Narrowband UVB treatment of progressive macular hypomelanosis
Journal of the American Academy of Dermatology
Moon-Bum Kim, MD, PhD, Gun-Wook Kim, MD, Hyun-Ho Cho, MD, Hyun-Je Park, MD,
Hoon-Soo Kim, MD, Su-Han Kim, MD, Byung-Soo Kim, MD, PhD, and Hyun-Chang Ko, MD Busan, Korea
INTRODUCTION
Progressive macular hypomelanosis (PMH) is an acquired hypopigmentation disorder that causes cosmetic problems.
It is characterized by hypopigmented macules, mostly on the trunk and upper extremities, without a previous history of inflammation, infection, or injury.
Skin lesions are symmetrically distributed, ill defined, discrete, or confluent macules.
On histological examination, no significant difference is observed between lesional and normal skin, except for a subtle decrease in melanin pigment in lesional epidermis.
PMH is diagnosed clinically after exclusion of other dermatoses with hypopigmentation , such as pityriasis versicolor, pityriasis alba, leprosy, and mycosis fungoides.
Although the pathogenesis of PMH is unknown Westerhof et al were able to demonstrate a relationship between hypopigmented macules and the bacterium Propionibacterium acnes.
No current standard treatment has been effective in producing consistent repigmentation.
Narrowbandeultraviolet B (NB-UVB) therapy in the treatment of PMH is not well documented; only one case study of the successful treatment of PMH using NB-UVB therapy has been reported.
However, no prospective study of the effect of NB-UVB in the treatment of PMH has been conducted. In view of the paucity of experience with NB-UVB therapy for PMH, we aimed to investigate the therapeutic efficacy of NB-UVB phototherapy, as well as the clinical features of PMH in Koreans.
METHODS
Patients
Patients who received treatment for PMH at Pusan National University Hospital (PNUH), Busan, South Korea, from January 2006 to September 2008 were enrolled in this study.
Diagnosis of PMH was made after evidence of other cutaneous diseases manifesting as hypopigmented macules had been excluded through potassium hydroxide mounts of skin scrapings, Wood’s light test, and biopsy.
To evaluate the efficacy of phototherapy, patients who received regular treatment (at least 6 times) with NB-UVB irradiation were included.
Patients were excluded if they had a history of any previous treatment for PMH at least 3 months prior to the start of the study or if they were sensitive to sunlight.
The study was approved by the institutional ethics committee, and the patients provided informed consent.
Treatment protocol
In our study , we used a UV7001K cabinet (Waldmann Medizintechnik) to treat patients with macular hypomelanosis.
Since most patients had Fitzpatrick skin types III, IV, or V, the minimal erythema dose (MED) was not calculated.
An initial dose of 300 to 350 mJ/cm2 was started in all patients and treatment was administered once or twice weekly. The dose was increased by approximately 20% on each subsequent visit until the optimal dose for obtaining minimal erythema in lesions was achieved.
If a patient experienced symptomatic erythema, burning sensation, or blistering, the irradiation treatment was either omitted or the dose was decreased by 20%.
Assessment
All of the patients were examined by the same dermatologist and photographs were taken at each visit to document the extent of repigmentation.
Response to treatment was assessed objectively by comparison of photographs taken before and after therapy. According to the extent of repigmentation relative to the baseline status, patients who responded to NB-UVB therapy were classified into Group A (>90% repigmentation), Group B (50%-90% repigmentation), and Group C (<50% repigmentation).
In addition, subjective assessment was undertaken by patients and scored on a 4-point scale as ++: satisfactory, +: improved, 0: no change, or - : worsening.
At each visit, patients filled in questionnaires on compliance and any side effects , including burning, dryness, stinging, and itching.
Statistical analysis
Statistical methods, including the Wilcoxon ranksum test and Kruskal-Wallis test, were employed to evaluate the relationship between treatment response and duration of disease, number of treatments, duration of treatment, and cumulative dose.
In addition, we performed logistic regression analysis to determine the predictors of recurrence.
All analyses were performed by using SPSS software (version 15.0; SPSS Inc, Chicago, IL), and a P value less than .05 was considered to be significant.
RESULTS
Baseline characteristics
A total of 23 patients with PMH were treated with NB-UVB. The demographics and baseline characteristics of
the 23 patients are presented in Table I.
Seven patients (31.0%) were men and 16 (69.0%) were women; their ages ranged from 24 to 39 years, with a mean age of 28.3 years.
The duration of disease ranged from 1 month to 10 years, with a mean duration of 42.7 months.
The lower back was the most commonly involved area (91.3%, n = 21), followed by the abdomen (73.9%, n = 17) and upper back (34.7%, n = 8).
19 patients had PMH lesions on 2 or more areas of trunk.
Only one patient had a familial history of PMH.
Assessment of repigmentation
Six patients were lost to follow-up before the completion of 6 treatments, leaving 17 patients who were eligible for analysis of the effect of NB-UVB therapy.
Although all of the patients who withdrew received 3 or more treatments with NB-UVB therapy, none complained of any side effects on each subsequent visit, and all 6 of these patients abruptly stopped treatment for personal reasons prior to completion of the study.
Among the remaining 17 patients, one patient received 8 treatments with NB-UVBand discontinued treatment because of dissatisfaction with the repigmentation. In this patient, the duration of PMH was 12 years and no objective repigmentation was observed.
Sixteen patients (94.1%) were observed with repigmentation of PMH lesions; however, the degree of repigmentation varied.
In the 16 patients with repigmentation,the mean number and cumulative UVB dose of phototherapy was 20.3 times and 13,919 mJ/cm2. In addition, the mean number of treatments required for the first repigmentation was 4.8.
Of these 16 patients, 9 (56.2%) had more than 90% repigmentation (Group A), 4 (25.0%) achieved 50% to 90% repigmentation (Group B), and 3 (18.8%) had less than 50% repigmentation (Group C) (Table II).
However, no significant differences in duration of disease, number of treatments, duration of treatment, or cumulative dose were observed among the groups (P >.05).
In addition, when evaluated by subjective assessment, all patients showed improvement. The detailed results of treatment for each patient were shown in Table III.
Up to the present time (13.2 ± 8.2 months of follow-up), no recurrence has been detected in 11 of the 16 patients (68.7%). However, in the remaining 5 patients (31.0%), hypopigmented patches reappeared at the same location within a mean period of 6 months after the cessation of NB-UVB therapy (Table IV).
The duration of disease was significantly shorter in the recurrence group than in the stable group (P < 0.05).
According to logistic regression analysis, the number of treatments, duration of treatment, and cumulative UVB were not predictive of recurrence.
The best responses (n = 10, 62.5%) were achieved for lesions located on the abdomen, compared with the back.
In the remaining 4 patients, no difference was observed according to location.
Adverse effects included a transient burning sensation in 7 patients (41.0%) and mild pruritus in 5 patients (29.0%).
DISCUSSION
Although several reports over the past 2 decades have documented PMH, it is not a well-recognized entity in clinical practice.
The clinical features of PMH are characterized by symmetrically distributed hypopigmented macules, predominantly located on the trunk and upper extremities.
Although PMH is usually asymptomatic, patients complain of the irregular appearance and progressive nature of the disease.
However, little information is available on the effectiveness of any treatment.
We review the clinical features of PMH in Koreans and then discuss the efficacy and possible mechanism of action of NBUVB therapy in the management of PMH.
PMH is a relatively common hypopigmentation disorder in young adults, particularly in women.
In a recently published study, Hwang et al reported that of 20 Korean patients, the proportion of males to females was 1:3, and the mean age at onset was 21.1 years.
Similarly, we found that the average age of the 23patients recruited in this study was 28.3 years and that there were 7 men and 16 women between the ages of 24 and 39 years.
Although the community prevalence of PMH is unknown, on the basis of our experience, it does not appear to be a rare condition.
Not all patients recognize PMH as a specific disease in need of treatment; therefore we assume that the total number of individuals with PMH is greater than the number who actually visit a hospital.
Reports related to the treatment of PMH are limited, with very few reports published in the literature to date.
In the only prospective study on the treatment of PMH, Relyveld et al reported that antimicrobial therapy combined with UVA irradiation was more effective than anti-inflammatory therapy in combination with UVA. They suggested that the therapeutic success of this combination therapy was probably related to the elimination of Propionibacterium acnes.
Although we acknowledge the findngs and results of Relyveld et al, it should be emphasized that PMH is usually an extensive disease involving the trunk; therefore topical application of antimicrobial agents is an inconvenient method of treatment.
According to a report published in 2007, NB-UVB therapy twice a week for 20 sessions is an efficient treatment for patients with PMH.
In addition, Relyveld et al have suggested that even though UVA radiation is not the solitary factor responsible for
treatment success, it results in faster repigmentation.
We speculated that UVB might also be as effective as UVA irradiation.
Because NB-UVB therapy is suitable for the treatment of extensive disease and it avoids the side effects associated with systemic medications, we have recommended it as the treatment of choice for young patients.
In our study, NB-UVB therapy alone was used successfully in 9 of 16 patients (56.2%) who showed more than 90% repigmentation.
We found that 13 of 16 patients (81.3%) experienced at least 50% repigmentation.
No apparent association was observed among the outcome groups in terms of duration of disease, number of treatments, duration of treatment, or cumulative dose.
Although we assumed that a longer duration of disease would be a factor associated with lower response to treatment, the actual results were contrary to what we expected.
The only factor that was found to influence the response to treatment was the location of lesions.
In our study, the abdomen showed better response than the back; however, the reason for this anatomical variation remains unclear.
Relapse was observed within 6 months after treatment cessation in 5 of 16 patients (31.3%).
On the basis of our results, we suggest 4 important points that should be considered before recommending NB-UVB therapy for PMH.
First, because an initial response was typically observed after a minimum of 4 to 5 treatments, at least 5 treatments should be administered before undertaking an initial evaluation of repigmentation.
Second, patients who had more than 90% repigmentation were treated with an average 20.9 sessions in order to achieve maximal repigmentation. Therefore this result indicates that treatment must be continued for approximately 20 sessions in order to achieve full repigmentation.
Third, patients who experienced a recurrence of PMH after treatment had a shorter duration of disease; therefore a cautious approach is needed when treating such patients.
Finally, the dose was subsequently increased by 10% to 20% per session, and treatments were performed once or twice weekly; however, we did not standardize the therapeutic interval or dose.
Clinical improvement of PMH after NB-UVB phototherapy is achieved by a gradual darkening of lesions, which in the best instances may become indistinguishable from normal skin.
This is in contrast to the pattern of repigmentation seen in vitiligo, which typically occurs via the development of perifollicular islands of new pigment
Fig 1. Complete repigmentation over the trunk in a 29-year-old man who received treatment
twice a week for 2 months.
Before treatment (A, C)
and after treatment (B, D).
Fig 2. Marked repigmentation over the trunk in a 26-year-old man who received treatment
twice a week for 4 months.
Before treatment (A, C)
and after treatment (B, D).
The mechanism of action of NB-UVB on PMH has yet to be elucidated.
Several theories have been proposed with regard to the etiology of PMH, including genetic factors, P acnes, and the process of melanization.
Among these, we approached from the perspective of a failure of melanization and obtained good results with NB-UVB therapy.
Kumarashinghe et al studied the ultrastructural features of melanocytes in Asian patients with PMH and suggested a functional defect in pigmentation or problems in melanin distribution.
Furthermore, Relyveld et al showed a decrease in the melanization of melanosomes in PMH, contributing to changes in the maturation, size, number, and distribution of melanosomes.
Although there is controversy with regard to the leading main cause of PMH, the eventual outcome in all cases is the failure of melanization.
We postulate that NB-UVB therapy prevents the final phenomenon, as has been demonstrated in previous studies on vitiligo.
UVB radiation is known to be an important factor in promoting the synthesis of melanin pigmentation in the skin.
Similar to PUVA therapy, NB-UVB may exert its effects by stabilization of the depigmentation process and stimulation of residual melanocytes.
In addition, compared with UVA, NB-UVB therapy has excellent antibacterial effects that inhibit growth of propionibacteria and Micrococcaceae bacteria.
There are several limitations to our study.
These include a small number of subjects examined and the fact that it was an uncontrolled and nonedoubleblind study.
Because of a higher success rate in Asian patients, skin color could be a factor affecting repigmentation in PMH.
There is currently no standard protocol for NB-UVB treatment and the treatment time differs for each patient.
Nevertheless, as mentioned above, NB-UVB monotherapy provides comparatively consistent results with minimal adverse effects.
In conclusion, NB-UVB phototherapy appears to be effective for patients with PMH.
Application of treatment is easy and convenient for both doctors and patients.
Hypopigmentation will be resolved after a couple of months, providing a good cosmetic result, as well as higher patient satisfaction.
In the future, large-scale, double-blind studies with controls should be performed to facilitate the standardization of NB-UVB therapy for PMH.
