Dose-dependent melanonychia by mitoxantrone

C Reinsberger, SG Meuth and H Wiendl

We report an unusual case of a 43-year old female patient suffering from multiple sclerosis, who was
treated with mitoxantrone. Few weeks after treatment initiation a hyperpigmentation of the patients
left thumb and index was noted. Following dose-reduction (from 12 to 10 mg/m
2
) and over the further
course of mitoxantrone treatment the discoloration slightly faded. Although mitoxantrone is known to
cause hyperpigmentation of various tissues this is the first report of melanonychia without hyperpig-
mentation of other tissue. Albeit speculative, pathogenesis of selective melanonychia by mitoxantrone
could involve selective activation of nail matrix melanocytes or endocrine disturbances involving mela-
nocyte stimulating hormone. Multiple Sclerosis 2009; 15: 11311132. http://msj.sagepub.com
Key words: melanonychia; mitoxantrone; multiple sclerosis; pigmentation; side effect
A 43-year-old Caucasian woman presented as an
outpatient with a 12-year history of multiple sclero-
sis. Past medical history otherwise was unremark-
able. During the initial relapsingremitting course
of disease, the patient experienced recurrent relapses
and subsequent disease progression (increase of
EDSS up to 5.0) despite immunomodulatory treat-
ment with both interferon -1b and interferon
-1a. Laboratory testing revealed neutralizing anti-
bodies against -interferons. Thus, the treatment
regimen was changed to mitoxantrone, which was
applied after excluding contraindications and
assured normal cardiac function every 3 months.
Initiation dose was 12 mg/m
2
. Because of pro-
nouncedly decreased white blood cell counts
(2.010
3
/L) subsequent infusions were applied at a
reduced dosage (10 mg/m
2
). Clinically, the patient
stabilized and disease progression was halted. Side
effects under therapy included occasional nausea
and vomiting, as well as secondary amenorrhea.
Few weeks after treatment initiation (in November,
2007), the patient noticed a hyperpigmentation of
her left thumb and index nails, which was first
observed between the second and third mitoxan-
trone treatment cycle and appeared as a dark colored
stripe (see Figure 1). Other finger and foot nails
showed no such changes. Following dose reduction
(from 12 to 10 mg/m
2
) and further treatment with
course of mitoxantrone, the discoloration slightly
faded. Rechallenge with a higher dose of mitoxan-
trone (12 mg/m
2
) lead to intensification of melano-
nychia in the earlier affected fingers, as reported by
the patient. Melanonychia associated with mitoxan-
trone treatment was diagnosed.
Various nail changes have been reported following
chemotherapy such as Beaus lines, onychomadesis
(nail dystrophy), onycholysis, periungal pyogenis
granulomas, and melanonychia [1]. Thus far, melano-
nychia has never been described after administration
of mitoxantrone. Following immune suppression
with mitoxantrone, the only reported nail affection
is onycholysis [2]. Although mitoxantrone is known
to cause hyperpigmentation of various tissues [3], this
is the first report of melanonychia without hyperpig-
mentation of other tissue. Other causes associated
with melanonychia were not present in the patient
and the patient did not present melanonychia before
the initiation of treatment with mitoxantrone. No
concomitant medication was applied. Melanonychia
striata, or longitudinal melanonychia, refers to any
linear tan, brown, or black pigmentation within the
nail that results from increased melanin deposition.
Causes of this pigmentation include topical medica-
tion, infections, systemic diseases, trauma, drugs, and
benign or malignant cellular proliferation [4]. Besides
history and clinical examination, the diagnosis of
the exact cause often requires biopsy especially to
exclude subungal melanoma. Albeit speculative,
pathogenesis of selective melanonychia by mitoxan-
trone could involve selective activation of nail
matrix melanocytes [5,6] or endocrine disturbances
involving melanocyte stimulating hormone [7].
Department of Neurology, University Hospital, Julius-Maximilians-University, Wuerzburg, Germany
Correspondence to: Department of Neurology, University Hospital, Julius-Maximilians-University, Josef-Schneider Str.
11, 97080 Wuerzburg, Germany. Email: Reinsberger_C@klinik.uni-wuerzburg.de
Received 21 January 2009; accepted 22 April 2009
CASE REPORT Multiple Sclerosis 2009; 15: 11311132
The Author(s), 2009. 10.1177/1352458509106616
Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
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Figure 1 Nail abnormalities occurred in the left thumb and index after first mitoxantrone application. Hyperpigmentation
was dose dependent and diminished after dose reduction.
1132 C Reinsberger et al.
Multiple Sclerosis 2009; 15: 11311132 http://msj.sagepub.com
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