Clinical and Experimental Dermatology
Cutaneous lupus erythematous and hereditary angio-oedema: a familial association A. L. Manley, N. Aldoori and S. E. Cockayne Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK doi: 10.1111/ced.12689
Hereditary angio-oedema (HAE) is defined as recurrent episodes of oedema of the skin, upper respiratory tract and gastrointestinal tract. It is inherited as an autosomal dominant trait, and is related to a quantitative or qualitative deficiency of C1 inhibitor. Patients with HAE have an increased frequency of autoimmune diseases.1 We report two members of the same family with HAE, who both developed cutaneous lupus erythematosus (CLE). The patient was a 17-year-old girl who presented with a photosensitive, well-defined, erythematous scaling rash on her cheeks and nose (Fig. 1a). She had a known personal and family history of HAE. A diagnosis of CLE was suspected. An autoantibody screen showed positive fine-speckled antinuclear and anti-Ro type (SS-A) antibodies but normal doublestranded-DNA antibodies, which supported the clinical diagnosis of CLE. Direct immunofluorescence (DIF) demonstrated IgG, IgM and C3 on the basement membrane zone at the dermoepidermal junction. Histopathology of the skin biopsy showed a mild inflammatory dermatosis with vacuolar-type interface changes. These findings, in combination with the DIF results, were consistent with the diagnosis of CLE. There were no features of systemic lupus erythematosus (SLE). The patient’s complement C4 level was reduced at < 0.04 g/L (normal 0.14–0.54 g/L), as was her C1 esterase inhibitor level < 0.06 g/L (0.15–0.35 g/L. C3 level was within the normal range at 0.7 g/L (0.75– 1.65 g/L). A diagnosis of discoid LE in association with HAE was made. Tacrolimus 0.1% ointment therapy and
(a)
(b)
Correspondence: Dr Nadia Aldoori, Department of Dermatology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 16 January 2015
ª 2015 British Association of Dermatologists
Figure 1 (a,b) Well-demarcated erythematous scaling rash on
both cheeks of (a) the patient and (b) her grandfather.
Clinical and Experimental Dermatology (2015) 40, pp949–950
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CPD • A memorable patient
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A memorable patient
photoprotection produced a sustained improvement in the CLE, while the HAE was well with doses of tranexamic acid and occasional C1 inhibitor concentrate as required. Interestingly, the patient’s maternal grandfather (now deceased) had also been a patient of ours, with a diagnosis of HAE associated with CLE (Fig. 1b). His CLE had been confirmed by skin biopsy, and his HAE had been extremely well controlled with danazol. These cases demonstrate an association between HAE and LE, which was initially described by Kohler et al. in 1974 in identical twin boys with chronic DLE and HAE. That report was more remarkable in that the twins’ mother and the daughter of one of the twins had both HAE and SLE.2 Since this initial report, there have been 26 reports of LE associated with HAE, and 4 of these were familial.3,4 A review of the reported cases of LE in association with HAE found several common characteristics, including a female predominance, and a high incidence of antinuclear antibodies, cutaneous manifestations and photosensitivity.3 However, the clinical severity of HAE does not always predict the development of LE,3 as seen in our patients. The association between HAE and LE is hypothesized to result from consumption of complement C4 by HAE, with consequent impaired clearance
950
Clinical and Experimental Dermatology (2015) 40, pp949–950
of apoptotic cells, leading to the fragmentation and release of intracellular antigens. This produces inflammation that could generate an autoantibody response and the development of autoimmunity.4 It has been suggested that improved control of HAE may produce lasting remission of SLE and reduce the chance of developing SLE-related organ damage.4 In summary, there seems to be a rare association between HAE and CLE, which can be familial, as demonstrated by the cases described here. It is important that patients with HAE and their healthcare practitioners are aware of the association of HAE with LE and other autoimmune disorders, in order for these to be diagnosed and treated in a timely manner.
References 1 Lipsker D, Hauptmann G. Cutaneous manifestations of complement deficiencies. Lupus 2010; 19: 1096–106. 2 Kohler PF, Percy J, Campion WM et al. Hereditary angioedema and “familial” lupus erythematosus in identical twin boys. Am J Med 1974; 56: 406–11. 3 Koide M, Shirahama S, Tokura Y et al. Lupus erythematosus associated with C1-inhibitor deficiency. J Dermatol 2002; 29: 503–7. 4 Khan S, Tarzi M, Dore P et al. Secondary systemic lupus erythematosus: an analysis of 4 cases of uncontrolled hereditary angioedema. Clin Immunol 2007; 123: 14–17.
ª 2015 British Association of Dermatologists
Cutaneous lupus erythematous and hereditary angio-oedema: a familial association A. L. Manley, N. Aldoori and S. E. Cockayne Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK doi: 10.1111/ced.12689
Hereditary angio-oedema (HAE) is defined as recurrent episodes of oedema of the skin, upper respiratory tract and gastrointestinal tract. It is inherited as an autosomal dominant trait, and is related to a quantitative or qualitative deficiency of C1 inhibitor. Patients with HAE have an increased frequency of autoimmune diseases.1 We report two members of the same family with HAE, who both developed cutaneous lupus erythematosus (CLE). The patient was a 17-year-old girl who presented with a photosensitive, well-defined, erythematous scaling rash on her cheeks and nose (Fig. 1a). She had a known personal and family history of HAE. A diagnosis of CLE was suspected. An autoantibody screen showed positive fine-speckled antinuclear and anti-Ro type (SS-A) antibodies but normal doublestranded-DNA antibodies, which supported the clinical diagnosis of CLE. Direct immunofluorescence (DIF) demonstrated IgG, IgM and C3 on the basement membrane zone at the dermoepidermal junction. Histopathology of the skin biopsy showed a mild inflammatory dermatosis with vacuolar-type interface changes. These findings, in combination with the DIF results, were consistent with the diagnosis of CLE. There were no features of systemic lupus erythematosus (SLE). The patient’s complement C4 level was reduced at < 0.04 g/L (normal 0.14–0.54 g/L), as was her C1 esterase inhibitor level < 0.06 g/L (0.15–0.35 g/L. C3 level was within the normal range at 0.7 g/L (0.75– 1.65 g/L). A diagnosis of discoid LE in association with HAE was made. Tacrolimus 0.1% ointment therapy and
(a)
(b)
Correspondence: Dr Nadia Aldoori, Department of Dermatology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 16 January 2015
ª 2015 British Association of Dermatologists
Figure 1 (a,b) Well-demarcated erythematous scaling rash on
both cheeks of (a) the patient and (b) her grandfather.
Clinical and Experimental Dermatology (2015) 40, pp949–950
949
D CP
CED
CPD • A memorable patient
D
CP
A memorable patient
photoprotection produced a sustained improvement in the CLE, while the HAE was well with doses of tranexamic acid and occasional C1 inhibitor concentrate as required. Interestingly, the patient’s maternal grandfather (now deceased) had also been a patient of ours, with a diagnosis of HAE associated with CLE (Fig. 1b). His CLE had been confirmed by skin biopsy, and his HAE had been extremely well controlled with danazol. These cases demonstrate an association between HAE and LE, which was initially described by Kohler et al. in 1974 in identical twin boys with chronic DLE and HAE. That report was more remarkable in that the twins’ mother and the daughter of one of the twins had both HAE and SLE.2 Since this initial report, there have been 26 reports of LE associated with HAE, and 4 of these were familial.3,4 A review of the reported cases of LE in association with HAE found several common characteristics, including a female predominance, and a high incidence of antinuclear antibodies, cutaneous manifestations and photosensitivity.3 However, the clinical severity of HAE does not always predict the development of LE,3 as seen in our patients. The association between HAE and LE is hypothesized to result from consumption of complement C4 by HAE, with consequent impaired clearance
950
Clinical and Experimental Dermatology (2015) 40, pp949–950
of apoptotic cells, leading to the fragmentation and release of intracellular antigens. This produces inflammation that could generate an autoantibody response and the development of autoimmunity.4 It has been suggested that improved control of HAE may produce lasting remission of SLE and reduce the chance of developing SLE-related organ damage.4 In summary, there seems to be a rare association between HAE and CLE, which can be familial, as demonstrated by the cases described here. It is important that patients with HAE and their healthcare practitioners are aware of the association of HAE with LE and other autoimmune disorders, in order for these to be diagnosed and treated in a timely manner.
References 1 Lipsker D, Hauptmann G. Cutaneous manifestations of complement deficiencies. Lupus 2010; 19: 1096–106. 2 Kohler PF, Percy J, Campion WM et al. Hereditary angioedema and “familial” lupus erythematosus in identical twin boys. Am J Med 1974; 56: 406–11. 3 Koide M, Shirahama S, Tokura Y et al. Lupus erythematosus associated with C1-inhibitor deficiency. J Dermatol 2002; 29: 503–7. 4 Khan S, Tarzi M, Dore P et al. Secondary systemic lupus erythematosus: an analysis of 4 cases of uncontrolled hereditary angioedema. Clin Immunol 2007; 123: 14–17.
ª 2015 British Association of Dermatologists
