Challenging Rheumatology

Cases

Robert H. Shmerling, MD

Clinical Chief/Rheumatology

Beth Israel Deaconess Medical Center

Harvard Medical School/Boston MA

Case 1

A 41 y/o woman is evaluated for intermittent pain and cyanosis of the fingers associated with exposure to cold temperatures. She does not smoke, and her efforts to keep room temperatures warm and to wear gloves and layers of clothing to maintain her core temperature have not been helpful. Examination: BP = 125/70 mm Hg, HR= 88/min. Skin exam is normal; radial and ulnar pulses are normal.

Which of the following is the most appropriate additional treatment for this patient?

A) Amlodipine

B) Isosorbide dinitrate

C) Prednisone

D) Propranolol

https://en.wikipedia.org/wiki/Raynaud_syndrome

Raynaud’s Phenomenon (A)

Best option: A – Amlodipine – calcium-channel blockers are first-line pharmacologic treatment (when Rx required)

◼ Isosorbide dinitrate – nitrates are less effective than calcium channel blockers, second-line agents

◼ Prednisone – ineffective for this non-inflammatory process

◼ Propranolol – ineffective and relatively contraindicated (may worsen vasospasm by “unmasking” alpha-mediated vasoconstriction)

• Cold-induced digital arterial spasm

• Color changes:

• reduced perfusion (white)

• ischemia (blue), then

• reperfusion hyperemia (red)

• Disruption of normal mechanisms controlling vessel reactivity

• Primary: common, benign, especially in young women;

significant ischemic disease rare in primary disease

• Secondary (associated with rheumatic disease):

• Abrupt onset, sclerodactyly, severe/difficult to control, digital

infarct or gangrene

• Associated rheumatic diseases – Systemic sclerosis

(Scleroderma; limited or diffuse), SLE, MCTD

• Limited disease: CREST (Calcinosis, Raynaud’s,

Esophageal dysmotility, Sclerodactyly, Telangiectasia)

Raynaud’s Phenomenon (A)

Raynaud’s Phenomenon

Nailfold microscopy

Normal

Raynaud’s Phenomenon

Management

◼ Non-pharmacologic may be all that’s needed – avoid cold!

◼ Education (e.g., core temperature matters, bundle up, use hand warmers)

◼ Thermostat adjustment

◼ Avoid triggers (e.g., frozen food section), avoid smoking

◼ Pharmacologic (off label)

◼ Vasodilators◼ calcium channel blocker is best initial therapy, e.g., nifedipine,

diltiazem, amlodipine

◼ ARBs, nitrates, prazosin, hydralazine, sildenafil, many others can be effective

◼ Vigilance for development of SLE, scleroderma (consider “screening” ANA, at least yearly assessment of symptoms, urinalysis, CBC)

Case 2

A 76 y/o man has a preoperative evaluation before total joint arthroplasty of the right knee; +Hx x 24-years of rheumatoid arthritis. Medications: methotrexate, folic acid, hydroxychloroquine, and prednisone. PE: bilateral ulnar deviation and swan neck deformities. Extension of the cervical spine is painful and decreased. Extension of the right knee is decreased by 10 degrees and flexion is limited to 110 degrees. Laboratory studies: normal, including the complete blood count, creatinine, and CXR

Which of the following preoperative diagnostic studies should be performed in this patient?

A) ESR and CRP

B) Cervical spine radiograph

C) Spirometry

D) Urinalysis

E) RF and anti-CCP

Cervical Spine Disease in Rheumatoid Arthritis (B)

◼ Unstable C-spine disease represents one of the few rheumatologic emergencies in RA, especially if atlantoaxial involvement◼ Myelopathy with sudden onset paraplegia

◼ Risk factors include:◼ Longstanding RA, especially seropositive (RF, anti-CCP)◼ Erosive disease◼ Extra-articular disease

◼ Should be suspected in setting of risk factors (as above) with suggestive clinical features including:◼ neck pain and loss of motion◼ radiculopathic symptoms (e.g., parasthesia, weakness in

extremities)◼ Occipital headache◼ Loss of coordination◼ Urinary incontinence or retention

Cervical Spine Disease in Rheumatoid Arthritis

◼ May be asymptomatic until late in course – so, important to consider in pre-op. evaluation if intubation planned

◼ Avoid intubation if possible

◼ Evaluation/treatment:

◼ risk assessment/neurologic examination

◼ c-spine radiographs in flexion & extension (for any patient with long-standing/aggressive RA prior to elective intubation) → consider MRI

◼ RF/anti-CCP – Useful for diagnosis, not for pre-op

◼ Spirometry – no clear role with no pulmonary symptoms

◼ ESR/CRP – non-specific, not likely to alter plans

◼ Urinalysis – with normal creatinine, unlikely to detect renal disease; no clear indication to test pre-Op in person without urinary symptoms

Spondylolisthesis (subluxation) of cervical spine in

rheumatoid arthritis

Rheumatoid arthritis – increased space from post. arch of C1 to ant. odontoid (dens)

Normal

Standard views of c-spine may miss instability – need flexion/extension views

Case 3

A 24 y/o woman with systemic lupus erythematosus (SLE) for 5 years

has been treated with low dose prednisone & hydroxychloroquine. Due

to recent rash and arthralgia, azathioprine was added to her regimen.

Today she feels much better.

Physical examination: T= 97.6 °F, BP= 130/76 mm Hg, HR=76/min.

She is cushingoid but otherwise examination is normal.

Lab studies: Hgb= 9.5 g/dL (baseline: 12.0), WBC=1600/µL (baseline:

4300), Platelet count =135,000/ µL (baseline 245); Complement

studies, anti-ds-DNA and urinalysis are normal.

Which of the following is the most likely cause of her laboratory

findings?

A) azathioprine

B) hydroxychloroquine

C) prednisone

D) active SLE

Case 3 – SLE (A)◼ SLE is a disease with protean manifestations

◼ Criteria are for studies but a useful guide◼ Revised in August 2019 (see next slide)

◼ This patient has pancytopenia – could be SLE-related

◼ But, always consider non-SLE possibilities: e.g., viral, drug-induced, marrow infiltration

◼ Flares are typically multi-organ

◼ Need to r/o other explanations – timing favors azathioprine-induced pancytopenia

2019 SLE Classification CriteriaHighlights:

• For research, not diagnosis (but good starting point)

▪ Must have +ANA, > 1:80, at least 1 clinical criterion & >10 points

▪ Weighted criteria

▪ No points for criterion if another likely explanation

▪ Only highest count used within a domain

▪ Fine print for each: eg, Non-scarring alopecia observed by a clinician or by photograph

Aringer M, et al. Arthritis Rheum (online Aug 2019)

Azathioprine is metabolized by xanthine oxidase (XO) and thiopurine methyltransferase (TPMT)

◼ inhibiting XO with allopurinol or febuxostat or having low TPMT levels predispose to myelotoxicity

◼ many experts suggest screening TPMT prior to azathioprine treatment

Other, less appealing choices:

◼ Hydroxychloroquine - not myelotoxic, not new

◼ Prednisone – usually raises WBC, not myelotoxic

◼ Active SLE - no symptoms/findings on exam; the cytopenias are “discordant” suggesting another cause

Pancytopenia in SLE

A. This patient probably has Granulomatosis with Polyangiitis(GPA).

B. Therapy for GPA should be initiated while awaiting the results of other studies.

C. The positive ANCA is probably due anti-MPO (anti-myelo-peroxidase).

D. The positive ANCA is probably not due to anti-MPO and may be related to this patient’s history of ulcerative colitis.

E. The positive ANCA is probably due to anti-PR3 (anti-proteinase-3), but such a result is not diagnostic of GPA.

Case 4A 34 y/o woman with ulcerative colitis feels well but is found microscopic hematuria. She reports mild sinus pressure and congestion for the past week. An anti-neutrophilic cytoplasmic antibody (ANCA) is ordered and returns positive in moderate titer with p-ANCA pattern. Which of the following is true?

A. This patient probably has Granulomatosis with Polyangiitis(GPA). Nonspecific symptoms, she feels well

B. Therapy for GPA should be initiated while awaiting the results of other studies. Diagnosis is not established, non-urgent scenario, toxic therapy

C. The positive ANCA is probably due to anti-MPO (anti-myeloperoxidase). Patient has ulcerative colitis, a known cause of p-ANCA without anti-MPO specificity.

D. The positive ANCA is probably not due to anti-MPO and may be related to this patient’s history of ulcerative colitis. Correct!

E. The positive ANCA is probably due to anti-PR3 (anti-proteinase-3), but such a result is not diagnostic of GPA.

Anti-PR3 specificity causes c-ANCA pattern (not p-ANCA)

Positive ANCA (D)

Antineutrophilic cytoplasmic antibody (ANCA)

c-ANCA (cytoplasmic) p-ANCA (peri-nuclear)Usually anti-

proteinase-3

(PR-3)

Often anti-

myeloperoxidase

(MPO)

Rheumatic Disease: c-ANCA/PR3 p-ANCA/MPO

Granulomatosis w/ polyangiitis 80% 10%

Microscopic polyangiitis 20% 50%

Eosinophilic Granulomatosis 10% 40%

w/ polyangiitis

Other vasculitides generally ANCA-negative: hypersensitivity, Henoch-Schönlein purpura (HSP), polyarteritis nodosa, GCA, Takayasu’s

ANTI-NEUTROPHIL CYTOPLASMIC

ANTIBODIES (ANCA)

Note: RA, SLE, Sjogren’s, other rheumatic disease may be associated with nonspecific p-ANCAs (non-MPO)

ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)

ANCA in non-rheumatic disease: cANCA/PR-3 pANCA/MPO

Idiopathic crescentic GN 10-20% 65-75%

Anti-GBM Disease 10% 30-40%

Nonspecific pANCAs (that is, not directed against MPO) also observed in:

• Ulcerative colitis & autoimmune hepatitis

• Cystic Fibrosis

• Infection: leprosy, malaria, SBE

• (Pre)eclampsia, diffuse alveolar hemorrhage, graft-versus-host disease

Positive ANCA

◼ A positive ANCA is not diagnostic of vasculitis

◼ Anti-PR-3 (with c-ANCA) and anti-MPO (with p-ANCA) are highly specific for ANCA-associated vasculitis or pauci-immune glomerulonephritis

◼ A negative ANCA is the rule for the smallest vessel vasculitides (e.g., Hypersensitivity Vasculitis) or the largest vessel vasculitides (e.g., Temporal Arteritis)

◼ A positive p-ANCA without anti-MPO is nonspecific and may be associated with ulcerative colitis & other conditions

Case 5The patient is a 36 y/o man with a chief complaint of arthralgia. For the last 2 years, he has experienced pain, stiffness and swelling in several fingers, toes, and left ankle that vary in intensity. Ibuprofen has provided modest relief. Physical examination reveals that the symptomatic joints are swollen, warm, and have limited motion. There is pitting of the fingernails. The appearance of his toes are demonstrated below.Which of the following is the most likely diagnosis?

A. OsteoarthritisB. Reactive arthritisC. Psoriatic arthritisD. Disseminated gonococcal

infectionE. Rheumatoid arthritis

◼ Clinical presentation:◼ Sausage digit (dactylitis) and tenosynovitis◼ Asymmetric oligoarthritis, especially DIPs◼ Symmetric polyarthritis◼ Spondylitis◼ Arthritis mutilans◼ Seronegative

◼ Overall – 15-30% of psoriasis◼Associated with nail pitting, extensive skin

disease◼Nail pitting may be the only cutaneous

manifestation of psoriasis

Case 5 – Psoriatic arthritis (C)

◼ Pharmacologic Management◼ NSAIDs, corticosteroid injections◼ Methotrexate (helps skin and joints), leflunomide◼ Anti-TNF agents (e.g., adalimumab, certolizumab,

etanercept, golimumab, infliximab)◼ Newer approved medications:

◼ apremilast (Otezla) – inhibits phosphodiesterase & tofacitinib (Xeljanz) – inhibits janus kinase →both oral!

◼ secukinumab (Cosentyx), ixekizumab (Taltz) – anti-IL-17◼ ustekinumab (Stelara) – anti-IL12 & anti-IL23

◼ Less appealing choices:◼ Osteoarthritis – inflammatory findings, nail pitting, dactylitis

don’t support dx◼ Reactive arthritis – nail pitting argues against this dx◼ Disseminated gonococcal infection – chronicity argues

against this dx◼ Rheumatoid arthritis – dactylitis, nail pitting, oligoarticular

presentation argue against this dx

Psoriatic arthritis

Arthritis mutilans

(variant of psoriatic arthritis)

Psoriatic arthritis“Pencil in cup”

erosion

Rheumatoid arthritismarginal erosion

Case 6A 25 y/o female preschool teacher describes 2 weeks of symmetric pain and stiffness in the small joints of the hands and feet. Physical examination is normal except for mild diffuse soft-tissue swelling of the hands and feet bilaterally. The metacarpo-phalangeal and metatarsophalangeal joints are tender to palpation.Laboratory studies: Blood counts and urinalysis - Normal

RF+ 1:80 ; ANA: + 1:40Which of the following tests will be most helpful in establishing this patient’s diagnosis?

A) Anti-cyclic citrullinated protein (anti-CCP)B) Anti-Smith antibodyC) IgM antibodies against parvovirus B19D) Anti-Jo-1 antibodyE) No further testing is necessary

Case 6 – Parvovirus B19 infection (C)

◼ An important mimic of RA

◼ Adults often have no rash or nonspecific exanthem; fatigue, joint pain, fever; kids tend to get “slapped cheek” rash

◼ “Vector” is young children◼ Day care workers, teachers, parents of young kids are at risk

◼ Self-limited, resolves within 4-6 weeks, NSAIDs useful

◼ Diagnosis is clinical & +IgM against Parvovirus B19 –appears 7-10 days after infection, present for months

◼ Other names: Erythema infectiosum, Fifth Disease

◼ Chronic infection in immunocompromised host; aplastic crisis with sickle-cell disease.

◼ May cause fetal hydrops and fetal death if disease occurs during pregnancy

◼ Transmission: respiratory secretions between humans

2010 ACR/EULAR classification criteria

for Rheumatoid Arthritis

Criteria to apply to those who:

• have at least 1 joint with definite clinical synovitis

• synovitis not better explained by another disease

Less appealing options:

• anti-CCP – RA is a reasonable consideration given polyarthritis of small joints but impossible to diagnose with symptoms for only 2 weeks; in addition, she has risk factors for parvovirus infection

• anti-Sm – given +ANA & polyarthritis, SLE is a consideration and +anti-Sm is specific for SLE, but no other suggestive features (photosensitive rash, serositis, cyotpenias, etc.); chronicity lacking

• anti-Jo-1 – one of the myositis-specific antibodies, found in dermatomyositis but no mention of muscle weakness, elevated CK, or rash

Parvovirus B19 infection

• The only virus in the parvoviridae family that infects humans

• Named for blood bank code (“B19”) of a viremic donor from whom it

was first identified

From: www.wadsworth.org/databank/hirez/gradyp2.gif

Case 7A 52 y/o woman has a history of hypercholesterolemia treated with atorvastatin for years. 6 months ago, she developed achy thigh muscles. At that time, laboratory studies revealed a serum creatine kinase (CK) level of 430 U/L (nl < 200 U/L) & her statin was stopped. Since then, CK has remained elevated. She is now nearly asymptomatic with minimal myalgia after long walks. Physical examination is normal, including motor examination. Laboratory studies reveal a serum CK level of 550 U/L and a normal serum thyroid-stimulating hormone level. Which of the following diagnostic studies would be warranted for this patient?

A. AldolaseB. Rheumatoid factorC. Erythrocyte sedimentation rateD. MRI scan of the thigh musclesE. Review of CK results prior to statin treatment

Case 7– Elevated CK (E)◼ In absence of weakness or rash, significance of mild-

moderate elevation in CK is uncertain◼ May be irrelevant to health◼ Extensive testing, empiric treatment often unnecessary

with minor/incidental CK findings◼ Statin-induced myopathy:

◼ Usually within weeks/months of starting statin◼ Myalgia with or without elevated CK◼ Improvement within weeks to months of stopping statin

◼ In presence of weakness or myalgia:◼ EMG - ? myopathy ◼ MRI - ? evidence of muscle inflammation, as guide to site

of biopsy◼ Muscle biopsy – depending on EMG and/or MRI results◼ Review old CK measures if available – if always mildly

elevated, may be “normal variant”

◼ Less optimal options:

◼ Aldolase – unnecessary as CK is sufficiently sensitive and specific measure of muscle disease

◼ RF - Occasionally positive in polymyositis and dermatomyositis but does not aid in diagnosis; no suggestion of rheumatoid arthritis

◼ ESR – Often normal or unimpressive in setting of idiopathic myositis, even if high, it is nonspecific

◼ MRI scan of proximal muscle groups – sensitive but nonspecific for inflammatory myopathy but may not be necessary (e.g., low suspicion of myositis without weakness, mildly increased CK), especially if CK elevation is unchanged

Elevated CK

Causes of elevated CPK: I’M TIRED

• I diopathic – varies by ethnicity, gender; men > women; African-American > Caucasian

• M yocardial, Metabolic – e.g. Becker's muscular dystrophy• T rauma, Tumor• I nfection – e.g., HIV, coxsackie, pyomositis, trichinosis• R heumatic disease - polymyositis, dermatomyositis,

inclusion body myositis; SLE, MCTD, vasculitis• E ndocrine – Hypothyroidism > hyperthyroidism, diabetic

myonecrosis• D rugs – especially statins, AZT, cocaine, many others

Elevated CK

MRI in

myositis

Case 8

A 48 y/o woman has a 4-month history of pain in the shoulders, neck, and lower back. She also has fatigue and difficulty sleeping. Review of systems otherwise negative. Physical examination is normal except for widespread soft-tissue pain to palpation. The joints are not swollen. CBC, ESR, CK and TSH are normal.

Which of the following is the most appropriate next step in this patient’s management?

A) Aerobic exercise programB) Rheumatoid factorC) ElectromyographyD) TramadolE) Prednisone

Case 8– Fibromyalgia (A)

◼ American College of Rheumatology criteria (Wolfe F, et al Arthritis Rheum 1990;33:160)◼ Widespread pain for 3 or

more months – both sides of the body, above & below the waist, & axial

◼ Pain in 11 or more 18 tender points with palpation at force of 4 kg (enough to make examiner’s nail blanch)

New Criteria (2019) for FibromyalgiaJ Pain. 2019:611

Diagnosis of exclusion – consider:• hypothyroidism • vitamin D deficiency• hypercalcemia• chronic viral infection (e.g., Hep.B or C, HIV)• spinal stenosis of C-spine and L-spine (older patients)• polymyalgia rheumatica (older patients)

Standard therapy of fibromyalgia: • tricyclic antidepressant in low doses, or• fluoxetine, or • cyclobenzaprine• newer agents: pregabalin (Lyrica), duloxetine (Cymbalta),

milnacipran (Savella)• nonpharmacologic approaches: exercise (especially aerobic),

conservative alternative therapies

Fibromyalgia

Arnold LM, et al. Arthritis Rheum. 2010;62:2745

Fibromyalgia Impact Questionnaire (FIQ) Scores during the 12-Week Intervention Period, According to Treatment Group.

Wang C et al. N Engl J Med 2010;363:743-754.

Tai Chi for Fibromyalgia

The other options:

◼ RF - No evidence of rheumatoid arthritis

◼ EMG - useful if myopathy or neuropathy suspected but CK result and muscle exam (limited by pain) don’t suggest myopathy (would expect painless weakness)

◼ Tramadol – Not particularly effective for fibromyalgia (the likely diagnosis), significant side effects

◼ Prednisone - not indicated for fibromyalgia (a non-inflammatory condition), unnecessary exposure to toxicity

Fibromyalgia

Case 9A woman with newly diagnosed systemic lupus erythematosus

(SLE) has been taking on non-steroidal anti-inflammatory drugs (NSAIDs) as needed. Which of the following is true?

A. Antimalarial therapy (e.g., hydroxychloroquine/Plaquenil) may protect her from major organ disease.

B. Her risk of developing cardiovascular disease is decreased compared with women without SLE.

C. She should be discouraged from becoming pregnant because pregnancy poses a major risk to her health and she is unlikely to deliver a healthy baby.

D. If she became pregnant, it would be important to know whether she is positive for anti-RNP as this autoantibody increases the risk of neonatal lupus.

E. None of the above.

HCQ Rx (less organ

damage)

No HCQ Rx

Arthritis Rheum, 2005; 52: 1473.

Asanuma,et al. NEJM 2003, 349;25

Prevalence of CAD is markedly increased in SLE

Case 9 - Answers

A. Antimalarial therapy (e.g., hydroxychloroquine/Plaquenil) may protect her from major organ disease. TRUE

B. Her risk of developing cardiovascular disease is decreased compared with women without SLE. No, it’s increased.

C. She should be discouraged from becoming pregnant because pregnancy poses a major risk to her health and she is unlikely to deliver a healthy baby. Successful pregnancies are now common in women with SLE.

D. If she became pregnant, it would be important to know whether she is positive for anti-RNP as this autoantibody increases the risk of neonatal lupus. Anti-Ro is the antibody that mediates neonatal lupus.

E. None of the above. Option A is true.

Case 10

This radiograph was obtained from a 74 y/o woman who

presented to the emergency room with a painful, warm and

swollen wrist.

Case 10 (continued)

Which one of the following statements is true regarding this patient and her x-ray?

A. The x-ray findings are specific for this patient’s condition.

B. The most likely diagnosis is septic arthritis.C. The most likely diagnosis is

rheumatoid arthritis.D. Tests of calcium, iron and

magnesium are appropriatefor this patient.

E. Colchicine is not effective forthis condition.

Case 10 (D)

Answers:

A. The x-ray findings are specific for this patient’s

condition. No, they are highly nonspecific.

B. The most likely diagnosis is septic arthritis. No,

much less likely than CPPD

C. The most likely diagnosis is rheumatoid arthritis. No,

monoarthritis would be highly atypical for RA

D. Tests of calcium, iron and magnesium are

appropriate for this patient. True!

E. Colchicine is not effective for

this condition. No, it can be

effective.

Case 11Which of the following is true regarding scleroderma-related lung disease?A. Pulmonary hypertension is more common in the diffuse form

of the disease than in the limited form (CREST).B. There are now a number of highly effective therapies to alter

the natural history of interstitial lung disease (ILD) associated with scleroderma.

C. Mycophenolate mofetil is the preferred therapy for scleroderma-associated ILD.

D. Cyclophosphamide is the preferred therapy for scleroderma-associated ILD.

E. Given the futility of treatment, no specific pharmacologic therapy is recommended for scleroderma-associated ILD.

Mycophenolate Mofetil versus Oral Cyclophosphamide inScleroderma-related Interstitial Lung Disease: Scleroderma Lung Study II (SLS-II), a double-blind, parallel group, randomisedcontrolled trial. Lancet Respir Med. 2016; 4: 708.

• Note: 1 year of CYC, 2 years of MMF

• Modest efficacy with either treatment (FVC, sx, HRCT, skin)

• Less toxicity with MMF

Case 11 - Answers

A. Pulmonary hypertension is more common in the diffuse form of the disease than in the limited form (CREST). FALSE, more w/CREST

B. There are now a number of highly effective therapies to alter the natural history of interstitial lung disease (ILD) associated with scleroderma. FALSE, modest at best

C. Mycophenolate mofetil is the preferred therapy for scleroderma-associated ILD. True.

D. Cyclophosphamide is the preferred therapy for scleroderma-associated ILD. FALSE

E. Given the futility of treatment, no specific pharmacologic therapy is recommended for scleroderma-associated ILD. FALSE

Case 12

A 68 y/o woman with a history of chronic renal insufficiency, CAD, and diuretic use complains of the acute onset of 1st

MTP pain and swelling over the last 24 hours. She recalls 2 similar episode in the past year that resolved after taking ibuprofen. Which of the following is true?

A. Treatment with pegloticase (Krystexxa) is indicated now.

B. Treatment with febuxostat (Uloric) is a better choice than allopurinol (Zyloprim) given her history of CAD.

C. Treatment with allopurinol is appropriate now.

D. A high uric acid level (eg, > 9.0 mg/dl) would secure the diagnosis.

E. The addition of lisinopril to her medical regimen may help lower her uric acid & reduce the frequency of arthritis flares.

Febuxostat (Uloric)◼ Approved in 2009 – xanthine oxidase inhibitor, once daily 40

mg or 80 mg tabs

◼ In pivotal trial: up to 45%-67% had adequately reduced U.A.

◼ Comparator: allopurinol – 42% had adequate U.A. suppression (but, it was underdosed at 200-300 mg/d)

◼ Expensive: $7-$12/pill ($11.75/pill per drugs.com on 7.28.19)

Pegloticase (Krystexxa)• Approved in 2010 for patients with severe, chronic gout who

do not respond to other treatments• Effective in about 40% of patients• Antibodies commonly produced that reduce effectiveness• IV infusion every 2 weeks; premedication with steroid &

antihistamine recommended• Even with steroids, 24% serious adverse infusion reactions,

6% anaphylaxis (can reduce these numbers by stopping drug if pre-Rx uric acid >6 mg/dl)

• Expensive (> 60K per year!)

All cause mortality:

Haz Ratio =1.2

Cardiovasc. mortality:

Haz. Ratio = 1.3

2018; 378:1200

Case 12 - Answers

A. Treatment with pegloticase (Krystexxa) is indicated now. No, other urate-lowering options are more appropriate.

B. Treatment with febuxostat (Uloric) is a better choice than allopurinol (Zyloprim) given her history of CAD. No, it’s the other way around (see NEJM 2018; 378:1200)

C. Treatment with allopurinol is appropriate now. True.

D. A high uric acid level (eg, > 9.0 mg/dl) would secure the diagnosis. No, hyperuricemia is common with or without gout.

E. The addition of lisinopril to her medical regimen may help lower her uric acid & reduce the frequency of arthritis flares. No, but losartan is uricosuric & can lower uric acid.

Case 13

A 74 year-old man complains of a new headache, jaw pain & diplopia. General physical and temporal artery examinations are normal. A recent ophthalmologic evaluation was normal.

His ESR is 82 mm/hr (0-20); blood counts & chemistry studies are normal.

Which of the following is true regarding his likely diagnosis?

A. Low dose prednisone (e.g., prednisone, 15-20 mg/d) is appropriate therapy

B. A negative temporal artery ultrasound would rule out temporal arteritis

C. Therapy with tocilizumab may be steroid-sparing

D. Anti-TNF therapy (eg, infliximab) has been approved for this condition

E. Associated vision loss is usually reversible with treatment

Case 13 - Answers

Likely dx: giant cell (temporal) arteritis – which is true?

A. Low dose prednisone (e.g., prednisone, 15-20 mg/d) is appropriate therapy FALSE – generally, high dose steroids (eg, prednisone, 1 mg/kg/d) is recommended

B. A negative temporal artery ultrasound would rule out temporal arteritis FALSE – US is not perfectly sensitive

C. Therapy with tocilizumab may be steroid-sparing – TRUE

D. Anti-TNF therapy (eg, infliximab) has been approved for this condition - FALSE

E. Associated vision loss is usually reversible with treatment –FALSE - usually permanent

Transmural inflammation with giant cells at media-intima border, and narrowed lumen. Weyand, C. M. et al. N Engl J Med 2003;349:160-169

Temporal Artery Biopsy: The Gold Standard

Predictors of a positive temporal artery biopsy

• Meta-analysis of 21 studies, n = 2680, 39% of referred patients had temporal arteritis (nearly all by bx)

• History: jaw claudication and diplopia - likelihood

• Examination: normal temporal arteries - likelihood

• Temp. artery beading, prominence, tenderness - likelihood

• ESR: normal value likelihood

(Smetana, JAMA 2002;287:92)

2017;377:317

◼ New recommendation: ultrasound as part of initial evaluation of suspected temporal arteritis or MRI for all suspected GCA → treat

if positive, biopsy if negative.

http://pacificvascular.com/cerebrovascular-evaluations/

Ann Rheum Dis. 2018;77:636

Case 14

A 38 year-old man complains of gradually increasing, nontraumatic left hip pain over 2 yrs. Symptoms are worse at night or walking, but lately he has noted rest pain. Treatment with NSAIDs, acetaminophen, and PT have been unhelpful. Examination is normal except for moderately reduced external rotation and no internal rotation in the left hip. Radiographs of the left hip reveal loss of joint space and marked sclerosis with osteophyte formation. Each of the following would be appropriate at this point except:

A. Order an anti-CCP and RFB. Review pediatric medical historyC. Refer to an Orthopedic SurgeonD. Order iron studies (Fe, TIBC)E. Review history of medications taken

in the past

Secondary OA

◼ Consider when OA present in atypical location or atypical patient (e.g., elbow, young adult)

◼ THE CHARMIN

• Trauma

• Hypermobility

• Endocrinopathy

• Crystal-induced

• Hemarthrosis

• Avascular necrosis

• Rheumatic disease

• Metabolic (esp. iron overload)

• Infection

• Newborn (congenital)

Other answers….

A. Order an anti-CCP and RF – TRUE(least appropriate); no suggestion

of inflammatory arthritis of small joints (RA-like disease) so no indication for these tests

B. Review pediatric medical history – e.g., .?septic arthritis

C. Refer to an Orthopedic Surgeon – may need THR

D. Order iron studies (Fe, TIBC) - ?hemochromatosis

E. Review history of medications taken in the past -?steroids → Avascular necrosis

Thank you for your attention.