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Systemic Lupus Erythematosus

Internist Update

Khaled Al Jarallah ,MD
FRCPC,FACP,FACR
Internist, Rheumatologist
Medical Department
Faculty of Medicine
Kuwait University

No disclosures related to the presentation

Learning objectives

• To highlight the natural history of SLE

• To develop a clinical approach to patient suspected
to have SLE

• To define your therapeutic strategies to each SLE
patient based upon activity, severity, organ damage,
and comorbidities

Multi-Systemic Autoimmune Disease

Heterogeneous disease

Lupus patient mind map ! .

Aetiology ? Genetics Hormonal Environmental .

Genes and Immunity 2009 . Genetics Moser K et al.

. The Rheumatologist 2011.Genetics Criswell LA et al.

Environmental • Ultraviolet light • Drugs • Infection • Smoking • Silica dust .

Pathogenesis Innate Adaptive Ann Rheum Dis 2010.69:1603–11 .

net .Pathogenesis www.dressage-de-chien.

Natural history of SLE Ann Rheum Dis 2010.69:1603–11 .

The 4 D’s clinical approach • Diagnostic workup • Disease activity assessment • Damage assessment • Design treatment goals .

Diagnostic workup • No gold standard test • Clinical reasoning • Classification criteria .

Tests • Exclude other diseases • Distinguish activity from chronicity • Prioritize active disease manifestations . Diagnostic workup • Identify disease manifestations • Perform Lab.

SLE target .

Which one is lupus rash ? A B C .

MCTD . dermatitis  Chronic autoimmune disorders: sjogrens. JIA  Vasculitis either primary or secondary to infection (Hep C. Lupus mimickers  Dermatological conditions: Rosocea. parvovirus B19 . EB virus) or malignancy  Kikuchi-Fujimoto disease  Multiple Sclerosis .HIV.

C4. Her disease manifestations consists of : • Fatigue • Hemolytic anemia • ANA + • Anti-Sm + • C3. Case presentation • A 25-year-old woman.CH50 Low .

Classification criteria for SLE Year American College of Rheumatology (ACR) classification 1971 Criteria for SLE classification developed 1982 Revised classification 1997 Revised again 2012 SLICC SLE Criteria .

000 /m) or 8 L.5 gm/day) 3 Raynaud's phenomenon 11 Cellular casts 4 Alopecia 12 Pleuritis or pericarditis 5 Photosensitivity 13 Psychosis or convulsions 6 Oral or nasal ulcers 14 Hemolytic anemia 7 Arthritis without or Leukocytopenia deformity (<4. serially or simultaneously . 1971 ACR criteria for classification of SLE Clinical Criteria Clinical Criteria 1 Facial erythema 9 Chronic false positive seologic test for syphilis 2 Discoid lupus 10 Proteinuria (>3.E cells (2 or more) Thrombocytopenia (<100.000 /m) Any of four or more criteria should be present .

1982 revised classification criteria Clinical Criteria 1 Malar Rash 2 Discoid Rash 3 Photosensitivity 4 Oral ulcers 5 Arthritis 6 Serositis 7 Renal Disorder 8 Neurologic Disorder 9 Hematologic disorder 10 Immunologic disorder 11 Antinuclear Antibody Any of four or more criteria should be present . serially or simultaneously .

False positive seologic test for syphilis for 6 9 Hematologic disorder months 10 Immunologic disorder 11 Antinuclear Antibody Any of four or more criteria should be present .Abnormal IgG/ IgM 5 Arthritis anticardiolipin 6 Serositis antibodies 2. 1997 Revised classification criteria Clinical Criteria Immunologic disorder a) Anti-DNA or 1 Malar Rash b) Anti. Positive Lupus 7 Renal Disorder anticoagulant 8 Neurologic Disorder 3. serially or simultaneously .Sm or 2 Discoid Rash c) Positive finding of 3 Photosensitivity antiphospholipid antibodies based on: 4 Oral ulcers 1.

2012-SLICC* classification criteria At least 1 clinical + at least 1 immunologic Criteria ( for a total of 4) OR Lupus Nephritis by biopsy with ANA or anti-dsDNA antibodies * Systemic Lupus International Collaborating Clinics Petri M et al. Arthritis Rheum 2012.64(8):2677-86 .

2012-SLICC classification criteria Clinical Criteria 1 Acute Cutaneous Lupus Lupus specific 2 Chronic Cutaneous Lupus 3 Oral or nasal ulcers 4 Non-scarring alopecia 5 Arthritis 6 Serositis 7 Renal Disorder 8 Neurologic Disorder 9 Hemolytic anemia 10 Leukopenia/ Lymphopenia 11 Thrombocytopenia .

Histopathologic findings of interface dermatitis .

Acute Cutaneous / Subacute Cutaneous Lupus • Malar rash • Bullous lupus • Toxic epidermal necrolysis • Maculopapular lupus rash • Photosensitive lupus rash • Nonindurated psoriasiform • Annular polycyclic rash .

Chronic Cutaneous Lupus • Discoid rash. localized & generalized • Hypertrophic ( verrucous ) lupus • Lupus panniculitis ( profundus ) • Lupus erythematosus tumidis • Chilblains lupus • Mucosal lupus • Lichen planus overlap .

SLE.Cutaneous manifestations .

2012-SLICC classification criteria Clinical Criteria 1 Acute Cutaneous Lupus 2 Chronic Cutaneous Lupus 3 Oral or nasal ulcers 4 Non-scarring alopecia 5 Arthritis 6 Serositis 7 Renal Disorder 8 Neurologic Disorder 9 Hemolytic anemia 10 Leukopenia/ Lymphopenia 11 Thrombocytopenia .

2012-SLICC classification criteria Immunologic Criteria 1 ANA 2 Anti-DNA 3 Anti.C4 or CH 50) 6 Direct Coombs test ( in absence of hemolytic anemia) .Sm 4 Antiphospholipid antibodies Lupus anticoagulant False+ rapid plasma reagin Anticardiolipin . IgG or IgM 5 Low complements (C3. IgA.IgA. IgG or IgM Anti-B2-glycoprotein I .

2012. Arthritis Rheum. Performance of the classifications as compared to the current ACR criteria on the sample based on 702 cases* Rule ‘Sensitivity’ ‘Specificity’ Misclassified cases (n) 1997 ACR 267/310 (86%) 365/392 (93%) 70 criteria SLICC criteria 292/310 (94%) 361/392 (92%) 49 *Petri M et al.64(8): 2677 .

Case presentation • A 25-year-old woman. Her disease manifestations consists of : • Fatigue • Hemolytic anemia • ANA + • Anti-Sm + • C3.CH50 Low .C4.

Saudi@ N=1000 N=1. Cumulative SLE features in different ethnic groups #European $Filipino India* Kuwait**. 98 96 *Lupus 1997. **1998. $Mod Rheumatol 2008.070 N=1366 N=732 Malar Rash 58 49 58 49 Discoid Rash 10 26 7 15 Photosensitivity 45 33 48 38 Oral ulcers 24 33 55 27 Arthritis 87 68 85 89 Serositis 29 12 22 41 Renal Disorder 37 47 73 49 Neurologic Disorder 23 13 51 24 Hematologic disorder 53 37 26 64 Immunologic disorder Anti-DNA 58 .Sm 13 29 25 VDRL 6 8 9 Antinuclear Antibody 94 . @2009. 68 74 Anti. #Medicine (Baltimore) 1993 .

Cumulative frequencies of SLE features Manifestation Frequency Constitutional symptoms 90%-95% Mucocutaneous involvement 80%-90% Musculoskeletal involvement 80%-90% Serositis 50%-70% Glomerulonephritis 40%-60% Neuropsychiatric involvement 40%-60% Autoimmune cytopenia 20%-30% Vitali C et al.Clin Exp Rheumatol 1992 .

The 4 D’s clinical approach • Diagnostic workup • Disease activity assessment • Damage assessment • Design treatment goals .

ECLAM. SRI • Activity. reversibility SELENA-SLEDAI .SLAM. severity. Disease activity assessment • Which instrument to choose? • SLEDAI .BILAG .

SLEDAI • Evaluates 24 lupus manifestations • Parameters are scored √ if present • Manifestation items are weighted with scores ranging from 1 to 8 • Scores are totaled – Mild: 0-5 – Moderate: 6-12 – Severe: 13-20 Bombardier C et al. 35:630-640 . 1992. Arthritis Rheum.

but must nonresponsive to narcotic analgesia. tender finger nodules. gangrene. or syndrome other intellectual function. infectious. serous exudate or hemorrhages in the choroid. marked loose associations. Exclude arteriosclerosis. . persistent headache. 8 1  0 Vasculitis Ulceration. SLEDAI SLEDAI Yes No Descriptor Definition Score 8 1  0 Seizure Recent onset. Exclude metabolic. retinal disturbance hemorrhages. 8 1  0 CVA New onset of cerebrovascular accident(s). rapid onset and fluctuating clinical features 8 1  0 Visual Retinal changes of SLE. disorganized. memory. or drug causes. may be migrainous. 8 1  0 Organic brain Altered mental function with impaired orientation. Include cytoid bodies. or catatonic behavior. or biopsy or angiogram proof of vasculitis. 8 1  0 Lupus headache Severe. periungual infarction. bizarre. 8 1  0 Psychosis Altered ability to function in normal activity. or optic neuritis. Include hallucinations. splinter hemorrhages. incoherence . marked illogical thinking. 8 1  0 Cranial nerve New onset of sensory or motor neuropathy involving cranial disorder nerves.

Exclude infectious cause. 2  1 0 Alopecia Abnormal. Exclude drug causes . or +ECG or echo 2  1 0 Low complement Decrease in CH50. or pleural thickening. associated with elevated CPK/ aldolase /EMG changes /biopsy showing myositis 4 1  0 Urinary casts Heme‑granular or red blood cell casts 4 1  0 Hematuria >5 red blood cells/high power field. 4 1  0 Pyuria > 5 white blood cells/high power field. effusion. 1  1 0 Thrombocytopenia < 100x109 platelets/L. 2  1 0 Increased DNA Increased DNA binding above normal range for binding testing laboratory. others 4 1  0 Proteinuria >0. infection. 1  1 0 Fever >38°C. or C4 below the lower limit of normal for testing laboratory. Exclude infection. 2  1 0 Rash Inflammatory type rash. patchy or diffuse loss of hair.5 gm/24 hours. 2 1  0 Mucosal ulcers Oral or nasal ulcerations 2 1  0 Pleurisy Pleuritic chest pain with pleural rub or effusion. C3. Exclude stone. Exclude drug causes 1  1 0 Leukopenia < 3x109 WBC/L. SLEDAI SLEDAI Yes No Descriptor Definition Score 4  1 0 Arthritis More than 2 joints with pain and signs of inflammation 4 1  0 Myositis Proximal muscle aching/weakness. 2 1  0 Pericarditis Pericardial pain with at least 1 of the following: rub.

The 4 D’s clinical approach • Diagnostic workup • Disease activity assessment • Damage assessment • Design treatment goals .

irreversibility . Damage assessment • Which instrument to choose? • SLICC/ACR damage index • Chronicity. damage.

SLICC/ACR damage Index • Validated & used in clinical trails • Records damage in 12 organs or systems • The damage must present in the last 6 month • High damage index correlate with poor prognosis .

1 • Claudication for 6 months 0.1 • Myocardial infarction ever (score 2 if > 1) 0.1 • Cranial or peripheral neuropathy 0.1 • Minor tissue loss (pulp space) 0.1 • Infarction or resection of bowel below duodenum spleen. ascertained by clinical assessment and present for at least 6 months unless otherwise stated.1 Cardiovascular Premature gonadal failure 0. .1 • Stricture or upper gastrointestinal tract surgery ever 0.1 • Skin ulceration (excluding thrombosis) for >6 months 0.2 • Pericarditis for 6 months.1 • Retinal change or optic atrophy 0.1 • Shrinking lung (radiograph) 0. not related to active inflammation) occurring since onset of lupus.1 • Muscle atrophy or weakness 0.1 • Scarring chronic alopecia 0.1 • ESRD 3 • Deforming or erosive arthritis 0.2 • Significant tissue loss ever ( loss of digit) (score 2 if >1 site) 0.1 • Seizures requiring therapy for 6 months 0.1 • Mesenteric insufficiency • Chronic peritonitis 0. or gall bladder ever.1 Neuropsychiatric • Cognitive impairment/ major psychosis 0. or venous stasis 0.1 pericardiectomy Damage (nonreversible change. swelling. for cause any (score 2 if > 1 site) 0.2 • Transverse myelitis 0.2 Diabetes (regardless of treatment) 0.1 • Valvular disease (murmur >3/6) 0. or 0.1.1.5 gm/24 h 0. SLICC/ACR damage Index Item Score Item Score Ocular Peripheral vascular • Any cataract ever 0.1 Pulmonary • Avascular necrosis (score 2 if >1) 0.1 Malignancy (exclude dysplasia) (score 2 if > 1 site) 0.1 • Cardiomyopathy (ventricular dysfunction) 0. The same lesion cannot be scored twice.1 • Tendon Rupture 0.1 Musculoskeletal • Proteinuria >3.1 • Angina or coronary artery bypass 0.1 • Extensive scarring other than scalp and pulp space 0.1.1 Skin • Pleural fibrosis (radiograph) 0. ulceration.1 • Osteomyelitis 0.2 • Pulmonary hypertension 0.1.1 • Osteoporosis with fracture or vertebral collapse 0.1 liver. 0.1.1 • Pulmonary fibrosis and radiograph) 0.1 • Pulmonary infarction (radiograph) 0.1 • Venous thrombosis.1 Renal • Estimated GFR <50% 0.1 Gastrointestinal • CVA ever (score 2 if >1) 0. Repeat episodes must occur at least 6 months apart to score 2.

SLE Disease assessment Disease Damage Disease Activity SLICC/ACR SLEDAI Damage Index Health Status Assessment SF-36 .

The 4 D’s clinical approach • Diagnostic workup • Disease activity assessment • Damage assessment • Design treatment goals .

Design treatment goals • Do good Control disease activity Prevent organ damage Prevent flares • Do no harm Safety profile Drugs Drugs related damage .

Retuximab ‘dialysis’ 10 year survival >60% Improvement in antibiotic antihypertensive.ACR 2012 . and antithrombotic therapies Adapted from Manzi S . 50% 10 year survival >80% 1960-1970s 2000-2010s 1940-1950 Cyclophosphamide Mycophenolate mofetil Antimalarials Azathioprine Biologics . Mortality and Treatment 1970-1990s Methotrexate Organ transplantation 1950-1954 Plasmapheresis Cyclosporine 2011 Corticosteroids Belimumab 5 year survival .

15:366 • Prevents seizure Ann Rheum Dis 2012.71:1502 • Reduction in CHB in neonatal lupus Circulation 2012 . Hydroxychloroquine • Reduction in flares N Engl J Med 1991.324:150 • Reduction in lipids Am J Med 1990.25:191 • Reduction in organ damage Arthritis Rheum 2005.52:1473 • Improved survival Lupus 2005.14:220 • Triples mycophenolate response Lupus 2006.89:322 • Reduction in thrombosis Scand J Rheumatol 1996.

2013 . Vitamin D Improved vitamin D level positively affects: • Disease activity (21% in odds in SLEDAI score 5or>) • Urine protein/Cr (15% in odds in urine pr/cr >0.5) • Systolic blood pressure Low vitamin D is associated with venous thrombosis Petri M et al. ACR abstracts 2012.

Ian N Bruce Issue 2 (Topical Reviews Series 7) Spring 2013 . Overview of management of SLE Establish diagnosis No major organ involvement • Antimalarials • Low-dose steroids Determine disease activity • Azathioprine/methotrexate Assess severity and organ involvement Lifestyle (sun avoidance) Major organ involvement Topical agents • Cyclophosphamide (IV) Symptomatic agents • Mycophenolate mofetil Manage co-morbidities • Calcineurin inhibitors (CyA/tarcolimus ) • Biologics (rituximab/belimumab) or • Enroll in a clinical trial Overview of the management of systemic lupus erythematosus -John A Reynolds.

2011 . Ther Adv Musculoskelet Dis.Treatment targets for SLE Adapted from Xiong W and Lahita RG.

cocolog-nifty.Treatment targets for SLE Ryo1m.com .

Types of Vaccinations Inactivated or killed Toxoids Live Attenuated Vaccines* vaccines Cholera Diphtheria BCG Meningococcal Tetanus Oral Typhoid Pneumococcal Typhoid Hemophilus Influenza B Herpes Zoster Hepatitis A. hypocomplementemia . low immunoglobulins.B Measles. Rubella HPV Varicella Polio ( Salk) Polio (oral) Seasonal influenza (IM) Seasonal influenza (Intra nasal) Japanese Encephalitis Yellow Fever Endemic typhus * Not recommended in SLE if on immunosuppressive or biologic medications. Mumps.

Conclusions “take home massages” • SLE is a heterogeneous multisystem disease which varies among races and ethnicities • SLE pathogenesis is complex with dysregulation of multiple arms of the immune system • Early lupus diagnosis and disease monitoring remains a challenge for treating physicians • SLICC 2012 revised SLE criteria improved the sensitivity and retained the specificity when compared with 1997 ACR classification .

distinguish activity from chronicity and prioritize active disease manifestations • Use the least toxic medicine and lowest dose to treat the most concerning disease manifestation • Balance the treatment of active disease verses the complications of the treatment . Conclusions “take home massages” • Set the treatment goals after Identifying disease manifestations. comorbidities.

Diagnostic criteria for Systemic Lupus Erythematosus: has the time come? Nat. American College of Rheumatology. Learning Resources • Bertsias GK et al .org . Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics Ann Rheum Dis 2008. 2012.eular. treatment. EULAR recommendations for the management of systemic lupus erythematosus.rheumatolgy.67:195–205 • Hahn BH. American College of Rheumatology guidelines for screening. Rheumatol.64:797-808 • www.org & www. and management of lupus nephritis. Arthritis Care Res . et al.9: 687-694 • Bertsias GK et al. Rev.2013.

Thank you for listening .