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Pigmented nail bands and mucocutaneous pigmentation in HIV-positive patients treated with zidovudine
Brief communications Pigmented nail bands and mucocutaneous pigmentation in HIV-positive patients treated with zidovudine M. Grau-Massanes, MD,a F. Millan, MD,a M. 1. Febrer, MD,a C. Pujol, MD,a V. A. Alegre, MD,a M. Salavert, MD,b V. Navarro, MD,b and A. Aliaga, MDa Valencia. Spain Pigmented nail bands in patients infectedwith the human immunodeficiency virus (HIV) receiving treatment with zidovudine (formerly azidothymidine, AZT) have been recently reported.!" We present three cases of nail and/or mucocutaneous pigmentation, with histologic findings in a nail biopsy specimen in one case.
Table I. Secondary effects of zidovudine Effect Medullar toxicity Neurologic symptoms
Gastrointestinal symptoms Cutaneous symptoms
1
Manifestations
Anemia, leukopenia Headache, asthenia, myalgias, insomnia, somnolence, paresthesia, dizziness, agitations, restlessness Nausea, vomiting, diarrhea, gastrointestinal/ abdominal pain, dyspepsia, anorexia Rash, acne, urticaria, melanonychia striata, cutaneomucous pigmentation
Case reports Case 1. A 26-year-old white woman, an HIV-seropositive parenteraldrug abuser, had two episodes of Pneumocystis carinii pneumonia. After 8 weeks of treatment with zidovudine (200 mg every 8 hours), pigmented longitudinal bands developedonthefingernails; thetoenails were lateraffected (Fig. 1). A bluish tingein all nail bedsand a brownish discoloration of the upperand lower labial mucosa were observed. Shealso had been taking acyclovir, folic acid, co-trimoxazole, isoniazid, rifampin, and ethambutol. Case 2. A 36-year-old white woman, an HTV-seropositive parenteraldrugabuser, hada history ofmiliary tuberculosis and pneumonia of undetermined cause. After 6 weeks oftreatment with zidovudine (200 mg every 8 hours), pigmented longitudinal bands developed on the fingernails. Toenail involvement, brownspots onthedorsal surface ofthetongue, anddiffuse pigmentation on both legs were subsequently observed. She also had been receiving acyclovir, folic acid, erythromycin, isoniazid, rifampin, and ethambutol. Case 3. A 23-year-old homosexual man with three previous episodes of P. carlnii pneumonia and cerebral toxoplasmosis had diffuse corporal, lingual, and gingival discoloration after 5 months of treatment with zidovudine (200 mg every 8 hours). He had also taken acyclovir, folic acid, co-trimoxazole, pyrimethamine, sulfadiazine, isoniazid, rifampin, and ethambutol. Histologic examination. All three patients showed anergy to skin testsand had an inverted T4/T8 ratio «OJ inall cases). A longitudinal nail biopsy specimen from a pigmented band that included nailplate, nail bed, nail matrix, andproximal nail fold wasobtained from patient 1. Histopathologic findings included From the Department of Dermatology' and the Infectious Diseases Unit,b Hospital General. Reprint requests: M. Grau-Massanes, MD. Department of Dermatology. Hospital General; Avda. Tres Cruces sin, 46014 Valencia,
Spain. 16/4/14393
deposits of brown pigmented granules throughout the epidermis. Thesegranules werepositive for melanin (with Masson's ammoniacal silver nitratestain).An increased number oflarge dendritic melanocytes in the basal and suprabasal layers was observed (3 to 5 melanocytes per 10 basal cells) (Fig. 2). Aggregates of melanin-filled macrophages were seen in the papillary dermis. A focal inflammatory infiltrate was also present.
Discussion. Zidovudine, a synthetic nucleoside, is an analogue of thymidine. It acts as an antiviral agent against retroviruses (including HIV) by interfering with reverse transcriptase," Its most frequent side effects are hematologic (Table I). New side effects are constantly being found.f 6 Recently, pigmented ungual bands have beendescribed in four black HIV-seropositive patients3,4 and in four white Hl'V-seropositive patientsl-" who were treated with zidovudine. Our white patients had dark skin (type III). Mucocutaneous pigmentation developed in association with pigmented nail bands. This association has not been previously reported.v" Pigmentation of nails, mucous membranes, and skin can occur in Addison's disease, Peutz-Jeghers syndrome, and Laugier-Hunzikersyndrome. Systemic pigmentation related to drugs has also been described." All three patients previously received several drugs, none of which are known to produce pigmentation. In all three patients pigmentation of the proximal part of the nail plate developed after at least 6 weeks of treatment with zidovudine, The pigmentation later involved the entire nail. In patient 2 the lesionsslowly faded after treatment was discontinued. This finding suggests that zidovudineis involved in the pigmentary change.
687
Journal of the American Academy of Dermatology
688 Brie] communications
Fig. 1. Case 1. Longitudinal pigmented nail bands with bluish discoloration of nail bed. Fig. 2. Large melanin granules (G) and dendritic melanocytes (M) throughout nail matrix (MX}. NP, Nail plate. (Ammoniacal silver nitrate stain; X400.)
REFERENCES 1. Furth PA, Kazakis AM. Nail pigmentation changes associated with azidothymidine (zidovudine) [Abstract]. Ann Intern Med 1987;107:350. 2. Pannwalker AP. Nail pigmentation in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107:943-4. 3. Gonzalcz-Lahoz JM, Garcia Aguado C, MartinezFernandez R, et al. Pigmentation azulada en las unas de los pacientes con SIDA: efecto colateral de la zidovudina? [Letter] Rev Clin Espan 1988;183:278-9. 4. Azon-Masoliver A, Mallolas J, Gatell J, et al. Zidovudineinduced nail pigmentation. Arch Dermatol 1988;124: 1570-1. 5. Riechman DD, Fieschl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double blind controlled trial. N Engl J Med 1987;317:192-7. 6. McEvoy GK, ed. American Hospital Formulary Service: drug information. Bethesda, Md.: American Society of Hospital Pharmacists, 1988:392-7.
7. Daniel CR, Scher RK. Nail changes secondary to systemic drugs or ingestants.J AMACAD DERMATOL 1984;10:250-8.
Acquired port-wine stain Mark W. Cobb, MD, and Leon Goldman, MD* Bethesda, Maryland, and San Diego, California Nevus flammeus is a common congenital malformation of mature capillaries that occur in up to 75% of newborns.' The most common type is the salmon patch, From the Department of Dermatology, Naval Hospital. The views expressed herein are those of the authors and do not reflect the officialpolicyor position of the Department of the Navy, Department of Defense, or the U.S. Government. No reprints available. *Dr. Goldman is at the Naval Hospital, San Diego, Calif.
Table I. Secondary effects of zidovudine Effect Medullar toxicity Neurologic symptoms
Gastrointestinal symptoms Cutaneous symptoms
1
Manifestations
Anemia, leukopenia Headache, asthenia, myalgias, insomnia, somnolence, paresthesia, dizziness, agitations, restlessness Nausea, vomiting, diarrhea, gastrointestinal/ abdominal pain, dyspepsia, anorexia Rash, acne, urticaria, melanonychia striata, cutaneomucous pigmentation
Case reports Case 1. A 26-year-old white woman, an HIV-seropositive parenteraldrug abuser, had two episodes of Pneumocystis carinii pneumonia. After 8 weeks of treatment with zidovudine (200 mg every 8 hours), pigmented longitudinal bands developedonthefingernails; thetoenails were lateraffected (Fig. 1). A bluish tingein all nail bedsand a brownish discoloration of the upperand lower labial mucosa were observed. Shealso had been taking acyclovir, folic acid, co-trimoxazole, isoniazid, rifampin, and ethambutol. Case 2. A 36-year-old white woman, an HTV-seropositive parenteraldrugabuser, hada history ofmiliary tuberculosis and pneumonia of undetermined cause. After 6 weeks oftreatment with zidovudine (200 mg every 8 hours), pigmented longitudinal bands developed on the fingernails. Toenail involvement, brownspots onthedorsal surface ofthetongue, anddiffuse pigmentation on both legs were subsequently observed. She also had been receiving acyclovir, folic acid, erythromycin, isoniazid, rifampin, and ethambutol. Case 3. A 23-year-old homosexual man with three previous episodes of P. carlnii pneumonia and cerebral toxoplasmosis had diffuse corporal, lingual, and gingival discoloration after 5 months of treatment with zidovudine (200 mg every 8 hours). He had also taken acyclovir, folic acid, co-trimoxazole, pyrimethamine, sulfadiazine, isoniazid, rifampin, and ethambutol. Histologic examination. All three patients showed anergy to skin testsand had an inverted T4/T8 ratio «OJ inall cases). A longitudinal nail biopsy specimen from a pigmented band that included nailplate, nail bed, nail matrix, andproximal nail fold wasobtained from patient 1. Histopathologic findings included From the Department of Dermatology' and the Infectious Diseases Unit,b Hospital General. Reprint requests: M. Grau-Massanes, MD. Department of Dermatology. Hospital General; Avda. Tres Cruces sin, 46014 Valencia,
Spain. 16/4/14393
deposits of brown pigmented granules throughout the epidermis. Thesegranules werepositive for melanin (with Masson's ammoniacal silver nitratestain).An increased number oflarge dendritic melanocytes in the basal and suprabasal layers was observed (3 to 5 melanocytes per 10 basal cells) (Fig. 2). Aggregates of melanin-filled macrophages were seen in the papillary dermis. A focal inflammatory infiltrate was also present.
Discussion. Zidovudine, a synthetic nucleoside, is an analogue of thymidine. It acts as an antiviral agent against retroviruses (including HIV) by interfering with reverse transcriptase," Its most frequent side effects are hematologic (Table I). New side effects are constantly being found.f 6 Recently, pigmented ungual bands have beendescribed in four black HIV-seropositive patients3,4 and in four white Hl'V-seropositive patientsl-" who were treated with zidovudine. Our white patients had dark skin (type III). Mucocutaneous pigmentation developed in association with pigmented nail bands. This association has not been previously reported.v" Pigmentation of nails, mucous membranes, and skin can occur in Addison's disease, Peutz-Jeghers syndrome, and Laugier-Hunzikersyndrome. Systemic pigmentation related to drugs has also been described." All three patients previously received several drugs, none of which are known to produce pigmentation. In all three patients pigmentation of the proximal part of the nail plate developed after at least 6 weeks of treatment with zidovudine, The pigmentation later involved the entire nail. In patient 2 the lesionsslowly faded after treatment was discontinued. This finding suggests that zidovudineis involved in the pigmentary change.
687
Journal of the American Academy of Dermatology
688 Brie] communications
Fig. 1. Case 1. Longitudinal pigmented nail bands with bluish discoloration of nail bed. Fig. 2. Large melanin granules (G) and dendritic melanocytes (M) throughout nail matrix (MX}. NP, Nail plate. (Ammoniacal silver nitrate stain; X400.)
REFERENCES 1. Furth PA, Kazakis AM. Nail pigmentation changes associated with azidothymidine (zidovudine) [Abstract]. Ann Intern Med 1987;107:350. 2. Pannwalker AP. Nail pigmentation in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107:943-4. 3. Gonzalcz-Lahoz JM, Garcia Aguado C, MartinezFernandez R, et al. Pigmentation azulada en las unas de los pacientes con SIDA: efecto colateral de la zidovudina? [Letter] Rev Clin Espan 1988;183:278-9. 4. Azon-Masoliver A, Mallolas J, Gatell J, et al. Zidovudineinduced nail pigmentation. Arch Dermatol 1988;124: 1570-1. 5. Riechman DD, Fieschl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double blind controlled trial. N Engl J Med 1987;317:192-7. 6. McEvoy GK, ed. American Hospital Formulary Service: drug information. Bethesda, Md.: American Society of Hospital Pharmacists, 1988:392-7.
7. Daniel CR, Scher RK. Nail changes secondary to systemic drugs or ingestants.J AMACAD DERMATOL 1984;10:250-8.
Acquired port-wine stain Mark W. Cobb, MD, and Leon Goldman, MD* Bethesda, Maryland, and San Diego, California Nevus flammeus is a common congenital malformation of mature capillaries that occur in up to 75% of newborns.' The most common type is the salmon patch, From the Department of Dermatology, Naval Hospital. The views expressed herein are those of the authors and do not reflect the officialpolicyor position of the Department of the Navy, Department of Defense, or the U.S. Government. No reprints available. *Dr. Goldman is at the Naval Hospital, San Diego, Calif.