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Clinical survey of hereditary angioedema
J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 1
ACEIs receiving (46%) than in ACEIs free patients (56%). In 9 of the 13 ACEIs-treated patients and in 30 of the 47 ACEIs-untreated patients data on thyroid function and/or autoantibodies were available. In 4 (44%) of the former and in 3 (10%) of the latter there was evidence of either frank hypothyroidism or thyroid autoantibody positivity. In 7 of the 13 patients withACEIscorrelated angioedema Cl-esterase inhibitor and C4 levels could be performed and tested normal. Of the 94 patients regularly treated with ACEIs, mostly rarnipril (76%), two (2%) had had at least two episodes of angioedema and had no evidence of thyroid disease. All episodes of ACEIs-induced angioedema had been mostly limited to the face (lips, eyelids, cheeks) and had never been life-threatening. In conclusion: 1. the frequency of ACEI treatment (mostly Enalapril) among patients with angioedema appears to be more common than previously reported and more often associated either with thyroid autoimmunity or overt thyroid disease 2. the occurence of angioedema in patients receiving ACEI treatment (mostly Ramipril) is also not rare 3. in our experience, ACEIs-correlated angioedema is generally benign. Follow-up studies of larger series will be helpful in making the decision about whether to withdraw ACEIs in patients with angioedema, especially in those who significantly benefit from such therapy.
371 EdemaMelkerss°n'R°senthalSyndrome:A Rare Causeof Orofacial Nina C Ramirez *, Richard F Lockey*, Roger W Fox *, Stephen J Kornfeld§ *University of South Florida, Tampa, FL §All Children's Hospital, St Petersburg, FL Two case reports of Melkersson-Rosenthal Syndrome (MRS), a rare clinical disorder, are described. The first is a 25-year-old male with painless swelling of his lower lip, beginning 1.5 years after the onset of right Bell's palsy. He had a furrowed tongue. Biopsy of the right bnccal mucosa reveals a perivascular inflammatory cell infiltrate consisting of lymphocytes and plasma cells. Case 2 is a 52-year-old male with a 14 month history of swelling of the left side of the face and periorbital region. He had no Bell's palsy and had mild fissuring of his tongue. Biopsy of the left eyelid skin and subcutaneous tissue reveals granulomatous inflammation. MRS is characterized by the triad of intermittent to persistent unilateral edema, Bell's palsy, and midline furrowing of the tongue (lingua plicata). However, only 30% of patients present with the entire triad. The most typical history is of swelling of the same region of the face which persists for variable periods or indefinitely. Facial lip swelling is the most common finding and usually occurs on the same side as does the Bell's palsy. Other areas of the body may also be edematous. Lingua plicata or congenital fissuring of the tongue is also associated with MRS. Facial nerve paralysis occurs in 30% to 50% of patients and may precede the edema by months or years. Pathogenesis of this syndrome is unknown. A biopsy of the edematous tissue can be normal or reveal noncaseating epithelioid granulomas with a perivascular lymphocytic infiltrate. No single treatment modality has been proven to be uniformly successful, although systemic or intralesional corticosteroids may be beneficial. MRS should be included in the differential diagnosis of persistent facial edema or angioedema.
372
Clinical Surveyof HereditaryAngioodema
SW Huang University of Florida, Gainesville, FL Hereditary angioedema (HAE) is a rare but potentially fatal disease. There are two clinical types, based on deficiency of quantity (Type 1) or functional level (Type 2) of C1 esterase inhibitor in the blood. Because of the similarity of clinical signs of HAE to those of other causes of angioedema, its presentation can be a challenge to clinicians. In order to understand the current data on demography, clinical manifestations, management, and patient concerns, a survey was conducted using the internet (www. hereditaryangioedema.com). Sixty-three patients responded and the data
Abstracts
8129
were analyzed. Patients were predominantly female, 89% (n=56). The patients were divided into three groups for comparison: Type 1, 60% (n=38); Type 2, 16% (n=10); and Type C, 24% (n=15) who did not know their type. Mean and median age of onset of symptoms were respectively: Type 1, 11.5 and 11.5, Type 2, 19.9 and 16.0, Type C, 18.7 and 16.0. The difference between Type 1 and the others was significant (p=0.04). The time (in years) between the onset and the diagnosis was: Type 1, 7.9; Type 2, 3.8; Type C, 4.9. Patients with positive parental history of HAE: Type 1, 37%; Type 2, 33%; Type C, 40%; with history of HAE in siblings: Type 1, 43%; Type 2, 17%; Type C, 44%. The five most common symptoms were: abdominal pain and swelling (70%); swelling of extremities (45%); throat and tongue swelling (25%); facial swelling (25%); nausea and vomiting (25%). Allergy-like symptoms were: itching in 11.1% (n=7) and rash in 9.5% (n=6). Hypotension only occurred in 1 patient. Fifty-two patients had surgeries and 35% (n= 18) developed signs of HAE, despite 10 being given precautionary measures. Twenty-four patients (38%) were on stanozolol, 18 (29.5%) daily and 6 (9.8%) every other day; 14 (23%) were on danazol, 13 (21.4%) daily and one (1.6%) every other day; 16 (25.3%) were on medication only on an as-needed basis; 75% of these were Type 1 patients. The average number of visits to the ER per year was 4.7; 17 (27.5%) didn't go at all, and one went 48 times. When seen in the ER, 13 (20.6%) were initially treated for anaphylaxis and 4 (6.3%) were treated for other diseases. Many (41.3%) patients felt that the physicians in the ER had poor or no knowledge of HAE; 5 (7.9%) carried their own identification of HAE to the ER. Thirty-three patients received epinephrine treatment, but only 9 (27%) felt that the shots were effective in relieving symptoms. The three major fears of the patients were: sudden closure of the airway (85%), intolerable pain (65%), and transmission of the disease to children (55%). Patients' satisfaction level with current management: good or satisfactory (26%), only fair (28%), poor or unsatisfactory (46%). Conclusions: Many HAE patients live in fear or uncertainty and are unsatisfied with their doctors' management of the disease. Physicians need to educate themselves to be more familiar with HAE.
373 C1 InhibitorDeficiencyand NormalC4 Bruce J Goldberg, E Park Kaiser-Permanente, Los Angeles, CA Angioedema due to C 1 inhibitor deficiency is described in the literature as being associated with decreased C4 both during and between acute attacks and with decreased C2 frequently only during acute attacks. Thus determination of C4 is often cited as a screen for C1 inhibitor deficiency. The reports in the literature referring to low C4 and C1 inhibitor appear to be largely anectodal. In this study we present our findings on a series of patients with abnormal C 1 inhibitor function and/or protein and normal C4. Between 1999 and 2001, our laboratory has detected 37 patients with abnormal C1 inhibitor function as determined by enzyme linked immunoabsorbent assay (Quidel ®, Mountain View, CA). All such patients were verified as having abnormal CI inhibitor function by repeat assay on the same or a freshly submitted specimen. All abnormal sera were then subjected to determination of C1 inhibitor protein and C4 protein by single radial immunodiffusion (The Binding Site Inc., San Diego, CA). Of the 37 patients with low C 1 inhibitor function, 13 (35 %) were found to have a normal C4 and 22 (59%) a normal C 1 inhibitor protein. Of the 22 patients with normal C1 inhibitor protein, 13 patients (59%) had a normal C4. No patients with both decreased C 1 inhibitor function and protein had a normal C4. Our results indicate that Type II C 1 inhibitor deficiency may be more common than previously reported (59% vs. 15%) and may be accompanied by normal C4 in close to 59% of patients. In contrast, Type I C1 inhibitor deficiency may always be associated with low C4. Thus, C l inhibitor functional assay would appear more useful as a screen for C 1 inhibitor deficiency than C4 or C 1 inhibitor protein assays.
ACEIs receiving (46%) than in ACEIs free patients (56%). In 9 of the 13 ACEIs-treated patients and in 30 of the 47 ACEIs-untreated patients data on thyroid function and/or autoantibodies were available. In 4 (44%) of the former and in 3 (10%) of the latter there was evidence of either frank hypothyroidism or thyroid autoantibody positivity. In 7 of the 13 patients withACEIscorrelated angioedema Cl-esterase inhibitor and C4 levels could be performed and tested normal. Of the 94 patients regularly treated with ACEIs, mostly rarnipril (76%), two (2%) had had at least two episodes of angioedema and had no evidence of thyroid disease. All episodes of ACEIs-induced angioedema had been mostly limited to the face (lips, eyelids, cheeks) and had never been life-threatening. In conclusion: 1. the frequency of ACEI treatment (mostly Enalapril) among patients with angioedema appears to be more common than previously reported and more often associated either with thyroid autoimmunity or overt thyroid disease 2. the occurence of angioedema in patients receiving ACEI treatment (mostly Ramipril) is also not rare 3. in our experience, ACEIs-correlated angioedema is generally benign. Follow-up studies of larger series will be helpful in making the decision about whether to withdraw ACEIs in patients with angioedema, especially in those who significantly benefit from such therapy.
371 EdemaMelkerss°n'R°senthalSyndrome:A Rare Causeof Orofacial Nina C Ramirez *, Richard F Lockey*, Roger W Fox *, Stephen J Kornfeld§ *University of South Florida, Tampa, FL §All Children's Hospital, St Petersburg, FL Two case reports of Melkersson-Rosenthal Syndrome (MRS), a rare clinical disorder, are described. The first is a 25-year-old male with painless swelling of his lower lip, beginning 1.5 years after the onset of right Bell's palsy. He had a furrowed tongue. Biopsy of the right bnccal mucosa reveals a perivascular inflammatory cell infiltrate consisting of lymphocytes and plasma cells. Case 2 is a 52-year-old male with a 14 month history of swelling of the left side of the face and periorbital region. He had no Bell's palsy and had mild fissuring of his tongue. Biopsy of the left eyelid skin and subcutaneous tissue reveals granulomatous inflammation. MRS is characterized by the triad of intermittent to persistent unilateral edema, Bell's palsy, and midline furrowing of the tongue (lingua plicata). However, only 30% of patients present with the entire triad. The most typical history is of swelling of the same region of the face which persists for variable periods or indefinitely. Facial lip swelling is the most common finding and usually occurs on the same side as does the Bell's palsy. Other areas of the body may also be edematous. Lingua plicata or congenital fissuring of the tongue is also associated with MRS. Facial nerve paralysis occurs in 30% to 50% of patients and may precede the edema by months or years. Pathogenesis of this syndrome is unknown. A biopsy of the edematous tissue can be normal or reveal noncaseating epithelioid granulomas with a perivascular lymphocytic infiltrate. No single treatment modality has been proven to be uniformly successful, although systemic or intralesional corticosteroids may be beneficial. MRS should be included in the differential diagnosis of persistent facial edema or angioedema.
372
Clinical Surveyof HereditaryAngioodema
SW Huang University of Florida, Gainesville, FL Hereditary angioedema (HAE) is a rare but potentially fatal disease. There are two clinical types, based on deficiency of quantity (Type 1) or functional level (Type 2) of C1 esterase inhibitor in the blood. Because of the similarity of clinical signs of HAE to those of other causes of angioedema, its presentation can be a challenge to clinicians. In order to understand the current data on demography, clinical manifestations, management, and patient concerns, a survey was conducted using the internet (www. hereditaryangioedema.com). Sixty-three patients responded and the data
Abstracts
8129
were analyzed. Patients were predominantly female, 89% (n=56). The patients were divided into three groups for comparison: Type 1, 60% (n=38); Type 2, 16% (n=10); and Type C, 24% (n=15) who did not know their type. Mean and median age of onset of symptoms were respectively: Type 1, 11.5 and 11.5, Type 2, 19.9 and 16.0, Type C, 18.7 and 16.0. The difference between Type 1 and the others was significant (p=0.04). The time (in years) between the onset and the diagnosis was: Type 1, 7.9; Type 2, 3.8; Type C, 4.9. Patients with positive parental history of HAE: Type 1, 37%; Type 2, 33%; Type C, 40%; with history of HAE in siblings: Type 1, 43%; Type 2, 17%; Type C, 44%. The five most common symptoms were: abdominal pain and swelling (70%); swelling of extremities (45%); throat and tongue swelling (25%); facial swelling (25%); nausea and vomiting (25%). Allergy-like symptoms were: itching in 11.1% (n=7) and rash in 9.5% (n=6). Hypotension only occurred in 1 patient. Fifty-two patients had surgeries and 35% (n= 18) developed signs of HAE, despite 10 being given precautionary measures. Twenty-four patients (38%) were on stanozolol, 18 (29.5%) daily and 6 (9.8%) every other day; 14 (23%) were on danazol, 13 (21.4%) daily and one (1.6%) every other day; 16 (25.3%) were on medication only on an as-needed basis; 75% of these were Type 1 patients. The average number of visits to the ER per year was 4.7; 17 (27.5%) didn't go at all, and one went 48 times. When seen in the ER, 13 (20.6%) were initially treated for anaphylaxis and 4 (6.3%) were treated for other diseases. Many (41.3%) patients felt that the physicians in the ER had poor or no knowledge of HAE; 5 (7.9%) carried their own identification of HAE to the ER. Thirty-three patients received epinephrine treatment, but only 9 (27%) felt that the shots were effective in relieving symptoms. The three major fears of the patients were: sudden closure of the airway (85%), intolerable pain (65%), and transmission of the disease to children (55%). Patients' satisfaction level with current management: good or satisfactory (26%), only fair (28%), poor or unsatisfactory (46%). Conclusions: Many HAE patients live in fear or uncertainty and are unsatisfied with their doctors' management of the disease. Physicians need to educate themselves to be more familiar with HAE.
373 C1 InhibitorDeficiencyand NormalC4 Bruce J Goldberg, E Park Kaiser-Permanente, Los Angeles, CA Angioedema due to C 1 inhibitor deficiency is described in the literature as being associated with decreased C4 both during and between acute attacks and with decreased C2 frequently only during acute attacks. Thus determination of C4 is often cited as a screen for C1 inhibitor deficiency. The reports in the literature referring to low C4 and C1 inhibitor appear to be largely anectodal. In this study we present our findings on a series of patients with abnormal C 1 inhibitor function and/or protein and normal C4. Between 1999 and 2001, our laboratory has detected 37 patients with abnormal C1 inhibitor function as determined by enzyme linked immunoabsorbent assay (Quidel ®, Mountain View, CA). All such patients were verified as having abnormal CI inhibitor function by repeat assay on the same or a freshly submitted specimen. All abnormal sera were then subjected to determination of C1 inhibitor protein and C4 protein by single radial immunodiffusion (The Binding Site Inc., San Diego, CA). Of the 37 patients with low C 1 inhibitor function, 13 (35 %) were found to have a normal C4 and 22 (59%) a normal C 1 inhibitor protein. Of the 22 patients with normal C1 inhibitor protein, 13 patients (59%) had a normal C4. No patients with both decreased C 1 inhibitor function and protein had a normal C4. Our results indicate that Type II C 1 inhibitor deficiency may be more common than previously reported (59% vs. 15%) and may be accompanied by normal C4 in close to 59% of patients. In contrast, Type I C1 inhibitor deficiency may always be associated with low C4. Thus, C l inhibitor functional assay would appear more useful as a screen for C 1 inhibitor deficiency than C4 or C 1 inhibitor protein assays.