Transcript PowerPoint-presentatie

EURIMM
European Institute of Molecular Medicine
Chronic Fatigue Immune
Dysfunction Syndrome
A Model for a Paradigm-change in
the Diagnosis and Therapy of
Chronic Diseases
Arnold Hilgers, M.D., EURIMM, Düsseldorf
EURIMM
European Institute of Molecular Medicine
Anamnesis
30-criteria-score (Hilgers et al., 1996)
Immune Balance Check
Humoral
Trigger Factors
Infections
Food
Environment
Cellular
Activation
Autoimmune
Cytokines
Genetic predisposition
Endocrine/Metabolism
Anti-oxidant capacity
Hormones
Metabolic enzyme activity
PUFA’s
Cardiovascular disease
Neurotransmitters
Risk for enhanced suppressor cell activity

Trigger Factor Elimination
Treatment
Immunomodulation
EURIMM
European Institute of Molecular Medicine
Anamnesis
30-Criteria-Score
Arnold Hilgers and Johannes Frank. Journal of Chronic Fatigue Syndrome,1996, Vol. 2 (4).
 45 criteria from Centers for Disease Control (CDC) definition of
chronic fatigue syndrome + 17 additional criteria
 385 patients (according CDC) were compared with 53 healthy
controls
 The first 30 symptoms that were significantly different between
the two groups led to the 30-Criteria-Score
Major criterium (fatigue/exhaustion) + 3 minor criteria
 High probability of disturbed immunebalance
EURIMM
European Institute of Molecular Medicine
30-Criteria-Score
Rank
Symptom
Rank
Symptom
1
fatigue/exhaustion
16
dryness of eye/mouth
2
lack of concentration
17
visual disorders
3
memory disorders
18
allergy
4
sleep disorders
19
nausea
5
myalgia
20
paresthesia
6
swings of mood
21
hair loss
7
headache
22
lymphadenopathia
8
respiratory infections
23
skin alterations
9
depression
24
dyscoordination
10
palpitation
25
chest pain
11
dizziness
26
personality changes
12
pharyngitis
27
skin rashes
13
dyspepsia
28
general infections
14
nocturnal sweat
29
muscle twitching
15
arthralgia
30
urinary infections
EURIMM
European Institute of Molecular Medicine
Immune Balance Check
Cellular
Leukocyte subsets
Lymphocyte subsets
Humoral
Electrophoresis, IgG
Complement activity
Activation
Activated T-cell
Humoral factors
Autoimmune
Auto-antibodies
Cytokines
Cytokines in plasma
Intracellular cytokines
EURIMM
European Institute of Molecular Medicine
Trigger Factors
Factor
Appearance
Detection
Infection
Viruses
Serology
Intracellular bacteria
PCR
Antigen detection
Lymphocyte Transformation Test
Food
Food components (f.e. cow milk)
Food additives (f.e. glutamate)
Environmental factors
Metals (incl. dental metals)
Fungi
Lymphocyte Transformation Test
(Type-IV allergy)
Lymphocyte Transformation Test
(Type-IV allergy)
EURIMM
European Institute of Molecular Medicine
Genetic predisposition
Determination of Single Nucleotide Polymorphisms (SNP’s)
Lack of anti-oxidant capacity
Risk factors for cardiovascular disease
Risk for enhanced suppressor cell activity
Metabolic disturbances
EURIMM
European Institute of Molecular Medicine
Neuro-endocrine/Metabolic Factors
Hormonal dysregulation
- modulates immune balance
- GH-axis, HPA-axis, sex hormones, …
Poly Unsaturated Fatty Acids (PUFA’s) and other lipids
- anti-oxidants
- direct influence on immune balance
- effect on brain neurotransmitters
Neurotransmitters
- modulates immune balance
- serotonin, tryptophan and metabolites
EURIMM
European Institute of Molecular Medicine
Neuro-endocrine/Metabolic Factors
Anti-oxidant capacity
Oxidative stress
- lipid peroxidation
- neutrophil function: oxidative burst
Anti-oxidants
- Zn, Se
- carnitine, gluthation, co-enzyme Q10
- Vit C, E, B6
- taurine, tyrosine, tryptophan
EURIMM
European Institute of Molecular Medicine
Treatment
Elimination of trigger factors
- Food (diet)
- Environment (eventual change environment)
- Antiviral/Antibacterial therapy
Immunomodulation
- Products of B- and T-cells
- Anti-oxidants to repair macrophage function
 Restoring Th1/Th2-balance
Nutriceuticals
- Substances to counteract genetic predisposition
- PUFA’s, 5HTP, …
EURIMM
European Institute of Molecular Medicine
Paradigm change
Classical Medicine
Psychic
Disease
Psychiatrist
Doctor 1
Organic
Doctor 2
Doctor 3
…
Treatment: symptomatic therapy
EURIMM
European Institute of Molecular Medicine
New Paradigm to Diagnose and Treat
Psychoneuroimmunological and Other Chronic Diseases
New Medicine
Universal 30-Criteria-Score


Disturbed Immune Balance
1.
Check immune balance
2.
Find trigger factor
3.
Restore immune balance
4.
Eliminate trigger factor
Treatment = Causal therapy
EURIMM
European Institute of Molecular Medicine
Patient 1
 Patient suffered from several CFS episodes and presented (together with parents)
with severe psychotic episode (Nov. 1995)
 Previous diagnosis was depression. Patient was due to be admitted to psychiatric
hospital.
 Laboratory findings
- stimulated immune system(CD8+CD38+) with leukopenia, reduced NKCA,
elevated sIL-2R and TNF-alpha
- abnormal B-cell function
- Helicobacter, Candida, and viral (EBV, HVZ) infection
- Type IV-allergy to many food supplements, fungi and dental metals.
- auto-antibodies to serotonin, gangliosides, phospholipids and keratin
 Treatment
- immunoglobulin i.v. with anti-oxidant infusion
- antiviral therapy (Zovirax)
- antibacterial therapy (standard triple therapy against Helicobacter)
EURIMM
European Institute of Molecular Medicine
Patient 1 (Ctd.)
 After treatment (Jan. 1996)
- patient recovered from psychosis and chronic fatigue
- patient started working again
 In Oct. 1996, patient presented again with CFS.
 elimination of trigger factors: diet and avoiding Aspergillus
Patient was also treated again for Helicobacter infection
Patient recovered
 Patient subsequently suffered form recurrent chronic fatigue, but was able to
work.
Every time there were recurrent viral infections and auto-antibody elevations.
Patient had a lot of allergies to food supplements and environmental factors.
EURIMM
European Institute of Molecular Medicine
Patient 1 (Ctd.)
 Nov. 2002
Patient presented with new severe psychotic episode
Now, laboratory findings were:
- no stimulated immune system, no auto-antibodies
- viral infections (EBV, HHV-6) and Chlamydia pneumonia infection
- high levels of IL-8 (>7500 pg/ml) and IL-6
 Treatment
- anti-bacterial treatment for Chlamyidia infection
- immunoglobulin i.v.
 Patient is now recovered from psychotic episode and chronic fatigue.
EURIMM
European Institute of Molecular Medicine
Summary Patient 1
Typical example of chronic disease due to disturbed immune balance
and leading to severe psychiatric symptoms
Trigger factors (infections, food, environment)
Chronic stimulated immune system
Severe psychiatric symptoms
Chronic fatigue
EURIMM
European Institute of Molecular Medicine
Patient 2
 Patient (age 34) presented in Aug. 2002
 Symptoms: chronic fatigue, panic attacks, stomach problems and depressive
episodes.
 Previous diagnosis: somatoform depression.
 Laboratory findings
- normal leukocyte number and function ongoing infections: CMV, EBV,
Chlamydia, Candida, Helicobacter, Borrelia, Yersinia, Mycoplasma
- auto-antibodies: gangliosides, serotonin
 Treatment
- immunoglobulin i.v.
- anti-oxidants
- anti-Helicobacter therapy
EURIMM
European Institute of Molecular Medicine
Patient 2 (Ctd.)
 Outcome (Nov. 2002)
- reduction of auto-antibodies
- remission of helicobacter infection
- still ongoing Borrelia-infection
 Further investigation showed reduced IGF-1 levels.
 Further treatment with growth hormone restored IGF-1.
Patient subsequently recovered from Borrelia infection.
 LTT showed Type-IV allergy to lamb meat and mollusc.
This is the probable cause of the stomach problems.
EURIMM
European Institute of Molecular Medicine
Summary Patient 2
 After doctor- and clinic Odyssey, without any positive
results and even worsening of the situation, present
condition is significantly improved in association
with reduced Borrelia load.
EURIMM
European Institute of Molecular Medicine
Patient 3
 Patient (age 55) presented in May 1996.
She was previous diagnosed as having psychosis.
 Findings
Chronic Fatigue Syndrome with:
- humoral immunodeficiency (IgG < 3g)
- anti-phospholipid syndrome
- chronic re-activating infections (Herpes viruses)
- reduced gluthation-S-transferase reduction
- pathological polymorphism of gluthation-S-transferase
- TNF-alpha elevation
EURIMM
European Institute of Molecular Medicine
Patient 3 (Ctd.)
 Treatment:
Immunoglobulin i.v.
 Improvement of symptoms and reduction of auto-antibodies
No alleviation of viral infections
 Additional treatment:
Antiviral therapy: Cymeven 5 mg, which had to be increased to 10 mg
 Elimination of viral infections (trigger factor)
EURIMM
European Institute of Molecular Medicine
Summary Patient 3
 Recovery after therapy so significant, that patient
could resume position as chief journalist of a
newspaper, after having been unable to carry out
any work for one and a half year.
EURIMM
European Institute of Molecular Medicine
Patient 4
 Patient was previously a healthy student from a family with high
social-economic status.
He was very intelligent with high grades at school and a good
sportsman.
 When the patient went to boarding-school, he developed a
depressive-like syndrome with lack of concentration, fatigue and
cognitive dysfunction.
His room was in an 300-year old building, with probably high
humidity.
Previous diagnosis was depression, but treatment failed.
EURIMM
European Institute of Molecular Medicine
Patient 4 (Ctd.)
 Laboratory findings:
- high TNF-alpha level
- auto-antibodies to serotonin
- elevated IgE and ECP
- LTT showed Type-IV allergy to 5 different fungi
 Treatment:
- immunoglobulins and anti-oxidants
- change of living environment (room in new building)
 Patient recovered from depressive symptoms and fatigue, and is
doing better in his studies.
Summary: Patient healed.