hot topics in podiatric dermatology evan rieder, md · acne pustulosis hyperostosis osteitis aka...
TRANSCRIPT
Dermatologist, Psychiatrist
Assistant Professor of Dermatology
The Ronald O. Perelman Department of
Dermatology
Hot Topics In Podiatric Dermatology
Evan Rieder, MD
The Ronald O. Perelman Department of Dermatology 2
Disclosures
Advisory Board Member:
UCB Pharmaceuticals
Consultant:
UCB Pharmaceuticals
Unilever
Podiatrists & Dermatologists
The Ronald O. Perelman Department of Dermatology
The Ronald O. Perelman Department of Dermatology 4
General Outline
Bumps
Stripes
Collimated Lights
The Power of Observation
The Ronald O. Perelman Department of Dermatology
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
Bumps
The Ronald O. Perelman Department of Dermatology
Outline
The Ronald O. Perelman Department of Dermatology
Common Podiatric Rashes
Keys To Differential Diagnosis
Uncommon Presentations
Bumps
The Ronald O. Perelman Department of Dermatology
Classic Psoriasis
Well-demarcatedErythematous plaqueSilvery 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
SynovitisAcnePustulosisHyperostosisOsteitis
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
The Ronald O. Perelman Department of Dermatology
Kline 2008
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
The Ronald O. Perelman Department of Dermatology
Sator PG et al, 2006
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
30
Melanonychia
Non-Melanocytic
Nail stainingFungal
MelanonychiaSubungual
hemorrhage
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-induced
Nail apparatus lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail pigmentation
Laugier-Hunzikersyndrome
Peutz Jegherssyndrome
Melanocytic hyperplasia
Benign
Nail matrix nevus
Malignant
Subungualmelanoma
31
Non-Melanocytic
Nail stainingFungal
MelanonychiaSubungual
hemorrhage
32
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.
J Am Acad Dermatol. 2015 Sep;73(3):e105-6. doi: 10.1016/j.jaad.2015.05.020.
Clinical Scenario
Location: Bilateral thumbnails, 2nd & 3rd
fingernails of dominant hand
Causes:
•Brown: hobbies, occupational exposure to
foods, clothing dyes
•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.
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
Nail Staining
Nail Staining
www.dailymail.co.uk/news/article-1384841/The-incredible-paintings-amputee-Chinese-artist-creates-pictures-toes-mouth.html
Huang Guofu
35
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
value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6.
Clinical Scenario
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
Lasers for Onychomycosis
Terushkin et al 2010
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)
39Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum
and the value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6.
Fungal Melanonychia
40Wang YJ, Sun PL. Fungal melanonychia caused by Trichophyton rubrum
and the value of dermoscopy. Cutis. 2014 Sep;94(3):E5-6.
Fungal Melanonychia: Dermoscopy
Ohn et al, JAAD 2017
• Pigmented streak
• Distal widening
• Yellowish streaks
• Jagged borders
• Spikes
41
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?
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.
Clinical Scenario
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
Subungual Hemorrhage
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
Summary: Non-Melanocytic
45
Melanonychia
Non-Melanocytic
Nail stainingFungal
MelanonychiaSubungual
hemorrhage
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-induced
Nail apparatus lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail pigmentation
Laugier-Hunzikersyndrome
Peutz Jegherssyndrome
Melanocytic hyperplasia
Benign
Nail matrix nevus
Malignant
Subungualmelanoma
Melanocyte activation: •Normal # of melanocytes with increased production of melanin epithelial
hyperpigmentation
Melanocyte hyperplasia:• Increased # of melanocytes (proliferation)
46
Melanonychia: Melanocytic
Dermoscopy: Melanocytic Activation v Proliferation
Melanocyte activation: thin, regular
gray lines on grayish background
v
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.
Melanin Melanocytes
48
Melanonychia
Non-Melanocytic
Nail stainingFungal
MelanonychiaSubungual
hemorrhage
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-induced
Nail apparatus lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail pigmentation
Laugier-Hunzikersyndrome
Peutz Jegherssyndrome
Melanocytic hyperplasia
Benign
Nail matrix nevus
Malignant
Subungualmelanoma
49
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-
induced
Nail apparatus
lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail
pigmentation
Laugier-Hunzikersyndrome
PeutzJeghers
syndrome
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
Melanocyte activation: single nail involved
Trauma-induced Melanonychia
51Photo courtesy: Dr. Shane Meehan
Don’t try this at
home!
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
Melanocyte activation: single nail involved
Nail apparatus Lentigo
54
Photos courtesy of: Dr. Jennifer Stein
55
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-
induced
Nail apparatus
lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail
pigmentation
Laugier-Hunzikersyndrome
PeutzJeghers
syndrome
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
Melanocyte activation: Multiple nails involved
Drug-induced melanonychia
57
G. Micali, F. Lacarrubba (Eds.) Dermatoscopy in clinical practice: beyond
pigmented lesions. Informa Healthcare Ltd, London; 2010.
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
Melanocyte activation: Multiple nails involved
Ethnic type nail pigmentation
59
Photo courtesy: Dr. Jennifer Stein
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
Melanocyte activation: Multiple nails involved
62
Melanonychia
Non-Melanocytic
Nail stainingFungal
MelanonychiaSubungual
hemorrhage
Melanocytic
Melanocyte activation
Single
Trauma-induced
Periungualtumor-induced
Nail apparatus lentigo
Multiple
Drug/systemic dz-induced
Ethnic type nail pigmentation
Laugier-Hunzikersyndrome
Peutz Jegherssyndrome
Melanocytic hyperplasia
Benign
Nail matrix nevus
Malignant
Subungualmelanoma
63
Melanocytic
Melanocyte hyperplasia
Nail matrix nevus
Subungualmelanoma
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
Melanocyte Proliferation
Nail Matrix Nevus
65
G. Micali, F. Lacarrubba (Eds.) Dermatoscopy in clinical practice: beyond pigmented
lesions. Informa Healthcare Ltd, London; 2010.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.
Subungual melanoma:
•Location: thumb > great toe > index finger
•(+) Hutchinson’s Sign, (+/-) nail dystrophy
•50% of pts recollect preceding trauma
66
Melanocyte Proliferation
Subungual Melanoma
67
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
Longitudinal Melanonychia Dermoscopy Summary
Ohn et al JAAD 2017.
(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
69
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.
ABCDEFs of Subungual Melanoma
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
Longitudinal Melanonychia - Conclusions
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)
Lasers for Onychomycosis
de Berker, 2009. Elewski BE, Charif MA. Gupta AK, et al 2000. Ghannoum MA, et al, 2000.
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)
Lasers for Onychomycosis
FDA.gov
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
Lasers for Onychomycosis
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017
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?
Lasers for Onychomycosis
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
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
Lasers for Onychomycosis
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
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?
Lasers for Onychomycosis
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
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
Lasers for Onychomycosis
Gupta & Versteeg, 2017; Bhatta et al, 2017
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
Lasers for Onychomycosis
Kalokasidis K et al. 2013. Ortiz AE et al, 2014. Carney et al, 2013. Haedersdal M et al, 2016. Gupta & Versteeg, 2017
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
Lasers for Onychomycosis
Francuzik et al 2016
Randomized Studies With A Comparison Group
Author Year Laser
Source
Wavelength (nm) No. of treated
patients
No. of nails Follow-
up (mo)
CRR (%) MCR (%) Rand
omized
Controlled
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*
83.9
Yes YesB
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
Lasers for Onychomycosis
Adapted from Wiznia et al, 2016; Karsai et al; Park et al; Kim et al
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 monthsM Reported as mean proximal nail plate clearance in millimetersC Reported as clinical clearance rateP Placebo-controlledS Subjects served as their own controlsA Nd:YAG with half the number of treatments served as control groupB Fingernails and toenails served as control groups for each otherT1 Oral terbinafine served as control groupT2, T3, T4 Topicals served as control group (T2 – terbinafine, T3 – naftifine, T4 – amorolfine)
Nd:YAG n = 352
CRR = 0-100%
MCR = 0-84%
f/u = 0-12 mo
Compelling (?) Data: Erbium & CO2
Author Year Fractionated Wavelength (nm) Fluence
(J/cm2) or
Power (W)
No. of patients No. of nails Follow-up (mo) CRR (%) MCR (%) Controlled
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
Lasers for Onychomycosis
CRR - Clinical Response Rate; Defined by linear clearing of the nail unless otherwise notedA Greater than 60% clear B Less than 5% nail affected
MCR - Mycologic Cure Rate; Defined by negative fungal culture unless otherwise noted
**Negative fungal microscopy (KOH)
***CO2 arm served as control v CO2 + topical
Adapted from Wiznia et al; Shi et al; Zhang et al; Zhou et al
Fractionated CO2
n = 190
CRR = 69-90%
MCR = 50-80%
3-12 tx, q2-4 wk
daily antifungal
Adverse Effects
•Pain
•Necrosis, especially in diabetics
•Risk of anesthesia
Lasers for Onychomycosis
Leverone et al, 2015
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
Lasers for Onychomycosis
Rivers et al 2016
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
Lasers for Onychomycosis
Image via greaterspringfield.nimbledeals.com
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
Lasers for Onychomycosis
Gupta et al 2016
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:
@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
The Ronald O. Perelman Department of Dermatology
Bhatta et al, 2016
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
The Ronald O. Perelman Department of Dermatology
Sotiriou et al, 2010; Amichai et al, 2010