-GOUT -Pseudogout Systemic sclerosis

A disease of Kings

Gout has been recognized from as early as the 4th century BC. Gout is an inflammatory arthritis associated with Hyperuricemia and intra- articular sodium urate crystals causing attacks of painful inflammation in one or more joints.

Acute gout

“Classic” – an obese, hypertensive man, age 30 to 50, frequent imbiber of alcohol (especially beer)

It is a true crystal deposition disease, defined as the pathological reaction of the joint or periarticular tissues to the presence of MonoSodium Urate Monohydrate(MSUM) crystals. It usually favoring lower rather than upper limbs especially first metatarsophalangeal & small joints of feet & hands.

There is progressive involvement of proximal joints& cartilages with bone damage & development of secondary OA.

The prevalence of gout is increasing mainly in developed countries. It increases with age with male to female ratio of 10:1. Primary gout is a male disease & is the most common cause of inflammatory arthritis in men over the age of 40. It rarely occurs before young adulthood ( when it suggests a specific enzyme defect),& seldom in premenopausal females.

Secondary gout due to renal impairment or drug therapy affects people over the age of 65 mainly & seen in women in whom there is an increased diuretic use. Serum uric acids are higher in men than women& positively correlate with obesity, age& ethnicity(being higher in Newzealands).

Hyperuricemia is defined as serum uric acid >7.1 mg/dl. 95% of hyperuricemic subjects never develop gout. Causes of primary gout: 1- 90% of cases are due to defective renal excretion of uric acid( under execretors).

2- 9% have intrinsic increased production of uric acid (overproducers). 3- 1% have specific inherited enzyme defect of purine synthesis & this is when the age is below 25 years.& in patients with urate stones. Risk factors for gout include DM, HT& alcohol intake. Secondary gout results from chronic hyperuricemia in patients with renal impairment, drug therapy especially aspirin, diuretics, cyclosporine& alcohol.

CLINICAL FEATURES Clinically, gout may present as asymptomatic hyperuricemia, acute arthritis, chronic arthritis, or chronic tophaceous gout.

Attacks of pain are rapid in onset, waking the patient in early morning. Single distal joint is often affected(first metatarsal joint- podagra), but eventually other joints are affected. The pain is associated with extreme tenderness that the patient is unable to wear a sock. The swelling is marked with overlying shiny red skin. Complete resolution of swelling & pain occur in 5-14 days.

When the attacks subside; pruritus & desquamation of overlying skin is common. Some patients have only mild attacks lasting few days(petit attacks). Other have one attack fallowed by other one(cluster attacks). Some patients have only one attack & other have repeated episodes with further deposition of MSUM.

Eventually chronic pain & joint damage occur. White colored tophaceous nodules are formed at the extensor surface of fingers, hand, feet, elbow& sometimes helix of the ear. These nodules may ulcerate & rupture& associated with local inflammation.

Renal stones occur in 10% of urate type in gout patients. Progressive renal disease is an important complication of untreated chronic tophaceous gout with subsequent glomerulosclerosis& pyelonephritis.

INVESTIGATIONS Definitive diagnosis requires identification of MSUM crystals in synovial fluid from joint, bursa or tophus. Synovial fluid reveals increased viscosity & turbidity ( > 90% neutrophils).

Hyperuricemia is usually evident, but normal serum uric acid does not exclude gout (uric acid falls as part of acute phase response in acute gout ). 24 hour urine collection for uric acid on low purine diet reveals overproducers.

Renal function test,RBS, serum lipid profile, evaluation of HT, CRP& ESR are all necessary investigations. X ray findings can be delayed until late in the disease, where there is joint space narrowing, gouty erosions(bony tophi), sclerosis& OA changes.

MANAGEMENT OF GOUT: a fast acting NSAIDs (naproxen, diclofenac sodium, indomethacin ) can give rapid relief of the pain & given as maintenance dose.

Oral colchicin( a potent neutrophils micro tubular assembly) can be very effective but associated with sever vomiting & diarrhea(1 mg loading dose then 0.5 mg 6 hourly) until symptoms abate. Joint aspiration with or without corticosteroid intraarticular injection can sometimes improve the symptoms.

Correction of predisposing factors of gout like DM, hyperlipidemia, HT, & avoidance of diuretics& treatment of obesity all are necessary.

Hypouricemic drugs are indicated for recurrent attacks of acute gout, tophi, evidence of bone or joint damage, renal disease& gout with high serum uric acid. Allopurinol in a dose of mg daily is the usual drug. It inhibits xanthine oxidase & reduces the conversion of hypoxanthine& xanthine to uric acid.

. Uricosuric drugs such as probenecid or sulfinpyrazone can achieve equivalent reduction in serum uric acid to Allopurinol.

Pseudogout It is an acute synovitis caused by deposition of Calcium Pyro Phosphate Dihydrate(CPPD) in hyaline & fibro cartilage of joints resulting in chondrocalcinosis. It is the most common cause of acute monoarthritis in elderly

. Shedding of crystals into a joint precipitates acute synovitis which resembles gout, except that it is more common in elderly females& usually affects knee joint or wrist. In young people it may be associated with hemochromatosis, hyperparathyroidism, or Wilson's disease.

Clinically, it is similar to OA & management is similar to gout but aspiration of synovial fluid& intra-articular corticosteroid injections are mandatory treatment options.

Systemic sclerosis

Thick skin of fingers and hands (limited scleroderma)

Morphea

calcinosis

Previously called SCLERODERMA, is a generalized disorder of connective tissue affecting the skin, internal organs & vasculature. This distinguishes it from localized scleroderma syndromes, such as morphea, that do not involve internal organs& are rarely associated with vasospasm( Raynaud's disease).

The clinical hallmark is the presence of sclerodactyly in combination with Raynaud's phenomenon or digital ischemia. The peak age of onset is the 4 th & 5 th decades of life with prevalence of / million population & 4:1 female :male ratio. It is rare in children.

It is subdivided into diffuse cutaneous systemic sclerosis(DCSS)& limited cutaneous systemic sclerosis(LCSS). LCSS is phenotypically grouped into the CREST syndrome(Calcinosis, Raynaud's, Esophageal involvement, Sclerodactyly, Telangiectasia).

ETIOLOGY & PATHOGENESIS :the etiology is unknown with no genetic, geographical or racial associations. Environmental factors are important in isolated cases, such as exposure to silica dust, vinyl chloride, hypoxyresins& trichloroethylene. Bleomycin which is a cytotoxic drug can cause a similar picture.

Early in the disease, there is infiltration of T-lymphocytes& fibroblast activation with increased type 1-collagen production resulting in symmetrical thickening, tightening & indurations of skin(sclerodactyly). In addition, there is an arteriolar narrowing & vessel wall inflammation with release of vasoconstrictors& platelet activation resulting in further ischemia.

DIAGNOSIS systemic sclerosis is a clinical diagnosis, based on the presence of sclerodactyly(finger pulp atrophy), beaking of nails(pseudoclubbing),atrophic nails,& telangiectasia(nail- fold capillaries. Most patients have positive ANA. 30% of diffuse type have antibodies to topo- isomerase(scl-70)& 10% of LCSS have antibodies to centromere.

Raynaud's phenomenon is common& may be the first clinical picture *

*cutaneous features: initially there is non pitting edema of fingers& tendon sheaths, then the skin becomes shiny, taut& distal skin creases disappear with involvement of the nose(peaked nose)& lips.

. Skin involvement distal to elbow& knee ( apart from face) is classified as LCSS or CREST. Involvement proximal to knee & elbow & on the trunk is classified as DCSS. There may be skin ulceration over pressure areas & pulp atrophy at finger tips.

Scleroderma sine scleroderma: skin is not affected, patients present with pulmonary fibrosis, renal crisis, cardiac failure or malabsorption. MSK features*: arthralgia, morning stiffness, muscle weakness& wasting due to myositis.

GIT* : smooth muscle atrophy& fibrosis in the lower two third of esophagus lead to acid reflex & esoghagitis which should be treated with proton pump inhibitors. Dysphagia & odynophagia may occur.

Involvement of stomach causes early satiety& outlet obstruction. watermelon stomach ( antral vascular ectasia) may cause occult upper GIT bleeding & this occurs in 20% of patients.

. Small intestine involvement leads to malabsorption, bacterial overgrowth,pain & constipation. Autonomic neuropathy may cause dilated small & large bowel & pseudo obstruction.

Cardiopulmonary diseases*: pulmonary involvement is a major cause of morbidity & mortality. Fibrosing alveolitis occurs mainly in diffuse disease & associated with positive anti topo-isomerase -1.

Pulmonary hypertension occurs in limited than diffuse type& characterized by progressive dyspnea, right sided heart failure, angina& associated with digital ischemia. Treatment includes vasodilators, continuous infusion of epoprostenol, oral endothelin-1 antagonist bosentan& heart- lung transplantation.

Renal features*: one of the main causes of death is hypertensive renal crises which characterized by malignant hypertension & renal failure. Treatment is usually with ACE inhibitors even in the presence of renal impairment. It is more common in topo-isomerase -1 positive diffuse type. Some clinicians use prophylactic ACE inhibitors to prevent this complication.

Causes of anemia in scleroderma: 1-iron deficiency from chronic oesophigitis 2-folate &vitaminB-12 deficiency from malabsorption 3- anemia of chronic disease 4-microangiopathic hemolytic anemia

MANAGEMENT& PROGNOSIS :5 years survival is approximately 70%. Risk factors at presentation that associated with poor prognosis include old age, DCSS type, protein urea, high ESR, low gas transfer factor for carbon monoxide(TLCO) & pulmonary HT.

Avoidance of peripheral cold exposure is important. Infection of ulcerated skin should be treated with heavy dose of antibiotics& for long time because the drug poorly penetrate the infected skin. e.g. flucloxacillin 500 mg 6 hourly. Calcium antagonists( nifedipine, amlodipine)& angiotensin 2 receptor antagonists(valsartan) may be effective for Raynaud's disease.

For digital ischemia, intermittent infusion of epoprostenol may be helpful. Corticosteroids & cytotoxic drugs are indicated for patients with myositis or alveolitis. D- pencillamine is effective for skin lesions. No agent has been shown to arrest or improve skin lesions.