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Narrow-band ultraviolet B phototherapy for early stage mycosis fungoides

European Journal of Dermatology. Volume 18, Numéro 6, 660-2, Novembre-Décembre 2008, Therapy

DOI : 10.1684/ejd.2008.0515

Summary

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.

Illustrations

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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