Acyclovir therapy for angioedema and chronic urticaria.

Angioedema and chronic urticaria result from a variety of causes. Our purpose was to study the therapeutic effect of oral acyclovir on selected patients, by observing the effect of acyclovir in a dosage of from 100 mg every six hours to 800 mg every four hours in fourteen patients with angioedema or chronic urticaria. Five of twelve patients with chronic urticaria and one patient each with hereditary angioedema and idiopathic angioedema noted complete remission with acyclovir therapy. Discontinuation of the acyclovir resulted in reappearance of the hives. Since these patients had high antibody titers to either herpes simplex virus or Epstein-Barr virus, we conclude that acyclovir produced its therapeutic effect by suppressing a circulating viral antigen.

    Angioedema
    DIAGNOSIS

 and

    chronic urticaria
    DIAGNOSIS

 result from a variety of causes. Our purpose was to study the therapeutic effect of

    oral acyclovir
    MEDICATION

 on selected patients, by observing the effect of

    acyclovir in a dosage of from 100 mg every six hours to 800 mg every four hours
    MEDICATION

 in fourteen patients with

    angioedema
    DIAGNOSIS

 or

    chronic urticaria
    DIAGNOSIS

. Five of twelve patients with

    chronic urticaria
    DIAGNOSIS

 and one patient each with

    hereditary angioedema
    DIAGNOSIS

 and

    idiopathic angioedema
    DIAGNOSIS

 noted

    complete remission
    SYMPTOMS

 with

    acyclovir therapy
    MEDICATION

.

    Discontinuation of the acyclovir
    MEDICATION

 resulted in

    reappearance of the hives
    SYMPTOMS

. Since these patients had

    high antibody titers to either herpes simplex virus or Epstein-Barr virus
    BIOCHEMICAL

, we conclude that

    acyclovir
    MEDICATION

 produced its therapeutic effect by

    suppressing a circulating viral antigen
    BIOCHEMICAL

.

Angioedema
chronic urticaria
angioedema
chronic urticaria
chronic urticaria
hereditary angioedema
idiopathic angioedema

complete remission
reappearance of the hives


Preoperative prophylaxis for C1 esterase-inhibitor deficiency in patients undergoing oral surgery: a report of three cases.

C1-inhibitor deficiency, or hereditary angioedema, is a genetic disorder characterized by recurrent circumscribed, nonpruritic, nonpitting subepithelial edema. Minor trauma to the tissue, such as tooth extraction, can trigger life-threatening laryngeal edema. The use of fresh frozen plasma and/or danazol before treatment prevents angioedema attacks. A critical review of the treatment regimen and prophylaxis for C1-inhibitor deficiency is presented, and three new cases are described.

    C1-inhibitor deficiency
    BIOCHEMICAL

, or

    hereditary angioedema
    DIAGNOSIS

, is a

    genetic disorder
    GENETICS

 characterized by

    recurrent circumscribed, nonpruritic, nonpitting subepithelial edema
    SYMPTOMS

.

    Minor trauma to the tissue
    SYMPTOMS

, such as

    tooth extraction
    MEDICATION

, can trigger

    life-threatening laryngeal edema
    SYMPTOMS

. The

    use of fresh frozen plasma and/or danazol before treatment
    MEDICATION

 prevents

    angioedema attacks
    SYMPTOMS

. A critical review of the treatment regimen and prophylaxis for

    C1-inhibitor deficiency
    BIOCHEMICAL

 is presented, and three new cases are described.

C1-inhibitor deficiency
C1-inhibitor deficiency


Hashimoto's thyroiditis associated with urticaria and angio-oedema: disappearance of cutaneous and mucosal manifestations after thyroidectomy.

A 60 year old woman affected by Hashimoto's thyroiditis presented with a history of recurring episodes of urticaria and angio-oedema. Clinical and laboratory evaluation of the patient excluded allergy to external agents, hereditary angio-oedema, and occult infections. A pathogenic relation between Hashimoto's thyroiditis and chronic urticaria/angio-oedema was suspected. However, treatment with L-thyroxine had no influence on the frequency and severity of the cutaneous and mucosal manifestations, which occurred almost daily and required repeated administration of steroids. The patient therefore underwent total thyroidectomy. Cytometric analysis of intrathyroidal lymphocyte subsets showed unusual abnormalities. Urticaria and angio-oedema completely remitted after surgery; 18 months postoperatively the patient was still asymptomatic.

A

    60 year old
    AGE

    woman
    GENDER

 affected by

    Hashimoto's thyroiditis
    DIAGNOSIS

 presented with a history of

    recurring episodes of urticaria
    SYMPTOMS

 and

    angio-oedema
    SYMPTOMS

.

    Clinical and laboratory evaluation
    PARACLINICAL

 of the patient

    excluded allergy to external agents
    NEG_FINDINGS

,

    hereditary angio-oedema
    NEG_FINDINGS

, and

    occult infections
    NEG_FINDINGS

. A pathogenic relation between

    Hashimoto's thyroiditis
    DIAGNOSIS

 and

    chronic urticaria/angio-oedema
    DIAGNOSIS

 was suspected. However,

    treatment with L-thyroxine had no influence on the frequency and severity of the cutaneous and mucosal manifestations
    NEG_FINDINGS

, which occurred almost daily and required

    repeated administration of steroids
    MEDICATION

. The patient therefore underwent

    total thyroidectomy
    MEDICATION

.

    Cytometric analysis of intrathyroidal lymphocyte subsets
    PARACLINICAL

 showed

    unusual abnormalities
    BIOCHEMICAL

.

    Urticaria and angio-oedema completely remitted
    SYMPTOMS

 after

    surgery
    MEDICATION

; 18 months postoperatively the patient was still

    asymptomatic
    NEG_FINDINGS

.

Hashimoto's thyroiditis
Hashimoto's thyroiditis
chronic urticaria/angio-oedema

repeated administration of steroids
total thyroidectomy
surgery


Autoimmune C1 inhibitor deficiency and angioedema.

C1 inhibitor (C1-INH) deficiency results in bouts of mucocutaneous edema and may be inherited (hereditary angioedema) or acquired (acquired angioedema). The syndrome of acquired angioedema, characterized by the adult onset of angioedema and by the lack of evidence of inheritance of the disease, may be associated with lymphoproliferative or other malignant diseases (type I) or with the presence of autoantibodies to C1-INH (type II); this is a rare variant form of C1-INH deficiency with angioedema. We report here a case of acquired C1-INH deficiency with angioedema, hypotension and abdominal discomfort observed in a 71-year-old man in whom complement abnormalities and autoantibodies against C1-INH have been observed and who was classified as having an autoimmune C1-INH deficiency. From the therapeutic point of view after resolution of the acute attacks, high doses of tranexamic acid have been able, at first, to decrease the frequency and the severity of the symptoms, and subsequently to provide a long symptom-free time.

    C1 inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 results in

    bouts of mucocutaneous edema
    SYMPTOMS

 and may be

    inherited
    GENETICS

 (

    hereditary angioedema)
    DIAGNOSIS

 or acquired (

    acquired angioedema)
    DIAGNOSIS

. The syndrome of

    acquired angioedema
    DIAGNOSIS

, characterized by the

    adult
    AGE

 onset of

    angioedema
    SYMPTOMS

 and by the

    lack of evidence of inheritance of the disease
    NEG_FINDINGS

, may be associated with

    lymphoproliferative or other malignant diseases
    DIAGNOSIS

 (

    type I)
    DIAGNOSIS

 or with the presence of

    autoantibodies to C1-INH
    BIOCHEMICAL

 (

    type II)
    DIAGNOSIS

; this is a rare variant form of

    C1-INH deficiency
    BIOCHEMICAL

 with

    angioedema
    SYMPTOMS

. We report here a case of

    acquired C1-INH deficiency
    BIOCHEMICAL

 with

    angioedema
    SYMPTOMS

,

    hypotension
    SYMPTOMS

 and

    abdominal discomfort
    SYMPTOMS

 observed in a

    71-year-old
    AGE

    man
    GENDER

 in whom

    complement abnormalities
    BIOCHEMICAL

 and

    autoantibodies against C1-INH
    BIOCHEMICAL

 have been

    observed
    BIOCHEMICAL

 and who was classified as having an

    autoimmune C1-INH deficiency
    BIOCHEMICAL

. From the therapeutic point of view after

    resolution of the acute attacks
    SYMPTOMS

,

    high doses of tranexamic acid
    MEDICATION

 have been able, at first, to

    decrease the frequency and the severity of the symptoms
    SYMPTOMS

, and subsequently to provide a

    long symptom-free time
    SYMPTOMS

.

C1 inhibitor (C1-INH) deficiency
autoantibodies to C1-INH
C1-INH deficiency
acquired C1-INH deficiency
complement abnormalities
autoantibodies against C1-INH
observed
autoimmune C1-INH deficiency


Long-term treatment of C1 inhibitor deficiency with epsilon-aminocaproic acid in two patients.

Most patients who have hereditary angioedema receive treatment with androgens or impeded androgens. epsilon-Aminocaproic acid (EACA) is another treatment for C1 inhibitor deficiency. In two patients with angioedema and attacks of abdominal pain due to C1 inhibitor deficiency, long-term treatment with EACA (for more than 2 decades in one of them) was associated with a substantial decrease in the frequency and severity of episodes. One patient had definite hereditary angioedema, and the other had probable hereditary angioedema but the family history was negative for the disease. The EACA therapy caused no major side effects.

Most patients who have

    hereditary angioedema
    DIAGNOSIS

 receive

    treatment with androgens or impeded androgens
    MEDICATION

.

    epsilon-Aminocaproic acid (EACA)
    MEDICATION

 is another treatment for

    C1 inhibitor deficiency
    BIOCHEMICAL

. In two patients with

    angioedema
    DIAGNOSIS

 and

    attacks of abdominal pain
    SYMPTOMS

 due to

    C1 inhibitor deficiency
    BIOCHEMICAL

,

    long-term treatment with EACA (for more than 2 decades
    MEDICATION

 in one of them) was associated with a

    substantial decrease in the frequency and severity of episodes
    SYMPTOMS

. One patient had

    definite hereditary angioedema
    DIAGNOSIS

, and the other had

    probable hereditary angioedema
    DIAGNOSIS

 but the

    family history was negative for the disease
    NEG_FINDINGS

. The

    EACA therapy
    MEDICATION

 caused

    no major side effects
    NEG_FINDINGS

.

hereditary angioedema
angioedema
definite hereditary angioedema
probable hereditary angioedema

C1 inhibitor deficiency
C1 inhibitor deficiency


Antibody to C1-inhibitor in a patient receiving C1-inhibitor infusions for treatment of hereditary angioneurotic edema with systemic lupus erythematosus reacts with a normal allotype of residue 458 of C1-inhibitor.

Patients with hereditary C4 deficiency are likely to have severe lupus erythematosus. A patient with hereditary angioneurotic edema (HANE) and systemic lupus erythematosus (SLE) had a chronic deficiency in C4 because the hereditary deficiency in C1-inhibitor allowed the C1 in her serum to become activated and then inactivate C4. An attempt was made to repair the C4 deficiency as well as the deficiency in C1-inhibitor by giving infusions of human C1-inhibitor in the hope of inducing remissions of both HANE and SLE. During treatment, antibody to C1-inhibitor developed in the patient; this cleared when the infusions were stopped. During subsequent treatment with danazol alone, measurable C1-inhibitor developed in the patient's serum, but levels of C4 were never significantly increased. Antibody to normal C1-inhibitor was not expected to develop in the patient because she is heterozygous for this autosomal dominant trait. A normal allotype (VAL or MET 458), which would have been in the preparation used but which the patient does not synthesize because she can produce only one allotype (MET 458), appears to have been immunogenic. The antibody isolated from the patient's serum reacted with C1-inhibitor from a normal individual known to be homozygous for 458-VAL but not with one from a homozygote for MET-458.

Patients with

    hereditary C4 deficiency
    BIOCHEMICAL

 are likely to have

    severe lupus erythematosus
    DIAGNOSIS

. A patient with

    hereditary angioneurotic edema (HANE)
    DIAGNOSIS

 and

    systemic lupus erythematosus (SLE)
    DIAGNOSIS

 had a

    chronic deficiency in C4
    BIOCHEMICAL

 because the

    hereditary deficiency in C1-inhibitor allowed the C1 in her serum to become activated and then inactivate C4
    BIOCHEMICAL

. An attempt was made to repair the

    C4 deficiency
    BIOCHEMICAL

 as well as the

    deficiency in C1-inhibitor
    BIOCHEMICAL

 by

    giving infusions of human C1-inhibitor
    MEDICATION

 in the hope of inducing

    remissions of both HANE and SLE
    DIAGNOSIS

. During treatment,

    antibody to C1-inhibitor developed
    BIOCHEMICAL

 in the patient; this cleared when

    the infusions were stopped
    NEG_FINDINGS

. During

    subsequent treatment with danazol alone
    MEDICATION

,

    measurable C1-inhibitor developed in the patient's serum
    BIOCHEMICAL

, but

    levels of C4 were never significantly increased
    NEG_FINDINGS

.

    Antibody to normal C1-inhibitor was not expected to develop
    NEG_FINDINGS

 in the patient because

    she
    GENDER

 is

    heterozygous for this autosomal dominant trait
    GENETICS

. A

    normal allotype (VAL or MET 458)
    GENETICS

, which would have been in the preparation used but which the patient does not synthesize because

    she can produce only one allotype (MET 458)
    GENETICS

, appears to have been immunogenic. The

    antibody isolated from
    BIOCHEMICAL

 the patient's serum reacted with C1-inhibitor from a normal individual known

    to be homozygous for 458-VAL
    GENETICS

 but not with one from a

    homozygote for MET-458
    GENETICS

.

severe lupus erythematosus
hereditary angioneurotic edema (HANE)
systemic lupus erythematosus (SLE)
remissions of both HANE and SLE

giving infusions of human C1-inhibitor
subsequent treatment with danazol alone


A point mutation in exon 7 of the C1-inhibitor gene causing type I hereditary angioedema.

The polymerase chain reaction and nucleotide sequence analysis have been used to characterize a point mutation in the seventh exon of one allele of the C1-inhibitor gene in a family with type I hereditary angioedema. A single base change (C-->T) at nucleotide 1482 in C1-inhibitor converted the codon for Gln-339 to a premature translation termination codon, TAG. Family studies suggest that this mutation is responsible for type I hereditary angioedema in a studied pedigree.

The

    polymerase chain reaction and nucleotide sequence analysis
    PARACLINICAL

 have been used to characterize a

    point mutation in the seventh exon of one allele of the C1-inhibitor gene
    GENETICS

 in a

    family with type I hereditary angioedema
    FAMILY

. A

    single base change (C-->T) at nucleotide 1482 in C1-inhibitor converted the codon for Gln-339 to a premature translation termination codon, TAG
    GENETICS

.

    Family studies
    PARACLINICAL

 suggest that this mutation is responsible for

    type I hereditary angioedema
    DIAGNOSIS

 in a studied pedigree.


Colorectal intussusception: an unusual gastrointestinal complication of hereditary angioedema.

A 21-year-old man with a history of hereditary angioedema presented with protracted abdominal pain which failed to respond to infusion of C1 inhibitor concentrate. Evaluation by CT scan revealed extensive colorectal intussusception requiring surgical intervention. Under replacement therapy with C1 inhibitor concentrate, both the operation under general anesthesia and the postoperative phase were uneventful. The intraoperative examination suggested initiation of intussusception by local mucosal edema in the transverse colon.

A

    21-year-old
    AGE

    man
    GENDER

 with a

    history of hereditary angioedema
    FAMILY

 presented with

    protracted abdominal pain
    SYMPTOMS

 which

    failed to respond to infusion of C1 inhibitor concentrate
    NEG_FINDINGS

. Evaluation by

    CT scan
    PARACLINICAL

 revealed

    extensive colorectal intussusception
    SYMPTOMS

 requiring

    surgical intervention
    MEDICATION

. Under

    replacement therapy with C1 inhibitor concentrate
    MEDICATION

, both the

    operation under general anesthesia
    MEDICATION

 and the postoperative phase were

    uneventful
    MEDICATION

. The

    intraoperative examination
    PARACLINICAL

 suggested

    initiation of intussusception by local mucosal edema in the transverse colon
    SYMPTOMS

.


Fresh frozen plasma prophylaxis for hereditary angioedema during pregnancy. A case report.

Hereditary angioedema (HAE) is an uncommon disorder of the complement system due to a deficiency or dysfunction of the inhibitor of the first component of complement (C1 INH). Clinically, HAE is characterized by episodic abdominal pain or edema of the extremities, face, larynx and vulva. Laryngeal edema is potentially lethal and accounts for mortality rates as high as 30%. Therapy is divided into short-term (fresh frozen plasma) and long-term (antifibrinolytic agents, hormonal therapy) prophylaxis, or acute treatment (epinephrine, steroids, antihistamines).

An 18 year-old, primiparous woman presented with a history of multiple episodes of abdominal pain, swelling of abdomen and extremities. A diagnosis of hereditary angioedema was made based on the patient's and family's history and on decreased levels of C1 INH and complement component 4. Standard prophylactic methods were contraindicated due to potential teratogenic effects. Fresh frozen plasma given twice weekly over 2.5 months resulted in reduction in the number and severity of attacks and allowed successful completion of pregnancy.

This is the first report of fresh frozen plasma therapy as a means of long-term prophylaxis in a pregnant woman. Fresh frozen plasma may serve as an alternate mode of long-term prophylaxis if the standard agents (antifibrinolytic, hormone) are unsuccessful or contraindicated.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    uncommon disorder of the complement system
    DIAGNOSIS

 due to a

    deficiency or dysfunction of the inhibitor of the first component of complement (C1 INH)
    BIOCHEMICAL

. Clinically,

    HAE
    DIAGNOSIS

 is characterized by

    episodic abdominal pain
    SYMPTOMS

 or

    edema of the extremities, face, larynx and vulva
    SYMPTOMS

.

    Laryngeal edema
    SYMPTOMS

 is potentially lethal and accounts for mortality rates as high as 30%. Therapy is divided into

    short-term (fresh frozen plasma) and long-term (antifibrinolytic agents, hormonal therapy) prophylaxis
    MEDICATION

, or

    acute treatment (epinephrine, steroids, antihistamines)
    MEDICATION

.

An

    18 year-old
    AGE

,

    primiparous
    AGE

    woman
    GENDER

 presented with a history of

    multiple episodes of abdominal pain
    SYMPTOMS

,

    swelling of abdomen and extremities
    SYMPTOMS

. A diagnosis of

    hereditary angioedema
    DIAGNOSIS

 was made based on the patient's and family's history and on

    decreased levels of C1 INH and complement component 4
    BIOCHEMICAL

.

    Standard prophylactic methods were contraindicated
    NEG_FINDINGS

 due to potential

    teratogenic effects
    SYMPTOMS

.

    Fresh frozen plasma given twice weekly over 2.5 months
    MEDICATION

 resulted in

    reduction in the number and severity of attacks
    SYMPTOMS

 and allowed

    successful completion of pregnancy
    MEDICATION

.

This is the first report of

    fresh frozen plasma therapy as a means of long-term prophylaxis
    MEDICATION

 in a

    pregnant
    AGE

    woman
    GENDER

.

    Fresh frozen plasma
    MEDICATION

 may serve as an

    alternate mode of long-term prophylaxis
    MEDICATION

 if

    the standard agents (antifibrinolytic, hormone) are unsuccessful or contraindicated
    NEG_FINDINGS

.


[The use of a C1-inhibior concentrate for short-term preoperative prophylaxis in two patients with hereditary angioedema].

A commercially available C1 inhibitor (C1-INH) concentrate was used for short-term prophylaxis before surgery in two patients with hereditary angioneurotic oedema. The patients suffered from recurrent subcutaneous and submucosal oedema of the face, extremities, and gastrointestinal tract as the result of a hereditary C1-INH deficiency. Both patients were receiving tranexamic acid or danazol therapy as oral long-term prophylaxis. Over the years the patients underwent several operations in regional and general anaesthesia, with mask ventilation or intubation. The C1-INH plasma concentrations measured preoperatively were always very low (0.02-0.06 g/l, normal range 0.15-0.35 g/l), despite the oral long-term prophylaxis. Substitution treatment with 500-1000 U C1-INH was performed 1 h before surgery. No side effects were seen following the concentrate infusions. With this substitution treatment no specific symptoms of hereditary angioneurotic oedema were recognized in either case. The measurement of C1-INH plasma concentration 2 h or 4 h after C1-INH substitution showed a marked rise in both patients, though normal values were not reached in either. We suggest that infusion of C1 concentrate is an appropriate form of preoperative substitution treatment in patients with hereditary angioneurotic oedema, in view of the lower risk of infection than with infusion of fresh-frozen plasma and the observed effectiveness.

A

    commercially available C1 inhibitor (C1-INH) concentrate
    MEDICATION

 was used

    for short-term prophylaxis before surgery
    MEDICATION

 in two patients with

    hereditary angioneurotic oedema
    DIAGNOSIS

. The patients suffered from

    recurrent subcutaneous and submucosal oedema of the face, extremities, and gastrointestinal tract
    SYMPTOMS

 as the result of a

    hereditary C1-INH deficiency
    BIOCHEMICAL

. Both patients were

    receiving tranexamic acid or danazol therapy as oral long-term prophylaxis
    MEDICATION

. Over the years the patients underwent

    several operations in regional and general anaesthesia
    MEDICATION

, with

    mask ventilation or intubation
    MEDICATION

.

    The C1-INH plasma concentrations measured preoperatively were always very low (0.02-0.06 g/l, normal range 0.15-0.35 g/l)
    BIOCHEMICAL

,

    despite the oral long-term prophylaxis
    NEG_FINDINGS

.

    Substitution treatment with 500-1000 U C1-INH was performed 1 h before surgery
    MEDICATION

.

    No side effects were seen following the concentrate infusions
    NEG_FINDINGS

. With this

    substitution treatment
    MEDICATION

    no specific symptoms of hereditary angioneurotic oedema
    NEG_FINDINGS

 were recognized in either case. The

    measurement of C1-INH plasma concentration 2 h or 4 h after C1-INH substitution showed a marked rise
    BIOCHEMICAL

 in both patients, though

    normal values were not reached
    NEG_FINDINGS

 in either. We suggest that

    infusion of C1 concentrate
    MEDICATION

 is an appropriate form of

    preoperative substitution treatment
    MEDICATION

 in patients with

    hereditary angioneurotic oedema
    DIAGNOSIS

, in view of the lower risk

    of infection
    SYMPTOMS

 than with

    infusion of fresh-frozen plasma
    MEDICATION

 and the observed effectiveness.

hereditary angioneurotic oedema
hereditary angioneurotic oedema


[Skin and hair].

Data deriving from comprehensive hospital monitoring systems suggest that drug-induced skin effects occur in 2-5% of patients receiving any drug medication. Exanthematous (maculopapular) reaction (75%) and urticaria with/without angioedema (30%) are the most frequent of all cutaneous reactions to drugs. The incidence of cutaneous reactions relates to the quantity of the drugs which is prescribed and consumed worldwide. Thus penicillin, sulfonamides and nonsteroidal antiinflammatory drugs show the highest rate of cutaneous side effects. Drug reactions may be classified as either predictable (e.g. chemotherapy-induced alopecia) or unpredictable. Unpredictable side effects of drugs may be the result of allergic (type I to IV) or non-allergic reactions. Hereditary and acquired enzyme deficiency and variations in metabolic pathway may delay drug metabolism and cause nonallergic, toxic side effects. Such a mechanism is known to occur in patients with a low acetylation rate under hydralazine, INH or sulfonamide treatment. Some immunologic although nonallergic factors may facilitate eruptions in patients with infectious mononucleosis under ampicillin medication and in AIDS patients on co-trimoxazole therapy. When a cutaneous drug reaction is diagnosed, withdrawal of the drug is recommended. In instances in which patients display mild drug eruptions and no alternative therapy is available, the drug may be continued. However, it should be kept in mind that mild morbiliform eruption is often the initial presentation of toxic epidermal necrolysis. In AIDS patients sulfonamides most frequently have been implicated as a risk factor for the development of toxic epidermal necrolysis. In other than type 1 hypersensitivity reactions, skin testing and in vitro tests have low sensitivity and specificity.

Data deriving from comprehensive hospital monitoring systems suggest that

    drug-induced skin effects
    SYMPTOMS

 occur in 2-5% of patients receiving any

    drug medication
    MEDICATION

.

    Exanthematous (maculopapular) reaction
    SYMPTOMS

 (75%) and

    urticaria with/without angioedema
    SYMPTOMS

 (30%) are the most frequent of all

    cutaneous reactions to drugs
    SYMPTOMS

. The incidence of

    cutaneous reactions
    SYMPTOMS

 relates to the quantity of the drugs which is prescribed and consumed worldwide. Thus

    penicillin
    SYMPTOMS

,

    sulfonamides
    MEDICATION

 and

    nonsteroidal antiinflammatory drugs
    MEDICATION

 show the highest rate of

    cutaneous side effects
    SYMPTOMS

.

    Drug reactions
    SYMPTOMS

 may be classified as either predictable (e.g.

    chemotherapy-induced alopecia
    SYMPTOMS

) or unpredictable.

    Unpredictable side effects of drugs
    SYMPTOMS

 may be the result of

    allergic (type I to IV) or non-allergic reactions
    DIAGNOSIS

.

    Hereditary and acquired enzyme deficiency
    GENETICS

 and

    variations in metabolic pathway
    GENETICS

 may

    delay drug metabolism
    BIOCHEMICAL

 and cause

    nonallergic, toxic side effects
    SYMPTOMS

. Such a mechanism is known to occur in patients with a

    low acetylation rate
    BIOCHEMICAL

 under

    hydralazine, INH or sulfonamide treatment
    MEDICATION

. Some

    immunologic although nonallergic factors
    NEG_FINDINGS

 may facilitate

    eruptions
    SYMPTOMS

 in patients with

    infectious mononucleosis
    DIAGNOSIS

 under

    ampicillin medication
    MEDICATION

 and in

    AIDS
    DIAGNOSIS

 patients on

    co-trimoxazole therapy
    MEDICATION

. When a

    cutaneous drug reaction
    SYMPTOMS

 is diagnosed,

    withdrawal of the drug
    MEDICATION

 is recommended. In instances in which patients display

    mild drug eruptions
    SYMPTOMS

 and

    no alternative therapy is available
    NEG_FINDINGS

, the drug may be continued. However, it should be kept in mind that

    mild morbiliform eruption
    SYMPTOMS

 is often the initial presentation of

    toxic epidermal necrolysis
    DIAGNOSIS

. In

    AIDS
    DIAGNOSIS

 patients

    sulfonamides
    DIAGNOSIS

 most frequently have been implicated as a risk factor for the development of

    toxic epidermal necrolysis
    DIAGNOSIS

. In other than

    type 1 hypersensitivity reactions
    DIAGNOSIS

,

    skin testing and in vitro tests
    PARACLINICAL

 have low sensitivity and specificity.

drug-induced skin effects
Exanthematous (maculopapular) reaction
urticaria with/without angioedema
cutaneous reactions to drugs
cutaneous reactions
penicillin
cutaneous side effects
Drug reactions
chemotherapy-induced alopecia
Unpredictable side effects of drugs
nonallergic, toxic side effects
eruptions
cutaneous drug reaction
mild drug eruptions
mild morbiliform eruption

delay drug metabolism
low acetylation rate


Hereditary angioedema caused by a point mutation of exon 7 in the C1 inhibitor gene.

Hereditary angioedema (HAE) is a genetic disease which may be detected serologically. We present a patient with HAE, in whom we examined the gene defect using the polymerase chain reaction. The patient presented with recurrent episodes of abdominal pain, or non-itchy swellings of the hands, feet, and penis. The serum levels of C1 inhibitor (C1-INH) and C4 were below normal. We determined that a single base change (C-->T) at nucleotide 1482 in the seventh exon was present in the C1-INH gene. This mutation converted the codon for the Gln-339 to a premature translation termination codon TAG. A point mutation in the C1-INH gene can cause type I HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    genetic disease
    GENETICS

 which may be detected serologically. We present a patient with

    HAE
    DIAGNOSIS

, in whom we examined the

    gene defect
    PARACLINICAL

 using the

    polymerase chain reaction
    PARACLINICAL

. The patient presented with

    recurrent episodes of abdominal pain
    SYMPTOMS

, or

    non-itchy swellings of the hands, feet, and penis
    SYMPTOMS

. The

    serum levels of C1 inhibitor (C1-INH) and C4 were below normal
    BIOCHEMICAL

. We determined that a

    single base change (C-->T) at nucleotide 1482 in the seventh exon was present in the C1-INH gene
    GENETICS

. This

    mutation converted the codon for the Gln-339 to a premature translation termination codon TAG
    GENETICS

. A

    point mutation in the C1-INH gene
    GENETICS

 can cause

    type I HAE
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
type I HAE


C1 inhibitor deficiency in a patient with rheumatoid arthritis--increased risk of adverse effects of penicillamine?

We report the coincidence of hereditary angioedema and rheumatoid arthritis in a male patient and in his father. During treatment with D-penicillamine the patient developed a transient lupus-like disorder with glomerulonephritis that resolved when D-penicillamine was discontinued. He later was diagnosed with malignant lymphoma. Impaired classical complement pathway function could have contributed to development of the drug reaction.

We report the coincidence of

    hereditary angioedema and rheumatoid arthritis
    DIAGNOSIS

 in a

    male
    GENDER

 patient

    and in his father
    FAMILY

. During

    treatment with D-penicillamine
    MEDICATION

 the patient developed a

    transient lupus-like disorder with glomerulonephritis
    DIAGNOSIS

 that resolved when

    D-penicillamine was discontinued
    MEDICATION

.

    He
    GENDER

 later was diagnosed with

    malignant lymphoma
    DIAGNOSIS

.

    Impaired classical complement pathway function
    BIOCHEMICAL

 could have contributed to development of the

    drug reaction
    SYMPTOMS

.

treatment with D-penicillamine
D-penicillamine was discontinued


[Hereditary angioneurotic edema in gynecology-obstetrics. Management].

Hereditary angioneurotic edema is a rare disease (250 cases currently identified in France). It is the most frequent among hereditary deficiencies of the complement system. This severe disease is fatal in 15-20% of the patients before 40 years of age. Death can be prevented if correct steps are taken in case of even minor trauma, which often trigger acute, potentially fatal, episodes. Danazol is used as preventive therapy before surgery and C1-esterase inhibitor or fresh frozen plasma is given for acute episodes. In case of obstetrical trauma, C1-esterase inhibitors should be used either as prophylaxy or as treatment. Fresh frozen plasma is used if C1-esterase inhibitors are not available. We report here our experience with three patients with known hereditary angioneurotic edema. Gynecology surgery was required in two.

    Hereditary angioneurotic edema
    DIAGNOSIS

 is a rare disease (250 cases currently identified in

    France
    ETHNICITY

). It is the most frequent among

    hereditary
    GENETICS

    deficiencies of the complement system
    BIOCHEMICAL

. This severe disease is fatal in 15-20% of the patients

    before 40 years of age
    AGE

.

    Death
    SYMPTOMS

 can be prevented if correct steps are taken in case of even

    minor trauma
    SYMPTOMS

, which often trigger

    acute, potentially fatal, episodes
    SYMPTOMS

.

    Danazol
    MEDICATION

 is used as

    preventive therapy before surgery
    MEDICATION

 and

    C1-esterase inhibitor or fresh frozen plasma
    MEDICATION

 is given for

    acute episodes
    SYMPTOMS

. In case of

    obstetrical trauma
    SYMPTOMS

,

    C1-esterase inhibitors
    MEDICATION

 should be used either as

    prophylaxy or as treatment
    MEDICATION

.

    Fresh frozen plasma
    MEDICATION

 is used if

    C1-esterase inhibitors are not available
    NEG_FINDINGS

. We report here our experience with three patients with known

    hereditary angioneurotic edema
    DIAGNOSIS

.

    Gynecology surgery
    MEDICATION

 was required in two.

Hereditary angioneurotic edema
hereditary angioneurotic edema

Death
minor trauma
acute, potentially fatal, episodes
acute episodes
obstetrical trauma


A mutation unique in serine protease inhibitors (serpins) identified in a family with type II hereditary angioneurotic edema.

Hereditary angioneurotic edema (HANE) is an autosomal dominant disease due to genetic alterations at the C1 inhibitor gene. Mutations within the C1 inhibitor gene are responsible for the molecular defect in type II HANE. Most of the dysfunctional proteins result from mutations involving the Arg-444 (the P-1 site of the reactive center) or amino acids NH2-terminal to the reactive center.

We have studied a Spanish family with type II HANE by using polymerase chain reaction (PCR) to amplify the exon eight of the C1 inhibitor gene. The purified 338-bp PCR product was subcloned and transformed into competent cells. After overnight cultures, we extracted the cloning vector from the positive colonies and sequenced both strands of the PCR product from each patient and healthy members of the family.

We show that affected individuals in this family have a missense mutation, changing an adenine to cytosine in the codon 445. This substitution changes threonine at the P-1' site of the reactive center to a proline. This mutation generates a new restriction site, recognized by Bsi YI.

To our knowledge, this is the first molecular defect characterized in a Spanish family with type II HANE, and to date, this is the first reported mutation at the P-1' site of the reactive center in individuals with type II HANE. This new mutation located at the reactive center emphasizes once more time the enormous heterogeneity of this gene.

    Hereditary angioneurotic edema (HANE)
    DIAGNOSIS

 is an

    autosomal dominant disease
    GENETICS

 due to

    genetic alterations at the C1 inhibitor gene
    GENETICS

.

    Mutations within the C1 inhibitor gene
    GENETICS

 are responsible for the

    molecular defect
    GENETICS

 in

    type II HANE
    DIAGNOSIS

. Most of the

    dysfunctional proteins
    GENETICS

 result from

    mutations involving the Arg-444 (the P-1 site of the reactive center) or amino acids NH2-terminal to the reactive center
    GENETICS

.

We have studied a

    Spanish
    ETHNICITY

    family with type II HANE
    FAMILY

 by using

    polymerase chain reaction (PCR) to amplify the exon eight of the C1 inhibitor gene
    PARACLINICAL

. The purified 338-bp PCR product was subcloned and transformed into competent cells. After

    overnight cultures
    PARACLINICAL

, we

    extracted the cloning vector from the positive colonies
    PARACLINICAL

 and

    sequenced both strands of the PCR product
    PARACLINICAL

 from each patient and healthy members of the family.

We show that affected individuals in this family have a

    missense mutation, changing an adenine to cytosine in the codon 445. This substitution changes threonine at the P-1' site of the reactive center to a proline
    GENETICS

. This mutation generates a new restriction site, recognized by Bsi YI.

To our knowledge, this is the first

    molecular defect
    GENETICS

 characterized in a

    Spanish
    ETHNICITY

    family with type II HANE
    FAMILY

, and to date, this is the first reported

    mutation at the P-1' site of the reactive center
    GENETICS

 in individuals with

    type II HANE
    DIAGNOSIS

. This

    new mutation located at the reactive center
    GENETICS

 emphasizes once more time the

    enormous heterogeneity of this gene
    GENETICS

.

Hereditary angioneurotic edema (HANE)
type II HANE
type II HANE


Hereditary angioneurotic oedema: current management in pregnancy.

A 20-year-old primiparous woman, with a history of type 1 hereditary angioneurotic oedema, presented for induction of labour. She was hirsute, obese and presented technical difficulties for both general and epidural/spinal anaesthesia. Her management included prophylactic C1 esterase inhibitors and epidural analgesia for pain relief. A spontaneous vaginal delivery was achieved and no adverse complications occurred. Five days after delivery she had abdominal pain which was investigated and resolved spontaneously. The management of this condition is discussed.

A

    20-year-old
    AGE

    primiparous
    GENDER

    woman
    GENDER

, with a

    history of type 1 hereditary angioneurotic oedema
    FAMILY

, presented for

    induction of labour
    MEDICATION

.

    She
    GENDER

 was

    hirsute
    SYMPTOMS

,

    obese
    MEDICATION

 and presented technical difficulties for both

    general and epidural/spinal anaesthesia
    MEDICATION

.

    Her
    GENDER

 management included

    prophylactic C1 esterase inhibitors
    MEDICATION

 and

    epidural analgesia
    MEDICATION

 for

    pain relief
    MEDICATION

. A

    spontaneous vaginal delivery
    MEDICATION

 was achieved and

    no adverse complications
    NEG_FINDINGS

 occurred. Five days after delivery

    she
    GENDER

 had

    abdominal pain
    SYMPTOMS

 which was investigated and resolved spontaneously. The management of this condition is discussed.

induction of labour
obese
general and epidural/spinal anaesthesia
prophylactic C1 esterase inhibitors
epidural analgesia
pain relief
spontaneous vaginal delivery


[Life threatening angioedema caused by acquired C1 inhibitor deficiency associated with paraproteinemia and livedo racemosa].

A 61-year-old patient with life-threatening angioneurotic oedema was found to have an acquired C1-inhibitor (C1-INH) deficiency. In addition to lowered serum levels of C1-INH (both protein concentration and enzymatic activity), C2, C4 and CH50, which are characteristic for the hereditary form of angioneurotic oedema, markedly lowered C1q was found, which is typical for the acquired form. There were no antibodies against C1-INH. Repeated thorough examination disclosed no neoplasm, though the presence of neoplasm has often been reported to be associated with the acquired C1-INH deficiency. However, the patient showed persistent paraproteinaemia and paraproteinuria and developed livedo reticularis. Treatment with danazol resulted in a rise of the complement fraction levels and cessation of angioneurotic oedema. Paraproteinaemia and livedo reticularis persisted unchanged.

A

    61-year-old
    AGE

 patient with

    life-threatening angioneurotic oedema
    SYMPTOMS

 was found to have an

    acquired C1-inhibitor (C1-INH) deficiency
    BIOCHEMICAL

. In addition to

    lowered serum levels of C1-INH (both protein concentration and enzymatic activity), C2, C4 and CH50
    BIOCHEMICAL

, which are characteristic for the hereditary form of

    angioneurotic oedema
    SYMPTOMS

,

    markedly lowered C1q was found
    BIOCHEMICAL

, which is typical for the acquired form. There were

    no antibodies against C1-INH
    NEG_FINDINGS

.

    Repeated thorough examination
    PARACLINICAL

 disclosed

    no neoplasm
    NEG_FINDINGS

, though the presence of neoplasm has often been reported to be associated with the

    acquired C1-INH deficiency
    BIOCHEMICAL

. However, the patient showed

    persistent paraproteinaemia
    BIOCHEMICAL

 and

    paraproteinuria
    BIOCHEMICAL

 and developed

    livedo reticularis
    SYMPTOMS

. Treatment with

    danazol
    MEDICATION

 resulted in a

    rise of the complement fraction levels
    BIOCHEMICAL

 and

    cessation of angioneurotic oedema
    SYMPTOMS

.

    Paraproteinaemia
    BIOCHEMICAL

 and

    livedo reticularis persisted unchanged
    NEG_FINDINGS

.

life-threatening angioneurotic oedema
angioneurotic oedema
livedo reticularis
cessation of angioneurotic oedema

no antibodies against C1-INH
no neoplasm
livedo reticularis persisted unchanged


Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed.

A

    26-year-old
    AGE

    woman
    GENDER

 with

    hereditary angineurotic oedema (HAE)
    SYMPTOMS

 presented at

    22 weeks gestation
    AGE

 with

    severe cutaneous necrosis similar to that seen in coumarin skin necrosis
    SYMPTOMS

.

    Protein S deficiency
    BIOCHEMICAL

 secondary to

    HAE
    DIAGNOSIS

 and

    pregnancy
    DIAGNOSIS

 was postulated.

    Treatment with heparin, C1-inhibitor concentrates, systemic steroids
    MEDICATION

 and

    surgical debridement
    MEDICATION

 resulted in a successful outcome for both mother and child. Subsequent investigations revealed

    normal levels of protein C, antithrombin III, total protein S, free protein S
    NEG_FINDINGS

 but

    reduced function protein S activity
    BIOCHEMICAL

 with

    evidence of activated protein C resistance
    BIOCHEMICAL

.

    Cutaneous necrosis
    SYMPTOMS

 has not been reported in associated with

    activated protein C resistance
    BIOCHEMICAL

 previously and the possible mechanisms are discussed.


Hereditary angioedema: an infrequent cause of abdominal pain with ascites.

Patients with hereditary angioedema have episodes of local swelling, usually affecting the face, extremities, upper airway, and gastrointestinal tract. Only infrequently does it cause recurrent abdominal pain (with or without ascites); however, because it has potentially life-threatening complications, an early diagnosis is important. We describe a case of type I hereditary angioedema (a quantitative deficit of C1 inhibitor), the sole initial symptom of which was severe recurrent and self-limited abdominal pain, accompanied by ascites during these episodes. During a 4-yr period of treatment with danazol, the patient was virtually asymptomatic, despite levels of C4 and C1 inhibitor that remained below normal limits, and there have been no major side effects that could be attributed to treatment with androgens.

Patients with

    hereditary angioedema
    DIAGNOSIS

 have

    episodes of local swelling, usually affecting the face, extremities, upper airway, and gastrointestinal tract
    SYMPTOMS

. Only infrequently does it cause

    recurrent abdominal pain (with or without ascites
    SYMPTOMS

); however, because it has potentially

    life-threatening complications
    SYMPTOMS

, an early diagnosis is important. We describe a case of

    type I hereditary angioedema
    DIAGNOSIS

 (a

    quantitative deficit of C1 inhibitor)
    BIOCHEMICAL

, the sole initial symptom of which was

    severe recurrent and self-limited abdominal pain
    SYMPTOMS

, accompanied by

    ascites
    SYMPTOMS

    during these episodes
    SYMPTOMS

. During a

    4-yr period of treatment with danazol
    MEDICATION

, the patient was

    virtually asymptomatic
    NEG_FINDINGS

, despite

    levels of C4 and C1 inhibitor that remained below normal limits
    BIOCHEMICAL

, and there have been

    no major side effects that could be attributed to treatment with androgens
    NEG_FINDINGS

.

hereditary angioedema
type I hereditary angioedema


[A fatal case of hereditary angioedema].

A 27 year old woman suffered from recurrent attacks of laryngeal oedema due to C1-inhibitor deficiency, and was treated with danazol and tranexamic acid. The trachea was intubated with great difficulty, twice on one occasion. Two and a half years later she was admitted to the Intensive Care Unit with dyspnoea and dysphagia. Tranexamic acid, corticosteroids, adrenaline (also inhalated), were administered intravenously, but dyspnoea progressed. During preparation for tracheostomy the patient suffered from sudden airway collapse. Attempts to ventilate by mask, puncture of the cricothyroid membrane and intubation were unsuccessful. A small tube was eventually inserted into the trachea after four minutes. The patient was then severely cyanotic with a pulse of thirty, and had dilated pupils. The next morning convulsions ensued and a CT scan showed cerebral oedema. In spite of treatment with pentothal, mannitol and hyperventilation she died. The authors advocate the use of intravenous infusion of C1-inhibitor concentrate, since traditional treatment is inadequate. Persons with hereditary angio-oedema should have a personal supply of C1-inhibitor at hand.

A

    27 year old
    AGE

    woman
    GENDER

 suffered from

    recurrent attacks of laryngeal oedema
    SYMPTOMS

 due to

    C1-inhibitor deficiency
    BIOCHEMICAL

, and was treated with

    danazol and tranexamic acid
    MEDICATION

. The

    trachea was intubated
    MEDICATION

 with great difficulty, twice on one occasion. Two and a half years later

    she
    GENDER

 was admitted to the

    Intensive Care Unit
    MEDICATION

 with

    dyspnoea
    SYMPTOMS

 and

    dysphagia
    SYMPTOMS

.

    Tranexamic acid, corticosteroids, adrenaline (also inhalated)
    MEDICATION

, were administered intravenously, but

    dyspnoea
    SYMPTOMS

 progressed. During preparation for

    tracheostomy
    MEDICATION

 the patient suffered from

    sudden airway collapse
    SYMPTOMS

.

    Attempts to ventilate by mask, puncture of the cricothyroid membrane and intubation were unsuccessful
    NEG_FINDINGS

. A

    small tube was eventually inserted into the trachea after four minutes
    MEDICATION

. The patient was then

    severely cyanotic with a pulse of thirty
    SYMPTOMS

, and had

    dilated pupils
    SYMPTOMS

. The next morning

    convulsions
    SYMPTOMS

 ensued and a

    CT scan
    PARACLINICAL

 showed

    cerebral oedema
    SYMPTOMS

. In spite of

    treatment with pentothal, mannitol and hyperventilation
    MEDICATION

    she
    GENDER

    died
    SYMPTOMS

. The authors advocate the use of

    intravenous infusion of C1-inhibitor concentrate
    MEDICATION

, since

    traditional treatment is inadequate
    NEG_FINDINGS

. Persons with

    hereditary angio-oedema
    DIAGNOSIS

 should have a personal supply of

    C1-inhibitor
    MEDICATION

 at hand.


Acquired deficiency in C1-inhibitor associated with signet ring cell gastric adenocarcinoma: a probable connection of antitumor-associated antibodies, hemolytic anemia, and complement turnover.

Acquired deficiency in C1-inhibitor (C1-INH) associated with malignancy is often asymptomatic because clinical manifestations are not dependent on a critical complement threshold (in contrast to hereditary C1-INH deficiency). Increased complement consumption involving different kinds of antibodies is the postulated mechanism for this disease, but other factors must play an important role.

A 76-year-old woman with unremarkable medical history experienced three episodes of angioedema over 6 months. Investigations revealed a complement profile characteristic of acquired deficiency in C1-INH, a hemolytic anemia, and a signet ring cell adenocarcinoma (linitis plastica). A gastrectomy and a splenectomy were performed. The postoperative course was characterized by a complete disappearance of the symptoms of angioedema and hemolytic anemia. A local recurrence of the tumor 5 months later could not be resected. The patient died 17 months after the initial surgery was performed.

Quantitative and functional analyses of the complement factors showed persistent excessive complement consumption. Markers of hemolytic anemia disappeared after tumor removal but recurred in the second part of the disease evolution. Immunohistochemical findings in tumor tissue showed loss of normal blood group antigens but expression of Lea antigen, as well as C1q deposition.

To explain the whole clinical and laboratory picture, we hypothesize a connection between tumor immunohistochemical profile, complement consumption, and hemolytic anemia. Tumor cell surface antigens might lead to a permanent but asymptomatic complement consumption that is worsened and becomes clinically manifest by superimposed hemolytic anemia caused by cross-reactive antibodies to newly expressed blood group antigens on tumor cells. This hypothesis should be confirmed by other observations.

    Acquired deficiency in C1-inhibitor (C1-INH)
    BIOCHEMICAL

 associated with

    malignancy
    DIAGNOSIS

 is often

    asymptomatic
    NEG_FINDINGS

 because

    clinical manifestations are not dependent on a critical complement threshold
    NEG_FINDINGS

 (in contrast to

    hereditary C1-INH deficiency
    BIOCHEMICAL

).

    Increased complement consumption involving different kinds of antibodies
    BIOCHEMICAL

 is the postulated mechanism for this disease, but other factors must play an important role.

A

    76-year-old
    AGE

    woman
    GENDER

 with

    unremarkable medical history
    NEG_FINDINGS

 experienced

    three episodes of angioedema over 6 months
    SYMPTOMS

. Investigations revealed a

    complement profile characteristic of acquired deficiency in C1-INH
    BIOCHEMICAL

, a

    hemolytic anemia
    BIOCHEMICAL

, and a

    signet ring cell adenocarcinoma (linitis plastica)
    DIAGNOSIS

. A

    gastrectomy
    MEDICATION

 and a

    splenectomy
    MEDICATION

 were performed. The postoperative course was characterized by a

    complete disappearance of the symptoms of angioedema
    SYMPTOMS

 and

    hemolytic anemia
    BIOCHEMICAL

. A

    local recurrence of the tumor 5 months later could not be resected
    SYMPTOMS

. The patient

    died
    SYMPTOMS

 17 months after the

    initial surgery
    MEDICATION

 was performed.

    Quantitative and functional analyses of the complement factors
    PARACLINICAL

 showed

    persistent excessive complement consumption
    BIOCHEMICAL

.

    Markers of hemolytic anemia disappeared
    BIOCHEMICAL

 after

    tumor removal
    MEDICATION

 but

    recurred
    SYMPTOMS

 in the second part of the disease evolution.

    Immunohistochemical findings
    PARACLINICAL

 in

    tumor tissue
    MICROSCOPIC

 showed

    loss of normal blood group antigens
    BIOCHEMICAL

 but

    expression of Lea antigen
    BIOCHEMICAL

, as well as

    C1q deposition
    MICROSCOPIC

.

To explain the whole clinical and laboratory picture, we hypothesize a connection between

    tumor immunohistochemical profile
    MICROSCOPIC

,

    complement consumption
    BIOCHEMICAL

, and

    hemolytic anemia
    BIOCHEMICAL

.

    Tumor cell surface antigens
    MICROSCOPIC

 might lead to a

    permanent but asymptomatic complement consumption
    BIOCHEMICAL

 that is worsened and becomes clinically manifest by

    superimposed hemolytic anemia
    BIOCHEMICAL

 caused by

    cross-reactive antibodies to newly expressed blood group antigens on tumor cells
    BIOCHEMICAL

. This hypothesis should be confirmed by other observations.

gastrectomy
splenectomy
initial surgery
tumor removal


Tonsillectomy in a patient with hereditary angioedema after prophylaxis with C1 inhibitor concentrate.

A 15-year-old young man with a history of recurrent streptococcal pharyngitis and hereditary angioedema presented for tonsillectomy. Preoperative physical examination was normal with the exception of enlarged pharyngeal tonsils with crypts and pustules; there was no evidence of angioedema. Laboratory studies were remarkable for a C4 level of 8 mg/dL (normal 20-50 mg/dL) and C1 inhibitor (C1 INH) level of 4 mg/dL (normal 11-26 mg/dL).

To report the use of C1 INH concentrate as prophylactic treatment for a patient with hereditary angioedema who required tonsillectomy.

The patient was treated with stanozolol 4 mg po quid and clindamycin 150 mg po tid during the week before the procedure. Two hours prior to surgery, he received 2300 plasma units of intravenous C1-inhibitor (Human) Vapor Heated, IMMUNO (IMMUNO Clinical Research Corporation, New York, NY).

Approximately eight hours after an uncomplicated tonsillectomy, the patient began to experience crampy abdominal pain, typical of his hereditary angioedema. Beginning 22 hours after surgery, he had facial swelling and complained of difficulty swallowing and the sensation of throat swelling. The symptoms resolved over the next eight hours. Serial laboratory examinations revealed: [table: see text]

We believe that the occurrence of abdominal pain, facial swelling, and difficulty swallowing suggests that this patient may have experienced a mild, generalized flare of hereditary angioedema during the postoperative period in spite of prophylactic therapy with both anabolic steroids and C1 INH concentrate. This serves as a reminder that patients with hereditary angioedema require close observation following invasive procedures even after premedication with stanozolol and C1 INH concentrate.

A

    15-year-old
    AGE

    young
    AGE

    man
    GENDER

 with a history of

    recurrent streptococcal pharyngitis
    DIAGNOSIS

 and

    hereditary angioedema
    DIAGNOSIS

 presented for

    tonsillectomy
    MEDICATION

.

    Preoperative physical examination was normal
    NEG_FINDINGS

 with the exception of

    enlarged pharyngeal tonsils with crypts and pustules
    SYMPTOMS

; there was

    no evidence of angioedema
    NEG_FINDINGS

.

    Laboratory studies
    PARACLINICAL

 were remarkable for a

    C4 level of 8 mg/dL (normal 20-50 mg/dL)
    BIOCHEMICAL

 and

    C1 inhibitor (C1 INH) level of 4 mg/dL (normal 11-26 mg/dL)
    BIOCHEMICAL

.

To report the use of

    C1 INH concentrate as prophylactic treatment
    MEDICATION

 for a patient with

    hereditary angioedema
    DIAGNOSIS

 who required

    tonsillectomy
    MEDICATION

.

The patient was

    treated with stanozolol 4 mg po quid and clindamycin 150 mg po tid during the week before the procedure
    MEDICATION

.

    Two hours prior to surgery
    MEDICATION

,

    he
    GENDER

    received 2300 plasma units of intravenous C1-inhibitor (Human) Vapor Heated, IMMUNO (IMMUNO Clinical Research Corporation
    MEDICATION

, New York, NY).

Approximately eight hours after an

    uncomplicated tonsillectomy
    MEDICATION

, the patient began to experience

    crampy abdominal pain
    SYMPTOMS

, typical of his

    hereditary angioedema
    DIAGNOSIS

. Beginning 22 hours after

    surgery
    MEDICATION

,

    he
    GENDER

 had

    facial swelling
    SYMPTOMS

 and complained of

    difficulty swallowing
    SYMPTOMS

 and the

    sensation of throat swelling
    SYMPTOMS

. The symptoms resolved over the next eight hours.

    Serial laboratory examinations
    PARACLINICAL

 revealed: [table: see text]

We believe that the occurrence of

    abdominal pain
    SYMPTOMS

,

    facial swelling
    SYMPTOMS

, and

    difficulty swallowing
    SYMPTOMS

 suggests that this patient may have experienced a

    mild, generalized flare of hereditary angioedema
    SYMPTOMS

 during the postoperative period in

    spite of prophylactic therapy with both anabolic steroids and C1 INH concentrate
    NEG_FINDINGS

. This serves as a reminder that patients with

    hereditary angioedema
    DIAGNOSIS

 require

    close observation
    PARACLINICAL

 following

    invasive procedures
    MEDICATION

 even after

    premedication with stanozolol and C1 INH concentrate
    MEDICATION

.

recurrent streptococcal pharyngitis
hereditary angioedema
hereditary angioedema
hereditary angioedema
hereditary angioedema


Type II hereditary angioedema: presentation and follow-up of three cases.

Three cases with a family history of type II hereditary angioedema (HAE) are presented, together with their progress following treatment with stanozolol. The development of patients with this drug was satisfactory in clinical terms, as it gave rise to virtually no side effects or angioedema episodes. Only patient 3 showed an elevation of hepatic enzyme (SGOT, SGPT) levels in serum, 2 months after starting treatment. C4 values of patient 2 attained sporadic normalization in the first five months of treatment, while the values corresponding to the other two patients remained below normal at all times. The activity of C1 inhibitor (C1-INH) remained below normal in all three cases. In patient 3, it was observed that circulating immunocomplex (CIC) monitoring was, together with clinical progress, a useful method for controlling HAE activity.

Three cases with a

    family history of type II hereditary angioedema (HAE)
    FAMILY

 are presented, together with their progress following treatment with

    stanozolol
    MEDICATION

. The development of patients with this drug was satisfactory in clinical terms, as it gave rise to virtually

    no side effects or angioedema episodes
    NEG_FINDINGS

. Only patient 3 showed an

    elevation of hepatic enzyme (SGOT, SGPT) levels in serum
    BIOCHEMICAL

, 2 months after starting treatment.

    C4 values
    BIOCHEMICAL

 of patient 2

    attained sporadic normalization
    BIOCHEMICAL

 in the first five months of treatment, while the values corresponding to the other two patients

    remained below normal
    BIOCHEMICAL

 at all times.

    The activity of C1 inhibitor (C1-INH) remained below normal
    BIOCHEMICAL

 in all three cases. In patient 3, it was observed that

    circulating immunocomplex (CIC) monitoring
    PARACLINICAL

 was, together with clinical progress, a useful method for controlling

    HAE activity
    BIOCHEMICAL

.


[Melkersson-Rosenthal syndrome].

Melkersson-Rosenthal's syndrome is characterized by recurrent or persistent oedema of the lips or the face; the fissured tongue, and intermittent paralysis of the facial nerve. Oligosymptomatic forms are more common than the triad. The syndrome is rarely encountered, it is aetiologycally obscure, the laboratory findings are not specific, but differential diagnosis is very complex, especially in conditions of recurrent and hereditary angioedema. The authors report two cases of the syndrome: the first with the triad and mild neurological symptoms, and the second with two syndrome elements, oedema of the lips and the fissured tongue. Pathohistological results of the biopsy samples of oral mucosa revealed the advanced phase with granulomatous lesions in one case, and early phase with oedema of the connective tissue and perivascular lymphocyte infiltration in the second. Allergic genesis was ruled out, based on negative results of numerous laboratory and clinical tests. Glycocorticoid therapy with antihistaminics and anabolica resulted in clinical improvement.

    Melkersson-Rosenthal's syndrome
    DIAGNOSIS

 is characterized by

    recurrent or persistent oedema of the lips or the face; the fissured tongue
    SYMPTOMS

, and

    intermittent paralysis of the facial nerve
    SYMPTOMS

.

    Oligosymptomatic
    SYMPTOMS

 forms are more common than the triad. The syndrome is rarely encountered, it is aetiologycally obscure, the

    laboratory findings are not specific
    NEG_FINDINGS

, but

    differential diagnosis
    PARACLINICAL

 is very complex, especially in conditions of

    recurrent
    DIAGNOSIS

 and

    hereditary angioedema
    DIAGNOSIS

. The authors report two cases of the syndrome: the first with the triad and

    mild neurological symptoms
    SYMPTOMS

, and the second with

    two syndrome elements
    SYMPTOMS

,

    oedema of the lips and the fissured tongue
    SYMPTOMS

.

    Pathohistological results of the biopsy samples of oral mucosa
    PARACLINICAL

 revealed the

    advanced phase with granulomatous lesions
    MICROSCOPIC

 in one case, and

    early phase with oedema of the connective tissue
    MICROSCOPIC

 and

    perivascular lymphocyte infiltration
    MICROSCOPIC

 in the second.

    Allergic genesis was ruled out
    NEG_FINDINGS

, based on

    negative results of numerous laboratory and clinical tests
    NEG_FINDINGS

.

    Glycocorticoid therapy with antihistaminics and anabolica
    MEDICATION

 resulted in

    clinical improvement
    SYMPTOMS

.

Melkersson-Rosenthal's syndrome
recurrent
hereditary angioedema


Hereditary angioedema presenting with adult respiratory distress syndrome.

Adult respiratory distress syndrome (ARDS) could be related to upper airway obstruction. Mechanical obstruction and complement activation could lead to ARDS development. We describe a patient with hereditary angioedema, laryngeal edema, and ARDS.

    Adult respiratory distress syndrome (ARDS)
    DIAGNOSIS

 could be related to

    upper airway obstruction
    SYMPTOMS

.

    Mechanical obstruction
    SYMPTOMS

 and

    complement activation
    BIOCHEMICAL

 could lead to

    ARDS
    DIAGNOSIS

 development. We describe a patient with

    hereditary angioedema
    DIAGNOSIS

,

    laryngeal edema
    SYMPTOMS

, and

    ARDS
    DIAGNOSIS

.

upper airway obstruction
Mechanical obstruction
laryngeal edema


[A case of hereditary angioedema].

The authors describe a case of hereditary angioedema in a female child of four years. Treatment with C1 human-immuno-inactivator. Good success of therapy.

The authors describe a case of

    hereditary angioedema
    DIAGNOSIS

 in a

    female
    GENDER

    child of four years
    AGE

.

    Treatment with C1 human-immuno-inactivator
    MEDICATION

. Good success of therapy.


Protein S deficiency in lupus erythematosus secondary to hereditary angio-oedema.

We report a child with lupus erythematosus secondary to type 2 hereditary angio-oedema (HAE). Reduced levels of free protein S were found. Total protein S, and C4 binding protein (C4bp) were normal, and there was no evidence of anticardiolipin antibodies or lupus anticoagulant. We postulate that reduced levels of C4, secondary to C1 inhibitor deficiency, resulted in increased binding of protein S to C4bp, leading to reduced levels of free protein S and thus functional deficiency of protein S.

We report a

    child
    AGE

 with

    lupus erythematosus
    DIAGNOSIS

 secondary to

    type 2 hereditary angio-oedema (HAE)
    DIAGNOSIS

.

    Reduced levels of free protein S were found
    BIOCHEMICAL

.

    Total protein S, and C4 binding protein (C4bp) were normal
    NEG_FINDINGS

, and there was

    no evidence of anticardiolipin antibodies or lupus anticoagulant
    NEG_FINDINGS

. We postulate that

    reduced levels of C4
    BIOCHEMICAL

, secondary to

    C1 inhibitor deficiency
    BIOCHEMICAL

, resulted in

    increased binding of protein S to C4bp
    BIOCHEMICAL

, leading to

    reduced levels of free protein S
    BIOCHEMICAL

 and thus

    functional deficiency of protein S.
    BIOCHEMICAL

lupus erythematosus
type 2 hereditary angio-oedema (HAE)


A de novo deletion in the C1 inhibitor gene in a case of sporadic hereditary angioneurotic edema.

A sporadic case of hereditary angioneurotic edema (HANE) is reported here. The patient was a 15-year-old girl who for 4 years had suffered recurrent episodes of urticaria-like erythema, followed by vomiting with abdominal pain. She was diagnosed as having Sjögren syndrome by results of sialography and serological studies, and moreover, it was also observed that the C1 inhibitor (C1-INH) activity in her plasma was very low during these episodes of urticarial erythema. Diagnosis of acquired angioneurotic edema (AANE) was excluded because the patient's plasma had no inhibitory effect on the C1-INH activity of normal individuals. Although neither of her parents had a history of HANE, we were able to show that the patient had HANE by Southern blot analysis using C1-INH cDNA as a probe. One of the patient's C1-INH gene alleles was revealed to have at least a 17-kb-length deletion including exons 5-8. Neither her parents nor her healthy brother showed any abnormalities on Southern blot analysis. The parent-child relationship in this family was confirmed by an HLA-typing study of all family members.

A sporadic case of

    hereditary angioneurotic edema (HANE)
    DIAGNOSIS

 is reported here. The patient was a

    15-year-old
    AGE

    girl
    GENDER

 who for 4 years had suffered

    recurrent episodes of urticaria-like erythema
    SYMPTOMS

, followed by

    vomiting
    SYMPTOMS

 with

    abdominal pain
    SYMPTOMS

.

    She
    GENDER

 was diagnosed as having

    Sjögren syndrome
    DIAGNOSIS

 by results of

    sialography
    PARACLINICAL

 and

    serological studies
    PARACLINICAL

, and moreover, it was also observed that

    the C1 inhibitor (C1-INH) activity in her plasma was very low
    BIOCHEMICAL

 during

    these episodes of urticarial erythema
    SYMPTOMS

.

    Diagnosis of acquired angioneurotic edema (AANE) was excluded
    NEG_FINDINGS

 because the patient's

    plasma had no inhibitory effect on the C1-INH activity of normal individuals
    NEG_FINDINGS

. Although

    neither of her parents had a history of HANE
    FAMILY

, we were able to show that the patient had

    HANE
    DIAGNOSIS

 by

    Southern blot analysis using C1-INH cDNA as a probe
    PARACLINICAL

.

    One of the patient's C1-INH gene alleles was revealed to have at least a 17-kb-length deletion including exons 5-8
    GENETICS

.

    Neither her parents nor her healthy brother showed any abnormalities on Southern blot analysis
    NEG_FINDINGS

.

    The parent-child relationship in this family was
    FAMILY

 confirmed by an

    HLA-typing study of all family members
    PARACLINICAL

.

hereditary angioneurotic edema (HANE)
Sjögren syndrome
HANE


Hereditary angioneurotic edema with severe hypovolemic shock.

Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients.

    Hereditary angioneurotic edema (HAE)
    DIAGNOSIS

 is characterized by

    recurrent attacks of edema of the upper airways, face, and limbs
    SYMPTOMS

, and/or

    abdominal pains
    SYMPTOMS

 sometimes

    mimicking surgical abdomen
    SYMPTOMS

. Our patient, a

    24-year-old
    AGE

    woman
    GENDER

, had undergone

    laparotomy
    MEDICATION

 on a previous attack, at which a

    large amount of serious peritoneal fluid
    MICROSCOPIC

 and

    edema of the intestinal wall
    SYMPTOMS

 were found. This time

    she
    GENDER

 presented with

    severe abdominal pain
    SYMPTOMS

 and

    profound hypovolemic shock
    SYMPTOMS

 requiring

    replacement of great amounts of fluids in addition to fresh frozen plasma
    MEDICATION

. There was

    no evidence of bleeding
    NEG_FINDINGS

, and the patient recovered rapidly. Based on clinical and

    ultrasonographic
    PARACLINICAL

 grounds and findings on

    previous laparotomy
    PARACLINICAL

, we concluded that the

    shock
    SYMPTOMS

 was produced by

    fluid sequestration in the peritoneal cavity and intestinal wall
    MICROSCOPIC

. We propose that patients with

    HAE
    DIAGNOSIS

 who present with

    abdominal pain
    SYMPTOMS

,

    hypotension
    SYMPTOMS

,

    hemoconcentration
    BIOCHEMICAL

, and

    leukocytosis
    BIOCHEMICAL

 form a distinct subgroup with a high risk of

    hypovolemic shock
    SYMPTOMS

. This dangerous development should be anticipated in these patients.

Hereditary angioneurotic edema (HAE)
HAE


Quincke's disease: nonhereditary angioneurotic edema of the uvula.

We report two cases of Quincke's disease, an isolated form of angioneurotic edema involving the uvula that is induced by several factors, including foods, drugs, and inhalants. Although Quincke's disease has prominent oral manifestations, it has only rarely been described in the dental literature. The rapid onset and progression of the disorder, combined with the risk of respiratory compromise, may result in a serious medial emergency. Clinical manifestations include a nonerythematous swollen uvula, fullness in the throat, and signs of airway obstruction. A hereditary form of angioneurotic edema is associated with a biochemical defect; this must be differentiated from nonhereditary, localized forms such as Quincke's disease to determine appropriate treatment and predict prognosis. Clinical features and laboratory tests can distinguish hereditary angioneurotic edema from the nonhereditary form.

We report two cases of

    Quincke's disease
    DIAGNOSIS

, an

    isolated form of angioneurotic edema involving the uvula
    SYMPTOMS

 that is induced by several factors, including

    foods
    SYMPTOMS

, drugs, and

    inhalants
    SYMPTOMS

. Although

    Quincke's disease
    DIAGNOSIS

 has

    prominent oral manifestations
    SYMPTOMS

, it has only rarely been described in the dental literature. The rapid onset and progression of the disorder, combined with the risk of

    respiratory compromise
    SYMPTOMS

, may result in a serious medial emergency. Clinical manifestations include a

    nonerythematous swollen uvula
    SYMPTOMS

,

    fullness in the throat
    SYMPTOMS

, and

    signs of airway obstruction
    SYMPTOMS

. A

    hereditary form of angioneurotic edema
    DIAGNOSIS

 is associated with a

    biochemical defect
    GENETICS

; this must be differentiated from

    nonhereditary, localized
    DIAGNOSIS

 forms such as

    Quincke's disease
    DIAGNOSIS

 to determine appropriate treatment and predict prognosis. Clinical features and

    laboratory tests
    PARACLINICAL

 can distinguish

    hereditary angioneurotic edema
    DIAGNOSIS

 from the

    nonhereditary form
    DIAGNOSIS

.

Quincke's disease
Quincke's disease
hereditary form of angioneurotic edema
nonhereditary, localized
Quincke's disease
hereditary angioneurotic edema
nonhereditary form


Familial cold urticaria. Investigation of a family and response to stanozolol.

Familial cold urticaria is a rare cutaneous and systemic reaction to cold with autosomal dominant inheritance, distinctive clinical features, and unknown pathogenesis. Release of a chymotrypsinlike substance has been postulated. To date, no effective treatment has been reported.

Eight cases from a large family pedigree are described. Three members showed a very favorable response in their cold urticaria, when treated with stanozolol; the response was reproducible. Histologic examination of an early lesion in one case revealed evidence of mast cell degranulation.

The biochemical observations are probably secondary epiphenomena. Correction of a deficiency of an inhibitory protein is a possible mechanism of action of stanozolol as in hereditary angioedema.

    Familial cold urticaria
    DIAGNOSIS

 is a

    rare cutaneous and systemic reaction to cold
    SYMPTOMS

 with

    autosomal dominant inheritance
    GENETICS

,

    distinctive clinical features
    SYMPTOMS

, and unknown pathogenesis.

    Release of a chymotrypsinlike substance
    BIOCHEMICAL

 has been postulated. To date, no effective treatment has been reported.

Eight cases from a large family pedigree are described. Three members showed a

    very favorable response in their cold urticaria
    SYMPTOMS

, when treated with

    stanozolol
    MEDICATION

; the response was reproducible.

    Histologic examination of an early lesion
    PARACLINICAL

 in one case revealed

    evidence of mast cell degranulation
    MICROSCOPIC

.

The

    biochemical observations
    SYMPTOMS

 are probably

    secondary epiphenomena
    SYMPTOMS

.

    Correction of a deficiency of an inhibitory protein
    BIOCHEMICAL

 is a possible mechanism of action of

    stanozolol
    MEDICATION

 as in

    hereditary angioedema
    DIAGNOSIS

.

Familial cold urticaria
hereditary angioedema


Angioedema presenting as chronic gastrointestinal symptoms.

Gastrointestinal complaints may be the presenting feature of patients with acquired or hereditary angioedema. We describe two patients with episodic nausea, abdominal pain, and cramping secondary to C1 inhibitor deficiency. In one patient, an acquired deficiency arose as a paraneoplastic syndrome with abdominal complaints preceding the diagnosis of an occult lymphoma. The second patient presented at age 61 with abdominal complaints secondary to a hereditary deficiency of C1 inhibitor. The patients' symptoms were due to gastrointestinal angioedema, resulting from episodic unregulated complement activation. The biochemical mechanism of this unusual syndrome and its diagnostic importance are discussed. A C1 inhibitor deficiency should be considered in patients with unexplained abdominal symptoms suggestive of intestinal pseudo-obstruction.

    Gastrointestinal complaints
    SYMPTOMS

 may be the presenting feature of patients with

    acquired
    DIAGNOSIS

 or

    hereditary
    GENETICS

    angioedema
    DIAGNOSIS

. We describe two patients with

    episodic nausea
    SYMPTOMS

,

    abdominal pain
    SYMPTOMS

, and

    cramping
    SYMPTOMS

 secondary to

    C1 inhibitor deficiency
    BIOCHEMICAL

. In one patient, an

    acquired deficiency
    BIOCHEMICAL

 arose as a

    paraneoplastic syndrome
    DIAGNOSIS

 with

    abdominal complaints
    SYMPTOMS

 preceding the diagnosis of an

    occult lymphoma
    DIAGNOSIS

. The second patient presented at

    age 61
    AGE

 with

    abdominal complaints
    SYMPTOMS

 secondary to a

    hereditary
    GENETICS

    deficiency of C1 inhibitor
    BIOCHEMICAL

. The patients' symptoms were due to

    gastrointestinal angioedema
    SYMPTOMS

, resulting from

    episodic unregulated complement activation
    BIOCHEMICAL

. The biochemical mechanism of this unusual syndrome and its diagnostic importance are discussed. A

    C1 inhibitor deficiency
    BIOCHEMICAL

 should be considered in patients with

    unexplained abdominal symptoms
    SYMPTOMS

 suggestive of

    intestinal pseudo-obstruction
    SYMPTOMS

.

Gastrointestinal complaints
episodic nausea
abdominal pain
cramping
abdominal complaints
abdominal complaints
gastrointestinal angioedema
unexplained abdominal symptoms
intestinal pseudo-obstruction

acquired
angioedema
paraneoplastic syndrome
occult lymphoma


IgA nephropathy in hereditary angioedema.

Hereditary angioedema is an autosomal dominant disorder of the complement system in which there is a deficiency of the inhibitor of the activated first component of complement. We have previously reported on three generations of a family with classic hereditary angioedema. Three members of this family have now developed IgA nephropathy. The association of hereditary angioedema with various immunoregulatory disorders has been previously reported but this is the first report of IgA nephropathy in association with this condition.

    Hereditary angioedema
    DIAGNOSIS

 is an

    autosomal dominant
    GENETICS

    disorder of the complement system
    DIAGNOSIS

 in which there is a

    deficiency of the inhibitor of the activated first component of complement
    BIOCHEMICAL

. We have previously reported on

    three generations of a family with classic hereditary angioedema
    FAMILY

. Three members of this family have now developed

    IgA nephropathy
    DIAGNOSIS

. The association of

    hereditary angioedema
    DIAGNOSIS

 with various

    immunoregulatory disorders
    DIAGNOSIS

 has been previously reported but this is the first report of

    IgA nephropathy
    DIAGNOSIS

 in association with this condition.

Hereditary angioedema
disorder of the complement system
IgA nephropathy
hereditary angioedema
immunoregulatory disorders
IgA nephropathy


Hereditary angioedema: uncomplicated maxillofacial surgery using short-term C1 inhibitor replacement therapy.

We report on the successful use of a pasteurized C1 inhibitor (C1-INH) concentrate during dental surgery of a patient affected by hereditary angioedema. The patient recovered fully without complications or side effects. Within 30 min, the first 1,000 U of C1-INH concentrate raised C1-INH concentration from 19 to 55% and function from 40 to 90% of the normal mean. When measured 4 h after the second injection, a further increase of the C1-INH concentration to 86% and a function of 106% relative to the normal mean was observed. Within 2 weeks C1-INH concentration returned to pretreatment level, while the function remained above this value. Serum liver enzyme values did not change and no anti-C1-INH alloantibodies were detected 10 months post-replacement therapy. We conclude that in patients affected by C1-INH deficiency, dental surgery and likely other traumatic procedures can be safely performed in conjunction with C1-INH replacement therapy even without preliminary treatment.

We report on the successful

    use of a pasteurized C1 inhibitor (C1-INH) concentrate during dental surgery
    MEDICATION

 of a patient affected by

    hereditary angioedema
    DIAGNOSIS

. The patient recovered fully

    without complications or side effects
    NEG_FINDINGS

. Within 30 min, the

    first 1,000 U of C1-INH concentrate raised C1-INH concentration from 19 to 55% and function from 40 to 90% of the normal mean
    MEDICATION

. When measured 4 h after the second injection, a

    further increase of the C1-INH concentration to 86% and a function of 106% relative to the normal mean
    BIOCHEMICAL

 was observed. Within 2 weeks

    C1-INH concentration returned to pretreatment level
    BIOCHEMICAL

, while

    the function remained above this value
    BIOCHEMICAL

.

    Serum liver enzyme values did not change
    NEG_FINDINGS

 and

    no anti-C1-INH alloantibodies were detected 10 months post-replacement therapy
    NEG_FINDINGS

. We conclude that in patients affected by

    C1-INH deficiency
    BIOCHEMICAL

,

    dental surgery
    MEDICATION

 and likely other

    traumatic procedures
    MEDICATION

 can be safely performed in

    conjunction with C1-INH replacement therapy
    MEDICATION

 even

    without preliminary treatment
    NEG_FINDINGS

.


[Anesthesia in a case of hereditary angioneurotic edema].

The case of a 51 year old woman diagnosed with hereditary angioneurotic edema (HANE) requiring hospital admission on one occasion is presented. The patient was scheduled for abdominal hysterectomy of uterine myomas. Upon presentation to the authors, the patient was not under treatment and was asymptomatic. The patient was given 1000 units of C1-INH two hours prior to surgery. The operation was performed under peridural anesthesia to which no complications were presented. Specific treatment included: short term prophylaxis prior to surgery with C1-INH or fresh plasma and/or antifibrinolytic and hormonal agents. The authors considered that the locoregional techniques are elective to avoid tracheal intubation.

The case of a

    51 year old
    AGE

    woman
    GENDER

 diagnosed with

    hereditary angioneurotic edema (HANE)
    DIAGNOSIS

 requiring

    hospital admission
    MEDICATION

 on one occasion is presented. The patient was scheduled for

    abdominal hysterectomy of uterine myomas
    MEDICATION

. Upon presentation to the authors, the patient was

    not under treatment
    NEG_FINDINGS

 and was

    asymptomatic
    NEG_FINDINGS

. The patient was

    given 1000 units of C1-INH two hours prior to surgery
    MEDICATION

. The

    operation
    MEDICATION

 was performed

    under peridural anesthesia
    MEDICATION

 to which

    no complications
    NEG_FINDINGS

 were presented. Specific treatment included:

    short term prophylaxis prior to surgery with C1-INH or fresh plasma and/or antifibrinolytic and hormonal agents
    MEDICATION

. The authors considered that the

    locoregional techniques
    MEDICATION

 are elective to

    avoid tracheal intubation
    MEDICATION

.

not under treatment
asymptomatic
no complications


Hereditary angioedema associated with pancreatitis.

A 44-year-old woman with C1q esterase inhibitor deficiency was seen in consultation for recurrent right upper quadrant abdominal discomfort, nausea, and vomiting. Each of these episodes was accompanied by concomitant peripheral edema. Initial diagnostic efforts were fruitless. In time, intermittent elevations in amylase and lipase developed, and a diagnosis of relapsing pancreatitis was made. We contend that the patient's recurrent acute pancreatitis is associated with her hereditary angioedema. Possible pathogenesis could involve intermittent intrapancreatic edema with partial ductal obstruction or loss of inhibition on the kallikrein-kinin system.

A

    44-year-old
    AGE

    woman
    GENDER

 with

    C1q esterase inhibitor deficiency
    BIOCHEMICAL

 was seen in consultation for

    recurrent right upper quadrant abdominal discomfort
    SYMPTOMS

,

    nausea
    SYMPTOMS

, and

    vomiting
    SYMPTOMS

. Each of these episodes was accompanied by concomitant

    peripheral edema
    SYMPTOMS

.

    Initial diagnostic efforts were fruitless
    NEG_FINDINGS

. In time,

    intermittent elevations in amylase and lipase developed
    BIOCHEMICAL

, and a diagnosis of

    relapsing pancreatitis
    DIAGNOSIS

 was made. We contend that the patient's

    recurrent acute pancreatitis
    DIAGNOSIS

 is associated with her

    hereditary angioedema
    DIAGNOSIS

. Possible pathogenesis could involve

    intermittent intrapancreatic edema
    SYMPTOMS

 with

    partial ductal obstruction
    SYMPTOMS

 or

    loss of inhibition on the kallikrein-kinin system
    BIOCHEMICAL

.

relapsing pancreatitis
recurrent acute pancreatitis
hereditary angioedema


Hereditary angioedema.

Hereditary angioedema is a rare disease resulting from a lack of functional C1 esterase inhibitor (C1 INH). Several genetic defects can cause decreased production of the protein or the synthesis of a biologically inactive form. A similar, acquired condition is occasionally seen, associated with malignancies or as an autoimmune process. Disease severity varies greatly among affected individuals. Most patients have cutaneous, laryngeal, or gastrointestinal edema, often in combinations. The symptoms may appear spontaneously or result from a stimulus, usually trauma. When clinical suspicion exists, measurement of the C4 level screens for the disease. An assay showing low serum C1 INH function confirms the diagnosis. When disease severity warrants, symptoms can be controlled with anabolic steroids or antifibrinolytics. Doses should be increased before symptom-provoking events. Emergencies are treated with plasma infusions, fluids, and pain control. Where available, C1 INH concentrate is the treatment of choice. Therapy can usually be monitored by control of symptoms. With appropriate therapy, most cases remain well controlled.

    Hereditary angioedema
    DIAGNOSIS

 is a rare disease resulting from a

    lack of functional C1 esterase inhibitor (C1 INH)
    BIOCHEMICAL

. Several

    genetic defects
    GENETICS

 can cause

    decreased production of the protein or the synthesis of a biologically inactive form
    BIOCHEMICAL

. A similar, acquired condition is occasionally seen, associated with

    malignancies
    DIAGNOSIS

 or as an

    autoimmune process
    DIAGNOSIS

. Disease severity varies greatly among affected individuals. Most patients have

    cutaneous, laryngeal, or gastrointestinal edema
    SYMPTOMS

, often in combinations. The symptoms may appear spontaneously or result from a stimulus, usually

    trauma
    SYMPTOMS

. When clinical suspicion exists,

    measurement of the C4 level
    PARACLINICAL

 screens for the disease. An assay showing

    low serum C1 INH function
    BIOCHEMICAL

 confirms the diagnosis. When disease severity warrants, symptoms can be controlled with

    anabolic steroids or antifibrinolytics
    MEDICATION

. Doses should be increased before

    symptom-provoking events
    SYMPTOMS

. Emergencies are treated with

    plasma infusions, fluids, and pain control
    MEDICATION

. Where available,

    C1 INH concentrate
    MEDICATION

 is the treatment of choice. Therapy can usually be monitored by control of symptoms. With appropriate therapy, most cases remain well controlled.

Hereditary angioedema
malignancies
autoimmune process


Hereditary angioedema type II--a study of two families.

Hereditary angioedema (HA) is caused by a quantitative or qualitative deficiency of C1 esterase inhibitor (C1 INH). We present a study of nine patients with HA belonging to two different families. The symptoms started before 10 years of age in most cases (78%). Facial edema (lips, eyes) and of the extremities (feet, hands) were the most frequent complaints. Three patients presented edema of the glottis and one of them underwent a tracheostomy twice. Laboratory tests, outside the acute crisis, revealed low levels of C4 in all patients. The serum levels of C1 INH were normal in seven patients; however, functional activity was not observed in any of them. After the use of a modified androgen (danazol), control of symptoms was observed in all patients, although functional activity was re-established in only five patients.

    Hereditary angioedema (HA)
    DIAGNOSIS

 is caused by a

    quantitative or qualitative deficiency of C1 esterase inhibitor (C1 INH)
    BIOCHEMICAL

. We present a study of nine patients with

    HA
    DIAGNOSIS

 belonging to two different families. The symptoms started

    before 10 years of age
    AGE

 in most cases (78%).

    Facial edema (lips, eyes) and of the extremities (feet, hands)
    SYMPTOMS

 were the most frequent complaints. Three patients presented

    edema of the glottis
    SYMPTOMS

 and one of them

    underwent a tracheostomy twice
    MEDICATION

.

    Laboratory tests
    PARACLINICAL

,

    outside the acute crisis
    PARACLINICAL

, revealed

    low levels of C4
    BIOCHEMICAL

 in all patients.

    The serum levels of C1 INH were normal
    NEG_FINDINGS

 in seven patients; however,

    functional activity was not observed in any of them
    NEG_FINDINGS

. After the

    use of a modified androgen (danazol)
    MEDICATION

,

    control of symptoms
    SYMPTOMS

 was observed in all patients, although

    functional activity was re-established
    SYMPTOMS

 in only five patients.

underwent a tracheostomy twice
use of a modified androgen (danazol)


Abdominal attack of hereditary angioedema associated with marked leucocytosis. A case report.

Hereditary angioedema (HAE) attacks are not usually associated with an increase of peripheral blood leucocytes. In a 25-year-old woman suffering from HAE a marked leucocytosis (31,000/mm3) with polynucleosis was observed during a severe attack of the disease. Awareness of the underlying disease, physical examination and the results of instrumental investigations allowed for appropriate treatment avoiding invasive procedures. A leucocytosis of the severity observed in our patient suggests that the abdominal attack of HAE can involve the peritoneum as well as the intestinal mucosa. Thus, in a patient with an attack of abdominal pain the presence of leucocytosis does not exclude the diagnosis of HAE.

    Hereditary angioedema (HAE) attacks
    DIAGNOSIS

 are not usually associated with an

    increase of peripheral blood leucocytes
    BIOCHEMICAL

. In a

    25-year-old
    AGE

    woman
    GENDER

 suffering from

    HAE
    DIAGNOSIS

 a

    marked leucocytosis (31,000/mm3) with polynucleosis
    BIOCHEMICAL

 was observed during a

    severe attack of the disease
    SYMPTOMS

. Awareness of the underlying disease, physical examination and the results of instrumental investigations allowed for appropriate treatment

    avoiding invasive procedures
    MEDICATION

. A

    leucocytosis of the severity
    BIOCHEMICAL

 observed in our patient suggests that the

    abdominal attack of HAE
    SYMPTOMS

 can

    involve the peritoneum as well as the intestinal mucosa
    SYMPTOMS

. Thus, in a patient with an

    attack of abdominal pain
    SYMPTOMS

 the presence of

    leucocytosis
    BIOCHEMICAL

 does not exclude the diagnosis of

    HAE
    DIAGNOSIS

.

Hereditary angioedema (HAE) attacks
HAE
HAE


Long-term follow-up of non-systemic lupus erythematosus glomerulonephritis in patients with hereditary angioedema: report of four cases.

Hereditary angioedema (HAE) is characterized by a deficiency in C1 inhibitor protein (C1 INH) and by clinical symptoms of episodic swelling of subcutaneous or mucosal tissue. It has rarely been reported in association with non-systemic lupus erythematosus (SLE) glomerulonephritis (GN). A recent report of two cases indicates the prognosis to be poor, with both patients progressing to chronic renal failure 8 and 20 years after diagnosis. This report describes the 5-year follow-up of a previously unreported case of an 8-year-old boy with HAE and non-SLE membranoproliferative glomerulonephritis (MPGN). The patient developed macroscopic hematuria, azotemia, and a vasculitic rash. Treatment included prednisone and cyclophosphamide, resulting in clinical improvement. The present report also summarizes the long-term follow-up of three previously reported cases of HAE and non-SLE GN, 25, 16, and 10 years after their initial presentation. Patients monitored for 25 and 16 years had MPGN and normal renal function and received no therapy. The third patient, monitored for 10 years, had segmental MPGN. This patient presented with urinary abnormalities and, after treatment with prednisone, had improvement in her hematuria. None of these four patients developed chronic renal failure. These observations indicate a variable outcome in patients with HAE and non-SLE GN.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterized by a

    deficiency in C1 inhibitor protein (C1 INH)
    BIOCHEMICAL

 and by clinical symptoms of

    episodic swelling of subcutaneous or mucosal tissue
    SYMPTOMS

. It has rarely been reported in association with

    non-systemic lupus erythematosus (SLE) glomerulonephritis (GN)
    DIAGNOSIS

. A recent report of two cases indicates the prognosis to be poor, with both patients progressing to

    chronic renal failure
    SYMPTOMS

 8 and 20 years after diagnosis. This report describes the 5-year follow-up of a previously unreported case of an

    8-year-old
    AGE

    boy
    GENDER

 with

    HAE
    DIAGNOSIS

 and

    non-SLE membranoproliferative glomerulonephritis (MPGN)
    DIAGNOSIS

. The patient developed

    macroscopic hematuria
    BIOCHEMICAL

,

    azotemia
    BIOCHEMICAL

, and a

    vasculitic rash
    SYMPTOMS

. Treatment included

    prednisone and cyclophosphamide
    MEDICATION

, resulting in

    clinical improvement
    SYMPTOMS

. The present report also summarizes the long-term follow-up of three previously reported cases of

    HAE and non-SLE GN
    DIAGNOSIS

, 25, 16, and 10 years after their initial presentation. Patients monitored for 25 and

    16 years
    AGE

 had

    MPGN
    DIAGNOSIS

 and

    normal renal function
    NEG_FINDINGS

 and

    received no therapy
    NEG_FINDINGS

. The third patient, monitored for 10 years, had

    segmental MPGN
    DIAGNOSIS

. This patient presented with

    urinary abnormalities
    SYMPTOMS

 and, after

    treatment with prednisone
    MEDICATION

, had

    improvement in her hematuria
    BIOCHEMICAL

. None of these four patients developed

    chronic renal failure
    NEG_FINDINGS

. These observations indicate a variable outcome in patients with

    HAE and non-SLE GN
    DIAGNOSIS

.

prednisone and cyclophosphamide
treatment with prednisone

normal renal function
received no therapy
chronic renal failure


Hereditary angioedema: a case with ascites yet no symptoms in the family.

An interesting case of hereditary angioedema in a 26-year-old female is reported, with a finding of transient effusion of fluid into the peritoneal cavity during the attacks. The patient suffered from recurrent abdominal pain for several years, but no family members had any similar symptoms. In spite of repeated hospital admissions and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of hereditary angioedema as a cause of acute and/or recurrent abdominal pain may avoid useless invasive procedures and lead to adequate treatment in other similar cases.

An interesting case of

    hereditary angioedema
    DIAGNOSIS

 in a

    26-year-old
    AGE

    female
    GENDER

 is reported, with a finding of

    transient effusion of fluid into the peritoneal cavity
    SYMPTOMS

 during the attacks. The patient suffered from

    recurrent abdominal pain for several years
    SYMPTOMS

, but

    no family members had any similar symptoms
    NEG_FINDINGS

. In spite of

    repeated hospital admissions
    MEDICATION

 and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of

    hereditary angioedema
    DIAGNOSIS

 as a cause of

    acute and/or recurrent abdominal pain
    SYMPTOMS

 may avoid

    useless invasive procedures
    NEG_FINDINGS

 and lead to adequate treatment in other similar cases.

hereditary angioedema
hereditary angioedema


Hereditary angioedema in a family.

Hereditary angioedema is an uncommon clinical condition. Life-long episodic brawny and non-itchy swelling of the extremities, face and trunk, with episodic abdominal pain and familial occurrence are the typical features. Oedema causing obstruction of airways may lead to suffocation and even death. The diagnosis can be confirmed by finding low levels of C1 esterase inhibitor, C4 and C2. Therapy with synthetic androgenic agents can ameliorate the condition to a large extent.

    Hereditary angioedema
    DIAGNOSIS

 is an uncommon clinical condition.

    Life-long episodic brawny and non-itchy swelling of the extremities, face and trunk
    SYMPTOMS

, with

    episodic abdominal pain
    SYMPTOMS

 and

    familial occurrence
    GENETICS

 are the typical features.

    Oedema causing obstruction of airways
    SYMPTOMS

 may lead to

    suffocation
    SYMPTOMS

 and even

    death
    SYMPTOMS

. The diagnosis can be confirmed by finding

    low levels of C1 esterase inhibitor, C4 and C2
    BIOCHEMICAL

. Therapy with

    synthetic androgenic agents
    MEDICATION

 can ameliorate the condition to a large extent.


[Hereditary angioedema. Control and treatment in 7 cases].

Hereditary angioedema (HAE) is due to a deficit of the C1 inhibitor (C1 INH) of a dominant autosomic inheritance. Seven patients are presented from a family with HAE, four of whom with poor prognosis due to the frequency and site of the angioedema. Prophylaxis was obtained with long-term danazol since antifibrinolytic drugs are not efficient in the prevention of outbreaks of angioedema. In three cases a concentrate of C1 INH was administered and in another as short term prophylaxis prior to surgery. C1 INH was more efficient under these indications than fresh plasma or antifibrinolytic drugs.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is due to a

    deficit of the C1 inhibitor (C1 INH)
    BIOCHEMICAL

    of a dominant autosomic inheritance
    GENETICS

. Seven patients are presented from a

    family with HAE
    FAMILY

, four of whom with poor prognosis due to the frequency and site of the

    angioedema
    SYMPTOMS

.

    Prophylaxis
    MEDICATION

 was obtained with

    long-term danazol
    MEDICATION

 since

    antifibrinolytic drugs are not efficient in the prevention of outbreaks of angioedema
    NEG_FINDINGS

. In three cases a

    concentrate of C1 INH
    MEDICATION

 was administered and in another

    as short term prophylaxis prior to surgery
    MEDICATION

.

    C1 INH
    MEDICATION

 was more efficient under these indications than

    fresh plasma or antifibrinolytic drugs
    MEDICATION

.