Throat infection, neck and chest pain and cardiac response: A persistent infection-related clinical syndrome

Abstract

Dizziness, chest discomfort, chest depression and dyspnea are a group of symptoms that are common complaints in clinical practice. Patients with these symptoms are usually informed that while neurosis consequent to coronary heart disease is excluded nonetheless they remain unhealthy with no rational explanation or treatment. 165 cases of these symptoms and 85 control subjects were reviewed and underwent further medical history inquiry, routine EKG test and cardiac ultrasound examination. Thirty-five patients received coronary artery angiography to exclude coronary heart disease. Serum myocardial autoantibodies against beta1-adrenoceptor, alpha-myosin heavy chain, M2-muscarinic receptor and adenine-nucleotide translocator were tested, and inflammatory cytokines and high sensitivity C-reaction protein were measured and lymphocyte subclass was assayed by flow cytometry. All patients had a complex of four symptoms or tetralogy: (1) persistent throat or upper respiratory tract infection, (2) neck pain, (3) chest pain and (4) chest depression or dyspnea, some of them with anxiety. Anti-myocardial autoantibodies (AMCAs) were present in all patients vs. 8% in controls. TNF-α, IL-1 and IL-6 were significantly higher in patients than in controls (P<0.01). CD3⁺ and CD4-CD8⁺ lymphocytes were significantly higher and CD56⁺ lymphocytes lower in patients than those in controls (P<0.01). The ratio of serum pathogen antibodies positive against Coxsackie virus-B, cytomegalovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae were all markedly higher in patients. These data led to identification of a persistent respiratory infection-related clinical syndrome, including persistent throat infection, neck spinal lesion, rib cartilage inflammation, symptoms of cardiac depression and dyspnea with or without anxiety.

Keywords

inflammation / chest pain / cardiac response / diagnosis

References

[1] KontosM.C., JesseR.L.. Evaluation of the emergency department chest pain patient. Am J Cardiol, 2000, 85(5Supplement1): 32-39

[2] MarsanR.J.Jr, ShaverK.J., SeaseK.L., et al. . Evaluation of a clinical decision rule for young adult patients with chest pain. Acad Emerg Med, 2005, 12(1): 26-31

[3] WatsonG.S.. Noncardiac chest pain: a rational approach to a common complaint. JAAPA, 2006, 19(1): 20-25

[4] OldenK.W.. Treatment of noncardiac chest pain of psychological origin. Curr Treat Options Gastroenterol, 2006, 9: 51-58

[5] StaudtA., MobiniR., FuM., et al. . beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes. Eur J Pharmacol, 2001, 423: 115-119

[6] CaforioA.L., GoldmanJ.H., HavenA.J., et al. . Evidence for autoimmunity to myosin and other heart-specific autoantigens in patients with dilated cardiomyopathy and their relatives. Int J Cardiol, 1996, 54: 157-163

[7] SchwimmbeckP.L., BlandN.K., SchultheissH.P., et al. . The possible value of synthetic peptides in the diagnosis and therapy of myocarditis and dilated cardiomyopathy. Eur Heart J, 1991, 12(SupplD): 76-80

[8] FuL.X., MagnussonY., BerghC.H., et al. . Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest, 1993, 91: 1964-1968

[9] SchwimmbeckP.L., SchwimmbeckN.K., SchultheissH.P., et al. . Mapping of antigenic determinants of the adenine- nucleotide translocator and coxsackie B3 virus with synthetic peptides: use for the diagnosis of viral heart disease. Clin Immunol Immunopathol, 1993, 68: 135-140

[10] BabaA., YoshikawaT., ChinoM., et al. . Characterization of anti-myocardial autoantibodies in Japanese patients with dilated cardiomyopathy. Jpn Circ J, 2001, 65: 867-873

[11] AgardA., BentleyL., HerlitzJ.. Experiences and concerns among patients being treated for atypical chest pain. Eur J Intern Med, 2005, 16: 339-344

[12] EslerJ.L., BockB.C.. Psychological treatments for noncardiac chest pain: recommendations for a new approach. J Psychosom Res, 2004, 56: 263-269

[13] ErikssonU., PenningerJ.M., KopfM.. Mechanisms of autoimmune heart disease. Drug Discovery Today: Disease Mechanisms, 2004, 1(3): 283-288

[14] YndestadA., HolmA.M., MullerF., et al. . Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res, 2003, 60: 141-146

[15] BasinkevichA.B., ShakhnovichR.M., MartynovaV.R., et al. . [Role of Chlamydia, mycoplasma and cytomegalovirus infection in the development of coronary artery disease]. Kardiologiia, 2003, 43: 4-9

[16] SmiejaM., GnarpeJ., LonnE., et al. . Multiple infections and subsequent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation, 2003, 107: 251-257

[17] ReunanenA., RoivainenM., KleemolaM.. Increased titer of antibodies to Mycoplasma pneumoniae may be associated with coronary heart disease. Atherosclerosis, 2005, 180: 209-210

[18] FuM.L., HoebekeJ., MatsuiS., et al. . Autoantibodies against Cardiac G-Protein-Coupled Receptors Define Different Populations with Cardiomyopathies but Not with Hypertension. Clin Immunol Immunopathol., 1994, 72(1): 15-20

[19] MatsuiS., FuM.L., KatsudaS., et al. . Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol, 1997, 29: 641-655

[20] MatsuiS., FuM.L., HayaseM., et al. . Active immunization of combined [beta]1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits. J Card Fail., 1999, 5(3): 246-254

[21] JahnsR., BoivinV., KrapfT., et al. . Modulation of beta1-adrenoceptor activity by domain-specific antibodies and heart failure-associated autoantibodies. J Am Coll Cardiol, 2000, 36: 1280-1287

[22] JahnsR., BoivinV., LohseM.J.. beta(1)-Adrenergic receptor function, autoimmunity, and pathogenesis of dilated cardiomyopathy. Trends Cardiovasc Med, 2006, 16: 20-24

[23] ManchadoC., OrusJ., VillarroyaF., et al. . Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy. J Mol Cell Cardiol, 2002, 34: 571-582

This project was supported by a grant from National Basic Research Program (973) of China (2007CB512004) and NSFC (30430320 & 30571841).