Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are diseases of uncertain etiology which may cause occupational,etc. disorders (Table 1).

Epidemiology of fibromyalgia is encountered in 2-4% cases in the population (Wolfe 1993). Women suffer more than men [ 1,2,3]. About 10 million Americans [4] suffer from FM syndrome. There are no epidemiologic data on FM/CFS in Eastern European countries - the former USSR republics, and quite often it remains an undiagnosed disease with neuro-endocrine and immunological changes.

The conclusion, drawn as a result of many studies, is that FM and CFS belong more to a psychosomatic rather than somatophilic diseases [5,6,7,8].

Understanding the problem, any patient who is complaining of the pain and fatigue should be assessed according to the associated signs and the pain intensity before confirming FM or CFS differential diagnosis (Table 1).

Table 1: Associated signs and symptoms (Wolfe 1990).

Other commonly reported symptoms include dizziness, trouble with memory and concentration, rashes and chronic itching (unpublished observations).

Misconception that FM/CFS is a psychosomatic disease, which is incurable and is diagnosed according the exclusion method ("wastepaper diagnosis"), as well as saying, that many of FMS patients are hypochondriacs, all this is not grounded and not to be supported as a conception.

Majority of patients can be helped by medicines, proteolytic and fibrinolytic enzymes, massage, physical exercises, keeping to a regular sleep regime and other medical procedures.

Anxiety, depression and other psychoneurotic disorders are more likely a result than the cause of this disease.

The idea expressed in the publications of the USA professor Garth L.Nicolson is that the basis for the pathogenesis of GWI (Gulf War Illness), CFS, FMS may be chlamydial, mycoplasmatic, viral or other bacterial infections [1]. Publications on Wensite make us draw conclusions that there are still not existing any etiopathogenetically grounded FMS/CFS treatment methods [9].

During 1981-2001, the Department of Urology at the Riga Clinical Hospital "Gailezers" treated 1997 chronic antibiotic-resistant chlamydial prostatitis patients from 13-80 yrs. From them, almost 15-20% patients, who had been diagnosed antibiotic-resistant chlamydial infection, experienced more or less marked chronic fatigue syndrome (CFS). Antibiotic resistance limits the possibilities of etiotropic treatment. CFS is the consequence of the inflammation caused by antibiotic-resistant systemic chlamydial infection.

Thus, pathogenetic therapy is directed towards enzyme therapy, by indicating plasminogen activators. Achieving the regression of the inflammation caused by chlamydia, regression of CFS is noticed accordingly. In 81,4% cases FM patients have CFS syndrome as well (Wolfe 1990), but etiopathogenetic processes are different and much harder to treat them. The choice of FM etiopathogenetic therapy is determined by the fact that the clinical tests of these patients (but not CFS) may be in norm, but their subjective feeling is very bad and tormenting.

Therefore psychiatrists and neurologists quite commonly consider FM/CFS as their profile patients, i.e. the psychosomatic disease. In fact, FM/CFS is a somatophilic disease. The clue for the differential diagnosis has to be looked for at the molecular level in relation to plasminogen activation, inhibition and the changes of physically-chemical properties of fibrinogen molecule in the direction of degradation. In coagulogram one can diagnose dyscoagulemia and dysfibrinogenemia, i.e. the disassociation of the characterizing values of hyper- and hypocoagulemia in one and the same patient simultaneously [10, 11, 12, 13].

The basis of the inflammatory dyscoagulemia is the depression of proteolytic and fibrinolytic enzyme systems and dysfibrinogenemia with changes of physically-chemical properties of fibrinogen molecules which are registered by coagulogram [14, 15].

The first problem of FM/CFS enzyme therapy is to overcome the barrier of antibiotic resistance.

The second problem is the differential diagnosis of intracellular persistence of chlamydia with a latent course, the possibilities of antigen and antibody elimination.

The third problem is the possibility of dyscoagulemia regression caused by the inflammation due to chlamydia.

If a patient with CFS is usually diagnosed dyscoagulemia with a tendency to hypocoagulemia, then in FM syndrome, dyscoagulemia is characterized by a pathologically high spontanous fibrinolysis up to 60%. FM dyscoagulemia has a paradoxical (involuntary) response to streptokinase, urokinase and tissue plasminogen activator (t-PA) Actilysi.

By treating with plasminogen activators, spontaneous fibrinolysis regresses up to the norm (10-15%). Pathologically increased spontaneous fibrinolysis regression and stabilisation occur not earlier than within 20-30 days, each day regularly receiving i/v plasminogen activators, preferably urokinase.

Clinical case I
( 23.10.2000 - 16.11.2000., 25 days, Case report Nr. 333121 - 00)
Patient M., 58 yrs.old, (Latvia), engineer in chemistry, is suffering for 6 years.

Diagnosis:
1. Chronic systemic chlamydial infection.
2. Antibiotic resistance.
3. Hypercoagulemia.
4. Reactive chlamydial polyarthritis.
5. Chronic fatigue syndrome.
6. Fibromyalgia susp. (FM)?

Prior to hospitalization, the patient had been diagnosed Chlamydia trachomatis antigen structures (+) and Chlamydia trachomatis antibodies in blood (+++) titre 1:16. On admission the patient was complaining of an extreme tiredness and weakness for whole 24 hours. She mentioned the pain all over the body, the pain in the joints of upper and lower limbs, morning stiffness, headaches, depression, dizziness, memory disturbances, problems to concentrate.

During 6 years prior to hospitalization, the patient had received antichlamydial antibiotic therapy, but due to antibiotic resistance, it turned out to be ineffective. As a result, the patient was hospitalized to start enzyme therapy with streptokinase and heparin, since coagulogram showed hypercoagulemia (Table 2).

During 25 days of enzyme therapy the patient was administered:

1) Streptokinase 10 000 - 15 000 e.u. i/v x once a day = 25 days = 1.480 000 e.u.
2) Heparin 5 000 u. i/v x once a day = 25 days, in total 125 000 u.

Bigger streptokinase doses (SK) could not be administered because of the allergic reaction of fever, t 38 and pains in the joints. SK doses were periodically decreased and increased again. Concurrently with SK, the patient was receiving antichlamydial antibiotics: doxycyclin 0,1 x three times a day = 50 caps., erythromycin 0,1 i/v x twice a day = 10 days, etc.

On the 22nd enzyme therapy day, the hypercoagulemia regressed (Table 2), pains in the joints, as well as CFS, disappeared. The patient was cured.

Conclusion:

Table 2: Coagulogram

Clinical case 2 
( Case report Nr. 26345 - 00, from 21.08. till 29.09.2000., 39 days)
Patient A., 57 yrs.old, (Latvia).
with chronic, relapsing (or reinfected from his spouse) chlamydial prostatitis, reactive polyarthritis and chronic fatigue syndrome (CFS), suffering for 10 years. He has repeatedly received enzyme therapy course with SK and antichlamydial antibiotics.

After the recurrent streptokinase course, CFS had always regressed. In cases of the relapse of chlamydial prostatitis or reinfection ( the wife - a carrier of chlamydial infection), chronic fatigue syndrome was recurring again.

On the last admission (21.08.2000.) the patient complained of great tiredness and weakness for the whole 24 hours. He mentioned the pain in the genitals, in the lower part of the abdomen, pain in the joints of fingers, wrist, elbow, shoulder, foot, as well as headaches, depression, sleep disturbances, memory problems and difficulties to concentrate. Clinical picture was that of polyarthritis.

Diagnosis:
1) Chronic relapsing (reinfectioned from the wife) prostatitis.
2) Reactive polyarthritis of urogenital origin.
3) Chronic fatigue syndrome.

During 39 days stay in the Department of Urology, the patient had received enzyme therapy with streptokinase and antichlamydial antibiotics:

1) Streptokinase 25 000 - 300 000 e.u. i/v x once a day, 39 days = 9. 975 000 e.u.
2) Heparin 5 000 u. i/v x once a day - 38 days = 190 000 u. i/v
3) Sol. Metrogil 0,5% 100 ml i/v x twice a day = 14 days = 28 vials
4) Erythromycin 0,1 x twice a day i/v = 15 days = 30 ampoules i/v
5) Cefazolin 1,0 x twice a2 day i/v = 15 days = 30 ampoules i/v
6) Vitamins and non-steroid antiinflammatory medicines.

As a result of the enzyme therapy, the inflammation processes completely regressed, fatigue syndrome disappeared.

At the end of the therapy, a moderate hypocoagulemia was achieved in the coagulogram:

The patient got cured. For prevention of reinfection, the patient's wife also underwent antichlamydial enzyme therapy course. After simultaneous treatment of either of them, chlamydial reinfection did not occur and no relapse was observed. No relapse of CFS was seen either.

Conclusion:

Clinical case 3
Patient J., 34 yrs.old, USA
(treated at the Dep. of Urology, Clinical Hospital "Gailezers" for 62 days). He has been suffering for 10 years, has been treated in the USA but with no progress.

Diagnosis made by the USA doctors:
1) Antibiotic-resistant systemic chlamydial (trachomatis, psittaci, pneumonia) infection.
2) Fibromyalgia (FM). Chronic fatigue syndrome (CFS).
3) Vasculitis of the small pelvis.

Extra to the USA doctors' diagnosis, "Gailezers" clinicians made a diagnosis:
4) Dyscoagulemia.
5) Dysfibrinogenemia.
6) Inflammation of urogenital venous plexus.
7) Sphincteritis of the anus.

On admission to the Dep. of Urology, Riga Clinical Hospital "Gailezers", the patient had 18 complaints:

impotence, due to which his wife had divorced him; marked tiredness and weakness all 24 hrs, depression, anxiety, spells of dizziness, sleep disturbances, paraesthesia, the pain in the small pelvis, the pain spread in many parts of the body, the pain and spasms in the leg muscles, the pain in the hands, the pain in the thorax with shallow wheezing breathing, morning stiffness, irritated bowel syndrome with frequent bowel movement and diarrheas, chronic rash, backache, memory and concentration disturbances.

The enzyme therapy was started with streptokinase (SK), but after 3 000 e.u. i/v infusion, the patient was seen to have a marked allergic and anaphylactic reactions. SK infusion was stopped. Enzyme therapy was continued by urokinase and Actilysi.

Therapy:
1. Urokinase - 25 000 - 50 000 u. x once a day, i/v, 41 days = 23 ampoules (2 400 000 u.)
2. Actilysi 5,0 - 50 mg x once a day, 40 days = 15 vials (750,0 mg)
3. Heparini - 5 000 u. x twice a day, 60 days = 300 000 u.
4. Sol. Metrogyl - 0,5% - 100,0 x twice a day, i/v , 15 days
5. Gentamycini - 80 mg x twice a day, 24 days
6. Erythromycini - 0,1 x twice a day, i/v, 39 days
7. Rocephini - 1,0 x twice a day, 25 days
8. Doxycylini - 0,1 x 3 times a day, 37 days
9. Wobenzym - 3 tabl. x three times a day, 55 days
10. Cycloferoni - 2,0 - i/m, every other day, in total - 25 ampoules
11. Azithromycini - 250 mg x once a day, 20 days
12. Sol. Zanocini - 200 mg x twice a day, i/v, 5 days = 10 vials
13. Sol. Dalacini - 600 mg x three times a day, 12 days
14. Body massage.

The patient was given antichlamydial enzyme-antibiotic therapy with urokinase and the tissue plasminogen activator (t-PA) Actilysi.

As a result of fibrinolytic therapy, dyscoagulemia and pathologically increased spontanous fibrinolysis regressed.

During the first six days of the enzyme therapy (from 15.-20.11.2000.), after receiving 300 000 urokinase i/v x once a day, spontaneous fibrinolysis from 65% was gradually decreasing to 22,2 - 29 - 31% - 17%, and got in norm 17-15%. Next 28 days the patient was receiving concurrently Actilysi and urokinase, and the spontanous fibrinolysis was in norm - 11,5-15,8% (Table 3).

During next 16 days, the patient was receiving Actilysi without urokinase. Spontaneous fibrinolysis was rising again from 18,4 to 47,6%. Subjective feeling of the patient got worse as well. Starting with 04.01.2001. urokinase was indicated again - 50 000 u. once a day. Spontaneous fibrinolysis (03.01.2001) was 47%. When treating by urokinase and t-Pa, spontaneous fibrinolysis normalized up to 12,4 - 15,9% with an adequate fribrinolytic activation response. Dyscoagulemia regressed. Vasculitis of the small pelvis disappeared because spontaneous adequate erections - impotence got cured. All 18 complaints which were marked on admission, disappeared, too (Table 4). When discharged from the hospital, the patient felt well and considered himself to be cured. The patient was treated.

Conclusions:

In cases of reinfection or a relapse, a repeated enzyme therapy with streptokinase may be necessary, considering the length of the remission.

Fibromyalgia is characterized by all clinical tests being in norm, except fot dyscoagulemia and pathologically high spontaneous fibrinolysis.

Fibromyalgia is a result of a pathology caused by the inflammation of physically-chemical properties of fibrinogen molecule, which is clinically manifest in the form of dyscoagulemia and increased spontaneous fibrinolytic activity with a paradoxical response to fibrinolyic enzyme system activation by SK, UK and t-PA.

Table Nr 3: Coagulogram

 

Literature:

1. Garth L. Nicolson, "Considerations when Undergoing Treatment of Gulf War III ness CFS/ FMS/ Rheumatoid Arthiritis", J.Medicine, 1998; 1: 123-128,
   http://www.immed.org/publications

2. Garth L. Nicolson, "Antibiotics/ Antivirals Recommended when Indicated Treatment of Gulf War III ness CFS/ FMS/ Arthiritis", http://www.immed.org/publications

3. Moira A. Smith, "Fibromyalgia and Chronic Fatigue Syndrome Treatment and Research", Australia, 2000, http://www.spirit.net.au/~masmith

4. F. Wolfe," The epidemiology of fibromyalgia",
   J Musculoskel Pain 1 (3/4): 137, 1993

5. D.Nye MD, "Guide to Fibromyalgia Syndrome", 2000, http://www.hsc.missouri.edu/~fibro

6. F. Wolfe,"Fibromyalgia: on diagnosis and certainty",  
   J Musculoskel Pain 1 (3/4): 17, 1993

7. Goldenberg DL, "Fibromyalgia and chronic fatigue syndrome: are they the same?", 
   J Musculoskel Med 7 : 19, 1990

8. Goldenberg DL et al, "High frequency of Fibromyalgia in patients with chronic fatigue syndrome seen in a primary care practice", Arthritis Rheum 33: 1132, 990

9. D.Nye MD, "Frequently Asked Questions about Fibromyalgia", 2000,
   http://www.hsc.missouri.edu/~fibro

10. Ivdra P., Platkajis E., Geldners I. Indications for enzyme therapy with streptase, urokinase and tissue plasminogen activator t-PA in chlamydial prostatitis. 1998. http://www.expo.lv/gailes/prostatitis.htm  

11. Platkajis E., Ivdra P., Miltins A., Geldners I., Ancupane I
    Clinical value of dynamics of streptokinase antibody level in antibiotic-resistant chlamydial prostatitis patients during enzyme therapy with streptokinase.1999 http://www.expo.lv/gailes/streptokinase.htm

12. Ivdra P., Zilevica A., Miltins A., Ancupane I.
    "Role of tissue plasminogen activator (t-PA) in enzyme therapy of antibiotic-resistant chlamydial
    prostatitis", Riga, 1999, http://www.expo.lv/gailes/actilyse_prostatitis.htm   

13. Ivdra P., Purmalis G., Geldners I.
    Streptokinaze ka plasminogena aktivacijas inhibitors. I Latvian Congress of Surgeons, May 29-20, 2000. Theses and poster report. 2000.01.16. http://www.expo.lv/gailes/viagra_streptase.htm  

14. P.Ivdra, G. Purmalis, A.Zilevica, I.Geldners, J.Zalkalns, I.Ancupane, A.Miltins,
    "Streptokinase as plasminogen activation inhibitor for chlamydial prostatitis patients", Riga , Latvian Association of Physicians-Chlamydiologists, 2000,
    http://www.expo.lv/gailes/streptokinase1.htm

15. P.Ivdra, J.Zalkalns, A.Zilevica,  I.Ancupane, I.Geldners, E.Baumanis,
    "Multidisciplinary problems in choosing proteolytic enzymes and their activators for Enzyme therapy of Antibiotic-resistant and Urogenital Chlamydiosis", Riga , Latvian Association of Physicians-Chlamydiologists, 2000,  http://www.expo.lv/gailes/enzyme.htm

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• PROTEINASES IN ENZYME THERAPY OF CHRONIC PROSTATITIS
• TREATMENT OF CHLAMYDIAL SPONDYLITIS
• STREPTOKINASE IN GERONTOLOGY
• SPECIFICITY OF ENZYME THERAPY IN TREATMENT OF LATE INFLAMMATORY FORMS OF PROSTATITIS
• POSSIBILITIES OF ENZYME THERAPY IN PAIN SYNDROME
• CHRONIC FATIGUE SYNDROME, FIBROMYALGIA ENZYME THERAPY
• ENZYME THERAPY OF ANTIBIOTIC-RESISTANT AND UROGENITAL CHLAMYDIOSIS
• STREPTOKINASE AS PLASMINOGEN ACTIVATION
• VIAGRA IN PROSTATITIS TREATMENT 
• ENZYME THERAPY WITH STREPTOKINASE
• CHLAMYDIAL PROSTATITIS
• ACTILYSE IN PROSTATITIS TREATMENT
• ENZYME THERAPY IN CHLAMYDIAL POLYARTHRITIS
• MEN PATHOLOGICAL CLIMACTERIC