Letters to the Editor
330
pressure-relieving pillow were introduced with a partial improvement in the lesions. Histological examination of the skin showed for all patients: dilated follicular infundibula filled with keratotic plugs extending into the dermis (Fig. 2a, c and e). There were a number of degenerated elastic fibres eliminated through the epidermis (Fig. 2b, d and f). Acquired perforating dermatosis comprises the perforating disorders occurring in adult patients: elastosis perforans serpiginosa (EPS), reactive perforating collagenosis, perforating folliculitis (PF) and Kyrle’s disease.3 A variety of diseases including kidney or hepatocellular carcinoma, have been associated with APD.4,5 We report here three adult patients treated with sorafenib for hepatocellular or renal cell carcinoma who developed APD in the form of PF and EPS. An only patient had a cholestatic syndrome. No patient had uncontrolled diabetes and/or renal failure. The skin eruption began 2, 38 and 2 months, respectively, after the initiation of sorafenib. It should be noted that in the second case the skin eruption began 2 months after the onset of pruritus associated with hepatic cholestasis. Four cases of PF occurring during sorafenib treatment have been described in the literature.1,6–8 Several mechanisms may explain the development of APD with sorafenib: 1 Disruption of epidermal homeostasis by the paradoxical activation of c-RAF, a serine/threonine kinase involved in epidermal tumourigenesis, resulting in reduced differentiation.9 2 Disruption of homeostasis of elastic fibres by decreased metalloproteinase-9 expression, which may account for the elimination of elastic fibres.2 3 Mechanical/traumatic factors promoting an increase in keratinocytes proliferation/differentiation ratio and increased elastic tissue.10 Precipitating traumatic factors were present in all patients. These are the first cases of APD involving both PF and EPS during sorafenib therapy. The simultaneous occurrence of PF and EPS in patients treated with sorafenib supports the concept of a continuous spectrum of APD.3 M. Severino-Freire,1 V. Sibaud,2 E. Tournier,3 C. Pauwels,1 C. Christol,4 L. Lamant,3 J. Hautier-Mazeereuw,1 J.-M. Peron,4 C. Paul,1 C. Bulai Livideanu1,* 1 Department of Dermatology, Paul Sabatier University, Toulouse University Hospital, 2Departement of Dermatology, Institut Claudius Regaud, 3Department of Anatomo Pathology, Toulouse University Hospital, 4Department of Hepatology, Toulouse University Hospital, Toulouse, France *Correspondence: C. Bulai Livideanu. E-mail: [email protected]
References 1 Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008; 144: 886–892.
JEADV 2016, 30, 320–386
2 Changchun Z, Jibing L, Yang L et al. MicroRNA-127a, a modulator of sorafenib induced a disintegrin and metalloproteinase 9 (ADAM9) down-regulation in hepatocellular carcinoma. FEBS Lett 2011; 585: 1828–1834. 3 Salhi A, Heid E, Grosshans E, Cribier B. Collagenose perforante reactionnelle. Ann Dermatol Venerol 2012; 139: 481–485. 4 Kurban M, Uthman I, Kibbi AG, Ghosn S. Acquired perforating dermatosis heralding metastatic renal cell carcinoma to the liver. Int J Dermatol 2008; 47: 1038–1040. 5 Lee YS, Vijayasingam S, Tan YO, Wong ST. Acquired perforating dermatosis associated with recurrent hepatocellular carcinoma. Int J Dermatol 1996; 35: 743–745. 6 Wolber C, Udvardi A, Tatzreiter G, Schneeberger A, Volc-Platzer B. Perforating folliculitis, angioedema, hand-foot syndrome, multiple cutaneous side effects in a patient treated with sorafenib. J Dtsch Dermatol Ges 2009; 7: 449–451. 7 Minami-Hori M, Ishida-Yamamoto A, Komatsu S, Iiduka H. Transient perforating folliculitis induced by sorafenib. J Dermatol 2010; 37: 833– 834. 8 Eberst E, Rigau V, Pageaux GP et al. Perforating folliculitis–like reaction related to sorafenib. Cutis 2014; 93: E8–E10. 9 Kern F, Niault T, Baccarini M. Ras and Raf pathways in epidermis development and carcinogenesis. Br J Cancer 2011; 104: 229–234. 10 Reichelt J. Mechanotransduction of keratinocytes in culture and in the epidermis. Eur J Cell Biol 2007; 86: 807–816. DOI: 10.1111/jdv.12720
Childhood bullous pemphigoid: report of 2 cases Editor Bullous pemphigoid is an immune-mediated subepidermal blistering disease associated with humoral and cell response directed against BP antigen 180 and 2301. Childhood BP is rare and lesions are more frequently localized to the acral areas, with palm and sole involvement1,2. A 6-month-old girl, previously healthy and with no familial history of bullous diseases, developed an eruption of bullous lesions, on an erythematous base, confluent, located in both hands and feet, with palm and sole involvement (Fig. 1a,b). She presented with multiple erythematous patches and plaques, with central and peripheral vesicles in the trunk and extremities (Fig. 1c). No mucosal involvement was detected. The eruption was present for a week, and there was no previous history of infection or vaccination. The child was otherwise well. There was leukocytosis (20.2 G/L) with eosinophilia (26.9%; 5.4 9 103/lL). Other laboratory findings were unremarkable. The biopsy showed a sub-epidermic blister in elimination containing eosinophils, no acantholysis and dermal eosinophil infiltration (Fig. 1d). Direct immunofluorescence (DIF) revealed linear reactivity for C3 along the dermal–epidermal junction (DEJ) and indirect immunofluorescence (IIF) revealed high
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
331
(a)
(b)
(c)
(d)
Figure 1 (a) Exuberant confluent bullous lesions, on an erythematous base, located in feet, with sole involvement; (b) Vesicles, tense bullae and erythematous papules and plaques in the left hand and forearm; (c) Erythematous plaque in the forearm, with multiple vesicles and some small crusts; (d) Sub-epidermal blister with serous material and eosinophils with re-epithelization (HE 409).
(a)
(b)
(c)
(d)
Figure 2 (a) Tense bullae on the soles; (b) Multiple ovaloid erythematous plaques, some with vesicles, on the forearm and abdomen. (c) Multiple vesicles and bullae with acral distribution. (d) Blister in elimination rich in eosinophils, with dermal lymphocyte and eosinophil infiltrates (HE 259). (e) DIF showing linear deposition of IgG in the epidermal basement membrane.
levels of IgG anti-BP180 (> 200 U/mL; n < 20 U/mL). No inter-epidermal auto-antibodies were detected (ELISA). A previously healthy 4-month-old boy presented with vesicles and tense bullae on the trunk, hands and feet with palm and sole involvement and ovaloid erythematous plaques on the face,
JEADV 2016, 30, 320–386
(e)
neck, abdomen and lower limbs (Fig. 2a–c). The lesions had appeared 10 days before, one week after an upper respiratory viral infection and 4-month vaccination (diphtheria, tetanus, pertussis, polio, Haemophilus influenza B and pneumococcus). There were no systemic symptoms.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
332
Laboratory findings were unremarkable. The histological examination showed a blister in elimination and dermal eosinophil infiltration (Fig. 2d). DIF revealed linear reactivity for IgG (Fig. 2e), IgM and C3 along the DEJ. High levels of IgG anti-BP180 (312 U/mL) were detected in IIF (ELISA). They were both treated with oral prednisolone (1.5 mg/kg/ day) and methylprednisolone aceponate 0.1% cream id. In case 1, there was complete remission within 2 months of the treatment. In case 2, there were relapses during the attempts to reduce the oral prednisolone, which was continued for 2.5 months. There was a complete remission within 3 months of treatment. They are both free of lesions after 18 months of follow-up. Childhood BP is a sub-epidermal blistering disease with eosinophil infiltration. There are 2 peaks of incidence: the first year of life (with facial lesions and acral distribution with palmo-plantar involvement1,3) and around the age of 83. In our case, an intra-epidermal vesicle was observed but, as biopsies were performed in lesions that were present for more than 1 week, we can suspect that the process of re-epithelialization might have been responsible for this histological finding. Vaccination has been reported as preceding the onset of childhood BP, raising the possibility of association between vaccination and childhood BP2,3. Because the number of vaccines in the first year of life is quite high, it is sometimes difficult to establish a causal relation3. Childhood BP is generally self-limited, with a good and rapid response to topical or systemic corticotherapy, being remission usually achieved within a few months. In case of resistance, other drugs can be used, such as dapsone, azathioprine, cyclosporine, intravenous immunoglobulins and mycophenolate mofetil2,3.
Plaque-like papular xanthoma: a new variant of non-Langerhans cell disease Editor So-called histiocytic (epithelioid) infiltrates occur in the skin as a secondary event, as the result of an underlying infection, dyslipidaemia or neoplasm, or as a primary proliferation of macrophages. In the latter, they can be divided into Langerhans cell disease (LCD) and non-LCD (n-LCD).1 n-LCD encompasses self-limited histiocytoses that affect solely the skin but also other entities associated with systemic disease, such as necrobiotic xanthogranuloma or xanthoma disseminatum.2 Xanthomas, on the contrary, correspond to the deposit of lipids in macrophages as a secondary event1 and can be classified according to clinical features and association with dyslipidaemia. The papular xanthoma (PX) first described by Winkelmann3 has features of both a secondary and primary macrophagic disorder and therefore its place among the xanthomatosis or the n-LCD histiocytosis is not completely clarified. Recently, a new variant of papular xanthoma has been described by Emberger et al.,4 who reported a 70-year-old normolipemic woman with a solitary, elevated red-yellow plaque in the submammary region, histologically consistent with papular xanthoma but with predominance of Touton
L. Ramos,1 O. Tellechea,1 A. Moreno,1 L. Martins,2 N. rio,2 C. Rodrigues3 Neves,2 G. Janua Servicßo de Dermatologia e Venereologia, Hospitais da Universidade de rio de Coimbra, 2Servicßo de Coimbra, Centro Hospitalar e Universita trico, Centro Hospitalar e Universita rio de Pediatria, Hospital Pedia Coimbra, 3Servicßo de Pediatria, Centro Hospitalar da Cova da Beira *Correspondence: L. Ramos. E-mail: [email protected]
1
References 1 Santos AL, Mota AV, Ramon J, Lopes JM, Azevedo F. An infant with bullous pemphigoid. Dermatol Online J 2007; 13: 17. 2 Aky n MA, Gunes T, Aky n L, Ohyama B, Kontas O, Hashimoto T. A newborn with bullous pemphigoid associated with linear IgA bullous dermatosis. Acta Dermatovenerol Alp Pannonica Adriat 2009; 18: 66–70. 3 Toyama T, Nakamura K, Kuramochi A, Ohyama B, Hashimoto T, Tsuchida T. Two cases of childhood bullous pemphigoid. Eur J Dermatol 2009; 19: 368–371. DOI: 10.1111/jdv.12724
JEADV 2016, 30, 320–386
Figure 1 Well-demarcated yellow to orange confluent plaques occupying the mandibular and submandibular region.
© 2014 European Academy of Dermatology and Venereology
330
pressure-relieving pillow were introduced with a partial improvement in the lesions. Histological examination of the skin showed for all patients: dilated follicular infundibula filled with keratotic plugs extending into the dermis (Fig. 2a, c and e). There were a number of degenerated elastic fibres eliminated through the epidermis (Fig. 2b, d and f). Acquired perforating dermatosis comprises the perforating disorders occurring in adult patients: elastosis perforans serpiginosa (EPS), reactive perforating collagenosis, perforating folliculitis (PF) and Kyrle’s disease.3 A variety of diseases including kidney or hepatocellular carcinoma, have been associated with APD.4,5 We report here three adult patients treated with sorafenib for hepatocellular or renal cell carcinoma who developed APD in the form of PF and EPS. An only patient had a cholestatic syndrome. No patient had uncontrolled diabetes and/or renal failure. The skin eruption began 2, 38 and 2 months, respectively, after the initiation of sorafenib. It should be noted that in the second case the skin eruption began 2 months after the onset of pruritus associated with hepatic cholestasis. Four cases of PF occurring during sorafenib treatment have been described in the literature.1,6–8 Several mechanisms may explain the development of APD with sorafenib: 1 Disruption of epidermal homeostasis by the paradoxical activation of c-RAF, a serine/threonine kinase involved in epidermal tumourigenesis, resulting in reduced differentiation.9 2 Disruption of homeostasis of elastic fibres by decreased metalloproteinase-9 expression, which may account for the elimination of elastic fibres.2 3 Mechanical/traumatic factors promoting an increase in keratinocytes proliferation/differentiation ratio and increased elastic tissue.10 Precipitating traumatic factors were present in all patients. These are the first cases of APD involving both PF and EPS during sorafenib therapy. The simultaneous occurrence of PF and EPS in patients treated with sorafenib supports the concept of a continuous spectrum of APD.3 M. Severino-Freire,1 V. Sibaud,2 E. Tournier,3 C. Pauwels,1 C. Christol,4 L. Lamant,3 J. Hautier-Mazeereuw,1 J.-M. Peron,4 C. Paul,1 C. Bulai Livideanu1,* 1 Department of Dermatology, Paul Sabatier University, Toulouse University Hospital, 2Departement of Dermatology, Institut Claudius Regaud, 3Department of Anatomo Pathology, Toulouse University Hospital, 4Department of Hepatology, Toulouse University Hospital, Toulouse, France *Correspondence: C. Bulai Livideanu. E-mail: [email protected]
References 1 Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008; 144: 886–892.
JEADV 2016, 30, 320–386
2 Changchun Z, Jibing L, Yang L et al. MicroRNA-127a, a modulator of sorafenib induced a disintegrin and metalloproteinase 9 (ADAM9) down-regulation in hepatocellular carcinoma. FEBS Lett 2011; 585: 1828–1834. 3 Salhi A, Heid E, Grosshans E, Cribier B. Collagenose perforante reactionnelle. Ann Dermatol Venerol 2012; 139: 481–485. 4 Kurban M, Uthman I, Kibbi AG, Ghosn S. Acquired perforating dermatosis heralding metastatic renal cell carcinoma to the liver. Int J Dermatol 2008; 47: 1038–1040. 5 Lee YS, Vijayasingam S, Tan YO, Wong ST. Acquired perforating dermatosis associated with recurrent hepatocellular carcinoma. Int J Dermatol 1996; 35: 743–745. 6 Wolber C, Udvardi A, Tatzreiter G, Schneeberger A, Volc-Platzer B. Perforating folliculitis, angioedema, hand-foot syndrome, multiple cutaneous side effects in a patient treated with sorafenib. J Dtsch Dermatol Ges 2009; 7: 449–451. 7 Minami-Hori M, Ishida-Yamamoto A, Komatsu S, Iiduka H. Transient perforating folliculitis induced by sorafenib. J Dermatol 2010; 37: 833– 834. 8 Eberst E, Rigau V, Pageaux GP et al. Perforating folliculitis–like reaction related to sorafenib. Cutis 2014; 93: E8–E10. 9 Kern F, Niault T, Baccarini M. Ras and Raf pathways in epidermis development and carcinogenesis. Br J Cancer 2011; 104: 229–234. 10 Reichelt J. Mechanotransduction of keratinocytes in culture and in the epidermis. Eur J Cell Biol 2007; 86: 807–816. DOI: 10.1111/jdv.12720
Childhood bullous pemphigoid: report of 2 cases Editor Bullous pemphigoid is an immune-mediated subepidermal blistering disease associated with humoral and cell response directed against BP antigen 180 and 2301. Childhood BP is rare and lesions are more frequently localized to the acral areas, with palm and sole involvement1,2. A 6-month-old girl, previously healthy and with no familial history of bullous diseases, developed an eruption of bullous lesions, on an erythematous base, confluent, located in both hands and feet, with palm and sole involvement (Fig. 1a,b). She presented with multiple erythematous patches and plaques, with central and peripheral vesicles in the trunk and extremities (Fig. 1c). No mucosal involvement was detected. The eruption was present for a week, and there was no previous history of infection or vaccination. The child was otherwise well. There was leukocytosis (20.2 G/L) with eosinophilia (26.9%; 5.4 9 103/lL). Other laboratory findings were unremarkable. The biopsy showed a sub-epidermic blister in elimination containing eosinophils, no acantholysis and dermal eosinophil infiltration (Fig. 1d). Direct immunofluorescence (DIF) revealed linear reactivity for C3 along the dermal–epidermal junction (DEJ) and indirect immunofluorescence (IIF) revealed high
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
331
(a)
(b)
(c)
(d)
Figure 1 (a) Exuberant confluent bullous lesions, on an erythematous base, located in feet, with sole involvement; (b) Vesicles, tense bullae and erythematous papules and plaques in the left hand and forearm; (c) Erythematous plaque in the forearm, with multiple vesicles and some small crusts; (d) Sub-epidermal blister with serous material and eosinophils with re-epithelization (HE 409).
(a)
(b)
(c)
(d)
Figure 2 (a) Tense bullae on the soles; (b) Multiple ovaloid erythematous plaques, some with vesicles, on the forearm and abdomen. (c) Multiple vesicles and bullae with acral distribution. (d) Blister in elimination rich in eosinophils, with dermal lymphocyte and eosinophil infiltrates (HE 259). (e) DIF showing linear deposition of IgG in the epidermal basement membrane.
levels of IgG anti-BP180 (> 200 U/mL; n < 20 U/mL). No inter-epidermal auto-antibodies were detected (ELISA). A previously healthy 4-month-old boy presented with vesicles and tense bullae on the trunk, hands and feet with palm and sole involvement and ovaloid erythematous plaques on the face,
JEADV 2016, 30, 320–386
(e)
neck, abdomen and lower limbs (Fig. 2a–c). The lesions had appeared 10 days before, one week after an upper respiratory viral infection and 4-month vaccination (diphtheria, tetanus, pertussis, polio, Haemophilus influenza B and pneumococcus). There were no systemic symptoms.
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
332
Laboratory findings were unremarkable. The histological examination showed a blister in elimination and dermal eosinophil infiltration (Fig. 2d). DIF revealed linear reactivity for IgG (Fig. 2e), IgM and C3 along the DEJ. High levels of IgG anti-BP180 (312 U/mL) were detected in IIF (ELISA). They were both treated with oral prednisolone (1.5 mg/kg/ day) and methylprednisolone aceponate 0.1% cream id. In case 1, there was complete remission within 2 months of the treatment. In case 2, there were relapses during the attempts to reduce the oral prednisolone, which was continued for 2.5 months. There was a complete remission within 3 months of treatment. They are both free of lesions after 18 months of follow-up. Childhood BP is a sub-epidermal blistering disease with eosinophil infiltration. There are 2 peaks of incidence: the first year of life (with facial lesions and acral distribution with palmo-plantar involvement1,3) and around the age of 83. In our case, an intra-epidermal vesicle was observed but, as biopsies were performed in lesions that were present for more than 1 week, we can suspect that the process of re-epithelialization might have been responsible for this histological finding. Vaccination has been reported as preceding the onset of childhood BP, raising the possibility of association between vaccination and childhood BP2,3. Because the number of vaccines in the first year of life is quite high, it is sometimes difficult to establish a causal relation3. Childhood BP is generally self-limited, with a good and rapid response to topical or systemic corticotherapy, being remission usually achieved within a few months. In case of resistance, other drugs can be used, such as dapsone, azathioprine, cyclosporine, intravenous immunoglobulins and mycophenolate mofetil2,3.
Plaque-like papular xanthoma: a new variant of non-Langerhans cell disease Editor So-called histiocytic (epithelioid) infiltrates occur in the skin as a secondary event, as the result of an underlying infection, dyslipidaemia or neoplasm, or as a primary proliferation of macrophages. In the latter, they can be divided into Langerhans cell disease (LCD) and non-LCD (n-LCD).1 n-LCD encompasses self-limited histiocytoses that affect solely the skin but also other entities associated with systemic disease, such as necrobiotic xanthogranuloma or xanthoma disseminatum.2 Xanthomas, on the contrary, correspond to the deposit of lipids in macrophages as a secondary event1 and can be classified according to clinical features and association with dyslipidaemia. The papular xanthoma (PX) first described by Winkelmann3 has features of both a secondary and primary macrophagic disorder and therefore its place among the xanthomatosis or the n-LCD histiocytosis is not completely clarified. Recently, a new variant of papular xanthoma has been described by Emberger et al.,4 who reported a 70-year-old normolipemic woman with a solitary, elevated red-yellow plaque in the submammary region, histologically consistent with papular xanthoma but with predominance of Touton
L. Ramos,1 O. Tellechea,1 A. Moreno,1 L. Martins,2 N. rio,2 C. Rodrigues3 Neves,2 G. Janua Servicßo de Dermatologia e Venereologia, Hospitais da Universidade de rio de Coimbra, 2Servicßo de Coimbra, Centro Hospitalar e Universita trico, Centro Hospitalar e Universita rio de Pediatria, Hospital Pedia Coimbra, 3Servicßo de Pediatria, Centro Hospitalar da Cova da Beira *Correspondence: L. Ramos. E-mail: [email protected]
1
References 1 Santos AL, Mota AV, Ramon J, Lopes JM, Azevedo F. An infant with bullous pemphigoid. Dermatol Online J 2007; 13: 17. 2 Aky n MA, Gunes T, Aky n L, Ohyama B, Kontas O, Hashimoto T. A newborn with bullous pemphigoid associated with linear IgA bullous dermatosis. Acta Dermatovenerol Alp Pannonica Adriat 2009; 18: 66–70. 3 Toyama T, Nakamura K, Kuramochi A, Ohyama B, Hashimoto T, Tsuchida T. Two cases of childhood bullous pemphigoid. Eur J Dermatol 2009; 19: 368–371. DOI: 10.1111/jdv.12724
JEADV 2016, 30, 320–386
Figure 1 Well-demarcated yellow to orange confluent plaques occupying the mandibular and submandibular region.
© 2014 European Academy of Dermatology and Venereology
