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Open Access 01-04-2019 | Fibromyalgia

The role of HHV-6 and HHV-7 infections in the development of fibromyalgia

Authors: Angelika Krumina, Svetlana Chapenko, Viktorija Kenina, Marija Mihailova, Inara Logina, Santa Rasa, Sandra Gintere, Ludmila Viksna, Simons Svirskis, Modra Murovska

Published in: Journal of NeuroVirology | Issue 2/2019

Abstract

Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) are immunomodulating viruses potentially affecting the nervous system. We evaluated the influence of HHV-6 and HHV-7 infections on fibromyalgia (FM) clinical course. Forty-three FM patients and 50 control group participants were enrolled. 39.50% (n = 17) FM patients had light A delta and C nerve fiber damage, 27.91% (n = 12) had severe A delta and C nerve fiber damage. 67.44% (n = 29) FM patients had loss of warm sensation in feet, loss of heat pain sensation, and increased cold pain sensation (34.90%, n = 15 in both findings). HHV-6 and HHV-7 genomic sequences in peripheral blood DNA in 23/43 (51.00%) and 34/43 (75.50%) of samples from FM patients and in 3/50 (6.00%) and 26/50 (52.00%) of samples from the control group individuals were detected. Active HHV-6 (plasma viremia) or HHV-7 infection was revealed only in FM patients (4/23, 17.40% and 4/34, 11.80%, respectively). A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). 23/43 patients from the FM group and control group participants HHV-6 and 34/45 HHV-7 did have infection markers. A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). No difference was found between detection frequency of persistent HHV-6 and HHV-7 infection between FM patients and the control group. Statistically significant correlation was observed between quantitation of changes in QST thermal modalities and HHV-6 infection. There was no correlation between A delta and C nerve fiber damage and HHV-7 infection.

Aaron LA, Burke MM, Buchwald D (2000) Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med 160(2):221–227CrossRefPubMed

Albin J, Neumann L, Buskila D (2008) Pathogenesis of fibromyalgia – a review. Joint Bone Spine 75:273–279CrossRef

Assumpacao A, Pagano T, Matsutani L, Ferreria EAG, Pereira BAC, Marques PA (2010) Quality of life and discriminating power of two questionnaires in fibromyalgia patients: fibromyalgia impact questionnaire and medical outcomes study 36-item short-form health survey. Rev Bras Fisioter 4:284–289CrossRef

Ballantyne J.C., Cousins M.J., Gimberardino M.A., McGrath P.A., Rajagopal M.R., Smith M.T., Sommer C., Wittink H. M., (2010) Fibromyalgia: a clinical update. Pain. Clinical updates 18:4

Balon R, Wise TN (2015) Clinical challenges in the biopsychosocial interface. Update on psychosomatics for the 21st century. Adv Psychosom Med Basel, Karger 34:78–79CrossRef

Bennett R (2005) The fibromyalgia impact questionnaire (FIQ): a review of its development, current version, operating characteristics and uses. Clin Exp Rheumatol 23(39):154–162

Berneman ZN, Ablashi DV, Li G, Eger-Fletcher M, Reitz MS, Hung CL, Brus I, Komaroff AL, Gallo RC (1992) Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc Natl Acad Sci U S A 89(21):10552–10556CrossRefPubMedPubMedCentral

Blumenstiel K, Gerhardt A, Rolke R, Bieber C, Tesarz J, Friederich HC, Eich W, Treede RD (2011) Quantitative sensory testing profiles in chronic back pain are distinct from those in fibromyalgia. Clin J Pain 27(8):682–690CrossRefPubMed

Borchers AT, Gershwin ME (2015) Fibromyalgia: a critical and comprehensive review. Clin Rev Allergy Immunol 49(2):100–151CrossRefPubMed

Branco JC, Bannwarth B, Failde I, Abello Carbonell J, Blotman F, Spaeth M, Saraiva F, Nacci F, Thomas E, Caubère JP, Le Lay K, Taieb C, Matucci-Cerinic M (2010) Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum 39(6):448–453CrossRefPubMed

Buchwald D, Goldenberg DL, Sullivan JL, Komaroff AL (1987) The “chronic, active Epstein-Barr virus infection” syndrome and primary fibromyalgia. Arthritis Rheum 30(10):1132–1136CrossRefPubMed

Cassisi G, Sarzi-Puttini P, Cazzola M (2011) Chronic widespread pain and fibromyalgia: could be some relationships with infections and vaccinations? Clan Exp Rheum 29(6 Supple 69):118–126

Chan PK, Ng HK, Hui M, Cheng AF (2001) Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J Med Virol 64(1):42–46CrossRefPubMed

Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia – Larrea L, Haanpaa M, Jesen TS, Serra J, Treede R-D (2010) EFNS guidelines of neuropathic pain assessment: revised 2009. Eur J Neurol 17:1010–1018CrossRefPubMed

da Silva LA, Kazyiama HH, Teixeira MJ, de Siqueira SR (2013) Quantitative sensory testing in fibromyalgia and hemisensory syndrome: comparison with controls. Rheumatol Int 33(8):2009–2017CrossRefPubMed

Dworkin RH, Fields HL (2005) Fibromyalgia from the perspective of neuropathic pain. J Rheumatol 75:1–5

Dyck PJ, Zimmerman I, Gillen DA, Johnson D, Karnes JL, O’Brien PC (1993) Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors. Neurology 43:1500–1508CrossRefPubMed

Fox C, Walker-Bone K (2015) Evolving spectrum of HIV-associated rheumatic syndromes. Best Pract Res Clin Rheumatol 29(2):244–258CrossRefPubMedPubMedCentral

Gustorff B, Poole C, Kloimsten H, Hacker N, Likar R (2013) Treatment of neuropathic pain with the capsaicin 8% patch: quantitative sensory testing (QST) in a prospective observational study identifies potential predictors of response to capsaicin 8% patch treatment. Scand J Pain 4(3):138–145CrossRefPubMed

Hagander LG, Midani HA, Kuskowski MA, Parry GJG (2000) Quantitative sensory testing: effect of site and skin temperature on thermal thresholds. Clin Neurophysiol 111:17–22CrossRefPubMed

Hakim AJ, Keer R, Grahame R (2010) Hypermobility, fibromyalgia and chronic pain. Churchil Livingstone. Elsevier, London, p 310

Hansen C, Hopf HC, Treede RD (1996) Paradoxical heat sensation in patients with multiple sclerosis. Evidence for a supraspinal integration for temperature sensation. Brain 199:1729–1736CrossRef

Hansson P, Backonja M, Bouhassira D (2007) Usefulness and limitations of quantitative sensory testing: clinical and research application in neuropathic pain states. Pain 129:256–259CrossRefPubMed

Hovaguimian A, Gibbons CH (2011) Diagnosis and treatment of pain in small fiber neuropathy. Curr Pain Headache Rep 15(3):193–200CrossRefPubMedPubMedCentral

Jiao J, Vincent A, Cha SS, Luedtke CA, Oh TH (2014) Relation of age with symptom severity and quality of life in patients with fibromyalgia. Mayo Clin Proc 8(2):199–206CrossRef

Klauenberg S, Maier C, Assion H-J, Hoffman A, Krumova EK, Magerl W, Scherens A, Treede R-D, Juckel G (2008) Depression and changed pain perception: hints for a central disinhibition mechanism. Pain 140:332–343CrossRefPubMed

Kole AK, Roy R, Kole DC (2013) Musculoskeletal and rheumatologic disorders in HIV infection: experience in tertiary referral centre. Indian J Sex Transm Dis 34(2):107–112CrossRef

Kondo K, Yamanishi K (2007) HHV-6A, 6B, and 7: molecular basis of latency and reactivation. In: Arvin A, Campadelli-Fiume G, Mocarski E et al (eds) Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge University Press, Cambridge Chapter 47

Kozanoglu E, Canataroglu A, Abayli B, Colakoglu S, Goncu K (2003) Fibromyalgia syndrome in patients with hepatitis C infection. Rheumatol Int 23(5):248–251CrossRefPubMed

Kozireva S, Uzameckis D, Barisevs M, Murovska M (2009) Sensitivity and reproducibly of polymerase chain reaction assays for detection of human herpesviruses 6 and 7. Proc Latvian Acad Sci 63:180–185

Lucas HJ, Brauch CM, Settas L, Theoharides TC (2006) Fibromyalgia—new concepts of pathogenesis and treatment. Int J Immunopathol Pharmacol 19(1):5–9CrossRefPubMed

Lusso P (2006) HHV-6 and immune system: mechanisms of immunomodulation and viral escape. J Clin Virol 37(Suppl 1):4–1CrossRef

Martinez-Livan M (2012) Fibromyalgia: when distress becomes (un)sympathetic pain. Pain Res Treat 2012:981565

McCarberg HB, Clow JD (2009) Fibromyalgia. Informa healthcare, New York, p 163CrossRef

Mohammad A, Carey JJ, Storan E, Scarry M, Coughlan RJ, Lee JM (2012) Prevalence of fibromyalgia among patients with chronic hepatitis C infection: relationship to viral characteristics and quality of life. J Clin Gastroenterol 46(5):407–412CrossRefPubMed

Pavlakovic G, Petzke F (2010) The role of quantitative sensory testing in the evaluation of musculoskeletal pain conditions. Curr Rheumatol Rep 12:455–461CrossRefPubMedPubMedCentral

Plauf DB, Rolke R, Nickel R, Treede RD, Daublander M (2009) Somatosensory profiles in subgroup of patients with myogenic temporomandibular disorders and fibromyalgia syndrome. Pain 147:72–83CrossRef

Rogal SS, Bielefeldt K, Wasan AD, Szigethy E, Lotrich F, DiMartini AF (2015) Fibromyalgia symptoms and cirrhosis. Dig Dis Sci 60(5):1482–1489CrossRefPubMed

Rolke R, Baron R, Maier C, Tolle TR, Treede R-D, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magrel W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B (2006) Quantitative sensory testing in the German research network on neuropathic pain (DFNS): standardized protocol and reference values. Pain 123:231–243CrossRefPubMed

Secchiero P, Carrigan DR, Asano Y, Benedetti L, Crowley RW, Komaroff AL, Gallo RC, Lusso P (1995) Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis 171(2):273–280CrossRefPubMed

Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giuliani MJ, Kincard JC, Ochoa JL, Parry GJ, Weimer LH (2003) Quantitative sensory testing. Report of the therapeutics and technology assessment subcommittee of American academy of neurology. Neurology 60(6):898–904CrossRefPubMed

Sydney PBH, Conti PCR (2011) Guidelines for somatosensory evaluation of temporomandibular dysfunction and orofacial pain patients. Rev Dor São Paulo 12(4):349–353

Tampina B, Slater H, Halla T, Lee G, Briffa NK (2012) Quantitative sensory testing somatosensory profiles in patients with cervical radiculopathy are distinct from those in patients with nonspecific neck-arm pain. Pain 153:2403–2414CrossRef

Themistocleus AC, Ramirez JD, Serra J, Bennett DLH (2014) The clinical approach to small fiber neuropathy and painful channelopathy. Pract Neurol

Tomsone V, Logina I, Millers A, Chapenko S, Kozireva S, Murovska M (2001) Association of human herpes virus 6 and human herpesvirus 7 with demyelinating diseases of the nervous system. J Neuro-Oncol 7:564–569

Uceyler N, Zeller D, Khan A-K, Kewenig S, Kittel – Schneider S, Schmid A, Casanova – Molla J, Reiners K, Sommer C (2013) Small fibre pathology in patients with fibromyalgia syndrome. Brain J Neurol 1–11

Valko PO, Bassetti CL, Bloch KE, Held U, Baumann CR (2008) Validation of the fatigue severity scale in a Swiss cohort. Sleep 31(11):1601–1607CrossRefPubMedPubMedCentral

Vartiainen N, Kallio-Laine K, Hlushchuk Y, Kirveskari E, Seppänen M, Autti H, Jousmäki V, Forss N, Kalso E, Hari R (2009) Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain. Pain 144(1):200–208CrossRefPubMed

Wiffen PJ, Derry S, Moore AR (2013) Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 12:CD006044

Wolfe F, Clauw D, Fitzcharkes M-A, Goldenberg DL, Katz RS, Mease P, Russell AS, Russel JI, Winfield JB, Yunus MB (2010) The American College of Rheumatology Preliminary Diagnostic Criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 62(5):600–610CrossRef

Yao K, Crawford JR, Komaroff AL, Ablashi DV, Jacobson S (2010) Review part 2: human herpesvirus-6 in central nervous system diseases. J Med Virol 82(10):1669–1678CrossRefPubMedPubMedCentral

Yoshikawa T, Asano Y (2000) Central nervous system complications in human herpesvirus 6 infection. Brain and Development 22(5):307–314CrossRefPubMed

Title: The role of HHV-6 and HHV-7 infections in the development of fibromyalgia
Authors: Angelika Krumina
Svetlana Chapenko
Viktorija Kenina
Marija Mihailova
Inara Logina
Santa Rasa
Sandra Gintere
Ludmila Viksna
Simons Svirskis
Modra Murovska
Publication date: 01-04-2019
Publisher: Springer International Publishing
Keywords: Fibromyalgia
Fibromyalgia
Published in: Journal of NeuroVirology / Issue 2/2019
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-018-0703-8

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The role of HHV-6 and HHV-7 infections in the development of fibromyalgia

Abstract

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