1. Rheumatology in Primary Care
10/03/19
Brian V Joachims, M.D.

2. Objectives
Identify characteristics consistent with a diagnosis of Lupus
Interpret ANA results
Identify characteristics of Rheumatoid Arthritis
Describe Spondyloarthropathy

3. Case 1 29 year-old Caucasian female presents with complaint of fatigue
Lab results:
ANA IFA 1:80, speckled pattern
Hgb 11.9
TSH 1.6
UA WNL
HCG neg

4. Lupus (?) Does our patient have lupus?
A) yes, because she has a positive ANA
B ) no, because the ANA isn’t high enough
C ) don’t know yet, need more information
D ) what’s lupus?

5. Lupus (!) Systemic Lupus Erythematosus (SLE)
Chronic autoimmune disease of unknown cause that can affect virtually any organ of the body
Clinical manifestations:
Constitutional symptoms
Cutaneous
Arthritis / arthralgias / myalgias
Renal GI
Pulmonary
Cardiac
CNS (Neurologic / Psychiatric)

6. Lupus (Constitutional Symptoms)
Fatigue
Most common complaint (up to 100% at some point during the course of disease)
Fever
Distinguish from other causes (infection, drug reaction, malignancy)
Myalgias
Severe muscle weakness or myositis uncommon
Weight change
May be related to disease or treatments

7. Lupus (Skin) Acute cutaneous lupus erythematosus (ACLE)
Localized (malar / butterfly rash)
Generalized
Subacute cutaneous lupus erythematosus (SCLE)
Annular
Papulosquamous
Drug-induced
Chronic cutaneous lupus erythematosus (CCLE)
Discoid lupus
Lupus panniculitis

8. Acute Cutaneous Lupus Erythematosus

9. Lupus (?) ANA (Anti-Nuclear Antibody)
The detection of antinuclear antibodies (ANA) in serum facilitates the diagnosis of patients with systemic lupus erythematosus (SLE) and related autoimmune diseases
The absence of ANA in the serum of a patient with suspected SLE also provides important information in that it makes the diagnosis much less likely

10. Antinuclear Antibody IFA – indirect immunofluorescence test
Homogeneous
Speckled
Centromere
Nucleolar
Solid phase assays (ELISA) – ANA, direct
Panel of antigens

11. ANA (IFA) Titer matters 1:40 1:160 Approx 30% of normal controls
97% of patients with SLE
1:160
Approx 5% of normal controls
95% of patients with SLE
Prevalence of ANA-associated diseases in the general population ~1%

12. ANA IFA

13. ANA IFA

14. Lupus Panel (Reichlin)
Panel of antigens:
Anti-dsDNA Ab
RNP Ab
Smith Ab
Rheumatoid Arthritis factor
Sjogren’s Anti-SS-A (Ro Ab)
Sjogren’s Anti-SS-B (La Ab)
Antichromatin Ab

15. Diagnosing Lupus Criteria Classification (not diagnostic)
ACR – American College of Rheumatology
SLICC – Systemic Lupus International Collaborating Clinics

16. SLICC Criteria Clinical criteria (“in the absence of other causes…”)
Acute cutaneous lupus
Chronic cutaneous lupus
Oral or nasal ulcers
Non-scarring alopecia
(not):
Male pattern
Hypothyroidism
Iron deficiency
Arthritis
Swelling or effusion – OR –
Tenderness in 2 or more joints and at least 30 minutes of morning stiffness

17. SLICC Criteria Clinical criteria (cont.) Serositis
Pleurisy, pleural effusions or pleural rub
Renal
Urine protein-to-creatinine ratio representing 500 mg pro/24 hours
- OR – RBC casts
Neurologic

18. SLICC Criteria Hemolytic anemia Leukopenia / Lymphopenia
DAT / direct Coombs
Leukopenia / Lymphopenia
WBC <4000/mm3
Lymph # <1000/mm3
Thrombocytopenia
Platelets <100,000/mm3

19. SLICC Criteria Immunologic criteria ANA Anti-dsDNA Anti-Sm
Antiphospholipid antibody
Lupus anticoagulant
Anticardiolipin antibody
Anti-2-glycoprotein
False positive RPR
Low complement (C3, C4 or CH50)
Direct Coombs’ test
In the absence of hemolytic anemia

20. RheumaHelper

21. Treatment Goals of therapy: ensure long-term survival
achieve the lowest possible disease activity
prevent organ damage
minimize drug toxicity
improve quality of life
educate patients about their role in disease management

22. Medications
Steroids IM
Oral (prednisone)
Disease-Modifying Anti-Rheumatic Drugs (DMARD’s) – “steroid-sparing” agents
Hydroxychloroquine
Methotrexate
Sulfasalazine
Azathioprine
Leflunomide

23. Hydroxychloroquine FDA-approved: Malaria
Chemoprophylaxis, acute attack
Off-label:
Lupus
Rheumatoid arthritis
Sjogren’s syndrome
Porphyria
Q fever

24. Hydroxychloroquine Marketed as Plaquenil in the U.S.
$11.88 (per pill)
Generic $ $4.36
GoodRx: $38.67 for 60 tablets
mg daily (200 mg tablets)
“Typical” dose – 400 mg daily
5 mg/Kg (80 Kg person – 400 mg)
Mechanism of action:
Antimalarial, blocks toll-like receptors
Impairs complement-dependent antigen-antibody reactions

25. Hydroxychloroquine Adverse reactions: Retinal toxicity / maculopathy
Potentially irreversible retinopathy
Associated with daily doses >5 mg/Kg
Duration of >5 years
Ophthalmologic exam – baseline / within the first year, followed by annual screening beginning after 5 years of use

26. “Bull’s-Eye” Maculopathy

27. Hydroxychloroquine Adverse reactions (cont.): Hematologic effects
Anemia
Leukopenia
Thrombocytopenia
No prescribed surveillance lab (“CBC at baseline and ‘periodically’”)
Skin discoloration
Dyschromia (skin and mucosal; black-blue color)

28. HCQ Dyschromia

29. HCQ Dyschromia

31. Case 2
Any-year-old any-ethnicity male/female presents with complaints of increasing joint pain, particularly in the hands, shoulders and ankles. The patient’s hands are typically swollen in the mornings and he/she has stiffness in most joints for about an hour after waking.

32. Case 2 Lab results: Rheumatoid factor 65.4 (0.0-13.9)
Anti-CCP 124 (0-19)
ESR 44
CRP 8.9 ( )

33. Rheumatoid Arthritis (?)
Does our patient have rheumatoid arthritis?
A) yes

34. Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology that primarily involves synovial joints

35. Synovial Joint

36. Synovitis

37. Rheumatoid Arthritis Synovitis (clinically):
Soft tissue swelling
Warmth over a joint
Joint effusion
Stiffness – “slowness or difficulty moving the joints when getting out of bed or after staying in one position too long, which involves both sides of the body and gets better with movement”
Morning – at least 30 minutes
Gelling – stiffness with / after rest during the day

38. Rheumatoid Arthritis Morning stiffness Better with activity Swelling
Warmth
Tenderness
Redness
Steroids helpful?

39. Rheumatoid Arthritis – Joint Distribution

40. Rheumatoid Factor (RF)
Rheumatoid factors are antibodies directed against the Fc portion of immunoglobulin G (IgG)
Found in 75 to 80 percent of RA patients at some time during the course of their disease
Titer matters:
RF titer of 1:40 or greater was 28 percent sensitive and 87 percent specific for RA
A titer of 1:640 or greater increased the specificity to 99 percent

41. CCP Antibodies
Anti-citrullinated peptide antibodies (ACPA, which include anticyclic citrullinated peptides)
More specific for rheumatoid arthritis than RF
Pearl: if low-titer RF (< 3 times upper limit of normal) and negative CCP, check for Hep C

42. Rheumatoid Arthritis

43. Swan Neck Deformity

44. Swan Neck

45. Boutonniere Deformity

46. Boutonniere

47. Not Just the Joints… Non-articular manifestations Osteopenia Myositis
Vasculitis
Skin disease
Eye involvement
Lung disease
Cardiac disease
Kidney disease

48. Treatment Methotrexate FDA-approved: Off-label: ALL Breast cancer
Non-Hodgkin’s lymphoma
Psoriasis
Rheumatoid arthritis
Off-label:
Crohn’s disease
Dermatomyositis / Polymyositis
SLE

49. Methotrexate Inhibits dihydrofolate reductase (DHFR)
Can tightly bind to DHFR and inhibit DNA synthesis and cell proliferation
mg weekly to begin
Literature indicates titrating to mg weekly
Adjust gradually to optimum response
Toxicity increased at doses >20 mg per week
Concomitant folic acid
1-5 mg daily
At least 5 mg per week

50. Methotrexate Adverse effects: Alopecia Stomatitis GI upset
Increasing Cr
Liver enzyme abnormalities
Thrombocytopenia
Anemia
Leukopenia
Pulmonary disease
Teratogenic

51. Methotrexate
• Pregnancy: [US Boxed Warning]: Methotrexate has been reported to cause fetal death and/or congenital abnormalities. Methotrexate is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Pregnant women with psoriasis or rheumatoid arthritis should not receive methotrexate. Some products are contraindicated in pregnant women.

52. Methotrexate
Methotrexate treatment should be discontinued for at least three months before attempting to become pregnant
© 2018 American College of Rheumatology

54. Case 3
39-year-old male with psoriasis presents with a 6-month history of progressive low back pain and stiffness which is most aggravating at rest. He indicates this is OK as long as he keeps moving.

55. Inflammatory Back Pain
In patients with chronic back pain >3 months:
4 out of 5:
Onset at age <40 (or 45) years
Insidious onset
Improvement with exercise
No improvement with rest
Pain at night (with improvement upon getting up)

56. Spondyloarthritis Ankylosing spondylitis (AS)
Nonradiographic axial SpA (nr-axSpA)
Peripheral SpA
SpA associated with psoriasis or psoriatic arthritis
SpA associated with Crohn disease and ulcerative colitis
Reactive arthritis (formerly called Reiter's syndrome)
Juvenile-onset SpA

57. Spondyloarthritis Peripheral arthritis
Enthesitis - inflammation around the enthesis, which is the site of insertion of ligaments, tendons, joint capsule, or fascia to bone, and is relatively specific to SpA
Dactylitis (sausage digits)

58. Enthesitis

59. Enthesitis

60. Enthesitis

61. Dactylitis (“Sausage Digit”)

62. Other Features Sacroiliitis HLA B27 Uveitis Psoriasis
Crohn’s colitis (IBD)
Good response to NSAID’s
Fam Hx of SpA
Elevated CRP
Preceding infection (reactive arthritis)

63. Biologic DMARD’s TNF-inhibitors Humira (Adalimumab)
Human monoclonal antibody
Enbrel (Etanercept)
Soluble receptor fusion protein
Remicade (Infliximab)
Chimeric (mouse / human) antibody

64. Biologic DMARD’s Anti-IL-6 Anti-IL-1 JAK inhibitors
Actemra (tocilizumab)
Anti-IL-1
Kineret (anakinra)
JAK inhibitors
Xeljanz (tofacitinib)

65. Biologic DMARD’s Anti-IL-17A Selective T-Cell Costimulation Blocker
Cosentyx (secukinumab)
Taltz (ixekizumab)
Selective T-Cell Costimulation Blocker
Orencia (abatacept)
Phosphodiesterase-4 Enzyme Inhibitor
Otezla (apremilast)