A 70-year-old man with a medical history significant for diabetes presents to the clinic with a complaint of yellowing of his toenails. He reports that he has difficulty trimming the nails. He denies prior nail trauma or pain. Upon examination, the nails of both feet are yellow, with breakages and subungual hyperkeratosis of the nail bed. No surrounding erythema or tenderness is noted. The patient is otherwise in good health.
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Onychomycosis is a fungal infection of the nails caused by dermatophytes, nondermatophytes, and yeast. It is the most common nail disease, accounting for up to 50% of all nail disorders.1,2 Approximately 2% to14% of the US population has onychomycosis.3 It is more prevalent in the elderly and is twice as common among men.2 Although onychomycosis is uncommon in children, its prevalence in this population is increasing due to occlusive footwear and exposure to locker rooms, swimming pools, and affected family members.4
Onychomycosis can be caused by various organisms, most commonly dermatophytes. Tinea unguium, or onychomycosis caused by dermatophytes, accounts for 90% and 50% of toenail and fingernail infections, respectively. Trichophyton rubrum and T mentagrophytes are the predominant dermatophytespecies. Nondermatophytes (ie, Scopulariopsis, Aspergillus, Fusarium, and Acremonium) are responsible for 20% of all cases, while species of Candida comprise the remaining 10% to 20%. Complex, multispecies infection is frequent, as is combined bacterial-fungal infection.1
Development of onychomycosis starts in the nail bed. Patients often initially have tinea pedis that invades the nail bed via small breakages in the nail. The nail bed attempts to eliminate the fungus through hyperkeratosis, resulting in damage to the nail matrix. The nail plate then separates and becomes distorted in the chronic total dystrophic stage of onychomycosis.5 Biofilm formation plays a role in the pathophysiology, causing increased virulence, antibiotic resistance, and host immune system evasion.6
Risk factors for onychomycosis include prior nail trauma, age, history of tinea pedis, diabetes, psoriasis, malignancy, exposure to infected household members, and genetic association with the HLA-DR8 serotype.1,2,5 Immunocompromised patients are at greater risk, especially those with defects in interleukin (IL)-17 and IL-22 production.7 Patients residing in temperate climates typically present with dermatophyte infection in the toenails, while those residing in hot, humid climates are more susceptible to yeast infection in their fingernails.2
Classic presentation of onychomycosis involves yellow, brittle nails and hyperkeratosis. Onycholysis and nail thickening increases over time and most often involves the big toenail. Patients may experience severe, localized pain. If found in conjunction with a black, violaceous nail plate, trauma likely contributed to the pathogenesis.1 One finding specific to onychomycosis is a dermatophytoma, which is a fungal abscess with yellowish-white or orange-brown streaks along the nail plate. Complications of severe disease include onychodystrophy, onychocryptosis, complete nail loss, cellulitis, osteomyelitis, and sepsis.1,5
The differential diagnosis for onychomycosis includes fungal melanonychia, traumatic onycholysis, psoriasis, lichen planus, onycholysis secondary to thyroid dysregulation, and malignancy.1,5 Dermoscopy can be used to distinguish onychomycosis, which presents with spikes, lines, and keratosis under the nail, from fungal melanonychia, which presents as triangular patterns with yellow-white streaks.8 Pitting, yellow-pink discoloration, or psoriatic skin or joint findings are more consistent with psoriasis of the nail.1
While clinical evaluation and dermoscopy can support a diagnosis of onychomycosis, diagnostic tests must be performed because of its similar appearance to other nail pathologies. The potassium hydroxide (KOH) test is a rapid in-office procedure with high specificity for onychomycosis that involves clipping the nail as proximally as possible and scraping the underside of the nail with a blade. The KOH dissolves large keratinocytes and allows for visualization of fungal hyphae or yeast cells; however, the fungal species cannot be determined. Histopathologic evaluation using a periodic acid-Schiff stain is also a sensitive test for fungus, but similarly cannot determine viability of or identify the causative species. Fungal culture allows for speciation of the causative fungi, but results may not be available for up to 1 month. Polymerase chain reaction, a DNA-amplification test that evaluates genes unique to fungal ribosomal RNA to diagnose onychomycosis, has high sensitivity and specificity, and results are available in several hours. Additional newer technologies include confocal microscopy, flow cytometry, infrared thermography, and mass spectrometry. In practice, KOH is used as the first-line test, followed by fungal culture. If the KOH test is negative initially, periodic acid-Schiff stain followed by fungal culture is the alternative diagnostic path.1,2,5
Antifungal agents are used for the treatment of onychomycosis, with systemic therapy being most effective.5,9 Terbinafine and itraconazole are broad-spectrum systemic antifungal agents approved for dermatophytes, some nondermatophytes, and Candida. Due to the length of time it takes for a nail to regrow, patients may wait 6 months (for fingernails) to 18 months (for toenails) before improvement is seen. Side effects of these drugs include liver toxicity and gastrointestinal symptoms. In particular, patients are advised to undergo liver function testing before starting terbinafine. Fluconazole, used off-label in the United States, is sometimes preferred over itraconazole because it does not depend on food or gastric pH for absorption; however, the drug should be avoided in patients who are breastfeeding. Topical ciclopirox is approved for mild to moderate onychomycosis. Although antifungal agents are necessary for eliminating fungi, laser therapy can help achieve aesthetic improvement of the nail. However, laser therapy requires multiple expensive treatment sessions and has demonstrated lower cure rates.5,9 Plasma therapy and photodynamic therapy are emerging treatments that are being evaluated for efficacy.
The patient in this case was diagnosed clinically. He was treated with oral terbinafine 250 mg/d for 90 days. At 1-year follow-up, the patient’s nails had vastly improved.
Riyad N.H. Seervai, BA, BS, is a medical student; Michelle Eugene Lee, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston, Texas.
- Lipner SR, Scher RK. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol. 2019;80(4):835-851.
- Gupta AK, Versteeg SG, Shear NH. Onychomycosis in the 21st century: an update on diagnosis, epidemiology, and treatment. J Cutan Med Surg. 2017;21(6):525-539.
- Gupta AK, Mays RR, Versteeg SG, et al. Global perspectives for the management of onychomycosis [published online December 25, 2018]. Int J Dermatol. doi: 10.1111/ijd.14346
- Solis-Arias MP, Garcia-Romero MT. Onychomycosis in children. A review Int J Dermatol. 2017;56(2):123-130.
- Bodman MA, Krishnamurthy K. Onychomycosis. StatPearls [internet]. Treasure Island, FL; 2018.
- Gupta AK, Foley KA. Evidence for biofilms in onychomycosis. G Ital Dermatol Venereol. 2019;154(1):50-55.
- Gupta AK, Carviel J, Shear NH. Onychomycosis and chronic fungal disease: exploiting a commensal disguise to stage a covert invasion. J Cutan Med Surg. 2018;22(3):318-322.
- Ohn J, Choe YS, Park J, Mun JH. Dermoscopic patterns of fungal melanonychia: a comparative study with other causes of melanonychia. J Am Acad Dermatol. 2017;76(3):488-493.e2.
- Lipner SR, Scher RK. Onychomycosis: treatment and prevention of recurrence.J Am Acad Dermatol. 2019;80(4):853-867.