Docetaxel chemotherapy is increasingly used in the treatment of castration-resistant prostate cancer. Cutaneous toxicity is common with docetaxel, occurring in up to 75% of cases. We present an unusual case of castration-resistant prostate cancer in which our patient developed recurrent but transient episodes of skin rash following each cycle of docetaxel. Initially, the rash was attributed to docetaxel cutaneous toxicity however a microbiological diagnosis of Trichophyton rubrum was subsequently made. We postulated that dexamethasone pre-medication transiently suppressed anti-fungal immunity, and indeed further flares were prevented by significantly reducing the dose of dexamethasone while continuing treatment with docetaxel

Azad, Arun

Jayarajan, Jyotsna

Kaufman, Melissa

English

PubMed

Springer - Publisher Connector

Case report
Open Access
Dexamethasone-induced flares of Trichophyton rubrum
masquerading as docetaxel cutaneous toxicity: a case report
Arun Azad1*, Melissa Kaufman2 and Jyotsna Jayarajan3
Addresses: 1Ludwig Institute for Cancer Research, University of Melbourne, Austin Hospital, Austin Health, 145-163 Studley Road, Heidelberg,
Victoria, Australia, 3084
2Department of Medicine, University of Melbourne, Austin Hospital, Austin Health, 145-163 Studley Road, Heidelberg, Victoria, Australia, 3084
3Department of Surgery, University of Melbourne, Austin Health, 145-163 Studley Road, Heidelberg, Victoria, Australia, 3084
Email: AA* - Arun_azad@hotmail.com; MK - mel_kauf@yahoo.com.au; JJ - jyotsnaj@gmail.com
*Corresponding author
Received: 23 January 2009 Accepted: 18 June 2009 Published: 23 July 2009
Cases Journal 2009, 2:8552 doi: 10.4076/1757-1626-2-8552
This article is available from: http://casesjournal.com/casesjournal/article/view/8552
© 2009 Azad et al.; licensee Cases Network Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Docetaxel chemotherapy is increasingly used in the treatment of castration-resistant prostate cancer.
Cutaneous toxicity is common with docetaxel, occurring in up to 75% of cases. We present an
unusual case of castration-resistant prostate cancer in which our patient developed recurrent but
transient episodes of skin rash following each cycle of docetaxel. Initially, the rash was attributed to
docetaxel cutaneous toxicity however a microbiological diagnosis of Trichophyton rubrum was
subsequently made. We postulated that dexamethasone pre-medication transiently suppressed anti-
fungal immunity, and indeed further flares were prevented by significantly reducing the dose of
dexamethasone while continuing treatment with docetaxel.
Introduction
Docetaxel chemotherapy is commonly used in castration-
resistant prostate cancer (CRPC). Cutaneous toxicity with
docetaxel is well recognised, manifesting in numerous
ways including palmar/plantar erythrodysaesthesia (PPE)
and nail changes (onycholysis, paronychia). We present a
fascinating case in which our patient developed recurrent
but transient episodes of skin rash resembling PPE
following each cycle of docetaxel. Initially docetaxel
cutaneous toxicity was suspected, however subsequently
a microbiological diagnosis of Trichophyton rubrum was
made. We postulated that dexamethasone pre-medication
transiently suppressed anti-fungal immunity, and indeed
further flares were prevented by significantly reducing the
dose of dexamethasone while continuing treatment with
docetaxel.
Case presentation
A 57 year old Caucasian male with CRPC commenced
docetaxel chemotherapy (75 mg/m2 intravenous three-
weekly) and oral prednisolone (5 mg twice daily). Routine
dexamethasone pre-medication (8 mg twice daily for three
days starting one day pre-docetaxel) was given to prevent
docetaxel hypersensitivity reactions. From cycles two to
four he complained of an itchy, erythematous rash of his
feet. The rash commenced one to two days after receiving
docetaxel, lasted for seven to ten days, and then resolved
spontaneously. He had no prior dermatological history.
Page 1 of 2
(page number not for citation purposes)
He did not smoke and drank minimal alcohol. He was of
Macedonian origin. He lived with his wife and was retired.
There was no relevant family history.
On examination, there was a sharply demarcated, erythe-
matous, macular rash involving the soles of his feet. There
was also non-tender onycholysis affecting both great toes.
Nail and skin scrapings were taken with Trichophyton
rubrum isolated on fungal culture. The patient continued
on docetaxel at 75mg/m2 for the next three cycles, however
a single dose of dexamethasone (8 mg intravenous) was
given as pre-medication one hour prior to docetaxel. The
patient also commenced oral terbinafine 250 mg daily for
four weeks. There were no further flares of T. Rubrum and
no hypersensitivity reactions. Treatment was stopped after
seven cycles of docetaxel because of progressive disease.
Discussion
The time course, distribution and appearance of the rash in
our patient were not helpful in conclusively differentiating
docetaxel cutaneous toxicity from a fungal infection.
Initially, we had suspected PPE since docetaxel is a
common cause of PPE [1]. Moreover, there was a temporal
relationship between the rash and treatment with doc-
etaxel. On the other hand, this temporal relationship also
existed for dexamethasone. Additionally, the absence of
palmar involvement was somewhat unusual for PPE. After
making a diagnosis of T. Rubrum, we then faced the
dilemma of how best to prevent further flares while not
compromising anti-cancer treatment.
We postulated that the dexamethasone pre-medication was
causing transient suppression of anti-fungal immunity
thereby predisposing to recurrent flares of T. Rubrum. Cell-
mediated immunity (CMI) plays a critical role in defence
against fungal infections [2]. Glucocorticoid therapy is a
major risk factor for fungal infections and can impair CMI
in numerous ways. This includes reduction of neutrophil
and macrophage accumulation at inflammatory sites [3,4],
and impaired phagocytic and microbicidal function of
macrophages [5]. In addition glucocorticoids induce
profound lymphopaenia, predominantly of T-cells and
particularly CD4 cells. Importantly, glucocorticoids also
reduce Th1 CD4 cell numbers more than Th2 CD4 cells
[6]. This preferential differentiation is significant since
Th1-mediated CMI is required for clearance of fungal
infections [7].
Like dexamethasone, prednisolone is a glucocorticoid but
it was unlikely to have contributed since it is less potent
than dexamethasone. Additionally, the dose of predniso-
lone was low and there was no temporal relationship to
the rash. We did consider the role of docetaxel, which can
theoretically impair CMI since it causes neutropaenia as
well as CD4 and CD8 lymphopaenia [8]. However, we felt
that dexamethasone was more likely to have contributed
to the flares of T. Rubrum and accordingly we substantially
reduced the dose of dexamethasone pre-medication while
maintaining the dose of docetaxel. This resulted in no
further flares during three cycles of treatment, suggesting
that we were correct. Our patient was also treated with oral
anti-fungal therapy, which was undoubtedly important in
preventing further flares.
Conclusions
With increasing use of docetaxel for CRPC, clinicians are
likely to encounter patients with skin-related problems.
Given that docetaxel causes skin toxicity in asmany as 75%
of patients [1], docetaxel is likely to be the culprit in the
vast majority of cases. Our case, while being a somewhat
unusual presentation of cutaneous fungal infection, high-
lights the importance of considering other causes.
Abbreviations
CRPC, castration-resistant prostate cancer; PPE, palmar/
plantar erythrodysaesthesia; CMI, Cell-mediated immunity.
Consent
Written informed consent was obtained from the patient
for publication of this case report. A copy of the written
consent is available for review by the Editor-in-Chief of
this journal.
Competing interests
The authors declare that they have no competing interests.
Authors’ contribution
AA conducted the literature review. All authors were
involved in writing and editing the manuscript. All authors
read and approved the final manuscript.
References
1. Nagore E, Insa A, Sanmartin O: Antineoplastic therapy-induced
palmar plantar erythrodysesthesia (‘hand-foot’) syndrome.
Incidence, recognition and management. Am J Clin Dermatol
2000, 1:225-234.
2. Crameri R, Blaser K: Allergy and immunity to fungal infections
and colonization. Eur Respir J 2002, 19:151-157.
3. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE:
Glucocorticoid therapy for immune-mediated diseases: basic
and clinical correlates. Ann Intern Med 1993, 119:1198-1208.
4. Gerlag DM, Haringman JJ, Smeets TJ, Zwinderman AH, Kraan MC,
Laud PJ, Morgan S, Nash AF, Tak PP: Effects of oral prednisolone
on biomarkers in synovial tissue and clinical improvement in
rheumatoid arthritis. Arthritis Rheum 2004, 50:3783-3791.
5. Fauci AS, Dale DC, Balow JE: Glucocorticosteroid therapy:
mechanisms of action and clinical considerations. Ann Intern
Med 1976, 84:304-315.
6. Ashwell JD, Lu FW, Vacchio MS: Glucocorticoids in T cell
development and function. Annu Rev Immunol 2000, 18:309-345.
7. Blanco JL, Garcia ME: Immune response to fungal infections. Vet
Immunol Immunopathol 2008, 125:47-70.
8. Kotsakis A, Sarra E, Peraki M, Koukourakis M, Apostolaki S,
Souglakos J, Mavromanomakis E, Vlachonikolis J, Georgoulias V:
Docetaxel-induced lymphopenia in patients with solid
tumors: a prospective phenotypic analysis. Cancer 2000,
89:1380-1386.
Page 2 of 2
(page number not for citation purposes)
Cases Journal 2009, 2:8552 http://casesjournal.com/casesjournal/article/view/8552


Dexamethasone-induced flares of masquerading as docetaxel cutaneous toxicity: a case report

Arun Azad

Melissa Kaufman

Jyotsna Jayarajan

Crossref