©Aldo González-Serva, MD
Boston, MA, USA
September 8, 2009

PAS IS NOT ALWAYS A DIAGNOSTIC PANACEA FOR DYSTROPHIC NAILS

The increasing use of the nail plate biopsy (NPB) stained with PAS in search of fungi has dramatically highlighted that many dystrophic nail plates thought as diagnostic of onychomycosis are fungus-free.

This brings chagrin to both the clinician and the pathologist. To the clinician, the concern is if a false negative is at play and, if not, what to do with this case of pseudo-onychomycosis. To the pathologist, the quandary is whether, in spite of careful screening fungi, the search for fungi has failed. After frantic minutes of examining the fruitless sections, further teeth-grinding ensues: “Has my skill to pick up a fungal needle from a keratinous haystack waned?” Was the sample not representative? What are the clinicians expecting tinea going to think of their pathologist for giving them so many “negatives”?

NEGATIVE PAS MAY BE REALLY NEGATIVE AFTER ALL

It is now obvious that many of the NPBs deemed negative by pathologists continue to be negative when a subsequent fungal culture from the same specimen is requested. This means that there is something such as pseudo-onychomycosis, indeed, unless some cases of tinea are so subtle to require rare molecular techniques for detecting the fungal genome.

Besides a modicum of genuine false-negatives that probably exists, it is evident that the nail field produces a limited range of clinical and histologic responses to various stimuli and conditions.

ENTITIES THAT MIMIC ONYCHOMYCOSIS

Well known are the similarities of psoriasis and onychomycosis, both producing a psoriasiform onychitis with intracorneal subungual microabscesses atop mounds of parakeratosis. In onychomycosis, however, fungal hyphae will be some microns away from the microabscess.

Tinea unguium will also be accompanied in some cases of an abundant spongiotic fluid, resembling serum that gets collected, sometimes in gigantic pools, within the abnormal subungual horn.

But not all spongiosis is fungal-induced. Current dermatology treatises speak of spongiotic disease of the nails without carving a specific niche for the term ‘eczematous onychitis’. It makes sense that the foot, so rich on expressions of atopy, is going to involve the nail field. Contact dermatitis, dishydrotic dermatitis and stasis dermatitis, to name the main ones, are common occurrences in the feet. Why not accepting that the same diseases could be expressed preferentially yet less distinctly in the nails than on the sole?

Therefore, psoriasiform onychitis on the biopsy, minus the presence of fungi on the PAS (repeated) or in nail cultures (following a negative NPB) should be considered an entity related to contact, atopic (dishydrotic) or stasis dermatitis, i.e., eczematous onychitis. If id reactions to tinea pedis are found in distant body regions (trunk or upper extremities), is not conceivable that an id reaction may occur in the nail field?

COROLLARY

The time to expand our range of pseudomycotic nail conditions is here. The first step is being confident that a thoroughly examined yet negative NPB stained with PAS is the basic tool to rule out onychomycosis. After that it is the opening of our minds that less understood signs of other diseases can be a source of crumbly, dystrophic and pseudomycotic nails.

Raffaele Gianotti consiglia di entrare in:  http://tray.dermatology.uiowa.edu/DPT/Path-Index.htm per entre in DermPathTutor: un tutoriale in dermatopatologia

Foto 1	Foto 2	Foto 3

Alcuni casi sono proprio quello che sembrano….altri, a volte, un po’ meno.

Le foto 1, 2 e 3 corrispondono allo stesso vetrino.

Allora qual è la tua diagnosi?

Cosa vi sembrano?

Sentiamo le vostre diagnosi…

Cordiali saluti.

Gli editori.

THE KOH METHOD FOR DETECTION OF NAIL FUNGI HAS BEEN BESTED: KNOW BY WHAT! POTASSIUM HYDROXIDE PREPS TODAY: IS IT WHAT YOU NEED?

The most widespread method to quickly detect fungal infection has traditionally been the use of KOH to soften and clear skin or nail scrapings, followed by direct or dye-mediated microscopic search for fungi.

When unstained, playing with the condenser and the iris of the microscope will bring forth from the coverslipped preparation the refractile hyphae or other fungal mycelia.

When a stain is used, a common one being ink, it will highlight the fungal wall and will make easier the detection of the fungi and the certainty that artifacts are not misinterpreted as hyphae or spores.

In the case of tinea corporis or pedis, the fungal elements may be relatively frequent or at least regularly distributed throughout the horny sample. In cornified material from the nail, in contrast, the fungal load may be low and the fungal elements could be irregularly distributed among the nail keratins, some of which may not have been procured by the clippings.

In addition, the practice of the KOH by the clinician will require some interruption of the flow of patients in the office for preparation and interpretation of the sample.

A NAIL PLATE BIOPSY STAINED WITH PAS IS BETTER

In consideration to the caveats of KOH examination, the alternative has arrived: the nail plate biopsy (NPB) processed with PAS stain. This progressive trend of substitution of a tedious KOH exam for a referral of the specimens to a histology lab and the reading by a colleague dermatopathologist is here to stay.

ADVANTAGES OF THE NAIL PLATE BIOPSY

Besides producing a permanent record of the nail search, a NPB will afford the examination of the specimen by one or many observers at times that do not hampered the flow of patients through the clinic.

In addition, more tissue is available to examination, as heaps and clumps of nail keratins are eliminated by thin sections on which no confusion is allowed.

Furthermore, the PAS will offer greater distinctiveness and contrast to the fungi than the tenuous demonstration gained by direct observation or the use of inks in a KOH preparation.

An additional advantage of the NPB is the possibility of performing, if needed in apparently negative PAS-stained nails, a high-contrast stain such as Gomori Methenamine Silver (GMS) on which rare and previously unperceived hyphae can be picked up more readily.

THE REAL CLINCHER FOR NAIL PLATE BIOPSIES WITH PAS STAIN

Besides the above advantages, the most important reason to use a NPB stained with PAS is the high rate of return of positive cases in nails suspected to harbor fungi. It is clear now that many other conditions of the nail look clinically like onychomycosis yet biopsies and cultures are negative.

Surprisingly high is the yield of NPB with PAS for fungi, clearly now in reported percentages that are greater than even fungal cultures. This counterintuitive failure of cultures may depend on degeneration of hyphae, which would become unable to grow in vitro while still keeping their tinctorial avidity for PAS stain. Among recent statistics informed in the literature is 33-92% positivity for PAS, rounding up on 48% success in identifying fungi vs. 25.83-59% % for fungal culture and even a higher sensitivity than KOH examination (25-82.5%). Our personal series of 2007, including 2651 nail plate biopsies stained with PAS, had the highest sensitivity reported in a large series of 65.54%! (92% positivity rate was in a series of 105 cases only…). No doubt that the most cost-benefit ratio is obtained from the nail clipping sent to a pathologist for PAS staining.

WHAT IMPROVEMENTS CAN BE EXPECTED ON NAIL PLATE BIOPSIES

A current limitation for NPBs is the lack of certainty about the speciation of the observed fungi. However, when a septate regular hyphae is seen, it is almost certain that we are dealing with a dermatophyte and so can be reported to the clinician. Yeasts are also easy to discriminate but molds are somewhat less certain to be unequivocally identified. At least, they can be suggested when irregular or globular mycelia are noted in the PAS-stained biopsy.

COROLLARY

A small revolution in the care of nail diseases has been brought by getting pathologists as your clinical partners. If you want fast results and expeditious therapy for mycotic nails, no doubt that the way is clipping away…

©Aldo González-Serva, MD

Dermatopathologist

Boston, MA, USA