Abstract
Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of female patients with fibromyalgia (FM) compared with patients with systemic sclerosis (SSc) and with healthy female controls. Olfactory functions were assessed in 24 patients with FM, 20 patients with SSc and 21 age-matched healthy controls. The sense of smell was evaluated using the Sniffin’ Sticks test including the three stages of smell: threshold, discrimination, and identification (TDI) of the different odors. The severity of fibromyalgia was assessed using the fibromyalgia impact questionnaire (FIQ). The short form 36 (SF-36) questionnaire was also completed in order to seek a relationship between the patients perception of quality of life and the different aspects of the smell sense. Depression was evaluated in both FM and SSc patients utilizing the Beck depression inventory-II (BDI-II) questionnaire. Patients with FM had significantly lower TDI smell scores compared with both SSc patients and healthy controls (p < 0.005, One-Way ANOVA). Hyposmia (defined as TDI scores below 30) were observed in 14 of 24 (42 %) patients with FM compared to 3 of 20 (15 %) patients with SSc and 1 of the healthy controls (4.3 %) (p < 0.02). FM patients had significantly lower thresholds of smell compared to both healthy controls and patients with SSc (p < 0.001), whereas for patients with SSc only the ability to discriminate between odors was impaired (p < 0.006). We could not detect any statistical correlation between smell abilities and clinical manifestation of SSc or the FIQ and SF-36 scores among FM patients. However the correlation between depression, defined by the BDI-II score, and the sense of smell differed between patients with FM and patients with SSc. As only among SSc patients a lower sense of smell correlated with a higher BDI-II score (p = 0.02). Our findings suggest that there is a decrease in the sense of smell both in FM and SSc patients compared with healthy controls. However these impairments differ between patients group and might represent different mechanisms that affect the sense of smell.
Similar content being viewed by others
References
Doty RL. Olfaction in Parkinson’s disease and related disorders. Neurobiol Dis. 2012;46:527–52.
Moberg PJ, Kamath V, Marchetto DM, Calkins ME, Doty RL, Hahn CG, Borgmann-Winter KE, Kohler CG, Gur RE, Turetsky BI. Meta-Analysis of olfactory function in schizophrenia, first-degree family members, and youths at-risk for psychosis. Schizophr Bull. 2013;40:50–9.
Ortega-Hernandez OD, Kivity S, Shoenfeld Y. Olfaction, psychiatric disorders and autoimmunity: is there a common genetic association? Autoimmunity. 2009;42:80–8.
Demarquay G, Ryvlin P, Royet JP. Olfaction and neurological diseases: a review of the literature. Rev Neurol (Paris). 2007;163:155–67.
Strous RD, Shoenfeld Y. To smell the immune system: olfaction, autoimmunity and brain involvement. Autoimmun Rev. 2006;6:54–60.
Leon-Sarmiento FE, Bayona EA, Bayona-Prieto J, Osman A, Doty RL. Profound olfactory dysfunction in myasthenia gravis. PLoS One. 2012;7:e45544.
Benkler M, Agmon-Levin N, Shoenfeld Y. Parkinson’s disease, autoimmunity, and olfaction. Int J Neurosci. 2009;119:2133–43.
Katzav A, Solodeev I, Brodsky O, Chapman J, Pick CG, Blank M, Zhang W, Reichlin M, Shoenfeld Y. Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system. Arthritis Rheum. 2007;56:938–48.
Katzav A, Ben-Ziv T, Chapman J, Blank M, Reichlin M, Shoenfeld Y. Anti-P ribosomal antibodies induce defect in smell capability in a model of CNS-SLE (depression). J Autoimmun. 2008;31:393–8.
Katzav A, Ben-Ziv T, Blank M, Pick CG, Shoenfeld Y, Chapman J. Antibody-specific behavioral effects: Intracerebroventricular injection of antiphospholipid antibodies induces hyperactive behavior while anti-ribosomal-P antibodies induces depression and smell deficits in mice. J Neuroimmunol. 2014;272:10–15.
Kivity S, Ortega-Hernandez OD, Shoenfeld Y. Olfaction—a window to the mind. Isr Med Assoc J. 2009;11:238–43.
Kivity S, Tsarfaty G, Agmon-Levin N, Blank M, Manor D, Konen E, Chapman J, Reichlin M, Wasson C, Shoenfeld Y, Kushnir T. Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus. Ann N Y Acad Sci. 2010;1193:70–7.
Moscavitch SD, Szyper-Kravitz M, Shoenfeld Y. Smell: integrating neurodegeneration and autoimmunity-a personal view. Acta Reumatol Port. 2009;34:190–6.
Moscavitch SD, Szyper-Kravitz M, Shoenfeld Y. Autoimmune pathology accounts for common manifestations in a wide range of neuro-psychiatric disorders: the olfactory and immune system interrelationship. Clin Immunol. 2009;130:235–43.
Perricone C, Agmon-Levin N, Shoenfeld N, de Carolis C, Guarino MD, Gigliucci G, Milana I, Novelli L, Valesini G, Perricone R, Shoenfeld Y. Evidence of impaired sense of smell in hereditary angioedema. Allergy. 2011;66:149–54.
Perricone C, Shoenfeld N, Agmon-Levin N, de Carolis C, Perricone R, Shoenfeld Y. Smell and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45:87–96.
Shoenfeld N, Agmon-Levin N, Flitman-Katzevman I, Paran D, Katz BS, Kivity S, Langevitz P, Zandman-Goddard G, Shoenfeld Y. The sense of smell in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1484–7.
Shoenfeld Y. To smell autoimmunity: anti-P-ribosomal autoantibodies, depression, and the olfactory system. J Autoimmun. 2007;28:165–9.
Ablin JN, Amital H, Ehrenfeld M, Aloush V, Elkayam O, Langevitz P, Mevorach D, Mader R, Sachar T, Amital D, Buskila D. Guidelines for the diagnosis and treatment of the fibromyalgia syndrome. Harefuah 2013;152:742–7, 751, 750.
Amital D, Fostick L, Polliack ML, Segev S, Zohar J, Rubinow A, Amital H. Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities? J Psychosom Res. 2006;61:663–9.
Amital D, Herskovitz C, Fostick L, Silberman A, Doron Y, Zohar J, Itsekson A, Zolti M, Rubinow A, Amital H. The premenstrual syndrome and fibromyalgia–similarities and common features. Clin Rev Allergy Immunol. 2010;38:107–15.
Amital H, Ablin J, Aloush V, Hauser W, Buskila D. The first Israeli fibromyalgia congress, February 2013. Isr Med Assoc J. 2013;15:789–92.
Fitzcharles MA, Shir Y, Ablin JN, Buskila D, Amital H, Henningsen P, Hauser W. Classification and clinical diagnosis of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines. Evid Based Complement Alternat Med. 2013;2013:528952.
Grodman I, Buskila D, Arnson Y, Altaman A, Amital D, Amital H. Understanding fibromyalgia and its resultant disability. Isr Med Assoc J. 2011;13:769–72.
Milstein R, Amital D, Arnson Y, Amital H. Retraumatization eliciting the presentation of fibromyalgia. Isr Med Assoc J. 2013;15:123–4.
Vishne T, Fostick L, Silberman A, Kupchick M, Rubinow A, Amital H, Amital D. Fibromyalgia among major depression disorder females compared to males. Rheumatol Int. 2008;28:831–6.
Wilbarger JL, Cook DB. Multisensory hypersensitivity in women with fibromyalgia: implications for well being and intervention. Arch Phys Med Rehabil. 2011;92:653–6.
Lotsch J, Kraetsch HG, Wendler J, Hummel T. Self-ratings of higher olfactory acuity contrast with reduced olfactory test results of fibromyalgia patients. Int J Psychophysiol. 2012;86:182–6.
Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013;25:707–13.
Merz EL, Malcarne VL, Assassi S, Nair DK, Graham TA, Yellman BP, Estrada YMR, Mayes MD. Biopsychosocial typologies of pain in a cohort of patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2014;66:567–74.
Milette K, Hudson M, Korner A, Baron M, Thombs BD. Sleep disturbances in systemic sclerosis: evidence for the role of gastrointestinal symptoms, pain and pruritus. Rheumatology (Oxford). 2013;52:1715–20.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Ellen CM, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. Classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747–55.
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. report of the multicenter criteria committee. Arthritis Rheum. 1990;33:160–72.
Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. 1997;22:39–52.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–83.
Neumann L, Berzak A, Buskila D. Measuring health status in Israeli patients with fibromyalgia syndrome and widespread pain and healthy individuals: utility of the short form 36-item health survey (SF-36). Semin Arthritis Rheum. 2000;29:400–8.
Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol. 1991;18:728–33.
Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck depression inventories-IA and -II in psychiatric outpatients. J Pers Assess. 1996;67:588–97.
Shean G, Baldwin G. Sensitivity and specificity of depression questionnaires in a college-age sample. J Genet Psychol. 2008;169:281–8.
Deems DA, Doty RL, Settle RG, Moore-Gillon V, Shaman P, Mester AF, Kimmelman CP, Brightman VJ, Snow JB Jr. Smell and taste disorders, a study of 750 patients from the University of pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg. 1991;117:519–28.
Mombaerts P. Love at first smell—the 2004 nobel prize in physiology or medicine. N Engl J Med. 2004;351:2579–80.
Masini CV, Holmes PV, Freeman KG, Maki AC, Edwards GL. Dopamine overflow is increased in olfactory bulbectomized rats: an in vivo microdialysis study. Physiol Behav. 2004;81:111–9.
Song C, Leonard BE. The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev. 2005;29:627–47.
Temmel AF, Quint C, Schickinger-Fischer B, Klimek L, Stoller E, Hummel T. Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch Otolaryngol Head Neck Surg. 2002;128:635–41.
Atanasova B, El-Hage W, Chabanet C, Gaillard P, Belzung C, Camus V. Olfactory anhedonia and negative olfactory alliesthesia in depressed patients. Psychiatry Res. 2010;176:190–6.
Pause BM, Miranda A, Goder R, Aldenhoff JB, Ferstl R. Reduced olfactory performance in patients with major depression. J Psychiatr Res. 2001;35:271–7.
Pause BM, Raack N, Sojka B, Goder R, Aldenhoff JB, Ferstl R. Convergent and divergent effects of odors and emotions in depression. Psychophysiology. 2003;40:209–25.
Pause BM, Hellmann G, Goder R, Aldenhoff JB, Ferstl R. Increased processing speed for emotionally negative odors in schizophrenia. Int J Psychophysiol. 2008;70:16–22.
Gross-Isseroff R, Luca-Haimovici K, Sasson Y, Kindler S, Kotler M, Zohar J. Olfactory sensitivity in major depressive disorder and obsessive compulsive disorder. Biol Psychiatry. 1994;35:798–802.
Pollatos O, Albrecht J, Kopietz R, Linn J, Schoepf V, Kleemann AM, Schreder T, Schandry R, Wiesmann M. Reduced olfactory sensitivity in subjects with depressive symptoms. J Affect Disord. 2007;102:101–8.
Drevets WC. Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci. 1999;877:614–37.
Drevets WC, Bogers W, Raichle ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol. 2002;12:527–44.
Wagner G, Koch K, Schachtzabel C, Reichenbach JR, Sauer H, Schlosser RG. Enhanced rostral anterior cingulate cortex activation during cognitive control is related to orbitofrontal volume reduction in unipolar depression. J Psychiatry Neurosci. 2008;33:199–208.
Drevets WC. Orbitofrontal cortex function and structure in depression. Ann N Y Acad Sci. 2007;1121:499–527.
Sheline YI, Gado MH, Price JL. Amygdala core nuclei volumes are decreased in recurrent major depression. NeuroReport. 1998;9:2023–8.
Whalen PJ, Shin LM, Somerville LH, McLean AA, Kim H. Functional neuroimaging studies of the amygdala in depression. Semin Clin Neuropsychiatry. 2002;7:234–42.
Croy I, Symmank A, Schellong J, Hummel C, Gerber J, Joraschky P, Hummel T. Olfaction as a marker for depression in humans. J Affect Disord. 2014;160:80–6.
Cox JJ, Sheynin J, Shorer Z, Reimann F, Nicholas AK, Zubovic L, Baralle M, Wraige E, Manor E, Levy J, Woods CG, Parvari R. Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. Hum Mutat. 2010;31:E1670–86.
Weiss J, Pyrski M, Jacobi E, Bufe B, Willnecker V, Schick B, Zizzari P, Gossage SJ, Greer CA, Leinders-Zufall T, Woods CG, Wood JN, Zufall F. Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature. 2011;472:186–90.
Zufall F, Pyrski M, Weiss J, Leinders-Zufall T. Link between pain and olfaction in an inherited sodium channelopathy. Arch Neurol. 2012;69:1119–23.
Doherty PC. On the nose: shared themes for the sensory and immune self. Nat Immunol. 2003;4:1043–5.
Appenzeller S, Carnevalle AD, Li LM, Costallat LT, Cendes F. Hippocampal atrophy in systemic lupus erythematosus. Ann Rheum Dis. 2006;65:1585–9.
Keiser HR, Henkin RI, Bartter FC, Sjoerdsma A. Loss of taste during therapy with penicillamine. JAMA. 1968;203:381–3.
Author information
Authors and Affiliations
Corresponding author
Additional information
Howard Amital and Nancy Agmon-Levin have contributed equally to this study.
Rights and permissions
About this article
Cite this article
Amital, H., Agmon-Levin, N., Shoenfeld, N. et al. Olfactory impairment in patients with the fibromyalgia syndrome and systemic sclerosis. Immunol Res 60, 201–207 (2014). https://doi.org/10.1007/s12026-014-8573-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12026-014-8573-5