Arthritis

The word `arthritis', literally means, “Inflammation of the joint." The term is used to describe a group of distinct diseases, primarily affecting joints of the body, all having related symptoms. These may include pain, swelling, and stiffness of the joints and surrounding areas. Arthritis can attack one or many joints, suddenly or more gradually over time, depending on the particular type one may have. Similarly the symptoms may be constant or may come and go (called as exacerbations and remissions), but generally the effects of arthritis are chronic, meaning that they will last for a long time, even life long.

Anatomy and Pathology: what is normal and what happens in arthritis?

The surfaces of the bones in the joint are normally covered with a thin layer called articular cartilage. This cartilage is smooth and slippery. When the joint bends or twists, the cartilage keeps the movement smooth and fluid. Finally, the joint itself is surrounded by the synovium, which is a thin layer of tissue that produces synovial fluid. This layer, plus thicker ligamentous tissue, forms a "capsule" around the joint, with the fluid inside keeping the joint well-lubricated. Each of our joints is built differently—some joints work as a hinge, others swivel, and some do a combination of several different types of motion. But all share a set of common characteristics. In most joints, two bones meet, end-to-end. They are connected to each other directly by ligaments, which are short fibrous strips of tissue placed at several different points in the joint, at different angles, holding the bones in the correct position during motion. Stability is also provided by the muscles surrounding the joint, which attach to the bone by tendons.

Arthritis is a condition that attacks the joints and tissues surrounding them, as well as other parts of the body in some types. The main pathology causing symptom in arthritis is the erosion of articular cartilages. As mentioned above, the function of these cartilages is to ensure smooth pain free movements of the joint and absorb stress. When these get eroded, bones come in direct contact with each other causing friction and painful movements. Other surrounding tissue may be directly or indirectly depending on the type of arthritis. The synovium, which is the layer producing the fluid for lubrication may get hypertrophied and produce more fluid causing swelling of the joint, the muscles surrounding the joint may get thinned (atrophied), The alignment of the limb may change due to asymmetrical wearing of the articular cartilage and ligaments may get loose (laxity).

What are the types of arthritis?

There are more than 100 different types of arthritis, some are more common than others. The four types that are the most prevalent in both the adult and children include:

• Osteoarthritis
• Rheumatoid Arthritis
• Gout and Pseudogout
• Ankylosing Spondylitis

Osteoarthritis

Osteoarthritis is a degenerative disease, usually affecting people over the age of 45. The degenerative process can be hastened by injury to a special joint. It occurs due to failure of chondrocytes to repair damaged cartilage or when there is a disparity between the stress applied and the chondrocyte response, wear vs repair. Osteoarthritis affects the protective cartilage that covers the bones, causing it to break down, becoming rough and even torn in places. The response of the body is to try to increase the joint surface in response and this produces ridges or spurs also known as osteophytes. This exposes the bone, causing additional friction in the joint, which damages the cartilage and bone even further as they rub together. Osteoarthritis more often affects the weight-bearing joints, such as the knees and hips, as well as the spine.

The specific causes of osteoarthritis are not known and is considered a part of the ageing spectrum. Why some people develop it early in life while others donot suffer from it even in an advanced stage is not clearly known, what is known however is that several factors can increase the risk for developing it. These include age, obesity, and overuse due to sports or occupational stresses.Thus osteoarthritis could be:

• Primary - no obvious cause
• Secondary - occurs following certain predisposing factors (such as previous trauma, congenital deformity, infection or a metabolic disorder).

The changes that occur at molecular level in osteoarthritis are

1. Increased water content (in contrast to decreased water content in normal ageing)  leading to weakening of type 2 collagen network.
2. Shorter chains and shifts in the concentration of proteoglycans. The chondroitin/keratin ratio is increased (opp. to ageing).
3. Disruption is caused by an increase in collagenase and proteoglycan-degrading enzyme (stromelysin & plasmin) concentration.
4. Rate of synthesis of DNA, collagen, and proteoglycans are increased
5. Increased levels of:
   1. Matrix Metalloproteinases (MMPs) (collagenase, gelatinase, and stromelysin).
   2. Cathepsins B and D
   3. IL1 - enhances enzyme synthesis & has a catabolic effect.
   4. IL6
   5. TNFa
   6. TGF beta
   7. GAGs and polysulfuric acid

Complications of Osteoarthritis: They could be -

1. Deformities
2. Subluxation
3. Ankylosis
4. Loose bodies leading to repeated locking and further progression.

Treatment of Osteoarthritis:

Depending on the severity of your osteoarthritis, your doctor may try one or a combination of several different courses of treatment. Because pain is the major complaint in osteoarthritis, treatment will focus on reducing that pain. Following are various modalities that may be used:

• Protection of affected joints from overloading
  • weight loss
  • use of walking stick
• Exercise of supporting muscles around joints to avoid wasting.
• Supportive measures such as pain relief by analgesics or NSAIDs.
• Hyaluronic acid injections
• Glucosamine & chondroitin 
• Surgical treatment - is indicated for patients with persistent symptoms and pain and ranges from arthroscopy to arthroplasty.
  • Realignment osteotomies may be done in younger patients to redistribute weight bearing load at the knee to prevent further damage.
  • In the most severe cases of osteoarthritis, joint replacement may be an appropriate treatment. Total joint replacement is also called `arthroplasty.' In a joint arthroplasty, the ends of the affected bones are resurfaced and replaced with a combination of plastic and metal components. These are more commonly performed on the hip and knee.
• New & Experimental Treatments:

1. Soft tissue grafts - periosteal / perichondral
2. Chondrocyte transplantation
3. Mosaicplasty (See Maitrise Orthopedique)
4. Artificial matrix - carbon fibre, collagen, polylactic acid
5. Fresh osteochondral grafts
6. Doxycycline - In animal studies, doxycycline inhibits cartilage collagenase activity and reduces the severity of osteoarthritis. (Although doxycycline is an antibiotic, it should not be thought that osteoarthritis is an infectious process)
7. Transforming growth factor beta (TGF beta) - packaged in liposomes can repair partial thickness articular cartilage lesions in animal models. 
8. Metalloproteinase inhibitors - drugs that inhibit enzymes responsible for cartilage matrix destruction  and block cytokines (proteins involved in the destruction).
9. Gene therapy - Genes that have either anti-arthritic or synthetic properties can be delivered into the joint via non-replicating viral vectors. Two human trials are presently underway in which a retrovirus is used to transfer human IL-1ra cDNA to the synovial lining of metacarpo-phalangeal joints of patients with rheumatoid arthritis. Although exciting and full of promise, the field of gene therapy still needs careful work and caution. In animal studies, for example, the transfer by gene therapy of TGF beta and BMP-7 to synovium and chrondroprogenitor cells resulted in death of the animals, possibly through overproduction of the proteins generated

The potential long-term treatment or cure of osteoarthritis really lies in the development of agents that reverse the balance between degradative and synthetic processes of the chondrocyte. 

 

Rheumatoid Arthritis: Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes pain, stiffness, and swelling in the joints, usually in a symmetrical pattern (identical body part – left and right). In this type of arthritis unlike in osteoarthritis, the joint lining (synovium), which is normally smooth and shiny, becomes inflamed, painful and swollen. The disease, which usually increases and decreases (exacerbates or goes in remission) over a long period of time, can cause damage to cartilage, bone, tendons and ligaments. RA can also cause systemic involvement like inflammation in the blood vessels and the outer lining of the heart and lungs. About 3% of women and one percent of men are affected by this disorder.

 

Classifying Rheumatoid Arthritis:

For classification purposes, a patient is said to have RA if he or she has satisfied at least 4 of the following 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded.

1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement.
2. Arthritis of 3 or more joint areas At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician; the 14 possible joint areas are right or left proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints, wrist, elbow, knee, ankle, and metatarsophalangeal (MTP) joints.
3. Arthritis of hand joints At least 1 area swollen (as defined above) in a wrist, MCP or PIP joint.
4. Symmetric arthritis Simultaneous involvement of the same joint areas (see 2 above) on both sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry).
5. Rheumatoid nodules Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician.
6. Serum rheumatoid factor Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects.
7. Radiographic changes Radiographic changes typical of RA on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized to or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify).

Common sites for RA include:

• Hands
• Wrists
• Elbows
• Shoulders
• Neck
• Hips
• Knees

Cause of Rheumatoid Arthritis:

RA is an autoimmune disease, which means our own immune system starts to attack some of your tissues. It is not exactly known what causes this autoimmune attack, but the most accepted hypothesis is that in a genetically susceptible individual, an environmental trigger (drugs, allergens, chemical or infection) causes an autoimmune attack.

Symptoms of Rheumatoid arthritis:

Rheumatoid arthritis has predominant involvement of different joints – in a characteristic exacerbating and remitting pattern. It has three phases – stage of synovitis, stage of destruction, and stage of deformity. The most common symptoms of RA are pain, swelling and stiffness in one or more joints. The pain may be similar to a headache or toothache. In some people, the joints can feel hot. Occasionally lumps of tissue known as rheumatoid nodules develop near the affected joint, usually near the elbow joint.

There may be involvement of organs other than other joint also known as systematic involvement. These include:

1. Nodules - in 20% of RA - skin, synovium, tendons, sclera, viscera
2. Lymphadenopathy (enlargement of the lymph glands)
3. Splenomegaly (enlargement of spleen)
4. Vasculitis (involvement of the vessels)
5. Myopathy ( Muscle involvement)
6. Sensory changes - neuropathy, or direct compression from synovitis
7. Visceral
   1. pericarditis (inflammation of  the lining of heart)
   2. pulmonary fibrosis, nodules, pleurisy

The combination of certain systemic involvement and Rheumatoid arthritis have been known as syndrome complexes, some of which are-

1. Felty's Syndrome - splenomegaly + leukopaenia
2. Still's Disease - fever, rash + splenomegaly
3. Sjorgen Syndrome - decreased salivary & lacrimal gland secretion & lymphoid proliferation

Lab Tests: Following lab tests may become abnormal-

1. Incr. ESR
2. Incr. CRP
3. Rheumatoid Factor +ve in 80% : This is probably an important marker not only for the diagnosis but also for the level of ongoing disease activity.

Potential Complications:

1. Fixed Deformities
2. Joint Rupture
3. Infection
4. Spinal cord compression 
5. Peripheral nerve compression
6. Vasculitis
7. Amyloidosis - proteinuria & progressive renal failure

Treatment: The main goals in treating RA are to relieve pain, reduce swelling, slow down the damage to the joints, and improve the person's ability to function.

1)    Stop the Synovitis

a)     Rest

b)    Drugs: While there is no cure for rheumatoid arthritis, some drugs can help control the disease. A rheumatologist will often suggest:

Nonsteroidal anti-inflammatories can be used and include:

o   Acetylsalicylic acid (aspirin)

o   Ibuprofen

o   Indomethacin

o   Naproxen

o   Tolmetin

Corticosteroids can also help ease pain and swelling and help slow the damage to the joints. Drugs that are corticosteroids include prednisone and cortisone.

There are also a group of drugs know as disease modifying antirheumatic drugs. These are also called DMARDs and they take much longer to act than the NSAIDs. Sometimes it can take weeks or months to begin to notice a change. But, the DMARDs may help slow the progress of the arthritis, too. There are more side effects to these drugs though and you will need to check with your doctor often. DMARDs include:

·       Antimalarial drugs

·       Gold compounds

·       Penicillamine

·       Sulfasalazine

c)     Synovectomy - chemical, irradiation, surgical.

 

2)    Prevent Deformity

a)     Splintage

b)    Physiotherapy

c)     Tendon repairs & joint stabilisation

 

3)    Reconstruct: Surgery, such as joint replacement, may be an option for some people

a)     Arthroplasty or joint replacement.

b)    Arthrodesis

c)     Osteotomy

 

4)    Rehabilitate

o   Occupational therapists - aids, support

o   Physiotherapy

.

Alternative Medicine: Some form of medicines like Ayurveda and homeopathy have also been tried but with limited success.

Prognosis:

• 10% improve after first attack of synovitis
• 60% have remissions & exacerbations
• 20% have severe joint erosions requiring multiple operations
• 10% become completely disabled

Poor prognostic signs:

1. Very high Rheumatoid Factor.
2. Peri-articular erosions on X rays.
3. Nodules
4. Muscle wasting
5. Joint contractures
6. Vasculitis or vessel involvement.

Ankylosing Spondylitis.

 

Contains information about ankylosing spondylitis, its possible cause, symptomatology, possible complications, treatment.

 

Ankylosing Spondylitis, Reiter’s disease, seronegative arthritis, HLA B 27, Enthesopathy, Chest expansion, DISH.

 

Ankylosing spondylitis (AS) is a form of arthritis that involves primarily the spine and joints of the extremities, such as the shoulders, hips and knees. It strikes young adults (usually men in their 30s), causing pain, stiffness, eye inflammation, and possible disability in severe cases. It makes hip, shoulders, ribs, back and neck stiff and sore and can cause a stiff, inflexible backbone.

AS is a member of the family of diseases that attack the spine called spondylarthropathies. The cause of AS is not known, but all of the spondylarthropathies share a common genetic marker, called HLA-B27, in most affected individuals. It has a strong familial tendency and a male predilection. It is more common in westerners, but has low incidence in Japenese and Negroid population.

Disease Pathology: There is a preferential involvement of ligaments and tendons known as Enthesopathy. There are two basic affections-

1. Synovitis of diarthrodial or synovial joints
   • Synovitis of the Sacro illiac joint in the back and the facet joints of veretebare causes destruction of articular cartilage and periarticular bone
   • The costovertebral joints (Rib articulating with back bone)  are commonly affected which causes reduced respiratory excursion
   • When other joints are affected the same changes occur
2. Inflammation of fibro-osseus junctions of syndesmotic joints
   • This affects the intervertebral discs, SI joint ligaments, manubriosternal joint, pubic symphysis and the bony insertions of large tendons

These changes in the joint occur in three stages-

1. Inflammatory reaction with round cell infiltration, granulation tissue and destruction of bone.
2. Replacement of the granulation tissue with fibrous tissue
3. Ossification of the fibrous tissue leading to ankylosis of joints

Symptoms of Ankylosing Spondylitis: The usual symptoms start with low back pain and often the diagnosis is delayed because symptoms are often attributed to more common back problems. A dramatic loss of flexibility in the lumbar spine is an early sign of AS. Although most symptoms begin in the lumbar and sacroiliac areas, they may involve the neck and upper back as well.The usual symptoms include:

• Insidious onset of backache and stiffness in an adolescent or young adult, recurring at a number of intervals over a number of years
• Pain may be referred into the buttock and be confused with sciatica
• Early in the disease process there is little to find on clinical examination apart from slight loss of the lumbar lordosis, limitation of extension of the spine and SI joint tenderness
• Later patients have the characteristic posture because of Loss of lumbar lordosis, thoracic kyphosis, forward thrust of the neck and flexed hips and knees
• In advanced cases the entire spine may be completely ankylosed or fused thus severely restricting the movements of back.
• Chest expansion is often markedly reduced
• Peripheral joints (shoulders, hips and knees) are involved in over 30% of cases

Extraskeletal manifestations : Often there is involvements of other organs that is other than bone, joint, ligaments and tendons-

• Eyes: uveitis and conjunctivitis in 20%
• Heart: aortic valve disease, carditis (rare)
• Lungs: pulmonary fibrosis (rare)
• GU: prostatitis

Investigations:

X-rays

• The cardinal sign and earliest feature is sacroiliitis, with the iliac side affected first followed by ankylosis
• Vertebral bodies become squared and later syndesmophytes form between the bodies, bridging several levels which can lead to "Bamboo" or "Rugger Jersey" spine
• Peripheral joints may show erosive arthropathy or ankylosis

Special Investigations

• Inflammatory markers are raised early in the disease
• HLA-B27 present in 90% of cases, but it is important to note that only a fraction of people with the HLA-B27 antigen develop ankylosing spondylitis

Treatment

The majority of patients despite the disease can lead an active life. The severity of joint involvement and the degree of systemic symptoms vary greatly from one individual to another. Early, accurate diagnosis and therapy may minimize years of pain and disability

Aims of treatment are:

1. General measures to maintain a satisfactory posture and preserve movement
   • Physiotherapy and exercise are to be encouraged
   • The aim is to remain as mobile as possible for as long as possible
2. NSAID's to help with pain and stiffness
   • These can help the patient to perform exercise but do not themselves affect the course of the disease
3. Surgery to correct deformity and restore mobility
   • Corrective osteotomies of the lumbar and cervical spine can be performed if the deformity is severe enough, but are potentially hazardous
   • Total joint replacement, especially THR may be needed, but they have a higher infection  and failure rates.

 Careful evaluation needed following cervical spine injury as they can have unstable fractures with a risk of developing non-union. Proper sleep and walking positions, coupled with abdominal and back exercises, help maintain posture. Continuing care is critical. AS is a lifelong problem, and people often fail to continue treatment, in which case permanent posture and mobility losses occur.

 

GOUT

Gout is a term used to describe a whole range of arthritis caused due to deposition of various microcrystals in joint (Mono sodium Urate (MSU) crystals, Calcium pyrophosphate dehydrate crystals (CPPD), Calcium hydroxyl apatite crystals (HA), and Calcium oxalate (CaOx) crystals).  The commonest of these which is often used synonomusly with gout is due to Mono sodium Urate deposition.

 It has following features either singly or in combination:

1.     Hyper Uricemia or excess of Uric acid: Uric acid is the final break down of purine metabolism in humans. Normally two third to three fourths of urate is excreted in urine and rest is secreted in intestine. Normal levels of uric acid in humans are 3.0 – 7.0 mg /dl, and a value greater than 7.0 mg /dl is termed as hyperuricemia.

2.     Attacks of acute, typically monoarticular (single joint involvement), inflammatory arthritis.

3.     tophaceous deposition of urate crystals in and around joints.

4.     Interstial deposition of urate crystals in renal parenchyma.

5.     Urolithiasis (stone)

The hall mark of gout is acute attack of painful arthritis involving one joint usually great toe or knee. The first attack begins explosively and is very painful. The agonizing pain is accompanied by signs of intense inflammation – swelling, redness, warmth, equisite tenderness, and occasionally low grade fever. If untreated, the attack usually peaks 24 – 48 hrs after the first symptoms and subsidies within 7 – 10 days. The skin over the involved part may come off as the episode resolves.  Any factor that either increases or decreases the serum urate level may precipitate an attack. Some of the provocative factors include – stress, trauma, infection, hospitalization, surgery, starvation, weight reduction, hyperalimentation, excessive food intake, alcohol and medications.

Some individual face only a single attack in their lifetime, others experience recuurence. Although the interval between the first and second attack may be over 40 years, three fourts have a second attack within 2 years. The term interval gout or intercritical gout describes the periods between attacks of acute arthritis when the individual has no joint complaints. Chronic gout is a term used for persistent polyarticular low grade pain with acute or subacute inflammation.

Diagnosis: A definitive diagnosis requires aspiration of the involved joint or tissue and demonstration of intracellular monososdium crystals in synovail fluid polymorphonuclear leukocytes or in tophaceous aggregates. Using polarized microscopy, the strong negative birefrigent needle shaped crystals can be demonstrated.

Treatment: Once the diagnosis of gouty arthritis is secure, the choice of therapeutic agents includes colchicines, non steroidal antiinflamatory drugs (NSAID’s) or intraarticular glucocorticoids.

Colchicine is given in oral dose of 0.6 mg every hour until improvement occurs, or gastrointestinal side effect occurs or 10 dose have been given without any relief occurs ( in which case the diagnosis needs to be questioned) Colchicine is highly effective but about 80 percent develop abdominall pain, diarrhea and nausea. Colchicine can also be given intravenously but the approach is risky.

NSAID’s are started when the diagnosis is not sure and usually begins with highest dose of the chosen agent. Intaraticular steroids may be used in patients who cannot take orally or are refractory to colchicine.

Treatment of Hyperuricemia: It si begun only when all the acute symptoms have subsided and the urate levels are constantly high. The aim is to keep urate levels below 5 mg/dl.  The treatment includes dietary modification and specific urate lowering agents. Most commonly used agent is an enzyme inhibitor of  xanthine oxidase (nvolved in purine metabolism) known as Allopurinol.