Chronic Fatigue Syndrome: Causes

Pathogenesis (disease development)

The cause of chronic fatigue syndrome (CFS; systemic exertion intolerance disorder (SEID)) has not yet been determined.Several theories are discussed that may contribute to its development.Various environmental factors are also thought to be involved in the development of CFS, but proof has not yet been provided.In addition, various viruses such as Epstein-Barr virus (EBV) are suspected to play a role in pathogenesis. Cytomegalovirus (CMV), parvovirus, brucella, toxoplasmosis, chlamydia pneumoniae, and enteroviruses are other possible infectious triggers, and immunologic factors are thought to be involved. This hypothesis is supported by a study of patients who had complained of chronic fatigue syndrome for some time: the cross-sectional study demonstrated elevated blood concentrations of 17 cytokines. Patients frequently had elevated levels of the cytokine TGF-beta (transforming growth factor; more antiinflammatory/inflammatory), whereas levels of resistin (proinflammatory cytokine/promoting inflammation) were lower than in controls; thirteen of the 16 cytokines had a proinflammatory effect.

Etiology (Causes)

Behavioral Causes

• Drug use
  • Heroin
  • Opiates or opioids (alfentanil, apomorphine, buprenorphine, codeine, dihydrocodeine, fentanyl, hydromorphone, loperamide, morphine, methadone, nalbuphine, naloxone, naltrexone, oxycodone, pentazocine, pethidine, piritramide, remifentanil, sufentanil, tapentadol, tilidine, tramadol)

Disease-related causes

• Immunodeficiencies
• Infections
  • Gastrointestinal infections (gastrointestinal infections) – depending on the infectious agent risk increase +40 to +80%.
• Post-infection hormonal dysregulation – disruption of the hormonal balance after infection.
• Psychosomatic disorders – especially with excessive concern for bodily functions.
• Psychosocial disorders

Medication (fatigue (sedation) caused by medication).

• Alpha-2 agonist (tizanidine).
• Alpha-sympathomimetics (alfuzosin, doxazosin, oxymetazoline, tamsulosin, terazosin).
• Alpha-sympatholytics (phenoxybenzamine).
• Analgesics
  • Coxibe (celecoxib, parecoxib)
  • Opioids (alfentanil, buprenorphine, dextropoxyphene, hydromorphone, levomethadone, meptazinol, morphine, nalbuphine, oxycodone, pentazocine, pethidine, piritramide, remifentanil, sufentanil, tilidine, tramadol)
• Anthelmintics (albendazole, diethylcarbamazine, mebendazole, niclosamide).
• Antiarrhythmics
  • Class Ic antiarrhythmics (flecainide, propafenone).
  • Cardiac glycosides (ß-acetyldigoxin, ß-methyldigoxin, digoxin, digitoxin).
• Antibiotics
  • Macrolides (azithromycin, clarithromycin, erythromycin).
  • Steroid antibiotics (fusidic acid).
• Antidepressants
  • Noradrenergic and specific serotonergic antidepressants (NaSSA) – mirtazapine.
  • Selective norepinephrine reuptake inhibitors (NARI) – reboxetine, viloxazine.
  • Selective serotonin–norepinephrine reuptake inhibitors (SSNRI) – duloxetine, venlafaxine.
  • Selective serotonin reuptake inhibitors (SSRI) – trazodone
  • Tetracyclic antidepressants (maprotiline, mianserine).
  • Tricyclic antidepressants (amitriptyline, amitriptyline oxide, clomipramine, desipramine, doxepin, imipramine, opipramol, nortriptyline, trimipramine).
• Antiemetics (scopolamine, dimenhydrinate, domperidone, metoclopramide (MCP)).
• Antiepileptic drugs (carbamazepine, clonazepam, gabapentin, oxcarbazepine, phenytoin, phenobarbital, pregabalin).
• Antihistamines (azelastine, cetirizine, clemastine, desloratardine, dimenhydrinate, dimetindene, diphenhydramine, ketotifen, loratadine, meclozine, promethazine, terfenadine).
• Antihypertensives (methyldopa).
• Antimalarials (artemether, dihydroartemisinin, lumefantrine).
• Antiparkinsonian agents (amantadine).
• Antiphlogistics (rifaximin)
• Antipsychotics (neuroleptics).
  • Conventional (Classical) antipsychotics (neuroleptics).
    • Butyrophenones – haloperidol, melperone.
    • Tricyclic neuroleptics – phenothiazines (fluphenazine).
  • Atypical antipsychotics (neuroleptics) – dopamine receptor antagonist (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, zotepine).
• Antivertiginosa (dimenhydrinate).
• Antitussives
  • Morphine derivatives (codeine, dihydrocodeine, hydrocodeine, dextromethorphan).
  • Non-opioid antitussives (levodropropizine, pentoxyverine).
• Anxiolytics (hydroxyzine).
• Α2-agonists (apraclonidine, brimonidine, clonidine).
• Beta-blockers, local (betaxolol, timolol).
• Beta-blockers, systemic
  • Nonselective beta-blockers (e.g., carvedilol, pindolol, propranolol, soltalol).
  • Selective beta blockers (e.g., atenolol, acebutolol, betaxolol, bisoprolol, celiprolol, nebivolol, metoprolol).
• Cannabinoids – cannabidiol (CBD), dronabinol (trans-delta-9-tetrahydrocannabinol, THC), nabilone, nabiximols.
• Carboanhydrase inhibitors, systemic (acetazolamide, dichlorophenamide, methazolamide).
• Dopamine agonists (prolactin inhibitors) (bromocriptine, lisuride).
• Dopamine antagonists (domperidone, metoclopramide (MCP))
• EGFR tyrosine kinase inhibitor (lapatinib).
• Hormones
  • Antiandrogens (cyproterone acetate)
  • Progestogens (dydrogesterone, progesterone; chlormadinone acetate, cyproterone acetate, desogestrel, dienogest, drospirenone, gestodene, levonorgestrel, norethisterone, norgestimate, nomegestrol).
  • Prolactin inhibitors (bromocriptine, cabergoline, lisuride, metergoline, quinagolide).
• Hypnotics/sedatives
  • Benzodiazepines (diazepam, lorazepam, midazolam, temazepam).
  • Clomethiazole
• Immunotherapeutics (mitoxantrone).
• Monoclonal antibodies (nivolumab, trastuzumab).
• Muscle relaxants (tetrazepam).
• Neurokinin antagonists (aprepitant, fosaprepitant).
• Nicotinic agonist (varenicline).
• NMDA (n-methyl-D-aspartate) receptor antagonist (memantine).
• Lithium
• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil).
• Proton pump inhibitors (proton pump inhibitors, PPI; acid blockers) – esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.
• Phytotherapeutics (valerian, St. John’s wort, passionflower).
• Sedatives
  • Benzodiazepines (alprazolam bentazepam, bromazepam, brotizolam, clobazam, clonazepam, clorazepate, clotiazepam, diazepam, etizolam, flunitrazepam, flurazepam, loprazolam, Lorazepam, Lormetazepam, Medazepam, Nitrazepam, Nordazepam, Oxazepam, Phenazepam, Prazepam, Temazepam, Tetrazepam* , Triazolam) [* Suspension of prescriptions since August 2013 due to. Serious skin reactions such as Stevens-Johnson syndrome or erythema multiforme]
• Spasmolytics (tolterodine,trospium chloride).
• Tyrosine kinase inhibitors (TKi)/angiogenesis inhibitors (pazopanib, sorafenib, sunitinib, vandetanib).
• Antivirals
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) – efavirenz, rilpivirine.
  • NS5A inhibitors (daclatasvir, ledipasvi, ombitasvir
  • Nucleos(t)idic polymerase (NS5B) inhibitors (sofosbuvir).
  • Protease inhibitors (paritaprevir).
• Cytostatic drugs (methotrexate, MTX).

Environmental pollution – intoxications (poisonings).

• Chemical substances such as amalgam or mercury.
• Environmental toxins such as lead, cadmium or ozone.