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Clinical Letters
DOI: 10.1111/j.1610-0387.2011.07716.x
Clinical Letter
Cetuximab-associated folliculitis
predominantly affecting the lower
limbs
Patrick A. Oberholzer, Luca Borradori, Helmut Beltraminelli
Department of Dermatology, Inselspital, University of Bern, Switzerland
A 61-year-old man presented with
adenocarcinoma of the distal descending
colon and extensive lymphatic metastasis. Following an initial left hemicolectomy and para-aortic lymphadenectomy,
he received chemotherapy with FOLFOX/bevacizumab. FOLFOX is a triple
combination therapy consisting of FOLinic acid, 5-Fluorouracil, and OXaliplatin. In addition, he also was given bevacizumab, which inhibits binding of VEGF
(vascular endothelial growth factor) to its
receptors VEGFR1 and VEGFR2. The
disease continued to progress despite treatment. The patient was switched to the
less toxic drug FOLFIRI (with IRInotecan instead of OXaliplatin). There was
renewed progression of disease including
skin metastases which were confirmed by
a biopsy. Pubic and bilateral inguinal
palliative percutaneous radiotherapy
(total 30 Gy) was performed. Along with
prior lymphadenectomy, therapy led to
chronic lymphedema and blockage of
venous drainage in both legs and subsequently to development of ulcers on the
lower legs, the medial aspects of the
thighs, and the scrotum.
Finally, cetuximab, an EGFR (epithelial
growth factor receptor) antagonist, was
703
added to the treatment scheme in addition to FOLFIRI (Table 1).
This led to development of follicularlyoriented papules and pustules, some of
which eroded and formed oozing, coalescing erosions or ulcerations on the
thighs, the ventral aspects of the lower
legs (Figure 1) and, to a lesser extent, the
pectoral regions. There was no facial involvement. The results of smears and
culture were negative for underlying bacterial or fungal (e.g., Malassezia furfur)
infection. Additional clinical signs included extremely dry fingertips with rhagades (pulpitis sicca) as well as paronychia affecting all fingernails. Treatment,
treatment duration, dermatological
adverse effects, and their management
are summarized in Table 1. In spite of
every attempt to bring the disease under
control, the patient died shortly after the
appearance of cetuximab-associated side
effects.
The EGFR receptor is expressed in about
80 % of all colorectal cancers [1]. In addition, 93 % of NSCLC (non-small cell
lung cancer) as well as the majority of
ORL, pancreatic and ovarian cancer exhibit up-regulation [2]. These types of
Table 1: Treatment schedule.
Treatment
Details of
therapy
Initial diagnosis
Duration
(mm/yyyy)
Dermatological adverse
effects (AE)
Treatment of dermatological
adverse effects
01/2007
Hemicolectomy
(left) and para-aortic
lymphadenectomy
02/2007
Afterward progressive,
chronic lymphedema and
Compression therapy and
blockage of venous drainage lymph drainage
in both legs (*)
FOLFOX plus
bevicizumab
12 cycles
07/2007–01/2008
FOLFIRI
12 cycles
05/2008–11/2008
Total dose
30 Gy
Continual worsening of (*)
and during 03/2009
additional ulcerations on
01/2009–02/2009
the lower legs, medial
aspects of the thighs, and
parts of the scrotum
Additional topical drying therapies and topical treatment with
combination drug
clotrimazole/hexamidine
9 cycles
03/2009 initial folliculitis
affecting the areas of the
skin described above, then
01/2009–06/2009
05/2009 pulpitis sicca and
progressive paronychia
affecting all nails
Local synthetic tanning agents
followed by topical application
of combination drug fusidic
acid/hydrocortisone acetate
along with systemic doxycycline
(dosage: 100–200 mg/daily)
Percutaneous radiotherapy of the pelvis
and testicle
FOLFIRI plus
cetuximab
Exitus letalis
07/2009
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© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2011/0909
704
Clinical Letters
References
1
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Figure 1: Clinical picture of the thigh and lower leg showing follicular bound papules and pustules,
partially progressing to confluent erosions and ulcerations.
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5
cancer may be appropriately treated with
EGFR antagonists such as panitumumab,
cetuximab, erlotinib, or gefitinib.
The most common side effects of EGFR
antagonists (39–100 %), which occur
quite rapidly (within the first three weeks
of therapy), are folliculitis, followed by
pulpitis sicca and paronychia of the
hands and feet [3–7]. EGFR-associated
folliculitis characteristically occurs in
areas of the skin rich in seborrheic glands
such as the forehead, cheeks, neckline,
and upper back. Studies have shown that
the severity of folliculitis is correlated
with the treatment response [5, 8]. Unfortunately, the cutaneous side effects of
treatment often lead to discontinuation
of chemotherapy [9]. Skin symptoms are
treated with topical steroids and antibacterial substances (e.g., fusidic acid and
betamethasone) as well as systemic antibiotics (e.g., doxycycline) initially 100–
200 mg/daily, then 50–100 mg/daily.
After discontinuing the use of EGFR antagonists and administering treatment as
described here, there is usually rapid and
complete healing of cutaneous symptoms – which paradoxically are often
perceived by the patient as more disturbing the underlying cancer.
Our patient was rather unique in that
the EGFR-associated folliculitis did not
affect typical sites such as the face, head,
and upper body, but instead involved almost exclusively the legs. We interpret
this atypical presentation as being related
to chronic lymphedema and blockage of
venous drainage in the lower extremities
(locus minoris resistentiae). If typical skin
lesions occur at atypical sites during
therapy, one should keep in mind other
circumstances or accompanying diseases;
in our patient this was skin damage due
to chronic lymphedema. Such factors
should be recalled in the diagnosis and
treatment of skin changes associated
with treatment.
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Correspondence to
Patrick A. Oberholzer, MD
Dermatologische Klinik
Inselspital
Universität Bern
CH-3010 Bern
Tel.: +41 (0)31-632-2094
Fax: +41 (0)31-632-2231
E-mail: [email protected]
Cunningham D, Humblet Y, Siena S,
Khayat D, Bleiberg H, Santoro A, Bets
D, Mueser M, Harstrick A, Verslype C,
Chau I, Van Cutsem E. Cetuximab
monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med
2004; 351: 337–45.
Perez-Soler R. HER1/EGFR targeting:
refining the strategy. Oncologist 2004;
9: 58–67.
Agero AL, Dusza SW, BenvenutoAndrade C, Busam KJ, Myskowski P,
Halpern AC. Dermatologic side effects
associated with the epidermal growth
factor receptor inhibitors. J Am Acad
Dermatol 2006; 55: 657–70.
Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors.
Nat Rev Cancer 2006; 6: 803–12.
Saltz LB, Meropol NJ, Loehrer PJ, Sr.,
Needle MN, Kopit J, Mayer RJ. Phase
II trial of cetuximab in patients with refractory colorectal cancer that expresses
the epidermal growth factor receptor. J
Clin Oncol 2004; 22: 1201–8.
Schimanski CC, Moehler M, Zimmermann T, Worns MA, Steinbach A,
Baum M, Galle PR. Cetuximab-induced skin exanthema: Improvement by a
reactive skin therapy. Mol Med Report
2010; 3: 789–93.
Tomkova H, Kohoutek M, Zabojnikova
M, Pospiskova M, Ostrizkova L,
Gharibyar M. Cetuximab-induced
cutaneous toxicity. J Eur Acad Dermatol Venereol 2010; 24: 692–6.
Susman E. Rash correlates with tumour
response after cetuximab. Lancet Oncol
2004; 5: 647.
Busam KJ, Capodieci P, Motzer R,
Kiehn T, Phelan D, Halpern AC. Cutaneous side-effects in cancer patients
treated with the antiepidermal growth
factor receptor antibody C225. Br J
Dermatol 2001; 144: 1169–76.
JDDG | 9 ˙2011 (Band 9)
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