Angioedema as a predominant symptom of Bordetella pertussis infection.

A 41-year-old woman was referred to our hospital with a 6-week history of severe angioedema, dyspnoea and coughing. Initial investigations focused on common causes of angioedema. Clinical presentation and resistance to treatment with antihistamines and steroids made histamine-mediated angioedema unlikely. Bradykinin-mediated angioedema, such as hereditary or drug-induced angioedema, was excluded by a thorough history investigation and laboratory testing for C1-esterase and C4.In rare cases, exogen pathogens cause angioedema. After profound testing for respiratory pathogens, Bordetella pertussis toxins IgA and IgG were found to be positive, indicating recent B. pertussis infection. Pertussis toxin may be responsible for increased vascular permeability causing angioedema. With adequate antibiotic treatment, the symptoms resolved quickly.This case is an example of an atypical presentation of B. pertussis infection in an unvaccinated adult. The recent resurgence of pertussis makes early diagnosis and disease prevention by vaccination crucial.

A

    41-year-old
    AGE

    woman
    GENDER

 was referred to our hospital with a

    6-week history
    SYMPTOMS

 of

    severe angioedema
    SYMPTOMS

,

    dyspnoea
    SYMPTOMS

 and

    coughing
    SYMPTOMS

. Initial investigations focused on common causes of

    angioedema
    SYMPTOMS

. Clinical presentation and

    resistance to treatment with antihistamines and steroids
    NEG_FINDINGS

 made

    histamine-mediated angioedema unlikely
    NEG_FINDINGS

.

    Bradykinin-mediated angioedema, such as hereditary or drug-induced angioedema
    NEG_FINDINGS

, was excluded by a thorough

    history investigation
    PARACLINICAL

 and laboratory testing for C1-esterase and C4.In rare cases,

    exogen pathogens
    DIAGNOSIS

 cause

    angioedema
    SYMPTOMS

. After

    profound testing for respiratory pathogens
    PARACLINICAL

,

    Bordetella pertussis toxins IgA and IgG were found to be positive
    BIOCHEMICAL

, indicating

    recent B. pertussis infection
    DIAGNOSIS

.

    Pertussis toxin
    DIAGNOSIS

 may be responsible for

    increased vascular permeability
    SYMPTOMS

 causing

    angioedema
    SYMPTOMS

. With

    adequate antibiotic treatment
    MEDICATION

, the symptoms resolved quickly.This case is an example of an atypical presentation of

    B. pertussis infection
    DIAGNOSIS

 in an unvaccinated

    adult
    AGE

. The recent resurgence of

    pertussis
    DIAGNOSIS

 makes early diagnosis and disease prevention by

    vaccination
    MEDICATION

 crucial.

6-week history
severe angioedema
dyspnoea
coughing
angioedema
angioedema
increased vascular permeability
angioedema

exogen pathogens
recent B. pertussis infection
Pertussis toxin
B. pertussis infection
pertussis

adequate antibiotic treatment
vaccination


Unusual presentation of linear wrist blisters associated with hereditary angioedema: The first case report in Taiwan.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract. It is most often caused by C1 esterase inhibitor (C1 INH) gene mutation. This swelling may lead to bradykinin release, resulting in recurrent, paroxysmal, painful angioedema. Blister formation is an uncommon cutaneous manifestation of HAE. Herein, we report a case of a patient with HAE who developed linear wrist blisters on her skin, with swelling, as a rare complication of HAE. She was treated with attenuated androgens (Danazol) for two weeks at our clinic, after which the blisters showed dramatic improvement. To date, only a few HAE cases have been reported across the world. Therefore, it is important to focus on and recognize the development of edema blisters as a flare of HAE, which could consequently avoid unnecessary dermatological diagnostic workup and treatment.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disease
    GENETICS

 characterized clinically by

    recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract
    SYMPTOMS

. It is most often caused by

    C1 esterase inhibitor (C1 INH) gene mutation
    BIOCHEMICAL

. This

    swelling
    SYMPTOMS

 may lead to

    bradykinin release
    BIOCHEMICAL

, resulting in

    recurrent, paroxysmal, painful angioedema
    SYMPTOMS

.

    Blister formation
    SYMPTOMS

 is an uncommon cutaneous manifestation of

    HAE
    DIAGNOSIS

. Herein, we report a case of a patient with

    HAE
    DIAGNOSIS

 who developed

    linear wrist blisters on her skin, with swelling
    SYMPTOMS

, as a rare complication of

    HAE
    DIAGNOSIS

.

    She
    GENDER

 was

    treated with attenuated androgens (Danazol) for two weeks
    MEDICATION

 at our clinic, after which

    the blisters showed dramatic improvement
    SYMPTOMS

. To date, only a few

    HAE
    DIAGNOSIS

 cases have been reported across the world. Therefore, it is important to focus on and recognize the development of

    edema blisters
    SYMPTOMS

 as a flare of

    HAE
    DIAGNOSIS

, which could consequently avoid

    unnecessary dermatological diagnostic workup
    NEG_FINDINGS

    and treatment
    NEG_FINDINGS

.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE


Acute Presentation of Undiagnosed Hereditary Angioedema of the Larynx: Averting Death.

Hereditary angioedema (HAE) differs from histamine-mediated angioedema in that it is resistant to steroids and antihistamines. Laryngeal attacks of this condition, if not diagnosed timely, carry a mortality rate up to 34%. Rarely, this disease goes undiagnosed until late adulthood and presents a life-threatening episode that poses a management challenge to the emergency physician. We report the case of a 48-year-old man who presented to the emergency department with progressive breathing difficulty two hours after consuming a carbonated drink. Clinical examination revealed supraglottic edema. He did not respond to steroids or antihistamines and required emergency tracheostomy to secure the airway due to failed intubation. Absence of symptoms such as itching or urticaria and inadequate response to steroids pointed to hereditary angioedema. Low complement factor 4 levels with low C1 esterase inhibitor functionality confirmed the diagnosis. This case report highlights the fact that delayed presentation of HAE can be life threatening and the diagnosis should be considered in all non-atopic adult patients with angioedema.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 differs from

    histamine-mediated angioedema
    NEG_FINDINGS

 in that it is

    resistant to steroids and antihistamines
    NEG_FINDINGS

.

    Laryngeal attacks
    SYMPTOMS

 of this condition, if not diagnosed timely, carry a mortality rate up to 34%. Rarely, this disease goes undiagnosed until

    late adulthood
    AGE

 and presents a

    life-threatening episode
    SYMPTOMS

 that poses a management challenge to the

    emergency physician
    PARACLINICAL

. We report the case of a

    48-year-old
    AGE

    man
    GENDER

 who presented to the emergency department with

    progressive breathing difficulty two hours after consuming a carbonated drink
    SYMPTOMS

.

    Clinical examination
    PARACLINICAL

 revealed

    supraglottic edema
    SYMPTOMS

.

    He
    GENDER

    did not respond to steroids or antihistamines
    NEG_FINDINGS

 and required

    emergency tracheostomy to secure the airway
    MEDICATION

 due to

    failed intubation
    NEG_FINDINGS

.

    Absence of symptoms such as itching or urticaria
    NEG_FINDINGS

 and

    inadequate response to steroids
    NEG_FINDINGS

 pointed to

    hereditary angioedema
    DIAGNOSIS

.

    Low complement factor 4 levels with low C1 esterase inhibitor functionality
    BIOCHEMICAL

 confirmed the diagnosis. This case report highlights the fact that delayed presentation of

    HAE
    DIAGNOSIS

 can be life threatening and the diagnosis should be considered in all

    non-atopic adult
    AGE

 patients with

    angioedema
    DIAGNOSIS

.

Hereditary angioedema (HAE)
hereditary angioedema
HAE
angioedema


A case of hereditary angioedema due to C1-inhibitor deficiency with recurrent abdominal pain diagnosed 40 years after the occurrence of the initial symptom.

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare disease, which induces an acute attack of angioedema mediated by bradykinin. HAE-C1-INH can cause serious abdominal pain when severe edema develops in the gastrointestinal tract. However, because it takes a long time, 13.8 years on average in Japan, from the occurrence of the initial symptom to the diagnosis due to low awareness of the disease, undiagnosed HAE-C1-INH patients sometimes undergo unnecessary surgical procedures for severe abdominal pain. We herein present a 56-year-old patient with HAE-C1-INH, who underwent numerous abdominal operations. He frequently needed hospitalization with the administration of opioid due to severe abdominal pain. However, after he was accurately diagnosed with HAE-C1-INH at 55 years of age, he could start self-administration for an acute attack with icatibant, a selective bradykinin B2 receptor antagonist. Consequently, he did not need hospitalizing for ten months after the beginning of the treatment. A series of an accurate diagnosis and appropriate treatment for HAE-C1-INH improved his quality of life. Thus, HAE-C1-INH should be considered, when we meet patients with unidentified recurrent abdominal pain. This case highlights significance of an early diagnosis and appropriate treatment for HAE-C1-INH.

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

 is a rare disease, which induces an

    acute attack of angioedema mediated by bradykinin
    SYMPTOMS

.

    HAE-C1-INH
    DIAGNOSIS

 can cause

    serious abdominal pain
    SYMPTOMS

 when

    severe edema develops in the gastrointestinal tract
    SYMPTOMS

. However, because it takes a long time, 13.8 years on average in

    Japan
    ETHNICITY

, from the occurrence of the initial symptom to the diagnosis due to low awareness of the disease, undiagnosed

    HAE-C1-INH
    DIAGNOSIS

 patients sometimes undergo

    unnecessary surgical procedures
    NEG_FINDINGS

 for

    severe abdominal pain
    SYMPTOMS

. We herein present a

    56-year-old
    AGE

 patient with

    HAE-C1-INH
    DIAGNOSIS

, who underwent

    numerous abdominal operations
    MEDICATION

.

    He
    GENDER

 frequently needed

    hospitalization with the administration of opioid
    MEDICATION

 due to

    severe abdominal pain
    SYMPTOMS

. However, after

    he
    GENDER

 was accurately diagnosed with

    HAE-C1-INH
    DIAGNOSIS

 at

    55 years of age
    AGE

,

    he
    GENDER

 could start

    self-administration for an acute attack with icatibant, a selective bradykinin B2 receptor antagonist
    MEDICATION

. Consequently,

    he
    GENDER

    did not need hospitalizing for ten months after the beginning of the treatment
    NEG_FINDINGS

. A series of an accurate diagnosis and appropriate treatment for

    HAE-C1-INH
    DIAGNOSIS

 improved his quality of life. Thus,

    HAE-C1-INH
    DIAGNOSIS

 should be considered, when we meet patients with

    unidentified recurrent abdominal pain
    SYMPTOMS

. This case highlights significance of an early diagnosis and appropriate treatment for

    HAE-C1-INH
    DIAGNOSIS

.


Capillary leak syndrome and disseminated intravascular coagulation after kidney transplantation in a patient with hereditary angioedema - A case report.

Hereditary angioedema (HAE) is a rare disease caused by the deficiency of C1 esterase inhibitor. HAE has a risk of life-threatening complications such as capillary leak syndrome (CLS) and disseminated intravascular coagulation (DIC).

A 42-year-old male patient with HAE presented for deceased-donor kidney transplantation. Prophylactic fresh frozen plasma (FFP) was given before surgery because of the risk of edema development. With careful management during anesthesia, there were no problems during surgery. However, generalized edema, hypotension, hypoalbuminemia, massive drainage of serosanguineous fluids from the intraabdominal space, and DIC occurred on the day after surgery. CLS was suspected and sustained hypotension with generalized edema became worse despite treatment with albumin, danazol, FFP, and vasoactive drugs. The patient's condition worsened despite intensive care and he died due to shock.

The anesthesiologist should prepare for the critical complications of HAE and prepare the appropriate treatment options.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare disease
    GENETICS

 caused by the

    deficiency of C1 esterase inhibitor
    BIOCHEMICAL

.

    HAE
    DIAGNOSIS

 has a risk of

    life-threatening complications
    SYMPTOMS

 such as

    capillary leak syndrome (CLS)
    SYMPTOMS

 and

    disseminated intravascular coagulation (DIC)
    SYMPTOMS

.

A

    42-year-old
    AGE

    male
    GENDER

 patient with

    HAE
    DIAGNOSIS

 presented for

    deceased-donor kidney transplantation
    MEDICATION

.

    Prophylactic fresh frozen plasma (FFP)
    MEDICATION

 was given before

    surgery
    MEDICATION

 because of the risk of

    edema development
    SYMPTOMS

. With careful management during anesthesia, there were

    no problems during surgery
    NEG_FINDINGS

. However,

    generalized edema
    SYMPTOMS

,

    hypotension
    SYMPTOMS

,

    hypoalbuminemia
    BIOCHEMICAL

,

    massive drainage of serosanguineous fluids from the intraabdominal space
    MICROSCOPIC

, and

    DIC
    SYMPTOMS

 occurred on the day after

    surgery
    MEDICATION

.

    CLS
    DIAGNOSIS

 was suspected and

    sustained hypotension
    SYMPTOMS

 with

    generalized edema became worse
    SYMPTOMS

    despite treatment with albumin, danazol, FFP, and vasoactive drugs
    NEG_FINDINGS

. The patient's condition worsened

    despite intensive care
    NEG_FINDINGS

 and

    he
    GENDER

    died
    SYMPTOMS

 due to

    shock
    SYMPTOMS

.

The

    anesthesiologist
    PARACLINICAL

 should prepare for the critical complications of

    HAE
    DIAGNOSIS

 and prepare the appropriate treatment options.

Hereditary angioedema (HAE)
HAE
HAE
CLS
HAE

deficiency of C1 esterase inhibitor
hypoalbuminemia

deceased-donor kidney transplantation
Prophylactic fresh frozen plasma (FFP)
surgery
surgery


Novel hereditary angioedema linked with a heparan sulfate 3-O-sulfotransferase 6 gene mutation.

Hereditary angioedema (HAE) is a potentially fatal disorder resulting in recurrent attacks of severe swelling. It may be associated with a genetic deficiency of functional C1 inhibitor or with normal C1 inhibitor (HAEnCI). In families with HAEnCI, HAE-linked mutations in the F12, PLG, KNG1, ANGPT1, or MYOF genes have been identified. In many families with HAEnCI the genetic cause of the disease is currently unknown.

The aim of this study was to identify a novel disease-linked mutation for HAEnCI.

The study methods comprised whole exome sequencing, Sanger sequencing analysis, pedigree analysis, bioinformatic analysis of the mutation, and biochemical analysis of parameters of the kallikrein-kinin (contact) system.

By performing whole exome sequencing on a multigenerational family with HAEnCI we were able to identify the heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6) mutation c.430A>T (p.Thr144Ser) in all 3 affected family members who were sequenced. This gene encodes HS-glucosamine 3-O-sulfotransferase 6 (3-OST-6), which is involved in the last step of HS biosynthesis. The p.Thr144Ser mutation is likely to affect the interaction between 2 β-sheets stabilizing the active center of the 3-OST-6 protein.

We conclude that mutant 3-OST-6 fails to transfer sulfo groups to the 3-OH position of HS, resulting in incomplete HS biosynthesis. This likely affects cell surface interactions of key players in angioedema formation and is a novel mechanism for disease development.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a potentially fatal disorder resulting in

    recurrent attacks of severe swelling
    SYMPTOMS

. It may be associated with a

    genetic deficiency of functional C1 inhibitor
    GENETICS

 or with

    normal C1 inhibitor
    NEG_FINDINGS

 (

    HAEnCI)
    DIAGNOSIS

. In families with

    HAEnCI
    DIAGNOSIS

,

    HAE
    DIAGNOSIS

    -linked mutations in the F12, PLG, KNG1, ANGPT1, or MYOF genes
    GENETICS

 have been identified. In many families with

    HAEnCI
    DIAGNOSIS

 the genetic cause of the disease is currently unknown.

The aim of this study was to identify a

    novel disease-linked mutation
    GENETICS

 for

    HAEnCI
    DIAGNOSIS

.

The study methods comprised

    whole exome sequencing
    PARACLINICAL

,

    Sanger sequencing analysis
    PARACLINICAL

,

    pedigree analysis
    PARACLINICAL

,

    bioinformatic analysis of the mutation
    PARACLINICAL

, and

    biochemical analysis of parameters of the kallikrein-kinin (contact) system
    PARACLINICAL

.

By performing

    whole exome sequencing
    PARACLINICAL

 on a

    multigenerational family with HAEnCI
    FAMILY

 we were able to identify the

    heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6) mutation c.430A>T (p.Thr144Ser)
    BIOCHEMICAL

 in all 3 affected family members who were sequenced. This gene encodes

    HS-glucosamine 3-O-sulfotransferase 6 (3-OST-6)
    BIOCHEMICAL

, which is involved in the last step of

    HS biosynthesis
    BIOCHEMICAL

. The

    p.Thr144Ser mutation is likely to affect the interaction between 2 β-sheets stabilizing the active center of the 3-OST-6 protein
    GENETICS

.

We conclude that

    mutant 3-OST-6 fails to transfer sulfo groups to the 3-OH position of HS
    GENETICS

, resulting in

    incomplete HS biosynthesis
    BIOCHEMICAL

. This likely affects cell surface interactions of key players in

    angioedema formation
    SYMPTOMS

 and is a novel mechanism for disease development.

Hereditary angioedema (HAE)
HAEnCI)
HAEnCI
HAE
HAEnCI
HAEnCI

recurrent attacks of severe swelling
angioedema formation


Successful treatment with Cinryze® replacement therapy of a pregnant patient with hereditary angioedema: a case report.

Hereditary angioedema (HAE) is a rare disease characterized with recurrent swelling of subcutaneous or mucosal tissue that resolves in approximately 3 days. It can be presented with peripheral edema, abdominal and life-threatening laryngeal angioedema. A variety of triggers are known to cause episodes of angioedema including estrogen exposure. There are different reports regarding the effect of pregnancy on HAE attacks, and in some patients, the pregnancy is a recognized triggering factor.

We present a female Caucasian patient with pre-existing HAE and disease exacerbations during pregnancy, requiring prophylactic use of plasma-derived C1 inhibitor concentrate. She was treated with Cinryze® replacement therapy throughout the pregnancy 1000 IU i.v. 48 times. She gave birth to a healthy male infant, via C-section. After the delivery, the patient was symptom-free for 6 months and required no treatment for HAE.

In the case presented, the angioedema attacks worsened as the pregnancy progressed. The treatment with Cinryze® replacement therapy was effective and safe during pregnancy, with no adverse effects on the infant.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare disease characterized with

    recurrent swelling of subcutaneous or mucosal tissue
    SYMPTOMS

 that resolves in approximately 3 days. It can be presented with

    peripheral edema
    SYMPTOMS

,

    abdominal
    SYMPTOMS

 and

    life-threatening laryngeal angioedema
    SYMPTOMS

. A variety of triggers are known to cause episodes of

    angioedema
    SYMPTOMS

 including

    estrogen exposure
    SYMPTOMS

. There are different reports regarding the effect of

    pregnancy
    DIAGNOSIS

 on

    HAE attacks
    DIAGNOSIS

, and in some patients, the

    pregnancy
    SYMPTOMS

 is a recognized triggering factor.

We present a

    female
    GENDER

    Caucasian
    ETHNICITY

 patient with

    pre-existing HAE
    DIAGNOSIS

 and

    disease exacerbations
    SYMPTOMS

 during

    pregnancy
    SYMPTOMS

, requiring

    prophylactic use of plasma-derived C1 inhibitor concentrate
    MEDICATION

.

    She
    GENDER

 was

    treated with Cinryze® replacement therapy throughout the pregnancy 1000 IU i.v. 48 times
    MEDICATION

.

    She
    GENDER

    gave birth to a healthy male infant, via C-section
    MEDICATION

. After the delivery, the patient was

    symptom-free for 6 months
    NEG_FINDINGS

 and

    required no treatment for HAE
    NEG_FINDINGS

.

In the case presented, the

    angioedema attacks worsened
    SYMPTOMS

 as the pregnancy progressed. The

    treatment with Cinryze® replacement therapy
    MEDICATION

 was effective and safe during

    pregnancy
    DIAGNOSIS

, with

    no adverse effects on the infant
    NEG_FINDINGS

.

Hereditary angioedema (HAE)
pregnancy
HAE attacks
pre-existing HAE
pregnancy

symptom-free for 6 months
required no treatment for HAE
no adverse effects on the infant


Colonic Intussusception Secondary to Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare genetic disease with numerous gastrointestinal manifestations. Intussusception, although rare, has been a reported complication with documentation of bowel wall edema on endoscopy during an acute flare. With the advent of synthetic C1 esterase inhibitors, this disease has become more effectively treatable. This case report shows a HAE flare complicated by colonic intussusception, treated with C1 esterase inhibitor, with complete endoscopic resolution seen on hospital day 5. This case provides evidence that with proper medical treatment, an HAE flare with intussusception has the potential to resolve without any further need for surgical or endoscopic intervention.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic disease
    GENETICS

 with numerous

    gastrointestinal manifestations
    SYMPTOMS

.

    Intussusception
    SYMPTOMS

, although rare, has been a reported complication with documentation of

    bowel wall edema
    SYMPTOMS

 on

    endoscopy
    PARACLINICAL

 during an

    acute flare
    SYMPTOMS

. With the advent of

    synthetic C1 esterase inhibitors
    MEDICATION

, this disease has become more effectively treatable. This case report shows a

    HAE flare
    DIAGNOSIS

 complicated by

    colonic intussusception
    SYMPTOMS

, treated with

    C1 esterase inhibitor
    MEDICATION

, with

    complete endoscopic resolution
    SYMPTOMS

 seen on hospital day 5. This case provides evidence that with proper medical treatment, an

    HAE flare
    DIAGNOSIS

 with

    intussusception
    SYMPTOMS

 has the potential to resolve

    without any further need for surgical or endoscopic intervention
    NEG_FINDINGS

.

Hereditary angioedema (HAE)
HAE flare
HAE flare

gastrointestinal manifestations
Intussusception
bowel wall edema
acute flare
colonic intussusception
complete endoscopic resolution
intussusception

synthetic C1 esterase inhibitors
C1 esterase inhibitor


Solifenacin-induced acute urticaria and angioedema: a rare adverse effect.

Antimuscarinics are first-line medication for management of overactive bladder with solifenacin being commonly prescribed. Angioedema is the swelling of mucosa and submucosal tissue. There are no published case reports of drug-induced angioedema involving solifenacin. We report a case of a 41-year-old man with spinal cord injury who presented with oedema of face, lips, tongue and associated pruritic urticaria after taking 5 mg of solifenacin. All other possible causes including food allergy, insect bite, hereditary angioedema, use of NSAIDs, ACE inhibitors and antibiotics were ruled out. The temporal association between solifenacin and angioedema and complete resolution of symptoms after discontinuing the drug suggest that solifenacin was the most probable cause of angioedema in our patient.

    Antimuscarinics
    MEDICATION

 are first-line medication for management of

    overactive bladder
    DIAGNOSIS

 with

    solifenacin
    MEDICATION

 being commonly prescribed.

    Angioedema
    DIAGNOSIS

 is the

    swelling of mucosa and submucosal tissue
    SYMPTOMS

. There are no published case reports of

    drug-induced angioedema
    DIAGNOSIS

 involving

    solifenacin
    MEDICATION

. We report a case of a

    41-year-old
    AGE

    man
    GENDER

 with

    spinal cord injury
    DIAGNOSIS

 who presented with

    oedema of face, lips, tongue
    SYMPTOMS

 and

    associated pruritic urticaria
    SYMPTOMS

 after

    taking 5 mg of solifenacin
    MEDICATION

. All other possible causes including

    food allergy, insect bite
    NEG_FINDINGS

,

    hereditary angioedema
    NEG_FINDINGS

,

    use of NSAIDs, ACE inhibitors and antibiotics were ruled out
    NEG_FINDINGS

. The

    temporal association between solifenacin
    SYMPTOMS

 and

    angioedema
    SYMPTOMS

 and

    complete resolution of symptoms after discontinuing the drug
    SYMPTOMS

 suggest that

    solifenacin
    MEDICATION

 was the most probable cause of

    angioedema
    DIAGNOSIS

 in our patient.

Antimuscarinics
solifenacin
solifenacin
taking 5 mg of solifenacin
solifenacin

overactive bladder
Angioedema
drug-induced angioedema
spinal cord injury
angioedema


Short-term Prophylaxis for Delivery in Pregnant Women with Hereditary Angioedema with Normal C1-Inhibitor.

To verify the efficacy of short-term prophylaxis for vaginal or cesarean section childbirth with plasma-derived C1-inhibitor concentrate in pregnant women. They should have hereditary angioedema (HAE) and normal plasma C1-inhibitor.

Case report of pregnant women diagnosed with HAE with normal C1-inhibitor who had been treated with intravenous C1-inhibitor concentrate for prophylaxis of angioedema attacks when hospitalized for delivery. The exon 9 of the Factor 12 (F12) genotyping gene was performed by automatic sequencing in all patients.

Three cases of pregnant women with HAE with normal serum level of C1-inhibitor are reported. The genetic test detected the presence of a pathogenic mutation in the F12 gene. Deliveries occurred uneventfully and patients had no HAE symptoms in the following 72 hours.

C1-inhibitor concentrate could be useful to prevent angioedema attacks during and after delivery.

To verify the efficacy of

    short-term prophylaxis for vaginal or cesarean section childbirth with plasma-derived C1-inhibitor concentrate
    MEDICATION

 in

    pregnant
    AGE

    women
    GENDER

. They should have

    hereditary angioedema (HAE)
    DIAGNOSIS

 and

    normal plasma C1-inhibitor
    NEG_FINDINGS

.

Case report of

    pregnant
    AGE

    women
    GENDER

 diagnosed with

    HAE
    DIAGNOSIS

 with

    normal C1-inhibitor
    NEG_FINDINGS

 who had been

    treated with intravenous C1-inhibitor concentrate for prophylaxis of angioedema attacks
    MEDICATION

 when

    hospitalized for delivery
    MEDICATION

.

    The exon 9 of the Factor 12 (F12) genotyping gene was performed by automatic sequencing
    PARACLINICAL

 in all patients.

Three cases of

    pregnant
    AGE

    women
    GENDER

 with

    HAE
    DIAGNOSIS

 with

    normal serum level of C1-inhibitor
    NEG_FINDINGS

 are reported. The

    genetic test
    PARACLINICAL

 detected the

    presence of a pathogenic mutation in the F12 gene
    GENETICS

. Deliveries occurred

    uneventfully
    MEDICATION

 and patients had

    no HAE symptoms in the following 72 hours
    NEG_FINDINGS

.

    C1-inhibitor concentrate
    MEDICATION

 could be useful to prevent

    angioedema attacks
    SYMPTOMS

 during and after

    delivery
    MEDICATION

.


Successful perioperative management of three patients with hereditary angioedema without C1 esterase inhibitor therapy: A developing country perspective.

Hereditary angioedema (HAE) is a rare inherited disorder characterized by sudden and unpredictable appearance of swelling. Surgical procedures, even minor ones, are known to precipitate an attack in these patients. C1 esterase inhibitor (C1-INH) therapy may be effective for short term prophylaxis in such situations. However, there is limited experience with short term prophylaxis in countries where C1-INH therapy is not available.

To report our experience of using short term prophylaxis for a dental procedure, a Cesarean section and a major hip surgery in one patient each with HAE in resource constrained settings.

All 3 patients were given FFP before and during the procedure. While the first (a 6-year-old girl) and third patient (a 60-year-old male) were already taking stanozolol and the dose was doubled 5 days before the surgery, the second patient (28-year-old woman) was not taking any prophylaxis and she was initiated on stanozolol on the day of Cesarean section. The first patient was also given additional FFP one day after the dental procedure. After the procedure, the dose of stanozolol was decreased to baseline in patient 1 and 3 while it was discontinued in patient 3. All 3 patients tolerated the procedures well and had no related episodes of angioedema.

Dental and other major surgical procedures in patients with HAE are known to precipitate an episode of angioedema. In countries where C1-INH therapy is not available, attenuated androgens and FFP may be used to prevent these episodes.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare inherited disorder
    GENETICS

 characterized by

    sudden and unpredictable appearance of swelling
    SYMPTOMS

.

    Surgical procedures
    MEDICATION

, even

    minor ones
    MEDICATION

, are known to precipitate an attack in these patients.

    C1 esterase inhibitor (C1-INH) therapy
    MEDICATION

 may be effective for

    short term prophylaxis
    MEDICATION

 in such situations. However, there is limited experience with

    short term prophylaxis
    MEDICATION

 in countries where

    C1-INH therapy
    NEG_FINDINGS

 is not available.

To report our experience of

    using short term prophylaxis for a dental procedure, a Cesarean section and a major hip surgery
    MEDICATION

 in one patient each with

    HAE
    DIAGNOSIS

 in resource constrained settings.

All 3 patients were

    given FFP before and during the procedure
    MEDICATION

. While the first (a

    6-year-old
    AGE

    girl
    GENDER

) and third patient (a

    60-year-old
    AGE

    male
    GENDER

) were

    already taking stanozolol and the dose was doubled 5 days before the surgery
    MEDICATION

, the second patient (

    28-year-old
    AGE

    woman
    GENDER

) was

    not taking any prophylaxis
    NEG_FINDINGS

 and

    she
    GENDER

 was

    initiated on stanozolol on the day of Cesarean section
    MEDICATION

. The first patient was

    also given additional FFP one day after the dental procedure
    MEDICATION

. After the procedure,

    the dose of stanozolol was decreased to baseline
    MEDICATION

 in patient 1 and 3 while

    it was discontinued
    MEDICATION

 in patient 3. All 3 patients tolerated the procedures well and had

    no related episodes of angioedema
    NEG_FINDINGS

.

    Dental and other major surgical procedures
    MEDICATION

 in patients with

    HAE
    DIAGNOSIS

 are known to precipitate an

    episode of angioedema
    SYMPTOMS

. In countries where

    C1-INH therapy is not available
    NEG_FINDINGS

,

    attenuated androgens and FFP
    MEDICATION

 may be used to prevent these episodes.

C1-INH therapy
not taking any prophylaxis
no related episodes of angioedema
C1-INH therapy is not available


Tranexamic acid for ACE inhibitor induced angioedema.

Tranexamic acid (TXA) is an antifibrinolytic agent which inhibits conversion of plasminogen to plasmin, a key step in kallikrein activation and bradykinin formation. Tranexamic acid is used in prophylactic management of hereditary angioedema; however, evidence for TXA in angiotensin converting enzyme (ACE) inhibitor-induced angioedema (ACEI-AE) is limited. We describe a patient who presented to the emergency department with ACEI-AE who was successfully treated with TXA. This case suggests that TXA may be a beneficial treatment modality in the management of ACEI-AE and warrants further investigation.

    Tranexamic acid (TXA) is an antifibrinolytic agent
    MEDICATION

 which

    inhibits conversion of plasminogen to plasmin
    BIOCHEMICAL

, a key step in

    kallikrein activation and bradykinin formation
    BIOCHEMICAL

.

    Tranexamic acid
    MEDICATION

 is used in

    prophylactic management
    MEDICATION

 of

    hereditary angioedema
    DIAGNOSIS

; however, evidence for

    TXA
    MEDICATION

 in

    angiotensin converting enzyme (ACE) inhibitor-induced angioedema (ACEI-AE)
    MEDICATION

 is limited. We describe a patient who presented to the emergency department with

    ACEI-AE
    DIAGNOSIS

 who was successfully treated with

    TXA
    MEDICATION

. This case suggests that

    TXA
    MEDICATION

 may be a beneficial treatment modality in the management of

    ACEI-AE
    DIAGNOSIS

 and warrants further investigation.


Hereditary Angioedema Attack in Utero and Treatment of the Mother and Fetus.

Hereditary angioedema (HAE), an inherited deficiency of functional C1 esterase inhibitor (C1-INH), is characterized by unpredictable recurrent episodes of painful and often disabling swelling in subcutaneous and/or submucosal tissues. We report the case of a 23-year-old woman with type I HAE who had abdominal, facial, and peripheral attacks throughout her first pregnancy. A facial HAE attack occurred at week 38 of her pregnancy, and symptoms improved after self-administration of 50 U/kg of recombinant human C1-INH (total dose, 3500 U), but soon after she had an unusual abdominal sensation. Ultrasonography detected fetal lower lip swelling (∼3 times the normal size) and limb swelling. Physical examination of the mother found cervical dilatation, indicating the final stages of labor. Two hours after treatment of her HAE attack, she spontaneously delivered a healthy male infant. Photographs taken within 2 minutes of delivery revealed resolution of the infant's facial edema, and the limb edema was resolved within 30 minutes. By 10 minutes postdelivery, the mother's facial attack had almost completely resolved. Ten months after birth, genetic analysis confirmed that the infant had type I HAE. This is the first documented case of an HAE attack in utero. Treatment of the mother with recombinant human C1-INH was effective for the maternal and fetal attacks, with resolution within approximately 2 to 2.5 hours for both patients.

    Hereditary angioedema (HAE)
    DIAGNOSIS

, an

    inherited deficiency of functional C1 esterase inhibitor (C1-INH)
    GENETICS

, is characterized by

    unpredictable recurrent episodes of painful and often disabling swelling in subcutaneous and/or submucosal tissues
    SYMPTOMS

. We report the case of a

    23-year-old
    AGE

    woman
    GENDER

 with

    type I HAE
    DIAGNOSIS

 who had

    abdominal, facial, and peripheral attacks
    SYMPTOMS

 throughout her first

    pregnancy
    DIAGNOSIS

. A

    facial HAE attack
    SYMPTOMS

 occurred at

    week 38 of her pregnancy
    MEDICATION

, and

    symptoms improved
    SYMPTOMS

 after

    self-administration of 50 U/kg of recombinant human C1-INH (total dose, 3500 U)
    MEDICATION

, but soon after

    she
    GENDER

 had an

    unusual abdominal sensation
    SYMPTOMS

.

    Ultrasonography
    PARACLINICAL

 detected

    fetal lower lip swelling (∼3 times the normal size)
    SYMPTOMS

 and

    limb swelling
    SYMPTOMS

.

    Physical examination of the mother
    PARACLINICAL

 found

    cervical dilatation
    SYMPTOMS

, indicating the

    final stages of labor
    SYMPTOMS

. Two hours after treatment of her

    HAE attack
    DIAGNOSIS

,

    she
    GENDER

    spontaneously delivered a healthy male infant
    MEDICATION

. Photographs taken within 2 minutes of delivery revealed

    resolution of the infant's facial edema
    SYMPTOMS

, and the

    limb edema was resolved within 30 minutes
    SYMPTOMS

. By 10 minutes postdelivery, the

    mother's facial attack had almost completely resolved
    SYMPTOMS

. Ten months after

    birth
    AGE

,

    genetic analysis
    PARACLINICAL

 confirmed that the

    infant
    AGE

 had

    type I HAE
    DIAGNOSIS

. This is the first documented case of an

    HAE attack
    DIAGNOSIS

 in

    utero
    AGE

.

    Treatment of the mother with recombinant human C1-INH
    MEDICATION

 was effective

    for the maternal and fetal attacks
    SYMPTOMS

, with resolution within approximately 2 to 2.5 hours for both patients.

Hereditary angioedema (HAE)
type I HAE
pregnancy
HAE attack
type I HAE
HAE attack


Vibratory Angioedema Subgroups, Features, and Treatment: Results of a Systematic Review.

Vibratory angioedema (VA) is a subtype of chronic inducible urticaria that manifests with erythematous wheals or angioedema after skin exposure to vibration. Because the condition is rare, the available information is limited.

To systematically review the clinical manifestations and treatment options of VA.

Relevant literature published until August 2020 was searched using the terms "vibratory urticaria," "vibratory angioedema," "vibratory-induced angioedema," and "vibratory-induced urticaria." Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations were applied to this systematic review.

On the basis of review of 22 studies (16 case reports, 4 case series, and 2 cohort studies) that had a combined total of 83 patients, we propose that VA be classified as hereditary VA (33.7%) and acquired VA (66.3%). Vibration-induced itching was frequent in both subgroups. Patients with hereditary VA more commonly had wheals and systemic symptoms, whereas patients with acquired VA more frequently had angioedema, burning, pain, or tingling. Although many VA treatments are used, there is little information on their efficacy. Most patients do not achieve complete control.

The novel VA classification proposed could help clinicians with the diagnostic workup of patients with VA. Because of the paucity of reported cases, firm recommendations for the treatment of VA are currently not possible. For patients with acquired VA, we suggest second-generation H1-antihistamines as the first-line treatment. Controlled therapeutic trials are needed and should be performed.

    Vibratory angioedema (VA)
    DIAGNOSIS

 is a subtype of

    chronic inducible urticaria
    DIAGNOSIS

 that manifests with

    erythematous wheals
    SYMPTOMS

 or

    angioedema
    SYMPTOMS

 after

    skin exposure to vibration
    SYMPTOMS

. Because the condition is rare, the available information is limited.

Relevant literature published until August 2020 was searched using the terms "

    vibratory urticaria
    DIAGNOSIS

," "

    vibratory angioedema
    DIAGNOSIS

," "

    vibratory-induced angioedema
    DIAGNOSIS

," and "

    vibratory-induced urticaria
    DIAGNOSIS

." Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations were applied to this systematic review.

On the basis of review of 22 studies (16 case reports, 4 case series, and 2 cohort studies) that had a combined total of 83 patients, we propose that

    VA
    DIAGNOSIS

 be classified as

    hereditary VA
    DIAGNOSIS

 (33.7%) and

    acquired VA
    DIAGNOSIS

 (66.3%).

    Vibration-induced itching
    SYMPTOMS

 was frequent in both subgroups. Patients with

    hereditary VA
    DIAGNOSIS

 more commonly had

    wheals
    SYMPTOMS

 and

    systemic symptoms
    SYMPTOMS

, whereas patients with

    acquired VA
    DIAGNOSIS

 more frequently had

    angioedema
    SYMPTOMS

,

    burning, pain
    SYMPTOMS

, or

    tingling
    SYMPTOMS

. Although many

    VA treatments
    MEDICATION

 are used, there is little information on their efficacy. Most patients do

    not achieve complete control
    NEG_FINDINGS

.

The novel VA classification proposed could help clinicians with the diagnostic workup of patients with

    VA
    DIAGNOSIS

. Because of the paucity of reported cases, firm recommendations for the treatment of

    VA
    DIAGNOSIS

 are currently not possible. For patients with

    acquired VA
    DIAGNOSIS

, we suggest

    second-generation H1-antihistamines
    MEDICATION

 as the first-line treatment. Controlled therapeutic trials are needed and should be performed.

Vibratory angioedema (VA)
chronic inducible urticaria
vibratory urticaria
vibratory angioedema
vibratory-induced angioedema
vibratory-induced urticaria
VA
hereditary VA
acquired VA
hereditary VA
acquired VA
VA
VA
acquired VA

erythematous wheals
angioedema
skin exposure to vibration
Vibration-induced itching
wheals
systemic symptoms
angioedema
burning, pain
tingling

VA treatments
second-generation H1-antihistamines


Novel Use of Fresh Frozen Plasma in Treating Hereditary Angioedema: A Success Story From Pakistan.

Hereditary angioedema (HAE) due to a C1-esterase inhibitor(C1-INH) deficiency is a rare and potentially life-threatening disorder. It is characterized by an episodic and self-limiting increase in vascular permeability. The condition manifests itself as recurrent attacks of swelling in any part of the body. The angioedema can cause the involvement of the respiratory tract, skin, and gastrointestinal tract. Laryngeal involvement can make the condition life-threatening. It does not respond well to conventional angioedema therapy of steroids, adrenaline, and antihistamines. The targeted therapy for HAE consists of plasma-derived or recombinant C1-INH, ecallantide, and icatibant or bradykinin receptor antagonist. In the absence of these therapies, it becomes difficult to manage this condition effectively. We present a case of hereditary angioedema, who presented with life-threatening laryngeal edema, causing asphyxia, leading to cardiac arrest. Due to a lack of availability of C1-INH concentrate, he was given fresh frozen plasma (FFP). His condition gradually improved, and he was successfully extubated after three days. This is the first time we are reporting a case from Pakistan in which the patient was successfully treated with FFP for an acute attack of hereditary angioedema.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 due to a

    C1-esterase inhibitor(C1-INH) deficiency
    BIOCHEMICAL

 is a rare and potentially life-threatening disorder. It is characterized by an

    episodic and self-limiting increase in vascular permeability
    SYMPTOMS

. The condition manifests itself as

    recurrent attacks of swelling in any part of the body
    SYMPTOMS

. The

    angioedema
    DIAGNOSIS

 can cause the

    involvement of the respiratory tract, skin, and gastrointestinal tract
    SYMPTOMS

.

    Laryngeal involvement
    SYMPTOMS

 can make the condition

    life-threatening
    SYMPTOMS

. It

    does not respond well to conventional angioedema therapy of steroids, adrenaline, and antihistamines
    NEG_FINDINGS

. The targeted therapy for

    HAE
    DIAGNOSIS

 consists of

    plasma-derived or recombinant C1-INH, ecallantide, and icatibant or bradykinin receptor antagonist
    MEDICATION

. In the absence of these therapies, it becomes difficult to manage this condition effectively. We present a case of

    hereditary angioedema
    DIAGNOSIS

, who presented with

    life-threatening laryngeal edema
    SYMPTOMS

, causing

    asphyxia
    SYMPTOMS

, leading to

    cardiac arrest
    SYMPTOMS

. Due to a

    lack of availability of C1-INH concentrate
    NEG_FINDINGS

,

    he
    GENDER

 was given

    fresh frozen plasma (FFP)
    MEDICATION

. His condition gradually improved, and he was

    successfully extubated after three days
    MEDICATION

. This is the first time we are reporting a case from

    Pakistan
    ETHNICITY

 in which the patient was successfully treated with

    FFP
    MEDICATION

 for an

    acute attack of hereditary angioedema
    DIAGNOSIS

.

Hereditary angioedema (HAE)
angioedema
HAE
hereditary angioedema
acute attack of hereditary angioedema


Misleading symptoms of hereditary angioedema type II mimicking familial mediterranean fever.

Hereditary angioedema (HAE) is a rare, debilitating and potentially life-threatening disease characterized by recurrent attacks of oedema. With the development of new therapies and better availability of diagnostic tools, important advances have been made. However, the disease still remains frequently misdiagnosed and inadequately treated. Familial Mediterranean fever (FMF) is an autoinflammatory syndrome comprised of serositis, fever, arthritis and skin involvement. Both diseases can cause severe abdominal pain resembling that of acute abdomen. We report a case of three family members that presented with various symptoms that could fit in a clinical picture of both diseases, only to confirm a diagnosis of HAE type II after a diagnostic delay of many years.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare, debilitating and

    potentially life-threatening
    SYMPTOMS

 disease characterized by

    recurrent attacks of oedema
    SYMPTOMS

. With the development of new therapies and better availability of diagnostic tools, important advances have been made. However, the disease still remains frequently misdiagnosed and

    inadequately treated
    NEG_FINDINGS

.

    Familial Mediterranean fever (FMF)
    DIAGNOSIS

 is an

    autoinflammatory syndrome
    DIAGNOSIS

 comprised of

    serositis
    DIAGNOSIS

,

    fever
    SYMPTOMS

,

    arthritis
    SYMPTOMS

 and

    skin involvement
    SYMPTOMS

. Both diseases can cause

    severe abdominal pain resembling that of acute abdomen
    SYMPTOMS

. We report a case of

    three family members
    FAMILY

 that presented with various symptoms that could fit in a clinical picture of both diseases, only to confirm a diagnosis of

    HAE type II
    DIAGNOSIS

 after a diagnostic delay of many years.

Hereditary angioedema (HAE)
Familial Mediterranean fever (FMF)
autoinflammatory syndrome
serositis
HAE type II


Acquired Angioedema due to C1 Inhibitor Deficiency Preceding Splenic Marginal Zone Lymphoma: Further Insights from Clinical Practice.

Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH) is a very rare disease. In clinical practice, it may be difficult to differentiate AAE-C1-INH from hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). In both conditions, patients are at an increased risk of death from asphyxiation due to upper airway obstruction. The association of AAE-C1-INH with lymphoproliferative and autoimmune diseases, and with presence of anti-C1-INH antibodies has been well documented, and treatment of the underlying condition may result in complete remission of angioedema.

To discuss the clinical evaluation, diagnosis, and treatment outcomes of AAE-C1-INH in the context of the care of 2 patients with recurrent isolated angioedema.

Two patients were followed up prospectively at our clinic. Measurements of C3, C4, C1-INH, and C1q levels were carried out by nephelometry, and the functional activity of C1-INH was determined by a chromogenic assay. Hematological investigation included morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology. Sequencing of the 8 exons and adjacent intronic regions of the SERPING1 gene was performed using the Sanger method.

Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up.

Close follow-up, including detailed clinical history, physical examination, and laboratory tests, of our patients with AAE-C1-INH was essential for the early diagnosis and successful treatment of the lymphoproliferative disease, leading to the resolution of the angioedema attacks.

    Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH)
    DIAGNOSIS

 is a very rare disease. In clinical practice, it may be difficult to differentiate

    AAE-C1-INH
    DIAGNOSIS

 from

    hereditary angioedema due to C1-INH deficiency (HAE-C1-INH)
    DIAGNOSIS

. In both conditions, patients are at an increased risk of

    death
    SYMPTOMS

 from

    asphyxiation
    SYMPTOMS

 due to

    upper airway obstruction
    SYMPTOMS

. The association of

    AAE-C1-INH
    DIAGNOSIS

 with

    lymphoproliferative and autoimmune diseases
    DIAGNOSIS

, and with

    presence of anti-C1-INH antibodies
    BIOCHEMICAL

 has been well documented, and treatment of the underlying condition may result in

    complete remission of angioedema
    SYMPTOMS

.

To discuss the clinical evaluation, diagnosis, and treatment outcomes of

    AAE-C1-INH
    MEDICATION

 in the context of the care of 2 patients with

    recurrent isolated angioedema
    SYMPTOMS

.

Two patients were followed up prospectively at our clinic.

    Measurements of C3, C4, C1-INH, and C1q levels
    BIOCHEMICAL

 were carried out by

    nephelometry
    PARACLINICAL

, and the

    functional activity of C1-INH
    BIOCHEMICAL

 was determined by a

    chromogenic assay
    PARACLINICAL

.

    Hematological investigation
    PARACLINICAL

 included

    morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology
    PARACLINICAL

.

    Sequencing of the 8 exons and adjacent intronic regions of the SERPING1 gene was performed using the Sanger method
    PARACLINICAL

.

Two patients were diagnosed with

    AAE-C1-INH associated with splenic marginal zone lymphoma
    DIAGNOSIS

 during follow-up.

    Close follow-up
    PARACLINICAL

, including

    detailed clinical history
    PARACLINICAL

,

    physical examination
    PARACLINICAL

, and

    laboratory tests
    PARACLINICAL

, of our patients with

    AAE
    DIAGNOSIS

-

    C1-INH
    MEDICATION

 was essential for the early diagnosis and successful treatment of the

    lymphoproliferative disease
    DIAGNOSIS

, leading to the

    resolution of the angioedema attacks
    SYMPTOMS

.

death
asphyxiation
upper airway obstruction
complete remission of angioedema
recurrent isolated angioedema
resolution of the angioedema attacks


Orthognathic Surgery in Hereditary Angioedema With Normal C1 Inhibitor: A Clinical Response to Concentrated C1 Inhibitor Against Angioedema Attack.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by episodes of localized swelling, often of life-threatening severity. HAE due to C1 inhibitor (C1-INH) deficiency is common and is divided into types 1 and 2, but HAE with normal C1-INH is exceedingly rare. Herein, we describe the case of a patient with HAE with normal C1-INH undergoing orthognathic surgery. A 24-year-old woman came to our hospital with a diagnosed jaw deformity and commenced preoperative orthodontic treatment before scheduled orthognathic surgery. During the preoperative period, she experienced mild hoarseness. The hoarseness worsened, and computed tomography revealed mild laryngeal edema. Serum C1-INH, C3, C4, and CH50 levels were normal. Her younger sister had reportedly experienced a similar episode of lip edema previously. These findings supported a diagnosis of HAE with normal C1-INH. She underwent orthognathic surgery in close consultation with a hematologist and anesthesiologist at the age of 33 years. The surgery was completed without complications. She reported throat tightness 4 days after surgery, although her facial swelling was consistent with the procedure performed and was not remarkable. Concentrated C1-INH was administered, and the throat tightness slowly resolved within approximately 1 hour. Twenty-five days after surgery, she was discharged with reduced facial swelling. In the present case, orthognathic surgery was performed successfully in a patient with the exceedingly rare condition of HAE with normal C1-INH, in close consultation with a hematologist and an anesthesiologist. Postoperative throat tightness was successfully treated via the administration of concentrated C1-INH. Concentrated C1-INH administration can be considered in patients with HAE and normal C1-INH who experience angioedemic attack, keeping in mind that it may be slow to take effect.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare autosomal dominant disorder
    GENETICS

 characterized by

    episodes of localized swelling
    SYMPTOMS

, often of

    life-threatening severity
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 due to

    C1 inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 is common and is divided into types 1 and 2, but

    HAE
    DIAGNOSIS

 with

    normal C1-INH
    NEG_FINDINGS

 is exceedingly rare. Herein, we describe the case of a patient with

    HAE
    DIAGNOSIS

 with

    normal C1-INH
    NEG_FINDINGS

 undergoing

    orthognathic surgery
    MEDICATION

. A

    24-year-old
    AGE

    woman
    GENDER

 came to our hospital with a diagnosed

    jaw deformity
    MEDICATION

 and

    commenced preoperative orthodontic treatment
    MEDICATION

 before

    scheduled orthognathic surgery
    MEDICATION

. During the preoperative period,

    she
    GENDER

 experienced

    mild hoarseness
    SYMPTOMS

. The

    hoarseness
    SYMPTOMS

 worsened, and

    computed tomography
    PARACLINICAL

 revealed

    mild laryngeal edema
    SYMPTOMS

.

    Serum C1-INH, C3, C4, and CH50 levels were normal
    NEG_FINDINGS

.

    Her
    GENDER

    younger sister had reportedly experienced a similar episode of lip edema previously
    FAMILY

. These findings supported a diagnosis of

    HAE
    DIAGNOSIS

 with

    normal C1-INH
    NEG_FINDINGS

.

    She
    GENDER

 underwent

    orthognathic surgery
    MEDICATION

 in close consultation with a

    hematologist
    PARACLINICAL

 and

    anesthesiologist
    PARACLINICAL

 at the

    age of 33 years
    AGE

. The

    surgery
    MEDICATION

 was completed

    without complications
    NEG_FINDINGS

.

    She
    GENDER

 reported

    throat tightness 4 days after surgery
    SYMPTOMS

,

    although her facial swelling was consistent with the procedure performed and was not remarkable
    NEG_FINDINGS

.

    Concentrated C1-INH was administered
    MEDICATION

, and the

    throat tightness slowly resolved
    SYMPTOMS

 within approximately 1 hour. Twenty-five days after

    surgery
    MEDICATION

,

    she
    GENDER

 was discharged with

    reduced facial swelling
    SYMPTOMS

. In the present case,

    orthognathic surgery
    MEDICATION

 was performed successfully in a patient with the exceedingly rare condition of

    HAE
    DIAGNOSIS

 with

    normal C1-INH
    NEG_FINDINGS

, in close consultation with a

    hematologist
    PARACLINICAL

 and an

    anesthesiologist
    PARACLINICAL

.

    Postoperative throat tightness
    SYMPTOMS

 was successfully treated via the

    administration of concentrated C1-INH
    MEDICATION

.

    Concentrated C1-INH administration
    MEDICATION

 can be considered in patients with

    HAE
    DIAGNOSIS

 and

    normal C1-INH
    NEG_FINDINGS

 who experience

    angioedemic attack
    SYMPTOMS

, keeping in mind that it may be slow to take effect.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE
HAE

episodes of localized swelling
life-threatening severity
mild hoarseness
hoarseness
mild laryngeal edema
throat tightness 4 days after surgery
throat tightness slowly resolved
reduced facial swelling
Postoperative throat tightness
angioedemic attack


Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema.

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-LRx is a ligand-conjugated antisense oligonucleotide designed for receptor-mediated delivery to hepatocytes. In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKKRx, for 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months. Treatment was accompanied by a reduction in the angioedema attack rate. (Funded by Amsterdam UMC.).

    Hereditary angioedema
    DIAGNOSIS

 is characterized by

    recurrent and unpredictable episodes of subcutaneous and mucosal swelling
    SYMPTOMS

 that can be

    life threatening
    SYMPTOMS

.

    IONIS-PKK-LRx is a ligand-conjugated antisense oligonucleotide
    MEDICATION

 designed for

    receptor-mediated delivery to hepatocytes
    MEDICATION

. In a compassionate-use pilot study, two patients with

    severe bradykinin-mediated angioedema
    DIAGNOSIS

 were initially

    administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKKRx, for 12 to 16 weeks
    MEDICATION

, after which they received

    IONIS-PKK-LRx at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months
    MEDICATION

. Treatment was accompanied by a

    reduction in the angioedema attack rate
    SYMPTOMS

. (Funded by Amsterdam UMC.).

Hereditary angioedema
severe bradykinin-mediated angioedema


Angioedema and Epinephrine Causing a Stress-Induced Cardiomyopathy.

Presentations of angioedema range from mild edema to immediate life-threatening airway involvement. Management is typically straightforward and dependent on the degree of presentation. In our case, a 61-year-old female presented with angioedema requiring immediate intubation. Before admission to the intensive care unit, a screening ECG was obtained that revealed ST segment elevations which redirected our patient to the cardiac catherization lab. Our patient was ultimately diagnosed with a stress-induced cardiomyopathy after initially presenting with ACE-inhibitor induced angioedema.

Presentations of

    angioedema
    DIAGNOSIS

 range from

    mild edema
    SYMPTOMS

 to

    immediate life-threatening airway involvement
    SYMPTOMS

. Management is typically straightforward and dependent on the degree of presentation. In our case, a

    61-year-old
    AGE

    female
    GENDER

 presented with

    angioedema
    DIAGNOSIS

 requiring

    immediate intubation
    MEDICATION

. Before

    admission to the intensive care unit
    MEDICATION

, a

    screening ECG
    PARACLINICAL

 was obtained that revealed

    ST segment elevations
    SYMPTOMS

 which redirected our patient to the

    cardiac catherization lab
    PARACLINICAL

. Our patient was ultimately diagnosed with a

    stress-induced cardiomyopathy
    DIAGNOSIS

 after initially presenting with

    ACE-inhibitor induced angioedema
    MEDICATION

.

angioedema
angioedema
stress-induced cardiomyopathy

immediate intubation
admission to the intensive care unit
ACE-inhibitor induced angioedema


Gastrointestinal manifestations of angioedema: a potential area of misdiagnosis.

Abdominal pain is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of abdominal pain is angioedema of the gastrointestinal tract due to recurrent angioedema without wheals. Abdominal involvement is very common in hereditary angioedema (HAE), but it is also described in acquired angioedema and allergic forms. In patients with HAE, the involvement of gastrointestinal tract with resultant abdominal pain occurs in 43-93% of cases. Attacks can involve the entire gastrointestinal tract, such as the oropharynx, small intestine, colon, liver, or pancreas. Pain is the most common gastrointestinal symptom, and it may occur for many years even without cutaneous or respiratory symptoms. The case report we included in this article emphasizes the importance of accurate evaluation of personal and family history in patients with a long history of acute, severe, and unexplained abdominal pain, and it gives an example of how diagnostic delay may be longer if gastroenterological symptoms are the predominant clinical presentation. Furthermore, sometimes the simultaneous presence of concomitant gastrointestinal disorders and HAE may cause difficulties in differential diagnosis. Gastroenterologists and other physicians should add HAE to their list of potential causes of unexplained abdominal pain. The initiation of appropriate prophylaxis and treatment will prevent needless suffering and useless surgical and medical procedures.

    Abdominal pain
    SYMPTOMS

 is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of

    abdominal pain
    SYMPTOMS

 is

    angioedema of the gastrointestinal tract
    SYMPTOMS

 due to

    recurrent angioedema
    SYMPTOMS

    without wheals
    NEG_FINDINGS

.

    Abdominal involvement
    SYMPTOMS

 is very common in

    hereditary angioedema (HAE)
    DIAGNOSIS

, but it is also described in

    acquired angioedema
    DIAGNOSIS

 and

    allergic forms
    DIAGNOSIS

. In patients with

    HAE
    DIAGNOSIS

, the

    involvement of gastrointestinal tract
    SYMPTOMS

 with resultant

    abdominal pain
    SYMPTOMS

 occurs in 43-93% of cases.

    Attacks can involve the entire gastrointestinal tract, such as the oropharynx, small intestine, colon, liver, or pancreas
    SYMPTOMS

.

    Pain
    SYMPTOMS

 is the most common

    gastrointestinal symptom
    SYMPTOMS

, and it may occur for many years even

    without cutaneous or respiratory symptoms
    NEG_FINDINGS

. The case report we included in this article emphasizes the importance of accurate evaluation of personal and family history in patients with a long history of

    acute, severe, and unexplained abdominal pain
    SYMPTOMS

, and it gives an example of how diagnostic delay may be longer if

    gastroenterological symptoms
    SYMPTOMS

 are the predominant clinical presentation. Furthermore, sometimes the simultaneous presence of

    concomitant gastrointestinal disorders
    SYMPTOMS

 and

    HAE
    DIAGNOSIS

 may cause difficulties in

    differential diagnosis
    PARACLINICAL

.

    Gastroenterologists
    PARACLINICAL

 and other physicians should add

    HAE
    DIAGNOSIS

 to their list of potential causes of

    unexplained abdominal pain
    SYMPTOMS

. The initiation of appropriate prophylaxis and treatment will prevent

    needless suffering
    SYMPTOMS

 and

    useless surgical and medical procedures
    NEG_FINDINGS

.

hereditary angioedema (HAE)
acquired angioedema
allergic forms
HAE
HAE
HAE


Hereditary C1 inhibitor deficiency associated with systemic lupus erythematosus.

Here, we report a family with two children (the elder son and younger daughter) diagnosed with juvenile-onset systemic lupus erythematosus (SLE) and the father diagnosed with hereditary angioedema. Serum C1 inhibitor (C1-INH) levels were low, and clinical exome next-generation sequencing detected a frameshift mutation in the SERPING-1 gene in all three patients. The mother had neither of the clinical phenotypes. The son had cutaneous symptoms, fever and polyarthralgia, along with lupus nephritis, and thus required rituximab therapy as well as mycophenolate mofetil and low-dose steroids to control disease activity. The daughter had a milder disease, with cutaneous manifestation, fever and polyarthralgia, and which was controlled with mycophenolate mofetil, hydroxychloroquine and low-dose steroids. Both children had never experienced angioedema. The father had a long history of self-limiting, non-life-threatening irregular episodes of subcutaneous angioedema and abdomen pain. He was not on any regular medication for these symptoms. We searched the literature for evidence of hereditary C1-INH deficiency associated with monogenic SLE or SLE-like-phenotype.

Here, we report a

    family with two children (the elder son and younger daughter) diagnosed with juvenile-onset systemic lupus erythematosus (SLE)
    FAMILY

 and the

    father diagnosed with hereditary angioedema
    FAMILY

.

    Serum C1 inhibitor (C1-INH) levels were low
    BIOCHEMICAL

, and

    clinical exome next-generation sequencing
    PARACLINICAL

 detected a

    frameshift mutation in the SERPING-1 gene
    GENETICS

 in all three patients. The

    mother had neither of the clinical phenotypes
    FAMILY

. The

    son
    GENDER

 had

    cutaneous symptoms
    SYMPTOMS

,

    fever
    SYMPTOMS

 and

    polyarthralgia
    SYMPTOMS

, along with

    lupus nephritis
    DIAGNOSIS

, and thus required

    rituximab therapy as well as mycophenolate mofetil and low-dose steroids to control disease activity
    MEDICATION

. The

    daughter
    GENDER

 had a milder disease, with

    cutaneous manifestation
    SYMPTOMS

,

    fever
    SYMPTOMS

 and

    polyarthralgia
    SYMPTOMS

, and which was controlled with

    mycophenolate mofetil, hydroxychloroquine and low-dose steroids
    MEDICATION

. Both children had

    never experienced angioedema
    NEG_FINDINGS

. The

    father had a long history of self-limiting, non-life-threatening irregular episodes of subcutaneous angioedema
    FAMILY

 and

    abdomen pain
    SYMPTOMS

.

    He
    GENDER

 was

    not on any regular medication for these symptoms
    NEG_FINDINGS

. We searched the literature for evidence of

    hereditary C1-INH deficiency
    BIOCHEMICAL

 associated with

    monogenic SLE
    DIAGNOSIS

 or

    SLE-like-phenotype
    DIAGNOSIS

.

cutaneous symptoms
fever
polyarthralgia
cutaneous manifestation
fever
polyarthralgia
abdomen pain

lupus nephritis
monogenic SLE
SLE-like-phenotype


Monoclonal gammopathy with significance: case series and literature review.

Monoclonal gammopathy of undetermined significance (MGUS) is considered an asymptomatic precursor of malignant lymphoid disorders. This case series and literature review shows that these monoclonal gammopathies can cause significant morbidity. We describe a patient with angioedema due to acquired C1-esterase inhibitor deficiency, a patient with cryoglobulinemia type II causing skin vasculitis and glomerulonephritis, and a patient with glomerulonephritis and nephrotic syndrome - all caused by a monoclonal gammopathy that can be classified as MGUS. Clinicians should be familiar with these consequences of monoclonal gammopathies. The term MGUS should only be used in patients without organ damage caused by monoclonal gammopathies.

    Monoclonal gammopathy of undetermined significance (MGUS)
    DIAGNOSIS

 is considered an asymptomatic precursor of

    malignant lymphoid disorders
    DIAGNOSIS

. This case series and literature review shows that these

    monoclonal gammopathies
    DIAGNOSIS

 can cause significant morbidity. We describe a patient with

    angioedema
    SYMPTOMS

 due to

    acquired C1-esterase inhibitor deficiency
    BIOCHEMICAL

, a patient with

    cryoglobulinemia type II
    DIAGNOSIS

 causing

    skin vasculitis
    DIAGNOSIS

 and

    glomerulonephritis
    DIAGNOSIS

, and a patient with

    glomerulonephritis
    DIAGNOSIS

 and

    nephrotic syndrome
    DIAGNOSIS

 - all caused by a

    monoclonal gammopathy
    DIAGNOSIS

 that can be classified as

    MGUS
    DIAGNOSIS

. Clinicians should be familiar with these consequences of

    monoclonal gammopathies
    DIAGNOSIS

. The term

    MGUS
    DIAGNOSIS

 should only be used in patients

    without organ damage caused by monoclonal gammopathies
    NEG_FINDINGS

.


Pregnancy-Induced Exacerbation of Hereditary Angioedema in a Multiparous Caucasian Female.

Hereditary angioedema (HAE) manifests due to a deficiency of the C1-esterase inhibitor and can present with life-threatening swelling of multiple body regions such as the face, hands, upper respiratory tract, and intestinal walls. The present case describes the manifestation and symptomatic exacerbation of HAE in a multiparous Caucasian female. Very few trials and cases are available on HAE exacerbations during pregnancy, and our case describes the timeline and treatment in order to add to the clinical awareness of the disease. It is necessary to treat these patients rapidly to avoid unnecessary morbidity and interventions. For the time being, our patient has been appropriately managed with icatibant.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 manifests due to a

    deficiency of the C1-esterase inhibitor
    BIOCHEMICAL

 and can present with

    life-threatening swelling of multiple body regions such as the face, hands, upper respiratory tract, and intestinal walls
    SYMPTOMS

. The present case describes the manifestation and

    symptomatic exacerbation
    SYMPTOMS

 of

    HAE
    DIAGNOSIS

 in a

    multiparous
    AGE

    Caucasian
    ETHNICITY

    female
    GENDER

. Very few trials and cases are available on

    HAE exacerbations
    DIAGNOSIS

 during

    pregnancy
    DIAGNOSIS

, and our case describes the timeline and treatment in order to add to the clinical awareness of the disease. It is necessary to treat these patients rapidly to avoid

    unnecessary morbidity and interventions
    NEG_FINDINGS

. For the time being, our patient has been appropriately managed with

    icatibant
    MEDICATION

.

Hereditary angioedema (HAE)
HAE
HAE exacerbations
pregnancy


Co-occurrence between C1 esterase inhibitor deficiency and autoimmune disease: a systematic literature review.

Hereditary angioedema (HAE) is caused by a SERPING1 gene defect resulting in decreased (Type I) or dysfunctional (Type II) C1 esterase inhibitor (C1-INH). The prevalence of autoimmune diseases (ADs) in patients with HAE appears to be higher than the general population. A systematic literature review was conducted to examine the co-occurrence between HAE and ADs.

PubMed/EMBASE were searched for English-language reviews, case reports, observational studies, retrospective studies, and randomized controlled trials up to 04/15/2018 (04/15/2015-04/15/2018 for EMBASE) that mentioned patients with HAE Type I or II and comorbid ADs. Non-human or in vitro studies and publications of C1-INH deficiency secondary to lymphoproliferative disorders or angiotensin-converting-enzyme inhibitors were excluded.

Of the 2880 records screened, 76 met the eligibility criteria and 155 individual occurrences of co-occurring HAE and AD were mentioned. The most common ADs were systemic lupus erythematosus (30 mentions), thyroid disease (21 mentions), and glomerulonephritis (16 mentions). When ADs were grouped by MedDRA v21.0 High Level Terms, the most common were: Lupus Erythematosus and Associated Conditions, n = 52; Endocrine Autoimmune Disorders, n = 21; Gastrointestinal Inflammatory Conditions, n = 16; Glomerulonephritis and Nephrotic Syndrome, n = 16; Rheumatoid Arthritis and Associated Conditions, n = 11; Eye, Salivary Gland and Connective Tissue Disorders, n = 10; and Immune and Associated Conditions Not Elsewhere Classified, n = 5.

Based on literature reports, systemic lupus erythematosus is the most common AD co-occurring with HAE Type I and II. Cause and effect for co-occurring HAE and AD has not been clinically established but could be related to lack of sufficient C1-INH function.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is caused by a

    SERPING1 gene defect
    GENETICS

 resulting in

    decreased (Type I) or dysfunctional (Type II) C1 esterase inhibitor (C1-INH)
    BIOCHEMICAL

. The prevalence of

    autoimmune diseases (ADs)
    DIAGNOSIS

 in patients with

    HAE
    DIAGNOSIS

 appears to be higher than the general population. A systematic literature review was conducted to examine the

    co-occurrence between HAE and ADs
    DIAGNOSIS

.

PubMed/EMBASE were searched for English-language reviews, case reports, observational studies, retrospective studies, and randomized controlled trials up to 04/15/2018 (04/15/2015-04/15/2018 for EMBASE) that mentioned patients with

    HAE Type I or II
    DIAGNOSIS

 and

    comorbid ADs
    DIAGNOSIS

.

    Non
    NEG_FINDINGS

-human or in vitro studies and publications of

    C1-INH deficiency
    BIOCHEMICAL

 secondary to

    lymphoproliferative disorders
    DIAGNOSIS

 or

    angiotensin-converting-enzyme inhibitors
    NEG_FINDINGS

 were excluded.

Of the 2880 records screened, 76 met the eligibility criteria and 155 individual occurrences of

    co-occurring HAE and AD
    DIAGNOSIS

 were mentioned. The most common

    ADs
    DIAGNOSIS

 were

    systemic lupus erythematosus
    DIAGNOSIS

 (30 mentions),

    thyroid disease
    DIAGNOSIS

 (21 mentions), and

    glomerulonephritis
    DIAGNOSIS

 (16 mentions). When

    ADs
    DIAGNOSIS

 were grouped by MedDRA v21.0 High Level Terms, the most common were:

    Lupus Erythematosus and Associated Conditions
    DIAGNOSIS

, n = 52;

    Endocrine Autoimmune Disorders
    DIAGNOSIS

, n = 21;

    Gastrointestinal Inflammatory Conditions
    DIAGNOSIS

, n = 16;

    Glomerulonephritis and Nephrotic Syndrome
    DIAGNOSIS

, n = 16;

    Rheumatoid Arthritis and Associated Conditions
    DIAGNOSIS

, n = 11;

    Eye, Salivary Gland and Connective Tissue Disorders
    DIAGNOSIS

, n = 10; and

    Immune and Associated Conditions Not Elsewhere Classified
    DIAGNOSIS

, n = 5.

Based on literature reports,

    systemic lupus erythematosus
    DIAGNOSIS

 is the most common

    AD co-occurring with HAE Type I and II
    DIAGNOSIS

. Cause and effect for

    co-occurring HAE and AD
    DIAGNOSIS

 has not been clinically established but could be related to

    lack of sufficient C1-INH function
    BIOCHEMICAL

.


C1-inhibitor Deficiency Induces Myositis-like Symptoms Via the Deposition of the Membrane Attack Complex in the Muscle.

We herein report a 56-year-old Japanese woman who had been diagnosed with hereditary angioedema. She experienced progressing muscle weakness and pain in the upper and lower extremities. Blood tests revealed a marked increase in creatine kinase levels; however, myositis-specific autoantibodies were not detected. Serum C1-inhibitor activity and C4 levels were low. A muscle biopsy showed mild muscle fiber necrosis and C5b-9 deposition in the endomysial capillary vessel walls and sarcolemma, mimicking necrotizing myopathy. These results suggest that C1-inhibitor deficiency induces myositis-like symptoms through the activation of the complement pathway and deposition of the membrane attack complex in the muscles.

We herein report a

    56-year-old
    AGE

    Japanese
    ETHNICITY

    woman
    GENDER

 who had been diagnosed with

    hereditary angioedema
    DIAGNOSIS

.

    She
    GENDER

 experienced

    progressing muscle weakness
    SYMPTOMS

 and

    pain in the upper and lower extremities
    SYMPTOMS

.

    Blood tests
    PARACLINICAL

 revealed a

    marked increase in creatine kinase levels
    BIOCHEMICAL

; however,

    myositis-specific autoantibodies were not detected
    NEG_FINDINGS

.

    Serum C1-inhibitor activity and C4 levels were low
    BIOCHEMICAL

. A

    muscle biopsy
    PARACLINICAL

 showed

    mild muscle fiber necrosis
    MICROSCOPIC

 and

    C5b-9 deposition in the endomysial capillary vessel walls and sarcolemma
    MICROSCOPIC

, mimicking

    necrotizing myopathy
    DIAGNOSIS

. These results suggest that

    C1-inhibitor deficiency
    BIOCHEMICAL

 induces

    myositis-like symptoms
    SYMPTOMS

 through the

    activation of the complement pathway
    BIOCHEMICAL

 and

    deposition of the membrane attack complex in the muscles
    MICROSCOPIC

.

hereditary angioedema
necrotizing myopathy

progressing muscle weakness
pain in the upper and lower extremities
myositis-like symptoms


Ultrasound findings in an abdominal crisis of a patient with hereditary angioedema.

ereditary Angioedema (HAE) is a rare autosomal-dominant disease caused by serum C1 inhibitor deficiency. This deficiency leads to an up-regulation of complement, activating the bradykinin pathway and causing vascular permeability and subsequent mucosal edema. Abdominal angioedema is a less recognized type of angioedema and the clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe one case of abdominal angioedema in a patient with known HAE that were diagnosed by ultrasound.

    ereditary Angioedema (HAE)
    DIAGNOSIS

 is a

    rare autosomal-dominant disease
    GENETICS

 caused by

    serum C1 inhibitor deficiency
    BIOCHEMICAL

. This

    deficiency
    BIOCHEMICAL

 leads to an

    up-regulation of complement, activating the bradykinin pathway
    BIOCHEMICAL

 and causing

    vascular permeability
    SYMPTOMS

 and subsequent

    mucosal edema
    SYMPTOMS

.

    Abdominal angioedema
    DIAGNOSIS

 is a less recognized type of

    angioedema
    DIAGNOSIS

 and the clinical signs may range from

    subtle, diffuse abdominal pain
    SYMPTOMS

 and

    nausea
    SYMPTOMS

, to

    overt peritonitis
    SYMPTOMS

. We describe one case of

    abdominal angioedema
    SYMPTOMS

 in a patient with known

    HAE
    DIAGNOSIS

 that were diagnosed by

    ultrasound
    PARACLINICAL

.

ereditary Angioedema (HAE)
Abdominal angioedema
angioedema
HAE

vascular permeability
mucosal edema
subtle, diffuse abdominal pain
nausea
overt peritonitis
abdominal angioedema


Hereditary angioedema: the challenges of cross-border family investigation and treatment.

Hereditary angioedema (HAE) is a rare genetic disorder characterised by recurrent swellings involving subcutaneous and submucosal tissue that can be potentially life threatening in cases involving the upper airway. In this case report, we present a Syrian refugee family with HAE who have lived in Denmark since 2014. The index patient is an 8-year-old girl diagnosed with HAE after being hospitalised in Denmark with an angioedema attack. Her younger sister and father were diagnosed later, following investigation of the family. Exploring the family history, deaths due to suffocation were described in previous generations and other family members based in Sweden, Germany, Turkey, Saudi Arabia, USA and Syria could also potentially be affected. This highlights the need for a cross-border effort to diagnose and treat this inherited disorder.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic disorder
    GENETICS

 characterised by

    recurrent swellings involving subcutaneous and submucosal tissue
    SYMPTOMS

 that can be potentially life threatening in cases

    involving the upper airway
    SYMPTOMS

. In this case report, we present a

    Syrian
    ETHNICITY

    refugee
    ETHNICITY

 family with

    HAE
    DIAGNOSIS

 who have lived in

    Denmark
    ETHNICITY

 since 2014. The index patient is an

    8-year-old
    AGE

    girl
    GENDER

 diagnosed with

    HAE
    DIAGNOSIS

 after being hospitalised in

    Denmark
    MEDICATION

 with an

    angioedema attack
    SYMPTOMS

.

    Her
    GENDER

    younger sister and father were
    FAMILY

 diagnosed later, following

    investigation of the family
    PARACLINICAL

. Exploring the family history,

    deaths due to suffocation were described in previous generations
    FAMILY

 and other

    family members based in Sweden
    FAMILY

,

    Germany
    ETHNICITY

,

    Turkey
    ETHNICITY

,

    Saudi Arabia
    ETHNICITY

,

    USA
    ETHNICITY

 and

    Syria
    ETHNICITY

    could also potentially be affected
    FAMILY

. This highlights the need for a cross-border effort to diagnose and treat this

    inherited disorder
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
HAE
inherited disorder

Syrian
refugee
Denmark
Germany
Turkey
Saudi Arabia
USA
Syria


Acquired C1-inhibitor deficiency due to splenic marginal zone lymhoma: Case Report.

We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the face and larynx. After thorough biochemical investigations, an acquired deficiency of C1-INH was suspected. To evaluate a potential underlying malignancy, a whole-body FDG-PET/CT was performed and showed solely a marked splenomegaly pointing towards a splenic marginal zone lymphoma, which was confirmed by pathological examination.With this case, we discuss the pathophysiology, diagnosis and management of recurrent acquired angioedema attacks as the first presentation of an underlying lymphoproliferative disease.

We present the case of a

    67-year-old
    AGE

    woman
    GENDER

 who suffered

    recurrent episodes of angioedema of the face and larynx
    SYMPTOMS

. After thorough

    biochemical investigations
    PARACLINICAL

, an

    acquired deficiency of C1-INH
    BIOCHEMICAL

 was suspected. To evaluate a potential underlying

    malignancy
    DIAGNOSIS

, a

    whole-body FDG-PET/CT
    PARACLINICAL

 was performed and showed solely a

    marked splenomegaly
    SYMPTOMS

 pointing towards a

    splenic marginal zone lymphoma
    DIAGNOSIS

, which was confirmed by

    pathological examination
    PARACLINICAL

.With this case, we discuss the pathophysiology, diagnosis and management of

    recurrent acquired angioedema attacks
    SYMPTOMS

 as the first presentation of an underlying

    lymphoproliferative disease
    DIAGNOSIS

.

malignancy
splenic marginal zone lymphoma
lymphoproliferative disease


[Peri-operative management of a pregnant patient with hereditary angioedema submitted to a cesarean-section: case report].

Hereditary angioedema is an autosomal dominant disorder, presenting as sudden and recurring episodes of variable severity of subcutaneous and mucosa edema that may occur spontaneously or in response to triggers. There are three knwon types of hereditary angioedema. The disorder is caused by decrease in the plasma level or change in the functional capacity of C1 inhibitor, with increase in bradykinin and in vascular permeability, and consequent edema. Several measures are required in the perioperative period in order to avoid an acute attack. Prophylaxis should be carried out throughout pregnancy before any surgical procedure, before dental procedures, upon airway handling, on patients with previous episodes of angioedema, and when there are significant changes in volemia. The literature is scarce in regard to the association between hereditary angioedema and pregnancy. We describe a successful case of a pregnant patient with type I hereditary angioedema submitted to a C-section.

    Hereditary angioedema
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

, presenting as

    sudden and recurring episodes of variable severity of subcutaneous and mucosa edema
    SYMPTOMS

 that may occur spontaneously or in response to triggers. There are three knwon types of

    hereditary angioedema
    DIAGNOSIS

. The disorder is caused by

    decrease in the plasma level or change in the functional capacity of C1 inhibitor
    BIOCHEMICAL

, with

    increase in bradykinin and in vascular permeability
    BIOCHEMICAL

, and consequent

    edema
    SYMPTOMS

. Several measures are required in the perioperative period in order to avoid an

    acute attack
    SYMPTOMS

.

    Prophylaxis
    MEDICATION

 should be carried out throughout

    pregnancy
    MEDICATION

 before

    any surgical procedure
    MEDICATION

,

    before dental procedures
    MEDICATION

,

    upon airway handling
    MEDICATION

, on patients with

    previous episodes of angioedema
    SYMPTOMS

, and when there are

    significant changes in volemia
    SYMPTOMS

. The literature is scarce in regard to the association between

    hereditary angioedema
    DIAGNOSIS

 and

    pregnancy
    DIAGNOSIS

. We describe a successful case of a

    pregnant
    AGE

 patient with

    type I hereditary angioedema
    DIAGNOSIS

    submitted to a C-section
    MEDICATION

.

Hereditary angioedema
hereditary angioedema
hereditary angioedema
pregnancy
type I hereditary angioedema

Prophylaxis
pregnancy
any surgical procedure
before dental procedures
upon airway handling
submitted to a C-section


Anaesthetic Approach for Patient with Hereditary Angioedema.

Hereditary Angioedema (HEA), a disease caused by a mutation in the gene that encodes for the production of the fraction C1 in the complement (C1-INH), is a rare pathology (1/50.000) that causes swelling of the skin and submucosa in various organs, either naturally triggered or provoked by physical and psychological traumas, infections, or by the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEIs). Surgical trauma may spur the HEA crisis, leading to complications such as the swelling of the respiratory tracts and hemodynamic instability. Thus, the pre-surgical approach to HEA patients requires a specific plan that ensures short term prophylaxis, careful intra-operative management, rescue therapy and intensive post-surgery care. We present a report on a video-laparoscopic cholecystectomy approach for a 28-year-old woman diagnosed with asthma and HEA with symptomatic choledocholithiasis. We opted for short-term prophylaxis and immunology with the intravenous application of C1-INH. Ultrasonography imaging showed arterial wall oedema, which could correspond to a manifestation of C1-INH deficiency in the wall of the manipulated arteries during ultrasonography-guided puncture. Once the patient recovered consciousness, she was transferred to the intensive care unit and was discharged on the 6th day of hospitalisation.

    Hereditary Angioedema (HEA)
    DIAGNOSIS

, a disease caused by a

    mutation in the gene that encodes for
    GENETICS

 the

    production of the fraction C1 in the complement (C1-INH)
    BIOCHEMICAL

, is a rare pathology (1/50.000) that causes

    swelling of the skin and submucosa in various organs
    SYMPTOMS

, either naturally triggered or provoked by

    physical and psychological traumas
    SYMPTOMS

,

    infections
    SYMPTOMS

, or by the use of

    nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEIs)
    MEDICATION

.

    Surgical trauma
    MEDICATION

 may spur the

    HEA crisis
    DIAGNOSIS

, leading to complications such as the

    swelling of the respiratory tracts
    SYMPTOMS

 and

    hemodynamic instability
    SYMPTOMS

. Thus, the

    pre-surgical
    MEDICATION

 approach to

    HEA
    DIAGNOSIS

 patients requires a specific plan that ensures

    short term prophylaxis
    MEDICATION

,

    careful intra-operative management
    MEDICATION

,

    rescue therapy
    MEDICATION

 and

    intensive post-surgery care
    MEDICATION

. We present a report on a

    video-laparoscopic cholecystectomy approach
    MEDICATION

 for a

    28-year-old
    AGE

    woman
    GENDER

 diagnosed with

    asthma
    DIAGNOSIS

 and

    HEA
    DIAGNOSIS

 with

    symptomatic choledocholithiasis
    DIAGNOSIS

. We opted for

    short-term prophylaxis
    MEDICATION

 and

    immunology with the intravenous application of C1-INH
    MEDICATION

.

    Ultrasonography imaging
    PARACLINICAL

 showed

    arterial wall oedema
    SYMPTOMS

, which could correspond to a manifestation of

    C1-INH deficiency in the wall of the manipulated arteries
    BIOCHEMICAL

 during

    ultrasonography-guided puncture
    PARACLINICAL

. Once the patient

    recovered consciousness
    SYMPTOMS

,

    she
    GENDER

 was

    transferred to the intensive care unit
    MEDICATION

 and was discharged on the 6th day

    of hospitalisation
    MEDICATION

.

Hereditary Angioedema (HEA)
HEA crisis
HEA
asthma
HEA
symptomatic choledocholithiasis


Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. Methods: We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Background:

    Hereditary prekallikrein (Fletcher factor) deficiency
    BIOCHEMICAL

 is a rare condition characterized by a

    prolonged activated partial thromboplastin time
    BIOCHEMICAL

.

    Inhibitors of plasma kallikrein
    MEDICATION

 have recently been approved for prophylaxis of

    hereditary angioedema
    DIAGNOSIS

 and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of

    long-term inhibition of this pathway
    MEDICATION

 by reviewing reported comorbidities in patients with

    hereditary prekallikrein deficiency
    BIOCHEMICAL

. Methods: We searched several medical literature databases for publications that reported data from patients with

    hereditary prekallikrein deficiency (<10% of normal
    BIOCHEMICAL

 and/or

    shortening of activated partial thromboplastin time on increased incubation time)
    BIOCHEMICAL

. Data reporting of

    cardiovascular
    SYMPTOMS

,

    bleeding
    SYMPTOMS

, and

    autoimmune-related diseases
    DIAGNOSIS

 were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with

    prekallikrein deficiency
    BIOCHEMICAL

) were included. Among 53 identified patients with

    prekallikrein deficiency
    BIOCHEMICAL

, 25 were explicitly defined as

    asymptomatic
    NEG_FINDINGS

, with

    no comorbidities
    NEG_FINDINGS

 mentioned in another three cases. Another 16 of the 53 patients were described as having undergone

    surgery or dental extractions
    MEDICATION

 with

    no complications
    NEG_FINDINGS

.

    Cardiovascular comorbidities
    SYMPTOMS

 were reported in 19 patients, mainly

    hypertension
    SYMPTOMS

 (9 patients) and

    cerebrovascular ischemia or stroke
    SYMPTOMS

 (5 patients).

    Excessive bleeding episodes after surgery
    SYMPTOMS

 were reported in four patients.

    Autoimmune-related diseases
    DIAGNOSIS

 were reported for three patients (two with

    Graves disease
    DIAGNOSIS

 and one with

    systemic lupus erythematosus
    DIAGNOSIS

). Conclusion: This review identified patients with

    hereditary prekallikrein deficiency
    BIOCHEMICAL

 who reported a spectrum of health outcomes from

    asymptomatic
    NEG_FINDINGS

 to infrequent reports of

    cardiovascular, bleeding, and autoimmune comorbidities
    SYMPTOMS

. The majority of the reports did

    not indicate any association between prekallikrein deficiency
    NEG_FINDINGS

    and comorbidities
    NEG_FINDINGS

; however, additional observation is required to confirm the long-term safety of

    plasma kallikrein inhibition
    MEDICATION

.

Inhibitors of plasma kallikrein
long-term inhibition of this pathway
surgery or dental extractions
plasma kallikrein inhibition

hereditary angioedema
autoimmune-related diseases
Autoimmune-related diseases
Graves disease
systemic lupus erythematosus


C1 Esterase Inhibitor for Ace-Inhibitor Angioedema: A Case Series and Literature Review.

Angiotensin-converting enzyme (ACE) inhibitors are a commonly prescribed and effective medication to treat hypertension. Although generally well tolerated, about 1% of patients will experience angioedema, a potentially life-threatening adverse drug reaction. This reaction is thought to be mediated via a buildup of bradykinin and does not typically respond to epinephrine, corticosteroids, or antihistamines. Alternative treatment strategies have been investigated, the bulk of which surround the use of therapies approved for hereditary angioedema.

Utilization of C1 esterase inhibitors at our institution was reviewed between 2016 and 2018 for treatment of ACE inhibitor-induced angioedema. We describe the clinical course of case series, along with a review of current literature.

Utilization of C1 esterase inhibitors for treating ACE inhibitor-induced angioedema is an uncommon therapy and has limited efficacy in our case series. Treatment did not result in rapid improvement of swelling, prevention of intubation, or prevention of intensive care unit admission.

Based on our case series, C1 esterase therapy should not be utilized routinely for ACE inhibitor-induced angioedema and is not expected to prevent intubation in severe cases.

    Angiotensin-converting enzyme (ACE) inhibitors
    MEDICATION

 are a commonly prescribed and effective medication to treat

    hypertension
    DIAGNOSIS

. Although generally well tolerated, about 1% of patients will experience

    angioedema
    DIAGNOSIS

, a

    potentially life-threatening adverse drug reaction
    SYMPTOMS

. This reaction is thought to be mediated via a

    buildup of bradykinin
    BIOCHEMICAL

 and does

    not typically respond to epinephrine, corticosteroids, or antihistamines
    NEG_FINDINGS

. Alternative treatment strategies have been investigated, the bulk of which surround the use of therapies approved for

    hereditary angioedema
    DIAGNOSIS

.

    Utilization of C1 esterase inhibitors
    MEDICATION

 at our institution was reviewed between 2016 and 2018 for treatment of

    ACE inhibitor-induced angioedema
    DIAGNOSIS

. We describe the clinical course of case series, along with a review of current literature.

    Utilization of C1 esterase inhibitors
    MEDICATION

 for treating

    ACE inhibitor-induced angioedema
    DIAGNOSIS

 is an uncommon therapy and has limited efficacy in our case series.

    Treatment did not result in rapid improvement of swelling
    NEG_FINDINGS

,

    prevention of intubation
    NEG_FINDINGS

, or

    prevention of intensive care unit admission
    NEG_FINDINGS

.

Based on our case series,

    C1 esterase therapy
    MEDICATION

 should not be utilized routinely for

    ACE inhibitor-induced angioedema
    NEG_FINDINGS

 and is

    not expected to prevent intubation
    NEG_FINDINGS

 in severe cases.

hypertension
angioedema
hereditary angioedema
ACE inhibitor-induced angioedema
ACE inhibitor-induced angioedema