Lasers in Surgery and Medicine 1:93-101 (1980)

Laser Therapy of Rheumatoid Arthritis

John A. Goldman, MD, Joseph Chiapella, MD, Helen Casey, PhD, Noah Bass, MD,
Jimmy Graham, MD, William McClatchey, MD, R . V. Dronavalli, MD, Richard
Brown, MD, William J. Bennett, WID, Stephen B. Miller, MD, Colon H. Wilson, MD,
Bobbie Pearson, OTR, Cosmo Haun, MD, Lydia Persinski, MS, Herb Huey, MS,
and Mike Muckerheide

From the Department of Medicine, Division o f Rheumatology-Immunology, The Woodruff

Medical Center, Emory University School of Medicine (J.A.G., J.C., H.C., N.B., J.G.,
W.McC., R. V.D.,R. B., W.J.B., S.B.M., C.H. W., C.H.); the Emory University Clinic (L.P.,
H. H.); the Hand Management Center, Center for Rehabilitation Medicine (B.P.); the
Center for Disease Control (H.C.), Atlanta, Georgia, and the A. Ward Ford Memorial
Institute, Wausau, Wisconsin (M.M.)

Thirty people with classical or definite rheumatoid arthritis received laser ex-
posure to a Q-switch neodymium laser that operated at 1.06 p m with an out-
put of 1 5 joules/cm2 for 30 nsec. One hand was lased at the proximal
interphalangeal (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 patients
noted 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 t o laser exposure. The exact
role that laser radiation has upon rheumatoid arthritis and its mechanism of
action remain t o be elucidated.

Key words: laser, rheumatoid arthritis, polyarthritis, connective tissue disease, immunologic disease

INTRODUCTION
Our earlier studies have shown that some people with rheumatoid arthritis who re-
ceived laser exposure to their joints noted improvement [ 11 . To evaluate critically the
effects of the laser on rheumatoid arthritis the following study was designed.
Address reprint requests to John A . Goldman, MD. Department of Medicine, Division of Rheumatology-
Immunology, Emory University Clinic, 1365 Clifton Road, NE, Atlanta, G A 30322.

0196-8092/80/0101-0093$02.00@ 1980 Alan R. Liss, Inc.

94 Goldman et a1

PATIENTS AND METHODS

Thirty people with classical or definite rheumatoid arthritis participated in this study.
They were classified by American Rheumatism Association criteria, 26 having classical and
four having definite rheumatoid arthritis [2, 31. There were 25 women and five men who
ranged in age from 22 to 73 years with an average of 53 years. The duration of their arthri-
tis ranged from one to 2 6 years with an average of 11.8 years.
People were eligible t o enter the study if they had active rheumatoid arthritis with
symmetrical involvement of both hands, They continued their previous treatment program
as outlined by their private physicians. All who entered the study participated with in-
formed consent, and the protocol was approved by the Human Investigations Committee
of Emory University School of Medicine.

Laser
The laser used is the American Optical 641 SB high radiance neodymium glass laser
system. It is a three-stage oscillator-amplifier pulsed device that operates in the Q-switch
mode at 1.06 pm (1,060 nm). The energy output of this infrared laser was 15-25 joules/
cmz with a pulse duration of 30 nsec. The emission wave-length of 1,060nm has a lind-
width of about 20 8.The output beam cross-section is circular with a diameter of 32 mm.
Measured beam diversion is less than 0.16 milliradians; full angle, half energy. The repeti-
tion rate at full output is one pulse every five minutes.

Study Design
The patients were seen for 13 different sessions. There was a control period that
included sessions 1 and 2, which were one week apart. Session 1 included the initial in-
take interview and physical examination. At that time, the patient saw both the physi-
cian and the occupational therapist. At session 2 the patient again saw the physician and
occupational therapist and these data were also included as control period observations.
Sessions 2 through 11 included 10 weekly sessions of lasing. Prior to lasing each week, the
patient saw both the physician and occupational therapist to assess the activity and func-
tional involvement of the arthritis of the hands. There were then follow-ups at session 12,
one month after the final lasing, and session 13, three months after the final lasing.
During these sessions the patients again saw the physician and occupational therapist.
Procedure
The procedure involved lasing the metacarpal phalangeal (ILICP) and proximal inter-
phalangeal (PIP) joints of one hand. The other hand was not lased, but was sham lased.
Neither the patient nor the physician or occupational therapist who evaloated the patients
on a weekly basis knew which hand was receiving the lasing. The laser instriiment super-
visor randomly alternated dominant hands and kept a secret code as to which hand re-
ceived the lasing. So that the patients would feel a sensation with lasing as well as with
sham lasing, compressed air was blown onto the impact area with each laser firing and
with each sham firing.
Laser Safety
The patient, laser instrument supervisor, and physician all wore protective glasses
with an optical density of 14 a t 1,060 nm. The laser room was light-tight with a nonreflec-
tive surface painted dark blue. At the time of lasing, the patient, physician, and laser in-
strument supervisor closed their eyes and turned their heads. There was a countdown with
 Laser Therapy of Rheumatoid Arthritis 95

each laser firing. The laser firing mechanism was controlled by a lock. The laser instrument
supervisor carried the key, and the laser could not be fired until the key was in place. The
physician then did the countdown and pushed the firing button. The laser personnel re-
quired eye examinations every three months, and the room was inspected by the Emory
University Radiation Safety Officer. The lasers could not fire unless the doors to the laser
room were locked. Interlocks were put on the doors to prevent firing in case the doors
were not completely shut. A warning light outside the laser laboratory was blinking at all
times during operation. Warning signs with the sunburst laser hazard signal were on all
doors as well as on the laser, designating this as a class IV laser.

Evaluation of the Patient

1) The occupational therapist evaluated hand function. The following evaluations
were performed [4].

a) Range of motion of MCP and PIP joints. In this method all motions of the joints
are measured from defined zero as beginning position. Thus the degree of motion is added
in the direction the joint moves from zero. Active motion is that motion obtained by the
joints with full flexion or extension force. The term “extension” is used for motions op-
posite to that of flexion to the zero starting position. The BeOK plastic goniometer was
used as the tool of measurement.
b) Circumferential measurement: Circumference was measured in centimeters using
the Sterling circumference measurer around the PIP joint of all digits.
c) Tip pinch in pounds: This was recorded by positioning the Preston pinch gauge
between the thumb and PIP joint of the index, middle, ring, and little fingers.
e) Flexion tip to distal palmar crease measurement: This records the distance that
the pulp of the finger lacks in touching the distal palmar crease in centimeters.
f) Grip strength in pounds: This was measured using the Preston hand dynamometer.

2) Evaluation by the physician included classification of the rheumatoid arthritis and

with each session recording

a) duration of morning stiffness

b) medication program
c) on a 0-4t scale, the PIP and MCP: 1) heat, 2 ) erythema, 3) tenderness, 4) pain on
motion, 5) swelling.

The physician also filled out a post-laser form after each laser operation. which re-
corded any comments the patient had about the lasing.

Laboratory Studies
These were initially done with session 1, which was the intake evaluation, with session
11, which was ten weeks after the lasing was initiated, and with session 13, three months
after the last lasing. Laboratory studies performed included a complete blood count with
differential; Westergren sedimentation rate. SMA 14. which included chemistries, antinu-
clear antibodies, rheumatoid factor, cryoglobulins, and a test for the detection of circulat-
ing immune complexes by platelet aggregation [ S ] ;complement consumption [6] ;and
polyethylene glycol precipitation [7-91. Roentgenograms of the hands were also taken
three times, at sessions 1, 11, and 13.
 96 GoIdman e t a1

Data Collection and Analysis

The data collected in this study was keypunched on computer cards. Computer
programs used:
1. BMDP3F - Multiway Frequency Tables - the Log Linear Model, Health Sciences
Computer Facility, University of California at Los Angeles, copyright 1977, Regents
University of California, program revised November 1978.
2. BMDPl F - 2-Way Frequency Tables - Measures of Association, Health Sciences
Computer Facility, University of California at Los Angeles, copyright 1977, Regents
University of California, Manual Program, revised November 1978.
3. BMDP2V - Analysis of Variance and Co-Variance including Repeated Measures,
Health Sciences Computer Facility, University of California at LQSAngeles, copyright
1977, Regents University of California at Los Angeles, program revised November 1978.
4. SPSS - Statistical Package for the Social Sciences for VS/9, version H, release
7.2, Nie N., T. Hall,J. Jenkins, K. Steinbrenner and D. Bent, McGraw-Hill (1975) New
York, (2nd Edition); revised Dec. 5 , 1977.

RESULTS

Physician Evaluation
During this study most patients noted some improvement in both hands. Twenty-one
noted improvement of both their MCP and PIP joints, 27 noted improvement of their PIP
joints, and 26 noted improvement of their MCP joints. As noted in Table I, during the
follow-up period this improvement noted during lasing tended t o decrease.

TABLE I. Patient Improvement of Both Hands Following Laser Exposure to One Hand, by Activity
Outcome Evaluation

Insert heads here

Both 21 During lasing

17 Follow-up
PIP 27 During lasing
23 Follow-up
MCP 26 During lasing
22 Follow-up

TABLE 11. Improvement With Laser by Time TABLE 111. Improvement With Laser by Side

Time Side
Response RX’) Response P(x’)
~

Heat 0.0001 * Heat 0.0588

Erythema 0.0001 * Erythema 0.0002 *
Pain 0.0001 * Pain 0.0006 *
Swelling 0.0001 * Swelling 0.8663
Tenderness 0.0001* Tenderness 0.0662

*= significant * = significant
 Laser Therapy of Rheumatoid Arthritis 97

When heat, erythema, pain, tenderness, and swelling were analyzed using the com-
puter program 3F, the changes over time were the same for each hand. The relationship
a m o y response, time, and side lased were similar. Using program l F , one can see (Table
11) that all of these variables improved with time. The changes are highly significant and
in each case the tendency was for a larger portion of the joints to be rated zero (0) as time
progressed. When looking at the response of heat, erythema, pain, swelling, and tenderness
as related to side, lased versus non-lased (Table HI), although there were significant differ-
ences between the lased and non-lased hand for erythema and pain, apparently when one
hand started to improve the other did also for all variables.
Occupational Therapist Evaluation
The objective data collected by the occupational therapists were analyzed using
program 2V for the analysis of variances of a repeated measure. The subjects were divided
into two groups: those with right-hand laser treatment and those with left-hand laser
treatment, t o see if this had any effect on the outcome of lasing versus nonlasing.

Lateral pinch. Lateral pinch was measured on each hand one time during the 13 ses-
sions. There were no significant differences for this variable.
Flexion. There were four measurements per hand per session. The effect of differ-
ences in flexion between the lased and nonlased side was not significant.
Grasp. Grasp was measured in each hand once per session. This response is the most
clear-cut. There is a significant difference in the lased and unlased hands which changes
over the visits (P = 0.0180). The difference is the same for people lased on the right and
on the left. The examination showed increase in grasp on the lased side over time and
stronger grasp on the lased side than on the unlased side. The mean grasp per treatment
visit was 29.33 pounds per square inch for the lased side versus 26.52 pounds per square
inch on the unlased side.
PIP joints. There were only 13 subjects with complete PIP flexion data; seven were
lased on the right and six were lased on the left. A multiple range test on the means did
not reveal any significant different subsets. Thus it appears that there was not a difference
with lasing of the PIP joints compared to the unlased joints.
MCP joints. Measurements of the MCP joint flexion did not show a significant dif-
ference between the lased and unlased side.
Tip pinch. There was an improved tip pinch for the lased side over time compared
to the unlased hand. This measurement was significant (P = 0.0194).
Laboratory data. The only significant change in laboratory data was between the
first and second platelet aggregation measurements (P = 0.025), using paired t-tests. The
first mean was 34.5, the second 17.8, and the third measurement was 21.14. No significant
difference in measurements could be seen with titer of rheumatoid factor, antinuclear anti-
body, or polyethylene glycol precipitates, or the results of the Westergren sedimentation
rates. The results of the complete blood counts and chemistries as recorded by SMA
showed no adverse results. X-ray studies showed no adverse effects due to lasing. Erosive
changes remained stable and no new erosions were identified. Bone density remained un-
changed. Changes in soft tissue swelling were noted, but these correlated with changes in
the activity of the arthritis.
 98 Goldman et a1

Adverse effects. All 30 patients noted stinging during laser treatment. Two people
noted erythema and two hyperpigmentation at the laser impact sites.

DISCUSSION
Laser radiation has shown multiple effects on various biological systems. The ratio-
nale to use the laser includes the following: 1) heat effect; 2) laser shock wave; 3 ) pigment
absorption; 4) immunosuppression/immunostimulation; 5) stimulation of wound healing;
6) distal effects beyond lased area; 7) pain relief.
Heat therapy has been used for rheumatic diseases for many years. The Romans
built baths to take advantage of heated water, and natural hot springs are used throughout
the world. Direct studies using both heat and cold have shown that both may improve the
amount of discomfort a patient feels [ 101 . The brief duration of the pulse of the neody-
mium laser used in this study would not give sustained heat. Thus it is doubtful that heat
alone would explain any laser effect. Along the pathway of high-energy laser radiation.
erythema and tissue necrosis can be seen [ 111 . It could be from this heat shock wave that
effects of laser therapy might be noted. Indeed, many of the patients on this study did
note burning and stinging at the site of impact, and post-impact erythema was noted in a
few. However, documentation of a direct erythematous and perhaps heat shock wave ef-
fect at the site of lasing does not necessarily mean effects within the joints could be related
to this mechanism, Also, depending on the laser wavelength used, different cells or sub-
cellular components might selectively absorb the light because of pigmentary differences,
and thus a spectrum of effects could be seen in various tissues.
Autoimmunity may be related to the pathogenesis of rheumatoid arthritis and the
damage that ensues may be directed by the immune system responding to self antigens
[ 12-14] . The patients not only had positive antinuclear antibodies, rheumatoid factors,
and cryoglobulins, but they also had circulating immune complexes. All of these serolog-
ical findings appear t o be due to autoimmune responsiveness.
The improvement seen by laser radiation could be related to the described immuno-
suppressive effect which can be achieved with various types of lasers. Simultaneous appli-
cation of the helium-neon and pulsed laser can achieve immunosuppressive effects with
minimal cell loss. The effect concerns T as well as B lymphocytes [ 151 . Ruby laser radia-
tion of the spleen of white rats injected with Brucella abortis 19 demonstrates that non-
focal splenic laser radiation suppresses the immunocellular reaction and function of im-
mune cells. This effects the synthesis of antibodies after the first antigen challenge and
also the second immunization. There is decrease in both the number of antibody-forming
cells and the titer of the amount of brucella antibodies noted .[l6] . However, Moskalik et
a1 noted that seven to 14 days after radiation with a neodymium glass laser of experimental
tumors on mouse hindlegs, the number of antibody-forming cells in the spleen increased
[ 171. In the peripheral blood, the number of rosette-forming cells as well as the capacity
for T lymphocytes to undergo blast transformation was decreased. Later all these signs re-
turned to the pretreatment values. This suggests that laser radiation can have both immuno-
suppressive and immunostimulative effects. Since some of the pathogenic mechanisms of
rheumatoid arthritis may be related to loss of control by suppressor T cells, the possibility
that laser radiation can be immunostimulative, stimulating suppressor T cells and thus being
helpful in regaining this loss of control is considered. Also in view of the autoimmune anti-
body production by patients with rheumatoid arthritis, there is the possibility that laser
radiation can be immunosuppressive, and therefore decrease some of this overactivity, es-
 Laser Therapy of Rheumatoid Arthritis 99

pecially of the B lymphocyte line. This could concur with some of the present-day drug
therapy of rheumatoid arthritis using immunosuppressive or immunostimulative therapy
[18-201. Our observation that the level of circulating immune complexes measured by
platelet aggregation dropped during lasing and then returned during follow-up may suggest
such immune modulation was occurring with our patients.
The laser may also affect the rheumatic process because of its influence on wound
healing. Helium-neon laser radiation of various wounds has been shown to be effective in
helping to improve wound healing [21]. The most pronounced shortening of the intervals
of healing of experimentally induced wounds in chinchilla rabbits was noted at 0.54 joules/
cm’. The helium-neon lasing appeared t o stimulate the reparative process and accelerate
the healing of these experimentally inflicted wounds. There was good development of nor-
mal epithelium, dermis, and loose subcutaneous tissue.
Stepanov et a1 [22] noted that radiation of cells within a helium-cadmium laser
heightened the stimulating activity of helium-neon laser radiation. Helium-neon radiation
alone brought out less effective stimulation, but restored almost to the control level the
mitotic activity of the cells. Mitotic activity depressed by ruby laser radiation could be
restored in this manner. Mester et a1 [23-251 have found low-energy helium-neon gas la-
sers to be effective in the treatment of various types of wounds, including coumarin-in-
duced skin necrosis. The stimulation effect of the laser on wound healing depends on col-
lagen production, on succinic acid dehydrogenase, lactic acid dehydrogenase, and nonspe-
cific esterase activities of the fibroblast cultures.
Immunoglobins and complement also appeared to be influenced [25]. In those pa-
tients who had improvement in their wounds with laser radiation, the serum IgM rose,
whereas the IgG decreased initially and then increased by the end of treatment. The IgM
returned to a lower level after completion of the therapy. In patients with skin ulcers that
were resistant to laser radiation, the IgM levels rose continuously, and the value of IgC af-
ter a temporary decrease returned to its initial value. Complement activity decreased during
laser therapy and returned to normal after completion. Thus possibly a direct influence 011
the immunological processes within an inflamed joint could occur with lasing.
Since most patients showed improvement not only on the lased but also on the non-
lased side, there might be effects of the laser apart from that due t o direct impact. It is
known that ruby laser treatment of human tumors and melanoma has been observed to
lead to progressive necrosis of tumor cells at sites peripheral to the initial radiation [ 2 6 ] .
Studies have shown that there can be an intracellular transfer of toxic components after
laser radiation [27]. Thus there is a possibility that cellular effects from laser radiation
could carry over to sites beyond that where lasing occurs. This might explain the improve-
ment in both hands noted by most patients. It is also possible that various products could
be released by laser radiation that might have effects elsewhere in the body. Neurotrans-
mitters can be released which may have distant effects. Laser radiation of Auerbach’s
plexus in the guinea pig ileum can release acetycholine [28] .
For relief of pain, laser acupuncture has been developed. This has been used for
various types of ailments, and has been observed to influence healing in various types of
rheumatic problems [29,30] . A variety of mechanisms of action has been suggested, in-
cluding bioluminescence and bioplasma. It has been suggested that acupuncture loci emit
light themselves. This is called bioluminescence [3 11 . This luminescence is said to follow a
24-hour rhythm and thus is comparable to the flow of Ch’i through the meridians every
24 hours. Also suggested is a mechanism of bioresidence between energy sources such as
lasers and a biosystem that is tuned to a complex pattern of resident frequencies. The
100 Goldman et a1

medium for this interaction is said to be “bioplasma,” the direct evidence for which comes
from experiments in Kirlian electrophotography [ 3 2 ] . That the relief of pain demonstrated
in some of our patients may be related t o a form of laser acupuncture is speculative.
Thus patients with rheumatoid arthritis receiving laser therapy note improvement
of their arthritis by both activity and hand function evaluation. The changes were usually
bilateral, although more improvement in grip strength and tip pinch and less erythema
and pain was noted on the lased side. The decrease in titer of circulating immune com-
plexes as measured by platelet aggregation may indicate a general improvement in the
overall activity of the rheumatoid disease or reflect specific immune modulation by lasing.
The mechanisms of improvement may be related to laser exposure, but the exact role that
laser radiation has upon rheumatoid arthritis and its mechanisms of action remains to
be elucidated.

ACKNOWLEDGMENTS

The authors would like to thank Sandra Stahl, PhD, Nashville, Tennessee, for trans-
lating the Russian literature, Ms Jennie Crook for preparing the manuscript, and
Bob Byers, PhD for the statistical evaluation.
This work was supported by grants from the A. Ward Ford Memorial Institute,
Wausau, Wisconsin, and the Irvine Young Foundation, Palmyra, Wisconsin.

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