Cjane Padilla

SYSTEMIC SCLEROSIS Diffuse and Limited Definition Also known as systemic scleroderma. It is a systemic connective tissue disease characterized by thickening of skin caused by accumulation of collagen and injuries to the smallest arteries. It is atype of auto-immune disorder in which the immune system mistakenly attacks and destroys healthy body tissue. Collagen – the main structural protein in connective tissues Pathophysiology The overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system would start to attack the chromosomes, the protein structure of a cell. This would lead to genetic malfunction of nearby genes. T cells accumulate in the skin; these are thought to secrete cytokines and other proteins that stimulate collagen deposition and stimulation of the fibroblast, a type of cell of the connective tissue. T-cells or T-lymphocytes are types of white blood cell that contribute to immune defences, accumulate in the skin and secrete cytokines stimulating deposition of collagen. Cytokines are a group of small protein important in cell signalling. When they are released, they affect the behaviour of other cells. Etiology Unknown. A buildup of collagen in the disease leads up to its symptoms. Risk Factors / Occurrence It occurs usually in women with ages 30 – 40 years of age. It is rare in the residents of Japan and China and more in black women than in white women. Environmental factors including exposure to pesticides, drugs like bleomycin and carbidopa, solvents like toluene and benzene, epoxy resin and silica. Signs and Symptoms 1. Diffuse Scleroderma – affects skin, as well as lungs, heart, kidneys and gastro-intestinal tract 2. Limited / localized scleroderma – affects skin of the face, neck, distal elbows and knees, and in late stages of the disease, causes isolated pulmonary hypertension, CREST syndrome C - Calcinosis Calcium deposits in the skin R – Raynaud’s Phenomenon Spasm of the blood vessels in response to cold or stress Treated with Nifedipine or other Calcium-channel blocker E- Esophageal dysfunction Acid reflux and decrease in motility of the esophagus Treated with a proton-pump inhibitor S – Sclerodactyly Thickening and tightening of the skin on the fingers and hands T – Telangiectasias Dilation of the capillaries causing red marks on the surface of the skin Skin Symptoms hardening and scarring skin may appear tight, reddish or scaly blood vessels may be more visible severe and recurrent itching of large skin areas hair loss small white lumps beneath the skin and sometimes ooze with a substance that looks like toothpaste skin turning blue in response to cold temperature Musculoskeletal (Bone and Muscle)Symptoms Joint pains Restricted joint mobility on hand caused by calcinosismyopathy or muscle weakness Lungs Symptoms Pulmonary hypertension Dry cough Shortness of breath Wheezing Digestive Tract Symptoms Reflux esophagitis – inflammation of the esophagus secondary to the flux of gastric contents Decreased motility of esophagus. Kidneys Symptoms Renal crisis – malignant hypertension, very high blood pressure with evidence of organ damage Treated with ACE inhibitors Azotema – kidney failure with accumulation ofwaste products in the blood Hematuria – blood in the urine Proteinuria – protein loss in the urine Diagnosis 1. Differential diagnosis of symptoms or clinical presentations 2. Clinical suspicion or Physical examination – evidence of skin symptoms like reddish, thick, and tight skin 3. Presence of auto antibodies in blood and urine tests a. Anti-centromere – an antibody occurring in auto-immune disorders b. Anti-topoisomere – an antibody directed against topoisomere, an enzyme that regulate winding of Deoxyribonucleic acid (DNA) in cell replication 4. Skin biopsy 5. Chest X-Ray 6. Echocardiography Management – there is no cure for scleroderma yet. Treatment is directed towards the symptoms I. Pharmacological A. Pain Management 1. Drug Class: NSAIDS 2. Generic name: Naproxen 3. Use: Anti-inflammatory 4. Mechanism of Action: Reversible inhibition of cyclooxigenase 1 (COX-1) and cyclooxigenase 2 (COX-2) enzymes. These are involved in the synthesis of prostaglandin, known as the pain chemical. 5. Side effects: Heartburn Constipation Diarrhea Ulcers stomach bleeding myocardial infarction stroke 6. Warnings and precautions: May reduce the efficacy of serotonin-specific reuptake inhibitor antidepressants. Ex. Fluoxetine, Paroxetine 7. Contraindications: Patients with heart disease as there is an increase risk of heart attack. Patients with history of stomach ulcer. 8. Recommended dosage: The recommended initial dose of naproxen sodium controlled-release is two 500 mg tablets (1000 mg) orally once a day. For patients requiring greater analgesic benefit, two 750 mg tablets (1500 mg) or three 500 mg tablets (1500 mg) may be used for a limited period. Thereafter, the total daily dose should not exceed two 500 mg tablets (1000 mg). B. Skin tightness 1. Drug class: Immunosuppressant 2. Generic name: Ciclosporin 3. Use: Intravenously, Decrease activity of the immune system in autoimmune disorders like scleroderma 4. Mechanism of Action:  It reduces the activity of the immune system by interfering with the activity and growth of T cells. 5. Side effects: Gingival hyperplasia – swelling of the gums convulsions peptic ulcers pancreatitis fever vomiting confusion dyspnea numbness and tingling particularly of the lips pruritus high blood pressure potassium retention  6. Warnings and Precautions: Cyclosporine can make you more likely to get infections or may worsen any current infections. Do not have immunizations or vaccinations. Driving or operating machinery, as this drug makes patients dizzy. 7. Contraindications: Patients with recent or current infection. Patients with uncontrolled high blood pressure. 8. Recommended dosage: >3 to 4 mg/kg/day 9. Counselling points: Brush your teeth and floss daily to minimize gingival hyperplasia. Wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). C. Kidney disease 1. Drug Class: ACE inhibitors 2. Generic name: Captopril Enalapril Ramipril 3. Use: Antihypertensive agents 4. Mechanism of Action: Angiotensin-converting enzyme inhibitors reduce the activity of the renin-angiotensin-aldosterone system (RAAS) as the primary etiologic (causal) event in the development of hypertension as a manifestation (outward indication) of renal disease. RAAS -  hormone system that regulates blood pressure and water (fluid) balance. 5. Side effects:  hypotension persistent cough  hyperkalemia headache dizziness fatigue nausea 6. Warnings and Precautions: Potassium supplements should be used in caution when taking ACE inhibitors. 7. Contraindications: Patients with impaired renal functions. Patients with angioedema. 8. Recommended dosage: Captopril – starting doe of 12.5mg twice to thrice daily, 450mg/day maximum Enalapril – 5mg daily, 40mg/day maximum Ramipril – 2.5mg daily, 20mg/day maximum 9. Counselling points: Monitor renal functions while taking these drugs. D. Pulmonary hypertension 1. Drug Class: Eicosanoids - A family of lipid molecules 2. Generic name: Epoprostenol 3. Use: Smooth muscle relaxation and vasodilator 4. Side effects: hypotension flushing chest pain anxiety dizziness bradycardia dyspnea abdominal pain musculoskeletal pain tachycardia 5. Contraindications: Patients with congestive heart failure. 6. Warnings and precautions: Should not be used chronically in patients who develop pulmonary edema during dose initiation. 7. Counselling points: Avoid abrupt withdrawal which may develop rebound pulmonary hypertension. Monitor patients for hemorrhagic complications because of the ability of epoprostenol to inhibit platelet aggregation or blood clotting. E. Raynaud’s Phenomenon 1. Drug Class: Calcium-Channel blockers 2. Generic Name: Nifedipine 3. Use: Vasodilator or antihypertensive 4. Mechanism of action: Prevent or reduce the opening of these channels to prevent calcium from rushing into the cell thereby reducing the effect like  excitation-contraction coupling of skeletal, smooth, and cardiac muscle and for hormone secretion in endocrine cells. 5. Side Effects: Dizziness Flushing Weakness Swelling ankles/feet Constipation Headache 6. Warnings and Precautions: Do not crush, chew, or break the capsule. Avoid eating grapefruit or drinking grapefruit juice while taking this medication. Grapefruit can increase the amount of certain medications in your bloodstream 7. Contraindications: Patients with heart problems like congestive heart failure. 8. Recommended dosage: 10- 20 mg three times daily For extended release tablets, 30 – 60mg daily 9. Counselling points: Do not drive or use machinery when taking this medication. Limit alcoholic beverages. II. Non-Pharmacological Treatment 1. Pulsed dye laser – uses a concentrated beam of light that targets blood vessels in the skin. 2. Physical therapy and exercise. Evauation of Therapeutic Outcomes A high clinical suspicion should be maintained. Yearly monitoring with pulmonary function tests and echocardiography help patients get appropriate and more efficient treatment. Close monitoring of skin and musculoskeletal symptoms remain the first gauge for tyreatment for systemic scleroderma.