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 C rohn’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

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

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 or 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.

Positive ANCA, Answer. 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

GPA, Treatment • 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.

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.