Letters to the editor
821
E. Cozzani,1,* M. Scaparro,1 F. Rongioletti,1 I. Pierri,2 N. Pimpinelli,3 A. Parodi1 1
Di.S.Sal. Section of Dermatology, San Martino-IRCCS-IST, Genoa, Italy, 2 Department of Hematology and Oncology, San Martino-IRCCS-IST, Genoa, Italy, 3Department of Surgery and Translational Medicine, Section Dermatology, University of Florence, Florence, Italy *Correspondence: E. Cozzani. E-mail: [email protected]
References 1 Bruggemann M, White H, Gaulard P et al. Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936. Leukemia 2007; 21: 215–221. 2 Salameh F, Barzilai A, Boum S, Trau H. Mycosis fungoides and CD30 + cutaneous T-cell lymphoma simulating pyoderma gangrenosum in a patient with ulcerative colitis. J Dermatol Case Rep 2009; 3: 30–33. 3 Carbia SG, Hochman A, Chain M et al. Mycosis fungoides presenting with exstensive pyoderma gangrenosum-like ulcers. J Eur Acad Dermatol Venereol 2002; 16: 401–404. 4 Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol 1993; 28: 973–980. 5 Kang SK, Chang SE, Choi JH, Sung KJ, Moon KC, Koh JK. Coexistence of CD30-positive anaplastic large cell lymphoma and mycosis fungoides. Clin Exp Dermatol 2002; 27: 212-215. 6 Marschalk o M, Csomor J, Eros N et al. Coexistence of primary cutaneous anaplastic large cell lymphoma and mycosis fungoides in a patient with B-cell chronic lymphocytic leukaemia. Br J Dermatol 2007; 157: 1291– 1293.
Figure 1 Urticarial and erythematous plaques with tense bullae on the face.
DOI: 10.1111/jdv.12418
Bullous pemphigoid in a patient with multiple sclerosis being treated with human immunoglobulin Editor Bullous pemphigoid (BP) is the commonest autoimmune bullous disease and is caused by autoantibodies towards two hemidesmossome glycoproteins – BP180 and BP230. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of central nervous system mediated by T lymphocytes. Sanders and Nelson first described the association of BP and chronic demyelinating diseases in 1965.1 There are 52 cases of this association described in the literature.2–5 We report the case of a 48-year-old man with MS diagnosed 18 years ago, with a 7.5 score in Kurtzke Expanded Disability Status Scale treated with intravenous human immunoglobulin
JEADV 2015, 29, 818–832
Figure 2 Histopathology (H&E staining) – subepidermal bulla with eosinophils and a scarce polymorphous inflammatory infiltrate in the underlying dermis.
(IVIG) in a dose of 0.4 g/kg per cycle, every 4 weeks for the last 7 years, who had developed erythematous patches and bullous lesions 2 months ago. At the physical examination, we observed urticarial, erythematous patches and plaques with tense bullae distributed over the face, trunk, members and oral mucosa, suggesting the clinical diagnosis of BP (Fig. 1). Histopathological confirmation revealed a subepidermal bulla with eosinophils and a scarce polymorphous inflammatory infiltrate in the underlying dermis (Fig. 2). The direct immunofluorescence showed a linear
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
822
basal deposition of anti-C3. Anti-basal membrane antibodies and anti-BP180 were detected by indirect immunofluorescence. Anti-thyroglobulin antibodies were positive. Treatment was initiated with prednisolone 1 mg/Kg per day and mycophenolate mophetil 2 g per day with good control of the dermatosis. After a 1-year follow-up, all the lesions have cleared with just residual millia on the hands’ dorsae. We emphasize the precocious age of development of BP in a MS patient, in accordance with other reported cases.2–5 This case illustrates a well-known association resulting in an 113–15-fold4 increase in the odds of developing BP. Although the aetiology of these chronic autoimmune disorders is still unknown, the neuronal isoform of BP antigen-1 raises the hypothesis of a shared antigen response due to the cross reactivity between the epithelial and neurological isoforms.6–8 Nonetheless, a recent report showed that basement membrane zone autoantibodies were not frequently present in MS sera in the absence of BP, maybe due to the protective effect of the blood–brain barrier.5 In our case, the development of BP in a patient treated with human immunoglobulin makes it an enigma to solve, perhaps explained for the significant lower dose that was used for MS treatment (0.2–0.4 g/kg) vs. the preconized dose for BP treatment (2 g/Kg), maybe not allowing for the necessary binding of the Fc portion of IVIG to BP antigens. To our knowledge, this is the first reported case of a MS patient treated with human immunoglobulin who developed BP. rio-Ferreira,1 M. Nora,2 A.F. Massa,1,* P. Varela,1 E. Oso A. Couceiro,3 A. Baptista1 1
Department of Dermatology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal, 2Department of Neurology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal, 3 Department of Pathology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal *Correspondence: A.F. Massa. E-mail: [email protected]
References 1 Sanders SL, Nelson CT. Pemphigus and pemphigoid. Med Clin North Am 1965; 49: 681–694. 2 Peramiquel L, Barnadas MA, Pimentel CL et al. Bullous pemphigoid and multiple sclerosis: a report of two cases with ELISA test. Eur J Dermatol 2007; 17: 62–66. 3 Langan SM, Groves RW, West J. The relationship between neurological disease and bullous pemphigoid: a population-based case-control study. J Invest Dermatol 2011; 131: 631–636. 4 Nielsen N, Frisch M, Rostgaard K et al. Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark. Mult Scler 2008; 14: 823–829. 5 Taghipour K, Kirtschig G, Palace J, Groves RW, Venning V, Wojnarowska F. The association of multiple sclerosis with bullous
JEADV 2015, 29, 818–832
pemphigoid: is there a shared antigen response? J Am Acad Dermatol 2012; 67: 160–161. 6 Brown A, Bernier G, Mathieu M et al. The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1. Nat Genet 1995; 10: 301–306. 7 Laffitte E, Burkhard PR, Fontao L et al. Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis? Br J Dermatol 2005; 152: 537–540. 8 Li L, Chen J, Wang B et al. Sera from patients with bullous pemphigoid (BP) associated with neurological diseases recognized BP antigen 1 in the skin and brain. Br J Dermatol 2009; 160: 1343–1345. DOI: 10.1111/jdv.12425
Tuberous sclerosis underlying neonatal poliosis Editor An 18-month-old child came to our attention because of his seizures and for a clear diagnosis of his mental development. The parents were not consanguineous and did not present any particular disease. At physical examination, tufts of white hair (poliosis) were found. According to the mother, they were present since the early days of life. Two of them, over the nuchal and parietal right areas, were very evident (Fig. 1a). Skin presented numerous achromic hypomelanotic macules, which appeared a few months after birth; some of them, over the trunk and limbs, were lanceolate. Heart ultrasounds revealed the presence of a rhabdomyoma at the level of the lower wall of the left ventricle (Fig. 1b). The presence of the cardiac hamartoma and hypochromia of hair, along with hypomelanotic macules over the skin, allowed us to diagnose tuberous sclerosis, which was subsequently confirmed by brain magnetic resonance imaging, showing cortical tubers (Fig. 1c). Hypomelanotic macules are the most frequent and earliest cutaneous sign of tuberous sclerosis.1 They appear in the first 6 months of life in 70% of cases, mainly affecting the trunk and the lower limbs. Head and neck are rarely involved.1 They are rarely present at birth and it is difficult to detect them in newborns with fair skin. However, a tuft of white hair (poliosis) at birth may be a useful sign for the early detection of tuberous sclerosis in newborns. In 1978, McWilliam et al.2 reported four patients with this feature, long before the introduction of the current diagnostic criteria in the literature. Subsequent reports seem to be extremely rare.3,4 The differential diagnosis of neonatal poliosis must take into account other disorders, such as Waardenburg syndrome, Piebaldism, and Vogt-Koyanagi syndrome, but these conditions are usually not easily confused with tuberous sclerosis. Follicular melanocytes, such as epidermal and ocular uveal melanocytes (choroid and
© 2014 European Academy of Dermatology and Venereology
821
E. Cozzani,1,* M. Scaparro,1 F. Rongioletti,1 I. Pierri,2 N. Pimpinelli,3 A. Parodi1 1
Di.S.Sal. Section of Dermatology, San Martino-IRCCS-IST, Genoa, Italy, 2 Department of Hematology and Oncology, San Martino-IRCCS-IST, Genoa, Italy, 3Department of Surgery and Translational Medicine, Section Dermatology, University of Florence, Florence, Italy *Correspondence: E. Cozzani. E-mail: [email protected]
References 1 Bruggemann M, White H, Gaulard P et al. Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936. Leukemia 2007; 21: 215–221. 2 Salameh F, Barzilai A, Boum S, Trau H. Mycosis fungoides and CD30 + cutaneous T-cell lymphoma simulating pyoderma gangrenosum in a patient with ulcerative colitis. J Dermatol Case Rep 2009; 3: 30–33. 3 Carbia SG, Hochman A, Chain M et al. Mycosis fungoides presenting with exstensive pyoderma gangrenosum-like ulcers. J Eur Acad Dermatol Venereol 2002; 16: 401–404. 4 Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol 1993; 28: 973–980. 5 Kang SK, Chang SE, Choi JH, Sung KJ, Moon KC, Koh JK. Coexistence of CD30-positive anaplastic large cell lymphoma and mycosis fungoides. Clin Exp Dermatol 2002; 27: 212-215. 6 Marschalk o M, Csomor J, Eros N et al. Coexistence of primary cutaneous anaplastic large cell lymphoma and mycosis fungoides in a patient with B-cell chronic lymphocytic leukaemia. Br J Dermatol 2007; 157: 1291– 1293.
Figure 1 Urticarial and erythematous plaques with tense bullae on the face.
DOI: 10.1111/jdv.12418
Bullous pemphigoid in a patient with multiple sclerosis being treated with human immunoglobulin Editor Bullous pemphigoid (BP) is the commonest autoimmune bullous disease and is caused by autoantibodies towards two hemidesmossome glycoproteins – BP180 and BP230. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of central nervous system mediated by T lymphocytes. Sanders and Nelson first described the association of BP and chronic demyelinating diseases in 1965.1 There are 52 cases of this association described in the literature.2–5 We report the case of a 48-year-old man with MS diagnosed 18 years ago, with a 7.5 score in Kurtzke Expanded Disability Status Scale treated with intravenous human immunoglobulin
JEADV 2015, 29, 818–832
Figure 2 Histopathology (H&E staining) – subepidermal bulla with eosinophils and a scarce polymorphous inflammatory infiltrate in the underlying dermis.
(IVIG) in a dose of 0.4 g/kg per cycle, every 4 weeks for the last 7 years, who had developed erythematous patches and bullous lesions 2 months ago. At the physical examination, we observed urticarial, erythematous patches and plaques with tense bullae distributed over the face, trunk, members and oral mucosa, suggesting the clinical diagnosis of BP (Fig. 1). Histopathological confirmation revealed a subepidermal bulla with eosinophils and a scarce polymorphous inflammatory infiltrate in the underlying dermis (Fig. 2). The direct immunofluorescence showed a linear
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
822
basal deposition of anti-C3. Anti-basal membrane antibodies and anti-BP180 were detected by indirect immunofluorescence. Anti-thyroglobulin antibodies were positive. Treatment was initiated with prednisolone 1 mg/Kg per day and mycophenolate mophetil 2 g per day with good control of the dermatosis. After a 1-year follow-up, all the lesions have cleared with just residual millia on the hands’ dorsae. We emphasize the precocious age of development of BP in a MS patient, in accordance with other reported cases.2–5 This case illustrates a well-known association resulting in an 113–15-fold4 increase in the odds of developing BP. Although the aetiology of these chronic autoimmune disorders is still unknown, the neuronal isoform of BP antigen-1 raises the hypothesis of a shared antigen response due to the cross reactivity between the epithelial and neurological isoforms.6–8 Nonetheless, a recent report showed that basement membrane zone autoantibodies were not frequently present in MS sera in the absence of BP, maybe due to the protective effect of the blood–brain barrier.5 In our case, the development of BP in a patient treated with human immunoglobulin makes it an enigma to solve, perhaps explained for the significant lower dose that was used for MS treatment (0.2–0.4 g/kg) vs. the preconized dose for BP treatment (2 g/Kg), maybe not allowing for the necessary binding of the Fc portion of IVIG to BP antigens. To our knowledge, this is the first reported case of a MS patient treated with human immunoglobulin who developed BP. rio-Ferreira,1 M. Nora,2 A.F. Massa,1,* P. Varela,1 E. Oso A. Couceiro,3 A. Baptista1 1
Department of Dermatology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal, 2Department of Neurology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal, 3 Department of Pathology, Centro Hospitalar de V.N.Gaia/Espinho, EPE, Vila Nova de Gaia, Portugal *Correspondence: A.F. Massa. E-mail: [email protected]
References 1 Sanders SL, Nelson CT. Pemphigus and pemphigoid. Med Clin North Am 1965; 49: 681–694. 2 Peramiquel L, Barnadas MA, Pimentel CL et al. Bullous pemphigoid and multiple sclerosis: a report of two cases with ELISA test. Eur J Dermatol 2007; 17: 62–66. 3 Langan SM, Groves RW, West J. The relationship between neurological disease and bullous pemphigoid: a population-based case-control study. J Invest Dermatol 2011; 131: 631–636. 4 Nielsen N, Frisch M, Rostgaard K et al. Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark. Mult Scler 2008; 14: 823–829. 5 Taghipour K, Kirtschig G, Palace J, Groves RW, Venning V, Wojnarowska F. The association of multiple sclerosis with bullous
JEADV 2015, 29, 818–832
pemphigoid: is there a shared antigen response? J Am Acad Dermatol 2012; 67: 160–161. 6 Brown A, Bernier G, Mathieu M et al. The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1. Nat Genet 1995; 10: 301–306. 7 Laffitte E, Burkhard PR, Fontao L et al. Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis? Br J Dermatol 2005; 152: 537–540. 8 Li L, Chen J, Wang B et al. Sera from patients with bullous pemphigoid (BP) associated with neurological diseases recognized BP antigen 1 in the skin and brain. Br J Dermatol 2009; 160: 1343–1345. DOI: 10.1111/jdv.12425
Tuberous sclerosis underlying neonatal poliosis Editor An 18-month-old child came to our attention because of his seizures and for a clear diagnosis of his mental development. The parents were not consanguineous and did not present any particular disease. At physical examination, tufts of white hair (poliosis) were found. According to the mother, they were present since the early days of life. Two of them, over the nuchal and parietal right areas, were very evident (Fig. 1a). Skin presented numerous achromic hypomelanotic macules, which appeared a few months after birth; some of them, over the trunk and limbs, were lanceolate. Heart ultrasounds revealed the presence of a rhabdomyoma at the level of the lower wall of the left ventricle (Fig. 1b). The presence of the cardiac hamartoma and hypochromia of hair, along with hypomelanotic macules over the skin, allowed us to diagnose tuberous sclerosis, which was subsequently confirmed by brain magnetic resonance imaging, showing cortical tubers (Fig. 1c). Hypomelanotic macules are the most frequent and earliest cutaneous sign of tuberous sclerosis.1 They appear in the first 6 months of life in 70% of cases, mainly affecting the trunk and the lower limbs. Head and neck are rarely involved.1 They are rarely present at birth and it is difficult to detect them in newborns with fair skin. However, a tuft of white hair (poliosis) at birth may be a useful sign for the early detection of tuberous sclerosis in newborns. In 1978, McWilliam et al.2 reported four patients with this feature, long before the introduction of the current diagnostic criteria in the literature. Subsequent reports seem to be extremely rare.3,4 The differential diagnosis of neonatal poliosis must take into account other disorders, such as Waardenburg syndrome, Piebaldism, and Vogt-Koyanagi syndrome, but these conditions are usually not easily confused with tuberous sclerosis. Follicular melanocytes, such as epidermal and ocular uveal melanocytes (choroid and
© 2014 European Academy of Dermatology and Venereology
