Onycholysis of the fingernails: Evaluation and management

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Onycholysis of the fingernails: Evaluation and management Paul Kechijian, M.D. New York, NY Onycholysis (ONY) of the fingernails is a common disorder that is diagnosed with ease but often managed with great difficulty. The full spectrum of causes is broad and not always readily apparent. In this review, an approach to the evaluation and management of ONY is offered. (J AM ACADDERMATOL 12:552-560, 1985.

Onycholysis (ONY) of the fingernails is a common disorder of variable (weeks to years) duration at presentation. The diagnosis of ONY is made with facility. Distally, and sometimes laterally, a cleft develops separating the nail plate from the nail bed; the presence of air and occasional keratinous material within this cleft diminishes light reflection from the nail bed and renders opaque the affected portion of the nail plate (Fig. 1). The onycholytic segment may contain pigmented debris (Fig. 2). The causes of ONY are numerous 1"6 (Table I). Careful history and physical examination, including inspection of the toenails, hands, feet, skin, hair, and mucosal surfaces, combined with appropriate diagnostic tests will usually enable the clinician to establish a cause and intervene with effective measures. The purpose of this review is to offer an approach for the evaluation and management of this challenging disorder. Nonmicrobial causes

Whether the result of microbial and/or nonmicrobial factors, most cases of ONY arise "from without"; they are exogenous in origin. Trauma, maceration, and contact with chemicals and nail care products are all potential causes and probably From the Nail Section, Department of Dermatology, New York University School of Medicine. Reprint requests to: Dr. Paul Kechijian, New York University School of Medicine, 562 First Ave., New York, NY 10016/212-340-6484.

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initiate most cases of ONY. Careful review of occupational and personal history (Table II), with particular reference to nail exposure and possible trauma, is, therefore, mandatory. Traumatic ONY may be caused by: (1) tearing the nail plate from its bed; (2) crushing the finger, as in a car door; (3) forcing a stylus between the nail plate and bed as in manicuring; (4) embedding foreign material under the nail plate with, for example, hair, dirt, or thorns."5 Maceration from prolonged immersion in a variety of aqueous solutions may cause ONY"5; ONY attributed in one instance to sodium hypochlorite exposure was more likely the result of overhydration from prolonged immersion in swimming pool water. 7 Occupation/hobby-related exposure to organic chemicals (e.g., gasoline, t paint removers,' hydrofluoric acid, 8 dicyanodiarnide, s and thioglycolates) may produce ONY. Application of enamel polish may promote maceration and subungual hyperkeratosis; application of nail enamel, base coats, hardeners, or artificial nails may induce allergic contact dermatitis of the nail bed; enamel solvents may produce irritant contact dermatitis. Each is a potential cause of ONY. 9 Successful therapy depends upon the elimination of exacerbating factor(s) by, for example, maintaining fingernails at shorter lengths, protecting the nails from water and chemicals with protective gloves worn in conjunction with moisture-absorbent cotton gloves, exercising care in job/hobby-related activities, and abstaining from the use of nail cosmetics. When counseling pa-

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Table I. Classification of onycholysis

Exogenous causes Nonmicrobial Trauma; '~ Maceration; .5.7 Chemicals 1,8 Nail cosmetics 9 Microbial Candida species4.6 DerrnatophytosisZ,3,6 Bacteria 4,6 Drugs Photoinduced t,13-20,23.29 Nonphotoinduced21.sz,30.34 Endogenous causes Dermatologic diseases Psoriasis~.35.37 Lichen planus T M Dermatitis T M Hyperhidrosis: Pachyonychia congenita3 Congenital ectodermal defect3 Pemphigus vegetans43 Lichen striatus44 Other26,45,46 Neoplastic disorders Squamous cell carcinoma47 Other Systemic diseases and states Yellow nail syndrome3 Shell nail syndromC Porphyfia4 Pellagra 4 Thyroid disease ''s Pregnancy ~.~ Iron deficiency anemias Impaired circulation3,~ Diabetes mellitus Syphilis ~,2,5 Congenital onycholysis5 Hereditary partial onycholysis3'5 Idiopathic acquired onycholysis~'3 tients, one should apprise the patient that fingernails grow at the rate of nearly 1 m m per week3; in spite of exemplary patient compliance, therefore, several months may elapse before the nail unit returns to normal. Microbial causes

Pathogens, in particular Candid: albicans, are the single m o s t common cause of ONY 4'~and probably invade nail beds that have been altered pre-

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Table II. Occupations associated with onycholysis

Housewivesa Washerwomen~ Domestics 1 Laundry workers~ Dish and bottle washers 2 Bartenders Typists Gardeners2 Farmers2 Cigar makers:

Leather and pelt workers: Poultry pluckers 3 Barbers/beauticians2 Brewers 2 Miners 2 Manual laborers 2 Nut crackers a Milkers: Confectionersz

viously by the exogenous factors noted above. Unless the etiology of ONY has been unequivocally established by careful history and physical examination, it is imperative that the examiner (1) perform a direct microscopic examination for fungi and yeast with potassium hydroxide and (2) collect suitable material for culture on Sabouraud's dextrose agar with and without cycloheximide and chloramphenicol.* Inspection alone will not reliably differentiate C. albicans-induced ONY from dermatophytic or bacterial ONY. Fungi that produce ONY will usually be found in the comified cells of the nail bed~°; Candida pseudohyphae are similarly located in the nail bed (Fig. 3). Hyphae or pseudohyphae may be demonstrated in scrapings from the nail bed. Samples are obtained by first clipping back the affected nail plate and then scraping, with a 1- to 2-mm curette, the soft keratinous material underlying the newly exposed portion of the nail bed (Fig, 4). To minimize the likelihood of false-negative results, it is imperative that the material be collected with care; indiscriminate sampling of thick pieces of nail plate or debris is unlikely to yield positive results. In the event that microscopic and culture examinations yield persistently negative results, punch biopsy of the nail plate and bed is indicated. This procedure is easily accomplished under local anesthesia and will usually not lead to permanent nail deformity. ~1 Biopsy may reveal the causative organism when "routine" tests fail z°, periodic acid-Schiff stain should always be done on biopsy *Head E: Laboratory diagnosis of the superficial fungal infections, Dermatology Clinics 2:93-108, 1984,

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specimens from the nail, even when nonmicrobial etiologies are suspected. When C. albicans is demonstrated, cure can be anticipated if two goals are accomplished: (1) a dry environment is provided and (2) appropriate topical anti-Candidal agents are rigorously applied. When prolonged immersion in water, use of nail cosmetics, or presence of exogenous nonmicrobial factors is causative, these factors must be eliminated (e.g., discontinue nail cosmetics, wash less frequently, wear protective gloves with a moisture-absorbing lining). In order to keep the affected nail bed dry and to allow for direct application of anticandidal agents, the onycholytic segment of the nail plate must be kept short by repeated clippings. The patient may return monthly for recutting of newly grown, unattached nail plate until clearing is attained. Frequent application of clear tincture of iodide diluted 1 : I with 70% isopropyl alcohol will provide both a dry environment and broad-spectrum antimicrobial therapy. The patient may also apply one of several topical antifungal/candidal agents (econazole, miconazole, clotrimazole, ciclopirox); these drugs eradicate both Candida species and dermatophytes*; lotion bases will enhance penetration. Gratifying results should supervene within several months if the procedures outlined are followed carefully. The decision to employ systemic anticandidal therapy, ketoconazole,t in the event that topical therapy fails will depend upon the individual needs of the patient (particularly the cosmetic consequences of ONY) and a careful analysis of the risk: benefit ratio. In those instances in which testing reveals dermatophytic ONY, ~,~'6,1°the patient will usually require systemic therapy with either griseofulvirt,~2.~the treatment of choice, or ketoconazole.~2,t Recent studies suggest that topical antifungal therapy with ciclopirox may be effective in tinea unguium§; this approach may be worthy of trial. It is probably best, especially in the latter circum*Smith EB: Topical antifungal agents. DermatologyClinics 2:109113, 1984. tHenry JC: Ketoconazole.Dermatology Clinics 2:121-128, 1984. ~:Beeker LE: Griseofulvin. Dermatology Clinics 2:115-120, 1984. §Smith EB: Topical antifungal agents. Dermatology Clinics 2:109111, 1984.

stance, to maintain a shortened nail plate until clearing supervenes. In general, bacteria are not a primary cause of ONY: rather, they secondarily inhabit the "lytic hotel. ''4 Only Pseudomonas aeruginosa and Cornyebacterium minutissimum appear capable of inducing ONyt; a moist environment favors habitation by these pathogens: Zaias 4 suggests clorox, diluted 1:4, a few drops applied three times daily, for the treatment of Pseudomonas ONY. Clear tincture of iodide in alcohol will also speed recovery, provided, of course, that exacerbating factors are eliminated and the affected nail bed is allowed to remain dry as outlined above. Drug causes

Adverse reactions to systemic medications may affect the nail unit as well as the skin and other organ systems. When drugs cause ONY, the nail bed or hyponychial region is the focus of the adverse reaction. Drug-induced ONY is usually pho. totoxic in origin13; all phototoxic agents are potentially capable of inducing ONY 14 (Table I/I), The tetracyclines (chlortetracycline,15 demethylchlortetracycline,16 doxycycline, 17'~s minocycline,19 and tetracycline,IS.2° share photosensitivity as a major side effect; of this group, minocycline is the least photosensitizing while doxycycline and demethylchlortetracycline are most likely to cause photoinduced problems. It is, therefore, not surprising that this widely prescribed class of drugs is frequently associated with drug-induced ONY. Two reports 21,22 suggest that tetracycline-induced ONY may occur in the absence of.other signs of photosensitivity. Ibsen and Andersen, 23 however, suggest that such"monosymptomatic" ONY may be photosensitive in origin, a result of the nail bed's greater sensitivity to ultraviolet radiation. Unless proved otherwise by phototesting, it is probably best to assume that ONY occurring in patients on phototoxic medications is photosensitive in origin. Benoxaprofen, a nonsteroidal anti-inflammatory drug (NSAID), is effective therapy for psoriasis and other disorders. 24 Like the tetracyclines, benoxaprofen is phototoxic and produces ONY: its action spectrum is in the long-wave ultraviolet range. 24,25Although this NSAID was taken off the

Volume 12 Number 3 March, 1985 market by the Food and Drug Administration because of drug-induced deaths, new NSAIDs targeted at psoriasis will undoubtedly be developed because of benoxaprofen's success in clearing psoriasis. As new NSAIDs become available, ONY should be anticipated. Chloramphenicol',26 and chlorpromazine27 have been reported to induce photo-onycholysis. Porphyria cutanea tarda induced by Norinyl-l, an oral contraceptive, has been reported to be associated with ONY. 28 Other drugs that induce porphyria cutanea tarda may "indirectly" cause ONY, as well. ONY has also been reported in a patient with mycosis fungoides treated with photochemotherapy. 29 The patient's nails returned to normal, in spite of continued photochemotherapy, when the nails were shielded from ultraviolet radiation. Doxorubicin 3°,31 (Adriamycin) and bleomycin3° have been associated with ONY. In these instances, the ONY was not photosensitive in origin but was probably mediated by drug-induced nail bed toxicity. ~ ONY has been produced by 5-fluorouracil following both topical and systemic administration. Five percent 5-fluorouracil cream employed under occlusion has been reported to produce ONY that resolved when therapy was discontinued; 2% 5fluorouracil solution employed in a similar fashion did not produce ONY. 32 Systemic 5-fluorouracil administered for gastric adenocarcinoma produced ONY that did not resolve in the 3 months between cessation of 5-fluorouracil therapy and the patient's death. 33 Retinoids produce side effects on many organ systems. Baran 34 reviewed effects of etretinate on the nail unit. Fragility with onychorrhexis and onychoschizia, onychomadesis and nail shedding, painful paronychia, and ingrown nails were all noted; ONY occurred rarely.

Endogenous dermatologic causes Psoriasis (PS) commonly affects the nail unit, with an incidence of nail involvement varying from 15% to as high as 90%; in addition, it may affect the nail unit in the absence of clinically evident psoriasis elsewhere.35Among the signs of psoriasis (pitting, ONY, nail plate discoloration,

Onycholysis of fingernails 555 subungual hyperkeratosis, splinter hemorrhages, "oil drop" sign, and severe crumbling of the nail plate), only pitting is more common than ONY. 35 In the presence of other signs of psoriasis, the diagnosis of psoriatic ONY may be made with relative confidence. In the absence of these signs and in the face of negative mycologic studies, the correct diagnosis should be established by biopsy. 1, The light microscopic features of nail unit psoriasis include: psoriasiform epithelial hyperplasia, thinned rete ridges, thinned suprapapillary plates, dilated tortuous papillary blood vessels, parakeratosis, and neutrophils within the hyperkeratotic zone of the hyperplastic nail bed.3~ Psoriatic ONY occurs within the nail bed and not at the junction of the nail bed and plate.37 Since tinea unguium and PS are histologically identical, a pe= riodic acid-Schiff or silver methenamine stain is necessary for the histologic differentiation of these two disorders. 36The absence of hyphae in the face of the histologic findings described favors the diagnosis of psoriasis; the presence of hyphae usually indicates that dermatophytes are of pathogenic importance. The presence of hyphae is not unequivocally diagnostic of tinea unguium, however, since psoriasis and tinea unguium may exist concurrently. 4,36 The response of psoriatic ONY to therapeutic intervention is less than ideal for two reasons: (1) therapy, when effective, may be of benefit for only short periods of time; repeated treatments may be required for long-term clearing; (2) despite heroic attempts by both patient and physician, the disease may be unresponsive to therapy. Nonetheless, therapeutic intervention is worthwhile. Initially, topical steroids with occlusion should be employed; the nail plate should be clipped back and steroids applied several times daily. This approach is painless and inexpensive. After a few weeks, the patient should return for follow-up. At this time the nail may be clipped back again and segments of newly grown onycholytic nail plate removed. If topical therapy fails, intralesional therapy may be undertaken with triamcinolone acetonide (2.5 mg/ml) injected directly into the affected nail bed.4 Delivery of an adequate volume of steroid suspension will lead to blanching of the nail bed. The distal finger should be anesthetized

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Figs. 1-4. For legends, see opposite page.

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Onycholysis of fingernails

with 2% lidocaine (Xylocaine) without epinephrine administered through a 30-gauge needle; injection into the proximal and lateral nail fold will lead to anesthesia within 5 to 10 minutes; once proximal anesthesia is obtained, the distal nail bed may, if necessary, be further anesthetized with additional lidocaine. It should be appreciated, however, that lidocaine injection into the skin is quite painful. Only the most dedicated patients tolerate this mode of therapy. It is probably wise to confine therapy to no more than three fingers on a single visit. Repeated injections at intervals of 3 to 4 weeks may lead to clearing. Higher concentrations (up to 10 mg/ml) m a y be attempted if initial therapy fails. One must advise the patient, however, that atrophy is a potential side effect of chronic corticosteroid administration; one should also apprise the patient that O N Y will persist in a significant proportion of patients in spite of this more aggressive therapy and that repeated injections may be required for long-term control of psoriatic ONY. In view of these numerous caveats, the physician should not fault the patient for poor compliance. Preliminary studies suggest that topical methoxypsoralen-ultraviolet A (UVA) may clear ONY in patients who fail to respond to intralesional triamcinolone acetonide. * In two patients, the onycholytic nail plate was ablated and 0,1% meth*Greenwald D, Keehijian P: Personal observation,August, 1984,

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Table III. Onycholysis due to drugs

Photoinduced Benoxaprofen:4, 2s Chloramphenicol~.26 Chlorpromazine27 ChlortetracyclinO Demethylehlortetracycline16 Doxycycline~7,~8 Minocycline19 Oral contraceptives2~ Psoralens29 Tetracycline~8,~°,23

Nonphotoinduced BleomycinJ° Doxorubicina°,a~ 5-FluorouraciP2,~3 Retinoids ~4

Tetracycline (?)21a2

oxypsoralen was applied to the nail bed. One hour later 0.25 joules/era 2 were delivered; increments of 0.25 joules/era 2 were administered during follow-up treatments. Systemic therapy is not indicated when psoriasis is confined to the nail unit. Lichen planus produces a greater variety of dystrophies but less frequent nail involvement (1%16%) than does psoriasis? s In a manner analogous to psoriasis, the nail bed may be affected in lichen planus, with resulting distaF ,4 or proximal subungual ONY. 39 Like psoriasis, lichen planus may be limited to the nail unit 4°,4t and may coexist with dermatophyte infections4; unlike psoriasis, ONY is unlikely to be the single presenting sign of lichen planus. When lichen planus is suspected, biopsy of the nail bed is indicated"; the characteristic histologic changes of lichen planus are found in the nail unit as well as the skin? 8 Initial therapy

Fig. 1. Normal nail units contrast sharply with onycholytic segments. OnycholYSiS is apparent as irregular opaque areas representing separation between the distal nail plate and the nail bed. Fig. 2. In this onycholytic segment, the more proximal onycholytic area is opaque and white. The distal onycholytic segment is green. This discoloration is due to P. aeruginosa. The lateral and proximal nail folds are unaltered, Fig. 3. In this photomicrograph, stained with periodic acid-Schiff, numerous pseudohyphae are present in the nail bed. These pseudohyphae, typical of Candida species, are composed of round to oval bodies that are joined end to end, forming elongated beadlike strands with irregular indentations along their periphery. Numerous budding yeast forms are also present. Abundant bacteria are present within clefts in the nail plate. (Original magnification, × 100.) Fig. 4. The onycholyfic nail plates have been removed with nail clippers. Samples from the hyperkeratotic nail bed are collected by curettage of the exposed nail bed and placed directly onto a glass slide; potassium hydroxide (KOH) examination and mycologic cultures are then completed.

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with topical steroids under occlusion should be attempted; if this therapy fails, intralesional triamcinolone acetonide may be administered in a manner analogous to that for psoriasis. Again, therapy may be neither completely effective nor longlasting. Dermatitis may involve the nail unit as well as the skin. 2,3,~Depending upon the focus of inflammation within the nail unit, a variety of ungual changes may supervene; nail bed involvement will lead to ONY. A careful and complete history and physical examination, with particular attention to the hands and feet, should enable the clinician to diagnose atopic, nummular, contact, or "dyshidrotic" dermatitis. Appropriate treatment of the underlying dermatitis should expedite resolution of ONY. Since dermatitides are rarely confined exclusively to the nail unit, a biopsy diagnosis of dermatitis-induced ONY will usually not be necessary. Occasionally therapy with topical or intralesional triamcinolone acetonide may be indicated. ONY may occur in association with hyperhidrosis2 and probably develops in a manner analogous to ONY resulting from prolonged immersion in aqueous solutions. Attempts to control hyperhidrosis with 20% aluminum chloride in alcohol may prove beneficial.42 ONY is a feature of pachyonychia congenita and congenital ectodermal defect: In both of these autosomal dominant disorders, ONY is not an isolated finding. The former is associated with marked subungual thickening, hyperkeratosis of the palms and soles, and white patches on the oral mucosa; in hidrotic ectodermal defect, the nails are affected in all cases; the scalp, in 50% of cases. ONY may be associated with pemphigus vegetans43 and other forms of pemphigus as well. ONY is unlikely to appear in the absence of other signs of this disorder, however. Nail unit involvement in lichen striatus has been reported. 44Among several lichen striatus-associated dystrophies reviewed by the authors (fraying, longitudinal ridging, splitting, shredding, and total nail loss), ONY was also noted. Two patients with hypoplastic enamel, ONY and hypohydrosis, were reported by Sastry et al. 4s Baran et a146reviewed the clinical and microbio-

logic features of 113 patients with primary ONY of the toenails; in most instances trauma played an essential role. Runne and Orfanos 26 reported two further causes of ONY: (1) epidermolysis bullosa simplex and (2) granulomatous purulent nail bed inflammation.

Neoplastic disorders Squamous cell carcinoma of the nail bed may masquerade as "subungual infection"47; one should always consider this diagnostic possibility when ONY involves the single finger of an elderly individual or when ONY fails to respond to "routine" measures. Biopsy ~t in such instances is clearly indicated. Other neoplasms, malignant melanoma, pyogenic granuloma, and warts, may also be associated with ONY. In these disorders, the primary problem should be apparent and managed accordingly. ONY was noted in one patient with mycosis fungoides.*

Systemic diseases and states ONY has been reported in nondermatologic as well as in primary cutaneous disorders. Yellow nail syndrome and shell nail syndrome are associated with ONY; both conditions are associated with pulmonary problems and may share a common pathogenesis: ONY occurs in three porphyrias (Bantu porphyria, erythropoietic protoporphyria, and porphyria cutanea tarda) and peUagra4; photosensitivity is an important feature of these disorders, a fact suggesting that light directly or indirectly mediates the development of ONY. Thyroid disease (both hypo- and hyper-) ~'s and pregnancy,~i 5 as well as iron deficiency anemia~ and peripheral circulatory impairment, 3'~ may be associated with ONY. Hypoxia may mediate the production of ONY in the latter two disorders. ONY occurs in patients with diabetes mellitus. Whether C. albicans initiates the condition or whether impaired circulation is critical in the production of ONY, therapy for C. albicans is indicated when infection is present. Since the preceding systemic disorders comprise *Kechijian P: Personal observation, February, 1984.

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a portion of the differential diagnosis of ONY, the clinician must consider these diagnoses during history and physical examination. When indicated, appropriate laboratory studies should be conducted to help confirm or exclude relevant diagnoses. Numerous instances of congenital and acquired syphilis associated with ONY are cited in reports from the pre-penicillin erala; it may be wise to consider this possibility and include serologic studies in the evaluation of ONY when the etiology is unclear. Congenital onyeholysis and hereditary partial onycholysis O N Y may also occur as an isolated finding in congenital O N Y 5 and in hereditary partial ONY3.~; these entities probably represent endogenous disorders o f the nail unit. Their etiology, however, is unknown. I d i o p a t h i c a c q u i r e d onyeholysis In spite of meticulous evaluation and management, some patients with acquired ONY defy classification and all manner of therapeutic attempts. It is these patients with idiopathic ONY who present the greatest difficulty for the clinician. 1 Usually, w o m e n are affected? The cosmetic results for these patients are not inconsequential; a compassionate ear is helpful. Also appropriate is a continued search for causal agent(s). It is well to keep in mind the fact that other signs of cutaneous or systemic disorders may develop following the original presentation of ONY. COMMENT An attempt has been made to clarify the problem of ONY. There are many causes, some more common than others. Each patient presents a different set of circumstances--not only of diagnostic and therapeutic importance but also of personal concern for the patient. A careful history and physical examination will usually enable the clinician to determine the cause of ONY. In some instances, laboratory examinations, including microscopic search for hyphae and pseudohyphae, mycologic culture, and biopsy, are necessary. None of these procedures is difficult or associated with high morbidity. Failure to include these examinations, when

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indicated, in one's evaluation lessens the likelihood of sucessful resolution of the disorder. With a systematic approach, however, most cases of ONY wilI be diagnosed and managed successfully. REFERENCES 1. Ray LF: Onycholysis: A classification and study. Arch Dermatol 88:181-185, 1963. 2. Pardo-Castello V, Pardo OA: Diseases of the nails, ed. 3. Springfield, IL, 1960, Charles C Thomas, Publisher, pp. 117-123, 238-241. 3. Samman PD: The nails in disease, ed. 3. London, 1978, W. Heinemann Medical Books Ltd., pp, 14-15, 20-21, 59-64, 88-90, 105-108, 119-121, 162-167, 171-178. 4. Zaias N: The nail in health and disease, ed. 1. Jamaica, NY, 1980, Spectrum Publications, pp. i04-105, 125132, 154, 163-169, 204. 5. Baran R: Principal modifications of the normal form of the nail, in Pierre M, editor:The nail, ed. 1, London, 1980, Churchill Livingstone, pp. 19-25. 6. Baran R: Onychia and paronychia of mycotic, microblal and parasitic origin, in Pierre M, editor: The nail, ed. 1. London, 1980, Churchill Livingstone, pp. 39-45. 7. CoskeyRJ: Onycholysisfrom sodium hypochlorite. Arch Dermatol 109:96, 1974. 8. Baran R: Acute onycholysisfrom rust-removing agents. Arch Dermatol 116:382-383, 1980. 9. Seher RK: Cosmetics and ancillary preparations for the care of nails. J AMACADDERMATOL6:523-528, 1982. 10. Scher RK, Ackerman AB: Subtle clues to diagnosis from biopsies oLnails: The value of nail biopsy for demonstrating fungi not demonstrable by microbiologic techniques. Am J Dermatopathol 2:55-56, 1980. 11. Scher RK: Punch biopsies of nails: A simple, valuable procedure, J Dermatol Surg Oncol 4:528-530, 1978. 12. Zaias N, Drachman D: A method for the determination of drug effectivenessin onychomycosis.J AMACADDERMATOL9:912-919, 1983. 13, Daniel CR III, Scher RK: Nail changes secondary to systemic drugs or ingestants. J AM Acht~ DEaMATOL 10:250-258, 1984. 14. Bruinsma W: A guide to drug eruptions, ed. 3. Meppel, Netherlands, 1982, Kdps Repro, pp. 43-46. 15. Norton LA: Nail disorders. J AMACADDERMATOL2:451467, 1980. 16. Orentreich N, Harber LC, Tromovitch, TA: Photosensitivity and photo-onyeholysisdue to demethylchlortetracycline. Arch Dermatol 83:730-737, 1961. 17. Yeanmougin M, Morel P, Civatte J: Photo-onycholysis due to doxycycline. Ann Dermatol Venereol 109:165166, 1982. 18. Frank SB, Cohen HJ, Minkin W: Photo-onycholysisdue to tetracyclinehydrochlorideand doxycycline. Arch Dermatol 103:520-521, 1971. 19. Kestel JL Jr: Photo-onycholysisfrom minocyeline. Side effects of minocycline therapy. Cutis 28:53-54, 1981. 20. Lasser AE, SteinerMM: Tetracyclinephoto-onycholysis. Pediatrics 61:98-99, 1978. 21. Kestel JL Jr: Tetracycline induced onycholysis unassociated with photosensitivity. Arch Dermatol 10~1:766, 1972.

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22. Kanwar AJ, Singh OP: Onycholysis secondary to tetracycline hydroehloride. Cuffs 23:657-658, 1979. 23. Ibsen HH, Andersen BL: Photo-onycholysis due to tetraeycline-hydrochloride. Acta Derm Vertereol (Stockh) 63:555-557, 1983. 24. Allen BR, Littlewood SM: Benoxaprofen: Effect on cutaneous lesions in psoriasis. Br Med J 285:1241-1244, 1982. 25. Greist MC, Ozols II, Ridolfo AS, Muus JC: The phototoxic effects of benoxaprofen and their management and prevention. Eur J Rheumato! Inflarnm 5:138-147, 1982. 26. Runne U, Orfanos CE: The human nail: Structure, growth and pathological changes. Curr Probl Dermatol 9:102149, 1981. 27. LeChat P, Lagier G, Rouveix B, Fontagne J: Side effects of drugs. Summary of 1975-1976 publications concerning the undesirable effects of medication. Therapie 32:423-458, 1977. 28. Byrne JPH, Boss JM, Dawber RPR: Contraceptive pillinduced porphyria cutanea tarda presenting with onycholysis of the fingernails. Postgrad Med J 52:535-538, 1976. 29. Mackie RM: Onyeholysis occurring during psoralen PUVA therapy. Clin Exp Dermatol 4:111-113, 1979. 30. Runne U, Pfeiff B, Mitrenga D: Brown nail bed and onycholysis due to adriamycin; swelling, pigmentation and hyperkeratosis due to bleomycin. Z Hautkr 55:15901593, 1980. 31. Manalo FB, Marks A, Davis HR Jr: Doxorubicitt toxicity: Onyeholysis, plantar callus formation, and epidermolysis. JAMA 233:56-57, 1975. 32. Shelley WB: Onycholysis due to topical 5-fluorouracil. Acta Derm Venereol (Stockh) 52:320-322, 1972. 33. Katz ME, Hansen TW: Nail plate-nail bed separation. An unusual side effect of systemic ffuorouraeil administration. Arch Dermatol U5:860-861, 1979. 34. Baran R: Therapeutic assessment and side effects of the aromatic retinoid on the nail apparatus. Ann Dermatol Venereol 109:367-371, 1982.

Journal of the American Academy of Dermatology

35. Kouskoukis CE, Scher RK, Lebovits PE: Psoriasis of the nails. Culls 31:169-174, 1983. 36. Kouskoukis CE, Scher RK, Ackerman AB: What histologic finding distinguishes onychomycosis and psoriasis? Am J Dermatopathol 5:501-503, 1983. 37. Robbins TO, Kouskoukis CE, Ackerman AB: Onycholysis in psoriatic nails. Am J Dermatopathol 5:39-43, 1983. 38. Scott MJ Jr, Scott MJ Sr: Ungual lichen planus: Lichen planus of the nail. Arch Dermatol 115:1197-1199, 1979. 39. Scher RK, Ackerman AB: Diagnosis of nail diseases by gross pathology (clinical lesions): Lichen planus. Am J Dermatopathol 5:375-376, 1983. 40. Burgoon CF Jr, Kostrzewa RM: Lichen planus limited to the nails. Arch Dermatol 100:371, 1969. 41. Seher RK, Fischbein R, Ackerman AB: Twenty-nail dys'trophy: A variant of lichen planus. 'Arch Dermatol 114:612-613, 1978. 42. Shelley WB, Hurley HJ Jr: Studies on topical antiperspirant control of axillary hyperhidrosis. Acta Derm Venereol (Stoekh) 55:241-260, 1975. 43. Leroy D, Lebrun J, Maillard V, et al: Pemphigus vegetans-like chronic pustular dermatitis of Hallopeau. Ann Dermatol Venereol 109:549-555, 1982. 44. Baran R, Dupr6 A, Lauret P, Puissant A: Lichen striatus with nail involvement. Report of four cases and review of the four cases in the literature. Ann Dermatol Venereol 106:885-891, 1979. 45. Sastry KARH, Rupreeht A, Suliman AM: Hypoplastic enamel, onycholysis and hypohydrosis: A report of two cases. J Oral Med 38:21-23, 1983. 46. Baran R, Badillet G: Primary onycholysis of the big toenails: A review of 113 cases. Br J Dermatol 106:529534, 1982. 47. Kouskoukis CE, Scher RK, Kopf AW: Squamous-cell carcinoma of the nail bed. J Dermatol Surg Oncol 8:853855, 1982.

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