e194
Correspondence
A case of refractory antilaminin c1 pemphigoid successfully treated with dexamethasone and mycophenolate mofetil
Antilaminin c1 pemphigoid is a rare subepidermal bullous disease. The disease is usually sensitive to glucocorticoids or low to moderate doses of immunosuppressant treatment. In this report, we describe a patient with refractory antilaminin c1 pemphigoid and summarize the reported cases in the English language literature. A 55-year-old Chinese man was referred to our outpatient clinic with erythema and blisters on his trunk and extremities as well as oral membrane involvement. A month prior, an acute eruption of erythematous and bullous lesions developed in his oral membrane, and then the lesions extended to the trunk (Fig. 1a), extremities (Fig. 1b), and scalp. Ocular and genital mucous membranes were not involved. He had no history of systemic disease. Histological examination of a skin biopsy from the upper arm revealed subepidermal blisters, and eosinophils and neutrophils were seen in the dermis (Fig. 1c). Direct immunofluorescence revealed linear C3 and IgG deposition at the basement membrane zone. Indi-
(a)
(b)
(c)
(d)
rect immunofluorescence using 1 M NaCl split skin was performed using antihuman IgG antiserum as a secondary antibody. Circulating anti-BMZ antibody reacted with the dermal side of the split (Fig. 1d). The index values of BP180, BP230, and type VII collagen antibody detected using ELISA kits (MBL, Nagoya, Japan) were negative. Immunoblotting studies revealed the circulating IgG autoantibodies were directed against a 200 kDa dermal protein (Fig. 1e), which confirmed a diagnosis of antilaminin c1 pemphigoid. The patient was started on intravenous immunoglobulin 400 mg/kg per day for the first five days of hospitalization and methylprednisolone 60 mg/day (1 mg/kg per day) for the first 10 days. The patient’s lesions were not adequately controlled by this treatment. The methylprednisolone was increased to 80 mg/day for five days and 120 mg/day for five days, but new eruptions of blisters occurred. Methylprednisolone treatment was then replaced by dexamethasone 20 mg/day, and mycophenolate mofetil, 1 g twice daily, was added. New lesions were controlled within three days, and blisters were dry and scabby during the next two weeks. Dexamethasone
(e)
Figure 1 (a) Erythema and erosions on the back. (b) Vesicle and erosions on the hand. (c) Histologic section with hematoxylin and eosin stain demonstrates a subepidermal blister containing neutrophils and eosinophils (original magnification 9 200) (d) Indirect immunofluorescence using 1 M NaCl split skin showed circulating anti-BMZ antibody reacted with the dermal side of the split. (e) Immunoblotting studies demonstrated 1:60 of the patients serum reacted with a 200 kDa band of the dermal extract in lane 1, corresponding to antilaminin c1 mAb in lane 2. The serum of a patient with EBA reacted with a 290 kDa band of the dermal extract (type VII collagen) in line 3. The patient’s serum did not react with the epidermal extract in lane 4. EBA, epidermolysis bullosa acquisita; mAb, monoclonal antibody International Journal of Dermatology 2015, 54, e182–e196
ª 2015 The International Society of Dermatology
Correspondence
Table 1 Reported cases of refractory antilaminin c1 pemphigoid in the previous literature
Patient no.
Age/sex
Clinical feature
Detected antigen (kDa)
Membrane involvement
Psoriasis
Effective treatment
19 210 34 45 53 68 76 87
66/F 28/M 65/M 64/F 53/F 66/M 73/M 83/M
LABD-like EBA-like EBA-like CP-like LABD-like BP-like BP-like BP-like
200 200 200/290 200/laminin c2 180/200 200 200 200
– – + + + – + +
– – – – – + – –
Plasmapheresis Prednisolone, azathioprine IVIG IVIG (died from sepsis) Methylprednisolone pulse therapy Plasmapheresis, cyclosporine Mycophenolate mofetil IVIG, mycophenolate mofetil
BP, bullous pemphigoid; CP, cicatricial pemphigoid; EBA, epidermolysis bullosa acquisita; F, female; IVIG, intravenous immunoglobin; LABD, linear IgA bullous dermatosis; M, male.
was tapered gradually over the subsequent four weeks of hospitalization and was converted over to equivalent doses of prednisone after hospital discharge to reduce adverse reactions. Prednisone and mycophenolate mofetil were tapered to 5 mg/day and 500 mg/day doses, respectively, over the next six months, and his condition was well controlled. Antilaminin c1 pemphigoid was first reported in 1996 by Zillikens et al.1 Since then there have been many reports of antilaminin c1 pemphigoid in the English medical literature. The patient described in this report is the second reported case in a Chinese patient.2 Many cases of antilaminin c1 pemphigoid are sensitive to the treatment of glucocorticoids, minocycline, dapsone, cyclosporine, and other therapies. Some cases are also refractory. Other anti-BMZ antibodies, such as antiBP180 NC16A,3 type VII collagen,4 and laminin c2,5 can be found in the serum of some of the refractory cases. Membrane involvement3–7 and psoriasis comorbidity8 may also be related to the refractory nature. The therapeutic methods applied to refractory cases are summarized in Table 1. At first, our patient was resistant to treatment with methylprednisolone. When dexamethasone was used as a substitute for methylprednisolone, the lesions were quickly controlled. The use of mycophenolate mofetil allowed the administration of corticosteroid to be reduced more quickly to minimize the side effects. In summary, we report a rare case of methylprednisoloneresistant antilaminin c1 pemphigoid that was successfully treated with dexamethasone and mycophenolate mofetil. This suggests that changing the form of glucocorticoid or combining glucocorticoid treatment with mycophenolate mofetil may help rapidly control refractory antilaminin c1 pemphigoid.
Li Zhiliang, MD Zhang Xiaodong,
MD
ª 2015 The International Society of Dermatology
Jin Peiying, MD Feng Suying, MD Wang Baoxi, MD Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing China E-mail: [email protected] Conflicts of interest: None. References 1 Zillikens D, Kawahara Y, Ishiko A, et al. A novel subepidermal blistering disease with autoantibodies to a 200-kda antigen of the basement membrane zone. J Invest Dermatol 1996; 106: 1333–1338. 2 Egan CA, Yee C, Zillikens D, et al. Anti-p200 pemphigoid: diagnosis and treatment of a case presenting as an inflammatory subepidermal blistering disease. J Am Acad Dermatol 2002; 46: 786–789. 3 Goto-Ohguchi Y, Nishie W, Akiyama M, et al. A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation. Dermatology 2009; 218: 265–271. 4 Pastar Z, Rados J, Lipozencic J, et al. Case of concurrent epidermolysis bullosa acquisita and anti-p200 pemphigoid – how to treat it? Int J Dermatol 2007; 46: 295–298. 5 Mitsuya J, Hara H, Ito K, et al. Metastatic ovarian carcinoma-associated subepidermal blistering disease with autoantibodies to both the p200 dermal antigen and the gamma 2 subunit of laminin 5 showing unusual clinical features. Br J Dermatol 2008; 158: 1354–1357. 6 Raffin D, Delaplace M, Roussel A, et al. [anti-p200 pemphigoid: remission under mycophenolate mofetil (cellcept(r))]. Ann Dermatol Venereol 2013; 140: 784–787. 7 Alloo A, Strazzula L, Rothschild B, et al. Refractory antilaminin gamma1 pemphigoid successfully treated with International Journal of Dermatology 2015, 54, e182–e196
e195
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intravenous immunoglobulin and mycophenolate mofetil. J Eur Acad Dermatol Venereol 2014; doi: 10.1111/jdv. 12352. [Epub ahead of print] 8 Ohata C, Fukuda S, Ishii N, et al. Refractory anti-laminin gamma1 pemphigoid with psoriasis vulgaris successfully treated by double-filtration plasmapheresis. Eur J Dermatol 2013; 23: 715–716. 9 Watanabe M, Tsunoda T, Tagami H. A subepidermal blistering dermatosis associated with coexistent IgG and
International Journal of Dermatology 2015, 54, e182–e196
IgA anti-dermal basement membrane zone antibodies; Demonstration of IgG antibodies reactive against a 200-kDa dermal antigen. Eur J Dermatol 2002; 12: 603–606. 10 Umemoto N, Demitsu T, Toda S, et al. A case of antip200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita. Br J Dermatol 2003; 148: 1058–1060.
ª 2015 The International Society of Dermatology
Correspondence
A case of refractory antilaminin c1 pemphigoid successfully treated with dexamethasone and mycophenolate mofetil
Antilaminin c1 pemphigoid is a rare subepidermal bullous disease. The disease is usually sensitive to glucocorticoids or low to moderate doses of immunosuppressant treatment. In this report, we describe a patient with refractory antilaminin c1 pemphigoid and summarize the reported cases in the English language literature. A 55-year-old Chinese man was referred to our outpatient clinic with erythema and blisters on his trunk and extremities as well as oral membrane involvement. A month prior, an acute eruption of erythematous and bullous lesions developed in his oral membrane, and then the lesions extended to the trunk (Fig. 1a), extremities (Fig. 1b), and scalp. Ocular and genital mucous membranes were not involved. He had no history of systemic disease. Histological examination of a skin biopsy from the upper arm revealed subepidermal blisters, and eosinophils and neutrophils were seen in the dermis (Fig. 1c). Direct immunofluorescence revealed linear C3 and IgG deposition at the basement membrane zone. Indi-
(a)
(b)
(c)
(d)
rect immunofluorescence using 1 M NaCl split skin was performed using antihuman IgG antiserum as a secondary antibody. Circulating anti-BMZ antibody reacted with the dermal side of the split (Fig. 1d). The index values of BP180, BP230, and type VII collagen antibody detected using ELISA kits (MBL, Nagoya, Japan) were negative. Immunoblotting studies revealed the circulating IgG autoantibodies were directed against a 200 kDa dermal protein (Fig. 1e), which confirmed a diagnosis of antilaminin c1 pemphigoid. The patient was started on intravenous immunoglobulin 400 mg/kg per day for the first five days of hospitalization and methylprednisolone 60 mg/day (1 mg/kg per day) for the first 10 days. The patient’s lesions were not adequately controlled by this treatment. The methylprednisolone was increased to 80 mg/day for five days and 120 mg/day for five days, but new eruptions of blisters occurred. Methylprednisolone treatment was then replaced by dexamethasone 20 mg/day, and mycophenolate mofetil, 1 g twice daily, was added. New lesions were controlled within three days, and blisters were dry and scabby during the next two weeks. Dexamethasone
(e)
Figure 1 (a) Erythema and erosions on the back. (b) Vesicle and erosions on the hand. (c) Histologic section with hematoxylin and eosin stain demonstrates a subepidermal blister containing neutrophils and eosinophils (original magnification 9 200) (d) Indirect immunofluorescence using 1 M NaCl split skin showed circulating anti-BMZ antibody reacted with the dermal side of the split. (e) Immunoblotting studies demonstrated 1:60 of the patients serum reacted with a 200 kDa band of the dermal extract in lane 1, corresponding to antilaminin c1 mAb in lane 2. The serum of a patient with EBA reacted with a 290 kDa band of the dermal extract (type VII collagen) in line 3. The patient’s serum did not react with the epidermal extract in lane 4. EBA, epidermolysis bullosa acquisita; mAb, monoclonal antibody International Journal of Dermatology 2015, 54, e182–e196
ª 2015 The International Society of Dermatology
Correspondence
Table 1 Reported cases of refractory antilaminin c1 pemphigoid in the previous literature
Patient no.
Age/sex
Clinical feature
Detected antigen (kDa)
Membrane involvement
Psoriasis
Effective treatment
19 210 34 45 53 68 76 87
66/F 28/M 65/M 64/F 53/F 66/M 73/M 83/M
LABD-like EBA-like EBA-like CP-like LABD-like BP-like BP-like BP-like
200 200 200/290 200/laminin c2 180/200 200 200 200
– – + + + – + +
– – – – – + – –
Plasmapheresis Prednisolone, azathioprine IVIG IVIG (died from sepsis) Methylprednisolone pulse therapy Plasmapheresis, cyclosporine Mycophenolate mofetil IVIG, mycophenolate mofetil
BP, bullous pemphigoid; CP, cicatricial pemphigoid; EBA, epidermolysis bullosa acquisita; F, female; IVIG, intravenous immunoglobin; LABD, linear IgA bullous dermatosis; M, male.
was tapered gradually over the subsequent four weeks of hospitalization and was converted over to equivalent doses of prednisone after hospital discharge to reduce adverse reactions. Prednisone and mycophenolate mofetil were tapered to 5 mg/day and 500 mg/day doses, respectively, over the next six months, and his condition was well controlled. Antilaminin c1 pemphigoid was first reported in 1996 by Zillikens et al.1 Since then there have been many reports of antilaminin c1 pemphigoid in the English medical literature. The patient described in this report is the second reported case in a Chinese patient.2 Many cases of antilaminin c1 pemphigoid are sensitive to the treatment of glucocorticoids, minocycline, dapsone, cyclosporine, and other therapies. Some cases are also refractory. Other anti-BMZ antibodies, such as antiBP180 NC16A,3 type VII collagen,4 and laminin c2,5 can be found in the serum of some of the refractory cases. Membrane involvement3–7 and psoriasis comorbidity8 may also be related to the refractory nature. The therapeutic methods applied to refractory cases are summarized in Table 1. At first, our patient was resistant to treatment with methylprednisolone. When dexamethasone was used as a substitute for methylprednisolone, the lesions were quickly controlled. The use of mycophenolate mofetil allowed the administration of corticosteroid to be reduced more quickly to minimize the side effects. In summary, we report a rare case of methylprednisoloneresistant antilaminin c1 pemphigoid that was successfully treated with dexamethasone and mycophenolate mofetil. This suggests that changing the form of glucocorticoid or combining glucocorticoid treatment with mycophenolate mofetil may help rapidly control refractory antilaminin c1 pemphigoid.
Li Zhiliang, MD Zhang Xiaodong,
MD
ª 2015 The International Society of Dermatology
Jin Peiying, MD Feng Suying, MD Wang Baoxi, MD Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing China E-mail: [email protected] Conflicts of interest: None. References 1 Zillikens D, Kawahara Y, Ishiko A, et al. A novel subepidermal blistering disease with autoantibodies to a 200-kda antigen of the basement membrane zone. J Invest Dermatol 1996; 106: 1333–1338. 2 Egan CA, Yee C, Zillikens D, et al. Anti-p200 pemphigoid: diagnosis and treatment of a case presenting as an inflammatory subepidermal blistering disease. J Am Acad Dermatol 2002; 46: 786–789. 3 Goto-Ohguchi Y, Nishie W, Akiyama M, et al. A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation. Dermatology 2009; 218: 265–271. 4 Pastar Z, Rados J, Lipozencic J, et al. Case of concurrent epidermolysis bullosa acquisita and anti-p200 pemphigoid – how to treat it? Int J Dermatol 2007; 46: 295–298. 5 Mitsuya J, Hara H, Ito K, et al. Metastatic ovarian carcinoma-associated subepidermal blistering disease with autoantibodies to both the p200 dermal antigen and the gamma 2 subunit of laminin 5 showing unusual clinical features. Br J Dermatol 2008; 158: 1354–1357. 6 Raffin D, Delaplace M, Roussel A, et al. [anti-p200 pemphigoid: remission under mycophenolate mofetil (cellcept(r))]. Ann Dermatol Venereol 2013; 140: 784–787. 7 Alloo A, Strazzula L, Rothschild B, et al. Refractory antilaminin gamma1 pemphigoid successfully treated with International Journal of Dermatology 2015, 54, e182–e196
e195
e196
Correspondence
intravenous immunoglobulin and mycophenolate mofetil. J Eur Acad Dermatol Venereol 2014; doi: 10.1111/jdv. 12352. [Epub ahead of print] 8 Ohata C, Fukuda S, Ishii N, et al. Refractory anti-laminin gamma1 pemphigoid with psoriasis vulgaris successfully treated by double-filtration plasmapheresis. Eur J Dermatol 2013; 23: 715–716. 9 Watanabe M, Tsunoda T, Tagami H. A subepidermal blistering dermatosis associated with coexistent IgG and
International Journal of Dermatology 2015, 54, e182–e196
IgA anti-dermal basement membrane zone antibodies; Demonstration of IgG antibodies reactive against a 200-kDa dermal antigen. Eur J Dermatol 2002; 12: 603–606. 10 Umemoto N, Demitsu T, Toda S, et al. A case of antip200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita. Br J Dermatol 2003; 148: 1058–1060.
ª 2015 The International Society of Dermatology
