Challenging Cases In Rheumatology Kuwait March 9, 2019 Fadi - - PowerPoint PPT Presentation

Challenging Cases In Rheumatology

Kuwait March 9, 2019

Fadi Badlissi, MD, MSc Director of the Musculoskeletal Medicine Unit The Orthopedic Department & Rheumatology Division HMFP/BIDMC Assistant Professor of Medicine Harvard Medical School

Disclosure

• No conflicts

Trigger Fingers

• 50 you female presented in 2000 with gradual onset right

index finger pain and swelling

• Underwent “radical flexor tenosynovectomy right index

finger, A1 pulley release”

• Pathology: “Synovial tissue with fibrin deposition and

acute inflammation”

• Her surgeon: “One day you will be diagnosed with an

autoimmune disease”

• 2001 “A1, partial A2 and C1 pulley release, right second

and right third fingers; radical flexor tenosynovectomy, right second and third fingers” for flexor tenosynovitis of the right index and right long fingers

Trigger Fingers, cont.

• She persisted to have pain and swelling in

both hands

• Rheumatoid factor (RF) neg, anti-cyclic

citrullinated peptide (Anti-CCP) neg

• PCP consulted a rheumatologist in 2004
• A diagnostic test was performed
• Do you have psoriasis?

Bilateral Knee Swelling

• 18 yo female with Crohn’s disease, presents to

the sports ortho clinic with a non traumatic bilateral knee pain

• She is from Chicago and had both knees aspirated

before coming to college, after working at a summer camp

• The pain is primarily anterior and has increased in

the last two weeks

• She had no previous steroid injections but had PT

and water therapy

• Jumping, kneeling, bending, and impact activities

elicit pain in the knees

Bilateral Knee Swelling, Cont.

• Exam: Bilateral knee moderate effusion, + mild

diffuse tenderness, ext 0, flex 120

• Referred to rheumatology for further

evaluation

• Synovial fluid

– WBC 3,925, PMN 35%, – RBC 125 – No crystals

Seronegative Question

• All of these diagnoses are part of seronegative

spondyloarthropathies EXCEPT:

• A. Psoriatic arthritis
• B. Ankylosing spondylitis
• C. Reactive arthritis/Reiter’s syndrome
• D. Inflammatory bowel disease assicated arthritis
• E. Rheumatoid Arthritis

Seronegative Answer

• All of these diagnoses are part of seronegative

spondyloarthropathies EXCEPT:

• A. Psoriatic arthritis
• B. Ankylosing spondylitis
• C. Reactive arthritis/Reiter’s syndrome
• D. Inflammatory bowel disease assicated arthritis
• E. Rheumatoid Arthritis

Knee Pain

• 39 yo male presented with acute pain and

swelling R knee

• Went to urgent care
• X-rays
• Treated with naproxen 500 mg twice daily

MRI Ordered

Axial FS

T2DSS

Knee Pain, Cont.

• Referred to orthopedic oncology
• CT guided biopsy

Chondrocalcinosis Weakly positively birefringent CPPD crystal

CPPD, Chondrocalcinosis (CC)

• CC: cartilage calcification, identified by

imaging or histological examination. This is not always due to CPPD and may occur as an isolated finding in an apparently otherwise normal joint or coexist with structural changes resembling osteoarthritis (OA)

» EULAR guidelines on CPPD, Ann Rheum Dis 2011

Calcium Pyrophosphate Deposition Diseases (CPPD)

• McCarty 1962
• 5% chronic polyarthritis

» McCarty DJ. Bull Rheum Dis 1975

• A great mimic for many arthropathies
• Pseudogout can look exactly like gout
• >50 year-old, risk doubles every decade
• Knee then wrists are the most common sites
• Diagnosis by crystals which could be more difficult to

find than monosodium urate crystals

• Radiographically, chondrocalcinosis

CPPD Question

• All of these are risk factors for calcium

pyrophosphate deposition disease (CPPD) EXCEPT:

• A. Gitelman’s disease
• B. Hypomagnesaemia
• C. Hypothyroidism
• D. Hemochromatosis
• E. Hyperparathyroidism

CPPD Answer

• All of these are risk factors for calcium

pyrophosphate deposition disease (CPPD) EXCEPT:

• A. Gitelman’s disease
• B. Hypomagnesemia
• C. Hypothyroidism
• D. Hemochromatosis
• E. Hyperparathyroidism

Risk factors

• Previous joint injury, post menisectomy
• Hereditary/familial predisposition to CPPD
• Specific diseases

– hemochromatosis – primary hyperparathyroidism (OR=3.03, 95% CI: 1.15 - 8.02) – hypophosphatasia – hypomagnesaemia (OR=13.5, 95% CI: 2.76 - 127.3) , Gitelman’s disease

» Jones AC, et al. Semin Arthritis Rheum 1992 » EULAR guidelines on CPPD, Ann Rheum Dis 2011

CPPD Clinical Presentations

• Asymptomatic CPPD, isolated CC, or
• steoarthritis (OA) with CC
• OA with CPPD: CPPD in a joint that also shows

changes of OA, on imaging or histological examination

• Acute calcium pyrophosphate (CPP) crystal

arthritis: acute onset synovitis with CPPD (replacing the term ‘pseudogout’)

• Chronic CPP crystal inflammatory arthritis:

chronic inflammatory arthritis associated with CPPD mimicking rheumatoid arthritis

CPPD In Kuwait

• Two out of 100 subjects presenting with knee

arthritis had radiographic chondrocalcinosis

• 85 (3%) out of 2726 patients seen by the

rheumatology service over 5 years had crystal induced arthritis

– 14 CPPD – 69 gout – 2 (others)

» Malaviya AN, et al. Ann Rheum Dis 2001

CPPD, Diagnosis

• Crystals are confirmatory
• Radiographs supportive but not diagnostic,

the lack of radiographic finding does not exclude the disease

• Ultrasound could be helpful in making the

diagnosis and differentiating it to a certain degree from gout

Ultrasound in CPPD versus Gout

Filippucci E, et al. Osteoarthritis Cartilage 2009 Normal hyaline cartilage of the femoral condyle Gout, double contour sign Hyperechoic spots, CPPD disease

CPPD, treatment

• OA with CPPD, treat as OA
• Acute:

– NSAIDs – Corticosteroids – Colchicine

• Chronic prevention: colchicine, NSAIDs
• Chronic CPPD:

– Colchicine – NSAIDs – Low dose corticosteroids – Hydroxychloroquine, MTX

• Treat secondary causes
• EULAR guidelines on CPPD, Ann Rheum Dis 2011

Positive ANCA

A 34 year-old woman with ulcerative colitis feels well but is found to have microscopic hematuria. She reports mild sinus pressure and congestion for the past week. She thinks that she may have had a fever for a day or

• two. An anti-neutrophilic cytoplasmic antibody (ANCA)

is ordered and returns positive in moderate titer with a p-ANCA pattern of immunofluorescence.

» Courtesy Slide from Robert H. Shmerling, M.D.

Positive ANCA, Cont.

Which of the following is true?

• A. The likely diagnosis is Granulomatosis

with Polyangiitis (GPA)

• B. Therapy for GPA (including corticosteroids plus rituximab
• r cyclophosphamide) should be initiated
• C. The positive ANCA is probably due to anti-MPO (anti-

myeloperoxidase)

• 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

• Courtesy Slide from Robert H. Shmerling, M.D.

A. This patient probably has Granulomatosis with Polyangiitis (GPA) NO - Nonspecific symptoms, not particularly sick B. Therapy for GPA (including corticosteroids and azathioprine) should be

• initiated. NO - Diagnosis is not established, non-urgent scenario, toxic

therapy, not appropriate therapy C. The positive ANCA is probably due to anti-MPO (anti-myeloperoxidase).

• Patients with UC often have p-ANCA that is NOT due to anti-MPO

(and therefore, nonspecific)

• 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 If due to anti-PR3, would expect a positive c-ANCA (not p-ANCA); ANCA results can be supportive but never diagnostic

Positive ANCA, Answer.

• RAVE trial: N Engl J Med. 2010;363:221 – Confirmed non-

inferiority of rituximab vs. cyclophosphamide for GPA and MPA

• Initial treatment:
• High dose steroids + Cyclophos. or Rituximab
• Add plasma exchange for rapidly deteriorating/severe

kidney dysfunction, pulmonary hemorrhage, con- comitantly positive anti-glomerular basement membrane (anti-GBM) autoantibody

• Corticosteroids + MTX (oral or parenteral) for milder

disease, e.g., not organ-threatening, not life threatening disease, non-renal

• Courtesy Slide from Robert H. Shmerling, M.D.

GPA, Treatment

Positive ANCA, Key Points

• A positive ANCA is not diagnostic of vasculitis and not a great

screening test unless GPA, EGPA, microscopic polyangiitis (MPA) or pauci-immune GN are under consideration

• A positive p-ANCA without anti-MPO is nonspecific and may

be associated with ulcerative colitis & other conditions

• Despite utility of ANCA testing, the gold standard for

diagnosis is tissue biopsy

• Treatment options for ANCA-associated vasculitis: Steroids,

CTX/RTX, MTX, azathioprine

» Courtesy Slide from Robert H. Shmerling, M.D.

Lupus

• A woman with newly diagnosed systemic lupus

erythematosus (SLE) has been doing well without specific therapy. Which of the following is true?

A.Her risk of developing cardiovascular disease is decreased compared with women without SLE B.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 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.Antimalarial therapy (e.g., hydroxychloroquine/Plaquenil) may protect her from major organ disease

» Courtesy Slide from Robert H. Shmerling, M.D.

Lupus, Answer.

• A woman with newly diagnosed systemic lupus

erythematosus (SLE) has been doing well without specific therapy. Which of the following is true?

A.Her risk of developing cardiovascular disease is decreased compared with women without SLE B.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 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.Antimalarial therapy (e.g., hydroxychloroquine/Plaquenil) may protect her from major organ disease

HCQ Rx (less organ damage) No HCQ Rx

Arthritis Rheum, 2005; 52: 1473.

Courtesy Slide from Robert H. Shmerling, M.D.

Asanuma,et al. NEJM 2003, 349;25

Prevalence of CAD is markedly increased in SLE

Swollen Hand

• 40 yo male carpenter presented to the ED with

acute worsening pain and swelling in his right wrist and hand

• Paresthesia along the median nerve distribution
• An attempt to aspirate the wrist yielded no fluid
• Hand surgery consulted

– Exam: mild swelling mostly over the volar aspect, pain with tenderness and pain with passive extension

Axial T1 Pre

Axial T1 FS Post

Axial STIR

Swollen Hand MRI Results & Course

• Tenosynovitis involving the 1st through the 5th

flexor tendons, most conspicuous just distal to the carpal tunnel

• He underwent R thumb incision and drainage
• f the flexor sheath, radical synovectomy from

carpal tunnel and open release

Swollen Hand Rheumatology Referral

• Intermittent arthralgias and stiffness for few

months

• Mild synovitis B wrists
• RF 119
• Anti CCP > 250

Rheumatoid Arthritis (RA)

• Prevalence 0.5-1%
• Age 25-55
• Female > male
• Polyarticular symmetric chronic inflammatory

arthritis

• Could present as monoarticular or oligoarticular

arthritis initially

• Small joints, but it can involve any joints
• There is an episodic form “palindromic RA”

Rheumatoid Arthritis

• A 46 year-old schoolteacher has recently been diagnosed with

rheumatoid arthritis after 3 weeks of polyarthritis involving the MCPs, wrists and knees. Her physician has recommended a second-line agent, methotrexate; she is unsure whether she should take this drug. Which of the following statements is true:

• A. She should not take methotrexate because the diagnosis

is not secure

• B. Early therapy with disease-modifying agents, including

methotrexate, is appropriate at this time to prevent expected development of erosions

• C. A high titer rheumatoid factor would confirm the diagnosis
• D. Radiographs now will probably demonstrate erosions at

the MCPs and/or wrists

• E. A negative anti-CCP antibody would rule out rheumatoid

arthritis

» Courtesy Slide from Robert H. Shmerling, M.D.

Rheumatoid Arthritis, Answer.

• A 46 year-old schoolteacher has recently been diagnosed with

rheumatoid arthritis after 3 weeks of polyarthritis involving the MCPs, wrists and knees. Her physician has recommended a second-line agent, methotrexate; she is unsure whether she should take this drug. Which of the following statements is true:

• A. She should not take methotrexate because the

diagnosis is not secure

• B. Early therapy with disease-modifying agents, including

methotrexate, is appropriate at this time to prevent expected development of erosions

• C. A high titer rheumatoid factor would confirm the diagnosis
• D. Radiographs now will probably demonstrate erosions at

the MCPs and/or wrists

• E. A negative anti-CCP antibody would rule out rheumatoid

arthritis

RA, Lab Tests

• RF (rheumatoid factor)

– Sensitivity 80% – Specificity 71%

• Anti-CCP (cyclic citrullinated peptides)

– Sensitivity 66% – Specificity 90%

• A third of subjects with + RF have + anti-CCP

antibodies

» Lee, DM et al. Ann Rheum Dis 2003

Stiff Shoulders

A 68 y/o woman develops the sudden onset of morning stiffness in the upper arms and thighs. She has difficulty arising from a chair due to stiffness and improves dramatically within the first 3 days of corticosteroid therapy. Which of the following is true regarding her condition?

• A. Physical examination is likely to demonstrate proximal muscle

weakness

• B. An MRI of her shoulder would likely demonstrate bursitis and

tenosynovitis

• C. At the time of presentation, her erythrocyte sedimentation

rate (ESR) would likely be normal

• D. An electromyogram (EMG) would demonstrate signs of

muscle irritability, such as insertional spikes and fibrillations.

• E. High dose corticosteroids (e.g., prednisone, 1 mg/kg/d) is

appropriate initial therapy for this condition

– Courtesy Slide from Robert H. Shmerling, M.D.

Stiff Shoulders, Answer.

A 68 y/o woman develops the sudden onset of morning stiffness in the upper arms and thighs. She has difficulty arising from a chair due to stiffness and improves dramatically within the first 3 days of corticosteroid therapy. Which of the following is true regarding her condition?

• A. Physical examination is likely to demonstrate proximal muscle

weakness

• B. An MRI of her shoulder would likely demonstrate bursitis

and tenosynovitis

• C. At the time of presentation, her erythrocyte sedimentation

rate (ESR) would likely be normal

• D. An electromyogram (EMG) would demonstrate signs of

muscle irritability, such as insertional spikes and fibrillations

• E. High dose corticosteroids (e.g., prednisone, 1 mg/kg/d) is

appropriate initial therapy for this condition

Polymyalgia Rheumatica, Cont.

• Management: low dose prednisone (usually 15-20 mg/day)

taper to lowest tolerated dose, ideal duration uncertain (avg: 2.5 yrs) but discontinue as soon as possible

• Less appealing choices:

A, D - Physical examination is likely to demonstrate proximal muscle weakness & EMG would show myopathic changes – FALSE – PMR is not a myopathy

• B. MRI would likely demonstrate bursitis and tenosynovitis –

TRUE – PMR is marked by inflammation of joints, tendons, & bursae

• C. ESR would likely be normal – FALSE – ESR is highly

sensitive

• E. High dose corticosteroids is appropriate initial therapy –

FALSE - low doses are sufficient

» Courtesy Slide from Robert H. Shmerling, M.D.

Age at least 50 (usually >70 years old)

• Acute onset of pain lasting weeks in 2 or more

“axial” areas, including neck, shoulder, pelvic girdle

• Morning stiffness for an hour or more
• Rapid response to low-dose corticosteroids (e.g.,

prednisone, 20 mg/day or less)

• Absence of another explanation for symptoms
• ESR of 40mm/hour or higher
• Courtesy Slide from Robert H. Shmerling, M.D

Polymyalgia Rheumatica (PMR)

Headache & Jaw Pain

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 (normal 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 giant

cell arteritis (GCA)

• C. Therapy with tocilizumab may be steroid-sparing
• D. Aspirin therapy is contraindicated
• E. Associated vision loss is usually reversible

Courtesy Slide from Robert H. Shmerling, M.D

Headache & Jaw Pain, Answer.

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 (normal 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 giant

cell arteritis (GCA)

• C. Therapy with tocilizumab may be steroid-sparing
• D. Aspirin therapy is contraindicated
• E. Associated vision loss is usually reversible

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 Courtesy Slide from Robert H. Shmerling, M.D

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
• TA beading, prominence, tenderness -  likelihood
• ESR: normal value  likelihood
• Courtesy Slide from Robert H. Shmerling, M.D

(Smetana, JAMA 2002;287:92)

• Courtesy Slide from Robert H. Shmerling, M.D.

Courtesy Slide from Robert H. Shmerling, M.D

Courtesy Slide from Robert H. Shmerling, M.D

Dyspnea

• A 44 year-old woman with a several year history of limited

cutaneous systemic sclerosis (limited scleroderma/CREST) now complains of dyspnea on exertion. High resolution CT scanning demonstrates evidence of interstitial lung disease (ILD). Cyclophosphamide therapy is under consideration. Which of the following is a true statement regarding this patient’s lung disease?

• A. Her risk of pulmonary hypertension with CREST syndrome is

lower than if she had diffuse systemic sclerosis

• B. There is no proven benefit to pharmacologic treatment for

her lung function

• C. Calcium channel blocker therapy may be helpful for her ILD
• D. Mycophenolate may be as effective for her ILD
• E. None of the above

» Courtesy Slide from Robert H. Shmerling, M.D

Dyspnea, Answer.

• A 44 year-old woman with a several year history of limited

cutaneous systemic sclerosis (limited scleroderma/CREST) now complains of dyspnea on exertion. High resolution CT scanning demonstrates evidence of interstitial lung disease (ILD). Cyclophosphamide therapy is under consideration. Which of the following is a true statement regarding this patient’s lung disease?

• A. Her risk of pulmonary hypertension with CREST syndrome is

lower than if she had diffuse systemic sclerosis

• B. There is no proven benefit to pharmacologic treatment for

her lung function

• C. Calcium channel blocker therapy may be helpful for her ILD
• D. Mycophenolate may be as effective for her ILD
• E. None of the above

CT scan at lung bases: bibasilar interstitial lung disease, patulous esophagus, bilateral pleural effusions

Courtesy Slide from Robert H. Shmerling, M.D

Cyclophosphamide: modest improvement in FVC vs. placebo

Tashkin, et al. N Engl J Med.. 2006;354:2655

Courtesy Slide from Robert H. Shmerling, M.D

Improved FVC Improved skin score

• Patients receiving mycophenolate (2 yrs) or cyclophosphamide (1

yr) had similar, modest improvements in FVC, skin score, dyspnea

• Less toxicity with mycophenolate mofetil (MMF)
• This has changed practice: MMF for ILD in scleroderma

(SLS-II-Lancet Respir Med; 2016;4:708) Courtesy Slide from Robert H. Shmerling, M.D

Good websites for patients:

• Harvard Medical School’s health website:

http://www.health.harvard.edu/

• National Library of Medicine:

http://medlineplus.gov/

• American College of Rheumatology:

www.rheumatology.org

• The Arthritis Foundation:

www.arthritis.org

• Courtesy Slide from Robert H. Shmerling, M.D

Online CME & Physician Resources

• http://cmeonline.med.harvard.edu/course_des

criptions.asp?Course_id=221&group_name=Me dicine2014

• http://bestpractice.bmj.com/best-

practice/welcome.html

One Swollen Knee

• 55 yo healthy woman who over Christmas

had squatted down and felt a pull on the

• utside portion of her right knee
• This pain persisted and slowly worsened over

the following months leading to difficulty walking

• She had stiffness and limited ROM
• She also noted slowly worsening swelling on

the distal lateral aspect of the thigh

One Swollen Knee, Exam

• Limited active ROM
• Better passive ROM, but limited
• Swelling over the distal lateral aspect of her

thigh and effusion

• Tenderness along the distal lateral aspect of

the thigh, as well as the lateral joint

One Swollen Knee, Imaging

• A popliteal mass-like cyst, that appears to

communicate with the tib-fib and knee joint

• ? Possible pigmented villonodular synovitis

(PVNS) with a more focal nodular focus located in the posterior aspect of the knee

• Moderate effusion and synovitis
• No internal derangement

Axial T2 FS

Sagital T2 FS

CT Guided Soft Tissue Biopsy Right Knee Mass

• Synovial tissue and fibrinous exudate with

acute and chronic inflammation, see note

• Note: Scant amount of viable lesion tissue is
• present. The differential diagnoses includes

tenosynovial giant cell tumor, and synovial inflammatory conditions

One Swollen Knee, Cont.

• What will you do next?

One Swollen Knee, Labs

• ESR: 60
• CRP: 9.6
• RF: 11
• Anti-CCP: neg
• A diagnostic test was performed

Lyme

• Early localized, erythema migrans, only 30% of

patients notice it

• Early disseminated

– Neurological – Carditis – Musculoskeletal, arthralgias – Skin

• Late

– Mono or oligoarticular arthritis, the knee is the most commonly affected joint

Lyme, Diagnosis

• Enzyme linked immunosorbent assay (ELISA)

– IgM, IgG – Could be negative in early Lyme – It may stay negative if treatment was initiated

• Western blot

– If ELISA is + – IgM 2/3 bands – IgG 5/10 bands