How do we diagnose lupus? Mariko Ishimori, MD Division of Rheumatology Cedars-Sinai Medical Center Assistant Clinical Professor of Medicine, UCLA

Topics of Discussion Types of lupus Challenges of making the diagnosis Elements of diagnosis Specific features and criteria

Types of lupus

Challenges of making the diagnosis

Elements of diagnosis

Specific features and criteria

What is lupus? Common name for a disorder known more formally as Lupus Erythematosus A disorder that predominantly affects women, particularly in their child-bearing years, but may be diagnosed in all age groups

Common name for a disorder known more formally as Lupus Erythematosus

A disorder that predominantly affects women, particularly in their child-bearing years, but may be diagnosed in all age groups

What is lupus? Not a simple disease with easy answers

Types of Lupus 70% = Systemic lupus erythematosus (SLE) 10% = Cutaneous lupus erythematosus (includes Discoid lupus erythematosus) 10% = Drug-induced lupus erythematosus 10% = Other overlap syndrome or mixed connective tissue disease (MCTD)

70% = Systemic lupus erythematosus (SLE)

10% = Cutaneous lupus erythematosus (includes Discoid lupus erythematosus)

10% = Drug-induced lupus erythematosus

10% = Other overlap syndrome or mixed connective tissue disease (MCTD)

Why is it so difficult to diagnose? Many lupus patients look healthy from the outside Initial symptoms may be non-specific (fatigue, achiness, stiffness, low grade-temps, swollen lymph nodes, rashes) Symptoms may develop slowly over months or years or may develop suddenly

Many lupus patients look healthy from the outside

Initial symptoms may be non-specific (fatigue, achiness, stiffness, low grade-temps, swollen lymph nodes, rashes)

Symptoms may develop slowly over months or years or may develop suddenly

A wide variety of symptoms and organ involvement may be present

A wide variety of symptoms and organ involvement may be present

Why is it so difficult to diagnose? No single laboratory test establishes the diagnosis Course of disease characterized by remissions and exacerbations Shortage of trained rheumatologists and limited exposure to field

No single laboratory test establishes the diagnosis

Course of disease characterized by remissions and exacerbations

Shortage of trained rheumatologists and limited exposure to field

Why is it so difficult to diagnose? Misunderstanding by other physicians as to how to diagnose lupus Symptoms may be attributed to “stress” or “a virus” or “emotional problems” Female-predominant diseases have historically have been understudied by academic medicine

Misunderstanding by other physicians as to how to diagnose lupus

Symptoms may be attributed to “stress” or “a virus” or “emotional problems”

Female-predominant diseases have historically have been understudied by academic medicine

Lupus: the “great imitator” Even with medical attention, it may take a while to be diagnosed Lupus can look like different diseases Some diseases it can be mistaken for include infections and cancer

Even with medical attention, it may take a while to be diagnosed

Lupus can look like different diseases

Some diseases it can be mistaken for include infections and cancer

What do we do to diagnose lupus? Medical history : You will tell your doctor about your symptoms and your doctor will also ask a lot of questions regarding symptoms and other problems

Medical history : You will tell your doctor about your symptoms and your doctor will also ask a lot of questions regarding symptoms and other problems

What do we do to diagnose lupus? Complete physical exam : Your doctor will look for rashes, oral ulcers, hair loss, evidence of arthritis, listen to your heart and lungs, and other signs that something is wrong

Complete physical exam : Your doctor will look for rashes, oral ulcers, hair loss, evidence of arthritis, listen to your heart and lungs, and other signs that something is wrong

What do we do to diagnose lupus? Laboratory testing of blood & urine : Blood and urine test may show if your immune system is overactive. Common tests include blood counts, urinalysis, creatinine and electrolytes, liver function tests, ESR, CRP, blood clotting tests, serologic or immunologic testing

Laboratory testing of blood & urine : Blood and urine test may show if your immune system is overactive.

Common tests include blood counts, urinalysis, creatinine and electrolytes, liver function tests, ESR, CRP, blood clotting tests, serologic or immunologic testing

What do we do to diagnose lupus? Skin or kidney biopsy : In certain patients, a minor surgical procedure is performed to remove a small sample of tissue. Tissue examined under the microscope can show signs of lupus

Skin or kidney biopsy : In certain patients, a minor surgical procedure is performed to remove a small sample of tissue. Tissue examined under the microscope can show signs of lupus

Systemic Lupus Erythematosus Multi-system disorder caused by tissue damage from antibody and immune complexes American College of Rheumatology (ACR) devised criteria for SLE in 1971 Out of eleven criteria, at least 4 must be present to meet the classification of SLE under this definition Includes 4 skin criteria, 4 organ criteria, 3 laboratory-based criteria

Multi-system disorder caused by tissue damage from antibody and immune complexes

American College of Rheumatology (ACR) devised criteria for SLE in 1971

Out of eleven criteria, at least 4 must be present to meet the classification of SLE under this definition

Includes 4 skin criteria, 4 organ criteria, 3 laboratory-based criteria

ACR Criteria for SLE 1. Photosensitivity (sun sensitivity) 2. Oral ulcers (mouth sores) 3. Malar rash (butterfly rash) 4. Discoid rash

1. Photosensitivity (sun sensitivity)

2. Oral ulcers (mouth sores)

3. Malar rash (butterfly rash)

4. Discoid rash

ACR Criteria for SLE Arthritis Serositis (inflammation of lung or heart lining) Kidney disorder (abnormal sediment or protein in urine) Neurologic disorder (seizures, psychosis without explanation) Blood abnormalities (hemolytic anemia, low white cell count, low platelet count) Immunologic disorder (anti-phospholipid antibody, lupus anticoagulant, anti-DNA, anti Smith, false positive syphilis test)

Arthritis

Serositis (inflammation of lung or heart lining)

Kidney disorder (abnormal sediment or protein in urine)

Neurologic disorder (seizures, psychosis without explanation)

Blood abnormalities (hemolytic anemia, low white cell count, low platelet count)

Immunologic disorder (anti-phospholipid antibody, lupus anticoagulant, anti-DNA, anti Smith, false positive syphilis test)

ACR Criteria for SLE 11. Positive anti-nuclear antibody (ANA) blood test ANA test is important as a screening tool and a diagnostic tool A positive ANA does NOT automatically mean a patient has lupus Can be positive in many healthy people, especially young women and in other conditions (recent infection, other autoimmune diseases)

11. Positive anti-nuclear antibody (ANA) blood test

ANA test is important as a screening tool and a diagnostic tool

A positive ANA does NOT automatically mean a patient has lupus

Can be positive in many healthy people, especially young women and in other conditions (recent infection, other autoimmune diseases)

Other symptoms Fatigue Low-grade fevers Achiness Swollen lymph nodes Pain on taking a deep breath Raynaud’s phenomenon Alopecia (loss of scalp hair) Headaches Cognitive difficulties (brain fog)

Fatigue

Low-grade fevers

Achiness

Swollen lymph nodes

Pain on taking a deep breath

Raynaud’s phenomenon

Alopecia (loss of scalp hair)

Headaches

Cognitive difficulties (brain fog)

Cutaneous lupus erythematosus 3 broad categories Acute cutaneous lupus erythematosus Subacute cutaneous lupus erythematosus Chronic cutaneous lupus erythematosus

3 broad categories

Acute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus

Chronic cutaneous lupus erythematosus

Acute Cutaneous LE May present with localized or generalized rash Most common manifestations are malar (butterfly) rash and photosensitivity Facial swelling may be severe in some patients Symptoms may be short-lived (days to weeks) Lesions do not result in scarring

May present with localized or generalized rash

Most common manifestations are malar (butterfly) rash and photosensitivity

Facial swelling may be severe in some patients

Symptoms may be short-lived (days to weeks)

Lesions do not result in scarring

Subacute Cutaneous LE Primarily a disease a Caucasian females Highly sensitive to sunlight and UV exposure Non-scarring lesions which have a typical biopsy appearance Associated with circulating antibodies to anti-Ro

Primarily a disease a Caucasian females

Highly sensitive to sunlight and UV exposure

Non-scarring lesions which have a typical biopsy appearance

Associated with circulating antibodies to anti-Ro

Chronic Cutaneous LE The most classic form is Discoid LE Often begin as reddish plaques, with scaling that may become thick and adherent, with a lighter central area. Scarring with central atrophy may occur

The most classic form is Discoid LE

Often begin as reddish plaques, with scaling that may become thick and adherent, with a lighter central area.

Scarring with central atrophy may occur

Drug-induced Lupus (DIL) Refers to a condition where patients receiving therapy with a known lupus inducing drug for at least 1 month (usually months to years) and develop: Autoantibodies or laboratory features of autoimmunity Clinical signs and symptoms associated with SLE Features include: joint and muscle aches, rash, fever, serositis, splenomegaly, ANA, anti-histone antibodies

Refers to a condition where patients receiving therapy with a known lupus inducing drug for at least 1 month (usually months to years) and develop:

Autoantibodies or laboratory features of autoimmunity

Clinical signs and symptoms associated with SLE

Features include: joint and muscle aches, rash, fever, serositis, splenomegaly, ANA, anti-histone antibodies

Drug-induced lupus Currently, 41 drugs have been associated with DIL Important to remember that not all patients who take these drugs will get DIL Highest risk drugs include procainamide (20% incidence) and hydralazine (5-8%incidence) during 1 year of therapy

Currently, 41 drugs have been associated with DIL

Important to remember that not all patients who take these drugs will get DIL

Highest risk drugs include procainamide (20% incidence) and hydralazine (5-8%incidence) during 1 year of therapy

Drugs implicated in DLE Procainamide (Pronestyl) Hydralazine (Apresoline) Quinidine (Quinaglute) Methyldopa (Aldomet) Captopril (Capoten) Chlorpromazine (Thorazine) Acebutol (Sectral) Phenytoin (Dilantin) Carbamazepine (Tegretol) Isoniazid/INH Minocycline (Minocin) D-penicilliamine (Cuprimine) Propylthoiuracil (propyl-thyracil)

Procainamide (Pronestyl)

Hydralazine (Apresoline)

Quinidine (Quinaglute)

Methyldopa (Aldomet)

Captopril (Capoten)

Chlorpromazine (Thorazine)

Acebutol (Sectral)

Phenytoin (Dilantin)

Carbamazepine (Tegretol)

Isoniazid/INH

Minocycline (Minocin)

D-penicilliamine (Cuprimine)

Propylthoiuracil (propyl-thyracil)

Drug-induced lupus Discontinuation of therapy with the offending drug usually results in prompt resolution of symptoms within days to weeks Eventually autoantibodies induced by the drug may decrease and/or resolve over time (months to years) Re-challenge with the drug will likely result in recurrence of DIL

Discontinuation of therapy with the offending drug usually results in prompt resolution of symptoms within days to weeks

Eventually autoantibodies induced by the drug may decrease and/or resolve over time (months to years)

Re-challenge with the drug will likely result in recurrence of DIL

Diagnosis of Lupus Remember: Every lupus patient reacts differently Two patients with a diagnosis of lupus may have very different manifestations!

Remember: Every lupus patient reacts differently

Two patients with a diagnosis of lupus may have very different manifestations!

Thank you!