U060: Updates from the Rheum-Derm Clinic2/18/2018, 7:00 AM - 8:00 AM, Room 4

Anna Haemel, MD

UCSF Dermatology Cutaneous Autoimmunity Program

Cutaneous Lupus

• Lupus specific• Acute cutaneous lupus erythematosus (ACLE)

• “Malar rash” sparing nasolabial fold

• Subacute cutaneous lupus erythematosus (SCLE)• Photodistributed annular or psoriasiform plaques

• Chronic cutaneous lupus erythematosus (CCLE)• Discoid lupus erythematosus, tumid lupus, lupus panniculitis, chilblain lupus

• Lupus non-specific• Vasculitis, vasculopathy, livedo reticularis, alopecia, urticaria, etc.

J Am Acad Dermatol. 1981 Apr;4(4):471-5.

Systemic Lupus International Collaborating Clinics (SLICC) –2012 vs ACR classification criteria

Arthritis Care Res (Hoboken). 2015 Aug;67(8):1180-5.

*For both: 4 criteria for SLE classification

*Sensitivity SLICC 93.2% versus 85.6% for ACR 1997

Typical lupus therapeutic ladder

INITIAL APPROACH

Sun protection

Vitamin D supplementation

Topicals: corticosteroids/calcineurin inhibitors

Intralesional steroids

Antimalarials: HCQ (or CQ)

(Systemic steroids if ++ activity)

NEXT STEPS

Then quinacrine

Then MTX (or MMF)

• Then second line systemics:• Dapsone, retinoids,

thalidomide

J Am Acad Dermatol. 2011 Dec;65(6):e179-93.

Arthritis Res Ther. 2012 Oct 17;14(5):R221.

Lupus therapeutic ladder

SECOND LINE SYSTEMICS

• Dapsone (50-200 mg/d)

• Systemic retinoids (acitretin, isotretinoin)

• Thalidomide (50-200 mg per day)

Newer treatment options to be considered…

• Lenalidomide

• Apremilast

• Belimumab

• Ustekinumab

• IVIG

• Trials

Lenalidomide

• Less toxicity, incl much less neuropathy, than with thalidomide

• A decrease of CLASI activity score of at least 50% may occur in up to 90% of pts

• Typical dose 2.5-10 mg/d

• Monitor CBC w diff weekly for first 2 mos then monthly thereafter

• Pregnancy prevention / REMS

• Some concern for thromboembolic tendency remains (ASA recommended)• …Pt declined

J Am Acad Dermatol. 2016 Jun;74(6):1248-51.

J Am Acad Dermatol. 2014 Mar;70(3):583-4.

Int J Dermatol. 2016 Aug;55(8):e431-9.

Arch Dermatol. 2009 Mar; 145(3): 303–306.

Apremilast

• Apremilast blocks IL-12, IL-23, TNF-a, INF- with subsequent suppression of Th1 and Th17-mediated immune responses

• In a study of 8 pts w discoid lupus, there was a significant decrease in disease activity scores w 20 mg twice daily

• Adverse events related to the drug were mild• Pt deferred – pre-existing depression Trial

J Drugs Dermatol. 2012 Oct;11(10):1224-6.

Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision)

• Recommend a maximum daily HCQ use of <5.0 mg/kg real weight

• No similar demographic data for CQ, but dose comparisons in older literature suggest using <2.3 mg/kg real weight

Ophthalmology 2016;123:1386-1394

Risk factors for antimalarial toxic retinopathy

• Daily dosage• Hydroxychloroquine > 5.0 mg/kg real weight

• Chloroquine > 2.3 mg/kg real weight

• Duration of use > 5 years assuming no other risk factors

• Renal disease w reduced GFR

• Concomitant drugs (tamoxifen)

• Macular disease (may affect screening and susceptibility)

Ophthalmology 2016;123:1386-1394

Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision)

• A baseline fundus examination should be performed

• Begin annual screening after 5 years for patients on recommended doses and without major risk factors

• Screening Tests: • Ideally automated visual fields combined with spectral-domain optical

coherence tomography (SD OCT)

• Modern screening should detect retinopathy before it is visible in the fundus

• Look beyond the central macula in Asian patients

Ophthalmology 2016;123:1386-1394

Zoster in SLE…• Patients with SLE are at much higher risk of zoster

compared to healthy patients of all ages

• Zoster vaccination in general population ≥60 years 51% reduction in zoster AND milder illness

• Retrospective cohort study of 463,541 Medicare beneficiaries 60 years and older with RA, PSO, AS, IBD 40% reduction in zoster• Amongst 633 patients on biologics no vaccine-induced

varicella or zoster

• Whether patients under 50 with autoimmune disease should receive zoster vaccination requires further study

Vaccine. 2013 Aug 12;31(36):3640-3

J Rheumatol. 2017 Jul;44(7):968-969

Shingles vaccination• General population

• Adults ≥60 years old (per CDC)

• ACR 2015 RA Guidelines• In patients ≥ 50 years, vaccinate before the patient receives

biologic therapy• After giving the herpes zoster vaccine, there should be a 2-week

waiting period before starting biologics• In patients currently receiving biologics, avoid live attenuated

vaccines

• CDC re immunosuppressed host• Avoid zoster vaccine in long-term immunosuppressive therapies

(this includes steroid dose ≥ 20 mg/d prednisone for 2+ weeks or similar)

• Delay vaccination at least 4 weeks after discontinuation of immunosuppressive therapy

Arthritis Rheumatol. 2016 Jan;68(1):1-26.

Pneumococcal vaccination

• Starting in 2014 the ACIP recommended routine use of PCV13 among adults aged ≥65 years (covers addl serotypes)

• Immunocompromised adults should also receive the 13-valent pneumococcal conjugate vaccine (PCV13)

Immunomodulators decrease vaccine efficacy

• Stopping MTX for 2 weeks before and 2 weeks after trivalent influenza vaccination increased satisfactory vaccine response (to 51.0%, over the 31.5% in pts who continued MTX), p = 0.04

• In systematic review, MTX was found to decrease response to pneumococcal vaccination and possibly influenza vaccination.

• The response to both pneumococcal vaccination and influenza vaccination is also reduced with rituximab but not with TNFi

Park JK et al. Ann Rheum Dis. 2017 May 3.

Hua C. Arthritis Care Res. 2014. July; 66(7).

The dermato “checklist”• Skin

• Bx for H&E and DIF• Sun protection• Topical steroids, calcineurin

inhibitors• (Systemic steroids)• Antimalarials• Dapsone• Immunomodulators (MTX,

MMF)• IVIG

• Muscle• Exam (shoulders, hips, neck)• Labs: CK, aldolase, myositis

panel• MRI• EMG/NCS• +/- biopsy• Rheum referral

• Cardiopulmonary• PFTs w DLCO• TTE• HRCT chest• Pulm referral

• HCM• PCP ppx• Check Hep B, C, TB• Vaccines• Bone health

• Cancer evaluation

How should the pt w dermatomyositis be assessed for possible cancer?• H&P

• Update age appropriate cancer screening

• No supporting guidelines regarding what to do beyond age appropriate screening

BUT…

• For white patients CT C/A/P

• For women pelvic ultrasound

• For Asian patients from southeast Asia eval for nasopharyngeal ca

Arch Dermatol. 2002 Jul;138(7):969-71.

Cancer risk in dermatomyositis

• No consensus regarding what type of screening and to what extent should the screening be performed

• Hematologic, lung, and ovarian cancers over-represented

• Newer imaging techniques such PET CT have been used to detect occult malignant disease in paraneoplastic conditions• However, one study found PET/CT to be comparable to broad conventional

screening for dermatomyositis

• Association w certain Abs (e.g. TIF1γ)

Am J Clin Dermatol. 2015 Apr;16(2):89-98.

Antibodies predict course(predict cancer)• Most (83%) cancer-associated DM patients have antibodies to either

TIF1γ or NXP2

• Testing now clinically available (e.g. Quest)

• The absence of these autoantibodies is strongly predictive of NO CANCER in DM patients• TIF1γ severe skin disease and lack of ILD

• NXP2 mild skin disease but severe systemic disease (myalgia, peripheral edema, dysphagia); male patients with cancer

Arthritis Rheum. 2013 Nov;65(11):2954-62.

Distinctive cutaneous features assoc w/ TIF-1γ

• Hypopigmented and telangiectatic (“red on white”) patches

• Palmar hyperkeratotic papules (verrucous, non-tender, “inverse Gottron”)

• Less likely ILD

J Am Acad Dermatol. 2015 Mar;72(3):449-55.

JAMA Dermatol. 2016 Sep 1;152(9):1049-51.

Ovoid palatal patch assoc w malignancy

• Associated with anti-TIF1-γ antibody (p=0.00066)

• Associated with female gender (p=0.01)

• Associated w clinically amyopathic disease (p = 0.03)

• Highly associated with internal malignancy (p = 0.004)

J Am Acad Dermatol. 2015 Mar;72(3):449-55.

JAMA Dermatol. 2016 Sep 1;152(9):1049-51.

Arthritis Rheumatol. 2017 Jun 6.

J Am Acad Dermatol. 2017 Jan;76(1):1-9.

2017 ACR guideline for prevention and treatment of glucocorticoid induced osteoporosis

• Released in June 2017

• Replaces 2010 guidelines

• Emphasizes shared decision making

• Special populations (e.g. peds, pregnant patients)

For all adults taking pred ≥ 2.5 mg/d for ≥ 3 mos

• Optimize Ca intake (800-1000 mg/d) and vitamin D intake (600-800 units/d)

• Lifestyle modifications (smoking cessation, weight bearing exercise, limiting ETOH to 1-2/d)

• AND stratify fracture risk, reassess over time