Longitudinal nail biopsy in evaluation of acquired nail dystrophies

Dermatologic surgery Longitudinal nail biopsy in evaluation of acquired nail dystrophies Ruth Hanna, M.D., Barbara M. Mathes, M.D., and Edward A. Krull, M.D.

Detroit, MI We reviewed longitudinal nail biopsies perfonned at Henry Ford Hospital on patients with acquired nail dystrophies to see whether the procedure did, indeed, provide useful diagnostic infonnation and to see which microscopic features were most helpful in histopathologic diagnosis. Clinical diagnoses included psoriasis, lichen planus, Darier's disease, isolated longitudinal defects, and diffuse thickening. We found that clinical diagnosis could be supported by histopathologic findings in eight of twenty cases of acquired nail dystrophy. Specifically, we were able to make a diagnosis of psoriasis in four cases, lichen planus in three cases, and Darier's disease in one case. The other twelve cases showed nonspecific eczematous changes. We conclude that the longitudinal nail biopsy may be a useful diagnostic tool in certain cases of acquired nail dystrophy. (J AM ACAD DERMATOL 14:803-809, 1986.)

The longitudinal nail biopsy permits structurally oriented histologic evaluation of the entire nail unit-proximal nail fold, nail matrix, nail bed, and hyponychium. The procedure is relatively easy to perform, and resultant scarring is usually minimal. Nevertheless, the longitudinal nail biopsy is not widely performed, possibly because of inexperience with surgical procedures on the nail unit and difficulty in histologic interpretation of specimens. Many dermatologists are not comfortable doing a biopsy involving nail matrix, since longitudinal nail biopsies that divide the matrix into two parts may lead to permanent deformity of the nail plate or a split nail. To minimize this problem, Zaias 1 recommends that biopsies be no greater than 3 mm in width. Biopsies extending through the proximal matrix greater than 3 mm in width usually require surgical mobilization and approximation of the matrix to prevent split nails. If the entire nail is From the Department of Dermatology, Henry Ford Hospital. Reprint requests to: Dr. Ruth Hanna, Department of Dermatology, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit. MI 482021 313-876-2172.

involved, as in our cases, a longitudinal biopsy of the side of the nail is done, resulting in a slight narrowing of the nail plate but without risk of a split nail. Although there have been reports describing histopathologic changes seen in certain nail disorders,2-6 to our knowledge no studies have been done to assess the usefulness of the procedure in specific clinical situations. Our experience with longitudinal nail biopsies on patients with acquired nail dystrophy was reviewed to detennine whether the procedure did indeed provide useful diagnostic information and to ascertain which microscopic features were most helpful in histopathologic diagnosis. MATERIALS AND METHODS All longitudinal nail biopsies performed by the Henry Ford Hospital Dermatology Department between January 1982 and October 1984 were retrospectively reviewed. Fifty-six longitudinal nail biopsies were obtained. The biopsies were performed for diagnostic purposes under the supervision of one of us (E. A. K.). Potassium hydroxide mounts and/or fungal cultures were negative in all cases. Specimens with the follow-

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M

Fig. 1. Longitudinal nail biopsy before incision (panel A) and after incision (panel B). A, Medial longitudinal incision. B, Lateral longitudinal incision. LNF, Lateral nail fold. M, Matrix. NB, Nail bed. NP, Nail plate. ing clinical impressions were included in the study: psoriasis, lichen planus, Darier's disease, and diffuse thickening. In all these cases, more than two nails were involved. Biopsies of longitudinal defects involving a single nail only were also included. Pigmented lesions, verrucae, and ingrown nails were excluded from the study. Twenty specimens were evaluated on the basis of these criteria. Our technic of longitudinal nail biopsy was as follows: After local infiltration with 1% plain lidocaine (Xylocaine), we removed a portion of the nail plate overlying the area from which the biopsy specimen was taken. One incision was made along the edge of the remaining nail plate through the nail bed, the entire matrix, and the proximal nail fold (Fig. 1). The second incision was made through the lateral nail fold parallel to the initial incision. The tissue between the two incisions was then excised by peeling it off from the underlying bone. The incision in the proximal nail fold was sutured. The wound was dressed with Telfa and wrapped tightly with gauze, which was removed at 48 hours and then changed daily by the patient until healing was complete. The specimen was fixed in formalin, routinely pro.cessed,embedded on edge, and stained with hematox-

ylin and eosin. Periodic acid-Schiff stains were done in cases in which fungal infection entered into the differential diagnosis clinically or histologically. All specimens were reviewed by a dermatopathologist (R. H.) who knew the clinical diagnosis. Histopathologic criteria were derived from review of previous reports. 2- 6 The criteria were divided into major and minor criteria, with major criteria being previously documented changes thought to be specific to the diagnosis and minor criteria being compatible with, but not specific for, the diagnosis. A diagnosis required at least one of the major criteria with or without minor criteria (Table I). Clinical data were independently obtained through a retrospective chart review without knowledge of the histopathologic diagnosis.

RESULTS

A diagnosis of psoriasis was suspected clinically in six cases (Table II). In fOUf of them there was a sufficient amount of histologic change to support the clinical impression. Diagnostic changes in these four specimens were confined to the nail bed epithelium and the hyponychium; the proximal nail fold and the matrix appeared normal or only

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Table I. Histopathologic diagnostic criteria Histopathologic changes Diagnosis

Psoriasis 2 •3

Lichen planus4.5

Darier's disease 6

Nonspecific eczematous changes

Maj or criteria

Minor criteria

Neutrophils in nail bed epithelium and in adherent parakeratotic nail plate fragments

Hyperkeratosis with parakeratosis Serumlike proteinaceous exudate within the horny layer Focal hypogranulosis Psoriasifonn hyperplasia of nail bed epithelium Dilated subepithelial blood vessels Hypergranulosis and hyperkeratosis of nail bed epithelium Increased eosinophilia of nail bed keratinocytes Epithelial hyperplasia with hyperkeratosis and parakeratosis Nuclear atypia of nail bed keratinocytes Nonspecific mononuclear dermal inflammation with exocytosis of inflammatory cells Dermal fibrosis

Lichenoid infiltrate abutting against matrix and bed "Sawtooth" acanthosis of nail bed epithelium Multinucleate epithelial giant cells in nail bed epithelium Hyperkeratosis + parakeratosis Acanthosis and spongiosis

moderately inflamed. Prominent hyperkeratosis with focal parakeratosis was noted in all cases. There was alternating hyper- and hypogranulosis. Trapped fragments of neutrophilic nuclei were seen in the parakeratotic stratum corneum overlying areas of hypogranulosis in all four cases (Fig. 2). In one case, proteinaceous, serumlike material was seen in the parakeratotic horny layer (Fig. 2). In one case, psoriasiform hyperplasia of the nail bed epithelium was noted; in the other three cases the degree of elongation of the rete ridges was thought to be normal for the anatomic site. In all cases the dermal capillaries were dilated, and a mild to moderate mononuclear inflammatory infiltrate was noted in the dermis. Previously established criteria4 •5 for lichen planus were seen histologically in three of seven cases submitted with a clinical impression of lichen planus (Figs. 3 and 4). Diagnostic histologic changes were seen in all portions of the nail unit in two cases, with matrix and nail bed involvement prominent in all three cases. A thick, adherent, orthokeratotic scale was consistently noted to be accompanied by hypergranulosis, acanthosis, and

increased eosinophilia of underlying keratinocytes. A dense, lichenoid mononuclear infiltrate was seen abutting the epithelium in all three cases. Exocytosis of inflammatory cells into the epithelium was seen focally in one case only. Spongiosis was not noted. In one case the nail bed epithelium exhibited a sawtooth pattern; this feature was absent in the other two cases, both of which demonstrated mild uniform acanthosis. The one case of Darier's disease demonstrated features thought to be consistent with, but not diagnostic of, Darier's disease, since they were not specific. These features included nail bed epithelial hyperplasia, with occasional keratinocytes demonstrating nuclear hyperchromatism and mild atypia. Specific changes of Darier's disease of the skin, including suprabasilar acantholysis and dyskeratosis with formation of corps ronds and grains, were not seen. Epithelial giant cells in Darier's nails, previously described by Zaias and Ackerman,6 were not observed. All the remaining specimens, including five isolated longitudinal defects and one diffuse plate thickening, demonstrated nonspecific eczematous

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Table II. Clinical and histopathologic diagnoses of acquired nail dystrophies Pathologic diagnosis

Clinical diagnosis and features Diagnosis

No. of patients

RIO psoriasis

6

RIO lichen planus

7

Dader's disease

Isolated longitudinal defects Diffuse thickening

5

I

Clinical features

Two or more nails with pits, onycholysis, subungual hyperkeratosis, nail bed discoloration, thickening and crumbling of plate Two or more nails with thinning of plate, longitudinal grooves or fissures, distal notching Multiple nails with longitudinal red and white streaks, with distal wedge-shaped defects Isolated nail with one or more longitudinal depressions, fissures, or ridges Diffuse thickening of multiple nails (no suspected clinical diagnosis)

No. of patients

Diagnosis

4 2

Psoriasis Nonspecific eczematous changes

3 4

Lichen planus Nonspecific eczematous changes Compatible with Darier's disease

5

Nonspecific eczematous changes Nonspecific eczematous changes

RIO: Rule out,

changes (Fig. 5). These changes consisted of varying degrees of hyperkeratosis of the nail bed, which was usually orthokeratotic but occasionally parakeratotic, The epithelium of the proximal nail fold, matrix, bed, and hyponychium often revealed mild to moderate spongiosis, with a nonspecific mononuclear infiltrate seen in the upper dermis. Exocytosis of inflammatory cells was noted in some specimens. Subepithelial fibrosis, frequently marked, was seen in various degrees in all these specimens. DISCUSSION

Clinical diagnosis of inflammatory disease of the nail unit can be a difficult problem, particularly in patients who do not manifest cutaneous disease elsewhere. Consequently the question of diagnostic nail biopsy frequently arises. Despite the relative simplicity of the procedure, it is not commonly performed in many centers-for several possible reasons. Although local anesthesia can be readily achieved, some patients are reluctant to have the nail. area surgically manipulated. Although scarring is usually minimal when the pro-

cedure is properly performed, focal permanent nail dystrophy can occasionally result. In addition, many dermatopathologists lack familiarity with interpretation of nail specimens, and improper biopsy technic and specimen processing can make histopathologic interpretation difficult. Finally, even if a diagnosis can be established by nail biopsy, the value of the biopsy may in some cases be dubious because therapeutic options in nail unit disorders are often limited. In this study we attempted to evaluate whether or not the longitudinal nail biopsy was helpful diagnostically. We also attempted to point out histologic features that were most helpful in microscopic diagnosis. We did not address the usefulness of the procedure with regard to prognosis and therapy, nor did we specifically address complications and cost-effectiveness. Our review shows that the clinical diagnosis could be supported by histopathologic findings in eight of twenty cases of acquired nail dystrophy. Specifically, seven of thirteen cases with the clinical impression of psoriasis or lichen planus had histopathologic changes consistent with previously

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Fig. 2. Psoriasis vUlgaris. Note trapped neutrophilic nuclei and serum in hyperkeratotic comeallayer. Periodic acid-Schiff stain was negative for fungi. (x 300.)

Fig. 3. Lichen planus. Orthokeratotic hyperkeratosis, hypergranulosis, and lichenoid infiltrate characteristic of lichen planus. (x 65.)

reported specific diagnostic criteria. A single case of clinically typical Darier's disease had histopathologic nail findings thought to be compatible, although not absolutely diagnostic. The remaining twelve cases exhibited nonspecific eczematous changes that could not be subclassified. We were particularly unsuccessful in diagnosing specimens in which only one nail was clinically involved (all five in this category were histopathologically nonspecific).

There are several possible explanations for our difficulty in interpreting some of our specimens. In some instances the specimen was not cut perpendicular to the skin surface; consequently, all areas of the nail unit were not adequately visualized and diagnostic features may have been obscured. In addition, the avulsion of the nail plate may have altered the tissue enough to affect the histopathologic interpretation, particularly by occasionally shearing off the upper portions of the

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Fig. 4. Sawtooth pattern of nail bed epithelium and lichenoid subepidermal infiltrate characteristic of lichen planus. (x 65.)

Fig. 5. Nail unit biopsy showing nonspecific eczematous changes. Note prominent hyperkeratosis and subepithelial fibrosis of nail bed (NS) , matrix (M), and proximal nail fold (PNF).

nail bed epithelium. Nail plate avulsion was done to avoid cutting artifact from the microtome moving through resistam nail plate when histologic sections were prepared. However, we plan to perform the procedure with the nail plate intact in a future study. Some of the cases that appeared nonspecific may represent an end-stage process in which chronic inflammation and fibrosis have replaced the more characteristic changes of specific diseases. Finally, some of the cases may indeed represent chronic eczema of the nail unit, although other eczematous changes were cHnically absent.

A clinical diagnosis of psoriasis was supported histologically when neutrophils were present in the adherent parakeratotic stratum corneum of the nail bed and hyponychium. This histologic finding was the only feature consistently noted that appears to be specific to psoriasis. Other pathologic changes of psoriasis described by Zaias2 (hyperkeratosis with parakeratosis, focal hypogranulosis, dilated dermal blood vessels) were present but were considered nonspecific, since they are seen in many specimens, including ingrown nail specimens that are routinely examined following partial resection.

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Proteinaceous, serumlike material within the stratum corneum, as described by Zaias/ was noted in only one case of psoriasis but was considered helpful diagnostically because it does appear to be a relatively specific finding when seen in the nail bed. Serum protein exudates have been noted in nail-fold biopsies in patients with connective tissue disease.? Psoriasiform hyperplasia of the rete ridges has been reported in the nail bed of psoriatic nails 2 ; with a single exception, this condition was not appreciated by us. The rete ridges of the nail bed are normally oriented parallel to one another and can appear uniformly shortened or elongated, depending on the angle of the cut. The degree of elongation of the nail bed rete ridges was thought to be normal for the anatomic site in three cases in which other diagnostic changes of psoriasis were present. Thus this feature was not thought to be particularly helpful in the diagnosis of nail-unit psoriasis. We determined lichen planus of the nail to be diagnostically distinct when we saw a thick orthokeratotic scale, hypergranulosis, increased eosinophilia of the keratinocytes, and a dense lichenoid infiltrate abutting the matrix and the bed epithelium. Changes in specimens exhibiting less classic features, such as spongiosis, focal parakeratosis, and prominent exocytosis of inflammatory cells, were classified as nonspecific eczematous changes. Clinically, lichen planus was suspected in some of these cases. Lichen planus of the oral mucosa appears to be less distinctive histopathologically than that of the skin; perhaps a similar situation exists for lichen planus of the nails. If these patients proceed to develop lichen planus elsewhere on the body, the histopathologic criteria for lichen planus of the nail unit might then be expanded to include these findings. The one case of Darier's disease is interesting in that it appeared to have some histopathologic features similar to those reported by Zaias and Ackerman. 6 However, since patients with Darier's

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nails tend to have obvious skin disease, the clinical importance of nail biopsy findings in this disease may be minimal. In summary, we were able to confirm many of the histologic findings first reported by Zaias and believe that a diagnosis of psoriasis and lichen planus of the nail unit can be made on nail-unit biopsy. Ability to diagnose by nail-unit biopsy can be useful in cases in which nail changes are present prior to skin disease and might prove therapeutically valuable, particularly in lichen planus, a destructive nail-unit disease in which aggressive early systemic corticosteroid therapy may prevent permanent anonychia. 5 Further studies of nail unit specimens are indicated; in particular, a blind review would be desirable to eliminate observer bias, which may have affected our results. Evaluations of multiple specimens of patients with confirmed diseases (psoriasis, lichen planus, and other disorders) and with nails in various stages of disease (acute, chronic, treated, and untreated) may provide more insights and broaden the diagnostic histopathologic criteria, enabling the clinician to make a more accurate diagnosis when only the nails are involved. The longitudinal nail biopsy may be an important diagnostic tool. Further evaluations of its efficacy, utility, and cost-effectiveness are awaited. REFERENCES 1. Zaias N: The longitudinal nail biopsy. J Invest Dennatol 49:406-408, 1967. . 2. Zaias N: Psoriasis of the nail. Arch DermatoI99:567-579, 1969. 3. Lewin K, DeWit S, Ferrington RA: Pathology of the fingernail in psoriasis. Br J Dermatol 86:555-563, 1972. 4. Zaias N: The nail in lichen planus. Arch Dennatol 101:264-271, 1970. 5. Scott MJ Jr, Scott MJ Sr: Ungual lichen planus. Arch DermatolllS:1197-1199, 1979. 6. Zaias N, Ackerman AB: The nail in Darier-White disease. Arch Dermatoll07:193-199, 1973. 7. Thompson RP, Frank EH, Maize JL, et al: Nailfold biopsy in scleroderma and related disorders. Arthritis Rheum 27:97-103, 1984.