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Presented by:
Sim Sui Theng
Hospital Miri
 Introduction
 Anatomy of a Nail

 Types of Onychomycosis

 Causes

 Oral Therapy

 Topical Therapy

 Patient Counseling

 Conclusion

 References

 Definition: Infection of the nail caused by fungi
such as dermatophytes, non-dermatophyte
moulds and yeasts (mainly Candida species)
 Classified as
 Distal and lateral subungual onychomycosis
 Superficial white onychomycosis (SWO)
 Proximal subungual onychomycosis (PSO)
 Candidial onychomycosis
 Total dystrophic onychomycosis


Fig 1: Normal Nail Anatomy

(1) Distal & lateral subungual
onychomycosis (DLSO)
 Majority case  due to dermatophyte
 Thickened & opacified nail plate

 Subungual hyperkeratosis

 Oncholysis

 Discoloration range from white to brown

 Edge of involved area  dystrophic

 Edge of nail area  eroded

(1) DLSO

Fig 1a: Distal lateral onychomycosis Fig 1b: Distal subungual onychomycosis
with surrounding erythema caused by T. rubrum.
(2) Superficial white
onychomycosis (SWO)
 Dermatophyte infection caused by: T.
 Less common than DLSO; affects the surface
of nail plate rather than nail bed
 Usually confined to the toenails

 Manifest as small, white speckled or powdery

patches on the surface of nail plate
 Nail become roughened and crumbles easily

(2) SWO

Fig 2a: Superficial onychomycosis

caused by T. mentagrophytes

Fig 2b: Superficial onychomycosis 8

(3) Proximal subungual
onychomycosis (PSO)
 Uncommon variety of dermatophyte infection:
often related to intercurrent disease
 Eg. Immunosuppressive (eg. HIV positive),
peripheral vascular disease, diabetes
 Presented as an area of leukonychia in the
proxymal nail fold  may extend deeper
layers of the nail
 Nail plate becomes white proximally and
remains normal distally
(3) PSO

Fig 3a: Proximal onychomycosis Fig 3b: Chronic tinea pedis and
Proximal onychomycosis
(4) Candidal Onychomycosis
 Infected by Candida yeasts
 Manifested as erythematous swelling of the
nail fold OR as separation of the nail plate
from its bed
 Presented in one of the four ways:
 Chronic paronychia with secondary nail dystrophy
 Distal nail infection
 Chronic mucocutaneous candidiasis
 Secondary candidiasis
(4) Candidal Onychomycosis

Fig 4: Candidal onychomycosis

(5) Total dystrophic
 Presented as a thickened, opaque and
yellow-brown nail and involves the entire nail
plate and matrix

Fig 5:Total dystrophic onychomycosis with the nail plate partially removed 13
 Caused by 3 main classes of fungi: dermatophytes, yeasts &
nondermatophyte molds
 Two major pathogens are responsible for 90% of all OM cases
 Trichophyton rubrum (70%)
 Trichophyton mentagrophytes (20%)
 Yeasts (8%) & nondermatophyte molds (2%)
 T. rubrum is the most common pathogen in DLSO and PSO
 T. mentagrophytes (often) and species of nondermatophyte
molds (rare) cause SWO
 Candida albicans primarily causes chronic mucocutaneous
candidiasis of the nail
 Risk factors: family history, ↑ age, poor health, warm climate,
participation in fitness activities, immunosuppression (HIV, drug
induced), communal bathing, and occlusive footwear
(1) Medical care
 Oral therapy

 Topical therapy

(2) Surgical care

 Antifungal drugs
 Griseofulvin (Fulvicin®, Gifulvin®, Gris-Peg®)
 Terbinafine (Lamisil®)
 Itraconazole (Sporanox®)
 Fluconazole (Diflucan®)
 Disadvantages: require longer Rx period &
more side effects

 Newer generation (terbinafine & itraconazole) replaced
older drug (griseofulvin)
 Griseofulvin has ↑ recurrence rates and ↓ clinical cure
rates Hofmann et al 1995

 Terbinafine has the highest efficacy compared to other

 Meta analysis found the following mycological cure rates
in RCT Gupta, Ryder & Johnson, 2004
Antifungal agent Mycological cure rate (%)
Terbinafine 76 ± 3
Itraconazole pulse therapy 63 ± 7
Griseofulvin 60 ± 6
Itraconazole continuous therapy 59 ± 5
Fluconazole 48 ± 5 17
Oral Antifungal Therapy
Antifungal agent Terbinafine Itraconazole Fluconazole
MOA Fungicidal acitivity. Ѳ squalene Fungistatic acitivity. Slows fungal Fungistatic activity.
epoxidase, which ↓ ergosterol cell growth by Ѳ ergosterol Disrupt cell membrane by
synthesis synthesis Ѳ sterol & CYP-450
Dosing Fingernails: Fixed dosage Fingernails:
250mg qid x 6/52 Fingernails: 200mg od x 6/52 150-300mg q week (12-
Toenails: 200mg od x 12/52 16/52)
Toenails: Pulse therapy
250mg qid x 12/52 Fingernails: 200mg bd Toenails:
x1/52,continue for 2 pulses 150-300mg q week (18-
Toenails: same; for 3 pulses 26/52)

Side effects Headache ↑ liver function test Headache

GI effects (diarrhea & Skin rash Skin rash
dyspepsia) ↑ triglycerides GI effects (Nausea,
Rash GI effects (Nausea, bloating, vomiting, diarrhea,
↑ liver enzymes diarrhea) abdominal pain)

Drug interactions ↓ tramadol, codeine Antacids, CCB, Sulphonyureas, Thiazides, rifampin,

↑ warfarin, SSRI,MAOI,TCA Tacrolimus, Cyclosporine, Statins,phenytoin, theophylline,
Rifampin ↑clearance Cisapride, Digoxin etc warfarin, cyclosporine
Contraindication Hypersensitivity rxn Hypersensitivity; x cisapride Hypersensivity rxn
Precaution Pregnancy: Risk B Pregnancy: Risk C Pregnancy: Risk C
Discontinue use if hepatobiliary Hepatic disease; achlorhydria, not Hepatitis, cholestasis,
dysfunction, neutropenia, recommended in breastfeeding, fulminant hepatic failure,
Stevens-Johnson syndrome, heart failure has been reported AIDS, malignancy
changes in ocular lens/retina 18
Safety & Monitoring
 Review patient’s medication list for potential
interactions when initiating oral antifungals
 Fluconazole & itraconazole  hepatotoxicity
 routine monitoring of LFT every 4-6 weeks
(serum aminotransferase & signs &
symptoms of hepatotoxicity)
 After antifungal therapy, disease-free nail
growth should be measured at every visit
(may take up to 1 year to look normal)
 Currently available nail lacquers: ciclopirox & amorolfine
 Consisted of:
 Fungicidally effective amount of antifungal agent in a clear, stable, film-
forming lacquer vehicle
 A water-insoluble film-forming polymer

 2-n-nonyl-1,3-dioxolane or similar penetration enhancer

 Volatile solvent

 Upon application to the nails, it provides a hard, clear, water-resistant film

containing antifungal agent
 Useful as adjunctive Rx in combination with oral therapy OR as prophylaxis in
patients cured by systemic agents
 Randomized trials reported higher mycological cure rates with combination
therapy (terbinafine + ciclopirox) than monotherapy with terbinafine

Gupta, 2005 20
Avner, Nir & Henri, 2005
Topical Agent: Ciclopirox
(Penlac 8%) Nail Lacquers
 MOA:
 Chelates with the polyvalent cations (Fe3+ & Al3+ ) that are involved in
fungal enzymatic activity  interrupts intracellular energy production &
toxic peroxide degradation
 Inhibits fungal nutrient uptake  depletion of amino acids & nucleotides
 protein synthesis ↓ (Fungicidal effect)
 Dosing:
 Apply once daily to affected nails can can be used up to 48 weeks
(indicated for infected nails w/o lunula involvement)
 Common side effects:
 Rash-related: periungual erythema, erythema of the proxymal nail fold

 Nail disorders eg shape change, irritation, ingrown toenail, discoloration

Gupta, Schouten & Lynch, 2005
Topical Agent: Amorolfine
(5%) Nail Lacquers
 MOA:
 Inhibits sterol biosynthesis  disrupts fungal cell membrane 
cell death
 Dosing:
 Apply once or twice weekly until clinical cure is achieved

 Usually 6/12 for fingernails & 1 year for toenail infections

 Common side effects:

 Burning, pruritus, vesicles, pain or stinging around the nail bed

Patient Counseling: How to
apply nail lacquer?
 It should be applied evenly over the entire nail plate and 5mm of surrounding skin
preferably at bedtime
 Area of application: Nail bed, hyponychium and the under surface of the nail plate
 Apply daily (ciclopirox) / twice weekly (amorolfine) on previous coat
 Wait 30 seconds for application to dry
 Wait 8 hours after application before washing or showering
 Remove previous coats with alcohol, file loose nail materials, and trim nails every
7 days
 Unattached, infected part of the nail should be removed by health care
professionals periodically (at least monthly)
 Contact with surrounding skin may produce mild, transient irritation (redness)
 Avoid contact with eyes and other internal route
 Do not remove product on daily basis

 Onychomycosis is not life-threatening, but it
can cause pain, discomfort, disfigurement
and may produce serious physical and
occupational limitations
 Psychosocial & emotional effects  affect
 Appropriate patient education should be
enhanced in order to improve patient’s
compliance to therapy
 Hofmann, H, Brautigam, M, Weidinger, G, Zaun, H. Treatment of toenail onychomycosis. A randomized, double-
blind study with terbinafine and griseofulvin. LAGOS II Study Group. Arch Dermatol 1995; 131:919.
 Gupta, AK, Ryder, JE, Johnson, AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of
onychomycosis. Br J Dermatol 2004; 150:537.
 Gupta, AK. Ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized,
evaluator-blinded study. J Drugs Dermatol 2005; 4:481.
 Avner, S, Nir, N, Henri, T. Combination of oral terbinafine and topical ciclopirox compared to oral terbinafine for
the treatment of onychomycosis. J Dermatolog Treat 2005; 16:327.
 Gupta, AK, Schouten, JR, Lynch, LE. Ciclopirox nail lacquer 8% for the treatment of onychomycosis: A Canadian
perspective. Skin Ther Lett 2005;10:1-3.
 Blumberg, M, Kantor, GR. Onychomycosis. eMedicine Dermatology 2007. Retrieved from:
 Shirwaikar, AA, Thomas,T, Shirwaikar A, Lobo,R, Prabhu, KS. Treatment of Onychomycosis: An Update. Indian
Journal of Pharmaceutical Sciences 2008; Nov-Dec:710-714.
 Jan, S, Bora, D, Bhise K. Preungual drug delivery systems of Terbinafine Hydrochloride Nail Lacquer. Asian
Journal of Pharmaceutics 2008; Jan:53-56.
 Goldstein, AO, Goldstein BG. Onychomycosis. UpToDate database system 2007.
 Lexi-Comp’s Drug Information Handbook, 13th Edition.
 British National Formulary 55, March 2008. British Medical Association.
 Micromedex Healthcare Series.

Any questions?