Life-threatening complications following orthognathic surgery in a patient with undiagnosed hereditary angioedema.

As described in the literature, hereditary angioedema (HAE) is an autosomal dominant disease that presents with recurrent events of angioedema caused by a) deficiency or b) functional alteration of the plasma protein C1 inhibitor (C1-inh); this enzyme is involved in the regulation of the complement, kallikrein-kinin, fibrinolytic, and coagulation systems. HAE is characterized by episodes of edema in the larynx, facial structures and tissues, gastrointestinal tract, or extremities. Laryngeal edema has been reported to occur predominantly after oral surgery. We describe the case of an 18-year-old Asiatic male, reporting an unremarkable medical history, who experienced complications following orthognathic surgery. Thirty hours post-op, the patient developed severe facial, pharyngeal, and glottic edema that compromised the airway, and an emergency tracheal intubation was performed. He was tested for C1-inh plasma levels, showing a sub-normal concentration and indicating a diagnosis of HAE. The patient received fresh-frozen plasma and improved throughout the day as his condition stabilized. Several cases of HAE following oral surgery have been reported, but, to the authors' knowledge, this is the first case reported following orthognathic surgery. This patient's treatment will be described, and a literature review of the disease and management methods will be provided.

As described in the literature,

    hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disease
    GENETICS

 that presents with

    recurrent events of angioedema
    SYMPTOMS

 caused by a)

    deficiency or
    BIOCHEMICAL

 b)

    functional alteration of the plasma protein C1 inhibitor (C1-inh)
    BIOCHEMICAL

; this enzyme is involved in the

    regulation of the complement, kallikrein-kinin, fibrinolytic, and coagulation systems
    BIOCHEMICAL

.

    HAE
    DIAGNOSIS

 is characterized by

    episodes of edema in the larynx, facial structures and tissues, gastrointestinal tract, or extremities
    SYMPTOMS

.

    Laryngeal edema
    SYMPTOMS

 has been reported to occur predominantly after

    oral surgery
    MEDICATION

. We describe the case of an

    18-year-old
    AGE

    Asiatic
    ETHNICITY

    male
    GENDER

, reporting an

    unremarkable medical history
    NEG_FINDINGS

, who experienced

    complications
    SYMPTOMS

 following

    orthognathic surgery
    MEDICATION

. Thirty hours post-op, the patient developed

    severe facial, pharyngeal, and glottic edema
    SYMPTOMS

 that

    compromised the airway
    SYMPTOMS

, and an

    emergency tracheal intubation
    MEDICATION

 was performed.

    He
    GENDER

 was tested for

    C1-inh plasma levels
    BIOCHEMICAL

, showing a

    sub-normal concentration
    BIOCHEMICAL

 and indicating a diagnosis of

    HAE
    DIAGNOSIS

. The patient received

    fresh-frozen plasma
    MEDICATION

 and improved throughout the day as his condition stabilized. Several cases of

    HAE
    DIAGNOSIS

 following

    oral surgery
    MEDICATION

 have been reported, but, to the authors' knowledge, this is the first case reported following

    orthognathic surgery
    MEDICATION

. This patient's treatment will be described, and a literature review of the disease and management methods will be provided.

oral surgery
orthognathic surgery
emergency tracheal intubation
fresh-frozen plasma
oral surgery
orthognathic surgery


Acute abdominal pain with a spontaneous resolution as a mark to the diagnosis of hereditary angioedema.

Accurate and timely diagnostics of acute abdominal pain, a common emergency, is crucial in decreasing unnecessary surgical interventions. We present the case of a patient, Xh. M. aged 21, transported to emergency after being wakened from sleep by severe, acute abdominal pain. The pain was non-radiating, colic, and associated with flatulence, nausea and vomiting. The family history was negative regarding Angioedema, which decreases but does not exclude the possible appearance of hereditary Angioedema. All laboratory and imaging findings were normal, besides the low levels of C4 complement component were 4.56 mg/dl (normal values 10-40), functional C1-esterase INH was 10.29% (normal values 80-130) C1-estrease inhibitor (protein) 4.58 mg/dl (normal values 16-33), indicating HAE typ I. Regardless of negative medical history in the family of hereditary angioedema, de novo mutation most probably led to her being the first case in the family. The case we have presented confirms the need to include hereditary angioedema as a differential diagnostic possibility in patients with acute abdominal pain, even more so as timely and precise diagnostics enable avoidance of unnecessary surgical interventions.

Accurate and timely diagnostics of

    acute abdominal pain
    SYMPTOMS

, a common emergency, is crucial in decreasing

    unnecessary surgical interventions
    NEG_FINDINGS

. We present the case of a patient, Xh. M.

    aged 21
    AGE

, transported to emergency after being

    wakened from sleep
    MEDICATION

 by

    severe, acute abdominal pain
    SYMPTOMS

. The

    pain was non-radiating, colic
    SYMPTOMS

, and associated with

    flatulence
    SYMPTOMS

,

    nausea
    SYMPTOMS

 and

    vomiting
    SYMPTOMS

. The

    family history was negative regarding Angioedema
    NEG_FINDINGS

, which decreases but does not exclude the possible appearance of

    hereditary Angioedema
    NEG_FINDINGS

.

    All laboratory and imaging findings were normal
    NEG_FINDINGS

, besides the

    low levels of C4 complement component were 4.56 mg/dl (normal values 10-40)
    BIOCHEMICAL

,

    functional C1-esterase INH was 10.29% (normal values 80-130) C1-estrease inhibitor (protein) 4.58 mg/dl (normal values 16-33)
    BIOCHEMICAL

, indicating HAE typ I. Regardless of

    negative medical history in the family of hereditary angioedema
    FAMILY

,

    de novo mutation
    GENETICS

 most probably led to

    her
    GENDER

    being the first case in the family
    FAMILY

. The case we have presented confirms the need to include

    hereditary angioedema
    DIAGNOSIS

 as a differential diagnostic possibility in patients with

    acute abdominal pain
    SYMPTOMS

, even more so as timely and precise diagnostics enable

    avoidance of unnecessary surgical interventions
    NEG_FINDINGS

.

acute abdominal pain
severe, acute abdominal pain
pain was non-radiating, colic
flatulence
nausea
vomiting
acute abdominal pain


Ecallantide for treatment of acute attacks of acquired C1 esterase inhibitor deficiency.

Acquired C1 inhibitor (C1-INH) deficiency exposes patients to angioedema recurrences (acquired angioedema [AAE]) mediated by bradykinin pathway activation. C1-INH replacement and specific inhibition of plasma kallikrein with ecallantide have been successful in the treatment of hereditary angioedema (HAE), a more common related disorder. C1-INH replacement has also been used in the treatment of AAE, but because of the underlying mechanism of rapid catabolism, some patients may not respond. As part of preclinical investigation of ecallantide, a potent bradykinin pathway inhibitor, we evaluated three AAE patients treated successfully with that agent. This study was designed to assess ecallantide for treatment of attacks in AAE. Three patients with AAE were treated a total of 12 times with various dosing regimens of ecallantide based on the protocols established for the studies using ecallantide in HAE (Evaluation of DX-88's Effects in Mitigating Angioedema trials). Response to therapy was also based on outcome measures determined by these protocols. Ecallantide effectively relieved symptoms in three patients with various manifestations of AAE over 12 acute episodes. Kallikrein inhibition with ecallantide appears effective in the treatment of AAE and may be an alternative for patients with resistance to C1-INH replacement therapy.

    Acquired C1 inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 exposes patients to

    angioedema recurrences
    SYMPTOMS

 (

    acquired angioedema [AAE]
    DIAGNOSIS

) mediated by

    bradykinin pathway activation
    BIOCHEMICAL

.

    C1-INH replacement
    MEDICATION

 and

    specific inhibition of plasma kallikrein
    MEDICATION

    with ecallantide
    MEDICATION

 have been successful in the treatment of

    hereditary angioedema (HAE)
    DIAGNOSIS

, a more common related disorder.

    C1-INH replacement
    MEDICATION

 has also been used in the treatment of

    AAE
    DIAGNOSIS

, but because of the underlying mechanism of

    rapid catabolism
    BIOCHEMICAL

, some patients may not respond. As part of preclinical investigation of

    ecallantide, a potent bradykinin pathway inhibitor
    MEDICATION

, we evaluated three

    AAE
    DIAGNOSIS

 patients treated successfully with that agent. This study was designed to assess

    ecallantide
    MEDICATION

 for treatment of attacks in

    AAE
    DIAGNOSIS

. Three patients with

    AAE
    DIAGNOSIS

 were treated a total of 12 times with various

    dosing regimens of ecallantide
    MEDICATION

 based on the protocols established for the studies using

    ecallantide
    MEDICATION

 in

    HAE
    DIAGNOSIS

 (Evaluation of

    DX-88
    MEDICATION

's Effects in Mitigating

    Angioedema
    DIAGNOSIS

 trials). Response to therapy was also based on outcome measures determined by these protocols.

    Ecallantide
    MEDICATION

    effectively relieved symptoms
    SYMPTOMS

 in three patients with

    various manifestations of AAE over 12 acute episodes
    SYMPTOMS

.

    Kallikrein inhibition with ecallantide
    MEDICATION

 appears effective in the treatment of

    AAE
    DIAGNOSIS

 and may be an alternative for patients with

    resistance to C1-INH replacement therapy
    NEG_FINDINGS

.

acquired angioedema [AAE]
hereditary angioedema (HAE)
AAE
AAE
AAE
AAE
HAE
Angioedema
AAE


[Undiagnosed hereditary angioedema in a patient undergoing emergency caesarean section].

Hereditary angioedema (HAE) is characterized by acute, recurrent attacks of localized edema. Surgical procedures, trauma, and infections have been considered as potential triggers of HAE. Although HAE is a rare genetic disorder, approximately 50-60% of all HAE patients are involved with at least one occurrence of upper airway obstruction. The airway trouble is the most life-threating complication in HAE patients because HAE-related edema does not respond to typical treatment, such as administration of epinephrine, antihistamines, or glucocorticoids. Indeed, mortality rates of laryngeal attack are estimated around 25% to 40%. Here we describe a case of undiagnosed HAE patient undergoing emergency caesarean section under neuraxial blockade. A 31-year-old woman showed multiple regions at her lip margin during surgery and rapidly developed lip swelling after admission to the ward. Neither respiratory nor hemodynamic instability was found during and after surgery. Immediately, in order to assess whether HAE caused these dermatological manifestations, we measured values of both complement component 4 (C4) and functional activity of C1-esterase inhibitor (C1-inh), a protein of the complement system. These laboratory data showed low levels, which were compatible with HAE definition. After commencement of C1-inhibitor replacement therapy, her lip swelling and erythema gradually disappeared without adverse drug reactions. The patient was finally discharged from our institution 10 days after surgery.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterized by

    acute, recurrent attacks of localized edema
    SYMPTOMS

.

    Surgical procedures
    MEDICATION

,

    trauma
    MEDICATION

, and

    infections
    SYMPTOMS

 have been considered as potential triggers of

    HAE
    DIAGNOSIS

. Although

    HAE
    DIAGNOSIS

 is a

    rare genetic disorder
    GENETICS

, approximately 50-60% of all

    HAE
    DIAGNOSIS

 patients are involved with at least one occurrence of

    upper airway obstruction
    SYMPTOMS

. The

    airway trouble
    SYMPTOMS

 is the most life-threating complication in

    HAE
    DIAGNOSIS

 patients because

    HAE-related edema does not respond to typical treatment, such as administration of epinephrine, antihistamines, or glucocorticoids
    SYMPTOMS

. Indeed, mortality rates of

    laryngeal attack
    SYMPTOMS

 are estimated around 25% to 40%. Here we describe a case of undiagnosed

    HAE
    DIAGNOSIS

 patient undergoing

    emergency caesarean section
    MEDICATION

 under

    neuraxial blockade
    MEDICATION

. A

    31-year-old
    AGE

    woman
    GENDER

 showed

    multiple regions at her lip margin
    SYMPTOMS

 during

    surgery
    MEDICATION

 and

    rapidly developed lip swelling
    SYMPTOMS

 after admission to the ward.

    Neither respiratory nor hemodynamic instability
    NEG_FINDINGS

 was found during and after

    surgery
    MEDICATION

. Immediately, in order to assess whether

    HAE
    DIAGNOSIS

 caused these

    dermatological manifestations
    SYMPTOMS

, we

    measured values of both complement component 4 (C4) and functional activity of C1-esterase inhibitor (C1-inh), a protein of the complement system
    BIOCHEMICAL

. These laboratory data showed

    low levels
    BIOCHEMICAL

, which were compatible with

    HAE
    DIAGNOSIS

 definition. After

    commencement of C1-inhibitor replacement therapy
    MEDICATION

, her

    lip swelling and erythema gradually disappeared
    SYMPTOMS

    without adverse drug reactions
    NEG_FINDINGS

. The patient was finally discharged from our institution 10 days after

    surgery
    MEDICATION

.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE
HAE
HAE


Acquired C1-inhibitor deficiency: a case report.

Angioedema due to C1--inhibitor deficiency may be hereditary (HAE) or acquired (AAE). AAE is a very rare condition, whose prevalence is possibly underestimated, as it is often unrecognized. AAE usually occurs after the fourth decade of life, and it is commonly associated to an underlying disease, mainly lymphoproliferative disorders. We report a 74-years old woman with recurrent episodes of angioedema involving upper airways in which diagnosis was obtained a long time after symptoms onset. A concomitant B cell leukaemia was also diagnosed This report stresses the importance of the recognition of AAE: a delayed diagnosis is indeed associated to the risk of severe life-threatening episodes, unresponsive to the usual therapy of common form of angioedema. AAE should be considered as a possible diagnosis in subjects with adult onset of angioedema: a careful clinical history is basic, since the clinical features and the time-course are often suggestive of the disease.

    Angioedema
    DIAGNOSIS

 due to

    C1--inhibitor deficiency
    BIOCHEMICAL

 may be

    hereditary
    GENETICS

    (HAE)
    DIAGNOSIS

 or

    acquired
    DIAGNOSIS

 (

    AAE)
    DIAGNOSIS

.

    AAE
    DIAGNOSIS

 is a very rare condition, whose prevalence is possibly underestimated, as it is often unrecognized.

    AAE
    DIAGNOSIS

 usually occurs

    after the fourth decade of life
    AGE

, and it is commonly associated to an underlying disease, mainly

    lymphoproliferative disorders
    DIAGNOSIS

. We report a

    74-years old
    AGE

    woman
    GENDER

 with

    recurrent episodes of angioedema involving upper airways
    SYMPTOMS

 in which diagnosis was obtained a long time after symptoms onset. A concomitant

    B cell leukaemia
    DIAGNOSIS

 was also diagnosed This report stresses the importance of the recognition of

    AAE
    DIAGNOSIS

: a delayed diagnosis is indeed associated to the risk of

    severe life-threatening episodes
    SYMPTOMS

,

    unresponsive to the usual therapy of common form of angioedema
    NEG_FINDINGS

.

    AAE
    DIAGNOSIS

 should be considered as a possible diagnosis in subjects with

    adult
    AGE

 onset of

    angioedema
    SYMPTOMS

: a careful clinical history is basic, since the clinical features and the time-course are often suggestive of the disease.

Angioedema
(HAE)
acquired
AAE)
AAE
AAE
lymphoproliferative disorders
B cell leukaemia
AAE
AAE


Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.

To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States.

Retrospective data mining analysis.

The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database.

Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91) was generated for these combination cases.

The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases.

To investigate reports of

    thrombotic events
    SYMPTOMS

 associated with the

    use of C1 esterase inhibitor products
    MEDICATION

 in patients with

    hereditary angioedema
    DIAGNOSIS

 in the United States.

    Retrospective data mining analysis
    PARACLINICAL

.

The United States Food and Drug Administration (FDA)

    adverse event reporting system (AERS) database
    PARACLINICAL

.

Case reports of

    C1 esterase inhibitor products
    MEDICATION

,

    thrombotic events
    SYMPTOMS

, and

    C1 esterase inhibitor product-associated thrombotic events
    MEDICATION

 (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a

    drug-associated adverse event
    SYMPTOMS

. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular

    drug-associated adverse event
    SYMPTOMS

 was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of

    thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze)
    SYMPTOMS

 were identified in patients with

    hereditary angioedema
    DIAGNOSIS

. A potential signal demonstrated by an

    IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91)
    BIOCHEMICAL

 was generated for these combination cases.

The extracted cases from the AERS indicate continuing reports of

    thrombotic events associated with
    SYMPTOMS

 the use of one

    C1 esterase inhibitor product
    MEDICATION

 among patients with

    hereditary angioedema
    DIAGNOSIS

. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of

    C1 esterase inhibitor product-associated thrombotic events
    SYMPTOMS

 among patients with

    hereditary angioedema
    DIAGNOSIS

 were identified in the extracted combination cases.

hereditary angioedema
hereditary angioedema
hereditary angioedema
hereditary angioedema


Angioedema associated with Crohn's disease: response to biologics.

A 46-year-old female patient with terminal ileum Crohn's disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn's disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn's disease that was successfully treated with anti-TNF-α agents.

A

    46-year-old
    AGE

    female
    GENDER

 patient with

    terminal ileum Crohn's disease
    DIAGNOSIS

 and

    ankylosing spondylitis
    DIAGNOSIS

 presented with

    recurrent angioedema
    SYMPTOMS

 and

    urticaria
    SYMPTOMS

. Investigations

    ruled out hereditary angioedema, and environmental or food allergen triggers
    NEG_FINDINGS

.

    She
    GENDER

 was diagnosed with

    chronic idiopathic urticaria with angioedema
    DIAGNOSIS

, and was treated with a

    trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine
    MEDICATION

. Due to

    ongoing bowel and arthritic complaints
    SYMPTOMS

,

    she
    GENDER

 was started on

    infliximab infusions
    MEDICATION

 and within

    2 treatments
    MEDICATION

,

    she
    GENDER

 had

    complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms
    SYMPTOMS

. Unfortunately

    she
    GENDER

 developed

    allergic reactions to the infliximab
    SYMPTOMS

 and was

    switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab
    MEDICATION

. Since then,

    she
    GENDER

 has had

    no further angioedema or urticaria
    NEG_FINDINGS

, and

    her
    GENDER

    Crohn's disease has been quiescent
    NEG_FINDINGS

. This is the first known case report of

    chronic idiopathic urticaria with angioedema coexistent with Crohn's disease
    DIAGNOSIS

 that was successfully treated with

    anti-TNF-α agents
    MEDICATION

.


Icatibant and ACE inhibitor angioedema.

Icatibant is a selective bradykinin 2 receptor antagonist, currently licensed for use in hereditary angioedema. Its benefit in ACE inhibitor angioedema is yet to be fully established. A handful of preliminary case reports suggest that it may be of benefit in reducing both symptom severity and possible hospital or intensive care admission. To date, there are no case reports of the usage of Icatibant in the emergency department in the UK. Here we report our experience of Icatibant in a 62-year-old gentleman presenting with severe oral, pharyngeal and laryngeal oedema while on an ACE inhibitor.

    Icatibant
    MEDICATION

 is a

    selective bradykinin 2 receptor antagonist
    MEDICATION

, currently licensed for use in

    hereditary angioedema
    DIAGNOSIS

. Its benefit in

    ACE inhibitor angioedema
    DIAGNOSIS

 is yet to be fully established. A handful of preliminary case reports suggest that it may be of benefit in reducing both symptom severity and possible

    hospital or intensive care admission
    MEDICATION

. To date, there are no case reports of the usage of

    Icatibant
    MEDICATION

 in the emergency department in the UK. Here we report our experience of

    Icatibant
    MEDICATION

 in a

    62-year-old
    AGE

    gentleman
    GENDER

 presenting with

    severe oral, pharyngeal and laryngeal oedema
    SYMPTOMS

 while

    on an ACE inhibitor
    MEDICATION

.

hereditary angioedema
ACE inhibitor angioedema


Familial amyloidotic polineuropathy and systemic lupus.

Familial amyloidotic polineuropathy is a genetic disorder, leading to systemic amyloid deposits, manifested as sensory-motor and autonomic neuropathy. In the Portuguese classical form, the disease is evident at a young age, and causes death if no specific treatment is received. Variability in penetrance, age of onset and clinical course has been published; environmental and genetic factors are believed to contribute to this variability. The authors report a case of a 51-year-old white female, with a medical history of acquired angioedema, late-onset familial amyloidotic polineuropathy and systemic lupus erythemathosus. The authors consider that these associated diseases could modulate their expression.

    Familial amyloidotic polineuropathy
    DIAGNOSIS

 is a

    genetic disorder
    GENETICS

, leading to

    systemic amyloid deposits
    MICROSCOPIC

, manifested as

    sensory-motor and autonomic neuropathy
    SYMPTOMS

. In the Portuguese classical form, the disease is evident at a

    young age
    AGE

, and causes

    death
    SYMPTOMS

 if

    no specific treatment is received
    NEG_FINDINGS

. Variability in penetrance, age of onset and clinical course has been published; environmental and genetic factors are believed to contribute to this variability. The authors report a case of a

    51-year-old
    AGE

    white
    ETHNICITY

    female
    GENDER

, with a

    medical history
    FAMILY

 of

    acquired angioedema
    SYMPTOMS

,

    late-onset familial amyloidotic polineuropathy
    DIAGNOSIS

 and

    systemic lupus erythemathosus
    DIAGNOSIS

. The authors consider that these associated diseases could modulate their expression.

sensory-motor and autonomic neuropathy
death
acquired angioedema


Angioedema in progressive muscular dystrophy: a case report.

Systemic allergic reactions, which include angioedema, are very common in clinical practice. There is great diversity in the etiological factors known to trigger angioedema, and in the pathogenetic mechanisms defining this condition. Beside the broad spectrum of immuno-allergic reactions involved in the angioedemic pathogenesis, this condition is known to also develop on the background of other disorders. These disorders may be of different etiology and have different pathogenesis (either non-immune or immune) but have one common feature referred to as "serological overlap". From research and clinical perspective, it is interesting to explore the combination of some rare neurological diseases, such as myopathies and in particular muscular dystrophies with systemic allergic reactions such as angioedema, urticaria and others. It is known that progressive muscular dystrophies (PMD) are hereditary diseases with different types of inheritance--X-chromosome recessive, X-chromosome dominant, autosomal dominant and others. In some forms, such as Duchenne muscular dystrophy (DMD), an increased expression of perforin in muscle is found which is evidence for involvement of the cellular immune response in the pathogenesis of myopathy. It is in this sense that it is interesting to explore and discuss a clinical case diagnosed as a facioscapulohumeral form of PMD, which also manifests angioedema with urticaria.

We present a 41-year-old male hospitalized in the Division of Occupational Diseases and Allergology at St. George University Hospital in Plovdiv who suffered two incidents of massive angioedema on the face, back and chest, accompanied by an itchy urticarial rash. In 1985, after hospitalization to the Clinic of Neurology, he was diagnosed with PMD of facioscapulohumeral type. The medical history could not reveal any of the most common etiologic factors such as drugs, food, insects and other allergens that may be associated with the systemic allergic reactions. The abnormalities we found (although they are only of specific indices of humoral immunity) give some reasons to assume the hypothesis of possible causation between the primary neurological disorder as a trigger for this kind of allergy.

The reported case demonstrates that in addition to the cellular immunity abnormalities we identified, the abnormalities in some components of humoral immunity should also be taken into consideration. Good knowledge of the allergic factors and the mechanisms of allergic reactions is of paramount importance for an efficacious approach to the problems faced by patients with such rare pathology.

    Systemic allergic reactions
    SYMPTOMS

, which include

    angioedema
    SYMPTOMS

, are very common in clinical practice. There is great diversity in the etiological factors known to trigger

    angioedema
    DIAGNOSIS

, and in the pathogenetic mechanisms defining this condition. Beside the broad spectrum of

    immuno-allergic reactions
    SYMPTOMS

 involved in the

    angioedemic pathogenesis
    SYMPTOMS

, this condition is known to also develop on the background of other disorders. These disorders may be of different etiology and have different pathogenesis (either

    non-immune
    DIAGNOSIS

 or immune) but have one common feature referred to as "

    serological overlap"
    SYMPTOMS

. From research and clinical perspective, it is interesting to explore the combination of some

    rare neurological diseases
    DIAGNOSIS

, such as

    myopathies
    DIAGNOSIS

 and in particular

    muscular dystrophies
    DIAGNOSIS

 with

    systemic allergic reactions
    SYMPTOMS

 such as

    angioedema
    SYMPTOMS

,

    urticaria
    SYMPTOMS

 and others. It is known that

    progressive muscular dystrophies (PMD)
    DIAGNOSIS

 are

    hereditary diseases
    GENETICS

 with

    different types of inheritance--X-chromosome recessive, X-chromosome dominant, autosomal dominant
    GENETICS

 and others. In some forms, such as

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, an

    increased expression of perforin in muscle
    MICROSCOPIC

 is found which is evidence for involvement of the

    cellular immune response
    BIOCHEMICAL

 in the pathogenesis of

    myopathy
    DIAGNOSIS

. It is in this sense that it is interesting to explore and discuss a clinical case diagnosed as a

    facioscapulohumeral form of PMD
    DIAGNOSIS

, which also manifests

    angioedema with urticaria
    SYMPTOMS

.

We present a

    41-year-old
    AGE

    male
    GENDER

 hospitalized in the Division of

    Occupational Diseases and Allergology
    PARACLINICAL

 at St. George University Hospital in

    Plovdiv
    ETHNICITY

 who suffered two incidents of

    massive angioedema on the face, back and chest
    SYMPTOMS

, accompanied by an

    itchy urticarial rash
    SYMPTOMS

. In 1985, after hospitalization to the Clinic of

    Neurology
    PARACLINICAL

,

    he
    GENDER

 was diagnosed with

    PMD of facioscapulohumeral type
    DIAGNOSIS

. The

    medical history could not reveal any of the most common etiologic factors such as drugs, food, insects and other allergens that may be associated with the systemic allergic reactions
    NEG_FINDINGS

. The abnormalities we found (although they are only of

    specific indices of humoral immunity
    BIOCHEMICAL

) give some reasons to assume the hypothesis of possible causation between the

    primary neurological disorder
    DIAGNOSIS

 as a trigger for this kind

    of allergy
    DIAGNOSIS

.

The reported case demonstrates that in addition to the

    cellular immunity abnormalities
    BIOCHEMICAL

 we identified, the

    abnormalities in some components of humoral immunity
    BIOCHEMICAL

 should also be taken into consideration. Good knowledge of the allergic factors and the mechanisms of

    allergic reactions
    SYMPTOMS

 is of paramount importance for an efficacious approach to the problems faced by patients with such rare pathology.

angioedema
non-immune
rare neurological diseases
myopathies
muscular dystrophies
progressive muscular dystrophies (PMD)
Duchenne muscular dystrophy (DMD)
myopathy
facioscapulohumeral form of PMD
PMD of facioscapulohumeral type
primary neurological disorder
of allergy


A novel mutation in exon 8 of C1 inhibitor (C1INH) gene leads to abolish its physiological stop codon in a large Chinese family with hereditary angioedema type I.

C1 inhibitor (C1INH) plays an important role in the classical pathway of the complement system. Mutations in C1INH gene cause quantitative or qualitative deficiencies in C1INH, which can lead to hereditary angioedema (HAE) type I or II. Here, we identified a novel frame-shift mutation c.1391-1445del55 (p.v464fsx556) in exon 8 in a large Chinese family with HAE type I. This 55 base pairs deletion abolishes the original stop codon and introduces a new stop codon 220 bp downstream of the original one, and leads to mutated C1INH protein prolonged from 500 to 556 amino acids. The levels of C4 and C1INH as well as C1INH activity in serum were significantly reduced in affected individuals. This is the first report of a novel mutation abolishing the physiological stop codon of C1INH gene in a large Chinese family with HAE type I.

    C1 inhibitor (C1INH)
    BIOCHEMICAL

 plays an important role in the

    classical pathway of the complement system
    BIOCHEMICAL

.

    Mutations in C1INH gene
    GENETICS

 cause

    quantitative or qualitative deficiencies in C1INH
    BIOCHEMICAL

, which can lead to

    hereditary angioedema (HAE) type I or II
    DIAGNOSIS

. Here, we identified a

    novel frame-shift mutation c.1391-1445del55 (p.v464fsx556) in exon 8
    GENETICS

 in a

    large Chinese
    ETHNICITY

 family with HAE type I. This

    55 base pairs deletion abolishes the original stop codon and introduces a new stop codon 220 bp downstream of the original one
    GENETICS

, and leads to

    mutated C1INH protein prolonged from 500 to 556 amino acids
    GENETICS

.

    The levels of C4 and C1INH as well as C1INH activity in serum were significantly reduced
    BIOCHEMICAL

 in affected individuals. This is the first report of a

    novel mutation abolishing the physiological stop codon of C1INH gene
    GENETICS

 in a

    large Chinese
    ETHNICITY

 family with HAE type I.


Current options for prophylactic treatment of hereditary angioedema in the United States: patient-based considerations.

Hereditary angioedema (HAE) results from mutations in the C1-esterase inhibitor (C1 INH) gene that decrease production of C1 INH or render it dysfunctional. HAE is characterized by recurrent, unpredictable, bradykinin-mediated edema of the extremities, face, genitalia, trunk, gastrointestinal tract, or upper airway. Attacks causing laryngeal edema can be fatal. Patients with HAE need medications for acute attacks; some also require prophylaxis. Management requires consideration of the patient's disease burden and effect on the patient's quality of life. This review examines an individualized approach to identifying HAE patients who may benefit from prophylaxis. A literature search was performed for HAE and prophylaxis. HAE guidelines, case reports, safety studies, and randomized, controlled clinical prophylaxis trials were selected. Authors provided cases demonstrating individualized prophylaxis. U.S. Food and Drug Administration-approved options for prophylaxis of HAE include attenuated androgens and nanofiltered C1 INH (C1 INH-nf). In other countries, pasteurized C1 INH and purified C1 INH are also available. Alternative therapies include fresh frozen plasma for preprocedural prophylaxis and antifibrinolytics for long-term prophylaxis. Attenuated androgens reduce attack frequency in many patients. Adverse effects include weight gain, virilization, increased hair growth, hypercholesterolemia, depression, and liver adenomas. C1 INH-nf reduces frequency of attacks and is well tolerated. Each patient with HAE has unique needs, based on the nature and frequency of past attacks, proximity to a medical center, occupation, and the patient's wishes. These factors should be used to create a patient-centered approach to management of HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 results from

    mutations in the C1-esterase inhibitor (C1 INH) gene
    GENETICS

 that

    decrease production of C1 INH or render it dysfunctional
    BIOCHEMICAL

.

    HAE
    DIAGNOSIS

 is characterized by

    recurrent, unpredictable, bradykinin-mediated edema of the extremities, face, genitalia, trunk, gastrointestinal tract, or upper airway
    SYMPTOMS

.

    Attacks causing laryngeal edema
    SYMPTOMS

 can be

    fatal
    SYMPTOMS

. Patients with

    HAE
    DIAGNOSIS

 need

    medications
    MEDICATION

 for

    acute attacks
    SYMPTOMS

; some also require

    prophylaxis
    MEDICATION

. Management requires consideration of the patient's disease burden and effect on the patient's quality of life. This review examines an individualized approach to identifying

    HAE
    DIAGNOSIS

 patients who may benefit from

    prophylaxis
    MEDICATION

. A literature search was performed for

    HAE
    DIAGNOSIS

 and

    prophylaxis
    MEDICATION

.

    HAE
    DIAGNOSIS

 guidelines, case reports, safety studies, and randomized, controlled clinical prophylaxis trials were selected. Authors provided cases demonstrating

    individualized prophylaxis
    MEDICATION

. U.S. Food and Drug Administration-approved options for

    prophylaxis
    MEDICATION

 of

    HAE
    DIAGNOSIS

 include

    attenuated androgens and nanofiltered C1 INH (C1 INH-nf)
    MEDICATION

. In other countries,

    pasteurized C1 INH
    MEDICATION

 and

    purified C1 INH
    MEDICATION

 are also available. Alternative therapies include

    fresh frozen plasma for preprocedural prophylaxis
    MEDICATION

 and

    antifibrinolytics for long-term prophylaxis
    MEDICATION

.

    Attenuated androgens
    MEDICATION

 reduce attack frequency in many patients.

    Adverse effects
    SYMPTOMS

 include

    weight gain
    SYMPTOMS

,

    virilization
    SYMPTOMS

,

    increased hair growth
    SYMPTOMS

,

    hypercholesterolemia
    SYMPTOMS

,

    depression
    SYMPTOMS

, and

    liver adenomas
    SYMPTOMS

.

    C1 INH-nf
    MEDICATION

    reduces frequency of attacks
    SYMPTOMS

 and is well tolerated. Each patient with

    HAE
    DIAGNOSIS

 has unique needs, based on the nature and frequency of past attacks, proximity to a medical center, occupation, and the patient's wishes. These factors should be used to create a patient-centered approach to management of

    HAE
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE
HAE
HAE
HAE


Successful perioperative management of a patient with C1 esterase inhibitor deficiency with a novel bradykinin receptor B2 antagonist.

We present the case of a 28-year-old female with a previous diagnosis of C1 esterase inhibitor deficiency presenting for dental extractions under general anaesthesia. Following prophylaxis with a new bradykinin receptor 2 antagonist (icatibant), surgery was carried out uneventfully with an unremarkable postoperative course.

We present the case of a

    28-year-old
    AGE

    female
    GENDER

 with a previous diagnosis of

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

 presenting for

    dental extractions
    MEDICATION

 under

    general anaesthesia
    MEDICATION

. Following

    prophylaxis with a new bradykinin receptor 2 antagonist (icatibant)
    MEDICATION

,

    surgery
    MEDICATION

 was carried out uneventfully with an

    unremarkable postoperative course
    SYMPTOMS

.


Recurrent anaphylactic reactions: an uncommon debut of lymphocytic hypophysitis.

We report on a 24-year-old male, with exercise-induced asthma and intermittent abdominal pain since puberty, who suffered from recurrent anaphylactic reactions. He also complained of occasional headaches. After extensive studies he was eventually diagnosed with idiopathic anaphylaxis, once the following diagnoses had been excluded: allergic origin [foods (including ω5-gliadin), latex and drugs], hydatidosis, carcinoid syndrome, systemic mastocytosis, autonomic epilepsy, hereditary angioedema, pheocromocitoma, Meckel diverticle, medullar thyroid carcinoma, leukemia, hyper-IgE and hypereosinophilic syndromes. Given the frequency and severity of the attacks, we started off-label treatment with omalizumab, initially well tolerated. Some days after the second dose the patient started to develop recurrent urticaria. Because of these new symptoms, blood work was repeated, and elevated TSH, decreased T4, positive antithyroid antibodies and decreased cortisol levels with normal ACTH were found. The antiadrenal autoantibodies were negative. The MRI showed a slight thickening of the infundibulum, without pituitary adenoma. Suspecting an autoimmune hypophysitis, we looked for antipituitary antibodies; the result was positive. A clinical picture of recurrent anaphylactic reactions, the result of complicated adrenal crises in an asthmatic patient, was a manifestation of lymphocytic hypophysitis, a rare chronic inflammatory disease of autoimmune etiology. One year after replacement therapy had been started, the patient remained asymptomatic.

We report on a

    24-year-old
    AGE

    male
    GENDER

, with

    exercise-induced asthma
    SYMPTOMS

 and

    intermittent abdominal pain
    SYMPTOMS

 since

    puberty
    AGE

, who suffered from

    recurrent anaphylactic reactions
    SYMPTOMS

.

    He
    GENDER

 also complained of

    occasional headaches
    SYMPTOMS

. After extensive studies he was eventually diagnosed with

    idiopathic anaphylaxis
    DIAGNOSIS

, once the following diagnoses had been excluded:

    allergic origin [foods (including ω5-gliadin), latex and drugs]
    NEG_FINDINGS

,

    hydatidosis
    DIAGNOSIS

,

    carcinoid syndrome
    DIAGNOSIS

,

    systemic mastocytosis
    DIAGNOSIS

,

    autonomic epilepsy
    DIAGNOSIS

,

    hereditary angioedema
    DIAGNOSIS

,

    pheocromocitoma
    DIAGNOSIS

,

    Meckel diverticle
    DIAGNOSIS

,

    medullar thyroid carcinoma
    DIAGNOSIS

,

    leukemia
    DIAGNOSIS

,

    hyper-IgE
    NEG_FINDINGS

 and

    hypereosinophilic syndromes
    DIAGNOSIS

. Given the frequency and severity of the attacks, we started

    off-label treatment with omalizumab
    MEDICATION

,

    initially well tolerated
    NEG_FINDINGS

. Some days after the second dose the patient started to develop

    recurrent urticaria
    SYMPTOMS

. Because of these new symptoms,

    blood work
    PARACLINICAL

 was repeated, and

    elevated TSH, decreased T4
    BIOCHEMICAL

,

    positive antithyroid antibodies
    BIOCHEMICAL

 and

    decreased cortisol levels
    BIOCHEMICAL

 with

    normal ACTH
    NEG_FINDINGS

 were found.

    The antiadrenal autoantibodies were negative
    NEG_FINDINGS

. The

    MRI
    PARACLINICAL

 showed a

    slight thickening of the infundibulum
    SYMPTOMS

,

    without pituitary adenoma
    NEG_FINDINGS

. Suspecting an

    autoimmune hypophysitis
    DIAGNOSIS

, we looked for

    antipituitary antibodies
    BIOCHEMICAL

; the result was positive. A clinical picture of

    recurrent anaphylactic reactions
    SYMPTOMS

, the result of

    complicated adrenal crises
    SYMPTOMS

 in an

    asthmatic
    DIAGNOSIS

 patient, was a manifestation of

    lymphocytic hypophysitis
    DIAGNOSIS

, a

    rare chronic inflammatory disease of autoimmune etiology
    DIAGNOSIS

. One year after

    replacement therapy
    MEDICATION

 had been started, the patient remained

    asymptomatic
    NEG_FINDINGS

.

exercise-induced asthma
intermittent abdominal pain
recurrent anaphylactic reactions
occasional headaches
recurrent urticaria
slight thickening of the infundibulum
recurrent anaphylactic reactions
complicated adrenal crises

off-label treatment with omalizumab
replacement therapy

elevated TSH, decreased T4
positive antithyroid antibodies
decreased cortisol levels
antipituitary antibodies


The first probable case of hereditary angioedema in Vietnam.

Hereditary angioedema (HAE) is rare disorder due to C1-inhibitor deficiency (C1-INH) that are debilitating and may be life-threatening. HAE is a lack of consensus concerning diagnosis, therapy, and management, particularly in Vietnam. In this case report, we report a 40-year-old male patient with typical clinical symptoms and family history but he showed normal C4 level, and we could not measure C1q and C1-INH level. However, the diagnosis of HAE can be made based on typical clinical symptoms and the favorable prophylactic response to danazol treatment. Based on these findings, we suggest that he has type I HAE, although he showed normal C4 level.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is rare disorder due to

    C1-inhibitor deficiency (C1-INH)
    BIOCHEMICAL

 that are debilitating and may be

    life-threatening
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 is a lack of consensus concerning diagnosis, therapy, and management, particularly in

    Vietnam
    ETHNICITY

. In this case report, we report a

    40-year-old
    AGE

    male
    GENDER

 patient with

    typical clinical symptoms
    SYMPTOMS

 and

    family history
    FAMILY

 but

    he
    GENDER

 showed

    normal C4 level
    NEG_FINDINGS

, and

    we could not measure C1q and C1-INH level
    NEG_FINDINGS

. However, the diagnosis of

    HAE
    DIAGNOSIS

 can be made based on typical clinical symptoms and the

    favorable prophylactic response
    SYMPTOMS

 to

    danazol treatment
    MEDICATION

. Based on these findings, we suggest that

    he
    GENDER

 has

    type I HAE
    DIAGNOSIS

, although

    he
    GENDER

 showed

    normal C4 level
    NEG_FINDINGS

.

Hereditary angioedema (HAE)
HAE
HAE
type I HAE

life-threatening
typical clinical symptoms
favorable prophylactic response


Switch to icatibant in a patient affected by hereditary angioedema with high disease activity: a case report.

Icatibant, an antagonist of the bradykinin B2 receptor, was approved for the treatment of acute attacks of hereditary angioedema in the EU in 2008. This paper presents the case of a 65-year-old woman affected by frequent acute attacks of hereditary angioedema who benefitted from a change of therapy to icatibant, following years of treatment with C1-inhibitor.

    Icatibant, an antagonist of the bradykinin B2 receptor
    MEDICATION

, was approved for the treatment of

    acute attacks of hereditary angioedema
    DIAGNOSIS

 in the EU in 2008. This paper presents the case of a

    65-year-old
    AGE

    woman
    GENDER

 affected by

    frequent acute attacks of hereditary angioedema
    SYMPTOMS

 who benefitted from a

    change of therapy to icatibant
    MEDICATION

, following

    years of treatment with C1-inhibitor
    MEDICATION

.


Etanercept is safely used for treating psoriatic arthritis in a patient complicated with type 1 hereditary angioedema.

Hereditary angioedema (HAE) is a life-threatening disorder caused by deficiency or dysfunction of the C1 inhibitor protein. Patients with HAE are restricted in various medical treatments, which can induce an HAE attack. We herein report the first case of psoriatic arthritis (PSA) with type 1 HAE successfully treated with 25 mg of etanercept without HAE attack. Etanercept may represent a useful choice for treating patients with HAE accompanied by intractable PSA and rheumatoid arthritis (RA).

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a life-threatening disorder caused by

    deficiency or dysfunction of the C1 inhibitor protein
    BIOCHEMICAL

. Patients with

    HAE
    DIAGNOSIS

 are restricted in various medical treatments, which can induce an

    HAE attack
    SYMPTOMS

. We herein report the first case of

    psoriatic arthritis (PSA)
    DIAGNOSIS

 with

    type 1 HAE
    DIAGNOSIS

 successfully treated with

    25 mg of etanercept
    MEDICATION

    without HAE attack
    NEG_FINDINGS

.

    Etanercept
    MEDICATION

 may represent a useful choice for treating patients with

    HAE
    DIAGNOSIS

 accompanied by

    intractable PSA
    DIAGNOSIS

 and

    rheumatoid arthritis (RA)
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
psoriatic arthritis (PSA)
type 1 HAE
HAE
intractable PSA
rheumatoid arthritis (RA)


Type I hereditary angioedema in Taiwan -- clinical, biological features and genetic study.

Hereditary angioedema (HAE) is a rare, autosomal dominant inherited disease which is caused by a genetic deficiency of C1 esterase inhibitor (C1 INH). There have only been a few case reports in Taiwan to date.

To describe the clinical features of type I HAE in Taiwanese patients.

Three unrelated Taiwanese families with type I HAE are reported, and one case of a family from a review of PubMed was reviewed. Clinical manifestations, diagnostic examinations, management and genetic studies were analyzed.

Including this report, 19 patients had low C1 INH and low C4 levels and were diagnosed with type I HAE. Only 11 (57.9%) patients were symptomatic. Recurrent skin swelling and edema over the four extremities or trunk were reported in all symptomatic patients (100%). 45.5% of the patients recalled laryngeal attacks and one patient died from asphyxia. 18.2% of the patients experienced abdominal symptoms. The age at the beginning of clinical symptoms ranged from 5 to 30 years (mean +/- SD: 20.82 +/- 7.88 years). The diagnosis tended to be delayed (range from 1 to 39 years; mean +/- SD: 8.45 +/- 11.04 years). Nine patients had a mutant C1 INH gene, and two patients received long-term prophylaxis with danazol.

The prevalence of hereditary angioedema in Taiwan is low. Persons with low levels of C1 INH who were clinically symptomatic accounted for only 57.9% of the cases in our study, which is far lower than previous reports from other countries. Ethnic differences may be the reason for this finding. Further genomic studies are needed to elucidate the genetic penetrance of C1 INH deficiency in Taiwan.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare, autosomal dominant inherited disease
    GENETICS

 which is caused by a

    genetic deficiency of C1 esterase inhibitor (C1 INH)
    GENETICS

. There have only been a few case reports in

    Taiwan
    ETHNICITY

 to date.

To describe the clinical features of

    type I HAE
    DIAGNOSIS

 in

    Taiwanese
    ETHNICITY

 patients.

Three unrelated

    Taiwanese
    ETHNICITY

 families with

    type I HAE
    DIAGNOSIS

 are reported, and one case of a family from a review of PubMed was reviewed. Clinical manifestations,

    diagnostic examinations
    PARACLINICAL

, management and

    genetic studies
    PARACLINICAL

 were analyzed.

Including this report, 19 patients had

    low C1 INH and low C4 levels
    BIOCHEMICAL

 and were diagnosed with

    type I HAE
    DIAGNOSIS

. Only 11 (57.9%) patients were symptomatic.

    Recurrent skin swelling
    SYMPTOMS

 and

    edema over the four extremities or trunk
    SYMPTOMS

 were reported in all symptomatic patients (100%). 45.5% of the patients recalled

    laryngeal attacks
    SYMPTOMS

 and one patient

    died
    SYMPTOMS

 from

    asphyxia
    SYMPTOMS

. 18.2% of the patients experienced

    abdominal symptoms
    SYMPTOMS

. The

    age at the beginning of clinical symptoms
    AGE

    ranged from 5 to 30 years (mean +/- SD: 20.82 +/- 7.88 years)
    AGE

. The diagnosis tended to be

    delayed (range from 1 to 39 years; mean +/- SD: 8.45 +/- 11.04 years)
    AGE

. Nine patients had a

    mutant C1 INH gene
    GENETICS

, and two patients received

    long-term prophylaxis with danazol
    MEDICATION

.

The prevalence of

    hereditary angioedema
    DIAGNOSIS

 in

    Taiwan
    ETHNICITY

 is low. Persons with

    low levels of C1 INH
    BIOCHEMICAL

 who were clinically symptomatic accounted for only 57.9% of the cases in our study, which is far lower than previous reports from other countries. Ethnic differences may be the reason for this finding. Further genomic studies are needed to elucidate the genetic penetrance of

    C1 INH deficiency
    BIOCHEMICAL

 in

    Taiwan
    ETHNICITY

.

Hereditary angioedema (HAE)
type I HAE
type I HAE
type I HAE
hereditary angioedema

Taiwan Taiwanese Taiwanese Taiwan Taiwan

low C1 INH and low C4 levels
low levels of C1 INH
C1 INH deficiency


Diagnosis and management of hereditary angioedema: an emergency medicine perspective.

Hereditary angioedema (HAE) is a rare and often debilitating condition associated with substantial morbidity and mortality in the absence of appropriate intervention. An underlying deficiency in functional C1-inhibitor (C1-INH) protein induces a vulnerability to unchecked activation of the complement, contact, and coagulation/fibrinolytic systems. The clinical consequence is a pattern of recurring attacks of non-pitting, non-pruritic edema, the urgency of which varies by the affected site. Laryngeal edema can escalate rapidly to asphyxiation, and severe cases of abdominal swelling can lead to hypovolemic shock.

This report reviews the emergency diagnosis and treatment of hereditary angioedema and the impact of recently introduced treatments on treatment in the United States.

Until recently, emergency physicians in the United States were hindered by the lack of rapidly effective treatment options for HAE attacks. In this article, general clinical and laboratory diagnostic procedures are reviewed against the backdrop of two case studies: one patient presenting with a known history of HAE and one with previously undiagnosed HAE. In many countries outside the United States, plasma-derived C1-INH concentrate has for decades been the first-line treatment for acute attacks. The end of 2009 ushered in a new era in the pharmacologic management of HAE attacks in the United States with the approval of two new treatment options for acute treatment: a plasma-derived C1-INH concentrate and a kallikrein inhibitor.

With access to targeted and effective treatments, emergency physicians are now better equipped for successful and rapid intervention in urgent HAE cases.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare and often debilitating condition associated with substantial morbidity and mortality in the absence of appropriate intervention. An underlying

    deficiency in functional C1-inhibitor (C1-INH) protein
    BIOCHEMICAL

 induces a

    vulnerability to unchecked activation of the complement, contact, and coagulation/fibrinolytic systems
    BIOCHEMICAL

. The clinical consequence is a pattern of

    recurring attacks of non-pitting, non-pruritic edema
    SYMPTOMS

, the urgency of which varies by the affected site.

    Laryngeal edema
    SYMPTOMS

 can

    escalate rapidly to asphyxiation
    SYMPTOMS

, and

    severe cases of abdominal swelling
    SYMPTOMS

 can lead to

    hypovolemic shock
    SYMPTOMS

.

This report reviews the emergency diagnosis and treatment of

    hereditary angioedema
    DIAGNOSIS

 and the impact of recently introduced treatments on treatment in the United States.

Until recently,

    emergency physicians
    PARACLINICAL

 in the United States were hindered by the lack of rapidly effective treatment options for

    HAE attacks
    DIAGNOSIS

. In this article, general clinical and laboratory diagnostic procedures are reviewed against the backdrop of two case studies: one patient presenting with a known history of

    HAE
    DIAGNOSIS

 and one with previously undiagnosed

    HAE
    DIAGNOSIS

. In many countries outside the United States,

    plasma-derived C1-INH concentrate
    MEDICATION

 has for decades been the first-line treatment for

    acute attacks
    DIAGNOSIS

. The end of 2009 ushered in a new era in the pharmacologic management of

    HAE attacks
    DIAGNOSIS

 in the United States with the approval of two

    new treatment options for acute treatment: a plasma-derived C1-INH concentrate and a kallikrein inhibitor
    MEDICATION

.

With access to targeted and effective treatments,

    emergency physicians
    PARACLINICAL

 are now better equipped for successful and rapid intervention in urgent

    HAE
    DIAGNOSIS

 cases.

Hereditary angioedema (HAE)
hereditary angioedema
HAE attacks
HAE
HAE
acute attacks
HAE attacks
HAE


Hereditary angioedema in childhood: a challenging diagnosis you cannot afford to miss.

Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of recurrent skin swellings and abdominal pain leading to several hospital admissions. The aim of this report is to direct focus on this rare disease, which can be treated effectively, to diminish morbidity and mortality of children suffering from undiagnosed HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare inherited
    GENETICS

 disease that is often difficult to diagnose. We report a case of a

    9-year-old
    AGE

    boy
    GENDER

 with a

    spontaneous mutation
    GENETICS

 causing

    HAE
    DIAGNOSIS

, diagnosed after a

    life-threatening episode of angioedema of the head and upper respiratory tract
    SYMPTOMS

 after a 5-year history of

    recurrent skin swellings
    SYMPTOMS

 and

    abdominal pain
    SYMPTOMS

 leading to

    several hospital admissions
    MEDICATION

. The aim of this report is to direct focus on this rare disease, which can be treated effectively, to diminish morbidity and mortality of

    children
    AGE

 suffering from undiagnosed

    HAE
    DIAGNOSIS

.


Migraine-like headache in a patient with complement 1 inhibitor deficient hereditary angioedema.

We report on an angioedema patient with a genetic defect in complement 1 inhibitor, manifesting migraine-like episodes of headache, effective prophylaxis with Danazol, and triptan for a treatment of acute clinical episode. The patient was 44-yr-old Korean man with abdominal pain and headache, who was brought into the Emergency Department of Seoul National University Hospital, Seoul. He suffered from frequent attacks of migraine-like headache (3-7 per month), pulsating in nature associated with nausea. Severities were aggravated by activity and his headache had shown recent progression with abdominal pain. No remarkable findings were observed on radiologic examination, brain magnetic resonance images and intracranial and extracranial magnetic resonance angiography. Danazol 200 mg every other day was subsequently used. Following administration of Danazol, symptoms showed improvement and the patient was discharged. While taking Danazol, the migraine-like episodes appeared to be prevented for about 2 yr. At the eighth month, he suffered a moderate degree of migraine-like headache; however, administration of naratriptan 2.5 mg resolved his problem. A case of genetic defect of C1-INH deficiency presented with headache episodes, and was controlled by Danazol and triptan. It suggests that pathogenic mechanism of headache in hereditary angioedema may be mediated by the neurogenic inflammatory-like physiology of migraine.

We report on an

    angioedema
    DIAGNOSIS

 patient with a

    genetic defect in complement 1 inhibitor
    GENETICS

, manifesting

    migraine-like episodes of headache
    SYMPTOMS

,

    effective prophylaxis with Danazol
    MEDICATION

, and

    triptan
    MEDICATION

 for a treatment of

    acute clinical episode
    SYMPTOMS

. The patient was

    44-yr-old
    AGE

    Korean
    ETHNICITY

    man
    GENDER

 with

    abdominal pain
    SYMPTOMS

 and

    headache
    SYMPTOMS

, who was brought into the Emergency Department of Seoul National University Hospital,

    Seoul
    ETHNICITY

.

    He
    GENDER

 suffered from

    frequent attacks of migraine-like headache (3-7 per month), pulsating in nature associated with nausea
    SYMPTOMS

. Severities were aggravated by activity and his

    headache had shown recent progression with abdominal pain
    SYMPTOMS

.

    No remarkable findings were observed
    NEG_FINDINGS

 on

    radiologic examination
    PARACLINICAL

,

    brain magnetic resonance images
    NEG_FINDINGS

 and

    intracranial and extracranial magnetic resonance angiography
    PARACLINICAL

.

    Danazol 200 mg every other day
    MEDICATION

 was subsequently used. Following

    administration of Danazol
    MEDICATION

,

    symptoms showed improvement
    SYMPTOMS

 and the patient was

    discharged
    MEDICATION

. While taking

    Danazol
    MEDICATION

, the

    migraine-like episodes appeared to be prevented for about 2 yr
    SYMPTOMS

. At the eighth month,

    he
    GENDER

 suffered a

    moderate degree of migraine-like headache
    SYMPTOMS

; however,

    administration of naratriptan 2.5 mg
    MEDICATION

 resolved his problem. A case of

    genetic defect of C1-INH deficiency
    GENETICS

 presented with

    headache episodes
    SYMPTOMS

, and was controlled by

    Danazol and triptan
    MEDICATION

. It suggests that pathogenic mechanism of

    headache
    DIAGNOSIS

 in

    hereditary angioedema
    DIAGNOSIS

 may be mediated by the

    neurogenic inflammatory-like physiology of migraine
    SYMPTOMS

.

angioedema
headache
hereditary angioedema

effective prophylaxis with Danazol
triptan
Danazol 200 mg every other day
administration of Danazol
discharged
Danazol
administration of naratriptan 2.5 mg
Danazol and triptan

No remarkable findings were observed
brain magnetic resonance images


Recurrent attacks of hereditary angioedema: a case of delayed diagnosis.

Hereditary angioedema is a rare disorder, and patients frequently endure long duration of symptoms, frequent physician visits, and unnecessary procedures prior to a diagnosis. Patients with novel mutations may experience especially long delays in diagnosis due to a lack of family history. This case demonstrates one such case in which diagnosis was delayed for many years. Improved physician awareness of the signs and symptoms of hereditary angioedema may prevent such delay for patients with this disorder in the future. Abdominal pain, angioedema, bradykinin, C1 inhibitor, hereditary, inherited, swelling.

    Hereditary angioedema
    DIAGNOSIS

 is a rare disorder, and patients frequently endure

    long duration of symptoms
    SYMPTOMS

,

    frequent physician visits
    NEG_FINDINGS

, and

    unnecessary procedures
    NEG_FINDINGS

 prior to a diagnosis. Patients with

    novel mutations
    GENETICS

 may experience especially long delays in diagnosis due to a

    lack of family history
    NEG_FINDINGS

. This case demonstrates one such case in which diagnosis was delayed for many years. Improved physician awareness of the signs and symptoms of

    hereditary angioedema
    DIAGNOSIS

 may prevent such delay for patients with this disorder in the future.

    Abdominal pain
    SYMPTOMS

,

    angioedema
    SYMPTOMS

,

    bradykinin
    BIOCHEMICAL

,

    C1 inhibitor
    BIOCHEMICAL

,

    hereditary
    GENETICS

,

    inherited
    GENETICS

,

    swelling
    SYMPTOMS

.

Hereditary angioedema
hereditary angioedema

long duration of symptoms
Abdominal pain
angioedema
swelling

frequent physician visits
unnecessary procedures
lack of family history


Hereditary angioedema: a case of near fatal laryngeal swelling in a 41-year-old woman.

Hereditary angioedema (HAE) is characterized by nonpitting, nonpruritic subcutaneous, or submucosal edema that may be accompanied by a nonpruritic serpentine erythematous rash. The swelling in this autosomal dominantly inherited disorder is mediated by uncontrolled localized bradykinin production. The extremities, face, gastrointestinal tract, genitalia, larynx, and trunk are commonly involved. Nearly one-third of patients who are not treated may suffer asphyxiation from a laryngeal attack. HAE symptoms overlap with other conditions that cause swelling. An accurate diagnosis is therefore crucial when considering therapy. Recently approved treatments for HAE swelling attacks include C1 esterase inhibitor concentrate and ecallantide. This case describes a 41-year-old woman who was treated ineffectively for more than 20 years, was switched to an effective therapy, but suffered near fatal laryngeal edema due to a missed dose of the effective therapy. The case underscores the need for increased awareness of HAE among clinicians and the importance of good compliance to therapy among patients with HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterized by

    nonpitting, nonpruritic subcutaneous, or submucosal edema
    SYMPTOMS

 that may be accompanied by a

    nonpruritic serpentine erythematous rash
    SYMPTOMS

. The

    swelling
    SYMPTOMS

 in this

    autosomal dominantly inherited
    GENETICS

 disorder is mediated by

    uncontrolled localized bradykinin production
    BIOCHEMICAL

.

    The extremities, face, gastrointestinal tract, genitalia, larynx, and trunk
    SYMPTOMS

 are commonly involved. Nearly one-third of patients who are not treated may suffer

    asphyxiation from a laryngeal attack
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 symptoms overlap with other conditions that cause

    swelling
    SYMPTOMS

. An accurate diagnosis is therefore crucial when considering therapy. Recently approved treatments for

    HAE swelling attacks
    DIAGNOSIS

 include

    C1 esterase inhibitor concentrate and ecallantide
    MEDICATION

. This case describes a

    41-year-old
    AGE

    woman
    GENDER

 who

    was treated ineffectively for more than 20 years
    NEG_FINDINGS

, was

    switched to an effective therapy
    MEDICATION

, but suffered

    near fatal laryngeal edema
    SYMPTOMS

 due to a

    missed dose of the effective therapy
    NEG_FINDINGS

. The case underscores the need for increased awareness of

    HAE
    DIAGNOSIS

 among clinicians and the importance of good compliance to therapy among patients with

    HAE
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
HAE swelling attacks
HAE
HAE


Successful management of hereditary angioedema during tonsillectomy: a case report.

Hereditary angioedema (HAE) is a rare genetic disorder causing a deficiency in C1 esterase inhibitor (C1-INH) that is manifested through unpredictable oedema. We describe a case of a patient with HAE who had previously been refused surgery for tonsillitis due to the potential for oedema, in whom regular monitoring of C1-INH levels combined with intensified therapy with danazol, tranexamic acid and C1-INH concentrate enabled an uncomplicated procedure with no oedema crisis. However, clinicians should be alerted that higher overall dosages of C1-INH concentrate for perioperative prophylaxis may be required than those typically used to treat acute HAE attacks.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic disorder
    GENETICS

 causing a

    deficiency in C1 esterase inhibitor (C1-INH)
    BIOCHEMICAL

 that is manifested through

    unpredictable oedema
    SYMPTOMS

. We describe a case of a patient with

    HAE
    DIAGNOSIS

 who had

    previously been refused surgery for tonsillitis
    NEG_FINDINGS

 due to the

    potential for oedema
    NEG_FINDINGS

, in whom

    regular monitoring of C1-INH levels
    PARACLINICAL

 combined with

    intensified therapy with danazol, tranexamic acid and C1-INH concentrate
    MEDICATION

 enabled an

    uncomplicated procedure
    MEDICATION

 with

    no oedema crisis
    NEG_FINDINGS

. However, clinicians should be alerted that

    higher overall dosages of C1-INH concentrate for perioperative prophylaxis
    MEDICATION

 may be required than those typically used to treat

    acute HAE attacks
    SYMPTOMS

.


A case of hereditary angioedema involving recurrent abdominal attacks.

A 44-year-old Japanese woman was diagnosed with type 1 hereditary angioedema (HAE) at the age of 30. In March 2007, she began suffering from severe abdominal pain due to intestinal edema. After treatment with C1-INH concentrate, her symptoms disappeared. However, during the subsequent three years, the frequency of the attacks increased continuously, and C1-INH concentrate was necessary for treatment of every attack. The increase in the number of attacks might have been due to the frequent injection of C1-INH concentrate or the deterioration of her disease course. In a genetic investigation, the patient was found to have a novel mutation in the C1-INH gene.

A

    44-year-old
    AGE

    Japanese
    ETHNICITY

    woman
    GENDER

 was diagnosed with

    type 1 hereditary angioedema (HAE)
    DIAGNOSIS

 at the

    age of 30
    AGE

. In March 2007,

    she
    GENDER

 began suffering from

    severe abdominal pain
    SYMPTOMS

 due to

    intestinal edema
    SYMPTOMS

. After

    treatment with C1-INH concentrate
    MEDICATION

,

    her
    GENDER

    symptoms disappeared
    SYMPTOMS

. However, during the subsequent three years, the frequency of the attacks increased continuously, and

    C1-INH concentrate
    MEDICATION

 was necessary for treatment of every attack. The increase in the number of attacks might have been due to the frequent

    injection of C1-INH concentrate
    MEDICATION

 or the deterioration of her disease course. In a

    genetic investigation
    PARACLINICAL

, the patient was found to have a

    novel mutation in the C1-INH gene
    GENETICS

.

severe abdominal pain
intestinal edema
symptoms disappeared

treatment with C1-INH concentrate
C1-INH concentrate
injection of C1-INH concentrate


Icatibant: a novel approach to the treatment of angioedema related to the use of angiotensin-converting enzyme inhibitors.

Angioedema related to the use of angiotensin-converting enzyme inhibitors (AE-ACEi) has, so far, been treated with antiallergic drugs with questionable results. Because angioedema in this setting is likely related to increased levels of bradikinin, we decided to use icatibant, a bradikinin receptor antagonist licensed for use in hereditary angioedema, in a patient with AE-ACEi. In the same patient, the time to resolution of the angioedema during previous attacks was about 2 days when classic antiallergic drug regimens were used; when icatibant was used, this time shortened to 10 hours. Icatibant is a promising drug in the treatment of AE-ACEi.

    Angioedema
    DIAGNOSIS

 related to the use of

    angiotensin-converting enzyme inhibitors (AE-ACEi)
    MEDICATION

 has, so far, been treated with

    antiallergic drugs
    NEG_FINDINGS

 with questionable results. Because

    angioedema
    DIAGNOSIS

 in this setting is likely related to

    increased levels of bradikinin
    BIOCHEMICAL

, we decided to use

    icatibant, a bradikinin receptor antagonist
    MEDICATION

 licensed for use in

    hereditary angioedema
    DIAGNOSIS

, in a patient with

    AE-ACEi
    DIAGNOSIS

. In the same patient, the time to

    resolution of the angioedema during previous attacks was about 2 days
    SYMPTOMS

 when

    classic antiallergic drug regimens were used
    NEG_FINDINGS

; when

    icatibant
    MEDICATION

 was used, this time shortened to 10 hours.

    Icatibant
    MEDICATION

 is a promising drug in the treatment of

    AE-ACEi
    DIAGNOSIS

.

Angioedema
angioedema
hereditary angioedema
AE-ACEi
AE-ACEi


Acute paediatric compartment syndrome of the hand caused by hereditary angiooedema.

Compartment syndrome of the leg and forearm are well described in the literature. However, compartment syndrome of the hand is rare and in children it is even rarer. Atraumatic hand compartment syndrome has not to our knowledge been previously reported. We describe a case of an atraumatic compartment syndrome of the hand in a child who underwent an urgent fasciotomy. The child was diagnosed with hereditary angiooedema. We highlight a rare but serious complication of a hereditary disease not commonly seen by the surgical community. We hope that this report raises the awareness of this condition, thereby reducing delays in reaching a prompt diagnosis.

    Compartment syndrome of the leg and forearm
    SYMPTOMS

 are well described in the literature. However,

    compartment syndrome of the hand
    DIAGNOSIS

 is rare and in

    children
    AGE

 it is even rarer.

    Atraumatic hand compartment syndrome
    SYMPTOMS

 has not to our knowledge been previously reported. We describe a case of an

    atraumatic compartment syndrome of the hand
    SYMPTOMS

 in a

    child
    AGE

 who underwent an

    urgent fasciotomy
    MEDICATION

. The

    child
    AGE

 was diagnosed with

    hereditary angiooedema
    DIAGNOSIS

. We highlight a rare but serious complication of a

    hereditary disease
    GENETICS

 not commonly seen by the surgical community. We hope that this report raises the awareness of this condition, thereby reducing delays in reaching a prompt diagnosis.

compartment syndrome of the hand
hereditary angiooedema


[Icatibant is a new treatment option in life-threatening angioedema triggered by angiotensin-converting enzyme inhibitor].

A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema.

A

    78 year-old
    AGE

    woman
    GENDER

 with

    life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema
    SYMPTOMS

 was

    unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine
    NEG_FINDINGS

.

    She
    GENDER

 was successfully treated with

    icatibant
    MEDICATION

 licensed for treatment of

    hereditary angioedema
    DIAGNOSIS

 knowing that both conditions involve

    bradykinin induced activation of bradykinin B2 receptors
    BIOCHEMICAL

. Randomised, controlled trials are warranted to document the efficacy of

    icatibant
    MEDICATION

 in

    ACE-i angioedema
    DIAGNOSIS

.


Successful long-term treatment with the bradykinin B2 receptor antagonist icatibant in a patient with hereditary angioedema.

Hereditary angioedema (HAE) is a rare, autosomal dominant disorder caused by a C1-esterase inhibitor (C1-INH) deficiency (type 1) or qualitative defect (type 2). It is characterized by recurrent subcutaneous or submucosal edema attacks in various organs with a frequency from a few attacks to over one hundred attacks per year.

We report on the treatment of 141 attacks in a patient with hereditary angioedema with the bradykinin B2 receptor antagonist icatibant.

During the entire observation period, efficacy of icatibant was maintained and not altered due to repeated administrations. No systemic or cardiovascular side affects were observed.

In the present case, icatibant proved to be an effective and safe drug for the symptomatic treatment of acute HAE attacks. Its efficacy was not impaired by repeated administrations over a three-year period in this patient.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare, autosomal dominant disorder
    GENETICS

 caused by a

    C1-esterase inhibitor (C1-INH) deficiency (type 1)
    BIOCHEMICAL

 or

    qualitative defect
    GENETICS

 (

    type 2)
    DIAGNOSIS

. It is characterized by

    recurrent subcutaneous or submucosal edema attacks in various organs
    SYMPTOMS

 with a frequency from a few attacks to over one hundred attacks per year.

We report on the treatment of

    141 attacks
    SYMPTOMS

 in a patient with

    hereditary angioedema
    DIAGNOSIS

 with the

    bradykinin B2 receptor antagonist icatibant
    MEDICATION

.

During the entire observation period,

    efficacy of icatibant
    SYMPTOMS

 was maintained and

    not altered due to repeated administrations
    NEG_FINDINGS

.

    No systemic or cardiovascular side affects
    NEG_FINDINGS

 were observed.

In the present case,

    icatibant
    MEDICATION

 proved to be an effective and safe drug for the

    symptomatic treatment
    MEDICATION

 of

    acute HAE attacks
    DIAGNOSIS

. Its efficacy was

    not impaired by repeated administrations over a three-year period
    NEG_FINDINGS

 in this patient.

Hereditary angioedema (HAE)
type 2)
hereditary angioedema
acute HAE attacks

rare, autosomal dominant disorder
qualitative defect


A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor.

In hereditary angioedema with normal C1-inhibitor two different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported in some families. In this study a novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018+24del72*), was identified in a family of Turkish origin, in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father. This deletion caused a loss of 48 bp of exon 9 (coding amino acids 324* to 340*) in addition to 24 bp of intron 9, including the authentic donor splice site of exon 9. The large deletion of 72 bp was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg* reported previously. Our findings confirm the association between F12 gene mutations modifying the proline-rich region of the FXII protein and hereditary angioedema with normal C1-inhibitor.

In

    hereditary angioedema
    DIAGNOSIS

 with

    normal C1-inhibitor
    NEG_FINDINGS

 two different

    missense mutations of codon p.Thr328* in the coagulation factor 12 gene
    GENETICS

 have been reported in some families. In this study a

    novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018+24del72*)
    GENETICS

, was identified in a

    family of Turkish origin
    FAMILY

    , in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father
    FAMILY

. This

    deletion caused a loss of 48 bp of exon 9 (coding amino acids 324* to 340*) in addition to 24 bp of intron 9, including the authentic donor splice site of exon 9
    GENETICS

.

    The large deletion of 72 bp was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg*
    GENETICS

 reported previously. Our findings confirm the association between

    F12 gene mutations modifying the proline-rich region of the FXII protein
    GENETICS

 and

    hereditary angioedema
    DIAGNOSIS

 with

    normal C1-inhibitor
    NEG_FINDINGS

.

hereditary angioedema
hereditary angioedema


A large heterozygous deletion including the entire C1 inhibitor gene in a sporadic case of hereditary angio-oedema.

C1 inhibitor (C1-INH) deficiency [hereditary or acquired angio-oedema (HAE or AAE)] is characterized by recurring episodes of subcutaneous or submucosal oedema. Many different mutations in the C1-INH gene have been identified as a cause of HAE. We investigated the molecular basis of the disease in a Japanese woman with sporadic HAE. Direct sequencing of genomic DNA revealed no point mutation in the C1-INH gene. Quantitative real-time PCR showed that the copy number of the C1-INH gene in the patient was half that of a healthy control. Furthermore, we identified a 650-kbp deletion on the chromosome, which included the C1-INH gene. We evaluated the correlation between the patient's attacks and her coagulation activity. The levels of D-dimer were high during the angio-oedema attacks, and often exceeded the normal range even during remission, thus the level of D-dimer reflected the activity of HAE in this patient.

    C1 inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 [

    hereditary or acquired angio-oedema (HAE or AAE)
    DIAGNOSIS

] is characterized by

    recurring episodes of subcutaneous or submucosal oedema
    SYMPTOMS

. Many different

    mutations in the C1-INH gene
    GENETICS

 have been identified as a cause of

    HAE
    DIAGNOSIS

. We investigated the molecular basis of the disease in a

    Japanese
    ETHNICITY

    woman
    GENDER

 with

    sporadic HAE
    DIAGNOSIS

.

    Direct sequencing of genomic DNA
    PARACLINICAL

 revealed

    no point mutation in the C1-INH gene
    NEG_FINDINGS

.

    Quantitative real-time PCR
    PARACLINICAL

 showed that the

    copy number of the C1-INH gene
    GENETICS

 in the patient was half that of a healthy control. Furthermore, we identified

    a 650-kbp deletion on the chromosome, which included the C1-INH gene
    GENETICS

. We evaluated the correlation between the patient's attacks and her

    coagulation activity
    BIOCHEMICAL

. The

    levels of D-dimer were high
    BIOCHEMICAL

 during the

    angio-oedema attacks
    SYMPTOMS

, and

    often exceeded the normal range
    BIOCHEMICAL

    even during remission
    NEG_FINDINGS

, thus the

    level of D-dimer
    BIOCHEMICAL

 reflected the activity of

    HAE
    DIAGNOSIS

 in this patient.

C1 inhibitor (C1-INH) deficiency
coagulation activity
levels of D-dimer were high
often exceeded the normal range
level of D-dimer

no point mutation in the C1-INH gene
even during remission


Hereditary angioedema: an unusual cause of genital swelling presenting to a genitourinary medicine clinic.

We report a case of a new diagnosis of hereditary angioedema (HAE) presenting with genital swelling to a genitourinary (GU) medicine clinic. There is often a significant delay in diagnosing HAE, but it commonly presents with genital swelling before manifesting as potentially life-threatening visceral attacks. This case highlights the fact that HAE should be considered as an important differential diagnosis of genital oedema, as early recognition may help to prevent more serious future visceral episodes.

We report a case of a new diagnosis of

    hereditary angioedema (HAE)
    DIAGNOSIS

 presenting with

    genital swelling
    SYMPTOMS

 to a

    genitourinary (GU) medicine
    PARACLINICAL

 clinic. There is often a significant delay in diagnosing

    HAE
    DIAGNOSIS

, but it commonly presents with

    genital swelling
    SYMPTOMS

 before manifesting as

    potentially life-threatening visceral attacks
    SYMPTOMS

. This case highlights the fact that

    HAE
    DIAGNOSIS

 should be considered as an important

    differential diagnosis
    PARACLINICAL

 of

    genital oedema
    SYMPTOMS

, as early recognition may help to

    prevent more serious future visceral episodes
    SYMPTOMS

.


Lack of increased prevalence of immunoregulatory disorders in hereditary angioedema due to C1-inhibitor deficiency.

Hereditary angioedema due to deficiency of C1-INH (HAE-C1-INH) is associated with enhanced consumption of the early complement components, which may predispose for autoimmune disease. We assessed the prevalence of such disorders among HAE- C1-INH patients and their impact on the natural course of HAE-C1-INH. Clinical data and immunoserological parameters of 130 HAE-C1-INH and 174 non-C1-INH-deficient patients with angioedema were analyzed. In our study, the incidence of immunoregulatory disorders was 11.5% in the population of HAE-C1-INH patients and 5.2% among non-C1-INH-deficient controls with angioedema. Immunoserology screening revealed a greater prevalence of anticardiolipin IgM (p=0.0118) among HAE-C1-INH patients, than in those with non-C1-INH-deficient angioedema. We did not find higher prevalence of immunoregulatory disorders among our HAE-C1-INH patients. However, in patients with confirmed immunoregulatory disorders, the latter influenced both the severity of HAE-C1-INH and the effectiveness of its long-term management. Appropriate management of the immunoregulatory disease thus identified improves the symptoms of HAE-C1-INH.

    Hereditary angioedema
    DIAGNOSIS

 due to

    deficiency of C1-INH (HAE-C1-INH)
    BIOCHEMICAL

 is associated with

    enhanced consumption of the early complement components
    BIOCHEMICAL

, which may predispose for

    autoimmune disease
    DIAGNOSIS

. We assessed the prevalence of such disorders among

    HAE- C1-INH
    DIAGNOSIS

 patients and their impact on the natural course of

    HAE-C1-INH
    DIAGNOSIS

. Clinical data and

    immunoserological parameters
    PARACLINICAL

 of 130

    HAE-C1-INH
    DIAGNOSIS

 and 174

    non-C1-INH-deficient
    NEG_FINDINGS

 patients with

    angioedema
    DIAGNOSIS

 were analyzed. In our study, the incidence of

    immunoregulatory disorders
    DIAGNOSIS

 was 11.5% in the population of

    HAE-C1-INH
    DIAGNOSIS

 patients and 5.2% among

    non-C1-INH-deficient
    NEG_FINDINGS

 controls with

    angioedema
    DIAGNOSIS

.

    Immunoserology screening
    PARACLINICAL

 revealed a greater

    prevalence of anticardiolipin IgM
    BIOCHEMICAL

 (p=0.0118) among

    HAE-C1-INH
    DIAGNOSIS

 patients, than in those with

    non-C1-INH-deficient angioedema
    NEG_FINDINGS

. We did not find higher prevalence of

    immunoregulatory disorders
    NEG_FINDINGS

 among our

    HAE-C1-INH
    DIAGNOSIS

 patients. However, in patients with confirmed

    immunoregulatory disorders
    DIAGNOSIS

, the latter influenced both the severity of HAE-C1-INH and the effectiveness of its long-term management. Appropriate management of the

    immunoregulatory disease
    DIAGNOSIS

 thus identified improves the symptoms of

    HAE-C1-INH
    DIAGNOSIS

.


An update on hereditary angioedema.

Hereditary angioedema affects approximately 1 in 50,000 individuals without gender or ethnic preference. Hereditary angioedema is caused by a decreased level (type I) or function (type II) of C1 inhibitor. Patients experience repeated episodes of angioedema involving sites that include the face, extremities, gastrointestinal tract, and larynx. Treatment involves measures to increase functioning levels of active C1 inhibitor through stimulation of endogenous pathways or exogenous supplementation. Additional therapies targeted at inhibition of bradykinin can also be used to treat episodes of angioedema. Treatment may be indicated for both acute episodes of angioedema and prevention of future episodes.

    Hereditary angioedema
    DIAGNOSIS

 affects approximately 1 in 50,000 individuals without gender or ethnic preference.

    Hereditary angioedema
    DIAGNOSIS

 is caused by a

    decreased level (type I) or function (type II) of C1 inhibitor
    BIOCHEMICAL

. Patients experience

    repeated episodes of angioedema involving sites that include the face, extremities, gastrointestinal tract, and larynx
    SYMPTOMS

. Treatment involves

    measures to increase functioning levels of active C1 inhibitor through stimulation of endogenous pathways or exogenous supplementation
    MEDICATION

. Additional therapies targeted at

    inhibition of bradykinin
    BIOCHEMICAL

 can also be used to treat episodes of

    angioedema
    DIAGNOSIS

. Treatment may be indicated for both

    acute episodes of angioedema
    SYMPTOMS

 and

    prevention of future episodes
    SYMPTOMS

.

Hereditary angioedema
Hereditary angioedema
angioedema


Treatment of laryngeal hereditary angioedema.

In the emergency department, patients with laryngeal swelling and an inconclusive patient history may receive treatment for allergy-mediated angioedema. Intubation may be necessary if the patient does not respond to treatment. Because angioedema subtypes respond to different interventions, a correct diagnosis is vital.

Review the differential diagnosis of angioedema and characteristics differentiating subtypes. Discuss therapies for angioedema subtypes. Introduce therapies for prevention and acute treatment of hereditary angioedema (HAE).

A 10-year-old girl presented with laryngeal swelling unresponsive to diphenhydramine, methylprednisolone, and epinephrine. It was later revealed that she had a family history of HAE, was C1 inhibitor deficient, and enrolled in a clinical study of acute HAE treatment. She was given 1000 units of nanofiltered C1 inhibitor and was able to swallow within 30 min. She was prescribed routine prophylaxis with C1 inhibitor concentrate and has had no subsequent severe HAE swelling attacks.

This case illustrates the need for providers to consider HAE in light of available diagnostic testing and recent Food and Drug Administration approval of specific therapies for HAE.

In the emergency department, patients with

    laryngeal swelling
    SYMPTOMS

 and an

    inconclusive patient history
    NEG_FINDINGS

 may receive treatment for

    allergy-mediated angioedema
    DIAGNOSIS

.

    Intubation
    MEDICATION

 may be necessary if the patient

    does not respond to treatment
    NEG_FINDINGS

. Because

    angioedema
    DIAGNOSIS

 subtypes respond to different interventions, a correct diagnosis is vital.

Review the

    differential diagnosis
    PARACLINICAL

 of

    angioedema
    DIAGNOSIS

 and characteristics differentiating subtypes. Discuss therapies for

    angioedema subtypes
    DIAGNOSIS

. Introduce therapies for prevention and

    acute treatment
    MEDICATION

 of

    hereditary angioedema (HAE)
    DIAGNOSIS

.

A

    10-year-old
    AGE

    girl
    GENDER

 presented with

    laryngeal swelling
    SYMPTOMS

    unresponsive to diphenhydramine, methylprednisolone, and epinephrine
    NEG_FINDINGS

. It was later revealed that

    she
    GENDER

 had a

    family history of HAE
    FAMILY

, was

    C1 inhibitor deficient
    BIOCHEMICAL

, and enrolled in a

    clinical study of acute HAE treatment
    MEDICATION

.

    She
    GENDER

 was given

    1000 units of nanofiltered C1 inhibitor
    MEDICATION

 and was

    able to swallow within 30 min
    SYMPTOMS

.

    She
    GENDER

 was prescribed

    routine prophylaxis with C1 inhibitor concentrate
    MEDICATION

 and has had

    no subsequent severe HAE swelling attacks
    NEG_FINDINGS

.

This case illustrates the need for providers to consider

    HAE
    DIAGNOSIS

 in light of available diagnostic testing and recent Food and Drug Administration approval of specific therapies for

    HAE
    DIAGNOSIS

.

laryngeal swelling
laryngeal swelling
able to swallow within 30 min

allergy-mediated angioedema
angioedema
angioedema
angioedema subtypes
hereditary angioedema (HAE)
HAE
HAE


[Facial edema as an earlier presenting sign of giant cell arteritis. Possible relationship with angioedema].

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown etiology occurring in the elderly. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated polymyalgia rheumatica represent the most typical and frequent features of the disease. However, facial edema is being more commonly recognized as a presenting symptom that may herald the disease. We present a case with facial edema as initial symptom and discuss if this rare symptom of GCA is due to hereditary or acquired angioedema.

    Giant cell arteritis (GCA)
    DIAGNOSIS

 is a

    chronic granulomatous vasculitis of unknown etiology
    DIAGNOSIS

 occurring in the

    elderly
    AGE

.

    New-onset headache
    SYMPTOMS

,

    scalp tenderness
    SYMPTOMS

,

    jaw claudication
    SYMPTOMS

,

    temporal artery abnormalities on physical examination
    SYMPTOMS

,

    visual symptoms
    SYMPTOMS

 and associated

    polymyalgia rheumatica
    DIAGNOSIS

 represent the most typical and frequent features of the disease. However,

    facial edema
    SYMPTOMS

 is being more commonly recognized as a presenting symptom that may herald the disease. We present a case with

    facial edema
    SYMPTOMS

 as initial symptom and discuss if this rare symptom of

    GCA
    DIAGNOSIS

 is due to hereditary or acquired

    angioedema
    DIAGNOSIS

.


Diagnosis and management of hereditary angioedema.

Hereditary angioedema (HAE) is characterized by sudden attacks of deep tissue swelling caused by C1 inhibitor deficiency. Swelling severity can vary from mild to severe, and some patients are at risk for disability and death from either asphyxiation or hypovolemic shock. Many HAE attacks are precipitated by trauma or stress. The extremities, genitalia, trunk, bowels, face, and larynx are commonly affected areas, but swelling can affect any single part of the body or multiple sites. Symptoms typically worsen over 24 to 36 hours and resolve within 48 hours. Because many symptoms of HAE overlap with those of other medical conditions, diagnosis may be delayed. A thorough family history can identify the signature symptoms of HAE, which include a family history of HAE, recurrent edema without urticaria, and symptomatic worsening during puberty. The author presents two hypothetical cases of HAE and reviews the clinical hallmarks of this condition, diagnostic tests, and available treatments.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterized by

    sudden attacks of deep tissue swelling
    SYMPTOMS

 caused by

    C1 inhibitor deficiency
    BIOCHEMICAL

.

    Swelling severity
    SYMPTOMS

 can vary from mild to severe, and some patients are at risk for

    disability
    SYMPTOMS

 and

    death
    SYMPTOMS

 from either

    asphyxiation
    SYMPTOMS

 or

    hypovolemic shock
    SYMPTOMS

. Many

    HAE
    DIAGNOSIS

 attacks are precipitated by

    trauma
    SYMPTOMS

 or

    stress
    SYMPTOMS

.

    The extremities, genitalia, trunk, bowels, face, and larynx
    SYMPTOMS

 are commonly affected areas, but

    swelling can affect any single part of the body or multiple sites
    SYMPTOMS

. Symptoms typically

    worsen over 24 to 36 hours
    SYMPTOMS

 and resolve within 48 hours. Because many symptoms of

    HAE
    DIAGNOSIS

    overlap with those of other medical conditions
    SYMPTOMS

, diagnosis may be delayed. A thorough

    family history
    PARACLINICAL

 can identify the signature symptoms of

    HAE
    DIAGNOSIS

, which include a

    family history of HAE
    FAMILY

,

    recurrent edema
    SYMPTOMS

    without urticaria
    NEG_FINDINGS

, and

    symptomatic worsening
    SYMPTOMS

 during

    puberty
    SYMPTOMS

. The author presents two hypothetical cases of

    HAE
    DIAGNOSIS

 and reviews the clinical hallmarks of this condition, diagnostic tests, and available treatments.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE


Initial presentation of hereditary angioedema as abdominal pain and ascites in puerperium: case report.

Hereditary angioedema is a rare genetic disorder resulting from an inherited deficiency or dysfunction of the C1 inhibitor. It is characterized by recurrent, circumscribed, and self-limiting episodes of cutaneous and mucous membrane swelling involving different organs. Hereditary angioedema may present with diverse clinical pictures, even within families with the same mutation. We present a first reported case of type 1 hereditary angioedema in a young woman presenting as recurrent abdominal pain associated with ascites without any other clinical features of hereditary angioedema, with initial presentation in puerperium. The recognition or awareness of hereditary angioedema as a cause of acute and/or recurrent abdominal pain associated with ascites is important, and may avoid unnecessary invasive procedures and facilitate appropriate treatment.

    Hereditary angioedema
    DIAGNOSIS

 is a

    rare genetic disorder
    GENETICS

 resulting from an

    inherited deficiency or dysfunction of the C1 inhibitor
    GENETICS

. It is characterized by

    recurrent, circumscribed, and self-limiting episodes of cutaneous and mucous membrane swelling involving different organs
    SYMPTOMS

.

    Hereditary angioedema
    DIAGNOSIS

 may present with diverse clinical pictures, even within

    families with the same mutation
    FAMILY

. We present a first reported case of

    type 1 hereditary angioedema
    DIAGNOSIS

 in a

    young
    AGE

    woman
    GENDER

 presenting as

    recurrent abdominal pain associated with ascites
    SYMPTOMS

    without any other clinical features of hereditary angioedema
    NEG_FINDINGS

, with initial presentation in

    puerperium
    AGE

. The recognition or awareness of

    hereditary angioedema
    DIAGNOSIS

 as a cause of

    acute and/or recurrent abdominal pain associated with ascites
    SYMPTOMS

 is important, and may avoid

    unnecessary invasive procedures
    NEG_FINDINGS

 and facilitate appropriate treatment.

Hereditary angioedema
Hereditary angioedema
type 1 hereditary angioedema
hereditary angioedema