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The pathology of visible blood vessels on the nasal septum in children with epistaxis
International Journal of Pediatric Otorhinolaryngology 75 (2011) 1032–1034
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
The pathology of visible blood vessels on the nasal septum in children with epistaxis Mary-Louise Montague a, Andrew Whymark a, Allan Howatson b,*, Haytham Kubba a a b
Department of Paediatric Otolaryngology, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, Scotland, United Kingdom Department of Pathology, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, Scotland, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 March 2011 Received in revised form 10 May 2011 Accepted 10 May 2011 Available online 15 June 2011
Objective: Epistaxis is common in children, but its cause remains unknown. About half the children who present with epistaxis have prominent vessels on the nasal septum. The aim of this study was to determine the pathological nature of the prominent septal vessels in children with recurrent epistaxis. Methods: 4 mm punch biopsies of the nasal septal mucosa were taken from 5 children undergoing nasal cautery under general anaesthesia. Results: Histology showed that the prominent vessels were thin-walled arterioles and capillaries with a surrounding inflammatory infiltrate. There was no evidence of venous varicosities or arterial microaneurysms. Conclusion: We postulate a mechanism for septal neovascularisation due to chronic low-grade inflammation as a cause for recurrent epistaxis in children. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Epistaxis Children Neovascularisation Nasal septum
1. Introduction Epistaxis is a common condition in children [1,2]. It is one of the commonest reasons for referral of children to a hospital ENT outpatient department. In contrast to adults the bleeding site in children is most frequently the anterior nasal septum [3,4]. The cause remains obscure, although digital trauma is often blamed [5]. We have recently shown that children with recurrent epistaxis are more likely to have colonisation of the nasal cavity with Staphylococcus aureus than controls [6] and we have suggested that chronic low-grade inflammation may cause irritation, crusting and digital trauma. Further supportive evidence for a microbiological cause for epistaxis comes from trials showing benefit from antiseptic nasal cream [7] but no benefit from simple emollients [8]. This cannot be the whole story, however, as about half the children seen with epistaxis have prominent vessels on the nasal septum [7]. Silver nitrate cautery to obliterate these vessels produces significant benefit in reducing the frequency of epistaxis [9] although the problem often recurs over the next few years [10]. The histopathological nature of these vessels is unknown. They have been called by various names including varicosities, microaneurysms and telangiectases and it is unknown whether they are congenital or acquired.
We therefore performed a study to biopsy the anterior nasal septal mucosa of children with recurrent epistaxis and visibly prominent vessels in order to determine their nature. 2. Methods Ethical approval was obtained from the Yorkhill Research Ethics Committee for a prospective departmental observational cohort study of children under 16 years requiring nasal cautery under general anaesthesia for recurrent epistaxis (Reference P12/04). Children who were found to have a specific intranasal pathology other than prominent vessels on the anterior nasal septum (e.g. rhinitis, vascular anomaly, neoplasm) were excluded from the study. Five consecutive children were recruited for the study. All were given a full explanation, both written and verbal. Signed consent for study participation was obtained from the parents. A single 4 mm circular punch biopsy was taken of the anterior nasal septal mucosa on the side with the most prominent surface vessels prior to silver nitrate cautery. A sterile disposable skin biopsy punch (Williams Medical Supplies) was used. The biopsies were formalin fixed, paraffin embedded, stained with haematoxylin and eosin and subjected to serial sectioning. Biopsy samples were all processed, examined by light microscopy and photographed by the same consultant paediatric pathologist. 3. Results
* Corresponding author. Tel.: +44 0141 2010297; fax: +44 0141 2010865. E-mail address: [email protected] (M.-L. Montague). 0165-5876/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2011.05.011
Five children were studied, of whom 3 were boys and 2 were girls. Their ages ranged from 3 to 8 years (mean age 5 years). All the
M.-L. Montague et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 1032–1034
1033
Fig. 1. The acute stage showing a fibrin thrombus occluding a vein which was the source of recent epistaxis (250). Fig. 3. The late stage of healing with re-epithelialized surface overlying a dilated blood vessel. Note the epithelium in the ‘healed’ area is squamous (i.e. squamous metaplasia with normal transitional epithelium adjacent (250).
Fig. 2. The interim or fibrin stage showing the stage of healing after a bleed with ‘pink’ fibrin lying between the blood vessel and the epithelial surface which is not quite re-epithelialized (250). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
children had recurrent epistaxis with visible prominent vessels on the anterior nasal septum, but had not been able to tolerate nasal cautery under topical anaesthesia. No child had a co-existing capillary haemangioma or other specific pathology. The children were treated with topical application of antiseptic cream for 2 weeks after the procedure and the biopsy site healed without perforation in all cases studied. In all cases the biopsy samples were adequate for study. Common histological features in all 5 cases included the presence of a chronic inflammatory cell infiltrate, numerous dilated thinwalled capillaries, foci of fibrin deposition and squamous metaplasia of epithelium. More detailed assessment showed a trend which afforded a pathological classification into three distinct stages—an acute stage (Fig. 1), an interim or fibrin stage (Fig. 2) and a late healing or re-epithelialization stage (Fig. 3). 4. Discussion A typical histopathological section of the anterior nasal septum reveals a mucosa of pseudostratified ciliated columnar epithelium and a submucosa of serous and mucin-secreting glands. The rich
Fig. 4. Typical histological section of anterior nasal septum showing intact transitional mucosa overlying the vascular submucosa (250).
vascular network of arterioles, capillaries and venules is found under the thin mucosa (Fig. 4). The perichondrium and quadrangular septal cartilage lie beneath these layers. The small study numbers reflect that nasal cautery under general anaesthesia is required infrequently. This is nonetheless the first study, as far as we are aware, to address the pathological nature of the prominent vessels seen in recurrent paediatric epistaxis. It is clear that these are not arterial microaneurysms, nor are they venous varicosities. They are thin-walled arterioles and capillaries that most closely resemble the new vessels that form in diabetic retinopathy. Histological analysis also showed evidence of an inflammatory infiltrate surrounding the vessels. This provides further evidence for the aggressive eradication of nasal Staphylococci with antiseptic creams. We postulate the following sequence of events in paediatric epistaxis. Firstly, the child’s nose becomes colonised with S. aureus. This causes low-grade inflammation with crusting and irritation. Nosebleeds at this point may be due to digital trauma, coupled with increased vascularity due to inflammation and trauma from the separation of crusts. With more prolonged inflammation, the release of inflammatory mediators leads to the growth of new
1034
M.-L. Montague et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 1032–1034
vessels (neovascularisation) giving rise to the visible, prominent vessels so commonly seen. Continued inflammation combined with digital trauma ultimately results in squamous metaplasia. While this sequence of events fits with the research evidence available so far, much of it is based on conjecture and further research would be necessary to prove it conclusively. This explanation is, however, the only coherent and comprehensive explanation for all the clinical features of paediatric epistaxis that we know. References [1] B. Petruson, Epistaxis in childhood, Rhinology 17 (1979) 83–90. [2] J.L. Guarisco, H.D. Graham 3rd, Epistaxis in children: causes, diagnosis and treatment, Ear Nose Throat J. 68 (1989) 522–538. [3] B. Petruson, Epistaxis, Acta Otolaryngol. Suppl. 317 (1974) 1–73.
[4] P. Murthy, E.L.K. Nilssen, S. Rao, L. McLymont, A randomized clinical trial of antiseptic nasal carrier cream and silver nitrate cautery in the treatment of recurrent anterior epistaxis, Clin. Otolaryngol. 24 (3) (1999) 228–231. [5] P. Joice, P. Ross, G. Robertson, P. White, The effect of hand dominance on recurrent idiopathic paediatric epistaxis, Clin. Otolaryngol. 33 (6) (2008) 570–574. [6] A.D. Whymark, D.P. Crampsey, L. Fraser, P. Moore, C. Williams, H. Kubba, Childhood epistaxis and nasal colonization with Staphylococcus aureus, Otolaryngol. Head Neck Surg. 138 (3) (2008) 307–310. [7] H. Kubba, C. MacAndie, M. Botma, J. Robison, M. O’Donnell, G. Robertson, et al., A prospective, single-blind, randomized controlled trial of antiseptic cream for recurrent epistaxis in childhood, Clin. Otolaryngol. 26 (6) (2001) 465–468. [8] S. Loughran, E. Spinou, W.A. Clement, R. Cathcart, H. Kubba, N.K. Geddes, A prospective, single-blind, randomised controlled trial of petroleum jelly (Vaseline) for recurrent paediatric epistaxis, Clin. Otolaryngol. 29 (2004) 266–269. [9] N Calder, S. Kang, L. Fraser, T. Kunanandam, J. Montgomery, H. Kubba, A doubleblind randomized controlled trial of management of recurrent nosebleeds in children, Otolaryngol. Head Neck Surg. 140 (5) (2009) 670–674. [10] S. Robertson, H Kubba, Long-term effectiveness of antiseptic cream for recurrent epistaxis in childhood: five-year follow up of a randomised, controlled trial, J. Laryngol. Otol. 122 (10) (2008) 1084–1087.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
The pathology of visible blood vessels on the nasal septum in children with epistaxis Mary-Louise Montague a, Andrew Whymark a, Allan Howatson b,*, Haytham Kubba a a b
Department of Paediatric Otolaryngology, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, Scotland, United Kingdom Department of Pathology, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, Scotland, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 March 2011 Received in revised form 10 May 2011 Accepted 10 May 2011 Available online 15 June 2011
Objective: Epistaxis is common in children, but its cause remains unknown. About half the children who present with epistaxis have prominent vessels on the nasal septum. The aim of this study was to determine the pathological nature of the prominent septal vessels in children with recurrent epistaxis. Methods: 4 mm punch biopsies of the nasal septal mucosa were taken from 5 children undergoing nasal cautery under general anaesthesia. Results: Histology showed that the prominent vessels were thin-walled arterioles and capillaries with a surrounding inflammatory infiltrate. There was no evidence of venous varicosities or arterial microaneurysms. Conclusion: We postulate a mechanism for septal neovascularisation due to chronic low-grade inflammation as a cause for recurrent epistaxis in children. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Epistaxis Children Neovascularisation Nasal septum
1. Introduction Epistaxis is a common condition in children [1,2]. It is one of the commonest reasons for referral of children to a hospital ENT outpatient department. In contrast to adults the bleeding site in children is most frequently the anterior nasal septum [3,4]. The cause remains obscure, although digital trauma is often blamed [5]. We have recently shown that children with recurrent epistaxis are more likely to have colonisation of the nasal cavity with Staphylococcus aureus than controls [6] and we have suggested that chronic low-grade inflammation may cause irritation, crusting and digital trauma. Further supportive evidence for a microbiological cause for epistaxis comes from trials showing benefit from antiseptic nasal cream [7] but no benefit from simple emollients [8]. This cannot be the whole story, however, as about half the children seen with epistaxis have prominent vessels on the nasal septum [7]. Silver nitrate cautery to obliterate these vessels produces significant benefit in reducing the frequency of epistaxis [9] although the problem often recurs over the next few years [10]. The histopathological nature of these vessels is unknown. They have been called by various names including varicosities, microaneurysms and telangiectases and it is unknown whether they are congenital or acquired.
We therefore performed a study to biopsy the anterior nasal septal mucosa of children with recurrent epistaxis and visibly prominent vessels in order to determine their nature. 2. Methods Ethical approval was obtained from the Yorkhill Research Ethics Committee for a prospective departmental observational cohort study of children under 16 years requiring nasal cautery under general anaesthesia for recurrent epistaxis (Reference P12/04). Children who were found to have a specific intranasal pathology other than prominent vessels on the anterior nasal septum (e.g. rhinitis, vascular anomaly, neoplasm) were excluded from the study. Five consecutive children were recruited for the study. All were given a full explanation, both written and verbal. Signed consent for study participation was obtained from the parents. A single 4 mm circular punch biopsy was taken of the anterior nasal septal mucosa on the side with the most prominent surface vessels prior to silver nitrate cautery. A sterile disposable skin biopsy punch (Williams Medical Supplies) was used. The biopsies were formalin fixed, paraffin embedded, stained with haematoxylin and eosin and subjected to serial sectioning. Biopsy samples were all processed, examined by light microscopy and photographed by the same consultant paediatric pathologist. 3. Results
* Corresponding author. Tel.: +44 0141 2010297; fax: +44 0141 2010865. E-mail address: [email protected] (M.-L. Montague). 0165-5876/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2011.05.011
Five children were studied, of whom 3 were boys and 2 were girls. Their ages ranged from 3 to 8 years (mean age 5 years). All the
M.-L. Montague et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 1032–1034
1033
Fig. 1. The acute stage showing a fibrin thrombus occluding a vein which was the source of recent epistaxis (250). Fig. 3. The late stage of healing with re-epithelialized surface overlying a dilated blood vessel. Note the epithelium in the ‘healed’ area is squamous (i.e. squamous metaplasia with normal transitional epithelium adjacent (250).
Fig. 2. The interim or fibrin stage showing the stage of healing after a bleed with ‘pink’ fibrin lying between the blood vessel and the epithelial surface which is not quite re-epithelialized (250). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
children had recurrent epistaxis with visible prominent vessels on the anterior nasal septum, but had not been able to tolerate nasal cautery under topical anaesthesia. No child had a co-existing capillary haemangioma or other specific pathology. The children were treated with topical application of antiseptic cream for 2 weeks after the procedure and the biopsy site healed without perforation in all cases studied. In all cases the biopsy samples were adequate for study. Common histological features in all 5 cases included the presence of a chronic inflammatory cell infiltrate, numerous dilated thinwalled capillaries, foci of fibrin deposition and squamous metaplasia of epithelium. More detailed assessment showed a trend which afforded a pathological classification into three distinct stages—an acute stage (Fig. 1), an interim or fibrin stage (Fig. 2) and a late healing or re-epithelialization stage (Fig. 3). 4. Discussion A typical histopathological section of the anterior nasal septum reveals a mucosa of pseudostratified ciliated columnar epithelium and a submucosa of serous and mucin-secreting glands. The rich
Fig. 4. Typical histological section of anterior nasal septum showing intact transitional mucosa overlying the vascular submucosa (250).
vascular network of arterioles, capillaries and venules is found under the thin mucosa (Fig. 4). The perichondrium and quadrangular septal cartilage lie beneath these layers. The small study numbers reflect that nasal cautery under general anaesthesia is required infrequently. This is nonetheless the first study, as far as we are aware, to address the pathological nature of the prominent vessels seen in recurrent paediatric epistaxis. It is clear that these are not arterial microaneurysms, nor are they venous varicosities. They are thin-walled arterioles and capillaries that most closely resemble the new vessels that form in diabetic retinopathy. Histological analysis also showed evidence of an inflammatory infiltrate surrounding the vessels. This provides further evidence for the aggressive eradication of nasal Staphylococci with antiseptic creams. We postulate the following sequence of events in paediatric epistaxis. Firstly, the child’s nose becomes colonised with S. aureus. This causes low-grade inflammation with crusting and irritation. Nosebleeds at this point may be due to digital trauma, coupled with increased vascularity due to inflammation and trauma from the separation of crusts. With more prolonged inflammation, the release of inflammatory mediators leads to the growth of new
1034
M.-L. Montague et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 1032–1034
vessels (neovascularisation) giving rise to the visible, prominent vessels so commonly seen. Continued inflammation combined with digital trauma ultimately results in squamous metaplasia. While this sequence of events fits with the research evidence available so far, much of it is based on conjecture and further research would be necessary to prove it conclusively. This explanation is, however, the only coherent and comprehensive explanation for all the clinical features of paediatric epistaxis that we know. References [1] B. Petruson, Epistaxis in childhood, Rhinology 17 (1979) 83–90. [2] J.L. Guarisco, H.D. Graham 3rd, Epistaxis in children: causes, diagnosis and treatment, Ear Nose Throat J. 68 (1989) 522–538. [3] B. Petruson, Epistaxis, Acta Otolaryngol. Suppl. 317 (1974) 1–73.
[4] P. Murthy, E.L.K. Nilssen, S. Rao, L. McLymont, A randomized clinical trial of antiseptic nasal carrier cream and silver nitrate cautery in the treatment of recurrent anterior epistaxis, Clin. Otolaryngol. 24 (3) (1999) 228–231. [5] P. Joice, P. Ross, G. Robertson, P. White, The effect of hand dominance on recurrent idiopathic paediatric epistaxis, Clin. Otolaryngol. 33 (6) (2008) 570–574. [6] A.D. Whymark, D.P. Crampsey, L. Fraser, P. Moore, C. Williams, H. Kubba, Childhood epistaxis and nasal colonization with Staphylococcus aureus, Otolaryngol. Head Neck Surg. 138 (3) (2008) 307–310. [7] H. Kubba, C. MacAndie, M. Botma, J. Robison, M. O’Donnell, G. Robertson, et al., A prospective, single-blind, randomized controlled trial of antiseptic cream for recurrent epistaxis in childhood, Clin. Otolaryngol. 26 (6) (2001) 465–468. [8] S. Loughran, E. Spinou, W.A. Clement, R. Cathcart, H. Kubba, N.K. Geddes, A prospective, single-blind, randomised controlled trial of petroleum jelly (Vaseline) for recurrent paediatric epistaxis, Clin. Otolaryngol. 29 (2004) 266–269. [9] N Calder, S. Kang, L. Fraser, T. Kunanandam, J. Montgomery, H. Kubba, A doubleblind randomized controlled trial of management of recurrent nosebleeds in children, Otolaryngol. Head Neck Surg. 140 (5) (2009) 670–674. [10] S. Robertson, H Kubba, Long-term effectiveness of antiseptic cream for recurrent epistaxis in childhood: five-year follow up of a randomised, controlled trial, J. Laryngol. Otol. 122 (10) (2008) 1084–1087.