Hot Topics In Podiatric Dermatology Evan Rieder, MD
Dermatologist, Psychiatrist Assistant Professor of Dermatology The Ronald O. Perelman Department of Dermatology Disclosures
Advisory Board Member: UCB Pharmaceuticals
Consultant: UCB Pharmaceuticals Unilever
The Ronald O. Perelman Department of Dermatology 2 Podiatrists & Dermatologists
The Ronald O. Perelman Department of Dermatology General Outline
Bumps Stripes Collimated Lights
The Ronald O. Perelman Department of Dermatology 4 The Power of Observation
The Ronald O. Perelman Department of Dermatology Robert Ryman, Untitled 1960-1961
The Ronald O. Perelman Department of Dermatology The Ronald O. Perelman Department of Dermatology The Ronald O. Perelman Department of Dermatology Bumps
The Ronald O. Perelman Department of Dermatology Outline
Common Podiatric Rashes Keys To Differential Diagnosis Uncommon Presentations
The Ronald O. Perelman Department of Dermatology Bumps
The Ronald O. Perelman Department of Dermatology Classic Psoriasis
Well-demarcated Erythematous plaque Silvery scale
Classic locations: Scalp, elbows, knees, buttocks
3% of the population
Nail, joint involvement common
Dx: clinical +/- biopsy
Tx: topical steroids, nbUVB, immunomodulators
The Ronald O. Perelman Department of Dermatology Psoriasis of the Foot & Lower Leg
May appear like classic plaque psoriasis
However may have different presentation
Patchy or generalized thickening and scaling of nearly entire surface of palms / soles without redness •Keratoderma
Greater associations with nail and joint psoriasis
Chronic, difficult to treat
The Ronald O. Perelman Department of Dermatology Palmoplantar Pustulosis
Different presentation
Palms and soles, especially lateral Localized or entire surface
Sterile pustules admixed with yellow-brown macules +/- scaly erythematous plaques
No longer considered psoriasis
10-25% of patients with palmoplantar pustulosis also have plaque psoriasis
The Ronald O. Perelman Department of Dermatology SAPHO Syndrome
May be associated with sterile inflammatory bone lesions
Synovitis Acne Pustulosis Hyperostosis Osteitis
AKA chronic recurrent multifocal osteomyelitis, pustulotic arthro- osteitis
Misdiagnosis, mistreatment common
Dermatology referral
The Ronald O. Perelman Department of Dermatology Psoriasis / Palmoplantar Pustulosis
Important differential diagnosis
Tinea pedis •Pustular or bullous variant
Eczematous dermatitis •Dyshidrotic •Contact (allergic or irritant)
Scabies
Uncommon diagnoses: •Bazex syndrome •Bullous disorders
The Ronald O. Perelman Department of Dermatology Common Differential Diagnoses
The Ronald O. Perelman Department of Dermatology Tinea pedis
Pruritic Macular Scaly (thin) Erythematous Leading edge of scale
KOH+
The Ronald O. Perelman Department of Dermatology Eczematous dermatidites
Dyshidrotic:
Tense, deep-seated vesicles of palms +/- soles
Intensely pruritic
The Ronald O. Perelman Department of Dermatology Eczematous dermatidites
Contact: Well-demarcated Erythematous Diffuse scale +/-Serous drainage +/-Vesicobullae
Distribution of contactant: e.g. cream, sandal
•May need patch testing •History is relevant
Kline 2008
The Ronald O. Perelman Department of Dermatology Scabies
Interdigital burrows: fingers > toes Severe pruritus Not restricted to palms and soles History is relevant
When widespread / on feet, think crusted
The Ronald O. Perelman Department of Dermatology Crusted scabies
Thick, crusted plaques Typically acral, may be generalized Dystrophic nails May not see burrows
Severe pruritus Socioeconomic considerations
The Ronald O. Perelman Department of Dermatology Uncommon Diagnoses
The Ronald O. Perelman Department of Dermatology Bazex Syndrome
Acrokeratosis Paraneoplastica
Psoriatic-appearing nails
Psoriasiform erythematous, squamous lesions of feet, ears, nose •Visible without disrobing •Not common areas for psoriasis
Assoc with UGI or respiratory malignancies Medical referral is mandatory
Sator PG et al, 2006
The Ronald O. Perelman Department of Dermatology Blistering Disorders
Bullous Pemphigoid •Erythematous wheals tense bullae (lower abdomen, thighs, forearms)
•May result in milia with healing
•May have underlying systemic illness or medication trigger
The Ronald O. Perelman Department of Dermatology Blistering Disorders
Epidermolysis Bullosa Acquisita •Erosions of feet / hands, tense vesicobullae that may be hemorrhagic
•May also result in milia with healing
•May be associated with IBD
The Ronald O. Perelman Department of Dermatology Take Home Points
Sometimes scaly red plaques are just psoriasis
Lower leg psoriasis may have an atypical presentation
Sometimes the differential diagnosis is broad
Observation of key clinical features can be very helpful in events when diagnosis is uncertain
Dermatologic +/- medical referral to rule out atypical syndromes or underlying systemic disease
The Ronald O. Perelman Department of Dermatology Stripes
(Longitudinal) Melanonychia
The Ronald O. Perelman Department of Dermatology Outline
Non-Melanocytic Melanocytic
Tips for Diagnosis Common & Rare Conditions
Image via regionalderm.com Melanonychia
Non- Melanocytic Melanocytic
Fungal Melanocyte Melanocytic Subungual activation Nail staining Melanonychia hemorrhage hyperplasia
Benign Malignant
Single Multiple
Nail matrix Subungual nevus melanoma
Trauma- Periungual Nail apparatus induced tumor-induced Laugier- lentigo Drug/systemic Ethnic type nail Peutz Jeghers Hunziker dz-induced pigmentation syndrome syndrome
30 Non- Melanocytic
Fungal Subungual Nail staining Melanonychia hemorrhage
31 Clinical Scenario
A patient presents for a routine exam and you see yellow discoloration of multiple fingernails. How can this help you meet your Clinical Quality Measures (CQM) for meaningful use?
Recording smoking status for patients 13 years or older is a core objective
Smoking cessation medical assistance is an additional set CQM
Hardin ME, Greyling LA, Davis LS. Nicotine staining of the hair and nails.32 J Am Acad Dermatol. 2015 Sep;73(3):e105-6. doi: 10.1016/j.jaad.2015.05.020. Nail Staining
Location: Bilateral thumbnails, 2nd & 3rd fingernails of dominant hand
Causes: •Brown: hobbies, occupational exposure to Hardin ME, Greyling LA, Davis LS. Nicotine staining of the hair and nails. foods, clothing dyes J Am Acad Dermatol. 2015 Sep;73(3):e105-6. doi: 10.1016/j.jaad.2015.05.020 •Yellow: smoking, nail polish (red)
Dermoscopy of Pigment: •Irregularly shaped •Well-demarcated border, may be parallel to PNF
Tx: Easily removed w/ 15 blade
33 Jin H, Kim JM, Kim GW, et al. Diagnostic criteria for and clinical review of melanonychia in Korean patients. J Am Acad Dermatol. 2016 Jan 30. Nail Staining
Huang Guofu
www.dailymail.co.uk/news/article-1384841/The-incredible-paintings-amputee-Chinese-artist-creates-pictures-toes-mouth.html Clinical Scenario
A 39yo man presents with 1 month of discoloration of multiple toenails. He is concerned about melanoma. He has no personal or family h/o of skin cancer.
What questions are important to ask this patient? -Medication history -Trauma
Most appropriate next steps? -PAS, fungal culture, +/- PCR -Dermoscopy
Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum and the 35 value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6. A Word On Dermoscopy
Non-invasive diagnostic test for evaluation of lesions of skin, hair, & nails
Low-powered microscope with contact or polarized light to reduce surface light-scatter interference
Image via: www.medicalexpo.com/prod/dermlite/product-79388-506390.html A Word On Dermoscopy
Helpful tool, low cost, portable
Eliminates biopsies
Pilot study of pigmented lesions shows that old dogs can learn new tricks
Pigmented lesions are much more difficult to assess than nails
Terushkin et al 2010
Lasers for Onychomycosis Fungal Melanonychia
Location: toenails > fingernails •Men > Women
Causes: Most common 1) Non-Dermatophyte, dematiaceous fungus: Scytalidium dimidiatum
2) Dermatophyte, nondematiaceous fungus: Trichophyton rubrum
38 Fungal Melanonychia
Clinical clue: often spares matrix
Dermoscopy of pigment: •Pigment streak w/ distal widening •Yellowish streaks w/ jagged borders composed of spikes
Dx: KOH, fungal Cx (cycloheximide-free media)
Tx: Azole (Fluconazole, Itraconazole); Allylamine (Terbinafine)
Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum 39 and the value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6. Fungal Melanonychia: Dermoscopy
• Pigmented streak • Distal widening
• Yellowish streaks • Jagged borders • Spikes
Ohn et al, JAAD 2017
Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum 40 and the value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6. Clinical Scenario
A 35yo construction worker presents to your clinic after slamming his hand in a door. You notice that the nail bed edges are disrupted. Would you perform a nail bed trephination for evacuation of the subungual hematomas? Are there any additional exams that you would order?
41 Bharathi RR, Bajantri B. Nail bed injuries and deformities of nail. Indian J Plast Surg. 2011 May;44(2):197-202. doi: 10.4103/0970-0358.85340. Subungual Hemorrhage
Location: single or multiple nails; toes > fingers (great toe)
Causes: trauma (overt episode, exercise)
Dermoscopy of pigment: purple- black: homogenous, globular & peripheral fading patterns
42
Photos courtesy: Dr. Jennifer Stein Subungual Hemorrhage
Dx: Serial dermoscopy (color fading & distal movement of features), does not involve matrix
Radiology: X-Ray of affected digit to r/o: • Fracture of distal phalanx • Extensor tendon avulsion of distal phalanx
Tx: Drainage indicated when: •1) Pain present & 2) Nail edges intact • Previously: nail bed trephination only for subungual hematomas <25-50% of nail surface (>25-50%, tx avulsion with repair of any underlying nail bed laceration) • More recently: if nail plate is partially adherent, not displaced out of PNF may leave nail plate in place and subungual hematoma may be trephined
43 Summary: Non-Melanocytic
Not all brown discoloration of the nail is due to melanin
Dermoscopy and non-invasive diagnostic testing may be of utility
Nail bed trephination may be indicated for hematomas of any size if the nail edges are not disrupted •If edges are disrupted higher likelihood of nail bed injury & associated distal phalanx fx may lead to a secondary nail deformity if not surgically repaired
44 Melanonychia
Non- Melanocytic Melanocytic
Fungal Melanocyte Melanocytic Subungual activation Nail staining Melanonychia hemorrhage hyperplasia
Benign Malignant
Single Multiple
Nail matrix Subungual nevus melanoma
Trauma- Periungual Nail apparatus induced tumor-induced Laugier- lentigo Drug/systemic Ethnic type nail Peutz Jeghers Hunziker dz-induced pigmentation syndrome syndrome
45 Melanonychia: Melanocytic
Melanocyte activation: • Normal # of melanocytes with increased production of melanin epithelial hyperpigmentation
Melanocyte hyperplasia: • Increased # of melanocytes (proliferation)
46 Dermoscopy: Melanocytic Activation v Proliferation
Melanocyte activation: thin, regular gray lines on grayish background
v Melanin Melanocytes Melanocyte proliferation: homogenous brown color of background band with:
- regular pattern of brown lines: longitudinal parallel lines w/ regular spacing & thickness
-irregular pattern of brown to black lines: w/ irregular spacing & thickness, disruption of parallelism
Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007 May;56(5):835-47. 2007 Feb 22. Melanonychia
Non- Melanocytic Melanocytic
Fungal Melanocyte Melanocytic Subungual activation Nail staining Melanonychia hemorrhage hyperplasia
Benign Malignant
Single Multiple
Nail matrix Subungual nevus melanoma
Trauma- Periungual Nail apparatus induced tumor-induced Laugier- lentigo Drug/systemic Ethnic type nail Peutz Jeghers Hunziker dz-induced pigmentation syndrome syndrome
48 Melanocytic
Melanocyte activation
Single Multiple
Trauma- Periungual Nail induced tumor- apparatus induced lentigo Laugier- Peutz Drug/systemic Ethnic type Hunziker Jeghers dz-induced nail pigmentation syndrome syndrome
49 Melanocyte activation: single nail involved
Trauma-induced: •Location: fingernails > toes (thumb, 2nd nail)
•Causes: occupational trauma, onychotillomania, overt trauma w/ nail plate deformity, repeated minor trauma to toe/s (may involve multiple digits)
•Dermoscopy of pigment: thin, regular gray lines on grayish background; abnormal surface of nail plate; (+) blood spots
50 Trauma-induced Melanonychia
Don’t try this at home!
Photo courtesy: Dr. Shane Meehan 51 Melanocyte activation: single nail involved
Periungual tumor-induced: •Location: fingernails, toenails
•Causes: digital mucous cyst, warts, fibromas, SCC, onychomatricoma
•Dermoscopy of pigment: thin, regular gray lines on grayish background; abnormal surface of nail plate; (-) blood spots
52 Melanocyte activation: single nail involved
Nail apparatus lentigo: •Location: fingernails (L thumb/2nd), toenails (R great toe)
•Cause: epithelial hyperpigmentation
•Dermoscopy of pigment: thin, regular gray lines on grayish background
53 Nail apparatus Lentigo
Photos courtesy of: Dr. Jennifer Stein
54 Melanocytic
Melanocyte activation
Single Multiple
Trauma- Periungual Nail induced tumor- apparatus induced lentigo Laugier- Peutz Drug/systemic Ethnic type Hunziker Jeghers dz-induced nail pigmentation syndrome syndrome
55 Melanocyte activation: Multiple nails involved
Drug/Systemic disease-induced:
•Location: fingernails > toenails
•Causes: Medications: .Antiretrovirals (Zidovudine, Lopinavir) .Chemotherapeutics (5-FU, MTX) .Antimalarials (Hydroxychloroquine) Systemic Disease: . Scleroderma, SLE, HIV, Addison’s Dz (Bissell’s lines)
56 Drug-induced melanonychia
G. Micali, F. Lacarrubba (Eds.) Dermatoscopy in clinical practice: beyond pigmented lesions. Informa Healthcare Ltd, London; 2010.
57 Melanocyte activation: Multiple nails involved
Ethnic type nail pigmentation: •Location: fingernails > toenails dark-skinned (Type V, VI) > light-skinned patients
•Dermoscopy of pigment: thin, regular gray lines on grayish background
58 Ethnic type nail pigmentation
Photo courtesy: Dr. Jennifer Stein
59 Melanocyte activation: Multiple nails involved
Laugier-Hunziker syndrome: •Adult onset; sporadic, AD
•Location: fingernails, oral mucosa (lips, buccal mucosa, tongue), genitals
•Dermoscopy of pigment: thin, regular gray lines on grayish background
60 Melanocyte activation: Multiple nails involved
Peutz Jeghers syndrome: •Congenital/Childhood onset; AD (STK11 mutation)
•Location: oral mucosa + genital + digits (rarely)
•Dermoscopy of pigment: thin, regular gray lines on grayish background
•Malignancy risk: GI, breast, others
61 Melanonychia
Non- Melanocytic Melanocytic
Fungal Melanocyte Melanocytic Subungual activation Nail staining Melanonychia hemorrhage hyperplasia
Benign Malignant
Single Multiple
Nail matrix Subungual nevus melanoma
Trauma- Periungual Nail apparatus induced tumor-induced Laugier- lentigo Drug/systemic Ethnic type nail Peutz Jeghers Hunziker dz-induced pigmentation syndrome syndrome
62 Melanocytic
Melanocyte hyperplasia
Nail matrix Subungual nevus melanoma 63 Melanocyte Proliferation
Nail matrix nevus: •Location: fingernails > toenails; single nail > multiple nails
•Dermoscopy of pigment: homogenous brown color of background band w/ regular pattern of brown lines: longitudinal parallel lines w/ regular spacing & thickness
64 Nail Matrix Nevus
G. Micali, F. Lacarrubba (Eds.) Dermatoscopy in clinical practice: beyond pigmented Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am lesions. Informa Healthcare Ltd, London; 2010. Acad Dermatol. 2007 May;56(5):835-47. Epub 2007 Feb 22.
65 Melanocyte Proliferation
Subungual melanoma: •Location: thumb > great toe > index finger
•(+) Hutchinson’s Sign, (+/-) nail dystrophy
•50% of pts recollect preceding trauma
66 Subungual Melanoma
Worrisome features: 1) Pigment wider at the base 2) Multiple, variegated uneven bands 3) Destruction of nail plate/associated dystrophy 4) Pigment beyond nail/Hutchinson’s sign
67 Longitudinal Melanonychia Dermoscopy Summary
Ohn et al JAAD 2017. ABCDEFs of Subungual Melanoma
(A) Age: peak incidence in 5th to 7th decades of life, AA, Asians, Native Americans (in whom subungual melanoma accounts for ≤ 1/3 of all melanoma)
(B) Brown-black band w/ breadth greater than 3 mm with variegated borders
(C) Change in nail band or lack of change in morphology despite adequate tx
(D) Digit most commonly involved: thumb > great toe > index finger
(E) Extension of the brown-black pigment onto the proximal and/or lateral nailfold (+ Hutchinson’s sign)
(F) Family or personal history of dysplastic nevus or melanoma
Levit EK, Kagen MH, Scher RK, et al. The ABC rule for clinical detection of subungual melanoma. J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):269-74.
69 Longitudinal Melanonychia - Conclusions
Most melanonychias are benign, but it is essential to r/o subungual melanoma
Detailed history, clinical exam & medication review are important for diagnosis
Dermoscopy may aid in diagnosis & monitoring
If in doubt, perform a nail matrix biopsy
70 Collimated Lights
Lasers for Onychomycosis
The Ronald O. Perelman Department of Dermatology Emerging Therapeutics in Nail Disease
Onychomycosis •Lasers •Photodynamic Therapy •Iontophoresis
Psoriasis •Lasers •Intense Pulsed Light
The Ronald O. Perelman Department of Dermatology Outline
Why lasers? Mechanisms Data Future Directions
Lasers for Onychomycosis Background
Onychomycosis: the most common nail disease affecting ~14% of the population • Multiple modalities of treatment • Orals • Topicals • Multimodal treatment
Challenges: • Nail plate • Patient compliance • Low cure rates • High rates of relapse • Uncertain follow-up time • Potential adverse events (e.g. hepatotoxicity, drug-drug interactions) de Berker, 2009. Elewski BE, Charif MA. Gupta AK, et al 2000. Ghannoum MA, et al, 2000.
Lasers for Onychomycosis Why Lasers?
Principle of Selective Thermolysis •Selective targeting of fungus? •Better penetration, reduced side effects, physician control
Six Lasers FDA Cleared for the “temporary increase of clear nail of patients with onychomycosis” •Based on Equivalence Data •Not on RCTs
•5 are Nd:YAG (1064nm), 1 is a diode (635/405nm)
FDA.gov
Lasers for Onychomycosis Mechanisms of Action
Ideally based on TRT of fungi or melanin
•Time required for heated tissue to lose 50% of heat through diffusion •Related to size of target chromophore •If time >TRT, target is not treated but collateral damage inflicted
In reality, most mechanisms are uncertain
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017
Lasers for Onychomycosis Mechanisms of Action
Nd:YAG: bulk heating
Selective photothermolysis? • T ↑ induced by energy absorption by lipids and moisture within fungal & host cells heat shock response affects transcription / translation death by induced cell imbalance • T. rubrum death within 15 min of exposure at 50ºC • T> 45ºC pain, necrosis in humans • Theoretically**, pulses should alleviate this • Lower temperatures can lead to fungistasis, but later spore germination
Fungistasis or fungicide?
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017; Carney et al 2013
Lasers for Onychomycosis Mechanisms of Action
QS lasers: selective photothermolytic and photomechanical effects • Which are target chromophores: melanin in cell wall or fungi?
• Light absorption peak for t. rubrum is 415nm
• Chitin, xanthomegnin, and melanin produced by t. rubrum • Pigments are virulence factors that protect fungi from host immune responses and ROS with destruction there could be an antifungal effect
• At 532nm QS Nd:YAG can suppress t. rubrum due to large amounts of xanthomegnin it contains • However only wavelengths 750 – 1300nm can penetrate the nail plate • At 1064nm, wavelength is beyond absorption spectrum
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017; Carney et al 2013
Lasers for Onychomycosis Mechanisms of Action
Nd:YAG Outstanding Issues
• TRTs of mycelia and spores are not precisely known
• Are short pulses sufficient for fungicide or only fungistasis?
• How long do elevated temperatures need to be sustained to kill spores without damaging surrounding tissues?
• Is there a mismatch between the wavelength needed to penetrate the nail plate and that required to target necessary chromophores?
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017; Carney et al 2013
Lasers for Onychomycosis Mechanisms of Action
Diode: antimicrobial plus increased immune response? • Dual wave, Non-thermal or “low level laser”
Antimicrobial • 405nm (blue) light: antimicrobial, antibacterial, antifungal effects
Increased immune response • 635nm (red) light: increase immune response by increasing circulation
Theory of photomodulation to increase immune activation: • Light exposure target chromophore (iron and copper-containing enzyme cytochrome C oxidase in the mitochondrial respiratory chain) increased production of mitochondrial products PMNs stimulated to generate additional ROS increased fungicidal capacity
Gupta & Versteeg, 2017; Bhatta et al, 2017
Lasers for Onychomycosis Mechanisms of Action
Erbium and CO2: ablative v fractionated • Vaporization of nail bed +/- enhanced topical drug delivery
fCO2 Photothermal effects On fungus
• ↑ tissue T direct fungicide as H2O converted to steam swelling, pressure microexplosions in fungi On microenvironment • Exfoliation and vaporization of target tissues remodeling and destruction of fungal growth environment
Enhanced topical drug delivery • Enhanced absorption via microscopic holes in nail bed
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017
Lasers for Onychomycosis General Data
Fraught with limitations Most reports are case series, uncontrolled trials without placebo or randomization Numbers of subjects are low Treatment numbers range from 1 – 12 sessions Follow-up ranges from 0 – 12 months Few pure laser studies: often use concomitant antifungals Measurements: no consistency • Type of onychomycosis • Species • Diagnosis (Culture / PAS) • Clinical measurements • How cure and clinical improvement defined • Fingers v toenails
47% of 1064nm device trials reported a positive response 60% reported clinical and mycologic cure in >50% of treated subjects
Francuzik et al 2016
Lasers for Onychomycosis Randomized Studies With A Comparison Group
Author Year Laser Wavelength (nm) No. of treated No. of nails Follow- CRR (%) MCR (%) Rand Controlled Source patients up (mo) omized Landsman et al. 2010, 2012 Diode 870, 930 26 26 9 35 38 Yes YesP
Zhang et al. 2012 Nd:YAG 1064 33 154 6 51-53 NA Yes YesA Hollmig et al. 2014 Nd:YAG 1064 17 57 12 0.24M 33** Yes Yes Li et al. 2014 Nd:YAG 1064 37 112 (50*, 62) 6 62.5 74* Yes YesB 83.9 Ortiz et al. 2014 Nd:YAG 1320 10 10 3 40C 50 Yes YesS Xu 2014 Nd:YAG 1064 15 31 6 64.52 77.42 Yes YesT1 El-Tatawy et al. 2015 Nd:YAG 1064 20 NA 6 100 80 Yes YesT2 Kim et al 2016 Nd:YAG 1064 56 217 6 76 15 Yes YesT3 Karsai et al 2017 Nd:YAG 1064 20 82 12 0 0 Yes Yes Park et al 2017 Nd:YAG 1064 128 NA 0 NA 72 Yes YesT4
CRR - Clinical Response Rate; Defined by linear clearing of the nail unless otherwise noted MCR - Mycologic Cure Rate; Defined by negative fungal culture unless otherwise noted * Fingernails **At 3 months M Reported as mean proximal nail plate clearance in millimeters C Reported as clinical clearance rate P Placebo-controlled S Subjects served as their own controls Nd:YAG n = 352 A Nd:YAG with half the number of treatments served as control group B Fingernails and toenails served as control groups for each other CRR = 0-100% T1 Oral terbinafine served as control group MCR = 0-84% T2, T3, T4 Topicals served as control group (T2 – terbinafine, T3 – naftifine, T4 – amorolfine) f/u = 0-12 mo Adapted from Wiznia et al, 2016; Karsai et al; Park et al; Kim et al
Lasers for Onychomycosis Compelling (?) Data: Erbium & CO2
Author Year Fractionated Wavelength (nm) Fluence No. of patients No. of nails Follow-up (mo) CRR (%) MCR (%) Controlled (J/cm2) or Power (W) Apfelberg et al. 1984 No 10600 NA 9 NA 6 NA 67* No Borovoy et al. 1992 No 10600 8-10 W 200 NA 36 75 NA No Lim et al. 2014 Yes 10600 160mJ 24 119 3 71 50 No Bhatta et al. 2016 Yes NA 99mJ 75 356 6 73 80 No Zhang et al. 2016 Yes 2940 35-62J/cm2 9 20 3 90 75 No Zhou et al. 2016 Yes 10600 10-15mJ 60 233 6 73A 57B Yes*** Shi et al. 2017 Yes 10600 15mJ 31 124 3 69* 74** No
Fractionated CO2 CRR - Clinical Response Rate; Defined by linear clearing of the nail unless otherwise noted n = 190 A Greater than 60% clear B Less than 5% nail affected MCR - Mycologic Cure Rate; Defined by negative fungal culture unless otherwise noted CRR = 69-90% **Negative fungal microscopy (KOH) MCR = 50-80% ***CO2 arm served as control v CO2 + topical 3-12 tx, q2-4 wk Adapted from Wiznia et al; Shi et al; Zhang et al; Zhou et al daily antifungal
Lasers for Onychomycosis Adverse Effects
•Pain •Necrosis, especially in diabetics •Risk of anesthesia
Leverone et al, 2015
Lasers for Onychomycosis How to Approach This?
Assume that lasers do not work and do not use them • A recent ”real-world” study (Rivers et al)
Use lasers for only selected indications • DLSO, in patients intolerant / unwilling to use prescriptions, those with better prognosis
Employ multimodal treatment • Time, money
Attempt fractionally ablative methods
Consider the language that is being used
Rivers et al 2016
Lasers for Onychomycosis Education
Dispel the notion of treatment of onychomycosis • Temporary increase in clear nail • Offer treatment for cosmesis only • Analogous to botulinum toxin, hyaluronic acid fillers
Set expectations
Recognize your own moral compass
Image via greaterspringfield.nimbledeals.com
Lasers for Onychomycosis Future Studies: Standardization
Lasers as monotherapy
How best to identify controls • Untreated digit of contra foot v untreated individuals
Follow-up times
Treat all affected nails to control for reinfection
Separate by onychomycosis subtype, location (fingers v toes) • Growth rates differ between fingers and toes as will time to treatment endpoints and measurements
Methods for quantifying clinical improvement • Cure rates – clinical and mycological • Cosmesis • Treatment
Gupta et al 2016
Lasers for Onychomycosis Lasers: The Bottom Line
Studies generally of poor quality, without standardization Comparisons difficult to make
The optimal non-ablative laser needs • Activity against melanin/fungal elements AND pulse duration matching TRT • Adequate nail penetration
Fractionated Erbium and CO2 • Initial data look promising • Mechanism makes sense
Lasers for Onychomycosis Conclusions
The differential diagnosis of podiatric rashes is broad and includes uncommon systemic conditions
Careful clinical examination can help narrow differentials
Most melanonychias are benign
Following an algorithm helps to demystify these conditions
Detailed history and examination, including dermoscopy, can help
Lasers hold promise for the cosmetic / medical treatment of onychomycosis
Data are early, methodologies are unsound, improved standards will help
The Ronald O. Perelman Department of Dermatology Acknowledgements
APMA Council for Nail Disorders
Chris Adigun, MD Kristen Lo Sicco, MD Euphemia Mu, MD Nicola Quatrano, MD Jennifer Stein, MD, PhD Antonella Tosti, MD Lauren Wiznia, MD
Questions: [email protected] @drevanrieder
The Ronald O. Perelman Department of Dermatology References – Bumps
1. Kline A. Allergic contact dermatitis of the foot after use of Mastisol skin adhesive: a case report. Foot and Ankle Online Journal 2008. doi: 10.3827/faoj.2008.0102.0002 2. Sator PG, Breier F, Gschnait F. Acrokeratosis paraneoplastica (Bazex's syndrome): Association with liposarcoma. J Am Acad Dermatol 2006; 55:1103.
All other clinical information and photos obtained from:
UpToDate VisualDx Dermnetnz.com
The Ronald O. Perelman Department of Dermatology References – Stripes
1. Bae SH, Kim NH, Lee JB, et al. Total melanonychia caused by Trichophyton rubrum mimicking subungual melanoma. J Dermatol. 2016 Apr 9. doi: 10.1111/1346-8138.13386. [Epub ahead of print] 2. Beggs AD, Latchford AR, Vasen HF, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010 Jul;59(7):975-86. 3. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007 May;56(5):835-47. Epub 2007 Feb 22. 4. Centers for Medicare and Medicaid Services. Medicare and Medicaid EHR incentive program: meaningful use stage 1 requirements overview, 2010. Published online July 28, 2010. Available at: URL: http://www.cms.gov/Regulations-and Guidance/Legislation/EHRIncentivePrograms/downloads/MU_Stage1_ReqOverview.pdf. Accessed May 11th, 2016. 5. Terushkin V et al. Analysis of the benign to malignant ratio of lesions biopsied by a general dermatologist before and after the adoption of dermoscopy. Arch Dermatol 2010; 146(3): 343-344. 6. Ohn J et al. Dermoscopic patterns of fungal melanonychia: a comparative study with other causes of melanonychia. J Am Acad Dermatol 2017; 76: 488-493. 7. Dean B, Becker G, Little C. The management of the acute traumatic subungual haematoma: a systematic review. Hand Surg. 2012;17(1):151-4. 8. Finch J, Arenas R, Baran R. Fungal melanonychia. J Am Acad Dermatol. 2012 May;66(5):830-41. 9. Hardin ME, Greyling LA, Davis LS. Nicotine staining of the hair and nails. J Am Acad Dermatol. 2015 Sep;73(3):e105-6. doi: 10.1016/j.jaad.2015.05.020 10. Jabbari A, Gonzalez ME, Franks AG Jr, Sanchez M. Laugier Hunziker syndrome. Dermatol Online J. 2010 Nov 15;16(11):23. 11. Jin H, Kim JM, Kim GW, et al. Diagnostic criteria for and clinical review of melanonychia in Korean patients. J Am Acad Dermatol. 2016 Jan 30. 12. Lee SW, Kim YC, Kim DK, et al. Fungal melanonychia. J Dermatol. 2004 Nov;31(11):904-9. 13. Levit EK, Kagen MH, Scher RK, et al. The ABC rule for clinical detection of subungual melanoma. J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):269-74. 14. Piraccini BM, Iorizzo M, Tosti A. Drug-induced nail abnormalities. Am J Clin Dermatol. 2003;4(1):31-7. 15. Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum and the value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6. 16. Youngchim S, Pornsuwan S, Nosanchuk JD, et al. Melanogenesis in dermatophyte species in vitro and during infection. Microbiology. 2011 Aug;157(Pt 8):2348-56. doi: 10.1099/mic.0.047928-0. Epub 2011 May 12.
The Ronald O. Perelman Department of Dermatology References – Collimated Lights
• Amichai B, Nitzan B, Mosckovitz et al. Iontophoretic delivery of terbinafine in onychomycosis: a preliminary study. Br J Dermatol 2010; 162: 46-50. • Apfelberg DB, Rothermel E, Widtfeldt A, Maser MR, Lash H. Preliminary report on use of carbon dioxide laser in podiatry. J Am Podiatry Assoc 1984;74:509-13. • Bhatta AK, Keyal U, Huang X, Zhao JJ. Fractional carbon-dioxide (CO2) laser-assisted topical therapy for the treatment of onychomycosis. J Am Acad Dermatol 2016. • Borovoy M, Tracy M. Noninvasive CO 2 laser fenestration improves treatment of onychomycosis. Clin Laser Mon 1992;10:123-4. • Carney C, Cantrell W, Warner J, Elewski B. Treatment of onychomycosis using a submillisecond 1064-nm neodymium:yttrium-aluminum-garnet laser. J Am Acad Dermatol 2013;69:578-82. • de Berker D. Clinical practice. Fungal nail disease. N Engl J Med 2009;360:2108-16. • El-Tatawy RA, Abd El-Naby NM, El-Hawary EE, Talaat RA. A comparative clinical and mycological study of Nd-YAG laser versus topical terbinafine in the treatment of onychomycosis. J Dermatolog Treat 2015;26:461-4. • Elewski BE, Charif MA. Prevalence of onychomycosis in patients attending a dermatology clinic in northeastern Ohio for other conditions. Arch Dermatol 1997;133:1172-3. • Francuzik W, Fritz K, Salavastru C. Laser therapies for onychomycosis - critical evaluation of methods and effectiveness. J Eur Acad Dermatol Venereol 2016. epub ahead of print’ • Ghannoum MA, Hajjeh RA, Scher R, et al. A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol 2000;43:641-8. • Gupta AK, Foley KA, Daigle, D. Clinical trials of lasers for toenail onychomycosis: the implications of new regulatory guidance. J Dermatol Treat 2017; 28(3): 264-270. • Gupta AK, Foley KA, Versteeg, SG. Lasers for onychomycosis: current status. J Cut Med Surg 2017; 21(2): 114-116.
The Ronald O. Perelman Department of Dermatology References – Collimated Lights
• Gupta AK, Jain HC, Lynde CW, Macdonald P, Cooper EA, Summerbell RC. Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter canadian survey of 15,000 patients. J Am Acad Dermatol 2000;43:244-8. • Gupta AG and Versteeg SG. A critical review of improvement rates for laser therapy used to treat toenail onychomycosis. JEADV 2017; 31: 1111-1118. • Haedersdal M, Erlendsson AM, Paasch U, Anderson RR. Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status. J Am Acad Dermatol 2016. • Hollmig ST, Rahman Z, Henderson MT, Rotatori RM, Gladstone H, Tang JY. Lack of efficacy with 1064-nm neodymium:yttrium-aluminum-garnet laser for the treatment of onychomycosis: a randomized, controlled trial. J Am Acad Dermatol 2014;70:911-7. • Karsai S et al. Treating onychomycosis with the short-pulsed 1064-nm-Nd:YAG laser: results of a prospective randomized controlled trial. JEADV 2017; 31: 175-180. • Kalokasidis K, Onder M, Trakatelli MG, Richert B, Fritz K. The Effect of Q-Switched Nd:YAG 1064 nm/532 nm Laser in the Treatment of Onychomycosis In Vivo. Dermatol Res Pract 2013;2013:379725. • Kim TI et al. A randomized comparative study of 1064nm Neodymium-doped yttrium aluminium garnet (Nd:Yag) laser and topical antifungal treatment of onychomycosis. Mycoses 2016; 59: 803-810. • Landsman AS, Robbins AH, Angelini PF, et al. Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light exposure. J Am Podiatr Med Assoc 2010;100:166-77. • Landsman AS, Robbins AH. Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light exposure: some follow-up observations at 270 days. J Am Podiatr Med Assoc 2012;102:169-71. • Leverone A, Guimaraes D, Bernardes-Engemann A, Orofino-Costa R. Partial necrosis of the hallux in a patient treated with laser for onychomycosis: is this procedure really worthwhile? Dermatol Surg 2015; 41(7): 869-72. • Li Y, Yu S, Xu J, Zhang R, Zhao J. Comparison of the efficacy of long-pulsed Nd:YAG laser intervention for treatment of onychomycosis of toenails or fingernails. J Drugs Dermatol 2014;13:1258-63. • Lim EH, Kim HR, Park YO, et al. Toenail onychomycosis treated with a fractional carbon-dioxide laser and topical antifungal cream. J Am Acad Dermatol 2014;70:918-23.
The Ronald O. Perelman Department of Dermatology References – Collimated Lights
• Nair AB, Vaka SRK, Murthy SN. Transungual delivery of terbinafine by iontophoresis in onychomycotic nails. Drug Dev Ind Pharm 2011; 37: 1253-1258. • Nair AB, Vaka SRK, Sammeta SM et al. Trans-ungual iontophoretic delivery of terbinafine. J Pharm Sci 2009; 98: 1788- 1796. • Ortiz AE, Avram MM, Wanner MA. A review of lasers and light for the treatment of onychomycosis. Lasers Surg Med 2014;46:117-24. • Ortiz AE, Truong S, Serowka K, Kelly KM. A 1,320-nm Nd: YAG laser for improving the appearance of onychomycosis. Dermatol Surg 2014;40:1356-60. • Park, KY et al. Randomized clinical trial to evaluate the efficacy and safety of combination therapy with short-pulsed 1064-nm Neodymium-doped Yttrium Aluminum Garnet laser and amorolfine nail lacquer for onychomycosis. Ann Dermatol 2017; 29 (6): 699-705. • Rivers JK et al. Real-world efficacy of 1064-nm Nd:YAG laser for the treatment of onychomycosis. J Cut Med Surg 2017; 21(2): 108-113. • Shi J et al. The efficacy of fractional carbon dioxide laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis. J Cos Laser Therapy 2017; 19 (6): 353-359. • Sotiriou EK-ET, Chaidemenos G, Apalla Z, Ioannides D. Photodynamic therapy for distal and lateral subungual toenail onychomycosis caused by Trichophyton rubrum: Preliminary results of a single-centre open trial. Acta Derm Venereol 2010; 90(2): 216-217. • Xu Y, Miao X, Zhou B, Luo D. Combined oral terbinafine and long-pulsed 1,064-nm Nd: YAG laser treatment is more effective for onychomycosis than either treatment alone. Dermatol Surg 2014;40:1201-7. • Wiznia LA, Quatrano, NA, Mu EW, Rieder EA. A clinical review of laser and light therapy for psoriasis and onychomycosis. Derm Surg 2016; accepted for publication
The Ronald O. Perelman Department of Dermatology References – Collimated Lights
• Zang K, Sullivan R, Shanks S. A retrospective study of non-thermal laser therapy for the treatment of toenail onychomycosis. J Clin Aesth Dermatol 2017; 10(5): 24-30. • Zhang J et al. Combination therapy for onychomycosis using a fractional 2940-nm Er:YAG laser and amorolfine lacquer. Lasers Med Sci 2016; 31: 1391-1396. • Zhang RN, Wang DK, Zhuo FL, Duan XH, Zhang XY, Zhao JY. Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis. Chin Med J (Engl) 2012;125:3288-91. • Zhou, BR et al. The efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis. Medicine 2016; 95: 44.
The Ronald O. Perelman Department of Dermatology Novel Therapeutics: Photodynamic Therapy
•Mechanism: free radicals
•Treatment parameters varied: 1-22 sessions, q1-8wks, wavelengths of light 470 – 750nm, fluence 18 – 228J/cm2
•Recent meta-analysis: 17 studies, 214 patients total, one RCT
•Strengths: minimal side effects, targeted, may work where other treatments have failed, across dermatophytes, molds, yeast; endonyx
•Weaknesses: early data, impractical – time intensive – requires significant debridement / avulsion / nail softening / nail drilling or fractionation
Bhatta et al, 2016
The Ronald O. Perelman Department of Dermatology Novel Therapeutics: Iontophoresis
•Mechanism: application of small current to increase transport of molecules via co-transport with water or ion flux
•May hold promise for enhancing absorption of topical antifungals
•Data: in vitro and one pilot study with questionable results
Sotiriou et al, 2010; Amichai et al, 2010
The Ronald O. Perelman Department of Dermatology