Lesson of the month 2: The limitations of steroid therapy in bradykinin-mediated angioedema attacks.

Acute angioedema attacks are conventionally treated with antihistamines and steroids, in line with a presumed mechanism of disease involving overwhelming mast-cell degranulation. This approach overlooks a small but important minority of cases in which attacks are bradykinin driven and exhibit poor responsiveness to steroid or anti-histamine therapy. These patients may have a family history of angioedema (hereditary angioedema), or a past medical history including B-cell lymphoproliferative disorders or autoimmune disease (acquired angioedema). Rather than steroid therapy, they respond to administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute, to control acute symptoms and reduce the probability of invasive airway insertion. In the long-term, they require C1 esterase inhibitor sparing therapy and a treat-the-cause approach to reduce the risk of recurrent attacks. We present here a case of a middle-aged woman who presented with recurrent angioedema of initially uncertain aetiology.

    Acute angioedema attacks
    SYMPTOMS

 are conventionally treated with

    antihistamines and steroids
    MEDICATION

, in line with a presumed mechanism of disease involving

    overwhelming mast-cell degranulation
    BIOCHEMICAL

. This approach overlooks a small but important minority of cases in which attacks are

    bradykinin driven
    SYMPTOMS

 and exhibit

    poor responsiveness to steroid or anti-histamine therapy
    NEG_FINDINGS

. These patients may have a

    family history of angioedema (hereditary angioedema
    FAMILY

), or a

    past medical history including B-cell lymphoproliferative disorders
    FAMILY

 or

    autoimmune disease (acquired angioedema)
    DIAGNOSIS

. Rather than

    steroid therapy
    MEDICATION

, they respond to

    administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute
    MEDICATION

, to

    control acute symptoms
    SYMPTOMS

 and

    reduce the probability of invasive airway insertion
    MEDICATION

. In the long-term, they require

    C1 esterase inhibitor sparing therapy
    MEDICATION

 and a

    treat-the-cause approach
    MEDICATION

 to reduce the risk of

    recurrent attacks
    SYMPTOMS

. We present here a case of a

    middle-aged
    AGE

    woman
    GENDER

 who presented with

    recurrent angioedema
    SYMPTOMS

 of

    initially uncertain aetiology
    NEG_FINDINGS

.

Acute angioedema attacks
bradykinin driven
control acute symptoms
recurrent attacks
recurrent angioedema


Treatment with icatibant in the management of drug induced angioedema.

Acute, drug-induced angioedema may not respond to standard therapies, because the pathogenetic mechanism that induces the pathology is not always mediated by histamine but, in certain instances, by bradykinin. A case of angioedema is reported here, in which allergic etiology was excluded by the non-response to antihistamines. Considering the clinical history (repeated use of drugs) and the ineffectiveness of standard therapy, it was decided to administer a beta2 receptor antagonist, icatibant. After 20 minutes, the patient reported a subjective improvement. The only form of angioedema for which this type of medication is licensed is the hereditary deficiency of C1 inhibitor. The use of icatibant for the treatment of other types of angioedema (which can also be life-saving if the airway is involved) is off label. The off-label use of a drug is allowed in the absence of a viable alternative therapy, if there is scientific evidence in the literature and if the prescriber takes responsibility. The case here reported draws attention to this therapeutic problem and underlines the fact that a life-threatening emergency can justify the use of icatibant.

    Acute, drug-induced angioedema
    DIAGNOSIS

 may

    not respond to standard therapies
    NEG_FINDINGS

, because the pathogenetic mechanism that induces the pathology is not always mediated by histamine but, in certain instances, by

    bradykinin
    BIOCHEMICAL

. A case of

    angioedema
    DIAGNOSIS

 is reported here, in which

    allergic etiology was excluded
    NEG_FINDINGS

 by the

    non-response to antihistamines
    NEG_FINDINGS

. Considering the clinical history (

    repeated use of drugs
    SYMPTOMS

) and the

    ineffectiveness of standard therapy
    NEG_FINDINGS

, it was decided to administer a

    beta2 receptor antagonist, icatibant
    MEDICATION

. After 20 minutes, the patient reported a

    subjective improvement
    SYMPTOMS

. The only form of

    angioedema
    DIAGNOSIS

 for which this

    type of medication
    MEDICATION

 is licensed is the

    hereditary deficiency of C1 inhibitor
    BIOCHEMICAL

. The use of

    icatibant
    MEDICATION

 for the treatment of other types of

    angioedema
    DIAGNOSIS

 (which can also be

    life-saving
    SYMPTOMS

 if the airway is involved) is off label. The

    off-label use of a drug
    MEDICATION

 is allowed in the absence of a viable alternative therapy, if there is scientific evidence in the literature and if the prescriber takes responsibility. The case here reported draws attention to this therapeutic problem and underlines the fact that a

    life-threatening emergency
    SYMPTOMS

 can justify the use of

    icatibant
    MEDICATION

.

Acute, drug-induced angioedema
angioedema
angioedema
angioedema

not respond to standard therapies
allergic etiology was excluded
non-response to antihistamines
ineffectiveness of standard therapy

bradykinin
hereditary deficiency of C1 inhibitor

repeated use of drugs
subjective improvement
life-saving
life-threatening emergency

beta2 receptor antagonist, icatibant
type of medication
icatibant
off-label use of a drug
icatibant


Hepatocellular carcinoma in a noncirrhotic liver after long-term use of danazol for hereditary angioedema.

We report a 57-year-old male who was treated with high-dose danazol for hereditary angioedema for more than 30 years; he developed hepatocellular carcinoma in the absence of cirrhosis. Despite surgical resection, he had a recurrence and received sorafenib, but had a poor skin tolerance. Such tumors arising after danazol are infrequent, and this case is highly unique due to the minor lesions found on the liver.

We report a

    57-year-old
    AGE

    male
    GENDER

 who was

    treated with high-dose danazol
    MEDICATION

 for

    hereditary angioedema
    DIAGNOSIS

    for more than 30 years
    MEDICATION

;

    he
    GENDER

 developed

    hepatocellular carcinoma
    DIAGNOSIS

 in the

    absence of cirrhosis
    NEG_FINDINGS

.

    Despite surgical resection
    NEG_FINDINGS

,

    he
    GENDER

 had a recurrence and received

    sorafenib
    MEDICATION

, but had a

    poor skin tolerance
    NEG_FINDINGS

. Such

    tumors
    SYMPTOMS

 arising after

    danazol
    MEDICATION

 are infrequent, and this case is highly unique due to the

    minor lesions found on the liver
    SYMPTOMS

.

treated with high-dose danazol
for more than 30 years
sorafenib
danazol

hereditary angioedema
hepatocellular carcinoma

absence of cirrhosis
Despite surgical resection
poor skin tolerance


Bradykinin B2 receptor antagonist off label use in short-term prophylaxis in hereditary angioedema.

Hereditary angioedema type I (HAE-C1-INH) is an inherited disorder characterized by repeated severe angioedema attacks mostly triggered by traumas, emotional stress, increased estrogen levels or surgical procedures, in particular, odontostomatological interventions. Icatibant, a bradykinin B2 receptor antagonist, has been approved for treatment of HAE attacks. In this paper we describe the off label administration of icatibant as short-term prophylaxis of dental extraction in a patient with HAE with the aim of preventing perioperative angioedema attacks. The drug showed an effective and safe profile. Thus, a short-term prophylaxis of angioedema attacks in patients with HAE may be arranged on a multidisciplinary basis, according to the clinical history of each single patients.

    Hereditary angioedema type I (HAE-C1-INH)
    DIAGNOSIS

 is an

    inherited disorder
    GENETICS

 characterized by

    repeated severe angioedema attacks
    SYMPTOMS

 mostly triggered by

    traumas
    SYMPTOMS

,

    emotional stress
    SYMPTOMS

,

    increased estrogen levels
    SYMPTOMS

 or

    surgical procedures
    MEDICATION

, in particular,

    odontostomatological interventions
    MEDICATION

.

    Icatibant, a bradykinin B2 receptor antagonist
    MEDICATION

, has been approved for treatment of

    HAE attacks
    DIAGNOSIS

. In this paper we describe the off label administration of icatibant as short-term prophylaxis of dental extraction in a patient with

    HAE
    DIAGNOSIS

 with the aim of preventing

    perioperative angioedema attacks
    SYMPTOMS

. The drug showed an effective and safe profile. Thus, a

    short-term prophylaxis of angioedema attacks
    MEDICATION

 in patients with

    HAE
    DIAGNOSIS

 may be arranged on a multidisciplinary basis, according to the clinical history of each single patients.

repeated severe angioedema attacks
traumas
emotional stress
increased estrogen levels
perioperative angioedema attacks


Gastrointestinal manifestations of hereditary angioedema diagnosed by ultrasound in the emergency department.

Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE). The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC) ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation, and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE.

    Abdominal angioedema
    DIAGNOSIS

 is a less recognized type of

    angioedema
    DIAGNOSIS

, which can occur in patients with

    hereditary angioedema (HAE)
    DIAGNOSIS

. The clinical signs may range from

    subtle, diffuse abdominal pain
    SYMPTOMS

 and

    nausea
    SYMPTOMS

, to

    overt peritonitis
    SYMPTOMS

. We describe two cases of

    abdominal angioedema
    DIAGNOSIS

 in patients with known

    HAE
    DIAGNOSIS

 that were diagnosed in the emergency department by

    point-of-care (POC) ultrasound
    PARACLINICAL

. In each case, the patient presented with

    isolated abdominal complaints
    SYMPTOMS

 and

    no signs of oropharyngeal edema
    NEG_FINDINGS

. Findings on

    POC ultrasound
    PARACLINICAL

 included

    intraperitoneal free fluid
    SYMPTOMS

 and

    bowel wall edema
    SYMPTOMS

. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires

    no ionizing radiation
    NEG_FINDINGS

, and can rule out alternative diagnoses,

    POC ultrasound
    PARACLINICAL

 holds promise as a valuable tool in the evaluation and management of patients with

    HAE
    DIAGNOSIS

.

Abdominal angioedema
angioedema
hereditary angioedema (HAE)
abdominal angioedema
HAE
HAE

subtle, diffuse abdominal pain
nausea
overt peritonitis
isolated abdominal complaints
intraperitoneal free fluid
bowel wall edema

no signs of oropharyngeal edema
no ionizing radiation


Hereditary angioedema and anxiety in oral surgery: a case series report.

Hereditary angioedema (HAE) is a rare disease, little known to medical and dental practitioners, but with an increasing hospitalization rate over the years. HAE is due to a C1 esterase inhibitor deficiency/dysfunction that leads to an increased vascular permeability. The airways are the most affected, and life-threatening laryngeal swelling may occur. Episodes of HAE have no clear cause, but they can be triggered by anxiety, invasive procedures, and trauma. HAE is an important issue in oral and maxillofacial surgery, otorhinolaryngology, endoscopy, emergency medicine, and anesthesiology because even simple procedures may cause laryngeal edema. Recommendations on the management of HAE include long- and short-term prophylaxis, and treatment for acute attacks, but the importance of controlling anxiety is underestimated. Here, we report on the perioperative management of nine HAE patients scheduled for oral surgery, with a brief review of the literature on this topic.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare disease, little known to medical and dental practitioners, but with an increasing hospitalization rate over the years.

    HAE
    DIAGNOSIS

 is due to a

    C1 esterase inhibitor deficiency/dysfunction
    BIOCHEMICAL

 that leads to an

    increased vascular permeability
    BIOCHEMICAL

. The airways are the most affected, and

    life-threatening laryngeal swelling
    SYMPTOMS

 may occur. Episodes of

    HAE
    DIAGNOSIS

 have

    no clear cause
    NEG_FINDINGS

, but they can be triggered by

    anxiety
    SYMPTOMS

,

    invasive procedures
    MEDICATION

, and

    trauma
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 is an important issue in

    oral and maxillofacial surgery
    MEDICATION

,

    otorhinolaryngology
    PARACLINICAL

,

    endoscopy
    PARACLINICAL

,

    emergency medicine
    PARACLINICAL

, and

    anesthesiology
    PARACLINICAL

 because even simple procedures may cause

    laryngeal edema
    SYMPTOMS

. Recommendations on the management of

    HAE
    DIAGNOSIS

 include

    long- and short-term prophylaxis
    MEDICATION

, and

    treatment
    MEDICATION

 for

    acute attacks
    SYMPTOMS

, but the importance of

    controlling anxiety
    MEDICATION

 is underestimated. Here, we report on the perioperative management of nine

    HAE
    DIAGNOSIS

 patients scheduled for

    oral surgery
    MEDICATION

, with a brief review of the literature on this topic.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE

life-threatening laryngeal swelling
anxiety
trauma
laryngeal edema
acute attacks

invasive procedures
oral and maxillofacial surgery
long- and short-term prophylaxis
treatment
controlling anxiety
oral surgery


Perioperative management of tooth extractions for a patient with hereditary angioedema.

Hereditary angioedema (HAE) is a rare genetic disorder that causes a deficiency in or dysfunction of C1 esterase inhibitor (C1-INH) and is clinically characterized by sudden and recurrent attacks of angioedema. Although almost any part of the body can be affected, HAE is of greatest concern and can be life-threatening when the upper airway is involved, particularly the larynx (laryngeal attack). HAE attacks can be triggered by physical or psychological stress or can arise spontaneously without any apparent trigger. Dental treatments and routine oral surgical procedures, such as tooth extraction, abound with factors that can trigger an attack of HAE. Indeed, several cases of death resulting from HAE attacks have been reported after such procedures. Therefore, patients with HAE are of special concern in dentistry and require precautionary preparations before treatment. This report describes the successful management of tooth extractions in a patient with HAE who was at high risk of an HAE-induced laryngeal attack.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic disorder
    GENETICS

 that causes a

    deficiency in or dysfunction of C1 esterase inhibitor (C1-INH)
    BIOCHEMICAL

 and is clinically characterized by

    sudden and recurrent attacks of angioedema
    SYMPTOMS

. Although almost any part of the body can be affected,

    HAE
    DIAGNOSIS

 is of greatest concern and can be

    life-threatening
    SYMPTOMS

 when the

    upper airway is involved, particularly the larynx (laryngeal attack)
    SYMPTOMS

.

    HAE attacks
    SYMPTOMS

 can be triggered by

    physical or psychological stress
    SYMPTOMS

 or can arise spontaneously

    without any apparent trigger
    NEG_FINDINGS

.

    Dental treatments
    MEDICATION

 and

    routine oral surgical procedures
    MEDICATION

, such as

    tooth extraction
    MEDICATION

, abound with factors that can trigger an

    attack of HAE
    SYMPTOMS

. Indeed, several cases of

    death
    SYMPTOMS

 resulting from

    HAE attacks
    SYMPTOMS

 have been reported after such procedures. Therefore, patients with

    HAE
    DIAGNOSIS

 are of special concern in dentistry and require precautionary preparations before treatment. This report describes the successful

    management of tooth extractions
    MEDICATION

 in a patient with

    HAE
    DIAGNOSIS

 who was at high risk of an

    HAE-induced laryngeal attack
    SYMPTOMS

.

Dental treatments
routine oral surgical procedures
tooth extraction
management of tooth extractions


[Hereditary angioedema: strange cause of abdominal pain].

Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance characterized by sudden attacks of peripheral swelling. Patients also commonly have episodic swelling of the wall of hollow viscera, including the bowel.

We present a 33-year-old previously healthy male with a complaint of acute-onset intense abdominal pain localized in the epigastrium. Pain irradiated to the right lower quadrant and was associated with five episodes of vomiting. Computed tomography showed thickening of the duodenal wall with liquid in the subphrenic space. Complementary laboratory tests showed low C4 complement levels (5.5 mg/dl) and 30% complement C1 inhibitor activity.

Hereditary angioedema is caused by a deficiency (type I) or dysfunction (type II) in complement C1 inhibitor. Abdominal associated with angioedema may manifest as severe acute-onset abdominal pain or as moderately severe chronic recurrent abdominal pain. Two medications are currently FDA-approved for the treatment of these patients.

    Hereditary angioedema
    DIAGNOSIS

 is an

    episodic swelling disorder
    DIAGNOSIS

 with

    autosomal dominant inheritance
    GENETICS

 characterized by

    sudden attacks of peripheral swelling
    SYMPTOMS

. Patients also commonly have

    episodic swelling of the wall of hollow viscera, including the bowel
    SYMPTOMS

.

We present a

    33-year-old
    AGE

 previously healthy

    male
    GENDER

 with a complaint of

    acute-onset intense abdominal pain localized in the epigastrium
    SYMPTOMS

.

    Pain irradiated to the right lower quadrant
    SYMPTOMS

 and was associated with

    five episodes of vomiting
    SYMPTOMS

.

    Computed tomography
    PARACLINICAL

 showed

    thickening of the duodenal wall with liquid in the subphrenic space
    SYMPTOMS

.

    Complementary laboratory tests
    PARACLINICAL

 showed

    low C4 complement levels (5.5 mg/dl)
    BIOCHEMICAL

 and

    30% complement C1 inhibitor activity
    BIOCHEMICAL

.

    Hereditary angioedema
    DIAGNOSIS

 is caused by a

    deficiency (type I) or dysfunction (type II) in complement C1 inhibitor
    BIOCHEMICAL

.

    Abdominal
    SYMPTOMS

 associated with

    angioedema
    DIAGNOSIS

 may manifest as

    severe acute-onset abdominal pain
    SYMPTOMS

 or as

    moderately severe chronic recurrent abdominal pain
    SYMPTOMS

. Two medications are currently FDA-approved for the treatment of these patients.

Hereditary angioedema
episodic swelling disorder
Hereditary angioedema
angioedema


The role of icatibant-the B2 bradykinin receptor antagonist-in life-threatening laryngeal angioedema in the ED.

Angioedema is a localized, sudden, transient, and often recurrent swelling of the deeper layers of the skin or mucosa with no epidermal component. It is caused by vasoactive substances that produce a transient increase in endothelial permeability. Angioedema involving the laryngeal components is a life-threatening situation for the patient,and it is a challenge for the emergency medicine physician to rapidly achieve a safety airway. Most cases of laryngeal angioedema are induced by histamine release; but 10% are bradykinin induced, which does not respond to the conventional algorithm of treating allergic induced angioedema. We present a case report of an angiotensin converting enzyme (ACE) inhibitor–induced laryngeal angioedema alleviated only after treatment with the new bradykinin receptor inhibitor medication icatibant which was licensed only for use in hereditary angioedema. We reviewed the literature for the use of icatibant in acquired drug-induced angioedema; and because of the similar pathogenesis between the hereditary angioedema and the ACE inhibitor–induced angioedema,we propose an algorithm for careful use of icatibantin life-threatening angioedema in the emergency department.

    Angioedema
    DIAGNOSIS

 is a

    localized, sudden, transient, and often recurrent swelling of the deeper layers of the skin or mucosa with no epidermal component
    SYMPTOMS

. It is caused by

    vasoactive substances
    SYMPTOMS

 that produce a

    transient increase in endothelial permeability
    BIOCHEMICAL

.

    Angioedema involving the laryngeal components
    SYMPTOMS

 is a life-threatening situation for the patient,and it is a challenge for the

    emergency medicine physician
    PARACLINICAL

 to rapidly achieve a safety airway. Most cases of

    laryngeal angioedema
    DIAGNOSIS

 are induced by

    histamine release
    BIOCHEMICAL

; but 10% are

    bradykinin induced
    BIOCHEMICAL

, which does

    not respond to the conventional algorithm of treating allergic induced angioedema
    NEG_FINDINGS

. We present a case report of an

    angiotensin converting enzyme (ACE) inhibitor–induced laryngeal angioedema
    MEDICATION

 alleviated only after treatment with the

    new bradykinin receptor inhibitor medication icatibant
    MEDICATION

 which was licensed only for use in

    hereditary angioedema
    DIAGNOSIS

. We reviewed the literature for the use of

    icatibant
    MEDICATION

 in

    acquired drug-induced angioedema
    DIAGNOSIS

; and because of the similar pathogenesis between the

    hereditary angioedema
    DIAGNOSIS

 and the

    ACE inhibitor–induced angioedema
    DIAGNOSIS

,we propose an algorithm for careful use of icatibantin

    life-threatening angioedema
    DIAGNOSIS

 in the emergency department.

Angioedema
laryngeal angioedema
hereditary angioedema
acquired drug-induced angioedema
hereditary angioedema
ACE inhibitor–induced angioedema
life-threatening angioedema


Tissue factor expression on the surface of monocytes from a patient with hereditary angioedema.

Hereditary angioedema (HAE) presents as severe angioedema, which is mostly due to the C1 inhibitor (C1-INH) gene mutations. Environmental factors, minor trauma and oral contraceptives have been reported to induce angioedema attack, but the trigger may often be uncertain. Activated factor XII controlled by C1-INH facilitates bradykinin generation and also regulates coagulation cascade, but the relationship between edema formation and coagulation is still unclear. We have described a 35-year-old female patient with HAE, presenting with frequent angioedema attacks in the absence of an apparent triggering factor. She showed higher levels of FDP and D-dimer during angioedema than those in remission. In addition, tissue factor (TF), an initiator of the extrinsic coagulation cascade, was expressed on the surface of monocytes. It was significantly higher than that of monocytes from healthy controls and tends to further increase during attacks. The expression of TF on monocytes may play a role in the induction of angioedema attacks in HAE by activating the coagulation pathway in association with reduced functions of C1-INH.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 presents as

    severe angioedema
    SYMPTOMS

, which is mostly due to the

    C1 inhibitor (C1-INH) gene mutations
    GENETICS

.

    Environmental factors
    SYMPTOMS

,

    minor trauma
    SYMPTOMS

 and

    oral contraceptives
    MEDICATION

 have been reported to induce

    angioedema attack
    SYMPTOMS

, but the trigger may often be uncertain.

    Activated factor XII controlled by C1-INH
    BIOCHEMICAL

 facilitates

    bradykinin generation
    BIOCHEMICAL

 and also

    regulates coagulation cascade
    BIOCHEMICAL

, but the relationship between

    edema formation
    SYMPTOMS

 and

    coagulation
    BIOCHEMICAL

 is still unclear. We have described a

    35-year-old
    AGE

    female
    GENDER

 patient with

    HAE
    DIAGNOSIS

, presenting with frequent

    angioedema attacks
    SYMPTOMS

 in the

    absence of an apparent triggering factor
    NEG_FINDINGS

.

    She
    GENDER

 showed

    higher levels of FDP and D-dimer
    BIOCHEMICAL

 during

    angioedema
    SYMPTOMS

 than those

    in remission
    NEG_FINDINGS

. In addition,

    tissue factor (TF)
    GENETICS

, an

    initiator of the extrinsic coagulation cascade
    BIOCHEMICAL

, was

    expressed on the surface of monocytes
    MICROSCOPIC

. It was significantly higher than that of monocytes from healthy controls and tends to further increase during attacks. The

    expression of TF on monocytes
    GENETICS

 may play a role in the induction of

    angioedema attacks
    SYMPTOMS

 in

    HAE
    DIAGNOSIS

 by

    activating the coagulation pathway
    BIOCHEMICAL

 in association with

    reduced functions of C1-INH
    BIOCHEMICAL

.

severe angioedema
Environmental factors
minor trauma
angioedema attack
edema formation
angioedema attacks
angioedema
angioedema attacks

C1 inhibitor (C1-INH) gene mutations
tissue factor (TF)
expression of TF on monocytes


Hereditary angioedema: A rare cause of recurrent abdominal pain.

Hereditary angioedema is a rare autosomal dominant inherited disease which is characterized by an episodic, self-limiting increase in vascular permeability. Symptoms commonly involve in nonpitting, nonpruritic skin swellings. We present a case of hereditary angioedema. The patinets complained of a recurrent abdominal pain without accompanying skin swelling whose diagnosis was delayed nearly 20 years and accepted an unnecessary surgery. According to the decreased serum C1-inhibitor and C4 concentration, the patient was finally diagnosed with hereditary angioedema type I. After treatment with danazole, the patient reported a significant decrease in the frequency of attacks and the severity of pain. HAE is a rare cause of abdominal pain, however it needs to be taken as one of the differential diagnosis of various acute abdomens in order to avoid unnecessary surgeries.

    Hereditary angioedema
    DIAGNOSIS

 is a

    rare autosomal dominant inherited disease
    GENETICS

 which is characterized by an

    episodic, self-limiting increase in vascular permeability
    SYMPTOMS

. Symptoms commonly involve in

    nonpitting, nonpruritic skin swellings
    SYMPTOMS

. We present a case of

    hereditary angioedema
    DIAGNOSIS

. The patinets complained of a

    recurrent abdominal pain
    SYMPTOMS

    without accompanying skin swelling
    NEG_FINDINGS

 whose diagnosis was delayed nearly 20 years and

    accepted an unnecessary surgery
    NEG_FINDINGS

. According to the

    decreased serum C1-inhibitor and C4 concentration
    BIOCHEMICAL

, the patient was finally diagnosed with hereditary angioedema type I. After treatment with

    danazole
    MEDICATION

, the patient reported a

    significant decrease in the frequency of attacks and the severity of pain
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 is a rare cause of

    abdominal pain
    SYMPTOMS

, however it needs to be taken as one of the

    differential diagnosis
    PARACLINICAL

 of various

    acute abdomens
    SYMPTOMS

 in order to avoid

    unnecessary surgeries
    NEG_FINDINGS

.

Hereditary angioedema
hereditary angioedema
HAE

without accompanying skin swelling
accepted an unnecessary surgery
unnecessary surgeries


Hereditary angioedema: children should be considered for training in self-administration.

Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality of life. Most studies have been conducted in adults. We report a 13-year-old boy who quickly learned self-administration, which resulted in reduced frequency and severity of attacks. The aim of this report is to emphasize that children should be considered for self-administration training and that the process does not have to be long or complicated.

    Hereditary angioedema
    DIAGNOSIS

 is an

    inherited disease
    GENETICS

 that causes

    periodic swelling attacks
    SYMPTOMS

, which can be

    life threatening
    SYMPTOMS

 and have a major effect on a patient's life. Studies have shown that

    home therapy
    MEDICATION

 for

    angioedema
    DIAGNOSIS

 reduces disease severity, leads to

    faster relief of symptoms
    SYMPTOMS

, and

    improves quality of life
    SYMPTOMS

. Most studies have been conducted in

    adults
    AGE

. We report a

    13-year-old
    AGE

    boy
    GENDER

 who

    quickly learned self-administration
    MEDICATION

, which resulted in

    reduced frequency and severity of attacks
    SYMPTOMS

. The aim of this report is to emphasize that

    children
    AGE

 should be considered for

    self-administration training
    MEDICATION

 and that the process does not have to be long or complicated.

home therapy
quickly learned self-administration
self-administration training


Hepatocellular carcinoma after danazol treatment for hereditary angio-oedema.

Hereditary angio-oedema is characterised by recurrent episodes of laryngeal, intra-abdominal, facial or peripheral oedema. Danazol can be used as prophylaxis for recurrent attacks. Hepatotoxicity is a recognised adverse effect of danazol. We report an exceptional case of a danazol-induced hepatocellular carcinoma in a 75-year-old patient with hereditary angio-oedema.

    Hereditary angio-oedema
    DIAGNOSIS

 is characterised by

    recurrent episodes of laryngeal, intra-abdominal, facial or peripheral oedema
    SYMPTOMS

.

    Danazol
    MEDICATION

 can be used as

    prophylaxis
    MEDICATION

 for

    recurrent attacks
    SYMPTOMS

.

    Hepatotoxicity
    DIAGNOSIS

 is a recognised

    adverse effect of danazol
    SYMPTOMS

. We report an exceptional case of a

    danazol-induced hepatocellular carcinoma
    DIAGNOSIS

 in a

    75-year-old
    AGE

 patient with

    hereditary angio-oedema
    DIAGNOSIS

.


[Another case of the rare complications of chronic lymphocytic leukemia: angioedema].

Angioedema is a rare but may be serious (laryngeal edema). This is a recurrent edema, subcutaneous and/or submucosal, whose cause is a hereditary or acquired deficiency in C1 inhibiteur (C1 inhibitor fraction of complement). We present the case of a 56 years old patient who showed recurrent episodes of swelling of the face and hands in association with chronic lymphocytic leukemia stage A. The exploration of the complement pathway has allowed retaining the diagnosis of acquired angioedema type I. The association of angioedema and lymphoproliferative syndrome is rare; we present this interesting case to discuss it from the literature data.

    Angioedema
    DIAGNOSIS

 is a rare but may be serious (

    laryngeal edema)
    SYMPTOMS

. This is a

    recurrent edema, subcutaneous and/or submucosal
    SYMPTOMS

, whose cause is a

    hereditary or acquired deficiency in C1 inhibiteur (C1 inhibitor fraction of complement)
    GENETICS

. We present the case of a

    56 years old
    AGE

 patient who showed

    recurrent episodes of swelling of the face and hands
    SYMPTOMS

 in association with chronic lymphocytic leukemia stage A. The

    exploration of the complement pathway
    PARACLINICAL

 has allowed retaining the diagnosis of acquired angioedema type I. The association of

    angioedema
    DIAGNOSIS

 and

    lymphoproliferative syndrome
    DIAGNOSIS

 is rare; we present this interesting case to discuss it from the literature data.

Angioedema
angioedema
lymphoproliferative syndrome


[Anesthesia for total hip arthroplasty in a patient with C1 inhibitor deficiency].

C1 inhibitor (INH) deficiency is characterized by the presence of angioedema of the extremities, face, airway and the gastrointestinal tract. Airway obstruction is the most common cause of mortality. A 78-year-old woman presented with repeated episodes of angioedema. These episodes were triggered by general anesthesia, dental extraction, venipuncture, vaccination and loxoprofen. The familiy history of similar symptoms was negative. C1 inhibitor concentrate was administered perioperatively for prophylaxis of attacks. Operation was performed under neurolept anesthesia and combined spinal-epidural anesthesia in order to avoid airway manipulation. Postoperative pain was controlled by patient-controlled epidural anesthesia to prevent attacks triggered by pain. The patient had angioedema on both lower extremities perioperatively but did not develop further attacks. Anesthesia was safely performed in a patient with C1 inhibitor deficiency scheduled for total hip arthroplasty.

    C1 inhibitor (INH) deficiency
    BIOCHEMICAL

 is characterized by the presence of

    angioedema of the extremities, face, airway and the gastrointestinal tract
    SYMPTOMS

.

    Airway obstruction
    SYMPTOMS

 is the most common cause of

    mortality
    SYMPTOMS

. A

    78-year-old
    AGE

    woman
    GENDER

 presented with

    repeated episodes of angioedema
    SYMPTOMS

. These episodes were triggered by

    general anesthesia
    MEDICATION

,

    dental extraction
    MEDICATION

,

    venipuncture
    MEDICATION

,

    vaccination
    MEDICATION

 and

    loxoprofen
    MEDICATION

.

    The familiy history of similar symptoms was negative
    NEG_FINDINGS

.

    C1 inhibitor concentrate was administered perioperatively
    MEDICATION

 for

    prophylaxis of attacks
    SYMPTOMS

.

    Operation
    MEDICATION

 was performed under

    neurolept anesthesia and combined spinal-epidural anesthesia
    MEDICATION

 in order to

    avoid airway manipulation
    MEDICATION

.

    Postoperative pain
    SYMPTOMS

 was controlled by

    patient-controlled epidural anesthesia
    MEDICATION

 to prevent

    attacks triggered by pain
    SYMPTOMS

. The patient had

    angioedema on both lower extremities
    SYMPTOMS

 perioperatively but

    did not develop further attacks
    NEG_FINDINGS

.

    Anesthesia
    MEDICATION

 was safely performed in a patient with

    C1 inhibitor deficiency
    BIOCHEMICAL

 scheduled for

    total hip arthroplasty
    MEDICATION

.

C1 inhibitor (INH) deficiency
C1 inhibitor deficiency


Anaesthetic Management of a Patient with Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Clinically, angioedema most often involves the upper extremities, face, neck and larynx. The most common cause of death is asphyxia related to laryngeal oedema. Attacks are triggered by many factors such as trauma, stress, infections and hormonal fluctuations. C1 esterase inhibitor concentrates, fresh frozen plasma (FFP), androgen steroids, quinine pathway inhibitors and antifibrinolytics can be used as treatment. In this case report, the anaesthetic management of a patient with hereditary angioedema undergoing laminectomy surgery is reported.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare autosomal dominant disorder
    GENETICS

 caused by

    reduced activity of the C1 esterase inhibitor
    BIOCHEMICAL

. Clinically,

    angioedema
    SYMPTOMS

 most often

    involves the upper extremities, face, neck and larynx
    SYMPTOMS

. The most common cause of

    death
    SYMPTOMS

 is

    asphyxia
    SYMPTOMS

 related to

    laryngeal oedema
    SYMPTOMS

. Attacks are triggered by many factors such as

    trauma
    SYMPTOMS

,

    stress
    SYMPTOMS

,

    infections
    SYMPTOMS

 and

    hormonal fluctuations
    SYMPTOMS

.

    C1 esterase inhibitor concentrates, fresh frozen plasma (FFP)
    MEDICATION

,

    androgen steroids
    MEDICATION

,

    quinine pathway inhibitors
    MEDICATION

 and

    antifibrinolytics
    MEDICATION

 can be used as treatment. In this case report, the

    anaesthetic management
    MEDICATION

 of a patient with

    hereditary angioedema
    DIAGNOSIS

 undergoing

    laminectomy surgery
    MEDICATION

 is reported.

Hereditary angioedema (HAE)
hereditary angioedema


Orthodontic treatment for a patient with hereditary angiodema: a case report.

Hereditary angiodema (HAE), also known as C1 esterase inhibitor deficiency, causes sufferers to experience episodic subcutaneous and submucosal oedema. These episodes can be triggered by dental treatment and manifest as life-threatening oedematous swelling in the head and neck region.

This case report reviews an adolescent with hereditary angiodema whose malocclusion required orthodontic intervention. Due to her complex and unpredictable reaction to dental treatment, various options were explored before determining the appropriate care pathway for this patient. Trial placement of a sectional fixed appliance tested the tissue reaction prior to comprehensive treatment including extractions and fixed orthodontic appliances.

This report demonstrates successful interdisciplinary management facilitating orthodontic care in a patient with HAE.

    Hereditary angiodema (HAE)
    DIAGNOSIS

, also known as

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

, causes sufferers to experience

    episodic subcutaneous and submucosal oedema
    SYMPTOMS

. These episodes can be triggered by

    dental treatment
    MEDICATION

 and manifest as

    life-threatening oedematous swelling in the head and neck region
    SYMPTOMS

.

This case report reviews an

    adolescent
    AGE

 with

    hereditary angiodema
    DIAGNOSIS

 whose

    malocclusion
    SYMPTOMS

 required

    orthodontic intervention
    MEDICATION

. Due to

    her
    GENDER

 complex and unpredictable reaction to

    dental treatment
    MEDICATION

, various options were explored before determining the appropriate care pathway for this patient.

    Trial placement of a sectional fixed appliance
    MEDICATION

 tested the tissue reaction prior to

    comprehensive treatment including extractions and fixed orthodontic appliances
    MEDICATION

.

This report demonstrates

    successful interdisciplinary management facilitating orthodontic care
    MEDICATION

 in a patient with

    HAE
    DIAGNOSIS

.

Hereditary angiodema (HAE)
hereditary angiodema
HAE


Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation.

    Vibratory angioedema
    SYMPTOMS

 is a rare form of

    physical urticaria
    DIAGNOSIS

,

    hereditary
    GENETICS

 or

    acquired
    DIAGNOSIS

, which occurs at

    body sites exposed to vibrations
    SYMPTOMS

. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by

    acquired vibratory angioedema
    SYMPTOMS

,

    relapsing after prolonged use of the instrument
    SYMPTOMS

 and

    resistant to systemic antihistamines and corticosteroids
    NEG_FINDINGS

, which successfully responded to

    therapy with low doses of amitriptyline and bromazepam
    MEDICATION

. A

    neuroinflammatory mechanism
    SYMPTOMS

 can be likely implicated in the pathogenesis of

    vibratory angioedema
    SYMPTOMS

, in line with many different

    cutaneous/mucosal diseases
    DIAGNOSIS

 involving a

    complex interplay of homeostatic/allostatic systems
    SYMPTOMS

. Furthermore, in

    mucosal diseases
    DIAGNOSIS

, such as

    vibratory angioedema
    DIAGNOSIS

,

    physical/psychological stressors
    SYMPTOMS

 have a relevant role. In such cases, because of the complex interplay

    between nervous and immune system
    SYMPTOMS

, the

    pharmacological activity of benzodiazepines
    MEDICATION

 and

    typical antidepressants
    MEDICATION

 may

    downregulate neuroinflammation
    SYMPTOMS

.

physical urticaria
acquired
cutaneous/mucosal diseases
mucosal diseases
vibratory angioedema


Recurrent angio-oedema--three cases of C1 inhibitor deficiency.

C1 Inhibitor deficiency is a rare disorder, characterised by recurrent angio-oedema of skin, upper respiratory and gastrointestinal tracts. It can be a mimicker of acute abdomen or anaphylaxis to drug or food and lead on to unnecessary overtreatment. Three case reports of such patients with history of recurrent abdominal pain and angio-oedema due to C1 Inhibitor deficiency is reported here.

    C1 Inhibitor deficiency
    BIOCHEMICAL

 is a rare disorder, characterised by

    recurrent angio-oedema of skin, upper respiratory and gastrointestinal tracts
    SYMPTOMS

. It can be a mimicker of

    acute abdomen
    SYMPTOMS

 or

    anaphylaxis to drug or food
    SYMPTOMS

 and lead on to

    unnecessary overtreatment
    NEG_FINDINGS

. Three case reports of such patients with history of

    recurrent abdominal pain
    SYMPTOMS

 and

    angio-oedema
    SYMPTOMS

 due to

    C1 Inhibitor deficiency
    BIOCHEMICAL

 is reported here.

C1 Inhibitor deficiency
C1 Inhibitor deficiency


[Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted.

    Type III hereditary angioedema
    DIAGNOSIS

 is a

    rare familial disorder
    GENETICS

 that has recently been described as a separate condition. Triggers for

    episodes of angioedema
    SYMPTOMS

 include

    surgery
    MEDICATION

,

    dental procedures
    MEDICATION

, and

    tracheal intubation maneuvers
    MEDICATION

. Since

    episodes affecting the upper airway
    SYMPTOMS

 are

    potentially life-threatening
    SYMPTOMS

,

    prophylactic treatment
    MEDICATION

 is recommended in these situations. The

    use of icatibant (Firazyr(®)), for prevention of angioedema
    MEDICATION

    prior to tracheal intubation
    MEDICATION

, is reported in a patient with

    type iii hereditary angioedema
    DIAGNOSIS

. A literature review on the anesthetic management of this condition was conducted.

Type III hereditary angioedema
type iii hereditary angioedema

episodes of angioedema
episodes affecting the upper airway
potentially life-threatening


A rare cause of recurrent priapism: hereditary angioedema.

Hereditary angioedema is a rare disease, which is caused by deficiency of compleman c1 esterase inhibitor regulatory protein in the compleman system. Priapism is involuntary, painful and prolonged erection of penis more than 4 h without sexual desire. In this case report, we elucidated a patient diagnosed with hereditary angioedema while he had recurrent priapism.

    Hereditary angioedema
    DIAGNOSIS

 is a rare disease, which is caused by

    deficiency of compleman c1 esterase inhibitor regulatory protein in the compleman system
    BIOCHEMICAL

.

    Priapism
    SYMPTOMS

 is

    involuntary, painful and prolonged erection of penis more than 4 h
    SYMPTOMS

    without sexual desire
    NEG_FINDINGS

. In this case report, we elucidated a patient diagnosed with

    hereditary angioedema
    DIAGNOSIS

 while

    he
    GENDER

 had

    recurrent priapism
    SYMPTOMS

.

Hereditary angioedema
hereditary angioedema


Improving patient outcomes in hereditary angioedema: reducing attack frequency using routine prevention with C1 inhibitor concentrate.

Hereditary angioedema (HAE) is a rare inherited disorder, characterised by recurrent oedema attacks in various regions of the body. In HAE, mutations in the C1 esterase inhibitor (C1-INH) gene result in decreased C1-INH concentrations (type I HAE) or functionally deficient C1-INH (type II HAE), leading to inappropriate activation of the kallikrein-kinin system and release of vasoactive mediators. Treatment of HAE aims to manage acute attacks (using replacement C1-INH or bradykinin B2 receptor antagonist) or prevent attacks through prophylaxis (using C1-INH or attenuated androgens). We present a case of a 67-year-old man with HAE who suffered a high number of breakthrough HAE attacks while undergoing long-term prophylaxis with attenuated androgens. Androgen therapy was safely discontinued and routine prevention therapy with C1-INH (1000 U) introduced as part of an individualised management approach, in line with published clinical trial data, which improved patient outcomes in terms of HAE attack frequency and severity.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare inherited disorder
    GENETICS

, characterised by

    recurrent oedema attacks in various regions of the body
    SYMPTOMS

. In

    HAE
    DIAGNOSIS

,

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

 result in

    decreased C1-INH concentrations
    BIOCHEMICAL

 (

    type I HAE
    DIAGNOSIS

) or

    functionally deficient C1-INH
    BIOCHEMICAL

 (

    type II HAE)
    DIAGNOSIS

, leading to

    inappropriate activation of the kallikrein-kinin system
    BIOCHEMICAL

 and

    release of vasoactive mediators
    BIOCHEMICAL

. Treatment of

    HAE
    DIAGNOSIS

 aims to manage

    acute attacks
    SYMPTOMS

 (using

    replacement C1-INH or bradykinin B2 receptor antagonist)
    MEDICATION

 or

    prevent attacks
    SYMPTOMS

 through

    prophylaxis (using C1-INH or attenuated androgens)
    MEDICATION

. We present a case of a

    67-year-old
    AGE

    man
    GENDER

 with

    HAE
    DIAGNOSIS

 who suffered a

    high number of breakthrough HAE attacks
    SYMPTOMS

 while

    undergoing long-term prophylaxis with attenuated androgens
    MEDICATION

.

    Androgen therapy was safely discontinued
    MEDICATION

 and

    routine prevention therapy with C1-INH (1000 U) introduced as part of an individualised management approach
    MEDICATION

, in line with published clinical trial data, which improved patient outcomes in terms of

    HAE attack
    SYMPTOMS

 frequency and severity.

Hereditary angioedema (HAE)
HAE
type I HAE
type II HAE)
HAE
HAE


Retropharyngeal pseudoabscess manifesting in nephrotic syndrome.

We describe a case of nephrotic syndrome that manifested as a retropharyngeal pseudoabscess. The patient was a 32-year-old man who presented with a short history of throat discomfort and a choking sensation. Laryngoscopy identified bulging of the posterior pharyngeal wall that partially occluded the laryngeal inlet. A lateral neck x-ray revealed that the prevertebral space was widened, and computed tomography detected fluid in the retropharyngeal and parapharyngeal spaces. Neck exploration revealed that the edema had been caused by nonsuppurative fluid. Biochemical analyses revealed marked hypoalbuminemia and heavy proteinuria suggestive of nephrotic syndrome. Following surgery, the patient's symptoms resolved. Aseptic effusion into the retropharyngeal space is rare; reported etiologies include internal jugular vein thrombosis, neoplasia, radiation therapy, trauma, acute calcific tendinitis, hereditary angioedema, and myxedema of hypothyroidism. To the best of our knowledge, this is the first case of nephrotic syndrome initially manifesting as retropharyngeal pseudoabscess to be reported in the literature. Thrombotic occlusion of the pharyngeal venous plexus secondary to hypercoagulability is a plausible explanation for such isolated retropharyngeal effusion.

We describe a case of

    nephrotic syndrome
    DIAGNOSIS

 that manifested as a

    retropharyngeal pseudoabscess
    SYMPTOMS

. The patient was a

    32-year-old
    AGE

    man
    GENDER

 who presented with a

    short history of throat discomfort
    SYMPTOMS

 and a

    choking sensation
    SYMPTOMS

.

    Laryngoscopy
    PARACLINICAL

 identified

    bulging of the posterior pharyngeal wall that partially occluded the laryngeal inlet
    SYMPTOMS

. A

    lateral neck x-ray
    PARACLINICAL

 revealed that

    the prevertebral space was widened
    SYMPTOMS

, and

    computed tomography
    PARACLINICAL

 detected

    fluid in the retropharyngeal and parapharyngeal spaces
    SYMPTOMS

.

    Neck exploration
    PARACLINICAL

 revealed that the

    edema had been caused by nonsuppurative fluid
    SYMPTOMS

.

    Biochemical analyses
    PARACLINICAL

 revealed

    marked hypoalbuminemia
    BIOCHEMICAL

 and

    heavy proteinuria
    BIOCHEMICAL

 suggestive of

    nephrotic syndrome
    DIAGNOSIS

. Following

    surgery
    MEDICATION

, the patient's symptoms resolved.

    Aseptic effusion into the retropharyngeal space
    SYMPTOMS

 is rare; reported etiologies include

    internal jugular vein thrombosis
    SYMPTOMS

,

    neoplasia
    SYMPTOMS

,

    radiation therapy
    MEDICATION

,

    trauma
    SYMPTOMS

,

    acute calcific tendinitis
    DIAGNOSIS

,

    hereditary angioedema
    DIAGNOSIS

, and

    myxedema of hypothyroidism
    DIAGNOSIS

. To the best of our knowledge, this is the first case of

    nephrotic syndrome
    DIAGNOSIS

 initially manifesting as

    retropharyngeal pseudoabscess
    SYMPTOMS

 to be reported in the literature.

    Thrombotic occlusion of the pharyngeal venous plexus
    SYMPTOMS

 secondary to

    hypercoagulability
    BIOCHEMICAL

 is a plausible explanation for such

    isolated retropharyngeal effusion
    SYMPTOMS

.

nephrotic syndrome
nephrotic syndrome
acute calcific tendinitis
hereditary angioedema
myxedema of hypothyroidism
nephrotic syndrome

marked hypoalbuminemia
heavy proteinuria
hypercoagulability


Postangioedema attack skin blisters: an unusual presentation of hereditary angioedema.

Hereditary angioedema (HAE) is an autosomal dominant disorder characterised by attacks of self-limited swelling affecting extremities, face and intra-abdominal organs, most often caused by mutations in the C1-inhibitor gene with secondary Bradykinin-mediated increased vascular permeability. We describe a 36-year-old man with a history of HAE who presented with painful interdigital bullae secondary to an acute oedema exacerbation. Biopsy and cultures of the lesions were negative and they resolved spontaneously. It is important to highlight and recognise the development of oedema blisters after resolution of a flare of HAE (only 1 previous case report), and hence avoid unnecessary dermatological diagnostic workup and treatment.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

 characterised by

    attacks of self-limited swelling affecting extremities, face and intra-abdominal organs
    SYMPTOMS

, most often caused by

    mutations in the C1-inhibitor gene
    GENETICS

 with secondary

    Bradykinin-mediated increased vascular permeability
    BIOCHEMICAL

. We describe a

    36-year-old
    AGE

    man
    GENDER

 with a history of

    HAE
    DIAGNOSIS

 who presented with

    painful interdigital bullae
    SYMPTOMS

 secondary to an

    acute oedema exacerbation
    SYMPTOMS

.

    Biopsy and cultures of the lesions were negative
    NEG_FINDINGS

 and they resolved spontaneously. It is important to highlight and recognise the development of

    oedema blisters
    SYMPTOMS

 after

    resolution of a flare of HAE
    SYMPTOMS

 (only 1 previous case report), and hence avoid

    unnecessary dermatological diagnostic workup and treatment
    NEG_FINDINGS

.

autosomal dominant disorder
mutations in the C1-inhibitor gene


Isolated non-hereditary angioneurotic oedema of uvula (Quincke's disease) in an adolescent.

A 19-year-old primipara woman was admitted in labour with positive vaginal swab for group B Streptococcus and given benzylpenicillin and ranitidine. She used Entonox for pain relief. She received bupivacaine in the epidural catheter and shortly after developed sensation of foreign body in her throat with muffled voice and isolated angioneurotic oedema of the uvula. She responded well to H1 and H2 histamine blockers and steroids and epinephrine were kept as standby. She recovered well soon after delivery. Penicillin, Entonox or bupivacaine seemed possible cause of the Quincke's disease. Hereditary form was ruled out by normal creatine kinase and reaction to bupivacaine by C1 esterase inhibitor assay. It can be associated with spectrum of anaphylactic reactions and the resuscitation team should be alerted. Airway maintenance should be the primary management strategy. Most cases respond to observation, oxygen therapy and antihistamines with or without steroids. Epinephrine may be required occasionally.

A

    19-year-old
    AGE

    primipara
    ETHNICITY

    woman
    GENDER

 was admitted in

    labour
    MEDICATION

 with

    positive vaginal swab for group B Streptococcus
    SYMPTOMS

 and given

    benzylpenicillin and ranitidine
    MEDICATION

.

    She
    GENDER

    used Entonox for pain relief
    MEDICATION

.

    She
    GENDER

    received bupivacaine in the epidural catheter
    MEDICATION

 and shortly after developed

    sensation of foreign body in her throat with muffled voice
    SYMPTOMS

 and

    isolated angioneurotic oedema of the uvula
    SYMPTOMS

.

    She
    GENDER

 responded well to

    H1 and H2 histamine blockers
    MEDICATION

 and

    steroids
    MEDICATION

 and

    epinephrine
    MEDICATION

 were kept as standby.

    She
    GENDER

 recovered well soon after

    delivery
    MEDICATION

.

    Penicillin, Entonox
    MEDICATION

 or

    bupivacaine
    MEDICATION

 seemed possible cause of the

    Quincke's disease
    DIAGNOSIS

.

    Hereditary form was ruled out
    NEG_FINDINGS

 by

    normal creatine kinase and reaction to bupivacaine by C1 esterase inhibitor assay
    NEG_FINDINGS

. It can be associated with

    spectrum of anaphylactic reactions
    SYMPTOMS

 and the

    resuscitation team
    PARACLINICAL

 should be alerted.

    Airway maintenance
    MEDICATION

 should be the primary management strategy. Most cases respond to

    observation
    MEDICATION

,

    oxygen therapy
    MEDICATION

 and

    antihistamines with or without steroids
    MEDICATION

.

    Epinephrine
    MEDICATION

 may be required occasionally.


A case of hereditary angioedema who presented with difficulty in urination and globe.

Hereditary angioedema (HEA) is a disease characterized by decreased levels or function of C1 esterase inhibitor (C1-INH). The symptoms of HEA in pediatric age group generally consist of recurrent episodes of soft tissue swelling. These symptoms can be transient, subtle, and varied in severity. Genitourinary system is rarely affected in this disease. Here, a three-year-old girl who presented with angioedema on her hands, fingers, and face, and had difficulty in urination and globe is reported. The aim of this case is to focus on this rare disease, hereditary angioedema, which presented with difficulty in urination and urinary globe.

    Hereditary angioedema (HEA)
    DIAGNOSIS

 is a disease characterized by

    decreased levels or function of C1 esterase inhibitor (C1-INH)
    BIOCHEMICAL

. The symptoms of

    HEA
    DIAGNOSIS

 in

    pediatric age group
    AGE

 generally consist of

    recurrent episodes of soft tissue swelling
    SYMPTOMS

. These symptoms can be transient, subtle, and varied in severity.

    Genitourinary system
    SYMPTOMS

 is rarely affected in this disease. Here, a

    three-year-old
    AGE

    girl
    GENDER

 who presented with

    angioedema on her hands, fingers, and face
    SYMPTOMS

, and had

    difficulty in urination and globe
    SYMPTOMS

 is reported. The aim of this case is to focus on this rare disease,

    hereditary angioedema
    DIAGNOSIS

, which presented with

    difficulty in urination
    SYMPTOMS

 and

    urinary globe
    SYMPTOMS

.

Hereditary angioedema (HEA)
HEA
hereditary angioedema


[Recurrent isolated angioedema as a result of acquired C1 inhibitor deficiency].

Isolated angioedema may be the presenting symptom of acquired C1 inhibitor (C1-INH) deficiency. C1-INH deficiency is associated with lymphoproliferative disorders. Treatment of the underlying disease can result in a complete reversal of clinical and complement abnormalities. We describe a 41-year-old woman who was referred to our emergency department with recurrent episodes of isolated angioedema. Initially, her angioedema was linked to the use of angiotensin receptor blockers. However, after discontinuation of this drug angioedema recurred. Additional investigations revealed the presence of acquired C1-INH deficiency caused by an indolent non-Hodgkin's lymphoma. Treatment with rituximab resulted in complete clinical and biochemical remission of the acquired angioedema.

    Isolated angioedema
    SYMPTOMS

 may be the presenting symptom of

    acquired C1 inhibitor (C1-INH) deficiency
    BIOCHEMICAL

.

    C1-INH deficiency
    BIOCHEMICAL

 is associated with

    lymphoproliferative disorders
    DIAGNOSIS

. Treatment of the underlying disease can result in a complete

    reversal of clinical and complement abnormalities
    BIOCHEMICAL

. We describe a

    41-year-old
    AGE

    woman
    GENDER

 who was referred to our emergency department with

    recurrent episodes of isolated angioedema
    SYMPTOMS

. Initially,

    her
    GENDER

    angioedema was linked to the use of angiotensin receptor blockers
    NEG_FINDINGS

. However, after

    discontinuation of this drug
    MEDICATION

    angioedema recurred
    SYMPTOMS

. Additional investigations revealed the presence of

    acquired C1-INH deficiency
    BIOCHEMICAL

 caused by an

    indolent non-Hodgkin's lymphoma
    DIAGNOSIS

. Treatment with

    rituximab
    MEDICATION

 resulted in

    complete clinical and biochemical remission of the acquired angioedema
    SYMPTOMS

.

lymphoproliferative disorders
indolent non-Hodgkin's lymphoma


Hereditary angioedema with an estrogen trigger in a 12-year-old.

Hereditary angioedema (HAE) is rare autosomal dominant genetic disorder, commonly affecting girls around the menarche, which manifests clinically as recurrent episodes of angioedema. Laryngeal edema can lead to asphyxiation and death. Traditionally hormones have been avoided in the management due a reported association with flares in the literature. This case describes an alternative management with a progestin.

A 12 year old HAE sufferer failed to receive relief from her symptoms of angioedema with standard treatment. A trial of depot medroxyprogesterone acetate has resulted in resolution of her symptoms for the last 14 months.

Although estrogens and progestins have been avoided in the management of HAE in the past, the reasons for this are based only on a small number of case reports. In this case, successful treatment with depot medroxyprogesterone acetate indicates that progestins, as an alternative management for estrogen-triggered HAE, certainly warrants further research.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is

    rare autosomal dominant genetic disorder
    GENETICS

, commonly affecting

    girls
    GENDER

    around the menarche
    AGE

, which manifests clinically as

    recurrent episodes of angioedema
    SYMPTOMS

.

    Laryngeal edema
    SYMPTOMS

 can lead to

    asphyxiation
    SYMPTOMS

 and

    death
    SYMPTOMS

. Traditionally

    hormones
    MEDICATION

 have been avoided in the management due a reported association with

    flares
    SYMPTOMS

 in the literature. This case describes an

    alternative management with a progestin
    MEDICATION

.

A

    12 year old
    AGE

    HAE
    DIAGNOSIS

 sufferer

    failed to receive relief from her symptoms of angioedema with standard treatment
    NEG_FINDINGS

. A

    trial of depot medroxyprogesterone acetate
    MEDICATION

 has resulted in

    resolution of her symptoms for the last 14 months
    SYMPTOMS

.

Although

    estrogens
    MEDICATION

 and

    progestins
    MEDICATION

 have been avoided in the management of

    HAE
    DIAGNOSIS

 in the past, the reasons for this are based only on a small number of case reports. In this case,

    successful treatment with depot medroxyprogesterone acetate
    MEDICATION

 indicates that

    progestins
    MEDICATION

, as an

    alternative management for estrogen-triggered HAE
    MEDICATION

, certainly warrants further research.


Life-threatening angioedema of the tongue: the detection of the RNA of B henselae in the saliva of a male patient and his dog as well as of the DNA of three Bartonella species in the blood of the patient.

Non-hereditary angioedema is a common disease with a prevalence between 5% and 19% and approximately half of the patients experience a swelling of the tongue. We report a case of a 49-year-old Caucasian man with a gross life-threatening angioedema of the tongue, whose attacks occurred every 4 weeks. The most frequent causes of angioedema were excluded. We detected DNA and RNA from Bartonella henselae in the blood and saliva of the patient and in the saliva of the patient's hunting dog. Treatment with azithromycin plus minocycline cleared the blood and saliva of RNA and DNA of Bartonella species, and the patient has been free from angioedema for 1 year. None of the therapy modalities used to treat the hereditary form or ACE or allergy-induced angioedema affect the detrimental course caused by Bartonella species. We therefore suggest that a molecular Bartonella test be included in the analysis of angioedema.

    Non-hereditary angioedema
    DIAGNOSIS

 is a common disease with a prevalence between 5% and 19% and approximately half of the patients experience a

    swelling of the tongue
    SYMPTOMS

. We report a case of a

    49-year-old
    AGE

    Caucasian
    ETHNICITY

    man
    GENDER

 with a

    gross life-threatening angioedema of the tongue
    SYMPTOMS

, whose attacks occurred

    every 4 weeks
    SYMPTOMS

. The most frequent causes of

    angioedema were excluded
    NEG_FINDINGS

. We

    detected DNA and RNA from Bartonella henselae in the blood and saliva of the patient and in the saliva of
    MICROSCOPIC

 the patient's

    hunting dog
    MICROSCOPIC

.

    Treatment with azithromycin plus minocycline
    MEDICATION

    cleared the blood and saliva of RNA and DNA of Bartonella species
    MICROSCOPIC

, and the patient has been

    free from angioedema
    NEG_FINDINGS

 for 1 year.

    None of the therapy modalities used to treat the hereditary form or ACE or allergy-induced angioedema
    NEG_FINDINGS

 affect the detrimental course caused by

    Bartonella species
    DIAGNOSIS

. We therefore suggest that a

    molecular Bartonella test
    PARACLINICAL

 be included in the analysis of

    angioedema
    DIAGNOSIS

.

Non-hereditary angioedema
Bartonella species
angioedema


ACE inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.

    Angiotensin-converting enzyme inhibitors (ACEI)
    MEDICATION

 are commonly prescribed for

    blood pressure control
    MEDICATION

 and

    renal protection
    MEDICATION

.

    ACEI angioedema
    DIAGNOSIS

 is a common problem in patients who are taking

    ACEI
    MEDICATION

, although, in most cases, the disorder is

    self-limited
    NEG_FINDINGS

, and

    spontaneous episodes of apparently unprovoked angioedema
    SYMPTOMS

 stop with the

    discontinuation of the medication
    MEDICATION

. In a subset of patients,

    hospitalization
    MEDICATION

 and even

    intubation
    MEDICATION

 are required for

    airway protection
    MEDICATION

. The diagnosis is made clinically. There are

    no laboratory studies
    NEG_FINDINGS

 that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation.

    Conventional treatment with regimens used to control allergic angioedema is ineffective in
    NEG_FINDINGS

 this condition. The mechanism of

    ACEI-induced angioedema
    DIAGNOSIS

 is thought to be related to its

    effect on the kallikrein-kinin system
    BIOCHEMICAL

.

    Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin
    BIOCHEMICAL

. Medications recently developed, primarily

    icatibant and ecallantide
    MEDICATION

, to control

    hereditary angioedema
    DIAGNOSIS

, a disorder also associated with

    kallikrein-kinin activation
    BIOCHEMICAL

, have been used to treat

    ACEI angioedema
    DIAGNOSIS

 with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials.

ACEI angioedema
ACEI-induced angioedema
hereditary angioedema
ACEI angioedema


Identification and characterization of a novel splice site mutation in the SERPING1 gene in a family with hereditary angioedema.

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant disease caused by mutations in SERPING1 gene. The main clinical feature of C1INH deficiency is the spontaneous edema of the subcutaneous and submucosal layers. More than 280 different mutations scattering the entire SERPING1 gene have been reported. We identified and characterized a new mutation in SERPING1 gene in a Spanish family with hereditary angioedema. The mutation (c.685 + 2 T > A) disrupts the donor splice site of intron 4 leading to the loss of exon 4 in mutant mRNA. We demonstrated that mutant mRNA is mostly degraded, probably by the surveillance pathway no-go mRNA decay. Bioinformatic analysis showed that the mutant protein, if produced, would be non-functional since the protein lacks a stretch of 45 amino acids affecting the functional RCL loop. Finally, we found a reduction of the wild-type mRNA expression in c.685 + 2 T > A carriers.

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH)
    DIAGNOSIS

 is a

    rare autosomal-dominant disease
    GENETICS

 caused by

    mutations in SERPING1 gene
    GENETICS

. The main clinical feature of

    C1INH deficiency
    BIOCHEMICAL

 is the

    spontaneous edema of the subcutaneous and submucosal layers
    SYMPTOMS

. More than 280 different

    mutations scattering the entire SERPING1 gene
    GENETICS

 have been reported. We identified and characterized a

    new mutation in SERPING1 gene
    GENETICS

 in a

    Spanish
    ETHNICITY

    family with hereditary angioedema
    FAMILY

. The

    mutation (c.685 + 2 T > A) disrupts the donor splice site of intron 4 leading to the loss of exon 4 in mutant mRNA
    GENETICS

. We demonstrated that

    mutant mRNA is mostly degraded
    GENETICS

, probably by the

    surveillance pathway no-go mRNA decay
    GENETICS

.

    Bioinformatic analysis
    PARACLINICAL

 showed that the mutant protein, if produced, would be

    non-
    NEG_FINDINGS

functional since the

    protein lacks a stretch of 45 amino acids affecting the functional RCL loop
    GENETICS

. Finally, we found a

    reduction of the wild-type mRNA expression in c.685 + 2 T > A carriers
    GENETICS

.


Life threatening angioedema in a patient on ACE inhibitor (ACEI) confined to the upper airway.

ACE inhibitors accounts for 8% of all cases of angioneurotic edema and the overall incidence is 0.1 to 0.7% of patients on ACE inhibitors. It is a leading cause (20-40%) of emergency room visits in the US with angioedema. We report a case of angioedema caused by ACE inhibitors confined to the upper airway after four years on treatment with Lisinopril which persisted for three weeks and required endotracheal intubation and subsequent tracheostomy due to delayed resolution. This case is one of the rare cases presented as upper airway edema which persisted for a long time.

A 60-year-old Sudanese male patient with osteoarthritis in both knees underwent bilateral total knee replacement under single-shot epidural anesthesia. He had significant past medical history of type II diabetes, bipolar affective disorder and hypertension managed with Lisinopril for the past four years. Postoperatively after 10 hours the patient desaturated and developed airway obstruction requiring intubation. Laryngoscopy revealed an edematous tongue and upper airway and vocal cords were not visualized. In view of this clinical picture a provisional diagnosis of angioedema secondary to Lisinopril was made and it was discontinued. CT scan of the neck and soft tissues revealed severe airway edema with snugly fitting endotracheal tube with no peritubal air. A repeat CT neck on the tenth postoperative day showed no signs of resolution and an elective tracheostomy was performed on the eleventh postoperative day. C1 inhibitor protein and C4 levels were assayed to exclude hereditary angioedema and were found to be within normal range. Decannulation of tracheostomy was done after airway edema resolved on the twenty-fourth postoperative day as confirmed by CT scan. Subsequently he was transferred to the ward and discharged home.

ACEI induced angioedema is a well-recognized condition. Early diagnosis based on a high index of suspicion, immediate withdrawal of the offending drug followed by supportive therapy is the cornerstone of management.

    ACE inhibitors
    MEDICATION

 accounts for 8% of all cases of

    angioneurotic edema
    SYMPTOMS

 and the overall incidence is 0.1 to 0.7% of patients on

    ACE inhibitors
    MEDICATION

. It is a leading cause (20-40%) of emergency room visits in the US with

    angioedema
    DIAGNOSIS

. We report a case of

    angioedema caused by ACE inhibitors confined to the upper airway
    SYMPTOMS

 after

    four years on treatment with Lisinopril
    MEDICATION

 which

    persisted for three weeks
    SYMPTOMS

 and required

    endotracheal intubation and subsequent tracheostomy
    MEDICATION

 due to

    delayed resolution
    SYMPTOMS

. This case is one of the rare cases presented as

    upper airway edema
    SYMPTOMS

 which

    persisted for a long time
    SYMPTOMS

.

A

    60-year-old
    AGE

    Sudanese
    ETHNICITY

    male
    GENDER

 patient with

    osteoarthritis in both knees
    MEDICATION

 underwent

    bilateral total knee replacement
    MEDICATION

 under

    single-shot epidural anesthesia
    MEDICATION

.

    He
    GENDER

 had significant past medical history of

    type II diabetes
    DIAGNOSIS

,

    bipolar affective disorder
    DIAGNOSIS

 and

    hypertension managed with Lisinopril for the past four years
    MEDICATION

. Postoperatively after 10 hours the patient

    desaturated
    SYMPTOMS

 and developed

    airway obstruction
    SYMPTOMS

 requiring

    intubation
    MEDICATION

.

    Laryngoscopy
    PARACLINICAL

 revealed an

    edematous tongue and upper airway
    SYMPTOMS

 and

    vocal cords were not visualized
    NEG_FINDINGS

. In view of this clinical picture a provisional diagnosis of

    angioedema secondary to Lisinopril
    DIAGNOSIS

 was made and it was discontinued.

    CT scan of the neck and soft tissues
    PARACLINICAL

 revealed

    severe airway edema
    SYMPTOMS

 with

    snugly fitting endotracheal tube with no peritubal air
    NEG_FINDINGS

. A

    repeat CT neck
    PARACLINICAL

 on the tenth postoperative day showed

    no signs of resolution
    NEG_FINDINGS

 and an

    elective tracheostomy
    MEDICATION

 was performed on the eleventh postoperative day.

    C1 inhibitor protein and C4 levels were assayed
    BIOCHEMICAL

 to exclude

    hereditary angioedema
    NEG_FINDINGS

 and were found to

    be within normal range
    NEG_FINDINGS

.

    Decannulation of tracheostomy
    MEDICATION

 was done after

    airway edema resolved
    SYMPTOMS

 on the twenty-fourth postoperative day as confirmed by

    CT scan
    PARACLINICAL

. Subsequently

    he
    GENDER

 was

    transferred to the ward and discharged home
    MEDICATION

.

    ACEI induced angioedema
    DIAGNOSIS

 is a well-recognized condition. Early diagnosis based on a high index of suspicion,

    immediate withdrawal of the offending drug
    MEDICATION

 followed by

    supportive therapy
    MEDICATION

 is the cornerstone of management.

angioedema
type II diabetes
bipolar affective disorder
angioedema secondary to Lisinopril
ACEI induced angioedema


Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: dramatic response to Anakinra.

Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory syndrome characterized by recurrent episodes of fever and localized inflammation. Clinical presentation can be very variable in terms of duration of fever attacks, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of migrating skin rash with myalgia that is sustained by monocytic inflammation.

We herein present the case of a family suffering from TRAPS who had been misdiagnosed for a long period of time and whose main symptom was migrating angioedema. Skin biopsy from one of the patients documented a monocytic panniculitis. All the living patients responded dramatically to anakinra treatment.

The classic symptom of migratory angioedema with myalgia in TRAPS can be produced by monocytic panniculitis.This manifestation is so characteristic of TRAPS that its occurrence, even in the absence of other manifestations, should prompt genetic analysis. Our patient's condition responded promptly to anakinra treatment.

    Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)
    DIAGNOSIS

 is a

    hereditary
    GENETICS

    autoinflammatory syndrome
    DIAGNOSIS

 characterized by

    recurrent episodes of fever
    SYMPTOMS

 and

    localized inflammation
    SYMPTOMS

. Clinical presentation can be very variable in terms of duration of

    fever attacks
    SYMPTOMS

, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of

    migrating skin rash with myalgia
    SYMPTOMS

 that is sustained by

    monocytic inflammation
    MICROSCOPIC

.

We herein present the case of a

    family suffering from TRAPS
    FAMILY

 who had been

    misdiagnosed for a long period of time
    NEG_FINDINGS

 and whose main symptom was

    migrating angioedema
    SYMPTOMS

.

    Skin biopsy
    PARACLINICAL

 from one of the patients documented a

    monocytic panniculitis
    MICROSCOPIC

. All the living patients responded dramatically to

    anakinra treatment
    MEDICATION

.

The classic symptom of

    migratory angioedema with myalgia
    SYMPTOMS

 in

    TRAPS
    DIAGNOSIS

 can be produced by

    monocytic panniculitis
    MICROSCOPIC

.This manifestation is so characteristic of

    TRAPS
    DIAGNOSIS

 that its occurrence, even in the absence of other manifestations, should prompt

    genetic analysis
    PARACLINICAL

. Our patient's condition responded promptly to

    anakinra treatment
    MEDICATION

.

recurrent episodes of fever
localized inflammation
fever attacks
migrating skin rash with myalgia
migrating angioedema
migratory angioedema with myalgia


Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review.

In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented.

In this article, three cases of

    hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor
    DIAGNOSIS

    )
    DIAGNOSIS

 are reported. The

    HAE
    DIAGNOSIS

 was initially described in

    women
    GENDER

    of the same family
    FAMILY

 in association with

    high-leveled estrogenic conditions
    SYMPTOMS

 such as the

    use of oral contraceptives
    MEDICATION

 and

    pregnancy
    SYMPTOMS

. There is

    no change in the C1 inhibitor
    NEG_FINDINGS

 as happens in other types of

    hereditary angioedema
    DIAGNOSIS

, and

    mutations are observed in the encoding gene of the XII factor of coagulation
    GENETICS

 in several patients. The current diagnosis is mainly clinical and treatment consists in the

    suspension of the triggering factors
    MEDICATION

 and

    control of acute symptoms
    SYMPTOMS

. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented.

high-leveled estrogenic conditions
pregnancy
control of acute symptoms

use of oral contraceptives
suspension of the triggering factors


Novel duplication in the F12 gene in a patient with recurrent angioedema.

Edema formation is mediated by histamine or bradykinin release and may have several hereditary and acquired causes. In hereditary forms of bradykinin-mediated angioedemas, mutations in the genes encoding C1-inhibitor (SERPING1) as well as coagulation factor XII (F12) have been described. We present a novel F12 gene mutation, a duplication of 18 base pairs (c.892_909dup) in a 37-year-old woman with recurrent angioedema and normal C1-inhibitor level. A single episode of facial edema in the family of the patient showed co-segregation with the mutation. This duplication is causing the repeated presence of 6 amino acids (p.298-303) in the same region of factor XII, as those three mutations described previously in cases of hereditary angioedema with normal C1-INH function. These results may confirm the importance of the proline-rich region of factor XII protein in edema formation.

    Edema formation
    SYMPTOMS

 is mediated by

    histamine or bradykinin release
    BIOCHEMICAL

 and may have several hereditary and acquired causes. In hereditary forms of

    bradykinin-mediated angioedemas
    DIAGNOSIS

,

    mutations in the genes encoding C1-inhibitor (SERPING1) as well as coagulation factor XII (F12)
    GENETICS

 have been described. We present a

    novel F12 gene mutation, a duplication of 18 base pairs (c.892_909dup)
    GENETICS

 in a

    37-year-old
    AGE

    woman
    GENDER

 with

    recurrent angioedema
    SYMPTOMS

 and

    normal C1-inhibitor level
    NEG_FINDINGS

. A

    single episode of facial edema
    FAMILY

    in the family of the patient showed co-segregation with the mutation
    FAMILY

.

    This duplication is causing the repeated presence of 6 amino acids (p.298-303) in the same region of factor XII, as those three mutations
    GENETICS

 described previously in cases of

    hereditary angioedema
    DIAGNOSIS

 with

    normal C1-INH function
    NEG_FINDINGS

. These results may confirm the importance of the

    proline-rich region of factor XII protein
    GENETICS

 in

    edema formation
    SYMPTOMS

.

Edema formation
recurrent angioedema
edema formation

bradykinin-mediated angioedemas
hereditary angioedema

normal C1-inhibitor level
normal C1-INH function


Anaesthesia Management of a Patient with Hereditary Angioedema with Prophylactic Administration of C1 Esterase Inhibitor: Case report and literature review.

Hereditary angioedema (HAE) is a rare disorder caused by a deficiency of C1 esterase inhibitor. Minor trauma and emotional stress are the most common initiating events leading to contact system activation and excessive uncontrolled bradykinin release. This manifests as angioedema, a vascular reaction of the deeper layers of the skin and mucous membranes, with vasodilatation and increased permeability resulting in tissue swelling. Severe angioedema can occur in the perioperative period, leading to fatal airway obstruction. We describe the anaesthetic management of a child with HAE for dental rehabilitation and provide an review of the relevant literature.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare disorder
    GENETICS

 caused by a

    deficiency of C1 esterase inhibitor
    BIOCHEMICAL

.

    Minor trauma
    SYMPTOMS

 and

    emotional stress
    SYMPTOMS

 are the most common initiating events leading to

    contact system activation
    SYMPTOMS

 and

    excessive uncontrolled bradykinin release
    BIOCHEMICAL

. This manifests as

    angioedema
    SYMPTOMS

, a

    vascular reaction of the deeper layers of the skin and mucous membranes
    SYMPTOMS

, with

    vasodilatation
    SYMPTOMS

 and

    increased permeability
    SYMPTOMS

 resulting in

    tissue swelling
    SYMPTOMS

.

    Severe angioedema
    SYMPTOMS

 can occur in the perioperative period, leading to

    fatal airway obstruction
    SYMPTOMS

. We describe the

    anaesthetic management
    MEDICATION

 of a

    child
    AGE

 with

    HAE
    DIAGNOSIS

 for

    dental rehabilitation
    MEDICATION

 and provide an review of the relevant literature.

anaesthetic management
dental rehabilitation


Does angiotensin-converting enzyme inhibitor use exacerbate hereditary angioedema?

Approximately 2% of angioedema (AE) patients have a hereditary or an acquired deficiency of the complement 1 (C1) esterase inhibitor (C1 INH) gene. Some case reports indicate an association between angiotensin-converting enzyme inhibitor (ACEI) use and exacerbation of hereditary AE (HAE).

The aim of this retrospective study is to investigate the association between HAE and ACEI use in a larger patient population.

A retrospective chart review of patients who presented with AE and patients with diagnostic serum assays for functional C1 INH, C1 INH antigenic protein, C1q, C1q immune complex (C1q IC), and complement 4 (C4) regardless of medical complaint. Descriptive statistics were used to analyze the data.

A total of 1594 patients had complement levels measured (136 C1 INH, 55 C1q, 10 C1q IC, and 1500 C4), of which 156 (9.7%) patients presented with AE. Angiotensin-converting enzyme inhibitor use was documented in 747 (47%) patients. Low C1 INH was detected in one patient with recurrent AE who was not taking ACEI. Another patient who presented with recurrent AE was found to have systemic lupus erythematosus with abnormal C4, C1q, and C1q IC, but normal C1 INH. A low C4 level was present in 94 patients, 4 of which had AE.

The risk of exacerbating HAE by ACEI might be present, but we did not find any association in this retrospective study. Further studies are needed to determine the existence of this association.

Approximately 2% of

    angioedema (AE)
    DIAGNOSIS

 patients have a

    hereditary or an acquired deficiency of the complement 1 (C1) esterase inhibitor (C1 INH) gene
    GENETICS

. Some case reports indicate an association between

    angiotensin-converting enzyme inhibitor (ACEI) use
    MEDICATION

 and

    exacerbation of hereditary AE (HAE)
    DIAGNOSIS

.

The aim of this retrospective study is to investigate the association between

    HAE
    DIAGNOSIS

 and

    ACEI use
    MEDICATION

 in a larger patient population.

A retrospective chart review of patients who presented with

    AE
    DIAGNOSIS

 and patients with

    diagnostic serum assays for functional C1 INH, C1 INH antigenic protein, C1q, C1q immune complex (C1q IC), and complement 4 (C4)
    PARACLINICAL

 regardless of medical complaint. Descriptive statistics were used to analyze the data.

A total of 1594 patients had

    complement levels measured
    BIOCHEMICAL

 (136

    C1 INH, 55 C1q, 10 C1q IC
    BIOCHEMICAL

, and

    1500 C4)
    BIOCHEMICAL

, of which 156 (9.7%) patients presented with

    AE
    DIAGNOSIS

.

    Angiotensin-converting enzyme inhibitor use
    MEDICATION

 was documented in 747 (47%) patients.

    Low C1 INH
    BIOCHEMICAL

 was detected in one patient with

    recurrent AE
    DIAGNOSIS

 who was

    not taking ACEI
    NEG_FINDINGS

. Another patient who presented with

    recurrent AE
    DIAGNOSIS

 was found to have

    systemic lupus erythematosus
    DIAGNOSIS

 with

    abnormal C4, C1q, and C1q IC
    BIOCHEMICAL

, but

    normal C1 INH
    NEG_FINDINGS

. A

    low C4 level
    BIOCHEMICAL

 was present in 94 patients, 4 of which had

    AE
    DIAGNOSIS

.

The risk of

    exacerbating HAE
    SYMPTOMS

 by

    ACEI
    MEDICATION

 might be present, but we

    did not find any association
    NEG_FINDINGS

 in this retrospective study. Further studies are needed to determine the existence of this association.

angioedema (AE)
exacerbation of hereditary AE (HAE)
HAE
AE
AE
recurrent AE
recurrent AE
systemic lupus erythematosus
AE

complement levels measured
C1 INH, 55 C1q, 10 C1q IC
1500 C4)
Low C1 INH
abnormal C4, C1q, and C1q IC
low C4 level

not taking ACEI
normal C1 INH
did not find any association


Signs and symptoms preceding acute attacks of hereditary angioedema: results of three recent surveys.

In patients with hereditary angioedema (HAE), premonitory symptoms ("prodromes") may appear hours to days before attack onset. It remains to be determined if prodromes could be useful indicators for early treatment initiation. Most published reports of prodromes have been limited to case reports or small case series. The common objective of several recent survey-based studies was to collect information relevant to prodromal patterns in patients with HAE. Three separate surveys solicited prodromal data from HAE patients. Although differences in survey methodologies permit only descriptive analysis of data, responses to the surveys provide the largest compilation of observational data on this topic to date. Prodromes were reported by 82.5-95.7% of patients surveyed. In one survey, about two-thirds of subjects reported experiencing prodromes before all or most acute HAE attacks, and only 6% of subjects noted the appearance of prodromes in <10% of all attacks. The most common types of prodromal symptoms were related to skin/soft tissue and gastrointestinal tract. Most prodromes were experienced hours to days before the onset of angioedema. A large percentage of surveyed subjects indicated being able to predict an impending HAE attack all or most of the time; <10% reported being rarely or never able to predict an attack. Although insufficient to establish the clinical role of prodromal symptoms, results of these surveys provide additional data on the scope of prodromes and could stimulate further research into the potential efficacy and cost-effectiveness of HAE attack prediction and prodrome-triggered interventions.

In patients with

    hereditary angioedema (HAE)
    DIAGNOSIS

,

    premonitory symptoms ("prodromes")
    SYMPTOMS

 may appear hours to days before attack onset. It remains to be determined if

    prodromes
    SYMPTOMS

 could be useful indicators for early treatment initiation. Most published reports of

    prodromes
    SYMPTOMS

 have been limited to case reports or small case series. The common objective of several recent survey-based studies was to collect information relevant to prodromal patterns in patients with

    HAE
    DIAGNOSIS

. Three separate surveys solicited prodromal data from

    HAE
    DIAGNOSIS

 patients. Although differences in survey methodologies permit only descriptive analysis of data, responses to the surveys provide the largest compilation of observational data on this topic to date.

    Prodromes
    SYMPTOMS

 were reported by 82.5-95.7% of patients surveyed. In one survey, about two-thirds of subjects reported experiencing

    prodromes before all or most acute HAE attacks
    SYMPTOMS

, and only 6% of subjects noted the

    appearance of prodromes in <10% of all attacks
    SYMPTOMS

. The most common types of

    prodromal symptoms were related to skin/soft tissue and gastrointestinal tract
    SYMPTOMS

. Most

    prodromes
    SYMPTOMS

 were experienced hours to days before the onset of

    angioedema
    SYMPTOMS

. A large percentage of surveyed subjects indicated being able to predict an

    impending HAE attack
    SYMPTOMS

 all or most of the time; <10% reported being

    rarely or never able to predict an attack
    NEG_FINDINGS

. Although insufficient to establish the clinical role of

    prodromal symptoms
    SYMPTOMS

, results of these surveys provide additional data on the scope of prodromes and could stimulate further research into the potential efficacy and cost-effectiveness of

    HAE
    DIAGNOSIS

 attack prediction and prodrome-triggered interventions.


C1 inhibitor concentrate treatment of multiple laryngeal attacks in a 53-year-old woman with hereditary angioedema.

This report describes a woman who experienced a high number of laryngeal hereditary angioedema (HAE) attacks during her participation in the IMPACT2 clinical trial of C1-INH concentrate. A 53-year-old caucasian female with a 31-year history of type 1 HAE experienced 16 laryngeal HAE attacks between 3 August 2006 and 23 February 2010, 15 of which were severe. All laryngeal attacks were successfully treated with C1-INH 20 U/kg, with a median onset of relief of 14 min and median time to complete resolution of symptoms of 20 h, and no need for redosing. The reliable success of C1-INH for these potentially fatal events is reassuring for both patients and prescribers.

This report describes a

    woman
    GENDER

 who experienced a

    high number of laryngeal hereditary angioedema (HAE) attacks
    SYMPTOMS

 during

    her
    GENDER

 participation in the

    IMPACT2 clinical trial of C1-INH concentrate
    MEDICATION

. A

    53-year-old
    AGE

    caucasian
    ETHNICITY

    female
    GENDER

 with a

    31-year
    AGE

 history of

    type 1 HAE
    DIAGNOSIS

 experienced 16

    laryngeal HAE attacks
    SYMPTOMS

 between 3 August 2006 and 23 February 2010, 15 of which were severe. All

    laryngeal attacks
    SYMPTOMS

 were successfully treated with

    C1-INH 20 U/kg
    MEDICATION

, with a

    median onset of relief of 14 min
    SYMPTOMS

 and

    median time to complete resolution of symptoms of 20 h
    SYMPTOMS

, and

    no need for redosing
    NEG_FINDINGS

. The reliable success of

    C1-INH
    MEDICATION

 for these

    potentially fatal events
    SYMPTOMS

 is reassuring for both patients and prescribers.


Successful treatment of acute hereditary angioedema attacks with self-administered icatibant in patients with venous access problems.

Hereditary angioedema is a rare and potentially fatal autosomal dominant disorder characterised by unpredictable skin, gastrointestinal tract or respiratory tract oedema. Plasma-derived C1-esterase inhibitors are effective in the prophylaxis or treatment of hereditary angioedema type I and II attacks, but must be administered intravenously. This may be problematic in patients with venous access difficulties. Icatibant, a bradykinin B2-receptor antagonist, is administered subcutaneously. In July 2008 icatibant received approval for healthcare professional-administered treatment of hereditary angioedema attacks in adults. In 2011 it received European Medicines Agency and US Food and Drug Administration licences for patient-administered treatment of hereditary angioedema attacks. Given these approvals, and with the appropriate training, icatibant could provide the opportunity for patients to self-administer treatment. This is one of the first long-term follow-up reports of patients with hereditary angioedema using self-administered icatibant. During follow-up, icatibant remained effective and patient satisfaction was high.

    Hereditary angioedema
    DIAGNOSIS

 is a rare and potentially fatal

    autosomal dominant disorder
    GENETICS

 characterised by

    unpredictable skin, gastrointestinal tract or respiratory tract oedema
    SYMPTOMS

.

    Plasma-derived C1-esterase inhibitors
    MEDICATION

 are effective in the prophylaxis or treatment of

    hereditary angioedema type I and II attacks
    DIAGNOSIS

, but must be administered intravenously. This may be problematic in patients with

    venous access difficulties
    SYMPTOMS

.

    Icatibant, a bradykinin B2-receptor antagonist
    MEDICATION

, is

    administered subcutaneously
    MEDICATION

. In July 2008

    icatibant
    MEDICATION

 received approval for

    healthcare professional-administered treatment
    MEDICATION

 of

    hereditary angioedema attacks
    DIAGNOSIS

 in

    adults
    AGE

. In 2011 it received European Medicines Agency and US Food and Drug Administration licences for

    patient-administered treatment of hereditary angioedema attacks
    MEDICATION

. Given these approvals, and with the appropriate training,

    icatibant
    MEDICATION

 could provide the opportunity for patients to

    self-administer treatment
    MEDICATION

. This is one of the first long-term follow-up reports of patients with

    hereditary angioedema
    DIAGNOSIS

 using

    self-administered icatibant
    MEDICATION

. During follow-up,

    icatibant
    MEDICATION

 remained effective and patient satisfaction was high.


Phenytoin induced life threatening macroglossia in a child.

Isolated acquired macroglossia of tongue rarely reported. It occurs due to causes like hereditary angioedema, localized angioedema, etc., Here we describe an 8-year-old boy developing life threatening localized angioedema of tongue due to phenytoin without any association with drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or pseudolymphoma encountered in rural medical college. Anticonvulsants, that is, phenytoin induced this isolated peculiar complication, which was not described before.

    Isolated acquired macroglossia of tongue
    SYMPTOMS

 rarely reported. It occurs due to causes like

    hereditary angioedema
    DIAGNOSIS

,

    localized angioedema
    DIAGNOSIS

, etc., Here we describe an

    8-year-old
    AGE

    boy
    GENDER

 developing

    life threatening localized angioedema of tongue
    SYMPTOMS

 due to

    phenytoin
    MEDICATION

    without any association with drug reaction with eosinophilia and systemic symptoms
    NEG_FINDINGS

    (DRESS) syndrome
    DIAGNOSIS

 or

    pseudolymphoma
    NEG_FINDINGS

 encountered in rural medical college.

    Anticonvulsants
    MEDICATION

, that is,

    phenytoin
    MEDICATION

 induced this

    isolated peculiar complication
    SYMPTOMS

, which was not described before.

hereditary angioedema
localized angioedema
(DRESS) syndrome