Diagnosis and clinical examination of patients with lesions of the joints in the outpatient setting.

Diagnosis and clinical examination of patients with lesions of the joints in the outpatient setting. The principles of evidence-based medicine (epidemiology, standards of diagnosis, prevention, treatment algorithms) in family practice doctor. Sanatorium – spa treatment.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown cause that primarily affects the peripheral joints in a symmetric pattern.

Fig. 1.  Joints affected by rheumatoid arthritis

(PIP joints – proximal interphalangeal joints

MCP joints – metacarpophalangeal joints)

Epidemiology

The worldwide incidence of RA is approximately 3 cases per 10,000 population, and the prevalence rate is approximately 1%. First-degree relatives of patients with RA have an increased frequency of disease (approximately 2-3%). Disease concordance in monozygotic twins is approximately 15-20%, suggesting that nongenetic factors play an important role. Because worldwide frequency is relatively constant, a ubiquitous infectious agent has been postulated to play an etiologic role. Rheumatoid arthritis occurs throughout the world and in all ethnic groups. Climate, altitude and geography do not appear to influence its prevalence but a higher proportion of patients in Western and urban communities have more severe and disabling disease. Females are 2-3 times more likely to develop RA than males. The disease starts most commonly between the third and fifth decades but the age of onset follows a normal distribution curve and no age group is exempted. Nevertheless, the disease is observed in both elderly persons and children.

RISK FACTORS:

Gender – Gender appears to play a major role in a person’s susceptibility to rheumatoid arthritis. Women are about three times more likely than men to develop rheumatoid arthritis.

Heredity – People with specific human leukocyte antigen (HLA) genes are more likely to develop rheumatoid arthritis than people without these genes. RA has a significant genetic component, and the so-called shared epitope of the HLA-DR4/DR1 cluster is present in up to 90% of patients with RA, although it is also present in more than 40% of controls.

Infection – Researchers suspect that infection with bacteria or viruses (eg, Mycoplasma organisms, Epstein-Barr virus, parvovirus, rubella) may be one of the factors initiating rheumatoid arthritis. However, at this time, there is no definite evidence linking infection to rheumatoid arthritis.

Cigarette smoking – Cigarette smoking may be another factor that initiates rheumatoid arthritis. The results of studies have not always agreed, but most studies suggest that cigarette smokers have an increased risk for rheumatoid arthritis. Furthermore, the risk appears to be related to the duration of smoking and not to the number of cigarettes smoked per day. There is also some evidence that cigarette smoking increases the likelihood that rheumatoid arthritis will be severe when it occurs.

Stress – Patients often report episodes of stress or trauma preceding the onset of their rheumatoid arthritis. Stress is extremely difficult to measure but some studies do suggest that “life events” (divorce, accidents, bereavement, etc) are more frequent in the six months preceding the onset of disease compared to the general population.

  Diet – There is no evidence that a particular diet causes rheumatoid arthritis, although a recent claim has implicated consumption of red meat. Some researchers have claimed that food intolerance in a minority of patients can make the disease worse and that elimination of such foods can help symptoms. There is also evidence that polyunsaturated fats (found in fish oils and some vegetable oils) have a weak anti-inflammatory effect.

Pathogenesis of RA

 RA is associated with a number of autoimmune responses, but whether autoimmunity is a secondary or primary event is still unknown. RA is triggered by exposure of an immunogenetically susceptible host to an arthritogenic microbial antigen”. This “genetic predisposition appears to be related to the histocompatibility genetic marker HLA-DR4, especially in those patients who maintain high titers of immunoglobulin M (IgM) «rheumatoid factor» (RFs). Genetic factors and immune system abnormalities contribute to disease propagation. The initiator of the RA process is an infectious or noxious agent which is yet to be fully identified and confirmed. Once this agent initiates an acute inflammatory synovitis,  auto-immune reaction results.  Instead of normal resolution after the acute response, the inflammatory process becomes chronic and self sustaining, even though the initiating factor has long disappeared.

Major cellular roles are played by CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and neutrophils, while B lymphocytes produce autoantibodies (ie, RFs). Abnormal production of numerous cytokines, chemokines, and other inflammatory mediators (eg, tumor necrosis factor alpha [TNF-alpha, interleukin (IL)–1, IL-6, transforming growth factor beta, IL-8, fibroblast growth factor, platelet-derived growth factor) have been demonstrated in patients with RA.  Synovial cell hyperplasia and endothelial cell activation are early events in the pathologic process that progresses to uncontrolled inflammation. Ultimately, inflammation and exuberant proliferation of synovium (ie, pannus) leads to destruction of various tissues such as cartilage, bone, tendons, ligaments, and blood vessels. Although the articular structures are the primary sites, other tissues are also affected.

After the initial synovial inflammation, the synovium becomes hypertrophied to form granulation tissue (pannus), which spreads over the cartilage surface causing destruction. At the ‘bare areas’ of the joint where bone is not covered with cartilage, pannus directly invades into the bone resulting in marginal erosions.  In the final stages, a fibrous or bony ankylosis of the joint takes place.

Fig. 2. General pathologic process of rheumatoid arthritis.

 A. Normal joint. Arrows indicate “bare areas”. B. Synovial proliferation.  Arrows indicate pannus. C. Bone and joint destruction. D. Ankylosis.

ClinicAL HISTORY

The joints most commonly affected by rheumatoid arthritis are in the hands, wrists, feet, ankles, knees, shoulders, and elbows. The disease typically causes inflammation symmetrically in the body, meaning the same joints are affected on both sides of the body. Symptoms of rheumatoid arthritis may begin suddenly or gradually. In the early stages of the condition, the arthritis typically affects the small joints farthest from the center of the body; as the condition progresses, the

arthritis may affect the mid-sized joints and eventually the large joints, such as the hip, and the spine. The following are the most common symptoms of rheumatoid arthritis in the hands. However, each individual may experience symptoms differently.

Patients often present with constitutional complaints including malaise, fever, fatigue, weight loss, and myalgias. They may report difficulty performing activities of daily living (eg, dressing, standing, walking, personal hygiene, using their hands). Most patients with the disease have an insidious onset. It may begin with systemic features, such as fever, malaise, arthralgias, and weakness, before the appearance of overt joint inflammation and swelling. A small percentage of patients (approximately 10%) have an abrupt onset with the acute development of synovitis and extra-articular manifestations. Spontaneous remission is uncommon, especially after the first 3-6 months.

Symptoms may include:

·        pain;

·        stiffness;

·        swelling over the joints;

·        decreased movement;

·        pain that is worse with movement of the joints;

·        bumps may be noted over the small joints;

·        difficulty performing activities of daily living (ADLs), such as tying shoes, opening jars, or buttoning shirts;

·        decrease ability to grasp or pinch.

Physical examination

I. Joint involvement is the characteristic feature of patients with RA. In general, the small joints of the hands and feet are affected in a relatively symmetric distribution. Those most commonly affected joints, in decreasing frequency, are the MCP, wrist, PIP, knee, MTP, shoulder, ankle, cervical spine, hip, elbow, and temporomandibular. Joints show inflammation with swelling, tenderness, warmth, and decreased range of motion. Atrophy of the interosseous muscles of the hands is a typical early finding. Joint and tendon destruction may lead to deformities such as ulnar deviation, boutonnière and swan-neck deformities, hammer toes, and occasionally joint ankylosis.

Other commonly observed musculoskeletal manifestations are tenosynovitis and associated tendon rupture (due to tendon and ligament involvement, most commonly involving the fourth and fifth digital extensor tendons at the wrist), periarticular osteoporosis due to localized inflammation and generalized osteoporosis due to systemic chronic inflammation, immobilization-related changes or corticosteroid therapy, and carpal tunnel syndrome. Most patients have muscle atrophy from disuse, which is often secondary to joint inflammation.

Table 1

Specific joints affected by rheumatoid arthritis

Fig. 3. Effect of rheumatoid arthritis on the hand: (left) early changes and (right) later deformity

Fig. 4. The rheumatoid arthritis  of the hands (the early stage)

Fig. 5. Severe rheumatoid arthritis of the hands.

Fig. 6.Ulnar drift of fingers

Fig. 7. Boutonnière and swan-neck finger deformities

Table 2

The affects of rheumatoid arthritis in the foot and ankle

Fig. 8. Manifestations of rheumatoid arthritis in the foot.

 Fig. 9. Severe rheumatoid arthritis of the foot

II. Effect of RA on organs and organ systems.

Table 3

Organs Affected by RA

1. Skin: Subcutaneous nodules (rheumatoid nodules) occur in many patients with RA whose RF value is abnormal. They are often present over pressure points (eg, olecranon). Rheumatoid nodules are painless lumps that appear beneath the skin. These nodules may move easily when touched or they may be fixed to deeper tissues They most often occur on the underside of the forearm and on the elbow, but they can also occur on other pressure points, including the back of the head, the base of the spine, the Achilles tendon, and the tendons of the hand.

Vasculitic lesions of the skin may manifest as palpable purpura or skin ulceration. Lesions may present as palpable purpura, skin ulcers, or digital infarcts.

Fig. 10. Vasculitis of the skin of the foot

Fig. 11. The rheumatoid nodules

Figure 12. Formation of callosities over nodules in metatarsophalangeal region.

Fig. 13. Small petechia and surrounding erythema are seen along the nailfold (A). After injection, the lesions are no longer present and the erythema has dramatically improved (B).

Fig. 14. Digital ischemia – this image shows a blood flow deficiency in the tip of the finger caused by an obstruction of the digital artery.

Fig. 15. The dermal vasculitic lesions

2. Eyes:  Keratoconjunctivitis sicca is common in RA and is often the initial manifestation of secondary Sjögren syndrome. The eye may also have episcleritis, uveitis, and nodular scleritis that may lead to scleromalacia.

Fig. 16. Scleritis – Inflammation of the sclera (the white of the eye) causing redness, light sensitivity and pain.

3. Lungs: RA involvement of the lungs may take several forms, including pleural effusions, interstitial fibrosis, nodules (Caplan syndrome), and bronchiolitis obliterans-organizing pneumonia.

4. Heart: The incidence of cardiovascular morbidity and mortality is increased in patients with RA. Nontraditional risk factors appear to play an important role. Myocardial infarction, myocardial dysfunction, and asymptomatic pericardial effusions are common; symptomatic pericarditis and constrictive pericarditis are rare. Myocarditis, coronary vasculitis, valvular disease, and conduction defects are occasionally observed.

5. Nervous system: Entrapment of nerves is common, such as with the mediaerve in carpal tunnel syndrome. Vasculitic lesions, mononeuritis multiplex, and cervical myelopathy may cause serious neurological consequences. A more diffuse symmetrical peripheral neuropathy can occur and is usually limited to symptoms and signs of mild ‘glove and stocking’ sensory loss. Cervical cord compression can result from subluxation of the cervical spine at the atlantoaxial joint or at a subaxial level. Atlantoaxial sub-luxation is a common finding in long-standing RA and can be diagnosed from lateral radiographs of the cervical spine taken in full flexion. Although usually associated with no more thaeck pain radiating to the occiput, it can result in cord compression and sudden death if the neck is manipulated inadvertently under an anaesthetic. Progressive cervical myelopathy may develop more insidiously with limb weakness, difficulty in holding up the head and tetraparesis. These problems occur more often following subluxation at a subaxial level and may require operative decompression and fixation

Fig. 17. Magnetic resonance image of cervical spine showing spinal cord compression at C1 and C2.

Blood: Most active patients have an anemia of chronic disease. Several hematologic parameters parallel disease activity, including normochromic-normocytic anemia, thrombocytosis, and eosinophilia, although the latter is uncommon. Leukopenia is a finding in patients with Felty syndrome.

7. Renal: The kidneys commonly are not affected directly by RA. Secondary involvement is common, including that due to medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], gold, cyclosporin), inflammation (eg, amyloidosis), and associated diseases (eg, Sjögren syndrome with renal tubular abnormalities).

8. GI: Intestinal involvement, as with kidney involvement, is often secondary to associated processes such as medication effects, inflammation, and other diseases. The liver is often affected in patients with Felty syndrome (ie, RA, splenomegaly, and neutropenia).

DIAGNOSIS

Laboratory tests:

1.               Markers of inflammation.  The erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) are nonspecific markers of inflammation. A high ESR and a high level of CRP suggest the presence of inflammation, but they do not indicate the cause of this inflammation. These markers are useful for distinguishing inflammatory arthritis, such as rheumatoid arthritis, from noninflammatory arthritis, such as osteoartritis. The  ESR and CRP, are associated with disease activity; additionally.

2.               Anemia  (hypochromic anemia )of chronic disease is common and correlates with disease activity.

3.               Thrombocytosis is common and is also associated with disease activity.

a.     Thrombocytopenia may be a rare adverse event of therapy and may occur in  patients with Felty syndrome.

4.               Leukocytosis may occur but is usually mild. Leukopenia may be a consequence of therapy or a component of Felty syndrome.

5.               Rheumatoid factor. RF is present in approximately 60-80% of patients with RA over the course of their disease but is present in fewer than 40% of patients with early RA.

6.               Antinuclear antibodies: These are present in approximately 40% of patients with RA, but test results for antibodies to most nuclear antibody subsets are negative.

7.               Synovial fluid analysis:

          a. an inflammatory synovial fluid (WBC count >2000/mL) is present with

          counts generally from 5,000-50,000/mL.

b.usually, neutrophil predominance (60-80%) is observed in the synovial fluid (in contrast with mononuclear cell predominance in the synovium).

c.      note that because of a transport defect, the glucose levels of pleural,

               pericardial, and synovial fluids from patients with RA are often low

              compared to serum glucose levels.

                                                                                                          Table 4

Laboratory findings in rheumatoid arthritis

  * Anaemia--normochromic or hypochromic, normocytic (if microcytic

  consider iron deficiency)

  * Thrombocytosis

  * Raised erythrocyte sedimentation rate

  * Raised C reactive protein concentration

  * Raised ferritin concentration as acute phase protein

  * Low serum iron concentration

  * Low total iron binding capacity

  * Raised serum globulin concentrations

  * Raised serum alkaline phosphatase activity

  * Presence of rheumatoid factor

Imaging Studies:

1.     Radiographs: Radiographs of the hands often are normal at presentation or may show swelling of soft tissue, loss of joint space, or periarticular osteoporosis. Erosions typical of rheumatoid arthritis develop within three years of the start of the disease in over 90% of patients who ultimately develop the erosions. Note that erosions may be present in the feet, even in the absence of pain and in the absence of erosions in the hands.

18. Radiograph showing rheumatoid erosions

Fig. 19. Rheumatoid arthritis

Fig. 20. Radiographic features of the rheumatoid foot

Fig. 21. X-rays demonstrate scalped or punched out lesions of bone destruction adjacent to the joint.

                                                                                                                    Table 5

Common radiological features of rheumatoid arthritis

Fig. 22. Radiographs
 of rheumatoid arthritis (III-IV st.)

2. MRI: Magnetic resonance imaging (MRI) scans are more sensitive than x-rays for detecting the bone damage caused by rheumatoid arthritis. Therefore, MRI scans may be more effective than x-rays for detecting the early changes of rheumatoid arthritis. MRI scans are also useful for assessing changes in the synovium (the joint lining) and for assessing compression of the cervical spinal cord. However, the cost of MRI scanning is much greater than that of plain x-rays, so MRI is not widely used to diagnose or follow the course of rheumatoid arthritis.This modality is primarily used in patients with abnormalities of the cervical spine; early recognition of erosions based on MRI images has been sufficiently validated.

3. Sonography: This allows recognition of effusions in joints that are not easily accessible (eg, hip joints, shoulder joints in obese patients) and cysts (Baker cysts). High-resolution ultrasound images may allow visualization of tendon sheaths, changes and degree of vascularization of the synovial membrane, and even erosions; however, this needs further validation. Sonography may be used as an office-based procedure.

4. Bone scanning: Findings may help to distinguish inflammatory from noninflammatory changes in patients with minimal swelling.

5. Densitometry: Findings are useful for helping diagnose changes in bone mineral density indicative of osteoporosis.

Histologic Findings: The lymphoplasmacytic infiltration of the synovium with neovascularization seen in RA is similar to that seen in other conditions characterized by inflammatory synovitis. Early rheumatoid nodules are characterized by small vessel vasculitis and later by granulomatous inflammation.

Rheumatoid arthritis is a disorder which is clinically defined, without specific biological borders.  Diagnosis is therefore primarily dependent on observation of the patient and fulfillment of a sufficient number of criteria as outlined by the American College of Rheumatology (1987 revision).

                                                                                                               Table 6

 Criteria for the diagnosis of rheumatoid arthritis (American College of Rheumatology, 1987 revision)

VIDEO

CLASSIFICATION

I.                   Severity is classified as mild, moderate, or severe.

  Mild — A person with mild RA has some of the following signs and symptoms:

• Joint pain

• Inflammation of at least three joints

• An absence of inflammation in tissues other than the joints

• Usually, a negative result on a rheumatoid factor test

• An elevated ESR or CRP level

• An absence of evidence of bone or cartilage damage on x-rays

  Moderate — A person with moderate rheumatoid arthritis has some combination of the following signs and symptoms:

• Between 6 and 20 inflamed joints

• Usually, no inflammation in tissues other than the joints

• An elevated ESR or CRP levels

• A positive result on a rheumatoid factor test

• Evidence of inflammation but no evidence of bone damage on x-rays

  Severe — A person with severe rheumatoid arthritis has one or more of the following signs and symptoms:

• More than 20 persistently inflamed joints or a rapid loss of functional abilities

• Elevated ESR or CRP levels

• Anemia related to chronic illness

• Low blood albumin level

• A positive result on a rheumatoid factor test, often with a high level

• Evidence of bone and cartilage damage on x-rays

• Inflammation in tissues other than joints

II. Stage of rheumatoid arthritis — The stage of RA also affects the treatment of this condition. The stage is determined by the duration of the condition and the presence of inflammation. There are three general stages: recent-onset, established, and end-stage rheumatoid arthritis.

  Recent-onset — A person with recent-onset RA meets the diagnostic criteria for the condition and has had evidence of inflammation for no more than six months. The treatment of recent-onset rheumatoid entails aggressive measures to slow or stop ongoing inflammation and protect the joints.

  Established — A person with established RA has had evidence of inflammation for at least six to twelve months and may have irreversible joint damage and loss of function. The treatment of established rheumatoid entails aggressive measures to slow or stop ongoing inflammation and measures to slow or prevent additional changes in joint structure and function.

  End-stage — A person with end-stage RA has little or no evidence of ongoing inflammation but often has significant joint damage with loss of function and deformity. The treatment of end-stage rheumatoid arthritis entails therapies that reduce pain and slow or prevent additional changes in joint structure and function.

Patients with end-stage RA may have pain due to joint damage rather than from inflammation. In this case, a clinician may recommend surgery to replace a damaged joint. However, some joints cannot be successfully replaced. For such joints, a surgical fusion to stop pain-producing movement of the affected joint may be recommended.

   When considering rheumatoid arthritis useful diagnostic tests include:

·        Raised acute phase reactants, e.g. ESR, CRP

·        Positive rheumatoid factor (in Northumberland this is RAPA and has a false positive rate of approximately 4%, especially at the low titres. Approximately 20% of patients with rheumatoid arthritis have a negative rheumatoid factor).

·        X-rays – erosions are often seen first at the MTP joints. Finding of erosions in x-rays of the hands and feet is significant.

                                                                                                                   Table 7

Differential diagnosis of

rheumatoid arthritis

     Psoriatic arthritis--always seronegative

     Primary nodal osteoarthritis

     Other connective tissue diseases

     Calcium pyrophosphate deposition disease

TREATMENT

   The main goals of treatment in rheumatoid arthritis are listed in table 6 below.

                                                                                                        Table 8

Goals of treatment

DRUG THERAPY — Drug therapy is the cornerstone of treatment for active RA. Drug therapy is appropriate for all patients, with the exception of some patients who are in remission. The goals of drug therapy are to achieve remission and prevent further damage of the joints and loss of function, without causing permanent or unacceptable side effects.

The type and intensity of drug therapy depends upon the severity of RA, presence of factors associated with a better or worse prognosis, effectiveness of previous treatments, and side effects. In most cases, the level of drug therapy is increased until inflammation is suppressed or drug side effects become unacceptable.

The challenge of drug therapy is to balance the side effects against the need to control inflammation. All patients with RA who use medications need regular medical care and laboratory tests to check for the presence of side effects. The frequency and type of testing is determined by the type of medication used. If side effects occur, they can often be minimized or eliminated by reducing the dose or switching to a different drug.

Four main classes of drugs are used to treat rheumatoid arthritis:

Simple analgesics — Simple analgesics relieve pain, but they have no effect on inflammation. Drugs in this class include acetaminophen (Tylenol®), tramadol (Ultram®), and capsaicin (Zostrix®). Use of narcotic analgesics such as such as codeine, oxycodone, and hydrocodone is generally discouraged because of the long term nature of rheumatoid arthritis and the risk of dependence and addiction. Patients with a badly damaged joint who cannot undergo joint replacement surgery may benefit from long term narcotic analgesics under the supervision of a rheumatologist.

Nonsteroidal anti-inflammatory drugs — Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and reduce minor inflammation, but they are not strong enough to alter the long term damaging effects of rheumatoid arthritis on the joints. Furthermore, NSAIDs must be taken continuously and at a specific dose to have an anti-inflammatory effect.

People with certain medical problems and those taking various medications are at increased risk of harmful effects of NSAIDs and should consult a doctor before deciding to taking an NSAID. Risk factors for harmful NSAID side effects include:

·        Older age — People over 65 years of age have an increased risk of developing ulcers when taking NSAIDs.

·        Gastrointestinal ulcer disease — Those who have had a stomach or intestinal ulcer are at an increased risk of having another one develop while taking an NSAID. People being treated for ulcers should generally not take NSAIDs or medications containing aspirin.

·        Bleeding — Those who have had bleeding from the stomach, upper intestine, or esophagus have an increased risk of recurrent bleeding due to NSAIDs. People using anticoagulant medications such as warfarin (Coumadin®) or heparin should generally not take NSAIDs or aspirin because of an increased risk of bleeding when both classes of drugs are used.

·        Fluid retention — People with medical conditions that require diuretic drugs, including heart failure, liver disease, and kidney damage, are at increased risk of kidney damage from NSAIDs and COX-2 selective drugs, such as celecoxib (Celebrex®).

·        Kidney damage — NSAIDs can worsen kidney function in people whose kidneys are not working normally, even those who do not show signs of fluid retention.

·        High blood pressure — NSAIDs can interfere with control of blood pressure. The effect is usually modest, and can often be corrected by increased doses of blood pressure medications.

·        Heart attacks and strokes — Recent reports have associated some NSAIDS (not aspirin), including COX-2 selective drugs, with coronary heart attacks and strokes, especially following prolonged use. Dosage and duration of exposure to NSAIDS should be minimized.

·        Aspirin allergy — People who have had hives (urticaria) or other symptoms of an allergy to aspirin should generally avoid use of any of the NSAIDs.

  Nonselective NSAIDs — Nonselective NSAIDs include over-the-counter drugs such as aspirin, ibuprofen, and naproxen and prescription-strength NSAIDs.

Lower doses of NSAIDs relieve pain, but higher doses and regular use are needed to suppress inflammation. Furthermore, even at anti-inflammatory doses, NSAIDs must usually be taken for two to four weeks before their true effectiveness is known. If the initial dose of NSAIDs does not improve symptoms, a clinician may recommend increasing the dose gradually or switching to another NSAID.

People taking an NSAID should not take a second NSAID at the same time. Taking an NSAID such as ibuprofen may interfere with the effects of low-dose aspirin that is being used to prevent stroke or heart attack. People taking daily low-dose aspirin should take the aspirin at least two hours before taking ibuprofen. Using selective NSAIDs with aspirin is an alternative.

The side effects of NSAIDs may include a rash or hypersensitivity reaction; abdominal pain; ulcers or gastrointestinal bleeding; altered kidney, liver, or bone marrow function; an increased tendency for bleeding; and, in older adults, altered function of the nervous system.

The risk of developing ulcers in the stomach or the first part of the small intestine (the duodenum) may be decreased by use of a COX-2 selective NSAID (see below) or by the addition of an anti-ulcer medication to a nonselective NSAID. Different classes of anti-ulcer agents that reduce gastrointestinal damage from NSAIDs include:

·        Inhibitor of stomach acid production — High doses of histamine blockers, such as famotidine (Pepcid®), and ordinary doses of the acid production inhibitors omeprazole (Prilosec®) and lansoprazole (Prevacid®) also provide protection against NSAID damage.

·        Misoprostol— Misoprostol (Cytotec®) protects the gastrointestinal tract from the effects of NSAIDs and can reduce the risk of gastrointestinal bleeding. Misoprostol’s frequent side effects include diarrhea, abdominal pain, and intestinal cramping.

  Selective NSAIDs — Selective NSAIDs (also called COX-2 inhibitors) are as effective as nonselective NSAIDs and are less likely to cause gastrointestinal injury and side effects. Celecoxib (Celebrex®) is the only COX-2 inhibitor currently available in the United States.

Selective NSAIDs are sometimes recommended for people who have had a peptic ulcer, gastrointestinal bleeding, or gastrointestinal upset when taking nonselective NSAIDs. However, persons who have had ulcers or bleeding that were not related to the use of NSAIDs may require an anti-ulcer drug along with a selective NSAID. In other words, the COX-2 selective NSAIDs have less potential to cause ulcers or gastrointestinal bleeding, but they do not prevent ulcers that have another source.

Rofecoxib (Vioxx®) and valdecoxib (Bextra®) were discontinued in 2004 when it was discovered that patients who took these medications had higher rates of myocardial infarctions (heart attacks) and strokes. It is not known if this problem occurs as a result of all COX-2 inhibitors. People with known coronary artery disease (eg, have had a myocardial infarction [heart attack], angina [chest pain due to narrowed heart arteries], a stroke, or narrowed arteries to the brain) or are at a higher than average risk for these diseases should probably avoid using COX-2 inhibitors until more information on the safety of this class of drugs becomes available. An alternative includes a combination of a nonselective NSAID and an anti-ulcer drug, as decribed above.

Selective NSAIDs are not recommended for people with kidney disease, congestive heart failure, or cirrhosis, people who take diuretics, and people who are sensitive to aspirin.

Steroids (glucocorticoids) — Steroids have strong anti-inflammatory effects. Drugs in this class include prednisone and prednisolone. Steroids may be taken orally, intravenously, or can be injected directly into a joint. Steroids quickly improve symptoms of rheumatoid arthritis such as pain and stiffness, and they also decrease joint swelling and tenderness.

However, steroids have only a modest effect on decreasing arthritis damage to cartilage and bone when used alone. Steroids are generally used in people with RA that is severe and is severely limiting a person’s ability to functioormally. For such people, steroid treatment may help control symptoms and preserve function until other, slower acting drugs begin to work.

Steroids have many side effects, including weight gain, worsening diabetes, promotion of cataracts in the eyes, thinning of bones (osteopenia and osteoporosis), and an increased risk of infection. Thus, when steroids are used, the goal is to use the lowest possible dose and duration of treatment.

Disease-modifying antirheumatic drugs — Disease-modifying antirheumatic drugs (DMARDs) can substantially reduce the inflammation of RA, although they act slowly when compared to steroids. However, they can help to reduce the use of steroids. Studies suggest that DMARDs can reduce or prevent joint damage, preserve joint structure and function, and enable a person to continue his or her daily activities.

Drugs in this class include hydroxychloroquine (Plaquenil®), methotrexate (Rheumatrex®), gold salts (Ridaura®, Solganal®), D-penicillamine (Depen®, Cuprimine®), sulfasalazine (Azulfidine®), azathioprine (Imuran®), leflunomide (Arava®), and cyclosporine (Sandimmune®, Neoral®).

Several weeks to months of treatment are ofteecessary before the effects of DMARDs become evident. An improvement in symptoms may require four to six weeks of treatment with methotrexate, one to two months of treatment with sulfasalazine, and two to three months of treatment with hydroxychloroquine. Even longer durations of treatment may be needed to derive the full benefits of these drugs.

Biologic response modifiers — Biologic response modifiers are medications used for treating RA that interfere with signaling pathways involved in inflammation. Drugs in this class include proteins that bind tumor necrosis factor (TNF), an important pro-inflammatory signaling molecule. Etanercept (Enbrel®), adalimumab (Humira®), and infliximab (Remicade®) are examples. Anakinra (Kineret®) is a biologic agent that acts to inhibit another cytokine, interleukin-1. Abatacept (Orencia®) interferes with activation of one type of lymphocytes (T cells) and rituximab (Rituxan®) depletes another type (B cells). TNF and interleukin-1 are made in large amounts in persons with RA.

Biologic response agents work rapidly, within two weeks for some medications (Enbrel®, Humira®, Remicade®) to within four to six weeks for others (Rituxan®, Orencia®). They may be used alone or in combination with other DMARDs, NSAIDs, and/or steroids. Because of their cost (generally more than $15, 000 per year in the United States), biologic response agents are often reserved for patients who have not responded fully to DMARDs or who caot tolerate DMARDs in doses large enough to control inflammation.

All biologic response modifiers must be injected. Humira®, Enbrel®, and Kineret® are injected under the skin by the patient, a family member, or nurse. Intravenous infusion is necessary for Remicade®, Orencia® and Rituxan®. This is typically done in a doctor’s office or clinic, and takes one to three hours to complete.

Drug safety and side effects — Many of the drugs used to treat rheumatoid arthritis have side effects when used at the dosages necessary to suppress inflammation. These side effects can range from annoying to intolerable or potentially life-threatening.

In general, all drugs, especially DMARDs, are not recommended for women who are pregnant or planning to become pregnant. Women who breast-feed should speak with their rheumatologist and their infant’s pediatrician for specific advice on drug safety.

Biologic response modifiers interfere with the immune system’s ability to fight infection and should not be used in people with serious infections. Careful screening for tuberculosis is necessary prior to anti-TNF therapy since the risk of developing active TB infection is increased. If there is evidence of prior infection with tuberculosis, treatment to prevent reactivation is recommended.

TNF-inhibitors are not recommended for patients who have lymphoma or have been treated for lymphoma in the past; patients with RA, especially those with severe disease, have an increased risk of lymphoma regardless of what treatment is used. TNF-inhibitors have been associated with a further increase in the risk of lymphoma in some studies; more research is needed to define this risk.

FACTORS AFFECTING DRUG THERAPY — The type and sequence of drugs used to treat RA depends upon three factors: the activity, severity, and stage of rheumatoid arthritis.

Expertise of the working capacity

Patients with RA, regardless of the course of the disease, its activity and progression rate, changes in joints and internal organs may be recognized as invalids of the III^rd , II ^nd  or i groups.

Rehabilitation is carried out by internists, physiotherapists and nurses:

1. In acute arthritis its important to immobilize the affected joint and to relieve pain. The joint should be functionally positioned, therefore a cast may be  required.

Local physiotherapeutic procedures may be applied (warmth).

2. In subacute arthritis physical exercises with gradual increase of the range of active and passive movements in the affected joint are indicated.

3. In chronic arthritis patients should be instructed to avoid excessive overstrain of the affected joint during the everyday activities. Varions methods facilitating walking may be applied. Special physical exercises and patient education may be useful.

OSTEOARTHRITIS

Osteoarthritis (OA) is a joint disease characterized by progressive loss of articular cartilage and reactive changes in the underlying bone.

Fig. 23.  Osteoarthritis

Epidemiology

Osteoarthritis is one of the most prevalent and disabling chronic conditions affecting older adults and a significant public health problem among adults of working age. The prevalence increases with age, and by the age of 65. The age of 65, 80% of people have some radiographic evidence of osteoarthritis, although only 25% may have symptoms. OA is the most common  from of arthritis.  Males and females are both affected but OA is more generalised and more severe in older women. Twin and family studies show the importance of genetic factors, particularly in the nodal form of primary generalised osteoarthritis, and associations have been reported with the HLA-AiBg and apantitrypsin MZ phenotypes. Obesity and body mass index are particularly associated with knee OA, while osteoporosis and smoking appear to have a modest protective effect. Cold, damp climates are associated with more symptoms but not with greater radiological prevalence.

Etiology and Risk Factors

Although osteoarthritis is especially common in older adults, its pathology of asymmetric joint cartilage loss, subchondral sclerosis (increased bone density), marginal osteophytes and subchondral cysts is the same in younger and older adults.¹ Primary osteoarthritis is the most common form and is usually seen in weight-bearing joints that have undergone abnormal stresses (e.g., from obesity or overuse). The precise etiology of osteoarthritis is unknown, but biochemical and biomechanical factors are likely to be important in the etiology and pathogenesis. Biomechanical factors associated with osteoarthritis include obesity, muscle weakness and neurologic dysfunction. In primary osteoarthritis, the common sites of involvement include the hands, hips, knees and feet. Secondary osteoarthritis is a complication of other arthropathies or secondary to trauma. Gout, rheumatoid arthritis and calcium pyrophosphate deposition disease are correlated with the onset of secondary osteoarthritis.

                                                                                             Table 9

The risk factors  of OA include:

Depending on the evidence for etiology, osteoarthritis may be classified as primary, when there is no obvious underlying cause, or secondary, when preceded by a predisposing disorder.

PATHOPHYSIOLOGY

Traditionally, OA has been considered a disease of articular cartilage. The current concept holds that OA involves the entire joint organ, including the subchondral bone and synovium.

OA has always been classified as a noninflammatory arthritis; yet, there is increasing evidence for inflammation occurring with cytokine and metalloproteinase release into the joint. Therefore, the term degenerative joint disease is no longer appropriate when referring to OA.

Fig. 24. A normal or unaffected joint demonstrating the articular surfaces and the joint space

Fig. 25. Normal and arthritis joins

The joints predominantly involved are weight bearing and include the knees, hips, cervical and lumbosacral spine, and feet. Other commonly affected joints include the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints of the hands.

Cartilage is grossly affected. Focal ulcerations eventually lead to cartilage loss and eburnation. Subchondral bone formation occurs as well, with development of bony osteophytes.

Fig. 26. The stationary phase of disease progression in osteoarthritis involves the formation of osteophytes or joint space narrowing.

Fig. 27. Osteoarthritis progresses further with obliteration of the joint space

Fig. 28. The appearance of subchondral cysts (cysts in the bone underneath the cartilage) indicates the erosive phase of disease progression in osteoarthritis.

Fig. 29. The last phase in the disease progression involves bone repair and remodeling. Large osteophytes form

Fig. 30. The pathogenesis of osteoarthritis

ClinicAL HISTORY

Osteoarthritis is primarily assessed through a history and physical examination. The cardinal symptom of osteoarthritis is pain. The typical patients with OA is middle-aged or has gradual onset  of pain and stiffness accompanied by loss of function. The joints most commonly involved include the distal and proximal interphalangeal joints of the hands, first carpometacarpal, cervical or lumbal intervertebral joints, first metatarsophalangeal, knees, and hips.

Fig.30. Common sites of involvement in primary osteoarthritis

The pain usually is mild, is worsened by use of the involved joints, and improves or is relieved with rest. Pain at rest and nocturnal pain are feature of severe disease or of local inflammation. Morning stiffness is common, but the duration is considerably shorter (often less than 30 minutes) than in active rheumatoid arthritis. Gel phenomenon, stiffness after inactivity is common and resolves within several minutes. In many instances, pain and stiffness are modified by weather changes, generally worsening with damp, cool, rainy weather. Muscle spasm, and tendon and capsular contractures also may be observed, depending on the site and duration of involvement. Pain caused by osteoarthritis may develop in any part of the involved joint or tissue. Typically, pain progresses gradually over time and increases with weight bearing. A patient with primary osteoarthritis seldom has any attributable systemic symptoms (e.g., fatigue or generalized weakness). The progression of symptoms in patients with osteoarthritis is fairly consistent. Mild discomfort first occurs in a joint when it is in high use, but the pain is relieved by rest. Symptoms progress to constant pain on use of the affected joint and finally, with more advanced joint involvement, pain occurs at rest and at night. Generally, little tenderness occurs outside the joint, but pain can occur with extremes in range of motion. Limitation of motion is often prominent.

PHYSICAL EXAMINATION. Bony enlargement with tenderness at the joint margins and periarticular tendons is common. Limitation of motion of the affected joint usually is related to osteophyte formation or severe cartilage loss. Heberden’s and Bouchard’s nodes are bony enlargements of distal and proximal interphalangeal joints, respectively. Mild signs of local inflammation may be present, but a hot, erythematous, markedly swollen joint suggests superimposed crystalline or infections arthritis. Crepitus, present among more than 90 % of patients with OA of the knee, is caused by irregularity of the opposing cartilage surface. 

Fig. 31. Heberden’s and Bouchard’s nodes

Cervical and lumbar pain may result from arthritis of the apophyseal joints, osteophyte formation, pressure on surrounding tissue and muscle spasm. Nerve root impingement causes radicular symptoms. Cervical and lumbar stenosis develop when facet joints hypertrophy, the disc degenerates and bulges, and the ligamentum flavum becomes lax and widens. The spinal canal narrows and compresses the cord. Posterior vertebral osteophytes may also contribute to cord compression. Patients may develop lumbar pain, extremity weakness, gait ataxia or abnormal neurologic findings. Pseudoclaudication is a characteristic feature of lumbar stenosis and is described as pain in the buttocks or thighs occurring with ambulation and relieved by rest. Hip pain is usually felt in the groin or the medial aspects of the thigh; however, it can be referred to the knee or buttocks and may be misdiagnosed as lumbar stenosis.

DIAGNOSIS

Laboratory tests:

No specific laboratory abnormalities are associated with OA.

1. The acute-phase reactants and erythrocyte sedimentation rate are not elevated.

2. Synovial fluid analysis usually indicates a white cell count less than 2000 per mm³ with a mononuclear predominance.

Imaging Studies:

     1. Radiography. The diagnosis usually is confirmed with radiographs.

       The radiographic hallmarks of primary osteoarthritis include nonuniform joint space loss, osteophyte formation, cyst formation and subchondral sclerosis. The initial radiographs may not show all of the findings. At first, only minimal, nonuniform joint space narrowing may be present. The involved joint spaces have an asymmetric distribution. As the disease progresses, subluxations may occur and osteophytes may form. Subchondral cystic changes can occur. These cysts may or may not communicate with the joint space, can occur before cartilage loss and have a sclerotic border. Subchondral sclerosis or subchondral bone formation occurs as cartilage loss increases and appears as an area of increased density on the radiograph. In the advanced stage of the disease, a collapse of the joint may occur; however, ankylosis does not usually occur in patients with primary osteoarthritis.

Bone demineralization and marginal erosions do not occur. The presence of these findings strongly suggests inflammatory arthritis.

Knee
When evaluating patients with osteoarthritis of the knee, AP and lateral radiographs allow an adequate evaluation of the medial and lateral joint spaces. To adequately assess the joint space, the AP view should be obtained with the patient in a standing position. The lateral view also allows evaluation of the patellofemoral joint; however, an additional view, known as the sunrise view, can offer even more information about this joint space.

Fig. 32. Anatomy of knee-joint             Fig.33. Osteoarthritis of the

                                                                                                               Medial Side of the Knee

Fig. 34. Osteoarthritis of the knee

Radiographic findings in patients with osteoarthritis include medial tibiofemoral and patellofemoral joint space narrowing, as well as subchondral new bone formation. Next, lateral subluxation of the tibia occurs, and osteophyte formation is most prominent medially. Lateral joint space narrowing can also occur but not as prominently as the medial narrowing. Cartilage is lost, and subchondral bone formation occurs. Marked osteophyte formation also occurs, and osteophytes are seen anteriorly and medially at the distal femur and proximal tibia, and posteriorly at the patella and the tibia.

Hand
The hand can be evaluated with AP and oblique views; however, more detail is evident with magnified views of the entire hand or of a specific joint. Magnification views are particularly helpful in evaluating the soft tissues and the fine detail of specific bone. The most commonly involved joints in the hand and wrist are the first carpometacarpal joints, the trapezionavicular joint and the proximal interphalangeal and distal interphalangeal joints. Joint space loss is nonuniform and asymmetric. Erosive changes are not seen in primary osteoarthritis. In cases where an underlying disease process (such as an inflammatory arthropathy) is present, secondary osteoarthritis can occur. Postmenopausal women may have a variant of osteoarthritis, known as erosive arthritis. Only erosive osteoarthritis has erosions and ankylosis. The distribution in the hands and the feet is similar to that of osteoarthritis.

Fig 36. Oblique (left) and AP (right) views of the hand demonstrate decreased joint space and subchondral sclerosis at the first carpal metacarpal joint (white arrows). There is old joint space loss at the PIP and DIP joints with relative sparing of the MCP joints. Osteophyte formation with soft tissue swelling and subchondral sclerosis is noted at the 2nd and 3rd DIP joints compatible with Heberden’s nodes (open arrows). (PIP = proximal interphalangeal; DIP = distal interphalangeal; MCP = metacarpal phalangeal)

Hips and Pelvis
AP views of the pelvis can be used to assess arthritic changes in the hips as well as the sacroiliac joints (Figure 4). Changes associated with the hip include superolateral joint space narrowing with subchondral sclerosis. The superolateral portion of the joint is the weight-bearing portion. Cystic changes can occur, and the femoral head can appear to be irregular.

The true synovial joint space of the sacroiliac joint occurs anteriorly and inferiorly. In osteoarthritis, bridging osteophytes develop and extend from the ilium to the sacrum. Sclerotic changes are also noted, but ankylosis or erosions do not usually develop as they do in spondyloarthropathies such as ankylosing spondylitis, psoriasis or Reiter’s syndrome.

Spine
Lateral and AP lumbar spine radiographs are adequate to allow identification of osteoarthritic changes in the apophyseal joints. Decreased joint space is noted between the superior and inferior facets. Sclerosis and cyst formation occur in osteoarthritis of the spine. Neural foraminal narrowing may result from the osteophyte formation. These changes can be seen on computed tomographic (CT) scans. Figure 5 illustrates neural foraminal narrowing caused by facet osteophyte formation. Similar changes are seen in the cervical spine. Primary osteoarthritic changes are not commonly seen in the thoracic spine. Osteoarthritis of the spine is often associated with degenerative joint disease.

Foot
In the foot, AP and lateral radiographs are adequate to assess osteoarthritic changes, but oblique and magnified views may be helpful if a detailed view of a joint space is required. The most common joint involved is the first metatarsophalangeal joint. Again, subchondral sclerosis, osteophyte formation and cystic changes are common. Lateral subluxation of the great toe results in a hallux valgus deformity. Osteoarthritic changes elsewhere in the foot, such as the subtalar joint, are usually caused by altered mechanics from congenital or acquired abnormalities (e.g., pes planus, fusion of two bones) or are secondary to another underlying arthropathy (e.g., psoriasis, Reiter’s syndrome).

2. CT scan. While a CT scan is not indicated for an initial evaluation or as routine follow-up, it may be helpful in the evaluation of the lumbar spine to check facet hypertrophy in the management of low back pain and spinal stenosis. This evaluation can also be accomplished with magnetic resonance imaging (MRI) studies, although the osseous detail is better appreciated with CT scan. MRI also can be helpful in evaluating cartilage loss but often is unnecessary because plain films provide adequate information. MRI studies should not be routinely performed in diagnosing osteoarthritis unless additional pathology is suspected (e.g., post-traumatic injuries, malignancy, neural foraminal impingement, infectious process).

  3. Ultrasonography can be helpful in diagnosing cystic changes in the soft tissue about the joints but is not useful in the initial diagnosis of osteoarthritis.

   4. Arthrocentesis of the affected joint can help exclude inflammatory arthritis, infection, or crystal arthropathy.

Histologically, the earliest changes occur in the cartilage. Proteoglycan staining is diminished, and, eventually, irregularity of the articular surface with clefts and erosions occurs.

Treatment

Treatment of osteoarthritis involves alleviating pain, attempting to rectify mechanical malalignment, and identifying and addressing manifestations of joint instability.

 Nonsteroidal Antiinflammatory Drugs, Cyclooxygenase-2 Inhibitors, and Acetaminophen.

For treating the pain of osteoarthritis of the knee, head-to-head randomized trials showed that nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are more efficacious than acetaminophen. However, the superiority of NSAIDs over acetaminophen (at doses of 4 g per day) is modest. In one large crossover trial, the average reduction in pain during the first treatment period, on a scale of 0 to 100, was 21 in patients treated with NSAIDs and 13 in those given acetaminophen (P<0.001). Because of the greater toxicity of NSAIDs, acetaminophen should be the first line of therapy. Acetaminophen appears less effective, however, among patients who have already received treatment with NSAIDs; in the crossover trial there was no improvement overall with acetaminophen in patients treated after a six-week course of NSAIDs. Low doses of antiinflammatory medications (e.g., 1200 mg of ibuprofen per day) are less efficacious but better tolerated than high doses (e.g., 2400 mg of ibuprofen per day). One strategy to decrease the potential gastric toxicity of conventional NSAIDs has been the use of COX-2 inhibitors, although the results of recent trials showing increased cardiovascular risk with these agents has limited their use. Alternatively, the combination of NSAIDs and misoprostol or proton-pump inhibitors has been shown in randomized trials to reduce the number of endoscopically confirmed ulcers associated with NSAIDs.

             Injections of Hyaluronic Acid

Injections of hyaluronic acid into the knee joint have been approved by the Food and Drug Administration for the treatment of osteoarthritis. However, data on efficacy are inconsistent. Two recent meta-analyses reported statistically significant but limited efficacy. In one meta-analysis, publication bias (preferential publication of positive studies) was seen, which can inflate meta-analysis estimates from published studies. The identification of two large, unpublished trials whose data showed no efficacy, and the observation that injections of hyaluronic acid appeared to be less effective in large than in small trials, suggest that even limited efficacy may be an overestimate.

            Glucosamine and Chondroitin Sulfate

Glucosamine and chondroitin sulfate are widely used for the treatment of osteoarthritis, although their mechanisms of action are unclear. Most randomized controlled trials have reported greater pain relief with treatment with either compound than with placebo and have found little toxicity, usually no more than that associated with placebo. Publication bias was found as part of a meta-analysis of published trials evaluating these treatments, and this suggests that efficacy results from only published reports may be inflated. Four trials published since this meta-analysis, including two that were large enough to detect modest treatment effects, have showo efficacy of glucosamine.

            Other Pharmacologic Therapies

In randomized trials, intraarticular corticosteroid injections have relieved pain more effectively than placebo for one to three weeks on average, after which their comparative efficacy wanes. Data are lacking about the optimal number or frequency of corticosteroid injections. Opiate analgesic agents are more efficacious than placebo in controlling pain, but side effects and dependence are concerns. Topical compounds such as capsaicin have been modestly better than placebo in reducing the pain of osteoarthritis of the knee.

            Nonpharmacologic Treatment

Too little attention is paid to nonpharmacologic treatments. In patients with osteoarthritis of the knee, weakness of the quadriceps muscles is caused by disuse and by inhibition of muscle contraction in the presence of adjacent capsular swelling (so-called arthrogenous muscle inhibition). The severity of pain is directly correlated with the degree of muscle weakness. Although strong muscles may promote structural deterioration in malaligned knees, strengthening the muscles is still important because stronger muscles improve the stability of the joints and lessen pain.

Exercises are likely to be most effective if they train muscles for the activities a person performs daily. Range-of-motion exercises, which do not strengthen muscles, and isometric exercises, which strengthen muscles, but not through a range of motion, are unlikely to be effective. To reduce pain and improve function, randomized trials have demonstrated the efficacy of isokinetic or isotonic strengthening (i.e., strengthening that occurs when a person flexes or extends the knee against resistance). Low-impact aerobic exercise is also effective in lessening pain. Exercise regimens may differ for persons with patellofemoral symptoms. If the knee hurts during an exercise, then that exercise should be avoided. The involvement of a physical therapist is often warranted.

In a recent randomized trial, the combination of exercise and modest weight loss (mean, 4.6 kg) — but not weight loss alone — reduced pain and improved physical function in patients with osteoarthritis of the knee as compared with education about nutrition, exercise, and arthritis. In a large controlled trial, acupuncture was shown to reduce pain in patients with osteoarthritis of the knee, as compared with no acupuncture and sham acupuncture, but the effect was small.

            Correction of Malalignment

Malalignment is induced over a long period by anatomic alterations of the joint and bone, and correcting it is challenging. Evidence from randomized trials is sparse regarding the efficacy of therapies to correct malalignment across the knee joint. In one trial of patients with osteoarthritis of the medial side of the knee and varus malalignment, wearing a neoprene sleeve over the knee decreased knee pain moderately and significantly as compared with no treatment; the use of a valgus brace (which also can lessen varus malalignment) decreased pain significantly more than the sleeve.

Other ways of correcting malalignment across the knee include the use of wedged insoles or orthotics in footwear. In patients with osteoarthritis and varus malalignment of the knees, a shoe wedge (thicker laterally) moves the center of loading laterally during walking, a change that extends from foot to knee, lessening medial load across the knee. Although such modifications to footwear decrease varus malalignment, one randomized trial showed no reduction in pain as compared with a neutral insert.

Patellofemoral pain may be caused by tilting or malalignment of the patella. Patellar realignment with the use of braces or tape to pull the patella back into the trochlear sulcus of the femur or reduce its tilt may lessen pain. In clinical trials in which tape was used to reposition the patella into the sulcus without tilt, knee pain was reduced as compared with placebo. However, patients may find it difficult to apply tape, and skin irritation is common. Commercial patellar braces are also available, but their efficacy has not been studied formally.

Expertise of the working capacity

Patients with I-II stage OA are issued a sick leave for the period of exacerbation. Patients with III-IV stage OA can  not work, their cases are analyzed by  special comission in order to establish an appropriate invalidity group (III, II, I).

Rehabilitation.

 Patients are supervised by a general  practitioner once a year. They are seen by an arthopedist-traumatologist, if needed. CBC and urinalysis are performed once a year, joint radiography is perfomed once a year, if needed. Two to three times a year pharmacological and phyciotherapeutic treatment are adminisered.

ANKYLOSING SPONDYLITIS

sacroiliitis

The sacroiliac joint is the joint between the sacrum, at the base of the spine, and the ilium of the pelvis, which are joined by ligaments. It is a strong, weightbearing synovial joint with irregular elevations and depressions that produce interlocking of the bones.

Fig. 39. Sacroiliac joint – skeleton view.

Fig. 40. Sacroiliac joint

Fig. 41. Periformis muscle and sacroiliac joint

Fig. 42. Articulations of pelvis. Anterior view

Fig. 43. Articulations of pelvis. Posterior view

Ligaments

Depending on the reference source cited, the anterior ligament may be described as just a thickening of the anterior joint capsule. The anterior ligament is certainly not as strong and well defined as are the posterior ligaments. The posterior sacroiliac (SI) ligaments can be further divided into short and long. There is a very strong structure which is called the dorsal interosseous ligament. This structure is stronger than bone; such that the pelvis will fracture before this structure tears. There is much we do not know regarding pelvic ligaments. For example it is known that ligaments become loose during pregnancy in response to hormones, especially relaxin; to allow widening of the joints during the birth process. We do not know if the interoseous membrane has the same type of receptors as the ligaments, and the specific ligament nerves (called mechanoreceptors/nociceptors) of the SI joint have not been studied in detail. The long and short SI ligaments can be palpated and the tone of the ligaments can be compared from one side of the body to the other.

Inflammation of this joint may be caused by sacroiliitis, one cause of disabling low back pain. With sacroiliitis, the individual may experience pain in the low back, buttocks and thighs, and may also have other symptoms of a rheumatic condition such as inflammation in the eyes or psoriasis. Another condition of the sacroiliac joint is called sacroiliac joint dysfunction (also termed SI joint dysfunction). While SI joint dysfunction also causes low back and leg pain, and results from inflammation of the sacroiliac joint, it differs from sacroiliitis in that its origin is a disruption in the normal movement of the joint (too much or too little movement in the joint).

Ankylosing spondylitis  – is a chronic inflammatory deaseses of the joints of the axial skeleton, manifested  clinically by pain and progressive stiffening of the spine.

Epidemiology

Ankylosing spondylitis is a disease with a peak onset in the second and third decades.  The age at onser is ussually in the late teens or early 20s. The incidence is greater in males than in females (a male to female ratio of about 4:1), and symptoms are more prominent in men, with ascending involvement of spine more likely to occur.

More than 90% of affected persons carry the histocompatibility antigen HLA-B27. The overall prevalence varies from 0.5-1% in most communities but is much greater in the Pima and Haida Indians who have a high prevalence of HLA-B27. First-degree relatives of patients with ankylosing spondylitis have a greatly increased incidence ofpsoriatic arthritis, inflammatory bowel disease and Reiter’s syndrome.

Fig. 44. The sacroiliitis

Chronic prostatitis is more common than would be anticipated but it is not possible to isolate organisms from prostatic fluid. Faecal carriage of some Klebsiella species is increased in ankylosing spondylitis and this may be related to exacerbation of the disease.

ClinicAL HISTORY

·        Chronic low backache in young adults, generally worst in the morning.

·        Progressive limitation of back motion and of chest expansion.

·        Transient (50 %) or permanent (25 %) peripheral arthritis.

·        Anterior uveitis in 20-25 %.

·        Diagnostic radiographic changes in sacroiliac joints.

·        Elevated ESR and negative serologic tests for rheumatoid factor.

·        HLA-B27 testing is most helpful when there is an indeterminate probability of disease.

The onset is usually gradual, with intermittent bouts of back pain that may radiate down the thighs.  As the disease advances symptoms progress in a cephalad direction and back motion becomes limited, with the normal lumbar curve flattened and the thoracic curvature exaggerated. Chest expansion is often limited as a consequence of costovertebral joint involvement.  Radicular symptoms due to cauda equina fibrosis may occur years after onset of the disease. In advanced cases, the entire spine becomes fused, allowing no motion in any direction.

Fig. 44. Location of sacroiliac joint pain

Fig. 45. Assessment for sacroiliac joint pain

 Transient acute arthritis of the peripheral joints occurs in about 50 % of cases, and permanent changes in the peripheral joints – most commonly the hips,  shoulders, and knees – are seen in about 25 %.

Spondylitic heart disease, characterized chiefly by atrioventricular conduction defects and aortic insufficiency, occurs in 3-5 % of patients with long-standing severe disease.

Anterior uveitis is associated in as many as 25 % of cases and may be a presenting feature.

Pulmonary fibrosis of the upper lobes, with progression to cavitation and bronchiectasis mimicking tuberculosis, may occur, characteristically long after the onset of skeletal symptoms.

Constitutional symptoms similar to those of rheumatoid arthritis are absent in most patients.

DIAGNOSIS

Modified New York criteria:

1.     Low back pain and stiffness of greater than three months duration, improving with exercise but not relieved by rest

2.     limitation of motion of the lumbar spine in both the sagittal and frontal planes

3.     limited chest expansion, relative to standart values for age and sex

4.     definite radiographic sacroiliitis: symmetric sacroilitis of 2-4 stage or asymmetric sacroilitis of 3-4 stage

Fig. 46. limitation of motion of the lumbar

Definite diagnosis of  ankylosing spondylitis: the presence of radiographic sacroiliitis associated with at least one clinical criterion.

Radiographic stages (The changes and progression of the lesions are usually symmetric):

1.     The earliest changes in the sacroiliac joints are blurring of the cortical margins of the subchondral bone, followed by erosions and sclerosis. Progression of the erosions leads to “pseudowidening” of the joint space.

2.     The moderate changes in the sacroiliac joints are narrowing of the joint space.

3. The latest changes in the sacroiliac joints are ankylosis

CLASSIFICATION OF THE  ANKYLOSING SPONDILITIS

(Chepoy, 1986)

I.      Clinical form

1.     central form (involvement of he spine)

2.     “root” form (involvement of he spine  and arthritis of the hips and shoulders)

3.     peripheral form (involvement of he spine and arthritis of  peripheral joints other   then  the hips and shoulders)

4.     scandinavial form (involvement of he spine and arthritis of  the hands and wrists)

5.     one of the forms associated with the involvement of the internal organs (heart,  aortic insufficiency,  kidneys)

II. Course :

1. Slowly progressive course

2. Slowly progressive course with alternating exacerbations

3. Rapidly progressive course

III. Radiographic stages (The changes and progression of the lesions are usually symmetric).

IV. Stages of activity:

1.     Mild

2.     Moderate

3.     Severe

V. Grade of Limitation of motion:

1. change of functional spine flexure.

2. patient have to change profession.

3. loss of the ability to work.

Laboratory tests.

The ESR is elevated in 85 % of cases, but serologic tests for rheumatoid factors are characteristically negative.

 Anemia may be  present but is often mild. HLA-B27 is found in 90 % of patients with ankylosing spondylitis. Because thise antigen occurs in 80 % of the healthy  white population (and 4 % of healthy blacks), it is not a specific diagnostic test.

Imaging Studies.

·        Radiograph, magnetic resonance imaging, or computed tomography (CT) scan

o   Sacroiliitis may be present and observed on either a radiograph, magnetic resonance imaging, or CT scan.

·         CT scan

·         Magnetic resonance imaging (MRI)

·        Single-photon emission computed tomography (SPECT)

The earliest radiographic changes are usually in the sacroiliac joints. In the first few months of the disease process, the sacroiliac changes may be detectable only by CT scanning. Later, erosion and sclerosis of these joints are evident on plain radiographs. Involvement of the apophysial joints of the spine, ossification of the annulus fibrosus, calcification of the anterior and lateral spine ligaments, and squaring  and generalized demineralization of the vertebral bodies may occur in more advanced stages. The term „bamboo spine”  has been used to discribe the late radiographic appearance of the spinal column.

Additional radiographic findings include periosteal new bone formation on the iliac crest, ischial tuberosities and calcanei, and alterations of the pubic symphysis and sternomanubrial joint similar to those of the sacroiliacs. Radiologic changes in peripheral joints, when present, tend to be asymmetric and lack the demineralization and erosions seen in rheumatoid arthritis.

TREATMENT

The general principles of managing chronic arthritis apply equally well to ankylosing spondyliris. The importance of postural and breathing exercises should be stressed.

Drug Therapy

The NSAIDs are used in  the treatment of this disorder. Of these, indomethacin appears to be the most effective, though it can be quite toxic. The dosage of indomethacin is usually 25-50 mg three times a day, but the smallest effective dose should be used. Indomethacin may produce a variety of untoward reactions, including, headache, giddiness, nausea and vomiting, peptic ulcer, renal insufficiency, depression, and psychosis. Other NSAIDs are valuable alternatives and may be used as primary therapy.

Sulfasalazine (1000 mg twice daily) is sometimes useful for the peripheral arthritis in patients with spondyloarthritis but has little symptomatic effect on spinal and sacroiliac joint disease.

Curiosly, corticosteroids have minimal impact on the arthritis – particularly the spondylitis – of ankylosing spondylitis.

Recent studies with tumor necrosis factor inhibitors demonstrate that these agents are highly effective in both the spinal and peripheral arthritis of ankylosing spondylitis. Either etanercept (25 mg subcutaneously twice a week) or infliximab (5 mg/kg every other month) is reasonable for patients whose symptoms are refactory to phsysical therapy and other interventions.

Expertise of the working capacity

Patients with ancylosing spondilitis, regardless of the course of the disease, its activity and progression rate, changes in joints and internal organs may be recognized as invalids of the III^rd , II ^nd  or i groups.

Rehabilitation

Patients are supervised by a general practitioner 2-4 times a year. They are seen by an orthopedict-traumatologist, E.N.T. – specialist, urologist, and a dentist once a year, by an ophthalmologist 1-2 a year, urinalysin-once a year, radiological examination of spine and hips – oncer a year, chest radiogram – oncer a year. ECG – 1-2 times a year. Two to three times a year pharmacological and physiotherapeutic treatment are administered. Hospitalization and resort treatment are advised if indicated. Job modification.

BIBLIOGRAPHY

1. Bongartz T, Sutton AJ, Sweeting MJ: Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006 May 17; 295(19): 2275-85.

2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.

3. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF: Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005 Nov; 52(11): 3381-90.

4. Felson DT. Epidemiology of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis. Oxford, England: Oxford University Press, 2003:9-16.

5. O’Dell JR: Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004 Jun 17; 350(25): 2591-602.

6. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001;44:1237-1247. 

7. Taylor PC, Steuer A, Gruber J: Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis. Arthritis Rheum 2006 Jan; 54(1): 47-53.