Journal of the American Academy of DermatologyVolume 28, Number 3 Brief communications 503

Hyperpigmentation in striae distensae after bleomycin treatment

Takuo Tsuji, MD, Phl)," and Motokazu Sawabe, MOb Nagoya and Osaka, Japan

Bleomycin, an antitumor antibiotic, has severaldose-related skin toxicities, including hyperpigmen­tation, sclerosis, gangrene, nail changes, anderythema in certain selected skin sites.!" Hyperpig­mentation occurs mainly on the pressure areas of theskin and fingernails- 3, 5 as well as in areas of irrita­tion or scratch marks. 1,4,7

This is the first report that describes hyperpig­mentation confined to striae distensae after treat­ment with bleomycin.

CASE REPORT

A 17-year-oldJapanese boy was found to have a germcell tumor in the left caudate nucleus and hypothalamusin April 1990. He was treated with radiation from AprilI I to June 10, 1990 and from Aug. 8 to Sept. 20, 1990(totaling 59 Gy), with a glucocorticosteroid (betarnetha­sone) from June 26 to Oct. 31, 1990 (totaling 420 mg),and with PYB (cisplatin,vincristine,and bleomycin) fromMay20to July 30,1990 (totaling 700 mg, 32 mg, and 204mg, respectively). In the middle of July he noticed linearatrophic skin lesions on his abdomen, gluteal areas, boththighs, and upper arms. When the atrophic lesions firstappeared, they were pink. Then they changed to darkbrown within a week and remained. He gained 12 kgwithin 3 months during the glucocorticoid therapy (51 to63 kg). On Sept. 10, 1990,he was referred to our Depart­ment of Dermatology for the linear, atrophic, and pig­mented lesions.

Physical examination revealed features of Cushingsyndrome including full-moon face and striae distensae,Two different types of striae distensae were seen. Oneconsisted of linear (less than 2 mm in width), atrophic,and white lesions on the lower part of both gluteal areas(Fig. 1). These had been present for about 3 years beforebleomycin was givenand were inflamed and wider at one

From the Department of Dermatology, Nagoya City University Med­icalSchool";and Ihe Department of Dermatology,Osaka City Uni­versity Medica: School.

Reprint requests: Takuo Tsuji, Department of Dermatology, NagoyaCity UniversityMedicalSchool, l-Kawasumi, Mizuho-cho,Mizuho­ku, Nagoya 467, Japan.

JAM ACI\D DERMI\TOI. 1993;28:503-5.

Copyright @ 1993by the American Academy of Dermatology, Inc.

0190-9622/93 $1.00+ .10 16/54/42128

Fig. 1. Dark-brown linear and atrophic lesionsare seenon outer thigh and upper gluteal area. White linear andatrophic lesions (arrow) are seen on lower gluteal area.

time. The other consistedof wider (5 to 12 mm in width),atrophic, and dark-brown lesions on both upper arms,outer and inner thighs, upper part of the gluteal areas, andabdomen (Fig. 1). Light microscopic study of a specimenfrom one of the dark-brown lesionsshowed a trophy oftheepidermis, hyperpigmentation of the basal layer, and finedegenerative collagen fibers in the dermis. Electronmicroscopicstudy of the same specimen showed increasednumbers of melanosomesin the basal cells and lower twoto three layers of thesquamous cells(Fig. 2). Melanocytcscontained various degrees of development of rnelano­somes,which were increased in number. Laboratory testsshowed corticotropin level, 48.5 pg/ml on April 17 and15.7pg/rnl on Dec. 11 (normal I°to 100pg/rnl) and se­rum cortisol level, 3.0 /lg/dl on April 17 and 5.4,ug/dl onDec. 11 (normal 10 to 15/lg/dl).

504 Brief communicationsJournal of the American Academy of Dermatology

March 1993

Fig. 2. Electron microscopy of specimen from one dark-brown lesion shows increased num­bers of melanosomes in the basal cells (B) and lower two to three layers of the squamous cells(8). D, Dermis; M, melanocyte. (Bar = 1 IJ,m.)

The pigmentation persisted until Jan. 14, 1991, whenwe last saw the patient. During that time, the pigmenta­tion had changed in intensity.

DISCUSSION

Striae distensae are characterized by linear,smooth, white-to-pink bands of atrophic-appearingskin. They are commonly seen during pregnancy,after a rapid gain or loss of weight in adolescence,with Cushing's disease or debilitating infection andillness, and during prolonged systemic or topical ad­renal corticosteroid therapy.?' 10

In general, when the striae distensae first appear,they are pink to violaceous. They may remain in thisstage for many months or years. Then, the colorgradually fades, and white lines, somewhat smallerthan the original striae, finally develop. [0, I I At thispoint, the dark-brown hyperpigmentation of thestriae is unusual. Several factors may be possiblethat could induce hyperpigmentation in the presentcase: (I) after inflammation, (2) Cushing's syn­drome, and (3) bleomycin. During the early stagesof striae distensae, inflammatory changes may beconspicuous. However, as mentioned earlier, brownpigmentation does not occur in the general healingprocess of the striae. In Cushing's syndrome pig­mentation of Addisonian pattern may occur, but notas a feature of our case. Bleomycin has a toxic effecton melanocytes, producing hyperpigrnentation.Bleomycin induces cellular damage by cleaving

chromosomes in internucleosomal regions and de­grading chromatin.l? This damage occurs far morereadily in nonproliferating and slowly proliferatingcell populations, such as the melanocyte. Increasedmelanogenesis had been demonstrated in melano­cytes in skin specimens taken from bleomycin­treated patients."

The fact that hyperpigmentation occurred duringthe PYB treatment and in a short time after thestriae had been noted suggests that bleomycininduced the hyperpigmentation. The total dose ofbleomycin (204 mg) is enough to induce hyperpig­mentation because in previousreports hyperpigmen­tat ion developed between 90 and 285 mg.4• 7 How­ever, the atrophic striae in the white striae distensaeare different and considered to have occurred as amanifestation of puberty . The reason that the hy­perpigmentation occurred in only newly formedstriae distensae is not clear. It may be possible thatincreased new blood vessels in the early stages ofstriae distensae allow increased quantities of thedrug to be delivered to selected skin sites." The factthat in this case the old white striae distensae did notturn brown after the bleomycin might prove this hy­pothesis.

REFERENCI~S

J. Yagoda A, Bijay M, Yound C, ct al, Bleomycin, an anti­tumor antibiotic. Ann Intern Med 1972;77:861-7D.

2. Halnan KE, Bleehen NM, Brewin TB, et al, Early clinical

Journal of the American Academy of DermatologyVolume 28, Number 3

experience with bleomycinin the UnitedKingdom in a se­riesof 105 patients. Br Med J 1972;4:635-8.

3. Kiefer O. Uberdie Nebenwirkungen der Bleornycin-ther­apie auf der Haut. Dermatologica 1973;146:229-43.

4. Cohen IS, Mosher MB, O'Keefe EJ, et al. Cutaneous tox­icityofbleomycin therapy.ArchDermatolI973;107:553-5.

5. Nixon DW. Alterations in nail pigment with cancer che­motherapy. Arch Intern Med 1976;136:1117-8.

6. MillerRAW.Nail dystrophy following intralesional injec­tions of bleomycin for a periungual wart. Arch Dermatol1984;120:963-4.

7. Lowitz BE. Streaking with bleomycin. N Engl J' Med1975;292: 1300-1.

Brie!communications 505

8. Blum RH, Carter SK, Agre K. A clinical review ofbleomycin-a new antineoplastic agent. Cancer 1973;31:903-14.

9. Hauser W. Zur Fruge der Entstehung der Striae cutisatrophicae. Dermatol Wochenschr 1958;138:1291-5.

10. EpsteinN W, Epstein WL, Epstein JH. Atrophicstriae inpatients with inguinal intertrigo. Arch Dermatol 1963;87:450-7.

11. Sisson WR. Colored striae in adolescent children. J Pedi­atr 1954;45:520-30.

12. Moore CW, Jones CS, Wall LA. Growth phase depen­dencyof chromatin cleavageand degradation by bleomy­cin. Antimicrob Agents Chemother 1989;33:1592-9.

Successful treatment of dermatitis herpetiformis with tetracycline andnicotinamide in a patient unable to tolerate dapsone

Alexander Zemtsov, MD, and Kenneth H. Neldner, MD Lubbock, Texas

The combination of niacinamide and tetracyclineor its derivatives has been used with varying degreesof success in the treatment of bullous pemphigoidand erythema elevatum diutinum.' : 2 Peoples andFivensonl recently reported that this combination isalso effective in the treatment of linear IgA derma­tosis. We add dermatitis herpetiformis (DR) to thislist.

CASE REPORT

A 32-year-old white woman had extremely pruriticflaccid blisters and urticarial papules that most prominenton her buttocks, face, and extensor surface of her arms.A biopsy specimen of an early lesionshowed a subepider­mal blister and collections of neutrophils in dermal papil­lae characteristic of DH. Direct immunofluorescence ofa biopsy specimen from unaffected skin showed granularIgA deposits in the basement membrane zone. Indirectimmunofluorescence was negative. Her glucose-6-phos­phate dehydrogenase enzyme activity was normal. Shewas treated with oral dapsone, 100 mg daily, with clear­ing of her skin lesions and reduction in her pruritus. Pre­treatment hemogram and electrolyte profile values werenormal and remained normal 2 and 4 weeks after initia­tion of therapy. Six weeks after dapsone therapy had been

From the Department of Dermatology, Texas Tech University Schoolof Medicine.

No reprints available.

J AM ACAD DERMATOL 1993;28:505-6.

Copyright © 1993 by the Americ an Academy of Dermatology, Inc.

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initiated shortness of breath, extreme fatigue, chiIls, fever,and arthralgias developed. Her temperature was 102° F.Her white blood cell count was 300/mm3, hemoglobin,8.8 gm; hematocrit, 25.8%; red blood cell count, 3.1 mil­lion/mm' ; and platelet count, 390,000. A bone marrowexamination showed a "normal cellular marrow withmaturation arrest of the granulocytic series." A diagno­sis of dapsone-induced agranulocytosis was made.

Filgastrim, a recombinant human granulocyte colony­stimulating factor (G-CSF) (Neupogen, Amgen, Inc.,Thousand Oaks, Calif.), was started within 24 hours.Within 3 days her total white blood cell count was 1500/mm-, but no neutrophils were present. After 3 weeks ofcontinuous infusion therapy with filgastrim, her bonemarrow had recovered, and the hemogram returned tonormal. However, a severe flareofher DH developed thatdid not respond to antihistamines and topical steroids .

She was then treated with oral nicotinamide, 500 mgthree times daily, and tetracycline, 500 mg. The pruritusresolved within 3 days, and by 2 weeks, the skin eruptionhad cleared. Because of a mild gastrointestinal upset, tet­racycline was changed to oral minocycline, 100 mg twicedaily, with improved tolerance. Discontinuation of eitherniacinamide or minocycline resulted in a flare of her DH.After 6 months of treatment, her skin remains clear. Sheis unwilling to take a gluten-free diet.

DISCUSSION

Forty years ago, Johnson and Binkley4 reportedsome efficacy for nicotinic acid in treating DR butnoted complete suppression of disease in only somepatients. We can only speculate on the mechanismof action of tetracycline and nicotinic acid in DR.