Case 77: Gout Presented by Nicole Valdez What is Gout? Characterized by hyperuricemia (elevated plasmic uric acid concentrations) and severe, recurrent bouts of arthritis caused by monosodium urate (MSU) crystals deposited in the joint spaces. Syndrome of abnormal purine metabolism or excretion. Existed for over 2,000 years and used to be known as “disease of kings” Usually not life-threatening, but can be painful, chronic, and disabling. Pathophysiology Patient’s Chief Complaints “I woke up in the middle of the night last evening and my right big toe felt as if it was on fire. It’s hot, swollen, and so tender that even the weight of a blanket on it is nearly intolerable. And there’s no way that I can put a shoe on.” History of Mr. J.H.’s Present Illness 47 year old male Severe pain in right great toe – wore open toe sandals to clinic Began previous evening and kept him up through the night (acute onset) Taking extra-strength acetaminophen to keep the pain under control Unable to bear weight on his right foot No history of injury to right foot Past Medical History Hypercholesterolemia X 9 years Hypertension (HTN) X 9 years Transient Ischemic Attack (TIA/Mini Stroke) 3 months ago, appears to have no residual neurological deficits Chronic sinus drainage/rhinitis (S/P laryngoscopy) Allergies: NKDA Medications Hydrochlorothiazide (HCTZ) 25 mg po QD with supper Aspirin (ASA) 325 mg po Q AM Atorvastatin 10 mg po QD Flunisolide 2 sprays each nostril QD Psudoephedrine 60 mg po Q6h PRN Patient Case Question Why should the use of psuedoephedrine by this patient by carefully monitored by the primary care provider? Patient already on Flunisolide (corticosteroid) for Nasal Rhinitis High use of a nasal decongestant could be detrimental. Family History Educated throughout high school Mother living with type 2 DM Father died at age 68 from osteosarcoma Four adult children are all healthy No siblings Social History Non-smoker Uses alcohol weekly (averages 5-6 drinks/week) Married x2 with 4 adult children (1 from 1st marriage) Employed 17 years as a truck driver and is frequently away on the road Lives with wife of 22 years, happily married Diet is heavy on red meat and other highpurine foods Causes and Risk Factors Genetics: ¼ people with gout have a postive family history. Medical conditions and medications can increase plasma and synovial urate concentrations and can cause secondary gout. Diabetes mellitus, dehydration, sickle cell anemia, and kidney disease Thiazide diuretics, low-dose aspirin, cyclosporine, and tacrolimus Plasma uric acid levels begin to increase at puberty in males and at menopause in females Adult males and postmenopausal females are at risk Causes and Risk Factors Foods that are rich in purines will increase frequency of attacks Consuming too much alcohol, especially beer can inhibit renal excretion of uric acid and can contribute to gout Causes and Risk Factors Obesity and trauma: excessive weight can cause trauma to weight-bearing joints and lead to uric acid deposits Starvation and rapid weight loss can also increase plasma uric acid concentrations Great toe is subject to chronic strain from walking Certain occupations, such as truck driving, may cause significant strain to the great toe and cause an attack. Review of Patient’s Systems Denies headache (HA) , dizziness, chest pain, SOB, and generalized swelling or tenderness Weight has increased approximately 15 lbs in the last year No previous episodes of joint pain Physical Examination General: White male in mild acute distress Vital Signs: BP 145/85 HR 92 RR 17 T 100.2 °F HT 6’1 WT 225 lbs Patient Case Questions Has an optimal target blood pressure management been reached in this patient? Normal BP 120/80 Normal BP for 47 yr old male is 127/84 High BP for 47 yr old male is 139/88 Other considerations: Patient has HTN and patient is in pain Are any of the patient’s vital signs consistent with a diagnosis of gout? Fever: Acute gout can cause a high fever and leukocytosis HTN: Acute pain from gout can cause a high BP by increasing sympathetic activity Obesity: Doubles gout risk. Patient Case Questions Is this patient underweight, Identify 8 risk factors from the overweight, obese or is this patient’s case study that predispose the weight considered normal and patient to gout. healthy for his height? Alcohol Patient height: 6’1” Diet Patient weight: 225 lbs Weight gain BMI = 29.7 = Overweight Male over 40 BMI over 30 is obese History of Hypertension HCTZ medication (diuretic) ASA medication Truck driver Physical Examination Neck/Lymph Nodes: Normal with no swelling, thyromegaly, masses or jugular vein distention Eyes: Pupils equal at 3mm, round and reactive to light and accomdation (PEARRLA). Normal funduscopic exam Lungs: Clear to Auscultation (CTA) Cardiac: Regular Rate and Rhythm (RRR). S1 and S2 with no extra cardiac sounds. No gallops, rubs or murmurs Abdomen: Non-tender and non-distended. No Hepatosplenomegaly (HSM). Normal bowel sounds. Physical Examination Musculoskeletal/Extremities: Pulses full throughout. Muscle strength 5/5 throughout. Right first metatarsophanlangeal joint hot, tender, erythematous, swollen Neuro: A&O x 3 . CNs II-XII intact. Deep Tendon Reflex Normal (DTRs 2+). Babsinski (−) Clinical Manifestation Most common presentation: sudden onset of pain and swelling in metatarsophalangeal joint of great toe Other sites: ankle, wrist, knee Clinical Manifestation Commonly confined to one joint, but can progress from one joint upward to involve more joints. Single joint is warm, erythematous, tender, and characterized by edema. Intercritical gout: asymptomatic intervals between acute attacks. Systemic signs of inflammation: fever up to 102F, chills, leukocytosis, and malaise Tophi: deposits of MSU crystals at extra-articular sites, such as the ear, along Achilles tendon, or prepatellar bursa. Characteristic of chronic gout Laboratory Tests Main procedure: joint aspiration (arthrocentesis) X-ray: acute attacks can’t be seen, but chronic gout appears as thickened regions Serum levels of uric acid may not be elevated, but in >95% of patients it is elevated (>7.5mg/dL) during an acute attack Erythrocyte sedimentation rate (ESR) can also be elevated during episode of gout. Laboratory Tests 24 hour urinary excretion of uric acid >1100 mg Serum urate concentration >13mg/dL Having both values above the indicated values gives the patient a 50% probability for developing urate kidney stones. Therapy Terminate acute attack Anti-inflammatory medications Prevent recurring attacks Diet Avoid hyperuricemic medications Use preventative medications: colchicine, uricosuric drugs, and allopurinol Gradual weight loss Prevent/reverse complications associated with MSU crystal deposits in joints Prevent kidney stones Therapy Acute attack medications: Non-steroidal antiinflammatory agents (NSAIDs) Indomethacin, ibuprofen, and naproxen Aspirin is a NSAID, but should be avoided Corticosteroids control most attacks Available if you can’t take NSAIDs orally Single joint attack intraarticular administration of triamcinolone Polyarticular gout: methylprednisolone (IV or PO) Laboratory Blood Test Results Na 140 meq/L K 4.2 meq/L Cl 106 meq/L HCO3 27 meq/L Uric acid 13.1 mg/dL Glu, fasting 120 mg/dL Hb 15.6 g/dL Hct 47% BUN 14 mg/dL WBC 13.3 X 103/mm3 Cr 0.9 mg/dL • Neurophils 73% • • • • Bands Monocytes Lymphocytes Eosinophils ESR T chol 3% 3% 20% 1% 15 mm/hr 189 mg/dL 24 hr Urinary Uric Acid: 985 mg/day X-Ray, Right Great Toe: Moderate, soft tissue edema; normal joint space; no erosions or sclerosis Laboratory Results Synovial Fluid Examination: Significant Polymorphonclear (PMN) infiltration. Monosodium urate (MSU) crystal confirmed microscopically with polarized light Patient Case Questions Identify 5 laboratory test values that are consistent with a diagnosis of gout? Synovial fluid analysis Presence of crystals Uric acid What is the significance of this patient’s fasting blood glucose concentration? Fasting = not eating Normal 60-110 mg/dL Normal 2.4- 7.4 mg/dL Patient 120 mg/dL Patient 13.1 mg/dL Undiagnosed diabetes ESR Normal (males): <10 mm/hr Patient 15 mm/hr CBC WBC (normal) 4,800-10,000/mm3 WBC (patient) 13,300/mm3 Differentiate between septic arthritis and gout 24 hr urinary uric acid Normal 250-750 mg/day Patient 985 mg/day Is there a need to adjust the patient’s dose of atorvastatin upward at this time? No Normal <200mg/dL Patient 189 mg/dL Patient Case Question Would probenecid, sulfinpyrazone, or allopurinol be more appropriate medication for this patient? Why? Since the patient is excreting >800 mg urate/day, allopurinol is required. Allopurinol decreases the synthesis of uric acid, rapidly lowers plasma urate, Probenecid is not used to treat acute attacks, and instead is used to prevent chronic attacks. Sulfinpyrazone is also used to and facilitates mobilization of MSU prevent attacks, but is also while shrinking tophi. contraindicated for this patient Allopurinol acts by inhibiting xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. because of the high rate of excretion of uric acid. Sources Bruyere, Harold J., Jr. "Case Study 77: Gout." 100 Case Studies in Pathophysiology. Philadelphia: Lippincott Williams & Wilkins, 2009. 366-69. Print. “Crystal Induced Joint Disease Part 1” http://whatwhen-how.com/acp-medicine/crystal-induced-jointdisease-part-1/ “ESR- The Test” http://labtestsonline.org/understanding/analytes/esr/tab /test/ “Gout Explained Inside Out” http://painbehindkneecure.com/gout-explained-insideout/ “Gout Pictures Slideshow- Causes, Symptoms, and Treatments of Gout” http://www.webmd.com/arthritis/ss/slideshow-gout “Uric Acid Test” http://www.healthline.com/health/uricacid-urine#Purpose2