Correspondence II
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Clearing of epidermolysis bullosa acquisita with cyclosporine To the Editor: After the publication by Crow et al. (J AM ACAD DERMATOL 1988;19:937-42) and more recently the brief communication by Layton and Cunliffe (J AM AeAO DERMATOL1990;22:535) concerning the apparent efficacy of eyclosporine for epidermolysis bullosa acquisita, we report a case in which cyclosporine failed to influence the course of the disease. Case report. A white man, aged 81 years, was admitted for a painful right hip after a fall. On admission an eruption was also noted on his forearms, hands, legs, and feet that had developed during the preceding 2 months. The involved areas demonstrated marked skin fragility with hemorrhagic blisters, erosiorts, and milia. A skin biopsy specimen showed subepidermal blistering with a mild inflammatory infiltrate and immunofluores~nce showed IgG, IgA, IgM, and C3 deposits at the basement membrane zone. Circulating antibody to the basement membrane zone was also demonstrated. All findings were compatible with a diagnosisof epidermolysisbullosa acquisita or the epidermolytic variant of bullous pemphigoid. Treatment was started with oral prednisolone, 40 mg daily. No improvement was seen in the blistering and further areas of blistering and erosion developed.All involvedareas were acutely painful, and required narcoticanalgesia. The patient's condition continued to worsen despite the addition of dapsone, 50 nag daily. A second skin biopsy specimen was obtained. A split-skin immunofluorescence technique demonstrated deposition of IgG on the dermal side of the split. Indirect immunofluorescence with a splitskin substrate also showed IgG binding to the dermal side of the split, thereby confirming a diagnosis of epidermolysis bttllosa acquisita. Cyclosporine was started at 4 mg/kg. Despite this treatment, the patient continued to have fresh blisters and his general condition deteriorated. Four weeks after cyclosporine was started, the dose was increased to 6 rng/kg but blistering continued and the patient's general condition continued to deteriorate. He died 1 week later. Commenl. Cyclosporine may well have a place in the treatment of epidermolysis bullosa aequisita but it failed to show any activity in this patient.
Richard B. Mallett, MB, MRCP, and Colin A. Holden, MD, MRCP St. Helier Hospital Carshalton, Surrey, England
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cence studies of the patient's salt-separated, perilesional skin as described by Gammon et al.2 and the indirect immunofluoreseence studies of the patient's serum with salt-separated, human skin substrate. 3 Their patient's disease did not improve with systemic prednisolone, 40 rag, or dapsone, 50 mg, per day. This lack of control with systemic steroids also is consistent with the diagnosis of EBA. The patient also did not improve with cyclosporine, 4 mg/kg per day for 4 weeks, or a 1-week course of a higher dose of cyclosporine at 6 mg/kg per day. As shown in Fig. 2 of our article (p. 939), our experience with eyclosporine is similar to that of Mallett and Holden; our patient did not show much response to cyclosporine until we used a prolonged course of 6 mg/kg per day, at which time the number of new blisters significantly decreased. Unfortunately, Mallett and Holden only had the opportunity to use this higher dose for I week because their patient died. We also wondered what the plasma levels of the drug were in their patient since the oral absorption of cyclosporine is variable. Including ours, there have been several reports of patients with well-documented EBA who have responded to, and improved with, eyclosporine.4-7 In all these reported succa~ses, the physicians used at least 6 mg/kg of eyelosporine to control the disease. Nevertheless, it is doubtful that cyelosporine will control every ease of EBA even if adequate doses are given because most therapeutic agents with proven efficacy are not successful 100% of the time. Therefore, if the patient has failed to respond to other therapeutic agents and there are no eontraindications, we believe that a trial of eyclosporine is warranted in cases of EBA in which the level of discomfort is significant. As we have emphasized previously, cyclosporine has a number of significant side effects, and we recommend that patients for whom cyclosporine is prescribed be managed by dermatologists in conjunction with a nephrologist.
Laura L. Crow, MD, a and David T. Woodley, MD, b University of North Carolina, Chapel Hill, a and Stanford University, Stanford, California b
REFERENCES Reply To the Editor: Although immunoeleetron microscopy of perilesional skin and Western immunoblotting I with the patient's serum were not performed, we believe that the patient described by Mallett and Holden truly did have epidermolysis builosa aequisita (EBA) and not bullous pemphigoid on the basis of the direct immunofluores1034
1. WoodleyDT, Briggaman RA, O'Keefe E J, et al. Identification of the skin basement membrane autoantlgen in epidermolysisbullosa acquisita. N Engl J Med 1984;310:1007-13. 2. Gammon WR, KowalewskiC, Chorzelski TP, et al. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosisof bullous pemphigoid and epidermolysis bullosa acquisita. J AM ACAD DER_MATOL 1990;22:664-70. 3. Gammon WR, Briggaman RA, Inman AO, et al. Differentiating anti-lamina lucida and anti--sublaminaderma anti-
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Clearing of epidermolysis bullosa acquisita with cyclosporine To the Editor: After the publication by Crow et al. (J AM ACAD DERMATOL 1988;19:937-42) and more recently the brief communication by Layton and Cunliffe (J AM AeAO DERMATOL1990;22:535) concerning the apparent efficacy of eyclosporine for epidermolysis bullosa acquisita, we report a case in which cyclosporine failed to influence the course of the disease. Case report. A white man, aged 81 years, was admitted for a painful right hip after a fall. On admission an eruption was also noted on his forearms, hands, legs, and feet that had developed during the preceding 2 months. The involved areas demonstrated marked skin fragility with hemorrhagic blisters, erosiorts, and milia. A skin biopsy specimen showed subepidermal blistering with a mild inflammatory infiltrate and immunofluores~nce showed IgG, IgA, IgM, and C3 deposits at the basement membrane zone. Circulating antibody to the basement membrane zone was also demonstrated. All findings were compatible with a diagnosisof epidermolysisbullosa acquisita or the epidermolytic variant of bullous pemphigoid. Treatment was started with oral prednisolone, 40 mg daily. No improvement was seen in the blistering and further areas of blistering and erosion developed.All involvedareas were acutely painful, and required narcoticanalgesia. The patient's condition continued to worsen despite the addition of dapsone, 50 nag daily. A second skin biopsy specimen was obtained. A split-skin immunofluorescence technique demonstrated deposition of IgG on the dermal side of the split. Indirect immunofluorescence with a splitskin substrate also showed IgG binding to the dermal side of the split, thereby confirming a diagnosis of epidermolysis bttllosa acquisita. Cyclosporine was started at 4 mg/kg. Despite this treatment, the patient continued to have fresh blisters and his general condition deteriorated. Four weeks after cyclosporine was started, the dose was increased to 6 rng/kg but blistering continued and the patient's general condition continued to deteriorate. He died 1 week later. Commenl. Cyclosporine may well have a place in the treatment of epidermolysis bullosa aequisita but it failed to show any activity in this patient.
Richard B. Mallett, MB, MRCP, and Colin A. Holden, MD, MRCP St. Helier Hospital Carshalton, Surrey, England
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cence studies of the patient's salt-separated, perilesional skin as described by Gammon et al.2 and the indirect immunofluoreseence studies of the patient's serum with salt-separated, human skin substrate. 3 Their patient's disease did not improve with systemic prednisolone, 40 rag, or dapsone, 50 mg, per day. This lack of control with systemic steroids also is consistent with the diagnosis of EBA. The patient also did not improve with cyclosporine, 4 mg/kg per day for 4 weeks, or a 1-week course of a higher dose of cyclosporine at 6 mg/kg per day. As shown in Fig. 2 of our article (p. 939), our experience with eyclosporine is similar to that of Mallett and Holden; our patient did not show much response to cyclosporine until we used a prolonged course of 6 mg/kg per day, at which time the number of new blisters significantly decreased. Unfortunately, Mallett and Holden only had the opportunity to use this higher dose for I week because their patient died. We also wondered what the plasma levels of the drug were in their patient since the oral absorption of cyclosporine is variable. Including ours, there have been several reports of patients with well-documented EBA who have responded to, and improved with, eyclosporine.4-7 In all these reported succa~ses, the physicians used at least 6 mg/kg of eyelosporine to control the disease. Nevertheless, it is doubtful that cyelosporine will control every ease of EBA even if adequate doses are given because most therapeutic agents with proven efficacy are not successful 100% of the time. Therefore, if the patient has failed to respond to other therapeutic agents and there are no eontraindications, we believe that a trial of eyclosporine is warranted in cases of EBA in which the level of discomfort is significant. As we have emphasized previously, cyclosporine has a number of significant side effects, and we recommend that patients for whom cyclosporine is prescribed be managed by dermatologists in conjunction with a nephrologist.
Laura L. Crow, MD, a and David T. Woodley, MD, b University of North Carolina, Chapel Hill, a and Stanford University, Stanford, California b
REFERENCES Reply To the Editor: Although immunoeleetron microscopy of perilesional skin and Western immunoblotting I with the patient's serum were not performed, we believe that the patient described by Mallett and Holden truly did have epidermolysis builosa aequisita (EBA) and not bullous pemphigoid on the basis of the direct immunofluores1034
1. WoodleyDT, Briggaman RA, O'Keefe E J, et al. Identification of the skin basement membrane autoantlgen in epidermolysisbullosa acquisita. N Engl J Med 1984;310:1007-13. 2. Gammon WR, KowalewskiC, Chorzelski TP, et al. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosisof bullous pemphigoid and epidermolysis bullosa acquisita. J AM ACAD DER_MATOL 1990;22:664-70. 3. Gammon WR, Briggaman RA, Inman AO, et al. Differentiating anti-lamina lucida and anti--sublaminaderma anti-
