Clinical variation in 2 related children with neuronopathic Gaucher disease.

The clinical features in 2 second cousins with neuronopathic Gaucher disease include slowly progressive ataxia, spasticity, myoclonus, and seizures with relative preservation of intellectual function. Organomegaly was noted only in Patient 1. Both patients had diffuse slowing with paroxysmal features in electroencephalograms and a deficiency of beta-glucosidase activity in leukocytes and skin fibroblast cultures. The parents of Patient 1 and the related father of Patient 2 had levels of beta-glucosidase activity consistent with the carrier state for Gaucher disease. The value of beta-glucosidase activity in the mother of Patient 2 suggests a different mutation, the result being a defective enzyme component not detectable by measuring total activity.

The clinical features in 2

    second cousins with neuronopathic Gaucher disease
    FAMILY

 include

    slowly progressive ataxia
    SYMPTOMS

,

    spasticity
    SYMPTOMS

,

    myoclonus
    SYMPTOMS

, and

    seizures
    SYMPTOMS

 with

    relative preservation of intellectual function
    NEG_FINDINGS

.

    Organomegaly
    SYMPTOMS

 was noted only in Patient 1. Both patients had

    diffuse slowing with paroxysmal features in electroencephalograms
    SYMPTOMS

 and a

    deficiency of beta-glucosidase activity in leukocytes and skin fibroblast cultures
    BIOCHEMICAL

.

    The parents of Patient 1 and the related father of Patient 2 had levels of beta-glucosidase activity consistent with the carrier state for Gaucher disease
    FAMILY

. The

    value of beta-glucosidase activity
    BIOCHEMICAL

 in the mother of Patient 2 suggests a

    different mutation
    GENETICS

, the result being a

    defective enzyme component not detectable by measuring total activity
    BIOCHEMICAL

.


[2 cases of reticulohistiocytosis].

Excerpts from case histories and the results of morphological examinations of organs and tissues of a man of 17 with Letterer-Siwe disease and a man of 26 with Gaucher's disease are presented. Noteworthy is the fact of morphological similarity of eosinophilic granulema and Letterer-Siwe disease and transition of the former into the latter.

Excerpts from case histories and the results of

    morphological examinations of organs and tissues
    PARACLINICAL

 of a

    man
    GENDER

 of 17 with

    Letterer-Siwe disease
    DIAGNOSIS

 and a

    man
    GENDER

 of 26 with

    Gaucher's disease
    DIAGNOSIS

 are presented. Noteworthy is the fact of

    morphological similarity of eosinophilic granulema
    MICROSCOPIC

 and

    Letterer-Siwe disease
    DIAGNOSIS

 and transition of the former into the latter.

Letterer-Siwe disease
Gaucher's disease
Letterer-Siwe disease


Peripheral cryoglobulinemic neuropathy in a patient with Gaucher's disease.

Cryoglobulinemia with peripheral cryoglobulinemic neuropathy is reported in a patient with Gaucher's disease. To the best of our knowledge, a similar relationship has not been previously described. The question whether the cryoglobulinemic neuropathy in this patient is related to Gaucher's disease, or is a mere coincidence, is discussed.

    Cryoglobulinemia with peripheral cryoglobulinemic neuropathy
    DIAGNOSIS

 is reported in a patient with

    Gaucher's disease
    DIAGNOSIS

. To the best of our knowledge, a similar relationship has not been previously described. The question whether the

    cryoglobulinemic neuropathy
    DIAGNOSIS

 in this patient is related to

    Gaucher's disease
    DIAGNOSIS

, or is a mere coincidence, is discussed.


[Gamma heavy chain disease associated with rheumatoid arthritis. Spontaneous disappearance of the pathologic protein].

The authors report the chance discovery in a man aged 53 years with serum positive rheumatoid arthritis, of gamma 3 heavy chain disease. The originality of this case depended on the absence of any detectable lymphoid proliferation and on the transient character of the pathological protein. Only the course after a long follow up will determine whether there is no incipient lymphoid proliferation and whether the heavy chain disease has disappeared permanently.

The authors report the chance discovery in a

    man
    GENDER

    aged 53 years
    AGE

 with

    serum positive rheumatoid arthritis
    BIOCHEMICAL

, of

    gamma 3 heavy chain disease
    DIAGNOSIS

. The originality of this case depended on the

    absence of any detectable lymphoid proliferation
    NEG_FINDINGS

 and on the

    transient character of the pathological protein
    BIOCHEMICAL

. Only the course after a long follow up will determine whether there is

    no incipient lymphoid proliferation
    NEG_FINDINGS

 and whether the

    heavy chain disease
    DIAGNOSIS

 has disappeared permanently.

gamma 3 heavy chain disease
heavy chain disease


Acute bilateral symmetrical pathologic fractures of the lateral tibial plateaus in a patient with Gaucher's disease.

A 41-year-old woman with Gaucher's disease developed bone crises of both proximal tibiae and of her spine concurrent with a syndrome of severe gastroenteritis. Three to six months later the bilateral symmetrical pathologic collapse of both lateral tibial plateaus occurred. The unusual occurrence of multiple bone crises with the gastroenteritis suggests a common causative agent, possibly a severe viremia.

A

    41-year-old
    AGE

    woman
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 developed

    bone crises of both proximal tibiae and of her spine
    SYMPTOMS

 concurrent with a

    syndrome of severe gastroenteritis
    SYMPTOMS

. Three to six months later the

    bilateral symmetrical pathologic collapse of both lateral tibial plateaus
    SYMPTOMS

 occurred. The unusual occurrence of

    multiple bone crises
    SYMPTOMS

 with the

    gastroenteritis
    SYMPTOMS

 suggests a common causative agent, possibly a

    severe viremia
    BIOCHEMICAL

.


Surface marker and other characteristics of Gaucher's cells.

A full surface marker study of the splenic storage cells in a case of Gaucher's disease largely substantiates the monocyte/histiocyte nature of Gaucher's cells. In addition, an apparent T-lymphocyte deficiency is demonstrated in the spleen and peripheral blood, and the possible significance of this finding is discussed.

A

    full surface marker study of the splenic storage cells
    PARACLINICAL

 in a case of

    Gaucher's disease
    DIAGNOSIS

 largely substantiates the

    monocyte/histiocyte nature of Gaucher's cells
    MICROSCOPIC

. In addition, an

    apparent T-lymphocyte deficiency is demonstrated in the spleen and peripheral blood
    BIOCHEMICAL

, and the possible significance of this finding is discussed.


Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation.

A patient with far-advanced adult type Gaucher's disease was treated with solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection. In some instances the enzyme-containing erythrocytes were coated with gamma globulin. No toxic side effects were observed after enzyme infusion. There were suggestive, but not conclusive, findings that enzyme infusion may have been beneficial. After therapy, there was a decrease in transfusion requirement, some improvement of liver function, possible decrease in liver size, and relief of subjective symptoms. Erythrocyte and plasma glucocerebroside levels were unchanged during therapy, but there was a possibly significant decrease in leukocyte and platelet levels of the glycolipid. No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity.

A patient with

    far-advanced adult type Gaucher's disease
    DIAGNOSIS

 was treated with

    solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection
    MEDICATION

. In some instances the

    enzyme-containing erythrocytes were coated with gamma globulin
    MEDICATION

.

    No toxic side effects
    NEG_FINDINGS

 were observed after

    enzyme infusion
    MEDICATION

. There were suggestive, but not conclusive, findings that

    enzyme infusion
    MEDICATION

 may have been beneficial. After therapy, there was a

    decrease in transfusion requirement
    MEDICATION

,

    some improvement of liver function
    SYMPTOMS

,

    possible decrease in liver size
    SYMPTOMS

, and

    relief of subjective symptoms
    SYMPTOMS

.

    Erythrocyte and plasma glucocerebroside levels were unchanged during therapy
    NEG_FINDINGS

, but there was a

    possibly significant decrease in leukocyte and platelet levels of the glycolipid
    BIOCHEMICAL

.

    No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity
    NEG_FINDINGS

.

some improvement of liver function
possible decrease in liver size
relief of subjective symptoms


Severe pulmonary involvement in adult Gaucher's disease. Report of three cases and review of the literature.

Three patients with "adult" Gaucher's disease with severe pulmonary involvement are described. The clinical course of these patients was characterized by hepatosplenomegaly in infancy, followed by the juvenile onset of dyspnea culminating in pulmonary failure and death. Pathologic examination of the lungs in these patients revealed not only massive infiltration of alveolar walls by Gaucher's cells but also clumps of these cells filling alveolar spaces and obliterating functional air exchanging tissue. The lack of neurologic involvement in these cases delineates them from the "juvenile" forms of Gaucher's disease whereas the malignant course and pulmonary involvement were atypical of the "adult" form. The severity of this type of Gaucher's disease makes it a good candidate for prenatal enzymatic diagnosis.

Three patients with

    "adult" Gaucher's disease
    DIAGNOSIS

 with

    severe pulmonary involvement
    SYMPTOMS

 are described. The clinical course of these patients was characterized by

    hepatosplenomegaly
    SYMPTOMS

 in

    infancy
    AGE

, followed by the

    juvenile onset of dyspnea
    SYMPTOMS

 culminating in

    pulmonary failure
    SYMPTOMS

 and

    death
    SYMPTOMS

.

    Pathologic examination of the lungs
    PARACLINICAL

 in these patients revealed not only

    massive infiltration of alveolar walls by Gaucher's cells
    MICROSCOPIC

 but also

    clumps of these cells filling alveolar spaces and obliterating functional air exchanging tissue
    MICROSCOPIC

. The

    lack of neurologic involvement
    NEG_FINDINGS

 in these cases delineates them from the "

    juvenile" forms of Gaucher's disease
    DIAGNOSIS

 whereas the

    malignant course
    SYMPTOMS

 and

    pulmonary involvement
    SYMPTOMS

 were atypical of the "adult" form. The severity of this type of

    Gaucher's disease
    DIAGNOSIS

 makes it a good candidate for

    prenatal enzymatic diagnosis
    AGE

.

"adult" Gaucher's disease
juvenile" forms of Gaucher's disease
Gaucher's disease

severe pulmonary involvement
hepatosplenomegaly
juvenile onset of dyspnea
pulmonary failure
death
malignant course
pulmonary involvement


Treatment of Gaucher's disease with liposome-entrapped glucocerebroside: beta-glucosidase.

An adult with Gaucher's disease was injected with liposomes containing human glucocerebroside: beta-glucosidase. After 13 months of treatment the lower border of the right hepatic lobe and moved up 3 cm, and the left lobe had shrunk. Reduction in the size of the liver was associated with relief of pressure symptoms in the left lower abdomen. Scans obtained after the injection of radiolabelled liposomes suggested improvement in function of the reticuloendothelial system.

An

    adult
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

 was

    injected with liposomes containing human glucocerebroside: beta-glucosidase
    MEDICATION

. After

    13 months of treatment
    MEDICATION

    the lower border of the right hepatic lobe and moved up 3 cm, and the left lobe had shrunk
    SYMPTOMS

.

    Reduction in the size of the liver
    SYMPTOMS

 was associated with

    relief of pressure symptoms in the left lower abdomen
    SYMPTOMS

. Scans obtained after the

    injection of radiolabelled liposomes
    PARACLINICAL

 suggested

    improvement in function of the reticuloendothelial system
    MICROSCOPIC

.


Neuropathic Gaucher's disease with normal 4-methylumbelliferyl-beta-glucosidase activity in the liver.

beta-Glucosidase activity was measured in control subjects and in five patients with neuropathic Gaucher's disease. In three patients with Gaucher's disease, methylumbelliferyl- and p-nitrophenyl-beta-d-glucopyranoside (4MU- and PNP-beta-glucosidase) activity was almost normal in the liver but markedly reduced in the spleen and fibroblasts. In the other patients with Gaucher's disease 4MU- and PNP-beta-glucosidase activity was also very much reduced in the liver, spleen, and fibroblasts. DEAE-cellulose column chromatography with a chloride gradient elution of the liver extract from a control subject and from two patients with Gaucher's disease, exhibiting normal 4MU- and PNP-beta-glucosidase activity, revealed the presence of two peaks of 4MU- and PNP-beta-glucosidase activity (fractions 1 and 2). pH activity curves of beta-glucosidases and Km measured with 4MU-beta-glucoside in fractions 1 and 2 from patients with Gaucher's liver were identical to those from the control liver. However, fractions 1 and 2 from infantile Gaucher's liver exhibited no activity measured with glucocerebroside whereas those from juvenile Gaucher's liver showed a considerable activity. Glucocerebroside was greatly accumulated in the liver, even though an almost normal activity of 4MU-beta-glucosidase was detected in three of the five patients studied.

    beta-Glucosidase activity
    BIOCHEMICAL

 was measured in control subjects and in five patients with

    neuropathic Gaucher's disease
    DIAGNOSIS

. In three patients with

    Gaucher's disease
    DIAGNOSIS

,

    methylumbelliferyl- and p-nitrophenyl-beta-d-glucopyranoside (4MU- and PNP-beta-glucosidase) activity was almost normal in the liver
    BIOCHEMICAL

 but

    markedly reduced in the spleen and fibroblasts
    BIOCHEMICAL

. In the other patients with

    Gaucher's disease
    DIAGNOSIS

    4MU- and PNP-beta-glucosidase activity was also very much reduced in the liver, spleen, and fibroblasts
    BIOCHEMICAL

.

    DEAE-cellulose column chromatography with a chloride gradient elution of the liver extract
    PARACLINICAL

 from a control subject and from two patients with

    Gaucher's disease
    DIAGNOSIS

, exhibiting

    normal 4MU- and PNP-beta-glucosidase activity
    NEG_FINDINGS

, revealed the presence of

    two peaks of 4MU- and PNP-beta-glucosidase activity (fractions 1 and 2)
    BIOCHEMICAL

.

    pH activity curves of beta-glucosidases and Km measured with 4MU-beta-glucoside in fractions 1 and 2
    BIOCHEMICAL

 from patients with

    Gaucher's liver
    MICROSCOPIC

 were identical to those from the control liver. However,

    fractions 1 and 2 from infantile Gaucher's liver
    MICROSCOPIC

 exhibited

    no activity measured with glucocerebroside
    NEG_FINDINGS

 whereas those from

    juvenile Gaucher's liver
    MICROSCOPIC

    showed a considerable activity
    BIOCHEMICAL

.

    Glucocerebroside was greatly accumulated in the liver
    MICROSCOPIC

, even though an

    almost normal activity of 4MU-beta-glucosidase was detected
    NEG_FINDINGS

 in three of the five patients studied.

neuropathic Gaucher's disease
Gaucher's disease
Gaucher's disease
Gaucher's disease


Juvenile Gaucher's disease with horizontal gaze palsy in three siblings.

Three children in a West African family had Gaucher's disease of juvenile onset (Type 3), and all showed an identical neurological disorder. The diagnosis was substantiated by histochemical demonstration of Gaucher cells in bone marrow, liver, and spleen, the finding of an excess of glucosyl ceramides in a liver extract, and a deficient activity of the enzyme beta-glucosidase in cultured skin fibroblasts. The neurological picture was characterised by myoclonic epilepsy, muscle wasting, hypotonia, pyramidal signs, some intellectual deterioration, and a striking disturbance of eye movements. The latter appears to result from specific involvement of the supranuclear pathways subserving lateral gaze. The distinctive features of this clinical syndrome are emphasised.

Three

    children
    AGE

 in a

    West African
    ETHNICITY

 family had

    Gaucher's disease of juvenile onset
    DIAGNOSIS

    (Type 3)
    DIAGNOSIS

, and all showed an

    identical neurological disorder
    SYMPTOMS

. The diagnosis was substantiated by

    histochemical demonstration of Gaucher cells in bone marrow, liver, and spleen
    MICROSCOPIC

, the finding of an

    excess of glucosyl ceramides in a liver extract
    MICROSCOPIC

, and a

    deficient activity of the enzyme beta-glucosidase in cultured skin fibroblasts
    BIOCHEMICAL

. The neurological picture was characterised by

    myoclonic epilepsy
    SYMPTOMS

,

    muscle wasting
    SYMPTOMS

,

    hypotonia
    SYMPTOMS

,

    pyramidal signs
    SYMPTOMS

,

    some intellectual deterioration
    SYMPTOMS

, and a

    striking disturbance of eye movements
    SYMPTOMS

. The latter appears to result from

    specific involvement of the supranuclear pathways subserving lateral gaze
    SYMPTOMS

. The distinctive features of this clinical syndrome are emphasised.


[Esophageal localizations of Crohn's disease].

Oesophageal localisations of Crohn's disease are perhaps not as rare as is classically supposed. The chance discovery of an oesophageal localisation of Crohn's disease led the authors to undertake routine study of the oesophagus in their last 18 patients suffering from the disorder. Each patient underwent endoscopic examination of the oesophagus with multiple biopsies. In 3 of them an oesophageal localisation of Crohn's disease could be demonstrated histologically with in addition, evidence of an epithelioid granuloma in 2 patients out of 3. The value of endoscopic biopsy thus appears to be certain in the diagnosis of this localisation, the influence of which on the course of the disease is not precisely known.

    Oesophageal localisations of Crohn's disease
    SYMPTOMS

 are perhaps not as rare as is classically supposed. The chance discovery of an

    oesophageal localisation of Crohn's disease
    SYMPTOMS

 led the authors to undertake

    routine study of the oesophagus
    PARACLINICAL

 in their last 18 patients suffering from the disorder. Each patient underwent

    endoscopic examination of the oesophagus with multiple biopsies
    PARACLINICAL

. In 3 of them an

    oesophageal localisation of Crohn's disease
    MICROSCOPIC

 could be demonstrated histologically with in addition, evidence of an

    epithelioid granuloma
    MICROSCOPIC

 in 2 patients out of 3. The value of

    endoscopic biopsy
    PARACLINICAL

 thus appears to be certain in the diagnosis of this localisation, the influence of which on the course of the disease is not precisely known.


Infantile Gaucher's disease: neuropathology, acid hydrolase activities and negative staining observations.

A case of infantile Gaucher's disease with widespread cerebral degenerative changes is presented. Neuropathological features included perivascular Gaucher cell infiltrates accompanied by periadventitial fibrogliosis, focal neuronophagia, Purkinje cell vacuolation and diffuse astrocytosis of cerebellar white matter, brain stem and spinal paracentral grey matter. Gaucher cell tubules were isolated from formalin fixed material. Negative staining confirmed the appearance of a coiled helical structure, 200--400 A in diameter composed of microfibrils. A relative deficiency of acid beta-glucosidase was found in spleen homogenate accompanied by a considerable increase in acid phosphohydrolase, N-acetylglucosaminidase, beta-glucuronidase and beta-galactosidase.

A case of

    infantile Gaucher's disease
    DIAGNOSIS

 with

    widespread cerebral degenerative changes
    SYMPTOMS

 is presented.

    Neuropathological
    SYMPTOMS

 features included

    perivascular Gaucher cell infiltrates
    MICROSCOPIC

 accompanied by

    periadventitial fibrogliosis
    MICROSCOPIC

,

    focal neuronophagia
    SYMPTOMS

,

    Purkinje cell vacuolation
    MICROSCOPIC

 and

    diffuse astrocytosis of cerebellar white matter, brain stem and spinal paracentral grey matter
    SYMPTOMS

.

    Gaucher cell tubules were isolated
    MICROSCOPIC

 from

    formalin fixed material
    PARACLINICAL

.

    Negative staining
    PARACLINICAL

 confirmed the

    appearance of a coiled helical structure, 200--400 A in diameter composed of microfibrils
    MICROSCOPIC

. A

    relative deficiency of acid beta-glucosidase was found in spleen homogenate
    BIOCHEMICAL

 accompanied by a

    considerable increase in acid phosphohydrolase, N-acetylglucosaminidase, beta-glucuronidase and beta-galactosidase
    BIOCHEMICAL

.


Coexistence of factor XI (plasma thromboplastin antecedent) deficiency and Gaucher's disease.

The findings of Factor XI (plasma thromboplastin antecedent) deficiency in a patient with Gaucher's disease was investigated. A family study, which included measurements of leukocyte glucocerebrosidase activity and Factor XI levels, revealed that the two genetic disorders segregated independently. One of 12 additional unrelated patients with Gaucher's disease showed a diminished Factor XI level and two of seven unrelated Factor XI-deficient patients showed decreased glucocerebrosidase activity. It is possible that the common occurrence of both genetic disorders results from a high gene frequency of both defects in Ashkenazic Jews.

The findings of

    Factor XI (plasma thromboplastin antecedent) deficiency
    BIOCHEMICAL

 in a patient with

    Gaucher's disease
    DIAGNOSIS

 was investigated. A

    family study
    PARACLINICAL

, which included

    measurements of leukocyte glucocerebrosidase activity and Factor XI levels
    PARACLINICAL

, revealed that the two

    genetic disorders
    GENETICS

 segregated independently. One of 12 additional unrelated patients with

    Gaucher's disease
    DIAGNOSIS

 showed a

    diminished Factor XI level
    BIOCHEMICAL

 and two of seven unrelated

    Factor XI-deficient
    BIOCHEMICAL

 patients showed

    decreased glucocerebrosidase activity
    BIOCHEMICAL

. It is possible that the common occurrence of

    both genetic disorders
    GENETICS

 results from a

    high gene frequency of both defects
    GENETICS

 in

    Ashkenazic Jews
    ETHNICITY

.

genetic disorders
both genetic disorders
high gene frequency of both defects


Factor IX deficiency in Gaucher disease. An in vitro phenomenon.

Low factor IX coagulant activity was demonstrated in a patient with Gaucher disease before and after splenectomy. The same abnormality was found in seven of ten additional patients studied. Possibly, abnormally retained sphingolipids inactivate or interfere with the action of certain procoagulants.

    Low factor IX coagulant activity
    BIOCHEMICAL

 was demonstrated in a patient with

    Gaucher disease
    DIAGNOSIS

 before and after

    splenectomy
    MEDICATION

. The same abnormality was found in seven of ten additional patients studied. Possibly,

    abnormally retained sphingolipids inactivate or interfere with the action of certain procoagulants
    MICROSCOPIC

.


Coexistence of Hodgkin's disease and Gaucher's disease.

A case of Hodgkin's disease associated with long-standing Gaucher's disease is presented and compared with the only previously reported case. The two diseases coexisted in lymph nodes both above and below the diaphragm, liver, bone marrow, and pancreas. The question of a possible relationship of the two diseases is discussed.

A case of

    Hodgkin's disease associated with long-standing Gaucher's disease
    DIAGNOSIS

 is presented and compared with the only previously reported case.

    The two diseases coexisted in lymph nodes both above and below the diaphragm, liver, bone marrow, and pancreas
    MICROSCOPIC

. The question of a possible relationship of the two diseases is discussed.


Ocular manifestations of Gaucher's disease.

A 27-year-old woman not only had the usual clinical and laboratory features of the adult form of Gaucher's disease but also had typical pingueculae and a peculiar lesion with a pigmented temporal edge in the fundus of her left eye. Bone-marrow aspiration demonstrated infiltration by Gaucher's cells and a biopsy of the conjuctival masses disclosed areas of infiltration by Gaucher's cell beneath normal epithelium.

A

    27-year-old
    AGE

    woman
    GENDER

 not only had the

    usual clinical and laboratory features of the adult form of Gaucher's disease
    SYMPTOMS

 but also had

    typical pingueculae
    SYMPTOMS

 and a

    peculiar lesion with a pigmented temporal edge in the fundus of her left eye
    SYMPTOMS

.

    Bone-marrow aspiration
    PARACLINICAL

 demonstrated

    infiltration by Gaucher's cells
    MICROSCOPIC

 and a

    biopsy of the conjuctival masses
    PARACLINICAL

 disclosed

    areas of infiltration by Gaucher's cell beneath normal epithelium
    MICROSCOPIC

.


Combined portal and vena caval hypertension in Gaucher disease: The value of preoperative venography.

Portal hypertension in Gaucher disease is unusual; the seventh known patient with this complication is reported. Prior to portacaval shunting in this child, a localized obstruction of the inferior vena cava at the subdiaphragmatic level was demonstrated by caval manometry and inferior vena cavography. At autopsy, centrilobular hepatic fibrosis seemed to be responsible for the portal hypertension. Nodular enlargement of the right and caudate lobes of the liver was the cause of the caval obstruction; elevated caval resistance may have contributed to the portal hypertension and possibly was responsible for failure of a portacaval anastomosis. The value of preoperative inferior vena cavography in addition to arterial portography in children with portal hypertension is stressed.

    Portal hypertension
    SYMPTOMS

 in

    Gaucher disease
    DIAGNOSIS

 is unusual; the seventh known patient with this complication is reported. Prior to

    portacaval shunting
    MEDICATION

 in this

    child
    AGE

, a

    localized obstruction of the inferior vena cava at the subdiaphragmatic level
    SYMPTOMS

 was demonstrated by

    caval manometry
    PARACLINICAL

 and

    inferior vena cavography
    PARACLINICAL

. At

    autopsy
    PARACLINICAL

,

    centrilobular hepatic fibrosis
    MICROSCOPIC

 seemed to be responsible for the

    portal hypertension
    SYMPTOMS

.

    Nodular enlargement of the right and caudate lobes of the liver
    SYMPTOMS

 was the cause of the

    caval obstruction
    SYMPTOMS

;

    elevated caval resistance
    SYMPTOMS

 may have contributed to the

    portal hypertension
    SYMPTOMS

 and possibly was responsible for

    failure of a portacaval anastomosis
    NEG_FINDINGS

. The value of

    preoperative inferior vena cavography
    PARACLINICAL

 in addition to

    arterial portography
    PARACLINICAL

 in

    children
    AGE

 with

    portal hypertension
    SYMPTOMS

 is stressed.


Infantile Gaucher's disease: glucocerebrosidase deficiency in peripheral blood leukocytes and cultured fibroblasts.

A patient with infantile Gancher's disease is described. A marked decrease of the activity of beta-glucosidase at the lower pH 4.2 was found in peripheral blood leukocytes, whereas in cultured skin fibroblasts the activity at both pH'S 4.2 and 5.2 was decreased. Examining the leukocytes of the heterozygous parents the activities of beta-glucosidase at both pH's were within the values of controls, but the ratio's of activity of pH 5.2 to that at pH 4.2 were increased lying between the ratio's from the patient and controls.

A patient with

    infantile Gancher's disease
    DIAGNOSIS

 is described. A

    marked decrease of the activity of beta-glucosidase at the lower pH 4.2 was found in peripheral blood leukocytes
    BIOCHEMICAL

, whereas

    in cultured skin fibroblasts
    MICROSCOPIC

    the activity at both pH'S 4.2 and 5.2 was decreased
    BIOCHEMICAL

. Examining the leukocytes of the heterozygous parents the

    activities of beta-glucosidase at both pH's were within the values of controls
    BIOCHEMICAL

, but the

    ratio's of activity of pH 5.2 to that at pH 4.2 were increased
    BIOCHEMICAL

 lying between the ratio's from the patient and controls.


Progressive myoclonic epilepsy due to Gaucher's disease in an adult.

A 39 year old Jewish male with a 22 year history of progressive myoclonic epilepsy was found to have Gaucher cells in his sternal bone marrow. The diagnosis of Gaucher's disease was confirmed by the demonstration of beta-glucosidase deficiency in fibroblasts. Although neurological involvement is extremely rare in adults with Gaucher's disease, this disease is another lipidosis which should be considered in patients with progressive myoclonic epilepsy.

A

    39 year old
    AGE

    Jewish
    ETHNICITY

    male
    GENDER

 with a 22 year history of

    progressive myoclonic epilepsy
    SYMPTOMS

 was found to have

    Gaucher cells in his sternal bone marrow
    MICROSCOPIC

. The diagnosis of

    Gaucher's disease
    DIAGNOSIS

 was confirmed by the demonstration of

    beta-glucosidase deficiency in fibroblasts
    BIOCHEMICAL

. Although

    neurological involvement
    SYMPTOMS

 is extremely rare in

    adults
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

, this disease is another

    lipidosis
    DIAGNOSIS

 which should be considered in patients with

    progressive myoclonic epilepsy
    SYMPTOMS

.

progressive myoclonic epilepsy
neurological involvement
progressive myoclonic epilepsy

Gaucher's disease
Gaucher's disease
lipidosis


Gaucher's disease associated with chronic lymphocytic leukaemia, gout and carcinoma.

A case report of Gaucher's disease associated with chronic lymphocytic leukaemia is described in a patient with gout and carcinoma of the sigmoid colon. This the first reported case of Gaucher's disease associated with chronic lymphocytic leukaemia.

A case report of

    Gaucher's disease associated with chronic lymphocytic leukaemia
    DIAGNOSIS

 is described in a patient with

    gout
    DIAGNOSIS

 and

    carcinoma of the sigmoid colon
    SYMPTOMS

. This the first reported case of

    Gaucher's disease associated with chronic lymphocytic leukaemia
    DIAGNOSIS

.


Gaucher's disease and benign monoclonal gammapathy. A case report with immunofluorescence study of bone marrow and spleen.

A case of chronic non-neuronopathic Gaucher's disease is presented. The diagnosis was based on the finging of typical Gaucher cells in the bone marrow spleen. The patient also had a benign monoclonal gammapathy. Immunofluorescence studies of bone marrow and spleen were performed using monospecif antisera against immunoglobulin heavy and light chains. The results indicate a monoclonal plasma cell proliferation in the bone marrow, whereas the distribution of plasma cells in the spleen was polyclonal. The combination of chronic Gaucher's disease and monoclonal gammapathy was also found in the patient's brother.

A case of

    chronic non-neuronopathic Gaucher's disease
    DIAGNOSIS

 is presented. The diagnosis was based on the

    finging of typical Gaucher cells in the bone marrow spleen
    MICROSCOPIC

. The patient also had a

    benign monoclonal gammapathy
    DIAGNOSIS

.

    Immunofluorescence studies of bone marrow and spleen
    PARACLINICAL

 were performed using

    monospecif antisera against immunoglobulin heavy and light chains
    BIOCHEMICAL

. The results indicate a

    monoclonal plasma cell proliferation in the bone marrow
    MICROSCOPIC

, whereas the

    distribution of plasma cells in the spleen was polyclonal
    MICROSCOPIC

. The

    combination of chronic Gaucher's disease and monoclonal gammapathy
    FAMILY

    was also found in the patient's brother
    FAMILY

.


Haemorrhagic pericardial effusion in adult Gaucher's disease.

A case of adult Gaucher's disease presenting with haemorrhagic pericardial effusion is reported. Three similar cases have been reported. The possible aetiological factors in this case are assessed, the likely cause being thrombocytopenia due to hypersplenism associated with Gaucher's disease.

A case of

    adult
    AGE

    Gaucher's disease
    DIAGNOSIS

 presenting with

    haemorrhagic pericardial effusion
    SYMPTOMS

 is reported. Three similar cases have been reported. The possible aetiological factors in this case are assessed, the likely cause being

    thrombocytopenia due to hypersplenism
    BIOCHEMICAL

 associated with

    Gaucher's disease
    MICROSCOPIC

.


Oral Surgery Procedures in a Patient Affected by Hereditary Angioedema Type I.

Hereditary Angioedema (HAE) is a rare disease characterized by a deficiency or a reduced function of the plasma protein C1 esterase inhibitor (C1-INH), which is involved in the downregulation of several inflammatory pathways. Patients affected by HAE suffer from episodic swellings of subcutaneous or submucosal tissues. Swellings can be caused by stress or dental and surgical procedures and can be life-threatening if the airways are involved. We have reported a clinical case of a patient affected by HAE type I who underwent oral surgery procedures under a short-term prophylaxis with C1-INH plasma-derived concentrate. The patient underwent a cyst removal, multiple tooth extractions, and an excisional biopsy with a prophylaxis with C1-INH plasma-derived concentrate and was hospitalized for 36 hours after the surgery to be monitored for possible HAE attacks. During the hospitalization, the patient did not show signs of swelling nor of HAE attacks. At 14 and 28 days after the surgery, the patient presented a good surgical healing. The prophylactic intravenous infusion of C1-INH concentrate was successful in preventing acute HAE attacks after oral surgery procedures.

    Hereditary Angioedema (HAE)
    DIAGNOSIS

 is a rare disease characterized by a

    deficiency or a reduced function of the plasma protein C1 esterase inhibitor (C1-INH)
    BIOCHEMICAL

, which is involved in the

    downregulation of several inflammatory pathways
    BIOCHEMICAL

. Patients affected by

    HAE
    DIAGNOSIS

 suffer from

    episodic swellings of subcutaneous or submucosal tissues
    SYMPTOMS

.

    Swellings
    SYMPTOMS

 can be caused by

    stress
    SYMPTOMS

 or

    dental and surgical procedures
    MEDICATION

 and can be

    life-threatening
    SYMPTOMS

 if the

    airways are involved
    SYMPTOMS

. We have reported a clinical case of a patient affected by

    HAE type I
    DIAGNOSIS

 who underwent

    oral surgery procedures
    MEDICATION

    under a short-term prophylaxis with C1-INH plasma-derived concentrate
    MEDICATION

. The patient underwent a

    cyst removal
    MEDICATION

,

    multiple tooth extractions, and an excisional biopsy
    MEDICATION

    with a prophylaxis with C1-INH plasma-derived concentrate
    MEDICATION

 and was

    hospitalized for 36 hours after the surgery
    MEDICATION

 to be monitored for possible

    HAE attacks
    SYMPTOMS

. During the hospitalization, the patient did

    not show signs of swelling nor of HAE attacks
    NEG_FINDINGS

. At 14 and 28 days after the surgery, the patient presented a

    good surgical healing
    SYMPTOMS

. The

    prophylactic intravenous infusion of C1-INH concentrate
    MEDICATION

 was successful in preventing

    acute HAE attacks
    SYMPTOMS

 after

    oral surgery procedures
    MEDICATION

.

Hereditary Angioedema (HAE)
HAE
HAE type I


An anesthetic experience of hereditary angioedema type I patient undertook total laparoscopic hysterectomy - A case report.

Hereditary angioedema (HAE) is an autosomal dominant disorder. The characteristic of HAE is recurrent angioedema episodes due to low C1 esterase inhibitor (C1-INH) level. HAE symptoms, especially those affecting oropharynx or larynx may develop respiratory distress syndrome due to impaired airway, which can be potentially fatal.

We report a clinical case of a 57 year-old female patient, with type I HAE, scheduled for total laparoscopic hysterectomy under general endotracheal anesthesia, which was done successfully without inducing airway edema. Danazol, which increases liver synthesis of C1- INH, was administered and fresh frozen plasma (FFP), which contained C1-INH, was transfused after induction.

For HAE patients, the greatest concern is that general anesthesia can induces upper airway edema by direct mucosal irritation by the endotracheal tube. The perioperative management should include both prophylactic increase of C1-INH production and on-demand administration of C1-INH or FFP.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

. The characteristic of

    HAE
    DIAGNOSIS

 is

    recurrent angioedema episodes
    SYMPTOMS

 due to

    low C1 esterase inhibitor (C1-INH) level
    BIOCHEMICAL

.

    HAE symptoms
    SYMPTOMS

, especially

    those affecting oropharynx or larynx
    SYMPTOMS

 may develop

    respiratory distress syndrome
    SYMPTOMS

 due to

    impaired airway
    SYMPTOMS

, which can be potentially fatal.

We report a clinical case of a

    57 year-old
    AGE

    female
    GENDER

 patient, with

    type I HAE
    DIAGNOSIS

, scheduled for

    total laparoscopic hysterectomy
    MEDICATION

 under

    general endotracheal anesthesia
    MEDICATION

, which was done successfully

    without inducing airway edema
    NEG_FINDINGS

.

    Danazol, which increases liver synthesis of C1- INH
    MEDICATION

, was administered and

    fresh frozen plasma (FFP), which contained C1-INH, was transfused after induction
    MEDICATION

.

For

    HAE
    DIAGNOSIS

 patients, the greatest concern is that

    general anesthesia
    MEDICATION

 can induces

    upper airway edema by direct mucosal irritation by the endotracheal tube
    SYMPTOMS

. The

    perioperative management
    MEDICATION

 should include both

    prophylactic increase of C1-INH production and on-demand administration of C1-INH or FFP
    MEDICATION

.

Hereditary angioedema (HAE)
HAE
type I HAE
HAE


A Rare Case of Dulaglutide-Associated Angioedema in a Male Patient.

Dulaglutide is an injectable glucagon-like peptide-1 receptor agonist approved for the treatment of adults with type 2 diabetes. Angioedema is defined as self-limiting edema, localized in the deeper layers of the skin and mucosa. Angioedema can be hereditary or acquired which can be allergic due to reactions to foods, insect bites and stings, and latex, drug-induced, caused by physical stimuli and associated with lupus erythematosus and hypereosinophilia. Angioedema represents a rare adverse event of glucagon-like peptide-1 receptor agonists. The only glucagon-like peptide-1 receptor agonist that has been mentioned to induce angioedema in literature is exenatide. We report the first case of dulaglutide-associated angioedema in a 72-year-old male in order to point out to the clinicians this potential rare side effect of this drug and its clinical significance.

    Dulaglutide
    MEDICATION

 is an

    injectable glucagon-like peptide-1 receptor agonist
    MEDICATION

 approved for the treatment of

    adults
    AGE

 with

    type 2 diabetes
    DIAGNOSIS

.

    Angioedema
    DIAGNOSIS

 is defined as

    self-limiting edema, localized in the deeper layers of the skin and mucosa
    SYMPTOMS

.

    Angioedema
    DIAGNOSIS

 can be

    hereditary
    GENETICS

 or

    acquired
    DIAGNOSIS

 which can be

    allergic due to reactions to foods, insect bites and stings, and latex
    SYMPTOMS

,

    drug-induced
    DIAGNOSIS

, caused by

    physical stimuli
    SYMPTOMS

 and associated with

    lupus erythematosus
    DIAGNOSIS

 and

    hypereosinophilia
    DIAGNOSIS

.

    Angioedema
    DIAGNOSIS

 represents a rare adverse event of

    glucagon-like peptide-1 receptor agonists
    MEDICATION

. The only

    glucagon-like peptide-1 receptor agonist
    MEDICATION

 that has been mentioned to induce

    angioedema
    SYMPTOMS

 in literature is

    exenatide
    MEDICATION

. We report the first case of

    dulaglutide-associated angioedema
    MEDICATION

 in a

    72-year-old
    AGE

    male
    GENDER

 in order to point out to the clinicians this potential rare side effect of this drug and its clinical significance.

type 2 diabetes
Angioedema
Angioedema
acquired
drug-induced
lupus erythematosus
hypereosinophilia
Angioedema


Hereditary Angioedema: A Gynecology and Obstetrics Perspective.

Hereditary angioedema is an autosomal dominant genetic disease that causes tissue edema mediated by bradykinin. The angioedema attacks have several triggers including stress, trauma, infection, and increased estrogens levels. This explains the greater incidence and clinical severity in women, which are usually asymptomatic until puberty, when the attacks begin to occur. It may involve multiple locations on the body, leading to complications, such as surgical intervention prompt by severe acute abdominal pain, and laryngeal edema that can culminate in death from asphyxia. This is of particular concern as this angioedema does not respond to life-saving medications commonly used in its treatment, namely, high doses of second-generation antihistamines, corticosteroids, and epinephrine. Hereditary angioedema attacks are treated with specific medication that includes icatibant, ecallantide, and C1 inhibitor, the latter being also used in short-term and long-term prophylaxis. There are other pharmacological strategies for long-term prophylaxis like lanadelumab, danazol, stanozolol, aminocaproic acid, and tranexamic acid. During pregnancy and lactation, the preferred treatment and prophylaxis is C1 inhibitor. We report a case of hereditary angioedema describing its chronological evolution over a period of a woman's life, and highlighting some of the specificities of this pathology that intersect with the specialty of Obstetrics and Gynecology. Our aim is to draw attention to these particularities, namely the triggering factors of crisis, the need for high suspicion of the diagnosis, and the treatment and prophylaxis options for pregnant and non-pregnant women that can make the difference between life and death. To achieve a favorable outcome, the multidisciplinary teamwork between the specialties of Immunoallergology and Obstetrics and Gynecology was crucial.

    Hereditary angioedema
    DIAGNOSIS

 is an

    autosomal dominant genetic disease
    GENETICS

 that causes

    tissue edema
    SYMPTOMS

 mediated by

    bradykinin
    BIOCHEMICAL

. The

    angioedema attacks
    SYMPTOMS

 have several triggers including

    stress
    SYMPTOMS

,

    trauma
    SYMPTOMS

,

    infection
    SYMPTOMS

, and

    increased estrogens levels
    BIOCHEMICAL

. This explains the greater incidence and clinical severity in

    women
    GENDER

, which are usually

    asymptomatic
    NEG_FINDINGS

 until

    puberty
    AGE

, when the attacks begin to occur. It may involve

    multiple locations on the body
    SYMPTOMS

, leading to complications, such as

    surgical intervention
    MEDICATION

 prompt by

    severe acute abdominal pain
    SYMPTOMS

, and

    laryngeal edema
    SYMPTOMS

 that can culminate in

    death
    SYMPTOMS

 from

    asphyxia
    SYMPTOMS

. This is of particular concern as this

    angioedema
    DIAGNOSIS

    does not respond to life-saving medications commonly used in its treatment, namely, high doses of second-generation antihistamines, corticosteroids, and epinephrine
    NEG_FINDINGS

.

    Hereditary angioedema attacks
    DIAGNOSIS

 are treated with

    specific medication that includes icatibant, ecallantide, and C1 inhibitor
    MEDICATION

, the latter being also used

    in short-term and long-term prophylaxis
    MEDICATION

. There are other

    pharmacological strategies for long-term prophylaxis
    MEDICATION

 like

    lanadelumab, danazol, stanozolol, aminocaproic acid, and tranexamic acid
    MEDICATION

. During

    pregnancy
    AGE

 and

    lactation
    AGE

, the preferred

    treatment and prophylaxis
    MEDICATION

 is

    C1 inhibitor
    MEDICATION

. We report a case of

    hereditary angioedema
    DIAGNOSIS

 describing its chronological evolution over a period of a

    woman
    GENDER

's life, and highlighting some of the specificities of this pathology that intersect with the specialty of Obstetrics and

    Gynecology
    PARACLINICAL

. Our aim is to draw attention to these particularities, namely the triggering factors of crisis, the need for high suspicion of the diagnosis, and the treatment and prophylaxis options for

    pregnant
    AGE

 and

    non-pregnant
    AGE

    women
    GENDER

 that can make the difference between life and

    death
    SYMPTOMS

. To achieve a favorable outcome, the

    multidisciplinary teamwork between the specialties of Immunoallergology and Obstetrics and Gynecology
    MEDICATION

 was crucial.

Hereditary angioedema
angioedema
Hereditary angioedema attacks
hereditary angioedema

tissue edema
angioedema attacks
stress
trauma
infection
multiple locations on the body
severe acute abdominal pain
laryngeal edema
death
asphyxia
death


Abdominal hereditary angio-oedema caught on magnetic resonance imaging.

A 17-year-old woman presented with a 3-year history of recurrent, severe abdominal pain with spontaneous resolution within a few days. An ultrasound revealed nothing more than free fluid within the pelvis. An MRI of the small bowel was done within 24 hours of abdominal pain onset, which revealed extensive submucosal oedema associated with moderate volume ascites. A repeat MRI of the small bowel after 72 hours showed near-complete resolution of these changes. Checking C1 inhibitor levels confirmed a diagnosis of hereditary angio-oedema with an abdominal presentation. This is a rare cause of recurrent abdominal pain and, to our knowledge, the first case in which MR images have been obtained during and after an acute attack.

A

    17-year-old
    AGE

    woman
    GENDER

 presented with a 3-year history of

    recurrent, severe abdominal pain
    SYMPTOMS

 with

    spontaneous resolution within a few days
    SYMPTOMS

. An

    ultrasound
    PARACLINICAL

 revealed

    nothing more than free fluid within the pelvis
    NEG_FINDINGS

. An

    MRI of the small bowel
    PARACLINICAL

 was done within 24 hours of

    abdominal pain onset
    SYMPTOMS

, which revealed

    extensive submucosal oedema associated with moderate volume ascites
    SYMPTOMS

. A

    repeat MRI of the small bowel after 72 hours
    PARACLINICAL

 showed

    near-complete resolution of these changes
    SYMPTOMS

.

    Checking C1 inhibitor levels
    BIOCHEMICAL

 confirmed a diagnosis of

    hereditary angio-oedema
    DIAGNOSIS

 with an

    abdominal presentation
    SYMPTOMS

. This is a rare cause of

    recurrent abdominal pain
    SYMPTOMS

 and, to our knowledge, the first case in which

    MR images
    PARACLINICAL

 have been obtained during and after an

    acute attack
    SYMPTOMS

.


[Prophylaxis in hereditary angioedema with normal C1 inhibitor].

Hereditary angioedema is an infrequent genetic disorder; which mainly manifests with cutaneous and mucosal swelling. Minor trauma may trigger potentially life-threatening events. In type I and II hereditary angioedema, plasma-derived C1-inhibitor concentrate can be used as short-term prophylaxis. For hereditary angioedema, prophylaxis is not yet standardized, but normal C1 inhibitor could be beneficial.

A 69-year-old woman, with a genetic diagnosis of hereditary angioedema with normal C1 inhibitor, who needed multiple dental extractions. The surgical procedure was performed under general anesthesia, using 1000 U of plasma-derived C1-inhibitor concentrate as prophylaxis an hour before. The patient was admitted in the ICU for postsurgical care and the outcome was good.

We highlight the possibility of successfully using plasma-derived C1-inhibitor concentrate as prophylaxis in patients with hereditary angioedema with normal C1 inhibitor.

    Hereditary angioedema
    DIAGNOSIS

 is an

    infrequent genetic disorder
    GENETICS

; which mainly manifests with

    cutaneous and mucosal swelling
    SYMPTOMS

.

    Minor trauma
    SYMPTOMS

 may trigger

    potentially life-threatening events
    SYMPTOMS

. In

    type I and II hereditary angioedema
    DIAGNOSIS

,

    plasma-derived C1-inhibitor concentrate
    MEDICATION

 can be used as

    short-term prophylaxis
    MEDICATION

. For

    hereditary angioedema
    DIAGNOSIS

,

    prophylaxis
    MEDICATION

 is not yet standardized, but

    normal C1 inhibitor
    BIOCHEMICAL

 could be beneficial.

A

    69-year-old
    AGE

    woman
    GENDER

, with a genetic diagnosis of

    hereditary angioedema
    DIAGNOSIS

 with

    normal C1 inhibitor
    NEG_FINDINGS

, who needed

    multiple dental extractions
    MEDICATION

. The

    surgical procedure
    MEDICATION

 was performed

    under general anesthesia
    MEDICATION

,

    using 1000 U of plasma-derived C1-inhibitor concentrate as prophylaxis an hour before
    MEDICATION

. The patient was

    admitted in the ICU for postsurgical care
    MEDICATION

 and the outcome was good.

We highlight the possibility of successfully using

    plasma-derived C1-inhibitor concentrate as prophylaxis
    MEDICATION

 in patients with

    hereditary angioedema
    DIAGNOSIS

 with

    normal C1 inhibitor
    NEG_FINDINGS

.

Hereditary angioedema
type I and II hereditary angioedema
hereditary angioedema
hereditary angioedema
hereditary angioedema

cutaneous and mucosal swelling
Minor trauma
potentially life-threatening events


Patient and caregiver perspectives on transitioning to oral prophylaxis in the emerging hereditary angioedema treatment landscape.

This report describes the successful transition of two familial patients with HAE from injectable to oral prophylaxis without tapering prior therapy or employing a complex transition protocol.

This report describes the successful transition of two familial patients with

    HAE
    DIAGNOSIS

    from injectable to oral prophylaxis
    MEDICATION

    without tapering prior therapy or employing a complex transition protocol
    NEG_FINDINGS

.


Tranexamic acid for ACE inhibitor induced angioedema - A case report.

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

    Tranexamic acid (TXA) is an antifibrinolytic agent
    MEDICATION

 which

    inhibits conversion of plasminogen to plasmin
    BIOCHEMICAL

, a key step in

    kallikrein activation and bradykinin formation
    BIOCHEMICAL

.

    Tranexamic acid
    MEDICATION

 is used in

    prophylactic management
    MEDICATION

 of

    hereditary angioedema
    DIAGNOSIS

; however, evidence for

    TXA
    MEDICATION

 in

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

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

    ACEI-AE
    DIAGNOSIS

 who was successfully treated with

    TXA
    MEDICATION

. This case suggests that

    TXA
    MEDICATION

 may be a beneficial treatment modality in the management of

    ACEI-AE
    DIAGNOSIS

 and warrants further investigation.


Resolution of Laryngeal Oedema in a Patient with Acquired C1-Inhibitor Deficiency. a Case Report.

Laryngeal oedema caused by acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a life-threatening condition. The swelling is bradykinin mediated and will not respond to the usual treatment with antihistamines, corticosteroids, or epinephrine. Instead, kallikrein-bradykinin-targeted therapies should be used promptly to prevent asphyxiation.

A 43 years old female presented at the Hereditary Angioedema Centre reporting a one-year history of peripheral, facial, and neck oedema. Treatment with antihistamines and corticosteroids had been ineffective. Laboratory results showed complement level deficiencies and monoclonal gammopathy characterised as immunoglobulin M. An abdominal ultrasound revealed splenomegaly. A bone marrow biopsy was normal. Based on these data, the diagnosis of C1-INH-AAE associated with monoclonal gammopathy of uncertain significance (MGUS) was made. As C1-INH-AAE can present with life-threatening, standard treatment-resistant laryngeal oedema, an emergency care treatment plan was proposed, and the patient was advised to present to the emergency department (ED) with this medical letter. Based on these recommendations, three laryngeal attacks were successfully treated in the ED with recombinant human C1-inhibitor (two attacks) and fresh frozen plasma (one attack). After these episodes, the patient was prescribed prophylactic treatment with antifibrinolytics. No further angioedema attacks were reported by the patient at the 18 months follow-up visit.

Because angioedema of the upper airways is a life-threatening condition, recognising the specific type of swelling by the emergency physician is critical in providing immediate and effective treatment to reduce the associated risk of asphyxiation. C1-INH-AAE being a rare disorder, patients should have available an emergency care treatment plan with recommendations of acute treatment possibilities.

    Laryngeal oedema
    SYMPTOMS

 caused by

    acquired angioedema due
    DIAGNOSIS

 to

    C1-inhibitor deficiency (C1-INH-AAE)
    BIOCHEMICAL

 is a life-threatening condition. The

    swelling
    SYMPTOMS

 is

    bradykinin mediated
    BIOCHEMICAL

 and

    will not respond to the usual treatment with antihistamines, corticosteroids, or epinephrine
    NEG_FINDINGS

. Instead,

    kallikrein-bradykinin-targeted therapies
    MEDICATION

 should be used promptly to prevent

    asphyxiation
    SYMPTOMS

.

A

    43 years old
    AGE

    female
    GENDER

 presented at the Hereditary

    Angioedema
    DIAGNOSIS

 Centre reporting a

    one-year history of peripheral, facial, and neck oedema
    SYMPTOMS

.

    Treatment with antihistamines and corticosteroids had been ineffective
    NEG_FINDINGS

.

    Laboratory results
    PARACLINICAL

 showed

    complement level deficiencies
    BIOCHEMICAL

 and monoclonal gammopathy characterised as immunoglobulin M. An

    abdominal ultrasound
    PARACLINICAL

 revealed

    splenomegaly
    SYMPTOMS

. A

    bone marrow biopsy was normal
    NEG_FINDINGS

. Based on these data, the diagnosis of

    C1-INH-AAE associated with monoclonal gammopathy of uncertain significance (MGUS)
    DIAGNOSIS

 was made. As

    C1-INH-AAE
    DIAGNOSIS

 can present with

    life-threatening, standard treatment-resistant laryngeal oedema
    SYMPTOMS

, an

    emergency care treatment plan
    MEDICATION

 was proposed, and the patient was advised to present to the emergency department (ED) with this medical letter. Based on these recommendations, three

    laryngeal attacks
    SYMPTOMS

 were successfully treated in the ED with

    recombinant human C1-inhibitor
    MEDICATION

 (two attacks)

    and fresh frozen plasma
    MEDICATION

 (one attack). After these episodes, the patient was prescribed

    prophylactic treatment with antifibrinolytics
    MEDICATION

.

    No further angioedema attacks
    NEG_FINDINGS

 were reported by the patient at the 18 months follow-up visit.

Because

    angioedema of the upper airways
    SYMPTOMS

 is a life-threatening condition, recognising the specific type of swelling by the

    emergency physician
    PARACLINICAL

 is critical in providing immediate and effective treatment to reduce the associated risk of

    asphyxiation
    SYMPTOMS

.

    C1-INH-AAE
    DIAGNOSIS

 being a

    rare disorder
    DIAGNOSIS

, patients should have available an

    emergency care treatment plan
    MEDICATION

 with recommendations of acute treatment possibilities.

C1-inhibitor deficiency (C1-INH-AAE)
bradykinin mediated
complement level deficiencies


Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis.

Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population.

To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases.

A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed.

Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses.

Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger's tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important.

The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.

Currently there is no systematic review and meta-analysis of the global incidence rates of

    anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines
    SYMPTOMS

 in the general adult population.

To estimate the incidence rates of

    anaphylactic and nonanaphylactic reactions
    SYMPTOMS

 after

    COVID-19 vaccines
    MEDICATION

 and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases.

Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination:

    anaphylaxis
    DIAGNOSIS

,

    non-anaphylaxis
    DIAGNOSIS

,

    anaphylactic reaction
    SYMPTOMS

,

    nonanaphylactic reaction
    SYMPTOMS

,

    anaphylactic/anaphylactoid shock
    DIAGNOSIS

,

    hypersensitivity
    DIAGNOSIS

,

    allergy reaction
    DIAGNOSIS

,

    allergic reaction
    DIAGNOSIS

,

    immunology reaction
    DIAGNOSIS

,

    immunologic reaction
    DIAGNOSIS

,

    angioedema
    SYMPTOMS

,

    loss of consciousness
    SYMPTOMS

,

    generalized erythema
    SYMPTOMS

,

    urticaria
    SYMPTOMS

,

    urticarial rash
    SYMPTOMS

,

    cyanosis
    SYMPTOMS

,

    grunting
    SYMPTOMS

,

    stridor
    SYMPTOMS

,

    tachypnoea
    SYMPTOMS

,

    wheezing
    SYMPTOMS

,

    tachycardia
    SYMPTOMS

,

    abdominal pain
    SYMPTOMS

,

    diarrhea
    SYMPTOMS

,

    nausea
    SYMPTOMS

,

    vomiting
    SYMPTOMS

 and

    tryptase
    BIOCHEMICAL

. We included studies in

    adults
    AGE

 of

    all ages
    AGE

 in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses.

Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421

    vaccine recipients
    MEDICATION

 [

    Pfizer-BioNTech
    MEDICATION

 (n = 14,505,399) and

    Moderna
    MEDICATION

 (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of

    anaphylaxis to both vaccines
    SYMPTOMS

 was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of

    nonanaphylactic reactions to both vaccines
    SYMPTOMS

 was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001).

    Vaccination with Pfizer-BioNTech
    MEDICATION

 resulted in

    higher anaphylactic reactions
    SYMPTOMS

 compared to

    Moderna
    MEDICATION

 (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However,

    lower incidence of nonanaphylactic reactions
    SYMPTOMS

 was associated with

    Pfizer-BioNTech
    MEDICATION

 compared to

    Moderna
    MEDICATION

 (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of

    anaphylaxis and nonanaphylactic reactions
    SYMPTOMS

 associated with

    mRNA COVID-19 immunization
    MEDICATION

 based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger's tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for

    anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines
    SYMPTOMS

 were

    female
    GENDER

    sex
    GENDER

 and

    personal history of atopy
    FAMILY

. The key

    triggers to anaphylactic and nonanaphylactic reactions
    SYMPTOMS

 identified in these studies included

    foods, medications, stinging insects or jellyfish
    SYMPTOMS

,

    contrast media, cosmetics and detergents, household products
    SYMPTOMS

, and

    latex
    SYMPTOMS

.

    Previous history of anaphylaxis
    FAMILY

; and comorbidities such as asthma,

    allergic rhinitis, atopic and contact eczema/dermatitis
    DIAGNOSIS

 and

    psoriasis
    DIAGNOSIS

 and

    cholinergic urticaria
    DIAGNOSIS

 were also found to be important.

The prevalence of

    COVID-19 mRNA vaccine-associated anaphylaxis
    DIAGNOSIS

 is very low; and

    nonanaphylactic reactions
    SYMPTOMS

 occur at higher rate, however,

    cutaneous reactions
    SYMPTOMS

 are largely

    self-limited
    NEG_FINDINGS

. Both

    anaphylactic and nonanaphylactic reactions
    SYMPTOMS

 should not

    discourage vaccination
    NEG_FINDINGS

.

COVID-19 vaccines
vaccine recipients
Pfizer-BioNTech
Moderna
Vaccination with Pfizer-BioNTech
Moderna
Pfizer-BioNTech
Moderna
mRNA COVID-19 immunization


Case report: Hereditary angioedema in pregnancy.

Hereditary angioedema (HAE) is a rare genetic condition associated with episodic swelling due to dysfunction of bradykinin regulation pathways. This is most frequently caused by low level and/or function of the C1-esterase inhibitor protein (C1INH) which is known as hereditary angioedema with C1 inhibitor deficiency (C1INH-HAE). Pregnancy and labour can precipitate an attack, but the majority of women have an uncomplicated, spontaneous vaginal delivery. Intravenous C1INH is the first-line therapy in pregnancy and breastfeeding. It should be given if any obstetric intervention is planned. Routine prophylactic administration for uncomplicated vaginal birth is not mandatory but may be appropriate if symptoms recur frequently during the third trimester. Pregnant women with C1INH-HAE should deliver in a hospital with C1INH replacement, fiberoptic intubation and front-of-neck access equipment readily available. A documented treatment plan should be developed within a multi-disciplinary team to pre-empt complications. We describe a case of C1INH-HAE diagnosed in pregnancy.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare genetic condition
    GENETICS

 associated with

    episodic swelling
    SYMPTOMS

 due to

    dysfunction of bradykinin regulation pathways
    BIOCHEMICAL

. This is most frequently caused by

    low level and/or function of the C1-esterase inhibitor protein (C1INH)
    BIOCHEMICAL

 which is known as

    hereditary angioedema with C1 inhibitor deficiency
    DIAGNOSIS

    (C1INH-HAE)
    DIAGNOSIS

.

    Pregnancy
    DIAGNOSIS

 and

    labour
    DIAGNOSIS

 can precipitate an attack, but the majority of

    women
    GENDER

 have an

    uncomplicated, spontaneous vaginal delivery
    MEDICATION

.

    Intravenous C1INH
    MEDICATION

 is the first-line therapy in

    pregnancy
    DIAGNOSIS

 and

    breastfeeding
    MEDICATION

. It should be given if

    any obstetric intervention
    MEDICATION

 is planned.

    Routine prophylactic administration for uncomplicated vaginal birth
    MEDICATION

 is not mandatory but may be appropriate if symptoms recur frequently during the third trimester.

    Pregnant
    AGE

    women
    GENDER

 with

    C1INH-HAE
    DIAGNOSIS

 should

    deliver
    MEDICATION

 in a hospital with

    C1INH replacement
    MEDICATION

,

    fiberoptic intubation
    MEDICATION

 and

    front-of-neck access equipment
    MEDICATION

 readily available. A documented treatment plan should be developed within a multi-disciplinary team to pre-empt complications. We describe a case of

    C1INH-HAE
    DIAGNOSIS

 diagnosed in

    pregnancy
    DIAGNOSIS

.


[Diagnosis of hereditary angioedema after thirty years of clinical manifestations].

Diagnosis and treatment of hereditary angioedema (HAE) are necessary to improve the quality of life and even the survival of patients.

A 52-year-old woman with angioedema for 30 years, which affects the face, tongue, and hands. It is asymmetric, with neither pruritus nor urticaria, without response to antihistamines or corticosteroids, with spontaneous resolution in 48 hours to 72 hours; with a family history of angioedema. Normal physical examination between exacerbations. Autoimmune and lymphoproliferative diseases were ruled out. Values of C1q, C4, C1-INH were normal. The diagnosis of HAE type C1-INH normal subtype Unknown was established. The total resolution of the crises was achieved after two months with androgen therapy. Outpatient follow-up has been given for four years and no angioedema crisis has been reported, which is associated with a radical change in the quality of life.

The patient was diagnosed with HAE after 30 years of clinical manifestations, after acquired angioedema was ruled out.

Diagnosis and treatment of

    hereditary angioedema (HAE)
    DIAGNOSIS

 are necessary to improve the quality of life and even the survival of patients.

A

    52-year-old
    AGE

    woman
    GENDER

 with

    angioedema for 30 years
    SYMPTOMS

, which

    affects the face, tongue, and hands
    SYMPTOMS

. It is asymmetric, with

    neither pruritus nor urticaria
    NEG_FINDINGS

,

    without response to antihistamines or corticosteroids
    NEG_FINDINGS

, with

    spontaneous resolution in 48 hours to 72 hours
    SYMPTOMS

; with a

    family history of angioedema
    FAMILY

.

    Normal physical examination between exacerbations
    NEG_FINDINGS

.

    Autoimmune and lymphoproliferative diseases were ruled out
    NEG_FINDINGS

.

    Values of C1q, C4, C1-INH were normal
    NEG_FINDINGS

. The diagnosis of

    HAE type C1-INH normal subtype Unknown
    DIAGNOSIS

 was established. The

    total resolution of the crises
    SYMPTOMS

 was achieved after

    two months
    MEDICATION

 with

    androgen therapy
    MEDICATION

.

    Outpatient follow-up
    MEDICATION

 has been given for four years and

    no angioedema crisis
    NEG_FINDINGS

 has been reported, which is associated with a

    radical change in the quality of life
    SYMPTOMS

.

The patient was diagnosed with

    HAE
    DIAGNOSIS

 after 30 years of clinical manifestations, after

    acquired angioedema was ruled out
    NEG_FINDINGS

.

hereditary angioedema (HAE)
HAE type C1-INH normal subtype Unknown
HAE

two months
androgen therapy
Outpatient follow-up


Hereditary Angioedema in Pregnancy.

Hereditary angioedema is a rare disease of potentially life-threatening attacks of angioedema that can affect patients of all ages, including women of childbearing age. Pregnancy can affect the course of the disease and the choice of treatment used. It is important for the care providers to recognize this disease and understand its mechanism in order to provide appropriate care for the patients.

The goal of this article is to provide an overview of hereditary angioedema and guideline for management of pregnant patients with hereditary angioedema.

A search of the available English language literature was performed on PubMed and Ovid MEDLINE using the key words hereditary angioedema and pregnancy. Additional articles were selected from the reference lists of the reviewed articles.

The data for hereditary angioedema in pregnant patients come from observational studies, case reports, retrospective reviews, and questionnaires. The course of hereditary angioedema can be variable between different patients and pregnancies. Plasma-derived C1 inhibitor concentrate is both safe and effective as treatment for attacks and as preventive therapy in pregnancy. With proper recognition, understanding of the disease, and appropriate medical management, most patients will undergo successful pregnancy and delivery.

Clinicians should maintain high suspicion for this disease when patients present with recurrent episodes of angioedema without urticaria or severe abdominal pains of unclear etiology. Treatment plans during pregnancy and delivery should be individualized, and the patient's care should be shared by a clinician experienced in the management of this disease.

    Hereditary angioedema
    DIAGNOSIS

 is a rare disease of

    potentially life-threatening attacks of angioedema
    SYMPTOMS

 that can affect patients of

    all ages
    AGE

, including

    women
    GENDER

 of

    childbearing age
    AGE

.

    Pregnancy
    AGE

 can affect the course of the disease and the choice of treatment used. It is important for the care providers to recognize this disease and understand its mechanism in order to provide appropriate care for the patients.

The goal of this article is to provide an overview of

    hereditary angioedema
    DIAGNOSIS

 and guideline for management of

    pregnant
    AGE

 patients with

    hereditary angioedema
    DIAGNOSIS

.

A search of the available English language literature was performed on PubMed and Ovid MEDLINE using the key words

    hereditary angioedema
    DIAGNOSIS

 and

    pregnancy
    DIAGNOSIS

. Additional articles were selected from the reference lists of the reviewed articles.

The data for

    hereditary angioedema
    DIAGNOSIS

 in

    pregnant
    AGE

 patients come from observational studies, case reports, retrospective reviews, and questionnaires. The course of

    hereditary angioedema
    DIAGNOSIS

 can be variable between different patients and pregnancies.

    Plasma-derived C1 inhibitor concentrate
    MEDICATION

 is both safe and effective as treatment for attacks and as

    preventive therapy
    MEDICATION

 in

    pregnancy
    DIAGNOSIS

. With proper recognition, understanding of the disease, and appropriate medical management, most patients will undergo

    successful pregnancy and delivery
    MEDICATION

.

Clinicians should maintain high suspicion for this disease when patients present with

    recurrent episodes of angioedema
    SYMPTOMS

    without urticaria
    NEG_FINDINGS

 or

    severe abdominal pains of unclear etiology
    SYMPTOMS

. Treatment plans during

    pregnancy
    MEDICATION

 and

    delivery
    MEDICATION

 should be individualized, and the patient's care should be shared by a clinician experienced in the management of this disease.

Hereditary angioedema
hereditary angioedema
hereditary angioedema
hereditary angioedema
pregnancy
hereditary angioedema
hereditary angioedema
pregnancy

Plasma-derived C1 inhibitor concentrate
preventive therapy
successful pregnancy and delivery
pregnancy
delivery


Hereditary angioedema. Diagnosis in an asymptomatic elderly woman.

Hereditary angioedema (HAE) is a rare disease with an autosomal dominant heredity pattern, due to mutations in the gene encoding the C1 esterase inhibitor. The onset of symptoms usually occurs during childhood. Clinically, it is characterized by repeated episodes of angioedema that may affect the skin, abdomen and larynx/pharynx. The occurrence of attacks and their severity are unpredictable and can be fatal without the appropriate treatment. We present the case of an asymptomatic 65-year-old woman, with a history of three adult children diagnosed with HAE. Despite the high probabilities of being a carrier of the mutation, she had not been previously studied. Diagnosis of HAE in a family member would require screening of all at-risk relatives. Early diagnosis is essential to establish a correct and timely therapeutic strategy in order to reduce the morbidity and mortality associated with the disease.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a

    rare disease
    DIAGNOSIS

 with an

    autosomal dominant heredity pattern
    GENETICS

, due to

    mutations in the gene encoding the C1 esterase inhibitor
    GENETICS

. The onset of symptoms usually occurs during

    childhood
    AGE

. Clinically, it is characterized by

    repeated episodes of angioedema that may affect the skin, abdomen and larynx/pharynx
    SYMPTOMS

. The occurrence of attacks and their severity are unpredictable and can be

    fatal
    SYMPTOMS

 without the appropriate treatment. We present the case of an

    asymptomatic
    NEG_FINDINGS

    65-year-old
    AGE

    woman
    GENDER

,

    with a history of three adult children diagnosed with HAE
    FAMILY

. Despite the high probabilities of being a carrier of the mutation,

    she
    GENDER

 had not been previously studied. Diagnosis of

    HAE
    DIAGNOSIS

 in a family member would require screening of all at-risk relatives. Early diagnosis is essential to establish a correct and timely therapeutic strategy in order to reduce the morbidity and mortality associated with the disease.

Hereditary angioedema (HAE)
rare disease
HAE


Acute Right Ventricular Dysfunction Secondary to Hereditary Angioedema Exacerbation.

This is a case report of a 31-year-old woman with past medical history of hereditary angioedema (HAE) who developed acute right ventricular dysfunction. The patient presented to the emergency department with complaints of acute abdominal pain and swelling. Her electrocardiogram demonstrated sinus tachycardia and T wave inversion in leads V1-V3, otherwise without findings suggestive of ischemia. Troponin was elevated at 1.83 ng/mL. A transthoracic echocardiogram showed normal left ventricular function with ejection fraction of 65-70%, but the right ventricle (RV) was dilated and severely hypokinetic and there was moderate tricuspid regurgitation. Patient was managed symptomatically for her HAE exacerbation. Her abdominal swelling resolved, troponins continued to trend down, and she was discharged home after three days. A follow up echocardiogram done six months later demonstrated normal RV function.

This is a case report of a

    31-year-old
    AGE

    woman
    GENDER

 with

    past medical history of hereditary angioedema (HAE)
    FAMILY

 who developed

    acute right ventricular dysfunction
    SYMPTOMS

. The patient presented to the emergency department with complaints of

    acute abdominal pain
    SYMPTOMS

 and

    swelling
    SYMPTOMS

.

    Her
    GENDER

    electrocardiogram
    PARACLINICAL

 demonstrated

    sinus tachycardia
    SYMPTOMS

 and

    T wave inversion in leads V1-V3
    SYMPTOMS

, otherwise

    without findings suggestive of ischemia
    NEG_FINDINGS

. Troponin was elevated at 1.83 ng/mL. A

    transthoracic echocardiogram
    PARACLINICAL

 showed

    normal left ventricular function
    NEG_FINDINGS

 with

    ejection fraction of 65-70%
    SYMPTOMS

, but

    the right ventricle (RV) was dilated and severely hypokinetic
    SYMPTOMS

 and there was

    moderate tricuspid regurgitation
    SYMPTOMS

. Patient was

    managed symptomatically
    MEDICATION

 for her

    HAE exacerbation
    DIAGNOSIS

. Her

    abdominal swelling resolved
    SYMPTOMS

,

    troponins continued to trend down
    BIOCHEMICAL

, and

    she
    GENDER

 was

    discharged home after three days
    MEDICATION

. A

    follow up echocardiogram
    PARACLINICAL

 done six months later demonstrated

    normal RV function
    NEG_FINDINGS

.

without findings suggestive of ischemia
normal left ventricular function
normal RV function

managed symptomatically
discharged home after three days


Management of hereditary angioedema type I and homozygous MTHFR mutation during pregnancy.

Hereditary angioedema (HAE) is an autosomal dominant disease, characterized by edema attacks resulting from quantitative and/or functional deficiency of the C1 inhibitor (C1-INH), which acts in controlling the complement, coagulation, fibrinolysis, and contact systems. The exacerbation of these systems results in decreased circulating levels of kallikrein and conversion of bradykinin. In addition, thrombophilia is related to the deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme, causing an increase in homocysteine, accumulation of atheromatous plaques, and arterial and venous thrombosis. The association of these conditions in related systems brings greater clinical risks to the patient. We report a female patient, aged 23 years, with HAE and homozygous MTHFR mutation, G2A1, carrier of HAE with crises since early childhood. The first pregnancy terminated with abortion due to gestational sac detachment. In the second pregnancy, at 5.1 weeks, she had bleeding and partial detachment of gestational sac. Thrombophilia tests confirmed homozygosity for the MTHFR enzyme. At the beginning of gestation, she had attacks of angioedema treated with fresh plasma, and at one occasion, she received treatment with a plasma-derived C1-INH esterase. During breastfeeding, she received prophylaxis with plasma-derived C1-INHdp. The course of HAE during pregnancy worsened. There are studies that discuss the occurrence of abortion due to attacks of angioedema. The patient's disease was associated with a homozygous MTHFR mutation, which probably caused the miscarriage. The control of both clinical situations is important for the success of pregnancy, so a combined action plan between obstetricians and HAE treatment specialists is essential.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is an

    autosomal dominant disease
    GENETICS

, characterized by

    edema attacks
    SYMPTOMS

 resulting from

    quantitative and/or functional deficiency of the C1 inhibitor (C1-INH), which acts in controlling the complement, coagulation, fibrinolysis, and contact systems
    BIOCHEMICAL

. The

    exacerbation of these systems
    BIOCHEMICAL

 results in

    decreased circulating levels of kallikrein and conversion of bradykinin
    BIOCHEMICAL

. In addition,

    thrombophilia
    DIAGNOSIS

 is related to the

    deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme
    BIOCHEMICAL

, causing an

    increase in homocysteine
    BIOCHEMICAL

,

    accumulation of atheromatous plaques
    SYMPTOMS

, and

    arterial and venous thrombosis
    SYMPTOMS

. The association of these conditions in related systems brings greater clinical risks to the patient. We report a

    female
    GENDER

 patient,

    aged 23 years
    AGE

, with

    HAE
    DIAGNOSIS

 and

    homozygous MTHFR mutation, G2A1
    GENETICS

, carrier of

    HAE
    DIAGNOSIS

 with

    crises
    SYMPTOMS

 since

    early childhood
    AGE

. The

    first pregnancy terminated
    MEDICATION

 with

    abortion
    SYMPTOMS

 due to

    gestational sac detachment
    SYMPTOMS

. In the second

    pregnancy
    DIAGNOSIS

,

    at 5.1 weeks
    MEDICATION

,

    she
    GENDER

 had

    bleeding and partial detachment of gestational sac
    SYMPTOMS

.

    Thrombophilia tests
    PARACLINICAL

 confirmed

    homozygosity for the MTHFR enzyme
    GENETICS

. At the beginning of

    gestation
    MEDICATION

,

    she
    GENDER

 had

    attacks of angioedema
    SYMPTOMS

    treated with fresh plasma
    MEDICATION

, and at one occasion,

    she
    GENDER

 received

    treatment with a plasma-derived C1-INH esterase
    MEDICATION

. During

    breastfeeding
    MEDICATION

,

    she
    GENDER

 received

    prophylaxis with plasma-derived C1-INHdp
    MEDICATION

. The course of

    HAE
    DIAGNOSIS

 during

    pregnancy
    DIAGNOSIS

 worsened. There are studies that discuss the occurrence of

    abortion
    SYMPTOMS

 due to

    attacks of angioedema
    SYMPTOMS

. The patient's disease was associated with a

    homozygous MTHFR mutation
    GENETICS

, which probably caused the

    miscarriage
    DIAGNOSIS

. The control of both clinical situations is important for the success of

    pregnancy
    DIAGNOSIS

, so a combined action plan between

    obstetricians
    PARACLINICAL

 and

    HAE
    DIAGNOSIS

 treatment specialists is essential.

Hereditary angioedema (HAE)
thrombophilia
HAE
HAE
pregnancy
HAE
pregnancy
miscarriage
pregnancy
HAE

autosomal dominant disease
homozygous MTHFR mutation, G2A1
homozygosity for the MTHFR enzyme
homozygous MTHFR mutation


Transition to lanadelumab-flyo from three medications for a hereditary angioedema patient with a variant in the SYTL2 gene: A case report.

Non-SERPING1 gene variant hereditary angioedema patients often need to take progesterone, attenuated androgens, and antifibrinolytics to control symptoms. These drugs may need to be tapered to extinction or reduced as lanadelumab-flyo reaches maximum concentration.

    Non-SERPING1 gene variant
    GENETICS

    hereditary angioedema
    DIAGNOSIS

 patients often need to take

    progesterone
    MEDICATION

,

    attenuated androgens, and antifibrinolytics
    MEDICATION

 to

    control symptoms
    SYMPTOMS

. These drugs may need to be

    tapered to extinction or reduced
    MEDICATION

 as

    lanadelumab-flyo
    MEDICATION

 reaches maximum concentration.


Clinical profile of hereditary angioedema from a tertiary care centre in India.

Hereditary angioedema (HAE) is a clinical condition which could be fatal if not identified and managed appropriately. Knowledge of this condition is mostly confined to individual case reports and literature reviews in India. In this retrospective study we describe HAE cases which presented to a tertiary care centre in India over a period of three and half years.

Clinical case records of forty-two HAE patients diagnosed based on clinical and laboratory features were accessed after due approval from the Ethics committee. C1 esterase inhibitor (C1 INH) and C4 levels were measured using nephelometry. All relevant data was entered into Microsoft EXCEL worksheet and analysed using simple statistical tools.

Among the 42 patients diagnosed as having HAE, 37 had low C1INH levels and were diagnosed to have type 1 HAE. The remaining 5 had normal C1 INH levels and were considered probable HAE based on family history and response to HAE specific treatment. The median age of onset of symptoms was 15 years (range 5-49) and median age at diagnosis, 27.5 years (range 5-55). The median delay in diagnosis was 10 years (range 1-27 years). Family history of HAE was observed in 52.6% and 29% reported deaths in the family with HAE like disease. Low dose androgens or tranexamic acid or both were prescribed in 64.2% of the patients. Orofacial edema was the commonest clinical presentation (76%) followed by edema of the extremities (38%), GI tract symptoms (19%) and genital involvement (11.9%).

Many cases of HAE may be going undetected in India. There is a need for clinical awareness and laboratory means to accurately identify and administer appropriate treatment.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a clinical condition which could be fatal if not identified and managed appropriately. Knowledge of this condition is mostly confined to individual case reports and literature reviews in

    India
    ETHNICITY

. In this retrospective study we describe

    HAE
    DIAGNOSIS

 cases which presented to a tertiary care centre in

    India
    ETHNICITY

 over a period of three and half years.

Clinical case records of forty-two

    HAE
    DIAGNOSIS

 patients diagnosed based on clinical and laboratory features were accessed after due approval from the Ethics committee.

    C1 esterase inhibitor (C1 INH) and C4 levels
    BIOCHEMICAL

 were

    measured using nephelometry
    PARACLINICAL

. All relevant data was entered into Microsoft EXCEL worksheet and analysed using simple statistical tools.

Among the 42 patients diagnosed as having

    HAE
    DIAGNOSIS

, 37 had

    low C1INH levels
    BIOCHEMICAL

 and were diagnosed to have

    type 1 HAE
    DIAGNOSIS

. The remaining 5 had

    normal C1 INH levels
    NEG_FINDINGS

 and were considered probable

    HAE
    DIAGNOSIS

 based on family history and response to

    HAE specific treatment
    DIAGNOSIS

. The

    median age of onset of symptoms was 15 years (range 5-49)
    AGE

 and

    median age at diagnosis, 27.5 years (range 5-55)
    AGE

. The

    median delay in diagnosis was 10 years (range 1-27 years)
    AGE

.

    Family history of HAE
    FAMILY

 was observed in 52.6% and 29% reported

    deaths in the family with HAE like disease
    FAMILY

.

    Low dose androgens or tranexamic acid or both
    MEDICATION

 were prescribed in 64.2% of the patients.

    Orofacial edema
    SYMPTOMS

 was the commonest clinical presentation (76%) followed by

    edema of the extremities
    SYMPTOMS

 (38%),

    GI tract symptoms
    SYMPTOMS

 (19%) and

    genital involvement
    SYMPTOMS

 (11.9%).

Many cases of

    HAE
    DIAGNOSIS

 may be going undetected in

    India
    ETHNICITY

. There is a need for clinical awareness and laboratory means to accurately identify and administer appropriate treatment.

Hereditary angioedema (HAE)
HAE
HAE
HAE
type 1 HAE
HAE
HAE specific treatment
HAE

Orofacial edema
edema of the extremities
GI tract symptoms
genital involvement


Angioedema with severe acute abdominal pain: Think of hereditary angioedema.

Angioedema can be either mast cell-(histamine-)mediated or bradykinin-mediated. Treatment approaches for the two types are very different, making differential diagnosis critical. Severe acute abdominal pain caused by intestinal angioedema is commonly misdiagnosed, especially when associated with bradykinin-mediated angioedema. After describing a typical clinical scenario and diagnostic journey of a patient with recurrent, undiagnosed abdominal pain due to hereditary angioedema (HAE), a rare variant of bradykinin-mediated angioedema, we delve into the classification and differential diagnosis of the various types of angioedema and provide an overview of appropriate management with an emphasis on the bradykinin-mediated types. Bradykinin-induced angioedema may be inherited or acquired and is infrequent compared to mast cell-mediated angioedema. HAE is a rare disease characterized by recurrent attacks of non-urticarial, nonpruritic edema usually affecting the face, respiratory tract, extremities, gastrointestinal tract, and genitalia. Unlike mast cell-mediated angioedema, painful abdominal symptoms are prevalent in bradykinin-mediated angioedema and are sometimes the only manifestation of an attack, increasing the likelihood of initial misdiagnosis as appendicitis or other forms of acute abdomen. It is important for gastroenterologists to be vigilant for the possibility of angioedema pathology in patients presenting with undiagnosed, recurrent, abdominal symptoms to facilitate accurate diagnosis and effective treatment.

    Angioedema
    DIAGNOSIS

 can be either

    mast cell-(histamine-)mediated
    BIOCHEMICAL

 or

    bradykinin-mediated
    DIAGNOSIS

. Treatment approaches for the two types are very different, making

    differential diagnosis
    PARACLINICAL

 critical.

    Severe acute abdominal pain
    SYMPTOMS

 caused by

    intestinal angioedema
    SYMPTOMS

 is commonly misdiagnosed, especially when associated with

    bradykinin-mediated angioedema
    DIAGNOSIS

. After describing a typical clinical scenario and diagnostic journey of a patient with

    recurrent, undiagnosed abdominal pain
    SYMPTOMS

 due to

    hereditary angioedema (HAE)
    DIAGNOSIS

, a rare variant of

    bradykinin-mediated angioedema
    DIAGNOSIS

, we delve into the classification and

    differential diagnosis
    PARACLINICAL

 of the various types of

    angioedema
    DIAGNOSIS

 and provide an overview of appropriate management with an emphasis on the

    bradykinin-mediated types
    DIAGNOSIS

.

    Bradykinin-induced angioedema
    DIAGNOSIS

 may be

    inherited or acquired
    GENETICS

 and is infrequent compared to

    mast cell-mediated angioedema
    DIAGNOSIS

.

    HAE
    DIAGNOSIS

 is a rare disease characterized by

    recurrent attacks of non-urticarial, nonpruritic edema usually affecting the face, respiratory tract, extremities, gastrointestinal tract, and genitalia
    SYMPTOMS

. Unlike

    mast cell-mediated angioedema
    NEG_FINDINGS

,

    painful abdominal symptoms
    SYMPTOMS

 are prevalent in

    bradykinin-mediated angioedema
    DIAGNOSIS

 and are sometimes the only manifestation of an attack, increasing the likelihood of

    initial misdiagnosis as appendicitis or other forms of acute abdomen
    NEG_FINDINGS

. It is important for

    gastroenterologists
    PARACLINICAL

 to be vigilant for the possibility of

    angioedema pathology
    DIAGNOSIS

 in patients presenting with undiagnosed,

    recurrent, abdominal symptoms
    SYMPTOMS

 to facilitate accurate diagnosis and effective treatment.

Angioedema
bradykinin-mediated
bradykinin-mediated angioedema
hereditary angioedema (HAE)
bradykinin-mediated angioedema
angioedema
bradykinin-mediated types
Bradykinin-induced angioedema
mast cell-mediated angioedema
HAE
bradykinin-mediated angioedema
angioedema pathology


Obstetric Anesthetic Management for Parturients with Hereditary Angioedema: A Case Report and Suggested Protocol.

Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.

    Hereditary angioedema (HAE)
    DIAGNOSIS

 is a disease manifested by

    repeated episodes of localized submucosal or subcutaneous edematous episodes
    SYMPTOMS

, potentially triggered by

    emotional stress
    SYMPTOMS

,

    mechanical trauma
    SYMPTOMS

, or

    intake of estrogens
    MEDICATION

. We present our experience managing two

    parturients
    AGE

 with

    HAE
    DIAGNOSIS

.

    Multidisciplinary care
    MEDICATION

 is essential for planning and executing the specialized care of these patients, and management included extensive planning among

    obstetric, anesthesiology
    PARACLINICAL

, and

    allergy and immunology teams
    PARACLINICAL

.

    Pregnancy
    DIAGNOSIS

 has been shown to have a variable effect on

    triggering HAE episodes
    SYMPTOMS

. First-line treatment includes

    C1 esterase inhibitor concentrate
    MEDICATION

, which can also be used for

    prophylaxis
    MEDICATION

 in high-risk patients.

    Neuraxial analgesia
    MEDICATION

 is recommended to

    avoid general anesthesia
    MEDICATION

 and was established early in both individuals.

    Vaginal delivery
    MEDICATION

 was well tolerated

    without need for emergent treatment for angioedema symptoms
    NEG_FINDINGS

.

Hereditary angioedema (HAE)
HAE
Pregnancy

intake of estrogens
Multidisciplinary care
C1 esterase inhibitor concentrate
prophylaxis
Neuraxial analgesia
avoid general anesthesia
Vaginal delivery


Subcutaneous C1-Inhibitor Concentrate for prophylaxis during pregnancy and lactation in a patient with C1-INH-HAE.

Subcutaneous plasma-derived human C1-Inhibitor concentrate (pdC1INH) may be safe and effective for long-term prophylaxis during pregnancy and lactation in hereditary angioedema patients.

    Subcutaneous plasma-derived human C1-Inhibitor concentrate (pdC1INH)
    MEDICATION

 may be safe and effective for

    long-term prophylaxis during pregnancy and lactation
    MEDICATION

 in

    hereditary angioedema
    DIAGNOSIS

 patients.