ARTICLE
Auteur(s) : Ting Xiao, Li-Xin Xia, Zhen-Hai Yang, Chun-Di
He, Xing-Hua Gao, Hong-Duo
Chen
Department of Dermatology, No. 1 Hospital of China Medical
University, 155 North Nanjing Street, Shenyang 110001, China
accepté le 22 Juillet 2008
Mycosis fungoides (MF) is the most common form of cutaneous T
cell lymphoma (CTCL). The natural course of MF is divided into
early stage (stages IA, IB and IIA) and advanced stage (stages IIB,
III and IV) [1]. Early stage MF manifests as itching, erythematous,
scaly patches or infiltrated plaques without involvement of lymph
nodes or visceral organs. Histopathologically, epidermotropism of T
cells or Pautrier’s abscess can be observed in the epidermis. Early
stage MF has long been treated with various skin-directed
therapies, including topical nitrogen mustard, topical carmustine,
topical corticosteroids, broad-band ultraviolet B (BB-UVB)
phototherapy, psoralen plus ultraviolet A (PUVA) photochemotherapy
and total skin electron beam radiation. Recently, many reports have
shown that narrow-band ultraviolet B (NB-UVB) phototherapy is
effective in the treatment of early stage MF [2-12]. NB-UVB was
given three times a week on nonconsecutive days as a standard
protocol in nearly all previous reports. Diederen et al.’s study
was the only one in which a twice weekly regimen of NB-UVB
phototherapy was administered. However, the treatment course in
their study was long (mean, 14 months). Herein we report eight
patients with early-stage MF treated by a twice weekly regimen of
NB-UVB phototherapy in relatively short courses.
Methods
Patients
In this retrospective study, eight adult patients with early-stage
MF were treated with NB-UVB phototherapy at the Department of
Dermatology of No. 1 Hospital of China Medical University, between
August 2002 and September 2006. They were followed up until
November 2007. In all patients, the diagnosis of MF was confirmed
histologically [13]. The stage of their disease was classified on
the basis of the TNM classification of the National Cancer
Institute workshop on MF [1].
Before treatment, all patients received a work-up of a complete
medical history, a complete physical and skin examination, some
laboratory examinations (including complete blood cell count, liver
and kidney function tests, serum lactate dehydrogenase levels,
CD4/CD8 flow cytometry, blood smear for Sezary cells), chest X-ray
and skin biopsy. Lymph node biopsy was performed in 3 patients with
a palpable lymph node at least 2 cm in diameter or with
multiple palpable lymph nodes at least 1 cm in diameter.
None received other phototherapies or photochemotherapies within
3 months before NB-UVB phototherapy. All patients were enrolled in
the study after giving their informed consent.
NB-UVB devices and the therapy regimen
NB-UVB phototherapy was given in a SS-04 UV phototherapy device
(Xigema, Shanghai, China) equipped with TL-01 fluorescent lamps
(Philips Company, Eindhoven, the Netherlands). NB-UVB was
311 nm ± 1 nm in wavelength. The irradiance was checked
with a special UV detector (Xigema, Shanghai, China). NB-UVB
therapy was given twice a week on nonconsecutive days. The initial
NB-UVB dose was 0.2 J/cm2. Dose increments were
made according to the previous erythema response. If there was no
erythema, 0.1 J/cm2 increments in dose were made.
The previous dose was repeated for mild erythema. If obvious
erythema with burning or pain occurred, the treatment was postponed
until recovery. Then the next dose was reduced to 50% of the
previous dose and the regimen was changed to
0.05 J/cm2 increments in the following sessions.
During each session of treatment, the eyes were protected using
UV-blocking goggles and the genital area was shielded in all male
patients. Patients were advised to protect themselves from
excessive exposure to sunlight. Patients used topical steroids in
areas inaccessible to NB-UVB radiation. 0.05% halometasone cream
was used twice daily for 2 to 3 weeks for lesions in the axillae,
inguina and gluteal folds which were inaccessible to NB-UVB
radiation. It was applied on less than 1% of body surface area.
Determination of clinical response
The clinical response to NB-UVB phototherapy was based on
determining the percentage of total body surface area affected by
the disease. It was determined as follows: complete response (CR),
at least 95% clearing of lesions; patial response (PR), at least
50% but less than 95% clearing; no response (NR), less than 50%
clearing [1]. Relapse was defined as clinically significant disease
requiring further treatment. The follow-up period ranged from 7 to
60 months (mean ± SD, 26.9 ± 19.7 months).
Results
Demographics
Eight patients (6 male, 2 female) were in stage IA (n = 2), IB (n =
3) and IIA (n = 3), respectively. The mean age of the 8 patients
was 49 ± 13.2 years (range, 37-78 years), and mean duration of
disease was 8.0 ± 7.2 years (range, 2 months to 20 years) (table 1). In the medical history, Case 3 had
a 5-year history of cutaneous amyloidosis (nodular type) on his
arms and legs. The skin type of all patients was type III except
Case 2 (type IV).
Table 1 Characterization of patients with early stage
mycosis fungoides and results of phototherapy
|
Patient No
|
Sex/Age
|
Skin type
|
Duration of disease (years)
|
Stage (TNM)
|
No. of treatments
|
Total dose (J/cm2)
|
Max. dose (J/cm2)
|
Clinical response
|
Time to relapse (months)
|
Previous UV treatment
|
Previous systemic treatment
|
|
1
|
M/58
|
III
|
0.2
|
IIA
|
22
|
9.0
|
0.65
|
PR
|
|
None
|
Antihistamines
|
|
2
|
M/40
|
IV
|
20
|
IIA
|
46
|
38.8
|
1.5
|
CR
|
Remission
|
None
|
None
|
|
3
|
M/78
|
III
|
13
|
IB
|
68
|
32.1
|
0.8
|
CR
|
5
|
None
|
Antihistamines
|
|
4
|
F/37
|
III
|
3
|
IA
|
16
|
5.3
|
0.5
|
CR
|
4
|
None
|
None
|
|
5
|
M/45
|
III
|
5
|
IA
|
22
|
15.7
|
1.0
|
CR
|
3
|
None
|
None
|
|
6
|
M/43
|
III
|
1
|
IIA
|
54
|
23.0
|
0.8
|
CR
|
Remission
|
None
|
None
|
|
7
|
F/47
|
III
|
15
|
IB
|
59
|
27.7
|
0.65
|
CR
|
8
|
None
|
None
|
|
8
|
M/44
|
III
|
7
|
IB
|
41
|
33.4
|
1.2
|
PR
|
|
None
|
None
|
NB-UVB phototherapy treatments
The mean total NB-UVB dose delivered to the patients was 23.1 ±
12.1 J/cm2 (range, 5.3-38.8 J/cm2)
in 41.0 ± 19.3 irradiations (range, 16-68) (table 1). The mean maximum daily dose of NB-UVB
was 0.89 ± 0.33 J/cm2 (range, 0.5-1.5
J/cm2).
Clinical response
NB-UVB phototherapy led to CR in 6 of 8 patients (75%) (figure 1), PR in 2
patients (25%). Patients in the CR group received a mean of 10.4 ±
5.8 weeks (range, 6-20 weeks), 23.4 ± 8.5 irradiations (range,
11-35) and 12.6 ± 4.7 J/cm2 cumulative NB-UVB dose
(range, 8.0-16.6 J/cm2) to reach CR. The 6 patients in
the CR group were in stage IA (n = 2), IB (n = 2) and IIA (n = 2),
respectively. The 2 patients in the PR group were in stage IB (n =
1) and IIA (n = 1). There was no association between duration of
the disease and clinical response. In the follow-up period, 2
patients with CR remained free of disease and the other 4 patients
relaspsed. The mean time to relapse was 5 ± 2.2 months (range, 3-8
months). All the 4 patients who relapsed did not accept maintenance
therapy and responded to a second course of NB-UVB phototherapy.
Adverse effects
Minor erythema was seen in 3 patients. The erythema generally
disappeared in one or two days. The treatment was continued at a
dose decreased by 0.05 to 0.1 J/cm2. No other side
effects were observed.
Disscussion
Early-stage (stages IA, IB and IIA) mycosis fungoides has long been
treated with various therapies including topical potent steroids,
topical nitrogen mustard, topical carmustine, PUVA, BB-UVB,
electron-beam radiotherapy, interferon-α and retinoids. However,
each of these modalities is associated with various adverse
effects. In the past few years, there has been accumulated evidence
showing that NB-UVB phototherapy has the same effect but is safer
than the previous methods [2-12]. The mechanism of NB-UVB
phototherapy in MF is still not fully clear. Inhibition of the
antigen-presenting function of Langerhans cells, induction of
apoptosis of clonal T cells, and inhibition of proliferation of
clonal T cells by NB-UVB may be among the possible explanations
[5].
To our knowledge, this is the second study showing that a twice
weekly regimen of NB-UVB phototherapy is effective for early-stage
MF. In the present study, six out of 8 patients with early-stage MF
(stage IA 2, IB 2 and IIA 2) received a mean of 10.4 ± 5.8 weeks
(range, 6-20 weeks), 23.4 ± 8.5 irradiations (range, 11-35) and
12.6 ± 4.7 J/cm2 cumulative NB-UVB dose (range,
8.0-16.6 J/cm2) to achieve CR. The response rate in this
study is similar to that of previous reports [2, 3, 5-7, 11, 12].
Interestingly, in the present study, the mean cumulative NB-UVB
dose to achieve CR, 12.6 J/cm2, was relatively
lower than that in previous reports using a three times weekly
regimen, such as Hofer et al.’s 16.3 J/cm2, Gathers
et al.’s 96.7 J/cm2, Ghodsi et al.’s 26 J/cm2
[2, 4, 6]. This may indicate that the patients in this geographic
region were more sensitive to NB-UVB. In fact, minor erythema
appeared in 3 patients at an initial dose of 0.2 J/cm2.
It is not surprising that the treatment period to reach CR in the
present study is longer than those of previous reports, in which a
three to four times weekly regimen was administered [2, 3]. This
may be due to fewer treatment sessions in each week. But the number
of irradiations to CR in the present study is similar to that of
previous reports in which a three to four times weekly regimen was
administered [2, 3, 12]. It seems that even in lower doses, NB-UVB
phototherapy is equally effective for early-stage MF in cases where
the number of treatment sessions needed have been reached. Four out
of 6 patients relapsed because they did not accept maintenance
NB-UVB phototherapy as the other 2 patients did. This may also
explain the quicker period to relapse in the present study than
that in previous reports [2, 3, 5-7, 11, 12]. With regard to the
two patients who had PR, Case 8 was plaque type MF and Case 1 had
an extremely low CD4/CD8 ratio (0.52, normal range is 1.2-1.8).
Similar to previous reports, the adverse effects of NB-UVB
phototherapy were slight in the present study. Similar to a
previous report, the responses to NB-UVB phototherapy among
patients with IA, IB and IIA did not tend to differ from each other
in the present study [7].
In summary, our findings further extend previous observations
that NB-UVB phototherapy is an effective and well-tolerated
treatment option for early stage MF, even in a twice weekly
regimen.
Acknowledgements
This work was supported in part by a grant from China Medical Board
(#00-734), a grant from the National Natural Science Foundation of
China (No. 30400389), and the Program for Innovative
Research Team in University (IRT0760) and a fund (20060159014) from
the Ministry of Education of China. Conflict of interest: none.
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