Chapter 11: Rheumatology

A few words on "rheumatology panels." Doing a "rheumatology panel" will never be the right answer. The diagnosis of rheumatologic disease is clinical with specific clinical criteria for each illness. While antinuclear antibody (ANA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other tests may be useful in supporting a clinical diagnosis and assessing disease activity, these tests have poor specificity and may be positive in a variety of disease states. A positive ANA without a clinical diagnosis is meaningless. Likewise, RF helps to gauge prognosis (seropositive vs. seronegative) in rheumatoid arthritis (RA), but has very limited value as a diagnostic test. RF may also be positive in sarcoidosis, viral infections (especially hepatitis C), and autoimmune diseases such as granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), as well as a variety of primary lung and liver diseases. ESR and CRP may support the clinical impression of inflammatory disease, but are again nonspecific.

A 43-year-old female presents with body aches and stiffness, which are worse in the morning. She further describes a low-grade fever and pain in her hands, feet, and left knee. She feels that her grip strength is diminished. These symptoms started rather abruptly 2 weeks ago and have not responded to acetaminophen.

She frequently camps with her family. She remembers that 1 week they could not go because her 8-year-old daughter had a fever, mild diarrhea, abdominal pain, and a skin rash ("legs, arms, and especially face were red and warm, and she seemed 'flushed' all the time"). Her daughter's symptoms resolved in a few days, she did not see a doctor, and no one else was sick. She has no other illnesses, and review of systems is otherwise negative.

On physical examination, her vitals are normal. She is unable to close her hands completely. Although the physical examination is somewhat limited by pain, there appears to be swelling of all metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, as well as mild erythema over the MCP joints bilaterally. In addition, upon examination of the left knee, the bulge sign (indicating effusion) is detected.

Question 11.1.1 If found on physical examination, which of the following would be LEAST useful in helping you in narrow your diagnosis?

A) Bilateral metatarsophalangeal (MTP) joint swelling and tenderness.

B) Painless oral ulcerations, with clean edges.

C) Firm, slightly tender subcutaneous nodules at the olecranon bursae.

D) A "bull's eye" rash in the right axilla.

E) Icterus and tender hepatomegaly.

Answer 11.1.1 The correct answer is "A." This patient presents with polyarticular inflammatory arthritis of unclear etiology. While important to note, MTP joint swelling would not add much to the picture of subacute, symmetrical, small joint polyarthritis that you have already found on examination. The differential diagnosis includes acute viral arthritis, specifically parvovirus B19 (due to the daughter's history of acute illness resembling erythema infectiosum), coxsackievirus, hepatitis B (hinted at in "E"), and HIV. Also on the differential will be Lyme disease ("D") (although small joint symmetrical arthritis would be atypical), RA ("C," the presence of rheumatoid nodules would be helpful although these would be unlikely in early disease), and other inflammatory disorders. "B," painless ulcerations, are classically associated with SLE (systemic lupus erythematosus), but it ought to be noted that lupus aphthae (ulcers) may be painful as well.

After you sneak off to do a little reading, you examine her again. She has no rash. You detect bilateral pain and swelling of the third and fourth MTP joints. There are no oral ulcerations and no lymphadenopathy. She is not icteric, and her abdomen is diffusely, mildly tender. There is no hepatomegaly. You decide to order some blood tests.

Question 11.1.2 If positive, which of the following tests would be MOST helpful in ruling in a specific rheumatologic diagnosis?

A) Positive ANA.

B) Elevated white count.

C) Positive parvovirus B19 IgM.

D) Positive urinalysis for white blood cells (WBCs).

E) Elevated ESR and CRP.

Answer 11.1.2 The correct answer is "C." The presence of IgM antibodies to parvovirus B19—or rising titers of IgG antibodies—indicates acute viral infection, which may present with symptoms and signs seen in this patient. "A," positive ANA, will not help you rule in a diagnosis at this point. While the ANA is a highly sensitive test, it is not specific and has a low positive predictive value. "B," "D," and "E" are all important findings, but would not lead you toward a specific diagnosis. "D," WBC in the urine could be from interstitial nephritis, a UTI, a nephritic urine from other causes, etc. Table 11-1 presents a framework for who should be tested for and diagnosed with RA.

Her laboratory results return as follows:

• Hepatitis B: Surface antibody positive, surface antigen negative.

• CMV: IgG positive, IgM negative.

• Parvovirus: IgG positive, IgM negative.

• RF: 200 (normal: <14 units)

• Anti-citrullinated protein antibody (ACPA)^∗: 64 units (strong positive >60 units)

• ANA: Negative.

• ESR: 58 mm/hr.

Note that based on results so far and according to Table 11-1, she has seven points (4–10 joints involved, high titers of RF and CCP antibody, and elevated ESR).

^∗Anti-citrullinated protein antibody (ACPA) is also known as anti-CCP (anti-cyclic citrullinated peptides). Anti-CCP antibodies are very specific for RA; however, their sensitivity is 67% and therefore may be negative in RA.

Question 11.1.3 Which of the following is the most appropriate next step?

A) Bilateral hand x-rays.

B) CT of the chest.

C) Smith antibody, double-stranded DNA (dsDNA), complement levels.

D) Start methotrexate 15 mg weekly by mouth and daily folic acid, with or without low-dose prednisone and follow up in 4 to 5 weeks.

E) Start prednisone 60 mg daily by mouth and follow up in 4 to 5 weeks.

Answer 11.1.3 The correct answer is "D." This patient most likely has seropositive RA (see criteria in Table 11-1). The patient should be started on a disease-modifying anti-rheumatic drug (DMARD), such as weekly methotrexate at a moderate dose, along with folic acid 1 mg daily and prednisone 10 to 20 mg daily. Evidence suggests that there is a "window of opportunity" when treating early RA and that an early remission may lead to sustained remission.

Note that investigating for any evidence of other systemic involvement should be included as part of the initial evaluation. It is appropriate to obtain CBC, liver function tests, electrolytes, BUN, creatinine, and urinalysis (to rule out glomerulonephritis). "A" is incorrect. She is presenting fairly early after the onset of symptoms, so it is unlikely that hand x-rays will provide any significant findings. "B" is also incorrect. Without further symptoms or signs of lung involvement (e.g., pulmonary osteoarthropathy and respiratory symptoms), a CT scan would be inappropriate. As to "C," she has no other symptoms of lupus and also had a negative ANA, so further testing for lupus (Smith antibody, dsDNA [also known as anti-native DNA antibodies], complement levels) is not appropriate. "E" is incorrect. Although steroids are indicated, low doses are fine; higher doses are rarely necessary and are associated with greater side effects. Therefore, early institution of a DMARD would be preferable.

She returns in 4 weeks and is now about 7 weeks into her illness. She reports a moderate response to your intervention (you started methotrexate 15 mg weekly with 1 mg folic acid daily, and prednisone 20 mg daily), but now she has 1 to 2 hours of morning stiffness. She continues to complain of pain in her hands and feet, with poor grip. In fact, she had to take time off from work during the last week. On examination, she has persistent swelling of MCPs 2 to 5 bilaterally and MTPs 3 and 4 bilaterally. You also note swelling in the left wrist and both knees, but tenderness is reduced and there is no erythema.

You take a step back and want to reassess the situation.

Question 11.1.4 What examination finding is so general that it would NOT help you support/reconsider your diagnosis?

A) Pleural rub auscultated on lung examination.

B) Firm, slightly tender subcutaneous nodules at the olecranon bursae.

C) Faint pink rash over chest, which is not visible 15 minutes later.

D) Reduced passive flexion in left knee.

E) Left foot drop.

Answer 11.1.4 The correct answer is "D." While important to note, limitation of passive movements of the knees is indicative only of knee effusion (or pain), which you have already observed, and is not specific for any particular etiology. She responded modestly to methotrexate and prednisone but clearly still has active arthritis. What can you use to expand or limit your differential diagnosis? Pleural friction rub ("A") is indicative of possible lupus. Diagnostic criteria for lupus include serositis, which may be detectable as a pleural rub on auscultation of the lungs (also, look for malar rash, discoid lesions, alopecia, and oral ulcerations). Although not part of the diagnostic criteria for the disease, RA may also present with pleuritis or pericarditis. Rheumatoid nodules ("B") are found in RA. A salmon-colored, evanescent macular rash ("C") would lead you to consider adult-onset Still disease. Still disease, also known as juvenile idiopathic arthritis (JIA, discussed in Chapter 13), presents with an evanescent rash, intermittent fever, and arthritis. "Adult onset" Still disease is Still disease with onset after age 16. In addition, RF and CCP antibodies are typically negative in adult-onset Still disease. A finding of isolated foot drop ("E") may be the result of mononeuritis multiplex, a feature of vasculitides, and paraneoplastic syndromes. In fact, foot drop is the most common weakness with mononeuritis multiplex followed by wrist drop. Mononeuritis multiplex is defined as injury of two or more named nerves secondary to a vasculitis.

Question 11.1.5 Since your patient is taking methotrexate, you caution her to avoid which of the following?

A) Aspirin.

B) Sulfonamide antibiotics.

C) Ibuprofen.

D) Folate.

E) Penicillin antibiotics.

Answer 11.1.5 The correct answer is "B." Methotrexate is a folate antagonist. Anti-folate medications, such as sulfonamide antibiotics, must be avoided in patients taking methotrexate because the combination may result in pancytopenia. Supplemental folate, 1 mg daily, reduces the adverse effects of methotrexate. Patients with RA are often treated with aspirin or NSAIDs in combination with methotrexate. Penicillin antibiotics can be administered safely with methotrexate, although methotrexate levels may increase by 8% or so.

At her first return visit, she had only mild improvement so you (rightly) added hydroxychloroquine (good job!). Initial hand x-rays demonstrate mild periarticular osteopenia. Liver function tests, urinalysis, CBC, BUN, and creatinine are normal. She returns 6 weeks after starting the hydroxychloroquine and is much improved, having returned to work full-time. She tells you that she still has problems with opening jars and about 45 minutes of morning stiffness, "but nothing like it was."

Question 11.1.6 What is the BEST course of action to follow now?

A) Continue her current therapy and follow up in 6 to 12 months with transaminases, RF, and hand x-rays.

B) Continue her current therapy and follow up in 3 to 4 months with transaminases, RF, and hand x-rays.

C) Continue current therapy and follow up in 3 to 4 months; arrange for monthly BUN, creatinine and CBC; and schedule for an annual ophthalmology examination.

D) Begin prednisone taper, continue other medications, and arrange for monthly transaminases and CBC; schedule for baseline ophthalmology exam; and schedule follow-up in another 2 to 3 months.

E) Instruct her to discontinue methotrexate, taper the prednisone dose, and continue hydroxychloroquine; arrange follow-up in 1 year.

Answer 11.1.6 The correct answer is "D." She seems to be responding to therapy, and a 3-month trial on her current medications (during which the methotrexate dose may be increased) is indicated. A slow prednisone taper should be initiated to minimize the cumulative dose of corticosteroids. Close follow-up is critical; she should contact you should symptoms return during the steroid taper. Guidelines for monitoring her DMARD regimen recommend measurement of transaminases and CBC every 8 to 12 weeks for methotrexate and routine eye examination to assess for hydroxychloroquine-related retinal toxicity. A baseline eye examination is necessary when starting hydroxychloroquine; annual screening should begin after 5 years, unless the patient is at high-risk for complications. Hand x-rays are recommended at 2-year intervals. "E" is incorrect: DMARD therapy reduces her risk of joint destruction and disease progression, and should not be discontinued.

At her next visit 3 months later, she feels better. Although she still has difficulty opening jars, she now has <30 minutes of morning stiffness and almost no pain. On examination, she has no rash, nodules, or evidence of serositis. She now has swelling over MCPs 2 to 4 on the right and 2 to 3 on the left. Her grip is still somewhat weak but improved. Laboratory data shows an ESR of 28 mm/hr, CRP 0.7 mg/dL, and normal transaminases and CBC. Her symptoms increased when she tapered prednisone to less than 10 mg/day, so she is taking 20 mg/day once again.

Question 11.1.7 Which of the following is the most appropriate next step?

A) Increase methotrexate to 25 mg weekly, continue hydroxychloroquine, and refer to rheumatology.

B) Stop methotrexate and switch to leflunomide 20 mg/day.

C) Increase prednisone to 60 mg daily.

D) Discontinue all medications except methotrexate.

E) Discontinue methotrexate, taper prednisone, and continue hydroxychloroquine.

Answer 11.1.7 The correct answer is "A." Despite her initial response, she has evidence of ongoing inflammatory activity by history and examination. Discontinuing or reducing medication is inappropriate. According to published guidelines, consultation with a rheumatologist is now indicated—if it had not been sought sooner. She has had a fair initial response to methotrexate, prednisone, and hydroxychloroquine. Further benefit may be gained with increasing the methotrexate dose. Addition of sulfasalazine would also be appropriate. If "triple" therapy with methotrexate, hydroxychloroquine, and sulfasalazine fails, she will need a biological agent. "B" is incorrect: since she had an initial response to methotrexate, and may show further efficacy at a higher dose, it would be wise to further increase the methotrexate dose, rather than substituting another agent (leflunomide … leflunomide is a nonbiologic immunosuppressant which can cause liver injury). "C" is incorrect: doses of prednisone this high are not indicated for RA.

Question 11.1.8 This patient wants to become pregnant. You can tell her that:

A) Symptoms remit in 70% of women during pregnancy.

B) She should avoid pregnancy while taking methotrexate.

C) RA is a contraindication to pregnancy.

D) Prednisone cannot be taken during pregnancy.

E) A and B.

Answer 11.1.8 The correct answer is "E," both "A" and "B" are correct. RA is an autoimmune disease, and it tends to remit during pregnancy when a woman is relatively immunosuppressed. Methotrexate is class X for pregnancy and is actually used in ectopic pregnancy to arrest fetal growth. Women taking methotrexate should use an effective form of contraception, and continue contraception for 3 months after stopping methotrexate. "D" is incorrect since prednisone is often used to control RA during pregnancy, when methotrexate is contraindicated. Prednisone does not cross the placenta, but use during pregnancy is associated with higher risk for gestational diabetes.

The patient is an avid runner and, prior to her diagnosis, participated in numerous outdoor activities. She is concerned about whether she will eventually become disabled.

Question 11.1.9 You can let her know that:

A) RA tends to progress without any remissions to involve almost all joints in all patients.

B) Prednisone-free disease remission has become the goal of treatment.

C) Patients with RA have the same life expectancy as the general public.

D) Renal involvement is common with RA and is a major source of morbidity and mortality.

E) She won't need to worry about having a life after she gets pregnant and has a child. All her energy will be absorbed by that little parasite … er, child.

Answer 11.1.9 The correct answer is "B." With the advent of new potent disease-modifying agents, it is now possible to achieve remission, that is, the absence or near absence of joint pain and swelling, in patients who have RA. "A" is incorrect. Untreated RA may progress to involve further joints, but not all joints are affected by RA. Classically, the distal interphalangeal joints are spared and, if there is DIP involvement, should prompt reassessment of the diagnosis. Moreover, treatment with DMARDs can, and frequently does, induce remission. "C" is incorrect. RA reduces the life expectancy by up to 10 years. "D" is incorrect. Renal disease is a rare complication of RA; however, it can be a result of some of the medications used to treat RA. Finally, "E". If she needs a life, she can buy them in bulk for cheap at Costco (Walmart also has them for cheap but they wear out too fast).

Which of the following must be tested for before beginning a biological agent to treat rheumatoid arthritis?

A) CMV

B) TB

C) Heart failure

D) Mucosal candidiasis

E) B and C

The correct answer is "E". There are a number of biologicals for treating rheumatoid arthritis that are TNF inhibitors. Etanercept (Enbrel) is a soluble TNF receptor antagonist. Infliximab (Remicade) and adalimumab (Humira) are monoclonal antibodies that bind TNF both at the cell and when it is in its soluble form. These drugs can also reduce the resistance to infection and promote malignancies. All of the TNF inhibitors essentially have the same efficacy. Any one of these agents can be added to MTX. Things to watch for with TNF inhibitors include serious infections including TB, fungal infections, and malignancies. Rule out TB and hepatitis B before starting TNF inhibitors. There is also a concern for worsening congestive heart failure in those with pre-existing disease. Thus, "E" is the correct answer. Mucocutaneous candidiasis is not a contraindication to TFN inhibitors and routine testing for CMV is not recommended.

Objectives: Did you learn to…

• Describe an appropriate diagnostic strategy for polyarthritis?

• Recognize the diagnostic criteria for RA?

• Develop a management strategy for RA?

• Recognize the importance of early DMARD therapy for RA?

• Identify the uses and adverse effects of medications used to treat RA?

A concerned mother brings in her 2-year-old son with a 1-week history of fever. She is worried because she had expected the fever to resolve by now. According to his mother, the patient also has a rash, poor appetite, and lethargy. On examination, he looks ill and his temperature is 39.0°C. There is a diffuse, erythematous, macular rash, and peeling skin on the fingertips. The oropharynx is injected and the tongue is bright red with white papillae. Cervical lymph nodes are enlarged and tender.

Based on the available information, what is your leading diagnosis?

A) Rheumatic fever.

B) Parvovirus B19 infection.

C) Kawasaki syndrome.

D) JIA.

E) Varicella infection.

The correct answer is "C." Kawasaki syndrome is an acute vasculitis of unknown etiology, which is most often seen in children. Kawasaki syndrome presents with at least 5 days of fever (you cannot make the diagnosis of Kawasaki disease without at least 5 days of fever), polymorphous rash, conjunctival injection, mucous membrane involvement (e.g., "strawberry" tongue), cervical lymphadenopathy, and extremity findings of erythema and desquamation. The usual treatment is aspirin and IVIG. Corticosteroid therapy is controversial and does not seem to improve outcomes. There may be cardiac involvement with the formation of coronary artery aneurysms.

"A," rheumatic fever, which is rare in developed countries, is recognized by the Jones criteria. The major Jones criteria consist of polyarthritis, carditis, Sydenham chorea, erythema marginatum, and subcutaneous nodules. (Here's a fun mnemonic: "JONES" with a heart shape in place of the "O," so that J = joints, O = carditis, N = nodules, E = erythema marginatum, and S = Sydenham chorea). "B" is incorrect. Generally, children do not appear this ill with parvovirus B19 infection (fifth disease). "D," JIA, would be unusual at such a young age, and is discussed in Chapter 13. "E" is incorrect, as this is obviously not varicella.

A 62-year-old male whom you have followed for hypertension for several years presents with complaints of worsening fatigue and aching in his back, shoulders, and neck. He notes 3 months of symptoms unresponsive to acetaminophen.

Further history reveals that your patient has experienced stiffness of the neck and shoulders each morning for over 30 minutes. He occasionally has difficulty getting out of bed due to pain. Vital signs are within normal limits. There is no evidence of synovitis of the hands, wrists, or elbows. Active range of motion in the neck and shoulders is slow but full. There is tenderness to palpation of the shoulders, upper back, and neck, but no apparent muscle atrophy.

Question 11.2.1 Which of the following is the most appropriate next step in the diagnosis of this illness?

A) Obtain an ESR and CRP.

B) Obtain a urinalysis.

C) Prescribe a diagnostic trial of corticosteroids.

D) Order a rheumatology panel, including ANA, uric acid, ESR, CRP, and RF.

E) Perform shoulder radiograph.

Answer 11.2.1 The correct answer is "A." This patient's presentation is consistent with the diagnosis of polymyalgia rheumatica (PMR). Elevations of ESR and/or CRP contribute further evidence to such a diagnosis and are useful in following the treatment of PMR. While a urinalysis ("B") may be important in some rheumatologic illnesses (e.g., lupus, Behçet syndrome), PMR is not likely to be associated with renal disease.

A trial of corticosteroid therapy ("C"), may be appropriate, but an ESR should be obtained first to more conclusively establish the diagnosis. At this point all we know is that he has bilateral shoulder and neck pain, which could be mechanical from the cervical spine, etc. As you already know from earlier discussion, "D" is incorrect; a "rheumatology panel" will typically include tests that are not indicated, and positive results can be misleading. In the absence of small joint symptoms or examination findings, an RF is not indicated in this case. Likewise there is no history to suggest an ANA-related disorder. "E" is incorrect. This patient does not need shoulder radiographs. In a patient with bilateral shoulder pain and neck pain, a neck radiograph may be more useful than shoulder imaging. Neck radiographs help to evaluate for cervical canal narrowing and degenerative disc disease, which may result in pain and neurologic findings in the upper extremities. An MRI of the neck might be useful if cervical spine disc disease or a syrinx were suspected. Diagnostic criteria for PMR are given in Table 11-2. Small joint synovitis, or puffy swelling of hands and feet, will occur in 20% of patients with PMR; and in these cases it is appropriate to check RF and anti-CCP during your initial evaluation.

Question 11.2.2 The sensitivity of an elevated ESR in the diagnosis of PMR and giant cell arteritis (GCA, AKA, temporal arteritis) is:

A) 100%.

B) 85%.

D) 50%.

E) 25%.

Answer 11.2.2 The correct answer is "B." Up to 15% of patients with PMR or GCA (a closely related disorder—keep reading) have a false-negative ESR. Using ESR and CRP together is 97% to 99% sensitive for GCA. Double false negatives of ESR and CRP are uncommon, but do occur. Thus, in the patient in whom GCA is suspected but in whom there is a normal ESR and/or CRP, biopsy is still recommended. In those suspected of PMR, a trial of corticosteroids is still recommended.

You order radiographs of the neck, which demonstrate mild degenerative disease. A CBC is unremarkable, except for a mild thrombocytosis. The ESR is 80 mm/hr. You relate these findings to the patient and tell him that your presumptive diagnosis is PMR.

Question 11.2.3 Which of the following is the most appropriate initial treatment in this case?

A) Naproxen 500 mg twice daily.

B) Prednisone 15 mg daily.

C) Aspirin 650 mg twice daily.

D) Prednisone 50 mg daily.

E) Referral to physical therapy.

Answer 11.2.3 The correct answer is "B." Prednisone is the treatment of choice in PMR. Doses of prednisone ranging from 10 to 20 mg daily are usually sufficient to control the disease. Higher doses (up to 30 mg/day) should be tried if there is no response in 1 to 2 weeks. If the patient fails to respond to 30 mg or less of prednisone, the diagnosis of PMR should be reconsidered. "A" is incorrect. NSAIDs may provide some symptomatic relief but are not the treatment for PMR. "C" is incorrect. It remains controversial whether low dose aspirin, 81 mg/day may decrease the risk of vision loss in giant cell arteritis. However, high-dose aspirin therapy without corticosteroids is not recommended. "E" is incorrect. Since patients usually respond quickly to corticosteroids, physical therapy is not necessary—although you could hardly be faulted for employing physical therapy as part of your overall treatment approach.

You prescribe prednisone 15 mg daily, aspirin 81 mg daily, and calcium and vitamin D supplementation. Your patient presents for follow-up 4 weeks later, reporting marked improvement. On examination, there is no joint inflammation, or muscle tenderness with range of motion exercises. His ESR is 20 mm/hr. You believe that the patient's disease is now in remission.

Question 11.2.4 Which of the following is the most appropriate next step in his management?

A) Discontinue prednisone and initiate naproxen.

B) Continue the current dose of prednisone for the next 12 months.

C) Continue the current dose of prednisone for the next 6 months.

D) Taper prednisone by 1 to 2 mg every 2 weeks to reach the minimum effective dose.

E) Taper prednisone by 5 mg over 2 weeks and then discontinue the drug.

Answer 11.2.4 The correct answer is "D." Relapse of PMR occurs more frequently when corticosteroids are abruptly discontinued or tapered too quickly. However, due to complications associated with corticosteroid therapy, the dose should be reduced as soon as possible; therefore, maintaining prednisone 15 mg daily for 6 to 12 months is inappropriate. The usual recommendation is to reduce the dose of prednisone by 10% every 1 to 2 weeks until the minimum effective dose is reached. While tapering prednisone, the patient should be monitored with an ESR and/or CRP every 2 to 4 weeks. If symptoms worsen, prednisone should be increased slightly to achieve symptomatic control. If the ESR increases to 40 mm/hr or greater and the patient is asymptomatic, consider continuing the same dose of prednisone until the ESR normalizes, then continue the taper. However, an isolated elevation in ESR without symptoms is not a reason to increase prednisone.

Question 11.2.5 Which of the following is true regarding the prognosis of PMR?

A) PMR is associated with an increased risk of mortality.

B) Most patients with PMR will require corticosteroid therapy for life.

C) Up to 50% of patients who initially have a successful remission will experience a relapse while tapering prednisone.

D) A relapse of PMR requires high-dose corticosteroids (prednisone 50 mg daily) for successful treatment.

Answer 11.2.5 The correct answer is "C." Relapses occur in 30% to 50% of patients after induction of remission and should be treated by resuming or increasing prednisone. Usually, successful treatment of a relapse requires increasing the prednisone dose by a few milligrams. "A" is incorrect. Although the pathogenesis of PMR is incompletely understood, it has features in common with vasculitides, including potential vascular complications of GCA. However, PMR is not associated with an increase in mortality. "B" is incorrect because PMR is a self-limited disease, and most patients recover within a few months to a few years. Thus, patients require prednisone for 6 months to 2 years, but prednisone therapy is typically not lifelong. Remote relapses of PMR after prednisone has been successfully stopped are seen in about 20% of cases, and can occur up to years later.

Your patient does well and is able to taper off prednisone over a year. Twelve months after stopping corticosteroids, he presents to the ED one night. His shoulder and neck pain and stiffness have returned, as well as severe fatigue and subjective fevers. He has lost 5 pounds over 2 weeks. He is now experiencing frequent left-sided headaches. Finally, he is most concerned about a new visual disturbance starting today. He notes that he has a "hole" in his vision. On physical examination, there is a prominent, tender vessel palpable at the left temporal area. Funduscopic examination of the left eye shows a pale disc with blurred margins. The remainder of the neurologic examination is normal. The ESR is 70 mm/hr.

Question 11.2.6 Which of the following is the most likely diagnosis for the visual symptoms?

A) Polymyalgia Rheumatica (PMR).

B) Stroke (CVA).

C) Giant cell arteritis (GCA).

D) Multiple sclerosis (MS).

E) Acute angle-closure glaucoma.

Answer 11.2.6 The correct answer is "C." Many of the patient's symptoms can be explained by PMR ("A"), but visual symptoms do not occur with this disease. GCA is a related diagnosis that is commonly seen in conjunction with PMR. Most experts now agree that PMR and GCA are different presentations of the same disease process. With the new symptoms of localized headache and tenderness of the temporal artery and the previously known findings consistent with PMR, this patient now meets diagnostic criteria for GCA (see Table 11-3). The visual symptoms described are typical of GCA and can occur acutely or chronically. As to the other answers, vision loss in multiple sclerosis is attributable to optic neuritis, which is associated with pain and presents initially in a younger population. Acute angle-closure glaucoma is associated with eye pain and redness. The lack of other symptoms makes stroke less likely.

Question 11.2.7 Which of the following is the most appropriate initial management of this patient?

A) Withhold treatment for now and arrange for temporal artery biopsy within 48 hours.

B) Refer to a neurologist as soon as possible.

C) Refer to an ophthalmologist as soon as possible.

D) Initiate prednisone 20 mg daily, and refer for temporal artery biopsy.

E) Admit and administer methylprednisolone 1 g intravenously (IV), and arrange for temporal artery biopsy.

Answer 11.2.7 The correct answer is "E." When symptoms of vision loss occur, IV methylprednisolone 15 mg/kg/day (up to 1 g) daily for 3 days, followed by prednisone 40 to 60 mg daily is the standard of care. Compared to PMR, higher doses of corticosteroids are necessary to treat GCA. In the absence of vision loss, prednisone doses of 40 to 60 mg QD are usually required to relieve symptoms. Consultation with ophthalmology is also necessary in providing proper care to the patient. "A" is incorrect. You do not want to withhold treatment from this patient whose vision is at risk (see "helpful tip" below). "B" and "C" are incorrect for the same reason. "D" is incorrect because a dose of 20 mg of prednisone is too low to be effective in GCA.

Six years after his diagnosis of GCA, your patient has experienced several remissions and relapses. Although he has been able to discontinue prednisone on occasion, he is now taking 5 mg daily with good symptomatic control.

One dark and stormy night, 3 AM in the ED—the weather is cold and the coffee is colder—your patient presents with tearing substernal chest pain radiating to his back. He is alert but anxious and diaphoretic. His left radial pulse is diminished compared to the right. His heart rate is 120 bpm, and his blood pressure is 92/56 mm Hg.

Question 11.2.8 Which of the following studies will confirm the most likely diagnosis?

A) Chest radiograph.

B) Chest CT.

C) ECG.

D) Venous blood gas.

E) Troponin-T.

Answer 11.2.8 The correct answer is "B." Your patient's symptoms are classic for a dissecting thoracic aortic aneurysm, which is often mistaken for a myocardial infarction. Thoracic aortic aneurysm is a late complication of GCA; aortic aneurysms generally occur an average of 6 to 7 years after the initial diagnosis of GCA. Thoracic aortic aneurysms occur 17 times more often in patients with GCA when compared to the general population. The diagnosis of thoracic aortic aneurysm is confirmed by CT scan of the chest, echocardiogram, or angiogram. While the other studies listed should be done, none of them are going to make the diagnosis of a dissecting aneurysm for you.

Objectives: Did you learn to…

• Describe the appropriate evaluation, including physical examination and laboratory tests, of diffuse pain in the older patient?

• Recognize the diagnostic criteria for PMR and GCA?

• Describe the appropriate management, including medical therapy, of PMR and GCA?

• Identify complications of PMR and GCA?

A 22-year-old graduate student presents to the ED on a Monday night with an acutely swollen left knee. He admits to "wild partying" over the weekend but only had "a couple of beers" (that is the "college couple" ….6 or 7). His knee was OK then. However, when he woke up this morning, he noticed the knee was swollen and painful (so was his head, but that's another matter). By early afternoon, he had difficulty bearing weight. He denies fever, but feels tired.

He reports a history of JIA (juvenile idiopathic arthritis, previously termed juvenile rheumatoid arthritis), and has had ankle and knee swelling previously, but not to this degree. He took prednisone intermittently, as well as hydroxychloroquine and methotrexate, for his JIA until age 18. He then continued on hydroxychloroquine until 8 months ago, when he stopped it because he felt fine. He denies any other medical problems. He smokes only when drinking—which happens way too often.

Question 11.3.1 What other information from the history would be most helpful in establishing the diagnosis?

A) Sexual history, including sexual orientation, practices, and last contact.

B) Personal or family history of gout or kidney stones.

C) History of IV drug use.

D) Family history of pseudogout.

E) A, B, and C.

Answer 11.3.1 The correct answer is "E." While all of these points are important in the history, this patient is too young to have pseudogout. While gout is unusual in young adults, there are uncommon syndromes of familial hyperuricemia and early gout. Although there are several possible etiologies for this patient's presentation, septic arthritis should be considered first and foremost due to its high morbidity and mortality. As such, the history and examination should focus on those clues that point toward an infectious etiology and its source. The clinician must also consider noninfectious inflammatory arthropathies. IV drug abuse can lead to a septic joint as can gonorrhea. Thus "A" and "B" are important parts of the history.

Your patient is heterosexual and thinks he had intercourse Saturday night but admits that his memory is somewhat blurry (maybe he had more than the "couple" of beers he claims). He denies a history of gout and IV drug use. He complains of poor sleep and feeling stiff in the mornings and evenings lately.

Question 11.3.2 What findings on physical examination would be LEAST helpful in determining the diagnosis?

A) A few vesiculopustular lesions on the back, arms, and legs.

B) Swollen, tender, nonerythematous MCP joints.

C) Nontender hepatomegaly.

D) Diastolic murmur at the right sternal border.

E) Whitish discharge from the tip of penis.

Answer 11.3.2 The correct answer is "C." Although nontender hepatomegaly may indicate presence of liver disease, it is unlikely to help identify the etiology of this patient's arthritis. Hepatitis B arthritis usually presents as a symmetric polyarthritis, although it can be migratory or additive (sequential joints becoming involved without resolution in the initial joints). Our patient has a single swollen, hot joint, which is unlikely to occur as a result of hepatitis. "A" is helpful: a vesiculopustular rash occurs in disseminated gonococcal infections. "B" is also helpful: the presence of other swollen joints should prompt consideration of noninfectious inflammatory arthritis, and the swelling of the MCPs in particular may be a clue for active RA. The detection of a diastolic murmur ("D") is very significant, since diastolic murmurs are almost always pathologic in adults, and may represent infective endocarditis. Finally, "E," penile discharge, can result from acute gonorrheal infections.

On examination, vital signs are significant only for tachycardia and fever (HR: 112 bpm, Temp: 38.2°C). He has no other swollen joints, rashes, heart murmurs, or penile discharge. You palpate a smooth, non-tender liver edge 2 cm below the costal margin; it percusses to 15 cm. You note mild cervical lymphadenopathy and whitish pharyngeal exudates.

Question 11.3.3 Which of the following is the most appropriate next step in the management of this patient?

A) Order hepatitis serologies.

B) Order blood cultures, urine PCR for chlamydia and gonorrhea, and abdominal ultrasound.

C) Administer ceftriaxone 1 g IV and inject the knee with triamcinolone.

D) Perform knee aspiration.

E) Prescribe prednisone 20 mg PO QD and arrange consultation with a rheumatologist.

Answer 11.3.3 The correct answer is "D." Did you get distracted by a big liver? If so, redirect your attention to the knee. The single most important step in evaluating acute monoarthritis is joint aspiration, which will allow differentiation between inflammatory and noninflammatory disease. Although blood cultures and urine PCR for chlamydia and gonorrhea should also be sent in this case, obtaining these studies must not delay joint aspiration. Without determining whether the arthritis is infectious, it would be inappropriate—and potentially hazardous to the patient—to start treatment with corticosteroids. Joint aspiration will provide a specimen for crystal examination. "C" and "E" are incorrect because you would not want to give corticosteroids—especially intra-articular corticosteroids—to a patient with an infected joint. Analysis of the synovial fluid will aid in determining the appropriateness of treating with antibiotics or anti-inflammatory medications. While you would probably use empiric antibiotics (treat as septic until proven otherwise), you will need to first obtain cultures (from the knee aspiration and blood).

You have obtained blood cultures and urine PCR for chlamydia and gonorrhea. A metabolic profile, CBC, and hepatitis B and C serologies are pending. Knee aspiration yields 45 cc of turbid, blood-tinged fluid.

Question 11.3.4 You send the synovial fluid for all sof the following studies EXCEPT:

A) Cell count and differential.

B) Crystal analysis.

C) Culture.

D) Glucose and protein.

E) Gram stain.

Answer 11.3.4 The correct answer is "D." In contrast to analysis of some other bodily fluids (e.g., cerebrospinal fluid [CSF], pleural fluid, and ascitic fluid), chemistry analysis on synovial fluid is of little diagnostic value. Low glucose levels in synovial fluid are associated with the degree of inflammation but do not help to determine its cause. Likewise, synovial protein levels do not help differentiate between types of arthritis. Cell count with differential, gram stain, and cultures should be routine when suspecting infection; crystal analysis is also part of the standard examination, but positive crystal analysis does not rule out concomitant infection.

The synovial fluid analysis reveals the following findings: 50,000 WBC/mm³, 95% polymorphonuclear cells, and no crystals. Gram stain shows Gram-negative diplococci. Cultures are pending. Gonorrhea and chlamydia PCR tests are also pending.

Question 11.3.5 What is the sensitivity of a synovial fluid white count of 100,000/mm³?

A) 30%

B) 40%

C) 50%

D) 60%

E) 75%

Answer 11.3.5 The correct answer is "A." Unfortunately a synovial white count of 100,000/mm³ is only 30% sensitive for a septic joint but is 99% specific. 50,000 WBC/mm³ is 62% sensitive and 92% specific while a WBC count of 25,000/mm³ is 75% sensitive and 73% specific. The point is that what we were taught in school about the synovial WBC count being >100,000/mm³ in a septic joint is wrong.

Question 11.3.6 Which of the following studies will be most important to the OVERALL care of this patient?

A) HIV testing and RPR.

B) Chest x-ray.

C) ANA and RF.

D) Uric acid.

E) ESR and CRP.

Answer 11.3.6 The correct answer is "A." His presentation is very suggestive of disseminated gonococcal infection with acute arthritis, and the presence of diplococci is virtually diagnostic. Therefore, the clinician must also consider the presence of other sexually transmitted diseases and screen the patient appropriately. Assays for hepatitis B and C and chlamydia have been sent, and tests for HIV and syphilis should now be performed. Also, the patient must be counseled regarding safe sexual practices (e.g., condom use, reduced alcohol use, become a monk ….). In this setting, the other studies are less relevant to his overall health.

Question 11.3.7 Which of the following is the most appropriate treatment plan for this patient?

A) Ceftriaxone 1 g IV once, followed by cefixime 400 mg twice daily by mouth for 14 days. Follow-up in 7 days.

B) Admit to hospital, administer ceftriaxone 1 g IV daily, and perform repeat knee aspirations.

C) Admit to the hospital and administer IV and intra-articular ceftriaxone 1 g daily.

D) Ciprofloxacin 500 mg by mouth twice daily for 14 days. Follow-up in 7 days.

E) Penicillin G 4 million units IV once, followed by amoxicillin 500 mg PO three times daily for 14 days. Follow-up with a rheumatologist.

Answer 11.3.7 The correct answer is "B." In order to ensure the best outcome, this patient should be admitted for monitoring and repeated joint aspiration. Purulent fluid tends to collect rapidly in the joint spaces in patients with septic arthritis, necessitating frequent drainage until antibiotics work and inflammation begins to subside. Most cases of gonococcal arthritis respond to needle aspiration, but arthroscopic or open debridement is occasionally necessary. Because IV antibiotics have good penetration into synovial fluid, intra-articular antibiotics are not recommended. When culture, PCR, and sensitivity results become available, antibiotic therapy should be tailored to the particular infectious agent and its susceptibilities.

Within 48 hours, your patient shows signs of improvement. His knee appears much better, there is no recurrent effusion, and he is afebrile. He wants to leave the hospital. By the way, his chlamydia PCR turned up positive.

Question 11.3.8 Which of the following management strategies do you recommend?

A) Continue the hospital admission and ceftriaxone 1 g IV daily.

B) Discharge with ciprofloxacin 500 mg by mouth twice daily.

C) Discharge with penicillin V 500 mg by mouth three times daily.

D) Discharge with cefixime 400 mg by mouth twice daily, and doxycycline 100 mg by mouth twice daily.

Answer 11.3.8 The correct answer is "D." Since the patient is improving, continued hospitalization and IV antibiotics are not needed. Thus, "A" is incorrect. Without knowing the antibiotic sensitivities of the gonococcus, you should assume that it is penicillin-resistant, making "C" a poor choice. Once local and systemic signs are resolving, you can safely discharge the patient with oral antibiotic therapy, using cefixime 400 mg twice daily (or an acceptable alternative based on culture and susceptibilities) to complete a 7 to 14 day course. In cases of gonococcal infection, you should always presumptively treat for concurrent chlamydia infection.

Question 11.3.9 What is the mortality rate of septic arthritis?

A) 0.5%

B) 5%

C) 10%

D) >15%

Answer 11.3.9 The correct answer is "C." The mortality rate of septic arthritis is 10%, with up to one-third of survivors having persistent joint problems, such as limited range of motion, pain, and swelling. Note that the mortality is probably not due to the infection alone but rather to a combination of the underlying illness (e.g., immunosuppression) plus the infection.

Objectives: Did you learn to…

• Describe the appropriate evaluation of monoarthritis?

• Appropriately manage a patient with septic arthritis?

• Identify risk factors for septic arthritis?

• Recognize the prognosis of septic arthritis?

A 55-year-old male presents to your office complaining of severe left knee pain of 2 days duration. Although he was also out partying over the weekend (is there a pattern here to the patients in our practice?), he went home early. He denies any previous history of knee pain or arthritis. He has felt feverish over the last 2 days. He recalls a similar episode of pain in his right great toe 2 years before, but the pain resolved in a few days and he did not seek medical attention. He has hypertension treated with chlorthalidone but is otherwise healthy. He drinks about a case of beer per week—unless he's been partying, in which case he doubles his effort. His family history is remarkable for osteoarthritis.

Physical examination reveals an uncomfortable-appearing obese male in no acute distress. His temperature is 37.9°C, blood pressure 168/98 mm Hg, and pulse 84 bpm. The left knee is red, warm, and diffusely tender with a palpable effusion. There are no visible or palpable subcutaneous nodules on the fingers, toes, or at the elbows.

Question 11.4.1 Which of the following is the most appropriate next step to accurately diagnose this condition?

A) Radiograph of the affected knee.

B) CBC.

C) Serum uric acid level.

D) Knee aspiration and synovial fluid analysis.

E) Diagnostic corticosteroid injection.

Answer 11.4.1 The correct answer is "D." We don't mean to sound like a broken record, but the diagnostic study of choice in a monoarthritis is synovial fluid analysis. Synovial fluid analysis allows the clinician to determine whether there is an inflammatory, infectious, or crystalline cause of the arthritis. "A" is incorrect. Radiographs are typically not helpful acutely in inflammatory arthritis (but would be indicated if there was trauma or suspicion of tumor). "B" and "C," a CBC is nonspecific and uric acid may be normal during an acute attack of gout. Neither of these laboratory results will be diagnostic. Finally, corticosteroid injection must be avoided in monoarthritis until the possibility of infection is eliminated.

You successfully aspirate 5 cc of slightly cloudy yellow synovial fluid from the left knee. While the patient is waiting, the laboratory reports the following findings: 5,000 WBC/mm³, Gram stain negative for bacteria, many needle-shaped negatively birefringent crystals are noted.

Question 11.4.2 These synovial fluid findings are most consistent with which of the following diagnoses?

A) Osteoarthritis.

B) Septic arthritis.

C) CPPD ("pseudogout").

D) Gout.

Answer 11.4.2 The correct answer is "D." Monosodium urate crystals of gout are needle-shaped as seen in this patient's synovial fluid (a good way to remember this is that being stuck with a needle hurts and so does gout). Calcium pyrophosphate dihydrate crystals are rod-, square-, or rhomboid-shaped and positively birefringent in polarized light. Thus, the synovial fluid findings given above are most consistent with gout. "A" and "B" are incorrect. Normally, synovial fluid contains <180 WBC/mm³, but it is generally considered noninflammatory if the WBC count is still <2,000/mm³. Low WBC counts are seen in the synovial fluid of osteoarthritic joints. Synovial fluid containing ≥2,000 WBC/mm³ is consistent with an inflammatory process. When there are >100,000 WBC/mm³, the monoarthritis is considered septic until proven otherwise (although as noted above this is only 30% sensitive for septic arthritis). See Table 11-4 for the diagnostic criteria for gout. Note that up to 20% of patients with a crystalline arthritis will have a coexisting septic arthritis (J Rheumatol. 2012; 39:157).

Question 11.4.3 In general, all of the following are risk factors for gout EXCEPT:

A) Tobacco use.

B) Alcohol use.

C) Obesity.

D) Diuretic use.

E) Family history.

Answer 11.4.3 The correct answer is "A." Your patient exhibits many of the risk factors for gout, which include male sex, obesity, high-protein diet, use of diuretics (either loop or thiazide), alcohol, and family history. However, tobacco use is not associated with gout.

Question 11.4.4 Which of the following is the next step in the management of this patient?

A) Prescribe allopurinol.

B) Prescribe acetaminophen.

C) Discontinue chlorthalidone.

D) Prescribe naproxen at a full anti-inflammatory dose.

E) Perform a therapeutic joint aspiration.

Answer 11.4.4 The correct answer is "D." An acute attack of gout should first be treated with NSAIDs, such as naproxen or indomethacin. The doses prescribed should be at the upper limit for the particular NSAID (e.g., naproxen 500 mg three times daily). Earlier treatment is associated with greater relief of symptoms and shorter duration of the acute event. Other potential first-line agents are colchicine and corticosteroids. The effectiveness of colchicine is best if started within 36 hours of onset of symptoms. Colchicine is typically prescribed as one dose of 1.2 mg, followed by 0.6 mg twice daily for 1 to 2 weeks, and then 0.6 mg daily for 2 to 6 months. Note that this is a much lower dose than we have prescribed in the past! Due to significant toxicity at high doses, it is no longer recommended to "titrate to diarrhea." Oral or intra-articular corticosteroid administrations are also options for patients who have contraindications to NSAIDs, who have failed NSAID therapy, or who have more severe attacks. Corticosteroids are just as efficacious as NSAIDs and may be more appropriate for patients with heart failure, ulcers, or kidney disease. Prednisone, 30 mg per day for five days is a reasonable dose. Narcotic pain medication may be needed as an adjunct to your anti-inflammatory, but will do nothing to shorten the duration of an attack.

"A" is incorrect. Allopurinol is indicated to treat hyperuricemia and prevent the next gout attack in patients who have had more than one attack in the last year (though some would treat those with a particularly bad attack even if <1/year.), when tophi are present, or, when single gout attack occurs with chronic kidney disease grade 2 or more. "B" is incorrect because acetaminophen lacks the anti-inflammatory properties of NSAIDs and is less effective. Discontinuing chlorthalidone, "C" (a thiazide diuretic), and switching to a non-diuretic anti-hypertensive is probably appropriate, but will not treat this gout attack. Joint aspiration is not therapeutic in gout, but may be helpful in pseudogout.

You start an NSAID. He returns in a few days to discuss his labs and x-rays. A radiograph of the left knee demonstrates an effusion but is otherwise unremarkable. His knee pain is much improved, and knee effusion is nearly resolved. His uric acid level is 10.1 mg/dL (the upper limit of normal for your lab is 7.2 mg/dL). CBC, creatinine, sodium, and potassium are normal. You instruct the patient to reduce his alcohol intake (especially beer) and try to lose weight to decrease his risk of gout attacks and for overall health. You schedule a follow-up visit, but he is a no-show and you don't see him again for more than a year (was it something you said?). When the patient returns 18 months later, he reports frequent use of naproxen, and at least five more acute attacks of gout. He continues to consume alcohol. His examination reveals no swollen or tender joints today, but there is a small whitish subcutaneous nodule overlying a toe PIP joint. Creatinine is 1.1 mg/dL, serum uric acid 10.5 (normal <7.2 mg/dL); liver enzymes and CBC are normal.

Question 11.4.5 Which is the most appropriate regimen to start now in this patient to reduce the frequency of gout attacks?

A) Twice-daily colchicine.

B) Daily allopurinol 300 to 600 mg

C) Daily probenecid.

D) Daily allopurinol 100 mg, with once- or twice-daily colchicine.

E) Daily probenecid and allopurinol.

Answer 11.4.5 The correct answer is "D." The presence of a tophus, and the history of more than one attack in the last year are both indications for starting long-term urate-lowering therapy. Colchicine administered once or twice daily has been shown to reduce the frequency of gout attacks 75% to 85%, and is especially useful as prophylaxis (prevention of the next gout attack) during the first 6 to 12 months of urate-lowering therapy. Starting allopurinol at a low dose of 100 mg daily and then increasing the dose every few weeks is less likely to provoke new gout attacks than starting at a larger dose. "B" is incorrect because it is a higher dose of allopurinol, given without prophylaxis, and could induce new gout attacks (which will make this patient think that your treatment is not very good, and that you are not a very good doctor).

Probenecid is a uricosuric agent that also reduces the frequency and severity of acute gout attacks but has multiple drug interactions (including allopurinol) and contraindications (e.g., decreased renal function, kidney stones, or presence of tophi). "C" is incorrect in this case because the patient now has tophaceous gout.

You prescribe allopurinol 100 mg daily and once daily colchicine, and schedule the patient to return every 2 to 4 weeks to re-check his uric acid level and make further allopurinol dose adjustments.

Question 11.4.6 The target for uric acid lowering in this patient is:

A) Less than 7.2 mg/dL, because this is the upper-limit of normal for a man his age.

B) Less than 6.0 mg/dL

C) Less than 5.0 mg/dL

D) Less than 3.14159 mg/dL, because precision counts

E) As low as possible.

Answer 11.4.6 The correct answer is "C." This patient has a tophus; in order to resolve tophi, and minimize the risk for further attacks, allopurinol should be increased in 100 mg steps until his uric acid level is consistently less than 5.0 mg/dL. Uric acid crystals start to form at serum levels >6.7 mg/dL, which is within the 95% confidence range in the adult population, so within the "normal"—but not necessarily "harmless"—range. "A" is not correct, as levels higher than 6.7 mg/dL would continue to cause gout attacks and will not resolve tophaceous deposits. "B" is the correct target for patients without evidence of tophi, but <6.0 mg/dL is not sufficient in this patient. "D" is the first few digits of the mathematical constant pi. We know you didn't fall for "D."

Uric acid is a normal product of purine metabolism. There have been some studies that show it may have some role in neuroprotection as well as fighting infection. Too much is bad, but too little ("E") could be a problem as well so we do not target uric acid to zero.

Question 11.4.7 All of the following are side effects of allopurinol EXCEPT:

A) Aseptic meningitis.

B) Rash.

C) Leukopenia.

D) Fever.

E) GI disturbance.

Answer 11.4.7 The correct answer is "A." Additional side effects include elevated liver enzymes, glomerulonephritis, aplastic anemia, and vasculitis. Hypersensitivity reactions are especially common in Chinese, Indians, and others from Asia in whom it is up to 15%. Consider checking for HLA-B^∗5801 in these groups before starting allopurinol. Not a pretty drug, but look on the bright side … it's not associated with meningitis!

It is 9 years later. Congress has passed a law banning the Kardashians from being on TV. Your favorite gout patient is back. He's had 9 years of acute intermittent gout attacks ("Of course I took my medication, Doc, but it didn't work so I stopped taking it"). He presents complaining of pain in his knees and feet that has been present for several months. He has also developed swelling and pain in his hands. The pain is less intense than his attacks of gout, but occurs in the same areas and never completely resolves between attacks. He has no morning stiffness, no muscle complaints, and no other systemic complaints. You find diffuse edema of both hands and palpable hard nodules on the knees, fingers, toes, and in the olecranon bursa.

Question 11.4.8 Which of the following is the most likely cause of his current symptoms?

A) RA.

B) Osteoarthritis.

C) Tophaceous gout.

D) PMR.

Answer 11.4.8 The correct answer is "C." This patient has a long history of acute intermittent gout. After years of acute attacks, patients with gout may develop a form of the disease called chronic tophaceous gout (the nodules are deposits of uric acid called tophi; tophus for a single nodule), in which the intercritical periods are no longer free of pain. There are no clinical associations between gout and the other rheumatic conditions mentioned and, therefore, no reason to suspect that another rheumatic disorder is causing the chronic pain.

Objectives: Did you learn to…

• Evaluate recurrent monoarthritis?

• Describe the diagnostic synovial fluid findings in gout?

• Define diagnostic criteria for gout?

• Manage a patient with gout and describe adverse effects of the medications used to treat gout?

• Identify the appropriate target uric acid level for urate-lowering therapy?

Citing your characteristic compassion and attention to detail, your "gout guy" (as he now calls himself) refers a friend he met at meeting of his favorite club, Gouty Retirees in Love with Life (GRILL). This friend of his is a 65-year-old female who reports a history of joint swelling, pain, and redness, usually involving her knees, wrists, and hands; she has never had first MTP joint involvement. Although she has never had a joint aspiration performed, she has been treated for gout for 5 years. She faithfully takes her medication but has found allopurinol unhelpful. She is currently asymptomatic, but uses ibuprofen for acute attacks. The joint examination is notable only for some knee crepitus and reduced wrist range of motion—but, again, she is currently asymptomatic.

Question 11.5.1 Which of the following studies is most appropriate for this patient?

A) Diagnostic knee injection with corticosteroids.

B) CBC.

C) RF.

D) Radiographs of the knees and wrists.

Answer 11.5.1 The correct answer is "D." The initial evaluation should include radiographs of the affected joints, which may lend clues to the diagnosis. Radiographs may reveal osteophyte formation typical of osteoarthritis, subchondral cysts, chondrocalcinosis typical of CPPD (calcium pyrophosphate dehydrate crystal deposition disease), or erosions with an overhanging edge typical of gout. Chondrocalcinosis is most often seen in the knees and triangular fibrocartilage of the wrists. "A," an injection of corticosteroids, might help relieve symptoms, but it will not be diagnostic. "B," CBC, is nonspecific and will not be helpful. "C," RF, is also unlikely to be helpful given this patient's symptoms, which are not suggestive of RA. Also, RF may be elevated in inflammatory arthritides other than RA, and so will not be helpful.

Your patient's knee radiographs demonstrate chondrocalcinosis (see Fig. 11-1). Examination of synovial fluid from the knee shows positively birefringent, rhomboid crystals consistent with CPPD (pseudogout) (maybe this is why her gout medicine wasn't working).

FIGURE 11-1. Chondrocalcinosis of the knee joint. (Note arrows highlighting calcification.)

Question 11.5.2 Which of the following do you recommend to decrease her risk of recurrent acute attacks of pseudogout?

A) Serial joint aspiration.

B) Daily allopurinol.

C) Twice-daily colchicine.

D) Serial intra-articular corticosteroid injections.

E) Chondroitin sulfate.

Answer 11.5.2 The correct answer is "C." Pseudogout is diagnosed by the presence of CPPD crystals (described above) in synovial fluid and/or typical x-ray findings (basically, chondrocalcinosis). Although prophylaxis is more predictably successful in gout, colchicine 0.6 mg BID has been shown to reduce the frequency of pseudogout attacks in CPPD. NSAIDs or colchicine may be used in acute attacks. "A" and "D" are incorrect. While joint aspiration and corticosteroid injection may be helpful during acute attacks, they have no role in prophylaxis. "B" is also incorrect. Since CPPD is not caused by abnormalities in uric acid metabolism, allopurinol has no role in the management of pseudogout. Finally, chondroitin sulfate is not useful in pseudogout.

Question 11.5.3 CPPD (pseudogout) is associated with which of the following?

A) Hypothyroidism.

B) Hyperparathyroidism.

C) Amyloidosis.

D) Hemochromatosis.

E) All of the above.

Answer 11.5.3 The correct answer is "E." All of the above are associated with pseudogout. Additional associated conditions include hypophosphatemia and hypomagnesemia. For this reason, order the following studies in patients newly diagnosed with CPPD: thyroid-stimulating hormone (TSH), calcium, phosphate, magnesium, transferrin saturation, and alkaline phosphatase.

Objectives: Did you learn to…

• Identify clinical and diagnostic characteristics of CPPD?

• Implement appropriate therapy for CPPD?

Cryoglobulinemia, a vasculitic disease caused by antibodies that precipitate in cold temperatures, is most often caused by which of the following viral infections?

A) HIV.

B) Hepatitis B.

C) Hepatitis C.

D) Parvovirus B19.

The correct answer is "C." Hepatitis C is found in 80% of vasculitis cases associated with mixed cryoglobulinemia. Although up to 50% of patients with hepatitis C will eventually express cryoglobulins, only a minority of patients have clinical vasculitis. As to the other options, hepatitis B and parvovirus B19 infection may cause a symmetric polyarthritis. HIV is less commonly a cause of cryoglobulinemia and is associated with reactive arthritis. The symptoms of mixed cryoglobulinemia associated with HCV infection typically include arthralgias, fever, renal disease, palpable purpura, and neuropathy.

A 13-year-old male presents to your office with his father. The patient complains of pain in his wrists, elbows, and knees bilaterally. He has felt fatigued and has been unable to work his usual summer job as a busboy at his father's restaurant. He complains of intermittent fevers and an evanescent rash that appears during febrile episodes but which is short lived. All of these symptoms have emerged in the last 6 weeks, after a week-long backpacking trip in the tick-infested woods of Minnesota. He has no significant past medical history. His only medication is acetaminophen daily for joint pain. He denies tobacco use, alcohol use, and sexual activity.

Question 11.6.1 The differential diagnosis should include all of the following EXCEPT:

A) Lyme disease.

B) JIA.

C) PMR.

D) Viral illness.

Answer 11.6.1 The correct answer is "C," of course. From earlier in the chapter, you will recall that the diagnosis of PMR is highly unusual in adults under the age of 50. JIA is a chronic arthritis of childhood that can present in a variety of ways, but must include arthritis of one or more joints, lasting 6 weeks or more, with symptom onset before age 16 years. Likewise, Lyme disease has several presentations, presenting with arthritis early or late in the course. Many viral illnesses can result in arthralgia and/or arthritis. Any of the diseases listed may have associated symptoms of fatigue, malaise, headache, and myalgia. One factor that makes Lyme disease a more likely diagnosis is the history of being outdoors in an endemic area (90% of Lyme disease in the United States occurs in New York, New Jersey, Connecticut, Rhode Island, Massachusetts, Pennsylvania, Wisconsin, and Minnesota).

Question 11.6.2 Which of the following findings on physical examination would be more consistent with Lyme disease than JIA?

A) Bell palsy.

B) Temperature ≥38°C.

C) Rash.

D) Lymphadenopathy.

E) A and C.

Answer 11.6.2 The correct answer is "A." All of the other findings are seen in both Lyme disease and JIA. Neurologic symptoms, including Bell palsy ("A") and even meningitis, may occur with Lyme disease but not JIA. Rash ("C") is present in both diseases but differs substantially. The characteristic rash of Lyme disease is erythema migrans. The rash of systemic-onset JIA (also known as Still Disease) is macular, salmon-pink, and brought on by heat. Erythema migrans occurs in about 80% of patients with acute Lyme disease. The lesion is often described as "targetoid," meant to convey a red circular rash with central clearing. However, most patients do not have the classic lesion. Instead, most patients present with a mildly to brightly erythematous patch in the axilla or belt line, where the tick bite occurs. The tick itself is rarely seen. Erythema migrans is usually not painful or pruritic. Both Lyme disease and JIA may have associated systemic findings, including fever and lymphadenopathy, so neither "B" nor "D" is a good discriminator.

Physical examination reveals a thin male in no acute distress. His temperature is 37.3°C, pulse 100 bpm, and blood pressure 120/70 mm Hg. Small, non-tender, mobile lymph nodes are palpable in the neck and axillae. There is a large, warm, erythematous patch with central clearing at the patient's left axilla. There is limited range of motion in his right wrist and left elbow. An effusion is palpable at the left knee, which is diffusely tender.

Question 11.6.3 If you were to aspirate the patient's knee—so often the right answer in this chapter—which of the following would you expect to find in the synovial fluid?

A) Greater than 100,000 WBC/mm³.

B) Predominance of eosinophils.

C) Monosodium urate crystals.

D) Spirochetes.

E) Predominance of polymorphonuclear cells.

Answer 11.6.3 The correct answer is "E." This patient is presenting now with classic features of Lyme disease. If synovial fluid is obtained in a patient with Lyme arthritis, analysis of the fluid reveals leukocytes, most commonly polymorphonuclear cells. "A" is incorrect. If the synovial fluid has >100,000 WBC/mm³, you should consider septic arthritis (arthritis in Lyme disease is mostly an immunological phenomenon rather than true septic arthritis). "B" is incorrect because eosinophils are not the predominant cell in synovial fluid of Lyme arthritis. "C" is wrong since monosodium urate crystals are observed in gout—an unlikely cause of this patient's joint complaints. Finally, "D" is wrong. In general, Borrelia burgdorferi spirochetes, the causative organism in Lyme disease, are not observed in the synovial fluid.

You strongly suspect Lyme disease. Because it is so swollen, you aspirate the joint and find slightly cloudy yellow fluid, with cell count 10,000/mm³, and 95% polymorphonuclear cells. Gram stain is negative and culture was subsequently found to be negative.

Question 11.6.4 Which of the following is true regarding laboratory tests for Lyme disease?

A) Serologic tests are reliable within 1 week of the tick bite.

B) Serologic tests are useful in screening for Lyme disease.

C) Blood cultures remain positive for B. burgdorferi for months after the tick bite.

D) Serologic tests remain positive for up to 10 years after antibiotic treatment.

E) The diagnosis of Lyme disease is based on serologic tests.

Answer 11.6.4 The correct answer is "D." Serologic tests for Lyme disease can remain positive for up to 10, and in some cases 20, years after exposure. Thus, serologic tests alone are not diagnostic of active Lyme disease. "E" is incorrect: the diagnosis of Lyme disease is clinical with laboratory tests used to confirm the diagnosis. A positive ELISA test is not adequate to make the diagnosis of Lyme disease. Positive or equivocal ELISA tests should be confirmed with Western blot analysis. "A" is incorrect: serologic assays may be falsely negative early in infection. "B" is incorrect. Lyme serology is set to be a very sensitive test: there are few false negatives assuming enough time has elapsed since Borrelia exposure, but it is not highly specific and there are many false positives. Because of the high false-positive rate, serologic assays should not be used as a screening tool in the general population but are a good step when Lyme disease is suspected. Most laboratories will automatically do a Lyme Western Blot study to confirm positive Lyme serology. "C" is incorrect: positive blood cultures for B. burgdorferi are rarely obtained. When cultures do grow B. burgdorferi, it is only early in the disease. Cultures of skin biopsied from the erythema migrans lesion are more likely to be positive.

Question 11.6.5 For this 13-year-old patient, whose weight is 50 kg and who has no known allergies, which course of therapy is safest and most efficacious?

A) Amoxicillin 500 mg by mouth three times daily for 1 week.

B) Ceftriaxone 2 g IM, single dose.

C) Doxycycline 100 mg by mouth twice daily for 4 weeks.

D) Levofloxacin 250 mg by mouth daily for 2 weeks.

E) Erythromycin 250 mg by mouth four times daily for 4 weeks.

Answer 11.6.5 The correct answer is "C." Recommended therapy for Lyme arthritis (without neurologic disease) is 4 weeks of either amoxicillin 500 mg three times daily, doxycycline 100 mg twice daily, or cefuroxime axetil 500 mg twice daily. This patient is old enough to take doxycycline, which is generally avoided in children <8 years old due to tooth discoloration. The duration of amoxicillin prescribed here is too short, so "A" is wrong. If this patient was younger and doxycycline was contraindicated, a 4-week course of amoxicillin or cefuroxime would be the preferred therapy. Ceftriaxone is prescribed when neurologic abnormalities are present (such as Bell palsy or meningitis), and it must be dosed daily for 2 to 4 weeks. Levofloxacin is not indicated for Lyme disease. Treatment with erythromycin for 4 weeks, while an acceptable alternative, appears to be less efficacious.

Several hours after starting antibiotics, the patient's father calls to reports worsening symptoms of fever, shaking, and dizziness.

Question 11.6.6 You recognize this condition as which of the following?

A) An allergic reaction to the antibiotic.

B) B. burgdorferi sepsis.

C) Secondary bacterial infection.

D) A cytokine-mediated reaction to the antibiotic-mediated killing of spirochetes (Jarisch–Herxheimer reaction).

E) The expected, natural course of Lyme disease.

Answer 11.6.6 The correct answer is "D." A Jarisch–Herxheimer reaction occurs in 5% to 15% of patients treated with antibiotics for Lyme disease. (Remember syphilis? Lyme is also a spirochete disease.) The reaction is mediated by the release of cytokines and occurs within hours of initial administration of antibiotics. In Lyme disease, the reaction is self-limited and usually resolves within a day. Only supportive treatment is necessary, and antibiotics should be continued (But hey, you know you got the diagnosis right!). "A" is incorrect because this reaction is not typical of a drug allergy. "B" is incorrect because B. burgdorferi does not cause sepsis. "C" is incorrect because it is unlikely that a secondary bacterial infection has occurred so quickly. Finally, this does not represent the natural history of Lyme disease ("E"). See Table 11-5 for more on the natural history of Lyme disease.

Since he spends much of his free time hunting deer in Minnesota (trying to shoot Bambi), your patient's father is worried about contracting Lyme disease himself.

Question 11.6.7 What do you recommend for primary prevention of Lyme disease?

A) Weekly tick checks.

B) N, N-diethyl-m-toluamide (DEET) application prior to hunting.

C) Daily doxycycline when in endemic areas.

D) Lyme vaccine.

E) Kill as many deer as possible in order to reduce the risk of Lyme disease transmission to humans.

Answer 11.6.7 The correct answer is "B." Primary prevention is best accomplished with the use of insect repellents when in endemic areas. Also, when in endemic areas, tick checks should be performed daily (not weekly as in answer "A"). A tick that has been attached for <24 hours is not likely to transmit B. burgdorferi. Unfortunately, the species that transmits Lyme disease (ticks of the Ixodes ricinus complex) are very small and difficult to see. "C" is incorrect. There is no role for routine prophylactic antibiotics. However, if a tick bite from the appropriate species is noticed, a single dose of doxycycline 200 mg administered orally reduces the risk of erythema migrans. The dose should be administered within 72 hours of a known I. ricinus tick bite. "D" is not an option for this patient. In 2002, the vaccine was removed from the U.S. market due to low demand. When it was available, antibody titers tended to wane quickly and protection was not complete. After the administration of three vaccinations, the efficacy of the vaccine to prevent Lyme disease was 76% at best. "E" is just plain wrong … what with Bambi and all … And furthermore, the white-footed field mouse, not the white-tailed deer, is the major reservoir of B. burgdorferi bacteria.

Objectives: Did you learn to…

• Describe the appropriate evaluation of polyarthritis?

• Diagnose Lyme disease?

• Describe the stages of Lyme disease?

• Implement appropriate therapy for Lyme disease?

• Discuss preventive strategies for Lyme disease and describe some of the complications of the disease?

A 42-year-old female who was referred by an orthopedic surgeon presents to your office with multiple joint complaints. The orthopedist has seen her for left knee pain, intermittent swelling, occasional "clicking and locking," present for about 10 years. After knee radiograph and examination, the orthopedist diagnosed a chronically damaged meniscus, but he wants the patient evaluated by you for her other joint complaints.

Laboratory data ordered by her orthopedist (apparently, just to confuse you) show an ANA 1:320 (speckled pattern) and an ESR 20 mm/hr. The patient moved to the United States from Guam 4 years ago. She reports poor sleep and feeling quite depressed. She feels that she has no friends, and she has had trouble adjusting to the colder weather. You notice she has a bottle of water with her and upon your specific questioning she states, "I have to sip some water throughout the day. I've done this for the last 15 years because my mouth gets so dry." Over the past twenty years, she has had numerous fillings for dental cavities. She denies problems with skin rash, swallowing, and eye pain. She does not use artificial tears.

Question 11.7.1 Which of the following findings in this patient is most likely to be a sign of inflammatory arthritis?

A) Spider angiomas (telangiectasia) on the back and abdomen.

B) A small cool left knee effusion ("bulge sign") with crepitus.

C) Presence of 16/18 fibromyalgia tender points, with nontender control points.

D) Incomplete left grip.

E) Presence of a holosystolic murmur at the left sternal border, without radiation.

Answer 11.7.1 The correct answer is "D." Although her symptoms are suggestive of fibromyalgia and depression, it is critical to differentiate between an inflammatory and a non-inflammatory condition, especially since many inflammatory disorders (e.g., SLE, RA, Sjögren syndrome) may masquerade as fibromyalgia. An incomplete grip in an otherwise healthy young woman is suggestive of synovitis, which can be further assessed by careful small joint examination. When synovitis is present, it is always abnormal and suggests an inflammatory arthritis, requiring further evaluation. "A" is incorrect because telangiectasias on the abdomen and trunk are typically related to liver disease, while those found on hands and nail beds are associated with systemic sclerosis and other rheumatic diseases. "B," a positive knee "bulge sign" (swelling of the knee joint that bulges inferiorly when compressed superiorly), indicates fluid in the left knee joint. But from the patient's history and your orthopedic colleague's determination, this finding is chronic and mechanical in nature. "C," the presence of 16/18 tender points, would argue for fibromyalgia but would not help to differentiate between inflammatory and non-inflammatory disorders. Additionally, identifying greater than 11 out of 18 tender points is no longer part of the diagnostic criteria for fibromyalgia (keep reading for details). Finally, a holosystolic murmur ("E"), localized to the left sternal border and present in a healthy young woman, is nonspecific and most likely functional. If there were other signs and symptoms of cardiac disease, the murmur might indicate a more serious disorder.

On physical examination, you find a "bulge sign" on the left knee, but no other joint swelling. She has 16/18 tender points and normal range of motion and strength. The neurological examination is grossly normal, except for poorly defined numbness and pain to touch on the left side of her face. You also notice a mildly tender, hard, nodular swelling behind the angle of the mandible on the left in the area of the parotid gland. Her oral mucosa appears dry. Her conjunctiva is mildly, symmetrically injected.

Question 11.7.2 All of the following studies and interventions are appropriate EXCEPT:

A) CBC, transaminases, ESR, CRP.

B) Anti-SS-A (Ro), anti-SS-B (La), anti-dsDNA, RF, serum protein electrophoresis.

C) Prescribe trazodone 50 mg PO at bedtime and recommend aerobic exercises.

D) Prescribe prednisone 20 mg PO daily, with calcium and vitamin D supplement.

E) Maxillofacial MRI.

Answer 11.7.2 The correct answer (and the thing to avoid right now) is "D." Although prednisone may be used to treat symptoms of autoimmune diseases, at this time the diagnosis is not secure, and initiating corticosteroid therapy exposes the patient to potentially unnecessary risk. She has findings of Sjögren syndrome—red (possibly dry) eyes, dry mouth, and enlarged parotid glands. However, the differential of mass in the parotid gland must include malignancy (e.g., lymphoma), sarcoidosis, and other autoimmune diseases. The laboratory tests offered in answers "A" and "B" may help assess other organ involvement of Sjögren syndrome and also aid in confirming the diagnosis. Other potential manifestations of Sjögren syndrome include generalized vasculitis, interstitial lung disease, cirrhosis, peripheral and cranial neuropathies, possibly thyroid disease, and renal disease leading to proteinuria and renal tubule dysfunction. Although not listed as an option, chest radiograph may also be helpful, assessing for findings associated with the diseases on your differential: Sjögren syndrome (interstitial lung disease), sarcoidosis (adenopathy and interstitial disease), and lymphoma (adenopathy). "E" is also important because although parotid enlargement may be seen in Sjögren syndrome, it is usually symmetrical and non-tender. An imaging study is appropriate to rule out a neoplastic process. Finally, "C" is correct. Her symptoms of fibromyalgia may respond to trazodone and exercise, and these low-risk interventions are appropriate at this juncture.

She starts trazodone and exercise and feels better. The tests you order return as follows: negative SSA, SSB, and dsDNA; elevated RF; no monoclonal protein on SPEP but diffusely elevated globulins. A chest x-ray is normal. Her ESR is 35 mm/hr and CRP 0.5. A maxillofacial MRI shows an enlarged left parotid, with an ill-defined 2 × 3 × 1.5 cm dense signal in the center without neurovascular compromise.

Question 11.7.3 What is the most appropriate next step in the management of this patient?

A) Continue your current management and adopt a "watchful waiting" approach.

B) Refer for biopsy of the left parotid.

C) Initiate prednisone 20 mg PO daily, with calcium and vitamin D.

D) Refer for minor salivary gland biopsy (lip biopsy).

E) MRI of the head and neck.

Answer 11.7.3 The correct answer is "B." Even though her presentation is suggestive of Sjögren syndrome, the presence of a mass-like formation on MRI is concerning for lymphoma, and further evaluation (e.g., biopsy) is required. Additionally, the negative SSA and SSB, while not excluding Sjögren syndrome, will make a biopsy necessary for diagnosis. Although a minor salivary gland biopsy ("D") is the most specific way to confirm a diagnosis of Sjögren syndrome, the first priority is to evaluate the parotid gland mass. The elevated RF and polyclonal gammopathy are consistent with Sjögren syndrome, and the ESR may be elevated due to increased globulins. MRI of the head and neck ("E") may provide some structural information but it is not in the diagnostic criteria for Sjögren Syndrome.

Results of the parotid gland biopsy report read, "Lymphocytic infiltrate, no malignant cells noted." You then order flow cytometry, and it has no markers for lymphoma. Her biopsy scar has healed nicely, and she has no pain or numbness. You believe that she probably has Sjögren syndrome.

Question 11.7.4 What would you do next?

A) CT chest/abdomen/pelvis.

B) Start prednisone 20 mg by mouth daily, with calcium and vitamin D.

C) Recommend sugarless lemon drops and artificial tears as needed and continued trazodone and exercise.

D) Wide excision of the parotid gland.

Answer 11.7.4 The correct answer is "C." Lemon drops (or anything sour for that matter) will stimulate saliva production, helping with her dry mouth. Artificial tears may also be indicated for dry eyes. At this time your working diagnosis is Sjögren syndrome, and definitive diagnosis by minor salivary gland biopsy (from the buccal mucosa of the lower lip) is not likely to alter your therapy; and "D" is way too aggressive anyway. Since she has responded to trazodone and exercise and there is no evidence of systemic involvement, no further anti-inflammatory therapy ("B") is warranted. If she were to develop arthritis or other signs of systemic involvement (e.g., cognitive dysfunction or peripheral neuropathy), prednisone would be an option. Further work-up for lymphoma, such as CT scanning ("A"), does not appear warranted. However, she will require active surveillance, since patients with Sjögren syndrome carry an increased risk of developing lymphoma.

Objectives: Did you learn to…

• Describe the appropriate evaluation of polyarthralgia and sicca symptoms?

• Evaluate a patient with probable Sjögren syndrome?

• Implement appropriate therapy for Sjögren syndrome?

Once again, your fabled diagnostic and therapeutic abilities have earned you a well-deserved referral. Your previous patient is so pleased with the way things are going that she refers her sister-in-law to you. The sister-in-law is 46 years old and reports having been diagnosed with fibromyalgia several months ago. She reports having all-over pain, all the time, which has been worsening for the last 5 years. You thank the patient for the referral … NOT. She takes only acetaminophen and codeine as needed for pain (she typically needs it four times per day). She does not exercise because it hurts too much. She drinks 2 liters of Mountain Dew a day, from sun-up to sundown. Her sleep is reported as poor and nonrestorative.

Question 11.8.1 Which of the following statements is true regarding management of fibromyalgia:

A) Fibromyalgia pain is increased during exercise, so exercise should be avoided.

B) Regular low impact exercise, and non-pharmacologic measures to improve sleep are more effective than medications for improving fibromyalgia-type pain.

C) SNRI agents such as duloxetine and milnacipran lead to rapid and long-term remission of fibromyalgia-type pain.

D) Both NSAIDs and prednisone are helpful for reducing fibromyalgia pain.

E) Opioids act on the central nervous system, which is why they are the most effective agents for treatment of fibromyalgia pain.

Answer 11.8.1 The correct answer is "B:" improved sleep through good sleep hygiene, and regular low-impact exercise are often more effective than medications for reducing fibromyalgia-type pain. Indeed, improving sleep and exercise (and identifying any underlying sleep disorder) are central to long-term management. "A" is incorrect: even when exercise is poorly tolerated due to pain, a program of stretching and gradually increasing exercise is very helpful to reduce pain over time. SNRI agents are helpful for reducing central pain sensitization, and are important adjunctive treatment to sleep and exercise, but they are not curative and do not provide rapid pain relief. "D" is incorrect: NSAIDs and prednisone are not effective for fibromyalgia-type pain. Opioids do act on the central nervous system, and can lead to short term reduction of fibromyalgia-type pain, but at the same time they increase central pain sensitization which can actually lead to worsening of pain (opioid-induced hyperalgesia).

Question 11.8.2 Which of the following is NOT an appropriate medication for treating fibromyalgia-type pain?

A) Hydrocodone/acetaminophen

B) Gabapentin or pregabalin

C) Amitriptyline

D) Duloxetine

E) Combination duloxetine and pregabalin

Answer 11.8.2 The correct answer is "A." Is there a theme emerging here? Narcotics will provide a short-term reduction in pain, but tend to worsen central sensitization and actually increase fibromyalgia pain over time; they should be avoided in managing this type of pain. All of the other agents have shown efficacy in improving pain associated with fibromyalgia. Tricyclic antidepressants have the best efficacy. SNRI agents such as duloxetine may be combined with a gabapentin or pregabalin as can tricyclics.

FIGURE 11-2. Tender points in fibromyalgia.

Question 11.8.3 All of the following are associated with fibromyalgia EXCEPT:

A) Irritable bowel syndrome.

B) Subjective fullness/swelling of hands and feet.

C) Paresthesias.

D) Fatigue.

E) Night sweats.

Answer 11.8.3 The correct answer is "E." All of the others are associated with fibromyalgia. Additional symptoms include headaches, depression, sleep disturbance (which may actually be the etiology), other GI symptoms, and urethral spasm with dysuria and urgency.

Objectives: Did you learn to…

• Identify typical symptoms of fibromyalgia?

• Define diagnostic criteria for fibromyalgia?

• Implement appropriate therapy for fibromyalgia?

All of the following diseases and conditions are secondary causes of osteoarthritis EXCEPT:

A) Fibromyalgia.

B) Hemochromatosis.

C) Hyperparathyroidism.

D) Amyloidosis.

E) Previous joint trauma.

The correct answer is "A." One of the most common secondary causes of osteoarthritis is previous joint trauma. Systemic diseases that can lead to osteoarthritis include hemochromatosis, hyperparathyroidism, and amyloidosis. Fibromyalgia does not cause osteoarthritis. Any disease that leads to a neuropathy, such as diabetes, can predispose to osteoarthritis (e.g., Charcot arthropathy).

A 25-year-old female presents to your office complaining of bifrontal headaches, occurring intermittently over the last year. Also, she complains of fatigue that seems to be slowly worsening. Over the last 2 to 3 months, she has developed generalized joint pain and stiffness. The remainder of the history, including a detailed review of systems, is unremarkable.

On physical examination, you find a thin female in no acute distress. She is afebrile with a blood pressure of 110/62 mmHg and a pulse of 72 bpm. The joint examination shows full range of motion and no swelling. There is mild anterior cervical lymphadenopathy. Close inspection of her skin reveals erythema of the malar eminences and the nose laterally, with involvement of the nasolabial folds. You note flaking and scaling in the eyebrows.

Question 11.9.1 The RASH is most characteristic of which of the following diagnoses?

A) Dermatomyositis.

B) SLE.

C) Seborrheic dermatitis.

D) Psoriasis.

Answer 11.9.1 The correct answer is "C." The classic rash of SLE is the malar, or "butterfly," rash with erythema over the malar eminences, bridging over the base of the nose. However, the nasolabial folds are spared with the lupus malar rash. Involvement of the nasolabial fold characteristically occurs in seborrheic dermatitis. In dermatomyositis, facial lesions involve the upper lids and have a light reddish-purple hue (the so called "heliotrope rash"). Flat-topped, violaceous papules over the knuckles (Gottron papules) are classic features of dermatomyositis. The typical lesions of psoriasis include erythematous papules and plaques with silvery scales, noted more commonly on extensor surfaces.

Question 11.9.2 Which of the following diagnoses or descriptions most accurately describes your patient's disease process at this point in time?

A) Fibromyalgia.

B) Somatoform disorder.

C) Polyarthritis.

D) Polyarthralgia.

E) RA.

Answer 11.9.2 The correct answer is "D." Your patient complains of pain in multiple joints but has no findings of inflammation of the joints; therefore, the designation of "polyarthralgia" fits best at this time. If multiple joints were inflamed, you would use the term polyarthritis. At this time, you do not have enough information to make any of the other diagnoses.

You screen for depression and anxiety and find neither. You recommend acetaminophen for joint pain and headaches and encourage her to exercise regularly. She returns 2 months later feeling worse. She has severe fatigue and joint pain, most commonly involving her hands and knees. She has taken a leave of absence from her job as a high school English teacher. New symptoms include sores in her mouth as well as chest pain, which is worse with inspiration. On examination, you note the presence of a cardiac friction rub. There is diffuse tenderness to palpation of both knees and a small effusion apparent in the left knee. Her left hand demonstrates slow, incomplete grip. The facial rash is barely noticeable. There are two nontender ulcerations of the oral mucosa. The remainder of the examination is unchanged from her previous visit.

Question 11.9.3 Her disease process and current findings are most suggestive of which of the following diagnoses?

A) Lymphoma.

B) SLE.

C) Fibromyalgia.

D) Reactive arthritis.

E) Limited scleroderma (CREST syndrome).

Answer 11.9.3 The correct answer is "B." While she does not meet all the criteria for a diagnosis of SLE, this presentation is more consistent with SLE than any of the other options. Several findings point toward SLE: arthritis, cardiac friction rub (presumably due to pericarditis), and painless oral ulcers. Keep reading for more on the diagnostic criteria for SLE.

Based on your history, you recognize that your patient may be at higher than normal risk for developing SLE.

Question 11.9.4 All of the following groups have a higher incidence of SLE than the general population EXCEPT:

A) Family members of patients with SLE.

B) Females.

C) Asian Americans.

D) Age in the third to fifth decades.

E) Caucasians.

Answer 11.9.4 The correct answer is "E." Compared to other groups, Caucasians have a lower risk of SLE. The peak incidence of SLE occurs in the third to fifth decades of life. Women are 5 to 10 times more likely than men to be diagnosed with SLE. First-degree relatives of patients with SLE are at higher risk as well. Twin studies have shown a 25% to 50% concordance rate among monozygotic twins.

You consider that this might represent drug-related lupus, but your patient denies using any medications except for acetaminophen.

Question 11.9.5 In drug-related lupus, you expect to see all of the following EXCEPT:

A) Negative ANA.

B) Rapid resolution of symptoms after discontinuing the drug.