The contents of these questions are taken from the Galderma Pre-Board Webinar. The Pre-Board Webinar is now an online course. For details, go to www.pre-board.com. The program will be available from April 15, 2016 to November 15, 2016.
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
b) Leukemic infiltrates
c) Subcorneal pustular dermatosis
d) Behçet syndrome
e) Erythema elevatum diutinum
2. These lesions are most characteristic of:
a) Drug-induced pemphigus
b) Pemphigus vulgaris
c) Paraneoplastic pemphigus
d) Pemphigus vegetans
e) Pemphigus erythematoides
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
a) Dominant dystrophic epidermolysis bullosa
b) Epidermolysis bullosa acquista
c) Porphyria cutanea tarda
d) Pseudoporphyria (drug induced)
e) Bullous disease of hemolysis
To learn the answers, go to page 2
{{pagebreak}}
BOARD REVIEW ANSWERS:
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome is a cutaneous reaction pattern that includes characteristic skin lesions, fever, neutrophilic leukocytosis, arthralgia, and an elevated erythrocyte sedimentation rate. Presentation lacking one or more of the systematic features is common. Lesions vary from erythematous papules and plaques with or without pustules to ulcerative-erosive lesions that closely resemble superficial or atypical pyoderma gangrenosum. Some view the erosive-ulcerative lesions as variant of pyoderma gangrenosum. Many of these patients have underlying myeloproliferative diseases.
Histology includes a dense accumulation of neutrophils in the upper dermis and in some cases, accumulation of neutrophils in the epidermis. Epidermis is necrotic or absent in erosive lesions. Sweet syndrome responds to glucocorticosteroids. Dapsone is another effective therapy, given the drug’s ability to dramatically inhibit neutrophil chemotaxis.
References
Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409.
von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-556.
Malone JC, Slong SP, Willis-Frank LA, et al. Vascular inflammation (vasculitis) in Sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol. 2002;138(3):345-349.
2. These lesions are most characteristic of:
c) Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune blistering disorder with characteristic clinical, pathological, and immune-pathologic features. Clinically, patients have painful mucosa (oral, pharyngeal, esophageal, conjunctival) erosions and blisters and a polymorphic eruption that includes erythema multiforme-like annular and targeted lesions in addition to blisters and erosions. Histologic changes include vacuolization of basal keratinocytes, keratinocyte necrosis, and acantholysis—sharing features of erythema multiforme and pemphigus. Direct immunofluorescence of perilesional skin shows ICS and often broad linear BMZ IgG deposits, the latter typical but not specific for erythema multiforme.
Patients typically have circulating antibodies that react with desmosomes in a wide variety of epithelial tissues including rat bladder epithelium. Immunologic hallmark of the disease is the presence in serum of IgG autoantibodies that immunoprecipitate epithelial proteins belonging to the plakin family of adhesion-related proteins. These include desmoplakin I (250 kD), BPAG I (230 kD), desmoplain II and envoplain (210 kD), periplakin I (190 kD), and an unidentified 170 kD protein. These autoantibodies represent serologic markers to malignancy. Paraneoplastic pemphigus sera also reacts with plectin (600 KD) and desmoglein III. Autoantibodies to the latter may be pathologic and responsible for the ability of paraneoplastic pemphigus sera to induce acantholysis in newborn mouse epithelium. Most patients have tumors of lymphoreticular origin. This disorder may be similar to a form of erythema multifrome major that is also associated with the presence in serum of autoantibodies to desmoplakin I and II.
References
Foedinger D, Sterniczky B, Elbe A, Anhalt G, Wolff K, Rappersberger K. Autoantibodies against desmoplakin I and II define a subset of patients with erythema mutliforme major. J Invest Dermatol. 1996;106(5):1012-1016.
Hashimoto T, Amagai M, Watanabe K, et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol. 1995;104(5):829-834.
Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999;112(2):153-156.
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999;40(5 Pt 1):649-671.
Stanley JR. Pathophysiology and therapy of pemphigus in the 21st century. J Dermatol. 2001;28(11):645-646.
Devries DT, Warren SJ. Recent advances in intraepidermal blistering disease. Adv Dermatol. 2002;18:203-245.
Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725-732.
Amagai M. Pemphigus vulgaris and its active disease mouse model. Curr Dir Autoimmun. 2008;10:167-181.
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
b) Epidermolysis bullosa acquista
EBA is an autoimmune blistering disease, which can occur in children and adults. It has multiple clinical presentations. The “classic” presentation resembles dystrophic epidermolysis bullosa, with scarring, dyspigmentation, and milia formation. The urticarial or bullous “inflammatory” variant mimics bullous pemphigoid. Primary mucosal variant mimics cicatricial pemphigold. Acral scarring variant has features most suggestive of porphyria cutanea tarda or variegate porphyria.
EBA is characterized by the presence of tissue-bound and circulating autoantibodies to (more often to the NC1 rather than to the triple-helical domain of) type IV collagen, the major component of the anchoring fibril. Pathogenesis of these autoantibodies has been proven in both in vitro and animal models. There is a higher risk of EBA among individuals having the HLA-DR2 phenotype. EBA has been associated with several diseases: systemic lupus erythematosus, amyloidosis, thyroiditis, multiple endocrinopathy syndrome, rheumatoid arthritis, pulmonary fibrosis, chronic lymphocytic leukemia, thymoma, and diabetes mellitus.
Of particular interest, subsets of EBA patients have had coexistent inflammatory bowel disease. As a correlate, a minority of patients with Crohn disease or ulcerative colitis, who lack any evidence of skin disease, have been found to have detectable anti-type VII collagen autoantibodies within their sera, suggesting that the association between EBA and inflammatory bowel disease is pathogenically quite plausible.
References
Freedberg IM, Fitzpatrick TB. Fitzpatrick’s Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Education; 1999:702-709.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Disease of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
Zillikens D. Acquired skin disease of hemidesmosomes. J Dermatol Sci. 1999;20(2):134-154.
Engineer L, Ahmed AR. Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol. 2001;44(5):818-828.
Remington J, Chen M, Burnett J, Woodley DT. Autoimmunity to type VII collagen: epidermolysis bullosa acquisita. Curr Dir Autoimmun. 2008;10:195-205.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine served on the faculty of the Departments of Dermatology and Epidemiology in the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill.
Ronald J. Feldman, MD, PhD, is assistant professor of dermatology at Emory University Hospital in Atlanta, GA.
The contents of these questions are taken from the Galderma Pre-Board Webinar. The Pre-Board Webinar is now an online course. For details, go to www.pre-board.com. The program will be available from April 15, 2016 to November 15, 2016.
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
b) Leukemic infiltrates
c) Subcorneal pustular dermatosis
d) Behçet syndrome
e) Erythema elevatum diutinum
2. These lesions are most characteristic of:
a) Drug-induced pemphigus
b) Pemphigus vulgaris
c) Paraneoplastic pemphigus
d) Pemphigus vegetans
e) Pemphigus erythematoides
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
a) Dominant dystrophic epidermolysis bullosa
b) Epidermolysis bullosa acquista
c) Porphyria cutanea tarda
d) Pseudoporphyria (drug induced)
e) Bullous disease of hemolysis
BOARD REVIEW ANSWERS:
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome is a cutaneous reaction pattern that includes characteristic skin lesions, fever, neutrophilic leukocytosis, arthralgia, and an elevated erythrocyte sedimentation rate. Presentation lacking one or more of the systematic features is common. Lesions vary from erythematous papules and plaques with or without pustules to ulcerative-erosive lesions that closely resemble superficial or atypical pyoderma gangrenosum. Some view the erosive-ulcerative lesions as variant of pyoderma gangrenosum. Many of these patients have underlying myeloproliferative diseases.
Histology includes a dense accumulation of neutrophils in the upper dermis and in some cases, accumulation of neutrophils in the epidermis. Epidermis is necrotic or absent in erosive lesions. Sweet syndrome responds to glucocorticosteroids. Dapsone is another effective therapy, given the drug’s ability to dramatically inhibit neutrophil chemotaxis.
References
Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409.
von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-556.
Malone JC, Slong SP, Willis-Frank LA, et al. Vascular inflammation (vasculitis) in Sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol. 2002;138(3):345-349.
2. These lesions are most characteristic of:
c) Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune blistering disorder with characteristic clinical, pathological, and immune-pathologic features. Clinically, patients have painful mucosa (oral, pharyngeal, esophageal, conjunctival) erosions and blisters and a polymorphic eruption that includes erythema multiforme-like annular and targeted lesions in addition to blisters and erosions. Histologic changes include vacuolization of basal keratinocytes, keratinocyte necrosis, and acantholysis—sharing features of erythema multiforme and pemphigus. Direct immunofluorescence of perilesional skin shows ICS and often broad linear BMZ IgG deposits, the latter typical but not specific for erythema multiforme.
Patients typically have circulating antibodies that react with desmosomes in a wide variety of epithelial tissues including rat bladder epithelium. Immunologic hallmark of the disease is the presence in serum of IgG autoantibodies that immunoprecipitate epithelial proteins belonging to the plakin family of adhesion-related proteins. These include desmoplakin I (250 kD), BPAG I (230 kD), desmoplain II and envoplain (210 kD), periplakin I (190 kD), and an unidentified 170 kD protein. These autoantibodies represent serologic markers to malignancy. Paraneoplastic pemphigus sera also reacts with plectin (600 KD) and desmoglein III. Autoantibodies to the latter may be pathologic and responsible for the ability of paraneoplastic pemphigus sera to induce acantholysis in newborn mouse epithelium. Most patients have tumors of lymphoreticular origin. This disorder may be similar to a form of erythema multifrome major that is also associated with the presence in serum of autoantibodies to desmoplakin I and II.
References
Foedinger D, Sterniczky B, Elbe A, Anhalt G, Wolff K, Rappersberger K. Autoantibodies against desmoplakin I and II define a subset of patients with erythema mutliforme major. J Invest Dermatol. 1996;106(5):1012-1016.
Hashimoto T, Amagai M, Watanabe K, et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol. 1995;104(5):829-834.
Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999;112(2):153-156.
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999;40(5 Pt 1):649-671.
Stanley JR. Pathophysiology and therapy of pemphigus in the 21st century. J Dermatol. 2001;28(11):645-646.
Devries DT, Warren SJ. Recent advances in intraepidermal blistering disease. Adv Dermatol. 2002;18:203-245.
Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725-732.
Amagai M. Pemphigus vulgaris and its active disease mouse model. Curr Dir Autoimmun. 2008;10:167-181.
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
b) Epidermolysis bullosa acquista
EBA is an autoimmune blistering disease, which can occur in children and adults. It has multiple clinical presentations. The “classic” presentation resembles dystrophic epidermolysis bullosa, with scarring, dyspigmentation, and milia formation. The urticarial or bullous “inflammatory” variant mimics bullous pemphigoid. Primary mucosal variant mimics cicatricial pemphigold. Acral scarring variant has features most suggestive of porphyria cutanea tarda or variegate porphyria.
EBA is characterized by the presence of tissue-bound and circulating autoantibodies to (more often to the NC1 rather than to the triple-helical domain of) type IV collagen, the major component of the anchoring fibril. Pathogenesis of these autoantibodies has been proven in both in vitro and animal models. There is a higher risk of EBA among individuals having the HLA-DR2 phenotype. EBA has been associated with several diseases: systemic lupus erythematosus, amyloidosis, thyroiditis, multiple endocrinopathy syndrome, rheumatoid arthritis, pulmonary fibrosis, chronic lymphocytic leukemia, thymoma, and diabetes mellitus.
Of particular interest, subsets of EBA patients have had coexistent inflammatory bowel disease. As a correlate, a minority of patients with Crohn disease or ulcerative colitis, who lack any evidence of skin disease, have been found to have detectable anti-type VII collagen autoantibodies within their sera, suggesting that the association between EBA and inflammatory bowel disease is pathogenically quite plausible.
References
Freedberg IM, Fitzpatrick TB. Fitzpatrick’s Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Education; 1999:702-709.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Disease of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
Zillikens D. Acquired skin disease of hemidesmosomes. J Dermatol Sci. 1999;20(2):134-154.
Engineer L, Ahmed AR. Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol. 2001;44(5):818-828.
Remington J, Chen M, Burnett J, Woodley DT. Autoimmunity to type VII collagen: epidermolysis bullosa acquisita. Curr Dir Autoimmun. 2008;10:195-205.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine served on the faculty of the Departments of Dermatology and Epidemiology in the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill.
Ronald J. Feldman, MD, PhD, is assistant professor of dermatology at Emory University Hospital in Atlanta, GA.
The contents of these questions are taken from the Galderma Pre-Board Webinar. The Pre-Board Webinar is now an online course. For details, go to www.pre-board.com. The program will be available from April 15, 2016 to November 15, 2016.
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
b) Leukemic infiltrates
c) Subcorneal pustular dermatosis
d) Behçet syndrome
e) Erythema elevatum diutinum
2. These lesions are most characteristic of:
a) Drug-induced pemphigus
b) Pemphigus vulgaris
c) Paraneoplastic pemphigus
d) Pemphigus vegetans
e) Pemphigus erythematoides
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
a) Dominant dystrophic epidermolysis bullosa
b) Epidermolysis bullosa acquista
c) Porphyria cutanea tarda
d) Pseudoporphyria (drug induced)
e) Bullous disease of hemolysis
,
The contents of these questions are taken from the Galderma Pre-Board Webinar. The Pre-Board Webinar is now an online course. For details, go to www.pre-board.com. The program will be available from April 15, 2016 to November 15, 2016.
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
b) Leukemic infiltrates
c) Subcorneal pustular dermatosis
d) Behçet syndrome
e) Erythema elevatum diutinum
2. These lesions are most characteristic of:
a) Drug-induced pemphigus
b) Pemphigus vulgaris
c) Paraneoplastic pemphigus
d) Pemphigus vegetans
e) Pemphigus erythematoides
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
a) Dominant dystrophic epidermolysis bullosa
b) Epidermolysis bullosa acquista
c) Porphyria cutanea tarda
d) Pseudoporphyria (drug induced)
e) Bullous disease of hemolysis
To learn the answers, go to page 2
{{pagebreak}}
BOARD REVIEW ANSWERS:
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome is a cutaneous reaction pattern that includes characteristic skin lesions, fever, neutrophilic leukocytosis, arthralgia, and an elevated erythrocyte sedimentation rate. Presentation lacking one or more of the systematic features is common. Lesions vary from erythematous papules and plaques with or without pustules to ulcerative-erosive lesions that closely resemble superficial or atypical pyoderma gangrenosum. Some view the erosive-ulcerative lesions as variant of pyoderma gangrenosum. Many of these patients have underlying myeloproliferative diseases.
Histology includes a dense accumulation of neutrophils in the upper dermis and in some cases, accumulation of neutrophils in the epidermis. Epidermis is necrotic or absent in erosive lesions. Sweet syndrome responds to glucocorticosteroids. Dapsone is another effective therapy, given the drug’s ability to dramatically inhibit neutrophil chemotaxis.
References
Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409.
von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-556.
Malone JC, Slong SP, Willis-Frank LA, et al. Vascular inflammation (vasculitis) in Sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol. 2002;138(3):345-349.
2. These lesions are most characteristic of:
c) Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune blistering disorder with characteristic clinical, pathological, and immune-pathologic features. Clinically, patients have painful mucosa (oral, pharyngeal, esophageal, conjunctival) erosions and blisters and a polymorphic eruption that includes erythema multiforme-like annular and targeted lesions in addition to blisters and erosions. Histologic changes include vacuolization of basal keratinocytes, keratinocyte necrosis, and acantholysis—sharing features of erythema multiforme and pemphigus. Direct immunofluorescence of perilesional skin shows ICS and often broad linear BMZ IgG deposits, the latter typical but not specific for erythema multiforme.
Patients typically have circulating antibodies that react with desmosomes in a wide variety of epithelial tissues including rat bladder epithelium. Immunologic hallmark of the disease is the presence in serum of IgG autoantibodies that immunoprecipitate epithelial proteins belonging to the plakin family of adhesion-related proteins. These include desmoplakin I (250 kD), BPAG I (230 kD), desmoplain II and envoplain (210 kD), periplakin I (190 kD), and an unidentified 170 kD protein. These autoantibodies represent serologic markers to malignancy. Paraneoplastic pemphigus sera also reacts with plectin (600 KD) and desmoglein III. Autoantibodies to the latter may be pathologic and responsible for the ability of paraneoplastic pemphigus sera to induce acantholysis in newborn mouse epithelium. Most patients have tumors of lymphoreticular origin. This disorder may be similar to a form of erythema multifrome major that is also associated with the presence in serum of autoantibodies to desmoplakin I and II.
References
Foedinger D, Sterniczky B, Elbe A, Anhalt G, Wolff K, Rappersberger K. Autoantibodies against desmoplakin I and II define a subset of patients with erythema mutliforme major. J Invest Dermatol. 1996;106(5):1012-1016.
Hashimoto T, Amagai M, Watanabe K, et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol. 1995;104(5):829-834.
Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999;112(2):153-156.
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999;40(5 Pt 1):649-671.
Stanley JR. Pathophysiology and therapy of pemphigus in the 21st century. J Dermatol. 2001;28(11):645-646.
Devries DT, Warren SJ. Recent advances in intraepidermal blistering disease. Adv Dermatol. 2002;18:203-245.
Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725-732.
Amagai M. Pemphigus vulgaris and its active disease mouse model. Curr Dir Autoimmun. 2008;10:167-181.
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
b) Epidermolysis bullosa acquista
EBA is an autoimmune blistering disease, which can occur in children and adults. It has multiple clinical presentations. The “classic” presentation resembles dystrophic epidermolysis bullosa, with scarring, dyspigmentation, and milia formation. The urticarial or bullous “inflammatory” variant mimics bullous pemphigoid. Primary mucosal variant mimics cicatricial pemphigold. Acral scarring variant has features most suggestive of porphyria cutanea tarda or variegate porphyria.
EBA is characterized by the presence of tissue-bound and circulating autoantibodies to (more often to the NC1 rather than to the triple-helical domain of) type IV collagen, the major component of the anchoring fibril. Pathogenesis of these autoantibodies has been proven in both in vitro and animal models. There is a higher risk of EBA among individuals having the HLA-DR2 phenotype. EBA has been associated with several diseases: systemic lupus erythematosus, amyloidosis, thyroiditis, multiple endocrinopathy syndrome, rheumatoid arthritis, pulmonary fibrosis, chronic lymphocytic leukemia, thymoma, and diabetes mellitus.
Of particular interest, subsets of EBA patients have had coexistent inflammatory bowel disease. As a correlate, a minority of patients with Crohn disease or ulcerative colitis, who lack any evidence of skin disease, have been found to have detectable anti-type VII collagen autoantibodies within their sera, suggesting that the association between EBA and inflammatory bowel disease is pathogenically quite plausible.
References
Freedberg IM, Fitzpatrick TB. Fitzpatrick’s Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Education; 1999:702-709.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Disease of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
Zillikens D. Acquired skin disease of hemidesmosomes. J Dermatol Sci. 1999;20(2):134-154.
Engineer L, Ahmed AR. Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol. 2001;44(5):818-828.
Remington J, Chen M, Burnett J, Woodley DT. Autoimmunity to type VII collagen: epidermolysis bullosa acquisita. Curr Dir Autoimmun. 2008;10:195-205.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine served on the faculty of the Departments of Dermatology and Epidemiology in the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill.
Ronald J. Feldman, MD, PhD, is assistant professor of dermatology at Emory University Hospital in Atlanta, GA.
The contents of these questions are taken from the Galderma Pre-Board Webinar. The Pre-Board Webinar is now an online course. For details, go to www.pre-board.com. The program will be available from April 15, 2016 to November 15, 2016.
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
b) Leukemic infiltrates
c) Subcorneal pustular dermatosis
d) Behçet syndrome
e) Erythema elevatum diutinum
2. These lesions are most characteristic of:
a) Drug-induced pemphigus
b) Pemphigus vulgaris
c) Paraneoplastic pemphigus
d) Pemphigus vegetans
e) Pemphigus erythematoides
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
a) Dominant dystrophic epidermolysis bullosa
b) Epidermolysis bullosa acquista
c) Porphyria cutanea tarda
d) Pseudoporphyria (drug induced)
e) Bullous disease of hemolysis
BOARD REVIEW ANSWERS:
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome is a cutaneous reaction pattern that includes characteristic skin lesions, fever, neutrophilic leukocytosis, arthralgia, and an elevated erythrocyte sedimentation rate. Presentation lacking one or more of the systematic features is common. Lesions vary from erythematous papules and plaques with or without pustules to ulcerative-erosive lesions that closely resemble superficial or atypical pyoderma gangrenosum. Some view the erosive-ulcerative lesions as variant of pyoderma gangrenosum. Many of these patients have underlying myeloproliferative diseases.
Histology includes a dense accumulation of neutrophils in the upper dermis and in some cases, accumulation of neutrophils in the epidermis. Epidermis is necrotic or absent in erosive lesions. Sweet syndrome responds to glucocorticosteroids. Dapsone is another effective therapy, given the drug’s ability to dramatically inhibit neutrophil chemotaxis.
References
Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409.
von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-556.
Malone JC, Slong SP, Willis-Frank LA, et al. Vascular inflammation (vasculitis) in Sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol. 2002;138(3):345-349.
2. These lesions are most characteristic of:
c) Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune blistering disorder with characteristic clinical, pathological, and immune-pathologic features. Clinically, patients have painful mucosa (oral, pharyngeal, esophageal, conjunctival) erosions and blisters and a polymorphic eruption that includes erythema multiforme-like annular and targeted lesions in addition to blisters and erosions. Histologic changes include vacuolization of basal keratinocytes, keratinocyte necrosis, and acantholysis—sharing features of erythema multiforme and pemphigus. Direct immunofluorescence of perilesional skin shows ICS and often broad linear BMZ IgG deposits, the latter typical but not specific for erythema multiforme.
Patients typically have circulating antibodies that react with desmosomes in a wide variety of epithelial tissues including rat bladder epithelium. Immunologic hallmark of the disease is the presence in serum of IgG autoantibodies that immunoprecipitate epithelial proteins belonging to the plakin family of adhesion-related proteins. These include desmoplakin I (250 kD), BPAG I (230 kD), desmoplain II and envoplain (210 kD), periplakin I (190 kD), and an unidentified 170 kD protein. These autoantibodies represent serologic markers to malignancy. Paraneoplastic pemphigus sera also reacts with plectin (600 KD) and desmoglein III. Autoantibodies to the latter may be pathologic and responsible for the ability of paraneoplastic pemphigus sera to induce acantholysis in newborn mouse epithelium. Most patients have tumors of lymphoreticular origin. This disorder may be similar to a form of erythema multifrome major that is also associated with the presence in serum of autoantibodies to desmoplakin I and II.
References
Foedinger D, Sterniczky B, Elbe A, Anhalt G, Wolff K, Rappersberger K. Autoantibodies against desmoplakin I and II define a subset of patients with erythema mutliforme major. J Invest Dermatol. 1996;106(5):1012-1016.
Hashimoto T, Amagai M, Watanabe K, et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol. 1995;104(5):829-834.
Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999;112(2):153-156.
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999;40(5 Pt 1):649-671.
Stanley JR. Pathophysiology and therapy of pemphigus in the 21st century. J Dermatol. 2001;28(11):645-646.
Devries DT, Warren SJ. Recent advances in intraepidermal blistering disease. Adv Dermatol. 2002;18:203-245.
Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725-732.
Amagai M. Pemphigus vulgaris and its active disease mouse model. Curr Dir Autoimmun. 2008;10:167-181.
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
b) Epidermolysis bullosa acquista
EBA is an autoimmune blistering disease, which can occur in children and adults. It has multiple clinical presentations. The “classic” presentation resembles dystrophic epidermolysis bullosa, with scarring, dyspigmentation, and milia formation. The urticarial or bullous “inflammatory” variant mimics bullous pemphigoid. Primary mucosal variant mimics cicatricial pemphigold. Acral scarring variant has features most suggestive of porphyria cutanea tarda or variegate porphyria.
EBA is characterized by the presence of tissue-bound and circulating autoantibodies to (more often to the NC1 rather than to the triple-helical domain of) type IV collagen, the major component of the anchoring fibril. Pathogenesis of these autoantibodies has been proven in both in vitro and animal models. There is a higher risk of EBA among individuals having the HLA-DR2 phenotype. EBA has been associated with several diseases: systemic lupus erythematosus, amyloidosis, thyroiditis, multiple endocrinopathy syndrome, rheumatoid arthritis, pulmonary fibrosis, chronic lymphocytic leukemia, thymoma, and diabetes mellitus.
Of particular interest, subsets of EBA patients have had coexistent inflammatory bowel disease. As a correlate, a minority of patients with Crohn disease or ulcerative colitis, who lack any evidence of skin disease, have been found to have detectable anti-type VII collagen autoantibodies within their sera, suggesting that the association between EBA and inflammatory bowel disease is pathogenically quite plausible.
References
Freedberg IM, Fitzpatrick TB. Fitzpatrick’s Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Education; 1999:702-709.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Disease of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
Zillikens D. Acquired skin disease of hemidesmosomes. J Dermatol Sci. 1999;20(2):134-154.
Engineer L, Ahmed AR. Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol. 2001;44(5):818-828.
Remington J, Chen M, Burnett J, Woodley DT. Autoimmunity to type VII collagen: epidermolysis bullosa acquisita. Curr Dir Autoimmun. 2008;10:195-205.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine served on the faculty of the Departments of Dermatology and Epidemiology in the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill.
Ronald J. Feldman, MD, PhD, is assistant professor of dermatology at Emory University Hospital in Atlanta, GA.
BOARD REVIEW ANSWERS:
1. There is a 6-week history of low-grade fever and arthralgia and a 3-week history of these lesions. A blood count showed a normocytic-normochromic anemia and neutrophilic leukocytosis. Smears and cultures were negative. Histology showed a defense infiltrate of neutrophils throughout the dermis, scattered neutrophils in the epidermis, and epidermal necrosis. The diagnosis is?
a) Sweet syndrome (acute febrile neutrophilic dermatosis)
Sweet syndrome is a cutaneous reaction pattern that includes characteristic skin lesions, fever, neutrophilic leukocytosis, arthralgia, and an elevated erythrocyte sedimentation rate. Presentation lacking one or more of the systematic features is common. Lesions vary from erythematous papules and plaques with or without pustules to ulcerative-erosive lesions that closely resemble superficial or atypical pyoderma gangrenosum. Some view the erosive-ulcerative lesions as variant of pyoderma gangrenosum. Many of these patients have underlying myeloproliferative diseases.
Histology includes a dense accumulation of neutrophils in the upper dermis and in some cases, accumulation of neutrophils in the epidermis. Epidermis is necrotic or absent in erosive lesions. Sweet syndrome responds to glucocorticosteroids. Dapsone is another effective therapy, given the drug’s ability to dramatically inhibit neutrophil chemotaxis.
References
Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409.
von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-556.
Malone JC, Slong SP, Willis-Frank LA, et al. Vascular inflammation (vasculitis) in Sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients. Arch Dermatol. 2002;138(3):345-349.
2. These lesions are most characteristic of:
c) Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune blistering disorder with characteristic clinical, pathological, and immune-pathologic features. Clinically, patients have painful mucosa (oral, pharyngeal, esophageal, conjunctival) erosions and blisters and a polymorphic eruption that includes erythema multiforme-like annular and targeted lesions in addition to blisters and erosions. Histologic changes include vacuolization of basal keratinocytes, keratinocyte necrosis, and acantholysis—sharing features of erythema multiforme and pemphigus. Direct immunofluorescence of perilesional skin shows ICS and often broad linear BMZ IgG deposits, the latter typical but not specific for erythema multiforme.
Patients typically have circulating antibodies that react with desmosomes in a wide variety of epithelial tissues including rat bladder epithelium. Immunologic hallmark of the disease is the presence in serum of IgG autoantibodies that immunoprecipitate epithelial proteins belonging to the plakin family of adhesion-related proteins. These include desmoplakin I (250 kD), BPAG I (230 kD), desmoplain II and envoplain (210 kD), periplakin I (190 kD), and an unidentified 170 kD protein. These autoantibodies represent serologic markers to malignancy. Paraneoplastic pemphigus sera also reacts with plectin (600 KD) and desmoglein III. Autoantibodies to the latter may be pathologic and responsible for the ability of paraneoplastic pemphigus sera to induce acantholysis in newborn mouse epithelium. Most patients have tumors of lymphoreticular origin. This disorder may be similar to a form of erythema multifrome major that is also associated with the presence in serum of autoantibodies to desmoplakin I and II.
References
Foedinger D, Sterniczky B, Elbe A, Anhalt G, Wolff K, Rappersberger K. Autoantibodies against desmoplakin I and II define a subset of patients with erythema mutliforme major. J Invest Dermatol. 1996;106(5):1012-1016.
Hashimoto T, Amagai M, Watanabe K, et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol. 1995;104(5):829-834.
Proby C, Fujii Y, Owaribe K, Nishikawa T, Amagai M. Human autoantibodies against HD1/plectin in paraneoplastic pemphigus. J Invest Dermatol. 1999;112(2):153-156.
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. 1999;40(5 Pt 1):649-671.
Stanley JR. Pathophysiology and therapy of pemphigus in the 21st century. J Dermatol. 2001;28(11):645-646.
Devries DT, Warren SJ. Recent advances in intraepidermal blistering disease. Adv Dermatol. 2002;18:203-245.
Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725-732.
Amagai M. Pemphigus vulgaris and its active disease mouse model. Curr Dir Autoimmun. 2008;10:167-181.
3. These lesions developed in an otherwise healthy 12-year-old child who had been on no medication. Porphyrin studies were negative. The most likely diagnosis is:
b) Epidermolysis bullosa acquista
EBA is an autoimmune blistering disease, which can occur in children and adults. It has multiple clinical presentations. The “classic” presentation resembles dystrophic epidermolysis bullosa, with scarring, dyspigmentation, and milia formation. The urticarial or bullous “inflammatory” variant mimics bullous pemphigoid. Primary mucosal variant mimics cicatricial pemphigold. Acral scarring variant has features most suggestive of porphyria cutanea tarda or variegate porphyria.
EBA is characterized by the presence of tissue-bound and circulating autoantibodies to (more often to the NC1 rather than to the triple-helical domain of) type IV collagen, the major component of the anchoring fibril. Pathogenesis of these autoantibodies has been proven in both in vitro and animal models. There is a higher risk of EBA among individuals having the HLA-DR2 phenotype. EBA has been associated with several diseases: systemic lupus erythematosus, amyloidosis, thyroiditis, multiple endocrinopathy syndrome, rheumatoid arthritis, pulmonary fibrosis, chronic lymphocytic leukemia, thymoma, and diabetes mellitus.
Of particular interest, subsets of EBA patients have had coexistent inflammatory bowel disease. As a correlate, a minority of patients with Crohn disease or ulcerative colitis, who lack any evidence of skin disease, have been found to have detectable anti-type VII collagen autoantibodies within their sera, suggesting that the association between EBA and inflammatory bowel disease is pathogenically quite plausible.
References
Freedberg IM, Fitzpatrick TB. Fitzpatrick’s Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Education; 1999:702-709.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Disease of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
Zillikens D. Acquired skin disease of hemidesmosomes. J Dermatol Sci. 1999;20(2):134-154.
Engineer L, Ahmed AR. Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol. 2001;44(5):818-828.
Remington J, Chen M, Burnett J, Woodley DT. Autoimmunity to type VII collagen: epidermolysis bullosa acquisita. Curr Dir Autoimmun. 2008;10:195-205.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine served on the faculty of the Departments of Dermatology and Epidemiology in the Schools of Medicine and Public Health at the University of North Carolina at Chapel Hill.
Ronald J. Feldman, MD, PhD, is assistant professor of dermatology at Emory University Hospital in Atlanta, GA.
