Lupus & Your Skin

Andrew G. Franks, Jr., M.D., FACP

Director, Skin Lupus CenterProfessor of Clinical Dermatology & Medicine (Rheumatology)

NYU School of Medicine

BrainSalivary, Parotid glandsThyroid

Heart, Lungs

GI tractKidneys

Special complications of pregnancy

Joints

Blood vessels

Skin

Heterogeneity of SLE

Skin Disease Overview

• How is lupus of the skin identified?• Can skin lupus be prevented?• What is the treatment of skin lupus?• Can damaged lupus skin be repaired?

Identification of Skin Disease

• Characteristic and unique features • Skin biopsy may be needed • Patients may have only skin lupus or the

disease may be present throughout the body (ie, systemic)

• Classifications help doctors to categorize patients and choose therapy

Acute Cutaneous Lupus

Present mostly in patients with systemic disease (SLE)

10:1 Female• Characteristic features:

Butterfly rash (malar rash, not scarring) Photosensitivity Blisters &/or erosions Diffuse hair loss (not permanent)

Subacute Cutaneous Lupus

• Mimics common diseases such as psoriasis or fungal infections

• Scaly red patches with clearing in center• Very Photosensitive, both UVB & UVA • Often drug-aggravated, but hard to prove• Anti-Ro Ab frequently present

Neonatal Lupus

• Anti-Ro antibodies can transfer from mother to child through the placenta

• Babies do not actually have lupus. They improve after several weeks as the mother’s antibodies no longer are in the baby’s blood stream

• UV light brings out the signs of the disease

(rash around the eyes)

Neonatal Lupus (Cont’d)

• No treatment of the skin required other than avoidance of UV light

• Can cause heart problems, liver problems, or low platelets in the baby

• Recommend high-risk pregnancy OB/GYN

Chronic Cutaneous Lupus

• 6:5 Female

• Is disk-shaped (discoid)

• Also known as Discoid Lupus (DLE)

• Seen commonly by dermatologists

Chronic Cutaneous Lupus (Cont’d)

Discoid “plaque” (DLE)

• Plugged hair follicles• Atrophy or thinning of the top layer of skin • Scale or hardness of the skin• Telangiectasias or “spider veins” • Erythema or reddening

Scarring & permanent hair loss can develop

If I Have Cutaneous Lupus, What are the Chances That I Will Develop Systemic Lupus?

Your doctor will keep watch for the following:

• Rash below the neck

• Related skin lesions

• High levels of ANA

• Protein in the urine

• Blood in the urine

• Generalized Joint pain

Prevention of Cutaneous Lupus

• Sunscreen & Sun Precautions• Fluorescent Light• Smoking (including secondary)• Hormone changes• Injury to skin, including personal

care products & heat• Infection• Diet & Nutrition• Alternative Medicines

UV Protection

• UVB (sunburn range) and UVA (non-sunburn range)

• UVB blocked by glass• UVA blocked by plastic

• UVA can go through car or office windows • Exposure can occur with artificial lights

(compact fluorescent) and older computer screens (not flat panel)

UV Protection (Cont’d)

• Suncreens marked with SPF numbers only block UVB which is helpful but not complete protection

• Important sunscreen reminders: UVA and UVB protection High SPF

• Mexoryl & Helioplex are new agents in sunscreen that offer good UVA protection

• “Star Rating” for UVA soon• Sun Protective clothing

Treatment1st Line•Antimalarials•Dapsone•Steroids

2nd Line•Retinoids•Thalidomide•Azathioprine•Methotrexate•Cyclophosphamide•Cyclosporine•Leflunamide

3rd Line•Rituxin•Remicade, Enbrel, Humira•Raptiva

Moving from Lab to Patient

Clinical Trials

• Every clinical trial is carefully designed & then approved by an IRB to answer certain research questions.

• A trial plan called a "protocol" indicates which study procedures will be done, when they’ll be done, by whom, and why.

• Initially drugs are tested for safety.• Subsequently, drugs are tested for efficacy and

compared to standard treatments or to placebo.

Types of Trials

Phase 1 Trials•Usually conducted in 20-80 healthy young adults•Determine safe and well-tolerated doses•Test “escalating” single doses & repeat doses•Provide an initial evaluation of how a drug is absorbed, metabolized and excreted

Types of Trials

Phase 2 Trials•Conducted in 100-300 individuals with the disease or condition•Determine safety in patients•Determine if drug is efficacious vs. placebo or active comparator•Determine optimal doses for efficacy and safety

Types of Trials

Phase 3 (Pivotal) Trials•Conducted in 1000-3000 individuals with the disease condition•Test the drug’s efficacy & compare to placebo &/or standard treatment•Monitor & reveal less common side effects

Types of Trials

Phase 4 Trials•Conducted after a drug is approved and on the market•Find out more about the drug’s long-term benefits, risks, and optimal use•Possibly test the drug in different populations e.g. children

Inclusion Criteria:• Diagnosis of cutaneous discoid lupus by clinical and

histopathological exam, 18 – 65 yrsExclusion Criteria:• Systemic lupus involving the internal organs • Systemic vasculitis • History of other clinically significant disease process • History of HIV, hepatitis B or C. • Concurrent use of immune modulating therapy • Evidence of incompletely treated tuberculosis • Pregnant or lactating female

PDE-4 Inhibitor in Cutaneous Lupus

AGFMD@AOL.COMwww.ClinicalTrials.gov

Topical Therapy

• Topical corticosteroids• Corticosteroid injections• Elidel (pimecrolimus) or Protopic

(tacrolimus)—can be helpful

Oral Medications

• First choice: antimalarials- Plaquenil (hydroxychloroquine, alone or combined)

• Second choice: dapsone, retinoids (Accutane or Soriatane), thalidomide

• Third choice: methotrexate, Imuran (azathioprine), CellCept (mycophenolate mofetil), Neoral (cyclosporine)

ChloroquineQuinacrine

What Determines Which Drug I Will Receive?

• Known drug allergies

• Other disease present (eg, diabetes)

• Age, gender

• Drug side effects

• Severity of disease • Skin only or SLE

Using Antimalarials

• Usually start with hydroxychloroquine

• May need initial blood tests

• Eye exam within the first month of treatment and annually

Using Antimalarials (Cont’d)

• Wait 6-8 weeks to see if it’s working

• If necessary, add quinacrine

• May switch to chloroquine

• Drug dose is dependent on body weight

Thalidomide

“Fast” response• Starts to work within 2 weeks, maximum

effect by 2 to 3 months

Effective in many patients who do not respond to antimalarials

Thalidomide Concerns

• Can cause nervous system problems (eg, numbness and tingling)

• Cannot be used in pregnant women

• Premature ovarian failure

• Increased risk of blood clots

Anti-TNF

• Effective in treating skin disease• Increases autoantibody production• Patients need to be selected carefully

Remicade, Enbrel, Humira

Repair of Damaged Skin•Reduction of Scars•Removal of Blood Vessels•Elimination of Dark Stains

Laser Surgery

• Can be helpful for treating scars, discoloration and blood vessels

• Patient MUST be in remission with no active lesions

• Does not affect the disease itself

Laser Surgery (Cont’d)

• Patients may be required to be on an antimalarial drug

• Dark-skinned patients can experience skin discoloration

• Patients need to have realistic expectations

Summary

Classifications of lupus help physicians make appropriate drug choices

A majority of patients respond well to antimalarials and topical steroids

Most patients who do not respond to antimalarials will respond to thalidomide or third or fourth line agents.

More treatments on the horizon!