/10.1111/j.1749-6632.2001.tb05828.x · DOI
  13. Wong GW, Zhuo L, Kimata K, Lam BK, Satoh N, Stevens RL (2014) Ancient origin of mast cells. Biochem Biophys Res Commun 451(2):314–318. https://doi.org/10.1016/j.bbrc.2014.07.124 · DOI · Paper page
  14. Crivellato E, Travan L, Ribatti D (2015) The phylogenetic profile of mast cells. Methods Mol Biol 1220:11–27. https://doi.org/10.1007/978-1-4939-1568-2_2 · DOI
  15. Crivellato E, Ribatti D (2010) The mast cell: an evolutionary perspective. Biol Rev Camb Philos Soc 85(2):347–360. https://doi.org/10.1111/j.1469-185X.2009.00105.x · DOI
  16. Afrin LB (2016) (2016) Mast cell activation disease and the modern epidemic of chronic inflammatory disease. Transl Res 174:33–59. https://doi.org/10.1016/j.trsl.2016.01.003 · DOI · Paper page
  17. Krystel-Whittemore M, Dileepan KN, Wood JG (2016) Mast cell: a multi-functional master cell. Front Immunol. https://doi.org/10.3389/fimmu.2015.00620 · DOI
  18. Afrin LB, Pöhlau D, Raithel M, Haenisch B, Dumoulin FL, Homann J, Mauer UM, Harzer S, Molderings GJ (2015) Mast cell activation disease: an underappreciated cause of neurologic and psychiatric symptoms and diseases. Brain Behav Immun 50:314–332. https://doi.org/10.1016/j.bbi.2015.07.002 · DOI · Paper page
  19. Frieri M (2018) Mast cell activation syndrome. Clin Rev Allergy Immunol 54(3):353–365. https://doi.org/10.1007/s12016-015-8487-6 · DOI
  20. Gilfillan AM, Austin SJ, Metcalfe DD (2011) Mast cell biology: introduction and overview. Adv Exp Med Biol 716:2–12. https://doi.org/10.1007/978-1-4419-9533-9_1 · DOI
  21. Elieh Ali Komi D, Wöhrl S, Bielory L (2020) Mast cell biology at molecular level: a comprehensive review. Clin Rev Allergy Immunol 58(3):342–365. https://doi.org/10.1007/s12016-019-08769-2 · DOI
  22. Molderings GJ (2015) The genetic basis of mast cell activation disease—looking through a glass darkly. Crit Rev Oncol Hematol 93(2):75–89. https://doi.org/10.1016/j.critrevonc.2014.09.001 · DOI · Paper page
  23. Velez TE, Bryce PJ, Hulse KE (2018) Mast cell interactions and crosstalk in regulating allergic inflammation. Curr Allergy Asthma Rep 18(5):1–7. https://doi.org/10.1007/s11882-018-0786-6 · DOI
  24. Kalesnikoff J, Galli SJ (2008) New developments in mast cell biology. Nat Immunol 9(11):1215–1223. https://doi.org/10.1038/ni.f.216 · DOI
  25. Fujimaki H, Imai T, Befus D (1992) Mast cell response to formaldehyde 2 Induction of stress-like proteins. Int Arch Allergy Immunol 98(4):332–338. https://doi.org/10.1159/000236207 · DOI
  26. Janiszewski J, Bienenstock J, Blennerhassett MG (1994) Picomolar doses of substance P trigger electrical responses in mast cells without degranulation. Am J Physiol 267:C138–C145 · DOI
  27. Molderings G, Haenisch B, Brettner S, Homann J, Menzen M, Dumoulin FL, Panse J, Butterfield J, Afrin LB (2016) Pharmacological treatment options for mast cell activation disease. Naunyn-Schmiedeberg’s Arch Pharmacol 389:671–694. https://doi.org/10.1007/s00210-016-1247-1 · DOI
  28. Wirz S, Molderings J (2017) Practical guide for treatment of pain in patients with systemic mast cell activation. Disease Pain Physician 20:E849–E861
  29. Caress SM, Steinemann AC (2004) Prevalence of multiple chemical sensitivities: a population-based study in the southeastern United States. Am J Public Health 94(5):746–747. https://doi.org/10.2105/ajph.94.5.746 · DOI
  30. Azuma K, Uchiyama I, Katoh T, Ogata H, Arashidani K, Kunugita N (2015) Prevalence and characteristics of chemical intolerance: a Japanese population-based study. Arch Environ Occup Health 70:341–353. https://doi.org/10.1080/19338244.2014.926855 · DOI
  31. Kreutzer R, Neutra RR, Lashuay N (1999) Prevalence of people reporting sensitivities to chemicals in a population-based survey. Am J Epidemiol 150(1):1–12. https://doi.org/10.1093/oxfordjournals.aje.a009908 · DOI
  32. Afrin LB, Molderings GJ (2014) A concise, practical guide to diagnostic assessment for mast cell activation disease. World J Hematol 3(1):1–17. https://doi.org/10.5315/wjh.v3.i1.1 · DOI
  33. Miller CS, Prihoda T (1999) The Environmental Exposure and Sensitivity Inventory (EESI): a standardized approach for measuring chemical intolerances for research and clinical applications. Toxicol Ind Health 15:370–385. https://doi.org/10.1177/074823379901500311 · DOI
  34. Palmer RF, Walker T, Kattari D, Rincon R, Perales RB, Jaén CR, Grimes C, Sundblad DR, Miller CS (2021) Validation of a brief screening instrument for chemical intolerance in a large U.S. National Sample. Int Environ Res Public Health 18:8714. https://doi.org/10.3390/ijerph18168714 · DOI
  35. Miller CS (1999) Are we on the threshold of a new theory of disease? Toxicant-induced loss of tolerance and its relationship to addiction and abdiction. Toxicol Environ Health 15(3–4):284–294. https://doi.org/10.1177/074823379901500302 · DOI
  36. SAS Institute Inc (2014) SAS® 9.4 statements: reference, 3rd edn. SAS Institute Inc., Cary, NC
  37. Bornschein S, Hausteiner C, Zilker T, Forst H (2002) Psychiatric and somatic disorders and multiple chemical sensitivity (MCS) in 264 ‘environmental patients.’ Psychol Med 32(8):1387–1394. https://doi.org/10.1017/S0033291702006554 · DOI
  38. Steinemann A (2019) International prevalence of chemical sensitivity, co-prevalence with asthma and autism, and effects from fragranced consumer products. Air Qual Atmos Health 12(5):519–527. https://doi.org/10.1007/s11869-019-00672-1 · DOI
  39. Miller CS (2000) Mechanisms of action of addictive stimuli. Addiction 96:115–139 · DOI
  40. Miller CS, Mitzel HC (1995) Chemical sensitivity attributed to pesticide exposure versus remodeling. Arch Environ Health 50(2):119–129. https://doi.org/10.1080/00039896.1995.9940889 · DOI
  41. Gibson PR, Nicole-Marie AE, Ruding LA (2003) Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity. Environ Health Perspect 111:12. https://doi.org/10.1289/ehp.5936 · DOI
  42. Roberts LJ (1988) Carcinoid syndrome and disorders of systemic mast-cell activation including systemic mastocytosis. Endocrinol Metab Clin North Am 17(2):415–436 · DOI
  43. Roberts LJ (1984) Recurrent syncope due to systemic mastocytosis. Hypertension 6(2, Pt 1):285–294 · DOI
  44. Li N, Zhang X, Dong H, Hu Y, Qian Y (2017) Bidirectional relationship of mast cells-neurovascular unit communication in neuroinflammation and its involvement in POCD. Behav Brain Res 322:60–69. https://doi.org/10.1016/j.bbr.2017.01.006 · DOI
  45. Meggs WJ (2017) The role of neurogenic inflammation in chemical sensitivity. Ecopsychology 9(2):83–89. https://doi.org/10.1089/eco.2016.0045 · DOI
  46. Meggs WJ (1995) Neurogenic switching: a hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity. Environ Health Perspect 103:54–56. https://doi.org/10.1289/ehp.9510354 · DOI
  47. Dantoft TM, Elberling J, Brix S, Szecsi PB, Vesterhauge S, Skovbjerg S (2014) An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity. Psychoneuroendocrinology 40:140–150. https://doi.org/10.1016/j.psyneuen.2013.11.012 · DOI
  48. Silverman AJ, Sutherland AK, Wilhelm M, Silver R (2000) Mast cells migrate from blood to brain. J Neurosci 20(1):401–408. https://doi.org/10.1523/JNEUROSCI.20-01-00401.2000 · DOI · Paper page
  49. Song Y, Lu M, Yuan H, Chen T, Han X (2020) Mast cell-mediated neuroinflammation may have a role in attention deficit hyperactivity disorder. Exp Ther Med 20:714–726. https://doi.org/10.3892/etm.2020.8789 · DOI
  50. Theoharides TC, Kempuraj D, Tagen M, Conti P, Kalogeromitroset D (2007) Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 217(1):65–78. https://doi.org/10.1111/j.1600-065X.2007.00519.x · DOI
  51. Theoharides TC (2017) Neuroendocrinology of mast cells: challenges and controversies. Exp Dermatol 26(9):751–759. https://doi.org/10.1111/exd.13288 · DOI
  52. Theoharides TC (2020) The impact of psychological stress on mast cells. Ann Allergy Asthma Immunol. https://doi.org/10.1016/j.anai.2020.07.007 · DOI
  53. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC (2015) Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther 37(5):984–995. https://doi.org/10.1016/j.clinthera.2015.04.002 · DOI · Paper page
  54. De Luca C, Scordo MG, Cesareo E, Pastore S, Mariani S, Maiani G, Stancato A, Loreti B, Valacchi G, Lubrano C, Raskovic D, De Padova L, Genovesi G, Korkina LG (2010) Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes. Toxicol Appl Pharmacol 248:285–292. https://doi.org/10.1016/j.taap.2010.04.017 · DOI
  55. Belpomme D, Campagnac C, Irigaray P (2015) Reliable disease biomarkers characterizing and identifying electrohypersensitivity and multiple chemical sensitivity as two etiopathogenic aspects of a unique pathological disorder. Rev Environ Health 30:251–271. https://doi.org/10.1515/reveh-2015-0027 · DOI
  56. Kimata H (2004) Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity. Int J Hyg Environ Health 207:159–163. https://doi.org/10.1078/1438-4639-00262 · DOI
  57. Xiong S, Rodgers K (1997) Effects of malathion metabolites on degranulation of and mediator release by human and rat basophilic cells. J Toxicol Environ Health 51(2):159–175. https://doi.org/10.1080/00984109708984019 · DOI
  58. Forsythe P (2015) The parasympathetic nervous system as a regulator of mast cell function. In: Hughes M, McNagny K (eds) Mast cells. Methods in molecular biology (methods and protocols), vol 1220. Humana Press, New York
  59. Lindsberg PJ, Strbian D, Karjalainen-Lindsberg ML (2010) Mast cells as early responders in the regulation of acute blood-brain barrier changes after cerebral ischemia and hemorrhage. J Cereb Blood Flow Metab 30:689–702. https://doi.org/10.1038/jcbfm.2009.282 · DOI
  60. Bunegin L, Mitzel HC, Miller CS, Gelineau JF, Tolstykh GP (2001) Cognitive performance and cerebrohemodynamics associated with the Persian Gulf Syndrome. Toxicol Ind Health 17(4):128–137. https://doi.org/10.1191/0748233701th100oa · DOI
  61. Medeiros WLG Junior, Bandeira IP, Franzoi AEA, Brandão WN, Santos Durão ACCD, Gonçalves MVM (2019). Mast cells: A key component in the pathogenesis of Neuromyelitis Optica Spectrum Disorder? Immunobiology. 224(5):706–709. https://doi.org/10.1016/j.imbio.2019.05.010 · DOI
  62. Pang X, Letourneau R, Rozniecki JJ, Wang L, Theoharides TC (1996) Definitive characterization of rat hypothalamic mast cells. Neuroscience 73(3):889–902. https://doi.org/10.1016/0306-4522(95)00606-0 · DOI
  63. Theoharides TC, Stewart JM, Hatziagelaki E, Kolaitis G (2015) Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Front Neurosci. https://doi.org/10.3389/fnins.2015.00225 · DOI
  64. Palmer RF, Jaén CR, Perales RB, Rincon R, Forster JN, Miller CS (2020) Three questions for identifying chemically intolerant individuals in clinical and epidemiological populations: The Brief Environmental Exposure and Sensitivity Inventory (BREESI). PLoS ONE. https://doi.org/10.1371/journal.pone.0238296 · DOI
  65. Hojo S, Sakabe K, Ishikawa S, Miyata M, Kumano H (2009) Evaluation of subjective symptoms of Japanese patients with multiple chemical sensitivity using QEESI©. Environ Health Prevent Med 14:267–275. https://doi.org/10.1007/s12199-009-0095-8 · DOI
  66. Yun MJ, Kang DM, Lee K-H, Kim YK, Kim JE (2013) Multiple chemical sensitivity caused by exposure to ignition coal fumes: a case report. Ann Occup Environ Med 25:32. https://doi.org/10.1186/2052-4374-25-32 · DOI
  67. Imai N, Imai Y (2011) Necessity of counseling institutions for sick building syndrome patients. In: Abdul-Wahab SA (ed) Sick building syndrome: in public buildings and workplaces, p 365. Springer, Berlin
  68. Shaik Y, Caraffa A, Ronconi G, Lessiani G, Conti P (2018) Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin. Central-Eur J Immunol 43(4):476–481. https://doi.org/10.5114/ceji.2018.81347 · DOI
  69. Oksaharju A, Kankainen M, Kekkonen RA, Lindstedt KA, Kovanen PT, Korpela R, Miettinen M (2011) Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. World J Gastroenterol 17(6):750–759. https://doi.org/10.3748/wjg.v17.i6.750 · DOI
  70. Taniguchi T, Wang JK, Spector S (1980) Properties of (3H) diazepam binding to rat peritoneal mast cells. Life Sci 27(2):171–178. https://doi.org/10.1016/0024-3205(80)90460-9 · DOI
  71. Haenisch B, Huber M, Wilhelm T, Steffens M, Molderings GJ (2013) Investigation into mechanisms mediating the inhibitory effect of 1,4-benzodiazepines on mast cells by gene expression profiling. Life Sci 92(6–7):345–351. https://doi.org/10.1016/j.lfs.2013.01.010 · DOI
  72. Heilbrun LP, Palmer RF, Jaen CR, Svoboda MD, Miller CS, Perkins J (2015) Maternal chemical and drug intolerances: potential risk factors for autism and attention deficit hyperactivity disorder (ADHD). J Am Board Fam Med 28(4):461–470. https://doi.org/10.3122/jabfm.2015.04.140192 · DOI
  73. Theoharides TC (2009) Autism spectrum disorders and mastocytosis. Int J Immunopathol Pharmacol 22(4):859–865. https://doi.org/10.1177/039463200902200401 · DOI
  74. Minton NA, Murray VSG (1988) A review of organophosphate poisoning. Med Toxicol Adverse Drug Exp 3:350–375. https://doi.org/10.1007/BF03259890 · DOI

Metadata

Authors
Miller, C. S., Palmer, R. F., Dempsey, T. T., Ashford, N. A., & Afrin, L. B.
Venue
Environmental Sciences Europe
Published
2021-11-17
Volume
33
Issue
1
ISSN
  • 2190-4707
  • 2190-4715
Cited by
31
References
6
Language
en
Funders
Marilyn Brachman Hoffman Foundation Fort Worth TX

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review