Mucosal Injury From Calcium Oxalate Crystals Resembling Anaphylaxis and Angioedema.

There are 215 families of plants that contain insoluble needle-shaped calcium oxalate crystals on the surface of their tissues. Upon mucosal contact, injury can cause extreme pain, soft-tissue swelling, salivation, dysphagia, and even aphonia. This presentation can resemble angioedema or anaphylaxis.

A 55-year-old Asian female presented to the emergency department complaining of oral pain, swelling, and numbness. Her family reported that she began to experience sharp pain of the tongue and lips immediately after eating "elephant root." Physical examination revealed a patient sitting in an upright position, leaning forward with pooling secretions. She had few lingual petechiae, a subtle diffuse erythema, and mild edema of the lower lip. Due to pain, she was unable to speak and swallow. Her vitals remained within normal limits. The patient was taking lisinopril for hypertension. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Injury by calcium oxalate crystals is a relatively common occurrence that will present to the emergency department. Although most exposures are benign, patients can develop critical illness, requiring emergent therapies and airway management. Due to the nature of presentation, exposure can easily be misdiagnosed as anaphylaxis or hereditary and drug-induced angioedema. Severe pain and the temporal relationship to plant ingestion distinguish insoluble calcium oxalate crystal exposure from these alternative causes of angioedema. There is minimal evidence-based data evaluating treatment of these injuries. Standard treatment regimen includes a local anesthetic, corticosteroids, opioids, and antihistaminergic agents. Given the relative low cost, ease of administration, and benign adverse effect profile, sodium bicarbonate rinse may have a role as an adjunct therapy, however, research is needed.

There are 215 families of plants that contain

    insoluble needle-shaped calcium oxalate crystals on the surface of their tissues
    MICROSCOPIC

. Upon

    mucosal contact
    SYMPTOMS

,

    injury
    SYMPTOMS

 can cause

    extreme pain
    SYMPTOMS

,

    soft-tissue swelling
    SYMPTOMS

,

    salivation
    SYMPTOMS

,

    dysphagia
    SYMPTOMS

, and even

    aphonia
    SYMPTOMS

. This presentation can resemble

    angioedema
    DIAGNOSIS

 or

    anaphylaxis
    SYMPTOMS

.

A

    55-year-old
    AGE

    Asian
    ETHNICITY

    female
    GENDER

 presented to the emergency department complaining of

    oral pain
    SYMPTOMS

,

    swelling
    SYMPTOMS

, and

    numbness
    SYMPTOMS

.

    Her
    GENDER

 family reported that

    she
    GENDER

 began to experience

    sharp pain of the tongue and lips
    SYMPTOMS

 immediately after

    eating "elephant root
    SYMPTOMS

." Physical examination revealed a patient

    sitting in an upright position
    SYMPTOMS

,

    leaning forward
    SYMPTOMS

 with

    pooling secretions
    SYMPTOMS

.

    She
    GENDER

 had

    few lingual petechiae
    SYMPTOMS

, a

    subtle diffuse erythema
    SYMPTOMS

, and

    mild edema of the lower lip
    SYMPTOMS

. Due to

    pain
    SYMPTOMS

,

    she
    GENDER

 was

    unable to speak and swallow
    NEG_FINDINGS

.

    Her
    GENDER

    vitals remained within normal limits
    NEG_FINDINGS

. The patient was

    taking lisinopril for hypertension
    MEDICATION

. WHY SHOULD AN

    EMERGENCY PHYSICIAN
    PARACLINICAL

 BE AWARE OF THIS?:

    Injury by calcium oxalate crystals
    DIAGNOSIS

 is a relatively common occurrence that will present to the emergency department. Although most exposures are

    benign
    NEG_FINDINGS

, patients can develop

    critical illness
    SYMPTOMS

, requiring

    emergent therapies
    MEDICATION

 and

    airway management
    MEDICATION

. Due to the nature of presentation,

    exposure
    SYMPTOMS

 can easily be misdiagnosed as

    anaphylaxis
    NEG_FINDINGS

 or

    hereditary and drug-induced angioedema
    DIAGNOSIS

.

    Severe pain
    SYMPTOMS

 and the

    temporal relationship to plant ingestion
    SYMPTOMS

 distinguish

    insoluble calcium oxalate crystal exposure
    DIAGNOSIS

 from these alternative causes of

    angioedema
    DIAGNOSIS

. There is minimal evidence-based data evaluating treatment of these injuries. Standard treatment regimen includes a

    local anesthetic, corticosteroids, opioids, and antihistaminergic agents
    MEDICATION

. Given the relative low cost, ease of administration, and

    benign adverse effect profile
    SYMPTOMS

,

    sodium bicarbonate rinse
    MEDICATION

 may have a role as an

    adjunct therapy
    MEDICATION

, however, research is needed.

unable to speak and swallow
vitals remained within normal limits
benign
anaphylaxis


Drug-induced Angioedema: A Rare Side Effect of Rosuvastatin.

Hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) are first-line medication for lowering serum cholesterol levels in the prevention of cardiovascular disease. Angioedema is the swelling of mucosa and submucosal tissue. There are no published cases of drug-induced angioedema involving rosuvastatin. We report a case of a 45-year-old female who presented with episodes of self-resolving edema of face, lips, and tongue after being on rosuvastatin. The patient denied any rash during these episodes and mentioned that self-medication with diphenhydramine did not relieve her symptoms. The patient was hemodynamically stable. The complement component 4 (C4), C1 esterase inhibitor, and complement component 1q (C1q) binding assay were within normal range. Therefore, the diagnosis of hereditary angioedema was effectively ruled out. The temporal relation between rosuvastatin and the development of angioedema and prompt resolution of symptoms after the drug discontinued suggest that rosuvastatin was the most probable culprit in the development of angioedema in our patient.

    Hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins)
    MEDICATION

 are first-line medication for

    lowering serum cholesterol levels
    BIOCHEMICAL

 in the prevention of

    cardiovascular disease
    DIAGNOSIS

.

    Angioedema
    DIAGNOSIS

 is the

    swelling of mucosa and submucosal tissue
    SYMPTOMS

. There are no published cases of

    drug-induced angioedema
    DIAGNOSIS

 involving

    rosuvastatin
    MEDICATION

. We report a case of a

    45-year-old
    AGE

    female
    GENDER

 who presented with

    episodes of self-resolving edema of face, lips, and tongue
    SYMPTOMS

 after being on

    rosuvastatin
    MEDICATION

. The patient

    denied any rash during these episodes
    NEG_FINDINGS

 and mentioned that

    self-medication with diphenhydramine did not relieve her symptoms
    NEG_FINDINGS

. The patient was

    hemodynamically stable
    NEG_FINDINGS

. The

    complement component 4 (C4), C1 esterase inhibitor, and complement component 1q (C1q) binding assay were within normal range
    BIOCHEMICAL

. Therefore,

    the diagnosis of hereditary angioedema was effectively ruled out
    NEG_FINDINGS

. The temporal relation between

    rosuvastatin
    MEDICATION

 and the development of

    angioedema
    SYMPTOMS

 and

    prompt resolution of symptoms after the drug discontinued
    SYMPTOMS

 suggest that

    rosuvastatin
    MEDICATION

 was the most probable culprit in the development of

    angioedema
    DIAGNOSIS

 in our patient.

cardiovascular disease
Angioedema
drug-induced angioedema
angioedema


Recurrent Acute Abdomen as the Main Manifestation of Hereditary Angioedema.

A diagnosis of hereditary angioedema is usually made with recurrent episodes of swelling of the subcutaneous tissue with a family history. We herein report a case in which recurrent acute abdomen was the main manifestation of hereditary angioedema. A 45-year-old womon presented with a 10-year history of recurrent severe abdominal pain. Abdominal computed tomography revealed remarkable submucosal edema of the ileum. A blood examination revealed grossly reduced complement C4 and CH50 with deficiency of C1-inhibitor. Genetic testing revealed a heterozygous nonsense mutation of the SERPING1 gene, and a diagnosis of hereditary angioedema was made. Hereditary angioedema should be listed as a differential diagnosis of recurrent acute abdomen.

A diagnosis of

    hereditary angioedema
    DIAGNOSIS

 is usually made with

    recurrent episodes of swelling of the subcutaneous tissue
    SYMPTOMS

 with a

    family history
    FAMILY

. We herein report a case in which

    recurrent acute abdomen
    SYMPTOMS

 was the main manifestation of

    hereditary angioedema
    DIAGNOSIS

. A

    45-year-old
    AGE

    womon
    GENDER

 presented with a 10-year history of

    recurrent severe abdominal pain
    SYMPTOMS

.

    Abdominal computed tomography
    PARACLINICAL

 revealed

    remarkable submucosal edema of the ileum
    SYMPTOMS

. A

    blood examination
    PARACLINICAL

 revealed

    grossly reduced complement C4 and CH50
    BIOCHEMICAL

 with

    deficiency of C1-inhibitor
    BIOCHEMICAL

.

    Genetic testing
    PARACLINICAL

 revealed a

    heterozygous nonsense mutation of the SERPING1 gene
    GENETICS

, and a diagnosis of

    hereditary angioedema
    DIAGNOSIS

 was made.

    Hereditary angioedema
    DIAGNOSIS

 should be listed as a

    differential diagnosis
    PARACLINICAL

 of

    recurrent acute abdomen
    SYMPTOMS

.

hereditary angioedema
hereditary angioedema
hereditary angioedema
Hereditary angioedema

grossly reduced complement C4 and CH50
deficiency of C1-inhibitor


Repeated attacks of type III hereditary angioedema with factor XII mutation during pregnancy.

In type III hereditary angioedema (HAE type III), the phenotype is the same as type I and type II disease, but the level and function of C1-esterase inhibitor (C1-INH) is normal. Hereditary angioedema type III has been described as an oestrogen-sensitive form because it can be triggered or aggravated by exposure to high oestrogen levels as seen during pregnancy, especially when associated with Factor XII mutation. This case report describes the evolution and management of repeated angioedema attacks during pregnancy in a woman with HAE, with normal levels and function of C1-INH (type III); and a mis-sense mutation of factor XII. The physiopathology and genetic features, the unpredictability of clinical manifestations and the management during pregnancy and delivery are discussed.

In

    type III hereditary angioedema (HAE type III)
    DIAGNOSIS

, the phenotype is the same as

    type I and type II disease
    DIAGNOSIS

, but the

    level and function of C1-esterase inhibitor (C1-INH) is normal
    NEG_FINDINGS

.

    Hereditary angioedema type III
    DIAGNOSIS

 has been described as an oestrogen-sensitive form because it can be triggered or aggravated by

    exposure to high oestrogen levels
    SYMPTOMS

 as seen during

    pregnancy
    SYMPTOMS

, especially when associated with

    Factor XII mutation
    GENETICS

. This case report describes the evolution and management of

    repeated angioedema attacks
    SYMPTOMS

 during

    pregnancy
    DIAGNOSIS

 in a

    woman
    GENDER

 with

    HAE
    DIAGNOSIS

, with

    normal levels and function of C1-INH (type III)
    NEG_FINDINGS

; and a

    mis-sense mutation of factor XII
    GENETICS

. The physiopathology and genetic features, the unpredictability of clinical manifestations and the management during

    pregnancy
    DIAGNOSIS

 and delivery are discussed.

exposure to high oestrogen levels
pregnancy
repeated angioedema attacks

Factor XII mutation
mis-sense mutation of factor XII


A hereditary angioedema screening on an index case: Turkey.

Hereditary angioedema (HAE) is characterised by recurrent episodes of angioedema and can be fatal.

The present study aimed to screen HAE.

A total of 60 individuals were screened. The frequency and severity of symptoms were scored from 0 to 8. Measurements were taken of C4 and C1 esterase inhibitor protein (C1-INH) levels. Mutation in the C1 inhibitor gene was examined in 9 patients with HAE.

A positive correlation between the C1 esterase inhibitor protein levels and C4 level was detected in the group as a whole (p < 0.001, r = 0.725, n = 60). Anegative correlation between the C1 esterase inhibitor protein level and severity score was observed in the whole group (p < 0.001, r = -0.486, n = 60). A negative correlation was also detected in the entire group between the C4 level and severity score (p = 0.002, r = -0.389, n = 60). In the patients with HAE, a positive correlation between the C1 esterase inhibitor protein level and C4 levels was detected (p = 0.034, r = 0.705, n = 9). A heterozygous c. 601A > T nonsense variant was identified at the C1 esterase inhibitor gene-SERPING1-in patients with Type 1 HAE.

It is well known that there is a prolonged delay in the diagnosis of HAE. The present study demonstrates that it is very important and even life-saving to screen for HAE on the basis of an index case.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is characterised by

    recurrent episodes of angioedema
    SYMPTOMS

 and can be

    fatal
    SYMPTOMS

.

The present study aimed to screen

    HAE
    DIAGNOSIS

.

A total of 60 individuals were screened. The frequency and severity of symptoms were scored from 0 to 8.

    Measurements were taken of C4 and C1 esterase inhibitor protein (C1-INH) levels
    PARACLINICAL

.

    Mutation in the C1 inhibitor gene
    GENETICS

 was examined in 9 patients with

    HAE
    DIAGNOSIS

.

A

    positive correlation between the C1 esterase inhibitor protein levels and C4 level
    BIOCHEMICAL

 was detected in the group as a whole (p < 0.001, r = 0.725, n = 60). Anegative correlation between

    the C1 esterase inhibitor protein level
    BIOCHEMICAL

 and severity score was observed in the whole group (p < 0.001, r = -0.486, n = 60). A negative correlation was also detected in the entire group between

    the C4 level
    BIOCHEMICAL

 and severity score (p = 0.002, r = -0.389, n = 60). In the patients with

    HAE
    DIAGNOSIS

, a

    positive correlation between the C1 esterase inhibitor protein level and C4 levels
    BIOCHEMICAL

 was detected (p = 0.034, r = 0.705, n = 9). A

    heterozygous c. 601A > T nonsense variant was identified at the C1 esterase inhibitor gene-SERPING1-
    GENETICS

in patients with

    Type 1 HAE
    DIAGNOSIS

.

It is well known that there is a prolonged delay in the diagnosis of

    HAE
    DIAGNOSIS

. The present study demonstrates that it is very important and even life-saving to screen for

    HAE
    DIAGNOSIS

 on the basis of an index case.

Hereditary angioedema (HAE)
HAE
HAE
HAE
Type 1 HAE
HAE
HAE


The Incidence and Frequency of Various Causes of Angioedema in Emergency Medicine.

Angioedema (AE) is a potentially life-threatening event. We investigated the etiology of AE, with the emphasis on bradykinininduced angioedema treatment in emergency medicine.

The retrospective study included 237 patients with AE, who were examined and treated in two hospitals (group A and B) in Croatia from 2009 to 2016. The location and duration of AE, data about chronic diseases and treatment, potential causative agents (food, drugs, insect bites and chemicals), physical examination data and the subsequent treatment were analyzed.

There was no statistical difference regarding age or comorbidities but there was a statistically significant difference in etiology between the groups (Chi-square, P=0.03). Renin-angiotensin-aldosterone system (RAAS) blocker induced AE was the main cause of emergency attendance in group A (37.5%) and among the leading causes in group B (18.8%). Bradykinin-induced AE (hereditary angioedema (HAE) and RAAS-AE) were the leading causes in a total of 75 (31.5%) patients. RAAS-AE was treated with glucocorticoids and antihistamines. HAE attacks in both groups (2/7 patients, 1.5/6%) were treated with specific therapy. Other causes of AE in groups A/B were insect bites (15/23 patients, 13.5/20%), use of antibiotics/analgetics (11/17 patients, 9/15%), gastroesophageal reflux disease (10/11 patients, 8/9%), neoplasms (5/6 patients, 4/5%) and idiopatic (32/31 patients, 26.5/26%). 21% of patients were hospitalized.

Bradykinin-mediated AE was the main cause of emergency attendance associated with AE. Advances in the treatment of HAE, with case reports of patients with RAAS-AE treated with C1 esterase inhibitor concentrate or bradykinin receptor antagonist, may prove to be a new, reliable and efficacious therapy option.

    Angioedema (AE)
    DIAGNOSIS

 is a potentially life-threatening event. We investigated the etiology of

    AE
    DIAGNOSIS

, with the emphasis on

    bradykinininduced angioedema treatment
    MEDICATION

 in emergency medicine.

The retrospective study included 237 patients with

    AE
    DIAGNOSIS

, who were examined and treated in two hospitals (group A and B) in

    Croatia
    ETHNICITY

 from 2009 to 2016. The location and duration of

    AE
    DIAGNOSIS

, data about chronic diseases and treatment,

    potential causative agents (food, drugs, insect bites and chemicals)
    SYMPTOMS

, physical examination data and the subsequent treatment were analyzed.

There was no statistical difference regarding age or comorbidities but there was a statistically significant difference in etiology between the groups (Chi-square, P=0.03).

    Renin-angiotensin-aldosterone system (RAAS) blocker induced AE
    MEDICATION

 was the main cause of emergency attendance in group A (37.5%) and among the leading causes in group B (18.8%).

    Bradykinin-induced AE (hereditary angioedema (HAE) and RAAS-AE)
    DIAGNOSIS

 were the leading causes in a total of 75 (31.5%) patients.

    RAAS-AE
    DIAGNOSIS

 was treated with

    glucocorticoids and antihistamines
    MEDICATION

.

    HAE attacks
    SYMPTOMS

 in both groups (2/7 patients, 1.5/6%) were treated with

    specific therapy
    MEDICATION

. Other causes of

    AE
    DIAGNOSIS

 in groups A/B were

    insect bites
    SYMPTOMS

 (15/23 patients, 13.5/20%),

    use of antibiotics/analgetics
    MEDICATION

 (11/17 patients, 9/15%),

    gastroesophageal reflux disease
    DIAGNOSIS

 (10/11 patients, 8/9%),

    neoplasms
    DIAGNOSIS

 (5/6 patients, 4/5%) and

    idiopatic
    DIAGNOSIS

 (32/31 patients, 26.5/26%). 21% of patients were

    hospitalized
    MEDICATION

.

    Bradykinin-mediated AE
    DIAGNOSIS

 was the main cause of emergency attendance associated with

    AE
    DIAGNOSIS

. Advances in the treatment of

    HAE
    DIAGNOSIS

, with case reports of patients with

    RAAS-AE
    DIAGNOSIS

 treated with

    C1 esterase inhibitor concentrate or bradykinin receptor antagonist
    MEDICATION

, may prove to be a new, reliable and efficacious therapy option.


Acquired angioedema in juvenile systemic lupus erythematosus: case-based review.

An acquired form of angioedema that is clinically similar but scarcer than the hereditary form may be caused, even more rarely, by the presence of an underlying autoimmune disease. We report a previously healthy 16-year-old girl with an acquired angioedema as a rare and initial presentation of systemic lupus erythematosus. The patient had no previous angioedema attack and no family history. She did not have any chronic diseases and did not use any medicine regularly. The patient was diagnosed with systemic lupus erythematosus with the presence of polyarthralgia, angioedema, leucopenia, and positivity of immunologic criteria. Her edema resolved with high-dose methylprednisolone and hydroxychloroquine slowly. In conclusion, new-onset angioedema in adolescent girls should be investigated to evaluate autoimmunity and the possibility of systemic lupus erythematosus. The related literature on acquired angioedema associated with systemic lupus erythematosus is also reviewed.

An

    acquired form of angioedema
    SYMPTOMS

 that is clinically similar but scarcer than the hereditary form may be caused, even more rarely, by the presence of an underlying

    autoimmune disease
    DIAGNOSIS

. We report a previously healthy

    16-year-old
    AGE

    girl
    GENDER

 with an

    acquired angioedema
    SYMPTOMS

 as a rare and initial presentation of

    systemic lupus erythematosus
    DIAGNOSIS

. The patient had

    no previous angioedema attack
    NEG_FINDINGS

 and

    no family history
    NEG_FINDINGS

.

    She
    GENDER

    did not have any chronic diseases
    NEG_FINDINGS

 and

    did not use any medicine regularly
    NEG_FINDINGS

. The patient was diagnosed with

    systemic lupus erythematosus
    DIAGNOSIS

 with the presence of

    polyarthralgia
    SYMPTOMS

,

    angioedema
    SYMPTOMS

,

    leucopenia
    BIOCHEMICAL

, and

    positivity of immunologic criteria
    BIOCHEMICAL

.

    Her
    GENDER

    edema
    SYMPTOMS

 resolved with

    high-dose methylprednisolone and hydroxychloroquine slowly
    MEDICATION

. In conclusion,

    new-onset angioedema
    SYMPTOMS

 in

    adolescent
    AGE

    girls
    GENDER

 should be investigated to evaluate

    autoimmunity
    DIAGNOSIS

 and the possibility of

    systemic lupus erythematosus
    DIAGNOSIS

. The related literature on

    acquired angioedema
    SYMPTOMS

    associated with systemic lupus erythematosus
    DIAGNOSIS

 is also reviewed.

acquired form of angioedema
acquired angioedema
polyarthralgia
angioedema
edema
new-onset angioedema
acquired angioedema

no previous angioedema attack
no family history
did not have any chronic diseases
did not use any medicine regularly

leucopenia
positivity of immunologic criteria


[Anaphylactic reaction to camomile tea].

The case of a man with type I allergy after the intake of camomile tea is presented. About 30 min after consumption he was hospitalised with palmar pruritus, swelling of the eyelids, upper lip and nasal mucosa as well as narrowness of the throat. Hereditary angioedema was excluded. The skin prick test confirmed the diagnosis of a type I allergy due to camomile tea.

The case of a

    man
    GENDER

 with

    type I allergy
    DIAGNOSIS

 after the

    intake of camomile tea
    MEDICATION

 is presented. About 30 min after consumption

    he
    GENDER

 was hospitalised with

    palmar pruritus
    SYMPTOMS

,

    swelling of the eyelids, upper lip and nasal mucosa
    SYMPTOMS

 as well as

    narrowness of the throat
    SYMPTOMS

.

    Hereditary angioedema was excluded
    NEG_FINDINGS

. The

    skin prick test
    PARACLINICAL

 confirmed the diagnosis of a

    type I allergy due to camomile tea
    DIAGNOSIS

.

type I allergy
type I allergy due to camomile tea


Suffocation due to Acute Airway Edema in a Patient with Hereditary Angioedema Highlighted the Need for Urgent Improvements in Treatment Availability in Japan.

A 42-year-old Japanese man with hereditary angioedema suffered accidental trauma to his jaw in Shizuoka Prefecture, Japan, which gradually caused facial edema. Since plasma-derived human C1 inhibitor (pdh C1-INH) was unavailable, he had to be transferred to Juntendo University Hospital in Tokyo. Due to his severe edema, he suffered asphyxiation leading to cardiopulmonary arrest upon arrival. The patient was resuscitated and promptly treated with pdh C1-INH. In Japan, the self-administration of pdh C1-INH is not allowed, and every prefecture does not always possess stocks of pdh C1-INH. This case emphasizes the need for urgent improvements in treatment availability in Japan.

A

    42-year-old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 with

    hereditary angioedema
    DIAGNOSIS

 suffered

    accidental trauma to his jaw
    SYMPTOMS

 in

    Shizuoka Prefecture
    ETHNICITY

,

    Japan
    ETHNICITY

, which gradually caused

    facial edema
    SYMPTOMS

. Since

    plasma-derived human C1 inhibitor (pdh C1-INH) was unavailable
    NEG_FINDINGS

,

    he
    GENDER

 had to be transferred to Juntendo University Hospital in

    Tokyo
    ETHNICITY

. Due to his

    severe edema
    SYMPTOMS

,

    he
    GENDER

 suffered

    asphyxiation
    SYMPTOMS

 leading to

    cardiopulmonary arrest
    SYMPTOMS

 upon arrival. The patient was

    resuscitated
    MEDICATION

 and

    promptly treated with pdh C1-INH
    MEDICATION

. In

    Japan
    ETHNICITY

, the

    self-administration of pdh C1-INH
    MEDICATION

 is not allowed, and every prefecture does not always possess

    stocks of pdh C1-INH
    NEG_FINDINGS

. This case emphasizes the need for urgent improvements in treatment availability in

    Japan
    ETHNICITY

.

Japanese
Shizuoka Prefecture
Japan
Tokyo
Japan
Japan

accidental trauma to his jaw
facial edema
severe edema
asphyxiation
cardiopulmonary arrest

resuscitated
promptly treated with pdh C1-INH
self-administration of pdh C1-INH


[Acquired C1 esterase inhibitor deficiency via bradykinin-mediated angioedema: Four cases].

Acquired C1-esterase inhibitor (C1-INH) deficiency angioedema (C1-INH-AAE) is a form of bradykinin-mediated angioedema. This rare disorder is due to acquired consumption of C1-INH, hyperactivation of the classic pathway of human complement, and potentially fatal recurrent angioedema symptoms. Clinical symptoms of C1-INH-AAE are very similar to those of hereditary angioedema (HAE) but usually appear after the fourth decade of life and induce abdominal pain less frequently. Laboratory tests are essential in establishing the diagnosis with low levels or abnormal structure and function of C1-INH. Most patients present C1-INH autoantibodies. Furthermore, C1q is reduced in AAE, contrary to HAE. The long-term prognosis is determined by associated hematologic malignancies.

We report 4 cases of C1-INH-AAE associated with lymphoproliferative disorders referred to the Reference Centre for Angioedema of Besançon, France. The patients were aged between 60 and 77 years. C1 INH antibodies were found in three patients. Symptoms were triggered by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) in 3 patients. Hematologic malignancy was present at diagnosis (one case of chronic lymphoid leukemia) or was diagnosed during follow-up (one case of indolent marginal zone non-Hodgkin lymphoma and two cases of monoclonal gammopathy).

C1-INH-AAE induced by ACE inhibitors or ARBs may be associated with hematologic malignancies. This form of revelation does not necessarily indicate a diagnosis of ACE or ARBs angioedema, and screening should therefore be performed for C1 Inh and C1q. An underlying hematologic malignancy should be routinely sought and the long-term prognosis determined.

    Acquired C1-esterase inhibitor (C1-INH) deficiency angioedema (C1-INH-AAE)
    BIOCHEMICAL

 is a form of

    bradykinin-mediated angioedema
    DIAGNOSIS

. This rare disorder is due to

    acquired consumption of C1-INH
    BIOCHEMICAL

,

    hyperactivation of the classic pathway of human complement
    BIOCHEMICAL

, and

    potentially fatal recurrent angioedema symptoms
    SYMPTOMS

. Clinical symptoms of

    C1-INH-AAE
    DIAGNOSIS

 are very similar to those of

    hereditary angioedema (HAE)
    DIAGNOSIS

 but usually appear

    after the fourth decade of life
    AGE

 and induce

    abdominal pain
    SYMPTOMS

 less frequently.

    Laboratory tests
    PARACLINICAL

 are essential in establishing the diagnosis with

    low levels or abnormal structure and function of C1-INH
    BIOCHEMICAL

. Most patients present

    C1-INH autoantibodies
    BIOCHEMICAL

. Furthermore,

    C1q is reduced
    BIOCHEMICAL

 in

    AAE
    DIAGNOSIS

, contrary to

    HAE
    DIAGNOSIS

. The long-term prognosis is determined by associated

    hematologic malignancies
    DIAGNOSIS

.

We report 4 cases of

    C1-INH-AAE
    BIOCHEMICAL

 associated with

    lymphoproliferative disorders
    DIAGNOSIS

 referred to the Reference Centre for

    Angioedema
    DIAGNOSIS

 of Besançon,

    France
    ETHNICITY

. The patients were

    aged between 60 and 77 years
    AGE

.

    C1 INH antibodies
    BIOCHEMICAL

 were found in three patients. Symptoms were triggered by

    angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)
    MEDICATION

 in 3 patients.

    Hematologic malignancy
    DIAGNOSIS

 was present at diagnosis (one case of

    chronic lymphoid leukemia
    DIAGNOSIS

) or was diagnosed during follow-up (one case of

    indolent marginal zone non-Hodgkin lymphoma
    DIAGNOSIS

 and two cases of

    monoclonal gammopathy
    DIAGNOSIS

).

    C1-INH-AAE
    BIOCHEMICAL

 induced by

    ACE inhibitors or ARBs
    MEDICATION

 may be associated with

    hematologic malignancies
    DIAGNOSIS

. This form of

    revelation
    SYMPTOMS

 does

    not necessarily indicate a diagnosis of ACE or ARBs angioedema
    NEG_FINDINGS

, and

    screening
    PARACLINICAL

 should therefore be performed for

    C1 Inh and C1q
    BIOCHEMICAL

. An underlying

    hematologic malignancy
    DIAGNOSIS

 should be routinely sought and the long-term prognosis determined.


In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case.

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH) is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50-200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH) injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

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

 is a rare,

    autosomal dominant disorder
    GENETICS

. The management of

    pregnant
    AGE

 patients with

    C1-INH-HAE
    DIAGNOSIS

 is a challenge for the physician.

    Intravenous plasma-derived nanofiltered C1-INH (pdC1INH)
    MEDICATION

 is the only recommended option throughout

    pregnancy
    MEDICATION

,

    postpartum
    AGE

    , and breastfeeding period
    MEDICATION

. In order to increase pregnancy rates, physicians use

    fertilization therapies increasing endogen levels of estrogens
    MEDICATION

. Therefore, these techniques can provoke an increase in the number and severity of

    edema attacks
    SYMPTOMS

 in

    C1-INH-HAE
    DIAGNOSIS

. Our patient is a

    32-year-old
    AGE

    female
    GENDER

, diagnosed with

    C1-INH-HAE type 1
    DIAGNOSIS

 since 2004.

    She
    GENDER

 had been

    taking danazol 50-200 mg/day for 9 years
    MEDICATION

. Due to

    her
    GENDER

 pregnancy plans in 2013,

    danazol was discontinued
    MEDICATION

.

    PdC1INH
    MEDICATION

 was prescribed regularly for

    prophylactic purpose
    MEDICATION

.

    Triplet pregnancy
    MEDICATION

 occurred by

    in vitro fertilization using luteinizing hormone-releasing hormone (LHRH) injections
    MEDICATION

. In our patient,

    LHRH injections were done four
    MEDICATION

 times

    without causing any severe attack during in vitro fertilization
    NEG_FINDINGS

.

    Angioedema did not worsen during pregnancy and delivery
    NEG_FINDINGS

 due to the

    prophylactic use of intravenous pdC1INH
    MEDICATION

 in our patient. According to the attack frequency and severity, there was no difference between the three

    pregnancy trimesters
    DIAGNOSIS

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

    C1-INH-HAE
    DIAGNOSIS

    receiving in vitro fertilization therapies
    MEDICATION

    without any angioedema attacks
    NEG_FINDINGS

 during

    pregnancy
    DIAGNOSIS

 and delivery and eventually

    having healthy triplets
    MEDICATION

 with the

    prophylactic use of intravenous pdC1INH
    MEDICATION

.


Usefulness of C1 esterase inhibitor protein concentrate in the management of hereditary angioedema of oropharyngeal tissue.

Hereditary angioedema is an autosomal-dominant disorder caused by mutation of the gene encoding the C1 esterase inhibitor (C1-INH). It manifests as painless, nonpruritic, nonpitting episodic swelling of the subcutaneous tissues, gastrointestinal, and upper respiratory tracts in the absence of urticaria. An attack typically takes 24 h to peak and resolves over 48-72 h. The most serious manifestation is a laryngeal attack associated with upper airway swelling. The aim of this case report is to describe the lifesaving use of a novel C1-INH protein concentrate in a patient with mild-to-moderate dyspnea caused by swelling of the upper airway (larynx) and tongue.

    Hereditary angioedema
    DIAGNOSIS

 is an

    autosomal-dominant disorder
    GENETICS

 caused by

    mutation of the gene encoding the C1 esterase inhibitor (C1-INH)
    GENETICS

. It manifests as

    painless, nonpruritic, nonpitting episodic swelling of the subcutaneous tissues, gastrointestinal, and upper respiratory tracts
    SYMPTOMS

 in the

    absence of urticaria
    NEG_FINDINGS

. An attack typically takes 24 h to peak and resolves over 48-72 h. The most serious manifestation is a

    laryngeal attack associated with upper airway swelling
    SYMPTOMS

. The aim of this case report is to describe the

    lifesaving use of a novel C1-INH protein concentrate
    MEDICATION

 in a patient with

    mild-to-moderate dyspnea
    SYMPTOMS

 caused by

    swelling of the upper airway (larynx) and tongue
    SYMPTOMS

.


Extremely Delayed Diagnosis of Type II Hereditary Angioedema: Case Report and Review of the Literature.

We present a case with extremely late diagnosis of type II hereditary angioedema (HAE). Given recent advances in HAE treatment, we want to bring physician awareness to this condition and aid in earlier detection. HAE is a disorder associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. Late diagnosis of HAE can lead to significant morbidity and is severely impairing due to recurring attacks. The diagnosis of HAE is ordinarily made during childhood and adolescence. Delayed diagnoses in early and middle adulthood have been documented in the literature. Gastrointestinal symptoms are common features of HAE and can be misdiagnosed as disease of primary gastrointestinal pathology, such as irritable bowel syndrome, recurrent pancreatitis, or appendicitis. These attacks are characterized by recurrent attacks of subcutaneous and submucosal edema without the presence of urticaria.We present a case of an elderly veteran whose diagnoses was extremely delayed into the eighth decade of life subsequent to unexplained abdominal symptoms. After diagnosis, the patient's symptoms were well controlled with medication due to advances in HAE treatment. To prevent further atypically delayed diagnoses, physicians should consider HAE in patients with recurrent attacks of unexplained abdominal pain.

We present a case with extremely late diagnosis of

    type II hereditary angioedema (HAE)
    DIAGNOSIS

. Given recent advances in

    HAE
    DIAGNOSIS

 treatment, we want to bring physician awareness to this condition and aid in earlier detection.

    HAE
    DIAGNOSIS

 is a disorder associated with

    episodes of angioedema of the face, larynx, lips, abdomen, or extremities
    SYMPTOMS

. Late diagnosis of

    HAE
    DIAGNOSIS

 can lead to significant morbidity and is severely impairing due to

    recurring attacks
    SYMPTOMS

. The diagnosis of

    HAE
    DIAGNOSIS

 is ordinarily made

    during childhood and adolescence
    AGE

. Delayed diagnoses in

    early and middle adulthood
    AGE

 have been documented in the literature.

    Gastrointestinal symptoms
    SYMPTOMS

 are common features of

    HAE
    DIAGNOSIS

 and can be

    misdiagnosed as disease of primary gastrointestinal pathology
    NEG_FINDINGS

, such as

    irritable bowel syndrome
    NEG_FINDINGS

,

    recurrent pancreatitis
    DIAGNOSIS

, or

    appendicitis
    DIAGNOSIS

. These attacks are characterized by

    recurrent attacks of subcutaneous and submucosal edema
    SYMPTOMS

    without the presence of urticaria
    NEG_FINDINGS

.We present a case of an

    elderly
    AGE

 veteran whose diagnoses was extremely delayed

    into the eighth decade of life
    AGE

 subsequent to

    unexplained abdominal symptoms
    SYMPTOMS

. After diagnosis, the patient's symptoms were well controlled with medication due to advances in

    HAE treatment
    MEDICATION

. To prevent further atypically delayed diagnoses, physicians should consider

    HAE
    DIAGNOSIS

 in patients with

    recurrent attacks of unexplained abdominal pain
    SYMPTOMS

.

type II hereditary angioedema (HAE)
HAE
HAE
HAE
HAE
HAE
recurrent pancreatitis
appendicitis
HAE


Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight.

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1-inhibitor levels, episodically undergoing normalization. Expression studies resulted in a drop in mutant C1-innhibitor secretion compared to wild-type. Notwithstanding, the purified proteins had similar features. Thermal denaturation experiments showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the Arg378Cys C1-inhibitor is secreted as an active, although quite unstable, monomer. However, it could bear a folding defect, occasionally promoting protein oligomerization and interfering with the secretion process, thus accounting for its plasma level variability. This defect is exacerbated by the nature of the mutation since the acquired cysteine leads to the formation of non-functional homodimers through inter-molecular disulphide bonding. All the proposed phenomena could be modulated by specific environmental conditions, rendering this mutant exceptionally vulnerable to mild stress.

    C1-inhibitor
    BIOCHEMICAL

 is a

    serine protease inhibitor (serpin) controlling complement and contact system activation
    BIOCHEMICAL

.

    Gene mutations
    GENETICS

 result in

    reduced C1-inhibitor functional plasma level
    BIOCHEMICAL

 causing

    hereditary angioedema
    DIAGNOSIS

, a

    life-threatening disorder
    DIAGNOSIS

. Despite a stable defect, the clinical expression of

    hereditary angioedema
    DIAGNOSIS

 is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the

    Arg378Cys C1-inhibitor mutant
    GENETICS

 found in a patient presenting

    reduced C1-inhibitor levels
    BIOCHEMICAL

, episodically undergoing

    normalization
    BIOCHEMICAL

.

    Expression studies
    PARACLINICAL

 resulted in a

    drop in mutant C1-innhibitor secretion compared to
    BIOCHEMICAL

 wild-type. Notwithstanding, the purified proteins had similar features.

    Thermal denaturation experiments
    PARACLINICAL

 showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the

    Arg378Cys C1-inhibitor
    GENETICS

 is secreted as an active, although quite unstable, monomer. However, it could bear a folding defect, occasionally promoting protein oligomerization and interfering with the secretion process, thus accounting for its

    plasma level variability
    BIOCHEMICAL

. This defect is exacerbated by the nature of the mutation since the

    acquired cysteine leads to the formation of non-functional homodimers through inter-molecular disulphide bonding
    GENETICS

. All the proposed phenomena could be modulated by specific environmental conditions, rendering this mutant exceptionally vulnerable to mild stress.

hereditary angioedema
life-threatening disorder
hereditary angioedema


[Vulvar angioedema during pregnancy].

Angioedema is a condition of acute and extensive fluid accumulation in skin or mucosae due to increased blood vessel permeability. Angioedema can have several causes, including pregnancy.

A healthy 33-year-old pregnant woman had acute, substantial swelling of the labia minora with no other symptoms. Based on clinical criteria, angioedema was diagnosed. Laboratory testing did not find any C1 inhibitor deficiency and hereditary angioedema was excluded for that reason. The swelling spontaneously disappeared within 2 weeks.

In this case, the cause of the angioedema could not be found and the swelling disappeared on its own. Investigation into the cause may nevertheless be relevant, since choice of therapy depends on the underlying mechanism.

    Angioedema
    DIAGNOSIS

 is a condition of

    acute and extensive fluid accumulation in skin or mucosae
    SYMPTOMS

 due to

    increased blood vessel permeability
    SYMPTOMS

.

    Angioedema
    DIAGNOSIS

 can have several causes, including

    pregnancy
    DIAGNOSIS

.

A healthy

    33-year-old
    AGE

    pregnant
    AGE

    woman
    GENDER

 had

    acute, substantial swelling of the labia minora
    SYMPTOMS

 with

    no other symptoms
    NEG_FINDINGS

. Based on clinical criteria,

    angioedema
    DIAGNOSIS

 was diagnosed.

    Laboratory testing did not find any C1 inhibitor deficiency
    NEG_FINDINGS

 and

    hereditary angioedema was excluded
    NEG_FINDINGS

 for that reason. The

    swelling spontaneously disappeared within 2 weeks
    SYMPTOMS

.

In this case,

    the cause of the angioedema could not be found
    NEG_FINDINGS

 and the

    swelling disappeared on its own
    SYMPTOMS

. Investigation into the cause may nevertheless be relevant, since choice of therapy depends on the underlying mechanism.

Angioedema Angioedema pregnancy angioedema


[Hereditary angioedema by C1 inhibitor-deficit: Diagnostic and therapeutic challenges. Case report].

Hereditary angioedema is a disease which manifests itself with episodes of spontaneous edema on skin, mucosal and airway. Treatment includes acute and prophylactic approach to minimize the attacks and severity. In many parts of the world, androgen derivatives, antifibrinolytic and fresh frozen plasma are the therapies available for prophylaxis.

16 years old teenager of without history of immune decease, has in the course of 1-year repetitive episodes of painless, non-pruritic angioedema, does not respond to antihistamine therapy, corticosteroids or adrenaline; fresh frozen plasma is applied in 1 occasion exacerbating episode with severity. The diagnosis is delayed because of the unavailability of the study in the country, so it is shipped abroad confirming the deficit of C1 Inhibitor (7.1 μg/mL). Initiating prophylactic therapy with Danazol, with subsequent episodes decreased.

The delay diagnosis involves considerable risk in these patients; the importance of long-term prophylactic treatment is ratified in the use of androgens, being as an available option in developing countries.

    Hereditary angioedema
    DIAGNOSIS

 is a disease which manifests itself with

    episodes of spontaneous edema on skin, mucosal and airway
    SYMPTOMS

. Treatment includes

    acute and prophylactic approach
    MEDICATION

 to minimize the attacks and severity. In many parts of the world,

    androgen derivatives, antifibrinolytic and fresh frozen plasma
    MEDICATION

 are the therapies available for

    prophylaxis
    MEDICATION

.

    16 years old
    AGE

    teenager
    AGE

 of

    without history of immune decease
    NEG_FINDINGS

, has in the course of 1-year

    repetitive episodes of painless, non-pruritic angioedema
    SYMPTOMS

,

    does not respond to antihistamine therapy, corticosteroids or adrenaline
    NEG_FINDINGS

;

    fresh frozen plasma
    MEDICATION

 is applied in 1 occasion

    exacerbating episode with severity
    SYMPTOMS

. The diagnosis is delayed because of the unavailability of the study in the country, so it is shipped abroad confirming the

    deficit of C1 Inhibitor (7.1 μg/mL)
    BIOCHEMICAL

. Initiating

    prophylactic therapy with Danazol
    MEDICATION

,

    with subsequent episodes decreased
    SYMPTOMS

.

The delay diagnosis involves considerable risk in these patients; the importance of

    long-term prophylactic treatment
    MEDICATION

 is ratified in the use of

    androgens
    MEDICATION

, being as an available option in developing countries.


Comparison of the Frequency of Angioedema Attack, before and during Pregnancy, in a Patient with Type I Hereditary Angioedema.

The patient was a 38-year-old Japanese woman who had been diagnosed with hereditary angioedema type I at 7 years of age based on her family history. She had undergone four pregnancies. She gave birth to a healthy baby girl after her first pregnancy and had reported few episodes of angioedema. However, she subsequently required abortions due to frequent angioedema episodes that occurred during her three subsequent pregnancies. Thus, our patient showed two clinical pregnancy courses. After treating her with C1-inhibitor concentrate, her symptoms of angioedema disappeared. The preventive use of C1 inhibitor concentrates should be considered in hereditary angioedema (HAE) patients with frequent angioedema attacks during pregnancy.

The patient was a

    38-year-old
    AGE

    Japanese
    ETHNICITY

    woman
    GENDER

 who had been diagnosed with

    hereditary angioedema type I
    DIAGNOSIS

 at

    7 years of age
    AGE

 based on her

    family history
    FAMILY

.

    She
    GENDER

 had

    undergone four pregnancies
    MEDICATION

.

    She
    GENDER

    gave birth to a healthy baby girl after her first pregnancy
    MEDICATION

 and had reported

    few episodes of angioedema
    SYMPTOMS

. However,

    she
    GENDER

 subsequently required

    abortions
    MEDICATION

 due to frequent

    angioedema episodes that occurred during her three subsequent pregnancies
    SYMPTOMS

. Thus, our patient showed

    two clinical pregnancy courses
    SYMPTOMS

. After treating

    her
    GENDER

 with

    C1-inhibitor concentrate
    MEDICATION

,

    her
    GENDER

    symptoms of angioedema disappeared
    SYMPTOMS

. The

    preventive use of C1 inhibitor concentrates
    MEDICATION

 should be considered in

    hereditary angioedema (HAE)
    DIAGNOSIS

 patients with

    frequent angioedema attacks
    SYMPTOMS

 during

    pregnancy
    SYMPTOMS

.

hereditary angioedema type I
hereditary angioedema (HAE)


Multiple doses of icatibant used during pregnancy.

Hereditary angioedema (HAE) is a life-long disease that often manifests by puberty. Treatment of attacks is essential to improve quality of life and to decrease morbidity and mortality. During pregnancy, treatment is limited because multiple treatment options, including icatibant, are not approved for use during pregnancy.

We report the outcomes of three pregnancies during which icatibant was used by a patient with HAE with normal C1-inhibitor for treatment of attacks. We also reviewed the literature for reports of icatibant use during pregnancy for outcomes and adverse events.

We report on a patient who treated herself with icatibant during three separate pregnancies. Postpartum follow-up verified the health of the mother and children. We also performed a complete literature search of medical literature data bases on icatibant use during pregnancy.

The patient in our report administered multiple doses of icatibant during three pregnancies. The child born from the first pregnancy and the child from the third pregnancy were born at term and without congenital anomalies. The child from the second pregnancy was 1-month preterm. All three children were developmentally normal. The literature search identified two case reports and one abstract of limited icatibant use without adverse events during pregnancy in patients with HAE. These pregnancies resulted in the births of healthy infants.

From a search of the literature, three cases of icatibant use during pregnancy resulted in healthy infants. In addition, we report that from icatibant use in three separate pregnancies, one infant was born prematurely, but there were no birth defects. From follow-up, the children continued meeting developmental milestones. This report adds to the acquisition of knowledge for drug adverse events during postmarketing surveillance for icatibant use during pregnancy.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a life-long disease that often manifests by

    puberty
    AGE

. Treatment of attacks is essential to improve quality of life and to decrease morbidity and mortality. During

    pregnancy
    AGE

, treatment is limited because multiple treatment options, including

    icatibant
    MEDICATION

, are not approved for use during

    pregnancy
    AGE

.

We report the outcomes of three

    pregnancies
    MEDICATION

 during which

    icatibant
    MEDICATION

 was used by a patient with

    HAE
    DIAGNOSIS

 with

    normal C1-inhibitor
    NEG_FINDINGS

 for

    treatment of attacks
    NEG_FINDINGS

. We also reviewed the literature for reports of

    icatibant use
    MEDICATION

 during

    pregnancy
    DIAGNOSIS

 for outcomes and adverse events.

We report on a patient who

    treated herself with icatibant during three separate pregnancies
    MEDICATION

.

    Postpartum follow-up
    PARACLINICAL

 verified the health of the mother and children. We also performed a complete literature search of medical literature data bases on

    icatibant use
    MEDICATION

 during

    pregnancy
    MEDICATION

.

The patient in our report

    administered multiple doses of icatibant during three pregnancies
    MEDICATION

. The

    child born from the first pregnancy and the child from the third pregnancy
    MEDICATION

 were born at term and

    without congenital anomalies
    NEG_FINDINGS

. The

    child from the second pregnancy was 1-month preterm
    AGE

. All three children were

    developmentally normal
    SYMPTOMS

. The literature search identified two case reports and one abstract of

    limited icatibant use
    MEDICATION

    without adverse events
    NEG_FINDINGS

 during

    pregnancy
    DIAGNOSIS

 in patients with

    HAE
    DIAGNOSIS

. These

    pregnancies
    MEDICATION

 resulted in the births of healthy infants.

From a search of the literature, three cases of

    icatibant use
    MEDICATION

 during

    pregnancy
    DIAGNOSIS

 resulted in healthy infants. In addition, we report that from

    icatibant use
    MEDICATION

 in three separate

    pregnancies
    DIAGNOSIS

, one

    infant
    AGE

 was

    born prematurely
    SYMPTOMS

, but there were

    no birth defects
    NEG_FINDINGS

. From

    follow-up
    PARACLINICAL

, the children

    continued meeting developmental milestones
    SYMPTOMS

. This report adds to the acquisition of knowledge for

    drug adverse events
    SYMPTOMS

 during

    postmarketing surveillance
    PARACLINICAL

 for

    icatibant use
    MEDICATION

 during

    pregnancy
    DIAGNOSIS

.

Hereditary angioedema (HAE)
HAE
pregnancy
pregnancy
HAE
pregnancy
pregnancies
pregnancy

normal C1-inhibitor
treatment of attacks
without congenital anomalies
without adverse events
no birth defects


Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack.

We studied the kinetics of C1-inhibitor (C1-INH) and other complement parameters in a self-limited edematous attack (EA) in a patient with hereditary angioedema due to C1-INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1-INH concentration and functional activity (C1-INHc+f), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period. The highest C1-INHc+f , C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase, and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1-INH did not increase after resolution of the attack suggesting that factors other than C1-INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs.

We studied the

    kinetics of C1-inhibitor (C1-INH) and other complement parameters
    BIOCHEMICAL

 in a

    self-limited edematous attack (EA)
    SYMPTOMS

 in a patient with

    hereditary angioedema
    DIAGNOSIS

 due to

    C1-INH deficiency
    BIOCHEMICAL

 to better understand the pathomechanism of the evolution, course, and complete resolution of

    EAs
    DIAGNOSIS

.

    C1-INH concentration and functional activity (C1-INHc+f), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period
    BIOCHEMICAL

.

    The highest C1-INHc+f , C4, and C1(q,r,s) levels were measured at baseline
    BIOCHEMICAL

, and

    their continuous decrease
    BIOCHEMICAL

 was observed during the entire observation period.

    C4 depletion
    BIOCHEMICAL

 started at

    prodromal phase
    BIOCHEMICAL

, and

    C4 was lowest after the maximum severity peak
    BIOCHEMICAL

. Compared to baseline,

    C4a level was four times higher 7 hours before the onset of the attack
    BIOCHEMICAL

.

    C1-INH did not increase after resolution of the attack
    BIOCHEMICAL

 suggesting that factors other than

    C1-INH
    BIOCHEMICAL

 may be important in this process.

    C4a
    BIOCHEMICAL

 may be a useful biomarker for the prediction of

    EAs
    DIAGNOSIS

.


Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review of Current Evidence.

Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema can occur at any point during therapy and, when severe, can require mechanical ventilation. Standard agents for anaphylactic reactions have limited efficacy for bradykinin-mediated angioedema and, therefore, agents approved for hereditary angioedema are increasingly prescribed for these patients.

This systematic review critically evaluates evidence describing the off-label use of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), complement 1 esterase inhibitor (C1-INH), icatibant, and ecallantide for treatment of ACEI-induced angioedema.

A PubMed search was conducted and articles were cross-referenced for additional citations. All full-text clinical trials, case series, and case reports published in the English language describing pharmacologic treatment of ACEI-induced angioedema were included. Thirty-seven publications detailing FFP, PCC, and regimens approved for hereditary angioedema, including icatibant, ecallantide, and C1-INH, are reviewed extensively.

While findings of decreased time to symptom resolution or a cessation in symptom progression have been reported with each of these therapies, additional data showing clinically relevant implications, such as reduced intensive care unit length of stay or avoidance of mechanical ventilation, are warranted, especially when taking cost into consideration. FFP has limited evidence demonstrating a benefit for treatment of ACEI-induced angioedema without consistent dosing strategies. However, given its wide availability and low potential for adverse reactions, FFP therapy may be reasonable. Of the novel agents traditionally used for hereditary angioedema, icatibant has the highest level of evidence and has been reported to be successful in limiting the progression of angioedema.

    Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema
    MEDICATION

 can occur at any point during therapy and, when severe, can require

    mechanical ventilation
    MEDICATION

.

    Standard agents for anaphylactic reactions
    NEG_FINDINGS

 have

    limited efficacy for bradykinin-mediated angioedema
    NEG_FINDINGS

 and, therefore, agents approved for

    hereditary angioedema
    DIAGNOSIS

 are increasingly prescribed for these patients.

This systematic review critically evaluates evidence describing the off-label use of

    fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), complement 1 esterase inhibitor (C1-INH), icatibant, and ecallantide
    MEDICATION

 for treatment of

    ACEI-induced angioedema
    DIAGNOSIS

.

A PubMed search was conducted and articles were cross-referenced for additional citations. All full-text clinical trials, case series, and case reports published in the English language describing

    pharmacologic treatment
    MEDICATION

 of

    ACEI-induced angioedema
    DIAGNOSIS

 were included. Thirty-seven publications detailing

    FFP, PCC, and regimens
    MEDICATION

 approved for

    hereditary angioedema
    DIAGNOSIS

, including

    icatibant, ecallantide, and C1-INH
    MEDICATION

, are reviewed extensively.

While findings of

    decreased time to symptom resolution
    SYMPTOMS

 or a

    cessation in symptom progression
    SYMPTOMS

 have been reported with each of these therapies, additional data showing clinically relevant implications, such as

    reduced intensive care unit length of stay
    MEDICATION

 or

    avoidance of mechanical ventilation
    MEDICATION

, are warranted, especially when taking cost into consideration.

    FFP
    MEDICATION

 has limited evidence demonstrating a benefit for treatment of

    ACEI-induced angioedema
    DIAGNOSIS

 without consistent dosing strategies. However, given its wide availability and

    low potential for adverse reactions
    SYMPTOMS

,

    FFP therapy
    MEDICATION

 may be reasonable. Of the novel agents traditionally used for

    hereditary angioedema
    DIAGNOSIS

,

    icatibant
    MEDICATION

 has the highest level of evidence and has been reported to be successful in

    limiting the progression of angioedema
    SYMPTOMS

.

hereditary angioedema
ACEI-induced angioedema
ACEI-induced angioedema
hereditary angioedema
ACEI-induced angioedema
hereditary angioedema

decreased time to symptom resolution
cessation in symptom progression
low potential for adverse reactions
limiting the progression of angioedema


Acute Genital Swelling Heralding C1 Esterase Inhibitor Deficiency in a Child.

A healthy 5-year-old boy presented to the emergency department with an acute genital swelling. He had no relevant family history. His presentation and blood investigations were consistent with C1 esterase inhibitor deficiency, mostly likely arising de novo. A rare cause of acute genital swelling and its management are discussed.

A healthy

    5-year-old
    AGE

    boy
    GENDER

 presented to the emergency department with an

    acute genital swelling
    SYMPTOMS

.

    He
    GENDER

 had

    no relevant family history
    NEG_FINDINGS

. His presentation and

    blood investigations
    PARACLINICAL

 were consistent with

    C1 esterase inhibitor deficiency
    BIOCHEMICAL

, mostly likely arising de novo. A rare cause of

    acute genital swelling
    SYMPTOMS

 and its management are discussed.

acute genital swelling
acute genital swelling


The Complex Interaction Between Polycystic Ovary Syndrome and Hereditary Angioedema: Case Reports and Review of the Literature.

Hereditary angioedema (HAE) is a rare but severe disease, with high risk of death, and attacks have been associated to high estrogen levels. Polycystic ovary syndrome (PCOS) is a common hyperandrogenic condition, which is frequently treated with combined oral contraceptives.

The aim of this study was to describe 2 clinical cases of young women diagnosed as having PCOS who developed HAE attacks after the introduction of combined estrogen-progestin pills to treat PCOS symptoms.

Literature review of sex hormones' role in genesis of HAE attacks and possible mechanisms involved.

In the cases reported, after initiation of combined contraceptives, patients presented with facial swelling with airway involvement (laryngeal edema) and abdominal pain. They had a familial history of angioedema and normal C1 inhibitor (C1-INH) levels, leading to the diagnosis of HAE with normal C1-INH (HAEnC1-INH) or HAE type III. After suspension of exogenous estrogen, patients remained asymptomatic from HAE.

HAEnC1-INH is an estrogen-dependent form of HAE. It is well established that exogenous estrogen triggers attacks of all types of HAE. However, this is the first description of the association between PCOS and HAE, in which PCOS could be masking HAE symptoms. We propose that PCOS might have a protective role regarding HAE attacks, because of its particular hormonal features, that is, hyperandrogenism and relative stable levels of estradiol. The use of combined estrogen-progestin compounds in women with PCOS and HAE must be avoided, and treatment must be individualized.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare but severe disease, with high risk of

    death
    SYMPTOMS

, and attacks have been associated to

    high estrogen levels
    BIOCHEMICAL

.

    Polycystic ovary syndrome (PCOS)
    DIAGNOSIS

 is a common

    hyperandrogenic
    SYMPTOMS

 condition, which is frequently treated with

    combined oral contraceptives
    MEDICATION

.

The aim of this study was to describe 2 clinical cases of

    young
    AGE

    women
    GENDER

 diagnosed as having

    PCOS
    DIAGNOSIS

 who developed

    HAE attacks
    SYMPTOMS

 after the

    introduction of combined estrogen-progestin pills
    MEDICATION

 to treat

    PCOS symptoms
    SYMPTOMS

.

Literature review of

    sex hormones
    SYMPTOMS

' role in

    genesis of HAE attacks
    SYMPTOMS

 and possible mechanisms involved.

In the cases reported, after

    initiation of combined contraceptives
    MEDICATION

, patients presented with

    facial swelling with airway involvement (laryngeal edema)
    SYMPTOMS

 and

    abdominal pain
    SYMPTOMS

. They had a

    familial history of angioedema
    FAMILY

 and

    normal C1 inhibitor (C1-INH) levels
    NEG_FINDINGS

, leading to the diagnosis of

    HAE
    DIAGNOSIS

 with

    normal C1-INH (HAEnC1-INH)
    NEG_FINDINGS

 or

    HAE type III
    DIAGNOSIS

. After

    suspension of exogenous estrogen
    MEDICATION

, patients remained

    asymptomatic from HAE
    NEG_FINDINGS

.

    HAEnC1-INH
    DIAGNOSIS

 is an

    estrogen-dependent form of HAE
    DIAGNOSIS

. It is well established that

    exogenous estrogen
    MEDICATION

 triggers

    attacks of all types of HAE
    SYMPTOMS

. However, this is the first description of the association between

    PCOS
    DIAGNOSIS

 and

    HAE
    DIAGNOSIS

, in which

    PCOS
    DIAGNOSIS

 could be

    masking HAE symptoms
    SYMPTOMS

. We propose that

    PCOS
    DIAGNOSIS

 might have a protective role regarding

    HAE attacks
    SYMPTOMS

, because of its particular hormonal features, that is,

    hyperandrogenism
    SYMPTOMS

 and

    relative stable levels of estradiol
    BIOCHEMICAL

. The use of

    combined estrogen-progestin compounds
    MEDICATION

 in

    women
    GENDER

 with

    PCOS
    DIAGNOSIS

 and

    HAE
    DIAGNOSIS

 must be avoided, and treatment must be individualized.

Hereditary angioedema (HAE)
Polycystic ovary syndrome (PCOS)
PCOS
HAE
HAE type III
HAEnC1-INH
estrogen-dependent form of HAE
PCOS
HAE
PCOS
PCOS
PCOS
HAE

high estrogen levels
relative stable levels of estradiol

normal C1 inhibitor (C1-INH) levels
normal C1-INH (HAEnC1-INH)
asymptomatic from HAE


Angioedema: Perioperative management.

To describe the perioperative management of a patient with acquired angioedema (AAE).

A 66-year-old Caucasian male presented from an outside hospital with a history of acquired angioedema and gastrointestinal stromal tumor-related intractable urticaria and mastocytosis. He was admitted for urgent laparoscopic partial gastrectomy, secondary to gastric outlet obstruction symptomatology. Previous combined attacks were characterized by a widespread rash, abdominal pain and respiratory distress resulting in hospitalization. Following preoperative consultation with the patient's allergist and a hospital pharmacist, he was treated preoperatively with fresh frozen plasma and his home prednisone dose. C1-inhibitor (Berinert®) was on standby along with epinephrine, given that the underlying etiology (C1- inhibitor deficiency vs histaminergic) was not known.

There were no intraoperative complications, and the patient was discharged home 3 days after the procedure.

Optimization of perioperative outcomes in patients, especially during urgent or emergent surgery, with a history of angioedema requires the development of a patient-specific perioperative plan, including prophylaxis, rescue therapies and opioid-sparing strategies.

To describe the perioperative management of a patient with

    acquired angioedema (AAE)
    DIAGNOSIS

.

A

    66-year-old
    AGE

    Caucasian
    ETHNICITY

    male
    GENDER

 presented from an outside hospital with a history of

    acquired angioedema
    DIAGNOSIS

 and

    gastrointestinal stromal tumor-related intractable urticaria
    DIAGNOSIS

 and

    mastocytosis
    DIAGNOSIS

.

    He
    GENDER

 was admitted for

    urgent laparoscopic partial gastrectomy
    MEDICATION

, secondary to

    gastric outlet obstruction symptomatology
    SYMPTOMS

. Previous combined attacks were characterized by a

    widespread rash
    SYMPTOMS

,

    abdominal pain
    SYMPTOMS

 and

    respiratory distress
    SYMPTOMS

 resulting in

    hospitalization
    MEDICATION

. Following preoperative consultation with the patient's

    allergist
    PARACLINICAL

 and a hospital pharmacist,

    he
    GENDER

 was

    treated preoperatively with fresh frozen plasma and his home prednisone dose
    MEDICATION

.

    C1-inhibitor (Berinert®) was on standby along with epinephrine
    MEDICATION

, given that the

    underlying etiology (C1- inhibitor deficiency vs histaminergic) was not known
    NEG_FINDINGS

.

There were

    no intraoperative complications
    NEG_FINDINGS

, and the patient was

    discharged home 3 days after the procedure
    MEDICATION

.

Optimization of perioperative outcomes in patients, especially during urgent or

    emergent surgery
    MEDICATION

, with a history of

    angioedema
    DIAGNOSIS

 requires the development of a patient-specific

    perioperative plan
    MEDICATION

, including

    prophylaxis
    MEDICATION

,

    rescue therapies
    MEDICATION

 and

    opioid-sparing strategies
    MEDICATION

.


Pediatric Hereditary Angioedema as a Cause of Acute Compartment Syndrome of the Hand and Forearm: A Case Report.

Compartment syndrome of the upper extremity is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity hereditary angioedema, an autosomal dominant disease resulting in edema in a variety of potential locations, including the extremities. This is only the second time hereditary angioedema has been mentioned in the literature as a cause of compartment syndrome.

We present a case of hereditary angioedema leading to hand and forearm compartment syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema was made by our Rheumatology colleagues with physical exam and a thorough history, and confirmed by laboratory studies.

Our patient presented with compartment syndrome of the hand and forearm and underwent hand and volar forearm fasciotomies. She was subsequently worked up for hereditary angioedema with laboratory results confirming the diagnosis. She was discharged after a 5-day hospitalization with prophylactic C1-inhibitor therapy.

Hereditary angioedema is a rare but known cause of compartment syndrome of the upper extremity, and must be considered when patients present with compartment syndrome of unknown etiology. This disease can be diagnosed by laboratory studies and symptoms can be controlled with medical therapy.

    Compartment syndrome of the upper extremity
    SYMPTOMS

 is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity

    hereditary angioedema
    DIAGNOSIS

, an

    autosomal dominant disease
    GENETICS

 resulting in

    edema in a variety of potential locations, including the extremities
    SYMPTOMS

. This is only the second time

    hereditary angioedema
    DIAGNOSIS

 has been mentioned in the literature as a cause of

    compartment syndrome
    DIAGNOSIS

.

We present a case of

    hereditary angioedema
    DIAGNOSIS

 leading to

    hand and forearm compartment syndrome
    SYMPTOMS

 in a

    13-year-old
    AGE

    pediatric
    AGE

 patient. Diagnosis of

    hereditary angioedema
    DIAGNOSIS

 was made by our

    Rheumatology colleagues
    PARACLINICAL

 with

    physical exam
    PARACLINICAL

 and a

    thorough history
    PARACLINICAL

, and confirmed by

    laboratory studies
    PARACLINICAL

.

Our patient presented with

    compartment syndrome of the hand and forearm
    SYMPTOMS

 and underwent

    hand and volar forearm fasciotomies
    MEDICATION

.

    She
    GENDER

 was subsequently worked up for

    hereditary angioedema
    DIAGNOSIS

 with

    laboratory results
    PARACLINICAL

 confirming the diagnosis.

    She
    GENDER

 was

    discharged after a 5-day hospitalization
    MEDICATION

 with

    prophylactic C1-inhibitor therapy
    MEDICATION

.

    Hereditary angioedema
    DIAGNOSIS

 is a rare but known cause of

    compartment syndrome of the upper extremity
    SYMPTOMS

, and must be considered when patients present with

    compartment syndrome of unknown etiology
    SYMPTOMS

. This disease can be diagnosed by

    laboratory studies
    PARACLINICAL

 and symptoms can be controlled with

    medical therapy
    MEDICATION

.

hereditary angioedema
hereditary angioedema
compartment syndrome
hereditary angioedema
hereditary angioedema
hereditary angioedema
Hereditary angioedema


Munchausen by proxy syndrome mimicking systemic autoinflammatory disease: case report and review of the literature.

Systemic autoinflammatory diseases (SAIDs) represent a growing number of monogenic, polygenic or multifactorial disorders that are often difficult to diagnose.

Here we report a patient who was initially erroneously diagnosed and treated for SAID. Symptoms consisted of recurrent fever, erythematous and/or blistering skin lesions, angioedema, susceptibility to bleeding, external ear infections and reversible anisocoria in the absence of laboratory evidence of systemic inflammation. After two and a half years of extensive diagnostic work-up and multiple empirical therapies, a final diagnosis of Munchausen by proxy syndrome (MBPS) was established.

The diagnosis of SAID needs to be carefully reassessed if measurable systemic inflammation is missing, and MBPS should be included in the differential diagnosis.

    Systemic autoinflammatory diseases (SAIDs)
    DIAGNOSIS

 represent a growing number of

    monogenic, polygenic or multifactorial disorders
    GENETICS

 that are often difficult to diagnose.

Here we report a patient who was

    initially erroneously diagnosed and treated for SAID
    NEG_FINDINGS

. Symptoms consisted of

    recurrent fever
    SYMPTOMS

,

    erythematous and/or blistering skin lesions
    SYMPTOMS

,

    angioedema
    SYMPTOMS

,

    susceptibility to bleeding
    SYMPTOMS

,

    external ear infections
    SYMPTOMS

 and

    reversible anisocoria
    SYMPTOMS

 in the

    absence of laboratory evidence of systemic inflammation
    NEG_FINDINGS

. After two and a half years of extensive

    diagnostic work-up
    PARACLINICAL

 and

    multiple empirical therapies
    MEDICATION

, a final diagnosis of

    Munchausen by proxy syndrome (MBPS)
    DIAGNOSIS

 was established.

The diagnosis of

    SAID
    DIAGNOSIS

 needs to be carefully reassessed if

    measurable systemic inflammation is missing
    NEG_FINDINGS

, and

    MBPS
    DIAGNOSIS

 should be included in the

    differential diagnosis
    PARACLINICAL

.


MR imaging of intestinal angioedema related to angiotensin-converting enzyme inhibitors: Report of three cases and review of literature.

Angioedema is a condition in which an increase in vascular permeability leads to the swelling of body tissues. There are both hereditary and acquired forms of the disease, with the latter often associated with the administration of angiotensin-converting enzyme inhibitor medication. Involvement of the intestinal tract is a rare manifestation of angioedema, and can present with abdominal pain, nausea, and vomiting. It is critical for radiologists to be aware of this entity, as they may have the only opportunity to make the diagnosis. We present three cases of intestinal angioedema diagnosed on MRI with discussion of the imaging findings.

    Angioedema
    DIAGNOSIS

 is a condition in which an

    increase in vascular permeability
    SYMPTOMS

 leads to the

    swelling of body tissues
    SYMPTOMS

. There are both

    hereditary
    GENETICS

 and acquired forms of the disease, with the latter often associated with the administration of

    angiotensin-converting enzyme inhibitor medication
    MEDICATION

.

    Involvement of the intestinal tract
    SYMPTOMS

 is a rare manifestation of

    angioedema
    DIAGNOSIS

, and can present with

    abdominal pain
    SYMPTOMS

,

    nausea
    SYMPTOMS

, and

    vomiting
    SYMPTOMS

. It is critical for

    radiologists
    PARACLINICAL

 to be aware of this entity, as they may have the only opportunity to make the diagnosis. We present three cases of

    intestinal angioedema
    DIAGNOSIS

 diagnosed on

    MRI
    PARACLINICAL

 with discussion of the imaging findings.

Angioedema
angioedema
intestinal angioedema

increase in vascular permeability
swelling of body tissues
Involvement of the intestinal tract
abdominal pain
nausea
vomiting


[A Case Report of Acute Angioedema that Showed Dramatic Response to Administration of a C1-inactivator].

Angioedema is characterized by rapid and severe swelling of the subcutaneous and submucosal tissues. Angioedema
involving the upper airway can lead to life-threatening airway obstruction, and needs prompt diagnosis and treatment.
Herein, we report a case of acute angioedema which was suspected as having been caused by estrogen imbalance. A 32-year-old woman who was taking a fertility drug for infertility treatment, presented with sudden swelling of the face and
neck region and breathing difficulty. Her symptoms continued to progress despite antibiotic and corticosteroid
administration. We suspected hereditary angioedema (HAE), and administered a C1-inactivator, which led to immediate
and dramatic resolution of the symptoms. Since the C4 and C1-inhibitor levels were normal, the possibility of HAE type
III was considered. However, another possibility was that her complicated hormonal condition, including oral intake of a
fertility drug, menstruation, and mental stress may have led to estrogen imbalance causing angioedema. Currently, a
variety of hormone therapies is widely used ; therefore, caution is needed against the development of estrogen-dependent
angioedema.

    Angioedema
    DIAGNOSIS

 is characterized by

    rapid and severe swelling of the subcutaneous and submucosal tissues
    SYMPTOMS

.

    Angioedema
involving the upper airway
    SYMPTOMS

 can lead to

    life-threatening airway obstruction
    SYMPTOMS

, and needs prompt diagnosis and treatment.
Herein, we report a case of

    acute angioedema
    DIAGNOSIS

 which was suspected as having been caused by

    estrogen imbalance
    BIOCHEMICAL

. A

    32-year-old
    AGE

    woman
    GENDER

 who was

    taking a fertility drug for infertility treatment
    MEDICATION

, presented with

    sudden swelling of the face and
neck region
    SYMPTOMS

 and

    breathing difficulty
    SYMPTOMS

.

    Her
    GENDER

 symptoms

    continued to progress despite antibiotic and corticosteroid
administration
    NEG_FINDINGS

. We suspected

    hereditary angioedema (HAE)
    DIAGNOSIS

, and

    administered a C1-inactivator
    MEDICATION

, which led to

    immediate
and dramatic resolution of the symptoms
    SYMPTOMS

. Since

    the C4 and C1-inhibitor levels were normal
    NEG_FINDINGS

, the possibility of

    HAE type
III
    DIAGNOSIS

 was considered. However, another possibility was that

    her
    GENDER

 complicated

    hormonal condition
    SYMPTOMS

, including

    oral intake of a
fertility drug
    MEDICATION

,

    menstruation
    SYMPTOMS

, and

    mental stress
    SYMPTOMS

 may have led to

    estrogen imbalance
    SYMPTOMS

 causing

    angioedema
    DIAGNOSIS

. Currently, a
variety of

    hormone therapies
    MEDICATION

 is widely used ; therefore, caution is needed against the development of

    estrogen-dependent
angioedema
    NEG_FINDINGS

.


Novel usage of fresh frozen plasma in hereditary angioedema.

Hereditary angioedema (HAE) is a rare and potentially life threatening autosomal dominant disease characterized by recurrent episodes of cutaneous and mucosal oedema. It results from reduced expression or loss of function of CI-esterase inhibitors (C1-INH). As opposed to the more common histamine-mediated angioedema, HAE does not respond well to conventional treatments with anti-histamines, steroids and adrenaline. Early recognition and timely intervention with the correct treatment are crucial particularly preventing airway obstruction. New disease specific treatment including plasma derived or recombinant C1-INH, ecallantide and icatibant have recently emerged and its appropriate use can reduce HAE-associated mortality and morbidity. However due to its costs, these disease specific treatments have yet to reach Malaysia. Despite that no randomized clinical trial on FFP has been performed, its efficacy in treating acute attacks of HAE is only demonstrated in case studies. This case report illustrates the successful treatment of acute HAE episode with FFP in a Malaysian government hospital setting.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a rare and potentially life threatening

    autosomal dominant disease
    GENETICS

 characterized by

    recurrent episodes of cutaneous and mucosal oedema
    SYMPTOMS

. It results from

    reduced expression or loss of function of CI-esterase inhibitors (C1-INH)
    BIOCHEMICAL

. As opposed to the more common

    histamine-mediated angioedema
    DIAGNOSIS

,

    HAE
    DIAGNOSIS

 does

    not respond well to conventional treatments with anti-histamines, steroids and adrenaline
    NEG_FINDINGS

. Early recognition and timely intervention with the correct treatment are crucial particularly preventing

    airway obstruction
    SYMPTOMS

. New

    disease specific treatment including plasma derived or recombinant C1-INH, ecallantide and icatibant
    MEDICATION

 have recently emerged and its appropriate use can reduce

    HAE
    DIAGNOSIS

-associated mortality and morbidity. However due to its costs, these disease specific treatments have yet to reach

    Malaysia
    ETHNICITY

. Despite that no randomized clinical trial on

    FFP
    MEDICATION

 has been performed, its efficacy in treating

    acute attacks of HAE
    SYMPTOMS

 is only demonstrated in case studies. This case report illustrates the successful treatment of

    acute HAE episode
    DIAGNOSIS

 with

    FFP
    MEDICATION

 in a

    Malaysian
    ETHNICITY

 government hospital setting.

Hereditary angioedema (HAE)
histamine-mediated angioedema
HAE
HAE
acute HAE episode


Hereditary angioedema (HAE): a cause for recurrent abdominal pain.

A 44-year-old Hispanic woman presented to the emergency room with a 2-day history of sudden onset of severe cramping left lower quadrant abdominal pain associated with ∼20 episodes diarrhoea. Abdominal CT scan exhibited bowel wall oedema and acute extensive colitis. On the basis of the preliminary diagnosis of acute abdomen, the patient was admitted under the surgical team and treated for acute colitis. Since her family history was significant for hereditary angioedema (HAE), complement studies were performed which revealed low complement C4 levels and abnormally low values of C1q esterase inhibitor. Thus, the diagnosis of HAE type I was established. This case report summarises that the symptoms of HAE are often non-specific, hence making the underlying cause difficult to diagnose.

A

    44-year-old
    AGE

    Hispanic
    ETHNICITY

    woman
    GENDER

 presented to the emergency room with a 2-day history of

    sudden onset of severe cramping left lower quadrant abdominal pain
    SYMPTOMS

 associated with

    ∼20 episodes diarrhoea
    SYMPTOMS

.

    Abdominal CT scan
    PARACLINICAL

 exhibited

    bowel wall oedema
    SYMPTOMS

 and

    acute extensive colitis
    DIAGNOSIS

. On the basis of the preliminary diagnosis of

    acute abdomen
    DIAGNOSIS

, the patient was

    admitted under the surgical team
    MEDICATION

 and treated for

    acute colitis
    DIAGNOSIS

. Since

    her
    GENDER

    family history was significant for hereditary angioedema (HAE)
    FAMILY

,

    complement studies
    PARACLINICAL

 were performed which revealed

    low complement C4 levels
    BIOCHEMICAL

 and

    abnormally low values of C1q esterase inhibitor
    BIOCHEMICAL

. Thus, the diagnosis of

    HAE type I
    DIAGNOSIS

 was established. This case report summarises that the symptoms of

    HAE
    DIAGNOSIS

 are often

    non-specific
    NEG_FINDINGS

, hence making the underlying cause difficult to diagnose.

acute extensive colitis
acute abdomen
acute colitis
HAE type I
HAE


C1-esterase inhibitor for short-term prophylaxis in a patient with hereditary angioedema with normal C1 inhibitor function.

Hereditary angioedema with normal C1-esterase inhibitor (HAE-nC1INH) perioperative is a rare condition which could have potential disastrous ramifications for the anesthesiologist in the perioperative period. However, there is limited evidence and/or guidelines on the optimal way to manage these patients. We present the case of a patient with HAE-nC1INH who was successfully managed in the perioperative period with plasma derived C1-esterase inhibitor (pdC1INH). A 29-year-old woman with a diagnosis of HAE-nC1INH presented to the preoperative consultation in preparation for an upcoming total thyroidectomy. She had a 14-year history of ongoing lip and facial edema sometimes necessitating emergency department visitation. Close consultation with her immunologist, transfusion medicine specialists, and anesthesia care providers allowed for a preoperative plan to provide the patient adequate prophylaxis. Both pdC1INH and tranexamic acid were given preoperatively. The patient underwent surgery with no complications. A multidisciplinary team of clinical immunologists, transfusion medicine specialists, and anesthesiologists facilitated the successful perioperative management of a patient with HAE-nC1INH; pdC1INH may a suitable prophylactic perioperative therapy for this rare patient population.

    Hereditary angioedema with normal C1-esterase inhibitor (HAE-nC1INH) perioperative
    DIAGNOSIS

 is a rare condition which could have potential disastrous ramifications for the anesthesiologist in the perioperative period. However, there is limited evidence and/or guidelines on the optimal way to manage these patients. We present the case of a patient with

    HAE-nC1INH
    DIAGNOSIS

 who was successfully

    managed in the perioperative period with plasma derived C1-esterase inhibitor (pdC1INH)
    MEDICATION

. A

    29-year-old
    AGE

    woman
    GENDER

 with a diagnosis of

    HAE-nC1INH
    DIAGNOSIS

 presented to the

    preoperative consultation
    PARACLINICAL

 in preparation for an upcoming

    total thyroidectomy
    MEDICATION

.

    She
    GENDER

 had a 14-year history of

    ongoing lip and facial edema
    SYMPTOMS

 sometimes necessitating

    emergency department visitation
    PARACLINICAL

. Close consultation with her

    immunologist
    PARACLINICAL

,

    transfusion medicine specialists
    PARACLINICAL

, and

    anesthesia care providers
    PARACLINICAL

 allowed for a

    preoperative plan
    MEDICATION

 to provide the patient

    adequate prophylaxis
    MEDICATION

.

    Both pdC1INH and tranexamic acid were given preoperatively
    MEDICATION

. The patient underwent

    surgery
    MEDICATION

 with

    no complications
    NEG_FINDINGS

. A multidisciplinary team of

    clinical immunologists
    PARACLINICAL

,

    transfusion medicine specialists
    PARACLINICAL

, and

    anesthesiologists
    PARACLINICAL

 facilitated the successful

    perioperative management
    MEDICATION

 of a patient with

    HAE-nC1INH
    DIAGNOSIS

;

    pdC1INH
    MEDICATION

 may a suitable

    prophylactic perioperative therapy
    MEDICATION

 for this rare patient population.


Hereditary haemorrhagic telangiectasia: to transplant or not to transplant - is there a right time for liver transplantation?

Hereditary haemorrhagic telangiectasia is characterized by arterio-venous malformations (AVM). It frequently involves the liver without clinical symptoms, but may lead to biliary ischaemia, portal hypertension, or fatal high-output heart failure. The indication of liver transplantation is controversial.

Herein, we report the case of a 65-year-old female patient with a 'double Osler syndrome' consisting of hereditary haemorrhagic telangiectasia (HHT) and type I hereditary angioedema diagnosed at the age of 25 and 22 years respectively.

Hereditary angioedema was treated with danazol for several decades until multiple hypoechogenic liver masses were detected. Albeit danazol treatment was replaced by C1 esterase inhibitor infusions, hepatocellular carcinoma was diagnosed at the age of 64 and the patient was listed for liver transplantation. HHT was marked by recurrent epistaxis until the age of 63 when severe intestinal bleeding occurred. At the age of 65, severe dyspnoea (NYHA class IV) developed and rapidly progressive high-output cardiac failure was diagnosed. Despite argon plasma coagulation to control bleeding from intestinal angiodysplasia, and treatment with bevacizumab to inhibit angiogenesis, the patient died from severe gastrointestinal bleeding associated with cardiogenic shock at the age of 66 before being transplanted.

The indication to list this patient for liver transplantation was debated several times before the diagnosis of hepatocellular carcinoma because of good general condition and low MELD score. Precise guidelines for screening and management of patients with hepatic HHT need to be better defined.

    Hereditary haemorrhagic telangiectasia
    DIAGNOSIS

 is characterized by

    arterio-venous malformations (AVM)
    SYMPTOMS

. It frequently involves the liver

    without clinical symptoms
    NEG_FINDINGS

, but may lead to

    biliary ischaemia
    SYMPTOMS

,

    portal hypertension
    SYMPTOMS

, or

    fatal high-output heart failure
    SYMPTOMS

. The indication of

    liver transplantation
    MEDICATION

 is controversial.

Herein, we report the case of a

    65-year-old
    AGE

    female
    GENDER

 patient with a '

    double Osler syndrome'
    DIAGNOSIS

 consisting of

    hereditary haemorrhagic telangiectasia (HHT)
    DIAGNOSIS

 and

    type I hereditary angioedema
    DIAGNOSIS

 diagnosed at the

    age of 25 and 22 years
    AGE

 respectively.

    Hereditary angioedema
    DIAGNOSIS

 was

    treated with danazol for several decades
    MEDICATION

 until

    multiple hypoechogenic liver masses
    SYMPTOMS

 were detected. Albeit

    danazol treatment
    MEDICATION

 was replaced by

    C1 esterase inhibitor infusions
    MEDICATION

,

    hepatocellular carcinoma
    DIAGNOSIS

 was diagnosed at the

    age of 64
    AGE

 and the patient was listed for

    liver transplantation
    MEDICATION

.

    HHT
    DIAGNOSIS

 was marked by

    recurrent epistaxis
    SYMPTOMS

 until the

    age of 63
    AGE

 when

    severe intestinal bleeding
    SYMPTOMS

 occurred. At the

    age of 65
    AGE

,

    severe dyspnoea (NYHA class IV)
    SYMPTOMS

 developed and

    rapidly progressive high-output cardiac failure
    SYMPTOMS

 was diagnosed. Despite

    argon plasma coagulation
    MEDICATION

 to

    control bleeding from intestinal angiodysplasia
    SYMPTOMS

, and

    treatment with bevacizumab to inhibit angiogenesis
    MEDICATION

, the patient

    died
    SYMPTOMS

 from

    severe gastrointestinal bleeding associated with cardiogenic shock
    SYMPTOMS

 at the

    age of 66
    AGE

 before being

    transplanted
    MEDICATION

.

The indication to list this patient for

    liver transplantation
    MEDICATION

 was debated several times before the diagnosis of

    hepatocellular carcinoma
    DIAGNOSIS

 because of

    good general condition
    SYMPTOMS

 and

    low MELD score
    BIOCHEMICAL

. Precise guidelines for screening and management of patients with

    hepatic HHT
    DIAGNOSIS

 need to be better defined.


C1 Esterase Inhibitor (Berinert) for ACE Inhibitor-Induced Angioedema: Two Case Reports.

To describe 2 cases of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema treated with C1 esterase inhibitor (human) [Berinert].

Case 1 is a 60-year-old Caucasian male with angioedema from lisinopril. He was initially treated with a conventional regimen of an antihistamine, methylprednisolone, epinephrine, and fresh frozen plasma. When symptoms did not resolve, intravenous C1 peptide esterase inhibitor (C1INH) was administered, with clinical improvement. Four hours later, symptoms returned and the patient underwent emergency tracheostomy. Case 2 is a 64-year-old Caucasian male who presented with angioedema due to enalapril. In the emergency department, he received conventional treatment. Endotracheal tube placement was unsuccessful. While the patient was undergoing intubation in the operating room, intravenous C1INH was administered resulting in quick improvement of symptoms.

Angioedema from ACEI occurs at an incidence of 0.7%. Conventional treatment may be of limited benefit due to the mechanism of the reaction. C1INHs, which are indicated for hereditary angioedema, have been utilized in treating ACEI-induced angioedema. According to the Naranjo algorithm scale, the patient in case 1 experienced angioedema that is probably related to lisinopril. C1INH was administered intravenously when symptoms progressed, despite conventional treatment. In case 2, the patient experienced angioedema, which is possibly related to enalapril, and was treated with C1INH.

C1INH (human) was a successful addition to the traditional management of 2 patients with angioedema due to ACEI.

To describe 2 cases of

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

 treated with

    C1 esterase inhibitor (human)
    MEDICATION

 [Berinert].

Case 1 is a

    60-year-old
    AGE

    Caucasian
    ETHNICITY

    male
    GENDER

 with

    angioedema
    DIAGNOSIS

 from

    lisinopril
    MEDICATION

.

    He
    GENDER

 was initially

    treated with a conventional regimen of an antihistamine, methylprednisolone, epinephrine, and fresh frozen plasma
    MEDICATION

. When

    symptoms did not resolve
    NEG_FINDINGS

,

    intravenous C1 peptide esterase inhibitor (C1INH) was administered
    MEDICATION

, with

    clinical improvement
    SYMPTOMS

. Four hours later,

    symptoms returned
    SYMPTOMS

 and the patient underwent

    emergency tracheostomy
    MEDICATION

. Case 2 is a

    64-year-old
    AGE

    Caucasian
    ETHNICITY

    male
    GENDER

 who presented with

    angioedema
    DIAGNOSIS

 due to

    enalapril
    MEDICATION

. In the emergency department,

    he
    GENDER

    received conventional treatment
    NEG_FINDINGS

.

    Endotracheal tube placement was unsuccessful
    NEG_FINDINGS

. While the patient was

    undergoing intubation in the operating room
    MEDICATION

,

    intravenous C1INH was administered
    MEDICATION

 resulting in

    quick improvement of symptoms
    SYMPTOMS

.

    Angioedema
    DIAGNOSIS

 from

    ACEI
    MEDICATION

 occurs at an incidence of 0.7%.

    Conventional treatment may be of
    NEG_FINDINGS

 limited benefit due to the mechanism of the reaction.

    C1INHs
    MEDICATION

, which are indicated for

    hereditary angioedema
    DIAGNOSIS

, have been utilized in treating

    ACEI-induced angioedema
    DIAGNOSIS

. According to the Naranjo algorithm scale, the patient in case 1 experienced

    angioedema that is probably related to lisinopril
    SYMPTOMS

.

    C1INH was administered intravenously
    MEDICATION

 when symptoms progressed,

    despite conventional treatment
    NEG_FINDINGS

. In case 2, the patient experienced

    angioedema
    DIAGNOSIS

, which is possibly related to

    enalapril
    MEDICATION

, and was treated with

    C1INH
    MEDICATION

.

    C1INH (human)
    MEDICATION

 was a successful

    addition to the traditional management
    MEDICATION

 of 2 patients with

    angioedema
    DIAGNOSIS

 due to

    ACEI
    MEDICATION

.

angioedema
angioedema
Angioedema
hereditary angioedema
ACEI-induced angioedema
angioedema
angioedema