Chlamydial Polyarthritis

POSSIBILITIES OF ENZYME THERAPY WITH STREPTOKINASE AND PLASMINOGEN ACTIVATOR (t-PA) IN CHLAMYDIAL POLYARTHRITIS OF UROGENITAL ORIGIN

Pavels Ivdra, Aija Zilevica, Alfreds Miltins, Inara Ancupane, Ivars Geldners
Riga Clinical Hospital No.7, Head doctor: E. Platkajis
LSU Medical Faculty, Latvian Association of Physicians - Chlamydiologists

Pavels Ivdra	Aija Zilevica	Alfreds Miltins	Inara Ancupane	Ivars Geldners

Urogenital system diseases caused by Clamydia trachomatis - uretritis, prostatitis, cystitis, paraprostatitis, epididymitis,etc. quite commonly may have complications of reactive polyarthritis and Reiter's syndrome.

Taking into account the duration of illness and clinical manifestations, there are distinguished:
- Fresh, infectious process (acute, subacute, torpid);
- Chronic process (with exacerbations,though it is difficult to differentiate it from superinfection,
reinfection or relapse);
- Persistent infection (latent carrier of chlamydia).

Polyarthritis which is persisting for less than 2 months is considered a fresh process; however, cases persisting for more than 2 months - a chronic process.

Chlamydial prostatitis of urogenital origin is characterized by antibiotic-resistance, which is encountered either in fresh, acute or chronic and persistant, infectious processes.

III-type or reactive arthritis is caused by infections of Yersinia, Shigella, Salmonella, Chlamydia, or by rheumatism. [1] In reactive polyarthritis caused by Chlamydia trachomatis, the infectious agent - antigen can be found in the urogenital system, peripheral lymph nodes or in any part of the body, except the joints, our present diagnostic possibilities are limited so far.

Chlamydial reactive arthritis is characterized by:

- acute onset;
- affects less than 10 joints;
- mainly the joints of the lower extremities are affected;
- tendosynovitis;
- no erosive lesion on X-ray;
- more than half of patients are found antibodies in blood against Chlamydia trachomatis
- chlamydiologists and rheumatologists are of the opinion that the treatment is possible for 1-18 months. [2]

As a rule, chlamydia are always parasitic and belong to prokaryote-type bacteria energodependent from host cells. If the treatment exceeds 2 months, it gives proof of the intracellularly persisting chlamydial antibiotic-resistance, the reason being fibrinolytic enzyme system defect at the cellular level,i.e., of tissue plasminogen activation. [3]

In order to decrease the antibiotic-resistance and the duration of treatment, it is useful to administer proteolytic, fibrinolytic enzymes and their activators - papain, streptokinase, urokinase and Actilyse. Fibrinolytic enzymes and their activators improve the pharmacokinetics of antibacterial drugs in tissues, increasing possibilities for dyscoagulaemia, hypercoagulaemia and hyperfibrinogenaemia regression. [4;5]

We learned that patients with urogenital chlamydial prostatitis may show secondary induced dyscoagulaemia on starting enzyme therapy with streptase, and clinical picture is is characterized by hyperfibrinogenaemia and suppressed spontaneous fibrinolytic activity.

It is important to diagnose the level of fibrinolytic enzymatic defect whether it is in tissues, blood, or it is dependant on physically chemical changes of fibrinogen molecule in the degradation direction with the activity rise of fibrinolysis inhibitors, or it is dependant on antistreptokinase titre dynamics. [6;7]

Decrease of fibrinogen concentration in blood under 4,0 g/l during the enzyme therapy with streptase is a positive curative reaction.

From 1981 to 1999 the Urology Department of Riga Clinical Hospital Nr.7 "Gailezers", 1783 chronic chlamydial prostatitis patients had undergone treatment. From them 7-10% were complaining of pain in the joints - polyarthritis, Reiter's syndrome.

Example 1

Patient, 28 yrs.old, soldier of the National Military Forces (NMF), was treated at the Urology Department for 18 days (case report n# 20253-99).

On admission he complained of the pain in the back, sacrum, the groin. The pain radiated to the right leg up to the foot joint and toes. Oedema of the first toe of the right foot. Oeadema was seen also in the external ankle area of the right foot joint. Pain in the left leg up to the knee joint. Pain in both joints of the lower jaw. Stiffness and pain of the nape.There were no urogenital complaints.

Case history. The patient became ill 1,5 months ago. He had caught cold during the military training, while three times forcing the obstacle of ice cold water. The disease started with t 38 C and pain in the joints. He was treated in Jelgava hospital and was diagnosed Chlamydia trachomatis. He was transferred to Riga Clinical Hospital Nr.3 due to antibiotic-resistance. Urogenital complaints did not develop due to latent course of prostatitis. On admission, the prostate was deformed, asymmetric because of paraprostatitis in the right side, of dough consistency, diffusely painful.

Clinical diagnosis:

1. Acute chlamydial, gardnerella, uroplasm prostatitis;
2. Paraprostatitis;
3. Infectious reactive polyarthritis of urogenital origin;
4. Inflammatory dyscoagulaemia.

Coagulogram values indicated to the evidence of hypercoagulaemia as a result of paraprostatitis, i.e., the inflammation in pelvis minor and urogenital venous plexus (phlebothrombosis of pelvis minor).

- Fibrinogen concentration in blood 7,6 g/l;
- Fibrinogen B (++);
- Spontaneous fibrinolysis 3%;
- Fibrinolysis 250' of plasma euglobulin fraction;
- Fibrinolysis 9' dependant on XII factor;
- Coalin time 60';
- Proteolytic resistance 160 u. indicate hypercoagulaemia;
- "C" reactive protein is above 6,0 mg/l.

During the enzyme therapy, the patient was given:

1.Streptase from 6000-250 000 e.u. i/v once a day for 18 days, in total 2 140 000 e.u. i/v;
2. Heparin 5000 u. i/v once a day for 18 days;
3. Because of paraprostatitis and gardnerellosis - Sol.Metrogil 0,5% 100 ml i/v twice a day for 9 days;
4.Because of ureaplasmosis - Sol.Gentamycini 80 mg i/m twice a day for 15 days;
5. Antichlamydial antibiotics: Doxycylini 0,1 - three times a day for 15 days; Eritromycini 0,1 - twice a day i/v for 15 days.

At the end of the treatment, the pain in the joints disappeared. Polyarthritis signs, hypercoagulaemia, paraprostatitis completely regressed.The prostate regain its normal size, became symmetrical, well-outlined, with deep posterior sulcus, smooth, elastic, painless. The patient was cured.

Conclusion:  Timely diagnosed, acute (subacute) poyarthritis of urogenital origin, treated by streptase, can be cured within some weeks.

The cause of hypercoagulaemia is the involvement of pelvis minor in the inflammatory process. An adequate, pathogenetic therapy with streptase and heparin allows to reduce the time of treatment up to 18 days.

If the time of treatment due to antibiotic-resistance exceeds 2 months, it points to the enzymatic effect of fibrinolytic enzyme system activation which is manifest as resistance to streptase and urokinase.Prior to enzyme therapy, the coagulogram values quite commonly may be in norm, however, when starting the treatment with streptase, a secondary induced hyperfibrinogenaemia and hypercoagulaemia or dyscoagulaemia may develop. The treatment of intracellularly persisting chlamydial diseases is one of the enzyme therapy problems which is the most difficult to solve because it calls for fibrinolytic enzyme system activation at the cellular level, i.e., intracellulary, but not in the peripheral blood circulation. Tissue plasminogen activator (t-PA) provides immediate intracellular fibrinolytic activity on the same day. However, fibrinolytic effect with streptokinase in peripheral blood circulation and intracellulary can be achieved only after 3-4 week- long desensibilization course. Actilyse (t-PA) is very, very expensive and only wealthy patients can afford it. Streptokinase is cheap and is available to wide population, but the course of treatment is much longer. Actilyse (t-PA) provides the reduction of the course of treatment for more than three times. Enzyme drugs, as the medication for therapy, depend on the financing sources in medicine , and not so much on the doctors' wish.

Example 2

An unemployed who cannot afford to buy Actilyse at the chemist's. Patient I.K., 52 yrs.old, hospitalized at the Urology Department of Riga Clinical Hospital Nr.7 and treated for 39 days (case history n#11023). He has been suffering from chronic chlamydial and cytomegalovirus prostatitis for more than 20 years. He was repeatedly treated at Valmieras hospital, Republican Dermatovenerological Preventive Centre, Riga Clinical Hospital Nr.7 "Gaiļezers", consulted at P.Stradiņš Hospital. Using DIF method with monoclonal antibodies,antigen structures of chlamydia (+) were detected. By IIF method, Clamydia trachomatis antibodies in blood (+) titre are 1:32. Clinical picture of the disease was manifest like Reiter's syndrome, i.e., uretritis-prostatitis, conjunctivitis, polyarthritis. The prostate was deformed, flat due to evident paraprostatitis on both sides, smoothed posterior sulcus, smooth, rigid, painful. Antibiotic therapy was ineffective.

Clinical diagnosis:

- Relapse of urogenital chlamydiosis
- Cytomegalovirus infection
- Exacerbation of chronic chlamydial and virus prostatitis
- Paraprostatitis
- Reactive polyarthritis - Reiter's syndrome
- Antibiotic-resistance

The patient was administered enzymoantibiotic therapy:

1. (SK) Streptase 2500 - 1 000 000 e.u. once a day, i/v for 38 days= 27 600 000 e.u.;
2. Heparin 5000 once a day for 36 days;
3. Because of paraprostatitis - Sol. Metrogil 0,5% 100 ml i/v twice a day for 10 days;
4. Erythromycin 0,1 twice a day i/v for 17 days;
5. Cephazolin 1,0 twice a day for 7 days;
6. Sol.Ciprinol 100 g twice a day for 5 days.

Starting with SK 22nd infusion day, 1 hour after introducing 1 000 000 e.u. i/v, we observed a positive sanogenous reaction which was similar to that of introducing tissue plasminogen activator (t-PA). (Table n#1)

Table No. 1  - Test results

Conclusion: If a patient has received streptokinase 3 years before and has achieved desensibilisation as a result, and if there is no secondary induced hyperfibrinogenaemia, then the clinical effect of tissue plasminogen activation could be achieved also with streptokinase without Actilyse but it called for a long-term, 39 days course of treatment.

Tissue plasminogen activation with streptase (SK) ensured the antigen structure of chlamydia and antibody elimination from cells. As a result, the inflammatory process in the prostate steadily regressed and Reiter's syndrome-like complaints disappeared. The prostate was well-outlined, normal size, symmetrical, smooth with deep posterior sulcus, elastic, painless. Polyarthritis disappeared. Choosing a more etiopathogenetically targeted therapy, the functional state of joints and a patient's life quality improve.

Not always it is possible to achieve tissue plasminogen activation as in the above described case. If a patient has inflammatory dyscoagulaemia, hypercoagulaemia due to urogenital venous plexus inflammation in the pelvis minor and hyperfibrinogenaemia, in such a case it is impossible to achieve a positive sanogenous reaction with SK because of the danger of side effects - anaphylactic reactions (collapse and shock).

One should be cautious against secondary induced hypercoagulaemia and hyperfibrinogenaemia at the very start of enzyme therapy after the first SK injections. It is important to take into account that even 6-8 hours after SK infusion, there may appear the so-called late allergic reactions with hyperpyrexia t 38 C, arthralgias, abdominal pain syndrome and collapse. To prevent the side effects mentioned, it is necessary to have Actilyse (t-PA) extra to SK.

Example 3  
Patient I.L. (case history n#7667-99), 37 yrs. old, has been suffering for more than 4,5 years. He was transferred from the regional hospital to Riga Clinical Hospital Nr. 7 "Gaiļezers" with the diagnosis:

Urogenital antibiotic-resistant chlamydial polyarthritis, calculous prostatitis, paraprostatitis, hypercoagulaemia, hyperfibrinogenaemia.

On admission he complained of the pain in the hand joints, knee joints, shoulder joints, backbone, sacrum.

In coagulogram - hyperfibrinogenaemia - fibrinogen A concentration in blood 6,7 g/l (norm 2,0-4,0 g/l); fibrinogen B (++); spontaneous fibrinolysis 6,3% (N=10 - 15%); ethanol test (+); proteolytic resistance 170 u. (N=110-140).

The patient received enzyme therapy with streptase for 42 days up to 500 000 e.u. Allergic reactions to SK did not allow to increase the daily dose. The dose of SK course reached 16 400 000 e.u. Hypercoagulaemia and hyperfibrinogenaemia did not regress, therefore it was necessary to indicate tissue plasminogen activator - Actilyse extra. The patient received t-PA for 8 days , the dose 10-25 mg i/v simultaneously with SK. As a result, tissue plasminogen activator's enzymatic defect to SK completely regressed.

Streptokinase (SK) became effective at the intracellular level. Fibrinolysis time of plasma euglobulin fraction decreased up to 20' (N=120-240). Antibiotic-resistance disappeared and complete elimination of chlamydial antigen structures was achieved.

Streptase together with Actilyse improved pharmacokinetics of antibacterial means in tissues. Pain in the joints disappeared only after sanation of prostatitis and urogenital venous plexus. Functional state of joints and the patient's life quality improved. The patient is cured.

CONCLUSIONS:

1. Early diagnosis of polyarthritis of urogenital origin makes it possible for timely indication of an adequate etiopathogenetic enzymoantibiotic therapy with streptase (SK) or Actilyse.

2. Patients with reactive polyarthritis and Reiter's syndrome must undergo rectal examination for timely diagnosing of local inflammation in the prostate and pelvis maior of urogenital origin.

3. First of all, it is necessary to cure the primary source of infection, i.e., prostatitis, paraprostatitis, the inflammation of urogenital venous plexus. Only after it is done, the polyarthritis signs begin to regress.

4. Polyarthritis which is lasting for more than 2 months should be considered a fresh process which can be effectively treated by streptase without Actilyse within 3 weeks.

5. In polyarthritis of urogenital origin one can encounter antibiotic resistance and allergy or anaphylaxis to streptokinase. Therapy may last as long as several months.

6. SK as plasminogen activator is not of single curative effect. Part of patients find it effective, others - less effective or even completely ineffective, if urokinase or plasminogen activator (t0PA) in small dosis are not indicated extra.

7. Fibrinolytic enzyme system activators - SK and t-PA improve the pharmacokinetics of antibacterial drugs in cells and tissues, ensures regression of intracellular enzymatic defect and chlamydial elimination.

8.SK positive curative effect is proved by decrease of fibrinogen concentration in blood under 4,0 g/l.

9. The first sign to cell plasminogen activation with SK is the decrease of euglobulin fraction fibrinolysis time interval from 120' to 0', the time when the clot is not formed.

10. The enzyme therapy with SK and t-PA is the method of choice with no alternatives for the treatment of reactive polyarthritis of urogenital origin.

REFERENCES

1. Saario L., Tovanen A.
   "Chlamydia pneumoniae as a cause of reactive arthritis".
   Clin.Rheumatol., 1992, 11:161

2. M.Domeika, A.Miltins, P.A.Mardh
   "Hlamidijas, to izraisitas cilveku un dzivnieku slimibas".
   Rīga, 1994.g., n#2, 44.-45.lpp.

3. P.Ivdra
   "Hroniska prostatita enzimterapijas indikacijas un antibiotikorezistences regresijas iespejas".
   "Latvijas Arsts", 1994.g., n#2, 120.-122.lpp.

4. Pavels Ivdra, Edvins Platkajis, Ivars Geldners
   "Indications for Enzyme Therapy with Streptase, Urokinase and Tissue
   Plasminogen Activator - t-PA in Chlamydial Prostatitis". 1998
   http://www.expo.lv/gailes/prostatitis.htm  

5. Pavels Ivdra, Aija Zilevica, Alfreds Miltins, Inara Ancupāne
   "Audu plazminogena aktivatora nozime antibiotikorezistenta hlamidiju prostatita enzimterapija".
   "Latvijas Arstu Zurnals", 1999/7, 40.-43.lpp.

6. Edvins Platkajis, Pavels Ivdra, Alfreds Miltins, Ivars Geldners, Inara Ancupane
   "Clinical Value of Dynamics of Streptokinase Antibody Level in Antibiotic-Resistant
   Chlamydial Prostatitis During Enzyme Therapy with Streptokinase". 01.14.1999
   http://www.expo.lv/gailes/streptokinase.htm

7. Pavels Ivdra, Aija Zilevica, Alfreds Miltins, Inara Ancupane
   "Role of Tissue Plasminogen Activator (t-PA) in Enzyme Therapy
   of Antibiotic-Resistant Clamydial Prostatitis". 99.06.08
   http://www.expo.lv/gailes/actilyse-prostatitis.htm

Back to start page

• 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