1. Onychomycosis Hai Ho, M.D.

2. Diagnosis? Psoriasis Pitting Nail involvement – 10-50% Usually along with skin lesions, but could be alone Could occur in eczema, fungal infection, and alopecia areta

3. Diagnosis? Psoriasis Pitting Onycholysis Yellow psoriatic debris under the nail causing nail separation

4. Diagnosis? Psoriasis Nail matrix involvement leading to nail deformity

5. Diagnosis? Onycholysis Painless separation of the nail from the nail bed Painless separation of the nail from the nail bed Causes: trauma (long nail in women), hyperthyroidism, prolonged immersion, psoriasis Causes: trauma (long nail in women), hyperthyroidism, prolonged immersion, psoriasis

6. Diagnosis? Traumatic onycholysis

7. Onycholysis May have secondary candida infection May have secondary candida infection Treatment Treatment Avoid long nail Avoid long nail Tinture containing miconazole under nail Tinture containing miconazole under nail Fluconazole for resistant case Fluconazole for resistant case

8. Diagnosis? Nail hypertrophy Cause: tight-fitted shoes or chronic trauma Cause: tight-fitted shoes or chronic trauma Treatment: filing or removing the nail with phenol Treatment: filing or removing the nail with phenol

9. Diagnosis? Leukonychia punctata Cause by cuticle manipulation or other mild trauma Cause by cuticle manipulation or other mild trauma

10. Diagnosis? Leukonychia

11. Diagnosis? Distal splitting nail Analogous to peeling of dry skin Analogous to peeling of dry skin Affected 20% of adults Affected 20% of adults Associated with water immersion and use of polish remover Associated with water immersion and use of polish remover Treatment Treatment Moisturizer Moisturizer B-complex vitamin biotin (2.5mg/day) for brittle nail B-complex vitamin biotin (2.5mg/day) for brittle nail

12. Diagnosis? Pincer nail Due to ?tight shoes Due to ?tight shoes Treatment Treatment Nail removal Nail removal Reconstruction of nail unit Reconstruction of nail unit

13. Diagnosis? Habit-tic onycholysis

14. Diagnosis? Median dystrophy

15. Moral of the story Cannot diagnose onychomycosis by visualization alone Cannot diagnose onychomycosis by visualization alone >50% of fungal-looking nail do not have fungal infection >50% of fungal-looking nail do not have fungal infection

16. Common organisms in onychomycosis? Dermatophytes Dermatophytes Trichophytum rubum Trichophytum rubum Trichophytum mentagrophytes Trichophytum mentagrophytes Contaminants or nonpathogens Contaminants or nonpathogens Aspergillus, Cephalosporium, Fusarium, and Scopulariopsis Aspergillus, Cephalosporium, Fusarium, and Scopulariopsis

17. Patterns of infection

18. Distal subungual onychomycosis Most common Most common Fungi invade the hyponychium and grow in the substance of nail plate, causing it to crumble Fungi invade the hyponychium and grow in the substance of nail plate, causing it to crumble Hyperkeratotic debris causes nail to separate from the bed Hyperkeratotic debris causes nail to separate from the bed

19. Distal subungual onychomycosis Linear channel Infection advance proximally Infection advance proximally Characteristic feature of fungal infection Characteristic feature of fungal infection

20. White superficial onychomycosis Commonly Trichophyton mentagrophytes Nail - white, soft, powdery

21. White superficial onychomycosis Nail Nail not thickened not thickened not separated from the nail bed not separated from the nail bed

22. Proximal subungual onychomycosis Commonly Trichophyton Rubrum Commonly Trichophyton Rubrum Invade the substance of nail plate, not the surface Invade the substance of nail plate, not the surface Hyperkeratotic debris causes the nail plate to separate from the nail bed Hyperkeratotic debris causes the nail plate to separate from the nail bed

23. Proximal subungual onychomycosis is associated with what disease? HIV

24. Candida onychomycosis Almost exclusively in chronic mucocutaneous candidiasis Almost exclusively in chronic mucocutaneous candidiasis Generally infect all fingernails Generally infect all fingernails Linear yellow or brown streaks grow and advance proximally Linear yellow or brown streaks grow and advance proximally

25. Candida onychomycosis Yellow areas with hyperkeratosis

26. Laboratory tests? KOH – improve detection with fluorochrome which binds with chitin in fungal cell wall and fluoresces KOH – improve detection with fluorochrome which binds with chitin in fungal cell wall and fluoresces Culture – gold standard Culture – gold standard Histological examination by periodic acid- Schiff (PAS) staining – equal to culture Histological examination by periodic acid- Schiff (PAS) staining – equal to culture

27. Obtaining specimen Subungal debris for KOH & cultureClip the nail for PAS & culture Fungi reside in the nail plate and cornified cells in the nail bed Hyphae in the nail plate may not be viable, so obtain specimen from nail bed for culture

28. KOH examination Hard nail plate and debris could be softened overnight with KOH Artifacts – lipid droplet between cells; eliminated by heat which separates cells

29. Culture Sabouraud's with antibiotics Sabouraud's with antibiotics Antibiotics suppress bacterial contaminants Antibiotics suppress bacterial contaminants Medium turn from yellow to red in 7-14 days – alkaline released by dermatophytes turn phenol (pH indicator) red Medium turn from yellow to red in 7-14 days – alkaline released by dermatophytes turn phenol (pH indicator) red ID the organism ID the organism

30. PAS staining In the presence of periodic acid, hydroxyl group of polysaccharide in fungal cell wall oxidized to aldehyde In the presence of periodic acid, hydroxyl group of polysaccharide in fungal cell wall oxidized to aldehyde Schiff reacts with aldehyde to stain fungal elements pinkish-red Schiff reacts with aldehyde to stain fungal elements pinkish-red False-negative – sampling error False-negative – sampling error

32. Options Systemic – terbinafine, itraconazole, fluconazole Systemic – terbinafine, itraconazole, fluconazole Topical Topical Mechanical Mechanical

33. Oral medications Terbinafine is more effective than itraconazole and fluconazole

34. Terbinafine vs. intermittent itraconazole Cure rate at 72 weeks Crawford F, et al. Arch Dermatol 2002; 138:811

35. Terbinafine vs. fluconazole Cure rate at 60 weeks Havu V, et al. Br J Dermatol 2000; 142(1):97.

36. Ineffective oral regimen Intermittent terbinafine Intermittent terbinafine Greseofulvin Greseofulvin

37. Regimen DrugDosage Fluconazole (Diflucan)One 150-mg dose each week for 9 months Itraconazole (Sporanox)200 mg/day for 12 weeks for toenails, 6 weeks for fingernails “Pulse dosing”: 400 mg/day for first week of each month Fingernails 2–3 pulses Toenails 3–4 pulses Terbinafine250 mg/day (12 weeks for toenails, 6 weeks for fingernails)

38. Adverse effect of terbinafine? Cholestatic hepatitis and blood dyscrasias Cholestatic hepatitis and blood dyscrasias LFT and CBC prior to and at 6 weeks during treatment LFT and CBC prior to and at 6 weeks during treatment

39. Adverse effect of itraconazole? Hepatitis for continuous but not intermittent regimen Hepatitis for continuous but not intermittent regimen LFT prior and at 6 weeks during treatment for continuous, not pulse, regimen LFT prior and at 6 weeks during treatment for continuous, not pulse, regimen

40. Drug interactions with itraconazole Cytochrome P450 system Cytochrome P450 system Arrhythmia with quinidine and primozile Arrhythmia with quinidine and primozile Rhabdomyolysis with HMG-CoA reductase inhibitors, such as atorvastatin Rhabdomyolysis with HMG-CoA reductase inhibitors, such as atorvastatin Sedation and apnea with benzodiazepines Sedation and apnea with benzodiazepines Decrease absorption with high gastric pH Decrease absorption with high gastric pH Avoid H2-blocker and PPI Avoid H2-blocker and PPI Take with food Take with food

41. Fluconazole Not FDA approval for onychomycosis Not FDA approval for onychomycosis First line for candida but could use for dermatophytes First line for candida but could use for dermatophytes Check LFT Check LFT

42. Prevent recurrence Prevent tinea pedis – powder to feet, protect feet in communal shower, change socks Prevent tinea pedis – powder to feet, protect feet in communal shower, change socks Avoid trauma by tight shoes Avoid trauma by tight shoes Ciclopirox nail lacquer 8% (PENLAC) 2 to 3 times a week Ciclopirox nail lacquer 8% (PENLAC) 2 to 3 times a week

43. Ciclopirox nail lacquer 8% (PENLAC) Cure rate at 48 weeks – 29% Cure rate at 48 weeks – 29% Apply to affected nail and 5 mm of surround skin daily Apply to affected nail and 5 mm of surround skin daily Remove PENLAC with alcohol weekly Remove PENLAC with alcohol weekly Remove infected nail frequently Remove infected nail frequently

44. Mechanical removal Surgery Surgery Nonsurgical avulsion of dystrophic nail, not normal one Nonsurgical avulsion of dystrophic nail, not normal one

45. Nonsurgical avulsion Apply 40% urea gel (Carmol-40 gel, Vanamide cream) with occlusive dressing Apply 40% urea gel (Carmol-40 gel, Vanamide cream) with occlusive dressing Remove the entire nail or cut the affected portion, followed by curetting to normal nail in 7-10 days Remove the entire nail or cut the affected portion, followed by curetting to normal nail in 7-10 days