Clinical and Experimental Dermatology
Pemphigus vulgaris presenting as erythema annulare centrifugum S. Aguilar-Duran,1 F. Deroide,2 J. Mee3 and M. Rustin1 1
Departments of Dermatology and 2Pathology, Royal Free Hospital, London, UK; and 3Immunodermatology Laboratory, St Thomas Hospital, London, UK
doi: 10.1111/ced.12581
A 45-year-old woman presented with a 3-year history of recurrent, enlarging, itchy, annular erythematous plaques on her trunk and limbs. The lesions had an indurated border, expanded centrifugally with central clearing (Fig. 1) and lasted up to 4 weeks, resolving to leave a brown discolouration. Apart from bariatric surgery in 2011 and treated hypothyroidism, the patient’s health was good and she was taking only dietary supplements. Treatment with topical antibiotics, topical antifungals and potent topical corticosteroids failed to produce any benefit. Following an initial diagnosis of erythema annulare centrifugum, the patient underwent extensive investigations, including full blood count, biochemistry, antinuclear antibody profile and a computed tomography scan of the chest and abdomen, which were normal. An oral and gynaecological evaluation did not reveal any abnormality. She had been treated empirically in another country with short courses of prednisolone, which had cleared the eruption but it relapsed promptly on discontinuation of prednisolone. Dapsone had also been prescribed, but discontinued because it caused haemolytic anaemia. Histological examination of a skin biopsy taken from the edge of an annular lesion on the patient’s left thigh identified marked spongiosis, with vesicles in the epidermis containing numerous eosinophils (Fig. 2a). The upper dermis was oedematous, and there was a dense perivascular lymphocytic infiltrate, which included eosinophils too. The deep dermis and the subcutis were spared. Diastase-pretreated periodic-acid– Schiff stain for fungal organisms was negative. Direct immunofluorescence (IMF) showed intercellular deposition of IgG (Fig. 2b) and C3 in the epidermis. Correspondence: Dr Silvia Aguilar-Duran, Department Dermatology, Royal Free Hospital, Pond Street, NW3 2QG, London, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest.
There was no IgA deposition. Indirect IMF was negative on normal human skin, but showed intercellular IgG antibodies on monkey oesophagus (Fig. 2c) to a titre of 1 : 800. Further serum analysis, using commercial ELISA kits (MESACUP Desmoglein Dsg1 and Dsg3 tests; MBL International, Woburn, MA, USA) were positive (positivity threshold of 30 U) for anti-desmoglein (Dsg)1 antibodies (65 U) and anti-Dsg3 antibodies (170 U). Based on the clinical presentation and the histological findings, a diagnosis of pemphigus vulgaris (PV) presenting as erythema annulare centrifugum (EAC) was made. A reducing course of prednisolone was commenced, with maintenance mycophenolate mofetil 2 g daily, resulting in remission of the lesions. EAC is one of the annular reactive inflammatory erythemas, which include erythema multiforme, necrolytic migratory erythema, erythema marginatum, erythema gyratum repens and annular erythema of infancy. It is considered to be a reactive eruption, and the most common underlying cause is a fungal infection, but viral or parasitic infections, drugs, autoimmune conditions, endocrinopathies, hypereosinophilic syndrome, and less frequently, an underlying malignancy,1 have all been associated. It has also been reported after major surgical procedures.2 In most cases, the cause cannot be identified. Presentation as an immunobullous disorder is rare, but it has been reported mainly with cases of IgA dermatosis.3 To our knowledge, there is only one case in the literature of PV presenting as EAC.4 Interestingly, our patient did not have mucosal involvement, which is present in almost all patients with PV at some point in their disease course. The characteristic histological feature of EAC is a tight ‘coat sleeve’ perivascular lymphohistiocytic infiltrate, which can be mainly superficial (in the papillary dermis), deep with the infiltrate present in the lower layers of the dermis or mixed. Eosinophils may occasionally be seen around superficial vessels. The early stages of PV can also present with eosino-
Accepted for publication 8 September 2014
ª 2015 British Association of Dermatologists
Clinical and Experimental Dermatology
1
D CP
CED
CPD • A memorable patient
D
CP
A memorable patient
(a)
(b)
(c)
Figure 2 (a) Marked spongiosis and a vesicle with eosinophils in
Figure 1 Annular erythematous plaques with raised borders and
the epidermis. A dense ‘coat sleeve’ perivascular lymphocytic infiltrate is also noted in the upper dermis (haematoxylin and eosin, original magnification 9 20). (b, c) Intercellular deposition of IgG on (b) direct immunofluorescence and (c) indirect immunofluorescence, using monkey oesophagus substrate.
central clearing on the right thigh of the patient.
philic spongiosis without any evidence of acantholysis,5 as in our case. Treatment of PV requires initially systemic steroids and the subsequent introduction of a steroid-sparing agent. It remains unclear which agent should be considered as first line, however, mycophenolate mofetil remains an excellent choice.6 The course of PV is variable, and there may be periodic fluctuations over many years, thus treatment should be continued long-term.
Learning points
•
PV is an immunobullous disease that can present as a reactive pattern such as EAC. • The characteristic acantholysis is not always present, especially in the early stages of the disease. • Long-term immunosuppressive treatment is needed for recalcitrant lesions.
2
Clinical and Experimental Dermatology
References 1 Chodkiewicz HM, Cohen PR. Paraneoplastic erythema annulare centrifugum eruption: PEACE. Am J Clin Dermatol 2012; 13: 239–46. 2 Thami GP, Sachdeva A, Kaur S et al. Erythema annulare centrifugum following pancreatico-biliary surgery. J Dermatol 2002; 29: 347–9. 3 Larregue M, Bressieux JM, Laidet B et al. [Erythema annulare centrifugum revealing IgA dermatitis of childhood]. Ann Dermatol Venereol 1986; 113: 1213–22. 4 Jeanmougin M, Bonvalet D, Bertail MA et al. [Pemphigus with clinical appearance of erythema annulare centrifugum]. Ann Dermatol Venereol 1982; 109: 775–6. 5 Ohyama M, Amagai M, Tsunoda K et al. Immunologic and histopathologic characterization of an active disease mouse model for pemphigus vulgaris. J Invest Dermatol 2002; 118: 199–204. 6 Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol 2012; 30: 78–83.
ª 2015 British Association of Dermatologists
Pemphigus vulgaris presenting as erythema annulare centrifugum S. Aguilar-Duran,1 F. Deroide,2 J. Mee3 and M. Rustin1 1
Departments of Dermatology and 2Pathology, Royal Free Hospital, London, UK; and 3Immunodermatology Laboratory, St Thomas Hospital, London, UK
doi: 10.1111/ced.12581
A 45-year-old woman presented with a 3-year history of recurrent, enlarging, itchy, annular erythematous plaques on her trunk and limbs. The lesions had an indurated border, expanded centrifugally with central clearing (Fig. 1) and lasted up to 4 weeks, resolving to leave a brown discolouration. Apart from bariatric surgery in 2011 and treated hypothyroidism, the patient’s health was good and she was taking only dietary supplements. Treatment with topical antibiotics, topical antifungals and potent topical corticosteroids failed to produce any benefit. Following an initial diagnosis of erythema annulare centrifugum, the patient underwent extensive investigations, including full blood count, biochemistry, antinuclear antibody profile and a computed tomography scan of the chest and abdomen, which were normal. An oral and gynaecological evaluation did not reveal any abnormality. She had been treated empirically in another country with short courses of prednisolone, which had cleared the eruption but it relapsed promptly on discontinuation of prednisolone. Dapsone had also been prescribed, but discontinued because it caused haemolytic anaemia. Histological examination of a skin biopsy taken from the edge of an annular lesion on the patient’s left thigh identified marked spongiosis, with vesicles in the epidermis containing numerous eosinophils (Fig. 2a). The upper dermis was oedematous, and there was a dense perivascular lymphocytic infiltrate, which included eosinophils too. The deep dermis and the subcutis were spared. Diastase-pretreated periodic-acid– Schiff stain for fungal organisms was negative. Direct immunofluorescence (IMF) showed intercellular deposition of IgG (Fig. 2b) and C3 in the epidermis. Correspondence: Dr Silvia Aguilar-Duran, Department Dermatology, Royal Free Hospital, Pond Street, NW3 2QG, London, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest.
There was no IgA deposition. Indirect IMF was negative on normal human skin, but showed intercellular IgG antibodies on monkey oesophagus (Fig. 2c) to a titre of 1 : 800. Further serum analysis, using commercial ELISA kits (MESACUP Desmoglein Dsg1 and Dsg3 tests; MBL International, Woburn, MA, USA) were positive (positivity threshold of 30 U) for anti-desmoglein (Dsg)1 antibodies (65 U) and anti-Dsg3 antibodies (170 U). Based on the clinical presentation and the histological findings, a diagnosis of pemphigus vulgaris (PV) presenting as erythema annulare centrifugum (EAC) was made. A reducing course of prednisolone was commenced, with maintenance mycophenolate mofetil 2 g daily, resulting in remission of the lesions. EAC is one of the annular reactive inflammatory erythemas, which include erythema multiforme, necrolytic migratory erythema, erythema marginatum, erythema gyratum repens and annular erythema of infancy. It is considered to be a reactive eruption, and the most common underlying cause is a fungal infection, but viral or parasitic infections, drugs, autoimmune conditions, endocrinopathies, hypereosinophilic syndrome, and less frequently, an underlying malignancy,1 have all been associated. It has also been reported after major surgical procedures.2 In most cases, the cause cannot be identified. Presentation as an immunobullous disorder is rare, but it has been reported mainly with cases of IgA dermatosis.3 To our knowledge, there is only one case in the literature of PV presenting as EAC.4 Interestingly, our patient did not have mucosal involvement, which is present in almost all patients with PV at some point in their disease course. The characteristic histological feature of EAC is a tight ‘coat sleeve’ perivascular lymphohistiocytic infiltrate, which can be mainly superficial (in the papillary dermis), deep with the infiltrate present in the lower layers of the dermis or mixed. Eosinophils may occasionally be seen around superficial vessels. The early stages of PV can also present with eosino-
Accepted for publication 8 September 2014
ª 2015 British Association of Dermatologists
Clinical and Experimental Dermatology
1
D CP
CED
CPD • A memorable patient
D
CP
A memorable patient
(a)
(b)
(c)
Figure 2 (a) Marked spongiosis and a vesicle with eosinophils in
Figure 1 Annular erythematous plaques with raised borders and
the epidermis. A dense ‘coat sleeve’ perivascular lymphocytic infiltrate is also noted in the upper dermis (haematoxylin and eosin, original magnification 9 20). (b, c) Intercellular deposition of IgG on (b) direct immunofluorescence and (c) indirect immunofluorescence, using monkey oesophagus substrate.
central clearing on the right thigh of the patient.
philic spongiosis without any evidence of acantholysis,5 as in our case. Treatment of PV requires initially systemic steroids and the subsequent introduction of a steroid-sparing agent. It remains unclear which agent should be considered as first line, however, mycophenolate mofetil remains an excellent choice.6 The course of PV is variable, and there may be periodic fluctuations over many years, thus treatment should be continued long-term.
Learning points
•
PV is an immunobullous disease that can present as a reactive pattern such as EAC. • The characteristic acantholysis is not always present, especially in the early stages of the disease. • Long-term immunosuppressive treatment is needed for recalcitrant lesions.
2
Clinical and Experimental Dermatology
References 1 Chodkiewicz HM, Cohen PR. Paraneoplastic erythema annulare centrifugum eruption: PEACE. Am J Clin Dermatol 2012; 13: 239–46. 2 Thami GP, Sachdeva A, Kaur S et al. Erythema annulare centrifugum following pancreatico-biliary surgery. J Dermatol 2002; 29: 347–9. 3 Larregue M, Bressieux JM, Laidet B et al. [Erythema annulare centrifugum revealing IgA dermatitis of childhood]. Ann Dermatol Venereol 1986; 113: 1213–22. 4 Jeanmougin M, Bonvalet D, Bertail MA et al. [Pemphigus with clinical appearance of erythema annulare centrifugum]. Ann Dermatol Venereol 1982; 109: 775–6. 5 Ohyama M, Amagai M, Tsunoda K et al. Immunologic and histopathologic characterization of an active disease mouse model for pemphigus vulgaris. J Invest Dermatol 2002; 118: 199–204. 6 Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol 2012; 30: 78–83.
ª 2015 British Association of Dermatologists
