Rheumatology questions

A 52-year-old woman comes to the physician complaining of severe pain in the left knee. She reports that it has been painful, warm, and red over the past day. She states that a similar episode occurred several months ago in her right big toe, which resolved spontaneously without treatment. She has not had any fevers, recent joint trauma, or weight loss. Past medical history is significant for hypertension and type 2 diabetes mellitus. She is currently on hydrochlorothiazide, metformin, and pravastatin. Temperature is 37.2°C (99.0°F), pulse is 88/min, respirations are 12/min, and blood pressure is 138/95 mmHg. Physical examination reveals swelling, erythema, and warmth of the left knee joint. It is tender to palpation with decreased active and passive range of motion. Which of the following is most likely to help establish the diagnosis? A Initiation of antibiotic therapy B Arthrocentesis C Lower extremity MRI D Serum uric acid levels E X-ray of the left knee

B Arthrocentesis Not D - Serum uric acid levels may be increased in patients with gout . However, this is not always the case, and oftentimes, uric acid levels can be normal or low even during acute episodes. There is a more reliable method to diagnose an acute gout attack . Not E - An x-ray of the left knee would be useful in detecting fractures and/or displacement of bones. This patient has no history of trauma, and therefore, an x-ray would likely not be useful in diagnosing the patient's condition. . Major takeaway In patients presenting with acute-onset joint pain in the absence of trauma, arthrocentesis should be performed. Arthrocentesis is therapeutic, as it reduces joint pressure, and diagnostic, since further laboratory testing of the synovial fluid can be done. Main explanation This middle-aged woman presenting with recurrent episodes of joint pain, erythema, and swelling requires an arthrocentesis to further investigate the underlying cause. A likely explanation for this patient's joint pain is gout attacks, which are caused by precipitation of urate crystals in the joints. Urate crystal deposition then stimulates the production of cytokines that recruit leukocytes. Arthrocentesis (aspiration of synovial fluid) of the knee joint has two benefits. First, it is therapeutic, as it relieves pressure from the joint. Second, it is also diagnostic, as additional tests of the aspirated fluid can be performed (e.g., Gram-stain, culture, microscopy). In order to diagnose gout attacks, polarized light microscopy should be utilized to identify needle-shaped, negatively birefringent monosodium urate crystals. Although this patient does not have a fever, Gram-staining and culture of the synovial fluid can be done to conclusively rule out septic arthritis.

A 53-year-old man comes to the physician complaining of a painless nodule on the back of the left heel. He has had several episodes of joint pain in the last 2 years, involving the toes and knees, that would often resolve after taking ibuprofen. He has not had any fevers, recent joint trauma, or weight loss. Past medical history is significant for hypertension and hyperlipidemia. He is currently on hydrochlorothiazide and pravastatin. He has been drinking 5-6 beers daily for the last 13 years. He denies tobacco or illicit substance use. Temperature is 37.0°C (98.6°F), pulse is 88/min, respirations are 12/min, and blood pressure is 138/95 mmHg. Physical examination reveals a nontender, hard, chalky nodule on the left Achilles tendon, as seen in the image below:Image reproduced from Wikimedia CommonsSimilar nodules are present on the left elbow and right external pinna of the ear. Further evaluation of this patient will most likely reveal which of the following? A Presence of rheumatoid factor antibodies B Chronic deposition of monosodium urate in joints C Positive human leukocyte antigen-B27 D Positive gram-staining of bone biopsy E Mutation in the HFE gene

B Chronic deposition of monosodium urate in joints Major takeaway Chronic, uncontrolled gout can result in solid urate deposition and tophi formation. Tophi often form on articular bone, cartilage, and tendons. Treatment of tophi consists of controlling the underlying gout and maintaining low serum urate levels. Main explanation This patient is presenting with hardened nodules on the Achilles tendon and external pinna of the ear; taking into account the history of recurrent joint pains, he likely has tophi formation secondary to chronic gout. Tophaceous gout is characterized by deposition of solid urate followed by chronic inflammation and destructive changes in the nearby connective tissue. Tophi often form on cartilage (e.g. external pinna of the ear), tendons, ligaments, and articular bone. Since tophi form secondary to urate deposition, treatment consists primarily of achieving and maintaining low levels of serum urate.

A 12-year-old boy is brought to the physician because of severe pain in his right big toe. He states the toe feels warm and looks swollen and red. He began chemotherapy last week for treatment of acute lymphoblastic leukemia. Temperature is 37.4°C (99.3°F), pulse is 77/min, respirations are 13/min, and blood pressure is 122/82 mm Hg. Physical examination reveals an erythematous and swollen right first metatarsophalangeal joint. It is tender to palpation with decreased active and passive range of motion. Therapy with which of the following medications could have prevented this patient's current condition? Elimination tool A Indomethacin B Colchicine C Allopurinol D Glucocorticoids E Aspirin

C Allopurinol Major takeaway Chemotherapy for lymphomas and leukemias can cause widespread lysis of tumor cells, resulting in an acute increase in serum uric acid. Aggressive hydration and allopurinol should be started in patients prior to treatment to prevent uric acid deposition in the joints and kidneys. Main explanation This patient is presenting with severe, acute onset pain in his right big toe shortly after initiating chemotherapy for acute lymphoblastic leukemia. He most likely has an acute gout attack secondary to tumor lysis syndrome. Widespread lysis of tumor cells can release significant amounts of intracellular components, such as potassium and uric acid. The acute increase in serum uric acid levels overwhelms the excretory capacity of the kidneys, causing uric acid to precipitate and crystallize in joints. Prophylaxis in patients, therefore, consists of aggressive hydration, often done intravenously (IV). The goal of IV hydration is to improve renal perfusion and glomerular filtration, and maintain high urine output to reduce the likelihood of uric acid precipitation in the tubules and oversaturation in the blood. In patients considered particularly high-risk for developing tumor lysis syndrome, allopurinol, an inhibitor of xanthine oxidase (the enzyme that converts metabolites into uric acid), can effectively decrease the formation of new uric acid.

A 61-year-old woman comes to the physician complaining of severe pain in the right knee. She reports that it has been painful, warm, and red over the past day. She states that similar symptoms occurred two-years ago in her left toe, which resolved spontaneously without treatment. Past medical history significant for hypertension and hyperlipidemia. Medications include pravastatin and hydrochlorothiazide. Temperature is 37.0°C (98.6°F), pulse is 98/min, respirations are 14/min, and blood pressure is 130/92 mmHg. Physical examination reveals swelling, erythema, and warmth of the right knee joint. It is tender to palpation with decreased active and passive range of motion. Arthrocentesis of the joint yields turbid fluid with a leukocyte count of 19,200/mm3. Gram stain is negative. Polarized light microscopy shows yellow, negatively birefringent crystals. Which of the following best describes the mechanism of the most appropriate pharmacotherapy for this patient's current symptoms? A Irreversible inhibition of cyclooxygenase enzymes B Inhibition of transcription factors C Reversible inhibition of cyclooxygenase enzymes D Inhibitor of xanthine oxidase E Inhibition of microtubule polymerization

C Reversible inhibition of cyclooxygenase enzymes Major takeaway Nonsteroidal anti-inflammatory drugs (NSAIDs), with the exception of aspirin, are used in the primary treatment of acute gout attacks. By inhibiting the synthesis of prostaglandins, a chemotactic mediator, NSIADs are able to prevent neutrophil migration and suppress the inflammatory process. Main explanation This patient is presenting with acute onset, severe pain of the right knee, and arthrocentesis reveals yellow, negatively birefringent crystals. These findings are diagnostic of an acute gout attack. Acute gout attacks begin with urate crystals precipitating in joints, causing the release of prostaglandins by synoviocytes. These chemotactic mediators recruit neutrophils to migrate into the joint space and amplify the ongoing inflammation process. Nonsteroidal anti-inflammatory drugs (NSAIDs), therefore, are pivotal in treating acute gout attacks. All NSAIDs (with the exception of aspirin) inhibit prostaglandin synthesis as well as inhibit urate crystal phagocytosis. In patients who are unable to tolerate NSAIDs (e.g., chronic kidney disease, gastrointestinal ulcers), intra-articular glucocorticoids and colchicine can be used as alternatives.

A 64-year-old woman comes to the physician complaining of pain in the right knee for the past day. The patient reports associated joint swelling, warmth, and redness. She says this has happened before in her knees and hips, but those episodes lasted for only a few hours and resolved spontaneously. She also reports feeling fatigued during the past several months, but attributes this to frequently waking up at night to urinate. The patient has also had to strain more than usual when having a bowel movement and frequently takes laxatives to help. Vital signs are within normal limits. Physical examination reveals swelling, erythema, and warmth of the right knee joint. It is tender to palpation with decreased active and passive range of motion. Laboratory studies show the following:Arthrocentesis of the right knee is performed. Gram stain is negative. Polarized light microscopy shows rhomboid-shaped, weakly positively birefringent crystals. Further evaluation of this patient is most likely to show which of the following? A Osteophyte formation and subchondral sclerosis of joints B Tophi formation on cartilage and tendons C Increased serum uric acid D Calcification of cartilage in joints E Positive rheumatoid factor antibodies

D Calcification of cartilage in joints Major takeaway Calcium pyrophosphate crystal deposition (CPPD), also known as "pseudogout", can occur idiopathically or secondary to hyperparathyroidism or hemochromatosis. Deposition can result in cartilage calcification of the affected joint, resulting in chondrocalcinosis that is typically visible on x-ray. Main explanation This patient is presenting with joint pain, fatigue, polyuria, and constipation, as well as laboratory studies showing hypercalcemia and elevated parathyroid hormone. She most likely has a parathyroid adenoma. Hyperparathyroidism is a significant risk factor for the development of calcium pyrophosphate crystal deposition (CPPD), which presents as gout-like joint pain (which explains why CPPD is also called "pseudogout") that classically affects the knee, although any joint can be affected. The polarized light microscopy findings of this patient's synovial fluid confirms the diagnosis; rhomboid-shaped, positively birefringent crystals are characteristic of CPPD. A particularly characteristic finding of chronic CPPD is chondrocalcinosis, which is deposition of calcium pyrophosphate crystals in various cartilage tissues across the body. The menisci of the knee is a common location for cartilage calcification, and the phenomenon is illustrated in the knee radiograph below (white arrows).

A 54-year-old man comes to the physician complaining of severe pain in the right knee for the past day. He states the knee is swollen, warm, and red. The patient had a similar episode that occurred in his right ankle last year, which resolved spontaneously without treatment. He also complains of increasing "tiredness" and loss of libido over the last 2 months, but he attributes the symptoms to recent stress at work. The patient has no significant past medical history. His father had a bleeding disorder, but the patient is unaware of the details. Temperature is 36.5°C (97.7°F), pulse is 54/min, respirations are 12/min, and blood pressure is 110/82 mmHg. Physical examination shows diffuse hyperpigmentation of the skin. The liver is palpated 3.5 cm below the costal margin. Laboratory studies reveal the following findings: Arthrocentesis of the right knee joint would most likely show which of the following? A Monosodium urate crystals B Gram-positive cocci forming clusters C Gram-negative diplococci D Calcium pyrophosphate dihydrate crystals E Large numbers of red blood cells

D Calcium pyrophosphate dihydrate crystals Major takeaway Hemochromatosis is a major predisposing factor for joint inflammation secondary to calcium pyrophosphate crystal deposition. On polarized light microscopy, the condition appears as rhomboid-shaped, positively birefringent crystals. Main explanation This patient is presenting with joint pain, loss of libido, hyperpigmentation, hepatomegaly, and elevated liver enzymes. He likely has underlying hemochromatosis. Hemochromatosis is caused by a mutation in the HFE gene and results in uncontrolled reabsorption of iron in the intestines. The excess iron deposits in various locations of the body, manifesting as a constellation of symptoms: pituitary deposition leads to hypopituitarism (e.g., hypothyroidism, loss of libido), dermal deposition leads to hyperpigmentation, and hepatic deposition leads to hepatomegaly, hepatocyte dysfunction, and elevated liver enzymes. Recurrent joint pain may be caused by deposition of calcium pyrophosphate (CPP) crystals in joint spaces. Pyrophosphate is a byproduct of adenosine triphosphate (ATP); excess iron in hemochromatosis may interfere with pyrophosphatase, an essential enzyme involved in metabolism of the byproduct. On polarized light microscopy, CPP crystals appear as rhomboid-shaped, positively birefringent crystals.

A 58-year-old woman comes to the physician complaining of severe left hip pain for the past day. She states the hip feels warm and looks enlarged. The patient has had multiple similar episodes in her knees, hips, and wrists over the last few years, for which she took ibuprofen as needed. Past medical history is significant for hypertension and type II diabetes mellitus, which are well managed with lisinopril and metformin, respectively. Vital signs are within normal limits. Physical examination shows an erythematous and swollen left hip joint. It is tender to palpation with decreased active and passive range of motion. Arthrocentesis of the left hip is performed. Gram stain is negative. Polarized light microscopy shows rhomboid-shaped, weakly positively birefringent crystals. Long-term therapy with which of the following medications is most helpful in reducing the recurrence rate of similar episodes? A Aspirin B Indomethacin C Probenecid D Allopurinol E Colchicine

E Colchicine Major takeaway Pseudogout , or calcium pyrophosphate deposition disease (CPPD), is caused by an inflammatory response to crystal deposition in joints. Daily, low-dose colchicine can help prophylactically reduce the recurrence of acute episodes. Main explanation Calcium pyrophosphate deposition (CPPD), more commonly known as pseudogout, commonly presents as sudden onset, severe pain of a joint, much like gout. However, aspiration of the synovial fluid in pseudogout demonstrates rhomboid-shaped, weakly positively birefringent crystals. The pathogenesis of CPPD is similar to that of gout. Calcium pyrophosphate crystals cause joint synovial cells to secrete proinflammatory cytokines such as IL-1, which recruits neutrophils and macrophages, further promoting the inflammatory process. Colchicine is an inhibitor of microtubule assembly. It is therefore hypothesized that the drug inhibits crystal endocytosis and/or presentation to intracellular inflammasomes, which helps prevent propagation of the inflammation process. Daily, low-dose colchicine, therefore, will help reduce future episodes of pseudogout attacks.

A 52-year-old man comes to the emergency department because of joint swelling, pain, and trouble walking. Physical examination shows his right knee is swollen and tender to palpation. An aspiration of the joint shows calcium pyrophosphate crystal accumulation. Which of the following findings will most likely be found upon microscopic examination of the synovial fluid? A Elevated eosinophils B Envelope-shaped crystals C Less than 1,000/uL white blood cells D Negatively birefringent needle shaped crystals E Positively birefringent rhomboid crystals

E - Positively birefringent rhomboid crystals Major takeaway The joint aspirate of a patient with chondrocalcinosis, also known as psuedogout, will be characterized by an elevated WBC count and the positively birefringent rhomboid shaped crystals of calcium pyrophosphate. Main explanation Chondrocalcinosis , also known as pseudogout, is characterized by calcium pyrophosphate deposition in joint spaces. Calcium pyrophosphate crystals appear rhomboid shaped, and are weak positively birefringent crystals on polarized microscopy of synovial fluid. In other words, when parallel, it will be blue under polarized light. This is in contrast to gout, in which the deposition of monosodium urate crystals cause similar symptoms. In gout, the crystals are needle shaped and negatively birefringent, so it will appear yellow when parallel. Another typical finding is chondrocalcinosis of the meniscal cartillage, as evidenced by white sclerotic changes in the joint space. It is important to aspirate a new-onset acutely inflamed joint to rule out septic arthritis. Gout and pseudogout can occur in any joint. However, the knee is most common location for pseudogout, while the metatarsophalangeal joint of the great toe and the metacarpophalangeal and proximal interphalangeal joints of the hands are more commonly affected in gout.

A 17-month-old boy is brought to the physician for developmental delay and aggressive behavior. The patient constantly bites his own finger tips, which has forced his parents to put mittens on his hands. He is unable to walk without assistance and has not yet said words like "mama." His parent states that she has occasionally noticed yellow, sand-like crystals in his diaper when she changes him. Vital signs are within normal limits. There is increased muscle tone in the extremities. Serum studies show an increased level of uric acid. Activity of which of the following enzymes is increased in this patient? A Dihydrofolate reductase B Phosphoribosyl pyrophosphate synthetase C Uridine monophosphate synthetase D Carbamoyl phosphate synthetase II E Hypoxanthine guanine phosphoribosyltransferase

Major takeaway Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a deficiency of the enzyme HGPRT. Lack of HGPRT results in failure to recycle purine bases and an increase in de novo purine production, resulting in hyperuricemia in young boys. Main explanation This child is presenting with signs of developmental delay, self-mutilating behaviors, and increased serum uric acid. He most likely has Lesch-Nyhan syndrome. Lesch-Nyhan syndrome is an X-linked recessive disorder resulting in a deficiency of the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT), which is necessary in the purine salvage pathway. Since purine waste-products are no longer able to be recycled for purine regeneration, they are instead metabolized into uric acid. Additionally, since recycling can no longer contribute to purine production, increased de novo purine synthesis is required, resulting in an increase in enzymes involved in purine synthesis, such as phosphoribosyl pyrophosphate (PRPP) synthetase. The combination of increased purine degradation and increased de novo purine synthesis (which results in even more purines being broken down into uric acid) leads to hyperuricemia. Symptoms in these patients are secondary to hyperuricemia. Urate crystals, often presenting as yellow-orange sand-like crystals, are often found in the diaper. Urate crystals can also deposit in joints, resulting in gout. Additionally, elevated serum uric acid levels interfere with proper neurologic development, resulting in the characteristic aggressive, self-mutilating behavior seen in these patients.

A 49-year-old man comes to the physician complaining of severe pain in the left knee. He also notes that the knee feels warm and looks red. The patient has not had similar symptoms before. Past medical history is significant for hyperlipidemia and hypertension. Current medications are pravastatin and lisinopril. He does not drink alcohol but has smoked one pack of cigarettes daily for the last 22 years. He drinks 2-3 cups of coffee daily. He drinks 2 glasses of milk every day prior to bed because it "helps him sleep." Vital signs are within normal limits. BMI is 37 kg/m2. Physical examination reveals swelling, erythema, and warmth of the left knee joint. It is tender to palpation with decreased active and passive range of motion. Arthrocentesis of the joint yields turbid fluid with a leukocyte count of 17,100/mm3. Gram stain is negative. Polarized light microscopy shows yellow, negatively birefringent crystals. Which of the following lifestyle changes is most likely to reduce recurrence of his current episode? A Begin drinking one glass of red wine daily B Cessation of cigarette smoking C Increase seafood consumption D Reduce coffee consumption E Weight reduction F Daily low-dose aspirin therapy

Weight reduction Major takeaway Acute gout attacks are caused by precipitation of uric acid secondary to overproduction or underexcretion. Overproduction can be the result of obesity as well as seafood and red meat consumption. Underexcretion can be the result of low-dose aspirin intake. Main explanation This patient is presenting with signs and diagnostic studies suggestive of an acute gout attack. Gout is caused by precipitation of elevated uric acid in the serum, resulting in crystal deposition in joints. Elevated uric acid levels are the result of overproduction or underexcretion of uric acid. Obesity is conclusively linked to higher serum levels of uric acid; adipose cells partake in purine degradation, and therefore, increased adipose tissue results in increased purine breakdown. Weight-loss can help lower serum uric acid and potentially decrease the risk of future attacks.