DOI: 10.1111/ipd.12117 CASE REPORT
Orthodontic treatment for a patient with hereditary angiodema: a case report KATE WALDON1, SOPHY KATHLEEN BARBER2 & RICHARD JAMES SPENCER3 1
Dental Core Trainee in Oral and Maxillofacial Surgery, Pinderfields Hospital, Wakefield, 2Speciality Registrar in Orthodontics, Pinderfields Hospital, Wakefield, and 3Consultant Orthodontist, Pinderfields Hospital, Wakefield, UK
International Journal of Paediatric Dentistry 2015; 25: 229–232 Background. Hereditary angiodema (HAE), also
known as C1 esterase inhibitor deficiency, causes sufferers to experience episodic subcutaneous and submucosal oedema. These episodes can be triggered by dental treatment and manifest as lifethreatening oedematous swelling in the head and neck region. Case Report. This case report reviews an adolescent with hereditary angiodema whose malocclu-
Introduction
Hereditary angio-oedema (HAE) is an autosomal dominant genetic disorder also known as C1 esterase inhibitor (C1-INH) deficiency [OMIM 606860]1. Predominantly an inherited condition, 25% can present as spontaneous genetic mutations2. HAE manifests as episodic subcutaneous and submucosal oedema in peripheral tissues, respiratory and gastrointestinal tracts, triggered by stress or trauma or occurring spontaneously2. HAE has an estimated mortality rate of 25–30% in untreated individuals following airway compromise and asphyxiation3,4. HAE concerns dentists as routine examinations and interventions (including dental impressions or simple restorations) may trigger an episode, through minor mucosal trauma or stress from dental anxiety. Previous reports outline oral surgery planning for HAE sufferers, primarily by infusion of C1 inhibitor concentrate pre-operatively; however, little information is available Correspondence to: R. James Spencer, Department of Oral and Facial, Pinderfields Hospital, Aberford Road, Wakefield, WF1 4DG, UK. E-mail: [email protected]
sion required orthodontic intervention. Due to her complex and unpredictable reaction to dental treatment, various options were explored before determining the appropriate care pathway for this patient. Trial placement of a sectional fixed appliance tested the tissue reaction prior to comprehensive treatment including extractions and fixed orthodontic appliances. Conclusion. This report demonstrates successful interdisciplinary management facilitating orthodontic care in a patient with HAE.
regarding orthodontic treatment where both planned extractions and the risk of chronic mucosal trauma from orthodontic appliances are potential triggers. Case report
In 2010, EA (age 13 years) was referred to the Orthodontic Department by her Paedodontist for advice regarding her malocclusion. EA had been diagnosed with Type 1 HAE at birth and was managed jointly by an Immunologist and a Paediatrician who recommended giving fresh frozen plasma or C1-INH prior to dental treatment. EA had multiple HAE related hospital admissions, one within the prior three years related to a spontaneous minor swelling in the head and neck, which fully resolved with a single-dose of C1INH concentrate. EA had class II division 1 malocclusion on class I skeletal base with 6 mm overjet, moderate crowding, unerupted maxillary canines and bilateral buccal crossbites (Fig. 1). These treatment options were discussed: 1) Accept malocclusion 2) Extract maxillary first premolars to encourage spontaneous canine position improve-
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
229
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K. Waldon, S. K. Barber & R. J. Spencer
Fig. 1. Pre-treatment intra-oral photographs (January 2012).
ment, likely resulting in residual space distal to the canines. 3) Comprehensive orthodontic treatment involving upper and lower extractions and fixed appliances. Treatment would have to be abandoned if fixed appliances were to trigger an acute angiodema episode, and if this happened after bi-maxillary extractions EA would be left with poorer occlusion than the other options would provide. A trial fixed appliance period pre-extraction could be used to assess tissue reaction and determine if comprehensive treatment was viable. A reflective interval was agreed, during which time EA received comprehensive dental care from her Paedodontist. This treatment was undertaken in hospital setting with 1000 units C1-INH concentrate pre-operatively. No soft tissue reactions were reported and recovery was uneventful. The Paedodontist reported that UL6 (FDI 26) was poor longterm prognosis, so when orthodontic intervention was considered this was the tooth of choice in that quadrant, but in other quadrants the ideal tooth for efficient orthodontic movement and outcome were chosen (Fig. 2).
Fig. 2. Pre-treatment DPT showing caries in the upper left first permanent molar.
EA and her parents considered the risks versus benefits of orthodontic treatment, and a process of informed consent led to the following care pathway. 1) Test bond up of sectional fixed appliances for one month 2) If no tissue reaction, extraction of UR4, UL6, LL5, LR5 with pre-operative 1000 units C1-INH concentrate. Sectional fixed appliances were placed in April 2012, with prophylactic tranexamic acid (on the recommendation of EA’s Clinical Immunologist). No tissue reaction was reported and EA underwent extractions with-
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Orthodontic treatment with HAE
231
Fig. 3. Intra-oral photographs taken 3 months after completion of orthodontic treatment (February 2014)
Table 1. Distribution of HAE type and resulting C1-ING expression2,5. Type of HAE
% affected
Effect on C1-INH
1 2 3
85 15 Rare
Reduced plasma concentration Abnormal function Not fully understood
out complications in June 2012. Comprehensive orthodontics with standard oral hygiene measures completed in November 2013 with excellent outcome (Fig. 3). Retention was provided with vacuumformed retainers scalloped away from the gingiva to reduce mucosal irritation. Throughout her treatment, EA did not report any occurrence of mucosal inflammation not was any noted at follow-up appointments. Discussion
HAE prevalence is 1/50,000 with no recorded gender or racial predilection2 (Table 1). C1 esterase inhibitor is involved in the inhibition
Table 2. Management of HAE. Scenario
Management
Acute HAE5
Procedural Prophylaxis3
● C1 inhibitor concentrate (Berinert Pâ) ● Kalikrein inhibitor (KALBITORâ, currently licensed in the US) ● Icatibant, a selective bradykinin receptor 2 antagonist (Firazyrâ) No standard protocol available. Current treatments include the following.
Lifelong Prophylaxis2,4
● C1 inhibitor concentrate (Berinert Pâ): recommended in children ● Androgens (danazol; risk of affecting maturation in children5) ● Antifibrinolytics (tranexamic acid) ● Icatibant (Firazyrâ) Little evidence for lifelong prophylaxis. Current treatments include the following. ● Androgens ● Antifibrinolytics ● C1 inhibitor concentrate (Berinert Pâ)
of kallikrein-kinin, contact, complement, and fibrinolytic plasma cascade activation. Reduced active C1-INH contributes to excessive production of bradykinin, in turn increasing vascular permeability and vasodilation leading to tissue fluid accumulation and the oedema associated
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
232
K. Waldon, S. K. Barber & R. J. Spencer
with HAE3. Acute angiodema carries a variable latency period of 20 min to 36 h, but often follows a pattern of worsening for 24 h after the trigger and subsiding in the following 24– 72 h2,4. Management of HAE Unlike many auto-immune conditions HAE does not respond to antihistamines or corticosteroids2 (Table 2). C1 inhibitor concentrate is prepared from human plasma and has a small but theoretical risk of pathogen transfer and development of resistance. Icatibant is a synthetic peptide and so has reduced risk of resistance, pathogen transfer, and religious objections. It is reported that up to 50% of acute presentations may have been triggered by dental treatment2. Fatal airway compromise has been reported following dental extraction although individual reactions are unpredictable. As with EA, all patients should be made aware that dental treatment may precipitate an acute attack and/ or manifest as a delayed reaction. As infection is also a risk factor for triggering an attack, potential sources of dental and oral infections should be treated prophylactically. Factors influencing treatment planning3;
1) Surgery in region of airway, such as oral surgery 2) Previous episodes of angiodema affecting the airway 3) Surgery necessitating airway device for anaesthesia 4) Consider provision of dental treatment in secondary care with appropriate prophylaxis and multi-disciplinary approach Acknowledgements
We would like to thank Mohamed Imran Suida and Esther McDerra for their involvement in the care of this patient. References 1 http://www.omim.org/entry/606860 (last accessed 03/ 04/2014). 2 Gompels MM, Lock RJ, Abinun M et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol 2005; 139: 379–394. Eratum: Clinical and Experimental Immunology 2005; 141: 189-90. 3 Senaratne KT, Cottrell AM, Prentice JL. Successful perioperative management of a patient with C1 esterase inhibitor deficiency with a novel bradykinin receptor B2 antagonist. Anaesth Intensive Care 2012; 40: 523–526. 4 Costantino G, Casazza G, Bossi I, Duca P, Cicacrdi M. Long-term prophylaxis in hereditary angio-oedema: a systematic review. BMJ Open 2012; 2: e000524. 5 Zuraw BL. Current and future therapy for hereditary angioedema. Clin Immunol 2005; 114: 10–16.
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Orthodontic treatment for a patient with hereditary angiodema: a case report KATE WALDON1, SOPHY KATHLEEN BARBER2 & RICHARD JAMES SPENCER3 1
Dental Core Trainee in Oral and Maxillofacial Surgery, Pinderfields Hospital, Wakefield, 2Speciality Registrar in Orthodontics, Pinderfields Hospital, Wakefield, and 3Consultant Orthodontist, Pinderfields Hospital, Wakefield, UK
International Journal of Paediatric Dentistry 2015; 25: 229–232 Background. Hereditary angiodema (HAE), also
known as C1 esterase inhibitor deficiency, causes sufferers to experience episodic subcutaneous and submucosal oedema. These episodes can be triggered by dental treatment and manifest as lifethreatening oedematous swelling in the head and neck region. Case Report. This case report reviews an adolescent with hereditary angiodema whose malocclu-
Introduction
Hereditary angio-oedema (HAE) is an autosomal dominant genetic disorder also known as C1 esterase inhibitor (C1-INH) deficiency [OMIM 606860]1. Predominantly an inherited condition, 25% can present as spontaneous genetic mutations2. HAE manifests as episodic subcutaneous and submucosal oedema in peripheral tissues, respiratory and gastrointestinal tracts, triggered by stress or trauma or occurring spontaneously2. HAE has an estimated mortality rate of 25–30% in untreated individuals following airway compromise and asphyxiation3,4. HAE concerns dentists as routine examinations and interventions (including dental impressions or simple restorations) may trigger an episode, through minor mucosal trauma or stress from dental anxiety. Previous reports outline oral surgery planning for HAE sufferers, primarily by infusion of C1 inhibitor concentrate pre-operatively; however, little information is available Correspondence to: R. James Spencer, Department of Oral and Facial, Pinderfields Hospital, Aberford Road, Wakefield, WF1 4DG, UK. E-mail: [email protected]
sion required orthodontic intervention. Due to her complex and unpredictable reaction to dental treatment, various options were explored before determining the appropriate care pathway for this patient. Trial placement of a sectional fixed appliance tested the tissue reaction prior to comprehensive treatment including extractions and fixed orthodontic appliances. Conclusion. This report demonstrates successful interdisciplinary management facilitating orthodontic care in a patient with HAE.
regarding orthodontic treatment where both planned extractions and the risk of chronic mucosal trauma from orthodontic appliances are potential triggers. Case report
In 2010, EA (age 13 years) was referred to the Orthodontic Department by her Paedodontist for advice regarding her malocclusion. EA had been diagnosed with Type 1 HAE at birth and was managed jointly by an Immunologist and a Paediatrician who recommended giving fresh frozen plasma or C1-INH prior to dental treatment. EA had multiple HAE related hospital admissions, one within the prior three years related to a spontaneous minor swelling in the head and neck, which fully resolved with a single-dose of C1INH concentrate. EA had class II division 1 malocclusion on class I skeletal base with 6 mm overjet, moderate crowding, unerupted maxillary canines and bilateral buccal crossbites (Fig. 1). These treatment options were discussed: 1) Accept malocclusion 2) Extract maxillary first premolars to encourage spontaneous canine position improve-
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
229
230
K. Waldon, S. K. Barber & R. J. Spencer
Fig. 1. Pre-treatment intra-oral photographs (January 2012).
ment, likely resulting in residual space distal to the canines. 3) Comprehensive orthodontic treatment involving upper and lower extractions and fixed appliances. Treatment would have to be abandoned if fixed appliances were to trigger an acute angiodema episode, and if this happened after bi-maxillary extractions EA would be left with poorer occlusion than the other options would provide. A trial fixed appliance period pre-extraction could be used to assess tissue reaction and determine if comprehensive treatment was viable. A reflective interval was agreed, during which time EA received comprehensive dental care from her Paedodontist. This treatment was undertaken in hospital setting with 1000 units C1-INH concentrate pre-operatively. No soft tissue reactions were reported and recovery was uneventful. The Paedodontist reported that UL6 (FDI 26) was poor longterm prognosis, so when orthodontic intervention was considered this was the tooth of choice in that quadrant, but in other quadrants the ideal tooth for efficient orthodontic movement and outcome were chosen (Fig. 2).
Fig. 2. Pre-treatment DPT showing caries in the upper left first permanent molar.
EA and her parents considered the risks versus benefits of orthodontic treatment, and a process of informed consent led to the following care pathway. 1) Test bond up of sectional fixed appliances for one month 2) If no tissue reaction, extraction of UR4, UL6, LL5, LR5 with pre-operative 1000 units C1-INH concentrate. Sectional fixed appliances were placed in April 2012, with prophylactic tranexamic acid (on the recommendation of EA’s Clinical Immunologist). No tissue reaction was reported and EA underwent extractions with-
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Orthodontic treatment with HAE
231
Fig. 3. Intra-oral photographs taken 3 months after completion of orthodontic treatment (February 2014)
Table 1. Distribution of HAE type and resulting C1-ING expression2,5. Type of HAE
% affected
Effect on C1-INH
1 2 3
85 15 Rare
Reduced plasma concentration Abnormal function Not fully understood
out complications in June 2012. Comprehensive orthodontics with standard oral hygiene measures completed in November 2013 with excellent outcome (Fig. 3). Retention was provided with vacuumformed retainers scalloped away from the gingiva to reduce mucosal irritation. Throughout her treatment, EA did not report any occurrence of mucosal inflammation not was any noted at follow-up appointments. Discussion
HAE prevalence is 1/50,000 with no recorded gender or racial predilection2 (Table 1). C1 esterase inhibitor is involved in the inhibition
Table 2. Management of HAE. Scenario
Management
Acute HAE5
Procedural Prophylaxis3
● C1 inhibitor concentrate (Berinert Pâ) ● Kalikrein inhibitor (KALBITORâ, currently licensed in the US) ● Icatibant, a selective bradykinin receptor 2 antagonist (Firazyrâ) No standard protocol available. Current treatments include the following.
Lifelong Prophylaxis2,4
● C1 inhibitor concentrate (Berinert Pâ): recommended in children ● Androgens (danazol; risk of affecting maturation in children5) ● Antifibrinolytics (tranexamic acid) ● Icatibant (Firazyrâ) Little evidence for lifelong prophylaxis. Current treatments include the following. ● Androgens ● Antifibrinolytics ● C1 inhibitor concentrate (Berinert Pâ)
of kallikrein-kinin, contact, complement, and fibrinolytic plasma cascade activation. Reduced active C1-INH contributes to excessive production of bradykinin, in turn increasing vascular permeability and vasodilation leading to tissue fluid accumulation and the oedema associated
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
232
K. Waldon, S. K. Barber & R. J. Spencer
with HAE3. Acute angiodema carries a variable latency period of 20 min to 36 h, but often follows a pattern of worsening for 24 h after the trigger and subsiding in the following 24– 72 h2,4. Management of HAE Unlike many auto-immune conditions HAE does not respond to antihistamines or corticosteroids2 (Table 2). C1 inhibitor concentrate is prepared from human plasma and has a small but theoretical risk of pathogen transfer and development of resistance. Icatibant is a synthetic peptide and so has reduced risk of resistance, pathogen transfer, and religious objections. It is reported that up to 50% of acute presentations may have been triggered by dental treatment2. Fatal airway compromise has been reported following dental extraction although individual reactions are unpredictable. As with EA, all patients should be made aware that dental treatment may precipitate an acute attack and/ or manifest as a delayed reaction. As infection is also a risk factor for triggering an attack, potential sources of dental and oral infections should be treated prophylactically. Factors influencing treatment planning3;
1) Surgery in region of airway, such as oral surgery 2) Previous episodes of angiodema affecting the airway 3) Surgery necessitating airway device for anaesthesia 4) Consider provision of dental treatment in secondary care with appropriate prophylaxis and multi-disciplinary approach Acknowledgements
We would like to thank Mohamed Imran Suida and Esther McDerra for their involvement in the care of this patient. References 1 http://www.omim.org/entry/606860 (last accessed 03/ 04/2014). 2 Gompels MM, Lock RJ, Abinun M et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol 2005; 139: 379–394. Eratum: Clinical and Experimental Immunology 2005; 141: 189-90. 3 Senaratne KT, Cottrell AM, Prentice JL. Successful perioperative management of a patient with C1 esterase inhibitor deficiency with a novel bradykinin receptor B2 antagonist. Anaesth Intensive Care 2012; 40: 523–526. 4 Costantino G, Casazza G, Bossi I, Duca P, Cicacrdi M. Long-term prophylaxis in hereditary angio-oedema: a systematic review. BMJ Open 2012; 2: e000524. 5 Zuraw BL. Current and future therapy for hereditary angioedema. Clin Immunol 2005; 114: 10–16.
© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
