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© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View.

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Presentation on theme: "© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View."— Presentation transcript:

1 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

2 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Terms of Use  The In the Clinic ® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for- profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets constitutes copyright infringement.

3 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. in the clinic Systemic Lupus Erythematosus

4 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Which patients are at elevated risk for lupus?  Early studies suggest genetic predisposition  HLA genes + early complement components  Single-gene risk factors account for just 1-2% of cases  >30 gene polymorphisms linked to lupus  Possible contributors in those genetically predisposed  Sex chromosome genes, sex hormones  Environmental influences  Diagnosed 9-times more often in women than men  More common and severe in women who are African American, Hispanic, other ethnic minorities

5 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Should clinicians screen patients for asymptomatic lupus if they are at increased risk?  Not recommended  Including those with a family history  Test for ANA produces too many false-positives  Detected in 3-5% of healthy individuals or patients with other autoimmune or infectious diseases  Serologic evidence may precede clinical manifestations  By 3 to 9 years  Treating during this clinically ‘silent’ period doesn’t halt or delay development

6 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Screening…  Single-gene mutations causing SLE are rare  Numerous gene variants are linked to lupus  Current evidence insufficient to support screening for them  ANA testing in asymptomatic individuals is not useful  Immune reaction to nuclear antigens is not SLE-specific  Can be detected in healthy individuals  May precede SLE manifestations by many years

7 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What symptoms or physical exam findings should prompt clinicians to consider lupus?  Weight loss, fatigue, low-grade fever  Initial presentation often mimics a viral syndrome  Arthralgias or arthritis  Morning stiffness, mild-to-moderate joint swelling  Non-erosive, affecting lg / sm joints; infrequent deformities  Jaccoud’s arthropathy present in %  Cutaneous manifestations (occur in up to 70%)  Acute: indurated or flat erythematous lesions  Subacute: annular lesions coalescing into polycyclic rash or papulosquamous lesions  Chronic: scarring indurated plaques that resolve with depigmentation (discoid lupus)

8 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What other clinical manifestations should clinicians look for when evaluating people who may have lupus?  Lupus is a multi-organ disease  May present in many ways  Can mimic infectious diseases, cancer, autoimmune conditions  ACR classification criteria facilitates systematic approach  Focuses on the most common SLE manifestations  4 of the 11 criteria required for classification  Highly sensitive + specific for diagnosing SLE  But patients with mild disease may be missed

9 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.  Malar rash: flat or raised erythema over malar eminences  Discoid rash: erythematous raised patches or atrophic scarring  Photosensitivity: skin rash from unusual reaction to sunlight  Oral ulcers: usually painless oral / nasopharyngeal ulcerations  Arthritis: nonerosive, involving ≥2 or more peripheral joints  Serositis: pleuritis or documented pericarditis  Renal disorder: persistent proteinuria >0.5 g/d or >3 (dipstick); cellular casts red cell, hgb, granular, tubular, or mixed  Neurologic disorder: seizures or psychosis  Hematologic disorder: hemolytic anemia with reticulocytosis; leukopenia <4000/mm ≥2 occasions; lymphopenia <1500/mm ≥2 or more occasions; thrombocytopenia < /mm  Immunologic disorder: anti-dsDNA; anti-Smith antibodies; antiphospholipid antibodies  ANA: in absence of drugs associated with drug-induced SLE

10 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What laboratory tests should clinicians use to diagnose lupus?  ANA  Negative ANA inconsistent with diagnosis of SLE  If positive, test for antigen-specific ANAs  Those targeting dsDNA or ribonucleoprotein complexes Ro/SSA, La/SSB Smith, RNP (extractable nuclear antigens)  Basic investigations for SLE  Complement C3 and C4  CBC, ESR, CRP, comprehensive metabolic panel  Urinalysis  Direct Coombs’ test (if hemolytic anemia + reticulocytosis)  Creatine phosphokinase (if muscle weakness)

11 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What other diagnoses should clinicians consider in patients with possible lupus?  Chronic fatigue syndrome  Fibromyalgia  Rheumatoid arthritis  Small or medium vessel vasculitides  Thrombotic thrombocytopenic purpura  Viral arthritis  Hematopoietic cancer  Malignant lymphoproliferative syndromes

12 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should clinicians consult with a rheumatologist or other specialist for diagnosing patients with possible lupus?  All patients  When manifestations and serologic studies suggest SLE  Goals  Timely, accurate diagnosis  Effective treatment of acute disease  Appropriate monitoring and dose adjustment  Early introduction of a steroid-sparing regimen

13 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Diagnosis…  Lupus often a diagnostic challenge  Multisystem (cutaneous, renal, respiratory, CV, CNS, GI)  Manifestations may characterize numerous other conditions  Use ACR classification criteria as a guide

14 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What medications are used to treat lupus?  Glucocorticoids  First-line agents for most manifestations  Dosage and duration based on clinical experience  Antimalarials  Hydroxychloroquine: cornerstone of SLE treatment  To prevent disease flares  NSAIDs  Immunosuppressive treatment  In lupus nephritis: based on histopathologic classifications  Other manifestations: treatment often includes immunosuppressives and a multidisciplinary approach

15 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians initiate therapy in a stable patient who is not having a flare?  Hydroxychloroquine and other antimalarials  Used to treat inflammatory arthritides for >50 years  Prevents relapses  Reduces risk for congenital heart block in neonatal SLE  Antithrombotic effects are important in antiphospholipid antibody-related prothrombotic diathesis  Well-tolerated with rare side effects (retinopathy; skin hyperpigmentation; neuromuscular or cardiac toxicity)

16 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose therapy for a patient who is having a flare?  IV glucocorticoids + immunosuppressive medications  For severe manifestations (lupus nephritis, alveolar hemorrhage, CNS vasculitis)  Withdraw glucocorticoids once remission achieved  Oral prednisone or methlyprednisolone  For arthritis, pleuropericarditis, cutaneous vasculitis, uveitis  Overlap: lupus manifestations, glucocorticoid complications  Osteoporosis, avascular bone necrosis, myopathy, psychosis  Glucocorticoid dosage, duration: rely on clinical experience  Prolonged medium-to-high dosing increases complications

17 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose drug therapy for cutaneous manifestations?  Commonly used topical treatments  Tacrolimus, R-salbutamol, or pimecrolimus  Clobetasol  Betamethasone  Photoprotection  Other treatments  Systemic hydroxychloroquine and chloroquine  Methotrexate  Mycophenolate mofetil  Azathioprine  Rituximab

18 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose drug therapy for arthritis?  First-line agents  Low-dose glucocorticoids  Antimalarials  Other treatment  Methotrexate (particularly in patients without other systemic manifestations)

19 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose and dose drug therapy for lupus nephritis?  Class I or II: no immunosuppressive therapy  Standard therapy: cyclophosphamide + IV glucocorticoids  Dose cyclophosphamide by total body surface area, adjusted for decreased creatinine clearance  Dose glucocorticoids using ACR recommendations  Newer regimen: mycophenolate mofetil + glucocorticoids  GI and hematologic toxicity common  Contraindicated in pregnancy (possibly teratogenic)  Class V: prednisone 0.5 mg/kg/d + mycophenolate mofetil  Class VI: preparation for renal replacement therapy  Class III or IV: treat aggressively

20 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1.  Maintenance therapy  Mycophenolate mofetil  Azathioprine  Both superior to cyclophosphamide  For patients who don’t respond to either  Calcineurin inhibitors (cyclosporine, tacrolimus)  Rituximab (monoclonal antibody against CD20)  Either in combination with glucocorticoids

21 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. Indications for kidney biopsy in SLE  Increasing serum creatinine  Without compelling alternative causes  Confirmed proteinuria ≥1.0gm per 24h  24-h urine specimens or spot protein/creatinine ratio  Combination of the following:  Proteinuria ≥0.5 gm per 24h + hematuria (≥5 RBCs/high- power field) or  Proteinuria ≥0.5 gm per 24h + cellular casts

22 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose drug therapy for membranous nephritis?  Pure membranous nephritis not associated with endocapillary proliferation  Presents with variable degree of proteinuria  Progression of renal dysfunction slow compared to class III or IV lupus nephritis  Treat with mycophenolate mofetil + steroids  Tacrolimus / azathioprine + steroids also effective

23 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose therapy for neuropsychiatric lupus?  Treatment relatively empirical  IV glucocorticoids, immunoglobulin, cyclophosphamide  Relapse may be more common in glucocorticoid vs cyclophosphamide treatment  Rituximab may be beneficial, but relapse rate seems high

24 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose therapy for respiratory manifestations?  Pleuritis  NSAIDs, low- to moderate-dose glucocorticoids  Abrupt diffuse alveolar hemorrhage  IV glucocorticoids + immunosupressants; consider plasmapheresis  Pulmonary hypertension  PDE-5 inhibitors, ERAs, and prostacyclin analogs may be used; with or without immunosuppressants  In interstitial lung disease: glucocorticoids, and, if poor response, cyclophosphamide or azathioprine  Acute lupus pneumonitis  High doses of glucocorticoids and cyclophosphamide

25 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians choose therapy for ocular manifestations?  Depends on severity and disease activity  Antimalarials  NSAIDs  Oral or IV glucocorticoids  Scleral or retinal involvement  Concomitant use of pulse glucocorticoids  Then 1 mg/kg prednisone equivalent + immunosuppressants  Retinal vasculitis and arterial or venous retinal occlusion with antiphospholipid antibodies  Immunosuppressants + antiplatelet agents / anticoagulation

26 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What new medications are available for treating systemic lupus?  Belimumab (1 mg/kg and 10 mg/kg dose)  Monoclonal antibody targeting B lymphocyte stimulator  Recently approved for treatment  Improves musculoskeletal, mucocutaneous manifestations  Improves immunological parameters  Fewer patients had worsening hematological parameters  Trials excluded patients with severe lupus nephritis or severe CNS manifestations

27 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians monitor patients who are being treated for lupus?  Routinely test: CBC, basic metabolic panel, urinalysis  Allows evaluation of target-organ manifestations  Routinely test?: dsDNA antibodies + C3 & C4 levels  Controversial for clinically stable patients  Treatment with prednisone of clinically stable but serologically active patients may avert severe flare  Monitor individual disease manifestations  Monitor for immunosuppressant toxicity  If treated with hydroxychloroquine: ophthalmological evaluation (particularly if >40y and treated for a long time)  Monitor for osteoporosis, osteonecrosis  Consider periodic lipid testing, ECHO

28 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What should clinicians do about immunizations in people with lupus?  All patients with SLE should receive  Influenza vaccine  Pneumococcal vaccine  Consider quadrivalent HPV vaccine  Well-tolerated, reasonably effective in stable SLE  No live attenuated vaccines if immunocompromised  If on >20mg/d prednisone or immunosuppressants  Including: herpes zoster, Flumist, MMR, smallpox  Tuberculin skin test recommended  If glucocorticoids or immunosuppressive use prolonged

29 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. How should clinicians modify treatment for pregnant patients?  Higher flare rate in pregnancy + immediate post-partum  Initial presentation with hematologic or renal manifestations during pregnancy not uncommon  Consider pregnancy-related abnormalities that mimic SLE (eclampsia, HELLP syndrome)  Treat active lupus manifestations  Use hydroxychloroquine and prednisone  Discontinuation associated with increased flare risk  If severe, consider IV glucocorticoids + azathioprine  Contraindicated: mycophenolate mofetil, methotrexate, cyclophosphamide

30 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should patients with lupus be hospitalized?  Severe thrombocytopenia  Severe or rapidly progressive renal disease  Suspected lupus pneumonitis or pulmonary hemorrhage  Chest pain or severe cardiovascular manifestations  CNS and neurological manifestations  Unexplained fever

31 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. When should clinicians consider consulting a rheumatologist or other specialist for treating patients with lupus?  Rheumatologist  Should be involved in the treatment of all lupus patients  Other specialists also may be involved  Depending on organ-specific disease manifestations

32 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. What non-drug therapies should clinicians recommend for lupus?  Low cholesterol diet  Exercise  Weight control  Smoking cessation  UV protection (to reduce flares from sun exposure)  Calcium and vitamin D (to prevent osteoporosis)  Routine dental evaluation

33 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (3): ITC2-1. CLINICAL BOTTOM LINE: Treatment…  Hydroxychloroquine  Prevents disease flares  Cornerstone of SLE treatment  Glucocorticoids  First-line for most SLE manifestations  Dose & duration based on clinical experience, consensus  Immunosuppressive treatment in lupus nephritis  Based on histopathologic classification  Guided by ACR recommendations  Treatment of other lupus manifestations  Based on clinical experience  Often immunosuppressive Rx + multidisciplinary approach


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