Narrowband UVB phototherapy for early-stage mycosis fungoides: evaluation of clinical and histopathological changes

Background Early‐stage (IA, IB, IIA) mycosis fungoides (MF) has long been treated with various agents including topical potent steroids, nitrogen mustard, carmustine, oral psoralen plus UVA (PUVA), broadband UVB, electron‐beam radiotherapy, interferon‐α and retinoids. However, each of these modalities is associated with various side‐effects. Narrowband UVB (NB‐UVB) therapy has the same effect but is safer to use than the other methods. Objective Our purpose in this prospective study was to determine the effects of NB‐UVB in early‐stage MF both clinically and histopathologically. Materials and methods Twenty‐three patients (20 men, three women, aged 27–78 years) with clinically and histologically confirmed MF were enrolled. Patients received NB‐UVB therapy three times a week. Clinical and histological responses, cumulative doses, total number of treatments, side‐effects and duration of remission period were noted. Results Six patients had stage IA MF, 15 patients stage IB and two patients stage IIA. Eighteen patients had patch stage and five patients had plaque stage histopathologically. All of the patients in the patch group had a complete response (CR). In the plaque group, three patients (60%) had a CR and two (40%) had partial (PR) or no clinical response (NR). The clinical response between patch and plaque groups was statistically significant. Regarding the histopathological findings, 17 (94.4%) had complete clearing and only one (5.6%) patient had a partial improvement in the patch group. In the plaque group, one (20%) patient had complete clearing and four (80%) patients had partial or no improvement. The difference between the two groups was statistically significant. In the patch group, the mean cumulative dose was 90.15 J/cm² and the mean number of treatments was 35.33. In the plaque group, the mean cumulative dose was 90.67 J/cm² and the mean total number of treatments was 39.40. The differences were not statistically significant, either between the mean cumulative dose or the mean number of treatments. The mean duration of follow‐up was 10.87 months (range 1–25 months). Only one of the patients had a relapse. Conclusions NB‐UVB therapy for patients with early‐stage MF is an effective and safe treatment with the effect lasting for months. We suggest that clinical clearance correlates with histological improvement except for patients in the plaque stage.     

窄谱中波紫外线治疗早期蕈样肉芽肿9例疗效观察

目的:观察窄谱中波紫外线(NB-UVB)治疗早期蕈样肉芽肿的疗效及不良反应。方法:使用NB-UVB照射治疗早期蕈样肉芽肿患者9例,初始照射剂量均定为0.5J/cm2。结果:9例患者中完全缓解5例,部分缓解2例,好转2例,有效率为78%。平均照射次数22次,平均累积照射剂量31.09J/cm2。不良反应主要为轻度红斑和瘙痒,其发生率为33%。结论:NB-UVB照射治疗早期蕈样肉芽肿疗效好,不良反应少,操作简便易行,为早期蕈样肉芽肿的治疗提供了一种有效的方法。     

Phototherapy of mycosis fungoides

Background/purpose: Among the primary cutaneous T‐cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow‐ and broadband UVB and 8‐methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.     

Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides

Combination therapy for mycosis fungoides (MF) has the potential to be synergistic, improve therapeutic efficacy and reduce toxicities. We present a patient with MF who improved on combination therapy with bexarotene and narrowband ultraviolet B (NB-UVB) therapy. The patient is an 81-year-old Caucasian male who initially presented with stage IB MF. After temporary improvement with NB-UVB phototherapy, he progressed to develop plaques and tumors. Psoralen and ultraviolet A therapy was contraindicated because of ophthalmologic disease. Addition of bexarotene 300 mg daily led to rapid clinical improvement in combination with NB-UVB. Interruption of NB-UVB during a prolonged hospitalization led to a clinical flare of lesions, despite continued treatment with bexarotene. Reinitiating NB-UVB was associated with clinical improvement. This report demonstrates that combination treatment with oral bexarotene and NB-UVB therapy may represent a safe alternative for the treatment of plaque-stage MF.     

Bcl‐2 expression in mycosis fungoides before and after PUVA therapy

PUVA is the first therapeutic choice in early stages of mycosis fungoides (MF). In this study the effect of PUVA on bcl‐2 expression in MF was assessed in 15 patients (three stage Ia and 12 stage Ib) and 10 controls. Two biopsies were taken from each patient before and after 24 sessions of PUVA therapy. Histopathological assessment and immunohistochemical staining for bcl‐2 was performed and showed positive bcl‐2 staining of lymphocytes in 53% of MF cases (8/15) before PUVA, with no statistically significant difference in the bcl‐2 level before and after PUVA therapy (P value 0.3). A statistically significant difference was found in the bcl‐2 level between control samples and MF patients' biopsies before (P value 0.02) and after PUVA therapy (P value 0.011). In conclusion, a lack of decline in the bcl‐2 level and the absence of clinical or histopathological correlation with the bcl‐2 level before and after PUVA therapy in MF patients suggest that PUVA‐induced apoptosis in MF cases may occur through pathways other than bcl‐2 inhibition.     

Local narrowband UVB phototherapy vs. local PUVA in the treatment of chronic hand eczema

BACKGROUND: Hand eczema is a chronic skin disorder characterized by a poor response to conventional therapies. Although local PUVA has been proven to be effective in the treatment of chronic hand eczema, little is known about the efficacy and safety of local narrowband UVB (TL-01) for this condition. The aim of our study was to compare the efficacy and safety of local narrowband UVB phototherapy with paint-PUVA in patients with chronic hand eczema of dry and dyshidrotic types unresponsive to conventional therapies. PATIENTS/METHODS: Fifteen patients (nine men and six women) with chronic hand eczema of dry and dyshidrotic types was included in this prospective, comparative study based on a left to right comparison pattern. The treatments were administered with local narrowband UVB irradiation on one hand and local paint-PUVA using 0.1% 8-methoxypsoralen gel on the other hand three times a week over a 9-week period. The NB-UVB irradiation was administered using a local NB-UVB system equipped with TL-01 lamps. The initial dose was 150 mJ/cm(2) for each patient. An increasing percentile dose schedule based on an increase of 20% was used in every session, until a final dose of 2000 mJ/cm(2) was reached. Evaluation of clinical scores was carried out every 3 weeks during the treatment period. RESULTS: Twelve of the 15 recruited patients completed the study. There was a statistically significant decrease in the mean clinical score at the third, sixth and nineth week in both groups. The difference in clinical response between the two treatment modalities was not statistically significant at the end of the 9-week treatment period. In the narrowband UVB-treated side, the tolerance of all the patients to the treatment was good all patients well-tolerated the treatment with the exception of mild xerosis that responded to topical emollients. CONCLUSION: Local narrowband UVB phototherapy regimen is as effective as paint-PUVA therapy in patients with chronic hand eczema of dry and dyshidrotic types.     

Treatment of pruritus in early‐stage hypopigmented mycosis fungoides with aprepitant

Pruritus is a symptom that significantly affects the patient's quality of life in cutaneous T cell lymphoma (CTCL). The most effective treatments are those that address the condition itself; however, it is often not possible to control this symptom. Lymphoma‐related pruritus normally becomes more severe as CTCL progresses, constituting an important factor for quality of life in these patients. Substance P is a neuromodulator which appears to play a key role in pruritus. Aprepitant is a neurokinin‐1 receptor antagonist affecting the substance P receptor. So far, several cases have been documented with an antipruritic response to the drug aprepitant in advanced‐stage mycosis fungoides (MF). In this paper, we describe an excellent response to aprepitant in a female patient with severe pruritus secondary to hypopigmented stage I MF. We would also like to stress the absence of nausea and vomiting of this combined therapy of interferon and aprepitant. Aprepitant could improve tolerance to interferon.     

Ultraviolet-B phototherapy is successful in Japanese patients with early-stage mycosis fungoides

UVB phototherapy is widely used for the treatment of psoriasis and atopic dermatitis, however, only limited reports evaluate its usefulness in the treatment of mycosis fungoides. We introduced UVB phototherapy to five patients with early-stage mycosis fungoides. All of them were classified as stage IB (erythematous stage), and none had obtained a satisfactory response to other therapies. After initial treatment with UVB phototherapy, all the patients obtained significant improvement in their skin lesions leaving pigmentary changes. After this satisfactory response was achieved, the same dose of UVB was administrated as a maintenance therapy with longer intervals between exposures. Histopathological examination of three patients revealed decreased numbers of inflammatory cells in both the epidermis and the dermis after the treatment. Immunohistochemical study showed that CD1a+/HLA-DR+ dendritic cells were present throughout the lesional epidermis before the treatment. In contrast, after the treatment, the dendritic cells in the epidermis were CD1a+/HLA-DR-. Although it remains unclear why only the expression of HLA-DR antigen was eliminated after treatment, we presume that this loss of HLA-DR antigen expression by epidermal Langerhans cells was, in part, responsible for the improvement of skin lesions. This preliminary study suggests that UVB phototherapy is an effective treatment for patients with early-stage mycosis fungoides.     

Paediatric psoriasis – narrowband UVB treatment

Narrowband UV‐B is a safe and efficacious option for the treatment of adult psoriasis. However, the use of this therapy has been limited in children due to its long‐term carcinogenic potential. It has proven to be an adequate alternative in patients whose condition is refractory to topical treatment. Aims To evaluate the efficacy and short‐term safety of narrowband UV‐B in the treatment of paediatric psoriasis, and to compare our results with those obtained in other studies on paediatric psoriasis. Materials and methods Over a period of 2 years and 4 months, we administered narrowband UV‐B to 20 children diagnosed with psoriasis that was refractory to topical therapy. The therapeutic response was measured using the Psoriasis Area and Severity Index (PASI). Results Between August 2005 and December 2007, 20 children received narrowband UV‐B. Their median age was 13 years (range, 5–17 years), and the median initial PASI score was 8.25 (2.7–22.2). A median of 28 (10–59) sessions was required to achieve clearance, reaching almost complete or total remission (median final PASI) in all but two patients. Six patients required a new therapeutic course because of relapse, and the mean duration of remission was 8 months (4–18). No patients experienced severe adverse events during therapy, and only one discontinued treatment, for unrelated reasons. Discussion and conclusion Narrowband UV‐B for the treatment of paediatric psoriasis has received little attention in the literature. This treatment has been limited in children because of its potential long‐term carcinogenic effects, and most information has been extrapolated from adults. Nevertheless, narrowband UV‐B phototherapy is an effective and well‐tolerated therapeutic alternative in paediatric patients with severe psoriasis.     

窄谱中波紫外线治疗早期蕈样肉芽肿的疗效观察

目的 探讨窄谱中波紫外线(NB-UVB)治疗早期蕈样肉芽肿(MF)的安全性及有效性.方法 19例患者中,男9例,女10例;年龄20～71岁,平均42.6岁,经组织病理检查证实为MF早期,临床分期ⅠA～ⅠB17例,ⅡA2例.每周NB-UVB照射2～3次,随访1～18个月.结果 13例完全缓解,5例部分缓解,1例无缓解.平均照射次数25.9次,平均累积照射剂量25.6J/cm².主要不良反应为红斑、瘙痒和色素沉着,患者均能耐受.结论 NB-UVB照射对早期MF疗效确切,不良反应较少.     

Efficacy of 8-methoxypsoralen vs. 5-methoxypsoralen plus ultraviolet A therapy in patients with mycosis fungoides

BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for early stage mycosis fungoides (MF). When 8-methoxypsoralen (8-MOP) is used in PUVA therapy, it often produces intolerance reactions such as nausea, vomiting and headache. OBJECTIVES: To investigate whether 5-methoxypsoralen (5-MOP) is a safe and effective alternative to 8-MOP in PUVA therapy for MF. METHODS: A retrospective database search and chart review was done to identify patients with MF who received PUVA with either 5-MOP or 8-MOP as initial monotherapy at our institution. Between 1990 and 2004, 14 patients [seven men and seven women; mean age 70 years, range 51-82; National Cancer Institute disease stages IA (n = 6) and IB (n = 8)] received 5-MOP, and 24 patients [21 men and three women; mean age 58 years, range 28-89; disease stages IA (n = 11), IB (n = 12) and IIB (n = 1)] received 8-MOP. RESULTS: Twelve of 14 patients (86%) in the 5-MOP group and 22 of 24 (92%) in the 8-MOP group had a complete response to PUVA. These two subgroups of complete responders did not differ significantly in terms of PUVA therapy duration, number of treatments or cumulative UVA dose. They also did not differ significantly in terms of relapse-free rate [8% (one of 12) vs. 23% (five of 22)] or time to relapse [17 months (range 4-31) vs. 14 months (range 4-33)]. Moreover, PUVA maintenance therapy with either 5-MOP or 8-MOP in a subset of patients [26% (nine of 34)] did not affect long-term relapse-free status either. CONCLUSIONS: 5-MOP and 8-MOP have comparable therapeutic efficacy when used in PUVA therapy for MF.     

PUVA plus interferon α2b in the treatment of advanced or refractory to PUVA early stage mycosis fungoides: a case series

Background The combination of PUVA with variable doses of systemically administered interferon α2b (IFN‐α2b) reduces the number of PUVA treatments and the dose of IFN‐α2b required to produce remission in all mycosis fungoides (MF) stages. Objectives To evaluate the efficacy of the combination of PUVA and IFN‐α2b in patients with late stage or refractory to treatment early stage MF. Methods The combination of PUVA three times weekly and IFN‐α2b 2–5 MU three times weekly was retrospectively reviewed in 22 patients. Kaplan–Meyer method and log‐rank test was used for statistical analysis. Results Twenty‐two patients were analysed, seven with refractory to PUVA early stage MF, seven with tumour stage, five with erythrodermic MF and three with Sézary syndrome (SS). The overall response rate (complete or partial response) was 68%, including 10 complete responses (CR) (45%) and five partial responses (PR) (23%). Significantly, more patients of the early stage group achieved CR compared with the advanced stage group (86% vs. 27%, P = 0.03). Within the advanced stage group, CR rates were 14% vs. 37% in stage IIB and III/SS patients respectively, but the difference was not statistically significant. Patients with early stage disease had a 2‐year PFS of 100% vs. 27% for the advanced stage group (P < 0.001). Sustained remissions (>2 years) were achieved in five out of six complete responders in the early stage group of patients. Conclusion This combination of IFN‐α2b and PUVA is an effective and safe treatment for refractory to treatment early stage MF patients as well as treatment‐naïve advanced stage patients. Its efficacy is more pronounced in the former patient group.     

Juvenile mycosis fungoides with large‐cell transformation: Successful treatment with psoralen with ultraviolet A light,interferon‐alfa,and localized radiation

Mycosis fungoides with large‐cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large‐cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large‐cell transformation shortly after administration of psoralen plus ultraviolet A, interferon‐alfa, and localized radiation.     

Broad band UVA: a possible reliable alternative to PUVA in the treatment of early-stage mycosis fungoides

UVA1 phototherapy was found to induce marked improvement in skin lesions of patients with stages IA and IB mycosis fungoides (MF). Broad band UVA (BB‐UVA) is composed of 80.1% UVA1, with similar mechanisms of action. Our aim was to evaluate the efficacy of BB‐UVA in the treatment of early‐stage MF. Thirty patients with early stage MF were included. They were divided into two equal groups receiving either BB‐UVA at 20 J/cm2/ session or PUVA three times/week for 40 sessions. Clinical and histopathological evaluations were performed before and after therapy in addition to immunohistochemical measurement of CD4+ cells and Bcl‐2. Patients were followed up for an average duration of 36 months. Comparable clinical and histopathological improvement was noted in MF patients in both groups. Clinical improvement graded ‘Excellent’ was achieved in 33% of patients in the BB‐UVA versus 13.3% in the psoralen and UVA (PUVA) group. Long‐term follow‐up indicated superiority of BB‐UVA over PUVA. BB‐UVA group showed a more rapid clearance rate, shorter time to achieve complete clearance, a longer disease‐free interval and lower relapse rate. The use of BB‐UVA in the treatment of early‐stage MF is comparable or even superior to PUVA regarding efficacy and remission periods.     

Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study

BACKGROUND: Psoralen ultraviolet A (PUVA) is a widely used first-line therapy for treatment of early cutaneous T-cell lymphoma. Narrow band UVB (UVB-NB) (311 nm) has been recently introduced as another effective line of treatment. It is postulated that the efficacy of UVB-NB could be enhanced by addition of psoralen. AIM: The aim of the present work was to compare the clinical and histopathologic efficacy of PUVA and UVB-NB in the treatment of early-stage MF (stages IA, IB and IIA), and to evaluate whether psoralen adds to the efficacy of UVB-NB or not. Patients and Methods: Twenty patients (stage IA, IB or IIA) were divided into two equal groups: group I received UVB-NB on the right body half vs. PUVA on the left side of the body for 48 sessions, and group II received PUVB-NB on the right side of the body vs. PUVA on the left side for 36 sessions. The sessions were administered three times weekly. RESULTS: In group I, almost equal results were obtained on both sides, i.e., UVB-NB and PUVA were equally effective in the treatment of early stages of MF, both clinically and histopathologically. In group II, PUVB-NB was found to be as effective as conventional PUVA in the treatment of early-stage mycosis fungoides, also on both clinical and histopathological grounds. CONCLUSION: UVB-NB phototherapy should be included among the initial therapeutic options of mycosis fungoides in view of its efficacy, convenience, and likelihood of fewer long-term adverse effects. Addition of psoralen does not seem to enhance its therapeutic efficacy.     

光化学疗法联合干扰素治疗蕈样肉芽肿30例

对30例蕈样肉芽肿(MF)患者(大多数属早期病程),用光化学疗法(PUVA)及小剂量α-干扰素进行联合治疗,PUVA的平均治疗剂量为102.8J/cm2,α-干扰素的平均治疗量为6×106U/周。治疗后总有效率为93.3%,其中完全缓解率为36.7%,无严重不良反应。结果证明PUVA联合干扰素治疗MF是安全有效的。     

A retrospective review of 20% vs. 10% incremental narrowband UVB regimens to treat psoriasis in skin phototypes III–V Koreans

Background: The optimal incremental dose regimen of narrowband UVB (NBUVB) phototherapy that will provide maximal efficacy and safety has not been determined for patients with brown skin and psoriasis.
Objective: To compare 20% and 10% incremental dose regimens of NBUVB phototherapy with respect to efficacy and safety in Korean patients with brown skin and psoriasis whose Fitzpatrick skin phototypes (SPT) are III–V.
Method: A retrospective study was designed to compare the 20% and 10% incremental dose groups with respect to the number of sessions, duration of treatment, maximum dose, cumulative dose until response, and adverse effects.
Results: The mean number of sessions was significantly lower, the duration of treatment was significantly shorter, and the maximum dose was significantly higher in the 20% incremental dose group. The cumulative dose was not significantly different between the two groups, and there was no statistically significant difference between the groups with respect to the percentage of total adverse effects.
Conclusion: Use of a 20% incremental dose regimen could be advantageous over a 10% incremental dose regimen in patients with brown skin and psoriasis because of a faster treatment response and higher efficacy without a significant increase in the risk of adverse effects.