Rheumatoid Arthritis

Vopr Kurortol Fizioter Lech Fiz Kult. 2015 May-Jun;92(3):11-3.

The influence of intravenous laser irradiation of the blood on the dynamics of leptin levels and the quality of life of the patients presenting with rheumatoid arthritis.

Burduli NN, Burduli NM.

Abstract

AIM:

The objective of the present study was to estimate the influence of intravenous laser irradiation of the blood on the dynamics of leptin levels and the quality of life of the patients presenting with rheumatoid arthritis.

MATERIAL AND METHODS:

A total of 132 patients at the age varying from 18 to 65 (mean 52.9 ± 11.3) years presenting with rheumatoid arthritis (RA) were available for the examination. The diagnosis of RA was based on the results of clinical, laboratory, and instrumental studies in accordance with the criteria of the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) dated 2010. The patients were divided into two groups. The control group was comprised of the patients who received the traditional medicamental treatment alone (n = 30) while the study group consisted of the patients given a course of intravenous laser irradiation of the blood in addition to the traditional medicamental treatment (n = 102).The course of intravenous laser therapy was performed with the use of a Matrix-VLOK apparatus (“Matrix”, Russia) by means of the VLOK + UBI procedure. Each course consisted of 10 sessions per patient without a break for the weekend.

RESULTS:

The data obtained indicate that the patients with rheumatoid arthritis had the increased plasma leptin level suggesting the development of the inflammatory process. Moreover, the quality of the patients’ life was deteriorated.

CONCLUSION:

The results of this study demonstrate that the combined treatment by means of low-intensity laser irradiation is accompanied by the normalization of the plasma leptin level, suppression of the inflammatory process, and a significant improvement of the quality of life of the patients suffering from rheumatoid arthritis.

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Dent Res J (Isfahan). 2015 May-Jun; 12(3): 215–223.
PMCID: PMC4432603

Comparative evaluation of low-level laser and systemic steroid therapy in adjuvant-enhanced arthritis of rat temporomandibular joint: A histological study

Faezeh Khozeimeh,1 Ahmad Moghareabed,2 Maryam Allameh,3 and Shahrzad Baradaran4
1Torabinejad Dental Research Center and Department of Oral Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2Dental Implant Research Center and Department of Periodontology, Isfahan University of Medical Sciences, Isfahan, Iran
3Torabinejad Dental Research Center and Department of Periodontology, Isfahan University of Medical Sciences, Isfahan, Iran
4Medical Laboratory, Isfahan, Iran
Address for correspondence: Dr. Maryam Allameh, Torabinejad Dental Research Center and Department of Periodontology, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran. E-mail:moc.oohay@hemalla_mayram
Author information ? Article notes ? Copyright and License information ?
Received 2013 Dec; Accepted 2014 May.

INTRODUCTION

Rheumatoid arthritis (RA), the most common form of inflammatory arthritis, is a progressive inflammatory disease that affects the joints. A significant percentage of patients with RA have symptoms and signs of temporomandibular joint (TMJ) involvement.[1] This is a far greater proportion than that in earlier studies,[2] as recently it is believed that TMJ involvement occurs even before the onset of clinical symptoms and autoantibody formation as well as synovial changes precede the clinical onset of the disease. In fact, all the prerequisites for osteoclast differentiation and bone erosion are found in this subclinical preliminary phase.[3] On the other hand, synovitis is not just a pure result of infiltration of the joint tissue by immune cells; rather it is a much more complex process, which consists of mononuclear immune cell infiltration and profound remodeling of the tissue architecture, such as the lining layer hyperplasia, fibrosis and vasculogenesis.[4] These changes provide a suitable setting for the generation of bone-resorbing cells, and the progress of the disease to a more debilitating and active phase.[3]

Rat adjuvant arthritis is an experimental model of RA, which has been widely used in previous studies.[5] Freund complete adjuvant (FCA) is composed of dead and dried mycobacterium tuberculosis in oil, which induces RA that is pathologically identical to that occurring in humans.[5]

Most of the time, RA exacerbates over time unless the inflammation is stopped or slowed by treatment.[2] There is no cure for RA, and the goal of treatment is remission, a state in which inflammation disappears or is very mild.[6] Despite the fact that not much time has elapsed since the initial report on the dramatic effects of cortisone in symptomatic treatment of RA,[7] glucocorticoids have become part of the gold standard of RA treatment and are widely used in this respect.[8] Administration of corticosteroids for RA management can be either intra-articular, local extra-articular or systemic.[9] Siró[10] reported that extra-articular management of cases is initially recommended. Intra-articular administration of steroids not only participates in erosive reactions in bone and cartilage,[11,12] but it also causes some systemic adverse effects.[13]

Of many anti-inflammatory steroid drugs used in the treatment of RA, dexamethasone, prednisone[14] and betamethasone[15] can be mentioned. Betamethasone is a synthetic, long-acting glucocorticoid that depresses formation, release, and activity of endogenous mediators of inflammation, including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. It also modifies body’s immune response.[16]

Recently, increasing concerns about the side effects of glucocorticoids have led to a decrease in their indiscriminate use in RA,[17] necessitating administration of new modalities in this field. Low-level laser therapy (LLLT) is one such promising therapy, introduced as an alternative non-invasive treatment for RA about 30 years ago.[18]

Several animal and human trials have demonstrated the modulatory effect of laser radiation on inflammatory markers[19] and cells.[20] The effectiveness of LLLT for RA is still controversial.[21] Many previous investigations have demonstrated dramatic effects of LLLT on relieving clinical symptoms of RA, including reduction in joint swelling,[19] pain[22] and morning stiffness[23] as well as improvement in health status.[22] Nonetheless, Schett[3] reported that even after remission of clinical symptoms, there might be synovitis and inflammation in the affected joint. Studies investigating the histopathological changes in resolution of RA with LLLT are scarce.

In a study by Alves et al.[24] on the histological effects of LLLT in early and late phases of RA, the ability of LLLT on modulating inflammatory responses, both in early as well as late progression stages of RA, was demonstrated. In another investigation, LLLT showed a dramatic effect in modulating inflammatory mediators (interleukin [IL-1?], IL-6) and cells (macrophages and neutrophils), which was in correlation with a reduction in histological inflammatory process.[25]

Although there are many studies assessing LLLT effectiveness in quenching the flame of inflammation, few studies have addressed the effects of LLLT in comparison with conventional treatments.[19,20]

With this perspective in mind, the present study was designed to investigate histological aspects of LLLT in comparison with a systemic corticosteroid in amelioration of TMJ inflammation.

MATERIALS AND METHODS

Animals

In this animal experimental study, 37 male Wistar rats, approximately 13?15 weeks old and weighing 250-300 g, were employed. The animals were kept under controlled conditions of light and temperature, with water and food provided. The study design and animal experimental procedures were approved by the Institutional Research Ethics Committee for Animal Investigations (Torabinejad Dental Research Center, Isfahan University of Medical Sciences).

For induction of arthritis in TMJ of rats, 50 mL[11] of an emulsion of FCA (Biojen, Mashhad, Iran) was injected into the left TMJ.[12] 7 days later, the animals were randomly distributed into three groups of 12 animals each, as follows:

  • LLLT group: Animals in this group underwent seven sessions of LLLT.
  • Steroid group: This group of animals received intra-peritoneal corticosteroid injection in a single dose.
  • Positive control group: The rats in this group received FCA injection but did not receive any treatment.

In addition, a rat served as the negative control, without receiving any intervention (neither arthritis induction nor treatment) to assess normal TMJ tissues in this rat model.

Low-level laser therapy procedure

For laser irradiation, the animals received a mild sedation of chloroform and were irradiated at an angle of 90° to the surface of the tissue over TMJ area. This region was scrupulously detected in each animal with palpation of a presumptive area, 5-10 mm posterior to the lateral eye canthus, while manipulating the mandible to provide movement of the condyle for further accurate identification of the joint position. Seven sessions of 60s LLLT was performed every other day during a 2-week period (physical parameters were selected in accordance to those applied in previous studies[24,26]).

Table 1 shows parameters and specifications of the laser device used in this experiment.

Table 1

Laser parameters and specifications

Systemic corticosteroid therapy

7 days after induction of arthritis, an intra-peritoneal injection of 1.2 mg/kg of betamethasone[11] was performed according to the technique employed by El-Hakim et al.[12]

Euthanasia and histological procedures

Half of the animals in each group and the rat kept as negative control were sacrificed for the histological procedure 3 weeks after FCA administration (immediately after completion of LLLT sessions: Early phase of evaluation, day 21). To do so, they were identified, weighed, and afterwards, subjected to euthanasia with a lethal dose of ether via inhalation. Thereafter, the left TMJ of each sacrificed rat was dissected by a sharp saw and then fixed in 10% formaldehyde for 24 h. After this period, they were decalcified using formic acid, embedded in paraffin blocks and 5-?m transverse sections were prepared. Slides containing two sections each were prepared and stained using hematoxylin-eosin.

Subsequently, to evaluate the late effects of each treatment modality, 2 weeks after sacrificing half of the animals in each group, the other half were subjected to the same procedure of euthanasia and slide preparation for histological assessment (late phase of evaluation, day 35).

Histopathological assessment

Histopathological evaluation was carried out under a light microscope in a ×400 field (Carl Zeiss Microscopy GmbH, Jena, Germany) by two expert independent pathologists (the intraclass correlation coefficient for grading inflammation features was 0.78). In order to quantify the outcomes analyzed in histological evaluation of the inflammatory events (synovial lining cell layers, vascularity and infiltration of immune cells), blinded operators used a standard scoring method according to Gynther et al. system[27] [Table 2]. In cases in which the synovial cell layers were to be counted, the pathologists chose an area whose status had been repeated in more than one-third of the entire specimen. Estimation of vascularity and inflammatory cells per square millimeter was carried out using grid counting slides (Ted Pella, Inc., California, USA). Both the number of vascular cross-sections per square millimeter and also the size of vessels were used in defining vascularity score of a specimen. Increased size of vessel cross-sections was determined in comparison with those in normal tissue (negative control).

Table 2

Gynther’s scoring system

Moreover, the pathologists investigated the presence of other signs of inflammation qualitatively, including fibrin deposition and synovial cell adhesion (the presence of closely opposed synovial cells intermingled with each other) for all the specimens.

Data analysis and statistics

Synovitis severity was graded from 0 to 16 by adding the scores of the three histological indices. Then, nonparametric Kruskal-Wallis and Mann-Whitney U-tests were used to compare the groups. Data were expressed as means and standard deviations. All the differences were considered significant at P < 0.05.

RESULTS

The histopathological changes, observed in rats injected with the FCA, confirmed the presence of acute inflammation in the synovium.

Positive control group, early and late phases

The synovial tissue appeared hyperplastic and showed a considerable number of inflammatory cells as well as dilated blood vessels in comparison to the negative control [Figure 1]. In addition to these features, an increase in the density of resident cells (synovial cell adhesion) and deposition of fibrous tissue [Figure 1] were observed in the majority of samples. In spite of a lower degree of inflammation scores in the late phase of assessment of the control group, compared to early evaluation of this group, the difference between these two stages was not significant (P = 0.132).

Figure 1

(a) Normal rat temporomandibular joint (TMJ) tissue (×100) showing a thin synovial membrane (synovium) without any evidence of inflammation. (b-d) Adjuvant-induced arthritis in rat TMJ showing: (b) Hypertrophic and hyperplastic synovial membrane

Laser group, early phase

Immediately after LLLT sessions, mild to moderate features of inflammation were still observed in the samples [Figure 2]. Moreover, the synovial cell lining in the majority of samples was >2–3 layers [Figure 2].

Figure 2

Laser group, early phase (×100), showing (a) moderate infiltration of inflammatory cells and slight hypervascularity. Inset: higher magnification (×400) of mononuclear inflammatory cells; (b) moderate hyperplasia of synovial lining layers

Steroid group, early phase

Two weeks after betamethasone administration, the synovial cell layers appeared normal without a significant inflammation or vasodilation [Figure 3]. However, there was still some evidence of fibrin deposition and fibrinous adhesion between closely opposed synovial membrane and articular surfaces in 50% of cases [Figure 3].

Figure 3

Steroid group, early phase, showing (a) normal synovial memberane (SM) and cartilage (×400); (b) increased synovial cell adhesion (×400); (c) floating fibrin in joint space (arrow) (×100).

Low-level laser therapy group, late phase

Evaluation of late effects of laser showed that LLLT succeeded in modifying the majority of changes due to arthritis [Figure 4].

Figure 4

Laser group, late phase, showing a thin layer of synovial memberane (SM) without any inflammation or fibrous tissue (×400).

Steroid group, late phase

In most cases, a marked inflammation was seen although it was milder than that in control samples at this stage. All the three inflammation indices under study were moderately higher in most samples [Figure 5].

Figure 5

Steroid group, late phase, showing a moderate increase in inflammatory infiltration and vascularity of synovial tissue (×400).

Table 3 shows the mean quantitative severity scores (±standard deviation) of synovitis in experimental and control groups.

Table 3

Mean values and standard deviations in studied groups*

The steroid- and laser-treated groups (early and late phases of treatment) presented a significant decrease in synovial inflammation severity, compared to the control group (P < 0.05). There was also a significant difference between the early and late effects of laser in a way that the late results were markedly better (P = 0.004). This result was contrary to betamethasone which showed a significantly better anti-inflammatory effect in the early phase of evaluation (14 days after administration) compared to the late phase (1-month after administration) (P = 0.002). There was no significant difference between LLLT in the late phase of evaluation and the early results of betamethasone (P = 0.485).

DISCUSSION

Great advances have been made since last decade in exploring the efficacy of LLLT in RA. Molecular[25] and clinical evidence[19,22,23] support the anti-inflammatory effects of this modality. In the present study, the early and late anti-inflammatory efficacy of LLLT and systemic corticosteroid therapy was compared in experimentally induced arthritis in rat TMJ.

The arthritis induced by FCA, in the present study, caused pathologic features similar to that of human disease.[4] The pathogenesis for the development of adjuvant arthritis is not fully understood. However, some have attributed this finding to the heat shock proteins and interactions with intestinal flora.[5]

Studies on RA have indicated that the synovial membrane has a dominant role in joint inflammation and destruction, suggested by the changes in synovial histology:

  • (1)
    Thickening of the synovial lining layer as a result of infiltration by CD68+ cells, and both proliferation and reduced apoptosis of type B synoviocytes;
  • (2)
    Neo-vascularization of the sub-surface layer;
  • (3)
    Infiltration of the sub-surface layer with T and B lymphocytes, plasma cells and macrophages; and
  • (4)
    Alteration of the adhesion molecule expression.[4] There are several histologic systems for grading synovial inflammation in TMJs.[27,28,29]

The system used in the present study was the one proposed by Gynther et al.,[27] the accuracy of which was tested by Suzuki et al. in 2001.[30] This system is based on a semi-quantitative evaluation of the following parameters:

  • (1)
    Synovial lining cell layers;
  • (2)
    Vascularity; and
  • (3)
    Inflammatory cell infiltration.

One of the differences between Gynther et al. system and other scoring scales is that all the parameters in this gradation will not necessarily have the same impact. The presence of inflammatory cells is considered more important for grading overall synovial inflammation and is therefore given higher scores, compared with other parameters. The other difference is that it considers even few inflammatory cells as an impressive factor in grading synovitis. It is in line with the results of previous studies which have demonstrated that the presence of several inflammatory cells is always indicative of synovial inflammation in the TMJ.[31] It is believed that human TMJ synovial inflammation differs from that in other synovial joints such as that in the knee, in a way that pronounced synovial inflammation is uncommon in the TMJ synovial lining.[27] Nevertheless, >60% of the rats showed pronounced inflammation in the positive control group of the present study. This discrepancy might be attributed to differences in histopathological features of human and rat models of RA.[5]

The delicacy of the synovial tissue and its partial adherence to articular bone made slide preparation difficult. However, this problem was resolved to a great extent in the present study by using Gynther et al. system for evaluation of the inflammation because in this system not an essentially complete intact synovial tissue is needed.

Previous studies have shown that only a small percentage of patients attain a sustained drug-free remission upon antirheumatic drug withdrawal.[32] This result was also confirmed in the present study, which showed disease exacerbation after betamethasone duration of action in the 4th week of investigation.

There are a large number of studies ranging from clinical controlled trials to molecular surveys to elucidate the efficacy of LLLT to manage RA and other rheumatic conditions. In a review study which explored the effect of nonpharmacological and nonsurgical interventions for patients with RA, it was concluded that there is some evidence that LLLT reduces pain and improves function.[33] In the present study, the GaAlAs diode laser, with a wavelength of 810-nm, energy density of 51 J/cm2 and output power of 200 mW, significantly reduced the inflammation of arthritic joints both in early and late phases of assessment. This result is in contrast with the results of a study by Kucuk et al.,[26] showing no significant difference between laser-treated and control groups in spite of relatively similar laser parameters applied in these two studies. The authors relate this diversity to differences in the methods used to assess inflammation. In Kucuk et al. study, the inflammation in TMJ was recorded through scintigraphic imaging, but in the present study, microscopic examination was used.

The results of the present study are in accordance with histological investigations carried out by Alves et al.[24] who reported a considerable anti-inflammatory effect of LLLT in collagen-induced RA model.

In the present study, the anti-inflammatory efficacy of LLLT in the early phase was significantly lower than that in the betamethasone-treated group, but in the late phase of the investigation, this result was vice versa. Studies comparing the effect of LLLT and conventional therapies in RA are scarce. Castano et al.[19] examined the anti-inflammatory effect of LLLT in comparison with dexamethasone for zymosan-induced arthritis in rats and demonstrated an almost equal effectiveness in these two modalities. Pallotta et al.[20] also compared the anti-inflammatory effect of infrared (810-nm) LLLT with diclofenac on rat experimental knee inflammation and documented a significant decrease in inflammation signs with both therapies.

With regard to the better outcomes of betamethasone in the early phase and LLLT in the later steps, it is suggested that perhaps a combination of the two approaches would bring great benefit in RA management.

It has been concluded from molecular studies that LLLT will start a complex of reactions,[34] which may persist for a long time afterwards. In the present study, the laser effect was evaluated in two phases:

  • (1)
    Immediately after completion of treatment course, and
  • (2)
    2 weeks after treatment to evaluate early and late effects of laser on joint inflammation.

It was shown that the laser effect in late phase was significantly better than the early stage.

In present study, in addition to a semi-quantitative evaluation of microscopic features of inflammation, the samples were also detected for any evidence of fibrin deposition and fibrinous adhesion between closely opposed synovial membranes; in this respect, these features were only observed in the positive control group and up to 50% of samples in early stage of steroid group. The inhibition of joint fibrinous tissue formation is not surprising in light of general catabolic actions of glucocorticoids on fibroblastic tissues.[35] However, the better late effect of these agents is noteworthy. This result is consistent with El-Hakim et al. findings,[12] which showed a less fibrinous state 6 weeks after intra-peritoneal injection of dexamethasone compared with earlier stages (1-week after injection). On the other hand, LLLT group (early and late phases) exhibited a lower rate of fibrin deposition and fibrinous adhesion compared with the positive control groups, indicating that LLLT was able to reduce synovial cell adhesions and secretion of fibrinous materials to joint space. Perhaps the efficacy of LLLT in eliminating morning stiffness symptoms and improving joint flexibility[23] is attributable to this issue.

The exact mechanism of action of LLLT in the treatment of RA is not yet well understood. It is however believed that it reduces the joint inflammation by suppressing the expression of auto-antigens[34] or inhibiting the expression of cytokines[25] involved in the inflammatory process. The authors of the present study believe that perhaps the better late effects of LLLT in the histological aspect is due to its bio-modulation effects (modulating effects on various biological events),[36] which was previously demonstrated in delayed phases postlaser therapy of wounds[37] and implants.[38] Nevertheless, the symptomatic effects of LLLT on joint inflammatory disorders, such as relief of pain, swelling and improvements in jaw movement, begin immediately after illumination.[23,39]

Despite many advantages in LLLT application for the treatment of RA, there are also some disadvantages, including an increased chair time and the number of treatment sessions in addition to its local effect, compared to systemic corticosteroid therapy.

A limitation of the present study was the lack of data on bone and cartilage changes in the joint.

Further studies are needed to investigate these results in chronic states of joint inflammation.

CONCLUSION

On the basis of the results of the present investigation, it can be concluded that 810-nm LLLT method has a long-term promising effect on reducing the inflammation of the TMJ, similar to betamethasone in earlier stages.

ACKNOWLEDGMENTS

This work was supported by a grant (393529) from the Vice Chancellor of Research of Isfahan University of Medical Sciences.

Footnotes

Source of Support: This work was supported by a grant from the Vice Chancellor of Research of Isfahan University of Medical Sciences.

Conflict of Interest: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article.

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Laser Ther. 2014 Sep 30;23(3):191-9. doi: 10.5978/islsm.14-OR-15.

Anti-inflammatory activities of light emitting diode irradiation on collagen-induced arthritis in mice (a secondary publication).

Kuboyama N1, Ohta M2, Sato Y3, Abiko Y4.

Author information

  • 1Department of Pharmacology, Nihon University School of Dentistry at Matsudo ; Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo.
  • 2Department of Oral Diagnosis, Nihon University School of Dentistry at Matsudo ; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo.
  • 3Department of Pharmacology, Nihon University School of Dentistry at Matsudo.
  • 4Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, ; Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo.

Abstract

BACKGROUND AND AIMS:

Rheumatoid arthritis (RA) is an auto-immune disease afflicting multiple joints of the body, where as a result of the increase in inflammatory cytokines and tissue destructive factors such as matrix metalloproteinase (MMP)-3, deterioration of the bones and cartilages of the joints occurs. The present investigation was carried out to study the anti-inflammatory activities of light emitting diode (LED) irradiation on hind paw inflammation in collagen-induced arthritis (CIA) mice models.

MATERIALS AND METHOD:

RA in the CIA mouse model was induced by immunization of DBA/1J mice with intradermal injections of an emulsion of bovine type II collagen and complete Freund’s adjuvant. A total of 20 CIA mice were subdivided into the following groups: control group, CIA group and 2 groups of LED irradiated CIA mice (LED groups) (n=5 per group). The mouse knee joint area in the LED groups (the 570 nm and 940 nm groups) was irradiated with LED energy, three times a week for 500 s per session over 8 weeks at a dose of 5 J/cm(2). The hind paw swelling was assessed by the increase in hind paw thickness. The serum levels of the inflammatory cytokines and arthritic factor MMP-3 were determined with an enzyme-linked immunosorbent assay (ELISA).

RESULTS:

In the LED-570 and LED-940 groups at 4 weeks after arthritis induction, the swelling inhibition index was 18.1±4.9 and 29.3±4.0 respectively. Interleukin (IL)-1?, IL-6 and MMP-3 serum levels were significantly lower in the LED-940 group.

CONCLUSIONS:

LED irradiation, particularly in the near-infrared was effective for inhibition of the inflammatory reactions caused by RA.

Vopr Kurortol Fizioter Lech Fiz Kult. 2014 May-Jun;(3):9-12.

[The influence of intravenous laser therapy on the endothelial function and the state of microcirculation in the patients presenting with rheumatoid arthritis].

[Article in Russian]
[No authors listed]

Abstract

AIM:

The objective of the present work was to study effects of low-level laser irradiation on the endothelial function and selected parameters of microcirculation in the patients presenting with rheumatoid arthritis.

MATERIAL AND METHODS:

This study included 132 patients at the age varying from 18 to 85 years presenting with rheumatoid arthritis. They were divided into 2 groups. The patients of the main group (n = 102) underwent daily intravenous laser blood irradiation during 10 days. The control group was comprised of 30 patients. Laser therapy was performed with the help of a laser therapeutic device Matrix – VLOK (“Matrix”, Russia) using alternation of two radiating heads: KI-VLOK-63 (wavelength 0.63 pm, for 15 minutes) and KI-VLOK-365 (wavelength 0.365 microm, for 5 minutes) in the continuous emission regime. The parameters of interest were measured before and after the treatment. The overall duration of intravenous laser irradiation of blood was 10 days without a break for the weekend.

RESULTS:

The data obtained suggest the improvement of the endothelial function and the microcirculation indices.

Lasers Med Sci. 2012 Apr 27. [Epub ahead of print]

Low-level laser therapy in different stages of rheumatoid arthritis: a histological study.

Alves AC, de Carvalho PD, Parente M, Xavier M, Frigo L, Aimbire F, Leal Junior EC, Albertini R.

Source

Post Graduate Program in Rehabilitation Sciences, Nove de Julho University (UNINOVE), Rua Vergueiro, 235, 01504-001, São Paulo, São Paulo, Brazil.

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p?<?0.05). We can conclude that LLLT is able to modulate inflammatory response both in early as well as in late progression stages of RA.

Phys Ther.  2011 May;91(5):665-74. Epub 2011 Mar 24.

Ex vivo soft-laser treatment inhibits the synovial expression of vimentin and a-enolase, potential autoantigens in rheumatoid arthritis.

Bálint G, Barabás K, Zeitler Z, Bakos J, Kékesi KA, Pethes A, Nagy E, Lakatos T, Bálint PV, Szekanecz Z.

Source

National Institute of Rheumatology and Physiotherapy, Frankel Leó Strasse 25-29, Budapest H-1023, Hungary. balintg@mail.datanet.hu

Abstract

BACKGROUND:

Soft-laser therapy has been used to treat rheumatic diseases for decades. The major effects of laser treatment may be dependent not on thermal mechanisms but rather on cellular, photochemical mechanisms. However, the exact cellular and molecular mechanisms of action have not been elucidated.

OBJECTIVE:

The aim of this study was to investigate the ex vivo effects of low-level laser treatment (with physical parameters similar to those applied previously) on protein expression in the synovial membrane in rheumatoid arthritis (RA).

DESIGN:

Synovial tissues were laser irradiated, and protein expression was analyzed.

METHODS:

Synovial membrane samples obtained from 5 people who had RA and were undergoing knee surgery were irradiated with a near-infrared diode laser at a dose of 25 J/cm(2) (a dose used in clinical practice). Untreated synovial membrane samples obtained from the same people served as controls. Synovial protein expression was assessed with 2-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry.

RESULTS:

The expression of 12 proteins after laser irradiation was different from that in untreated controls. Laser treatment resulted in the decreased expression of ?-enolase in 2 samples and of vimentin and precursors of haptoglobin and complement component 3 in 4 samples. The expression of other proteins, including 70-kDa heat shock protein, 96-kDa heat shock protein, lumican, osteoglycin, and ferritin, increased after laser therapy.

LIMITATIONS:

The relatively small sample size was a limitation of the study.

CONCLUSIONS:

Laser irradiation (with physical parameters similar to those used previously) resulted in decreases in both ?-enolase and vimentin expression in the synovial membrane in RA. Both proteins have been considered to be important autoantigens that are readily citrullinated and drive autoimmunity in RA. Other proteins that are expressed differently also may be implicated in the pathogenesis of RA. Our results raise the possibility that low-level laser treatment of joints affected with RA may be effective, at least in part, by suppressing the expression of autoantigens. Further studies are needed.

Lasers Med Sci.  2011 May 4. [Epub ahead of print]

Low-level laser irradiation treatment reduces CCL2 expression in rat rheumatoid synovia via a chemokine signaling pathway.

Zhang L, Zhao J, Kuboyama N, Abiko Y.

Source

Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, 870-1, Sakaecho-Nishi 2, Matsudo, Chiba, 271-8587, Japan.

Abstract

Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to the destruction of cartilage and bone. Although low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA, the molecular mechanisms underlying its effectiveness remain unclear. To investigate possible LLLI-mediated antiinflammatory effects, we utilized a collagen-induced arthritis (CIA) rat model and analyzed gene expression profiles in the synovial membranes of the knee joint. Total RNA was isolated from the synovial membrane tissue of the joints of untreated CIA rats or CIA rats treated with LLLI (830 nm Ga-Al-As diode), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes), coupled with Ingenuity pathways analysis (IPA). DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and that LLLI treatment significantly decreased CIA-induced CCL2 mRNA levels. IPA revealed that chemokine signal pathways were involved in the activation of CCL2 production. These microarray data were further validated using real-time PCR and reverse transcription PCR. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats treated with LLLI. These findings suggest that decreased CCL2 expression may be one of the mechanisms involved in LLLI-mediated RA inflammation reduction.

Phys Ther.  2011 Mar 24. [Epub ahead of print]

Ex Vivo Soft-Laser Treatment Inhibits the Synovial Expression of Vimentin and {alpha}-Enolase, Potential Autoantigens in Rheumatoid Arthritis.

Bálint G, Barabás K, Zeitler Z, Bakos J, Kékesi KA, Pethes A, Nagy E, Lakatos T, Bálint PV, Szekanecz Z.

National Institute of Rheumatology and Physiotherapy, Frankel Leó Strasse 25-29, Budapest H-1023, Hungary.

Abstract

Background Soft-laser therapy has been used to treat rheumatic diseases for decades. The major effects of laser treatment may be dependent not on thermal mechanisms but rather on cellular, photochemical mechanisms. However, the exact cellular and molecular mechanisms of action have not been elucidated. Objective The aim of this study was to investigate the ex vivo effects of low-level laser treatment (with physical parameters similar to those applied previously) on protein expression in the synovial membrane in rheumatoid arthritis (RA). Design Synovial tissues were laser irradiated, and protein expression was analyzed.

METHODS: /b> Synovial membrane samples obtained from 5 people who had RA and were undergoing knee surgery were irradiated with a near-infrared diode laser at a dose of 25 J/cm(2) (a dose used in clinical practice). Untreated synovial membrane samples obtained from the same people served as controls. Synovial protein expression was assessed with 2-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry.

RESULTS: /b> The expression of 12 proteins after laser irradiation was different from that in untreated controls. Laser treatment resulted in the decreased expression of ?-enolase in 2 samples and of vimentin and precursors of haptoglobin and complement component 3 in 4 samples. The expression of other proteins, including 70-kDa heat shock protein, 96-kDa heat shock protein, lumican, osteoglycin, and ferritin, increased after laser therapy. Limitations The relatively small sample size was a limitation of the study.

CONCLUSIONS: /b> Laser irradiation (with physical parameters similar to those used previously) resulted in decreases in both ?-enolase and vimentin expression in the synovial membrane in RA. Both proteins have been considered to be important autoantigens that are readily citrullinated and drive autoimmunity in RA. Other proteins that are expressed differently also may be implicated in the pathogenesis of RA. Our results raise the possibility that low-level laser treatment of joints affected with RA may be effective, at least in part, by suppressing the expression of autoantigens. Further studies are needed

Lasers Surg Med. 2009 Apr;41(4):282-90

Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes.

Yamaura M, Yao M, Yaroslavsky I, Cohen R, Smotrich M, Kochevar IE.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

BACKGROUND AND OBJECTIVE: Low level light therapy (LLLT) is being evaluated for treating chronic and acute pain associated with rheumatoid arthritis (RA) and other inflammatory diseases. The mechanisms underlying the effectiveness of LLLT for pain relief in RA are not clear. The objectives of this study were to determine whether LLLT decreased production of pro-inflammatory cytokines by cells from RA joints, and, if so, to identify cellular mechanisms.

STUDY DESIGN/MATERIALS AND METHODS: Synoviocytes from RA patients were treated with 810 nm radiation before or after addition of tumor necrosis factor-alpha (TNF-alpha). mRNA for TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured after 30, 60, and 180 minutes using RT-PCR. Intracellular and extracellular protein levels for 12 cytokines/chemokines were measured at 4, 8, and 24 hours using multiplexed ELISA. NF-kappaB activation was detected using Western blotting to follow degradation of IkappaBalpha and nuclear localization of the p65 subunit of NF-kappaB.

RESULTS: Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the mRNA level of TNF-alpha and IL-1beta in RA synoviocytes. This treatment using 25 J/cm(2) also decreases the intracellular levels of TNF-alpha, IL-1beta, and IL-8 protein but did not affect the levels of seven other cytokines/chemokines. TNF-alpha-induced activation of NF-kappaB is not altered by 810 nm radiation using 25 J/cm(2).

CONCLUSIONS: The mechanism for relieving joint pain in RA by LLLT may involve reducing the level of pro-inflammatory cytokines/chemokines produced by synoviocytes. This mechanism may be more general and underlie the beneficial effects of LLLT on other inflammatory conditions.

Lasers Surg Med. 2008 Sep;40(7):468-76.

Topical delivery of methotrexate via skin pretreated with physical enhancement techniques: low-fluence erbium:YAG laser and electroporation.

Lee WR, Shen SC, Fang CL, Zhuo RZ, Fang JY.

Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan.

Abstract

BACKGROUND AND OBJECTIVE: The high hydrophilicity and molecular weight of methotrexate (MTX) make it difficult to deliver via the skin route for treating psoriasis or rheumatoid arthritis. The objective of this study was to enhance and optimize the skin permeation of MTX using two physical techniques: an erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation.

METHODS: In vitro skin permeation was performed using horizontal side-by-side diffusion cells. The animal model utilized nude mice. The skin where epidermal hyperproliferation was reproduced by repeated barrier abrogation was also used as a permeation barrier for MTX delivery.

RESULTS: Application of the laser and electroporation significantly enhanced the permeation of MTX. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the laser fluence. Using electroporation, treatment with 10 pulses resulted in a twofold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 minutes resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence (1.4 J/cm(2)) was applied. Hyperproliferative skin generally showed a greater variability of MTX flux and lower permeation.

CONCLUSION: The results shown in the present study encourage further investigation of laser- and electroporation-assisted topical drug delivery.

Swiss Med Wkly. 2007 Jun 16;137(23-24):347-52.

Effect of low level laser therapy in rheumatoid arthritis patients with carpal tunnel syndrome.

Ekim A, Armagan O, Tascioglu F, Oner C, Colak M.

Osmangazi University, Department of Physical Therapy and Rehabilitation, Eskisehir, Turkey.

OBJECTIVE: the aim of the present study was to evaluate the efficacy of low level laser therapy (LLLT) in patients with rheumatoid arthritis (RA) with carpal tunnel syndrome (CTS).

MATERIAL AND METHODS: a total of 19 patients with the diagnosis of CTS in 19 hands were included and randomly assigned to two treatment groups; LLLT (Group 1) (10 hands) with dosage 1.5 J/ per point and placebo laser therapy group (Group 2) (9 hands). A Galium-Aluminum-Arsenide diode laser device was used as a source of low power laser with a power output of 50 mW and wavelength of 780 nm. All treatments were applied once a day on week days for a total period of 10 days. Clinical assessments were performed at baseline, at the end of the treatment and at month 3. Tinel and Phalen signs were tested in all patients. Patients were evaluated for such clinical parameters as functional status scale (FSS), visual analogue scale (VAS), symptom severity scale (SSS) and grip-strength. However, electrophysiological examination was performed on all hands. Results were given with descriptive statistics and confidence intervals between group means at 3 months adjusted for outcome at baseline and for the difference between unadjusted group proportions.

RESULTS: clinical and electrophysiological parameters were similar at baseline in both groups. Improvements were significantly more pronounced in the LLLT group than placebo group. A comparison between groups showed significant improvements in pain score and functional status scale score. Group mean differences at 3 months adjusted at baseline were found to be statistically significant for pain score and functional status scale score. The 95% significant confidence intervals were [-15 – (-5)] and [-5 – (-2)] respectively. There were no statistically significant differences in other clinical and electrophysiological parameters between groups at 3 months.

CONCLUSIONS: our study results indicate that LLLT and placebo laser therapy seems to be effective for pain and hand function in CTS. We, therefore, suggest that LLLT may be used as a good alternative treatment method in CTS patients with RA.

Used by the kind permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org

The Effects of Laser Therapy in the Early Stages of Rheumatoid Arthritis Onset

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, being 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:

  • Tumefaction of joints was evaluated on a 3-degrees scale (0 = joint without tumefaction; 1= moderate tumefaction; 2 = severe tumefaction);
  • Pain by movement of joints was evaluated on a 4-degrees scale (0 = without pain; 1=slight pain; 2 = moderate pain; 3 = severe pain);
  • Severity of movement’s amplitude was evaluated on a 5-degrees scale (0 = without loss of movement; 1 = 25% limitation of movement; 2 = 50% limitation of movement; 3 = 75% limitation of movement; 4 = total loss of movement);

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

RESPONSE GROUP 1 (Laser) GROUP 2 (Placebo Laser + NSAIDs) GROUP 3 (NSAIDs)
Good 86 % 50 % 40 %
Satisfactory 14 % 33 % 35 %
Unchanged 17 % 25 %

Evolution of Patients with RA after 1 Year of Treatment

CLINICAL FEATURES GROUP 1 GROUP 2 GROUP 3
Remission 76 % 44 % 35 %
Stable Arthritis 14 % 33 % 35 %
Active Arthritis 10 % 23 % 30 %

Phys Ther. 2007 Dec;87(12):1697-715. Epub 2007 Sep 25.

Effectiveness of nonpharmacological and nonsurgical interventions for patients with rheumatoid arthritis: an overview of systematic reviews.

Christie A, Jamtvedt G, Dahm KT, Moe RH, Haavardsholm EA, Hagen KB.

National Resource Centre for Rehabilitation in Rheumatology, Diakonhjemmet Hospital, PO Box 23 Vindern, 0319 Oslo, Norway. anne.christie@nrrk.no

Abstract

Conclusions based on systematic reviews of randomized controlled trials are considered to provide the highest level of evidence about the effectiveness of an intervention. This overview summarizes the available evidence from systematic reviews on the effects of nonpharmacological and nonsurgical interventions for rheumatoid arthritis (RA). Systematic reviews of studies of patients with RA (aged >18 years) published between 2000 and 2007 were identified by comprehensive literature searches. Methodological quality was independently assessed by 2 authors, and the quality of evidence was summarized by explicit methods. Pain, function, and patient global assessment were considered primary outcomes of interest. Twenty-eight systematic reviews were included in this overview. High-quality evidence was found for beneficial effects of joint protection and patient education, moderate-quality evidence was found for beneficial effects of herbal therapy (gamma-linolenic acid) and low-level laser therapy, and low-quality evidence was found for the effectiveness of the other interventions. The quality of evidence for the effectiveness of most nonpharmacological and nonsurgical interventions in RA is moderate to low.

J Rheumatol Suppl. 2005 Jan;72:21-4.

What else can I do but take drugs?  The future of research in nonpharmacological treatment in early inflammatory arthritis.

Li LC.

Ottawa Health Research Institute and The Arthritis Society, Ontario Division, Ottawa, Ontario K1Y 4E9, Canada. lli@ohri.ca

Abstract

Nonpharmacological treatments, including physiotherapy and occupational therapy, have assumed a complementary role to drug therapy in managing inflammatory arthritis. Clinicians and researchers are facing 3 major challenges concerning the use of these treatments. First, strong evidence is only present in a few nonpharmacological interventions, such as exercise, patient education, and low level laser in the treatment of rheumatoid arthritis. The evidence on the majority of interventions is, however, weak or inconclusive. Second, knowledge is lacking on the elements associated with models of nonpharmacological care. The multidisciplinary team approach has been viewed as the standard for arthritis treatment; however, the team structure and the communication style among team members vary around the world. The influence of these elements on treatment success remains unclear. Finally, disparities in knowledge management and translation in nonpharmacological research have hindered the clinical use of these treatments and the growth of research in the field. To address the challenges, the author is recommending 4 research priorities for nonpharmacological treatments: 1. Evaluation of less well-studied interventions; 2. Understanding the relationships among rehabilitation-related variables and disability; 3. Development and evaluation of innovative care models; and 4. Design and evaluation of knowledge transfer innovations.

Phys Ther. 2004 Nov;84(11):1016-43.

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Electrotherapy and Thermotherapy Interventions in the Management of Rheumatoid Arthritis in Adults.

Ottawa Panel.

Abstract

BACKGROUND AND PURPOSE: The purpose of this project was to create guidelines for electrotherapy and thermotherapy interventions in the management of adult patients (>18 years of age) with a diagnosis of rheumatoid arthritis according to the criteria of the American Rheumatism Association (1987).

METHODS: Using Cochrane Collaboration methods, the Ottawa Methods Group identified and synthesized evidence from comparative controlled trials. The group then formed an expert panel, which developed a set of criteria for grading the strength of the evidence and the recommendation. Patient-important outcomes were determined through consensus, provided that these outcomes were assessed with a validated and reliable scale.

RESULTS: The Ottawa Panel developed 8 positive recommendations of clinical benefit. Lack of evidence meant that the panel could not gauge the efficacy of electrical stimulation.

DISCUSSION AND CONCLUSION: The Ottawa Panel recommends the use of low-level laser therapy, therapeutic ultrasound, thermotherapy, electrical stimulation, and transcutaneous electrical nerve stimulation for the management of rheumatoid arthritis.

Lik Sprava. 2004 Mar;(2):30-5.

Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on functional indices of immune cells in patients with rheumatoid arthritis.

[Article in Russian]

Petrov AV.

Abstract

Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.

The effect of laser therapy in complex treatment of patients with rheumatoid arthritis.

Korolkova O M et al.

115 patients with rheumatoid arthritis (RA) of II-III degrees were treated with basic RA medications and infrared laser. In a control group of 20 patients only basic medication was given. 10 areas of the body were irradiated daily, increasing the dose every day during a period of 8-10 days. The effectiveness of the therapy was controlled through laboratory tests on i.a. inflammatory agents and the activity of lipid peroxidation. The results were statistically significant. The best effect was found in patients with degree II RA. Steroid medication could be reduced 8-10 days earlier in this group of patients and in some cases the medication could even be excluded. Degree III patients had a more moderate benefit of the laser treatment.

Cochrane Database Syst Rev. 2005 Oct 19;(4):CD002049.

Low level laser therapy (Classes I, II and III) for treating rheumatoid arthritis.

Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K, Morin M, Shea B, Tugwell P.

University of Ottawa, School of Rehabilitation Sciences, Faculty of Health Sciences, 451 Smyth Road, Ottawa, Ontario, Canada K1H-8M5. lbrossea@uottawa.ca

Update of: Cochrane Database Syst Rev. 2000;(2):CD002049.

Abstract

BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about ten years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. This review is an update of the original review published in October 1998. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA.

SEARCH STRATEGY: We initially searched MEDLINE, EMBASE (from 1998), the registries of the Cochrane Musculoskeletal Group and the field of Rehabilitation and Related Therapies as well as the Cochrane Central Register of Controlled Trials (CENTRAL) up to June 2001. This search has now been updated to include articles published up to June 2005.

SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors.

DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested using chi-squared. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Dichotomous outcomes were analyzed with relative risks.

MAIN RESULTS: A total of 222 patients were included in the five placebo-controlled trials, with 130 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 1.10 points (95% CI: 1.82, 0.39) on visual analogue scale relative to placebo, reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0.8 to 1.7). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference observed between the control and treatment hand for morning stiffness duration, and also no significant improvement in pain relief RR 13.00 (95% CI: 0.79 to 214.06). However, only one study was included as using the contralateral limb as control.

AUTHORS’ CONCLUSIONS: LLLT could be considered for short-term treatment for relief of pain and morning stiffness for RA patients, particularly since it has few side-effects. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints. There is clearly a need to investigate the effects of these factors on LLLT effectiveness for RA in randomized controlled clinical trials.

Lik Sprava. 2004 Mar;(2):30-5.

Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on functional indices of immune cells in patients with rheumatoid arthritis.

[Article in Russian]

Petrov AV.

Abstract

Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.

Pathophysiology. 2001 Aug;8(1):35-40.

Laser irradiation as a potential pathogenetic method for immunocorrection in rhematoid arthritis.

Timofeyev VT, Poryadin GV, Goloviznin MV.

Departments of Internal Disease and Pathophysiology, Russian State Medical University, Moscow, Russia

We investigated the immunocorrective and clinical effect in 75 rheumatoid patients treated with intravenous laser blood irradiation. A relation between the positive immunotropic (as well as therapeutic) effect and the pre-existent immune status of each patient was revealed. A well-defined effect was found in patients with a low level of CIC and a normal count of functional-competent T-cells. ILIB provided some symptomatic but unstable relief in patients with a high level of CIC and a high functional activity of T-lymphocytes. There was no effect in patients with a high level of CIC and decreased number of lymphocytes.

Aerosp Am. 2000 Apr;38(4):24-5.

From growing plants to killing tumors.

Flinn ED.

edflinn@pipeline.com

Abstract

NASA: A technique called photodynamic therapy, originally developed for commercial plant growth research on the Space Shuttle, has been used by surgeons in two successful operations for brain tumors. The device uses pin-head-size light emitting diodes (LEDs) that release long, cool, wavelengths of light which activate photosensitive antineoplastic drugs. The device is being adapted to non-space uses through a Small Business Innovation Research grant. The LEDs also are used to treat skin cancer, psoriasis, and rheumatoid arthritis. Research is being conducted regarding LED use in wound healing, tissue growth, and prevention of muscle and bone atrophy in astronauts.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 Mar-Apr;(2):13-8.

The combined laser therapy of rheumatoid arthritis

[Article in Russian]
Sidorov VD, Mamiliaeva DR, Derevnina NA, Reformatskaia SIu.

Low-intensity infrared laser radiation to the tympanic vessels was studied as one of the hemophysiotherapeutic methods and as a component of combined treatment in which it accompanies local transcutaneous laser radiation of the affected joints. It is shown that immunomodulation is feasible under noninvasive interauricular laser effect on hemostasis. Indications for both laser regimens are formulated. Joint exposure to transcutaneous laser radiation is contraindicated if the affected joints have an exudative component of inflammation

Rheum Dis Clin North Am. 2000 Feb;26(1):75-81, viii-ix.

Photopheresis and autoimmune diseases.

Mayes MD.

Division of Rheumatology, Wayne State University, Detroit, Michigan, USA. mmayes@oncgate.roc.wayne.edu

Abstract

Although several case reports and case series suggest efficacy for photopheresis in the treatment of autoimmune diseases, few controlled studies have been conducted to test this hypothesis. After a decade of interest, multiple case reports, open trials, and one controlled study, the role of photopheresis in autoimmune disease remains to be established. Controlled multi-center trials in rheumatoid arthritis, SLE, and scleroderma may be costly but are clearly necessary for proper evaluation of this therapy

Vopr-Kurortol-Fizioter-Lech-Fiz-Kult. 1999; (3): 35-43.

The interauricular laser therapy of rheumatoid arthritis.

Interaurikuliarnaia lazernaia terapiia revmatoidnogo artrita.

Sidorov-V-D, Mamiliaeva-D-R, Gontar-E-V, Reformatskaia-SIu.

Investigations have proved the ability of interauricular low- intensity infrared laser therapy (0.89 nm, 7.6 J/cm) to produce anti- inflammatory, immunomodulating action in patients with rheumatoid arthritis. The method has selective, pathogenetically directed immunomodulating effect the mechanism of which is similar to that of basic antirheumatic drugs and of intravenous laser radiation of blood. This laser therapy can be used as an alternative to intravenous blood radiation being superior as a noninvasive method. Interauricular laser therapy can potentiate the effects of nonsteroid anti-inflammatory drugs, cytostatics and diminish their side effects.

Scand J Rheumatol. 1998;27(6):454-7.

Cortical photostimulation with filtered visible light as a treatment for rheumatoid arthritis.

Madrid L, Issacharoff M, Bianchi J, Postiglioni M, Bruen A.

Research Methods Section, Faculty of Medicine, Univ.Nac.Tucuman, San Miguel de Tucuman, Argentina.

Abstract

Not all extraocular photoreceptors in the human brain have been identified or their functions determined. The efferent and afferent fibres between the orbital frontal cortex and the hypothalamus cannot be overlooked in the context of the neuro-endocrine-immune feedback loop. It is suggested here that there are extraocular photoreceptors in the orbital frontal cortex, conceivably crucial for immunoregulation. The orbital frontal cortex of 7 volunteers with rheumatoid arthritis (RA) was photostimulated through the roof of the orbits with filtered visible light in sessions of 12, 14 and 16 minutes for a period of 6 weeks. Within 5 weeks, a significant decrease in the rheumatoid factor titres of 6 subjects was observed together with marked clinical improvement in 4 cases.

Lik Sprava. 1995 May-Jun;(5-6):77-80.

The combined use of diprospan and laser irradiation of the joints in rheumatoid arthritis patients.

[Article in Ukrainian]

Lysenko HI, Handzha IM, Matiukha LF, Volobuieva ZV.

Abstract

An evaluation was done of effectiveness of diprospane (prolonged action glucocorticosteroid) in rheumatoid arthritis. There have been studied parameters characterizing the articular syndrome, laboratory values during the course of complex therapy that incorporated intraarthrous administration of diprospane and a course of laser irradiation of the joints against a background of intake of non-steroid antiinflammatory preparations and basis therapy with methotrexate. Topical therapy incorporated into the complex of therapeutic measures applied in patients with rheumatoid arthritis was found to be associated with most stable and pronounced effect, especially in the arthrous form of the malady. Combined use of intraarthrous administration of diprospane and a course of laser therapy permits achieving a favourable effect after a single administration of this drug preparation.

Ter Arkh. 1994;66(5):38-41.

The mechanism of the action of laser therapy in rheumatoid arthritis.

[Article in Russian]

Kozlova IS, Tsurko VV, Piriazeva NA, Volkova ZI, Kariakina EV, Nikolaev VI, Mul’diiarov PIa.

48 patients with rheumatoid arthritis (RA) were exposed to He-Ne laser radiation. Due to the course of the above laser therapy the patients displayed reduced levels of E and F2 alpha prostaglandins, a trend to a decrease of lipid peroxidation products, glycosaminoglycans and collagen-peptidase activity. This evidences for suppression of the inflammation and destruction in the connective tissue. Catalase activity in red cells enhanced. The authors point to high efficacy of low-intensity He-Ne laser in moderate rheumatoid inflammation.

CLINICAL APPLICATION OF GaAlAs 830 NM DIODE LASER IN TREATMENT OF RHEUMATOIC ARTHRITIS

Kanji Asada, Yasutaka Yutani, Akira Sakawa and Akira Shimazu.

Department of Orthopaedic Surgery, Osaka City University Medical School, Japan

The authors have been involved in the treatment of rheumatoid arthritis (RA), in particular chronic poly-arthritis and the associated pain complaints. The biggest problem facing such patients is joint contracture, leading to bony ankylosis. This in turn severely restricts the range of motion (ROM) of the RA-affected joints, thereby seriously restricting the patient’s quality of life (QOL). The authors have determined that in these cases, daily rehabilitation practice is necessary to maintain the patient’s QOL at a reasonable level. The greatest problem in the rehabilitation practice is the severe pain associated with RA-affected joints, which inhibits restoration of mobility and improved ROM. LLLT or low reactive level laser therapy has been recognized in the literature as having been effective in pain removal and attenuation. The authors accordingly designed a clinical trial to assess the effectiveness of LLLT in RA related pain (subjective self-assessment) and ROM improvement (objective documented data). From July 1988 to June 1990, 170 patients with a total of 411 affected joints were treated using a GaAlAs diode laser system (830 nm, 60 mW C/W). Patients mean age was 61 years, with a ratio of males: females of 1: 5.25 (16%: 84%). Effectiveness was graded under three categories: excellent (remarkable improvement), good (clearly apparent improvement), and unchanged (little or no improvement). For pain attenuation, scores were: excellent&emdash;59.6%; good&emdash;30.4%; unchanged&emdash;10%. For ROM improvement the scores were: excellent&emdash;12.6%; good&emdash;43.7%; unchanged&emdash;43.7%. This gave a total effective rating for pain attenuation of 90%, and for ROM improvement of 56.3%.

Lasers Surg Med.  1994;15(3):290-4.

Histological studies on the rheumatoid synovial membrane irradiated with a low energy laser.

Amano A, Miyagi K, Azuma T, Ishihara Y, Katsube S, Aoyama I, Saito I.

Department of Internal Medicine, Toyoko Hospital, St. Marianna University, Kanagawa, Japan.

Abstract

The beneficial effects of low energy laser irradiation on rheumatoid arthritis (RA) joints have been reported, but the mechanisms of action of low energy lasers in RA are unclear. The synovial membrane in cases of RA was studied histologically to observe the effects of low energy laser irradiation. Fourteen knee joints of RA cases, which had been scheduled for arthroplasty, were irradiated with a gallium-aluminium-arsenide (Ga-Al-As) laser (790 nm in wavelength and 10 mW of output power) prior to the surgical operation, at six points of the external aspect of the knee joint for 80 seconds at each points once a day for 6 days. On the day following the last irradiation, pieces of synovial membrane from the lateral irradiated area and from the median nonirradiated area as a control were resected during the arthroplasty. The histological findings of the irradiated synovial membrane showed flattening of epithelial cells, decreased villous proliferation, narrowed vascular lumen, and less infiltration of inflammatory cells compared with those of nonirradiated synovia. The evaluation of slides was done in a blinded manner, and significant differences was seen by Wilcoxon’s t-test (P < 0.01). Histological findings suggested that the low energy laser irradiation induced suppression of inflammation in the synovial membrane of RA.

Ter Arkh. 1994;66(1):29-32.

The choice of the method for intravascular laser therapy in rheumatoid arthritis.

[Article in Russian]

Zvereva KV, Gladkova ND, Grunina EA, Logunov PL.

Abstract

A randomized placebo-controlled study was made of the clinical efficacy of four different methods of intravascular laser blood irradiation (ILBI) with helium-neon laser in 150 patients suffering from rheumatoid arthritis (RA). As to ILBI methods used, the most remarkable clinical effect was produced by daily procedures. The positive effect of ILBI was of liminal character bearing in mind the power range examined whereas the negative effect of irradiation was dose-dependent. ILBI may cause an exacerbation of the inflammatory process in RA whatever the single dose and frequency of procedures. The best clinical effect with daily ILBI was attained in women, individuals with the presence of rheumatoid factor but with low titers thereof, and in patients with initial stages of RA and minimum inflammation activity. The efficacy of ILBI may be predicted on the basis of the patient’s clinical findings.

Ter Arkh. 1989;61(12):124-7.

The laser therapy of rheumatoid arthritis

[Article in Russian]

Soroka NF.

Abstract

About 300 patients with rheumatoid arthritis (RA) underwent multimodality treatment including laser radiation of varying wavelengths. Use was made of helium-neon, infrared, argon and helium-cadmium lasers. A new method of combined laser therapy by radiation of helium-cadmium and helium-neon lasers is described. A scheme of optimal parameters and types of laser radiation recommended for the treatment of different clinical varieties of RA is provided.

Ter Arkh. 1985;57(8):37-9.

Anti-inflammatory and immunosuppressive effects in patients with rheumatoid arthritis.

[Article in Russian]

Tupikin GV.

Abstract

The clinical and laboratory findings were examined of 10 patients with seropositive rheumatoid arthritis (RA) treated with a first applied technique of intravenous irradiation of the circulating blood with helium-neon laser combined with external irradiation of the inflamed joints. A distinct antiinflammatory and immunosuppressant effect was attained in all the RA patients. In 80% of the test subjects, the rheumatoid blood factor reduced to 1:20 titres. The treatment method did not cause any side effects or complications and shortened the time of the patients’ stay at hospital.

Lasers Surg Med 1980;1(1):93-101

LASER THERAPY OF RHEUMATOID ARTHRITIS

Goldman JA, Chiapella J, Casey H, Bass N, Graham J, McClatchey W, Dronavalli RV, Brown R, Bennett WJ, Miller SB, Wilson CH, Pearson B, Haun C, PersinskiL, Huey H, Muckerheide M

Thirty people with classical or definite rheumatoid arthritis received laser exposure to a Q-switch neodymium laser that operated at 1.06 micrometer with an output of 15 joules/cm2 for 30 nsec. One hand was lased at the proximalinterphalangeal (PIP) and metacarpal phalangeal (MCP) joints, whereas the other hand was sham lased. The patient, physician, and occupational therapy evaluators did not know which hand was being lased. Twenty-one patientsnoted improvement of both their MCP and PIP joints of both hands during laser therapy. Twenty-seven noted improvement of their PIP joints and 26
noted improvement of the MCP joints during therapy. Heat, erythema, pain, swelling, and tenderness all improved with time in both hands, but the lased hand had more significant improvement in erythema and pain. There was also significant improvement in grasp and tip pressure on the lased side. The level of circulating immune complexes as measured by platelet aggregation decreased during lasing. The improvement may be related to laser exposure. The exact role that laser radiation has upon rheumatoid arthritis and its mechanism of action remain

LASER THERAPY IN RHEUMATOLOGY

Judit Ortutay M.D., Klara Barabas M.D., Ph.D., *Adam Mester MD

National Institute of Rheumatology and Physiotherapy, Budapest *Semmelweis University, Faculty of Medicine, Dept. of Diagnostic Radiology and Oncotherapy, National Laser Therapy Centre, Peterfy Sandor Teaching Hospital, Budapest

Barabas irradiated first the joints of rheumatoid arthritis (RA) patients without skin ulcer. In the first open study objectively the range of motion and circumference of the treated joints were measured, Ritchie index as semiobjective parameter, subjective parameters as joint tenderness and pain on a visual analogous scale (VAS) were registered. The walking time was registered as a functional disability parameter. Laboratory activity parameters and the 99mTechnetium index was measured. The second part of the clinical study was double blinded, Infra Red (10mW and 100 mW) lasers were used versus dummy devices with the same outlook. The third part of the study were in vitro experiments. Synovial membranes of rheumatoid arthritis patients The DNA/RNA ratio of the RA group was compared to the control group. Significant difference was detected between the two groups. The fourth phase of clinical studies was to detect the effects of laser irradiation in other rheumatic diseases: psoriatic arthritis, sacroileitis, osteoarthritis, entesopathy, tenosynovitis, bursitis calcarea, fibromyalgia, localised muscle spasm, periarthritis humeroscapularis etc. The different wavelengths (604, 630, 660, 670, 690, 750, 780, 790, 820, 830, 904, 1053, 1219 nm,) were compared (30 – 100 mW) with other physiotherapy modalities, like ultrasound. Acknowledgement: The Central Research Institute of the Hungarian Academy of Sciences and LASOTRONIC AG (Switzerland) was helping the research.

Cochrane Database Syst Rev. 2000;(2):CD002049.

Low level laser therapy (classes I, II and III) in the treatment of rheumatoid arthritis.

Brosseau L, Welch V, Wells G, deBie R, Gam A, Harman K, Morin M, Shea B, Tugwell P.

School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H-8M5. lbrossea@uottawa.ca

BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about 10 years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the registries of the Cochrane Musculoskeletal group and the field of Rehabilitation and Related Therapies as well as the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, we selected only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently select trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested with Cochran’s Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: A total of 204 patients were included in the five placebo-controlled trials, with 112 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0. 8 to 1.7 cm). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference between the control and treatment hand, but all hands improved in terms of pain relief and disease activity. REVIEWER’S CONCLUSIONS: In summary, LLLT for RA is beneficial as a minimum of a four-week treatment with reductions in pain and morning stiffness. On the one hand, this meta-analysis found that pooled data gave some evidence of a clinical effect, but the outcomes were in conflict, and it must therefore be concluded that firm documentation of the application of LLLT in RA is not possible. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints.

Ter Arkh. 1994;66(1):29-32.

The choice of the method for intravascular laser therapy in rheumatoid arthritis.

[Article in Russian]

Zvereva KV, Gladkova ND, Grunina EA, Logunov PL.

A randomized placebo-controlled study was made of the clinical efficacy of four different methods of intravascular laser blood irradiation (ILBI) with helium-neon laser in 150 patients suffering from rheumatoid arthritis (RA). As to ILBI methods used, the most remarkable clinical effect was produced by daily procedures. The positive effect of ILBI was of liminal character bearing in mind the power range examined whereas the negative effect of irradiation was dose-dependent. ILBI may cause an exacerbation of the inflammatory process in RA whatever the single dose and frequency of procedures. The best clinical effect with daily ILBI was attained in women, individuals with the presence of rheumatoid factor but with low titers thereof, and in patients with initial stages of RA and minimum inflammation activity. The efficacy of ILBI may be predicted on the basis of the patient’s clinical findings.

Br J Rheumatol. 1994 Feb;33(2):142-7.

Low level laser therapy is ineffective in the management of rheumatoid arthritic finger joints.

Hall J, Clarke AK, Elvins DM, Ring EF.

Rehabilitation Laboratory, Royal National Hospital for Rheumatic Diseases, Bath.

Low level laser therapy (LLLT) is a relatively new and increasingly popular form of electrotherapy. It is used by physiotherapists in the treatment of a wide variety of conditions including RA despite the lack of scientific evidence to support its efficacy. A randomized, double-blind and placebo-controlled study was conducted to evaluate the efficacy of LLLT. The patient sample consisted of chronic RA patients with active finger joint synovitis. Forty RA patients with involvement of some or all of MCP or PIP joints were recruited. Following random allocation they received either active or placebo laser three times a week for 4 weeks. Measurements were taken prior to entry, after the treatment, 1 month and 3 months at follow-up. The groups were well matched in terms of age, sex, disease duration and severity. Few significant differences were noted in grip strength, duration of morning stiffness, joint tenderness, temperature of inflamed joints, range of movement or pain either within or between groups. Using these irradiation parameters the efficacy of LLLT is ineffective.

THE EFFECTIVENESS OF LASER THERAPY IN COMPLEX TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

O.M. Korolkova, V.T. Burlachuk, O.V. Gordienko, E.A. Afanasevskaya

Voronezh State Medical Academy, Voronezh Regional Hospital, Voronezh, Russia

The purpose of this research is to evaluate the effectiveness of laser therapy among patients with different extents of rheumatoid arthritis (RA) disease. There has been a study of 115 patients with RA activity II-III (the main group) who apart from the basic therapy also received laser treatment.

The apparatus ALT “Mustang” with the power of 2-10 W and infrared wave range has been used. The laser influence has been aimed at the area of a damaged joint. The du-ration of laser influence is from 5 to 17 minutes, adding 1-2 minutes daily. The number of fields is 10, the number of treatment procedures -8-10, The control group consists of 20 patients with RA (basic therapy only).

The control of effectiveness of the therapy was based on the complex laboratory data, including definition of non-specific factors of inflammation and the factors of activity of lipid peroxidation.

The greatest effect of the therapy has been achieved in the main group of patients with activity II. In comparison with the control group we managed to receive improve-ment 8-10 days earlier which allowed us to reduce the demand of steroids and in case of 20 patients even cancel taking them. We received statistically reliable fall of the activity of inflammation and lipid peroxidation. More moderate effect of the therapy was reached treating patients from the main group with activity III.

THE USE OF SUPRAVASCULAR BLOOD RADIATION WITH INFRARED LASER FOR TREATMENT OF SECONDARY VASCULITIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Y.L. Grinstein, S.V. Ivlev

Medical Academy. Krasnoyarsk, Russia

The purpose of this work was to study the opportunity of the use of supravascular blood radiation with infrared laser (IR-laser) for the treatment of secondary vasculitis in patients with rheumatoid arthritis (RA). The investigation included 12 patients with RA and secondary vasculitis signs. They received a course of supravascular blood radiation with IR-Iaser (wavelength 820-850 nm, 7-10 procedures). Control group consisted of 8 patients. Placebo laser therapy (LT) was administered to 7 patients. Such characteristics as hemostasis properties, a state of microcirculation in bulbar conjunctiva vessels were studied in all patients before and after treatment. It was revealed significant decrease of both XIIa-depended fibrinolysis and Willibrand’s factor level. The improvement of blood rheological properties was confirmed by a decrease of erythrocyte aggregation and im-provement of its deformability. Bulbar conjunctival microscopia revealed significant diminution of intravascular change index, significant increase of arteriola-venula ratio. The improvement of nephritis manifestations (significant decrease of proteinuria level). The changes of hemostasis parameters microcirculation system were not significant in patients receiving both placebo LT and conventional therapy. Conclusions: 1) It was re-vealed significant diminution of endothelium lesion and XIla-depended fibrinolysis resto-ration after IR-laser therapy in patients with RA and secondary vasculitis. 2) Both micro-circulation state in bulbar conjunctiva vessels and blood rheological properties signifi-cantly improve after IR-laser therapy. It is confirmed by a significant improvement of erythrocyte deformability and a decrease of its aggregation. 3) IR-laser therapy leads to urinary syndrome regression.

DIAGNOSTIC SIGNIFICANCE OF THE IMMUNITY INDICES INVESTIGATION IN THE USE OF LASER THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THE DISEASE COURSE PROGNOSIS

A.V. Nikitin, V.D. Khvan, E.F. Yevstratova

Medical Academy, Voronezh, Russia

The results of the examination of the patients with rheumatoid arthritis (RA) have shown the systemic lesion of all the links of the immune system. Many-sided positive in-fluence of low energy laser irradiation on the impairment of immune homeostasis has been shown. The aim of the investigation was to study the possibility of the low energy laser irradiation use in patients with RA depending on some immunity indices and the disease course prognosis. 60 patients with RA at the age of more than 16 years old hav-ing inflammatory process activity of the I-II degrees according to the RA criteria of the American Rheumatological Association classification have been examined. 30 patients of the control group underwent the conventional treatment with non-steroid anti-inflammatory drugs, basic treatment with delagil and physiotherapy. 30 patients of the main group underwent the conventional treatment and laser therapy on the joints by the infra-red laser installation “UZOR” with the wavelength of 0,89 um, the output power of 2 mW in combination with the above-vein blood irradiation by the helium-neon laser in-stallation “ALOK-1? with the output power of 0,6 mW. The treatment was carried out daily during 15 days. The immunity indices analysis before and after the treatment in both groups has established their obvious improvement in patients treated by laser irra-diation: T-lympocytes (CD3 (p<0.05), immunoglobulins ? (p<0.05), T-helpers inductors (CD4+) (p<0.05). The positive dynamics of the immunity indices in the studied group cor-related with the clinical improvement of the patients condition and depended on the marked immunity indices changes before the treatment, such as T-lymphocytes (CD3), T-helpers inductors (CD4+), immunoglobulins C. The marked positive dynamics of the abovementioned indices were not observed in the control group.