REVIEW

DISORDERS OF THE NAILS AND HAIR ASSOCIATED WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION NEIL S. PROSE, M.D., KIM G. ABSON, M.D., AND RICHARD K. SCHUR, M.D.

Since the first case reports in 1981 of Kaposi's sarcoma in homosexual tnen, numerous dermatologic manifestations of human immunodeficiency virus (HIV) infection in both adults and children have been recognized. Included among these are a variety of diseases that primarily or secondarily affect the nails and hair. Sotne of these, such as proxitnal white subungual onychotnycosis are well-defined clinical entities, which appear to be related to the effects of HIV infection on the itnmune system. Others, such as nail dyschromia, are results of therapy for Hiv infection. Still others, such as changes in the length and consistency of hair, are less well understood, but may prove to be significant as our knowledge of HIV infectioti continues to evolve.

NAIL DISORDERS

Disease of the nail is observed in up to 32% of patients with symptomatic Hiv infection.' In some patients, these may provide an early clue for the presence of HIV infection or for the worsening of immune dysfunction. Onychomycosis The incidence of dermatophytosis in patients who are seropositive for Hiv is similar to that observed in control groups.^ In one study, dermatophytes were recovered frotn the feet of 37.3% of 83 HlV-seropositive homosexual men and 31.8% of 110 HIV-seronegative homosexual men.^ The difference between these two groups was not interpreted to be statistically significant. Trichophyton rubrum was the predominant species in both groups of patients, and Trichophyton mentagrophytes and Epidermophyton floccosum were seen with decreasitig frequency. In the same study, 16 of 46 men with advanced Htv infection developed toenail changes with yellowish disFrom the Departments of Dermatology and Pediatrics, Duke University School of Medicine, Durham, North Carolina, and Columbia University College of Physicians and Surgeons, New York, New York. Address for correspondence: Neil S. Prose, M.D., Pediatric Dermatology, Box 3252, Duke University Medical Center, Durham, NC 27710.

coloration (Fig. 1). Among these patients, dermatophytes were isolated from toenails and/or toe clefts in 11. Another study on the prevalence of cutaneous disease in HIV infection revealed that 25% of 117 patients with acquired itiimunodeficiency syndrotne (AIDS) or AiDS-related cotnplex suffered from onychomycosis and/or tinea pedis.'' The causative organisms were not identified in this study, and there were no controls. Dompmartin et al. examined 62 patients with HIV infection and otiychomycosis over a period of 26 months.'' Fifty-four patients (87.1%) had lesions of the feet, five patients (8%) had involvement of the hands, and three patietits (4.8%) had both fingernail atid toenail involvetnent. An associated mycotic pahnoplantar keratodertna was present in a number of cases, and rapid spread frotn nail to nail was frequently observed. Trichophyton rubrum was the most commonly isolated fungus (58%). Trichophyton mentagrophytes and Epidermophyton floccosum were isolated in 9.7% and 4.8% of patients. Other causative organisms included Candida albicans (11.3%) and Pityrosporum ovale(3.7%). Among the 62 patients who were followed in this study, 55 (88.7%) presented with proximal white subungual onychotniycosis. This fortn of nail disease was originally described in Hiv-infected patients in 1986, atTd its occurretnce has since been documented by several clinical investigators.''"'* Although proximal subungual onychotnycosis may rarely occur in healthy individuals after trauma to the tiail, its presence seems to be associated with an underlying immune deficiency.' In imtnune suppressed patients, trauma does not appear to be a precipitating factor. In proximal white subungual onychomycosis, the dermatophyte penetrates the stratutn corneutn of the proximal nail fold and invades the under surface of the nail plate. The proximal nail plate becomes white, but the stnooth surface of the nail is not affected. The area of white discoloration sotnetitnes extends to involve the entire tiail plate, and complete nail dystrophy may result (Fig. 2).^ Because of the underlying immune disorder, HlVassociated onychomycosis tnay be difficult to treat. Ten AIDS patients with onychomycosis were treated with 1% ciclopirox olamine cream.'" Clinical irnprovement was noted after 3 rnotiths of therapy. 453

International Journal of Dermatology Vol. 31, No. 7, July 1992

Hyperpigmentation of some or all nails occurred in 39% of one group of patients receiving zidovudine.^^ Nail pigmentation due to this drug is more common in black than in white patients.^''•^^ The zidovudine dyschromia is not related to drug dosage, HIV risk group, or to severity of HIV infection.^'•^'' Discoloration ranges from shades of blue and purple to brown-black. Nail pigmentation begins proximally and progresses distally and may include the free edge of the nail plate (Fig. A)." The pattern of nail dyschromia varies from patient to patient. While the majority have longitudinal streaks, both transverse bands and diffuse pigmentation of the nail are observed.^^•^*' In the majority of patients, the thumbnail is the first nail involved, and toenail hyperpigmentation follows fingernail dyschromia.^'' AZT-induced nail dyschromia may be associated with pigmentation of the mucous membranes," the palms and soles,^'' or rarely, the entire skin surface." Zidovudine-induced nail dyschromia is caused by increased melanogenesis of the nail matrix melanocyte.^^ Fontana staining of clippings from involved nails revealed melanin granules within the nail plate.^'^'^'' A longitudinal nail biopsy from a pigmented band revealed deposits of melanin granules throughout the epidermis and an increased number of dendritic melanocytes in the basal and suprabasal cell layers of the nail bed and matrix." Melanin-filled melanophages were noted in the papillary dermis. Hyperpigmentation of the nails and skin has occasionally been reported in patients with HIV infection who bave not received zidovudine.^'''" The meaning of this unusual finding is not known.

Candidal infection may cause onycholysis or destruction of the nail plate in patients with Hiv infection.'•'* We have seen several children in whom nail changes of this type were accompanied by chronic candidal paronychiae of the proximal and lateral nail folds of several fingers." In addition, chronic mucocutaneous candidiasis with candidal granuloma of the nail unit is also seen. Scopulariopsis brevicaulis is a saprophytic mold, which may rarely infect the damaged nail. Destruction of fingernails and toenails by this organism has been reported in AIDS.^'" Nail infection with Alternaria sp. has also been documented in a patient with HIV infection.' Treatment with either griseofulvin or ketoconazole is effective for most cases of AlDS-related onychomycosis. Higher than usual doses of these drugs may be required in order to have a significant impact on nail infection, and in some cases, completely resistant organisms may develop. Griseofulvin and ketoconazole are not effective against the saprophytic infections (e.g., Scopulariopsis, Aspergillus), and itraconazole, which is not yet commercially available, appears to be the drug of choice. Fluconazole is sometimes effective in cases of severe candidiasis. Herpes Simplex Severe herpetic infection of the distal fingers in patients with HIV infection has been reported.'^''^ We recently treated one 2-year-old child with HIV infection who developed a severe and chronic herpetic whitlow of the thumb of one hand (Fig. 3). This infection was accompanied by severe herpetic gingivostomatitis. The involvement of the soft tissues around the nail resulted in loss of the growing nail on that finger.

Yellow Nails

Psoriasis and Reiter's Syndrome

The existence of the yellow nail syndrome in patients with AIDS is somewhat controversial. Chernosky and Finley described yellow discoloration of the distal nails, ridging, and opaqueness in four of eight patients with AIDS and Pneumocystis carinii pneumonia.-''' The authors believe that this finding is related to yellow nail syndrome, a triad of yellow nails, lymphedema, and pleural effusion, which was originally described by Samman and White.^•'' Arguing against the presence of yellow nail syndrome in these patients are the following: (1) the absence of lymphedema and pleural effusion in any of the patients described; (2) the limitation of yellowish discoloration to the distal half of the nail; (3) the absence of exaggerated lateral curvature of the nail; (4) the failure to document slow nail growth; and (5) the failure to exclude fungal infection by repeated culture of each patient's nails.'''"''*' The high correlation between discoloration of the nails and the presence of tinea pedis and onychomycosis in patients with AIDS suggests that there may indeed be a fungal etiology for this condition.^

The association between Hiv infection and a disease spectrum that includes psoriasis, psoriatic arthropathy, and Reiter's syndrome was first reported in 1987.''''''' In patients with psoriasis and/or Reiter's syndrome, the typical nail changes include pitting, subungual hyperkeratosis, and lateral and distal onycholysis. Remission of AIDS-associated psoriasis, including severe nail changes, after administration of zidovudine (AZT) has been reported.'^"" Other medications that have been used with success include etretinate,^" co-trimoxazole,^' and

Zidovudine-Induced Nail Dyschromia Blue, brown, or black discoloration of the nails was originally reported in two black patients with AIDS during therapy with zidovudine (AZT).^^ Since this original report, a distinctive nail dyschromia associated with zidovudine has been reported by a number of observers.^''"•'^ 454

Nail and Hair Disorders Prose, Abson, and Scher

Figure 1.

Severe onychomycosis in a 37-year-old man with

AIDS.

Figure 2. Proximal white subungual onychomycosis in a patient with HIV infection. (Courtesy of M. Joyce Rico, M.D.)

Beau's Lines Beau's lines have been described in patients with AIDS and AIDS-related complex.** These transverse ridges across the nail are seen in association with episodes of severe illness. A correlation between the presence of Beau's lines and transient serum zinc depletion has been suggested.^' Decreased serum zinc levels have been demonstrated in patients with AIDS."*"

HAIR DISORDERS

Figure 3.

Tinea Capitis

Herpetic whitlow with nail deformity in a 2-year-

old boy with AIDS.

Severe tinea capitis with significant hair loss has been reported in several adult patients with AIDS.** We have observed two children with extensive tinea capitis due to Trichophyton tonsurans. In one case, there was extension of fungal infection onto a major portion of the face, and rapid recurrence of the dermatophytosis aft'er the completion of a 6 week course of griseofulvin.*" Scalp infection with Scopulariopsis brevicaulis., resulting in alopecia, has also been observed in patients with AIDS.'*'^"''*^ Oral itraconazole may be required in patients with this form of infection.

tients with HIV infection. Casanova et al. described three patients who developed very long eyelashes.'" A similar finding was observed by Roger et al. in a 25year-old woman with AIDS,''* and by Straka et al. in several children with HIV infection.''^ Alopecia Areata The association between HIV infection and alopecia areata has been described by several authors.'"^"''' In one patient, hair regrowth began 6 months after the initiation of zidovudine therapy.'"'

Change in Hair Length and Consistency Leonidas reported on four black men with AIDS who developed profound alterations in their hair pattern several years after the first appearance of symptoms."*^ Their hair became longer, softer, and silky, and was occasionally discolored. A similar finding was noted by Kinchelow et al., who observed that several black patients with HIV infection experienced spontaneous straightening of the hair.'''' This change was found to be independent of nutritional status and, in one patient, preceded the development of clinical AIDS by 6 months. A possibly related phenomenon is hypertrichosis of the eyelashes, which is occasionally observed in pa-

Graying Sudden graying of the hair has been reported in association with HIV infection." The mechanism may be similar to that of AIDS-related vitiligo.^^

CONCLUSIONS

HIV infection is associated with a wide variety of disorders of the nails and hair. In some cases, the prompt recognition of these disorders by the dermatologist may 455

International Journal of Dermatology Vol. 31, No. 7, July 1992

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Figure 4. Bluish discoloration of the proximal nails due to treatment with zidovudine. (Courtesy of M. Joyce Rico, M.D.)

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provide a clue to the diagnosis of Hiv-related illness. The early detection of HIV infection has become increasingly important with the availability of antiviral therapy. In patients with previously diagnosed HIV infection, tbe disorders discussed herein may be a significant source of psychologic and physical discomfort. In order to provide the best care for these patients, the practicing dermatologist must be fully informed of the spectrum of nail and hair disease that may occur in patients with AIDS and less severe forms of HIV disease.

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"Life and Death" tattoo on a molecular biologist. Tattoo art by Ed Hardy of San Francisco. From the World of Tattoos collection, Honolulu, HL Submitted by Norman Goldstein, M.D., Honolulu, HL 457

Disorders of the nails and hair associated with human immunodeficiency virus infection.

REVIEW DISORDERS OF THE NAILS AND HAIR ASSOCIATED WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION NEIL S. PROSE, M.D., KIM G. ABSON, M.D., AND RICHARD K...
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