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Angioneurotic edema
Angioneurotic
edema
J. K. Barclay, M.D.X., P.A.C.D.S., L.D.S.R.C.S.,* and J. L. Edwards, B.D.S., P.D.S.R.C.S., P.A.C.D.S.,** Dune&n, New Zealand UNIVERSITY
OF
OTAGO
DENTAL
SCHOOL
Angioneurotic edema is a rare but possible cause of acute facial swelling. TWO types are recognized-hereditary and nonhereditary. Although they may present in a similar manner, their management is quite different. The nonhereditary form can present a problem in diagnosis and is an embarrassment rather than a threat to the patient. Hereditary angioneurotic edema, however, may threaten the airway and thus endanger the patient’s life. As trauma may precipitate an attack, dental treatment of a traumatic nature should be carried out in a hospital.
T
he diagnosis of an acute facial swelling is a common enough problem for the dentist. The usual causes are infection, trauma, hematoma, and very occasionally emphysema. Angioneurotic edema, or angioedema, is another rare cause of swelling that may appear suddenly. Although it can involve any region of the body, the face and oral soft tissues are not uncommonly affected. The overlying skin is usually of normal color, but on occasions it may become pink. The swelling is painless and transitory and involves the subcutaneous and submucosal tissues. It occurs as a result of dilatation of the small blood vessels and transudation of fluid through the capillary walls. The increased capillary permeability is believed to be allergic or neurogenic in origin.2 Two separate types of angioneurotic edema are now recognized-a rare nonhereditary or sporadic form and an even more rare hereditary type. The nonhereditary type may be regarded as a giant form of urticaria and can occur as an allergic response or as a result of infection, trauma, or emotional stress. The face, hands, feet, and genitals are the skin areas most frequently involved. Edema of the glottis is seldom a problem in the nonhereditary form of this condition. As the same site may be affected on numerous occasions,1 the sporadic form of angioneurotic edema may be annoying for the patient, but it is seldom dangerous. It may represent a diagnostic problem for the doctor. On the other hand, hereditary angioneurotic edema carries a more serious prognosis. It may be distinguished from other forms of angioedema by the hereditary absence or functional deficiency of a normally occurring inhibitor of esterase activity associated with the first component of complement.4 Visceral *Senior **Senior
552
Lecturer Dental
in Oral Surgeon,
Surgery, Dunedin
Department of Oral Public Hospital.
Surgery.
Volume Number
32 4
Angioneurotic
edema
553
manifestations in the form of pain and vomiting are frequent, and edema of the glottis with respiratory obstruction has eventually proved fatal in about 25 per cent of the affected persons. 3 Adrenalin, corticosteroids, isoprenaline, and antihistamines have all been used in an attempt to control the progress of this edema but have met with scant success.6 However, active intervention is probably necessary only in the presence of abdominal pain or when the airway is endangered. The prophylactic administration of e. aminocaproic acid may reduce the incidence of acute attacks of hereditary angioneurotic edema. Such treatment is not successful in all patients with this complaint, and it is not without unwanted side effects.5 Dental treatment may trigger an attack of angioneurotic edema, and gross swelling of the lips and lower face have been reported following dental extractions.7 The details of this case history suggest that it was probably a hereditary angioneurotic edema, although it was not recognized as such at the time. More recently Pickering and colleagues6 have reported two patients with hereditary angioneurotic edema who were successfully treated with fresh frozen plasma containing the specific esterase inhibitor. In one patient progressive edema of the glottis was reversed, and in the other abdominal pains and vomiting were relieved within 90 minutes following transfusion, Angioneurotic edema is sufficiently uncommon that few case reports are published in the literature, and the diagnosis and management of this problem are seldom covered in standard dental texts. The four case histories which follow illustrate the need for a recognition of angioneurotic edema as a rare cause of facial and oral swelling. CASE
1
A 22-year-old married woman complained of swelling of the right cheek; the swelling had at no time been painful. It had occurred for the first time 5 weeks prior to examination, and the patient’s medical practitioner had prescribed a course of antibiotics. The swelling had resolved within 2 days. When it returned a week later, she was referred by her medical practitioner to her dentist, who treated her for pericoronitis associated with an impacted, partly erupted lower third molar. Complete resolution of the swelling occurred again, only to be followed by another episode a few weeks later. At this stage the patient was referred to us. The patient had a firm, edematous, purplish pink, nontender swelling of the lower right face (Fig. 1). Her medical history was noncontributory. No submandibular or cervical lymphadenitis was present, and the patient was afebrile. Although the lower right third molar was impacted, there was no clinical evidence of pericoronitis. During the examination the patient drew attention to a pink, raised swelling which had suddenly arisen on the flexor surface of her right wrist. In view of the history and clinical findings, a provisional diagnosis of nonhereditary angioneurotic edema was made, and the patient was referred to a dermatologist, who prescribed antihistamines for a l-month trial period. A week later, on her second visit to the dermatologist, a 5-day course of tetracycline was prescribed in lieu of the antihistamine, and within 24 hours a large facial swelling developed. This minor emergency sent the patient back to her medical practitioner, who, in turn, stopped the tetracycline and prescribed another type of antihistamine. Complete resolution of the facial swelling again occurred within 24 to 36 hours. Five days later the facial swelling reappeared, and on this occasion the lips were involved. The medical practitioner prescribed yet another type of antihistamine and a combined nasal decongestant and bronchodilator. Again the swelling resolved within 36 hours. A few days later the patient left New Zealand for Australia and was lost to follow-up.
554
Barclay
Pig. CASE
I.
Swelling
and Edwards
of the
right
Oral October,
masseteric
area;
periphery
outlined
with
Surg. 1971
arrows.
2
As a result of dental neglect, a 33-year-old housewTife required full-mouth extractions, which were carried out under nasotracheal anesthesia. There was no significant medical history, and the results of routine preoperative screening tests were all within normal limits. General anesthesia and extractions were completed without complication, and the patient was extubated and returned to the recovery ward. About 20 minutes later the patient’s lips began to swell, and the swelling continued to increase in size until both cheeks and infraorbital regions were affected. Almost as quickly as the swelling commenced, it began to resolve, until 35 minutes after extubation only the lips and perioral tissues were involved (Fig. 2). The swelling was fairly tense but caused the patient no real distress. At no time was the patient’s airway endangered, and no treatment was given. Her appearance returned to normal within 36 hours (Fig. 3). A diagnosis of nonhereditary angionenrotic edema was made with the thought that it might have been an allergic response to an agent used on or around the lips during the operation. Consequently, patch tests were carried out on the skin preparation, 2 per cent lidocaine spray, lubricating jelly, French chalk, and petroleum jolly. All responses proved to be negative. CASE
3
A 24year-old male undergraduate student was referred by his physician with a complaint of a swollen lower lip. The patient had awakened that morning to find the lower half of his left face and lower lip severely swollen. Although the swelling had already begun to subside, a B-day course of antibiotic capsules had been prescribed. When examined, the patient was in no great distress but was still somewhat alarmed by the sudden appearance of the swelling. The swelling, which visibly decreased in size over a 30.minute period, was somewhat tender to palpation and the overlying skin was of normal color. No demonstrable dental or oral cause for the swelling could be found, and there was no personal or familial history of similar occurrences. The patient was due to take a professional examination the following day but said that this caused him no undue concern. A diagnosis of nonhereditary angioneurotic edema was made, and the course of antibiotics was withheld. Resolution was complete within 6 to 7 hours of waking, and to date there has been no further swelling.
Volume Number
32 4
Angioneurotic
edema
555
Fig. 2
Fig. Fig.
CASE
b. Angioneurotic edema of the lips. 3. Complete resolution 36 hours later.
4
The 6-year-old daughter of a known sufferer of hereditary angioneurotic edema was referred for dental treatment. The family tree had been extensively investigated by the Human Genetics Unit of the University of Otago Medical School. Five generations had been involved to date, and five deaths had occurred which could be attributed to glottic edema. The patient had her first attack of edema at the age of 3, when the buttock, back, then the arm, hand, and, finally, the face was involved. The attack lasted 5 days. Episodes of swelling, characteristic of the condition, have occurred regularly, and minor trauma has often been a precipitating factor. Some of these swellings have involved the face and lips, but as yet none have caused respiratory distress. Episodes of abdominal pain and vomiting have also occurred on a number of occasions. Prophylaxis with a combined antihistaminic and alpha adrenergic blocking agent have subjectively reduced the frequency and severity of the attacks, as has isoprenaline during acute episodes. The patient had a well-cared-for dentition, and there had been no previous dental extractions. Conservative dental procedures had been carried out without difficulty and without the use of local anesthesia. Extraction of three deciduous teeth was required for orthodontic reasons, and, because of the relationship between minor trauma and episodes of edema, the patient was admitted to the hospital. The teeth were carefully extracted under nitrous oxide-oxygen-halothane anesthesia via a nasal mask. There was no postoperative edema, and the patient was discharged on the following day. She has continued on the same prophylactic regime.
DISCUSSION
In Case 1 it appears that infection was thought to be the cause of the facial swelling, as on more than one occasion antibiotics were prescribed. Although two classic signs of inflammation were present (swelling and redness), the of pain made this diagnosis unlikely. Various antihistamines complete absence were also given on three occasions. It is interesting to note that, no matter
556
Barclay
and
Edwards
Oral October,
Surg. 1971
what form of drug therapy was prescribed, the swelling always resolved within 36 hours. It is likely that resolution would have occurred in the absence of any treatment, as it did in Cases2 and 3. The emotional stress of an important professional examination may have been the precipitating factor in Case 3. Antibiotics were prescribed, as in Case 1, on the assumption that the swelling was infective in origin. It appears that swellings of this nature nmy bc misdiagnosed, presumably because of their rarity. When a diagnosis of nonhereditary angioneurotic edema is made, active t,reatment is probably not warranted, although continued observation of the patient is obviously a wise precaution. Even though dental extractions were completed without complications in Cast 4, it is necessary that patients with known hereditary angioneurotic edema who require dental extractions be treated in the hospita.1. Should the operative trauma precipitate an acute attack of edema, facilities would then be available to treat complications. Treatment may include tracheostomy or t,he infusion of fresh frozen plasma. It would also seem a scnsiblc precaution t,o administer a general anesthetic via a na.sal mask rather than a nasotrachcal tuhc. CONCLUSION
Angioneurotic edema is a rare but possible cause of acute facial swelling. Two t,ypes are recognizecl---hereditary and nonhereditary. Although these may present in a similar manner, their management is quite different. The nonhereditary form can present a problem in diagnosis and is an embarrassment rather than a threat to t,he patient. Hereditary angioneurotic edema, however, may threaten t,he airway and t,hus endanger the patient’s life. As trauma may precipitate an attack, dental treatment of a traumatic nature should be carried out in a hospital. 1Ve would like to thank Dr. E. G. ?&Queen, his referral of the patient in (‘ase 4.
Professor
of
Clinical
Pharmacology,
for
REFERENCES
1. Abbott, W. I).: Periodic Edema of Hand With Seven Day Cycle, J. A. M. A. 100: 1328. 1320, 1933. 2. Anderson, W. A. D.: Pathology, ed. 5, St. Louis, 1966, The C. V. Mosby Company, p. 81. 3. Beeson, P. B., and McDermott, W.: Textbook of Medicine, ed. 12, Philadelphia, 1967, W. B. Saunders Company, p. 439. 4. Donaldson, V. H., and Evans, R. R.: A Biochemical Abnormality in Hereditary dngioneurotic Edema, Am. J. Med. 35: 37-4!, 1963. 5. Lundh, B., Laurell, A. B., Wetterqvlst, H., White, T., and Granerus, G.: A Case of Hereditary Angioneurotic Edema, Successfully Treated With E. Aminocaproic Acid, Clin. Exp. Immunol. 3: 733-745, 1968. 6. Pickering, R. J., Kelly, J. R., Good, R. A., and Gewurz, H.: Replacement Therapy in Hereditary Angioedema, Lancet 1: 326-330, 1969. 7. Senley, V.: Angioneurotic oedema, Aust. J. Dent. 58: 11-13, 1954. Reprint +equests to: Dr. J. K. Barclay Department of Oral University of Otago P. 0. Box 647 Dunedin, C. 1, h’ew
Surgery Dental Zealand
School
edema
J. K. Barclay, M.D.X., P.A.C.D.S., L.D.S.R.C.S.,* and J. L. Edwards, B.D.S., P.D.S.R.C.S., P.A.C.D.S.,** Dune&n, New Zealand UNIVERSITY
OF
OTAGO
DENTAL
SCHOOL
Angioneurotic edema is a rare but possible cause of acute facial swelling. TWO types are recognized-hereditary and nonhereditary. Although they may present in a similar manner, their management is quite different. The nonhereditary form can present a problem in diagnosis and is an embarrassment rather than a threat to the patient. Hereditary angioneurotic edema, however, may threaten the airway and thus endanger the patient’s life. As trauma may precipitate an attack, dental treatment of a traumatic nature should be carried out in a hospital.
T
he diagnosis of an acute facial swelling is a common enough problem for the dentist. The usual causes are infection, trauma, hematoma, and very occasionally emphysema. Angioneurotic edema, or angioedema, is another rare cause of swelling that may appear suddenly. Although it can involve any region of the body, the face and oral soft tissues are not uncommonly affected. The overlying skin is usually of normal color, but on occasions it may become pink. The swelling is painless and transitory and involves the subcutaneous and submucosal tissues. It occurs as a result of dilatation of the small blood vessels and transudation of fluid through the capillary walls. The increased capillary permeability is believed to be allergic or neurogenic in origin.2 Two separate types of angioneurotic edema are now recognized-a rare nonhereditary or sporadic form and an even more rare hereditary type. The nonhereditary type may be regarded as a giant form of urticaria and can occur as an allergic response or as a result of infection, trauma, or emotional stress. The face, hands, feet, and genitals are the skin areas most frequently involved. Edema of the glottis is seldom a problem in the nonhereditary form of this condition. As the same site may be affected on numerous occasions,1 the sporadic form of angioneurotic edema may be annoying for the patient, but it is seldom dangerous. It may represent a diagnostic problem for the doctor. On the other hand, hereditary angioneurotic edema carries a more serious prognosis. It may be distinguished from other forms of angioedema by the hereditary absence or functional deficiency of a normally occurring inhibitor of esterase activity associated with the first component of complement.4 Visceral *Senior **Senior
552
Lecturer Dental
in Oral Surgeon,
Surgery, Dunedin
Department of Oral Public Hospital.
Surgery.
Volume Number
32 4
Angioneurotic
edema
553
manifestations in the form of pain and vomiting are frequent, and edema of the glottis with respiratory obstruction has eventually proved fatal in about 25 per cent of the affected persons. 3 Adrenalin, corticosteroids, isoprenaline, and antihistamines have all been used in an attempt to control the progress of this edema but have met with scant success.6 However, active intervention is probably necessary only in the presence of abdominal pain or when the airway is endangered. The prophylactic administration of e. aminocaproic acid may reduce the incidence of acute attacks of hereditary angioneurotic edema. Such treatment is not successful in all patients with this complaint, and it is not without unwanted side effects.5 Dental treatment may trigger an attack of angioneurotic edema, and gross swelling of the lips and lower face have been reported following dental extractions.7 The details of this case history suggest that it was probably a hereditary angioneurotic edema, although it was not recognized as such at the time. More recently Pickering and colleagues6 have reported two patients with hereditary angioneurotic edema who were successfully treated with fresh frozen plasma containing the specific esterase inhibitor. In one patient progressive edema of the glottis was reversed, and in the other abdominal pains and vomiting were relieved within 90 minutes following transfusion, Angioneurotic edema is sufficiently uncommon that few case reports are published in the literature, and the diagnosis and management of this problem are seldom covered in standard dental texts. The four case histories which follow illustrate the need for a recognition of angioneurotic edema as a rare cause of facial and oral swelling. CASE
1
A 22-year-old married woman complained of swelling of the right cheek; the swelling had at no time been painful. It had occurred for the first time 5 weeks prior to examination, and the patient’s medical practitioner had prescribed a course of antibiotics. The swelling had resolved within 2 days. When it returned a week later, she was referred by her medical practitioner to her dentist, who treated her for pericoronitis associated with an impacted, partly erupted lower third molar. Complete resolution of the swelling occurred again, only to be followed by another episode a few weeks later. At this stage the patient was referred to us. The patient had a firm, edematous, purplish pink, nontender swelling of the lower right face (Fig. 1). Her medical history was noncontributory. No submandibular or cervical lymphadenitis was present, and the patient was afebrile. Although the lower right third molar was impacted, there was no clinical evidence of pericoronitis. During the examination the patient drew attention to a pink, raised swelling which had suddenly arisen on the flexor surface of her right wrist. In view of the history and clinical findings, a provisional diagnosis of nonhereditary angioneurotic edema was made, and the patient was referred to a dermatologist, who prescribed antihistamines for a l-month trial period. A week later, on her second visit to the dermatologist, a 5-day course of tetracycline was prescribed in lieu of the antihistamine, and within 24 hours a large facial swelling developed. This minor emergency sent the patient back to her medical practitioner, who, in turn, stopped the tetracycline and prescribed another type of antihistamine. Complete resolution of the facial swelling again occurred within 24 to 36 hours. Five days later the facial swelling reappeared, and on this occasion the lips were involved. The medical practitioner prescribed yet another type of antihistamine and a combined nasal decongestant and bronchodilator. Again the swelling resolved within 36 hours. A few days later the patient left New Zealand for Australia and was lost to follow-up.
554
Barclay
Pig. CASE
I.
Swelling
and Edwards
of the
right
Oral October,
masseteric
area;
periphery
outlined
with
Surg. 1971
arrows.
2
As a result of dental neglect, a 33-year-old housewTife required full-mouth extractions, which were carried out under nasotracheal anesthesia. There was no significant medical history, and the results of routine preoperative screening tests were all within normal limits. General anesthesia and extractions were completed without complication, and the patient was extubated and returned to the recovery ward. About 20 minutes later the patient’s lips began to swell, and the swelling continued to increase in size until both cheeks and infraorbital regions were affected. Almost as quickly as the swelling commenced, it began to resolve, until 35 minutes after extubation only the lips and perioral tissues were involved (Fig. 2). The swelling was fairly tense but caused the patient no real distress. At no time was the patient’s airway endangered, and no treatment was given. Her appearance returned to normal within 36 hours (Fig. 3). A diagnosis of nonhereditary angionenrotic edema was made with the thought that it might have been an allergic response to an agent used on or around the lips during the operation. Consequently, patch tests were carried out on the skin preparation, 2 per cent lidocaine spray, lubricating jelly, French chalk, and petroleum jolly. All responses proved to be negative. CASE
3
A 24year-old male undergraduate student was referred by his physician with a complaint of a swollen lower lip. The patient had awakened that morning to find the lower half of his left face and lower lip severely swollen. Although the swelling had already begun to subside, a B-day course of antibiotic capsules had been prescribed. When examined, the patient was in no great distress but was still somewhat alarmed by the sudden appearance of the swelling. The swelling, which visibly decreased in size over a 30.minute period, was somewhat tender to palpation and the overlying skin was of normal color. No demonstrable dental or oral cause for the swelling could be found, and there was no personal or familial history of similar occurrences. The patient was due to take a professional examination the following day but said that this caused him no undue concern. A diagnosis of nonhereditary angioneurotic edema was made, and the course of antibiotics was withheld. Resolution was complete within 6 to 7 hours of waking, and to date there has been no further swelling.
Volume Number
32 4
Angioneurotic
edema
555
Fig. 2
Fig. Fig.
CASE
b. Angioneurotic edema of the lips. 3. Complete resolution 36 hours later.
4
The 6-year-old daughter of a known sufferer of hereditary angioneurotic edema was referred for dental treatment. The family tree had been extensively investigated by the Human Genetics Unit of the University of Otago Medical School. Five generations had been involved to date, and five deaths had occurred which could be attributed to glottic edema. The patient had her first attack of edema at the age of 3, when the buttock, back, then the arm, hand, and, finally, the face was involved. The attack lasted 5 days. Episodes of swelling, characteristic of the condition, have occurred regularly, and minor trauma has often been a precipitating factor. Some of these swellings have involved the face and lips, but as yet none have caused respiratory distress. Episodes of abdominal pain and vomiting have also occurred on a number of occasions. Prophylaxis with a combined antihistaminic and alpha adrenergic blocking agent have subjectively reduced the frequency and severity of the attacks, as has isoprenaline during acute episodes. The patient had a well-cared-for dentition, and there had been no previous dental extractions. Conservative dental procedures had been carried out without difficulty and without the use of local anesthesia. Extraction of three deciduous teeth was required for orthodontic reasons, and, because of the relationship between minor trauma and episodes of edema, the patient was admitted to the hospital. The teeth were carefully extracted under nitrous oxide-oxygen-halothane anesthesia via a nasal mask. There was no postoperative edema, and the patient was discharged on the following day. She has continued on the same prophylactic regime.
DISCUSSION
In Case 1 it appears that infection was thought to be the cause of the facial swelling, as on more than one occasion antibiotics were prescribed. Although two classic signs of inflammation were present (swelling and redness), the of pain made this diagnosis unlikely. Various antihistamines complete absence were also given on three occasions. It is interesting to note that, no matter
556
Barclay
and
Edwards
Oral October,
Surg. 1971
what form of drug therapy was prescribed, the swelling always resolved within 36 hours. It is likely that resolution would have occurred in the absence of any treatment, as it did in Cases2 and 3. The emotional stress of an important professional examination may have been the precipitating factor in Case 3. Antibiotics were prescribed, as in Case 1, on the assumption that the swelling was infective in origin. It appears that swellings of this nature nmy bc misdiagnosed, presumably because of their rarity. When a diagnosis of nonhereditary angioneurotic edema is made, active t,reatment is probably not warranted, although continued observation of the patient is obviously a wise precaution. Even though dental extractions were completed without complications in Cast 4, it is necessary that patients with known hereditary angioneurotic edema who require dental extractions be treated in the hospita.1. Should the operative trauma precipitate an acute attack of edema, facilities would then be available to treat complications. Treatment may include tracheostomy or t,he infusion of fresh frozen plasma. It would also seem a scnsiblc precaution t,o administer a general anesthetic via a na.sal mask rather than a nasotrachcal tuhc. CONCLUSION
Angioneurotic edema is a rare but possible cause of acute facial swelling. Two t,ypes are recognizecl---hereditary and nonhereditary. Although these may present in a similar manner, their management is quite different. The nonhereditary form can present a problem in diagnosis and is an embarrassment rather than a threat to t,he patient. Hereditary angioneurotic edema, however, may threaten t,he airway and t,hus endanger the patient’s life. As trauma may precipitate an attack, dental treatment of a traumatic nature should be carried out in a hospital. 1Ve would like to thank Dr. E. G. ?&Queen, his referral of the patient in (‘ase 4.
Professor
of
Clinical
Pharmacology,
for
REFERENCES
1. Abbott, W. I).: Periodic Edema of Hand With Seven Day Cycle, J. A. M. A. 100: 1328. 1320, 1933. 2. Anderson, W. A. D.: Pathology, ed. 5, St. Louis, 1966, The C. V. Mosby Company, p. 81. 3. Beeson, P. B., and McDermott, W.: Textbook of Medicine, ed. 12, Philadelphia, 1967, W. B. Saunders Company, p. 439. 4. Donaldson, V. H., and Evans, R. R.: A Biochemical Abnormality in Hereditary dngioneurotic Edema, Am. J. Med. 35: 37-4!, 1963. 5. Lundh, B., Laurell, A. B., Wetterqvlst, H., White, T., and Granerus, G.: A Case of Hereditary Angioneurotic Edema, Successfully Treated With E. Aminocaproic Acid, Clin. Exp. Immunol. 3: 733-745, 1968. 6. Pickering, R. J., Kelly, J. R., Good, R. A., and Gewurz, H.: Replacement Therapy in Hereditary Angioedema, Lancet 1: 326-330, 1969. 7. Senley, V.: Angioneurotic oedema, Aust. J. Dent. 58: 11-13, 1954. Reprint +equests to: Dr. J. K. Barclay Department of Oral University of Otago P. 0. Box 647 Dunedin, C. 1, h’ew
Surgery Dental Zealand
School