Update on Gout. It s important for D.P.M. s to understand this acute metabolic disease.

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1 CLINICAL PODIATRY Goals To provide the podiatrist with information regarding gout and its therapy. Objectives After reading this article, the podiatrist should be able to do the following: 1) Identify the epidemiological features of gout. Update on Gout It s important for D.P.M. s to understand this acute metabolic disease. 2) Describe the signs and symptoms associated with the disease. 3) Compare the role of uric acid in normal physiology as well as in pathophysiology. 4) Construct a rational therapeutic approach for the treatment of acute gout and/or hyperuricemia. 5) List the major advantages and disadvantages of drugs used to treat acute gout and hyperuricemia. 6) Counsel patients regarding the appropriate administration, adverse effects, and drug interactions associated with the drugs used in acute gout and hyperuricemia. Welcome to Podiatry Management s CME Instructional program. Our journal has been approved as a sponsor of by the Council on Podiatric. You may enroll: 1) on a per issue basis (at $17.50 per topic) or 2) per year, for the special introductory rate of $109 (you save $66). You may submit the answer sheet, along with the other information requested, via mail, fax, or phone. In the near future, you may be able to submit via the Internet. If you correctly answer seventy (70%) of the questions correctly, you will receive a certificate attesting to your earned credits. You will also receive a record of any incorrectly answered questions. If you score less than 70%, you can retake the test at no additional cost. A list of states currently honoring CPME approved credits is listed on pg Other than those entities currently accepting CPME-approved credit, Podiatry Management cannot guarantee that these CME credits will be acceptable by any state licensing agency, hospital, managed care organization or other entity. PM will, however, use its best efforts to ensure the widest acceptance of this program possible. This instructional CME program is designed to supplement, NOT replace, existing CME seminars. The goal of this program is to advance the knowledge of practicing podiatrists. We will endeavor to publish high quality manuscripts by noted authors and researchers. If you have any questions or comments about this program, you can write or call us at: Podiatry Management, P.O. Box 490, East Islip, NY 11730, (631) or us at bblock@prodigy.net. Following this article, an answer sheet and full set of instructions are provided (p. 246). Editor Getty Images By H. David Bergman, Ph.D. Gout is a chronic metabolic disease associated with hyperuricemia, recurrent arthritis, and inflammation of the great toe and joints. Gout has been written about, laughed at, and associated with a variety of myths. The disease was first described as a foot seizure. It was thought to be caused by a drop of poison that entered the joint. The term gout originated from this belief, because it is derived from the Latin word gutta or drop. Hippocrates believed that gout resulted from an Continued on page APRIL/MAY 2004 PODIATRY MANAGEMENT 239

2 Gout... excessive amount of phlegm that settled in the joints. Others attributed the disease to excessive wine, food, and sex. During the 19th century, myth succumbed to chemistry when Sir Arthur Garrod demonstrated the presence of elevated uric acid concentrations in the blood of individuals with gout, and postulated that the inflammatory reaction was caused by the deposition of urate crystals around the joints. Epidemiology Gout occurs in about 0.3% of the population in the United States. Men are affected 10 times more often than women, and the mean age is about 45 years. The onset in women is usually postmenopausal and accounts for a small percentage of the cases. Children have lower urate levels than adults; however, at puberty, there is a rise in urate levels which usually remains constant until middle age. Gout is considered to be a familial disease because 25% of the close relatives of individuals with gout will exhibit hyperuricemia. Although hyperuricemia may occur as a result of enzyme deficiencies, no single inherited trait seems to be associated with its occurrence. Therefore, this disorder appears to be polygenic. Hyperuricemia has been associated with a variety of other problems, including diet, obesity, renal disease, excessive alcohol intake, and various types of stress. Therefore, it is important that all factors be evaluated in assessing the cause of hyperuricemia. Uric Acid and Gout Because uric acid and its activity is the primary feature associated with gout, it is important to be familiar with its physiology and chemistry. Uric acid is not metabolized in man. It serves no biochemi- TABLE 1 CRITERIA THAT SUGGEST GOUT AS A DIAGNOSIS 1) More than one attack of arthritis 2) Development of maximum inflammation within one day 3) Oligoarthritis attack 4) Redness over joint 5) Painful or swollen first metatarsophalangeal joint 6) Unilateral attack on first metatarsophalangeal joint 7) Unilateral attack on tarsal joint 8) Tophus 9) Hyperuricemia 10) Asymmetric swelling within a joint cal function, and is formed from purines via degradation of xanthines. The purines result from enzymatic degradation of tissue and from dietary intake. The miscible pool of uric acid in normal man is approximately 1,200 mg with a daily turnover of 700 mg to 800 mg. Renal excretion of uric acid accounts for two-thirds Gout is considered to be a familial disease because 25% of the close relatives of individuals with gout will exhibit hyperuricemia. of the uric acid eliminated from the body. The other one-third can be accounted for by secretion into the gastrointestinal tract and eventual degradation by bacteria. The quantity of uric acid secreted into the gastrointestinal tract does not appear to be of any major significance as a contributing cause of hyperuricemia. Uric acid is poorly soluble in water; and at a urine ph of 5, the solubility is only 6 mg% to 8 mg%. Uric acid is completely filtered by the glomeruli, but 98% of it is reabsorbed in the proximal renal tubule. Most of the uric acid appearing in the final urine occurs because of renal secretion. From this brief description of the chemistry and physiology of uric acid, it is obvious that any alteration in ph, purine metabolism, and/or renal function could result in an increase in serum uric acid that could lead to the formation of urate crystals and, consequently, to acute gout. Clinical Findings A definite diagnosis of acute gout requires demonstration of sodium urate crystals in the affected joint. In some instances, gout may occur without the presence of sodium urate crystal deposits. The American Rheumatism Association has developed a list of 10 criteria that are associated with gout (Table 1). If an individual has six or more of the suggested criteria present, then a probable diagnosis of gout can be established. The suggested criteria are particularly valuable in establishing a di- Continued on page PODIATRY MANAGEMENT APRIL/MAY

3 Gout... agnosis when a definite one cannot be ascertained (i.e., by aspiration of fluid from the affected joint) prior to initiation of therapy. Because other conditions (such as sarcoid arthritis) resemble gout, it is important to establish a definite diagnosis in order to maintain appropriate treatment. The major symptoms of gout are associated with the precipitation of excess uric acid from saturated body fluids. The acute inflammation of gout is believed to result from the phagocytosis of urate crystals by polymorphonuclear cells, with a release of vasoactive humoral agents. This eventually results in a generalized inflammatory reaction that causes a local increase in acidity and a further reduction in uric acid solubility. Clinically, the major features of gout include tophaceous deposits of urates and periodic attacks of acute joint pain. The disease often has a sudden onset, is frequently nocturnal, and may or may not be associated with an obvious precipitating cause. The metatarsophalangeal joint of the great toe is the most susceptible joint, but joints of the feet, ankles, and knees are also commonly affected. As the attack progresses, the pain becomes more intense. During an acute attack, there is leukocytosis, fever, and an elevated erythrocyte sedimentation rate (ESR). Urate crystals usually can be found on aspiration of tophus. Other problems associated with gout that may be present include renal disease and hypertension. A definite diagnosis of acute gout requires demonstration of sodium urate crystals in the affected joint. Therefore, it is important that patients be observed and appropriately screened for these and related conditions. Hyperuricemia Associated Disorders Most patients with the classical manifestations of gout are considered to have primary gout, whereas gout that develops as a complication of another disease (such as leukemia) is classified as secondary gout. Blood dyscrasias, which are seen in leukemia, multiple myelomia, hemolytic anemia, Hodgkin s disease, and related disorders, are associated with gout in some cases. Hyperuricemia has been tied to such endocrine disorders as myxedema, hypoparathyroidism, and hyperparathyroidism. Renal disease with deposits of urates has been related to the occurrence of gout. Certain hereditary diseases, such as glycogen storage disease, are associated with excessive purine synthesis and hyperuricemia. Iatrogenic (drug-induced) gout has been reported with certain diuretic drugs (Table 2). Renal retention of uric acid can be caused by salicylates in doses of less than 2 grams per day, while high doses will often produce uricosuria. Tubular secretion of urate has been greatly inhibited by pyrazinamide. Values for serum uric acid do not always correlate with the occurrence of gout. Hyperuricemia may be asymptomatic. These patients should be treated conservatively by increasing fluid intake, gradually reducing weight, if needed, and having them monitored periodically by a qualified health professional. Although the level at which Continued on page 242 TABLE 2 DRUGS & CHEMICALS THAT ALTER CONCENTRATION OF SERUM URIC ACID INCREASE CONCENTRATION Alcohol chemotherapeutic drugs Ethambutol Levodopa pyrazinamide salicylates (less than 2 Gm/day) Diuretics Nicotinic acid Cylosporine DECREASE CONCENTRATION acetohexamide allopurinol mannitol probenecid salicylates (greater than 5 Gm/day) sulfinpyrazone APRIL/MAY 2004 PODIATRY MANAGEMENT 241

4 Gout... serum uric acid becomes abnormal has not been clearly established, most individuals with sustained levels greater than 10 mg% develop gout. Diet Regulation Dietary restrictions for gout patients are not as important today as in the past because effective drugs are now available. However, patients should avoid food or drinks that will precipitate attacks of acute gout, and should avoid those same foods during acute attacks. The foods that cause problems for gout patients contain large quantities of purine, e.g., organ meats. Eating such foods could result in large quantities of nitrogen in the urine, which would further complicate the disease state. In overweight patients with hyperuricemia, gradual weight reduction by caloric restriction should be recommended. Not only is it a good method for weight reduction, but it also often causes a reduction in serum urate concentration without use of medication. Treatment of Gout The therapeutic approach for gout and hyperuricemia patients is initially directed at terminating the acute inflammation. Once the initial objective of overcoming pain and inflammation with rapid and aggressive therapy is met, antihyperuricemic therapy should be instituted. The long-term goal of therapy is to prevent recurrence of the acute attacks by reducing the body stores of urate and reversing the effects of urate deposits. The primary goal of therapy in acute gout is to relieve pain and restore the affected joint to normal function. The drugs most frequently used to treat this type of gout are NSAID s and colchicine. Indomethacin is the NSAID used most often. Like the other NSAID s, indomethacin is em- The therapeutic approach for gout and hyperuricemia patients is initially directed at terminating the acute inflammation. ployed in a large dose for a brief period of time (one week or less). Indomethacin is effective in treating acute gout even when treatment is delayed several days from onset of symptoms. It exerts its effects through inhibition of prostaglandin synthesis. Indomethacin is considered less toxic than colchicine when used for short periods of time. It has analgesic, antipyretic, and anti-inflammatory actions. It has been administered in an initial oral dose of 75 mg followed by 50 mg every 6 hours for 2 days; then the dosage is tapered to 50 mg every 8 hours for 1 or 2 days. The side-effects of indomethacin include fluid and sodium retention, headache, vertigo, nausea, diarrhea, activation of peptic ulcer, and gastrointestinal bleeding. Indomethacin should not be used in patients with a history of peptic ulcer, blood dyscrasia, or congestive heart failure. Other NSAID s, such as ibuprofen, naproxen, fenoprofen and piroxicam, have been used to treat acute gout. Doses of these drugs are shown in Table 3. Colchicine Colchicine, although not effective in other inflammatory joint diseases, is very effective in the treatment of acute attacks of gout. It provides relief in approximately 90% of patients with acute gout, provided treatment is initiated during the early stages of an attack. Benefit may begin as soon as 6 or 8 hours after the first dose and complete remission should occur within 72 hours. Although it has been used for many years, the exact mechanism of colchicine s action in the treatment of gout is unknown. The primary mechanism of action is postulated to be associated with the inhibition of the production or release of materials in the cell that are responsible for The exact mechanism of colchicine s action in the treatment of gout is unknown. urate-induced inflammation. Colchicine is rapidly absorbed from the gastrointestinal tract and reaches peak serum concentrations within two hours. The half-life in normal subjects is one hour, but this is prolonged in patients with liver disease. Hepatic metabolism and excretion in the feces are the primary methods involved in drug elimination. The dosage regimen employed with colchicine is unusual. An initial dose of 1 mg followed by 0.5 mg every hour until symptoms subside, until 8 to 10 mg are administered, or gastrointestinal toxicity develops. The incidence of gastrointestinal adverse effects is approximately 75%. Although paregoric or other drugs provide relief of abdominal discomfort, oral colchicine should be avoided in patients with gastrointestinal disease, peptic ulcer disease, or a history of internal bleeding. However, colchicine may be administered to these patients via the intravenous route in 0.9% sodium chloride. Although gastrointestinal toxicity is minimal by this method, small venous sites should not be used because extravasation will lead to local necrosis and severe pain for the patient. The intravenous dose of colchicine that may be used is 2 mg to 3 mg. If needed, an additional 0.5 mg to 1 mg every 6 hours may be administered until a maximum dose of 5 mg is accumulated. Such gastrointestinal symptoms as nausea, vomiting, diarrhea, and abdominal pain are the most common adverse effects. Serious adverse effects include bone marrow depression and renal, hepatic, and neurologic toxicity, but these are rare and occur primarily in patients Continued on page PODIATRY MANAGEMENT APRIL/MAY

5 Gout... with underlying renal and/or hepatic disease. Phenylbutazone Phenylbutazone is an alternative drug that can be employed in attacks of acute gout. Phenylbutazone is administered in a dose of mg initially, then 200 mg four times a day for two days and 100 mg four times a day for two additional days. As with the other drugs used to treat acute gout, phenylbutazone should not be used for more than a one-week period. Short-term use reduces the chances for severe side effects such as bone marrow toxicity, but gastrointestinal side effects are common. Phenylbutazone can increase the effects of sulfonylurea hypoglycemic agents and oral anticoagulants. Treatment of Hyperuricemia The decision to treat hyperuricemia must be based on careful evaluation, because it usually results in patients taking daily medication for life. The decision is usually based on the potential consequences of not treating the patient. For example, asymptomatic hyperuricemia in an elderly patient probably will not result in severely debilitating joint disease; therefore, in most such cases, treatment would not be initiated. When serum uric acid concentration is consistently elevated, tophi can develop in the joints, soft tissues, and kidneys. Therefore, even in the absence of symptoms, treatment should be considered for middle-aged patients with serum uric acid concentrations of 10 mg% or more. Continued on page 244 TABLE 3 NSAID S COMMONLY USED IN THE TREATMENT OF GOUT DRUG Naproxen Ibuprofen Fenoprofen Piroxicam DOSAGE Initially 500 mg PO, then 250 mg q8h 800 mg PO q8h 800 mg PO q8h 40 mg/day PO for 5 days EXAMPLES OF DRUGS USED TO TREAT GOUT AND HYPERURICEMIA GENERIC NAME Allopurinol Colchicine Fenoprofen Ibuprofen Indomethacin Naproxen Phenylbutazone Piroxicam Probenecid Sulfinpyrazone Sulindac BRAND NAME EXAMPLE Zyloprim Marketed Generically Nalfon Rufen Indocin Naprosyn Butazolidin Feldene Benemid Anturane Clinoril APRIL/MAY 2004 PODIATRY MANAGEMENT 243

6 Gout... Appropriate medication use can result in a decrease in the size of the tophi if the drugs are administered indefinitely. Unlike drugs used for treating acute gout, all those used to treat chronic hyperuricemia can precipitate attacks of acute gout, and should not be used to treat such attacks. The drugs used to treat chronic hyperuricemia include the uricosuric agents, probenecid and sulfinpyrazone, and the xanthine oxidase inhibitor, allopurinol. Uricosuric Agents Probenecid increases the renal excretion of uric acid. It is rapidly and well absorbed when administered orally, and is highly bound to plasma proteins. The half-life of probenecid is approximately 9 hours. Although the drug is safe and well tolerated, common complaints include gastrointestinal distress and hypersensitivity. Because uricosurics cause an increase in renal uric acid excretion, there is an opportunity for uric acid kidney stones to occur. Therefore, a low initial dose of 250 mg twice daily is used. This can be increased by 250 mg daily every 7 days until a maximum of 3,000 mg per day is achieved. Probenecid has been associated with drug-drug interactions with aspirin, penicillins, cephalosporins, rifampin, sulfinpyrazone, and NSAID s. Sulfinpyrazone, like probenecid, inhibits the tubular reabsorption of uric acid. The drug is well absorbed from the gastrointestinal tract and has a half-life of approximately 3 hours. It is highly bound to plasma proteins and eliminated by tubular secretion. Therapy is usually initiated with a 50 mg dose twice daily and 100 mg daily can be added every 7 days until a maximum daily dose of 400 mg is achieved. Allopurinol Allopurinol is a unique drug that represents a different approach to the treatment of hyperuricemia. It is structurally similar to hypoxanthine and acts by inhibition of xanthine oxidase. Xanthine oxidase promotes the conversion of hypoxanthine and Allopurinol prevents the formation of uric acid by its action as a xanthine oxidase inhibitor. xanthine to uric acid. Therefore, allopurinol prevents the formation of uric acid by its action as a xanthine oxidase inhibitor. Because it prevents the formation of uric acid, allopurinol is an agent especially useful in patients with severe gout who are subject to uric acid stone formation. These problems would occur more frequently in patients with poor renal function; therefore, allopurinol in reduced doses could be a vitally important agent for such patients. Allopurinol is not only an inhibitor of, but also a substrate for, xanthine oxidase. The product of the allopurinol-xanthine oxidase reaction is oxypurinol, which is also an inhibitor of xanthine oxidase. Although allopurinol has a serum half-life of less than two hours, oxypurinol is treated by the human kidney as if it were uric acid. It is extensively reabsorbed, resulting in a half-life of more than 20 hours. This is very useful because it allows the parent drug allopurinol to be administered as a single daily dose, if desired. Patients with impaired renal function will require less drug or longer dosing intervals than those with normal renal function. The dose for allopurinol ranges from 200 mg to 600 mg daily with the average dose being 300 mg once a day. In some cases, the effective dose will decrease after several months of therapy. The drug does not significantly alter the action of uricosuric agents, nor do the uricosuric agents significantly affect allopurinol. Unfortunately, oxypurinol elimination is increased by uricosuric drugs; therefore, because oxypurinol contributes significantly to the effectiveness of allopurinol, the combination of allopurinol with uricosuric agents may not be useful in some patients. However, allopurinol can be, and often is, used in combination with colchicine. Allopurinol is generally a welltolerated drug. Its major side effects involve gastrointestinal distress, hypersensitivity reactions, and liver dysfunction. Bone marrow depression also has occurred, but this is very rare. Patients with impaired renal function appear to have more side effects. Allopurinol prolongs the anticoagulant effect of dicumarol, and blocks the metabolism of mercaptopurine and azathioprine by xanthine oxidase. Because allopurinol is a xanthine oxidase inhibitor, there is no immediate increased elimination of urates, which could result in urate stones in the kidney. This, as well as the fact that allopurinol (in reduced doses) can be used more effectively in patients with renal dysfunction, provides an advantage for this drug over the uricosuric agents. Hyperuricemia Hyperuricemia is a chronic problem that requires therapy for the life of the patient. Gout is an acute disease that often involves drugs with complex dosage regimens and adverse effects that usually enhance the patient s discomfort. The podiatrist must be knowledgeable regarding both the acute and chronic problems and be able to counsel patients regarding their appropriate use of drugs. Bibliography 1. Porter R, Rousseau GS: Gout, Yale University Press, Emmerson BT: Getting Rid of Gout, 2nd ed, Oxford University Press, Pharmacotherapy, 5th ed, McGraw Hill, Emmerson BT: The Management of Gout, N Eng J Med. 334: 445, Dr. Bergman is Dean of the School of Pharmacy at the Southwestern Oklahoma State University. 244 PODIATRY MANAGEMENT APRIL/MAY

7 E X A M I N A T I O N See answer sheet on page ) Gout A) is associated with hypouricemia B) occurs in about 10% of the U.S. population C) is considered to be familial D) occurs primarily in young women 2) Approximately what level of uric acid is associated with the development of gout in most individuals? A) 20 mg% B) 10 mg% C) 1 mg% D) 10 grams% 3) Gout A) is primarily a disease of men B) frequently occurs in children C) is always associated with a gout gene D) is the same as lupus 4) Which of the following inhibits xanthine oxidase? A) salicylates B) probenecid C) sulfinpyrazone D) allopurinol 5) Which criteria suggest gout as a diagnosis? A) redness over joint B) tophus C) hyperuricemia D) All of the above 6) Which of the following can result in alterations in serum uric acid? A) colchicine B) alopecia C) ph D) indomethacin 7) Phenylbutazone A) should be used for at least six weeks to determine effectiveness B) is used in a dose of 4 gram daily C) may cause bone marrow toxicity D) directly affects serum uric acid level 8) Probenecid A) has a half-life of about 9 hours B) must be administered intravenously C) is administered in a 5 mg daily dose D) is not bound to plasma proteins 9) Which of the following drugs interact(s) with allopurinol? A) colchicine B) azathioprine C) vitamin C D) A & C 10) Which drug could be used in patients with chronic hyperuricemia and renal dysfunction? A) allopurinol B) probenecid C) sulfinpyrazone D) aspirin 11) Which of the following agents have been associated with hyperuricemia? A) diuretics B) high doses of salicylates C) vitamin C D) all of the above 12) Indomethacin A) directly affects serum uric acid levels B) is used in a dose of 0.5 mg every hour C) is considered more toxic than colchicine D) none of the above 13) Colchicine A) is eliminated primarily via renal pathways B) causes gastrointestinal adverse effects in about 75% of patients C) must be used alone D) is always administered intravenously 14) Which are clinical features of acute gout? A) elevated ESR, leukopenia B) leukocytosis, reduced ESR C) leukocytosis, elevated ESR D) fever, leukopenia 15) Gout associated with leukemia is classified as A) secondary gout B) leukemia hyperuricemia C) drug-induced gout D) primary gout Continued on page APRIL/MAY 2004 PODIATRY MANAGEMENT 245

8 E X A M I N A T I O N (cont d) 16) Probenecid A) blocks uric acid formation B) cures gout C) is used in a dose of 10 milligrams a day D) increases the renal excretion of uric acid 17) Sulfinpyrazone A) has a half-life of approximately 3 hours B) is administered subcutaneously C) has a maximum daily dose of 10 milligrams D) blocks the formation of uric acid 18) Colchicine A) is the drug of choice for many inflammatory diseases B) is used to treat acute attacks of gout C) acts by increasing the elimination of uric acid D) is used in a dose of 100 milligrams a day 19) Which of the following drugs may decrease uric acid concentration? A) colchicine B) ethanol C) nicotinic acid D) none of the above 20) Salicylates A) are used as a drug of choice for gout B) may increase uric acid concentration in doses of less than 2 grams/day C) may reduce uric acid concentration in doses of more than 5 grams/day D) B & C See answer sheet on page 247. PM s CPME Program Welcome to the innovative Education Program brought to you by Podiatry Management Magazine. Our journal has been approved as a sponsor of by the Council on Podiatric. Now it s even easier and more convenient to enroll in PM s CE program! You can now enroll at any time during the year and submit eligible exams at any time during your enrollment period. PM enrollees are entitled to submit ten exams published during their consecutive, twelve month enrollment period. Your enrollment period begins with the month payment is received. For example, if your payment is received on September 1, 2003, your enrollment is valid through August 31, If you re not enrolled, you may also submit any exam(s) published in PM magazine within the past twelve months. CME articles and examination questions from past issues of Podiatry Management can be found on the Internet at All lessons are approved for 1.5 hours of CE credit. Please read the testing, grading and payment instructions to decide which method of participation is best for you. Please call (631) if you have any questions. A personal operator will be happy to assist you. Each of the 10 lessons will count as 1.5 credits; thus a maximum of 15 CME credits may be earned during any 12-month period. You may select any 10 in a 24-month period. The Podiatry Management Magazine CME program is approved by the Council on Podiatric Education in all states where credits in instructional media are accepted. This article is approved for 1.5 Education Contact Hours (or 0.15 CEU s) for each examination successfully completed. PM s CME program is valid in all states except Kentucky. Home Study CME credits now accepted in Pennsylvania 246 PODIATRY MANAGEMENT APRIL/MAY

9 Enrollment/Testing Information and Answer Sheet Note: If you are mailing your answer sheet, you must complete all info. on the front and back of this page and mail with your check to: Podiatry Management, P.O. Box 490, East Islip, NY Credit cards may be used only if you are faxing or phoning in your test answers. TESTING, GRADING AND PAYMENT INSTRUCTIONS (1) Each participant achieving a passing grade of 70% or higher on any examination will receive an official computer form stating the number of CE credits earned. This form should be safeguarded and may be used as documentation of credits earned. (2) Participants receiving a failing grade on any exam will be notified and permitted to take one re-examination at no extra cost. (3) All answers should be recorded on the answer form below. For each question, decide which choice is the best answer, and circle the letter representing your choice. (4) Complete all other information on the front and back of this page. (5) Choose one out of the 3 options for testgrading: mail-in, fax, or phone. To select the type of service that best suits your needs, please read the following section, Test Grading Options. TEST GRADING OPTIONS Mail-In Grading To receive your CME certificate, complete all information and mail with your check to: Podiatry Management P.O. Box 490, East Islip, NY There is no charge for the mail-in service if you have already enrolled in the annual exam CPME program, and we receive this exam during your current enrollment period. If you are not enrolled, please send $17.50 per exam, or $109 to cover all 10 exams (thus saving $66 over the cost of 10 individual exam fees). Facsimile Grading To receive your CPME certificate, complete all information and fax 24 hours a day to Your CPME certificate will be dated and mailed within 48 hours. This service is available for $2.50 per exam if you are currently enrolled in the annual 10-exam CPME program (and this exam falls within your enrollment period), and can be charged to your Visa, MasterCard, or American Express. If you are not enrolled in the annual 10-exam CPME program, the fee is $20 per exam. Phone-In Grading You may also complete your exam by using the toll-free service. Call from 10 a.m. to 5 p.m. EST, Monday through Friday. Your CPME certificate will be dated the same day you call and mailed within 48 hours. There is a $2.50 charge for this service if you are currently enrolled in the annual 10-exam CPME program (and this exam falls within your enrollment period), and this fee can be charged to your Visa, Mastercard, American Express, or Discover. If you are not currently enrolled, the fee is $20 per exam. When you call, please have ready: 1. Program number (Month and Year) 2. The answers to the test 3. Your social security number 4. Credit card information In the event you require additional CPME information, please contact PMS, Inc., at ENROLLMENT FORM & ANSWER SHEET Please print clearly...certificate will be issued from information below. Name Soc. Sec. # Please Print: FIRST MI LAST Address CityState Zip Charge to: Visa MasterCard American Express Card # Exp. Date Note: Credit card payment may be used for fax or phone-in grading only. Signature Soc. Sec.# Daytime Phone State License(s) Is this a new address? Yes No Check one: I am currently enrolled. (If faxing or phoning in your answer form please note that $2.50 will be charged to your credit card.) I am not enrolled. Enclosed is a $17.50 check payable to Podiatry Management Magazine for each exam submitted. (plus $2.50 for each exam if submitting by fax or phone). I am not enrolled and I wish to enroll for 10 courses at $ (thus saving me $66 over the cost of 10 individual exam fees). I understand there will be an additional fee of $2.50 for any exam I wish to submit via fax or phone. Over, please 247

10 ENROLLMENT FORM & ANSWER SHEET (cont d) EXAM #4/04 Joint Disorders (Christman) EXAM #5/04 Gout (Bergman) Circle: 1. A B C D 11. A B C D Circle: 1. A B C D 11. A B C D 2. A B C D 12. A B C D 2. A B C D 12. A B C D 3. A B C D 13. A B C D 3. A B C D 13. A B C D 4. A B C D 14. A B C D 4. A B C D 14. A B C D 5. A B C D 15. A B C D 5. A B C D 15. A B C D 6. A B C D 16. A B C D 6. A B C D 16. A B C D 7. A B C D 17. A B C D 7. A B C D 17. A B C D 8. A B C D 18. A B C D 8. A B C D 18. A B C D 9. A B C D 19. A B C D 9. A B C D 19. A B C D 10. A B C D 20. A B C D 10. A B C D 20. A B C D LESSON EVALUATION LESSON EVALUATION Please indicate the date you completed this exam How much time did it take you to complete the lesson? hours minutes How well did this lesson achieve its educational objectives? Very well Well Please indicate the date you completed this exam How much time did it take you to complete the lesson? hours minutes How well did this lesson achieve its educational objectives? Very well Well Somewhat Not at all Somewhat Not at all What overall grade would you assign this lesson? A B C D Degree Additional comments and suggestions for future exams: What overall grade would you assign this lesson? A B C D Degree Additional comments and suggestions for future exams: 248 PODIATRY MANAGEMENT APRIL/MAY