Derm Update February, 2017

1. Derm UpdateFebruary, 2017 Matthew J. Deeths, M.D., Ph.D. Mountain West Dermatology Grand Junction, CO

2. Contents • Management of keratinocyte carcinoma- SCC, AK • Mohs AUC • New and old drugs for psoriasis • Melanoma update • Surgical pearls • Simplifying acne treatment • Atopic dermatitis news • Review of UV and Vitamin D data • The long and short of onychomycosis

3. 9. Onychomycosis • Differential diagnosis? • Not all funky nails are fungal

10. Differential diagnosis • Trauma and secondary infection • Hiking • Running • Old age, nail growth slows • Psoriasis • Other things

11. What we DID and why • What • Scrapings for KOH prep, if negative… culture • Treat positive with PO terbinafine 250mg PO 3-6 months • Check LFT’s every 4-8 weeks on drug • Why • Drug was expensive and thought to cause hepatitis about 1:10,000 patients • What we didn’t do • Treat with latest new-fangled topical

12. What we DO and why • What • Decide on clinical grounds if its fungal and if so, treat with PO terbinafine 250mg PO 3-6 months • Why • Studies have shown derms can diagnosis onychomycosis clinically 90% specificity, and cultures and KOH are less sensitive then that • Drug is cheap now • Approximately zero cases of liver failure requiring transplant in last 10 years due to terbinafine • What we don’t do • Check labs • Treat with latest new-fangled topical • Treat with laser- Podiatrists doing this

14. 8. UV and Vitamin D • Western Colorado • Ground zero for UV radiation • UVA • 10X more • Goes through glass • Photoaging>mutagenic • UVB • Blocked by glass and most sunscreens

16. How to answer the sunscreen question • K.I.S.S. • Sun screen SHOULD BE LAST line of defense, or at most 1/5 of the solution • Clothing- collared shirt, no tank tops, tight woven long sleeves, hats (not cap) • Plan ahead- Find a shady place to work or play mid day, or stay indoors • Use a sunscreen on lips, dorsal hands (and forearms) and lower ½ of face • SPF 30 or better • Contains Zinc (tinted with iron oxide) or avobenzone

18. Vitamin D • We put this one to rest about 2 years ago? • Data supporting Vit D preventing cancer- debunked • Same old story- Vitamin D + Calcium = Strong Bones • You guys know more about this then me • AAD and Endocrinologists recommend if deficient take supplement

20. 7. The Latest on Atopic Dermatitis • One really cheap treatment • One, OK maybe 2, soon to come really expensive treatments

22. Prevention: Cheap • Risk factors: • Race: Asian, Hispanic, African American • Parents have it • Parents have seasonal allergies, asthma • Breast feeding- Nope • No soy- Nope • No peanuts- Nope • No cats- Nope • Extra cats- Nope (but happier kiddo?)

23. Prevention: Cheap • Answer: Less bathing- Empirical based on atopic derm following the installation of plumbing • Answer: Daily emollient use in 1st 6 mos., several studies 2014, J. Clin. Immunol. 2014, 134: 824-830; J. Allergy Clin. Immunol. 2014; JAMA Pediatrics 2016, Dec. 5, doi: 10.1001 • Prospective: 50% reduction in incidence of atopic derm at follow-up • Don’t need fancy cream • Petrolatum cheapest • Cetaphil cream, available generic, easy to use

25. Treatment: Less cheap, mostly safe • Topical steroids for flares 1-2 weeks • Emollients

26. Treatment: Expensive- yes; Safe- maybe • Old expensive topicals… Not much better then vehicle (i.e. emollient) • Topical Tacrolimus or pimecrolimus • New expensive topicals… Don’t use it…”Eucrisa” crisaborole… PDE4 inhibitor… 30% better then vehicle…60% improved (vs. 30% with emollient alone) • New systemic agent • Injectable “biologic drug” • Dupilumab- Due out this March…Blocks TH2 cytokines IL-4 and IL-13…$30,000 per year…Self injected every 2 weeks… 74% vs. 18% improvement vs. placebo (Lancet 387:40-52), “without significant safety concerns” • “Use new drugs quickly, while they are still safe!” • I still use UV rx, methotrexate and azathioprine • “The devil you know”

28. 6. Acne Treatment Has Gotten Much Easier  • Should be much easier? • Mild- Topical • Moderate- Males topical or isotretinoin -Females topical plus spironolactone • Severe- isotretinoin

29. Mild • Topical- Best options now OTC • No rx topical antibiotic… 1% clindamycin- OUT • Use OTC 10% Benzoyl peroxide once daily • Generic $4 • No tretinoin cream • Use OTC Differin Gel, about $11 at Walmart, once daily • Can use both together at the same time • Watch irritation, no scrubbing, gentle cleanser, moisturize with SPF • Try every other day for sensitive skin • Not spot treatment • Set expectations: Use it 10 weeks, you’ll have 50% less pimples

31. Moderate • This is the female who is not satisfactorily improved with topical rx, cannot tolerate or has pretty severe disease and expected 50% improvement is not going to be enough • PO antibiotics, short term only, doxycycline>minocycline may cause inflammatory bowel disease (Am. J. Gastroenterol. 2010; 105:2610-2616, retrospective study) • OCP’s thromboembolism risk • Spironolactone 25-100mg BID… No serious side effects.. Breast tenderness, menstrual irregularities, decrement in libido, mood changes • Don’t need labs

32. Severe • Isotretinoin- Not as bad as everyone thought… Finally the truth • Does not cause pregnancy… but requires iPledge STILL • Does not cause inflammatory bowel disease • Does not cause suicide (but does improve self esteem) • Does not usually cause liver damage • Check labs once at 6 weeks • Does cause elevated TG and cholesterol temporarily • Rule of 1/3’s • 1/3 relapse • 1/3 cured • 1/3 need topical rx

34. 5. Save Packaging, Money and Time in Outpatient Surgery • Use exam gloves for minor surgery • Rates of infection after minor outpatient surgical procedures, e.g. skin cancer excision, similar with clean bulk exam gloves vs. sterile surgical gloves • 493 pts randomized nonsterile clean boxed gloves or sterile gloves, “minor skin excisions”, about 9% rate of wound infection both groups. Med. J. Aust. 2015; (1):27-31 • Several smaller studies before this • Meta-analysis 14 articles, 11,071 pts, JAMA Derm. 2016, Sep 1; 152(9):1008-1014 • 1.9% infections non-sterile gloves vs. 2.0% sterile gloves • I’ve been doing this for about 1.5 years… Have not seen more infections • If you haven’t already started, its not necessary to prep skin prior to infusion of anesthesia for biopsies

36. 4a. Melanoma Treatment • Several new drugs, last 2 years or so • Combination of ipilimumab(CTLA4 inhibitor) and nivolumab (PD-1 inhibitor), FDA approved combination rx gives about 30% long term remission in stage IV melanoma • Vemurafenib and dabrafenib- Selective kinase inhibitors- more along the lines of traditional chemotherapy- several months added survival in stage IV disease

37. 4b. Melanoma work-up • Melanoma in situ stage T0 • excise 5 mm margin • Stage T1a- thin melanomas, < 1mm and no dermal mitoses or ulceration… Low risk, 95% survival at 5 years • Excise 1 cm margin • Skin exams q-6-12 mos • That’s it • Stage T1b (<1 mm with mitoses or ulceration) intermediate risk… ~85% survival at 5 years • These are much more common then higher stage melanomas and thus more cumulative mortality in population, even though risk of progression per incident is smaller • Excise as above +/-sentinel lymph node biopsy • GENE EXPRESSION PROFILING??? • Stage T2 (1-2 mm thick) and above, send to oncology for consideration of imaging, for staging work-up; and to surgery for excision with sentinal lymph node bx (SNLNBx)

38. 4b. Melanoma- What is gene expression profiling? • Not some sort of immigration policy • Probably will replace SLNBx… much cheaper and non-invasive • RT-PCR on biopsy material • No additional tissue required • Done if biopsy shows T1b melanoma… Maybe someday on T1a also? • Looks at expression of 31 genes in melanoma- compares these against profiles of previously studied melanoma with known outcomes to predict biologic behavior of the melanoma in question

39. 4b. Melanoma- What is gene expression profiling? • Castle Biosciences patented test, called DecisionDx-Melanoma • Validated in large studies- DOI 10.1158/1078-0432.CCR-13-3316, January 2015 and, and others • Able to identify subset of SLNBx negative pts who go on to develop mets. • Will be seeing more of this, call me if you have questions or send pts over for discussion

40. 4. Melanoma • Oncologists don’t want to see stage T1a, T1b patients… • These patients need skin exams and directed ROS and regional lymph node exam for new primary melanomas, their risk of a new primary is much higher then their risk of systemic recurrence • They don’t need scans • As time goes by Gene Expression Profiling (GEP) may replace sentinel lymph node biopsy (SLNBx) • T1a: Do the excision yourself or send to me, and schedule skin exams for ever • T1b: Same as above except consider SLNBx, for that they go to ENT or general surgery, then back to you or derm for skin exams

43. 3. Old-New and New-New Drugs for Psoriasis • Biologics- check for occult Hep B and C infection anf TB, also cocci, histo and blastoserologies if from endemic areas • Old-New • TNF inhibitors- Etanercept, weakling of the group, will be generic in months… biosimilar approval, should help costs • I use adalimumab first.. Biosimilar in about a year… easy to use- one shot every other week • Really good long term safety record- I see patients every 1-2 years to see how there doing and give them refills, recheck above tests and get LFT’s and CBC and review signs of systemic infection

44. 3. Old-New and New-New Drugs for Psoriasis • New-New drugs • Biologics- Many or most will not be approved by insurance without trial of adalimumab first • Ustekinumab next oldest, about 7 years old… I use this first line as dosing is easier • Same baseline testing • Others ixekinumab, secukinumab and others… very effective good safety profile so far • Using these second or third line… because their newer and insurance won’t usually cover first • May become first line in a few years • FYI: Apremilast- PO QD dosing, gives about 60% improvement, that may be enough • No known side effects except weight loss, about 5% at one year

46. 2. Mohs AUC • Skip it… just know there are appropriate use criteria (AUC) and you can google them… most BCC can be treated with ED&C or excision

47. 1. Management of spectrum of cutaneous squamous cell carcinoma (SCC) • Actinic keratosis (AK)- Lag time of 30-40 years to develop • Damage first 40 years never goes away • Educate on sun precautions • First 40 years of damage comes out worse at age 80 vs. age 60 • Age 90, watch out! • If they have a few AK at age 60, untreated by age 80, many and some SCC • By age 90 w/o treatment high risk of metastatic SCC • Pt specific risk for metastatic SCC of skin: Age >80, male, CLL, immune deficiency, more then 8 previous SCC • Tumor specific risk: Pseudo-adenoid histology, invasion to fat or muscle, greater then 1 cm diameter

48. AK • No good treatment • Cryo- treat a lot, best for thicker • Fluorouracil- Poor response of scalp, non-compliance, recurrence after few years, resistance after a few treatments, danger of self treatment and false sense of security (with all pt administered rx) • 2 weeks BID face and ears and neck • 4 weeks BID scalp and upper limbs • Immiquimod- Very good rx for facial AK, requires 5 weeks rx • Ingenolmebutate- 2-3 days, price prohibitive o/w good • Photodynamic therapy- administered in office- field rx using aminolevulonic acid and “blue light” • They always seem to have AK, see previous slide