Onychomycosis treatment is challenging, as many patients do not respond to therapeutic intervention, and of those that do respond, recurrence of disease occurs frequently. There are a number of factors that contribute to these therapeutic failures. Understanding these factors is key for effective patient education on their treatment options, setting their expectations for likelihood of response, and for developing strategies to prevent recurrence at the conclusion of therapy.

There are multiple prognostic factors that play a central role in determining how effectively a patient will respond to the treatment. A key factor is the severity of the nail disease. Determining the severity of onychomycosis disease is a critical part of the evaluation and ability to predict response to treatment. A patient with only mild disease is more likely to respond to treatment than a patient with moderate disease; and similarly, a patient with moderate disease has a better chance of responding to treatment than does a patient with severe disease [1]. Major features that contribute to onychomycosis disease severity include percentage of nail involvement, matrix involvement, existence of a dermatophytoma, and degree of subungual hyperkeratosis. These are the parameters that contribute to the onychomycosis severity index (OSI) [1]. An additional factor of the nail disease that contributes to prognosis is the number of nails involved. The more nails involved, the more extensive is the disease and the poorer is the prognosis. Long-standing infections tend to be more severe, as spontaneous resolution of onychomycosis is rare and disease duration is often >5 years [2].

However, there are a number of factors that contribute to a patient’s onychomycosis prognosis that are independent of the severity of their nail disease. These include patient behaviors such as risk for nail trauma from shoe selection, participation in sports, and hygiene behaviors [2, 3]. Nail trauma facilitates invasion of the dermatophyte by providing an uninhibited pathway of infection. Chronic nail trauma, or a chronically malformed nail, potentially is forever vulnerable to infection, making sustained clearance incredibly difficult [4].

In addition, factors related to the patient’s health status are critical to the prognostic evaluation. Comorbid conditions such as old age [5], diabetes mellitus [6, 7], peripheral vascular disease [8, 9], and/or psoriasis [2] all portend a poor response to treatment. These conditions often lead to slow or poor nail growth, due to poor circulation, and/or chronic nail trauma, due to diabetic neuropathy or arthritic gate abnormalities.

Immunosuppression, whether due to a complication from diabetes mellitus, autoimmune disease, HIV, or iatrogenic, contributes to poor response to treatment for onychomycosis [10, 11]. Patients that are immunosuppressed due to one or more of these factors need to be prepared for the possibility of treatment failure.