assessment would require nail matrix biopsy. To conclude, although the diagnosis of Hailey-Hailey disease cannot be established only on longitudinal white bands, we consider them to be a helpful sign. Disclosure. Financial support: none. Conflict of interest: none. 1 Dermatology Department, Hôpital du Bocage, 2, boulevard Maréchal de Lattre de Tassigny, 21079 Dijon cedex, France 2 Clinical Research Unit, Centre Hospitalier Universitaire de Dijon, France
Blandine BEL1 Agnès SOUDRY-FAURE2 Pierre VABRES1
1. Michel B. Commentary: Hailey-Hailey disease, familial benign chronic pemphigus. Arch Dermatol 1982; 118: 781-3. 2. Burge SM. Hailey-Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol 1992; 126: 275-82. 3. Kumar R, Zawar V. Longitudinal leukonychia in Hailey-Hailey Disease: a sign not to be missed. Dermatol Online J 2008; 14: 7. 4. Meawad OB, Assaf HM. Longitudinal white streaks of fingernails: a useful clinical marker in genital verrucoid Hailey-Hailey disease. J Eur Acad Dermatol Venereol 1995; 5: 177-80. 5. Kirtschig G, Gieler U, Happle R. Treatment of Hailey-Hailey disease by dermabrasion. J Am Acad Dermatol 1993; 28: 784-6. 6. Pan Y, Gareau DS, Scope A, Rajadhyaksha M, Mullani NA, Marghoob AA. Polarized and nonpolarized dermoscopy: the explanation for the observed differences. Arch Dermatol 2008; 144: 828-9. 7. Bel B, Jeudy G, Vabres P. Dermoscopy of longitudinal leukonychia in Hailey-Hailey disease. Arch Dermatol 2010; 146: 1204. doi:10.1684/ejd.2014.2412
Anti-laminin ␥1 pemphigoid associated with pustular psoriasis It is well known that psoriasis vulgaris and bullous diseases such as bullous pemphigoid and anti-laminin ␥1 pemphigoid occasionally coexist [1]. However, coexistence of generalized pustular psoriasis (GPP) and bullous disease is uncommon. We report a case of GPP treated with narrow band ultraviolet B (UVB) followed by anti-laminin ␥1 pemphigoid. An 82-year-old Japanese man presented with scaly erythema on the extremities which had appeared a year before. He had been diagnosed as having psoriasis vulgaris and treated with topical corticosteroids and vitamin D3. A year later, erythema with pustules was noted and gradually expanded on the abdomen and extremities with fever (figure 1A). A skin biopsy specimen taken from the femur revealed intraepidermal spongiform pustules (figure 1B). The diagnosis of pustular psoriasis was made and therapy with topical corticosteroids and narrow band UVB was started. Three weeks later, however, edematous erythema without pustules was noted on his extremities. In addition, vesicles appeared on his arms, legs and EJD, vol. 24, n◦ 5, September-October 2014
A
B
E
200 µm
C
1
2
3
4
200 kDa
D
500 µm
Figure 1. A) Erythema with small pustules on the abdomen. B) Biopsy specimen showed intraepidermal spongiform pustule (hematoxylin–eosin stain, Scale bars: 200m). C) Scaly erythemas with small vesicles on the forearm. D) A subepidermal blister formed, containing a lot of neutrophils and some eosinophils (hematoxylin–eosin stain, Scale bars: 500m). E) Immunoblot analysis identified a circulating IgG antibody against 200kDa antigen in the dermal extract. Lane 1 epidermolysis bullosa acquisita (EBA) positive control, Lane 2 anti-laminin ␥1 pemphigoid positive control, Lane 3 Normal control, Lane 4 Patient.
trunk (figure 1C). Histopathologically, subepidermal blisters had formed, containing many neutrophils and some eosinophils (figure 1D). Direct immunofluorescence examination showed deposition of IgG and C3 along the basement membrane zone (BMZ). The n-serrated pattern, which is reported to be found in p200 pemphigoid [2], was observed. Indirect immunofluorescence staining detected serum IgG antibodies, which reacted to the BMZ and demonstrated linear IgG staining on the dermal side of 1M NaCl-split skin. Immunoblot analysis using the serum identified IgG antibodies against a 200kDa but not a 290kDa antigen in the extracts of dermis (figure 1E) and showed no antibodies against desmoglein 1, desmoglein 3, envoplakin, periplakin, 180 kDa and 230 kDa antigens in the extracts of epidermis. From these results, the diagnosis of anti-laminin ␥1 pemphigoid was made. Two hundred mg (4 mg/kg) of cyclosporine and 15 mg (0.3 mg/kg) of prednisolone were needed to control both pustular psoriasis and anti-laminin ␥1 pemphigoid. Anti-laminin ␥1 pemphigoid is an autoimmune subepidermal bullous disease, first reported in 1996 by Zillikens et al [3]. At the same time Chen et al. reported this bullous disease combined with psoriasis vulgaris [4]. Autoantibodies reacting to a 200 kDa antigen were detected [3, 4]. A 200kDa protein has recently been identified as a laminin ␥1 subunit and the name ‘anti-laminin ␥1 pemphigoid’ was proposed [5]. Although cases with anti-laminin ␥1 pemphigoid associated with psoriasis vulgaris have frequently been reported, the pathogenesis remains unclear. The presumed mechanism is that inflammation of psoriasis and/or treatment such as ultraviolet therapy, expose the BMZ antigen to the immune system [6]. In our case, anti-laminin ␥1 pemphigoid developed after three weeks of UVB treatment. It is possible that UVB therapy participated in the development of pemphigoid in our case although it could be that pemphigoid appeared coincidentally regardless of UVB therapy and that UVB exposure uncovered the subclinical pemphigoid. Anti-laminin ␥1 pemphigoid associated with pustular psoriasis is rare among those with psoriasis, three cases, however, have been reported, including our case [7, 8]. Bullous disease should be considered as
629
a differential diagnosis when blister and/or refractory edematous erythema develops in psoriatic patients. Our case and reported cases indicate that pustular psoriasis as well as psoriasis vulgaris can be complicated by anti-laminin ␥1 pemphigoid. Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan 2 Department of Dermatology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan 3 Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi, Abeno, Osaka 545-8585, Japan
Maki IGARASHI1 Yuichiro TSUNEMI1 Hiroshi KOGA2 Takashi HASHIMOTO2 Chiharu TATEISHI3 Daisuke TSURUTA3 Masamitu ISHII3 Makoto KAWASHIMA1
1. Grunwald MH, David M, Feuerman EJ. Coexistence of psoriasis vulgaris and bullous diseases. J Am Acad Dermatol 1985; 13: 224-8. 2. Vodegel RM, Jonkman MF, Pas HH, et al. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. Br J Dermatol 2004; 151: 112-8. 3. Zillikens D, Kawahara Y, Ishiko A, et al. A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone. J Invest Dermatol 1996; 106: 465-70. 4. Chen KR, Shimizu S, Miyakawa S, et al. Coexistence of psoriasis and an unusual IgG-mediated subepidermal bullous dermatosis: identification of a novel 200-kDa lower lamina lucida target antigen. Br J Dermatol 1996; 134: 340-6. 5. Dainichi T, Kurono S, Ohyama B, et al. Anti-laminin gamma-1 pemphigoid. Proc Natl Acad Sci USA 2009; 106: 2800-5. 6. Kawahara Y, Zillikens D, Yancey KB, et al. Subepidermal blistering disease with autoantibodies againist a novel dermal 200kDa antigen. J Dermatol Sci 2000; 23: 93-102. 7. Miyakura T, Yamamoto T, Tashiro A, et al. Anti-p200 pemphigoid associated with annular pustular psoriasis. Eur J Dermatol 2008; 18: 481-2. 8. Saeki H, Hayashi N, Komine M, et al. A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease? Br J Dermatol 1996; 134: 1525. doi:10.1684/ejd.2014.2419
Annular lupus erythematosus profundus A 16-year-old Japanese female visited our hospital on 2012. She had noticed asymptomatic erythema on her cheeks about 4 years previously. Other similar lesions gradually appeared on the cheeks without centrifugal spreading, showing an annular distribution. Physical examination identified annular indurated erythema on the bilateral cheeks (figure 1A). She had no other symptoms. Complete blood cell counts were within normal limits. Serum C3 level was 115 mg/dL and C4 was 22 mg/dL. Autoantibodies including anti-nuclear, anti-SS-DNA, anti-DS-DNA,
630
anti-Sm, anti-Ro (SS-A), and anti-La (SS-B) antibodies were not detected. Histopathological examination of biopsy specimens from indurated erythematous plaques on her right cheek revealed slight vacuolar degeneration of the basal layer of the epidermis, perifollicular and perivascular lymphocytic infiltrations in the dermis, and lobular panniculitis with lymphocytic infiltrations (figure 1B). Colloidal iron staining showed abundant mucin deposition in the dermis and subcutaneous tissue. Immunohistochemical analysis showed no marked deviation for CD3, CD4, CD8, and CD20 staining. The percentage of CD123-positive cells was evaluated using immunohistochemical staining with anti-human CD123 antibody (clone 7G3; BD Bioscience, CA, USA). CD123-positive cells were counted in 5 different 400-fold magnification fields under a light microscope, which revealed that the percentage of CD123positive cells was 2.2% among infiltrated mononuclear cells. Direct immunofluorescence examination of a biopsy specimen showed deposition of IgM and C3 in the basement membrane zone of the epidermis. Oral prednisolone at 20 mg a day and topical tacrolimus were initiated. Significant improvement of the lesions was obtained within 4 weeks and the induration disappeared within 6 weeks. Neither recurrence of the eruption nor the occurrence of systemic collagen diseases has been observed; however, some scaring remained at the site of erythema. We diagnosed the patient with lupus erythematosus profundus (LEP) showing an annular configuration. 14 cases of LEP, including our case, have been reported to present unusual configurations, such as linear, arc-shaped and annular, in the English literature [1-7] (table 1). These involved 6 males and 8 females. The mean age of these patients was 22.6 years (range: 6 to 57 years), which is younger than the 36.8 years (range: 12-59 years) of usual LEP [8]. The scalp was involved in half of these cases, although the most common sites of involvement of LEP are the face and upper limbs [9]. Male-pattern baldness was not observed in all male cases with scalp involvement. There were two arc-shaped cases and two cases with annular erythema, including our case, besides a linear configuration [3, 6, 7]. As shown in table 1, all linear cases follow Blaschko’s lines. Since arc-shaped lesions seem to be parts of an annular lesion, it is not appropriate to discuss whether arc-shaped and annular lesions follow Blaschko’s lines. The mechanism of how linear cases of LEP follow Blaschko’s lines is currently unclear [3]. It is said that genetic mosaicism of keratinocytes in Blaschko’s lines and some external factors (sun exposure or viral infection) may cause the linear
A
B
Figure 1. A) Initial clinical presentation. Annular indurated erythema was observed on her right cheek. B) Histopathological findings of indurated erythema. Lobular panniculitis with lymphocytic infiltrations (hematoxylin and eosin, original magnification ×100). EJD, vol. 24, n◦ 5, September-October 2014
Blandine BEL1 Agnès SOUDRY-FAURE2 Pierre VABRES1
1. Michel B. Commentary: Hailey-Hailey disease, familial benign chronic pemphigus. Arch Dermatol 1982; 118: 781-3. 2. Burge SM. Hailey-Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol 1992; 126: 275-82. 3. Kumar R, Zawar V. Longitudinal leukonychia in Hailey-Hailey Disease: a sign not to be missed. Dermatol Online J 2008; 14: 7. 4. Meawad OB, Assaf HM. Longitudinal white streaks of fingernails: a useful clinical marker in genital verrucoid Hailey-Hailey disease. J Eur Acad Dermatol Venereol 1995; 5: 177-80. 5. Kirtschig G, Gieler U, Happle R. Treatment of Hailey-Hailey disease by dermabrasion. J Am Acad Dermatol 1993; 28: 784-6. 6. Pan Y, Gareau DS, Scope A, Rajadhyaksha M, Mullani NA, Marghoob AA. Polarized and nonpolarized dermoscopy: the explanation for the observed differences. Arch Dermatol 2008; 144: 828-9. 7. Bel B, Jeudy G, Vabres P. Dermoscopy of longitudinal leukonychia in Hailey-Hailey disease. Arch Dermatol 2010; 146: 1204. doi:10.1684/ejd.2014.2412
Anti-laminin ␥1 pemphigoid associated with pustular psoriasis It is well known that psoriasis vulgaris and bullous diseases such as bullous pemphigoid and anti-laminin ␥1 pemphigoid occasionally coexist [1]. However, coexistence of generalized pustular psoriasis (GPP) and bullous disease is uncommon. We report a case of GPP treated with narrow band ultraviolet B (UVB) followed by anti-laminin ␥1 pemphigoid. An 82-year-old Japanese man presented with scaly erythema on the extremities which had appeared a year before. He had been diagnosed as having psoriasis vulgaris and treated with topical corticosteroids and vitamin D3. A year later, erythema with pustules was noted and gradually expanded on the abdomen and extremities with fever (figure 1A). A skin biopsy specimen taken from the femur revealed intraepidermal spongiform pustules (figure 1B). The diagnosis of pustular psoriasis was made and therapy with topical corticosteroids and narrow band UVB was started. Three weeks later, however, edematous erythema without pustules was noted on his extremities. In addition, vesicles appeared on his arms, legs and EJD, vol. 24, n◦ 5, September-October 2014
A
B
E
200 µm
C
1
2
3
4
200 kDa
D
500 µm
Figure 1. A) Erythema with small pustules on the abdomen. B) Biopsy specimen showed intraepidermal spongiform pustule (hematoxylin–eosin stain, Scale bars: 200m). C) Scaly erythemas with small vesicles on the forearm. D) A subepidermal blister formed, containing a lot of neutrophils and some eosinophils (hematoxylin–eosin stain, Scale bars: 500m). E) Immunoblot analysis identified a circulating IgG antibody against 200kDa antigen in the dermal extract. Lane 1 epidermolysis bullosa acquisita (EBA) positive control, Lane 2 anti-laminin ␥1 pemphigoid positive control, Lane 3 Normal control, Lane 4 Patient.
trunk (figure 1C). Histopathologically, subepidermal blisters had formed, containing many neutrophils and some eosinophils (figure 1D). Direct immunofluorescence examination showed deposition of IgG and C3 along the basement membrane zone (BMZ). The n-serrated pattern, which is reported to be found in p200 pemphigoid [2], was observed. Indirect immunofluorescence staining detected serum IgG antibodies, which reacted to the BMZ and demonstrated linear IgG staining on the dermal side of 1M NaCl-split skin. Immunoblot analysis using the serum identified IgG antibodies against a 200kDa but not a 290kDa antigen in the extracts of dermis (figure 1E) and showed no antibodies against desmoglein 1, desmoglein 3, envoplakin, periplakin, 180 kDa and 230 kDa antigens in the extracts of epidermis. From these results, the diagnosis of anti-laminin ␥1 pemphigoid was made. Two hundred mg (4 mg/kg) of cyclosporine and 15 mg (0.3 mg/kg) of prednisolone were needed to control both pustular psoriasis and anti-laminin ␥1 pemphigoid. Anti-laminin ␥1 pemphigoid is an autoimmune subepidermal bullous disease, first reported in 1996 by Zillikens et al [3]. At the same time Chen et al. reported this bullous disease combined with psoriasis vulgaris [4]. Autoantibodies reacting to a 200 kDa antigen were detected [3, 4]. A 200kDa protein has recently been identified as a laminin ␥1 subunit and the name ‘anti-laminin ␥1 pemphigoid’ was proposed [5]. Although cases with anti-laminin ␥1 pemphigoid associated with psoriasis vulgaris have frequently been reported, the pathogenesis remains unclear. The presumed mechanism is that inflammation of psoriasis and/or treatment such as ultraviolet therapy, expose the BMZ antigen to the immune system [6]. In our case, anti-laminin ␥1 pemphigoid developed after three weeks of UVB treatment. It is possible that UVB therapy participated in the development of pemphigoid in our case although it could be that pemphigoid appeared coincidentally regardless of UVB therapy and that UVB exposure uncovered the subclinical pemphigoid. Anti-laminin ␥1 pemphigoid associated with pustular psoriasis is rare among those with psoriasis, three cases, however, have been reported, including our case [7, 8]. Bullous disease should be considered as
629
a differential diagnosis when blister and/or refractory edematous erythema develops in psoriatic patients. Our case and reported cases indicate that pustular psoriasis as well as psoriasis vulgaris can be complicated by anti-laminin ␥1 pemphigoid. Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan 2 Department of Dermatology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan 3 Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi, Abeno, Osaka 545-8585, Japan
Maki IGARASHI1 Yuichiro TSUNEMI1 Hiroshi KOGA2 Takashi HASHIMOTO2 Chiharu TATEISHI3 Daisuke TSURUTA3 Masamitu ISHII3 Makoto KAWASHIMA1
1. Grunwald MH, David M, Feuerman EJ. Coexistence of psoriasis vulgaris and bullous diseases. J Am Acad Dermatol 1985; 13: 224-8. 2. Vodegel RM, Jonkman MF, Pas HH, et al. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. Br J Dermatol 2004; 151: 112-8. 3. Zillikens D, Kawahara Y, Ishiko A, et al. A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone. J Invest Dermatol 1996; 106: 465-70. 4. Chen KR, Shimizu S, Miyakawa S, et al. Coexistence of psoriasis and an unusual IgG-mediated subepidermal bullous dermatosis: identification of a novel 200-kDa lower lamina lucida target antigen. Br J Dermatol 1996; 134: 340-6. 5. Dainichi T, Kurono S, Ohyama B, et al. Anti-laminin gamma-1 pemphigoid. Proc Natl Acad Sci USA 2009; 106: 2800-5. 6. Kawahara Y, Zillikens D, Yancey KB, et al. Subepidermal blistering disease with autoantibodies againist a novel dermal 200kDa antigen. J Dermatol Sci 2000; 23: 93-102. 7. Miyakura T, Yamamoto T, Tashiro A, et al. Anti-p200 pemphigoid associated with annular pustular psoriasis. Eur J Dermatol 2008; 18: 481-2. 8. Saeki H, Hayashi N, Komine M, et al. A case of generalized pustular psoriasis followed by bullous disease: an atypical case of bullous pemphigoid or a novel bullous disease? Br J Dermatol 1996; 134: 1525. doi:10.1684/ejd.2014.2419
Annular lupus erythematosus profundus A 16-year-old Japanese female visited our hospital on 2012. She had noticed asymptomatic erythema on her cheeks about 4 years previously. Other similar lesions gradually appeared on the cheeks without centrifugal spreading, showing an annular distribution. Physical examination identified annular indurated erythema on the bilateral cheeks (figure 1A). She had no other symptoms. Complete blood cell counts were within normal limits. Serum C3 level was 115 mg/dL and C4 was 22 mg/dL. Autoantibodies including anti-nuclear, anti-SS-DNA, anti-DS-DNA,
630
anti-Sm, anti-Ro (SS-A), and anti-La (SS-B) antibodies were not detected. Histopathological examination of biopsy specimens from indurated erythematous plaques on her right cheek revealed slight vacuolar degeneration of the basal layer of the epidermis, perifollicular and perivascular lymphocytic infiltrations in the dermis, and lobular panniculitis with lymphocytic infiltrations (figure 1B). Colloidal iron staining showed abundant mucin deposition in the dermis and subcutaneous tissue. Immunohistochemical analysis showed no marked deviation for CD3, CD4, CD8, and CD20 staining. The percentage of CD123-positive cells was evaluated using immunohistochemical staining with anti-human CD123 antibody (clone 7G3; BD Bioscience, CA, USA). CD123-positive cells were counted in 5 different 400-fold magnification fields under a light microscope, which revealed that the percentage of CD123positive cells was 2.2% among infiltrated mononuclear cells. Direct immunofluorescence examination of a biopsy specimen showed deposition of IgM and C3 in the basement membrane zone of the epidermis. Oral prednisolone at 20 mg a day and topical tacrolimus were initiated. Significant improvement of the lesions was obtained within 4 weeks and the induration disappeared within 6 weeks. Neither recurrence of the eruption nor the occurrence of systemic collagen diseases has been observed; however, some scaring remained at the site of erythema. We diagnosed the patient with lupus erythematosus profundus (LEP) showing an annular configuration. 14 cases of LEP, including our case, have been reported to present unusual configurations, such as linear, arc-shaped and annular, in the English literature [1-7] (table 1). These involved 6 males and 8 females. The mean age of these patients was 22.6 years (range: 6 to 57 years), which is younger than the 36.8 years (range: 12-59 years) of usual LEP [8]. The scalp was involved in half of these cases, although the most common sites of involvement of LEP are the face and upper limbs [9]. Male-pattern baldness was not observed in all male cases with scalp involvement. There were two arc-shaped cases and two cases with annular erythema, including our case, besides a linear configuration [3, 6, 7]. As shown in table 1, all linear cases follow Blaschko’s lines. Since arc-shaped lesions seem to be parts of an annular lesion, it is not appropriate to discuss whether arc-shaped and annular lesions follow Blaschko’s lines. The mechanism of how linear cases of LEP follow Blaschko’s lines is currently unclear [3]. It is said that genetic mosaicism of keratinocytes in Blaschko’s lines and some external factors (sun exposure or viral infection) may cause the linear
A
B
Figure 1. A) Initial clinical presentation. Annular indurated erythema was observed on her right cheek. B) Histopathological findings of indurated erythema. Lobular panniculitis with lymphocytic infiltrations (hematoxylin and eosin, original magnification ×100). EJD, vol. 24, n◦ 5, September-October 2014
