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Dermatomyositis pemphigoides: A case with coexistent dermatomyositis and bullous pemphigoid
Volume 27 Number 5, Part 2 November 1992 REFERENCES
1. Takatsuki K, Uchiyama T, Sagawa K, et al. Adult T-cell leukemia in Japan. In: Seno S, Takaku F, Irino S, eds. Top9its in hematology. Amsterdam: ElsevierScience Publishers, 1977:73-6. 2. Yamaguchi K, Nishimura H, Kawano F, et al. A proposal for smoldering adult T-ceil leukemia: diversity in clinical pictures of adult T-cell leukemia. Jpn J Cliff Oncol 1983; 13(suppl 2):189-200. 3. Chan HL, Su IJ, Kuan YZ, et al. Cutaneous manifestation of adult T-cell leukemia/lymphoma. J AM ACADDERMATOL 1985;13:213-9. 4. Lutzner M, Edelson R, Schein P, et al. Cutaneous T-cell lymphoma: the Sezary syndrome, mycosis fungoides, and related disorders. Ann Intern Med 1975;83:534-52.
Adult T-cell leukemia 5. Miller K, CoIeman CN, Fawcett HD, et al. Sezary syndrome: a model for migration of T lymphocytes to skin. N Engl J Med 1980;303:89-92. 6. NickoloffBJ, GriffithsCEM, Baadsgaard O, et al. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 in Sezary syndrome. JAMA 1989; 261:2217-21. 7. Maeda K and Takahashi M. Characterization of skin infiltrating ceils in adult T-cell leukemia/lymphoma: clinical, histologicaland immunohistochemical studies on eight cases. Br J Dermatol 1989;121:603-12. 8. Edelson RL, Kirkpatrick CH, Shevach EM, et al. Preferential cutaneous infiltration by neoplastic thymus-derived lymphocytes. Ann Intern Med 1974;80:685-92.
Dermatomyositis pemphigoides: A case with coexistent dermatomyositis and bullous pemphigoid M a r y Glover, MB, BS, M R C P , and Im Leigh, BSc, F R C P London, England We describe a patient with coexistent dermatomyositis and bullous pemphigoid; both appeared within a few weeks. Protein blotting showed binding of the patient's serum to the classic 220 kd bullous pemphigoid antigen. Because of the close temporal association of the two disorders, we believe that they are almost certainly etiologically linked. One possibility is that exposure of basement membrane antigens by dermatomyositis led to exposure of bullous pemphigoid antigen and subsequent antibody formation. (J AM ACAD DERMA'rOE 1992;27:849-52.) W e describe a 65-year-old man who developed both dermatomyositis and bullous pemphigoid (BP) within a few weeks. A diagnosis of BP was confirmed by results of protein blotting, which demonstrated that the patient's serum showed binding to the classic 220 kd BP antigen. W e propose that the coexistence of the two disorders m a y have resulted from disruption of the basement m e m b r a n e zone by the dermatomyositis, which led to exposure of the BP antigen. CASE REPORT A 65-year-old-man developed an itchy, scaling eruption on the scalp, neck, and back of the hands. Two weeks later blisters appeared on his scalp and neck and he had muscle aches. In 1984 the patient had two myocardialinfarctions, and since then he had been taking nifedipine, From the Departmentof Dermatology,The Royal LondonHospital, Reprint not available. 16/4/34729
Fig. 1. Dorsum of hand shows Gottron's papules, streaky erythema, and erythematous, bolstered nail folds. 849
850
Journal of the American Academy of Dermatology
Glover and Leigh
Fig. 2. Tense bulla on back of neck.
Fig. 3. Biopsy specimen of erythematous area on dorsum of hand shows basal layer change and hyaline bodies. (Xl00.)
isosorbide mononitrate, propranolol, glyeeryl trinitrate, and ibuprofen. When he was first examined approximately 6 weeks after onset, he had erythema of the face and scalp and linear erythema along the dorsum of the fingers, with Gottron's papules on the knuckles (Fig. 1). He also had bolstered nail folds with dilated capillaries and ragged cuticles. Tense bullae were found on the back of the neck (Fig. 2), the upper back, and the vermillion border of the lower lip; in addition, several erosions appeared on the neck, scalp, forehead, and one eyelid. Two small ulcers were observed on the buccal mucosa, and he had mild proximal muscle weakness.
Creatine kinase activity was within the normal range, and antinuclear antibody was not detected. Electromyographic examination showed a myopathic pattern. Findings of a muscle biopsy specimen showed a florid, inflammatory myopathy with "moth-eaten" fibers, some necrotic muscle fibers, and a diffuse inflammatory cell infiltrate. Findings of a biopsy specimen from the dorsum of the hand showed loci of basal layer degeneration and colloid bodies with early subepidermal blister formation (Fig. 3). Findings of a biopsy specimen from a bulla on the neck showed a subepidermal split containing fibrin and eosinophils (Fig. 4); the blister on the lip showed a subcpithelial bulla.
Volume 27 Number 5, Part 2 November 1992
Dermatornyositispemphigoides 851
Fig. 4. Biopsy specimen of blister on back of neck shows a subepidermal split containing inflammatory cells. (•
Direct immunofluorescencetesting of perilesional skin and oraI mucosa demonstrated strong linear IgG and C3 at the basement membrane zone. Indirect immunofluoreseence testing showed IgG binding to the roof and base of I M sodium chloride split skin. Results of protein blotting with a previously described techniquO demonstrated that the patient's serum showed binding to the clfissic220 kd BP antigen. Extensive investigations for malignancy were negative. The patient was treated initially with prednisolone, 60 mg/day. Azathioprine was introduced, and the dosage of prednisolone was reduced. Two years later he remains well and his condition is controlled with azathiaprine alone. DISCUSSION This patient had the typical clinical, histologic, and electromyographic features of dermatomyositis. Creatine kinase levels that are within normal limits, as in this patient, occur in approximately 5% of patients with dermatomyositis. 2 The findings of immunofluorescence testing and the demonstration that his serum was bound to the 220 kd classic BP antigen demonstrate that he also had BP. The pattern Of staining on 1 M sodium chloride split skin with binding to both the epidermal and dermal side is unusual and occurs in only approximately 3% of cases of BP3; binding is typically confined to the epidermal side. The cause of this combined staining pattern is unknown, but may reflect bridging of the lamina lucida by large macromolecules. Several case reports have described dermatomyositis with coexistent vesicular and bullous le-
sions,4, 5 but without immunofluorescence studies, it is difficult to know whether these patients had BP. One patient in particular 6 had features that were similar to our patient, with scaling of the scalp and fingertips and periorbital edema, followed a few weeks later by the development of weakness of proximal muscles and numerous vesicobullous lesions. Findings of a muscle biopsy specimen showed an active myositis, and findings of a skin biopsy specimen showed a subepidermal bulla containing eosinophils and polymorphs. Unfortunately no immunofluorescence studies were conducted. In BP evidence exists both in vivo and in vitro that autoantibody binding to the BP antigen, which appears to be a major hemidesmosome plaque protein, is involved in pathogenesis. 7"L~What initiates the production of the antibody is not known, although it is presumed to follow alteration of the BP antigen.1 l One possible explanation for the association of BP and dermatomyositis in this patient is that basal layer damage from the dermatomyositis may have exposed or released basement membrane zone antigens, including the BP antigen, which may have led to the formation of antibodies, with the subsequent production of blisters in areas not clinically affected by dermatomyositis. An analogous process is believed to occur in lichen planus pemphigoides. 12Antibodies to the classic 220 kd BP antigen have been found in some patients with lichen planus pemphigoides, whereas others have had antibodies to a distinct 200 kd protein. (Davis et al., Lichen planus
852
Journal of the American Academy of Dermatology
Glover and Leigh
pemphigoides; its relationship to bullous pemphigoid [manuscript in preparation].) Because the a p p e a r a n c e of B P is so unusual in dermatomyositis, other factors must be involved. Although photosensitivity is not a recognized feature of BP, it has been described in dermatomyositis. 13 This patient had a holiday in the sun shortly before his s y m p t o m s developed, and it is of interest t h a t most o f his bullae were on sun-exposed skin. W e also considered a possible role for the medications he was taking, but similar cases have not been reported. BP has been described in association with numerous a u t o i m m u n e diseases~4-tg; whether these associations are m o r e t h a n coincidental is unclear. Because of the close t e m p o r a l association of the dermatomyositis and the B P in this patient, we believe they are almost certainly etiologically linked. REFERENCES 1. Tatnall FM, Whitehead PC, Black MM, et al. Identification of epidermolysis bullosa acquisita antigen by LH7.2 monoclonal antibody: use in diagnosis. Br J Dermatol 1989;120:533-9. 2. Bohan A, Peter JB, Bowman RL, et al. A computer assisted analysis of 153 patients with polymyositis and dermatomyosiris. Medicine 1977;56:255-86. 3. Logan RA, Bhogal B, Das AK, et al. Localisation of bullous pemphigoid antibody--an indirect immunofluorescence study of 228 eases using a split-skin technique. Br J Dermatol 1987;117:471-8. 4. Findlay GH, Price EA, Van Rensburg CRJ. Dermatomyosiris with vesicular and bullous lesions. S Afr Med J 1951;25:60-5. 5. Holmes JM. A case of acute dermatomyositis. Br Med J 1948;2:511-3. 6. Peck SM, Lefkovits AM. Bullous pemphigoid with poly-
7.
8.
9.
10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
myositis and coexisting contact dermatitis. Arch Dermatol 1966;94:672-4. Mutasim DF, Morrison LH, Takahashi Y, et al. Definition of bullouspemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes. J Invest Dermatol 1989;92:225-30. Westgate GE, Weaver AC, Couchman JR. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes. J Invest Dermatol 1985;84:2l 8-24. Gammon WR, Lewis DM, Carlo JR, et al. Pemphigoid antibody mediated attachment of peripheral blood leukocytes at the dermal-epidermal junction of human skin. J Invest Dermatol 1980;75:303-6. Naito K, Morioka S, Ogawa H. The pathogenetic mechanisms of blister formation in bullous pemphigoid. J Invest Dermatol 1982;79:303-6. Sams WM, Gammon WR. Mechanism of lesion production in pemphigus and pemphigoid.J AM ACADDERMATOL 1980;6:431-41. Stingl G, Holubar K. Co-existence of lichen planus and bullous pemphigoid. An Immunopathological study. Br J Dermatol 1975;93:313-20. Garcin R, Lapresle J, Gruner J, et al. Les Polymyosites.Rev Neurol (Paris) 1955;92:465. Gianni JM, Callen JP, Gruber GG. Bullous pemphigoid and rheumatoid arthritis. J AN ACAD DERMATOL1981; 4:695-7. Chuang TY, Korkij W, Soltani K, et at. Increased frequency of diabetes mellitus in patients with buUous pemphigoid. J AM ACAD DERMATOL1984;11:1099-2002. Leibovici V, Ron N, Goldenhersch M, et al. Co-existence of pemphigus and bullous pemphigoid. Int J Dermatol 1989;28:259-60. Barth JH, Kelly SE, Wojnarowska F, et al. Pemphigoid and ulcerative colitis. J AM ACADDERMATOL1988;19:303-8. Simon CA, Winkleman RK. Bullous pemphigoid and glomerulonephritis: report of four cases. J AM ACADDERMATOL1986;14:456-60. Black MM, What is going on in lichen planus2 Clin Exp Dermatol 1977;2:303-10.
1. Takatsuki K, Uchiyama T, Sagawa K, et al. Adult T-cell leukemia in Japan. In: Seno S, Takaku F, Irino S, eds. Top9its in hematology. Amsterdam: ElsevierScience Publishers, 1977:73-6. 2. Yamaguchi K, Nishimura H, Kawano F, et al. A proposal for smoldering adult T-ceil leukemia: diversity in clinical pictures of adult T-cell leukemia. Jpn J Cliff Oncol 1983; 13(suppl 2):189-200. 3. Chan HL, Su IJ, Kuan YZ, et al. Cutaneous manifestation of adult T-cell leukemia/lymphoma. J AM ACADDERMATOL 1985;13:213-9. 4. Lutzner M, Edelson R, Schein P, et al. Cutaneous T-cell lymphoma: the Sezary syndrome, mycosis fungoides, and related disorders. Ann Intern Med 1975;83:534-52.
Adult T-cell leukemia 5. Miller K, CoIeman CN, Fawcett HD, et al. Sezary syndrome: a model for migration of T lymphocytes to skin. N Engl J Med 1980;303:89-92. 6. NickoloffBJ, GriffithsCEM, Baadsgaard O, et al. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 in Sezary syndrome. JAMA 1989; 261:2217-21. 7. Maeda K and Takahashi M. Characterization of skin infiltrating ceils in adult T-cell leukemia/lymphoma: clinical, histologicaland immunohistochemical studies on eight cases. Br J Dermatol 1989;121:603-12. 8. Edelson RL, Kirkpatrick CH, Shevach EM, et al. Preferential cutaneous infiltration by neoplastic thymus-derived lymphocytes. Ann Intern Med 1974;80:685-92.
Dermatomyositis pemphigoides: A case with coexistent dermatomyositis and bullous pemphigoid M a r y Glover, MB, BS, M R C P , and Im Leigh, BSc, F R C P London, England We describe a patient with coexistent dermatomyositis and bullous pemphigoid; both appeared within a few weeks. Protein blotting showed binding of the patient's serum to the classic 220 kd bullous pemphigoid antigen. Because of the close temporal association of the two disorders, we believe that they are almost certainly etiologically linked. One possibility is that exposure of basement membrane antigens by dermatomyositis led to exposure of bullous pemphigoid antigen and subsequent antibody formation. (J AM ACAD DERMA'rOE 1992;27:849-52.) W e describe a 65-year-old man who developed both dermatomyositis and bullous pemphigoid (BP) within a few weeks. A diagnosis of BP was confirmed by results of protein blotting, which demonstrated that the patient's serum showed binding to the classic 220 kd BP antigen. W e propose that the coexistence of the two disorders m a y have resulted from disruption of the basement m e m b r a n e zone by the dermatomyositis, which led to exposure of the BP antigen. CASE REPORT A 65-year-old-man developed an itchy, scaling eruption on the scalp, neck, and back of the hands. Two weeks later blisters appeared on his scalp and neck and he had muscle aches. In 1984 the patient had two myocardialinfarctions, and since then he had been taking nifedipine, From the Departmentof Dermatology,The Royal LondonHospital, Reprint not available. 16/4/34729
Fig. 1. Dorsum of hand shows Gottron's papules, streaky erythema, and erythematous, bolstered nail folds. 849
850
Journal of the American Academy of Dermatology
Glover and Leigh
Fig. 2. Tense bulla on back of neck.
Fig. 3. Biopsy specimen of erythematous area on dorsum of hand shows basal layer change and hyaline bodies. (Xl00.)
isosorbide mononitrate, propranolol, glyeeryl trinitrate, and ibuprofen. When he was first examined approximately 6 weeks after onset, he had erythema of the face and scalp and linear erythema along the dorsum of the fingers, with Gottron's papules on the knuckles (Fig. 1). He also had bolstered nail folds with dilated capillaries and ragged cuticles. Tense bullae were found on the back of the neck (Fig. 2), the upper back, and the vermillion border of the lower lip; in addition, several erosions appeared on the neck, scalp, forehead, and one eyelid. Two small ulcers were observed on the buccal mucosa, and he had mild proximal muscle weakness.
Creatine kinase activity was within the normal range, and antinuclear antibody was not detected. Electromyographic examination showed a myopathic pattern. Findings of a muscle biopsy specimen showed a florid, inflammatory myopathy with "moth-eaten" fibers, some necrotic muscle fibers, and a diffuse inflammatory cell infiltrate. Findings of a biopsy specimen from the dorsum of the hand showed loci of basal layer degeneration and colloid bodies with early subepidermal blister formation (Fig. 3). Findings of a biopsy specimen from a bulla on the neck showed a subepidermal split containing fibrin and eosinophils (Fig. 4); the blister on the lip showed a subcpithelial bulla.
Volume 27 Number 5, Part 2 November 1992
Dermatornyositispemphigoides 851
Fig. 4. Biopsy specimen of blister on back of neck shows a subepidermal split containing inflammatory cells. (•
Direct immunofluorescencetesting of perilesional skin and oraI mucosa demonstrated strong linear IgG and C3 at the basement membrane zone. Indirect immunofluoreseence testing showed IgG binding to the roof and base of I M sodium chloride split skin. Results of protein blotting with a previously described techniquO demonstrated that the patient's serum showed binding to the clfissic220 kd BP antigen. Extensive investigations for malignancy were negative. The patient was treated initially with prednisolone, 60 mg/day. Azathioprine was introduced, and the dosage of prednisolone was reduced. Two years later he remains well and his condition is controlled with azathiaprine alone. DISCUSSION This patient had the typical clinical, histologic, and electromyographic features of dermatomyositis. Creatine kinase levels that are within normal limits, as in this patient, occur in approximately 5% of patients with dermatomyositis. 2 The findings of immunofluorescence testing and the demonstration that his serum was bound to the 220 kd classic BP antigen demonstrate that he also had BP. The pattern Of staining on 1 M sodium chloride split skin with binding to both the epidermal and dermal side is unusual and occurs in only approximately 3% of cases of BP3; binding is typically confined to the epidermal side. The cause of this combined staining pattern is unknown, but may reflect bridging of the lamina lucida by large macromolecules. Several case reports have described dermatomyositis with coexistent vesicular and bullous le-
sions,4, 5 but without immunofluorescence studies, it is difficult to know whether these patients had BP. One patient in particular 6 had features that were similar to our patient, with scaling of the scalp and fingertips and periorbital edema, followed a few weeks later by the development of weakness of proximal muscles and numerous vesicobullous lesions. Findings of a muscle biopsy specimen showed an active myositis, and findings of a skin biopsy specimen showed a subepidermal bulla containing eosinophils and polymorphs. Unfortunately no immunofluorescence studies were conducted. In BP evidence exists both in vivo and in vitro that autoantibody binding to the BP antigen, which appears to be a major hemidesmosome plaque protein, is involved in pathogenesis. 7"L~What initiates the production of the antibody is not known, although it is presumed to follow alteration of the BP antigen.1 l One possible explanation for the association of BP and dermatomyositis in this patient is that basal layer damage from the dermatomyositis may have exposed or released basement membrane zone antigens, including the BP antigen, which may have led to the formation of antibodies, with the subsequent production of blisters in areas not clinically affected by dermatomyositis. An analogous process is believed to occur in lichen planus pemphigoides. 12Antibodies to the classic 220 kd BP antigen have been found in some patients with lichen planus pemphigoides, whereas others have had antibodies to a distinct 200 kd protein. (Davis et al., Lichen planus
852
Journal of the American Academy of Dermatology
Glover and Leigh
pemphigoides; its relationship to bullous pemphigoid [manuscript in preparation].) Because the a p p e a r a n c e of B P is so unusual in dermatomyositis, other factors must be involved. Although photosensitivity is not a recognized feature of BP, it has been described in dermatomyositis. 13 This patient had a holiday in the sun shortly before his s y m p t o m s developed, and it is of interest t h a t most o f his bullae were on sun-exposed skin. W e also considered a possible role for the medications he was taking, but similar cases have not been reported. BP has been described in association with numerous a u t o i m m u n e diseases~4-tg; whether these associations are m o r e t h a n coincidental is unclear. Because of the close t e m p o r a l association of the dermatomyositis and the B P in this patient, we believe they are almost certainly etiologically linked. REFERENCES 1. Tatnall FM, Whitehead PC, Black MM, et al. Identification of epidermolysis bullosa acquisita antigen by LH7.2 monoclonal antibody: use in diagnosis. Br J Dermatol 1989;120:533-9. 2. Bohan A, Peter JB, Bowman RL, et al. A computer assisted analysis of 153 patients with polymyositis and dermatomyosiris. Medicine 1977;56:255-86. 3. Logan RA, Bhogal B, Das AK, et al. Localisation of bullous pemphigoid antibody--an indirect immunofluorescence study of 228 eases using a split-skin technique. Br J Dermatol 1987;117:471-8. 4. Findlay GH, Price EA, Van Rensburg CRJ. Dermatomyosiris with vesicular and bullous lesions. S Afr Med J 1951;25:60-5. 5. Holmes JM. A case of acute dermatomyositis. Br Med J 1948;2:511-3. 6. Peck SM, Lefkovits AM. Bullous pemphigoid with poly-
7.
8.
9.
10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
myositis and coexisting contact dermatitis. Arch Dermatol 1966;94:672-4. Mutasim DF, Morrison LH, Takahashi Y, et al. Definition of bullouspemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes. J Invest Dermatol 1989;92:225-30. Westgate GE, Weaver AC, Couchman JR. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes. J Invest Dermatol 1985;84:2l 8-24. Gammon WR, Lewis DM, Carlo JR, et al. Pemphigoid antibody mediated attachment of peripheral blood leukocytes at the dermal-epidermal junction of human skin. J Invest Dermatol 1980;75:303-6. Naito K, Morioka S, Ogawa H. The pathogenetic mechanisms of blister formation in bullous pemphigoid. J Invest Dermatol 1982;79:303-6. Sams WM, Gammon WR. Mechanism of lesion production in pemphigus and pemphigoid.J AM ACADDERMATOL 1980;6:431-41. Stingl G, Holubar K. Co-existence of lichen planus and bullous pemphigoid. An Immunopathological study. Br J Dermatol 1975;93:313-20. Garcin R, Lapresle J, Gruner J, et al. Les Polymyosites.Rev Neurol (Paris) 1955;92:465. Gianni JM, Callen JP, Gruber GG. Bullous pemphigoid and rheumatoid arthritis. J AN ACAD DERMATOL1981; 4:695-7. Chuang TY, Korkij W, Soltani K, et at. Increased frequency of diabetes mellitus in patients with buUous pemphigoid. J AM ACAD DERMATOL1984;11:1099-2002. Leibovici V, Ron N, Goldenhersch M, et al. Co-existence of pemphigus and bullous pemphigoid. Int J Dermatol 1989;28:259-60. Barth JH, Kelly SE, Wojnarowska F, et al. Pemphigoid and ulcerative colitis. J AM ACADDERMATOL1988;19:303-8. Simon CA, Winkleman RK. Bullous pemphigoid and glomerulonephritis: report of four cases. J AM ACADDERMATOL1986;14:456-60. Black MM, What is going on in lichen planus2 Clin Exp Dermatol 1977;2:303-10.