Rheumatic Disease and HIV Infection

2. Rheumatic Diseaseand HIV Infection Dr M Jokar

3. اهداف • هدف کلی: آشنایی با انواع علائم روماتیسمی در جریان HIV • اهداف جزئی: • آشنایی با Painful articular syndrome • آشنایی با HIV–associated arthritis • آشنایی با آرتریت پسوریاتیک در مبتلایان به عفونت HIV • آشنایی با DILS • آشنایی با درگیری عضلات در جریان HIV

4. HIV • Myriad of clinical manifestations affecting every organ system • Rheumatic manifestations can occur in late stages or be the first presenting symptom • Frequency 1-60%– varies with ethnicity, geography, HIV stage, antiretroviral treatment

5. Articular considerations in HIV

6. PAINFUL ARTICULAR SYNDROME • Severe bone and joint pain • Self-limited syndrome • Lasting less than 24 hours • Few objective clinical findings • Late stages of HIV infection • Knee, elbow, shoulders

7. HIV ASSOCIATED ARTHRITIS • Oligoarthritis • Lower extremities • Self-limited • Lasting less than 6 weeks • Knees, ankles, metatarsophalangeal joints, wrists , elbows, metacarpophalangeal , interphalangeal joints

8. REACTIVE ARTHRITIS

9. PSORIATIC ARTHRITIS • Psoriatic rash can be extensive • Arthritis is predominantly polyarticular, lower limb, and progressive

10. Diffuse infiltrativelymphocytosis syndrome (DILS) • Sjogren’s-like disease • Significant, painless parotid gland enlargement • Sicca symptoms – xerostomia • Anti-SSA, Anti-SSB negative • CD8 inflammatory infiltrate • Prominent extraglandular symptoms including RTA, PM, lymphocytic hepatitis, lymphoma, VII nerve palsy

12. Myopathies • Myalgias – associated with viremia, FMS • PM – with signs/symptoms similar to HIV negative patient but ? milder; with/without skin disease • Zidovudine- associated myopathy

13. خلاصه در مبتلایان به عفونت HIV سندرمهای روماتیسمی مختلفی دیده می شود که مهمترین آنها عبارتند از: • Painful articular syndrome • HIV–associated arthritis • DILS • Polymyositis

14. Common Rheumatologic Tests: Evaluation and Interpretation Dr M. Jokar

15. اهداف هدف کلی: آشنانی با تفسیر تست های آزمایشگاهی در بیماریهای روماتیسمی اهداف جزئی: • آشنایی با تفسیر CBC در بیماریهای روماتیسمی • آشنایی با تفسیر پروتئین های فاز حاد در بیماریهای روماتیسمی • آشنایی با تفسیر اتوآنتی بادیها در بیماریهای روماتیسمی • آشنایی با تجزیه مایع مفصلی در بیماریهای روماتیسمی

16. indication for a test • Screen for a particular disease • Help confirm a specific diagnosis • Evaluate disease activity • Assess for target organ involvement • Monitor for drug toxicity

17. Before ……. • Interpret a test result • Sensitivity • Specificity • positive and negative predictive values

18. Sensitivity Proportion of patients with a disease who have a positive test result Specificity Proportion of persons without a disease who have a negative test result

19. Predictive value • likelihood or lack of the disease based on a positive or negative test result • Negative predictive value (NPV) • True negative/(true negative + false negative) • Positive predictive value (PPV) • True positive/(true positive + false positive)

20. CBC • Leukocytosis • Leukopenia • Lymphocytosis • Lymphopenia

21. CBC • Anemia • Anemia of chronic di. • Hemolytic anemia • Iron de. • Megaloblastic anemia

22. CBC • Thrombocytosis • Thrombocytopenia

23. Acute phase reactants • Heterogeneous group of proteins synthesized in liver in response to inflammation • Fibrinogen • Serum Amyloid A • Haptoglobin • C-reactive protein • Alpha-1-antitrypsin

24. Acute phase protein response Adapted from Gitlin JD, Colten HR in Pick E, Landy M [eds]: Lymphokines.14;123,1987.

25. Common markers of inflammation • ESR • Indirect measure of changes in acute-phase reactants and quantitative Igs

26. Mechanism of elevated ESR • If higher concentration of asymmetrically charged acute-phase protein or hypergammaglobulinemia occurs, dielectric constant of plasma increases and dissipates inter-RBC repulsive forces, leads to closer aggregation of RBCs, so they fall faster, and cause ESR elevation

27. Noninflammatory conditions with elevated ESR • Aging • Female sex • Obesity • Pregnancy

28. Rule of thumb • Age-adjusted upper limit normal for ESR • Male: age/2 • Female: (age + 10)/2

29. Causes of markedly elevated ESR • ESR >100 • Infection, bacterial • CTD (GCA, PMR, SLE, vasculitides • Malignancy: lymphomas, myeloma, etc • Other causes

30. Causes of extremely low ESR • ESR ~ 0mm/hr • Agammaglobulinemia • Afibrinogenemia/dysfibrinogemia • Extreme polycythemia (Hematocrit >65%) • Increased plasma viscosity

31. C-reactive protein (CRP) • Acute phase reactant produced by liver • Response to IL-6, other cytokines • Rises and falls quickly • Elevation within 4 hr of tissue injury • Peak at 24-72 hr • Half-life ~18 hr

32. Rule of thumb • CRP <0.2 mg/dL: normal • CRP 0.2-1.0 mg/dL: indeterminate (may be seen in smoking, DM) • CRP >1.0 mg/dL: inflammatory • Levels > 10mg/dL suggest bacterial infection (up to 85%), or possibly systemic vasculitis, metastatic cancer

33. Antinuclear antibodies (ANA)

34. Current ANA measurement • Fluorescence microscopy • HEp-2 cells (derived from human epithelial tumor cell line) incubated with pt’s serum • FluoresceinatedAb added, binds to pt’s Abs bound to nucleus

35. ANA • High sensitivity in SLE, but poor specificity • Positive ANA has predictive value of only 11% • ANA found in 5-10% of pts without CTD • Healthy pts, chronic infections (e.g., Hep C), multiple meds, etc.

36. Condition SLE Drug induced lupus MCTD Autoimmune liver dz Sjogren’s syndrome Polymyositis RA % ANA-positive 99% 95-100% 95-100% 60-100% 75-90% 30-80% 30-50% ANA

37. Condition Multiple sclerosis Pts with silicone breast implants Healthy relatives of pts with SLE Neoplasms Normal elderly (>70 yrs) % ANA-positive 25% 15-25% 20% ANA

38. ANA • Is the ANA a good screening test for SLE? • If entire population was screened, more normal individuals would be detected with positive ANA than SLE pts. by ~50:1

39. ANA • Clinical value of ordering an ANA test can be dramatically enhanced when there is a reasonable pre-test probability of an autoimmune disease

40. ANA patterns • Homogeneous (diffuse) • SLE, drug-induced SLE, other diseases

41. ANA patterns • Rim (peripheral) • SLE, autoimmune hepatitis

42. ANA patterns • Speckled • SLE, MCTD, Sjogren’s, Scleroderma, other dz

43. ANA patterns • Nucleolar • Scleroderma, hepatocellular carcinoma

44. ANA profile • If screening ANA is positive and additional info needed to further delineate type of autoimmune disease • In extremely rare instances, ANA may be negative but SS-A antibodies may be detected in pts. with an SS-A associated disease

45. ANA Profile

46. Antiphospholipid antibodies • Heterogeneous group of Ab that bind to plasma proteins, have affinity for phospholipid surfaces • AnticardiolipinAb (ACL) • Lupus anticoagulant (LAC) • Beta 2-glycoprotein I

47. Antiphospholipid antibodies • ACL measured by ELISA assay for IgG, IgM, and IgAisotypes • LAC measured by phospholipid-dependent screening test, if prolonged, add 1:1 mix with normal plasma - if no correction, LAC present • Beta 2-glycoprotein I measured by ELISA

48. Antiphospholipid antibodies • Conditions with positive aPL • ~8% normal population • chronic infections e.g., HIV, Hep C • Medications e.g., phenothiazines, hydralazine, phenytoin, procainamide, quinidine • ~20% pts. with systemic vasculitis • ~15% pts. with recurrent miscarriage • ~50% pts. with SLE

49. Antiphospholipid antibodies • ~50% pts. with SLE and aPL will develop a thrombotic event • ~3-7% pts. per year who have aPL will experience a new thrombotic event • Overall positive predictive value of an aPL for future CVA, venous thrombosis, or recurrent MC is between 10-25%

50. Anticytoplasmic Antibodies • Often more helpful in diagnosis than antibodies against nuclear antigens • Seen with multiple autoimmune diseases and several forms of vasculitis