From Herb Extracts to NSAIDs
By Lucio Victor, Jr.
Considered the number one crippler in the United States, rheumatoid arthritis (RA) affects 36 million Americans each year causing an estimated loss of 95 billion dollars in productivity alone on top of the reduction in quality of life and direct healthcare expenses. About 17 percent of cases result in disability mostly people over 35 years of age.5
RA is a global health problem that affects between one to two percent of the global population accounting for about 9 million physician visits and 250,000 hospitalizations annually.
Facts and Figures
RA has been observed and recorded through time. It has been reported to have affected nomadic hunters, cave men, ancient Egyptians2,4 and juvenile American Indians.6 Tribesmen who live simple lives and in extremes of climate such as the Masai in Africa and the Laplanders in Finland are just as affected.1,3 North American epidemiological studies reveal variations in prevalence by ethnic, socioeconomic, and age groups. The rate is 15.2 percent among Caucasians, 15.5 among African-Americans, 11.3 among Hispanics, and 7.3 among Asians and Pacific islanders. But race, ethnicity, and climate are not factors associated with the disease.
Gender-wise, three out of four afflicted individuals are females, and although the majority of sufferers belong to the older age group, the pediatric and adolescent population are not spared from the juvenile form of RA. Prevalence rises with increasing age. Among persons 35 years old, the prevalence is 0.3 percent vis-a-vis 10 percent among those ages 65 and above. In ten percent of afflicted persons, the onset is sudden and severe; in 20 percent the onset is in a few weeks while 70 percent have an insidious onset.
RA is an autoimmune disorder thought to be triggered by an infectious agent either a virus (rubella, Epstein-Barr, Herpes, or retrovirus) or bacteria (mycoplasma, mycobacteria or enterobacteria) and is highly associated with HLA DR4 and/or HLA DR1 antigens. Although 20 to 30 percent of the world's population is thought to harbor genes for these antigens, only one percent will eventualy develop RA.
RA is a persistent inflammation of the synovium of the articular surfaces of bones. Although the main manifestation is within the joints, extraarticular manifestations in other organs like the skin, lungs, blood vessels, heart, and nerves may also be observed.
Up to 85 percent of patients with RA may also be seropositive for antibodies called rheumatoid factor (RF). These antibodies work against the body's defenses and may indicate an abnnormal immune response. While present in three to five percent of normal healthy individuals, RF level is relatively higher in afflicted persons and is known to amplify the disease process. This is why patients with active disease and high levels of RF have one of the poorest prognosis. In fact, RA is estimated to shorten life span by five to ten years.
A person is said to be positive for RA if for a minimum of six weeks he fullfils four out of the seven diagnostic criteria set by the American Rheumatism Association (ARA). These are: morning stiffness at least an hour long; soft tissue swelling in at least three joints; joint swelling in the hands, knuckles and wrist; joints symmetrically effected; subcutaneous swellings; positive RF and radiologic evidence of bone destruction or bone loss in and around the joints of the hands.
Extracts, Liniments and Baths
 Early quack medicine and hypothetical cures for arthritis ranged from remedies that work to those that are now considered absurd. Although the cures failed to distinguish what form of arthritis they were supposed to treat, poultices of various herbs and roots to daily baths in hot springs seemed like the only notable remedies. Likewise "cure-all" extracts taken orally were as ineffective as the liniments applied on the afflicted areas of the body. Whatever the culture or era, humankind has been on the long and arduous road searching for a cure that will relieve the most obvious symptoms of articular pain, deformity, and swelling.
Probably, the only homeopathic remedy that has survived the ages is the application of heat or ice on affected joints. Also known as thermotherapy, this palliative procedure makes use of hot or ice packs, cryotherapy, or faradic baths.
A metaanalysis by the Cochrane Collaboration Group revelaed no significant difference between the use of wax and therapeutic ultrasound as well as between wax and faradic bath with ultrasound. The metaanalysis concluded that superficial moist heat and cryotherapy can be used for palliative therapy without harmful effects. They also found out that paraffin wax baths combined with exercise was effective for arthritic hands.
The group also reviewed balneotherapy (hydrotherapy or spa therapy), another age, old solution where afflicted joints are immersed in warm water to soothe the pain. Ten randomized controlled trials with a patient population of 607 almost unanimously concluded that balneotherapy helps relieve pain.
Although thermotherapy and balneotherapy do not belong to the primary modes of RA treatment, they have-along with electrotherapy and prescribed exercise-gained wide acceptance as an adjunct to standard medical treatment. Electrotherapy, particularly Transcutaneous Electronic Nerve Stimulation (TENS) which makes use of ultrasound, infrared or pulses of short wave, has been found to significantly reduce pain while helping increase the mobility of affected joints. Lastly, dynamic exercise therapy is shown to improve physical capacity particularly when combined with other treatment modes.
The Real McCoy
While adjunct therapy has been useful in easing RA pain, pharmacotherapeutic agents remain the most important components of RA therapy. Different classes of drugs have been developed throughout the years. They address RA by tackling different levels of the disease process. Appropriate pharmacologic intervention with adjunct treatment can reduce disability by about 30 percent in a span of 10 to 20 years.
Four main categories of medical intervention are available. These are the
nonsteroidal antiinflammatory drugs (NSAIDs), disease modifying antirheumatic drugs (DMARDs), corticostreoids and biologicals. NSAIDs and DMARDs are the most widely used while corticosteroids are delivered intraarticularly especially during flare-ups. Biologicals are more novel forms of pharmacotherapy and though many are still undergoing clinical trials, it may not take long before these therapeutic options become available.
Since pain is the earliest and most commonly felt symptom in RA, the initial treatment is usually the prescription of NSAIDs. Acting on the inflammatory phase of the disease, NSAIDs block the conversion of arachidonic acid into all forms of prostaglandins by inhibiting both cyclooxygenase 1 and 2 (COX 1 and 2) enzymes responsible for such action. With nonproduction of the prostaglandins, pain mediation via specific prostaglandins cannot proceed.
Patients respond differently to the many NSAIDs available today, though it is very difficult to say which individuals will respond well to a specific NSAID. Ibuprofen, naproxen, piroxicam, and diclofenac are but some of the more widely used medications. These have been effective in curbing pain and swelling as well as stiffness and early bone loss. However, as the disease progresses to the proliferative phase and bone loss accelerates and the synovium and tendons thicken to form a pannus, DMARDs may have to be used.
More than half of the time, NSAIDs have been combined with a DMARD to control RA progression. Several studies have shown that the combined effect of NSAID and DMARD can significantly improve quality of life. DMARDs such as azathioprine, penicillamine, auranofin, antimalarials, cyclophosphamide sulfasalazine, methotrexate, and cyclosporin have now gained more use in the therapy of RA.
DMARDs are used not only for the treatment of RA. In fact, many were introduced not for RA but for other diseases. Antimalarials have been used against Plasmodium for the treatment of malaria but have found significant use in RA. Methotrexate, cyclophospamide, and cyclosporin have gained use in autoimmune disorders and in transplantation. Methotrexate is also used as an anticancer. Sadly, some patients discontinue use of DMARDs because it takes time before their effects manifest.
Latest research has seen the development of NSAIDs that specifically block the COX 2 enzyme, which is specifically associated with the production of prostaglandins in pain mediation. This way, other prostaglandins needed by the body will still be produced. Examples of such drugs are celecoxib, rofecoxib, and meloxicam. Recently, the prostaglandin misoprostol was combined with the NSAID diclofenac. The combination retains the efficacy of diclofenac in terms of antiinflammation and analgesia while the gastrointestinal tract is protected with the presence of misoprostol.
In some cases where bone erosion and pain is very severe, and especially when function is nearly lost, joint replacement may be considered. Over the past decade, more and more patients are availing of this type of procedure. Materials used such as stainless steel or ceramic do not induce an inflammatory response, hence there is no fear of rejection. However, just like in any other surgical procedure, patients will have to be cleared to ensure they can undergo surgery. Postoperative pain and inflammation secondary to the surgical procedure could be addressed with NSAIDs or other analgesic medications.
Decades of research have shown there is no cure that can single-handedly rid anyone of RA and the pain it brings. Therapy for RA, juvenile or otherwise, is for life. Improvement of quality of life and efficacy of treatment modalities are best met when the modalities are used to complement each other.
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