Letters to the Editor
Rafael Salido‑Vallejo, Gloria Garnacho‑Saucedo, José Carlos Moreno‑Giménez, Francisco M. Camacho‑Martínez1 Department of Dermatology, Hospital Universitario Reina Sofía, Córdoba, 1Department of Dermatology, School of Medicine, Hospital Universitario Virgen Macarena, Seville, Spain Address for correspondence: Dr. Rafael Salido Vallejo, M.D. C/Jose Manuel Rodriguez López, No. 7, Córdoba ‑ 302 14005, Spain. E‑mail: [email protected]
REFERENCES 1. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: A review of 60 cases. J Am Acad Dermatol 2012;67:955‑61. 2. Kossard S, Shiell RC. Frontal fibrosing alopecia developing after hair transplantation for androgenetic alopecia. Int J Dermatol 2005;44:321‑3. 3. Dlova NC, Goh CL. Frontal fibrosing alopecia in an African man. Int J Dermatol 2013. [In Press]. 4. Vañó‑Galván S, Molina‑Ruiz AM, Serrano‑Falcón C, Arias‑Santiago S, Rodrigues‑Barata AR, Garnacho‑Saucedo G, et al. Frontal fibrosing alopecia: A multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670‑8. 5. Miteva M, Camacho I, Romanelli P, Tosti A. Acute hair loss on the limbs in frontal fibrosing alopecia: A clinicopathological study of two cases. Br J Dermatol 2010;163:426‑8. 6. Ramaswamy P, Mendese G, Goldberg LJ. Scarring alopecia of the sideburns: A unique presentation of frontal fibrosing alopecia in men. Arch Dermatol 2012;148:1095‑6. 7. Samrao A, Chew AL, Price V. Frontal fibrosing alopecia: A clinical review of 36 patients. Br J Dermatol 2010;163:1296‑300. 8. Camacho FM. Lonely hair sign: Not specific for frontal fibrosing alopecia. Arch Dermatol 2012;148:1208‑9. Access this article online Quick Response Code:
Website: www.ijdvl.com DOI: 10.4103/0378-6323.144183 PMID: *****
Bullous pemphigoid clinically presenting as lichen amyloidosis Sir, A 42‑year‑old male presented to our hospital with complaints of moderately itchy, pigmented, papular lesions over the lower limbs for the last 2 years. There was mild itching to start with, following which the patient noticed gradual appearance of papules over his shins. There was no preceding history of any drug intake. On examination, there were multiple, discrete, closely‑set skin‑colored and pigmented papules of varying sizes symmetrically present over the antero‑lateral aspect and 544
calves of lower limbs symmetrically [Figure 1]. There was a sharp demarcation line between the lesions and normal skin. Individual papules were of about 1 cm in diameter, non‑tender with mild scaling but without oozing or excoriation. No other body site including mucosae, scalp, or nails was involved. We clinically suspected the case to be lichen amyloidosis and skin biopsy was sent with a request to the pathologist for a Congo red stain. Histopathological examination (HPE) revealed marked hyperkeratosis, normal to thinned‑out stratum malphigii, mild spongiosis along with a subepidermal bulla. There was a considerable collection of eosinophils, both in the blister cavity and in the upper dermis along with neutrophils and lymphocytes [Figures 2]. There was no evidence of any amyloid deposits with Congo red stain. These features were suggestive of bullous pemphigoid and subsequent perilesional skin biopsy for direct immunofluorescentce (DIF) examination showed deposition of IgG and C3 in the basement membrane zone [Figure 3]. Since topical clobetasol propionate, 0.05% ointment did not reduce the lesion count and size, we treated the patient with oral prednisolone 60 mg/day. The lesions regressed, but on gradual tapering to 20 mg of prednisolone per day over 8 weeks, the lesions stared recurring again. At this point, we lost the patient to follow up. Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder occurring in elderly individuals >60 years of age. There is tissue‑bound and circulating autoantibody against BP230 and BP180. In addition, there is an autoreactive cell‑mediated immune response against BP180.[1] Histopathology shows a subepidermal cleft with eosinophilic spongiosis and eosinophilic and mononuclear cell infiltrates in the upper dermis; direct immunoflourescence demonstrates presence of fine, linear continuous deposits of IgG and/or C3 along the epidermal basement membrane. Several clinical variants of bullous pemphigoid have been described including localized (such as pretibial pemphigoid, around stomas, vulvar and perineal region in female, at the site of irradiation or confined to paralyzed limb), isolated palmo‑plantar involvement (dyshidrosiform pemphigoid), dermatitis herpetiformis‑like (vesicular pemphigoid) erythrodermic bullous pemphigoid, lichen planus pemphigoides, gestational pemphigoid[2] and the rare pemphigoid incipiens (elderly patients with itchy BP like lesions but a negative DIF in the presence of circulating anti‑BP180 and/or BP230 antibodies).[3] Prurigo nodularis‑like
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
Letters to the Editor
Figure 1: Multiple discrete close-set papules in lower limb
Figure 2: Subepidermal blister with upper dermal eosinophil and lymphocyte collection within the blister cavity (H and E, x400)
and nodules distributed predominantly over lower limbs and shoulders. Blisters may precede or follow the development of nodules by many months, at the site of the nodule or on uninvolved skin.[4,5] Since the lesions were very close‑set and uniformly distributed in our patient, we did not consider pemphigoid nodularis as a possible differential diagnosis. The marked acanthosis and elongation of rete ridges with corresponding changes in the papillary dermis observed in pemphigoid nodularis were also not seen in our patient. Epidermolysis bullosa (EB) pruriginosa, a rare variant of dystrophic EB, may be considered in the differential diagnosi as a similar late presentation with subepidermal blisters and inflammatory infiltrate including eosinophils have been reported.[6] Lack of past history of trauma‑induced blistering, absence of a family history, lack of involvement of nails and a positive DIF helped to differentiate our case from EB pruriginosa. However, we could not carry out an electron microscopy examination, nor could we demonstrate any missense mutation in COL 7A1 gene (described in EB pruriginosa) as we did not have access to these investigations at our institute.[7] The age of onset of disease in our patient was much less than the usual for bullous pemphigoid; in addition, he did not develop clinical vesicles or bullae even after 2 years of onset of the lesions. He had closely‑set papules uniformly distributed only over the lower limbs, resembling the papules of cutaneous amyloidosis. A single case has been reported in the literature as ‘lichen amyloidosis with subepidermal blister’ where the patient presented with multiple itchy keratotic papules and plaques on trunk and extremities with intermingled erosions and vesicles. The case was clinically reminiscent of prurigo nodularis but histopathology showed subepidermal bulla with amyloid deposit in the dermal papillae, visible on Dylon and Congo red staining. Direct immunofluorescence was normal.[8] In contrast, our case did not demonstrate any amyloid deposit in the dermal papillae.
Projna Biswas, Ishad Aggarwal, Debashis Sen, Atoka Sumi, Arghyaprasun Ghosh1
Figure 3: Direct immunoflourescence showing presence of fine, linear continuous deposits along the epidermal basement membrane (x100)
pemphigoid (nodular pemphigoid) is a variant where elderly women present with excoriated papules
Departments of Dermatology, Institute of Post Graduate Medical Education and Research, 1 Radha Gobinda Kar Medical College, Kolkata, West Bengal, India Address for correspondence: Dr. Projna Biswas, Depatrment of Dermatology, Institute of Post Graduate Medical Education and Research, Kusumba (SDPark), PO‑Narendrapur, PS‑Sonarpur, Kolkata ‑ 700 103, West Bengal, India. E‑mail: [email protected]
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
545
Letters to the Editor
REFERENCES 1. Culton DA, Liu Z, Diaz LA. Bullous pemphigoid.In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Editors. Fitzpatrick’s Dermatology in General Medicine. 8th ed.New York: McGraw‑Hill; 2012.p. 608‑16. 2. Borradori L, BernardP. Pemphigoidgroup. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 2nd ed. Spain: Mosby Elsevier; 2008.p. 137‑48. 3. Tambe S, Häfliger S, Borradori L. Clinical challenges and recent advances in the diagnosis of bullous pemphigoid. Expert Rev Dermatol 2013;8:407‑16. 4. Borradori L, Prost C, Wolkenstein P, Bernard P, Baccard M, Morel P. Localized pretibialpemphigoid and pemphigoidnodularis. J Am Acad Dermatol 1992;27:863‑7. 5. Cliff S, Holden CA. Pemphigoidnodularis: A report of three cases and review of the literature. Br J Dermatol 1997;136:398‑401. 6. Vivehanantha S, Carr RA, McGrath JA, Taibjee SM, Madhogaria S, Ilchyshyn A. Epidermolysisbullosapruriginosa: A case with prominent histopathologic inflammation. JAMA Dermatol 2013;149:727‑31. 7. Shi BJ, Feng J. A novel missense mutation in the COL7A1 gene causes epidermolysisbullosapruriginosa. Clin Exp Dermatol 2009;34:e975‑8. 8. Kuroda K, Mizoguchi M. Lichen amyloidosus with subepidermal blister formation. Eur J Dermatol 2004;14:262‑3. Access this article online Quick Response Code:
Website: www.ijdvl.com DOI: 10.4103/0378-6323.144184 PMID: *****
Recurrent blisters in a case of resolving Stevens–Johnson syndrome/toxic epidermal necrolysis Sir, Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially life‑threatening, mainly drug‑induced conditions characterized by widespread apoptosis of keratinocytes provoked by the activation of cell‑mediated cytotoxic reaction and amplified by cytokines, mainly granulysin. Dry skin and heat intolerance are common complaints among survivors of SJS/TEN.[1] We report a patient with SJS/TEN overlap who developed recurrence of vesicles and bullae several days after the initial healing of lesions due to sweat retention which simulated a fresh episode of SJS/TEN. 546
A 51‑year‑old woman who had rectal cancer with lung and brain metastases was admitted to our burn center because of phenytoin induced SJS/TEN overlap. Phenytoin had been introduced 32 days before the skin rash to control seizures after whole brain radiotherapy. On physical examination, the patient exhibited conjunctivitis, oral mucositis, and generalized maculopapular rash characterized by atypical targetoid lesions with centrally darkened macules and blisters. She was treated with supportive care including empiric antibiotics (piperacillin/ tazobactam), nutritional support, fluid and electrolyte replacement, wound dressing, heating lamps to prevent hypothermia, and pain control. After 6 days of treatment, most of the detached skin lesions started to heal gradually without development of new lesions. However, on day 12 of admission, multiple clear water drop‑like vesicles and bullae, 1-30 mm in size erupted rapidly on thighs, bathing trunk areas, neck, and arms over 1 day. At that point, there was no new mucositis or targetoid lesion [Figure 1]. Because new episodes of SJS could not be ruled out, we analyzed the fluid content from blisters for the presence of granulysin which was not detected. Skin biopsy from a new vesicle revealed intracorneal blister overlying eccrine ducts and completely re‑epithelialized skin without apoptotic keratinocytes [Figure 2]. Based on the clinical and histopathologic findings, we hypothesized that the formation of these new blisters was secondary to fluid retention, but not persistent or recurrent SJS/TEN. Furthermore, because the location of new blisters was mainly on areas exposed to heating lamp we hypothesized that excessive
a
b
Figure 1: Multiple new clear fluid-filled blisters, 1-30 mm in size, erupted rapidly on (a) trunk, (b) arms, thighs, and neck in 1 day during remission stage. Re-epithelialization of the original detached wound could be seen on chest
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
Copyright of Indian Journal of Dermatology, Venereology & Leprology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Rafael Salido‑Vallejo, Gloria Garnacho‑Saucedo, José Carlos Moreno‑Giménez, Francisco M. Camacho‑Martínez1 Department of Dermatology, Hospital Universitario Reina Sofía, Córdoba, 1Department of Dermatology, School of Medicine, Hospital Universitario Virgen Macarena, Seville, Spain Address for correspondence: Dr. Rafael Salido Vallejo, M.D. C/Jose Manuel Rodriguez López, No. 7, Córdoba ‑ 302 14005, Spain. E‑mail: [email protected]
REFERENCES 1. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: A review of 60 cases. J Am Acad Dermatol 2012;67:955‑61. 2. Kossard S, Shiell RC. Frontal fibrosing alopecia developing after hair transplantation for androgenetic alopecia. Int J Dermatol 2005;44:321‑3. 3. Dlova NC, Goh CL. Frontal fibrosing alopecia in an African man. Int J Dermatol 2013. [In Press]. 4. Vañó‑Galván S, Molina‑Ruiz AM, Serrano‑Falcón C, Arias‑Santiago S, Rodrigues‑Barata AR, Garnacho‑Saucedo G, et al. Frontal fibrosing alopecia: A multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670‑8. 5. Miteva M, Camacho I, Romanelli P, Tosti A. Acute hair loss on the limbs in frontal fibrosing alopecia: A clinicopathological study of two cases. Br J Dermatol 2010;163:426‑8. 6. Ramaswamy P, Mendese G, Goldberg LJ. Scarring alopecia of the sideburns: A unique presentation of frontal fibrosing alopecia in men. Arch Dermatol 2012;148:1095‑6. 7. Samrao A, Chew AL, Price V. Frontal fibrosing alopecia: A clinical review of 36 patients. Br J Dermatol 2010;163:1296‑300. 8. Camacho FM. Lonely hair sign: Not specific for frontal fibrosing alopecia. Arch Dermatol 2012;148:1208‑9. Access this article online Quick Response Code:
Website: www.ijdvl.com DOI: 10.4103/0378-6323.144183 PMID: *****
Bullous pemphigoid clinically presenting as lichen amyloidosis Sir, A 42‑year‑old male presented to our hospital with complaints of moderately itchy, pigmented, papular lesions over the lower limbs for the last 2 years. There was mild itching to start with, following which the patient noticed gradual appearance of papules over his shins. There was no preceding history of any drug intake. On examination, there were multiple, discrete, closely‑set skin‑colored and pigmented papules of varying sizes symmetrically present over the antero‑lateral aspect and 544
calves of lower limbs symmetrically [Figure 1]. There was a sharp demarcation line between the lesions and normal skin. Individual papules were of about 1 cm in diameter, non‑tender with mild scaling but without oozing or excoriation. No other body site including mucosae, scalp, or nails was involved. We clinically suspected the case to be lichen amyloidosis and skin biopsy was sent with a request to the pathologist for a Congo red stain. Histopathological examination (HPE) revealed marked hyperkeratosis, normal to thinned‑out stratum malphigii, mild spongiosis along with a subepidermal bulla. There was a considerable collection of eosinophils, both in the blister cavity and in the upper dermis along with neutrophils and lymphocytes [Figures 2]. There was no evidence of any amyloid deposits with Congo red stain. These features were suggestive of bullous pemphigoid and subsequent perilesional skin biopsy for direct immunofluorescentce (DIF) examination showed deposition of IgG and C3 in the basement membrane zone [Figure 3]. Since topical clobetasol propionate, 0.05% ointment did not reduce the lesion count and size, we treated the patient with oral prednisolone 60 mg/day. The lesions regressed, but on gradual tapering to 20 mg of prednisolone per day over 8 weeks, the lesions stared recurring again. At this point, we lost the patient to follow up. Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder occurring in elderly individuals >60 years of age. There is tissue‑bound and circulating autoantibody against BP230 and BP180. In addition, there is an autoreactive cell‑mediated immune response against BP180.[1] Histopathology shows a subepidermal cleft with eosinophilic spongiosis and eosinophilic and mononuclear cell infiltrates in the upper dermis; direct immunoflourescence demonstrates presence of fine, linear continuous deposits of IgG and/or C3 along the epidermal basement membrane. Several clinical variants of bullous pemphigoid have been described including localized (such as pretibial pemphigoid, around stomas, vulvar and perineal region in female, at the site of irradiation or confined to paralyzed limb), isolated palmo‑plantar involvement (dyshidrosiform pemphigoid), dermatitis herpetiformis‑like (vesicular pemphigoid) erythrodermic bullous pemphigoid, lichen planus pemphigoides, gestational pemphigoid[2] and the rare pemphigoid incipiens (elderly patients with itchy BP like lesions but a negative DIF in the presence of circulating anti‑BP180 and/or BP230 antibodies).[3] Prurigo nodularis‑like
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
Letters to the Editor
Figure 1: Multiple discrete close-set papules in lower limb
Figure 2: Subepidermal blister with upper dermal eosinophil and lymphocyte collection within the blister cavity (H and E, x400)
and nodules distributed predominantly over lower limbs and shoulders. Blisters may precede or follow the development of nodules by many months, at the site of the nodule or on uninvolved skin.[4,5] Since the lesions were very close‑set and uniformly distributed in our patient, we did not consider pemphigoid nodularis as a possible differential diagnosis. The marked acanthosis and elongation of rete ridges with corresponding changes in the papillary dermis observed in pemphigoid nodularis were also not seen in our patient. Epidermolysis bullosa (EB) pruriginosa, a rare variant of dystrophic EB, may be considered in the differential diagnosi as a similar late presentation with subepidermal blisters and inflammatory infiltrate including eosinophils have been reported.[6] Lack of past history of trauma‑induced blistering, absence of a family history, lack of involvement of nails and a positive DIF helped to differentiate our case from EB pruriginosa. However, we could not carry out an electron microscopy examination, nor could we demonstrate any missense mutation in COL 7A1 gene (described in EB pruriginosa) as we did not have access to these investigations at our institute.[7] The age of onset of disease in our patient was much less than the usual for bullous pemphigoid; in addition, he did not develop clinical vesicles or bullae even after 2 years of onset of the lesions. He had closely‑set papules uniformly distributed only over the lower limbs, resembling the papules of cutaneous amyloidosis. A single case has been reported in the literature as ‘lichen amyloidosis with subepidermal blister’ where the patient presented with multiple itchy keratotic papules and plaques on trunk and extremities with intermingled erosions and vesicles. The case was clinically reminiscent of prurigo nodularis but histopathology showed subepidermal bulla with amyloid deposit in the dermal papillae, visible on Dylon and Congo red staining. Direct immunofluorescence was normal.[8] In contrast, our case did not demonstrate any amyloid deposit in the dermal papillae.
Projna Biswas, Ishad Aggarwal, Debashis Sen, Atoka Sumi, Arghyaprasun Ghosh1
Figure 3: Direct immunoflourescence showing presence of fine, linear continuous deposits along the epidermal basement membrane (x100)
pemphigoid (nodular pemphigoid) is a variant where elderly women present with excoriated papules
Departments of Dermatology, Institute of Post Graduate Medical Education and Research, 1 Radha Gobinda Kar Medical College, Kolkata, West Bengal, India Address for correspondence: Dr. Projna Biswas, Depatrment of Dermatology, Institute of Post Graduate Medical Education and Research, Kusumba (SDPark), PO‑Narendrapur, PS‑Sonarpur, Kolkata ‑ 700 103, West Bengal, India. E‑mail: [email protected]
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
545
Letters to the Editor
REFERENCES 1. Culton DA, Liu Z, Diaz LA. Bullous pemphigoid.In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Editors. Fitzpatrick’s Dermatology in General Medicine. 8th ed.New York: McGraw‑Hill; 2012.p. 608‑16. 2. Borradori L, BernardP. Pemphigoidgroup. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 2nd ed. Spain: Mosby Elsevier; 2008.p. 137‑48. 3. Tambe S, Häfliger S, Borradori L. Clinical challenges and recent advances in the diagnosis of bullous pemphigoid. Expert Rev Dermatol 2013;8:407‑16. 4. Borradori L, Prost C, Wolkenstein P, Bernard P, Baccard M, Morel P. Localized pretibialpemphigoid and pemphigoidnodularis. J Am Acad Dermatol 1992;27:863‑7. 5. Cliff S, Holden CA. Pemphigoidnodularis: A report of three cases and review of the literature. Br J Dermatol 1997;136:398‑401. 6. Vivehanantha S, Carr RA, McGrath JA, Taibjee SM, Madhogaria S, Ilchyshyn A. Epidermolysisbullosapruriginosa: A case with prominent histopathologic inflammation. JAMA Dermatol 2013;149:727‑31. 7. Shi BJ, Feng J. A novel missense mutation in the COL7A1 gene causes epidermolysisbullosapruriginosa. Clin Exp Dermatol 2009;34:e975‑8. 8. Kuroda K, Mizoguchi M. Lichen amyloidosus with subepidermal blister formation. Eur J Dermatol 2004;14:262‑3. Access this article online Quick Response Code:
Website: www.ijdvl.com DOI: 10.4103/0378-6323.144184 PMID: *****
Recurrent blisters in a case of resolving Stevens–Johnson syndrome/toxic epidermal necrolysis Sir, Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially life‑threatening, mainly drug‑induced conditions characterized by widespread apoptosis of keratinocytes provoked by the activation of cell‑mediated cytotoxic reaction and amplified by cytokines, mainly granulysin. Dry skin and heat intolerance are common complaints among survivors of SJS/TEN.[1] We report a patient with SJS/TEN overlap who developed recurrence of vesicles and bullae several days after the initial healing of lesions due to sweat retention which simulated a fresh episode of SJS/TEN. 546
A 51‑year‑old woman who had rectal cancer with lung and brain metastases was admitted to our burn center because of phenytoin induced SJS/TEN overlap. Phenytoin had been introduced 32 days before the skin rash to control seizures after whole brain radiotherapy. On physical examination, the patient exhibited conjunctivitis, oral mucositis, and generalized maculopapular rash characterized by atypical targetoid lesions with centrally darkened macules and blisters. She was treated with supportive care including empiric antibiotics (piperacillin/ tazobactam), nutritional support, fluid and electrolyte replacement, wound dressing, heating lamps to prevent hypothermia, and pain control. After 6 days of treatment, most of the detached skin lesions started to heal gradually without development of new lesions. However, on day 12 of admission, multiple clear water drop‑like vesicles and bullae, 1-30 mm in size erupted rapidly on thighs, bathing trunk areas, neck, and arms over 1 day. At that point, there was no new mucositis or targetoid lesion [Figure 1]. Because new episodes of SJS could not be ruled out, we analyzed the fluid content from blisters for the presence of granulysin which was not detected. Skin biopsy from a new vesicle revealed intracorneal blister overlying eccrine ducts and completely re‑epithelialized skin without apoptotic keratinocytes [Figure 2]. Based on the clinical and histopathologic findings, we hypothesized that the formation of these new blisters was secondary to fluid retention, but not persistent or recurrent SJS/TEN. Furthermore, because the location of new blisters was mainly on areas exposed to heating lamp we hypothesized that excessive
a
b
Figure 1: Multiple new clear fluid-filled blisters, 1-30 mm in size, erupted rapidly on (a) trunk, (b) arms, thighs, and neck in 1 day during remission stage. Re-epithelialization of the original detached wound could be seen on chest
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2014 | Vol 80 | Issue 6
Copyright of Indian Journal of Dermatology, Venereology & Leprology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
