1. The diagnosis is:
a) Transient acantholytic dermatosis
b) Familial benign pemphigus (Hailey-Hailey disease)
c) Darier disease
d) Epidermolysis bullosa simplex
e) Bullous pemphigoid
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
a) Idiopathic chronic angioedema
b) Chronic urticaria
c) Urticarial vasculitis
d) Acquired angioedema with C1 esterase inhibitor deficiency
e) Hereditary angioneurotic edema
3. What is the probability this condition will progress
to a systemic disease?
a) Greater than 90%
b 25% to 50%
c) About 10%
d) About 3% to 5%
e) Less than 1%
To learn the answer, go to page 2
{{pagebreak}}
BOARD REVIEW ANSWERS
1. The diagnosis is:
b) Familial benign pemphigus (Hailey-Hailey disease)
Familial benign pemphigus (Hailey-Hailey disease) is a haploinsufficiency of the enzyme ATP2C1. The ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary 
protein to be made and the cells of the skin do not adhere together properly. The disease may be localized or generalized. It is usually localized to the upper trunk, shoulders, neck, and intertriginous areas. Erythematous, eczematous, and mildly vesicular lesions shown here are typical. Secondary infection is common and may be one explanation for why a variety of antibiotics have been beneficial in selected patients. In contrast to all other forms of pemphigus, perilesional skin from patients with Hailey-Hailey disease is characteristically direct immunofluorescence-negative.
Reference
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:642-645.
Hu Z, Bonifas JM, Beech J, et al. “Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.”. Nat. Genet. 2000; 24(1): 61–5.
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
e) Hereditary angioneurotic edema
Hereditary angioneurotic edema is an autosomal dominant disease caused by a deficiency in functional C1-inhibitor (“C1-esterase inhibitor”), the result of mutations in the C1-inhibitor gene. C1-inhibitor, a member of the serpin family of serine protease inhibitors, inhibits several complement proteases, plasma kallikrein, coagulations factors Xia and XIIa, and plasmin, leading to the generation of vasoconstrictors including bradykinin. An associated laboratory finding is a decreased level of C4.
Its clinical onset may be as early as age 2 or 3 and worsens with puberty. Severe angioedema may recur every 7 to 14 days and may be precipitated by stress or minor trauma. A classic precipitating event is a dental procedure. The abdomen and oropharynx may be involved, leading to significant morbidity, unnecessary surgery, or even death. Long-term prophylaxis includes the use of 17α-alkylated androgens and/or antifibrinolytic agents. Other autoimmune diseases, most notably glomerulonephritis, may be associated with hereditary angioneurotic edema. Of the cases of hereditary angioneurotic edema, 85% have mutations which decrease both antigenic and functional levels of this protein.
In very rare kindreds, both levels are normal; most of these patients have gain-of-function mutations in coagulations factor XII that may result in increased production of bradykinin. Acquired C1-inhibitor deficiency is clinically similar to hereditary angioneurotic edema but differs by the lack of positive family history and usually later (ie, middle age) onset. Unlike the hereditary form, patients with acquired disease have decreased levels of C1q.
References
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. ˆ 2008;100(1 suppl 2):S30-S40.
3. What is the probability this condition will progress to a systemic disease?
e) Less than 1%
Morphea, also known as localized scleroderma, has typical clinical features including hypopigmented, indurated (sclerotic) plaques that vary from a few centimeters to many centimeters in diameter. The lesions may be preceded by erythema or surrounded by a 
violaceous halo in the early “inflammatory” stage. Eventually most lesions resolve, leaving hypopigmented patches. Linear and guttate variants do occur. The disease is usually localized but may become generalized. Progression of morphea (without systemic symptoms or signs) into systemic scleroderma is rare. Patients with morphea may have active serologies and in one series about 40% were antinuclear antibody
References
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:2156-2167.
Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104(6):849-857.
Lamberts RJ, Lynch PJ. Nodular cutaneous mucinosis associated with lupus erythematosus. Cutis. 1981;28(3):294-295, 297-299.
Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.
Krafchik BR. Localized morphea in children. Adv Exp Med Biol. 1999;455:49-54.
Sehgal VN, Srivastava G, Aggarwal AK, Behi PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. Int J Dermatol. 2002;41(8):467-475.
1. The diagnosis is:
a) Transient acantholytic dermatosis
b) Familial benign pemphigus (Hailey-Hailey disease)
c) Darier disease
d) Epidermolysis bullosa simplex
e) Bullous pemphigoid
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
a) Idiopathic chronic angioedema
b) Chronic urticaria
c) Urticarial vasculitis
d) Acquired angioedema with C1 esterase inhibitor deficiency
e) Hereditary angioneurotic edema
3. What is the probability this condition will progress
to a systemic disease?
a) Greater than 90%
b 25% to 50%
c) About 10%
d) About 3% to 5%
e) Less than 1%
BOARD REVIEW ANSWERS
1. The diagnosis is:
b) Familial benign pemphigus (Hailey-Hailey disease)
Familial benign pemphigus (Hailey-Hailey disease) is a haploinsufficiency of the enzyme ATP2C1. The ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary 
protein to be made and the cells of the skin do not adhere together properly. The disease may be localized or generalized. It is usually localized to the upper trunk, shoulders, neck, and intertriginous areas. Erythematous, eczematous, and mildly vesicular lesions shown here are typical. Secondary infection is common and may be one explanation for why a variety of antibiotics have been beneficial in selected patients. In contrast to all other forms of pemphigus, perilesional skin from patients with Hailey-Hailey disease is characteristically direct immunofluorescence-negative.
Reference
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:642-645.
Hu Z, Bonifas JM, Beech J, et al. “Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.”. Nat. Genet. 2000; 24(1): 61–5.
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
e) Hereditary angioneurotic edema
Hereditary angioneurotic edema is an autosomal dominant disease caused by a deficiency in functional C1-inhibitor (“C1-esterase inhibitor”), the result of mutations in the C1-inhibitor gene. C1-inhibitor, a member of the serpin family of serine protease inhibitors, inhibits several complement proteases, plasma kallikrein, coagulations factors Xia and XIIa, and plasmin, leading to the generation of vasoconstrictors including bradykinin. An associated laboratory finding is a decreased level of C4.
Its clinical onset may be as early as age 2 or 3 and worsens with puberty. Severe angioedema may recur every 7 to 14 days and may be precipitated by stress or minor trauma. A classic precipitating event is a dental procedure. The abdomen and oropharynx may be involved, leading to significant morbidity, unnecessary surgery, or even death. Long-term prophylaxis includes the use of 17α-alkylated androgens and/or antifibrinolytic agents. Other autoimmune diseases, most notably glomerulonephritis, may be associated with hereditary angioneurotic edema. Of the cases of hereditary angioneurotic edema, 85% have mutations which decrease both antigenic and functional levels of this protein.
In very rare kindreds, both levels are normal; most of these patients have gain-of-function mutations in coagulations factor XII that may result in increased production of bradykinin. Acquired C1-inhibitor deficiency is clinically similar to hereditary angioneurotic edema but differs by the lack of positive family history and usually later (ie, middle age) onset. Unlike the hereditary form, patients with acquired disease have decreased levels of C1q.
References
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. ˆ 2008;100(1 suppl 2):S30-S40.
3. What is the probability this condition will progress to a systemic disease?
e) Less than 1%
Morphea, also known as localized scleroderma, has typical clinical features including hypopigmented, indurated (sclerotic) plaques that vary from a few centimeters to many centimeters in diameter. The lesions may be preceded by erythema or surrounded by a 
violaceous halo in the early “inflammatory” stage. Eventually most lesions resolve, leaving hypopigmented patches. Linear and guttate variants do occur. The disease is usually localized but may become generalized. Progression of morphea (without systemic symptoms or signs) into systemic scleroderma is rare. Patients with morphea may have active serologies and in one series about 40% were antinuclear antibody
References
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:2156-2167.
Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104(6):849-857.
Lamberts RJ, Lynch PJ. Nodular cutaneous mucinosis associated with lupus erythematosus. Cutis. 1981;28(3):294-295, 297-299.
Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.
Krafchik BR. Localized morphea in children. Adv Exp Med Biol. 1999;455:49-54.
Sehgal VN, Srivastava G, Aggarwal AK, Behi PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. Int J Dermatol. 2002;41(8):467-475.
1. The diagnosis is:
a) Transient acantholytic dermatosis
b) Familial benign pemphigus (Hailey-Hailey disease)
c) Darier disease
d) Epidermolysis bullosa simplex
e) Bullous pemphigoid
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
a) Idiopathic chronic angioedema
b) Chronic urticaria
c) Urticarial vasculitis
d) Acquired angioedema with C1 esterase inhibitor deficiency
e) Hereditary angioneurotic edema
3. What is the probability this condition will progress
to a systemic disease?
a) Greater than 90%
b 25% to 50%
c) About 10%
d) About 3% to 5%
e) Less than 1%
,
1. The diagnosis is:
a) Transient acantholytic dermatosis
b) Familial benign pemphigus (Hailey-Hailey disease)
c) Darier disease
d) Epidermolysis bullosa simplex
e) Bullous pemphigoid
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
a) Idiopathic chronic angioedema
b) Chronic urticaria
c) Urticarial vasculitis
d) Acquired angioedema with C1 esterase inhibitor deficiency
e) Hereditary angioneurotic edema
3. What is the probability this condition will progress
to a systemic disease?
a) Greater than 90%
b 25% to 50%
c) About 10%
d) About 3% to 5%
e) Less than 1%
To learn the answer, go to page 2
{{pagebreak}}
BOARD REVIEW ANSWERS
1. The diagnosis is:
b) Familial benign pemphigus (Hailey-Hailey disease)
Familial benign pemphigus (Hailey-Hailey disease) is a haploinsufficiency of the enzyme ATP2C1. The ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary protein to be made and the cells of the skin do not adhere together properly. The disease may be localized or generalized. It is usually localized to the upper trunk, shoulders, neck, and intertriginous areas. Erythematous, eczematous, and mildly vesicular lesions shown here are typical. Secondary infection is common and may be one explanation for why a variety of antibiotics have been beneficial in selected patients. In contrast to all other forms of pemphigus, perilesional skin from patients with Hailey-Hailey disease is characteristically direct immunofluorescence-negative.
Reference
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:642-645.
Hu Z, Bonifas JM, Beech J, et al. “Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.”. Nat. Genet. 2000; 24(1): 61–5.
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
e) Hereditary angioneurotic edema
Hereditary angioneurotic edema is an autosomal dominant disease caused by a deficiency in functional C1-inhibitor (“C1-esterase inhibitor”), the result of mutations in the C1-inhibitor gene. C1-inhibitor, a member of the serpin family of serine protease inhibitors, inhibits several complement proteases, plasma kallikrein, coagulations factors Xia and XIIa, and plasmin, leading to the generation of vasoconstrictors including bradykinin. An associated laboratory finding is a decreased level of C4.
Its clinical onset may be as early as age 2 or 3 and worsens with puberty. Severe angioedema may recur every 7 to 14 days and may be precipitated by stress or minor trauma. A classic precipitating event is a dental procedure. The abdomen and oropharynx may be involved, leading to significant morbidity, unnecessary surgery, or even death. Long-term prophylaxis includes the use of 17α-alkylated androgens and/or antifibrinolytic agents. Other autoimmune diseases, most notably glomerulonephritis, may be associated with hereditary angioneurotic edema. Of the cases of hereditary angioneurotic edema, 85% have mutations which decrease both antigenic and functional levels of this protein.
In very rare kindreds, both levels are normal; most of these patients have gain-of-function mutations in coagulations factor XII that may result in increased production of bradykinin. Acquired C1-inhibitor deficiency is clinically similar to hereditary angioneurotic edema but differs by the lack of positive family history and usually later (ie, middle age) onset. Unlike the hereditary form, patients with acquired disease have decreased levels of C1q.
References
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. ˆ 2008;100(1 suppl 2):S30-S40.
3. What is the probability this condition will progress to a systemic disease?
e) Less than 1%
Morphea, also known as localized scleroderma, has typical clinical features including hypopigmented, indurated (sclerotic) plaques that vary from a few centimeters to many centimeters in diameter. The lesions may be preceded by erythema or surrounded by a violaceous halo in the early “inflammatory” stage. Eventually most lesions resolve, leaving hypopigmented patches. Linear and guttate variants do occur. The disease is usually localized but may become generalized. Progression of morphea (without systemic symptoms or signs) into systemic scleroderma is rare. Patients with morphea may have active serologies and in one series about 40% were antinuclear antibody
References
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:2156-2167.
Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104(6):849-857.
Lamberts RJ, Lynch PJ. Nodular cutaneous mucinosis associated with lupus erythematosus. Cutis. 1981;28(3):294-295, 297-299.
Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.
Krafchik BR. Localized morphea in children. Adv Exp Med Biol. 1999;455:49-54.
Sehgal VN, Srivastava G, Aggarwal AK, Behi PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. Int J Dermatol. 2002;41(8):467-475.
1. The diagnosis is:
a) Transient acantholytic dermatosis
b) Familial benign pemphigus (Hailey-Hailey disease)
c) Darier disease
d) Epidermolysis bullosa simplex
e) Bullous pemphigoid
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
a) Idiopathic chronic angioedema
b) Chronic urticaria
c) Urticarial vasculitis
d) Acquired angioedema with C1 esterase inhibitor deficiency
e) Hereditary angioneurotic edema
3. What is the probability this condition will progress
to a systemic disease?
a) Greater than 90%
b 25% to 50%
c) About 10%
d) About 3% to 5%
e) Less than 1%
BOARD REVIEW ANSWERS
1. The diagnosis is:
b) Familial benign pemphigus (Hailey-Hailey disease)
Familial benign pemphigus (Hailey-Hailey disease) is a haploinsufficiency of the enzyme ATP2C1. The ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary protein to be made and the cells of the skin do not adhere together properly. The disease may be localized or generalized. It is usually localized to the upper trunk, shoulders, neck, and intertriginous areas. Erythematous, eczematous, and mildly vesicular lesions shown here are typical. Secondary infection is common and may be one explanation for why a variety of antibiotics have been beneficial in selected patients. In contrast to all other forms of pemphigus, perilesional skin from patients with Hailey-Hailey disease is characteristically direct immunofluorescence-negative.
Reference
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:642-645.
Hu Z, Bonifas JM, Beech J, et al. “Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.”. Nat. Genet. 2000; 24(1): 61–5.
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
e) Hereditary angioneurotic edema
Hereditary angioneurotic edema is an autosomal dominant disease caused by a deficiency in functional C1-inhibitor (“C1-esterase inhibitor”), the result of mutations in the C1-inhibitor gene. C1-inhibitor, a member of the serpin family of serine protease inhibitors, inhibits several complement proteases, plasma kallikrein, coagulations factors Xia and XIIa, and plasmin, leading to the generation of vasoconstrictors including bradykinin. An associated laboratory finding is a decreased level of C4.
Its clinical onset may be as early as age 2 or 3 and worsens with puberty. Severe angioedema may recur every 7 to 14 days and may be precipitated by stress or minor trauma. A classic precipitating event is a dental procedure. The abdomen and oropharynx may be involved, leading to significant morbidity, unnecessary surgery, or even death. Long-term prophylaxis includes the use of 17α-alkylated androgens and/or antifibrinolytic agents. Other autoimmune diseases, most notably glomerulonephritis, may be associated with hereditary angioneurotic edema. Of the cases of hereditary angioneurotic edema, 85% have mutations which decrease both antigenic and functional levels of this protein.
In very rare kindreds, both levels are normal; most of these patients have gain-of-function mutations in coagulations factor XII that may result in increased production of bradykinin. Acquired C1-inhibitor deficiency is clinically similar to hereditary angioneurotic edema but differs by the lack of positive family history and usually later (ie, middle age) onset. Unlike the hereditary form, patients with acquired disease have decreased levels of C1q.
References
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. ˆ 2008;100(1 suppl 2):S30-S40.
3. What is the probability this condition will progress to a systemic disease?
e) Less than 1%
Morphea, also known as localized scleroderma, has typical clinical features including hypopigmented, indurated (sclerotic) plaques that vary from a few centimeters to many centimeters in diameter. The lesions may be preceded by erythema or surrounded by a violaceous halo in the early “inflammatory” stage. Eventually most lesions resolve, leaving hypopigmented patches. Linear and guttate variants do occur. The disease is usually localized but may become generalized. Progression of morphea (without systemic symptoms or signs) into systemic scleroderma is rare. Patients with morphea may have active serologies and in one series about 40% were antinuclear antibody
References
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:2156-2167.
Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104(6):849-857.
Lamberts RJ, Lynch PJ. Nodular cutaneous mucinosis associated with lupus erythematosus. Cutis. 1981;28(3):294-295, 297-299.
Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.
Krafchik BR. Localized morphea in children. Adv Exp Med Biol. 1999;455:49-54.
Sehgal VN, Srivastava G, Aggarwal AK, Behi PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. Int J Dermatol. 2002;41(8):467-475.
BOARD REVIEW ANSWERS
1. The diagnosis is:
b) Familial benign pemphigus (Hailey-Hailey disease)
Familial benign pemphigus (Hailey-Hailey disease) is a haploinsufficiency of the enzyme ATP2C1. The ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary protein to be made and the cells of the skin do not adhere together properly. The disease may be localized or generalized. It is usually localized to the upper trunk, shoulders, neck, and intertriginous areas. Erythematous, eczematous, and mildly vesicular lesions shown here are typical. Secondary infection is common and may be one explanation for why a variety of antibiotics have been beneficial in selected patients. In contrast to all other forms of pemphigus, perilesional skin from patients with Hailey-Hailey disease is characteristically direct immunofluorescence-negative.
Reference
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:642-645.
Hu Z, Bonifas JM, Beech J, et al. “Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.”. Nat. Genet. 2000; 24(1): 61–5.
2. This patient, her mother, and brother had repeated episodes of nonpruritic lesions like these for many years. An acute episode of dyspnea following a visit to her dentist necessitated hospitalization for a “drug reaction.” The diagnosis is:
e) Hereditary angioneurotic edema
Hereditary angioneurotic edema is an autosomal dominant disease caused by a deficiency in functional C1-inhibitor (“C1-esterase inhibitor”), the result of mutations in the C1-inhibitor gene. C1-inhibitor, a member of the serpin family of serine protease inhibitors, inhibits several complement proteases, plasma kallikrein, coagulations factors Xia and XIIa, and plasmin, leading to the generation of vasoconstrictors including bradykinin. An associated laboratory finding is a decreased level of C4.
Its clinical onset may be as early as age 2 or 3 and worsens with puberty. Severe angioedema may recur every 7 to 14 days and may be precipitated by stress or minor trauma. A classic precipitating event is a dental procedure. The abdomen and oropharynx may be involved, leading to significant morbidity, unnecessary surgery, or even death. Long-term prophylaxis includes the use of 17α-alkylated androgens and/or antifibrinolytic agents. Other autoimmune diseases, most notably glomerulonephritis, may be associated with hereditary angioneurotic edema. Of the cases of hereditary angioneurotic edema, 85% have mutations which decrease both antigenic and functional levels of this protein.
In very rare kindreds, both levels are normal; most of these patients have gain-of-function mutations in coagulations factor XII that may result in increased production of bradykinin. Acquired C1-inhibitor deficiency is clinically similar to hereditary angioneurotic edema but differs by the lack of positive family history and usually later (ie, middle age) onset. Unlike the hereditary form, patients with acquired disease have decreased levels of C1q.
References
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
Bowen T, Cicardi M, Bork K, et al. Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. ˆ 2008;100(1 suppl 2):S30-S40.
3. What is the probability this condition will progress to a systemic disease?
e) Less than 1%
Morphea, also known as localized scleroderma, has typical clinical features including hypopigmented, indurated (sclerotic) plaques that vary from a few centimeters to many centimeters in diameter. The lesions may be preceded by erythema or surrounded by a violaceous halo in the early “inflammatory” stage. Eventually most lesions resolve, leaving hypopigmented patches. Linear and guttate variants do occur. The disease is usually localized but may become generalized. Progression of morphea (without systemic symptoms or signs) into systemic scleroderma is rare. Patients with morphea may have active serologies and in one series about 40% were antinuclear antibody
References
Fitzpatrick TB, ed. Dermatology in General Medicine, 4th ed. New York, NY: McGraw-Hill Book Co; 1993:2156-2167.
Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104(6):849-857.
Lamberts RJ, Lynch PJ. Nodular cutaneous mucinosis associated with lupus erythematosus. Cutis. 1981;28(3):294-295, 297-299.
Tuffanelli DL. Localized scleroderma. Semin Cutan Med Surg. 1998;17(1):27-33.
Krafchik BR. Localized morphea in children. Adv Exp Med Biol. 1999;455:49-54.
Sehgal VN, Srivastava G, Aggarwal AK, Behi PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. Int J Dermatol. 2002;41(8):467-475.
