Vancomycin-associated linear IgA dermatosis A report of three cases Sarah Carpenter, MD, Daniel Berg, MD, Navjeet Sidhu-Malik, MD, Russell P. Hall III, MD, and M. Joyce Rico, MD Durham, North Carolina Background: Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering
disease that is rarely associated with drug exposure. Objective: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. Methods: Direct and indirect immunofluorescence ass a ys were performed to characterize the immunoreactants, determine the subclass of the 19A deposits, and map the site of antibody deposition. Results: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA[ only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. Conclusion: Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA[localized to the sub1amina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis. (J AM ACAD DERMATOL 1992;26:45-8.) Linear IgA disease is a subepidermal bullous disease characterized on direct immunofluorescence of perilesional skin by the linear deposition of IgA at the dermoepidermal basement membrane zone (BMZ).I, 2 The pathogenesis oflinear IgA disease is unknown, but a linear IgA dermatosis has been reported in association with drug exposure. 3-6 We report the development of an acute blistering eruption in three patients after the administration of vancomycin. All demonstrated linear deposits of IgA at the BMZ on direct immunofluorescence of perilesional skin. CASE REPORTS Summaries ofthe three patients are presented in Table I.
Case 1. A 54-year-old black man with no previous history of skin disease was treated for a bowel perforation secondary to a diverticular abscess. After a small-bowel resection, he was treated with vancomycin, ceftazidime, From the Department of Medicine, Division of Dermatology, Duke University Medical Center and the Durham Veterans Administration Medical Center.
Accepted for publication June 27,1991. Reprint requests: M. Joyce Rico, MD, Box 3135, DUMC, Durham, NC 27710. 16/1/32062
metronidazole, and ranitidine. On day 10 of vancomycin therapy, blanching macules and papules were observed on his abdomen and chest, which during the next 24 hours spread to involve his proximal extremities and became bullous. No mucosal involvement was noted. A biopsy specimen revealed a subepidermal blister with a polymorphous infiltrate, including numerous polymorphonuclear leukocytes (PMNs) in the dermis and blister fluid. Antibiotics were discontinued and within 24 hours no new bullae formed. The patient healed without scarring or milia and was free of skin disease 9 months later. Case 2. A 72-year-old woman with no previous history of skin disease was admitted for surgical treatment of an ovarian adenocarcinoma. An intraabdominal abscess developed postoperatively, and the patient was treated with vancomycin, clindamycin, gentamicin, and ranitidine. After 1week of therapy, an abrupt onset of hemorrhagic tense bullae occurred on her trunk and extremities (Fig. 1). The palms and soles were involved but the mucosae were spared. A biopsy specimen revealed a subepidermal blister with a polymorphous infiltrate, including numerous PMNs. Antibiotics were stopped with abatement of the blistering process within 48 hours and healing of previous sites of involvement during the next 2 weeks. She remains free of her blistering disorder 7 months after initial presentation. Case 3. A 54-year-old white man had a·l O-day history of asymptomatic erythematous papules and plaques on his wrists and abdomen with scattered blisters and
45
46
Journal of the American Academy of Dermatology
Carpenter et al.
Fig. 1. Patient 2. Multiple hemorrhagic bullae over dorsum of hands.
Table I. Summary of cases Coexisting conditions
Case No.
I
54 M
2
72 F
3
54 M
Concurrent medications
Oinical appearance
Clinical course
Rapid clearing Free bowel Ceftazidime Elkins-Sinn Coalescing bullae after stopping perforation from Metronidazole over torso and vancomycin diverticular abscess Dopamine upper extremities; no mucosal Ranitidine involvement Ovarian Coalescing tense Slow clearing Clindamycin Eli Lilly after stopping hemorrhagic bullae adenocarcinoma, Gentamicin over trunk, upper all antibiotics intraabdominal Ranitidine abscess and lower extremities, palms, and soles; no mucosal involvement Osteomyelitis Continued Erythematous papules None Eli Lilly on wrists, trunk with vancomycin for scattered erosions and an additional one intact blister 3 weeks with no progression of disease; cleared after stopping vancomycin
erosions. He had been receiving home-based intravenous therapy with vancomycin for osteomyelitis of the femur for 3 weeks. The patient was otherwise in good health and was receiving no other medications. Histologic examination of an early papule revealed focal interface changes with subepidermal blistering and a polymorphous infiltrate including scattered eosinophils. Vancomycin was continued for an additional 3 weeks after the diagnosis of linear IgA dennatosis was made, during which time papules and blisters continued to develop, which were occasionally pruritic, on the forearms, legs, and trunk. When
vancomycin therapy was stopped, his eruption cleared and he remains free of lesions 6 months later. IMMUNOFLUORESCENCE Biopsy specimens ofperilesional skin were examined by direct immunofluorescence for the presence of immunoglobulin, complement, and fibrinogen deposits with fluorescein-conjugated, affinity-purified, heavy-chain specific antibodies directed against human IgG, IgA, IgM, IgE, C3, and fibrinogen (Tago, Burlingame, Calif.). For isotyping experiments, cryostat-cut sections of skin
Volume 26 Number I January 1992
Vancomycin-associated linear IgA dermatosis 47
Fig. 2. Patient 2. Direct immunofluorescence of biopsy specimen from normal-appearing skin adjacent to involved area reveals homogeneous linear deposition of IgA only at the dermoepidermaljunction. Section was stained with fluorescein-conjugated goat antihuman IgA and examined by immunofluorescence. (X400.) from the patients with vancomycin-associated linear IgA dermatosis and controls were incubated with isotype-speciflc, mouse antihuman IgAI and IgA2 (gift of J. Kearney) and counterstained with affinity-purified, fluorescein-conjugated goat antimouse IgG (Tago).7 To localize further IgA deposits within the BMZ, perilesional skin specimens were incubated in 1 moljL sodium chloride (NaCl) solution for 48 hours at 4° C, mounted in OCT Compound, and stained as already described, with fluorescein-conjugated goat antihuman IgA antibodies. 8 To control for the level ofcleavage within the BMZ, these saline-split sections were also stained with bullous pemphigoid (BP) serum, followed by f1uoresceinconjugated goat antihuman IgG. The presence of circulating anti~BMZ antibody in the serum from patients 2 and 3 was assayed by indirect immunofluorescence on 1 mol/L NaCI-split skin. 9 RESULTS Review of pharmacy and hospital records revealed that two of the patients received an Eli Lilly & Company product whereas one patient received vancomycin manufactured by Elkins-Sinn, Inc. The patients who received the Lilly product received formulations from different lot numbers. On direct immunofluorescence of perilesional skin biopsy specimens, all patients had a homogeneous linear band of IgA at the BMZ (Fig. 2). No deposits of C3, fibrinogen, IgG, IgM, or IgE were seen. Isotyping revealed the presence of IgAI only; no IgA2 was seen. Incubation of the biopsy speci-
mens in 1 mo1JL N aCl skin splitting buffer, resulted in a split within the lamina lucida, confirmed by the demonstration of BP antigen in the blister roof. Staining the split skin for IgA revealed the linear deposition of IgA on the dermal side of the split in all three patients. That is, in these three patients with vancomycin-associated linear IgA disease, the IgA was deposited below the lamina lucida-associated BP antigen. No circulating anti-BMZ antibodies were detected with indirect immunofluorescence. DISCUSSION Linear IgA bullous disease is a vesiculobullous eruption characterized in part by the presence of linear deposits of IgA at the dermoepidermal junction. Although the pathogenesis of idiopathic linear IgA bullous disease is unknown, this disorder is believed to be autoantibody mediated.?' 10, 11 Several authors have reported single cases of a linear IgA dermatosis in association with the administration of vancomycin, lithium, dic1ophenac, or glibenc1amide. 3-6 In each case the eruption resolved when the implicated medication was stopped but recurred with rechallenge. Our observation of an acute blistering dermatosis with linear deposits of IgA at the BMZ in three patients treated with vancomycin confirms and extends the previous case report that associates this agent with the development of a linear IgA dermatosis.
Journal of the American Academy of Dermatology
48 Carpenter et al. The vancomycin that the patients received was supplied by two different manufacturers and isolated by different techniques (Dr. M. Zeckel, Eli Lilly & Co., personal communication, January 1991). Thus the reaction is not restricted to a specific manufacturer or isolation procedure. The clinical presentation of our patients varied from widespread hemorrhagic blisters to asymptomatic red papules and plaques with minimal blistering. The previously reported cases of drug-associated linear IgA dermatosis have also described heterogeneous clinical presentations. As also noted in the previous case reports, mucosal involvement was not seen and all patients healed without scarring after the discontinuation of vancomycin. Histologically, the predominant cell type in the infiltrates varied in our patients as previously reported in patients with idiopathic linear IgA disease and drug-associated linear IgA dermatosis. 12 In two patients PMNs predominated, whereas in patient 3, eosinophils predominated. Further characterization of the immune deposits by isotyping revealed that all three patients had IgAI only. No circulating anti-BMZ IgA antibodies were detected in our patients. These findings are similar to those found in patients with sporadic linear IgA disease: IgAI and not IgA2, is typically seen and only 13% to 30% of patients have circulating anti-BMZ antibodies.?' 11 Immunoelectron microscopy of skin biopsy specimens from patients with sporadic linear IgA disease reveals two patterns of IgA deposition within the BMZ; most commonly the IgA deposits are at the sublamina densa region. However, in some series lamina lucida deposits are more frequent. I, 2, 11, 13 With a recently described technique for localizing in vivo-bound IgO deposits by direct inununofluorescence on saline-split skin, we have demonstrated that the IgA deposited in our patients with vancomycinassociated linear IgA dermatosis localized on the floor of the blister, whereas BP antigen localized to
the blister roof. The localization of IgA deposits below the BP antigen suggests that in these patients, the IgA deposits are localized within the sublamina densa. REFERENCES 1. Yaoita H, Katz S1. Immunoelectron microscopic localization ofIgA in skin of patients with dermatitis herpetiformis. J Invest DermatoI1976;67:502-6. 2. Lawley TJ, Strober W, Yaoita H, et al. Small intestinal biopsies and HLA types in dermatitis herpetiformis patients with granular and linear IgA skin deposits. J Invest DermatoI1980;74:9-12. 3. Vaatainen N, Fraki JE, Hyvonen M, et al. Purpura with a linear epidermodermal deposition of IgA. Acta Derm Venereal (Stockh) 1983;63:169-70. 4. Gabrielsen TO, Staerfelt F, Thune PO. Drug-induced bullous dermatosis with linear 19A deposits along the basement membrane. Acta Derm VenereoI1981;61:439-40. 5. Baden LA, Apovian C, Imber MJ, et al. Vancomycininduced linear IgA bullous dermatosis. Arch Dermatol 1988;124:1186-8. 6. McWhirter JD, HashimotoK, Fayne S. Linear IgA bullous dermatosis related to lithium carbonate. Arch Dermatol 1987;123:1120-2. 7. Hall RP, Lawley TJ. Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. J ImmunoI1985;135:1760-5. 8. Gammon WR, Kowalewski C, Chorzelski TP, et al. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J AM ACAD DERMATOL 1990;22:664"70. 9. Gammon WR, Briggaman RA, Inman AO, et aL Differentiating anti-lamina lucida and anti-sublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin. J Invest Dermatol 1984;82:139-44. 10. Leonard IN, Haffenden GP, Ring NP, et aL Linear IgA disease in adults. Br J DermatoI1982;107:301-16. 11. Bhogal B, Wojnarowska F, Marsden RA, et aL Linear IgA bullous dermatosis of adults and children: an immuneelectron microscopic study. Br J DermatoI1987;117:289-
96.
12. Blenkinsopp WK, Haffenden GP, Fry L, et al. Histology of linear IgA disease, dermatitis herpetiformis, and bullous pemphigoid. Am J DermatopathoI1983;5:547-54. 13. ZoneJJ, TaylorTB, KadunceDP, etal. Identificationofthe cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis. J Clio Invest 1990;85:812-20.
disease that is rarely associated with drug exposure. Objective: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. Methods: Direct and indirect immunofluorescence ass a ys were performed to characterize the immunoreactants, determine the subclass of the 19A deposits, and map the site of antibody deposition. Results: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA[ only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. Conclusion: Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA[localized to the sub1amina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis. (J AM ACAD DERMATOL 1992;26:45-8.) Linear IgA disease is a subepidermal bullous disease characterized on direct immunofluorescence of perilesional skin by the linear deposition of IgA at the dermoepidermal basement membrane zone (BMZ).I, 2 The pathogenesis oflinear IgA disease is unknown, but a linear IgA dermatosis has been reported in association with drug exposure. 3-6 We report the development of an acute blistering eruption in three patients after the administration of vancomycin. All demonstrated linear deposits of IgA at the BMZ on direct immunofluorescence of perilesional skin. CASE REPORTS Summaries ofthe three patients are presented in Table I.
Case 1. A 54-year-old black man with no previous history of skin disease was treated for a bowel perforation secondary to a diverticular abscess. After a small-bowel resection, he was treated with vancomycin, ceftazidime, From the Department of Medicine, Division of Dermatology, Duke University Medical Center and the Durham Veterans Administration Medical Center.
Accepted for publication June 27,1991. Reprint requests: M. Joyce Rico, MD, Box 3135, DUMC, Durham, NC 27710. 16/1/32062
metronidazole, and ranitidine. On day 10 of vancomycin therapy, blanching macules and papules were observed on his abdomen and chest, which during the next 24 hours spread to involve his proximal extremities and became bullous. No mucosal involvement was noted. A biopsy specimen revealed a subepidermal blister with a polymorphous infiltrate, including numerous polymorphonuclear leukocytes (PMNs) in the dermis and blister fluid. Antibiotics were discontinued and within 24 hours no new bullae formed. The patient healed without scarring or milia and was free of skin disease 9 months later. Case 2. A 72-year-old woman with no previous history of skin disease was admitted for surgical treatment of an ovarian adenocarcinoma. An intraabdominal abscess developed postoperatively, and the patient was treated with vancomycin, clindamycin, gentamicin, and ranitidine. After 1week of therapy, an abrupt onset of hemorrhagic tense bullae occurred on her trunk and extremities (Fig. 1). The palms and soles were involved but the mucosae were spared. A biopsy specimen revealed a subepidermal blister with a polymorphous infiltrate, including numerous PMNs. Antibiotics were stopped with abatement of the blistering process within 48 hours and healing of previous sites of involvement during the next 2 weeks. She remains free of her blistering disorder 7 months after initial presentation. Case 3. A 54-year-old white man had a·l O-day history of asymptomatic erythematous papules and plaques on his wrists and abdomen with scattered blisters and
45
46
Journal of the American Academy of Dermatology
Carpenter et al.
Fig. 1. Patient 2. Multiple hemorrhagic bullae over dorsum of hands.
Table I. Summary of cases Coexisting conditions
Case No.
I
54 M
2
72 F
3
54 M
Concurrent medications
Oinical appearance
Clinical course
Rapid clearing Free bowel Ceftazidime Elkins-Sinn Coalescing bullae after stopping perforation from Metronidazole over torso and vancomycin diverticular abscess Dopamine upper extremities; no mucosal Ranitidine involvement Ovarian Coalescing tense Slow clearing Clindamycin Eli Lilly after stopping hemorrhagic bullae adenocarcinoma, Gentamicin over trunk, upper all antibiotics intraabdominal Ranitidine abscess and lower extremities, palms, and soles; no mucosal involvement Osteomyelitis Continued Erythematous papules None Eli Lilly on wrists, trunk with vancomycin for scattered erosions and an additional one intact blister 3 weeks with no progression of disease; cleared after stopping vancomycin
erosions. He had been receiving home-based intravenous therapy with vancomycin for osteomyelitis of the femur for 3 weeks. The patient was otherwise in good health and was receiving no other medications. Histologic examination of an early papule revealed focal interface changes with subepidermal blistering and a polymorphous infiltrate including scattered eosinophils. Vancomycin was continued for an additional 3 weeks after the diagnosis of linear IgA dennatosis was made, during which time papules and blisters continued to develop, which were occasionally pruritic, on the forearms, legs, and trunk. When
vancomycin therapy was stopped, his eruption cleared and he remains free of lesions 6 months later. IMMUNOFLUORESCENCE Biopsy specimens ofperilesional skin were examined by direct immunofluorescence for the presence of immunoglobulin, complement, and fibrinogen deposits with fluorescein-conjugated, affinity-purified, heavy-chain specific antibodies directed against human IgG, IgA, IgM, IgE, C3, and fibrinogen (Tago, Burlingame, Calif.). For isotyping experiments, cryostat-cut sections of skin
Volume 26 Number I January 1992
Vancomycin-associated linear IgA dermatosis 47
Fig. 2. Patient 2. Direct immunofluorescence of biopsy specimen from normal-appearing skin adjacent to involved area reveals homogeneous linear deposition of IgA only at the dermoepidermaljunction. Section was stained with fluorescein-conjugated goat antihuman IgA and examined by immunofluorescence. (X400.) from the patients with vancomycin-associated linear IgA dermatosis and controls were incubated with isotype-speciflc, mouse antihuman IgAI and IgA2 (gift of J. Kearney) and counterstained with affinity-purified, fluorescein-conjugated goat antimouse IgG (Tago).7 To localize further IgA deposits within the BMZ, perilesional skin specimens were incubated in 1 moljL sodium chloride (NaCl) solution for 48 hours at 4° C, mounted in OCT Compound, and stained as already described, with fluorescein-conjugated goat antihuman IgA antibodies. 8 To control for the level ofcleavage within the BMZ, these saline-split sections were also stained with bullous pemphigoid (BP) serum, followed by f1uoresceinconjugated goat antihuman IgG. The presence of circulating anti~BMZ antibody in the serum from patients 2 and 3 was assayed by indirect immunofluorescence on 1 mol/L NaCI-split skin. 9 RESULTS Review of pharmacy and hospital records revealed that two of the patients received an Eli Lilly & Company product whereas one patient received vancomycin manufactured by Elkins-Sinn, Inc. The patients who received the Lilly product received formulations from different lot numbers. On direct immunofluorescence of perilesional skin biopsy specimens, all patients had a homogeneous linear band of IgA at the BMZ (Fig. 2). No deposits of C3, fibrinogen, IgG, IgM, or IgE were seen. Isotyping revealed the presence of IgAI only; no IgA2 was seen. Incubation of the biopsy speci-
mens in 1 mo1JL N aCl skin splitting buffer, resulted in a split within the lamina lucida, confirmed by the demonstration of BP antigen in the blister roof. Staining the split skin for IgA revealed the linear deposition of IgA on the dermal side of the split in all three patients. That is, in these three patients with vancomycin-associated linear IgA disease, the IgA was deposited below the lamina lucida-associated BP antigen. No circulating anti-BMZ antibodies were detected with indirect immunofluorescence. DISCUSSION Linear IgA bullous disease is a vesiculobullous eruption characterized in part by the presence of linear deposits of IgA at the dermoepidermal junction. Although the pathogenesis of idiopathic linear IgA bullous disease is unknown, this disorder is believed to be autoantibody mediated.?' 10, 11 Several authors have reported single cases of a linear IgA dermatosis in association with the administration of vancomycin, lithium, dic1ophenac, or glibenc1amide. 3-6 In each case the eruption resolved when the implicated medication was stopped but recurred with rechallenge. Our observation of an acute blistering dermatosis with linear deposits of IgA at the BMZ in three patients treated with vancomycin confirms and extends the previous case report that associates this agent with the development of a linear IgA dermatosis.
Journal of the American Academy of Dermatology
48 Carpenter et al. The vancomycin that the patients received was supplied by two different manufacturers and isolated by different techniques (Dr. M. Zeckel, Eli Lilly & Co., personal communication, January 1991). Thus the reaction is not restricted to a specific manufacturer or isolation procedure. The clinical presentation of our patients varied from widespread hemorrhagic blisters to asymptomatic red papules and plaques with minimal blistering. The previously reported cases of drug-associated linear IgA dermatosis have also described heterogeneous clinical presentations. As also noted in the previous case reports, mucosal involvement was not seen and all patients healed without scarring after the discontinuation of vancomycin. Histologically, the predominant cell type in the infiltrates varied in our patients as previously reported in patients with idiopathic linear IgA disease and drug-associated linear IgA dermatosis. 12 In two patients PMNs predominated, whereas in patient 3, eosinophils predominated. Further characterization of the immune deposits by isotyping revealed that all three patients had IgAI only. No circulating anti-BMZ IgA antibodies were detected in our patients. These findings are similar to those found in patients with sporadic linear IgA disease: IgAI and not IgA2, is typically seen and only 13% to 30% of patients have circulating anti-BMZ antibodies.?' 11 Immunoelectron microscopy of skin biopsy specimens from patients with sporadic linear IgA disease reveals two patterns of IgA deposition within the BMZ; most commonly the IgA deposits are at the sublamina densa region. However, in some series lamina lucida deposits are more frequent. I, 2, 11, 13 With a recently described technique for localizing in vivo-bound IgO deposits by direct inununofluorescence on saline-split skin, we have demonstrated that the IgA deposited in our patients with vancomycinassociated linear IgA dermatosis localized on the floor of the blister, whereas BP antigen localized to
the blister roof. The localization of IgA deposits below the BP antigen suggests that in these patients, the IgA deposits are localized within the sublamina densa. REFERENCES 1. Yaoita H, Katz S1. Immunoelectron microscopic localization ofIgA in skin of patients with dermatitis herpetiformis. J Invest DermatoI1976;67:502-6. 2. Lawley TJ, Strober W, Yaoita H, et al. Small intestinal biopsies and HLA types in dermatitis herpetiformis patients with granular and linear IgA skin deposits. J Invest DermatoI1980;74:9-12. 3. Vaatainen N, Fraki JE, Hyvonen M, et al. Purpura with a linear epidermodermal deposition of IgA. Acta Derm Venereal (Stockh) 1983;63:169-70. 4. Gabrielsen TO, Staerfelt F, Thune PO. Drug-induced bullous dermatosis with linear 19A deposits along the basement membrane. Acta Derm VenereoI1981;61:439-40. 5. Baden LA, Apovian C, Imber MJ, et al. Vancomycininduced linear IgA bullous dermatosis. Arch Dermatol 1988;124:1186-8. 6. McWhirter JD, HashimotoK, Fayne S. Linear IgA bullous dermatosis related to lithium carbonate. Arch Dermatol 1987;123:1120-2. 7. Hall RP, Lawley TJ. Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. J ImmunoI1985;135:1760-5. 8. Gammon WR, Kowalewski C, Chorzelski TP, et al. Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J AM ACAD DERMATOL 1990;22:664"70. 9. Gammon WR, Briggaman RA, Inman AO, et aL Differentiating anti-lamina lucida and anti-sublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin. J Invest Dermatol 1984;82:139-44. 10. Leonard IN, Haffenden GP, Ring NP, et aL Linear IgA disease in adults. Br J DermatoI1982;107:301-16. 11. Bhogal B, Wojnarowska F, Marsden RA, et aL Linear IgA bullous dermatosis of adults and children: an immuneelectron microscopic study. Br J DermatoI1987;117:289-
96.
12. Blenkinsopp WK, Haffenden GP, Fry L, et al. Histology of linear IgA disease, dermatitis herpetiformis, and bullous pemphigoid. Am J DermatopathoI1983;5:547-54. 13. ZoneJJ, TaylorTB, KadunceDP, etal. Identificationofthe cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis. J Clio Invest 1990;85:812-20.
