About The Author Dr Manoj R.

kandoi is the founder president of Institute of Arthritis Care & Prevention an NGO involved in the field of patient education regarding arthritis. Besides providing literature to patient & conducting symposiums, the institute is also engaged in creating patients Self Help Group at every district level. The institute also conducts a certificate course for healthcare professionals & provide fellowship to experts in the field of arthritis. The author has many publications to his credit in various journals. He has also written a book The Basics Of Arthritis for healthcare professionals. The author can be contacted at: Dr manoj R. kandoi C-202/203 Navare Arcade Shiv Mandir Road, Opposite Dena Bank Shiv mandir Road, Opposite Dena bank Shivaji Chawk, Ambarnath(E) Dist: Thane Pin:421501 State: Maharashtra Ph: (0251)2602404 Country: India Membership Application forms of the IACR for patients & healthcare professionals can be obtained from. Institute of Arthritis Care & Prevention C/o Ashirwad Hospital Almas mension, SVP Road, New Colony, Ambarnath(W) Pin:421501 Dist: Thane State: Maharashtra Country: India Ph: (0251) 2681457 Fax: (0251)2680020 Mobile ;9822031683 Email: drkandoi@yahoo.co.in Preface: Studies have shown that people who are well informed & participate actively in their own care experience less pain & make fewer visits to the doctor than do other people with arthritis. Unfortunately in India & many third world countries we do not have patient education & arthritis self management programs as well as support groups. This is an attempt to give a brief account of various arthritis, their prevention & self management methods which can serve as useful guide to the patients of arthritis. It would be gratifying if the sufferers of the disease knew most of what is given in the book. Acknowledgement\ I am thankful to Dr (Mrs) Sangita Kandoi for her immense help in proofreading & for her invaluable suggestions. The help rendered by Nisha Jaiswal is probably unrivalled. Thanks also to vidya, praveen, rizwana and parvati for their continous support throughout the making of the book. The author is grateful to his family for the constant inspiration they offered. The author alone is responsible for the shortcoming in this piece of work. He welcomes suggestions for improvement from the readers.

Gouty Arthritis:
Introduction: Gout is characterized by an altered purine metabolism with deposition of uric acid salts in connective tissues such as cartilage (of joints or of the ears), the walls of bursa and ligaments. Etiology: Exact etiology not known Hereditary predisposition postulated Any rapid change in uric acid can precipitate acute gouty attack. Increased uric Acid -Sustained alcohol consumption -High purine intake -Diuretic use -Low dose aspirin intake -Excessive cell turnover (e.g. myelopoliferative diseases, cancers) -Hypertension -Intrinsic renal disease -Cyclosporine use. Rapidly decreased Uric Acid -High dose aspirin use -Use of uricosurics or allopurinol -Sudden stoppage of alcohol consumption

Types: 1. Primary gout: This can be due to overproduction or underexcretion. a. Underexcretors: Decreased excretion of uric acid by the kidneys b. Overproducers: Increased production of uric acid 2. Secondary gout: This is acquired from underlying conditions such as polycythemia, multiple myeloma or sickle cell or other haemoglobinopathies. Pathology: Normal Physiology Denovo biosynthesis Nucleotides Diet Nucleosides Bases Urate Urine Tophi Intestine Salvage pathways Nuclei acids

The total body urate pool is the net result between urate production & excertion. Pathophysiology of acute gout attack: Hyperuricemia ? factors Precipiation of urate crystals in joints

Phagocytosis by neutrophis

Activation of hageman factor

Damage to lysosomes Lysis of neutrophils

Kinin production complement activation

Release of crystals

Release of lysomal enzymes

Acute inflammation

Pathophysiology of chronic gout: Underexcretors Overproducers

Serum urate levels

Sodium Biurate formation Deposition in periarticular connective tissue and damaged articular cartilage and non articular cartilage.

Disorganisation of joint due to deposition in joint cartilage and ligaments

Gouty tophi at - Cartilage of ear -Olecrenon bursa etc.

Tophus: The pathognomic tissue lesion of gout is the tophus. The tophus is a mass of crystalline or amorphous urates surrounded by an intense inflammatory reaction of macrophages, lymphocytes and fibroblasts as large foreign body type giant cells. Clinical menifestation: A. More commonly in in males above 40 years of age & in postmenopausal females. B. Arthritis: Acute onset pain, erythema, edema & stiffness of joints involving mainly peripheral joints (such as toes, tarsus, ankle & hands) called PODAGRA. First metatarsophalangeal joints is often the first joint to be affected because of repeated exposures to microtrauma & a lower temperature compared to body temperature. C. Bursitis: Most commonly olecranon bursa is affected & it becomes distended with fluid, there may be palpable deposits ot uric acid salts. D. Nodules at ligamentum patella & ear cartilage due to gouty tophi deposition. E. Renal invlovement: Three types of lesions may be seen. 1. Urate Nephropathy: It results from the deposition of crystals in the medullary interstitium, the pyramids & papillae. 2. Acute Obstructive Renal Failure: It results from intratubular deposition of free uric acid crystals. There cases are more common in secondary gout due to chemotherapy or in myeloproliferative disorder. 3. Uric acid stone formation is common in patients excreting more than 1100 mg of uric acid per day. F) Palms of hands may show white streaks along the creases (plasterer's hand). Fever and crystal induced arthropathies: Fever with temperature > 39 C accompanied with leukocytosis is common gout & pseudogout. In 40% of these cases serum uric acid levels are normal making differential diagnosis of crystal-induced arthritis from septic arthritis difficult. X-ray features: Soft tissue swelling around the joint. 'C' shaped punched out lesions in subchondral region with sclerotic base. Irregular soft tissue densities due to tophaceous deposits. Role of laboratory studies in DID of crystalline arthropathies: The joint aspiration must be done & synovial fluid sent for following analysis: 1. Cell count & Differential: A WBC count < 50,000 cells/mm is more suggestive of crystalline arthropathy. WBC count more than that does not rule out gout. 2. Crystal Analysis under polarized microscopy: This is a definitive diagnostic tests for determining appropriate crystal (monosodium urate in acute gouty arthritis & calcium pyrophosphate in acute pseudogout). 3. Gram stain, routine culture & sensitivity.

Serum uric acid as a diagnostic marker for gout: 1. Large number of general population have hyperuricemia, yet 19 out of 20 patients remain asymptomatic throughout life 2. In about 40% of case of acute gout attacks, serum uric acid levels are normal. 3. Certain general medical conditions associated with asymptomatic hyperuricemia include hypertension, obesity, heavy alcohol use, atherosclerosis, ischaemic heart disease & impaired glucose tolerance.

Differential diagnosis: Acute gouty arthritis: Infectious Arthritis Rheumatoid Arthritis Acute pseudogout Acute seronegative inflammatory arthritis Chronic tophaceous gout: Nodular Rheumatoid Arthritis Osteoarthritis DID of punched-out erosions in extremity bones: 1. Gout 2. Rheumatoid arthritis 3. Osteoauthritis 4. Sarcoid 5. Multiple myeloma 6. Hand-schullar -christian disease 7. Hyper parathyroidism 8. Leprosy Course: Recurrent attacks occur with normal joint between the acute attacks which last for few days. In cases of chronic gout the affected joints are severely disorganized. Treatment: Goals: Relieve the signs & symptoms of acute attack Reduce uric acid levels Reduce & if possible, eliminate the factors that produce gout

Treatment: Treatment protocol

Acute attack colchichin, oral or intravenous NSAIDS especially indomethacin or naproxen intraarticular Steroids

Frequent attacks chronic gout

To reduce serum uric acid levels

Allopurinol

Uricosurics

Acute Attack: A. Patient is placed on absolute bed rest. B. Immobilization of affected limb is done. Local cold or heat therapy may be used. C. Adequate fluid intake, diet inclusive of glycine & rich in carbohydrate is advised. D. Alcohol must be avoided. Drug therapy: Drugs commonly used in acute gout attacks are: 1. Colchicine: Oral or intravcl10us 2. NSAIDS ( Indomethacin, Naproxen are most commonly used) 3. Intra-articular corticosteroids. a. Colchicine: Mode of action: I. It inhibits the phagocytosis of urate crystals by neutrophils. II. It interferes with transport of phagocytosed materials to the lysosomes. III. It's interference with chemotactive response is believed to reduce joint inflammation. Dosage and administration: It is generally administered as 1 mg orally as an initial dose, followed by 0.5 mg every 2 hours until gastrointestinal discomfort or diarrhea develops or until a total dose of 8 mg has been given. Relief of clinical signs & symptoms is usually reached within 2 days. Alternatively it may be given as an IV initial dose of 2 mg followed by two separate doses of 1 mg at 6 hours interval, with total dose not exceeding 4 mg with the first 24 hours. Precautions: The dose should be halved in the elderly & in patients with renal & hepatic dysfunctions. The risk of renal, hepatic & CNS injury is more with parenteral route. Drugs like cimitidine or erythromycin are known to have harmful drug interaction with colchicin. It is contraindicated,ln pregnancy & lactation.

Role of NSAIDS in acute attack: a. Indomethacin 50 mg orally 4-6 hourly until attack subsides, then tapered off over 7 -10 days b. Phenylbutazone 200 mg tds after food c. Corticotrophin gel: 60-100 units in daily for 2-3 days may terminate severe attack Interval period Hyperuricemia (< 9 mg/dl.) - Periodic examination - Dietary restriction of purine rich food - Gradual weight reduction - Avoidance of drugs like thiazides or cytotoxicdrugs - Prophylactic drug therapy not indicated. Hyperuricemia > 9 mg/dl. - Prophylactic drug therapy - Other preventive measures

Indications for prophylactic therapy / interval therapy: Recurrent Attacks Tophaceous gout Presence of renal disease Family history of renal or heart disease Young patient with high uric acid levels (> = 9 mg/lr) Diet in chronic gout: It should be low in purines & fats No sweet bread, kidney, liver, meat extracts, peas, beans & lentils Prophylactic drug therapy: It includes: 1. Colchicin 2. Allopurinol 3. Uricosuric agents I. Colchicin: It is a safe and effective drugs which prevents acute attacks. Since it does not have uricosuric effect and does not affect tophceaus deposition, it should be combined with uricosuric drugs or allopurinol. The suggested doss is 0.5 mg/day or twice daily. II. Allopurinol: It is an inhibitor of the enzyme anthine oxidase; there by preventing the final step in the production of uric acid. By reducing serum urate and maintaining it at that level, the size of urate deposits can be reduced and progression of renal lesion is halted. Dosage and administration: It is started at 300 mg/day. In order to avoid exacerbation of acute gaut due to sudden and rapid changes in uric acid levels a lower dose of 100 mg/day is started which is gradually increased by 100 mg/week till the desired levels are reached.

Indications: 1. Patients with gout and a. Evidence of urate overproduction (24 hour urinary uric acid> 800 mg) b. Nephrolithiasis c. Renal insufliciency (creatinine clearance < 80 ml/min) d. Tophaceous deposits. e. Age over 60 years or f. Inability to take uricosuric agents because of inaffectiveness or intolerance. . 2. Patient with nephrolithiasis of any type plus urinary uric acid excertion greater than 600 mg / day 3. Patient with or at risk for acute uric acid nephropathy 4. Patient with renal calculi composed of 2,8 - dihydroxyadenine Contraindication: Children, acute gout. Precaution: Should not be used along with iron therapy To maintain adequate fluid intake Renal or hepatic impairement ADR: These include Bone marrow supression Hepatitis Stevens Johnson syndrome Urticaria Acute renal failure Vasculitis Fever III. Uricosuric agents: These act by increasing renal excretion of uric acid and are effective in the treatment of uncomplicated cases of gout. Due to high risk of urolithiasis with these medication, these are contraindicated in renal diseases. Dosage: Probenecid is effective at the dose of 1-2 gm/day Sulfinpyrazone is initially started as 50- 100 mg twice daily with a gradual increase to 200 mg twice daily. Precautions: a. Adequate fluid intake must be maintained. b. Sodium bicarbonate 1 gm three times a day to maintain alkaline urine levels is recommended. c. Probenecid prolongs the half-life of penicillin, heparin, salicylates and indomethacin. d. Intermittent treatment or the cessation of drug therapy may lead to recurrence of acute attacks within 6 months and formation of tophi within 3 years. Uratelowering drug therapy therefore Should be continue lifelong.

Medications with uricosuric Activity: -ACTH -Probencid -Ascorbic acid -Phenylbutazone -Calcitonin -Salicylates (>2g/d)

-Citrate -Estrogen -Glucocorticoids

-Sulfinpyrazone -Radiographic contrast agent -Glycopyrrolate

Orthopaedic measures: 1. Immobilization and splintage for prevention of joint destruction. 2. Large tophi that interfere with joint and tendon motion may be removed.

Principles of surgery in gouty lesion: 1. Avoidance of local anaesthesia, which might interfere with local blood supply 2. Colchicin therapy few days prior to surgery and for a similar period postoperatively 3. Incisions parallel with course of blood vessels. 4. Sharp dissection 5. Loose suturing to allow escape of liquified deposits 6. Pressure dressing 7. Avoidance of prolonged splintage which may cause stiffness.

Arthritis due to deposition of calcium crystals CPPD Deposition Disease (calcium pyrophosphate dihydrate) Pathogenesis: The deposition of CPDD crystals in articular cartilage, synovium & periarticular ligaments & tendons is most common in elderly more than 65 years of age. Conditions associated with CPDD disease Aging Disease associated: Primary hyperparathyroidism Hemochromatosis Hypophosphasia Hypomagnesemia Chronic tophacecus gaut Postmeniscectomy Epiphysical dysplasias , Hereditary: e.g. French, Swedish, English, Japanese etc. Clinical menifestations: The deposition is polyarticular in atleast 2-3rd of patients. The knee joint is the joint most frequently affected. Unlike osteoarthritis metacorpophalangeal, wrist, elbow, shoulder & ankle joint may also be involved. Rarely tempnomandibular joint & ligament flavum of the spinal canal are involved. In 50% of cases fever may be present making it difficult to differentiate from pygenic arthritis.

Clinical types

Asymptomatic

Acute Pseudogout

Subacute

Chronic

Pseudorheumatoid

Pseudoosteoarthritis Arthritis

Pseudoneuropathic Arthropathy

Acute attacks may be precipitated by trauma, surgery of joint or even a long walk. Rapid decline in serum calcium levels specially in severe medical illness or after surgery (especially parathyroidectomy) can lead to pseudogout. Isolated pseudogout: An acute inflammatory episode involving a large joint such as knee with h/o remissions or exacerbation: Usually there are no significant systemic menifestations. Pseudorheumatoid arthritis: It resembles rheumatoid disease, involving knees. Wrists, elbows and metacarpophalangeal joints. It is the least common menifestation of pseudogout. Pseudo- osteoarthritis: Bilateral symmetrical, acute, isolated inflammatory episodes of arthritis super imposed on osteoarthritic changes involving knees, wrists, shoulders, elbows and ankles may be seen. Asymptomatic: Incidental findings in largely asymptomatic joint. Severe generalized febrile disorder: It is associated with high fever, elevated WBC count, elevated ESR and polyarticular joint involvement. X-rays: It may show punctate and/or linear radiolense deposits in fibrocartilaginous joint monisci or articular hyaline cartilage. Definitive Diagnosis: It is based on demonstration of rod shaped or rhomboid crystals with weak positive birefringence in synovial fluid. Clinical sequalae: 1. Induction or enhancement of peculiar form of osteoarthritis. 2. Induction of severe resorptive disease mimicking charcot's arthritis. 3. Production of symmetric proliferative synovitis, clinically similar to RA & frequently seen in familial forms with early onset. 4. Intervertebral disk & ligament calcification with restriction of spinal mobility, mimicking ankylosing spondylitis 5. Spinal stenosis

Treatment

Symptomatic presentation NSAID Local aspiration Intraarticular steroid injection Crystals and particles seen in synovial fluid: Monosodium urate crystals CPPD, calcium hydroxyapetite Calcium oxalate crystals Injectable steroid crystals Lipid droplets Foreign organic matter (e.g. plant thorn) Metal debris from prosthetic joint Cholesterol crystal

Prophylactic (intercritical interval) law dose colchicin

Calcium HA deposition disease HA which is the primary mineral of bone & teeth, sometimes get deposited in areas of tissue damage mimicking other crystal deposition disease. Conditions associated with HA deposition disease: Aging Osteoarthritis Haemorragic shoulder effusions in the elderly (Millwaukees shoulder) Destructive arthropathy Tendinitis. bursitis Disease associated: Hyperparathyroidism Renal failure I long-term dialysis Connective tissue disease Heterotropic calcification following stroke, spinal cord injury Heriditary: Bursitis, arthritis Tumoral calcinosis

Clinical menifestations - More common in elderly - It may be associated with acute and/or chronic damage to the joint capsule, tendon, bursa, articular surface

with sometimes both periarticular and articular deposits coexisting - Commonest joints involved are knees, shoulders, hips & fingers - Clinically types: -Asymptomatic radiographic abnormalities -Acute synovitis -Tendinitis -Chronic destructive arthopathy Laboratory findings: X-rays: It may/ may not show calcification with or without destruction Synovial fluid: - Predominantly mononuclear, cell count is usually < 2000 cells / uL but not more Than 50,000 cells/uL - Individual crystals are very small, nonbifrigent & can only be seen by electronmicroscopy Treatment: It is similar to CPPD disease Caox deposition disease Primary oxalosis is a rare heriditary metabolic disorder with poor prognosis. Secondary oxalate deposition may occur in end stage renal disease, those on long-term hemodialysis or peritoneal dialysis. Clinical features: There are similar to other crystal deposition Deposits have been documented in fingers, wrists, elbows, knees, ankles & feet. Diagnosis: Diagnosis is based on demonstration of bipyramidal crystals having strong positive birefrigence on polarized microscope. Treatment: It is similar to other deposition disease.