Fundamentals of Rheumatoid Arthritis and various

Homoeopathic trials in patients of Rheumatoid arthritis:

An update

Dr. Mohit Mathur (Reader NFSG), Dept. of Practice of Medicine, Nehru

Homoeopathic Medical Collage & Hospital, B-block, Defence colony, New Delhi
(India) PIN-110024.

INTRODUCTION
Rheumatoid Arthritis1 (RA), the chronic inflammatory joint disease, is a
symmetrical, destructive and deforming polyarthritis affecting small and large
synovial joints with a variety of extra articular features and associated systemic
disturbance and presence of circulating antiglobulin antibodies.

EPIDEMIOLOGY:
The prevalence of RA is approximately 0.8% of the population (range 0.3 to
2.1%); women are affected approximately three times more often than men.
AETIOLOGY:
Although the cause of RA remains obscure, it has been suggested that RA
might be a manifestation of the response to an infectious agent in a genetically
susceptible host. A number of causative agents suggested include
Mycoplasma, Epstein-Barr virus, cytomegalovirus, parvovirus and rubella virus
and the process by which an infectious agent might cause chronic
inflammatory arthritis with a characteristic distribution also remains unknown.
However, there is evidence that disease is triggered by Th1 lymphocyte
activation and production of proinflammatory cytokines such as IL1, TNF-alpha
and IL-6 in genetically predisposed individuals with defined HLA class-II
haplotypes. HLA-DR4 is the major susceptibility haplotype in most ethnic
groups.

PATHOGENESIS:
The disease is characterized by persistent synovitis. The inflamed synovium
shows increased number of synovial lining cells along with perivascular
infiltration with mononuclear cells. As the process continues, the synovium
becomes edematous and protrudes into the joint cavity as villous projections.
The rheumatoid synovium is characterized by the presence of a number of
secreted products of activated lymphocytes, macrophages, and fibroblasts. The
local production of these cytokines and chemokines accounts for many of the
pathologic and clinical manifestations of rheumatoid arthritis. The activity of
chemokines and cytokines appears to account for many of the features of
rheumatoid synovitis, including the synovial tissue inflammation, synovial fluid
accumulation, synovial proliferation, and cartilage and bone damage, as well as
the systemic manifestations.

CLINICAL MANIFESTATIONS:
RA has an insidious onset, with joint pain, stiffness and symmetrical swelling of
a number of peripheral joints. Initially pain may be experienced only on
movement of joints, but rest pain and prolonged early morning stiffness are
characteristics. RA most often causes symmetric arthritis with characteristic
involvement of certain specific joints such as proximal inter-phalangeal and
metacarpo-phalangeal joints. The distal inter-phalangeal joints are rarely
involved. Synovitis of the wrist joint and elbow joint is a uniform feature of RA.
Characteristic changes of the hand include radial deviation at the wrist with
ulnar deviation of the digits, with palmar subluxation of the proximal
phalanges(Z deformity); hyperextension of the proximal inter-phalangeal
joints, with compensatory flexion of the distal inter-phalangeal joints (swan
neck deformity); flexion contracture of the proximal inter-phalangeal joints
and extension of the distal inter-phalangeal joints(boutonniere deformity) and
hyperextension of the first inter-phalangeal joint and flexion of the first
metacarpo-phalangeal joint with consequent loss of thumb mobility and pinch
Typical joint changes develop in the feet include eversion at the hindfoot,
plantar subluxation of the metatarsal heads, widening of the forefoot, hallux
valgus and lateral deviation and dorsal subluxation of toes. . The small joints of
the fingers and toes are first to be affected. As the disease advances, muscle
atrophy, and tendon sheath and joint destruction result in limitation of joint
mobility, joint instability, subluxation and deformities. Anterior subluxation of
the metacarpo-pharyngeal joints is common, with ulnar deviation of the
fingers. The disease is characterized by Swan-neck deformity, the boutonniere
deformity(Fixed flexion of the proximal interphalangeal joint and extension of
the terminal interphalangeal joints), Tenosynovitis and bursitis and Popliteal
cyst in the knee with many extra-articular manifestations.
Investigations:
1. Rheumatoid factor:
No tests are specific for diagnosing RA. However, rheumatoid factors, which
are autoantibodies reactive with the Fc portion of IgG, are found in more than
two-thirds of adults with the disease. Widely utilized tests largely detect IgM
rheumatoid factors. The presence of rheumatoid factor is not specific for RA.
Rheumatoid factor is found in 5% of healthy persons. In addition, a number of
conditions besides RA are associated with the presence of rheumatoid factor.
These include systemic lupus erythematosus, Sjogrens syndrome, chronic liver
disease, sarcoidosis, interstitial pulmonary fibrosis, infectious mononucleosis,
hepatitis B, tuberculosis, leprosy, syphilis, subacute bacterial endocarditis,
visceral leishmaniasis, schistosomiasis, and malaria.
The presence of rheumatoid factor does not establish the diagnosis of RA as
the predictive value of the presence of rheumatoid factor in determining a
diagnosis of RA is poor. However, the presence of rheumatoid factor can be of
prognostic significance because patients with high titers tend to have more
severe and progressive disease with extraarticular manifestations.
A number of additional autoantibodies may be found in patients with RA,
including antibodies to filaggrin and citrullinated proteins. Some of these may
be useful in diagnosis in that they may occur early in the disease before
rheumatoid factor is present or may be associated with aggressive disease.
2. Normochromic, normocytic anemia
It is frequently present in active RA. It is thought to reflect ineffective
erythropoiesis. In general, anemia and thrombocytosis correlate with disease
activity. The white blood cell count is usually normal, but a mild leukocytosis
may be present. Leukopenia may also exist without the full-blown picture of
Feltys syndrome. Eosinophilia, when present, usually reflects severe systemic
disease.
3. The erythrocyte sedimentation rate
It is increased in nearly all patients with active RA. The levels of a variety of
other acute-phase reactants including ceruloplasmin and C-reactive protein are
also elevated, and generally such elevations correlate with disease activity and
the likelihood of progressive joint damage.
4. Synovial fluid analysis
Synovial fluid analysis confirms the presence of inflammatory arthritis,
although none of the findings is specific. The fluid is usually turbid, with
reduced viscosity, increased protein content, and a slightly decreased or
normal glucose concentration. The white cell count varies between 5 and
50,000/microlitre; polymorphonuclear leukocytes predominate. Total
haemolytic complement, C3, and C4 are markedly diminished in synovial fluid.
 5. Radiographic evaluation
Salient radiographic features include Juxtaarticular osteopenia which may
become apparent within weeks of onset. Loss of articular cartilage and bone
erosions develop after months of sustained activity.
Homoeopathic clinical research in rheumatoid arthritis:
Homoeopathy offers an effective treatment for chronic immune mediated
disease conditions such as rheumatoid arthritis. Several clinical trials across the
world have been conducted to validate the efficacy of homoeopathic
intervention in the treatment of rheumatoid arthritis. A synopsis of some
important trials is provided below:

Gibson 1978 study2: this pilot study was a controlled trial evaluating efficacy of
homoeopathic intervention against analgesics and placebo. The patients who
received homoeopathy did better than those who received salicylate and
patients on homoeopathic treatment did not experience toxic effects. But the
study was criticized as patients who received homoeopathic treatment were
allowed to continue their previous anti-inflammatory drugs whereas the
patients who received salicylates had to discontinue all other previous anti
inflammatory drugs. Also, since the patients who received homoeopathic
treatment were seen by different doctors from those being given salicylate, it
was argued that the better response of the patients on homoeopathy was due
to doctor and not the drug.

Gibson 1980 study3: To overcome the deficiencies of the previous trial, in 1980,
Gibson conducted a double blind clinical therapeutic trial in which a group of
23 patients of rheumatoid arthritis on orthodox first-line anti-inflammatory
treatment plus homoeopathy were compared with a similar group of 23
patients on orthodox first-line treatment plus an inert preparation. There was
a significant improvement in subjective pain, articular index, stiffness and grip
strength in those patients receiving homoeopathic remedies whereas there
was no significant change in the patients who received placebo. Two
physicians were involved in prescribing for the patients and there were no
significant differences in the results which they obtained. No side effects were
observed with the homoeopathic remedies.

Andrade 1991 study4: this was a 6 month double blind randomized controlled
trial comparing homoeopathy and placebo in the treatment of rheumatoid
arthritis. 23 patients who received homoeopathic treatment were compared
with a placebo group of 21 patients on multiple outcome measures which
included clinical measures of disease activity such as Ritchies articular index,
duration of morning stiffness, grip strength etc. and also for daily requirement
for NSAIDs and prednisone. Intragroup comparison between outset and end
showed a significant improvement with homoeopathic treatment for 3 of 5
observed variables. The treatments were generally equally effective in most
assessments. There was no statistically significant difference between groups.
Adverse effects were scarcely and comparably reported in both groups and did
not require a change in therapy.
P. Fisher 20015: A 6 month randomized double blind RCT in RA was conducted
by P. Fischer wherein patients with definite RA receiving either stable dose of
single NSAIDs for more than 3months or single DMARD with or without NSAIDs
for more than 6 months were included for the study. No evidence was found
that active homoeopathy improves the symptoms of RA, over 3 months in
patients attending a routine clinic who are stabilized on NSAIDs or DMARDs.

CCRH (India)6, carried out a pilot study to assess the effectiveness of 3

predefined homoeopathic drugs (Rhus tox, Pulsatilla and Medorrhinum) on
immunological markers of Rheumatoid Arthritis (acute phase reactants and
inflammatory cytokines in the blood wherein Pulsatilla and Rhus tox showed
significant improvement in patients VAS compared to the placebo group.

References:

1. Lipsky PE. Rheumatoid arthritis. Harrisons Principles of Internal

Medicine. (16th edition) New Delhi; McGraw Hill, 2005. 1968-1977

2. Gibson RG, Gibson SL, MacNeill AD, Gray GH, Dick WC, Buchanan WW.
Salicylates and homoeopathy in rheumatoid arthritis: preliminary
observations. Br J Clin Pharmacol. 1978 Nov; 6(5): 391395.
3. Gibson R.G., Gibson S.L.M., MacNEILL A.D., et al. Homoeopathic Therapy
in Rheumatoid Arthritis: Evaluation of DoubleBlind Clinical Trial. Br. J.
Clin. Pharmac. 1980; 9: 453-459.
4. Andrade L.E.C., Ferraz M.B., Atra E., et al. A Randomized Controlled Trial
to Evaluate the Effectiveness of Homoeopathy in Rheumatoid Arthritis.
Scand. J. Rheumatology 1991; 20: 204-208.
5. Fischer P, Scott DL. A randomized controlled trial of homeopathy in
rheumatoid arthritis. Rheumatology 2001; 40: 1052-1055.
6. Rao P, Prasanna M N. Immunological studies on rheumatoid arthritis
treated with homoeopathic drugs: results of the pilot study. IJRH 2008;
2: 42-49.