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

photo credit: africanleadershipacademy.org

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

photo credit: studyblue.com

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

Photo credit: clinicalcases.org

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

Photo credit: commons.wikipedia.org

SLE Clinical Criteria:Hemolytic anemia

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

Photo credit: de.wikipedia.org

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

Photo credit: en.wikipedia.org

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

Photo credit: cdaarthritis.com

SLE Clinical Criteria:Synovitis

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

Photo credit: entindia.info

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

Photo credit: globalskinatlas.com

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

photo credit: beasleyallen.com

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

photo credit: customink.com

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