CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Blue vitiligo following intralesional injection of psoralen combined with ultraviolet B radiation therapy J. A. Zhang, J. B. Yu, Y. Lv and P. Thapa Department of Dermatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China doi:10.1111/ced.12537
Summary
A 23-year-old Chinese man presented with a 16-month history of white patches on his abdomen and neck. He had previously received an intralesional injection of psoralen along with narrowband psoralen ultraviolet B radiation (PUVB) therapy. Blue macules had appeared in and around the injection sites 1 week later. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches. Histological examination revealed an absence of epidermal melanocytes and pigment in the basal layer, as well as deposition of melanophages between collagen bundles or surrounding blood vessels and appendages in the middle and lower parts of the dermis. A diagnosis of blue vitiligo was made. The blue colour faded gradually over time. Our case provides direct evidence to support the previous surmise that PUVB can contribute to blue vitiligo. To our knowledge, this is only the fourth reported case of blue vitiligo in the English literature.
Vitiligo is a common depigmenting skin disease of unknown aetiology, characterized by acquired hypomelanosis of the skin and hair, and the development of white macules related to the selective loss of melanocytes.1 Clinically, vitiligo has some rare subtypes, including trichrome vitiligo,2 inflammatory vitiligo with raised borders,3 follicular vitiligo4 and blue vitiligo.5–7 Blue vitiligo, first described by Ivker et al. in 1994,5 is an extremely rare, unique variant of vitiligo, characterized clinically by blue–grey appearance of the skin, and histologically by the presence of numerous dermal melanophages and the absence of epidermal melanocytes.7 To date, there have been only three reported cases of blue vitiligo.5–7 Although previous reports have attributed this rare condition to psoralen plus ultraviolet A radiation (PUVA) therapy, there is no direct evidence to support this speculation. We report a case of blue vitiligo that developed in and Correspondence: Dr Jian Bin Yu, Department of Dermatology, First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou City, Henan Province 450052, China E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 June 2014
ª 2014 British Association of Dermatologists
around injection sites following intralesional injection of psoralen combined with ultraviolet B radiation (PUVB) therapy in a patient with vitiligo, which resolved gradually after discontinuation of the combination therapy.
Report A 23-year-old Chinese man presented with a 16month history of white patches on his abdomen and neck. A band-like white lesion was initially noted on the patient’s lower right abdomen, which gradually expanded to involve his neck, chest and left leg. He was diagnosed with vitiligo at a small clinic, and he received intralesional injection of psoralen (not recognized as standard treatment in China) plus narrowband (NB)-UVB radiation therapy. Three to four hours after this combination treatment, red macules and scattered blisters developed within the white patches. One week later, blue macules appeared in and around the injection sites, within the original white patches. All treatments were discontinued, and the patient was admitted to our hospital. On physical examination, multiple, well-defined depigmented patches were seen, involving the patient’s
Clinical and Experimental Dermatology (2015) 40, pp301–304
301
Blue vitiligo following PUVB therapy J. Zhang et al.
lower right abdomen, neck, chest and left leg. Pigmentation was visible at the edges of some lesions. There were no white hairs in the lesions. The white lesion on the lower right abdomen was band-like, and perifollicular pigment retention was noted within the lesions. The lesions on the neck and left leg had an irregular shape. Blue macules with an unclear boundary and variation in shade were visible over the depigmented patches on the patient’s lower right abdomen, neck and chest (Fig. 1a,b). No obvious abnormalities were detected in organs other than the skin. The vitiliginous lesions had been stable over the past 6 months and did not vary seasonally. There was no similar condition in the patient’s family. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches (Fig. 1c,d). Histological examination of the blue patch on the lower right abdomen revealed an absence of epidermal melanocytes and pigment in the basal layer, scattered infiltration of inflammatory cells surrounding blood vessels in the upper part of the dermis (Fig. 2a), and deposition of melanophages between collagen bundles, or surrounding blood vessels and appendages in the middle and lower part of the dermis (Fig. 2b). Immunohistochemistry stains revealed Melan-Apositive spindle or dendritic cells in the dermis (Fig. 2c,d).
Based on the above findings, a diagnosis of blue vitiligo was made. The patient was treated with several medications, including oral vitiligo pills, topical halometasone cream and tacrolimus ointment, and the blue colour faded gradually over time. Blue vitiligo is extremely rare, and there have been only three cases reported previously in the literature: a 42-year-old woman,5 a 47-year-old man6 and a 23year-old woman.7 Therefore, the present case represents only the fourth reported case of this rare disease. Table 1 shows the clinical features of blue vitiligo in the three previously reported cases and our case. Compared with the previously reported cases, the present case has two unique features. First, blue– grey spots appeared after intralesional injection of psoralen combined with UVB radiation therapy, whereas in the previous reports, psoralen was given systemically.5,6 Second, the blue–grey spots were consistently distributed in and around the injection sites, and this observation has not been reported previously. Thus, our case provides more convincing evidence to support the previous speculation that psoralen plus UV phototherapy can contribute to blue vitiligo. The mechanism behind the appearance of blue–grey macules is currently still unclear. Ivker et al.5 believed that dermal pigmentation, resulting from postinflammatory hyperpigmentation, caused blue skin due to
(a)
(b)
(c)
(d)
Figure 1 (a,b) Blue–grey macules over the depigmented patches on (a) neck, chest and (b) lower right abdomen. (c,d) Dermoscopy revealed blue patches and reticular telangiectasia within the white patches.
302
Clinical and Experimental Dermatology (2015) 40, pp301–304
ª 2014 British Association of Dermatologists
Blue vitiligo following PUVB therapy J. Zhang et al.
(a)
(b)
(c)
(d)
Figure 2 (a) In the blue patch, there was an absence of epidermal melanocytes and pigment in the basal layer, with a scattered infiltra-
tion of inflammatory cells surrounding blood vessels in the upper part of the dermis (Melan-A, original magnification 9 200), and (b) deposition of melanophages between collagen bundles, or surrounding blood vessels and appendages in the middle and lower parts of the dermis (haematoxylin and eosin, original magnification 9 200). Melan-A-positive spindle or dendritic cells were found in the dermis. Original magnification (c) 9 100; (d) 9 200. Table 1 Clinical features of blue vitiligo in four reported cases. Duration of lesions
Previous treatment
Onset of blue discolouration
42
6 weeks
PUVA
Unknown
M
47
2 years
NB-UVB
3
F
23
1 month
None
1 month after NBUVB treatment Unknown
4
M
23
16 months
Intralesional injection of psoralen plus NB-UVB
1 week after psoralen injection
Patient
Sex
1
M
2
Age, years
Lesion sites Forearms and calves Scalp, arms, legs and trunk Forearm, hands and areola Neck, abdomen, chest and leg
Sites of blue skin
Reference
Forearms
Ivkeret et al.5
Legs and trunk Forearm
Hamzavi et al.6
Neck and abdomen
Chandrashekar et al.7 Present case
NB-UVB, narrowband ultraviolet B radiation; PUVA, psoralen plus ultraviolet A radiation.
the Tyndall effect. However, the source of the dermal pigmented particles remains unclear, and they might not originate from the epidermis, owing to the lack of
ª 2014 British Association of Dermatologists
epidermal melanocytes in patients with vitiligo.8 We found Melan-A-positive spindle or dendritic cells in the dermis of our patient’s biopsy. Furthermore, previous
Clinical and Experimental Dermatology (2015) 40, pp301–304
303
Blue vitiligo following PUVB therapy J. Zhang et al.
studies showed that both melanocytes and melanocyte stem cells exist in the dermis.9 Thus, we believe that the blue macules are associated with the melanin of dermal melanocytes, which might be activated by intralesional injection of psoralen plus NB-UVB radiation therapy, or might be induced and differentiated from melanocyte stem cells. Future studies are required to test these theories. Clinically, blue vitiligo should be distinguished from blue naevus with overlying vitiligo,10 as depigmented patches and blue macules can be found in lesions of both conditions. In the former, depigmented patches appear first, followed by the presence of blue macules within the lesions, whereas with the latter, the blue macules are already existing when the depigmented patches develop. In the current case, the blue–grey colour faded gradually over time. This observation is consistent with the case reported by Ivker et al.,5 in which the blue colour vanished 4 months later. Therefore, we speculate that blue vitiligo might disappear spontaneously when the triggering factor (i.e., medications or phototherapy) does not exist. This is probably because dermal melanophages can gradually excrete melanin from the body. Thus, treatments for blue vitiligo should focus on the management of depigmented patches, and no special treatments are required for this unique vitiligo. In conclusion, we document a rare case of blue vitiligo that developed in and around injection sites following intralesional injection of psoralen combined with UVB radiation therapy in a patient with vitiligo. Because of the extreme rarity of the disease, awareness and knowledge of this condition by dermatologists should be emphasized. As blue vitiligo can resolve spontaneously after the absence of triggering factor(s), no special treatments are required for this rare variant of vitiligo.
Learning points ● Blue vitiligo is an extremely rare, unique vari-
ant of vitiligo, characterized clinically by a blue– grey appearance of the skin, and histologically by the presence of numerous dermal melanophages and the absence of epidermal melanocytes. ● Blue vitiligo was first described by Ivker et al. in 1994. ● There have only been three cases reported previously in the literature.
304
Clinical and Experimental Dermatology (2015) 40, pp301–304
● Blue vitiligo occurs mainly in young and mid-
dle-aged adults. ● The blue discolouration of blue vitiligo often
develops in typical vitiliginous lesions after phototherapy. ● Blue–grey spots exist only in some of the lesions and vary in shade, with an irregular shape and an unclear boundary with the surrounding typical vitiliginous lesions. ● The blue–grey spots tend to subside gradually, and no special treatment is required.
References 1 Alikhan A, Felsten LM, Daly M et al. Vitiligo: a comprehensive overview. Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol 2011; 65: 473–91. 2 Hann SK, Kim YS, Yoo JH et al. Clinical and histopathologic characteristics of trichrome vitiligo. J Am Acad Dermatol 2000; 42: 589–96. 3 Tanioka M, Takahashi K, Miyachi YI. Narrowband ultraviolet b phototherapy for inflammatory vitiligo with raised borders associated with sjogren’s syndrome. Clin Exp Dermatol 2009; 34: 418–20. 4 Ezzedine K, Amazan E, Seneschal J et al. Follicular vitiligo: a new form of vitiligo. Pigment Cell Melanoma Res 2012; 25: 527–9. 5 Ivker R, Goldaber M, Buchness MR. Blue vitiligo. J Am Acad Dermatol 1994; 30: 829–31. 6 Hamzavi I, Shiff N, Martinka M et al. Spectroscopic assessment of dermal melanin using blue vitiligo as an in vivo model. Photodermatol Photoimmunol Photomed 2006; 22: 46–51. 7 Chandrashekar L. Dermatoscopy of blue vitiligo. Clin Exp Dermatol 2009; 34: e125–6. 8 Le Poole IC, van den Wijngaard RM, Westerhof W et al. Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation. J Invest Dermatol 1993; 100: 816–22. 9 Ahn JJ, Lee JH, Shin MK et al. Two cases of vitiligo developed on the persisting dermal melanocytosis: is there a difference between epidermal melanocytes and dermal melanocytes? Ann Dermatol 2013; 25: 226–8. 10 Wang P, Cheng Y, Yang H et al. Acquired patch-type blue nevus with overlying vitiligo: a case report. Int J Dermatol 2012; 51: 568–70.
ª 2014 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Blue vitiligo following intralesional injection of psoralen combined with ultraviolet B radiation therapy J. A. Zhang, J. B. Yu, Y. Lv and P. Thapa Department of Dermatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China doi:10.1111/ced.12537
Summary
A 23-year-old Chinese man presented with a 16-month history of white patches on his abdomen and neck. He had previously received an intralesional injection of psoralen along with narrowband psoralen ultraviolet B radiation (PUVB) therapy. Blue macules had appeared in and around the injection sites 1 week later. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches. Histological examination revealed an absence of epidermal melanocytes and pigment in the basal layer, as well as deposition of melanophages between collagen bundles or surrounding blood vessels and appendages in the middle and lower parts of the dermis. A diagnosis of blue vitiligo was made. The blue colour faded gradually over time. Our case provides direct evidence to support the previous surmise that PUVB can contribute to blue vitiligo. To our knowledge, this is only the fourth reported case of blue vitiligo in the English literature.
Vitiligo is a common depigmenting skin disease of unknown aetiology, characterized by acquired hypomelanosis of the skin and hair, and the development of white macules related to the selective loss of melanocytes.1 Clinically, vitiligo has some rare subtypes, including trichrome vitiligo,2 inflammatory vitiligo with raised borders,3 follicular vitiligo4 and blue vitiligo.5–7 Blue vitiligo, first described by Ivker et al. in 1994,5 is an extremely rare, unique variant of vitiligo, characterized clinically by blue–grey appearance of the skin, and histologically by the presence of numerous dermal melanophages and the absence of epidermal melanocytes.7 To date, there have been only three reported cases of blue vitiligo.5–7 Although previous reports have attributed this rare condition to psoralen plus ultraviolet A radiation (PUVA) therapy, there is no direct evidence to support this speculation. We report a case of blue vitiligo that developed in and Correspondence: Dr Jian Bin Yu, Department of Dermatology, First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou City, Henan Province 450052, China E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 4 June 2014
ª 2014 British Association of Dermatologists
around injection sites following intralesional injection of psoralen combined with ultraviolet B radiation (PUVB) therapy in a patient with vitiligo, which resolved gradually after discontinuation of the combination therapy.
Report A 23-year-old Chinese man presented with a 16month history of white patches on his abdomen and neck. A band-like white lesion was initially noted on the patient’s lower right abdomen, which gradually expanded to involve his neck, chest and left leg. He was diagnosed with vitiligo at a small clinic, and he received intralesional injection of psoralen (not recognized as standard treatment in China) plus narrowband (NB)-UVB radiation therapy. Three to four hours after this combination treatment, red macules and scattered blisters developed within the white patches. One week later, blue macules appeared in and around the injection sites, within the original white patches. All treatments were discontinued, and the patient was admitted to our hospital. On physical examination, multiple, well-defined depigmented patches were seen, involving the patient’s
Clinical and Experimental Dermatology (2015) 40, pp301–304
301
Blue vitiligo following PUVB therapy J. Zhang et al.
lower right abdomen, neck, chest and left leg. Pigmentation was visible at the edges of some lesions. There were no white hairs in the lesions. The white lesion on the lower right abdomen was band-like, and perifollicular pigment retention was noted within the lesions. The lesions on the neck and left leg had an irregular shape. Blue macules with an unclear boundary and variation in shade were visible over the depigmented patches on the patient’s lower right abdomen, neck and chest (Fig. 1a,b). No obvious abnormalities were detected in organs other than the skin. The vitiliginous lesions had been stable over the past 6 months and did not vary seasonally. There was no similar condition in the patient’s family. Dermoscopy revealed blue spots and reticular telangiectasia within the white patches (Fig. 1c,d). Histological examination of the blue patch on the lower right abdomen revealed an absence of epidermal melanocytes and pigment in the basal layer, scattered infiltration of inflammatory cells surrounding blood vessels in the upper part of the dermis (Fig. 2a), and deposition of melanophages between collagen bundles, or surrounding blood vessels and appendages in the middle and lower part of the dermis (Fig. 2b). Immunohistochemistry stains revealed Melan-Apositive spindle or dendritic cells in the dermis (Fig. 2c,d).
Based on the above findings, a diagnosis of blue vitiligo was made. The patient was treated with several medications, including oral vitiligo pills, topical halometasone cream and tacrolimus ointment, and the blue colour faded gradually over time. Blue vitiligo is extremely rare, and there have been only three cases reported previously in the literature: a 42-year-old woman,5 a 47-year-old man6 and a 23year-old woman.7 Therefore, the present case represents only the fourth reported case of this rare disease. Table 1 shows the clinical features of blue vitiligo in the three previously reported cases and our case. Compared with the previously reported cases, the present case has two unique features. First, blue– grey spots appeared after intralesional injection of psoralen combined with UVB radiation therapy, whereas in the previous reports, psoralen was given systemically.5,6 Second, the blue–grey spots were consistently distributed in and around the injection sites, and this observation has not been reported previously. Thus, our case provides more convincing evidence to support the previous speculation that psoralen plus UV phototherapy can contribute to blue vitiligo. The mechanism behind the appearance of blue–grey macules is currently still unclear. Ivker et al.5 believed that dermal pigmentation, resulting from postinflammatory hyperpigmentation, caused blue skin due to
(a)
(b)
(c)
(d)
Figure 1 (a,b) Blue–grey macules over the depigmented patches on (a) neck, chest and (b) lower right abdomen. (c,d) Dermoscopy revealed blue patches and reticular telangiectasia within the white patches.
302
Clinical and Experimental Dermatology (2015) 40, pp301–304
ª 2014 British Association of Dermatologists
Blue vitiligo following PUVB therapy J. Zhang et al.
(a)
(b)
(c)
(d)
Figure 2 (a) In the blue patch, there was an absence of epidermal melanocytes and pigment in the basal layer, with a scattered infiltra-
tion of inflammatory cells surrounding blood vessels in the upper part of the dermis (Melan-A, original magnification 9 200), and (b) deposition of melanophages between collagen bundles, or surrounding blood vessels and appendages in the middle and lower parts of the dermis (haematoxylin and eosin, original magnification 9 200). Melan-A-positive spindle or dendritic cells were found in the dermis. Original magnification (c) 9 100; (d) 9 200. Table 1 Clinical features of blue vitiligo in four reported cases. Duration of lesions
Previous treatment
Onset of blue discolouration
42
6 weeks
PUVA
Unknown
M
47
2 years
NB-UVB
3
F
23
1 month
None
1 month after NBUVB treatment Unknown
4
M
23
16 months
Intralesional injection of psoralen plus NB-UVB
1 week after psoralen injection
Patient
Sex
1
M
2
Age, years
Lesion sites Forearms and calves Scalp, arms, legs and trunk Forearm, hands and areola Neck, abdomen, chest and leg
Sites of blue skin
Reference
Forearms
Ivkeret et al.5
Legs and trunk Forearm
Hamzavi et al.6
Neck and abdomen
Chandrashekar et al.7 Present case
NB-UVB, narrowband ultraviolet B radiation; PUVA, psoralen plus ultraviolet A radiation.
the Tyndall effect. However, the source of the dermal pigmented particles remains unclear, and they might not originate from the epidermis, owing to the lack of
ª 2014 British Association of Dermatologists
epidermal melanocytes in patients with vitiligo.8 We found Melan-A-positive spindle or dendritic cells in the dermis of our patient’s biopsy. Furthermore, previous
Clinical and Experimental Dermatology (2015) 40, pp301–304
303
Blue vitiligo following PUVB therapy J. Zhang et al.
studies showed that both melanocytes and melanocyte stem cells exist in the dermis.9 Thus, we believe that the blue macules are associated with the melanin of dermal melanocytes, which might be activated by intralesional injection of psoralen plus NB-UVB radiation therapy, or might be induced and differentiated from melanocyte stem cells. Future studies are required to test these theories. Clinically, blue vitiligo should be distinguished from blue naevus with overlying vitiligo,10 as depigmented patches and blue macules can be found in lesions of both conditions. In the former, depigmented patches appear first, followed by the presence of blue macules within the lesions, whereas with the latter, the blue macules are already existing when the depigmented patches develop. In the current case, the blue–grey colour faded gradually over time. This observation is consistent with the case reported by Ivker et al.,5 in which the blue colour vanished 4 months later. Therefore, we speculate that blue vitiligo might disappear spontaneously when the triggering factor (i.e., medications or phototherapy) does not exist. This is probably because dermal melanophages can gradually excrete melanin from the body. Thus, treatments for blue vitiligo should focus on the management of depigmented patches, and no special treatments are required for this unique vitiligo. In conclusion, we document a rare case of blue vitiligo that developed in and around injection sites following intralesional injection of psoralen combined with UVB radiation therapy in a patient with vitiligo. Because of the extreme rarity of the disease, awareness and knowledge of this condition by dermatologists should be emphasized. As blue vitiligo can resolve spontaneously after the absence of triggering factor(s), no special treatments are required for this rare variant of vitiligo.
Learning points ● Blue vitiligo is an extremely rare, unique vari-
ant of vitiligo, characterized clinically by a blue– grey appearance of the skin, and histologically by the presence of numerous dermal melanophages and the absence of epidermal melanocytes. ● Blue vitiligo was first described by Ivker et al. in 1994. ● There have only been three cases reported previously in the literature.
304
Clinical and Experimental Dermatology (2015) 40, pp301–304
● Blue vitiligo occurs mainly in young and mid-
dle-aged adults. ● The blue discolouration of blue vitiligo often
develops in typical vitiliginous lesions after phototherapy. ● Blue–grey spots exist only in some of the lesions and vary in shade, with an irregular shape and an unclear boundary with the surrounding typical vitiliginous lesions. ● The blue–grey spots tend to subside gradually, and no special treatment is required.
References 1 Alikhan A, Felsten LM, Daly M et al. Vitiligo: a comprehensive overview. Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol 2011; 65: 473–91. 2 Hann SK, Kim YS, Yoo JH et al. Clinical and histopathologic characteristics of trichrome vitiligo. J Am Acad Dermatol 2000; 42: 589–96. 3 Tanioka M, Takahashi K, Miyachi YI. Narrowband ultraviolet b phototherapy for inflammatory vitiligo with raised borders associated with sjogren’s syndrome. Clin Exp Dermatol 2009; 34: 418–20. 4 Ezzedine K, Amazan E, Seneschal J et al. Follicular vitiligo: a new form of vitiligo. Pigment Cell Melanoma Res 2012; 25: 527–9. 5 Ivker R, Goldaber M, Buchness MR. Blue vitiligo. J Am Acad Dermatol 1994; 30: 829–31. 6 Hamzavi I, Shiff N, Martinka M et al. Spectroscopic assessment of dermal melanin using blue vitiligo as an in vivo model. Photodermatol Photoimmunol Photomed 2006; 22: 46–51. 7 Chandrashekar L. Dermatoscopy of blue vitiligo. Clin Exp Dermatol 2009; 34: e125–6. 8 Le Poole IC, van den Wijngaard RM, Westerhof W et al. Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation. J Invest Dermatol 1993; 100: 816–22. 9 Ahn JJ, Lee JH, Shin MK et al. Two cases of vitiligo developed on the persisting dermal melanocytosis: is there a difference between epidermal melanocytes and dermal melanocytes? Ann Dermatol 2013; 25: 226–8. 10 Wang P, Cheng Y, Yang H et al. Acquired patch-type blue nevus with overlying vitiligo: a case report. Int J Dermatol 2012; 51: 568–70.
ª 2014 British Association of Dermatologists
