Autoantibody-mediated acquired deficiency of C1 inhibitor.

During the past 25 years, three forms of deficiency of the inhibitor of the first component of complement (C1 inhibitor) with angioedema have been recognized; two forms are hereditary and one is acquired. As compared with hereditary angioedema, the syndrome of acquired C1-inhibitor deficiency is rare, and it is usually associated with lymphoproliferative diseases. We report another type of acquired C1-inhibitor deficiency with angioedema. Two patients with recurrent angioedema but no associated diseases were found to have IgG1 autoantibodies against C1 inhibitor. The anti-C1-inhibitor antibodies prevented binding of C1 inhibitor to activated C1s. Both patients had 60 to 70 percent of normal levels of C1 inhibitor, but it was functionally inactive, with a molecular weight of 96,000 (normal C1 inhibitor, 105,000). In vitro studies of the patients' serum revealed degradation of 125I-labeled 105,000-dalton C1 inhibitor into the inactive 96,000-dalton molecule, caused by activated C1s and not found in normal human serum. We conclude that these cases of acquired C1-inhibitor deficiency resulted from a blockade of C1-inhibitor function by the anti-C1-inhibitor antibodies and from subsequent inactivation of C1 inhibitor by the now uncontrolled enzyme, activated C1s. As in other forms of C1-inhibitor deficiency, the unopposed activation of the complement system led to angioedema.

During the past 25 years, three forms of

    deficiency of the inhibitor of the first component of complement (C1 inhibitor)
    BIOCHEMICAL

 with

    angioedema
    SYMPTOMS

 have been recognized; two forms are

    hereditary
    GENETICS

 and one is acquired. As compared with

    hereditary angioedema
    DIAGNOSIS

, the syndrome of

    acquired C1-inhibitor deficiency
    BIOCHEMICAL

 is rare, and it is usually associated with

    lymphoproliferative diseases
    DIAGNOSIS

. We report another type of

    acquired C1-inhibitor deficiency
    BIOCHEMICAL

 with

    angioedema
    SYMPTOMS

. Two patients with

    recurrent angioedema
    SYMPTOMS

 but

    no associated diseases
    NEG_FINDINGS

 were found to have

    IgG1 autoantibodies against C1 inhibitor
    BIOCHEMICAL

. The

    anti-C1-inhibitor antibodies prevented binding of C1 inhibitor to activated C1s
    BIOCHEMICAL

. Both patients had

    60 to 70 percent of normal levels of C1 inhibitor, but it was functionally inactive, with a molecular weight of 96,000 (normal C1 inhibitor, 105,000)
    BIOCHEMICAL

.

    In vitro studies of
    PARACLINICAL

 the patients' serum revealed

    degradation of 125I-labeled 105,000-dalton C1 inhibitor into the inactive 96,000-dalton molecule, caused by activated C1s
    BIOCHEMICAL

 and

    not found in normal human serum
    BIOCHEMICAL

. We conclude that these cases of

    acquired C1-inhibitor deficiency
    BIOCHEMICAL

 resulted from a

    blockade of C1-inhibitor function by the anti-C1-inhibitor antibodies
    BIOCHEMICAL

 and from subsequent

    inactivation of C1 inhibitor by the now uncontrolled enzyme, activated C1s
    BIOCHEMICAL

. As in other forms of

    C1-inhibitor deficiency
    BIOCHEMICAL

, the

    unopposed activation of the complement system
    NEG_FINDINGS

 led to

    angioedema
    SYMPTOMS

.

angioedema
angioedema
recurrent angioedema
angioedema

hereditary angioedema
lymphoproliferative diseases


[Hereditary angioneurotic edema. Treatment of a pseudosurgical digestive attack with C1 inhibitor concentrate].

Although anabolic androgens can be used to prevent acute attacks of hereditary angioneurotic oedema, these are still observed. When they are severe, and even more so when they involve the larynx or the abdominal viscera, an emergency treatment is necessary, ideally with the purified C1-inhibitor (C1-INH) administered by intravenous infusion. In a case with pseudo-surgical abdominal symptoms, this treatment was followed by an unusually dramatic regression of all symptoms. Serial laboratory examinations showed an increase in C1-INH and C2 plasma levels and in the number of basophils within less than 30 minutes; the increase in C4 levels occurred later. Thus, C1-INH is very effective in the treatment of acute hereditary angioneurotic oedema, but the product is not widely available; it should be reserved to severe forms affecting the larynx and the viscera.

Although

    anabolic androgens
    MEDICATION

 can be used to prevent

    acute attacks of hereditary angioneurotic oedema
    SYMPTOMS

, these are still observed. When they are severe, and even more so when they

    involve the larynx or the abdominal viscera
    SYMPTOMS

, an

    emergency treatment
    MEDICATION

 is necessary, ideally with the

    purified C1-inhibitor (C1-INH) administered by intravenous infusion
    MEDICATION

. In a case with

    pseudo-surgical abdominal symptoms
    SYMPTOMS

, this treatment was followed by an

    unusually dramatic regression of all symptoms
    SYMPTOMS

.

    Serial laboratory examinations
    PARACLINICAL

 showed an

    increase in C1-INH and C2 plasma levels and in the number of basophils within less than 30 minutes
    BIOCHEMICAL

; the

    increase in C4 levels
    BIOCHEMICAL

 occurred later. Thus,

    C1-INH
    MEDICATION

 is very effective in the treatment of

    acute hereditary angioneurotic oedema
    DIAGNOSIS

, but the product is not widely available; it should be reserved to

    severe forms affecting the larynx and the viscera
    SYMPTOMS

.


[A case report of hereditary angioedema and studies on the serum components of complement, C1-inactivator and proteinase inhibitors during edema attack].

Sixteen years old girl was admitted because of for the past ten years' frequent edema attack and abdominal pain. Laboratory examination revealed hypocomplementemia, marked depletion of the fourth component of complement and low level of C1-inactivator. Familial studies revealed that her mother was also hypocomplementemic and in low level of C1-inactivator. Serial studies performed on the alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin during edema attack. The fourth component of complement and C1-inactivator were markedly depleted in remission and attack. Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator during attack. In contrast, alpha 1-antitrypsin and alpha 2-macroglobulin did not change. The present study may explain that Hageman factor fragments, activated by C1s, promotes kinin generation via kalikrein activation. And the condition that complete functional deficiency of C1-inactivator was main role in this circuit. Fibrynolysis and late components of complement was less influence on edema attack.

    Sixteen years old
    AGE

    girl
    GENDER

 was admitted because of for the past ten years' frequent

    edema attack
    SYMPTOMS

 and

    abdominal pain
    SYMPTOMS

.

    Laboratory examination
    PARACLINICAL

 revealed

    hypocomplementemia
    BIOCHEMICAL

,

    marked depletion of the fourth component of complement
    BIOCHEMICAL

 and

    low level of C1-inactivator
    BIOCHEMICAL

.

    Familial studies
    PARACLINICAL

 revealed that

    her
    GENDER

    mother was also hypocomplementemic
    FAMILY

    and in low level of C1-inactivator
    FAMILY

.

    Serial studies
    PARACLINICAL

 performed on the

    alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin
    BIOCHEMICAL

 during

    edema attack
    SYMPTOMS

.

    The fourth component of complement and C1-inactivator were markedly depleted in remission
    BIOCHEMICAL

 and attack.

    Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator
    BIOCHEMICAL

 during attack. In contrast,

    alpha 1-antitrypsin and alpha 2-macroglobulin did not change
    NEG_FINDINGS

. The present study may explain that

    Hageman factor fragments, activated by C1s
    BIOCHEMICAL

,

    promotes kinin generation via kalikrein activation
    BIOCHEMICAL

. And the condition that

    complete functional deficiency of C1-inactivator
    BIOCHEMICAL

 was main role in this circuit.

    Fibrynolysis and late components of complement
    BIOCHEMICAL

 was less influence on

    edema attack
    SYMPTOMS

.

edema attack
abdominal pain
edema attack
edema attack


Hereditary angioneurotic oedema: a neglected diagnosis.

A case of hereditary angioneurotic oedema, which was only diagnosed after presentation to several hospital departments, is reported. It was then discovered that the mother of the patient had the same condition but that, unusually, it appeared to have been in remission for more than 20 years. This disease, due to C1 esterase inhibitor deficiency, is potentially fatal but easily treatable. The diagnosis is often missed.

A case of

    hereditary angioneurotic oedema
    DIAGNOSIS

, which was only diagnosed after presentation to several hospital departments, is reported. It was then discovered that

    the mother of the patient had the same condition
    FAMILY

 but that, unusually, it appeared to have been

    in remission for more than 20 years
    MEDICATION

. This disease, due to

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

, is potentially fatal but easily treatable. The diagnosis is often missed.


A family with hereditary angioedema and multiple immunologic disorders.

A 58-year-old man with end-stage renal disease treated with long-term ambulatory peritoneal dialysis gave a history of hereditary angioedema. Results of testing of his serum for antinuclear antibody were strongly positive, and a titer of 1:2,560 for antiribosomal antibody was documented. Three of his six children reported multiple medical problems, including episodic swelling, discoid lupus, and arthritis. An indepth study of this kindred showed a number of associated immunologic disturbances. Three children had decreased C1 esterase inhibitor and decreased C4 levels. T cell enumeration revealed low proportions of suppressor cells in these three children as well as in another unaffected child. Serum IgM level was low in the propositus, and IgG level was also decreased in one of the affected children. HLA typing failed to show a clear association of class I or class II antigens with hereditary angioedema. Family members tested did not demonstrate anti-SS-A, anti-SS-B, antinuclear antibody, anti-double-stranded DNA, anti-Sm, or anti-ribonuclear protein antibodies.

A

    58-year-old
    AGE

    man
    GENDER

 with

    end-stage renal disease
    DIAGNOSIS

    treated with long-term ambulatory peritoneal dialysis
    MEDICATION

 gave a history of

    hereditary angioedema
    DIAGNOSIS

. Results of

    testing of his serum for antinuclear antibody
    PARACLINICAL

 were

    strongly positive
    BIOCHEMICAL

, and a

    titer of 1:2,560 for antiribosomal antibody
    BIOCHEMICAL

 was documented. Three of his six children reported

    multiple medical problems
    SYMPTOMS

, including

    episodic swelling
    SYMPTOMS

,

    discoid lupus
    DIAGNOSIS

, and

    arthritis
    DIAGNOSIS

. An indepth study of this kindred showed a number of associated

    immunologic disturbances
    SYMPTOMS

. Three children had

    decreased C1 esterase inhibitor
    BIOCHEMICAL

 and

    decreased C4 levels
    BIOCHEMICAL

.

    T cell enumeration
    BIOCHEMICAL

 revealed

    low proportions of suppressor cells
    BIOCHEMICAL

 in these three children as well as in another unaffected child.

    Serum IgM level was low in the propositus
    BIOCHEMICAL

, and

    IgG level was also decreased in one of the affected children
    BIOCHEMICAL

.

    HLA typing failed to show a clear association of class I or class II antigens with hereditary angioedema
    NEG_FINDINGS

.

    Family members tested did not demonstrate anti-SS-A, anti-SS-B, antinuclear antibody, anti-double-stranded DNA, anti-Sm, or anti-ribonuclear protein antibodies
    NEG_FINDINGS

.

end-stage renal disease
hereditary angioedema
discoid lupus
arthritis

multiple medical problems
episodic swelling
immunologic disturbances


[Contraception and pregnancy in hereditary angioedema].

The frequent first clinical manifestation of hereditary angioedema (HAE) in pubertal patients and the more frequent attacks of edema during menstruation indicate that the condition is affected by hormones. Medication with oral contraceptives containing estrogens can lead to severe attacks of edema. On the other hand, HAE mostly shows a favorable development in pregnancy. Despite the substantial trauma of delivery, complications are rare. In view of the literature report of a death and our own observation of potentially dangerous edema in the postpartal phase in one patient, it appears to us to be advisable to administer 500 units C1 inactivator prophylactically before the expulsive phase of birth in HAE patients. Oral contraceptives should not be administered.

The frequent first clinical manifestation of

    hereditary angioedema (HAE)
    DIAGNOSIS

 in

    pubertal
    AGE

 patients and the more frequent

    attacks of edema during menstruation
    SYMPTOMS

 indicate that the condition is affected by

    hormones
    SYMPTOMS

.

    Medication with oral contraceptives containing estrogens
    MEDICATION

 can lead to

    severe attacks of edema
    SYMPTOMS

. On the other hand,

    HAE
    DIAGNOSIS

 mostly shows a favorable development in

    pregnancy
    AGE

. Despite the substantial trauma of delivery, complications are rare. In view of the literature report of a

    death
    SYMPTOMS

 and our own observation of

    potentially dangerous edema in the postpartal phase
    SYMPTOMS

 in one patient, it appears to us to be advisable to

    administer 500 units C1 inactivator prophylactically before the expulsive phase of birth
    MEDICATION

 in

    HAE
    DIAGNOSIS

 patients.

    Oral contraceptives
    MEDICATION

 should not be administered.


[Formation of IgG antibodies to C1 inhibitor as the cause of life-threatening angioedema].

A clinical picture with recurrent (in some cases potentially fatal) edema of skin and internal organs based not on a hereditary C1 inhibitor deficiency, but an acquired loss of C1 inhibitor activity due to antibodies is described for the first time in two patients. The clinical symptoms commenced in middle age patients between 40 and 46 years old. Anti C1 antibodies of the IgG were found in both patients. Quantitatively, these C1 inhibitor protein was in the lower range of normal, whereas no inhibitor activity could be demonstrated functionally. The function of the complement components C1, C2 and C4 was greatly reduced. The therapeutic use of C1 inhibitor concentrate at a high doses (6 X 500 U) as well as administration of high-dose corticosteroids in several emergency situations was unsuccessful.

A clinical picture with

    recurrent (
    SYMPTOMS

in some cases

    potentially fatal) edema of skin and internal organs
    SYMPTOMS

 based not on a

    hereditary C1 inhibitor deficiency
    NEG_FINDINGS

, but an

    acquired loss of C1 inhibitor activity due to antibodies
    BIOCHEMICAL

 is described for the first time in two patients. The clinical symptoms commenced in

    middle age
    AGE

 patients

    between 40 and 46 years old
    AGE

.

    Anti C1 antibodies of the IgG
    BIOCHEMICAL

 were found in both patients. Quantitatively,

    these C1 inhibitor protein was in the lower range of normal
    BIOCHEMICAL

, whereas

    no inhibitor activity could be demonstrated functionally
    NEG_FINDINGS

.

    The function of the complement components C1, C2 and C4 was greatly reduced
    BIOCHEMICAL

. The

    therapeutic use of C1 inhibitor concentrate at a high doses (6 X 500 U)
    MEDICATION

 as well as

    administration of high-dose corticosteroids
    NEG_FINDINGS

 in several emergency situations

    was unsuccessful
    NEG_FINDINGS

.


Anaesthetic implications of hereditary angioneurotic oedema.

Hereditary angioneurotic oedema (HANE) presents the danger of laryngeal oedema that may, among other causes, be triggered by the anaesthetist's manipulation of the patient's airway. Local and regional anaesthesia are usually recommended. This report pertains to a patient who successfully tolerated general endotracheal anaesthesia and whose management included prophylactic treatment with danazol and fresh-frozen plasma.

    Hereditary angioneurotic oedema (HANE)
    DIAGNOSIS

 presents the danger of

    laryngeal oedema
    SYMPTOMS

 that may, among other causes, be triggered by the

    anaesthetist
    PARACLINICAL

's

    manipulation of the patient's airway
    MEDICATION

.

    Local and regional anaesthesia
    MEDICATION

 are usually recommended. This report pertains to a patient who successfully tolerated

    general endotracheal anaesthesia
    MEDICATION

 and whose management included

    prophylactic treatment with danazol and fresh-frozen plasma
    MEDICATION

.


Hereditary angioedema: preliminary report on skin biopsy finding of fibrin and/or C4 through immunofluorescence.

Hereditary angioedema is considered an inherited disorder of the complement system, manifested by repeated crises of angioedema involving the skin, the gastrointestinal and respiratory tracts. Biopsies of normal skin obtained from 5 patients, diagnosed with hereditary angioedema, were found to be positive for fibrin and in one case also positive for C4. The sections stained with anti-fibrin serum showed fibrin deposits around isolated epidermal cells, while C4 staining revealed a homogeneous pattern along the epidermis. Fluorescence patterns and laboratory findings before and after treatment with danazol and/or anti-fibrinolytic treatment are reported.

    Hereditary angioedema
    DIAGNOSIS

 is considered an

    inherited disorder of the complement system
    GENETICS

, manifested by

    repeated crises of angioedema involving the skin, the gastrointestinal and respiratory tracts
    SYMPTOMS

.

    Biopsies of normal skin
    PARACLINICAL

 obtained from 5 patients, diagnosed with

    hereditary angioedema
    DIAGNOSIS

, were found to be

    positive for fibrin
    MICROSCOPIC

 and in one case also

    positive for C4
    BIOCHEMICAL

. The

    sections stained with anti-fibrin serum
    PARACLINICAL

 showed

    fibrin deposits around isolated epidermal cells
    MICROSCOPIC

, while

    C4 staining revealed a homogeneous pattern along the epidermis
    MICROSCOPIC

. Fluorescence patterns and laboratory findings before and after treatment with

    danazol and/or anti-fibrinolytic treatment
    MEDICATION

 are reported.

Hereditary angioedema
hereditary angioedema


Recurrent angioedema: familial and oestrogen-induced.

We report two sisters who both have had severe attacks of urticaria and angioedema only when taking the contraceptive pill and during the latter half of pregnancy. Although they exhibited many features in common with hereditary angioedema (HAO), the C1 esterase inhibitor levels and other complement components were consistently normal, including levels measured during pregnancy and at the height of the eruption after oestrogen challenge. Aetiological factors in relation to other patterns and causes of urticaria are discussed.

We report two

    sisters who both have
    FAMILY

 had

    severe attacks of urticaria and angioedema
    SYMPTOMS

 only when

    taking the contraceptive pill
    MEDICATION

 and during the

    latter half of pregnancy
    MEDICATION

. Although they exhibited

    many features in common with hereditary angioedema (HAO)
    SYMPTOMS

,

    the C1 esterase inhibitor levels and other complement components were consistently normal
    NEG_FINDINGS

, including

    levels measured during pregnancy
    BIOCHEMICAL

 and at the height of the eruption after

    oestrogen challenge
    MEDICATION

. Aetiological factors in relation to other patterns and causes of

    urticaria
    DIAGNOSIS

 are discussed.

taking the contraceptive pill
latter half of pregnancy
oestrogen challenge


A case of hereditary angioneurotic edema associated with systemic lupus erythematosus.

A pedigree of C1 inhibitor (C1 INH) deficiency associated with positive LE cell and an elevated titer of DNA antibodies and antinuclear factor (ANF) and nephropathy was presented. The proband of this family was diagnosed as having definite systemic lupus erythematosus (SLE) after a clinical course of several year since her first visit to our hospital and because of the lack of hemolytic activity of complement (CH50), in spite of the absence of idiopathic edema, C1 INH levels were 1.2 mg/dl (3.8% NHS) determined as antigen and 65 site forming unit (SFU) (5.8% NHS) determined by hemolytic assay in her blood. Her mother and brother had characteristic idiopathic edema of her face, larynx, hand and bowel and they had low levels of C1 INH of 1.8 mg/dl (5.8% NHS) and 4.8 mg/dl (15.5% NHS) respectively in their blood. On the basis of these findings, this family was diagnosed as having a pedigree of hereditary angioneurotic edema (HANE) which is supposedly an inherited autosomal positive trait. Actually, however, the proband's serological and hematological indices became positive and progressed year by year, which implies that SLE was absent for the first several years. It might be said that this interesting clinical course indicates that SLE appeared chronologically as a hereditary deficiency in one of the complement components in this case. In concurrence with the general observation that recurrent viral infections due to the deficiency of complement components are presumed to be responsible for SLE-like disease. Her levels of several kinds of anti-virus antibodies were high. Methylprednisolone helped normalize her level of C1 INH and ameliorate the clinical course.

A pedigree of

    C1 inhibitor (C1 INH) deficiency
    BIOCHEMICAL

 associated with

    positive LE cell
    BIOCHEMICAL

 and an

    elevated titer of DNA antibodies and antinuclear factor (ANF)
    BIOCHEMICAL

 and

    nephropathy
    DIAGNOSIS

 was presented. The proband of this family was diagnosed as having definite

    systemic lupus erythematosus (SLE)
    DIAGNOSIS

 after a clinical course of several year since her first visit to our hospital and because of the

    lack of hemolytic activity of complement (CH50)
    NEG_FINDINGS

, in spite of the

    absence of idiopathic edema
    NEG_FINDINGS

,

    C1 INH levels were 1.2 mg/dl (3.8% NHS) determined as antigen and 65 site forming unit (SFU) (5.8% NHS) determined by hemolytic assay in her blood
    BIOCHEMICAL

.

    Her
    GENDER

    mother and brother had characteristic idiopathic edema of her face, larynx, hand and bowel
    FAMILY

 and they had

    low levels of C1 INH of 1.8 mg/dl (5.8% NHS) and 4.8 mg/dl (15.5% NHS) respectively in their blood
    BIOCHEMICAL

. On the basis of these findings, this

    family was diagnosed as having a pedigree of hereditary angioneurotic edema (HANE)
    FAMILY

 which

    is supposedly an inherited autosomal positive trait
    GENETICS

. Actually, however, the proband's

    serological and hematological indices became positive
    BIOCHEMICAL

 and progressed year by year, which implies that

    SLE was absent for the first several years
    NEG_FINDINGS

. It might be said that this interesting clinical course indicates that

    SLE
    DIAGNOSIS

 appeared chronologically as a

    hereditary
    GENETICS

    deficiency in one of the complement components
    BIOCHEMICAL

 in this case. In concurrence with the general observation that

    recurrent viral infections
    SYMPTOMS

 due to the

    deficiency of complement components
    BIOCHEMICAL

 are presumed to be responsible for

    SLE-like disease
    DIAGNOSIS

.

    Her
    GENDER

    levels of several kinds of anti-virus antibodies were high
    BIOCHEMICAL

.

    Methylprednisolone
    MEDICATION

 helped

    normalize her level of C1 INH
    BIOCHEMICAL

 and

    ameliorate the clinical course
    SYMPTOMS

.

nephropathy
systemic lupus erythematosus (SLE)
SLE
SLE-like disease

recurrent viral infections
ameliorate the clinical course


Rapidly developing, edematous swelling of the upper lip.

Clinicians should distinguish between hereditary and non-hereditary angioedema, as management of patients varies significantly with each. As many patients with hereditary angioedema have had serious episodes of edema associated with dental procedures, it is important that dentists understand the nature of this disease and its treatment. The potential for airway obstruction by laryngeal edema requires a knowledge and preparedness for initiation of life-support measures.

Clinicians should distinguish between

    hereditary
    DIAGNOSIS

 and

    non-hereditary angioedema
    DIAGNOSIS

, as management of patients varies significantly with each. As many patients with

    hereditary angioedema
    DIAGNOSIS

 have had

    serious episodes of edema
    SYMPTOMS

 associated with

    dental procedures
    MEDICATION

, it is important that dentists understand the nature of this disease and its treatment. The potential for

    airway obstruction
    SYMPTOMS

 by

    laryngeal edema
    SYMPTOMS

 requires a knowledge and preparedness for initiation of

    life-support measures
    MEDICATION

.

hereditary
non-hereditary angioedema
hereditary angioedema

serious episodes of edema
airway obstruction
laryngeal edema


[Preoperative preparation and postoperative monitoring of a patient with hereditary angioneurotic edema].

Hereditary angioneurotic oedema is an autosomal dominant disorder associated with serum deficiency of functionally active C1 inhibitor protein. This decrease is characterized by episodic swelling of subcutaneous tissues, of abdominal viscera and of the upper airway. Attacks of angioneurotic oedema, sometimes fatal when involving the upper airway, can occur during any surgery. It is therefore necessary to prepare affected patients before surgery. This review article describes the various preventive treatments used to avoid attacks during surgery: antifibrinolytic agents, androgens, fresh frozen plasma, C1 esterase inhibitor concentrate. Preoperative management of one patient with angioneurotic oedema using danazol and C1 esterase inhibitor concentrate is reported.

    Hereditary angioneurotic oedema
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

 associated with

    serum deficiency of functionally active C1 inhibitor protein
    BIOCHEMICAL

. This decrease is characterized by

    episodic swelling of subcutaneous tissues, of abdominal viscera and of the upper airway
    SYMPTOMS

.

    Attacks of angioneurotic oedema
    SYMPTOMS

, sometimes

    fatal when involving the upper airway
    SYMPTOMS

, can occur during any

    surgery
    MEDICATION

. It is therefore necessary to prepare affected patients before

    surgery
    MEDICATION

. This review article describes the various

    preventive treatments
    MEDICATION

 used to avoid attacks during

    surgery
    MEDICATION

:

    antifibrinolytic agents
    MEDICATION

,

    androgens
    MEDICATION

,

    fresh frozen plasma
    MEDICATION

,

    C1 esterase inhibitor concentrate
    MEDICATION

.

    Preoperative management
    MEDICATION

 of one patient with

    angioneurotic oedema
    SYMPTOMS

 using

    danazol and C1 esterase inhibitor concentrate
    MEDICATION

 is reported.


Hereditary angioedema: polymorphism.

Four patients with hereditary angioedema were studied. All had low values of C4, C1 INH, (CH 50) complement activity and circulating immune complexes. This report takes into account the different aspects that this disease can present, often quite different from the classical description of hereditary angioedema.

Four patients with

    hereditary angioedema
    DIAGNOSIS

 were studied. All had

    low values of C4, C1 INH, (CH 50) complement activity
    BIOCHEMICAL

 and

    circulating immune complexes
    BIOCHEMICAL

. This report takes into account the different aspects that this disease can present, often quite different from the classical description of

    hereditary angioedema
    DIAGNOSIS

.

hereditary angioedema
hereditary angioedema


Dental management of patients with hereditary angioedema: report of case.

Dental management and treatment of a patient with hereditary angioedema can be accomplished safely and satisfactorily in an outpatient setting by a dentist in collaboration with a physician. However, as acute attacks can occur as a complication of treatment, we recommend that dental treatment be provided in a hospital environment with adequate medical emergency resources.

    Dental management and treatment
    MEDICATION

 of a patient with

    hereditary angioedema
    DIAGNOSIS

 can be accomplished safely and satisfactorily in an outpatient setting by a

    dentist
    MEDICATION

 in collaboration with a physician. However, as

    acute attacks
    SYMPTOMS

 can occur as a complication of treatment, we recommend that

    dental treatment
    MEDICATION

 be provided in a hospital environment with adequate medical emergency resources.

Dental management and treatment
dentist
dental treatment


Dialysis leukopenia and hypoxemia in a patient without measurable complement activity.

We have studied complement activity, total leukocyte counts, PO2 and acid-base balance during a single hemodialysis with cuprophan membranes in a patient with hereditary angioedema and C3NeF-positive chronic membranoproliferative glomerulonephritis. Before, during and after the dialytic procedure plasma complement activity (total hemolytic complement, classical and alternative pathway activities) was not detectable and no C3-conversion occurred, while profound leukopenia (from 8,500 to 1,800 leukocytes/microliter) and hypoxemia (from 101.8 to 86 mmHg PO2) were found within 20 min from the initiation of hemodialysis. Similar results were obtained by studying the same parameters during two additional hemodialytic procedures. In vitro experiments showed that the patient's C3 could not be converted, either by cuprophan or zymosan, a specific and potent complement activator, even under optimal experimental conditions. Our data demonstrate that complement activation is not the only possible mechanism responsible for early leukopenia (as well as hypoxemia) during dialysis with cuprophan membranes.

We have studied

    complement activity
    BIOCHEMICAL

,

    total leukocyte counts
    BIOCHEMICAL

,

    PO2
    BIOCHEMICAL

 and

    acid-base balance
    BIOCHEMICAL

 during a

    single hemodialysis with cuprophan membranes
    MEDICATION

 in a patient with

    hereditary angioedema
    DIAGNOSIS

 and

    C3NeF-positive chronic membranoproliferative glomerulonephritis
    BIOCHEMICAL

. Before, during and after the

    dialytic procedure
    MEDICATION

    plasma complement activity (total hemolytic complement, classical and alternative pathway activities) was not detectable
    BIOCHEMICAL

 and

    no C3-conversion occurred
    BIOCHEMICAL

, while

    profound leukopenia (from 8,500 to 1,800 leukocytes/microliter)
    BIOCHEMICAL

 and

    hypoxemia (from 101.8 to 86 mmHg PO2)
    BIOCHEMICAL

 were found within 20 min from the initiation of

    hemodialysis
    MEDICATION

. Similar results were obtained by studying the same parameters during two additional

    hemodialytic procedures
    MEDICATION

.

    In vitro experiments
    PARACLINICAL

 showed that

    the patient's C3 could not be converted, either by cuprophan or zymosan, a specific and potent complement activator
    BIOCHEMICAL

, even under optimal experimental conditions. Our data demonstrate that

    complement activation
    BIOCHEMICAL

 is not the only possible mechanism responsible for

    early leukopenia
    BIOCHEMICAL

 (as well as

    hypoxemia
    BIOCHEMICAL

) during

    dialysis with cuprophan membranes
    MEDICATION

.


Guillain-Barré syndrome following danazol and corticosteroid therapy for hereditary angioedema.

A case of hereditary angioedema secondary to C1 esterase inhibitor deficiency associated with lupus-like nephritis is reported. The patient was initially treated with both corticosteroids and danazol and subsequently had Guillain-Barré syndrome together with appearance of circulating immune complexes and an increase in total complement and C1q, C3, C4, B, and C1 esterase inhibitor levels. Guillain-Barré syndrome might be secondary to danazol therapy since this drug could increase both circulating immune complex production and complement synthesis, thereby providing additional substrate for the underlying immune complex disease. Normalization of complement might therefore be hazardous in lupus with underlying complement deficiency states.

A case of

    hereditary angioedema
    DIAGNOSIS

 secondary to

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

 associated with

    lupus-like nephritis
    DIAGNOSIS

 is reported. The patient was

    initially treated with both corticosteroids and danazol
    MEDICATION

 and subsequently had

    Guillain-Barré syndrome
    DIAGNOSIS

 together with

    appearance of circulating immune complexes
    MICROSCOPIC

 and an

    increase in total complement and C1q, C3, C4, B, and C1 esterase inhibitor levels
    BIOCHEMICAL

.

    Guillain-Barré syndrome
    DIAGNOSIS

 might be secondary to

    danazol therapy
    MEDICATION

 since this drug could

    increase both circulating immune complex production and complement synthesis
    BIOCHEMICAL

, thereby providing additional substrate for the underlying

    immune complex disease
    MICROSCOPIC

.

    Normalization of complement
    BIOCHEMICAL

 might therefore be hazardous in

    lupus
    DIAGNOSIS

 with underlying

    complement deficiency states
    BIOCHEMICAL

.

hereditary angioedema
lupus-like nephritis
Guillain-Barré syndrome
Guillain-Barré syndrome
lupus


[Respiratory manifestations in hereditary angioneurotic edema].

Hereditary angioneurotic oedema is an autosomal dominant state associated with a quantitative, and sometimes purely functional, deficiency of C1 esterase inhibitor (C1 INH). The clinical manifestations may begin during adulthood or childhood; they are periodical and of varying severity. Beside oedema of the skin and digestive disorders, respiratory disorders are bound to attract attention. They consist of laryngeal oedema, which may end in lethal asphyxia if tracheotomy is not performed, or, exceptionally, of pulmonary oedema requiring assisted ventilation, as in the case reported here. The diagnosis, suspected in the presence of a decrease in CH50 and C4, is confirmed by a quantitative assay of C1 INH, which is low, and/or by the Fong and Good's functional tests. The physiopathological mechanisms are complex. They involve complement activation through the classical route, and activation of the coagulation system contact phase. Patients with severe attacks now benefit from treatment with preparations of C1 INH in high concentrations. The best treatment, however, is prophylactic, using testosterone derivatives, danazol and stanozolol, which can be prescribed for long periods taking into account their usually moderate side-effects.

    Hereditary angioneurotic oedema
    DIAGNOSIS

 is an

    autosomal dominant state
    GENETICS

 associated with a

    quantitative,
    BIOCHEMICAL

 and sometimes

    purely functional, deficiency of C1 esterase inhibitor (C1 INH)
    BIOCHEMICAL

. The clinical manifestations may begin during

    adulthood
    AGE

 or

    childhood
    AGE

; they are periodical and of varying severity. Beside

    oedema of the skin
    SYMPTOMS

 and

    digestive disorders
    SYMPTOMS

,

    respiratory disorders
    DIAGNOSIS

 are bound to attract attention. They consist of

    laryngeal oedema
    SYMPTOMS

, which may end in

    lethal asphyxia
    SYMPTOMS

 if

    tracheotomy
    MEDICATION

 is not performed, or, exceptionally, of

    pulmonary oedema
    SYMPTOMS

 requiring

    assisted ventilation
    MEDICATION

, as in the case reported here. The diagnosis, suspected in the presence of a

    decrease in CH50 and C4
    BIOCHEMICAL

, is confirmed by a

    quantitative assay of C1 INH, which is low
    BIOCHEMICAL

, and/or by the

    Fong and Good's functional tests
    PARACLINICAL

. The physiopathological mechanisms are complex. They involve

    complement activation through the classical route
    BIOCHEMICAL

, and

    activation of the coagulation system contact phase
    BIOCHEMICAL

. Patients with

    severe attacks
    SYMPTOMS

 now benefit from

    treatment with preparations of C1 INH in high concentrations
    MEDICATION

. The best treatment, however, is

    prophylactic, using testosterone derivatives, danazol and stanozolol
    MEDICATION

, which can be prescribed

    for long periods
    MEDICATION

 taking into account their usually

    moderate side-effects
    SYMPTOMS

.

Hereditary angioneurotic oedema
respiratory disorders

oedema of the skin
digestive disorders
laryngeal oedema
lethal asphyxia
pulmonary oedema
severe attacks
moderate side-effects


Acute airway obstruction following tooth extraction in hereditary angioedema.

Life threatening airway obstruction occurred following a single tooth extraction in a patient who had hereditary angioedema, despite preoperative administration of FFP and danazol. Emergency intubation was performed in the operating room, and assisted respiration was required during the acute attack. The clinician should be aware that an acute attack of HAE may occur even though recommended medical management regimens are followed and should be prepared for emergency airway control.

    Life threatening airway obstruction
    SYMPTOMS

 occurred following a

    single tooth extraction
    MEDICATION

 in a patient who had

    hereditary angioedema
    DIAGNOSIS

,

    despite preoperative administration of FFP and danazol
    NEG_FINDINGS

.

    Emergency intubation
    MEDICATION

 was performed in the

    operating room
    MEDICATION

, and

    assisted respiration
    MEDICATION

 was required during the

    acute attack
    SYMPTOMS

. The clinician should be aware that an

    acute attack of HAE
    SYMPTOMS

 may occur even though recommended medical management regimens are followed and should be prepared for

    emergency airway control
    MEDICATION

.

Life threatening airway obstruction
acute attack
acute attack of HAE

single tooth extraction
Emergency intubation
operating room
assisted respiration
emergency airway control


Allergic urticaria and hereditary angioedema. Independent association in the same patient.

A patient presented with both allergic urticaria and hereditary angioedema. The two conditions occurred independently, the urticaria being associated with allergy to food (which could be managed by control of the diet), whereas the angioedema was associated with C1 esterase inhibitor deficiency.

A patient presented with both

    allergic urticaria
    DIAGNOSIS

 and

    hereditary angioedema
    DIAGNOSIS

. The two conditions occurred independently, the

    urticaria
    DIAGNOSIS

 being associated with

    allergy to food
    SYMPTOMS

 (which could be managed by

    control of the diet)
    MEDICATION

, whereas the

    angioedema
    DIAGNOSIS

 was associated with

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

.

allergic urticaria
hereditary angioedema
urticaria
angioedema


Hereditary angioedema and pregnancy.

Hereditary angioedema is a relatively uncommon disease that may affect women during their reproductive years. A case report of a pregnancy complicated by hereditary angioedema, followed by a review of the literature, is presented. Although the disease usually follows a benign course, maternal mortality has been noted. Features unique to pregnancy are discussed. Knowledge of the pathophysiology and possible complications is essential for the proper management of the pregnancy.

    Hereditary angioedema
    DIAGNOSIS

 is a relatively uncommon disease that may affect

    women
    GENDER

    during their reproductive years
    AGE

. A case report of a

    pregnancy
    DIAGNOSIS

 complicated by

    hereditary angioedema
    DIAGNOSIS

, followed by a review of the literature, is presented. Although the disease usually follows a benign course,

    maternal mortality
    SYMPTOMS

 has been noted. Features unique to

    pregnancy
    DIAGNOSIS

 are discussed. Knowledge of the pathophysiology and possible complications is essential for the proper management of the

    pregnancy
    DIAGNOSIS

.

Hereditary angioedema
pregnancy
hereditary angioedema
pregnancy
pregnancy


[Anesthesia in a patient with hereditary angioedema].

One of the most serious manifestations of hereditary angioneurotic edema is the occurrence of an acute airway obstruction due to laryngeal edema. The anesthetic technique of choice is a conduction rather than an intubation anesthesia. In the treatment of an acute attack steroids and antihistamines are commonly ineffective. Specific prophylactic and therapeutic measures involving the infusion of fresh-frozen plasma and treatment with Danazol are described.

One of the most serious manifestations of

    hereditary angioneurotic edema
    DIAGNOSIS

 is the occurrence of an

    acute airway obstruction due to laryngeal edema
    SYMPTOMS

. The anesthetic technique of choice is a

    conduction rather than an intubation anesthesia
    MEDICATION

. In the treatment of an acute attack

    steroids and antihistamines are commonly ineffective
    NEG_FINDINGS

. Specific

    prophylactic and therapeutic measures involving the infusion of fresh-frozen plasma and treatment with Danazol
    MEDICATION

 are described.


Hereditary angioedema and coronary arteritis.

A 30-year-old white male with hereditary angioedema developed substernal chest pain with multiple arterial stenoses at coronary angiography. Histopathologic studies of the fibromembranous thickening removed from the left coronary artery at the time of the revascularization procedure revealed an inflammatory lesion compatible with an arteritis. The significance of this association in the spectrum of immunologically-mediated disorders in hereditary angioedema is discussed.

A

    30-year-old
    AGE

    white
    ETHNICITY

    male
    GENDER

 with

    hereditary angioedema
    DIAGNOSIS

 developed

    substernal chest pain
    SYMPTOMS

 with

    multiple arterial stenoses
    SYMPTOMS

 at

    coronary angiography
    PARACLINICAL

.

    Histopathologic studies of the fibromembranous thickening removed from the left coronary artery
    PARACLINICAL

 at the time of the

    revascularization procedure
    MEDICATION

 revealed an

    inflammatory lesion compatible with an arteritis
    MICROSCOPIC

. The significance of this association in the spectrum of

    immunologically-mediated disorders
    DIAGNOSIS

 in

    hereditary angioedema
    DIAGNOSIS

 is discussed.

hereditary angioedema
immunologically-mediated disorders
hereditary angioedema

substernal chest pain
multiple arterial stenoses


[Hereditary angioneurotic edema. Clinical syndrome and therapy].

Hereditary angioneurotic edema is transmitted as an autosomal dominant disease. It is characterized by a deficiency of the C1 esterase inhibitor. Clinical manifestations are periodic swelling of the extremities, face, upper airways and abdominal viscera. We described one patient to demonstrate the clinical features and current treatment. Danazol therapy is discussed.

    Hereditary angioneurotic edema
    DIAGNOSIS

 is

    transmitted as an autosomal dominant disease
    GENETICS

. It is characterized by a

    deficiency of the C1 esterase inhibitor
    BIOCHEMICAL

. Clinical manifestations are

    periodic swelling of the extremities, face, upper airways and abdominal viscera
    SYMPTOMS

. We described one patient to demonstrate the clinical features and current treatment.

    Danazol therapy
    MEDICATION

 is discussed.


[Hereditary angioedema. A clinical and immunologic contribution based on our 8 clinical cases under long-term treatment with androgens].

The literature on hereditary angioedema is reviewed and the case histories of 5 women and 3 men are reported. Special importance is attached to the results of therapy over 222 months of treatment with danazol and 40 months with stanozolol. The effects of androgen therapy on complement factor C4 and on C1-inhibitor are described.

The literature on

    hereditary angioedema
    DIAGNOSIS

 is reviewed and the case histories of 5

    women
    GENDER

 and 3

    men
    GENDER

 are reported. Special importance is attached to the results of

    therapy over 222 months of treatment with danazol and 40 months with stanozolol
    MEDICATION

. The effects of

    androgen therapy
    MEDICATION

 on

    complement factor C4 and on C1-inhibitor
    BIOCHEMICAL

 are described.


A study of familial lupus erythematosus-like disease and hereditary angio-oedema treated with danazol.

Immunological and genetic studies were performed in a family in which the mother and five siblings had hereditary angio-oedema (HAE). LE cells, antinuclear factors, antibodies to double-stranded DNA and positive direct Coombs' test were not found in any of the subjects. One female sibling had a lupus erythematosus-like illness with skin lesions of the face which responded to danazol treatment. Laboratory evidence of HAE was obtained in the entire kindred and all the siblings shared HLA haplotype AIB7 inherited from the deceased mother.

    Immunological and genetic studies
    PARACLINICAL

 were performed in a

    family in which the mother and five siblings had hereditary angio-oedema (HAE)
    FAMILY

.

    LE cells
    BIOCHEMICAL

,

    antinuclear factors
    BIOCHEMICAL

,

    antibodies to double-stranded DNA
    BIOCHEMICAL

 and

    positive direct Coombs' test were not found in any of the subjects
    NEG_FINDINGS

. One

    female
    GENDER

    sibling had a lupus erythematosus-like illness
    FAMILY

 with

    skin lesions of the face
    SYMPTOMS

 which responded to

    danazol treatment
    MEDICATION

.

    Laboratory evidence of HAE
    SYMPTOMS

 was obtained

    in the entire kindred
    FAMILY

 and

    all the siblings shared HLA haplotype AIB7 inherited from the deceased mother
    FAMILY

.

LE cells
antinuclear factors
antibodies to double-stranded DNA

skin lesions of the face
Laboratory evidence of HAE


Management of the airway in patients with angioedema.

Angiodema can be frequently encountered in clinical practice, and usually represents transient areas of tissue edema and erythema. In general, lesions involve the deep dermis as well as subcutaneous or submucosal sites and can affect multiple organ systems, including the respiratory and gastrointestinal tracts. Although the underlying cause for the angioedema is frequently not known, it can result from atopy, specific antigen sensitivities, physical stimuli, as well as disorders that affect the complement cascade. These latter entities may be congenital or acquired. Pathogenesis for angioedema is generally thought to be activation of mast cells or basophils, with subsequent release of histamine and other mediator products which can induce inflammatory changes. In most patients with physical and allergic causes of angioedema, swelling can usually be treated with epinephrine, antihistamines and/or steroids. Management of the airway in such patients is usually symptomatic, although certain patients require hospitalization for supervised care. On the other hand, patients with hereditary angioedema do not often respond well to these agents. In such patients, we currently add infusions of epsilonaminocaproic acid as well as nembulized racemic epinephrine to our therapeutic regimen, but even this may not be satisfactory. At the National Institute of Allergy and Infectious Disease, endotracheal intubation is usually preferred to tracheostomy for securing a temporary airway, though certain patients may require placement of tracheostomies for better control of the airway. Patients with frequent recurrences of airway obstruction are rarely seen--even among those patients with known hereditary angioedema. However, such patients may require tracheal fenestrations to secure long-term protection of the airway. The Institute's experiences in the management of patients with angioedema are reviewed, and therapies employed are described.

    Angiodema
    DIAGNOSIS

 can be frequently encountered in clinical practice, and usually represents

    transient areas of tissue edema and erythema
    SYMPTOMS

. In general,

    lesions involve the deep dermis as well as subcutaneous or submucosal sites
    SYMPTOMS

 and can

    affect multiple organ systems, including the respiratory and gastrointestinal tracts
    SYMPTOMS

. Although the underlying cause for the

    angioedema
    DIAGNOSIS

 is frequently not known, it can result from

    atopy
    GENETICS

,

    specific antigen sensitivities
    SYMPTOMS

, physical stimuli, as well as disorders that affect

    the complement cascade
    BIOCHEMICAL

. These latter entities may be congenital or acquired. Pathogenesis for

    angioedema
    DIAGNOSIS

 is generally thought to be

    activation of mast cells or basophils
    MICROSCOPIC

, with subsequent

    release of histamine and other mediator products
    MICROSCOPIC

 which can induce

    inflammatory changes
    SYMPTOMS

. In most patients with

    physical and allergic causes
    SYMPTOMS

 of

    angioedema
    SYMPTOMS

, swelling can usually be treated with

    epinephrine, antihistamines and/or steroids
    MEDICATION

.

    Management of the airway
    MEDICATION

 in such patients is usually symptomatic, although certain patients require

    hospitalization for supervised care
    MEDICATION

. On the other hand, patients with

    hereditary angioedema
    DIAGNOSIS

 do

    not often respond well to these agents
    NEG_FINDINGS

. In such patients, we currently add

    infusions of epsilonaminocaproic acid as well as nembulized racemic epinephrine to our therapeutic regimen
    MEDICATION

, but even this may not be satisfactory. At the National Institute of Allergy

    and Infectious Disease
    DIAGNOSIS

,

    endotracheal intubation
    MEDICATION

 is usually preferred to

    tracheostomy for securing a temporary airway
    MEDICATION

, though certain patients may require

    placement of tracheostomies
    MEDICATION

 for

    better control of the airway
    MEDICATION

. Patients with

    frequent recurrences of airway obstruction
    SYMPTOMS

 are rarely seen--even among those patients with known

    hereditary angioedema
    DIAGNOSIS

. However, such patients may require

    tracheal fenestrations to secure long-term protection of the airway
    MEDICATION

. The Institute's experiences in the management of patients with

    angioedema
    DIAGNOSIS

 are reviewed, and therapies employed are described.

Angiodema
angioedema
angioedema
hereditary angioedema
and Infectious Disease
hereditary angioedema
angioedema


[Hereditary angioedema. A hereditary disorder in the synthesis of the complement system].

Hereditary angioedema is characterized by recurrent attacks of painless, non itching edema of the face and limbs and sometimes by abdominal symptoms. It is due to a deficiency of functional inhibitor of the first component of complement (C1 Inh). We present a case where a normal antigenic level of C1 Inh was found but no functional activity was present (B variant). A short review is given of the pathogenesis, heredity, diagnosis and treatment of the disease.

    Hereditary angioedema
    DIAGNOSIS

 is characterized by

    recurrent attacks of painless, non itching edema of the face and limbs
    SYMPTOMS

 and sometimes by

    abdominal symptoms
    SYMPTOMS

. It is due to a

    deficiency of functional inhibitor of the first component of complement (C1 Inh)
    BIOCHEMICAL

. We present a case where a

    normal antigenic level of C1 Inh was found
    NEG_FINDINGS

 but

    no functional activity was present
    NEG_FINDINGS

 (B variant). A short review is given of the pathogenesis, heredity, diagnosis and treatment of the disease.


Angioneurotic oedema in the elderly.

A patient presented at the age of 72 years with a life long history of at least 60 years of abdominal crises described by the patient as 'bilious vomiting or migraine'. However, a careful clinical and family history suggested a diagnosis of hereditary angioneurotic oedema and this was confirmed by complement studies. Treatment with oral ethinyltestosterone (Danazol) was successful in abolishing her attacks, initially at a dose of 600 mg. per day and laterally at the low dose of 200 mg per day.

A patient presented at the

    age of 72 years
    AGE

 with a

    life long history of at least 60 years
    SYMPTOMS

 of

    abdominal crises
    SYMPTOMS

 described by the patient as '

    bilious vomiting or migraine'
    SYMPTOMS

. However, a

    careful clinical and family history
    PARACLINICAL

 suggested a diagnosis of

    hereditary angioneurotic oedema
    DIAGNOSIS

 and this was confirmed by

    complement studies
    PARACLINICAL

.

    Treatment with oral ethinyltestosterone (Danazol)
    MEDICATION

 was successful in

    abolishing her attacks
    SYMPTOMS

,

    initially at a dose of 600 mg. per day and laterally at the low dose of 200 mg per day.
    MEDICATION

life long history of at least 60 years
abdominal crises
bilious vomiting or migraine'
abolishing her attacks


Hereditary angioneurotic edema: clinical management and case report.

Hereditary angioneurotic edema, although a rare clinical entity, can be fatal if diagnosis and appropriate therapy are not instituted before the performance of routine dental and oral surgical procedures. The pathophysiology, physical findings, and therapeutic treatment modalities have been reviewed, and a case involving both restorative and surgical dental intervention has been presented.

    Hereditary angioneurotic edema
    DIAGNOSIS

, although a rare clinical entity, can be fatal if diagnosis and appropriate therapy are not instituted before the performance of

    routine dental and oral surgical procedures
    MEDICATION

. The pathophysiology, physical findings, and therapeutic treatment modalities have been reviewed, and a case

    involving both restorative and surgical dental intervention
    MEDICATION

 has been presented.


C1 inhibitor deficiency simulating systemic lupus erythematosus.

A 48-year-old Japanese woman with systemic lupus erythematosus-like lesions of the skin and lips was found to have hereditary angio-oedema. Complement studies revealed low CH50, C1q, C4 and C1 inhibitor levels, with normal C3 and C5 levels. Dramatic clinical improvement followed fresh normal human blood transfusion and systemic betamethasone administration, while the deficient complement component levels were unchanged.

A

    48-year-old
    AGE

    Japanese
    ETHNICITY

    woman
    GENDER

 with

    systemic lupus erythematosus-like lesions of the skin and lips
    SYMPTOMS

 was found to have

    hereditary angio-oedema
    SYMPTOMS

.

    Complement studies
    PARACLINICAL

 revealed

    low CH50, C1q, C4 and C1 inhibitor levels
    BIOCHEMICAL

, with

    normal C3 and C5 levels
    BIOCHEMICAL

.

    Dramatic clinical improvement
    SYMPTOMS

 followed

    fresh normal human blood transfusion
    MEDICATION

 and

    systemic betamethasone administration
    MEDICATION

, while the

    deficient complement component levels were unchanged
    BIOCHEMICAL

.

fresh normal human blood transfusion
systemic betamethasone administration


Familial angioedema associated with C1 esterase-inhibitor deficiency. A new genetic variant in hereditary angioedema?

In the absence of a positive family history for hereditary angioedema (HAE), both siblings in a family were found to have clinical and laboratory findings similar to those in HAE. Both siblings became symptom free after receiving danazol treatment, accompanied by a subnormal rise in C1 esterase inhibitor and C4 levels. As both siblings and their father share HLA haplotype A2, B7, the influence of other HLA loci on the clinical expression of this disorder should be considered. Although the disorder found in these siblings may be inherited as a recessive disorder, which to our knowledge has never been described before, or may have developed as the result of spontaneous genetic mutation, it is more appropriate to classify these two cases as familial angioedema until proved otherwise.

In the

    absence of a positive family history for hereditary angioedema (HAE)
    NEG_FINDINGS

,

    both siblings in a family were found to have clinical and laboratory findings similar to those in HAE
    FAMILY

. Both siblings

    became symptom free
    NEG_FINDINGS

 after receiving

    danazol treatment
    MEDICATION

, accompanied by a

    subnormal rise in C1 esterase inhibitor and C4 levels
    BIOCHEMICAL

. As

    both siblings and their father share HLA haplotype A2, B7
    FAMILY

, the influence of

    other HLA loci
    GENETICS

 on the clinical expression of this disorder should be considered. Although the

    disorder found in these siblings
    FAMILY

 may be

    inherited as a recessive disorder
    GENETICS

, which to our knowledge has never been described before, or may have developed as the result of

    spontaneous genetic mutation
    GENETICS

, it is more appropriate to classify these two cases as

    familial angioedema
    DIAGNOSIS

 until proved otherwise.

other HLA loci
inherited as a recessive disorder
spontaneous genetic mutation


[Acquired angioneurotic edema caused by acquired deficiency of C1 esterase inhibitor disclosing lymphoproliferative syndrome. Apropos of a case, review of the literature].

One case of acquired angio-neurotic oedema is described and discussed with the other cases recorded in literature since Caldwell's one in 1972. This entity is characterized by: --the late onset of angio-oedema but its presence only in about half cases, --a complement deficiency resulting from the lack of C1-esterase inhibitor, --the absence of familial identical cases, --the great frequency of associated illnesses overall lympho-proliferative diseases, --the therapeutic response to either etiologic treatment of the associated disease or to the symptomatic effect of drugs used in hereditary angio-neurotic oedema.

One case of

    acquired angio-neurotic oedema
    DIAGNOSIS

 is described and discussed with the other cases recorded in literature since Caldwell's one in 1972. This entity is characterized by: --the

    late onset of angio-oedema
    SYMPTOMS

 but its presence only in about half cases, --a

    complement deficiency
    BIOCHEMICAL

 resulting from the

    lack of C1-esterase inhibitor
    BIOCHEMICAL

, --the

    absence of familial identical cases
    FAMILY

, --the great frequency of associated illnesses overall

    lympho-proliferative diseases
    DIAGNOSIS

, --the therapeutic response to

    either etiologic treatment of the associated disease or to the symptomatic effect of drugs
    MEDICATION

 used in

    hereditary angio-neurotic oedema
    DIAGNOSIS

.

acquired angio-neurotic oedema
lympho-proliferative diseases
hereditary angio-neurotic oedema

complement deficiency
lack of C1-esterase inhibitor


Clinical presentation and diagnosis of hereditary angio-oedema in five families.

The clinical features of 16 patients with deficiency of C1 esterase inhibitor are described. Severity ranged from no symptoms in 2 young subjects to repeated and severe abdominal pain and angio-oedema. Diagnostic techniques are described and the ease with which the diagnosis can be established is emphasized. A functional assay is required in addition to immunological determination of the protein in order to detect a minority of patients who have ineffective inhibitor. Experience of treatment with tranexamic acid is reviewed and its place in management in relation to androgens is discussed.

The clinical features of 16 patients with

    deficiency of C1 esterase inhibitor
    BIOCHEMICAL

 are described. Severity ranged from

    no symptoms
    SYMPTOMS

 in 2 young subjects to

    repeated and severe abdominal pain
    SYMPTOMS

 and

    angio-oedema
    SYMPTOMS

. Diagnostic techniques are described and the ease with which the diagnosis can be established is emphasized. A

    functional assay
    PARACLINICAL

 is required in addition to

    immunological determination of the protein
    PARACLINICAL

 in order to detect a minority of patients who have

    ineffective inhibitor
    BIOCHEMICAL

. Experience of

    treatment with tranexamic acid
    MEDICATION

 is reviewed and its place in management in relation to

    androgens
    MEDICATION

 is discussed.

deficiency of C1 esterase inhibitor
ineffective inhibitor

no symptoms
repeated and severe abdominal pain
angio-oedema

treatment with tranexamic acid
androgens


Purification and characterization of two functionally distinct forms of C1 inhibitor from a patient with angioedema.

A minority of patients with hereditary angioedema (HAE) have normal concentrations of a dysfunctional C1 inhibitor protein (C1INH) in their plasmas. We purified C1INH from the plasmas of one such patient before and during treatment with the anabolic steroid stanozolol. Both the pretreatment plasma and plasma obtained during stanozolol treatment contained varying amounts of two extremely similar C1INH proteins that were functionally distinct. The pretreatment plasma contained primarily (94%) dysfunctional C1INH that did not inactivate or complex with either purified C1s, activated Hageman factor, or kallikrein and small amounts (6%) of functionally normal C1INH. Stanozolol treatment increased the plasma concentrations of both of these proteins as well as the proportion (23%) of functional C1INH in the plasma. The purified dysfunctional and functional C1INHs had identical or nearly identical molecular sizes, charges, amino acid compositions, and amino sugar contents, and could not be distinguished physicochemically from each other or from normal C1INH. From these studies of purified C1INH proteins we concluded that HAE associated with dysfunctional C1INH is due to a defect at the structural locus for one C1INH gene and that both the dysfunctional C1INH gene and the normal C1INH gene products are present in the plasma of the affected subject. Treatment with stanozolol comparably increased the synthesis of both C1INH proteins. The disproportionate rise in the level of the normal C1INH protein is consistent with the view that it is more rapidly catabolized as a consequence of its interaction with the proteases it inactivates.

A minority of patients with

    hereditary angioedema (HAE)
    DIAGNOSIS

 have

    normal concentrations of a dysfunctional C1 inhibitor protein (C1INH) in their plasmas
    NEG_FINDINGS

. We

    purified C1INH from the plasmas
    BIOCHEMICAL

 of one such patient before and during

    treatment with the anabolic steroid stanozolol
    MEDICATION

. Both the pretreatment plasma and plasma obtained during

    stanozolol treatment
    MEDICATION

 contained

    varying amounts of two extremely similar C1INH proteins
    BIOCHEMICAL

 that were functionally distinct. The

    pretreatment plasma contained primarily (94%) dysfunctional C1INH that did not inactivate or complex with either purified C1s, activated Hageman factor, or kallikrein
    BIOCHEMICAL

 and

    small amounts (6%) of functionally normal C1INH
    BIOCHEMICAL

.

    Stanozolol treatment
    MEDICATION

    increased the plasma concentrations of both of these proteins as well as the proportion (23%) of functional C1INH in the plasma
    BIOCHEMICAL

. The

    purified dysfunctional and functional C1INHs
    BIOCHEMICAL

 had identical or nearly identical molecular sizes, charges,

    amino acid compositions, and amino sugar contents
    BIOCHEMICAL

, and could not be distinguished physicochemically from each other or from normal

    C1INH
    NEG_FINDINGS

. From these studies of

    purified C1INH proteins
    BIOCHEMICAL

 we concluded that

    HAE
    DIAGNOSIS

 associated with

    dysfunctional C1INH
    BIOCHEMICAL

 is due to a

    defect at the structural locus for one C1INH gene
    GENETICS

 and that both the

    dysfunctional C1INH gene and the normal C1INH gene products are present in the plasma
    GENETICS

 of the affected subject.

    Treatment with stanozolol
    MEDICATION

 comparably

    increased the synthesis of both C1INH proteins
    BIOCHEMICAL

. The

    disproportionate rise in the level of the normal C1INH protein
    BIOCHEMICAL

 is consistent with the view that it is

    more rapidly catabolized
    BIOCHEMICAL

 as a consequence of its

    interaction with the proteases it inactivates
    BIOCHEMICAL

.


Ophthalmological examination of patients in long-term treatment with tranexamic acid.

Fourteen patients with hereditary angioneurotic oedema (Quincke' oedema) treated for an average period of 6 years (ranging from 15 months to 8 years) with tranexamic acid was given an ophthalmological examination in order to reveal any possible toxic damages caused by the treatment. As large doses of tranexamic acid given to animals have been shown to result in retinal degeneration, the examination was focused on checking the retinal function. A complete ophthalmic examination revealed no toxic effects in the eyes of any of the patients. No retinal damages were found that could have been caused by the tranexamic acid. The central corneal thickness was normal.

Fourteen patients with

    hereditary angioneurotic oedema (Quincke' oedema
    DIAGNOSIS

)

    treated for an average period of 6 years (ranging from 15 months to 8 years) with tranexamic acid
    MEDICATION

 was given an

    ophthalmological examination
    PARACLINICAL

 in order to reveal any possible

    toxic damages
    SYMPTOMS

 caused by the treatment. As

    large doses of tranexamic acid
    MEDICATION

 given to animals have been shown to result in

    retinal degeneration
    SYMPTOMS

, the examination was focused on

    checking the retinal function
    PARACLINICAL

. A

    complete ophthalmic examination
    PARACLINICAL

 revealed

    no toxic effects in the eyes of any of the patients
    NEG_FINDINGS

.

    No retinal damages were found that could have been caused by the tranexamic acid
    NEG_FINDINGS

.

    The central corneal thickness was normal
    NEG_FINDINGS

.


Hereditary angioedema: association with IgA deficiency and otolaryngologic disorders.

Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by recurrent edema of the oropharynx, the extremities, and by abdominal pain. This disorder is caused by a defect in the C1 esterase inhibitor (C1 INH) which inhibits the first component of complement (C1). Four generations of a family are described and laboratory data of five individuals of this family are given as these individuals presented for general otolaryngologic procedures. The mortality of acute laryngeal edema is described to vary from 6% to 54% and may necessitate a tracheotomy as a life saving measure A deficiency of IgA is also noted in this family, and to our knowledge, this is the first time this has been shown in association with HAE. Present therapy consists of long utilization of danazol, an attenuated androgen. Recently a partially purified C1 INH has been reported for acute episodes of HAE, and preliminary results are promising.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

 characterized by

    recurrent edema of the oropharynx, the extremities
    SYMPTOMS

, and by

    abdominal pain
    SYMPTOMS

. This disorder is caused by a

    defect in the C1 esterase inhibitor (C1 INH) which inhibits the first component of complement (C1)
    BIOCHEMICAL

. Four generations of a family are described and laboratory data of five individuals of this family are given as these individuals presented for

    general otolaryngologic procedures
    MEDICATION

. The mortality of

    acute laryngeal edema
    SYMPTOMS

 is described to vary from 6% to 54% and may necessitate a

    tracheotomy
    MEDICATION

 as a

    life saving measure
    MEDICATION

 A

    deficiency of IgA
    BIOCHEMICAL

 is also noted in this family, and to our knowledge, this is the first time this has been shown in association with

    HAE
    DIAGNOSIS

. Present therapy consists of

    long utilization of danazol, an attenuated androgen
    MEDICATION

. Recently a

    partially purified C1 INH
    MEDICATION

 has been reported for

    acute episodes of HAE
    DIAGNOSIS

, and preliminary results are promising.

Hereditary angioedema (HAE)
HAE
acute episodes of HAE


Successful use of danazol for hereditary angio-oedema.

A 10-year-old boy with severe hereditary angio-oedema was given danazol, 200 mg each day. There was a pronounced reduction in the frequency and severity of oedema.

A

    10-year-old
    AGE

    boy
    GENDER

 with

    severe hereditary angio-oedema
    SYMPTOMS

 was given

    danazol, 200 mg each day
    MEDICATION

. There was a

    pronounced reduction in the frequency and severity of oedema
    SYMPTOMS

.


Hypertension: a complication of danazol therapy.

Danazol is a semisynthetic androgen that is used in the treatment of endometriosis and hereditary angioedema. Although fluid retention and weight gain are well-known complictaions of danazol therapy, to our knowledge hypertension has not been previously documented with the use of this drug. We have studied a patient with hereditary angioedema who exhibited a reproducible hypertension with danazol therapy. Based on our investigation, the resultant hypertension was primarily volume dependent. The hypertension in this patient failed to respond to propranolol hydrochloride, while it normalized with the administration of a small dose of a diuretic. In view of the growing indications for therapy with danazol, increasing numbers of susceptible patients may be at risk of having drug-induced hypertension develop. We, therefore, recommend that blood pressure be routinely monitored in patients receiving this drug.

    Danazol
    MEDICATION

 is a

    semisynthetic androgen
    MEDICATION

 that is used in the treatment of

    endometriosis
    DIAGNOSIS

 and

    hereditary angioedema
    DIAGNOSIS

. Although

    fluid retention
    SYMPTOMS

 and

    weight gain
    SYMPTOMS

 are well-known complictaions of

    danazol therapy
    MEDICATION

, to our knowledge

    hypertension
    DIAGNOSIS

 has not been previously documented with the use of this drug. We have studied a patient with

    hereditary angioedema
    DIAGNOSIS

 who exhibited a

    reproducible hypertension
    SYMPTOMS

 with

    danazol therapy
    MEDICATION

. Based on our investigation, the resultant

    hypertension
    SYMPTOMS

 was primarily

    volume dependent
    SYMPTOMS

. The

    hypertension
    SYMPTOMS

 in this patient

    failed to respond to propranolol hydrochloride
    NEG_FINDINGS

, while it normalized with the

    administration of a small dose of a diuretic
    MEDICATION

. In view of the growing indications for therapy with

    danazol
    MEDICATION

, increasing numbers of susceptible patients may be at risk of having

    drug-induced hypertension
    DIAGNOSIS

 develop. We, therefore, recommend that

    blood pressure
    PARACLINICAL

 be routinely monitored in patients receiving this drug.

endometriosis
hereditary angioedema
hypertension
hereditary angioedema
drug-induced hypertension

fluid retention
weight gain
reproducible hypertension
hypertension
volume dependent
hypertension


Hereditary angioneurotic oedema.

HAE is transmitted by an autosomal dominant gene. It is due to a defect in the complement system and should be distinguished from the other two types of angio-oedema, i.e. allergic and idiopathic types. Pathogenesis and treatment are discussed and two new cases of HAE have been reported here. I would stress here two points: first, that the family should be investigated for the possibility of HAE; secondly, that the patient should carry a medical card similar to those carried by haemophilic patients, containing the diagnosis, name of the G.P. and emergency treatment.

    HAE
    DIAGNOSIS

 is

    transmitted by an autosomal dominant gene
    GENETICS

. It is due to a

    defect in the complement system
    BIOCHEMICAL

 and should be distinguished from the other two types of

    angio-oedema
    DIAGNOSIS

, i.e. allergic and

    idiopathic types
    DIAGNOSIS

. Pathogenesis and treatment are discussed and two new cases of

    HAE
    DIAGNOSIS

 have been reported here. I would stress here two points: first, that the family should be investigated for

    the possibility of HAE
    FAMILY

; secondly, that the patient should carry a medical card similar to those carried by

    haemophilic
    DIAGNOSIS

 patients, containing the diagnosis, name of the G.P. and

    emergency treatment
    MEDICATION

.

HAE
angio-oedema
idiopathic types
HAE
haemophilic


[Hereditary angioneurotic edema: study of serum complement and therapeutic trial with tranexamic acid (author's transl)].

Three familial generations (five members with hereditary angioneurotic edema) have been evaluated under clinical and immunological standpoints. A therapeutic trial with tranexamic acid was carried out. The five members with hereditary angioneurotic edema showed: decreased values of total hemolytic activity (CH50), deficit of C4 (between 8 and 23 percent of the normal value), and normal levels of C3 and C9. C3PA was normal in four members and decreased in one. Asymptomatic familial members had normal serum complement levels; only three cases showed diminished values of CH50, C4, C-1-INH and C3PA. Therapeutic trial with tranexamic acid demonstrated the usefulness of this agent in the treatment of angioneurotic edema; it showed slighter adverse reactions than those derived from other therapeutic modalities. Screening of asymptomatic familial members is pointed out in order to detect low plasma values of C1-IHN.

Three

    familial generations (five members with hereditary angioneurotic edema
    FAMILY

) have been evaluated under clinical and immunological standpoints. A

    therapeutic trial with tranexamic acid
    MEDICATION

 was carried out. The five members with

    hereditary angioneurotic edema
    SYMPTOMS

 showed:

    decreased values of total hemolytic activity (CH50)
    BIOCHEMICAL

,

    deficit of C4 (between 8 and 23 percent of the normal value)
    BIOCHEMICAL

, and

    normal levels of C3 and C9
    BIOCHEMICAL

.

    C3PA was normal
    NEG_FINDINGS

 in four members and

    decreased
    BIOCHEMICAL

 in one.

    Asymptomatic familial members
    NEG_FINDINGS

 had

    normal serum complement levels
    NEG_FINDINGS

; only three cases showed

    diminished values of CH50, C4, C-1-INH and C3PA
    BIOCHEMICAL

.

    Therapeutic trial with tranexamic acid
    MEDICATION

 demonstrated the usefulness of this agent in the treatment of

    angioneurotic edema
    SYMPTOMS

; it showed

    slighter adverse reactions
    SYMPTOMS

 than those derived from other therapeutic modalities. Screening of

    asymptomatic familial members
    PARACLINICAL

 is pointed out in order to detect

    low plasma values of C1-IHN
    BIOCHEMICAL

.

therapeutic trial with tranexamic acid
Therapeutic trial with tranexamic acid

hereditary angioneurotic edema
angioneurotic edema
slighter adverse reactions

C3PA was normal
Asymptomatic familial members
normal serum complement levels


Bladder involvement in hereditary angioedema.

We report on a patient with bladder involvement in hereditary angioedema. The patient had documented hereditary angioedema with episodes involving the skin and gastrointestinal tract. He presented with gross hematuria at age 36 and had also had gross hematuria at ages 16 and 20. Cytoscopic examination revealed raised hemorrhagic lesions in the vesical walls. Biopsy specimens of the lesions showed normal mucosa with submucosal edema. The lesions resolved when the angioedema was better controlled.

We report on a patient with

    bladder involvement
    SYMPTOMS

 in

    hereditary angioedema
    DIAGNOSIS

. The patient had documented

    hereditary angioedema with episodes involving the skin and gastrointestinal tract
    DIAGNOSIS

.

    He
    GENDER

 presented with

    gross hematuria
    SYMPTOMS

 at

    age 36
    AGE

 and had also had

    gross hematuria
    SYMPTOMS

 at

    ages 16 and 20
    AGE

.

    Cytoscopic examination
    PARACLINICAL

 revealed

    raised hemorrhagic lesions in the vesical walls
    SYMPTOMS

.

    Biopsy specimens
    PARACLINICAL

 of the lesions showed

    normal mucosa with submucosal edema
    SYMPTOMS

.

    The lesions
    SYMPTOMS

 resolved when the

    angioedema
    SYMPTOMS

 was better controlled.


[Hereditary angio-oedema: complement levels under treatment with danazol (author's transl)].

A mother and her son are described who both suffer from hereditary angiooedema. Both were treated with Danazol, a synthetic derivative of ethisterone. The prophylactic clinical effect seemed obvious, and also the serum concentration of the complement component C4, which had regularly been lower before treatment, became normal. However, no change of the serum concentration of the C1 esterase inhibitor could be demonstrated; this is in contrast to observations of other authors.

A

    mother
    GENDER

 and her

    son
    GENDER

 are described who both suffer from

    hereditary angiooedema
    DIAGNOSIS

. Both were treated with

    Danazol, a synthetic derivative of ethisterone
    MEDICATION

. The

    prophylactic clinical effect
    SYMPTOMS

 seemed obvious, and also the

    serum concentration of the complement component C4, which had regularly been lower before treatment
    BIOCHEMICAL

    , became normal
    BIOCHEMICAL

. However,

    no change of the serum concentration of the C1 esterase inhibitor could be demonstrated
    NEG_FINDINGS

; this is in contrast to observations of other authors.


Plasmapheresis in hereditary angioneurotic edema and systemic lupus erythematosus.

A patient had hereditary angioneurotic edema coincident with systemic lupus erythematosus. This condition resulted in loss of hair, arthralgia, leukoplakia, collitis, and a nephrotic syndrome due to proliferative glomerulonephritis. The renal lesion was resistant to treatment with high-dose prednisolone and cyclophosphamide; however, sustained remission occurred after plasmapheresis. The patient has remained well for over two years since this procedure.

A patient had

    hereditary angioneurotic edema
    SYMPTOMS

 coincident with

    systemic lupus erythematosus
    DIAGNOSIS

. This condition resulted in

    loss of hair
    SYMPTOMS

,

    arthralgia
    SYMPTOMS

,

    leukoplakia
    SYMPTOMS

,

    collitis
    SYMPTOMS

, and a

    nephrotic syndrome
    DIAGNOSIS

 due to

    proliferative glomerulonephritis
    DIAGNOSIS

. The

    renal lesion
    SYMPTOMS

    was resistant to treatment with high-dose prednisolone and cyclophosphamide
    NEG_FINDINGS

; however,

    sustained remission
    SYMPTOMS

 occurred after

    plasmapheresis
    MEDICATION

. The patient has remained well for over two years since this procedure.

hereditary angioneurotic edema
loss of hair
arthralgia
leukoplakia
collitis
renal lesion
sustained remission

systemic lupus erythematosus
nephrotic syndrome
proliferative glomerulonephritis


Hereditary angioneurotic edema: immunochemical 'activity' without clinical expression.

An 11-year-old white female with focal glomerulonephritis was found to have an absence of functional C1 esterase inhibitor. C1 esterase inhibitor measured by immunochemical means, however, was only slightly reduced. After an initial time period marked by variable hypocomplementemia, presumably due to immune complex formation associated with the nephritis, immunochemical signs of active and severe hereditary angioneurotic edema (HANE) developed. These have been unremitting for 3 1/2 years. Clinical signs of HANE, however, have never developed. Thus, during this time, there have been no clinical abnormalities despite the fact that free C1 esterase activity has been persistently present in this patient's serum and serum levels of functional C1 esterase inhibitor, C2 and C4 have been continuously less than 2% of normal. It appears, therefore, that this patient has an unusual form of HANE mainifested solely by the complement alterations seen during symptomatic attacks but without clinical expression of that serologic activity.

An

    11-year-old
    AGE

    white
    ETHNICITY

    female
    GENDER

 with

    focal glomerulonephritis
    DIAGNOSIS

 was found to have an

    absence of functional C1 esterase inhibitor
    BIOCHEMICAL

.

    C1 esterase inhibitor measured by immunochemical means
    BIOCHEMICAL

, however,

    was only slightly reduced
    BIOCHEMICAL

. After an initial time period marked by

    variable hypocomplementemia
    BIOCHEMICAL

, presumably due to

    immune complex formation associated with the nephritis
    MICROSCOPIC

,

    immunochemical signs of active and severe hereditary angioneurotic edema (HANE)
    SYMPTOMS

 developed. These have been unremitting for 3 1/2 years.

    Clinical signs of HANE
    NEG_FINDINGS

, however,

    have never developed
    NEG_FINDINGS

. Thus, during this time, there have been

    no clinical abnormalities
    NEG_FINDINGS

 despite the fact that

    free C1 esterase activity has been persistently present in this patient's serum
    BIOCHEMICAL

 and

    serum levels of functional C1 esterase inhibitor, C2 and C4 have been continuously less than 2% of normal
    BIOCHEMICAL

. It appears, therefore, that this patient has an unusual form of

    HANE
    DIAGNOSIS

 mainifested solely by the

    complement alterations
    BIOCHEMICAL

 seen during

    symptomatic attacks
    SYMPTOMS

 but

    without clinical expression of that serologic activity
    NEG_FINDINGS

.


Acquired angioedema and hypocompleentemia in a patient with myelofibrosis. Effect of danazol treatment.

This paper reports the findings of an "acquired" hereditary angioedema-like syndrome in a patient with myelofibrosis. No previous personal or family history of angioedema was present. The serum complement pattern showed a marked reduction of Cl esterase inhibitor, Clq and C4. All family members had a normal complement profile. Because of frequent attacks of laryngeal angioedema, prophylactic treatment with danazol was started. A striking clinical response was observed as well as a normalizing effect on the underlying biochemical abnormality.

This paper reports the findings of an "

    acquired" hereditary angioedema-like syndrome
    DIAGNOSIS

 in a patient with

    myelofibrosis
    DIAGNOSIS

.

    No previous personal or family history of angioedema was present
    NEG_FINDINGS

. The

    serum complement pattern
    BIOCHEMICAL

 showed a

    marked reduction of Cl esterase inhibitor, Clq and C4
    BIOCHEMICAL

.

    All family members had a normal complement profile
    NEG_FINDINGS

. Because of

    frequent attacks of laryngeal angioedema
    SYMPTOMS

,

    prophylactic treatment with danazol
    MEDICATION

 was started. A

    striking clinical response
    SYMPTOMS

 was observed as well as a

    normalizing effect on the underlying biochemical abnormality
    BIOCHEMICAL

.


Hereditary angioedema: lack of close linkage with markers on chromosome 6, with data on other markers.

Members of two Australian families with type A Hereditary Angioedema (HAE), having affected individuals in three generations, were typed for a large number of genetic marker systems in a search for close linkage with the locus controlling C1 inhibitor (C1 inh). The evidence from both families indicated lack of close linkage with HLA or with the loci for Bf and GLO on chromosome 6. Very close linkage was also excluded between the locus for C1 inh and the loci for 6PGD, PGM1 and MNSs. The other markers were not informative, but data on all systems showing variation are reported. The publication of similar data for other kindreds will help to determine lod scores for the probability of linkage between the C1 inh locus and loci controlling common protein polymorphisms. Linkage studies of this kind could establish whether the loci controlling type A and B HAE are identical or separate.

Members of two

    Australian
    ETHNICITY

 families with

    type A Hereditary Angioedema (HAE)
    DIAGNOSIS

, having

    affected individuals in three generations
    FAMILY

, were typed for a large number of

    genetic marker systems
    PARACLINICAL

 in a search for close linkage with the locus

    controlling C1 inhibitor (C1 inh)
    BIOCHEMICAL

. The evidence from both families indicated

    lack of close linkage with HLA or with the loci for Bf and GLO on chromosome 6
    NEG_FINDINGS

.

    Very close linkage was also excluded between the locus for C1 inh and the loci for 6PGD, PGM1 and MNSs
    NEG_FINDINGS

. The other

    markers were not informative
    NEG_FINDINGS

, but data on all systems showing variation are reported. The publication of similar data for other kindreds will help to determine lod scores for the probability of linkage between the

    C1 inh locus and loci controlling common protein polymorphisms
    GENETICS

. Linkage studies of this kind could establish whether the loci controlling

    type A and B HAE
    DIAGNOSIS

 are identical or separate.

type A Hereditary Angioedema (HAE)
type A and B HAE


Hereditary angioneurotic edema: report of case.

A case report in which the management of a patient with hereditary angioneurotic edema requiring oral surgery is presented. A review of the literature with emphasis on the clinical features, etiology, diagnosis, and treatment is also presented.

A case report in which the management of a patient with

    hereditary angioneurotic edema
    DIAGNOSIS

 requiring

    oral surgery
    MEDICATION

 is presented. A review of the literature with emphasis on the clinical features, etiology, diagnosis, and treatment is also presented.


Reticulate erythema--a prodrome in hereditary angio-oedema.

A previously undescribed short-lived non-puritic reticulate erythema has been noted in several members of unrelated families with hereditary angio-oedema. The eruption which may be widespread can last from 1 to 4 days and usually immediately precedes an overt attack of hereditary angio-oedema although this is not invariable, and swellings may occur in areas not previously involved by the erythema. Histology including immunohistology probably shows no specific changes.

A previously undescribed

    short-lived non-puritic reticulate erythema
    SYMPTOMS

 has been noted in several members of

    unrelated families with hereditary angio-oedema
    FAMILY

. The

    eruption which may be widespread
    SYMPTOMS

 can last from 1 to

    4 days
    SYMPTOMS

 and usually immediately precedes an

    overt attack of hereditary angio-oedema
    SYMPTOMS

 although this is not invariable, and

    swellings may occur in areas not previously involved by the erythema
    SYMPTOMS

.

    Histology including immunohistology
    PARACLINICAL

 probably shows

    no specific changes
    NEG_FINDINGS

.


Hereditary angioedema controlled with danazol. Report of a case.

Hereditary angioedema is a condition which should be approached with caution and concern for the patient. The fact that the disease can be fatal cannot be overemphasized. The routine medical history should include questions aimed at identifying these patients. If the angioedema patient is to be treated, provisions must be made for maintenance of an adequate airway. This should include intubation if deemed necessary, and the practitioner should be prepared for a tracheostomy. Close observation following extubation is indicated. A case report in which the patient was controlled with danazol, a synthetic androgen, has been presented. The primary advantage of this drug is a decrease in the various side effects which have been associated with other therapeutic agents used previously in the treatment of hereditary angioedema.

    Hereditary angioedema
    DIAGNOSIS

 is a condition which should be approached with caution and concern for the patient. The fact that the disease can be fatal cannot be overemphasized. The routine medical history should include questions aimed at identifying these patients. If the

    angioedema
    DIAGNOSIS

 patient is to be treated, provisions must be made for

    maintenance of an adequate airway
    MEDICATION

. This should include

    intubation
    MEDICATION

 if deemed necessary, and the practitioner should be prepared for a

    tracheostomy
    MEDICATION

.

    Close observation following extubation
    MEDICATION

 is indicated. A case report in which the patient was controlled with

    danazol, a synthetic androgen
    MEDICATION

, has been presented. The primary advantage of this drug is a

    decrease in the various side effects which have been associated with
    SYMPTOMS

 other therapeutic agents used previously in the treatment of

    hereditary angioedema
    DIAGNOSIS

.

Hereditary angioedema
angioedema
hereditary angioedema

maintenance of an adequate airway
intubation
tracheostomy
Close observation following extubation
danazol, a synthetic androgen


[Danazol treatment of hereditary angioneurotic oedema (author's transl)].

Danazol, an attenuated androgen, was administered to four patients with hereditary angioneurotic oedema, with rapid and complete response without side-effects. The follow-up period has now been up to 17 months. In all patients there was an indirect indication that their hormonal state influenced the course of the disease.

    Danazol, an attenuated androgen
    MEDICATION

, was administered to four patients with

    hereditary angioneurotic oedema
    DIAGNOSIS

, with rapid and complete response

    without side-effects
    NEG_FINDINGS

. The follow-up period has now been up to 17 months. In all patients there was an indirect indication that their hormonal state influenced the course of the disease.


Acquired C1 esterase inhibitor deficiency and angioedema: a review.

A case of acquired C1INH deficiency with angioedema is described. Fifteen cases are thus far recorded. The clinical syndrome of angioedema in these patients closely resembles hereditary angioedema (HAE). Most cases are associated with a paraprotein, cryoglobulin, or autoantibody, which presumably initiates C1 activation and C1 Inhibitor consumption. C1INH, C4 and C2 levels are low in acquired C1INH deficiency, as in HAE. A distinguishing feature is that C1 titers are very low in the acquired disease and only minimally depressed, if at all, in HAE. Most cases have appeared in patients with an underlying lymphoproliferative or autoimmune disease. Therapy is directed at the underlying disorder, but androgen therapy may be helpful in preventing attacks. Future potential therapeutic approaches are discussed.

A case of

    acquired C1INH deficiency
    BIOCHEMICAL

 with

    angioedema
    SYMPTOMS

 is described. Fifteen cases are thus far recorded. The clinical syndrome of

    angioedema
    DIAGNOSIS

 in these patients closely resembles

    hereditary angioedema (HAE)
    DIAGNOSIS

. Most cases are associated with a

    paraprotein, cryoglobulin
    BIOCHEMICAL

, or

    autoantibody
    BIOCHEMICAL

, which presumably initiates

    C1 activation and C1 Inhibitor consumption
    BIOCHEMICAL

.

    C1INH, C4 and C2 levels are low
    BIOCHEMICAL

 in

    acquired C1INH deficiency
    BIOCHEMICAL

, as in

    HAE
    DIAGNOSIS

. A distinguishing feature is that

    C1 titers are very low in the acquired disease
    BIOCHEMICAL

 and

    only minimally depressed, if at all, in HAE
    NEG_FINDINGS

. Most cases have appeared in patients with an underlying

    lymphoproliferative or autoimmune disease
    DIAGNOSIS

. Therapy is directed at the underlying disorder, but

    androgen therapy
    MEDICATION

 may be helpful in preventing attacks. Future potential therapeutic approaches are discussed.


Prophylaxis of attacks of hereditary angioedema.

Danazol, an attentuated androgen, has been suggested as an effective agent for the prophylaxis of attacks of hereditary angioedema. Four patients, with a clinical history of hereditary angioedema and a demonstrated depression of the serum inhibitor of the first component of complement (C1 INH) and the fourth component of complement (C4), were entered into a study to determine the minimum effective dose of this agent. All four of the patients had been experiencing attacks at least monthly, but they had only six attacks during a total of 60 patient months of Danazol therapy. The minimum effective dose varied from 100 to 400 mg/day. The drug appeared to work by increasing the level of serum C1 INH which reached the normal range in two of four patients. Side effects were only the anticipated menstrual irregularities in the female patients. Danazol appears to be an efficacious drug for prophylaxis of hereditary angioedema.

    Danazol, an attentuated androgen
    MEDICATION

, has been suggested as an effective agent for the prophylaxis of

    attacks of hereditary angioedema
    DIAGNOSIS

. Four patients, with a clinical history of

    hereditary angioedema
    DIAGNOSIS

 and a

    demonstrated depression of the serum inhibitor of the first component of complement (C1 INH) and the fourth component of complement (C4)
    BIOCHEMICAL

, were entered into a study to determine the minimum effective dose of this agent. All four of the patients had been experiencing attacks at least monthly, but they had only six attacks during a total of

    60 patient months of Danazol therapy
    MEDICATION

. The minimum effective dose varied from

    100 to 400 mg/day
    MEDICATION

. The drug appeared to work by

    increasing the level of serum C1 INH which reached the normal range
    BIOCHEMICAL

 in two of four patients. Side effects were only the

    anticipated menstrual irregularities
    SYMPTOMS

 in the

    female
    GENDER

 patients.

    Danazol
    MEDICATION

 appears to be an efficacious drug for prophylaxis of

    hereditary angioedema
    DIAGNOSIS

.

Danazol, an attentuated androgen
60 patient months of Danazol therapy
100 to 400 mg/day
Danazol

attacks of hereditary angioedema
hereditary angioedema
hereditary angioedema


Hereditary angioneurotic oedema.

Hereditary angioedema (HAE) is characterised by episodic swelling of the extremities, face, larynx and recurrent abdominal pain, which can mimic the acute abdomen. Trauma of the larynx may result in acute airway obstruction. The management of emergency anaesthesia for Caesarean section of a patient with documented HAE is described and the special problems presented discussed. The methods of prophylaxis available are considered and the use of fresh frozen plasma advocated.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterised by

    episodic swelling of the extremities, face, larynx
    SYMPTOMS

 and

    recurrent abdominal pain
    SYMPTOMS

, which can mimic the

    acute abdomen
    SYMPTOMS

.

    Trauma of the larynx
    SYMPTOMS

 may result in

    acute airway obstruction
    SYMPTOMS

. The management of

    emergency anaesthesia for Caesarean section
    MEDICATION

 of a patient with documented

    HAE
    DIAGNOSIS

 is described and the special problems presented discussed. The methods of prophylaxis available are considered and the

    use of fresh frozen plasma
    MEDICATION

 advocated.


Hereditary angio-oedema: treatment with danazol. Report of a case.

An 8-year-old boy with hereditary angio-oedema was treated with danazol under close endocrinological supervision. The boy's C1 esterase inhibitor (C1inh) and C4 levels increased rapidly to near normal values under a daily dose of 400 mg and were maintained at about 50% of the normal by maintenance doses of 200 mg danazol every other day. Throughout the entire treatment period (11 months) the boy has been maintained free from attacks of angio-oedema. No hormonal imbalance was detected in the follow-up period. Our results indicate that danazol should be suitable for the treatment of HAE not only in adults but also in prepubescent children.

An

    8-year-old
    AGE

    boy
    GENDER

 with

    hereditary angio-oedema
    DIAGNOSIS

 was treated with

    danazol
    MEDICATION

 under

    close endocrinological supervision
    PARACLINICAL

. The

    boy
    GENDER

's

    C1 esterase inhibitor (C1inh) and C4 levels increased rapidly to near normal values
    BIOCHEMICAL

 under a

    daily dose of 400 mg and were maintained at about 50% of the normal
    MEDICATION

 by

    maintenance doses of 200 mg danazol every other day
    MEDICATION

. Throughout the

    entire treatment period (11 months
    MEDICATION

) the

    boy
    GENDER

 has been maintained

    free from attacks of angio-oedema
    NEG_FINDINGS

.

    No hormonal imbalance
    NEG_FINDINGS

    was detected
    NEG_FINDINGS

 in the

    follow-up period
    PARACLINICAL

. Our results indicate that

    danazol
    MEDICATION

 should be suitable for the treatment of

    HAE
    DIAGNOSIS

 not only in

    adults
    AGE

 but also in

    prepubescent children
    AGE

.

free from attacks of angio-oedema
No hormonal imbalance
was detected