A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.

Anticoagulants are commonly associated with hemorrhagic complications. However, rare hypersensitivity drug reactions associated with direct oral anticoagulants (DOACs) in form of cutaneous reactions such as urticaria as well as angioedema can have significant burden owing to increase in morbidity and mortality. Angioedema can be allergic, hereditary or idiopathic and can occur in isolation, in combination with urticaria as contributing component of anaphylaxis. With increase in the use of DOACs over warfarin as choice of anticoagulant in the treatment of atrial fibrillation (AF) as well as venous thromboembolism (VTE), recent post marketing surveillance has identified several reports of adverse drug reactions. This case report describes the clinical course of patient being treated for VTE, who experienced rivaroxaban-induced urticaria and angioedema. We further provide evidence for cross-reactivity to dabigatran manifested as significant cutaneous reaction. Patient was transitioned to warfarin with enoxaparin bridge and tolerated it well without any complications.

    Anticoagulants
    MEDICATION

 are commonly associated with

    hemorrhagic complications
    SYMPTOMS

. However, rare

    hypersensitivity drug reactions associated with direct oral anticoagulants (DOACs)
    SYMPTOMS

 in form of

    cutaneous reactions
    SYMPTOMS

 such as

    urticaria
    DIAGNOSIS

 as well as

    angioedema
    SYMPTOMS

 can have significant burden owing to increase in morbidity and mortality.

    Angioedema
    DIAGNOSIS

 can be allergic,

    hereditary
    DIAGNOSIS

 or

    idiopathic
    DIAGNOSIS

 and can occur in isolation, in combination with

    urticaria
    DIAGNOSIS

 as contributing component of

    anaphylaxis
    DIAGNOSIS

. With increase in the use of

    DOACs
    MEDICATION

 over

    warfarin
    MEDICATION

 as choice of

    anticoagulant
    MEDICATION

 in the treatment of

    atrial fibrillation (AF)
    DIAGNOSIS

 as well as

    venous thromboembolism (VTE)
    DIAGNOSIS

, recent post marketing surveillance has identified several reports of

    adverse drug reactions
    SYMPTOMS

. This case report describes the clinical course of patient being treated for

    VTE
    DIAGNOSIS

, who experienced

    rivaroxaban-induced urticaria
    DIAGNOSIS

 and

    angioedema
    SYMPTOMS

. We further provide evidence for

    cross-reactivity to dabigatran
    SYMPTOMS

 manifested as

    significant cutaneous reaction
    SYMPTOMS

. Patient was

    transitioned to warfarin with enoxaparin bridge
    MEDICATION

 and tolerated it well

    without any complications
    NEG_FINDINGS

.

urticaria
Angioedema
hereditary
idiopathic
urticaria
anaphylaxis
atrial fibrillation (AF)
venous thromboembolism (VTE)
VTE
rivaroxaban-induced urticaria


Recurrent swelling and pain in the abdomen and joints in a patient with hereditary angioedema and Ehlers-Danlos syndrome.

A 23-year-old woman was referred to the allergy and immunology clinic for recurrent abdominal, cutaneous and joint swelling and pain with a history of mucosal infections since childhood. Her history and clinical findings were suggestive of two rare and complex disorders, hereditary angioedema (HAE) and Ehlers-Danlos syndrome (EDS). Her recurrent episodes of abdominal and joint pain were initially misattributed to more common diagnoses such as esophagitis, depression and chronic pain syndrome. However, the coexistence of HAE and EDS likely contributed to a delay in diagnoses as the combination of these two rare but overlapping disorders is less understood by physicians. She had persistently low levels of C4 and C1-esterase inhibitor (C1-INH) with low to low-normal C1-esterase function, normal C1Q and no C1Q antibodies. In the setting of recurrent abdominal pain with cutaneous swelling, this supported the diagnosis of HAE type I. The increase in joint extensibility with recurrent shoulder subluxations since childhood was a manifestation of EDS. Although no known genetic mutations were identified for EDS, her diagnosis was confirmed by a geneticist based on her clinical phenotype. Before the diagnosis of HAE and EDS, our patient had at least 100 visits/year to the emergency department/hospitalisations for these recurrent symptoms. After starting on C1-INH replacement therapy, the frequency has decreased 10-fold. She also noted a 70% improvement in her quality of life. Familiarity with these rare disorders will assist healthcare providers in recognising HAE and EDS and include them as part of their differential diagnoses. Early diagnosis is important for a patient's well-being as both these chronic disorders have been associated with poor quality of life. Additionally, proper diagnoses will reduce healthcare costs by preventing unnecessary procedures due to misdiagnoses. Proper treatment will help to decrease hospitalisations and avoidance of life-threatening consequences (such as asphyxiation from fatal laryngeal attacks of HAE and rupture of aneurysms in EDS).

A

    23-year-old
    AGE

    woman
    GENDER

 was referred to the

    allergy and immunology
    PARACLINICAL

 clinic for

    recurrent abdominal, cutaneous and joint swelling and pain
    SYMPTOMS

 with a

    history of mucosal infections
    SYMPTOMS

 since

    childhood
    AGE

.

    Her
    GENDER

 history and clinical findings were suggestive of two rare and complex disorders,

    hereditary angioedema (HAE)
    DIAGNOSIS

 and

    Ehlers-Danlos syndrome (EDS)
    DIAGNOSIS

.

    Her
    GENDER

    recurrent episodes of abdominal and joint pain
    SYMPTOMS

 were

    initially misattributed to more common diagnoses such as esophagitis, depression
    NEG_FINDINGS

 and

    chronic pain syndrome
    DIAGNOSIS

. However, the

    coexistence of HAE and EDS
    DIAGNOSIS

 likely contributed to a delay in diagnoses as the combination of these two rare but overlapping disorders is less understood by physicians.

    She
    GENDER

 had

    persistently low levels of C4 and C1-esterase inhibitor (C1-INH) with low to low-normal C1-esterase function
    BIOCHEMICAL

,

    normal C1Q
    NEG_FINDINGS

 and

    no C1Q antibodies
    NEG_FINDINGS

. In the setting of

    recurrent abdominal pain
    SYMPTOMS

 with

    cutaneous swelling
    SYMPTOMS

, this supported the diagnosis of HAE type I. The

    increase in joint extensibility
    SYMPTOMS

 with

    recurrent shoulder subluxations
    SYMPTOMS

 since

    childhood
    AGE

 was a manifestation of

    EDS
    DIAGNOSIS

. Although

    no known genetic mutations were identified for EDS
    NEG_FINDINGS

,

    her
    GENDER

 diagnosis was confirmed by a

    geneticist
    PARACLINICAL

 based on

    her
    GENDER

 clinical phenotype. Before the diagnosis of

    HAE
    DIAGNOSIS

 and

    EDS
    DIAGNOSIS

, our patient had at least 100 visits/year to the emergency department

    /hospitalisations
    MEDICATION

 for these

    recurrent symptoms
    SYMPTOMS

. After starting on

    C1-INH replacement therapy
    MEDICATION

, the frequency has decreased 10-fold.

    She
    GENDER

 also noted a

    70% improvement in her quality of life
    SYMPTOMS

. Familiarity with these

    rare disorders
    DIAGNOSIS

 will assist healthcare providers in recognising

    HAE
    DIAGNOSIS

 and

    EDS
    DIAGNOSIS

 and include them as part of their

    differential diagnoses
    PARACLINICAL

. Early diagnosis is important for a patient's well-being as both these

    chronic disorders
    DIAGNOSIS

 have been associated with

    poor quality of life
    SYMPTOMS

. Additionally, proper diagnoses will reduce healthcare costs by preventing

    unnecessary procedures due to misdiagnoses
    NEG_FINDINGS

. Proper treatment will help to decrease hospitalisations and avoidance of

    life-threatening consequences (such as asphyxiation from fatal laryngeal attacks of HAE
    SYMPTOMS

 and

    rupture of aneurysms in EDS
    SYMPTOMS

).

hereditary angioedema (HAE)
Ehlers-Danlos syndrome (EDS)
chronic pain syndrome
coexistence of HAE and EDS
EDS
HAE
EDS
rare disorders
HAE
EDS
chronic disorders

/hospitalisations
C1-INH replacement therapy


Hereditary angio-oedema as a rare cause of small-bowel obstruction.

A 52-year-old man with known hereditary angio-oedema (HAE) presented with a 2-day history of progressive severe abdominal pain, distension, nausea, vomiting and constipation. CT of his abdomen and pelvis showed small-bowel obstruction and ascites. HAE is a rare autosomal dominant disorder caused by a C1 esterase deficiency and involves episodic oedema of subcutaneous and mucosal tissues. It commonly affects the face and limbs, causing deformity; the respiratory tract, causing life-threatening laryngeal swelling; and the gastrointestinal tract, causing small-bowel obstruction. An infusion of a C1 esterase inhibitor was given to the patient. His symptoms resolved within 6 hours, and a repeat CT showed complete resolution 24 hours later. Small-bowel obstruction in HAE is often misdiagnosed, leading to ineffective treatment and unnecessary surgery. Therefore, this should be suspected in patients with HAE presenting with an acute abdomen, and clinicians should understand the unique treatment required.

A

    52-year-old
    AGE

    man
    GENDER

 with known

    hereditary angio-oedema (HAE)
    DIAGNOSIS

 presented with a 2-day history of

    progressive severe abdominal pain
    SYMPTOMS

,

    distension
    SYMPTOMS

,

    nausea
    SYMPTOMS

,

    vomiting
    SYMPTOMS

 and

    constipation
    SYMPTOMS

.

    CT of his abdomen and pelvis
    PARACLINICAL

 showed

    small-bowel obstruction
    SYMPTOMS

 and

    ascites
    SYMPTOMS

.

    HAE
    DIAGNOSIS

 is a

    rare autosomal dominant disorder
    GENETICS

 caused by a

    C1 esterase deficiency
    BIOCHEMICAL

 and involves

    episodic oedema of subcutaneous and mucosal tissues
    SYMPTOMS

. It commonly

    affects the face and limbs
    SYMPTOMS

, causing

    deformity; the respiratory tract
    SYMPTOMS

, causing

    life-threatening laryngeal swelling
    SYMPTOMS

; and the

    gastrointestinal tract
    SYMPTOMS

, causing

    small-bowel obstruction
    SYMPTOMS

. An

    infusion of a C1 esterase inhibitor
    MEDICATION

 was given to the patient. His

    symptoms resolved within 6 hours
    SYMPTOMS

, and a

    repeat CT
    PARACLINICAL

 showed

    complete resolution
    SYMPTOMS

 24 hours later.

    Small-bowel obstruction
    SYMPTOMS

 in

    HAE
    DIAGNOSIS

 is often

    misdiagnosed
    NEG_FINDINGS

, leading to

    ineffective treatment and unnecessary surgery
    NEG_FINDINGS

. Therefore, this should be suspected in patients with

    HAE
    DIAGNOSIS

 presenting with an

    acute abdomen
    SYMPTOMS

, and clinicians should understand the unique treatment required.

hereditary angio-oedema (HAE)
HAE
HAE
HAE


Self-administration of icatibant in acute attacks of Type I hereditary angioedema: A case report and review of hereditary angioedema.

Hereditary angioedema (HAE) is a rare group of genetic disease characterized by non-itchy swelling of subcutaneous and submucosal tissues of the extremities, genitalia, gastrointestinal tract, and upper airways, which can be life threatening. Moreover, unpredictability and recurrence of HAE attacks significantly affect patients' quality of life. Short- and long-term prophylaxis is used to decrease the severity and frequency of attacks, but during severe or potentially severe acute episodes, treatment with C1-INH replacement or icatibant is mandatory. Icatibant is a selective bradykinin B2 receptor antagonist that has been licensed for self-administration at home, resulting in earlier treatment of the attack and quicker recovery, less emergency admittance with a significant improvement of patients' quality of life, and decrease of health care costs. The authors present a case of a young woman, affected by Type I HAE, who has been successfully treated with icatibant on demand at home, resulting in reduction of emergency admissions and improvement of quality of life. The authors also review the different types HAE, their clinical aspects, diagnosis, and management.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare group of genetic disease
    DIAGNOSIS

 characterized by

    non-itchy swelling of subcutaneous and submucosal tissues of the extremities, genitalia, gastrointestinal tract, and upper airways
    SYMPTOMS

, which can be

    life threatening
    SYMPTOMS

. Moreover,

    unpredictability
    SYMPTOMS

 and

    recurrence of HAE attacks
    SYMPTOMS

 significantly affect patients' quality of life.

    Short- and long-term prophylaxis
    MEDICATION

 is used to decrease the severity and frequency of attacks, but during

    severe or potentially severe acute episodes
    SYMPTOMS

,

    treatment with C1-INH replacement or icatibant
    MEDICATION

 is mandatory.

    Icatibant is a selective bradykinin B2 receptor antagonist
    MEDICATION

 that has been licensed for

    self-administration at home
    MEDICATION

, resulting in

    earlier treatment of the attack
    MEDICATION

 and

    quicker recovery
    SYMPTOMS

,

    less emergency admittance
    MEDICATION

 with a significant improvement of patients'

    quality of life
    SYMPTOMS

, and decrease of health care costs. The authors present a case of a

    young
    AGE

    woman
    GENDER

, affected by

    Type I HAE
    DIAGNOSIS

, who has been successfully treated with

    icatibant
    MEDICATION

 on demand at home, resulting in

    reduction of emergency admissions
    MEDICATION

 and

    improvement of quality of life
    SYMPTOMS

. The authors also review the different types

    HAE
    DIAGNOSIS

, their clinical aspects, diagnosis, and management.

Hereditary angioedema (HAE)
rare group of genetic disease
Type I HAE
HAE


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

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.

We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency.

We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted.

Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. 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 onewith systemic lupus erythematosus).

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.

    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.

We attempted to conservatively assess the impact of

    long-term inhibition of this pathway
    MEDICATION

 by reviewing reportedcomorbidities in patients with

    hereditary prekallikrein deficiency
    BIOCHEMICAL

.

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

    hereditaryprekallikrein deficiency (<10% of normal
    BIOCHEMICAL

 and/or

    shortening of activated partial thromboplastin time on increased incubationtime
    BIOCHEMICAL

    )
    BIOCHEMICAL

. Data reporting of

    cardiovascular
    DIAGNOSIS

,

    bleeding
    DIAGNOSIS

, and

    autoimmune-related diseases
    DIAGNOSIS

 were extracted.

Of 1966 publications screened, 45 publications (which represented 53 patients with

    prekallikrein deficiency
    BIOCHEMICAL

) wereincluded. 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 onewith

    systemic lupus erythematosus
    DIAGNOSIS

).

This review identified patients with

    hereditary prekallikrein deficiency
    BIOCHEMICAL

 who reported a spectrum of health outcomes from

    asymptomatic
    SYMPTOMS

 to

    infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities
    SYMPTOMS

. The majority of the reports did not indicate any association between

    prekallikrein deficiency
    BIOCHEMICAL

    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
cardiovascular
bleeding
autoimmune-related diseases
Autoimmune-related diseases
Graves disease
systemic lupus erythematosus

asymptomatic
no comorbidities
no complications
and comorbidities


[Postoperative angioedema induced by angiotensin-converting enzyme inhibitor: case report].

Angioedema is a potentially fatal condition that may occur at any time in the perioperative period. It may result from histamine release, hypersensitivity reaction to drugs, or be triggered by bradykinin, in non-allergic reactions of hereditary or acquired etiology. The aim of this report is to report a case of angioedema in the early postoperative period in a patient on antihypertensive medication involving angiotensin-converting enzyme inhibitors.

A 67-year-old male, Afro-descendant, hypertensive, and taken enalapril maleate underwent orthopedic shoulder surgery under general anesthesia combined with brachial plexus block. The procedure lasted 3hours uneventfully. After discharge from the post-anesthesia care unit, the patient presented with angioedema and severe airway impairment. Tracheal intubation was attempted but it was impossible due to edema affecting the lips, tongue, and oropharyngeal region Emergency cricothyroidotomy was performed. The onset of angioedema had no causal relationship with the administration of any medication; there were no cutaneous manifestations and also not response to therapy for hypersensitivity reaction to drugs, such as antihistamines, corticoid, and adrenaline. It was considered to be mediated by bradykinin, as the patient had already had two similar episodes and was on regular medication (enalapril). The evolution was satisfactory.

Angioedema is a potentially fatal condition when it affects the airway, and should be recognized by anesthesiologists and physicians working in the emergency departments.

    Angioedema
    DIAGNOSIS

 is a potentially fatal condition that may occur at any time in the perioperative period. It may result from

    histamine release
    BIOCHEMICAL

,

    hypersensitivity reaction to drugs
    SYMPTOMS

, or be triggered by

    bradykinin
    SYMPTOMS

, in

    non-allergic reactions of hereditary or acquired etiology
    NEG_FINDINGS

. The aim of this report is to report a case of

    angioedema
    DIAGNOSIS

 in the early postoperative period in a patient on

    antihypertensive medication involving angiotensin-converting enzyme inhibitors
    MEDICATION

.

A

    67-year-old
    AGE

    male
    GENDER

,

    Afro-descendant
    ETHNICITY

,

    hypertensive
    SYMPTOMS

, and

    taken enalapril maleate
    MEDICATION

 underwent

    orthopedic shoulder surgery
    MEDICATION

 under

    general anesthesia combined with brachial plexus block
    MEDICATION

. The procedure lasted 3hours uneventfully. After

    discharge from the post-anesthesia care unit
    MEDICATION

, the patient presented with

    angioedema
    SYMPTOMS

 and

    severe airway impairment
    SYMPTOMS

.

    Tracheal intubation
    MEDICATION

 was attempted but

    it was impossible
    NEG_FINDINGS

 due to

    edema affecting the lips, tongue, and oropharyngeal region
    SYMPTOMS

 Emergency

    cricothyroidotomy
    MEDICATION

 was performed. The onset of

    angioedema
    SYMPTOMS

 had

    no causal relationship with the administration of any medication
    NEG_FINDINGS

; there were

    no cutaneous manifestations
    NEG_FINDINGS

 and also

    not response to therapy for hypersensitivity reaction to drugs, such as antihistamines, corticoid, and adrenaline
    NEG_FINDINGS

. It was considered to be mediated by

    bradykinin
    BIOCHEMICAL

, as the patient had already had

    two similar episodes
    SYMPTOMS

 and was on

    regular medication (enalapril)
    MEDICATION

. The evolution was satisfactory.

    Angioedema
    DIAGNOSIS

 is a potentially fatal condition when it

    affects the airway
    SYMPTOMS

, and should be recognized by

    anesthesiologists
    PARACLINICAL

 and physicians working in the emergency departments.


An 82-year-old man with recurrent angioedema.

Angioedema is a potentially life-threatening swelling condition that can occur either in isolation or in the context of other syndromes, e.g., anaphylaxis. Angioedema is typically asymmetric, lasts for hours to days, is not gravity dependent, and is often nonpitting. Recurrent angioedema is typically associated with histaminergic and bradykinin-mediated causes, some of which can indicate underlying etiologies with high morbidity or mortality. The differential diagnosis for acute angioedema can include anaphylaxis, chronic urticaria with angioedema, medications such as angiotensin-converting-enzyme inhibitors, hereditary C1 esterase inhibitor defects, and acquired defects; however, the cause is often idiopathic, and effective therapy can be elusive. In this article, we described a unique etiology of a case of isolated recurrent angioedema that improved when the possible underlying cause was successfully treated.

    Angioedema
    DIAGNOSIS

 is a potentially

    life-threatening swelling condition
    SYMPTOMS

 that can occur either in isolation or in the context of other syndromes, e.g.,

    anaphylaxis
    DIAGNOSIS

.

    Angioedema
    SYMPTOMS

 is typically

    asymmetric
    SYMPTOMS

,

    lasts for hours to days
    SYMPTOMS

, is

    not gravity dependent
    NEG_FINDINGS

, and is often

    nonpitting
    SYMPTOMS

.

    Recurrent angioedema
    SYMPTOMS

 is typically associated with

    histaminergic and bradykinin-mediated causes
    SYMPTOMS

, some of which can indicate underlying etiologies with high morbidity or mortality. The

    differential diagnosis
    PARACLINICAL

 for

    acute angioedema
    DIAGNOSIS

 can include

    anaphylaxis
    DIAGNOSIS

,

    chronic urticaria with angioedema
    DIAGNOSIS

,

    medications such as angiotensin-converting-enzyme inhibitors
    MEDICATION

,

    hereditary C1 esterase inhibitor defects
    GENETICS

, and

    acquired defects
    GENETICS

; however, the cause is often

    idiopathic
    NEG_FINDINGS

, and effective therapy can be elusive. In this article, we described a unique etiology of a case of

    isolated recurrent angioedema
    SYMPTOMS

 that improved when the possible underlying cause was successfully treated.

Angioedema
anaphylaxis
acute angioedema
anaphylaxis
chronic urticaria with angioedema


Acquired complement C1 esterase inhibitor deficiency in a patient with a rare SERPING1 variant with unknown significance.

Angioedema (AE) is caused by a wide range of diseases and pharmaceuticals; it can become life-threatening when located to the airways. Patients with deficiency or malfunction of complement C1 esterase inhibitor (hereditary or acquired) experience recurrent AE due to an accumulation of the vasoactive mediator bradykinin (BK). Complement C1 inhibitor normally decreases BK production, so a reduced function hereof causes increased levels. The diagnosis of hereditary or acquired AE can be difficult due to similarities to allergic reactions (swelling, abdominal pain, rash). We describe a 35-year-old man presenting with upper-airway AE progressing rapidly and promptly required cricothyroidotomy. Complement and autoantibody screening together with sequencing of SERPING1 were performed and gave the diagnosis of acquired complement C1 esterase inhibitor deficiency. The patient is unusual to have this disease before the age of 40 years. No associated comorbidities were found. It is important to know that antiallergic medication is not effective in BK-mediated AE.

    Angioedema (AE)
    DIAGNOSIS

 is caused by a wide range of diseases and pharmaceuticals; it can become

    life-threatening
    SYMPTOMS

 when located to the airways. Patients with

    deficiency or malfunction of complement C1 esterase inhibitor
    BIOCHEMICAL

 (

    hereditary
    GENETICS

 or acquired) experience

    recurrent AE
    SYMPTOMS

 due to an

    accumulation of the vasoactive mediator bradykinin (BK)
    BIOCHEMICAL

.

    Complement C1 inhibitor normally decreases BK production
    BIOCHEMICAL

, so a

    reduced function hereof
    BIOCHEMICAL

 causes

    increased levels
    BIOCHEMICAL

. The diagnosis of

    hereditary or acquired AE
    DIAGNOSIS

 can be difficult due to

    similarities to allergic reactions (swelling, abdominal pain, rash)
    SYMPTOMS

. We describe a

    35-year-old
    AGE

    man
    GENDER

 presenting with

    upper-airway AE
    SYMPTOMS

 progressing rapidly and promptly required

    cricothyroidotomy
    MEDICATION

.

    Complement and autoantibody screening
    PARACLINICAL

 together with

    sequencing of SERPING1
    PARACLINICAL

 were performed and gave the diagnosis of

    acquired complement C1 esterase inhibitor deficiency
    BIOCHEMICAL

. The patient is unusual to have this disease

    before the age of 40 years
    AGE

.

    No associated comorbidities
    NEG_FINDINGS

 were found. It is important to know that

    antiallergic medication is not effective
    NEG_FINDINGS

 in

    BK-mediated AE
    DIAGNOSIS

.

Angioedema (AE)
hereditary or acquired AE
BK-mediated AE


[Marginal Féréol-Besnier erythema: rare manifestation during acute articular rhumatism].

This study reports the case of a 3-year old female child with a 1-year history of rash manifesting as discoid plaques with pink, non-itchy, rounded and oval, polycyclic, confluent macular areas measuring 1-3 cm in diameter, with central clearing evolving in stages, with repeated regression and reappearance. The child was admitted to the Emergency Department with respiratory distress, fever and aggravation of pre-existing skin lesions becoming diffuse. Mitral holosystolic murmur with an intensity of grade 4/6 was recorded by cardiac auscultation. Cardiac ultrasound showed acute massive mitral insufficiency with valvular vegetations. Laboratory tests showed inflammation with a CRP level of 300 mg/l and a sedimentation rate of 60 mm in the first hour and ASLO levels were very high (1600 IU/ml). The diagnosis of infectious endocarditis due to valvular rheumatic heart disease was retained. After stabilization, antibiotic therapy and mitral valve surgery in emergency, the dermatological lesions regressed in a few days but the haemodynamic condition of the child deteriorated rapidly with sudden death. Besnier erythema is a rare cutaneous manifestation of acute articular rhumatism. Physicians should not neglect this rare but useful clinical sign, especially in patients with subclinical valvular involvement in order to avoid potential late cardiac complications. The three differential diagnoses included: ringworm, urticaria, and erythema due to hereditary angioedema.

This study reports the case of a

    3-year old
    AGE

    female
    GENDER

    child
    AGE

 with a

    1-year
    AGE

 history of

    rash manifesting as discoid plaques with pink, non-itchy, rounded and oval, polycyclic, confluent macular areas measuring 1-3 cm in diameter, with central clearing evolving in stages
    SYMPTOMS

, with

    repeated regression and reappearance
    SYMPTOMS

. The

    child
    AGE

 was admitted to the Emergency Department with

    respiratory distress
    SYMPTOMS

,

    fever
    SYMPTOMS

 and

    aggravation of pre-existing skin lesions becoming diffuse
    SYMPTOMS

.

    Mitral holosystolic murmur with an intensity of grade 4/6
    SYMPTOMS

 was recorded by

    cardiac auscultation
    PARACLINICAL

.

    Cardiac ultrasound
    PARACLINICAL

 showed

    acute massive mitral insufficiency with valvular vegetations
    SYMPTOMS

.

    Laboratory tests
    PARACLINICAL

 showed

    inflammation with a CRP level of 300 mg/l and a sedimentation rate of 60 mm in the first hour
    BIOCHEMICAL

 and

    ASLO levels were very high (1600 IU/ml)
    BIOCHEMICAL

. The diagnosis of

    infectious endocarditis due to valvular rheumatic heart disease
    DIAGNOSIS

 was retained. After

    stabilization, antibiotic therapy
    MEDICATION

 and

    mitral valve surgery
    MEDICATION

 in emergency,

    the dermatological lesions regressed in a few days
    SYMPTOMS

 but

    the haemodynamic condition of the child deteriorated rapidly
    SYMPTOMS

 with

    sudden death
    SYMPTOMS

.

    Besnier erythema
    SYMPTOMS

 is a rare

    cutaneous manifestation of acute articular rhumatism
    SYMPTOMS

. Physicians should not neglect this rare but useful clinical sign, especially in patients with

    subclinical valvular involvement
    SYMPTOMS

 in order to avoid potential

    late cardiac complications
    SYMPTOMS

. The three differential diagnoses included:

    ringworm
    DIAGNOSIS

,

    urticaria
    DIAGNOSIS

, and

    erythema due to hereditary angioedema
    DIAGNOSIS

.

stabilization, antibiotic therapy
mitral valve surgery


Acquired C1-inhibitor deficiency presenting with nephrotic syndrome.

Acquired C1-inhibitor (C1-INH) deficiency is a rare and potentially life-threatening disorder, which presents with recurrent attacks of non-pitting oedema to the face, airway, limbs or gastrointestinal tract. It is often associated with underlying B-cell lymphoproliferative disorders. We describe a case of a 73-year-old man with acquired C1-INH deficiency who presented with nephrotic syndrome due to glomerular IgM deposition, secondary to an underlying secretory lymphoplasmacytic lymphoma. Both the acquired C1-INH deficiency and the nephrotic syndrome resolved when the underlying B-cell lymphoma was treated with rituximab and bendamustine, suggesting the underlying lymphoproliferative malignancy was driving both disorders.

    Acquired C1-inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 is a rare and potentially life-threatening disorder, which presents with

    recurrent attacks of non-pitting oedema to the face, airway, limbs or gastrointestinal tract
    SYMPTOMS

. It is often associated with underlying

    B-cell lymphoproliferative disorders
    DIAGNOSIS

. We describe a case of a

    73-year-old
    AGE

    man
    GENDER

 with

    acquired C1-INH deficiency
    BIOCHEMICAL

 who presented with

    nephrotic syndrome
    DIAGNOSIS

 due to

    glomerular IgM deposition
    MICROSCOPIC

, secondary to an underlying

    secretory lymphoplasmacytic lymphoma
    DIAGNOSIS

. Both the

    acquired C1-INH deficiency
    BIOCHEMICAL

 and the

    nephrotic syndrome
    SYMPTOMS

 resolved when the underlying

    B-cell lymphoma
    DIAGNOSIS

 was

    treated with rituximab and bendamustine
    MEDICATION

, suggesting the underlying

    lymphoproliferative malignancy
    DIAGNOSIS

 was driving both disorders.

B-cell lymphoproliferative disorders
nephrotic syndrome
secretory lymphoplasmacytic lymphoma
B-cell lymphoma
lymphoproliferative malignancy


Lupus enteritis as the only active manifestation of systemic lupus erythematosus: A case report.

Lupus enteritis is a rare manifestation of systemic lupus erythematosus (SLE). Diagnosis of this condition is difficult, especially in the absence of other symptoms related to active SLE. We present the case of a 25-year-old female with lupus enteritis as the sole initial manifestation of active SLE.

A 25-year-old African American female presented to the Emergency Department complaining of diffuse abdominal pain, diarrhea, nausea, and vomiting for 2 days. Her past medical history was significant for seasonal allergies and family history was pertinent for discoid lupus in her father and SLE in a cousin. The patient's vital signs on presentation were normal. Her physical exam was remarkable for significant lower abdominal tenderness without guarding or rigidity. A computed tomography of the abdomen and pelvis revealed marked circumferential wall thickening and edema of the proximal and mid small bowel predominantly involving the submucosa. Our main differential diagnoses were intestinal angioedema and mesenteric vein thrombosis. However, mesenteric vessels were patent, and laboratory testing for hereditary angioedema showed a normal C1 Esterase Inhibitor level and low C3 and C4 levels. Infectious work-up was negative. Autoimmune tests showed elevated anti-nuclear antibodies (ANA) (13.6), anti-Smith antibody, and anti-ribonucleoprotein (anti-RNP) antibody. The patient was diagnosed with SLE enteritis. She was maintained on bowel rest, given intravenous hydration, and started on methylprednisolone 60 mg IV daily. She had significant improvement in her abdominal pain, diarrhea, and emesis after 2 days of treatment. Steroids were tapered and maintained on Hydroxychloroquine with no relapses one year after presentation.

This case of lupus enteritis represents a rare manifestation of SLE. Diagnosis requires clinical suspicion, characteristic imaging and laboratory tests. Endoscopic appearance and biopsies usually yield non-specific findings. High dose steroids are the preferred treatment modality for moderate and severe cases.

    Lupus enteritis
    DIAGNOSIS

 is a rare manifestation of

    systemic lupus erythematosus (SLE)
    DIAGNOSIS

. Diagnosis of this condition is difficult, especially in the

    absence of other symptoms related to active SLE
    NEG_FINDINGS

. We present the case of a

    25-year-old
    AGE

    female
    GENDER

 with

    lupus enteritis
    DIAGNOSIS

 as the sole initial manifestation of

    active SLE
    DIAGNOSIS

.

A

    25-year-old
    AGE

    African American
    ETHNICITY

    female
    GENDER

 presented to the Emergency Department complaining of

    diffuse abdominal pain
    SYMPTOMS

,

    diarrhea
    SYMPTOMS

,

    nausea
    SYMPTOMS

, and

    vomiting
    SYMPTOMS

    for 2 days
    SYMPTOMS

.

    Her
    GENDER

 past medical history was significant for

    seasonal allergies
    SYMPTOMS

 and

    family history was pertinent for discoid lupus in her father and SLE in a cousin
    FAMILY

. The patient's

    vital signs
    NEG_FINDINGS

 on presentation

    were normal
    NEG_FINDINGS

.

    Her
    GENDER

 physical exam was remarkable for

    significant lower abdominal tenderness
    SYMPTOMS

    without guarding or rigidity
    NEG_FINDINGS

. A

    computed tomography of the abdomen and pelvis
    PARACLINICAL

 revealed

    marked circumferential wall thickening and edema of the proximal and mid small bowel predominantly involving the submucosa
    SYMPTOMS

. Our main differential diagnoses were

    intestinal angioedema
    DIAGNOSIS

 and

    mesenteric vein thrombosis
    SYMPTOMS

. However,

    mesenteric vessels were patent
    NEG_FINDINGS

, and

    laboratory testing
    PARACLINICAL

 for

    hereditary angioedema
    NEG_FINDINGS

 showed a

    normal C1 Esterase Inhibitor level and low C3 and C4 levels
    NEG_FINDINGS

.

    Infectious work-up was negative
    NEG_FINDINGS

.

    Autoimmune tests
    PARACLINICAL

 showed

    elevated anti-nuclear antibodies (ANA) (13.6), anti-Smith antibody, and anti-ribonucleoprotein (anti-RNP) antibody
    BIOCHEMICAL

. The patient was diagnosed with

    SLE enteritis
    DIAGNOSIS

.

    She
    GENDER

 was

    maintained on bowel rest
    MEDICATION

,

    given intravenous hydration
    MEDICATION

, and

    started on methylprednisolone 60 mg IV daily
    MEDICATION

.

    She
    GENDER

 had

    significant improvement in her abdominal pain, diarrhea
    SYMPTOMS

, and

    emesis
    SYMPTOMS

 after

    2 days of treatment
    MEDICATION

.

    Steroids were tapered
    MEDICATION

 and

    maintained on Hydroxychloroquine
    MEDICATION

 with

    no relapses
    NEG_FINDINGS

 one year after presentation.

This case of

    lupus enteritis
    DIAGNOSIS

 represents a rare manifestation of

    SLE
    DIAGNOSIS

. Diagnosis requires

    clinical suspicion
    PARACLINICAL

,

    characteristic imaging
    PARACLINICAL

 and

    laboratory tests
    PARACLINICAL

.

    Endoscopic appearance
    PARACLINICAL

 and

    biopsies
    PARACLINICAL

 usually yield

    non-specific findings
    NEG_FINDINGS

.

    High dose steroids
    MEDICATION

 are the preferred treatment modality for moderate and severe cases.

Lupus enteritis
systemic lupus erythematosus (SLE)
lupus enteritis
active SLE
intestinal angioedema
SLE enteritis
lupus enteritis
SLE


Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause.

Hereditary angioedema (HAE) is a potentially life-threatening group of conditions that is often underdiagnosed or misdiagnosed. As HAE is typically diagnosed by detecting C1 inhibitor deficiency, there is a critical need for methods that can identify affected individuals with normal C1 inhibitor. The recent discovery of associations between PLG K330E and ANGPT1 A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing.

We analyzed genome sequences from a generally healthy population cohort of 2820 adults and identified PLG K330E in one individual. Subsequent review of this participant's medical history revealed symptoms clinically attributed to allergy of unknown etiology but that are consistent with published descriptions of HAE patients carrying the PLG K330E variant. The participant, a 31 year old female, reported lip and tongue angioedema, without wheals, which did not respond to treatment with steroids or antihistamines.

The genotype-first approach demonstrated that detection of PLG K330E in undiagnosed or misdiagnosed individuals can identify patients actually affected with HAE-U. The genetic diagnosis will facilitate selection of appropriate treatment, discontinuation of therapies ineffective for this condition, and timely diagnosis of affected family members. The results support a role of PLG K330E in the pathogenesis of HAE and suggest that genetic testing be considered as an approach to diagnose patients with unexplained angioedema.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a potentially life-threatening group of conditions that is often

    underdiagnosed or misdiagnosed
    NEG_FINDINGS

. As

    HAE
    DIAGNOSIS

 is typically diagnosed by detecting

    C1 inhibitor deficiency
    BIOCHEMICAL

, there is a critical need for methods that can identify affected individuals with

    normal C1 inhibitor
    NEG_FINDINGS

. The recent discovery of

    associations between PLG K330E and ANGPT1 A119S
    GENETICS

 and

    HAE of unknown genetic cause (HAE-U)
    DIAGNOSIS

, has raised the possibility that

    genetic evaluation
    PARACLINICAL

 could be used to diagnose

    HAE-U
    DIAGNOSIS

 in patients with

    unexplained angioedema
    NEG_FINDINGS

 or

    non-confirmatory laboratory testing
    NEG_FINDINGS

.

We

    analyzed genome sequences
    PARACLINICAL

 from a generally healthy population cohort of 2820 adults and identified

    PLG K330E
    GENETICS

 in one individual. Subsequent review of this participant's medical history revealed

    symptoms clinically attributed to allergy of unknown etiology
    NEG_FINDINGS

 but that are consistent with published descriptions of

    HAE
    DIAGNOSIS

 patients carrying the

    PLG K330E variant
    GENETICS

. The participant, a

    31 year old
    AGE

    female
    GENDER

, reported

    lip and tongue angioedema
    SYMPTOMS

,

    without wheals
    NEG_FINDINGS

, which

    did not respond to treatment with steroids or antihistamines
    NEG_FINDINGS

.

The genotype-first approach demonstrated that detection of

    PLG K330E
    GENETICS

 in undiagnosed or misdiagnosed individuals can identify patients actually affected with HAE-U. The

    genetic diagnosis
    PARACLINICAL

 will facilitate selection of appropriate treatment,

    discontinuation of therapies ineffective for
    NEG_FINDINGS

 this condition, and timely diagnosis of affected family members. The results support a role of

    PLG K330E
    GENETICS

 in the pathogenesis of

    HAE
    DIAGNOSIS

 and suggest that

    genetic testing
    PARACLINICAL

 be considered as an approach to diagnose patients with

    unexplained angioedema
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
HAE of unknown genetic cause (HAE-U)
HAE-U
HAE
HAE
unexplained angioedema


Catheter-based local analgesia for the fractured mandible in a patient with a history of hereditary angioedema.

Hereditary angioedema is a rare genetic condition causing episodes of angioedema-including life-threatening laryngeal oedema. Episodes can be unpredictable, or triggered by factors such as trauma, drugs or dental treatment. When faced with a patient with a fractured mandible, who has had a severe attack of angioedema when prescribed either ibuprofen or codeine based analgesia, this required an alternative approach to analgesia. Using a catheter and local anaesthesia, we were able to keep the patient comfortable, and pain free.

    Hereditary angioedema
    DIAGNOSIS

 is a

    rare genetic condition
    GENETICS

 causing

    episodes of angioedema-
    SYMPTOMS

including

    life-threatening laryngeal oedema
    SYMPTOMS

. Episodes can be unpredictable, or triggered by factors such as

    trauma
    SYMPTOMS

, drugs or

    dental treatment
    MEDICATION

. When faced with a patient with a

    fractured mandible
    MEDICATION

, who has had a

    severe attack of angioedema
    SYMPTOMS

 when

    prescribed either ibuprofen or codeine based analgesia
    MEDICATION

, this required an

    alternative approach to analgesia
    MEDICATION

. Using a

    catheter and local anaesthesia
    MEDICATION

, we were able to keep the patient comfortable, and

    pain free
    NEG_FINDINGS

.

episodes of angioedema-
life-threatening laryngeal oedema
trauma
severe attack of angioedema


Hereditary Angioedema-Associated Acute Pancreatitis in C1-Inhibitor Deficient and Normal C1-Inhibitor Patients: Case Reports and Literature Review.

Abdominal pain due to intestinal swellings is one of the most common manifestations in hereditary angioedema (HAE). Bowel swellings can cause severe abdominal pain, nausea, vomiting, and diarrhea, which may lead to misdiagnosis of gastrointestinal disorders. In rare cases, HAE abdominal attacks can be accompanied by acute pancreatitis. Here, we report 3 patients with HAE and acute pancreatitis and present a literature review of similar cases. Patients with confirmed diagnosis of HAE secondary to C1-inhibitor (C1-INH) deficiency (n = 2) and HAE with normal C1-INH and F12 mutation (F12-HAE) (n = 1) were included. Pancreatitis was diagnosed based on clinical symptoms and high lipase and amylase levels. Three HAE patients were diagnosed with acute pancreatitis based on increased amylase levels during severe abdominal swelling episodes. Two were previously diagnosed with HAE type I and one with F12-HAE. Pancreatitis was efficiently treated in two patients using Icatibant, with pain relief within hours. When conservatively treated, pancreatitis pain took longer time to resolve. Eighteen pancreatitis cases in HAE with C1-INH deficiency were previously reported and none in F12-HAE. Most patients (12/18) underwent invasive procedures and/or diagnostic methods. Although rare, severe abdominal HAE attacks could cause pancreatitis; HAE-specific treatments may be efficient for HAE-associated pancreatitis. HAE should be considered as a differential diagnosis of acute idiopathic pancreatitis. To our knowledge, this is the first report of HAE-associated pancreatitis in a F12-HAE patient treated with Icatibant.

    Abdominal pain due to intestinal swellings
    SYMPTOMS

 is one of the most common manifestations in

    hereditary angioedema (HAE)
    DIAGNOSIS

.

    Bowel swellings
    SYMPTOMS

 can cause

    severe abdominal pain
    SYMPTOMS

,

    nausea
    SYMPTOMS

,

    vomiting
    SYMPTOMS

, and

    diarrhea
    SYMPTOMS

, which may lead to misdiagnosis of

    gastrointestinal disorders
    DIAGNOSIS

. In rare cases,

    HAE abdominal attacks
    SYMPTOMS

 can be accompanied by

    acute pancreatitis
    DIAGNOSIS

. Here, we report 3 patients with

    HAE
    DIAGNOSIS

 and

    acute pancreatitis
    DIAGNOSIS

 and present a literature review of similar cases. Patients with confirmed diagnosis of

    HAE
    DIAGNOSIS

 secondary to

    C1-inhibitor (C1-INH) deficiency
    BIOCHEMICAL

 (n = 2) and

    HAE
    DIAGNOSIS

 with

    normal C1-INH and F12 mutation
    NEG_FINDINGS

 (

    F12-HAE)
    DIAGNOSIS

 (n = 1) were included.

    Pancreatitis
    DIAGNOSIS

 was diagnosed based on

    clinical symptoms
    SYMPTOMS

 and

    high lipase and amylase levels
    BIOCHEMICAL

. Three

    HAE
    DIAGNOSIS

 patients were diagnosed with

    acute pancreatitis
    DIAGNOSIS

 based on

    increased amylase levels
    BIOCHEMICAL

 during

    severe abdominal swelling episodes
    SYMPTOMS

. Two were previously diagnosed with

    HAE type I
    DIAGNOSIS

 and one with

    F12-HAE
    DIAGNOSIS

.

    Pancreatitis
    DIAGNOSIS

 was efficiently treated in two patients using

    Icatibant
    MEDICATION

, with

    pain relief within hours
    SYMPTOMS

. When

    conservatively treated
    MEDICATION

,

    pancreatitis pain
    SYMPTOMS

 took longer time to resolve. Eighteen

    pancreatitis
    DIAGNOSIS

 cases in

    HAE
    DIAGNOSIS

 with

    C1-INH deficiency
    BIOCHEMICAL

 were previously reported and none in

    F12-HAE
    DIAGNOSIS

. Most patients (12/18) underwent

    invasive procedures
    MEDICATION

 and/or diagnostic methods. Although rare,

    severe abdominal HAE attacks
    SYMPTOMS

 could cause

    pancreatitis
    DIAGNOSIS

;

    HAE-specific treatments
    MEDICATION

 may be efficient for

    HAE-associated pancreatitis
    DIAGNOSIS

.

    HAE
    DIAGNOSIS

 should be considered as a

    differential diagnosis
    PARACLINICAL

 of

    acute idiopathic pancreatitis
    DIAGNOSIS

. To our knowledge, this is the first report of

    HAE-associated pancreatitis
    DIAGNOSIS

 in a

    F12-HAE
    DIAGNOSIS

 patient treated with

    Icatibant
    MEDICATION

.

hereditary angioedema (HAE)
gastrointestinal disorders
acute pancreatitis
HAE
acute pancreatitis
HAE
HAE
F12-HAE)
Pancreatitis
HAE
acute pancreatitis
HAE type I
F12-HAE
Pancreatitis
pancreatitis
HAE
F12-HAE
pancreatitis
HAE-associated pancreatitis
HAE
acute idiopathic pancreatitis
HAE-associated pancreatitis
F12-HAE

C1-inhibitor (C1-INH) deficiency
high lipase and amylase levels
increased amylase levels
C1-INH deficiency

Icatibant
conservatively treated
invasive procedures
HAE-specific treatments
Icatibant


Identification and Mapping of a 2,009-bp DNA Deletion in SERPING1 of a Hereditary Angioedema Patient.

We report a heterozygous, 2,009 base pairs (bps) genomic DNA deletion within the SERPING1 gene that has not previously been reported in a case of type I hereditary angioedema (HAE). The patient is a 28-year-old Han Chinese female living in Hong Kong who has suffered from recurrent angioedema since adolescence, with increasing attack frequency as she entered adulthood; in the past, episodes occurred annually, but now occur every two to three months. The affected areas are not itchy and include common sites such as the left and right forearms, but without throat involvement. The patient also experiences epigastric pain. The patient's mother suffers from similar symptoms. A mutation in the serine protease inhibitor, clade G, member 1 (SERPING1) gene is associated with HAE. Patients with HAE type I commonly carry either a small deletion within SERPING1 or a truncated transcript. We performed a multiplex ligation-dependent probe amplification (MLPA) assay on our indexed patient. Our result suggests a 2,009 bps deletion spanning across exons 5 and 6 within SERPING1. Although earlier literature has described other large DNA deletions encasing exons 5 and 6 in SERPING1, these DNA rearrangements were larger in size between 4 and 6 kbps, and the breakpoint locations were generally not determined due to technical constraints (Pappalardo et al., 2000; Duponchel et al., 2001; Roche et al., 2005; Loules et al., 2018; and Göβwein et al., 2008). Our report describes mapping of this 2,009 bps in SERPING1. Using a combination of molecular techniques, we were able to confirm and locate this large heterozygous genomic DNA deletion that includes both exons 5 and 6 of SERPING1.

We report a

    heterozygous, 2,009 base pairs (bps) genomic DNA deletion within the SERPING1 gene
    GENETICS

 that has not previously been reported in a case of

    type I hereditary angioedema (HAE)
    DIAGNOSIS

. The patient is a

    28-year-old
    AGE

    Han Chinese
    ETHNICITY

    female
    GENDER

 living in

    Hong Kong
    ETHNICITY

 who has suffered from

    recurrent angioedema
    SYMPTOMS

 since

    adolescence
    AGE

, with increasing attack frequency as

    she
    GENDER

 entered

    adulthood
    AGE

; in the past, episodes occurred annually, but now occur every two to three months. The

    affected areas are not itchy and include common sites such as the left and right forearms
    SYMPTOMS

, but

    without throat involvement
    NEG_FINDINGS

. The patient also experiences

    epigastric pain
    SYMPTOMS

.

    The patient's mother suffers from similar symptoms
    FAMILY

. A

    mutation in the serine protease inhibitor, clade G, member 1 (SERPING1) gene
    GENETICS

 is associated with

    HAE
    DIAGNOSIS

. Patients with

    HAE type I
    DIAGNOSIS

 commonly carry either a

    small deletion within SERPING1 or a truncated transcript
    GENETICS

. We performed a

    multiplex ligation-dependent probe amplification (MLPA) assay
    PARACLINICAL

 on our indexed patient. Our result suggests a

    2,009 bps deletion spanning across exons 5 and 6 within SERPING1
    GENETICS

. Although earlier literature has described other

    large DNA deletions encasing exons 5 and 6 in SERPING1
    GENETICS

, these

    DNA rearrangements
    GENETICS

 were

    larger in size between 4 and 6 kbps
    SYMPTOMS

, and the breakpoint locations were generally not determined due to technical constraints (Pappalardo et al., 2000; Duponchel et al., 2001; Roche et al., 2005; Loules et al., 2018; and Göβwein et al., 2008). Our report describes mapping of this

    2,009 bps in SERPING1
    GENETICS

. Using a combination of molecular techniques, we were able to confirm and locate this

    large heterozygous genomic DNA deletion that includes both exons 5 and 6 of SERPING1
    GENETICS

.

type I hereditary angioedema (HAE)
HAE
HAE type I


Hereditary Angioedema Type 1 with Recurrent Dizziness.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient's hands and fingers appeared mild. Laboratory examinations revealed a low C4 and C1 inhibitor (INH) activity. A direct sequencing analysis of C1INH revealed a pathogenic gene mutation. Based on these results, she was diagnosed with hereditary angioedema (HAE) type 1. These findings indicate that HAE can cause recurrent dizziness, and it should therefore be included in the differential diagnosis in patients with recurrent neurologic symptoms, even in the absence of severe edema.

A

    41-year-old
    AGE

    woman
    GENDER

 presented with

    recurrent dizziness
    SYMPTOMS

. After an attack of

    dizziness
    SYMPTOMS

,

    she
    GENDER

 felt

    edematous sensations in her hands
    SYMPTOMS

. However, according to photographs taken during the attack,

    the edema on the back of the patient's hands and fingers appeared mild
    SYMPTOMS

.

    Laboratory examinations
    PARACLINICAL

 revealed a

    low C4 and C1 inhibitor (INH) activity
    BIOCHEMICAL

. A

    direct sequencing analysis of C1INH
    PARACLINICAL

 revealed a

    pathogenic gene mutation
    GENETICS

. Based on these results,

    she
    GENDER

 was diagnosed with

    hereditary angioedema (HAE) type 1
    DIAGNOSIS

. These findings indicate that

    HAE
    DIAGNOSIS

 can cause

    recurrent dizziness
    SYMPTOMS

, and it should therefore be included in the

    differential diagnosis
    PARACLINICAL

 in patients with

    recurrent neurologic symptoms
    SYMPTOMS

, even in the

    absence of severe edema
    NEG_FINDINGS

.


Anesthetic Management of a Patient With Hereditary Angioedema for Oral Surgery.

Hereditary angioedema (HAE) is a rare genetic disease that results from deficiency or dysfunction of C1 inhibitor (C1-INH). This disease is characterized by sudden attacks of angioedema. When edema occurs in the pharynx or larynx, it can lead to serious airway compromise, including death. Physical and/or psychological stress can trigger an attack. Dental treatment, including tooth extraction, is also a recognized trigger. We report a case of a 20-year-old male with HAE who required impacted third molar extractions. C1-INH concentrate was administered 1 hour before surgery, which was completed under deep intravenous sedation. This report describes the anesthetic management of a patient with HAE and reviews treatment options and concerns.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic disease
    GENETICS

 that results from

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

. This disease is characterized by

    sudden attacks of angioedema
    SYMPTOMS

. When

    edema occurs in the pharynx or larynx
    SYMPTOMS

, it can lead to

    serious airway compromise
    SYMPTOMS

, including

    death
    SYMPTOMS

. Physical and/or

    psychological stress
    SYMPTOMS

 can trigger an attack.

    Dental treatment
    MEDICATION

, including

    tooth extraction
    MEDICATION

, is also a recognized trigger. We report a case of a

    20-year-old
    AGE

    male
    GENDER

 with

    HAE
    DIAGNOSIS

 who required

    impacted third molar extractions
    MEDICATION

.

    C1-INH concentrate was administered 1 hour before surgery
    MEDICATION

, which was completed under

    deep intravenous sedation
    MEDICATION

. This report describes the

    anesthetic management
    MEDICATION

 of a patient with

    HAE
    DIAGNOSIS

 and reviews treatment options and concerns.

sudden attacks of angioedema
edema occurs in the pharynx or larynx
serious airway compromise
death
psychological stress


New approach in prophylactic treatment of a challenged HAE patient.

Hereditary angioedema (HAE) is a relapsing swelling disorder which can cause severe pain, affect quality of life and potentially be life threatening with involvement of the airways. We present a 34-year-old immigrant who suffered from very frequent and severe HAE attacks. The attacks often involved the face, mouth and the airways. She often went to the hospital for treatment, where the language barrier made the situation complicated. The traditional therapy for HAE was not successful treating this patient. In June 2017, off-label treatment with prophylactic subcutaneous complement C1-inhibitor concentrate was initiated. The treatment was very successful and the patient has not been hospitalised since. Treatment for HAE is nowadays under investigation, and many drugs are under development. Especially, medication which works prophylactically and is administered orally or subcutaneously is in the horizon.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    relapsing swelling disorder
    DIAGNOSIS

 which can cause

    severe pain
    SYMPTOMS

,

    affect quality of life
    SYMPTOMS

 and potentially be

    life threatening
    SYMPTOMS

 with

    involvement of the airways
    SYMPTOMS

. We present a

    34-year-old
    AGE

    immigrant
    ETHNICITY

 who suffered from

    very frequent and severe HAE attacks
    SYMPTOMS

. The attacks often

    involved the face, mouth and the airways
    SYMPTOMS

.

    She
    GENDER

 often went to the hospital for treatment, where the language barrier made the situation complicated. The

    traditional therapy for HAE was not successful treating
    NEG_FINDINGS

 this patient. In June 2017,

    off-label treatment with prophylactic subcutaneous complement C1-inhibitor concentrate
    MEDICATION

 was initiated. The treatment was very successful and the patient has

    not been hospitalised
    NEG_FINDINGS

 since. Treatment for

    HAE
    DIAGNOSIS

 is nowadays under investigation, and many drugs are under development. Especially,

    medication which works prophylactically and is administered orally or subcutaneously
    MEDICATION

 is in the horizon.

Hereditary angioedema (HAE)
relapsing swelling disorder
HAE


Melkersson-Rosenthal syndrome: a case report of a rare disease with overlapping features.

Melkersson-Rosenthal syndrome (MRS) is a rare, neuro-mucocutaneous disease which presents as orofacial swelling, facial palsy and fissured tongue. These symptoms may occur simultaneously or, more frequently, with a oligosymptomatic or monosymptomatic pattern. Swelling, that is the most common initial finding, may mimic hereditary or acquired angioedema, a disorder caused by histamine or bradykinin-mediated plasma-leakage affecting subcutaneous and/or submucosal tissue. The differential diagnosis of MRS includes also chronic inflammatory and infective diseases characterized by granulomatous infiltration, as well as rosacea, contact dermatitis, allergic reactions and Bell's palsy.

A 71-year old, non-allergic female patient with no familial and personal history of angioedema presented, a few days after a possible herpes simplex or varicella-zoster virus infection, with monolateral facial paraesthesia and lower lip edema. After temporary remission of symptoms on oral steroids and antihistamines, she showed swelling recurrence refractory to valaciclovir therapy and a subsequent course of antihistamines. The clinical picture and a previous history of non-Hodgkin lymphoma prompted us to rule out an acquired form of paraneoplastic, C1-inhibitor (C1-INH) deficiency: C1q and both antigen and functional C1-INH tested normal, whilst we found low plasma levels of C3 and C4 possibly related to the parallel detection of antiphospholipid antibodies. Thus, we hypothesized a non-histaminergic, idiopathic form of angioedema and planned further therapy with tranexamic acid and the leukotriene receptor antagonist montelukast. Treatment failure with both drugs finally suggested a Melkersson-Rosenthal syndrome, which was confirmed by histologic findings of non caseating granulomas on lip biopsy.

Melkersson-Rosenthal syndrome may occur with rather non-specific symptoms and overlap with alternative conditions, including recurrent angioedema. No specific biomarkers for MRS exist and clinical diagnosis is often of exclusion. The finding of complement or immune alterations, as in our patient, may be further confounding and justify the need for skin or mucosal biopsy to establish a correct diagnosis and prescribe targeted therapy.

    Melkersson-Rosenthal syndrome (MRS)
    DIAGNOSIS

 is a rare,

    neuro-mucocutaneous disease
    DIAGNOSIS

 which presents as

    orofacial swelling
    SYMPTOMS

,

    facial palsy
    SYMPTOMS

 and

    fissured tongue
    SYMPTOMS

. These symptoms may occur simultaneously or, more frequently, with a

    oligosymptomatic or monosymptomatic pattern
    SYMPTOMS

.

    Swelling
    SYMPTOMS

, that is the most common initial finding, may mimic

    hereditary or acquired angioedema
    DIAGNOSIS

, a disorder caused by

    histamine or bradykinin-mediated plasma-leakage affecting subcutaneous and/or submucosal tissue
    BIOCHEMICAL

. The

    differential diagnosis
    PARACLINICAL

 of

    MRS
    DIAGNOSIS

 includes also

    chronic inflammatory and infective diseases
    DIAGNOSIS

 characterized by

    granulomatous infiltration
    MICROSCOPIC

, as well as

    rosacea
    DIAGNOSIS

,

    contact dermatitis
    DIAGNOSIS

,

    allergic reactions
    DIAGNOSIS

 and

    Bell's palsy
    DIAGNOSIS

.

A

    71-year old
    AGE

,

    non-allergic
    NEG_FINDINGS

    female
    GENDER

 patient with

    no familial and personal history of angioedema
    NEG_FINDINGS

 presented, a few days after a possible

    herpes simplex or varicella-zoster virus infection
    DIAGNOSIS

, with

    monolateral facial paraesthesia
    SYMPTOMS

 and

    lower lip edema
    SYMPTOMS

. After

    temporary remission of symptoms
    SYMPTOMS

 on

    oral steroids and antihistamines
    MEDICATION

,

    she
    GENDER

 showed

    swelling recurrence
    SYMPTOMS

    refractory to valaciclovir therapy and a subsequent course of antihistamines
    NEG_FINDINGS

. The clinical picture and a

    previous history of non-Hodgkin lymphoma
    NEG_FINDINGS

 prompted us to

    rule out an acquired form of paraneoplastic, C1-inhibitor (C1-INH) deficiency
    NEG_FINDINGS

:

    C1q and both antigen and functional C1-INH tested normal
    NEG_FINDINGS

, whilst we found

    low plasma levels of C3 and C4
    BIOCHEMICAL

 possibly related to the

    parallel detection of antiphospholipid antibodies
    BIOCHEMICAL

. Thus, we hypothesized a

    non-histaminergic, idiopathic form of angioedema
    NEG_FINDINGS

 and planned further

    therapy with tranexamic acid and the leukotriene receptor antagonist montelukast
    MEDICATION

.

    Treatment failure with both drugs
    NEG_FINDINGS

 finally suggested a

    Melkersson-Rosenthal syndrome
    DIAGNOSIS

, which was confirmed by histologic findings of

    non caseating granulomas
    MICROSCOPIC

 on

    lip biopsy
    PARACLINICAL

.

    Melkersson-Rosenthal syndrome
    DIAGNOSIS

 may occur with

    rather non-specific symptoms
    SYMPTOMS

 and overlap with alternative conditions, including

    recurrent angioedema
    SYMPTOMS

. No specific biomarkers for

    MRS
    DIAGNOSIS

 exist and clinical diagnosis is often of exclusion. The finding of

    complement or immune alterations
    BIOCHEMICAL

, as in our patient, may be further confounding and justify the need for

    skin or mucosal biopsy
    PARACLINICAL

 to establish a correct diagnosis and prescribe

    targeted therapy
    MEDICATION

.


Wolf in the sheep's clothing: intestinal angioedema mimicking infectious colitis.

Hereditary angioedema (HAE) is a relatively rare clinical entity that can potentially cause life-threatening airway or intestinal oedema, patients with the latter usually presents with symptoms of gastroenteritis like vomiting, diarrhoea and abdominal pain. Here, we present a unique case of a less recognised type of HAE that is type III in a patient who presented with signs and symptoms consistent with infectious colitis. She previously had similar episodes and was managed multiple times with antibiotics, with no satisfactory response. There, she underwent extensive diagnostic evaluation. On the basis of findings of further investigations on the current visit, she was eventually diagnosed with intestinal angioedema. To the best of our knowledge, the present paper represents the third reported case of type III HAE-induced intestinal angioedema. Additionally, we undertake a literature review of HAE.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a relatively rare clinical entity that can potentially cause

    life-threatening airway or intestinal oedema
    SYMPTOMS

, patients with the latter usually presents with symptoms of

    gastroenteritis
    SYMPTOMS

 like

    vomiting
    SYMPTOMS

,

    diarrhoea
    SYMPTOMS

 and

    abdominal pain
    SYMPTOMS

. Here, we present a unique case of a less recognised

    type of HAE
    DIAGNOSIS

 that is

    type III
    DIAGNOSIS

 in a patient who presented with

    signs and symptoms consistent with infectious colitis
    SYMPTOMS

.

    She
    GENDER

    previously had similar episodes
    NEG_FINDINGS

 and was

    managed multiple times with antibiotics, with no satisfactory response
    NEG_FINDINGS

. There,

    she
    GENDER

 underwent extensive diagnostic evaluation. On the basis of findings of further investigations on the current visit,

    she
    GENDER

 was eventually diagnosed with

    intestinal angioedema
    DIAGNOSIS

. To the best of our knowledge, the present paper represents the third reported case of

    type III HAE-induced intestinal angioedema
    DIAGNOSIS

. Additionally, we undertake a literature review of

    HAE
    DIAGNOSIS

.


Chemotherapy in Patients with Hereditary Angioedema.

Hereditary angioedema (HAE) is an autosomal dominant hereditary disorder characterized by episodic swelling of many body regions (especially throat and abdomen), potentially triggered by medication. No data are available for HAE in patients with cancer assigned to standard chemotherapy. The aim of our study was to identify circulating mediators potentially predictive of acute HAE attacks during chemotherapy.

Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers and for routine haematochemistry were performed in a 42-year-old male affected by type 2 HAE during standard adjuvant oxaliplatin/fluorouracil-based chemotherapy administered for stage III radically resected rectal cancer. Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment. Mann-Whitney U-test was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy.

Pre-chemotherapy values of tested variables (day 0) were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml. A significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional. Four HAE attacks were observed, they started from the forth cycle of treatment and all were manageable. Changes in C3, D-dimers and C1-inhibitor functional preceded the attacks.

The stress induced by chemotherapy such a standard oxaliplatin/fluorouracil increases the risk of attacks in patients with HAE. However, circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional may serve as early predictors of acute HAE crisis.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant hereditary disorder
    GENETICS

 characterized by

    episodic swelling of many body regions (especially throat and abdomen)
    SYMPTOMS

, potentially triggered by

    medication
    MEDICATION

. No data are available for

    HAE
    DIAGNOSIS

 in patients with

    cancer
    DIAGNOSIS

 assigned to

    standard chemotherapy
    MEDICATION

. The aim of our study was to identify

    circulating mediators
    BIOCHEMICAL

 potentially predictive of

    acute HAE attacks
    SYMPTOMS

 during

    chemotherapy
    MEDICATION

.

    Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers
    PARACLINICAL

 and

    for routine haematochemistry
    PARACLINICAL

 were performed in a

    42-year-old
    AGE

    male
    GENDER

 affected by

    type 2 HAE
    DIAGNOSIS

 during

    standard adjuvant oxaliplatin/fluorouracil-based chemotherapy
    MEDICATION

 administered for

    stage III radically resected rectal cancer
    MEDICATION

.

    Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment
    MEDICATION

.

    Mann-Whitney U-test
    PARACLINICAL

 was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy.

    Pre-chemotherapy values of tested variables
    BIOCHEMICAL

 (day 0)

    were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml
    BIOCHEMICAL

. A

    significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional
    BIOCHEMICAL

. Four

    HAE attacks
    SYMPTOMS

 were observed, they started from the

    forth cycle of treatment
    MEDICATION

 and all were manageable.

    Changes in C3, D-dimers and C1-inhibitor functional
    BIOCHEMICAL

 preceded the attacks.

The

    stress
    SYMPTOMS

 induced by

    chemotherapy such a standard oxaliplatin/fluorouracil
    MEDICATION

 increases the risk of attacks in patients with

    HAE
    DIAGNOSIS

. However,

    circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional
    BIOCHEMICAL

 may serve as early predictors of

    acute HAE crisis
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
cancer
type 2 HAE
HAE
acute HAE crisis


Hereditary Angioedema Type II: First Presentation in Adulthood with Recurrent Severe Abdominal Pain.

A 27-year-old Emirate man presented to Cleveland Clinic Abu Dhabi emergency department with a 4 year history of recurrent episodes of severe swellings affecting different parts of his body. He used to get 2 swelling episodes every week affecting either his face, hands, feet or scrotum and severe abdominal pain twice a week. Abdominal CT scan and a colonoscopy showed bowel wall oedema. There was no family history of similar complaint or of hereditary angioedema (HAE). Complement studies confirmed the diagnosis of HAE type II. He was commenced on danazol 100 mg twice daily and his symptoms resolved. This case report highlights the importance of considering HAE in patients with recurrent unexplained abdominal pain even in the absence of positive family history of HAE.

A

    27-year-old
    AGE

    Emirate
    ETHNICITY

    man
    GENDER

 presented to Cleveland Clinic Abu Dhabi emergency department with a 4 year history of

    recurrent episodes of severe swellings affecting different parts of his body
    SYMPTOMS

. He used to get

    2 swelling episodes every week affecting either his face, hands, feet or scrotum
    SYMPTOMS

 and

    severe abdominal pain
    SYMPTOMS

 twice a week.

    Abdominal CT scan
    PARACLINICAL

 and a

    colonoscopy
    PARACLINICAL

 showed

    bowel wall oedema
    SYMPTOMS

. There was

    no family history of similar complaint
    NEG_FINDINGS

    or of hereditary angioedema (HAE)
    NEG_FINDINGS

.

    Complement studies
    PARACLINICAL

 confirmed the diagnosis of

    HAE type II
    DIAGNOSIS

.

    He
    GENDER

 was commenced on

    danazol 100 mg twice daily
    MEDICATION

 and his

    symptoms resolved
    SYMPTOMS

. This case report highlights the importance of considering

    HAE
    DIAGNOSIS

 in patients with

    recurrent unexplained abdominal pain
    SYMPTOMS

 even in the

    absence of positive family history of HAE
    NEG_FINDINGS

.


Consequences of Misdiagnosed and Mismanaged Hereditary Angioedema Laryngeal Attacks: An Overview of Cases from the Romanian Registry.

Emergency department (ED) physicians frequently encounter patients presenting with angioedema. Most of these involve histamine-mediated angioedema; however, less common forms of angioedema (bradykinin-mediated) also occur. It is vital physicians correctly recognize and treat this; particularly since bradykinin-mediated angioedema does not respond to antihistamines, corticosteroids or epinephrine and hereditary angioedema (HAE) laryngeal attacks can be fatal. Here we present four case reports illustrating how failures in recognizing, managing, and treating laryngeal edema due to HAE led to asphyxiation and death of the patient. Recognition of the specific type of angioedema is critical for rapid and effective treatment of HAE attacks. Bradykinin-mediated angioedema should be efficiently differentiated from the most common histamine-mediated form. Improved awareness of HAE and the associated risk of life-threatening laryngeal edema among emergency physicians, patients, and relatives and clear ED treatment protocols are warranted. Moreover, appropriate treatments should be readily available to reduce fatalities associated with laryngeal edema.

    Emergency department (ED) physicians
    PARACLINICAL

 frequently encounter patients presenting with

    angioedema
    DIAGNOSIS

. Most of these involve

    histamine-mediated angioedema
    DIAGNOSIS

; however, less common forms of

    angioedema (bradykinin-mediated)
    DIAGNOSIS

 also occur. It is vital physicians correctly recognize and treat this; particularly since

    bradykinin-mediated angioedema
    DIAGNOSIS

    does not respond to antihistamines, corticosteroids or epinephrine
    NEG_FINDINGS

 and

    hereditary angioedema (HAE
    DIAGNOSIS

)

    laryngeal attacks
    SYMPTOMS

 can be

    fatal
    SYMPTOMS

. Here we present four case reports illustrating how

    failures in
    NEG_FINDINGS

 recognizing, managing, and treating

    laryngeal edema
    SYMPTOMS

 due to

    HAE
    DIAGNOSIS

 led to

    asphyxiation
    SYMPTOMS

 and

    death
    SYMPTOMS

 of the patient. Recognition of the specific type of

    angioedema
    DIAGNOSIS

 is critical for rapid and effective treatment of

    HAE attacks
    DIAGNOSIS

.

    Bradykinin-mediated angioedema
    DIAGNOSIS

 should be efficiently differentiated from the most common

    histamine-mediated form
    DIAGNOSIS

. Improved awareness of

    HAE
    DIAGNOSIS

 and the associated risk of

    life-threatening laryngeal edema
    SYMPTOMS

 among emergency physicians, patients, and relatives and clear ED treatment protocols are warranted. Moreover, appropriate treatments should be readily available to reduce

    fatalities
    SYMPTOMS

 associated with

    laryngeal edema
    SYMPTOMS

.

angioedema
histamine-mediated angioedema
angioedema (bradykinin-mediated)
bradykinin-mediated angioedema
hereditary angioedema (HAE
HAE
angioedema
HAE attacks
Bradykinin-mediated angioedema
histamine-mediated form
HAE

laryngeal attacks
fatal
laryngeal edema
asphyxiation
death
life-threatening laryngeal edema
fatalities
laryngeal edema


Lethal manifestations of angioedema.

An 86-year-old woman with a history of angioedema was found dead at her home address. She had recently complained of a swollen tongue. At autopsy the tongue was grossly edematous, protruding from the mouth. There was also marked edema of the tonsillar fossae, epiglottis and glottic inlet, causing critical obstruction. Histology of the tongue and upper airway demonstrated marked submucosal edema. Death was attributed to upper airway obstruction due to angioedema of the tongue, oropharynx and glottic inlet. Angioedema is characterized by localized non-pitting edema of the deep dermis and subcutaneous/submucosal tissues. It may be acute or chronic, acquired or inherited. Sudden death may result from critical airway occlusion, although both stroke and ischemic heart disease are known to occur. Post mortem genetic testing for hereditary variants can be conducted for SERPING1 gene and F12 gene/THR328 mutations.

An

    86-year-old
    AGE

    woman
    GENDER

 with a history of

    angioedema
    DIAGNOSIS

 was found

    dead
    SYMPTOMS

 at her home address.

    She
    GENDER

 had recently complained of a

    swollen tongue
    SYMPTOMS

. At

    autopsy
    PARACLINICAL

 the

    tongue was grossly edematous, protruding from the mouth
    SYMPTOMS

. There was also

    marked edema of the tonsillar fossae, epiglottis and glottic inlet
    SYMPTOMS

, causing

    critical obstruction
    SYMPTOMS

.

    Histology of the tongue and upper airway
    PARACLINICAL

 demonstrated

    marked submucosal edema
    SYMPTOMS

.

    Death
    SYMPTOMS

 was attributed to

    upper airway obstruction
    SYMPTOMS

 due to

    angioedema of the tongue, oropharynx and glottic inlet
    SYMPTOMS

.

    Angioedema
    DIAGNOSIS

 is characterized by

    localized non-pitting edema of the deep dermis and subcutaneous/submucosal tissues
    SYMPTOMS

. It may be acute or chronic, acquired or

    inherited
    GENETICS

.

    Sudden death
    SYMPTOMS

 may result from

    critical airway occlusion
    SYMPTOMS

, although both

    stroke
    SYMPTOMS

 and

    ischemic heart disease
    DIAGNOSIS

 are known to occur.

    Post mortem genetic testing
    PARACLINICAL

 for

    hereditary variants
    GENETICS

 can be conducted for

    SERPING1 gene and F12 gene/THR328 mutations
    GENETICS

.

angioedema
Angioedema
ischemic heart disease


The physician and hereditary angioedema friend or foe: 62-year diagnostic delay and iatrogenic procedures.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by episodes of acute subcutaneous swelling, and/or recurrent severe abdominal pain. The disease is potentially fatal if the upper-airway is involved. Iatrogenic harm can occur if HAE is not considered in the differential diagnosis, the specialists are not aware of the natural history, diagnosis and treatment of HAE, or as a result of unnecessary surgical and other iatrogenic interventions.

We present the case of a 72-year-old man who began suffering recurrent abdominal pain at the age of 8 years. The pain led to frequent emergency department visits, three emergency surgical interventions, and 5 endoscopies before C1-INH-HAE was diagnosed at the age of 70. Infrequent subcutaneous swellings were attributed to unknown allergic reactions that were not related to the primary diagnosis of abdominal pain. Family history was positive for recurrent abdominal pain and angioedema but was ignored until the propositus' grandson developed recurrent severe oro-facial edema attacks. The boy's mother searched the worldwide web and found educational materials on a patient association website. She suggested complement C4 and C1-INH testing that led to the appropriate diagnosis of C1-INH-HAE type 1 in her son and his grandfather.

This report emphasizes the importance of accurately evaluating personal and family history in patients with a long history of recurrent, acute, severe but medically unexplained abdominal pain and cutaneous swellings. Here, the diagnosis of HAE was overlooked for 62 years and the focus on abdominal complaints led to numerous surgical interventions without consideration of the full differential diagnosis. Screening family members from all generations for unrecognized angioedema, abdominal pain, and measurement of C1-INH and C4 are essential for accurate and timely diagnosis of HAE.

    Hereditary angioedema due to C1 inhibitor deficiency
    DIAGNOSIS

    (C1-INH-HAE)
    DIAGNOSIS

 is a

    rare autosomal dominant disease
    GENETICS

 characterized by

    episodes of acute subcutaneous swelling
    SYMPTOMS

, and/or

    recurrent severe abdominal pain
    SYMPTOMS

. The disease is potentially

    fatal
    SYMPTOMS

 if

    the upper-airway is involved
    SYMPTOMS

.

    Iatrogenic harm
    SYMPTOMS

 can occur if

    HAE
    DIAGNOSIS

 is not considered in the

    differential diagnosis
    PARACLINICAL

, the specialists are not aware of the natural history, diagnosis and treatment of

    HAE
    DIAGNOSIS

, or as a result of

    unnecessary surgical and other iatrogenic interventions
    NEG_FINDINGS

.

We present the case of a

    72-year-old
    AGE

    man
    GENDER

 who began suffering

    recurrent abdominal pain
    SYMPTOMS

 at the

    age of 8 years
    AGE

. The pain led to

    frequent emergency department visits
    MEDICATION

,

    three emergency surgical interventions
    MEDICATION

, and

    5 endoscopies
    MEDICATION

 before

    C1-INH-HAE
    DIAGNOSIS

 was diagnosed at the

    age of 70
    AGE

.

    Infrequent subcutaneous swellings
    SYMPTOMS

 were attributed to

    unknown allergic reactions
    NEG_FINDINGS

 that were not related to the primary diagnosis of

    abdominal pain
    NEG_FINDINGS

.

    Family history was positive for recurrent abdominal pain and angioedema
    FAMILY

    but was ignored
    NEG_FINDINGS

 until the

    propositus' grandson developed recurrent severe oro-facial edema attacks
    FAMILY

. The

    boy
    GENDER

's mother searched the worldwide web and found educational materials on a patient association website.

    She
    GENDER

 suggested

    complement C4 and C1-INH testing
    PARACLINICAL

 that led to the appropriate diagnosis of

    C1-INH-HAE type 1 in her son and his grandfather
    DIAGNOSIS

.

This report emphasizes the importance of accurately evaluating personal and family history in patients with a long history of

    recurrent, acute, severe but medically unexplained abdominal pain
    SYMPTOMS

 and

    cutaneous swellings
    SYMPTOMS

. Here, the diagnosis of

    HAE
    DIAGNOSIS

 was overlooked for 62 years and the focus on

    abdominal complaints
    SYMPTOMS

 led to numerous

    surgical interventions
    MEDICATION

 without consideration of the full

    differential diagnosis
    PARACLINICAL

.

    Screening family members from all generations
    PARACLINICAL

 for unrecognized

    angioedema
    DIAGNOSIS

,

    abdominal pain
    SYMPTOMS

, and

    measurement of C1-INH and C4
    BIOCHEMICAL

 are essential for accurate and timely diagnosis of

    HAE
    DIAGNOSIS

.

frequent emergency department visits
three emergency surgical interventions
5 endoscopies
surgical interventions


Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen.

Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family history. The underlining cause may be malignant or due to autoimmune diseases, but some cases remain idiopathic.

We report a case of a 75 year old woman suffering from recurrent episodes of angioedema since the age of 66, considered first induced by treatment with angiotensin-converting-enzyme inhibitors (ACEI). She continued to have angioedema attacks during 6 years after discontinuation of ACEI, until evaluation in our clinic in 2014, when C1 inhibitor esterase (C1-INH) deficiency was confirmed. The extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative. C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements, but no diagnostic criteria for diseases known to induce C1-INH deficiency could be found. We first initiated daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months. During the last and most severe attack, with the first facial and laryngeal edema, we have switched to attenuated androgen danazol. The evolution was very good, with prompt remission of angioedema and significant increase of C1-INH and C4 plasma levels after 2 weeks of daily danazol use. She completed 3 years of continuous treatment with low daily maintenance dose of danazol (ongoing), with no angioedema attack. We closely monitored C1-INH and C4 plasma levels, possible danazol side effects and any signs suggesting late onset of C1-INH deficiency causal disease.

We reported a particular case of rare angioedema due to acquired deficiency of C1-inhibitor, which has no clear cause after long follow-up, but good response to attenuated androgen. We concluded that the awareness of angioedema due to C1-INH deficiency should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases.

    Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE)
    DIAGNOSIS

 is a rare disease

    sharing some clinical and laboratory similarities
    SYMPTOMS

 with

    hereditary angioedema
    DIAGNOSIS

, but with late onset and

    no positive family history
    NEG_FINDINGS

. The underlining cause may be

    malignant
    DIAGNOSIS

 or due to

    autoimmune diseases
    DIAGNOSIS

, but some cases remain

    idiopathic
    DIAGNOSIS

.

We report a case of a

    75 year old
    AGE

    woman
    GENDER

 suffering from

    recurrent episodes of angioedema
    SYMPTOMS

 since the

    age of 66
    AGE

, considered first induced by

    treatment with angiotensin-converting-enzyme inhibitors (ACEI)
    MEDICATION

.

    She
    GENDER

 continued to have

    angioedema attacks
    SYMPTOMS

 during 6 years after

    discontinuation of ACEI
    MEDICATION

, until evaluation in our clinic in 2014, when

    C1 inhibitor esterase (C1-INH) deficiency
    BIOCHEMICAL

 was confirmed. The

    extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative
    NEG_FINDINGS

.

    C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements
    BIOCHEMICAL

, but

    no diagnostic criteria for diseases known to induce C1-INH deficiency could be found
    NEG_FINDINGS

. We first initiated

    daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months
    MEDICATION

. During the last and most severe attack, with the

    first facial and laryngeal edema
    SYMPTOMS

, we have

    switched to attenuated androgen danazol
    MEDICATION

. The evolution was very good, with

    prompt remission of angioedema
    SYMPTOMS

 and

    significant increase of C1-INH and C4 plasma levels
    BIOCHEMICAL

 after

    2 weeks of daily danazol use
    MEDICATION

.

    She
    GENDER

 completed

    3 years of continuous treatment with low daily maintenance dose of danazol (ongoing)
    MEDICATION

, with

    no angioedema attack
    NEG_FINDINGS

. We closely monitored

    C1-INH and C4 plasma levels
    BIOCHEMICAL

, possible

    danazol side effects
    SYMPTOMS

 and any signs suggesting

    late onset of C1-INH deficiency causal disease
    SYMPTOMS

.

We reported a particular case of

    rare angioedema
    DIAGNOSIS

 due to

    acquired deficiency of C1-inhibitor
    BIOCHEMICAL

, which has

    no clear cause after long follow-up
    NEG_FINDINGS

, but good response to

    attenuated androgen
    MEDICATION

. We concluded that the awareness of

    angioedema
    DIAGNOSIS

 due to

    C1-INH deficiency
    BIOCHEMICAL

 should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases.


Non-Surgical Management of Colo-Colonic Intussusception in Patients with Hereditary Angioedema.

BACKGROUND Hereditary angioedema (HAE) is an autosomal disease caused either by deficiency or presence of a non-functioning C1 inhibitor. The lack or non-functionality of said inhibitors leads to activation of an inflammatory cascade, which result in cutaneous and mucosal edema. Most patients with HAE present with either cutaneous, laryngeal/pharyngeal, or gastrointestinal exacerbations. An uncommon gastrointestinal manifestation of HAE is an intussusception, which in most cases require invasive/surgical management. CASE REPORT A 17-year-old Hispanic female patient with past medical history of HAE, presented with a 4-day history of episodic abdominal pain, worsening during the last 2 days with associated nausea, vomiting, and bright red blood per rectum. The abdominal ultrasound performed at our institution showed an elongated region of hypoechoic and hyperechoic concentric rings, raising suspicion of an intussusception. The patient was treated conservatively, with 30 mg of ecallantide and a unit of fresh frozen plasma (FFP). Follow-up abdominopelvic computed tomography scan was performed approximately 20 hours after the administration of fresh frozen plasma revealing complete interval resolution of the colo-colonic intussusception. Subsequently, the patient was kept under hospital care for the next 4 days with adequate progression of diet and without recurrence of intussusception. CONCLUSIONS To the best of our knowledge, most cases of patient with HAE presenting with intussusception have been treated with invasive/surgical procedures. In our case, conservative management has proven successful to reduce edema with subsequent non-surgical reduction of the intussusception. By directly targeting the pathophysiologic aspects of HAE, an unnecessary invasive procedure, as well as its potential complications, were avoided.

BACKGROUND

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal disease
    GENETICS

 caused either by

    deficiency or presence of a non-functioning C1 inhibitor
    BIOCHEMICAL

. The

    lack or non-functionality of said inhibitors
    BIOCHEMICAL

 leads to

    activation of an inflammatory cascade
    BIOCHEMICAL

, which result in

    cutaneous and mucosal edema
    SYMPTOMS

. Most patients with

    HAE
    DIAGNOSIS

 present with either

    cutaneous, laryngeal/pharyngeal, or gastrointestinal exacerbations
    SYMPTOMS

. An uncommon

    gastrointestinal
    SYMPTOMS

 manifestation of

    HAE
    DIAGNOSIS

 is an

    intussusception
    SYMPTOMS

, which in most cases require

    invasive/surgical management
    MEDICATION

. CASE REPORT A

    17-year-old
    AGE

    Hispanic
    ETHNICITY

    female
    GENDER

 patient with

    past medical history of HAE
    FAMILY

, presented with a

    4-day history of episodic abdominal pain
    SYMPTOMS

,

    worsening during the last 2 days
    SYMPTOMS

 with associated

    nausea
    SYMPTOMS

,

    vomiting
    SYMPTOMS

, and

    bright red blood per rectum
    SYMPTOMS

. The

    abdominal ultrasound
    PARACLINICAL

 performed at our institution showed an

    elongated region of hypoechoic and hyperechoic concentric rings
    SYMPTOMS

, raising suspicion of an

    intussusception
    SYMPTOMS

. The patient was treated

    conservatively, with 30 mg of ecallantide and a unit of fresh frozen plasma (FFP)
    MEDICATION

.

    Follow-up abdominopelvic computed tomography scan
    PARACLINICAL

 was performed approximately 20 hours after the

    administration of fresh frozen plasma
    MEDICATION

 revealing

    complete interval resolution of the colo-colonic intussusception
    SYMPTOMS

. Subsequently, the patient was

    kept under hospital care for the next 4 days
    MEDICATION

 with

    adequate progression of diet
    MEDICATION

 and

    without recurrence of intussusception
    NEG_FINDINGS

. CONCLUSIONS To the best of our knowledge, most cases of patient with

    HAE
    DIAGNOSIS

 presenting with

    intussusception
    SYMPTOMS

 have been treated with

    invasive/surgical procedures
    MEDICATION

. In our case,

    conservative management
    MEDICATION

 has proven successful to

    reduce edema
    SYMPTOMS

    with subsequent non-surgical reduction of the intussusception
    MEDICATION

. By directly targeting the pathophysiologic aspects of

    HAE
    DIAGNOSIS

, an

    unnecessary invasive procedure
    MEDICATION

, as well as its potential complications, were avoided.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE


Hereditary angioedema: a mother diagnosing her child using Google as a diagnostic aid.

Hereditary angioedema (HAE), due to C1-inhibitor deficiency, is a rare autosomal dominant and potentially life-threatening disease characterised by recurrent oedema attacks of skin, mucosa and viscera. Due to the rarity and the fact that symptoms of HAE imitate other forms of angioedema and other conditions, HAE may be misdiagnosed, especially in emergency settings. Consequently, patients with HAE may experience significant delays in diagnosis. Without an accurate diagnosis patients with HAE may not receive proper treatment. At times 'Doctor Google' may be an important tool in establishing the diagnosis. The aim of this case report is to emphasise the importance of listening to patients and relatives and being humble to 'Doctor Google'. Furthermore, the aim is to remind all healthcare personal of HAE and the importance of considering the rare differential diagnoses to common symptoms.

    Hereditary angioedema (HAE)
    DIAGNOSIS

, due to

    C1-inhibitor deficiency
    BIOCHEMICAL

, is a

    rare autosomal dominant
    GENETICS

 and potentially life-threatening disease characterised by

    recurrent oedema attacks of skin, mucosa and viscera
    SYMPTOMS

. Due to the rarity and the fact that symptoms of

    HAE
    DIAGNOSIS

 imitate other forms of

    angioedema
    SYMPTOMS

 and other conditions,

    HAE
    DIAGNOSIS

 may be misdiagnosed, especially in emergency settings. Consequently, patients with

    HAE
    DIAGNOSIS

 may experience significant delays in diagnosis. Without an accurate diagnosis patients with

    HAE
    DIAGNOSIS

 may

    not receive proper treatment
    NEG_FINDINGS

. At times 'Doctor Google' may be an important tool in establishing the diagnosis. The aim of this case report is to emphasise the importance of listening to patients and relatives and being humble to 'Doctor Google'. Furthermore, the aim is to remind all healthcare personal of

    HAE
    DIAGNOSIS

 and the importance of considering the rare differential diagnoses to common symptoms.

Hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE