You are here: Home Science behind Pathogenesis Th1 Spectrum Disorder
Home
Table of Contents

Th1 Spectrum Disorder

Th1 Spectrum Disorder refers to the group of chronic inflammatory diseases, which are caused by the Th1 pathogens, a microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms. of bacteria which include L-formDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria., biofilmA structured community of microorganisms encapsulated within a self-developed protective matrix and living together., and intracellular bacterial forms. Although the exact species and forms of bacteria, as well as the location and extent of the infection, vary between one patient suffering from chronic disease and the next, the disease process is common: bacterial pathogens persist and reproduce by disabling the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease..

Although patients who become infected with the Th1 pathogens are given a variety of diagnoses, there are often no clear cut distinctions between one disease and the next. Rather, symptoms frequently overlap creating a spectrum of illness in which diseases are more connected to one another than mutually exclusive disease states.

The evidence that chronic disease is ultimately a spectrum disorder caused by a common infectious cause includes:

  • comorbidity of inflammatory diseases overlap observed between patients suffering distinctly defined diseases
  • the infrequency with which patients suffer from just a single disease or condition
  • failure of diagnostic compartmentalization: the frequent difficulty doctors have in clearly and definitively diagnosing a patient

Conflict in theories

Traditionally, diseases are understood to be discrete and have their own respective and distinct pathologies. This theory of disease has been advanced by researchers intent upon pinpointing the human genes which they theorize cause disease. The existence of a vast network of clinical specialists and sub-specialists only reinforces this idea.

According to the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., the range of chronic diseases is caused by a common etiology or disease process. Patients accumulate Th1 pathogens, which proliferate by disabling the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. and consequently weakening the innate immune response.

Comorbidity of inflammatory diseases

When the Th1 pathogens compromise the immune response, they make it easier for other types of bacteria in other locations to infect the body as well. This phenomenon is known as comorbidity. Although a comorbid condition is traditionally understood to be unrelated to the underlying condition, the sheer number of common comorbidities points to a common pathology.

Epidemiological research may have its share of liabilities, but one contribution it has made is in demonstrating the strong connections between seemingly disparate diseases as evidenced by the number of patients who share diagnoses with two or more “unrelated” disease processes.

The following wheel shows how truly related chronic diseases are. Each “spoke” represents a published study which has demonstrated a significant statistical relationship between patients suffering from one disease and the next.

The following paragraph contains links to all the studies alluded to in the above chart. Please note that some of the disease names are links to articles discussing those diseases in further detail.

allergies 1 alopecia areata 2 3 Alzheimer's disease & dementia 4 5 ankylosing spondylitis 6 7 8 anorexia nervosa 9 anxiety disorders 10 11 12 13 14 15 16 17 18 arthritis 19 20 21 22 23 24 25 asthma 26 27 28 29 30 31 32 33 34 35 36 37 bipolar disease 38 39 40 41 cancer 42 43 44 45 cardiac disease 46 47 48 49 50 51 52 53 54 55 cardiovascular disease 56 57 58 59 60 celiac disease 61 62 63 64 chronic fatigue syndrome 65 66 67 chronic obstructive pulmonary disease 68 depression 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 diabetes 86 87 88 89 90 91 92 diabetes, type1 93 94 95 diabetes, type2 96 fibromyalgia 97 98 Guillain-Barré syndrome 99 100 hypertension 101 102 inflammatory bowel disease (Crohn's disease and ulcerative colitis) 103 104 105 106 107 108 109 110 111 112 113 114 115 116 lupus 117 118 119 120 121 multiple chemical sensitivity 122 multiple sclerosis 123 124 125 126 127 128 129 myasthenia gravis 130 obesity 131 132 133 134 135 obsessive compulsive disorder 136 137 138 139 140 osteoporosis 141 142 143 144 Parkinson's disease 145 146 147 148 periodontal disease 149 150 pernicious anemia 151 psoriasis 152 153 154 155 156 rheumatoid arthritis 157 158 159 sarcoidosis 160 161 schizophrenia 162 163 164 scleroderma 165 Sjogren's syndrome 166 167 168 169 thyroiditis (Graves' disease and Hashimoto's thyroiditis) 170 171 172 173 174 175 176 uveitis 177 178 vitiligo 179

Infrequency with which patients suffer from only a single disease

25% of Americans have more than one chronic condition.

To control for confounding variables, researchers often exclude patients with more than one condition from research studies even though they represent the majority of patients. Jeste et al made this observation in patients with schizophrenia180 and there's no reason to think it's any different with other patient groups.

A recent survey of Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. patients, discussed in Amy Proal's presentation at Congress on Autoimmunity, showed that of those with Hashimoto's Thyroiditis, only 8% had been diagnosed with Hashimoto's alone.

The challenge of diagnosing diseases caused by bacteria

Many doctors are reluctant to say that chronic diseases are caused by bacterial pathogens and for a couple reasons.

No consistent symptom presentation

Medicine has difficulty diagnosing disorders where there is no consistently identified anatomic abnormality or documented metabolic/physiological dysfunction.181

Diagnoses are driven by perceived therapeutic options

What a clinician thinks causes many of the ill-defined chronic diseases may in fact be shaped by available treatment options for that disease.

Consider dentists. Most dentists will readily concede that bacteria cause plaque and tooth decay. The fact that a dentist can employ a therapy against plaque (in this case, manually removing plaque) clearly shapes their opinion about the etiology of the disease. That the intervention is at least temporarily effective also has something to do with it, but perhaps not as much as most people might imagine.

When it comes to lethargy or exercise intolerance or difficulty breathing or any number of other symptoms of disease, the explanation for the disease's etiology is often driven by the available mainstream treatment options, of which very few are effective. These options are themselves highly influenced by pharmaceutical companies which have a vested interest in selling a drug or treatment. In their drive to differentiate themselves and their product, these companies will overemphasize the distinctions among diseases when there may be no such fundamental differences.

False assurance of diagnostic compartmentalization

Another challenge relates to how diseases are segmented into categories even when the nature of the diseases themselves don't warrant such fine-graded distinctions.

One who pores through the articles of a medical textbook could easily form the impression that diseases are discrete, well-defined and mutually exclusive. The reality is that the nature of illness is such that diagnosis is often inexact. Over the past few decades, the sensitivity and specificity of diagnostic tests has, in many cases, increased dramatically. Yet, neither precision nor accuracy is useful when two test results for a patient suggest conflicting diagnoses.

To resolve this ambiguity, epidemiologists have developed a kind of stop-gap measure: rubrics - many of them “evidence-based” - for diagnosing disease. A rubric is a checklist of sorts. Doctors who diagnose according to a rubric look to see if a patient has at least a certain number of classical symptoms - say, eight of the twelve symptoms listed. Given that the vagaries of any one chronic disease are determined by patients' unique pea soup, that is, their particular mix of Th1 pathogens, the traditional methods for diagnosis leave a great deal to be desired.

Patients presenting with prototypical cases of a given disease tend to be the exception rather than the rule. They may have some of the classical symptoms of a given disease but not others. Also, patients may have symptoms that are unique to a different disease. Patients with symptoms of chronic disease could present five different doctors with the same set of symptoms and get five different diagnoses, and many have!

Excessive testing

In the face of uncertainty and ambiguity, a clinician's natural response might be to order a battery of tests. After all, the more information clinicians obtain, the more confidence they have in the validity of their diagnoses, even when such confidence may not be justified on the basis of the information obtained.

In his paper, “Our stubborn quest for diagnostic certainty: a cause of excessive testing,” JP Kassirer writes:

Absolute certainty in diagnosis is unattainable, no matter how much information we gather, how many observations we make, or how many tests we perform. Our task is not to attain certainty, but rather to reduce the level of diagnostic uncertainty enough to make optimal therapeutic decisions…. We continue to test excessively, partly because of our discomfort with uncertainty.

Jerome Kassirer, MD 182

A single diagnosis for chronic inflammatory disease

Given that all of the so-called autoimmune diseases and chronic infections are a variation of the Th1 inflammatory process, neither a specific diagnostic label or identification of specific pathogens is needed to begin the Marshall Protocol (MP). With the MP, patients identify Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. with simple blood tests and then confirm the presence of occult microbes with a therapeutic probe. As treatment continues, the presence of the immune system reactions confirms the continuing efficacy of treatment. And finally, symptom resolution, absence of immune system reactions and normal blood work indicate recovery.

Where the MP is unique is that I set out to kill pathogens which have never been fully identified, whose exact nature is still largely unknown. I did this based on an understanding of the pathogens' biochemical effects on the body, and the consequent understanding of how they must therefore be exerting that effect…. We have focused on the commonalities, rather than the differences, between immune disease syndromes, and this tends to make it easier to distinguish the forest from the trees.

Trevor Marshall, PhD

A corollary of this principle is that attempts to compare one patient's disease with another's are futile. Certainly there is a great deal of variability in the location and severity of infection and the corresponding symptoms, but ultimately there is no fundamental difference between the state of patients' disease states and there is, therefore, no difference in their ultimate recovery trajectories.

Read more:

Notes and comments

TECHEDIT

References

1) , 26) , 93) , 170) Spector SL Overview of comorbid associations of allergic rhinitis. J Allergy Clin Immunol. 1997;99:S773-80.
2) , 15) , 71) Koo JY, Shellow WV, Hallman CP, Edwards JE Alopecia areata and increased prevalence of psychiatric disorders. Int J Dermatol. 1994;33:849-50.
3) , 64) , 67) , 95) , 100) , 116) , 121) , 129) , 130) , 151) , 156) , 159) , 165) , 169) , 176) , 179) Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB Epidemiology of autoimmune diseases in Denmark. J Autoimmun. 2007;29:1-9.
4) , 78) Cummings JL, Masterman DL Depression in patients with Parkinson's disease. Int J Geriatr Psychiatry. 1999;14:711-8.
5) , 131) Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K Central obesity and increased risk of dementia more than three decades later. Neurology. 2008;71:1057-64.
6) , 20) , 56) , 158) Han C, Robinson DW Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33:2167-72.
7) , 22) , 111) , 177) Loftus EV Jr Inflammatory bowel disease extending its reach. Gastroenterology. 2005;129:1117-20.
8) , 161) Sezer I, Melikoglu MA, Cay HF, Kocabas H, Kacar C A co-occurrence of sarcoidosis and ankylosing spondylitis: a case report. Rheumatol Int. 2008;28:605-7.
9) , 14) , 140) Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K Comorbidity of anxiety disorders with anorexia and bulimia nervosa. Am J Psychiatry. 2004;161:2215-21.
10) , 137) Lensi P, Cassano GB, Correddu G, Ravagli S, Kunovac JL, Akiskal HS Obsessive-compulsive disorder. Familial-developmental history, symptomatology, comorbidity and course with special reference to gender-related differences. Br J Psychiatry. 1996;169:101-7.
11) , 12) , 39) , 40) , 69) , 160) Goracci A, Fagiolini A, Martinucci M, Calossi S, Rossi S, Santomauro T, Mazzi A, Penza F, Fossi A, Bargagli E, Pieroni MG, Rottoli P, Castrogiovanni P Quality of life, anxiety and depression in sarcoidosis. Gen Hosp Psychiatry. 2008;30:441-5.
13) , 70) , 139) Addolorato G, Capristo E, Stefanini GF, Gasbarrini G Inflammatory bowel disease: a study of the association between anxiety and depression, physical morbidity, and nutritional status. Scand J Gastroenterol. 1997;32:1013-21.
16) , 73) Lecrubier Y The impact of comorbidity on the treatment of panic disorder. J Clin Psychiatry. 1998;59 Suppl 8:11-4; discussion 15-6.
17) , 28) Ortega AN, Huertas SE, Canino G, Ramirez R, Rubio-Stipec M Childhood asthma, chronic illness, and psychiatric disorders. J Nerv Ment Dis. 2002;190:275-81.
18) , 75) , 146) , 148) Shulman LM, Taback RL, Bean J, Weiner WJ Comorbidity of the nonmotor symptoms of Parkinson's disease. Mov Disord. 2001;16:507-10.
19) , 49) , 105) , 153) Christophers E Comorbidities in psoriasis. Clin Dermatol. 2007;25:529-34.
21) , 32) , 33) , 34) , 107) , 108) , 109) , 110) Bernstein CN, Wajda A, Blanchard JF The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology. 2005;129:827-36.
23) , 35) , 44) , 55) , 57) , 88) , 144) Adams RJ, Wilson DH, Taylor AW, Daly A, Tursan d'Espaignet E, Dal Grande E, Ruffin RE Coexistent chronic conditions and asthma quality of life: a population-based study. Chest. 2006;129:285-91.
24) , 118) , 174) Mihailova D, Grigorova R, Vassileva B, Mladenova G, Ivanova N, Stephanov S, Lissitchky K, Dimova E Autoimmune thyroid disorders in juvenile chronic arthritis and systemic lupus erythematosus. Adv Exp Med Biol. 1999;455:55-60.
25) , 37) , 45) , 60) , 63) , 92) Caughey GE, Vitry AI, Gilbert AL, Roughead EE Prevalence of comorbidity of chronic diseases in Australia. BMC Public Health. 2008;8:221.
27) , 103) , 123) , 152) , 157) Weng X, Liu L, Barcellos LF, Allison JE, Herrinton LJ Clustering of inflammatory bowel disease with immune mediated diseases among members of a northern california-managed care organization. Am J Gastroenterol. 2007;102:1429-35.
29) , 74) Goodwin RD, Olfson M, Shea S, Lantigua RA, Carrasquilo O, Gameroff MJ, Weissman MM Asthma and mental disorders in primary care. Gen Hosp Psychiatry. 2003;25:479-83.
30) , 134) Hasler G, Gergen PJ, Ajdacic V, Gamma A, Eich D, Rössler W, Angst J Asthma and body weight change: a 20-year prospective community study of young adults. Int J Obes (Lond). 2006;30:1111-8.
31) , 135) Gennuso J, Epstein LH, Paluch RA, Cerny F The relationship between asthma and obesity in urban minority children and adolescents. Arch Pediatr Adolesc Med. 1998;152:1197-200.
36) , 83) Goldney RD, Ruffin R, Fisher LJ, Wilson DH Asthma symptoms associated with depression and lower quality of life: a population survey. Med J Aust. 2003;178:437-41.
38) , 136) Perugi G, Akiskal HS, Pfanner C, Presta S, Gemignani A, Milanfranchi A, Lensi P, Ravagli S, Cassano GB The clinical impact of bipolar and unipolar affective comorbidity on obsessive-compulsive disorder. J Affect Disord. 1997;46:15-23.
41) , 79) , 132) McElroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE, Nemeroff CB Are mood disorders and obesity related? A review for the mental health professional. J Clin Psychiatry. 2004;65:634-51, quiz 730.
42) , 52) , 80) Krishnan KR, Delong M, Kraemer H, Carney R, Spiegel D, Gordon C, McDonald W, Dew M, Alexopoulos G, Buckwalter K, Cohen PD, Evans D, Kaufmann PG, Olin J, Otey E, Wainscott C Comorbidity of depression with other medical diseases in the elderly. Biol Psychiatry. 2002;52:559-88.
43) , 113) Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005;100:2724-9.
46) , 162) Hennekens CH, Hennekens AR, Hollar D, Casey DE Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005;150:1115-21.
47) , 163) Cohn T, Prud'homme D, Streiner D, Kameh H, Remington G Characterizing coronary heart disease risk in chronic schizophrenia: high prevalence of the metabolic syndrome. Can J Psychiatry. 2004;49:753-60.
48) , 145) Karrar A, Sequeira W, Block JA Coronary artery disease in systemic lupus erythematosus: A review of the literature. Semin Arthritis Rheum. 2001;30:436-43.
50) , 68) , 87) , 102) , 142) Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:549-55.
51) , 150) Gotsman I, Lotan C, Soskolne WA, Rassovsky S, Pugatsch T, Lapidus L, Novikov Y, Masrawa S, Stabholz A Periodontal destruction is associated with coronary artery disease and periodontal infection with acute coronary syndrome. J Periodontol. 2007;78:849-58.
53) , 81) Parker G, Heruc G, Hilton T, Olley A, Brotchie H, Hadzi-Pavlovic D, Owen C, Friend C, Walsh WF Explicating links between acute coronary syndrome and depression: study design and methods. Aust N Z J Psychiatry. 2006;40:245-52.
54) , 82) Stafford L, Berk M, Reddy P, Jackson HJ Comorbid depression and health-related quality of life in patients with coronary artery disease. J Psychosom Res. 2007;62:401-10.
58) , 85) Burvill P, Johnson G, Jamrozik K, Anderson C, Stewart-Wynne E Risk factors for post-stroke depression. Int J Geriatr Psychiatry. 1997;12:219-26.
59) , 90) Huxley R, Barzi F, Woodward M Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332:73-8.
61) , 62) , 94) , 171) Fasano A Systemic autoimmune disorders in celiac disease. Curr Opin Gastroenterol. 2006;22:674-9.
65) , 66) , 97) , 98) , 104) Aaron LA, Burke MM, Buchwald D Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med. 2000;160:221-7.
72) , 122) Caccappolo-van Vliet E, Kelly-McNeil K, Natelson B, Kipen H, Fiedler N Anxiety sensitivity and depression in multiple chemical sensitivities and asthma. J Occup Environ Med. 2002;44:890-901.
76) , 147) Menza MA, Robertson-Hoffman DE, Bonapace AS Parkinson's disease and anxiety: comorbidity with depression. Biol Psychiatry. 1993;34:465-70.
77) , 154) Gupta MA, Schork NJ, Gupta AK, Kirkby S, Ellis CN Suicidal ideation in psoriasis. Int J Dermatol. 1993;32:188-90.
84) , 89) Goldney RD, Phillips PJ, Fisher LJ, Wilson DH Diabetes, depression, and quality of life: a population study. Diabetes Care. 2004;27:1066-70.
86) , 101) , 133) , 155) McNeely MJ, Boyko EJ Diabetes-related comorbidities in Asian Americans: results of a national health survey. J Diabetes Complications. 2005;19:101-6.
91) , 112) Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review. Inflamm Bowel Dis. 2007;13:225-34.
96) , 149) Emrich LJ, Shlossman M, Genco RJ Periodontal disease in non-insulin-dependent diabetes mellitus. J Periodontol. 1991;62:123-31.
99) , 120) Paradowski B, Koszewicz M, Grodzicka I [Chronic demyelinative polyneuropathy Guillain-Barré type in the course of systemic lupus erythematosus ] Pol Merkur Lekarski. 2001;10:105-6.
106) , 124) Kimura K, Hunter SF, Thollander MS, Loftus EV Jr, Melton LJ 3rd, O'Brien PC, Rodriguez M, Phillips SF Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc. 2000;75:802-6.
114) , 143) Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin YC, Yang H, Hewison M, Adams JS Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut. 2004;53:1129-36.
115) , 178) Johnson LA, Wirostko E, Wirostko WJ Crohn's disease uveitis. Parasitization of vitreous leukocytes by mollicute-like organisms. Am J Clin Pathol. 1989;91:259-64.
117) , 141) Lee C, Almagor O, Dunlop DD, Manzi S, Spies S, Chadha AB, Ramsey-Goldman R Disease damage and low bone mineral density: an analysis of women with systemic lupus erythematosus ever and never receiving corticosteroids. Rheumatology (Oxford). 2006;45:53-60.
119) , 168) , 175) Scofield RH Autoimmune thyroid disease in systemic lupus erythematosus and Sjögren's syndrome. Clin Exp Rheumatol. 1996;14:321-30.
125) , 172) Sloka JS, Phillips PW, Stefanelli M, Joyce C Co-occurrence of autoimmune thyroid disease in a multiple sclerosis cohort. J Autoimmune Dis. 2005;2:9.
126) , 173) Karni A, Abramsky O Association of MS with thyroid disorders. Neurology. 1999;53:883-5.
127) , 166) Sandberg-Wollheim M, Axéll T, Hansen BU, Henricsson V, Ingesson E, Jacobsson L, Larsson A, Lieberkind K, Manthorpe R Primary Sjögren's syndrome in patients with multiple sclerosis. Neurology. 1992;42:845-7.
128) , 167) Miró J, Peña-Sagredo JL, Berciano J, Insúa S, Leno C, Velarde R Prevalence of primary Sjögren's syndrome in patients with multiple sclerosis. Ann Neurol. 1990;27:582-4.
138) , 164) Tibbo P, Kroetsch M, Chue P, Warneke L Obsessive-compulsive disorder in schizophrenia. J Psychiatr Res. 2000;34:139-46.
180) Jeste DV, Gladsjo JA, Lindamer LA, Lacro JP Medical comorbidity in schizophrenia. Schizophr Bull. 1996;22:413-30.
181) Gardner JW, Gibbons RV, Hooper TI, Cunnion SO, Kroenke K, Gackstetter GD Identifying new diseases and their causes: the dilemma of illnesses in Gulf War veterans. Mil Med. 2003;168:186-93.
182) Kassirer JP Our stubborn quest for diagnostic certainty. A cause of excessive testing. N Engl J Med. 1989;320:1489-91.
Last modified: 01.29.2010 by paulalbert
© 2010, Autoimmunity Research Foundation. All Rights Reserved.