ARTICLE
Onycholysis is an infrequent secondary effect of drug therapy, the antineoplastic
agents being the drugs usually implicated. Docetaxel, a drug pertaining
to the taxanes family, has been recently associated with nail bed dyschromia
and onycholysis [1]. Similar alterations secondary to another chemically
related antineoplastic drug, paclitaxel, have been described, but they
are rare. We observed two patients with nail alterations induced by paclitaxel
therapy.
Case 1
A 67-year-old woman was diagnosed in July 1994 as having infiltrating
ductal carcinoma of the breast (T4N3M1). She was treated with simple mastectomy,
axillar unbridling, radiotherapy and chemotheraphy (cyclophosphamide,
adriamycin and 5-fluoruracile). Chemotherapic courses resulted in haematological
toxicity, mucositis and gastrointestinal toxicity. In June 1998, local
relapse with supraclavicular lymphadenopathy and without response to 5-fluoruracile
was detected. Paclitaxel therapy (60 mg/m2/weekly) was instituted
and 3 months later she developed a regular erythematous-brown hemosiderine
like discoloration of three nail beds of finger nails and toenails that
spared the lunula, and slight onycholysis. No bleeding or ulceration of
the nail bed was observed (Fig.
1).
These nail changes were attributed to paclitaxel, but the treatment
was not discontinued. The nails alterations remained unchanged and she
had no loss of the nails.
Case 2
A 51 year-old-woman was treated in an oncology department for bilateral,
ductal carcinoma of the breast, with positive axillar lymphadenopathies
and bone and lung metastases. Chemotherapy with adriamycin and G-CSF was
started. Three weeks later paclitaxel 80 mg/m2/weekly was added.
She received three cycles of paclitaxel therapy and five months after
the beginning of this treatment, she reported pain in the nails of the
hands and feet. The exploration revealed unpainful onycholysis, subungueal
distal hyperkeratosis and Beau lines in several nails (Fig.
2). Like the first case no bleeding or ulceration of the nail
bed was observed. The treatment was continued and the nail alterations
remained until several months after the end of the paclitaxel therapy.
Comment
Paclitaxel is a semisynthetic diterpene of vegetal origin pertaining
to the taxanes family. This agent is isolated from Taxus brevifolia,
a Pacific yew, and its mechanism of antineoplastic activity, not fully
understood, is related to a disruption of the dynamic equilibrium within
the microtubule system, resulting in an inhibition of the cell replication
with blocking of the cells in the late G2 phase and M phase
of the cell cycle [2]. This drug is usually used in antineoplastic treatments
for malignant tumours.
The most frequent skin reaction to paclitaxel is a complete sudden alopecia,
reversible when the drug is discontinued. Hypersensitivity reactions [3]
and radiation recall dermatitis resulting in extensive desquamation and
cutaneous necrosis [4] have been occasionally observed. A generalized
pustular reaction secondary to paclitaxel treatment has been also reported
[5]. Pigmentation and discoloration of the nail bed have been reported
in only 2% of treated patients, and onycholysis is rarely mentioned, only
four cases by Flory et al [6-8].
Other antimitotic agents, different from the taxol family can induce
onycholysis, 5-fluorouracile, mitozantrone, etoposide, doxorubicin, methotrexate
and leucovorin [9]. Onycholysis induced by paclitaxel is similar to onycholysis
caused by docetaxel and other antimitotic agents, but probably less severe.
Painful onycholysis and bleeding or ulceration of the nail bed are not
frequent with paclitaxel therapy although the drug is not stopped and
usually the quality of life is not altered by the nail alterations.
The mechanism of onycholysis produced by the antimitotic agents remains
obscure. In our cases, onycholysis was associated with other nail changes
and discoloration, Beau lines and subungueal hyperkeratosis suggest an
alteration of the matrix and the nail bed produced by the drug.
Nail changes induced by docetaxel are varied and frequent [10] because
they occur in approximately 35% of treated patients. The pigmentary changes,
nail bed discoloration and onycholysis observed in our case were identical
to the case reported by Jacob et al. [1] caused by docetaxel, and
seem to be related to the chemical similarity between these two drugs.
Nail alterations are not unusual in patients treated with drugs of the
taxol family and they are usually well tolerated. Nevertheless these nail
disturbances and their relevance should be known by the patients.
Article accepted on 25/10/99
REFERENCES
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