C. Ailioaie, M. D. 
Medical Office for Laser Therapy, Iassy, RO 
Laura Marinela Lupusoru-Ailioaie, M. D.
"Al.I.Cuza" University, Dept. of Medical Physics, Iassy, RO

CONTENTS

1.PURPOSE:
To study the effects of laser therapy, in comparison with other modality trials (NSAIDs), at the onset of (RA).

2.SUBJECTS and METHODS: 
In the study 59 patients were included, in the first 6 - 12 months from RA onset. The patients were divided into three groups: Group 1 (21 patients) received laser therapy; Group 2 (18 patients) was submitted to placebo laser therapy and NSAIDs medication; Group 3 (20 patients) was treated only with NSAIDs. Physical therapy was instituted in all three groups. A GaAIAs diode laser (830 nm, maximum output power 200 mW) was used. During 4 months, courses of laser therapy - once daily for 8 days, monthly - were administered to Group 1 and laser placebo Group 2. The density of energy (2 - 4 J/cm2) and frequency (5 Hz or 10 Hz) were dependent on the number and severity of pain in affected joints.

3.RESULTS: 
The analysis of the clinical and biological parameters at the end of treatment showed a statistical significant decrease of duration of morning stiffness of pain at rest and during movements and improved acute phase reactants. The overall efficacy rate in these studies was 86% in group 1, 50% in the placebo laser group, and 40% in group 3.

4.DISCUSSION and CONCLUSIONS: 
After 4 months of treatment, our investigations showed that infra-red laser therapy was able to restore function, to relieve pain and to avoid the complications of the disease or NSAIDs therapy (digestive or renal) at RA onset, beeing the most perspective modality of treatment.


INTRODUCTION

Rheumatic diseases are frequently multisystematic in nature and chronic in duration. They represent the clinical manifestations of chronic inflammation of the tissues of the musculoskeletal system, blood vessels, and skin.

Rheumatoid Arthritis (RA) has a great importance for medical practice, because it is today the most frequent rheumatoid disease. Great majority of autors agree that the main therapy in RA is based on nosteroidal anti-inflammatory drugs (NSAIDs), as the first group of drugs utilised all over the World. Although very helpful in the most worrisome involve the gastrointestinal tract and kidneys.

Recent experimental and clinical studies emphasise that infrared laser rays of relatively low power density, and wavelenghts which posses the greatest penetrating capacity, have a major role on the cells involved in the immune and inflammatory responses at synovial membrane level.

In the present study we have investigated the effects of laser as a non-medication therapy, comparatively with the traditional NSAIDs trials, in an attempt to reveal new pathogenic mechanisms of RA.

MATERIALS AND METHODS

In the period 1997-1998, 59 patients were included in the study (from 19 to 62 years old), in the first 6-12 months from RA onset.

The criteria of study were the following:

Clinical criteria: arthritis with a 6-12 months onset, presence of inflammatory synovial fluids, contracture of dry-joints, tenosynovitis or bursitis, regional muscular dystrophy, eventual ankylosis of joints in the morning, acute or chronic iridocyclitis, fever, myalgia. The diagnosis for RA was according to ARA criteria.

The functional indices for assessment of pain and joint inflammation were the following:

Laboratory criteria: blood indices (haemoglobina, leukocytes, platelets, serum immunoglobulins, rheumatoid factor, erythrocyte sedimentation rate [ESR] and C-reactive protein, T lymphocytes, NK cells = natural killer cells), synovial biopsy specimens and synovial fluid analysis.

Radiological criteria:soft tissue swelling, osteoporosis and periarticular osteopenia, cartilage narrowing, carpal and other erosions, growth changes and synovial inflammatory activity - were analysed on conventional plain films and by Magnetic Resonance Imaging (MRI). 
X-rays radiographs taken in the early stages of the rheumatoid arthritis indicated no visible or minor changes, in conformity to Steinbrocker criteria. MRI, performed with a GIROSCAN T5 II, was a useful diagnostic modality at patients with painful joints. MRI - determined synovial membrane volumes were correlated with the overall histological assessment of synovial inflammatory activity.

Other examinations: ophtalmological examination (routine slit lamp examination); X-rays diagnosis eso-gastro-duodenal; fibroscopic examination; renal and hepatic functional probes. The patients were divided into 3 groups: Group 1 (21 patients) received laser therapy; Group 2 (18 patients) was submitted to placebo laser therapy and NSAIDs medication; Group 3 (20 patients) was treated only with NSAIDS.

It has been used a GaAIAs diode laser (830 nm, maximum output power 200 mW). During 4 months, courses of laser therapy - once daily for 8 days, monthly - were administered to Group 1 and laser placebo Group 2. The density of energy (2-4 J/cm2) and frequency (5 Hz or 10 Hz) were dependent on the nember and severity of pain in affected joints.

The initial treatment with NSAIDS in Groups 2 and 3 was prescribed with Diclofenac, without exceeding 150 mg/day - in two doses - in the morning and in the afternoon, after meals. In the protocol of treatment were included, as adjuvant medication for the relief of severe pain: Panadeine (1 - 3 tablets/day), Mydocalm (1 - 3 tablets/day) Calcium and vitamins.

Clinical features and laboratory findings were evaluated before the treatment and after 4 months of treatment. The patients were clinically re-evaluated after one year from the beginning of the treatment. The selected parameters were analysed with Student's test.

RESULTS

Analysing the 3 groups of patients diagnosed with RA under consideration, it comes out that there were no important differences as concerns the clinical and biological features at the beginning of trestment (Table 1).

Because the synovial membrane is the primary site of inflammation in joints with RA, there were performed synovial biopsies in 4 patients from Group 1; the overall historical assessment of chronic synovitis was well correlated with MRI - determined synovial membrane's aspect, being possible to exclude the knee tuberculosis. MRI presents significant advantages for non-invasive diagnosis of RA, and proved accuracy by patients with paintful knee, no visible modified X-rays radiographs and slightly increased acute phase reactants (Figure 1 ). 

After 4-months trial of treatment, we noticed that 86% of the patients from Group 1 were going to respond well and to experience a favourable outcome, in comparison with 50% of the patients from Group 2, and only 40% from Group 3, respectively. By these patients, we remarked the decrease of the number of sweelling joints and pain, an improved duration of morning stiffness and better preservation of joint function.

The laser radiation made possible not only the optimum treatment in pain-reduction therapy, but also get an improvement and/or a recovery of patients.

The laser therapy had a direct influence on the immune systém by increasing the number of NK lymphocytes, while T lymphocytes remained quatitavely unmodified, but possibly with a better function (Table 2).

Clinical evaluation of the patients after one year enabled us to conclude about the efficacy of treatment in the three groups. The remission was achieved in the greatest percentage (76%) by the patients of Group 1, in comparison with Groups 2 and 3, which did not receive laser therapy. In all three groups there were patients with active arthritis, but the smallest percentage (10%) was obtained in Group 1, witch demonstrates a greater effectiveness of laser therapy in comparison with the NSAIDs-therapy. In Groups 2 and 3, the patients have manifested adverse reaction to NSAIDs - therapy. The serious side effects were reactions cutaneous hypersensitivity, gastrointestinal reaction, renal and hepatic reactions (Table 4).


DISCUSSIONS

The treatment with soft lasers that operate on mW power level has substantially reduced the systemic and local clinical symptomatology, in a very good agreement with the evolution of the biological features in the Group 1.

The influence of laser on the immune system has been evidenced in medical literature; immunological effects on leukocytes, T, B and NK-lymphocytes, macrophages and other cells result in local and systemic effects through a compex mechanism of actions, which is not yet definitively elucidated.

We proposed in figure 2, a scheme to explain our clinical and biological results of the applied laser therapy. We consider that in the early stages of RA onset, laser irradiation of synovial membrane could directly control the autoimmune mechanism by reducing the local and systemic inflammatory response (Figure 2).

MRI of the synovial membrane performed in our experiments was able to visualise the specific laser therapeutic response. The new MRI techniques can perform extremely sophysticated examinations and will monitor in the future, arthritis at its onset.

The obtained effects of laser therapy, have revealed the special quality of laser beam to interact with cells, to determine a controlled biochemical conversion of energy and to influence the cellular metabolism in RA, as is proposed in figure 3.

We present a functional diagram, which could explain the interactive laser mechanisms at membrane level and its action on the up-mentioned metabolism (Figure 4).

CONCLUSIONS

Laser radiation made possible not only the optimum treatment in pain reduction therapy, but also brought an improvement and recovery of patients, demonstrating the greatest effectiveness, in comparison with NSAIDs therapy in the early stages of RA onset.

MRI of the synovial membrane performed in our experiments was able to visualize the specific laser therapeutic response and in the future will facilitate the monitoring of arthritis at its onset.

The laser therapy had a direct influence on the immune system by controlling the number of lymphocytes and improving their function.

Even the action mechanism is very complex, the laser therapy is the most perspective method of today non-medication therapy.


TABLES

Response of Patients with RA after 4 - Months Trial 

Evolution of Patients with RA after 1 Year of Treatment