1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
a) Prednisone
b) Prednisone plus azathioprine
c) Antimalarials
d) Plasmaphoresis
e) Sulfones
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
a) Antibodies to Ro/SSA
b) Antibodies to double-stranded DNA
c) Antibodies to histone
d) Antibodies to phospholipid
e) Antibodies to Rh
3. Autoantibodies in this disease bind:
a) Desmoglein 1
b) Keratin intermediate filaments
c) Desmoglein 3
d) Vimentin
e) Type VI collagen
To learn the answers, go to page 2
ANSWERS:
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
e) Sulfones
This patient has bullous SLE which may respond dramatically to dapsone. Features of bullous eruption of SLE include:
• Clinical—a widespread chronic recurrent bullous eruption with a predilection for sun-exposed skin, meets SLE criteria of the American Rheumatism Association, and usually responds to dapsone.
• Histologic—a subepidermal blister usually without basal cell vacuolization. An acute neutrophil-predominant inflammatory reaction in the upper dermis and at the BMZ, usually associated with papillary microabscesses resembling those characteristic of dermatitis herpetiformis. Leukocytoclastic venulitis may also be present.
• Ultrastructural—dermal-epidermal separation below the lamina densa in more advanced disease (note: may be instead within the lamina lucida in very early disease, prior to the presence of marked injury of the anchoring fibrils).
• Immunohistology—direct immunofluorescence may show linear-homogenous IgG, IgA, and/or IgM, and C components.
• Immunoelectron microscopy—immunoglobulin deposits are on and/or just beneath the lamina densa.
• Serologic—IgG anti-BMZ antibodies bind to type VII collagen.
References
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. 1982;97(2):165-170.
Current Concepts in Skin Disorders. 1986:6:4.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
d) Antibodies to phospholipid
The features associated with antibodies to phospholipid (lupus anticoagulant) include chronic headaches, spontaneous abortions, thromboembolic events, and livedo. Arthralgias, photosensitivity, serositis, and a positive ANA are also features. This combination of findings is being reported with an increased frequency, suggesting a possible cause and effect between hypercoagulability/thrombotic events and antibodies to phospholipid. Other features associated with lupus anticoagulant include thrombocytopenia, Coombs-positive anemia, cutaneous ulcerations, and gangrene. These latter cutaneous manifestations are thought to be due to hypercoagulability/thrombosis. The lupus anticoagulant is an IgG/IgM antibody that reacts with the prothrombin activator complex (Xa, V, phospholipid) in vitro to prolong the partial thromboplastin time. Contrary to its name, it appears to be associated with hypercoagulability in vivo, possibly by inhibition of endothelial cell prostacyclin and fibrinolytic activity. The lupus anticoagulant gets its name from its association with lupus erythematosus, but it occurs in association with other disorders or as an idiopathic isolated event. There is evidence that the antibodies responsible for a false-positive VDRL test result may cross-react with antigens recognized by lupus anticoagulant antibodies.
References
Crob JJ, Bonerandi JJ. Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. J Am Acad Dermatol. 1986;15(2 Pt 1):211-219. Am J Med Sci. 1987;193:1.
Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275.
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol. 1999;26(3):591-596.
Bick RL. Antiphospholipid thrombosis syndrome. Clin Appl Thromb Hemost. 2001;7(4):241-258. J Nephrol. 2002;1:342.
Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med. 2002;95(7):336-342.
3. Autoantibodies in this disease bind:
a) Desmoglein 1
Pemphigus foliaceus clinically presents with extensive scaling and crusting. It is confirmed by routine histology and direct immunofluorescence. The disease is characterized by IgG autoantibodies against desmoglein 1, a 160-kD glycoprotein present in the keratinocyte desmosomes throughout the entire epidermis. In human skin, desmoglein 3, the targeted protein in pemphigus vulgaris, is present only in the basal layer and in the suprabasal layer directly overlying it. In the absence of the co-presence of desmoglein 3 in the uppermost epidermis, autoantibody binding to desmoglein 1 therefore results in uncompensated injury to the uppermost epidermis, explaining why blisters arise only in the most superficial portion of the epidermis in patients with pemphigus foliaceus. Yet, direct immunofluorescence reveals intercellular staining throughout the entire epidermis.
References
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461-468.
Hanakawa Y, Matsuyoshi N, Stanley JR. Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in keratinocyte adhesion. J Invest Dermatol. 2002;119(1):27-31.
Dasher D, Rubenstein D, Diaz LA. Pemphigus foliaceus. Curr Dir Autoimmun. 2008;10:182-194.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine is currently professor of medicine dermatology and pediatrics at the Vanderbilt University School of Medicine in Nashville, TN.
Ron J. Feldman, MD, PhD, is an assistant professor in thr department of dermatology at Emory University School of Medicine in Atlanta, GA.
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
a) Prednisone
b) Prednisone plus azathioprine
c) Antimalarials
d) Plasmaphoresis
e) Sulfones
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
a) Antibodies to Ro/SSA
b) Antibodies to double-stranded DNA
c) Antibodies to histone
d) Antibodies to phospholipid
e) Antibodies to Rh
3. Autoantibodies in this disease bind:
a) Desmoglein 1
b) Keratin intermediate filaments
c) Desmoglein 3
d) Vimentin
e) Type VI collagen
ANSWERS:
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
e) Sulfones
This patient has bullous SLE which may respond dramatically to dapsone. Features of bullous eruption of SLE include:
• Clinical—a widespread chronic recurrent bullous eruption with a predilection for sun-exposed skin, meets SLE criteria of the American Rheumatism Association, and usually responds to dapsone.
• Histologic—a subepidermal blister usually without basal cell vacuolization. An acute neutrophil-predominant inflammatory reaction in the upper dermis and at the BMZ, usually associated with papillary microabscesses resembling those characteristic of dermatitis herpetiformis. Leukocytoclastic venulitis may also be present.
• Ultrastructural—dermal-epidermal separation below the lamina densa in more advanced disease (note: may be instead within the lamina lucida in very early disease, prior to the presence of marked injury of the anchoring fibrils).
• Immunohistology—direct immunofluorescence may show linear-homogenous IgG, IgA, and/or IgM, and C components.
• Immunoelectron microscopy—immunoglobulin deposits are on and/or just beneath the lamina densa.
• Serologic—IgG anti-BMZ antibodies bind to type VII collagen.
References
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. 1982;97(2):165-170.
Current Concepts in Skin Disorders. 1986:6:4.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
d) Antibodies to phospholipid
The features associated with antibodies to phospholipid (lupus anticoagulant) include chronic headaches, spontaneous abortions, thromboembolic events, and livedo. Arthralgias, photosensitivity, serositis, and a positive ANA are also features. This combination of findings is being reported with an increased frequency, suggesting a possible cause and effect between hypercoagulability/thrombotic events and antibodies to phospholipid. Other features associated with lupus anticoagulant include thrombocytopenia, Coombs-positive anemia, cutaneous ulcerations, and gangrene. These latter cutaneous manifestations are thought to be due to hypercoagulability/thrombosis. The lupus anticoagulant is an IgG/IgM antibody that reacts with the prothrombin activator complex (Xa, V, phospholipid) in vitro to prolong the partial thromboplastin time. Contrary to its name, it appears to be associated with hypercoagulability in vivo, possibly by inhibition of endothelial cell prostacyclin and fibrinolytic activity. The lupus anticoagulant gets its name from its association with lupus erythematosus, but it occurs in association with other disorders or as an idiopathic isolated event. There is evidence that the antibodies responsible for a false-positive VDRL test result may cross-react with antigens recognized by lupus anticoagulant antibodies.
References
Crob JJ, Bonerandi JJ. Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. J Am Acad Dermatol. 1986;15(2 Pt 1):211-219. Am J Med Sci. 1987;193:1.
Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275.
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol. 1999;26(3):591-596.
Bick RL. Antiphospholipid thrombosis syndrome. Clin Appl Thromb Hemost. 2001;7(4):241-258. J Nephrol. 2002;1:342.
Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med. 2002;95(7):336-342.
3. Autoantibodies in this disease bind:
a) Desmoglein 1
Pemphigus foliaceus clinically presents with extensive scaling and crusting. It is confirmed by routine histology and direct immunofluorescence. The disease is characterized by IgG autoantibodies against desmoglein 1, a 160-kD glycoprotein present in the keratinocyte desmosomes throughout the entire epidermis. In human skin, desmoglein 3, the targeted protein in pemphigus vulgaris, is present only in the basal layer and in the suprabasal layer directly overlying it. In the absence of the co-presence of desmoglein 3 in the uppermost epidermis, autoantibody binding to desmoglein 1 therefore results in uncompensated injury to the uppermost epidermis, explaining why blisters arise only in the most superficial portion of the epidermis in patients with pemphigus foliaceus. Yet, direct immunofluorescence reveals intercellular staining throughout the entire epidermis.
References
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461-468.
Hanakawa Y, Matsuyoshi N, Stanley JR. Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in keratinocyte adhesion. J Invest Dermatol. 2002;119(1):27-31.
Dasher D, Rubenstein D, Diaz LA. Pemphigus foliaceus. Curr Dir Autoimmun. 2008;10:182-194.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine is currently professor of medicine dermatology and pediatrics at the Vanderbilt University School of Medicine in Nashville, TN.
Ron J. Feldman, MD, PhD, is an assistant professor in thr department of dermatology at Emory University School of Medicine in Atlanta, GA.
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
a) Prednisone
b) Prednisone plus azathioprine
c) Antimalarials
d) Plasmaphoresis
e) Sulfones
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
a) Antibodies to Ro/SSA
b) Antibodies to double-stranded DNA
c) Antibodies to histone
d) Antibodies to phospholipid
e) Antibodies to Rh
3. Autoantibodies in this disease bind:
a) Desmoglein 1
b) Keratin intermediate filaments
c) Desmoglein 3
d) Vimentin
e) Type VI collagen
,
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
a) Prednisone
b) Prednisone plus azathioprine
c) Antimalarials
d) Plasmaphoresis
e) Sulfones
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
a) Antibodies to Ro/SSA
b) Antibodies to double-stranded DNA
c) Antibodies to histone
d) Antibodies to phospholipid
e) Antibodies to Rh
3. Autoantibodies in this disease bind:
a) Desmoglein 1
b) Keratin intermediate filaments
c) Desmoglein 3
d) Vimentin
e) Type VI collagen
To learn the answers, go to page 2
ANSWERS:
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
e) Sulfones
This patient has bullous SLE which may respond dramatically to dapsone. Features of bullous eruption of SLE include:
• Clinical—a widespread chronic recurrent bullous eruption with a predilection for sun-exposed skin, meets SLE criteria of the American Rheumatism Association, and usually responds to dapsone.
• Histologic—a subepidermal blister usually without basal cell vacuolization. An acute neutrophil-predominant inflammatory reaction in the upper dermis and at the BMZ, usually associated with papillary microabscesses resembling those characteristic of dermatitis herpetiformis. Leukocytoclastic venulitis may also be present.
• Ultrastructural—dermal-epidermal separation below the lamina densa in more advanced disease (note: may be instead within the lamina lucida in very early disease, prior to the presence of marked injury of the anchoring fibrils).
• Immunohistology—direct immunofluorescence may show linear-homogenous IgG, IgA, and/or IgM, and C components.
• Immunoelectron microscopy—immunoglobulin deposits are on and/or just beneath the lamina densa.
• Serologic—IgG anti-BMZ antibodies bind to type VII collagen.
References
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. 1982;97(2):165-170.
Current Concepts in Skin Disorders. 1986:6:4.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
d) Antibodies to phospholipid
The features associated with antibodies to phospholipid (lupus anticoagulant) include chronic headaches, spontaneous abortions, thromboembolic events, and livedo. Arthralgias, photosensitivity, serositis, and a positive ANA are also features. This combination of findings is being reported with an increased frequency, suggesting a possible cause and effect between hypercoagulability/thrombotic events and antibodies to phospholipid. Other features associated with lupus anticoagulant include thrombocytopenia, Coombs-positive anemia, cutaneous ulcerations, and gangrene. These latter cutaneous manifestations are thought to be due to hypercoagulability/thrombosis. The lupus anticoagulant is an IgG/IgM antibody that reacts with the prothrombin activator complex (Xa, V, phospholipid) in vitro to prolong the partial thromboplastin time. Contrary to its name, it appears to be associated with hypercoagulability in vivo, possibly by inhibition of endothelial cell prostacyclin and fibrinolytic activity. The lupus anticoagulant gets its name from its association with lupus erythematosus, but it occurs in association with other disorders or as an idiopathic isolated event. There is evidence that the antibodies responsible for a false-positive VDRL test result may cross-react with antigens recognized by lupus anticoagulant antibodies.
References
Crob JJ, Bonerandi JJ. Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. J Am Acad Dermatol. 1986;15(2 Pt 1):211-219. Am J Med Sci. 1987;193:1.
Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275.
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol. 1999;26(3):591-596.
Bick RL. Antiphospholipid thrombosis syndrome. Clin Appl Thromb Hemost. 2001;7(4):241-258. J Nephrol. 2002;1:342.
Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med. 2002;95(7):336-342.
3. Autoantibodies in this disease bind:
a) Desmoglein 1
Pemphigus foliaceus clinically presents with extensive scaling and crusting. It is confirmed by routine histology and direct immunofluorescence. The disease is characterized by IgG autoantibodies against desmoglein 1, a 160-kD glycoprotein present in the keratinocyte desmosomes throughout the entire epidermis. In human skin, desmoglein 3, the targeted protein in pemphigus vulgaris, is present only in the basal layer and in the suprabasal layer directly overlying it. In the absence of the co-presence of desmoglein 3 in the uppermost epidermis, autoantibody binding to desmoglein 1 therefore results in uncompensated injury to the uppermost epidermis, explaining why blisters arise only in the most superficial portion of the epidermis in patients with pemphigus foliaceus. Yet, direct immunofluorescence reveals intercellular staining throughout the entire epidermis.
References
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461-468.
Hanakawa Y, Matsuyoshi N, Stanley JR. Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in keratinocyte adhesion. J Invest Dermatol. 2002;119(1):27-31.
Dasher D, Rubenstein D, Diaz LA. Pemphigus foliaceus. Curr Dir Autoimmun. 2008;10:182-194.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine is currently professor of medicine dermatology and pediatrics at the Vanderbilt University School of Medicine in Nashville, TN.
Ron J. Feldman, MD, PhD, is an assistant professor in thr department of dermatology at Emory University School of Medicine in Atlanta, GA.
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
a) Prednisone
b) Prednisone plus azathioprine
c) Antimalarials
d) Plasmaphoresis
e) Sulfones
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
a) Antibodies to Ro/SSA
b) Antibodies to double-stranded DNA
c) Antibodies to histone
d) Antibodies to phospholipid
e) Antibodies to Rh
3. Autoantibodies in this disease bind:
a) Desmoglein 1
b) Keratin intermediate filaments
c) Desmoglein 3
d) Vimentin
e) Type VI collagen
ANSWERS:
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
e) Sulfones
This patient has bullous SLE which may respond dramatically to dapsone. Features of bullous eruption of SLE include:
• Clinical—a widespread chronic recurrent bullous eruption with a predilection for sun-exposed skin, meets SLE criteria of the American Rheumatism Association, and usually responds to dapsone.
• Histologic—a subepidermal blister usually without basal cell vacuolization. An acute neutrophil-predominant inflammatory reaction in the upper dermis and at the BMZ, usually associated with papillary microabscesses resembling those characteristic of dermatitis herpetiformis. Leukocytoclastic venulitis may also be present.
• Ultrastructural—dermal-epidermal separation below the lamina densa in more advanced disease (note: may be instead within the lamina lucida in very early disease, prior to the presence of marked injury of the anchoring fibrils).
• Immunohistology—direct immunofluorescence may show linear-homogenous IgG, IgA, and/or IgM, and C components.
• Immunoelectron microscopy—immunoglobulin deposits are on and/or just beneath the lamina densa.
• Serologic—IgG anti-BMZ antibodies bind to type VII collagen.
References
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. 1982;97(2):165-170.
Current Concepts in Skin Disorders. 1986:6:4.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
d) Antibodies to phospholipid
The features associated with antibodies to phospholipid (lupus anticoagulant) include chronic headaches, spontaneous abortions, thromboembolic events, and livedo. Arthralgias, photosensitivity, serositis, and a positive ANA are also features. This combination of findings is being reported with an increased frequency, suggesting a possible cause and effect between hypercoagulability/thrombotic events and antibodies to phospholipid. Other features associated with lupus anticoagulant include thrombocytopenia, Coombs-positive anemia, cutaneous ulcerations, and gangrene. These latter cutaneous manifestations are thought to be due to hypercoagulability/thrombosis. The lupus anticoagulant is an IgG/IgM antibody that reacts with the prothrombin activator complex (Xa, V, phospholipid) in vitro to prolong the partial thromboplastin time. Contrary to its name, it appears to be associated with hypercoagulability in vivo, possibly by inhibition of endothelial cell prostacyclin and fibrinolytic activity. The lupus anticoagulant gets its name from its association with lupus erythematosus, but it occurs in association with other disorders or as an idiopathic isolated event. There is evidence that the antibodies responsible for a false-positive VDRL test result may cross-react with antigens recognized by lupus anticoagulant antibodies.
References
Crob JJ, Bonerandi JJ. Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. J Am Acad Dermatol. 1986;15(2 Pt 1):211-219. Am J Med Sci. 1987;193:1.
Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275.
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol. 1999;26(3):591-596.
Bick RL. Antiphospholipid thrombosis syndrome. Clin Appl Thromb Hemost. 2001;7(4):241-258. J Nephrol. 2002;1:342.
Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med. 2002;95(7):336-342.
3. Autoantibodies in this disease bind:
a) Desmoglein 1
Pemphigus foliaceus clinically presents with extensive scaling and crusting. It is confirmed by routine histology and direct immunofluorescence. The disease is characterized by IgG autoantibodies against desmoglein 1, a 160-kD glycoprotein present in the keratinocyte desmosomes throughout the entire epidermis. In human skin, desmoglein 3, the targeted protein in pemphigus vulgaris, is present only in the basal layer and in the suprabasal layer directly overlying it. In the absence of the co-presence of desmoglein 3 in the uppermost epidermis, autoantibody binding to desmoglein 1 therefore results in uncompensated injury to the uppermost epidermis, explaining why blisters arise only in the most superficial portion of the epidermis in patients with pemphigus foliaceus. Yet, direct immunofluorescence reveals intercellular staining throughout the entire epidermis.
References
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461-468.
Hanakawa Y, Matsuyoshi N, Stanley JR. Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in keratinocyte adhesion. J Invest Dermatol. 2002;119(1):27-31.
Dasher D, Rubenstein D, Diaz LA. Pemphigus foliaceus. Curr Dir Autoimmun. 2008;10:182-194.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine is currently professor of medicine dermatology and pediatrics at the Vanderbilt University School of Medicine in Nashville, TN.
Ron J. Feldman, MD, PhD, is an assistant professor in thr department of dermatology at Emory University School of Medicine in Atlanta, GA.
ANSWERS:
1. This patient has systemic lupus erythematosus (SLE). Histology of a lesion showed a subepidermal blister with neutrophilic papillary microabscesses. Direct and indirect immunofluorescence showed homogeneous deposits of IgG, IgA, and C3 at the basement membrane zone (BMZ) and an IgG anti-BMZ antibody at a titer of 1:40. Initial therapy for the eruption should be:
e) Sulfones
This patient has bullous SLE which may respond dramatically to dapsone. Features of bullous eruption of SLE include:
• Clinical—a widespread chronic recurrent bullous eruption with a predilection for sun-exposed skin, meets SLE criteria of the American Rheumatism Association, and usually responds to dapsone.
• Histologic—a subepidermal blister usually without basal cell vacuolization. An acute neutrophil-predominant inflammatory reaction in the upper dermis and at the BMZ, usually associated with papillary microabscesses resembling those characteristic of dermatitis herpetiformis. Leukocytoclastic venulitis may also be present.
• Ultrastructural—dermal-epidermal separation below the lamina densa in more advanced disease (note: may be instead within the lamina lucida in very early disease, prior to the presence of marked injury of the anchoring fibrils).
• Immunohistology—direct immunofluorescence may show linear-homogenous IgG, IgA, and/or IgM, and C components.
• Immunoelectron microscopy—immunoglobulin deposits are on and/or just beneath the lamina densa.
• Serologic—IgG anti-BMZ antibodies bind to type VII collagen.
References
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern Med. 1982;97(2):165-170.
Current Concepts in Skin Disorders. 1986:6:4.
Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin. 1993;11(3):535-547.
2. This 35-year-old woman had a history of arthralgias, photosensitivity, pleurisy, chronic headaches, spontaneous abortion, and pulmonary embolus. Antinuclear antibody (ANA) was 1:1280 and cryoglobulins were negative. Which of these autoantibodies may be involved?
d) Antibodies to phospholipid
The features associated with antibodies to phospholipid (lupus anticoagulant) include chronic headaches, spontaneous abortions, thromboembolic events, and livedo. Arthralgias, photosensitivity, serositis, and a positive ANA are also features. This combination of findings is being reported with an increased frequency, suggesting a possible cause and effect between hypercoagulability/thrombotic events and antibodies to phospholipid. Other features associated with lupus anticoagulant include thrombocytopenia, Coombs-positive anemia, cutaneous ulcerations, and gangrene. These latter cutaneous manifestations are thought to be due to hypercoagulability/thrombosis. The lupus anticoagulant is an IgG/IgM antibody that reacts with the prothrombin activator complex (Xa, V, phospholipid) in vitro to prolong the partial thromboplastin time. Contrary to its name, it appears to be associated with hypercoagulability in vivo, possibly by inhibition of endothelial cell prostacyclin and fibrinolytic activity. The lupus anticoagulant gets its name from its association with lupus erythematosus, but it occurs in association with other disorders or as an idiopathic isolated event. There is evidence that the antibodies responsible for a false-positive VDRL test result may cross-react with antigens recognized by lupus anticoagulant antibodies.
References
Crob JJ, Bonerandi JJ. Cutaneous manifestations associated with the presence of the lupus anticoagulant. A report of two cases and a review of the literature. J Am Acad Dermatol. 1986;15(2 Pt 1):211-219. Am J Med Sci. 1987;193:1.
Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275.
Merkel PA, Chang Y, Pierangeli SS, Harris EN, Polisson RP. Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases. J Rheumatol. 1999;26(3):591-596.
Bick RL. Antiphospholipid thrombosis syndrome. Clin Appl Thromb Hemost. 2001;7(4):241-258. J Nephrol. 2002;1:342.
Keswani SC, Chauhan N. Antiphospholipid syndrome. J R Soc Med. 2002;95(7):336-342.
3. Autoantibodies in this disease bind:
a) Desmoglein 1
Pemphigus foliaceus clinically presents with extensive scaling and crusting. It is confirmed by routine histology and direct immunofluorescence. The disease is characterized by IgG autoantibodies against desmoglein 1, a 160-kD glycoprotein present in the keratinocyte desmosomes throughout the entire epidermis. In human skin, desmoglein 3, the targeted protein in pemphigus vulgaris, is present only in the basal layer and in the suprabasal layer directly overlying it. In the absence of the co-presence of desmoglein 3 in the uppermost epidermis, autoantibody binding to desmoglein 1 therefore results in uncompensated injury to the uppermost epidermis, explaining why blisters arise only in the most superficial portion of the epidermis in patients with pemphigus foliaceus. Yet, direct immunofluorescence reveals intercellular staining throughout the entire epidermis.
References
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. 1999;103(4):461-468.
Hanakawa Y, Matsuyoshi N, Stanley JR. Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in keratinocyte adhesion. J Invest Dermatol. 2002;119(1):27-31.
Dasher D, Rubenstein D, Diaz LA. Pemphigus foliaceus. Curr Dir Autoimmun. 2008;10:182-194.
Jo-David Fine, MD, MPH, FRCP, is board certified in internal medicine, dermatology, and diagnostic and laboratory immunodermatology. Dr Fine is currently professor of medicine dermatology and pediatrics at the Vanderbilt University School of Medicine in Nashville, TN.
Ron J. Feldman, MD, PhD, is an assistant professor in thr department of dermatology at Emory University School of Medicine in Atlanta, GA.
