lupus update for primary care providers 2014

SLE Update for PCPs 2014

Donald Thomas, MD, FACP, FACRArthritis and Pain Associates of PG County

Assistant Professor of MedicineUniformed Services University of the Health Sciences,

Bethesda

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LUPUS- Women of

childbearing age- More severe dz in

younger patients- 1/200 African

American women of child bearing age

LUPUS- Women of

childbearing age- More severe dz in

younger patients- 1/200 African

American women of child bearing age

- “Invisible disease”- Average of 4-6

years before diagnosis

LUPUS- Women of

childbearing age- More severe dz in

younger patients- 1/200 African

American women of child bearing age

- “Invisible disease”- Average of 4-6 years

before diagnosis

- 5-10% die within 10 years of dx

Whitney- 24 yo

Whitney- Born 12/14/88- Died 2/20/13 from

SLE

photo credit: facebook.com/Lupus –Wall- Remembering- those- who- have- lost- their- Battle

photo credit: sometimesitslupus.com

Lupus prognosis- 95% of patients live 10 years or longer- Most patients live a long normal life with proper

treatment- Best prognosis:

- Early diagnosis- Proper medical care (doctors, medications, tests,

educated)

What we will cover- New “classification criteria” for systemic lupus- What labs to order for lupus workup- Correction of lupus triggers

- Low vit D, UV light, smoking, sulfa antibiotics

- Ensure vaccines are obtained- Resources to recommend to college students with

lupus

American College of Rheumatology (ACR) Classification Criteria for SLE

1982- 4 out of 14 criteria = SLE- Classification criteria = for research purposes only

- Not recommended for diagnostic purposes

- 2004: embarked upon revision

Revision of SLE classification criteria- Missing in 1982 criteria

- Low complements- Antiphospholipid antibodies

- 1982 weighted towards cutaneous dz (4 of 14 criteria)- Excluded biopsy proven lupus nephritis as sole manifestation- Neuro lupus only included psychosis and seizures

- ACR lists 18 potential neurologic disorders in neuropsychiatric lupus

- Could only use one type of low blood count- LE cell prep no longer used

Revision of SLE classification criteria- Diagnosed SLE patients vs those meeting

classification- Many patients with early SLE didn’t meet criteria- By the time they do they are:

- Older- Had established disease longer- More end-organ damage

SLICC: SLE classification criteria- SLE occurs if

- Biopsy proven lupus nephritis + ANA or dsDNA

- OR- 4 out of 17 criteria- At least 1 from “Clinical Criteria” and from “Immunologic

Criteria”

SLICC SLE classification criteriaClinical Criteria (11)

- Renal- Alopecia, nonscarring- Serositis- Hemolytic anemia

- Oral and nasal ulcers- Neurologic

- Synovitis- Chronic cutaneous lupus (discoid)- Acute and subacute cutaneous lupus- Leucopenia/lymphopenia- Platelets, low

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SLE Clinical Criteria:Renal

- Random urine protein/creatinine ratio ≥ 0.500- 25 hour urine protein ≥500 mg protein/24 hours- Red blood cell casts on urine microscopy

SLE Clinical Criteria:Alopecia, nonscarring

- Diffuse thinning- Hair fragility, broken hair- “Lupus hair”- Rule out alopecia areata, drugs, iron deficiency,

androgenic alopecia- Grows back

CellCept

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SLE Clinical Criteria:Serositis

- Pleuritis- “Typical pleurisy” > 1 day- Pleural effusions- Pleural rub

- Pericarditis- “Typical pericardial pain” > 1 day (worse with lying, better

sitting forward)- Pericardial effusion- Pericardial rub- + ECG

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SLE Clinical Criteria:Hemolytic anemia

- Direct Coombs antibody positive- High reticulocyte count- Low haptoglobin - Increased indirect bilirubin

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SLE Clinical Criteria: Oral and nasal ulcers

- Oral ulcers- Palate, buccal, tongue- Often painless

- Nasal ulcers- Rule out:

- Vasculitis- Behçet’s disease- Infections (HSV)- Inflammatory bowel disease- Reactive arthritis

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SLE Clinical Criteria:Neuropsychiatric

- Seizures- Psychosis- Mononeuritis multiplex

- in absence of a 1° vasculitis- Myelitis- Peripheral or Cranial neuropathy

- R/o diabetes, infection (Lyme), 1° vasculitis- Acute confusional state

- R/o toxic, metabolic, uremia, infection, drugs

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SLE Clinical Criteria:Synovitis

- ≥ 2 joints- Swelling or effusion OR- Tender joints + AM stiffness ≥ 30 minutes

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SLE Clinical Criteria:Chronic cutaneous lupus

- Discoid lupus- Hypertrophic (verrucous) lupus- Lupus panniculitis (profundus)- Discoid lupus/lichen planus overlap- Lupus erythematosus tumidus- Chilblains lupus- Mucosal lupus

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SLE Clinical Criteria:Acute cutaneous lupus ORSubacute cutaneous lupus

- Malar rash (don’t count discoid)- Toxic necrolysis variant of SLE- Maculopapular lupus rash- Photosensitive lupus rash- Bullous lupus

- SCLE:- Non-indurated psoriasiform- Annular polycyclic

SLE Clinical Criteria:Leucopenia/Lymphopenia

- WBC < 4000/mm3 (once)- R/o Felty’s syndrome, drugs, portal hypertension

- Lymphs < 1000/mm3 (once)- R/o steroids, drugs, infections (virus)

SLE Clinical Criteria:Platelets, low

- Platelets< 100,000 (once)- R/o TTP, drugs, portal hypertension

SLE Immunologic Criteria (6)- ANA- Anti-ds DNA- Antiphospholipid antibodies

- Lupus anticoagulant- False positive RPR- Anticardiolipin antibody- Beta-2 glycoprotein antibody

- Low complements (C3, C4, CH50)- Direct Coombs’ test (in absence of hemolytic anemia)

2012 criteria vs 1982criteria- Out of 702 patient scenarios……….- Misclassified patients: 7% vs 10%- Sensitivity: 94% vs 86%- Specificity: 92% vs 93% (not statistically different)

“… if you use the classification

criteria to diagnose SLE... I promise not

to tell anyone.”

Michelle Petri, MD: Medical Director Lupus Clinic Johns Hopkins

When to suspect SLE:- Renal (proteinuria)- Alopecia- Serositis (pleuritic chest pain)- Hemolytic anemia (all low blood counts)

- Oral and nasal ulcers- Neurologic problems

- Synovitis (joint pains)- Chronic cutaneous lupus (discoid)- Acute cutaneous lupus (malar rash, rash with sun exposure)- Leukopenia/lymphopenia and Platelets, low

- Blood clots- Raynaud’s phenomenon

Work-up for SLE:- Basic/Initial

- ANA by IFA (indirect fluorescence assay)- CBC- Urinalysis with reflex microscopy- Random urine protein/creatine ratio- ESR, CRP, SPEP- 25-OH vitamin D

- If pleuritic chest pain- CXR- ECG- Echocardiogram

Work-up for SLE:- If positive ANA by IFA

- ds-DNA- ENA (Smith, RNP)- Sjögren's panel (SSA/SSB)- Ribosomal-P antibody- C3, C4, CH50 complements- Direct Coombs’ test- Antiphospholipid antibodies

- RPR with reflex FTA- Anticardiolipin antibodies (IgM, IgG, IgA)- Lupus anticoagulant- Beta-2 glycoprotein I antibodies (IgM, IgG, IgA)

- Inflammatory arthritis:- CPK, RF, CCP, Lyme, HLA-B27, ASO, IgM Parvovirus

Correct triggers of lupus- Low vitamin D levels- UV light- Smoking- Sulfa antibiotics

Low vitamin D and SLE- White blood cell membranes have Vit D receptors- Higher prevalence of low Vit D in SLE patients- More severe SLE at presentation associated with lower

Vit D- Lower Vit D levels occur during SLE flares- Low vitamin D correlated with flares

Correcting low vitamin D as tx- Petri M et al, Vitamin D and SLE, Arthr &

Rheum;65(7):1865-71- 1006 patients, 128 weeks- 25[OH]D < 40 ng/mL- TX = 50,000 IU ergocalciferol (vit D2) + daily calcium with

200 IU vit D3

- Results:- - ≥ 20 ng/mL increase 25[OH]D associated with:

- .22 decrease in SELENA/SLEDAI (P = .032)- 21% decrease in having a SELENA/SLEDAI ≥ 5- Random urine/protein decreased by 2% (P = .0001)- 15% decrease in odds of having urine/prot > .5

Vit D as treatment for SLE- Treat patients with 25[OH]D < 40 ng/mL- Aim for a level of around 40 ng/mL or higher

Ultraviolet light

Ultraviolet light

Skin

cellNUCLEUS

Ultraviolet light

Skin

cellNUCLEUS cell

NUCLEUS

damage

Ultraviolet light

Skin

cellNUCLEUS

Antinuclear antibodiesCause increased lupus activity

Dose of UV light = Strength X Time

X 15 minutes

Dose of UV light = Strength X Time

X 15 minutes

X all day long

UV protection = SLE treatment- Wear sunscreen daily even if don’t go outside- Reapply if go outside- Use sunscreen vs UVA and UVB + waterproof + high

SPF- Wide brimmed hat- UV protectant clothes- Add Rit Sunguard to wash- Avoid outside 10 AM – 3 PM

Stop smoking if have lupus- Tobacco contains hydrazine

- Hydrazine known to increase lupus activity

- Smoking decreases effectiveness of Plaquenil- Smoking is associated with increased lupus prevalence- Smoking associated with more severe lupus

Avoid sulfa antibiotics in SLE- Increased risk for lupus flares- Ask patients to include Bactrim and Septra in allergies

Infection = #2 cause of death in SLE- Make sure all patients get yearly flu shot

HPV-associated cancers = high in SLE- Dreyer L et al, High Incidence of Potentially Virus-

Induced Malignancies in SLE, Arth & Rheum, 2011;63(10):3032-37

- Increased HPV-associated cancers - Anal cancer- Vulvovaginal- Cervical- Non-melanoma skin cancer

- Nath R et al, High risk of Human Papillomavirus Type-16 infections and of development of squamous intraepithelial lesions in systemic lupus erythematosus patients, A&R, 2007;57(4):619-25

- High levels of HPV-16 infection and abnormal colposcopy in newly diagnosed SLE women

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All patients ≤ 26 yo should receive Gardasil series

Resources for college students with lupus

- Lupus Foundation of America DC/MD/VA chapter- Patient Navigator service- www.lupus.org/dmv- 888-787-5380

- “Lupus Secrets” handout (last page)- Social Media:

- Facebook: Lupus Encyclopedia- www.facebook.com/LupusEncyclopedia- Daily tips and facts about lupus- I answer questions posted by patients

- Numerous Facebook patient support groups

Summary- SLICC new SLE classification criteria

- 4 out of 17- at least 1 from “clinical” and 1 from “immunologic”

- Basic initial workup: ANA, CBC, UA- Do additional labs if ANA+- Refer to rheumatologist ASAP

- Begin tx: Vitamin D, Sunscreen, no cigarettes- Vaccines:

- Annual flu shot- Gardasil series

- Resources are available

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References 1:Agmon-Levin N et al. International recommendations for

the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73:17-23

Amital H et al. Serum concentration of 25-OH vitamin D in patients with SLE are inversely related to disease activity. Ann Rheum Dis.2010,69:1155-57.

Birmingham DJ et al. Evidence that abnormally large seasonal declines in vitamin D status may trigger SLE flare in non-African Americans. Lupus. 2012;21(8):855-64

Bonakdar ZS et al. Vitamin D deficiency and its association with disease activity in new cases of systemic lupus erythematosus. Lupus.2011;20:1155-60

References 2:Boeckler P et al. Association of cigarette

smoking but not alcohol consumption with cutaneous lupus erythematosus. Arch of Derm. 2009;145(9):1012-16

Cooper G et al. Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents. Rheum (Oxford). 2010;49(11):2172-80

Dreyer L et al. High incidence of potentially virus-induced malignancies in systemic lupus erythematosus. Arth & Rheum. 2011;63(10):3032-37

References 3:Ghaussy NO et al. Cigarette smoking and

disease activity in systemic lupus erythematosus. J of Rheum. 2003;30:1215-21

Isenberg DA et al. The Systemic Lupus International Collaborating Clinics (SLICC) group – It was 20 years ago today. Lupus. 2011;20:1426-32

Mok CC et al. Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus. Lupus. 2012;21:36-42

References 4:Nath Ret al. High risk of human papilloma

virus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arth & Rheum. 2007;57(4):619-25

Petri M et al. Vitamin D in SLE. Arth & Rheum. 2013;65(7):1865-71

Petri M et al. Derivation and validation of the systemic Lupus International Collaborating Clinics classification criteria for SLE. Arthr & Rheum. 2012:2677-86

References 5:Petri M & Magder L. Classification criteria

for SLE. Lupus. 2004;13:829-37Pons-Estel GJ et al. The ACR and the SLICC

criteria for SLE in two multiethnic cohorts. Lupus. 2014;23:3-9

Rahman P et al. Smoking interferes with efficacy of antimalarial therapy in cutaneous lupus. J of Rheum. 1998;25:1716-19

Ruiz-Irastorza G et al. Changes in vitamin D levels in patients with SLE. Arthr Care & Research. 2010;62(8):1160-65