A Guide To Detecting Nail Pathology

   As all those who specialize in the treatment of lower extremity ailments will acknowledge, there is nothing uncommon about nail unit pathology. Though pristine appearing nail units are commonplace in children, advancing age may bring a combination of acute and chronic trauma, neoplastic processes, non-infectious dermatological diseases, and bona-fide mycotic and non-mycotic infections that take their toll. These stressors manifest as alterations in nail color, shape and/or texture.    Too often in mainstream medicine, there is a tendency to attribute such changes within the nail unit solely to onychomycosis, leading clinicians to rely on oral or topical antifungal medications as “silver bullets” in their management. Such ill-fated reliance may lead to presumed drug inefficacy as even a perfect antifungal can only eradicate the organism if it is there. Often fungal infections are indeed present but represent a secondary phenomenon affecting a nail unit that was originally altered by a different pathologic process. In these cases, the best that one can hope for is a mycotic cure but a clinical failure.    To fine tune our management of patients with nail unit dystrophy, we might benefit by viewing the problem as a constellation of several factors as opposed to equating nail unit dystrophy with onychomycosis. By assessing all the possible contributors to the nail unit abnormality, we will recognize the various processes that must be addressed in addition to, or in lieu of, antifungal therapy.

A Guide To The Pathogenesis Of Nail Unit Dystrophy And Onychomycosis

   Abnormal epithelial keratinization is the single most important process in the development of an overwhelming majority of nail unit dystrophy cases. The body’s outer surface, oral cavity, anus and vagina are covered by stratified squamous epithelium. The principal feature that distinguishes the skin of the body from the mucosa of the genital tract or oral cavity is surface keratinization or a stratum corneum. The surface skin requires keratin to protect us from water loss but the mucosa has no such requirement.    This does not mean that the mucosa cannot become keratinized. In fact, stimuli such as persistent trauma, inflammation and exposure to the external elements routinely lead to mucosal keratinization as might various neoplastic processes. Classic examples of such abnormal keratinization include: that which occurs in the oral cavity in people who perpetually bite their inner cheeks or routinely dip tobacco; that which might occur in association with severe vaginal or uterine prolapse; or that which occurs naturally in circumcised men.    Discourse on the topic of abnormal epithelial keratinization is pertinent to the subject of nail unit dystrophy for several reasons. Foremost, in the overwhelming majority of cases, nail unit dystrophy is the product of abnormal nail bed and matrical keratinization. It does not arise as the result of an abnormality in the nail plate itself. Unlike when keratinization occurs at exposed sites, when a stimulus leads to keratinization of the nail bed, the overlying (and usually unremarkable) nail plate serves as a barrier that prevents keratin from being sloughed and leads to its accumulation.    Whether the stimulus is microtrauma, psoriasis, onycholysis, lichen planus or squamous cell carcinoma, nail bed keratinization may result in “dystrophic nails” that are clinically indistinguishable. It is only with some superficial patterns of onychomycosis not associated with nail bed keratinization and some cases of late stage total dystrophic onychomycosis (with florid infiltration of the nail plate itself) that one can make a diagnosis of “onychomycosis” with reasonable surety based on clinical findings alone.    Nail bed keratinization also has significance in the development of onychomycosis. The healthy nail unit is relatively resistant to fungal infections. However, this does not mean that infections can never involve otherwise healthy nail units. For instance, Trichophyton mentagrophytes is known for its ability to invade the dense keratin of the superficial surface of healthy nail plates occasionally.    Despite such exceptions, dermatophytes and particularly saprophytic molds, in most instances, find it difficult to directly infiltrate the dense keratin of the nail plate. Such pathogens will much more readily infiltrate the loose keratin of the stratum corneum. The keratin of the stratum corneum is similar to and becomes continuous with the keratin that is formed by the nail bed in pathologic states. Since pathologic fungi so readily infiltrate both the stratum corneum and nail bed-derived keratin, and these surfaces are in contact with each other, such nail bed keratinization serves as an important precursor to the development of onychomycosis.    In most cases, onychomycosis manifests as the result of a series of events. The first event in the development of the majority of onychomycosis cases is the induction of pathologic nail bed keratinization. This breaks down the integrity of the nail unit, providing a portal of entry for the infectious elements. The second event in the development of onychomycosis is the development of tinea pedis. Once there is an active fungal infection involving the surface keratin of the skin of the foot, there is a conduit through which the infectious elements can enter the loose subungual keratin. This leads to further degradation of the integrity of the nail unit over time.    Subsequent events in the development of onychomycosis are the establishment of a bona-fide infection and the progression of that infection. In a minority of instances, the extent of the infection will progress to include both the subungual keratin and the actual nail plate. This florid pattern of infiltration has been designated as the total dystrophic subtype of onychomycosis.

How To Identify The Various Types Of Nail Unit Dystrophy

   To diagnose and manage dystrophic abnormalities of the nail unit appropriately, and to set realistic goals for our patients on antifungal therapy, avoid a narrow vision of how such processes arise. Feeding into such narrow-mindedness with regard to nail unit dystrophy is the current classification of onychomycosis, which designates patterns of involvement by assuming that all portions of abnormal nail unit are indeed the result of a fungal infection.    For example, consider a completely abnormal nail unit secondary to trauma or psoriasis that acquires a secondary fungal infection only distally within the subungual keratin. This would be called “total dystrophic” onychomycosis, although this is not the case. Alternatively, many clinicians readily diagnose distal subungual onychomycosis based on the clinical impression despite the fact that traumatic onycholysis not yet complicated by a fungal infection at all may be clinically indistinguishable.    For better conceptualization of the various mechanisms that lead to nail unit dystrophy, I like to organize them into different subsets. In this context, I view nail unit dystrophy as four distinct types (see “A Guide To The Four Types Of Nail Unit Dystrophy” below).    Type 1 is not infected by fungal organisms and does not exhibit nail bed keratinization. Examples of type 1 nail unit dystrophy include median nail dystrophy and the pitting that one sees in association with psoriasis (usually on the nail units of the fingers).    Type 2 nail unit dystrophy is also not mycotic. However, unlike type 1, there is keratinization of the nail bed. The most common form of type 2 nail unit dystrophy is that which arises in response to persistent microtrauma. The various forms of type 2 nail unit dystrophy function as precursors to the development of onychomycosis.    The remaining two classes of nail unit dystrophy involve an active fungal infection. When onychomycosis begins as a primary phenomenon and not as the result of a precursory lesion, it is classified as type 3 nail unit dystrophy. In some cases, the fungal infection will induce pathologic keratinization of the nail bed while it does not do so in other cases. This class of nail unit dystrophy (type 3) is therapeutically distinct from type 4. Unless nail bed keratinization causes the nail unit to expand sufficiently to lead to superimposed microtrauma, one may adequately treat this with antifungal therapy alone. Unfortunately, type 3 primary mycotic onychodystrophy is relatively uncommon.    The final subtype of nail unit dystrophy is type 4. This class of nail unit dystrophy consists of all cases of onychomycosis that eventuate as the result of a precursor condition (i.e. nail bed keratinization). In other words, type 4 nail unit dystrophy is usually engrafted upon what had been type 2 nail unit dystrophy. Such keratinization may not be frankly expansive. For example, onycholysis (pathologic detachment of the nail plate from the nail bed) leads to nail bed keratinization but it may not lead to a significantly thicker nail unit. Type 4 nail unit dystrophy is much more common than has been appreciated by mainstream medicine. Treating this form of nail unit dystrophy solely with antifungals often results in a mycologic cure but a clinical failure.

Key Insights On Non-Mycotic Nail Unit Dystrophy

   Nail unit abnormalities may be induced by any process that causes nail bed keratinization, altered patterns of nail plate growth or compromised nail plate integrity. While compromised nail plate integrity may occur with some degree of regularity in patients with diabetes mellitus or peripheral vascular disease, the overwhelming majority of nail unit dystrophy cases stem from pathologic nail bed keratinization with or without superimposed onychomycosis. I strongly believe that the most common mechanism for the development of this abnormal keratinization is related to persistent microtrauma.    Onycholysis probably ranks a distant second in frequency as a cause of nail bed keratinization. An underappreciated cause of focal onycholysis is the acute or chronic inflammation that one sees in association with infections of the nail unit (an acute or chronic paronychia). This probably explains the association between such infections and the occasional development of onychomycosis at the previously infected site. As noted earlier, any condition that causes nail bed keratinization will predispose people with active tinea pedis to develop onychomycosis.    Given that microtrauma alone may play a significant role in the pathogenesis of nail unit dystrophy and in serving as the most common precursor for the development of onychomycosis, one should assess its potential role in the development of nail unit dystrophy in all individuals with keratinizing (type 2 or type 4) nail unit dystrophy.    Most causes of persistent nail unit microtrauma are either biomechanical or structural. Biomechanical causes include hallux rigidus, flexible hammertoe or mallet toe deformity, and varus rotation of the fifth digit as the result of lateral column instability. Hallux rigidus may lead to persistent microtrauma due to either distal compensatory functional hallux extensus or compressive forces directed through the distal hallux during the propulsive phase of gait. The digits most commonly affected by biomechanically predisposed microtrauma are the hallux, second digit and fifth digit. Not surprisingly, these are also the toes most often affected by onychomycosis.    Patients who are structurally predisposed to persistent microtrauma might have broad forefeet or a tendency to wear ill-fitting pointed toe shoes. Either scenario may result in persistent trauma to the medial hallux or lateral fifth toe as they press into the corresponding side of the toe box. An alternate structural cause of persistent microtrauma is Morton’s foot type, which results in microtrauma involving the nail unit of the long second digit upon the distal toe box. Again, most of the structural abnormalities that might predispose an individual to endure microtrauma involve the hallux, second digit or fifth digit.    Of course, microtrauma and onycholysis are not the only causes of non-mycotic onychodystrophy. Other common causes include chronic spongiotic dermatitis (eczematous dermatitis/allergic contact dermatitis), psoriasis and diabetes mellitus to name a few. Although we spend much time during our podiatric education memorizing other clinical curiosities of the nail unit, it is rare to see most of these entities in clinical practice. Even when one does identify these nail conditions, they tend to involve the faster growing and more pristine fingernails.    Onychomycosis, which arises without the benefit of a precursory lesion (type 3) but induces keratinization of the nail bed, may eventually be complicated by superimposed microtrauma. As is often the case, a positive feedback cycle may develop. This begins with a fungal infection that causes the onset of nailbed keratinization and leads to subsequent expansion of the nail unit. In turn, the thickening nail unit results in increased pressure due to limited room within the toe box (microtrauma). As might be expected, the superimposed microtrauma precipitates additional keratinization and so on. Once microtrauma is fully entrenched in the cycle of nail bed keratinization, eradicating the fungal infection alone may not result in a clinical cure but would facilitate a mycologic cure in the face of a clinical failure.

Why You Should Rethink The Management Of Nail Unit Dystrophy

   In rethinking our approach to the management of nail unit dystrophy, we have to accept that there might be and usually is more going on within a dystrophic nail unit than simply a fungal infection. Reviewing all possible contributing factors to that nail unit abnormality is imperative for maximizing the effectiveness of therapy and putting forth realistic expectations when instituting medical therapy. In some instances, making biomechanical adjustments and adjusting shoegear may accomplish more toward the resolution of nail unit dystrophy than implementing antifungal therapy.    Eliminating microtrauma is essential to managing nail unit dystrophy if it is contributing to the nail unit abnormality. Even if the problem began as a purely mycotic nail, once there is microtrauma secondary to thickening of the nail unit, debulking is imperative. This will reduce pressure and thereby eliminate microtrauma as a contributor to the positive feedback cycle of nail bed keratinization. Using keratolytic agents, particularly those with hydrating properties, can help thwart the reestablishment of a thickened nail unit. The combination of manual debridement, avulsion and follow-up keratolytic therapy may also aid in the eventual reattachment of a lytic nail. One should perform debulking in conjunction with the appropriate biomechanical manipulations and shoegear modifications to ensure a long-term remedy.    If there are other potential causes of the nail unit abnormality, one should appropriately assess and address them in the treatment plan. Patients with psoriasis and nail unit dystrophy may or may not have psoriatic involvement of the nail units. Clinicians should avoid guesswork in this context as treating psoriatic nails may be quite challenging and often requires medications with potential side effects such as oral retinoids.

Essential Pointers On Diagnostic Testing

   This point mandates a brief discussion on the available testing methods for diagnosing onychomycosis. Most clinicians in mainstream medicine tend to equate nail unit dystrophy that manifests as the result of nail bed keratinization with onychomycosis unless an alternate cause such as psoriasis is undeniably evident.    Using this manner of thinking, a culture might seem to be sufficient as a sole testing method to augment the clinical diagnosis of onychomycosis. The preeminent problem with culture is that the presence of a living fungal element on or within dystrophic nail unit tissue does not necessarily mean that the pathologic changes are being caused by that organism. Most saprophytic molds that have been attributed with the ability to cause onychomycosis are also ubiquitous within the environment and should also be expected as contaminants in association with non-mycotic keratinizing nail unit dystrophy (type 2).    An additional problem that limits mycologic culture as a sole laboratory test in the context of nail unit dystrophy is its inability to recognize non-fungal forms of pathology. In the face of a negative PAS reaction, changes related to trauma or psoriasis may be suggested, if not definitively diagnosed, with histopathology. In addition, histopathology may allow one to diagnose potential squamous cell carcinomas and even melanomas that may give the clinical appearance of onychomycosis. Indeed, such tumors would go wholly undiagnosed if the clinician had instead sent the affected tissue for culture. A final deficiency that may be attributed to culture is a level of sensitivity that is far below PAS with histopathology.1,2

A Guide To The Four Types Of Nail Unit Dystrophy

   Type 1- Non-mycotic, non-keratinizing nail unit dystrophy    • Traumatic (matrical): median nail dystrophy    • Metabolic: Beau’s lines, diabetes mellitus/peripheral vascular disease    • Inflammatory: psoriatic pitting    • Genetic: some forms of ectodermal dysplasia    Type 2- Non-mycotic, hyperkeratotic nail unit dystrophy    • Trauma/microtrauma (nail bed): traumatic keratinizing nail unit dystrophy, onycholysis    • Metabolic: diabetes mellitus    • Inflammatory: psoriatic keratinizing nail unit dystrophy    Type 3- Primary mycotic nail unit dystrophy    • Keratinizing    Dermatophytic (T. rubrum)    Saprophytic (S. brevicaulis)    Yeasts (rare Candida sp.)    • Non-keratinizing    Dermatophytes (T. mentagrophytes)    Saprophytic molds (rare Fusarium sp.)    Yeasts (Candida sp.)    Type 4- Secondary mycotic nail unit dystrophy    • Any form of type 2 nail unit dystrophy complicated by dermatophytic or non-dermatophytic onychomycosis

In Summary

   Due to a superior understanding of pedal biomechanics, structural abnormalities and ailments that might compromise the nail unit, podiatrists are in a unique position to set themselves completely apart from alternate specialties in diagnosing and managing nail unit dystrophy.    We can best do so by identifying all potential contributors to the development of the nail unit disorder and using all the tools at our disposal. Once the clinician has identified the various contributors to this disorder, he or she can proceed to pursue appropriate treatment. Even the best antifungals should not be seen as cure-alls for keratinizing nail unit dystrophy. Dr. Bakotic is the Director of the Institute for Podiatric Pathology in Pompano Beach, Fla. He is also a Diplomate of the American Board of Pathology. Dr. Bakotic thanks Joseph Hackel, MD, and Dennis Shavelson, DPM, whose insight helped shaped the concepts in this article. References 1. Borkowski P, Williams M, Holewinski J, Bakotic B. Onychomycosis: an analysis of 50 cases and a comparison of diagnostic techniques. J Am Podiatr Med Assoc. 91(7):351-5, 2001. 2. Weinberg JM, Koestenblatt EK, Tutrone WD, Tishler HR, Najarian L. Comparison of diagnostic methods in the evaluation of onychomycosis. J Am Acad Dermatol. 2003 Aug;49(2):193-7.
 

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CE Exam #145 Choose the single best response to each question listed below. 1) What is the most important process in the development of the majority of nail unit dystrophy cases? a) Onychomycosis b) Abnormal epithelial keratinization c) Microtrauma d) None of the above 2) Nail unit dystrophy is the product of … a) ... matrical keratinization and an abnormal nail bed. b) ... matrical keratinization and tinea pedis. c) ... an abnormal nail bed. d) none of the above 3) In most instances, dermatophytes and particularly saprophytic molds … a) ... have difficulty infiltrating the loose keratin of the stratum corneum. b) ... easily infiltrate the dense keratin of the nail plate. c) ... readily infiltrate the loose keratin of the stratum corneum. d) None of the above 4) In the development of the majority of onychomycosis cases, the first precipitating event is … a) ... tinea pedis. b) ... degradation of nail unit integrity. c) ... induction of pathologic nail bed keratinization. d) None of the above 5) Type 2 nail unit dystrophy … a) ... is mycotic with no nail bed keratinization. b) ... rarely arises in response to persistent microtrauma. c) ... is rarely a precursor to onychomycosis. d) None of the above 6) Which of the following statements is true about type 4 nail unit dystrophy? a) It usually forms upon what had been type 2 nail unit dystrophy. b) It is not infected by fungal organisms and exhibits no nail plate keratinization. c) Treating it solely with antifungals often results in a clinical cure. d) Examples of this form of nail unit dystrophy include median nail dystrophy and pitting in association with psoriasis. 7) Biomechanical causes of persistent nail unit microtrauma include … a) ... mallet toe deformity. b) ... hallux rigidus. c) ... varus rotation of the fifth digit. d) All of the above 8) Biomechanically predisposed microtrauma commonly affects … a) ... the third, fourth and fifth digits. b) ... the hallux, second digit and fifth digit. c) ... the hallux, first digit and third digit. d) ... the first and second digits. 9) Which of the following statements is false about keratolytic agents? a) Clinicians should avoid using them as prolonged use may lead to recurrence of a thickened nail unit. b) The combination of manual debridement, avulsion and follow-up keratolytic therapy may aid in reattaching a lytic nail. c) Using these agents, particularly those with hydrating properties, can help thwart the reestablishment of a thickened nail unit. d) All of the above 10) Which of the following statements is true in regard to cultures? a) A culture is usually sufficient as a sole testing method to augment the clinical diagnosis of onychomycosis. b) In regard to culturing, the presence of a living fungal element on or within dystrophic nail unit tissue does not necessarily mean the pathologic changes are being caused by that organism. c) Cultures have a higher level of sensitivity than PAS with histopathology. d) All of the above Instructions for Submitting Exams Fill out the enclosed card that appears on the following page or fax the form to NACCME at (610) 560-0502. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.