Many patients and clinicians favor the less effective and more expensive topical agents due to fear of side effects such as hepatotoxicity with the cheaper systemic agents

The American Academy of Dermatology recommends confirmatory testing first as a means to reduce wasteful spending and treatment-associated side effects, but this recommendation was based on data from a 1999 study.

Mikailov and colleagues note, two main changes have happened since then:

  1. The price of oral terbinafine has plummeted from over $500 to as low as $10 for a 3-month course; and

  2. New, highly effective but pricey topical antifungals (efinaconazole, tavaborole) are now approved by the US Food and Drug Administration for the treatment of onychomycosis, with more topicals under development.

Oral terbinafine may cause rare liver injury.  Investigators calculated the cost to avoid harm when treating patients with empirical terbinafine. Based on prior data,[3] they estimated that 75% of all patients presenting with nail dystrophy had onychomycosis. Using this disease prevalence, empirical treatment with terbinafine saved $47 per patient vs the KOH screening model and $135 per patient vs pretreatment PAS evaluation. In contrast, screening with KOH scraping or confirmatory PAS testing as a prerequisite for treatment with efinaconazole 10% saved $272 or $406 per treated nail, respectively.

Perhaps most strikingly, it would take up to $90.2 million of PAS testing to prevent a single case of clinically relevant hepatotoxicity from oral terbinafine.


VIEWPOINT

Is pretreatment confirmation of onychomycosis before prescribing oral terbinafine therapy no longer necessary? Mikailov and colleagues' thought-provoking analysis certainly supports this conclusion, with some important caveats.

- Terbinafine, while highly effective against dermatophyte infections, will not clear onychomycosis caused by a yeast or saprophyte; oral azoles such as itraconazole would be the appropriate treatment in such cases, which are best differentiated from dermatophytes through fungal culture.

- Patients at greater risk for terbinafine-induced hepatotoxicity (eg, history of hepatitis, alcohol consumption, taking potentially hepatotoxic medications such as statins) may also benefit from confirmatory testing prior to starting terbinafine; Mikailov and colleagues' cost analysis does not "carve out" this higher-risk subset. Nevertheless, the risk for clinically apparent liver injury from oral terbinafine has been greatly exaggerated and occurs in as few as 1 in 50,000 to 100,000 treatments, with even rarer instances of durable clinical sequelae.[4]

One thing seems clear though: As long as topical antifungal agents such as efinaconazole remain astronomically expensive, there will still be a cost-saving role for confirmatory testing to "nail down" the diagnosis of onychomycosis first.

(Adapted from: http://www.medscape.com/viewarticle/861840_2)



  • Comments (22)
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  • Quote:

    As I do the AV for our conferences, and we frequently have the very bright and accomplished Warren Joseph, DPM as a speaker, I've had the opportunity to hear him lecture on onychomycosis and tinea pedis more times than I'd like to admit.  And he strongly concurs with Dr. Bristow's assertion that tinea pedis occurs as a precursor to onychomycosis in most cases, and not just a single isolated case of tinea pedis...generally recurrent, chronic tinea.  I stronly agree with the often neglected issue of treating the environment where the foot lives, that being the shoe.  It is relatively easy to treat tinea of the foot compared with tinea of the shoe.  Shoes are largely quite porous and readily harbor T. Rubrum.  Experience has taught me that if the shoe is not treated, there will be recurrence.  Effectively treating onychomycosis is far from easy and is one of many areas where podiatrists excel in comparison with dermatologists and PCPs..but only if they see it as the chronic disease that it is.

    The second pearl, from Dr. Bristow's excellent article concerns T. rubrum's pathogenic infiltration of the nail apperatus. Lacking the enzyme to infiltrate the healthy nail directly, the usual route is from skin to nail bed and from nail bed to the nail. Clearly then, when a nail is damaged already, from whatever cause, the process is aided in providing an additional access route for T. rubrum. Either way, the treatment has to work at the level of the nail bed. I am certain we all know that information, already, but this is an elegant explanation. And emphasized the need to treat skin and nail. And hosiery and footwear, actively and prophylactically.

  • As I do the AV for our conferences, and we frequently have the very bright and accomplished Warren Joseph, DPM as a speaker, I've had the opportunity to hear him lecture on onychomycosis and tinea pedis more times than I'd like to admit.  And he strongly concurs with Dr. Bristow's assertion that tinea pedis occurs as a precursor to onychomycosis in most cases, and not just a single isolated case of tinea pedis...generally recurrent, chronic tinea.  I stronly agree with the often neglected issue of treating the environment where the foot lives, that being the shoe.  It is relatively easy to treat tinea of the foot compared with tinea of the shoe.  Shoes are largely quite porous and readily harbor T. Rubrum.  Experience has taught me that if the shoe is not treated, there will be recurrence.  Effectively treating onychomycosis is far from easy and is one of many areas where podiatrists excel in comparison with dermatologists and PCPs..but only if they see it as the chronic disease that it is.

  • Quote:

    I concur and was just reporting what I see clinically.

    The conclusion that tinea pedis plays such a dominant role surprised me too ... but that's where the evidence points. Perhaps we need to be more suspicious of the possibility especially when the clinical signs are not so obvious - i.e. a low grade infection. Maybe we need to spend as much time with the Wood's lamp as the dermatoscope.

  • I concur and was just reporting what I see clinically.
  • Quote:

    -" virtually all onychomycosis stems from a chronic fungal foot infection" I humbly disagree. I think it plays a role but not virtually all. I also find it to be more common in the second nail rather than the third and I think the reason is because the second toe is frequently longer than the first or third. Just my findings.


    Jeff,

    I neglected to add that Dr. Bristows commentary is based on published research. I did not include the references because it's too much work. Any interested reader can check this out for additional clarification.  This is not entirely his personal opinion but rather reflects the opinion of the researchers, and the scientific community.  

    My interpretation is this: the study reporting the findings of nail predominance report accurately. But this finding can only be extrapolated to the study population. There can be variations in study populations. By way of example. Lets's hypothesize your study population has a higher incidence of patients with long second toes. The toe is more likely to rub on the shoe and cause chronic trauma to the nail plate. Other studies have identified population groups with a higher incidence of the 'Egyptian" foot morphology. There are Greek, or Roman morphological variations. Superimpose the effect of function, on foot types, and a whole bunch of additional possibilities open up. That's why it's important to analyze research findings in the context of a study and to resist the temptation to make presumptions or draw conclusions on abstracts, in isolation.

  • -" virtually all onychomycosis stems from a chronic fungal foot infection"

    I humbly disagree. I think it plays a role but not virtually all.

    I also find it to be more common in the second nail rather than the third and I think the reason is because the second toe is frequently longer than the first or third.

    Just my findings.
  • I still receive a copy of the British journal of Podiatry (Podiatry Now). I like to keep a finger on the pulse on podiatry issues, UK. By coincidence, the January edition features an article about onychomycosis with the title "Be Sure of the Cure when Treating Onychomycosis", Dr. I Bristow.

    In this article, Dr. Bristow discuss diagnosis, addresses mycological v clinical cure and treatment.

    Here are some key points, from this work:

    - before a treatment is instigated, a positive diagnosis of onychomycosis is required

    - onychomycosis is only responsible for 40-50% of all nail dystrophies

    - visual diagnosis has been reported to be reasonable accurate, with one study demonstrating that up to 67% of nails could be correctly diagnosed on appearance alone

    - current UK guidelines from the British Association of Dermatologists and NICE strongly recommend that any patient with suspected onychomycosis should have laboratory confirmation before treatment

    - testing has a high false-negative rate, suggested to be around 30%+

    -most patients are more interested to know their nail will look normal and are less interested in mycological cure but a patient should be counselled this may not be the case even when the fungus is eradicated; expectations should be tempered

    -nail infection is often a recurrent problem, one study demonstrating a 87% / 5-year re-infection rate after mycological cure. This emphasizes the need to implement prophylactic measures after successful treatment.

    - virtually all onychomycosis stems from a chronic fungal foot infection

    - T. rubrum is the most common causative agent and typically spreads along the surface of the nail bed, under the hyponichium causing inflammation of the nail bed and nail lifting (onycholysis)

    - nails most commonly affected: hallux nails, third & fifth toenail

    - trauma is considered to be the primary pre-cursor reason for affecting some nails more often than others.  Though rarely discussed in papers, toe & foot shape/ function(and associated trauma) are identified in one study. 

  • Dennis - can you expand on your bias that you speak of? Where is the bias?
  • Quote:
    We are thinking exactly the same. Interventions biologic, chemotherapeutic, biomechanical, pedorthic, lifestyle, herbal, etc., need to be considered/done on FIRM CLINICAL GROUNDS, which is what you are really arguing. The fact that available approaches to mechanical nail dystrophy with and without infection are limited but evolving is promising, and nothing I ever said about laboratory confirmation dismisses the multifactorial etiology of nail dystrophy, including infection.

    Consensus Bryan. Consensus..

    I would add that we both agree on the need to test before prescribing Terbinafine long term.

    Dennis

  • Quote:

    Good question Dennis. So do a very impressive number of podiatrists proceed without laboratory confirmation? Definitely yes. Do a very impressive number of dermatologists proceed without laboratory confirmation? More than I would expect but MUCH, MUCH LESS than podiatrists. This is well documented in the literature. As to which group's protocols dictate any standard of care I am not certain, but personally, I believe it to be sub standard to not obtain lab confirmation in evaluation and treatment of nail dystrophy when anything beyond debridement is being contemplated. Again, only because the condition we are talking about is RELATIVELY banal is this discourse taking place. A surgeon palpating a breast lump would never proceed without knowing the biology if what he or she is treating. I make no judgement about anyone else, but when a failed antifungal regimen is referred to me, which happens often, and I get a blank stare from the patient when I ask if the "onychomycosis" was laboratory confirmed, both the patient and myself have the same "WTF?" feeling.

    Understandable - but that's likely as much a matter of failure of communication. Or a patient 'feigning' as such. Ya, some patients do enjoy the blame game, don't they?

    A different set of circumstance might exist when a fee paying patient is given all of the information and supportive data and provided with the opportunity to participate in the decision making process. Informed consent.

    Another factor is confidence in the clinical diagnosis. There will be those nails which simply yell "onychomycosis" at the patient AND the doctor. Other cases where it's less clear. And quite a few cases when it's a mixed presentation. Yes, you might clear that fungal component but the onychauxic nail that's left behind may never return to normal - no matter what you do. A patient ought to know about this.

    Biomechanics may well play a role in this scenario. I suspect ill-fitting shoes might play an equal, or bigger role.  It can be a tough gig to persuade a patient that poor foot biomechanics plays a big role in their yellow nails and they need pads and colored tape and/or an expensive foot orthosis. Or maybe Hyprocure? So says Doctor (A). We each can make up our own minds about that. That very same doctor-shopping patient is told by Doctor (B) they simply have a nail infection - take Lamisil, says Doctor (B) .... and take off that silly colored tape. 

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