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Sympathetic neuropathy and dysphagia following doxycycline sclerotherapy
International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case report
Sympathetic neuropathy and dysphagia following doxycycline sclerotherapy Kevin L. Wang, Robert H. Chun *, Joseph E. Kerschner, Cecille G. Sulman Medical College of Wisconsin, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 May 2013 Accepted 3 July 2013 Available online 6 August 2013
This case report demonstrates neurologic sequela following treatment with doxycycline sclerotherapy. A six-week-old child presented with respiratory distress from a macrocystic lymphatic malformation, extending from the skull base to the anterior mediastinum. Following doxycycline sclerotherapy, the airway symptoms resolved; however, the child developed silent aspiration and Horner’s syndrome. Two months following treatment the patient resumed oral diet and at one year post-intervention there has been no recurrence of symptoms, with only mild ptosis remaining. While neuropathies following doxycycline sclerotherapy have been described, aspiration has never been documented. This case demonstrates a single patient’s clinical course and resolution of their neuropathies. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Doxycycline sclerotherapy Lymphatic malformation Complication Aspiration Horner’s syndrome
1. Introduction Lymphatic malformations (LM) are common, benign head and neck tumors seen in children [1–4]. They are the result of errors in embryonic development leading to abnormal lymphatic capillaries that become cystic [1–5]. These cystic spaces can enlarge, especially from infection or an inflammatory response, and compress surrounding structures, including the airway and esophagus [1–3,5]. There exist several different interventions for LM including sclerotherapy and surgical excision [2–6]. Multiple studies have shown the effectiveness and excellent safety profile of doxycycline as a sclerosant used in sclerotherapy [1–7]. Potential complications from doxycycline sclerotherapy typically include pain, fever, infection, and skin irritation [1,3–7]. Neurologic complications, including Horner’s syndrome (unilateral miosis, ptosis, with or without anhidrosis), have proven to be rare with only a limited number of documented cases in larger studies [1,5,7,8]. There have been no documented cases of aspiration following doxycycline sclerotherapy. Furthermore, none have detailed the individual presentation and imaging of LM, course of doxycycline sclerotherapy treatment, resulting complications of Horner’s syndrome and aspiration, and resolution. We are reporting the case of a six-week-old child who underwent doxycycline sclerotherapy for a macrocystic LM compressing on the
* Corresponding author at: 9000 West Wisconsin Avenue, PO Box 1997, Suite 550, Children’s Hospital Clinics Building, Pediatric Otolaryngology Offices, Milwaukee, WI 53226, United States. Tel.: +1 414 266 8383; fax: +1 414 266 2693. E-mail address: [email protected] (R.H. Chun). 0165-5876/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2013.07.005
airway, resulting in complications of Horner’s syndrome and silent aspiration. 2. Case report A six-week-old female infant presented to the Children’s Hospital of Wisconsin from an outside hospital (OSH) with a four-day history of respiratory distress. The patient was born full term via cesarean section due to maternal tachycardia. No other complications during pregnancy or following birth. Over the previous four days, the patient experienced respiratory distress, cough, rhinorrhea, sneeze, and decreased enteral intake without aspiration symptoms. On the fourth day, the patient was admitted to the pediatric intensive care unit (PICU) of an OSH due to continued respiratory distress, including tracheal tugging and intercostal retractions. The patient received Decadron, nebulized epinephrine, and was placed on continuous positive airway pressure (CPAP). She continued to have signs of respiratory distress, which necessitated intubation after transfer to the Children’s Hospital of Wisconsin. Workup for infection, including lumbar puncture, blood culture, and urine culture, was negative. Following failure of extubation trials, flexible and rigid bronchoscopies were performed and showed no evidence of tracheal disease, but demonstrated a retropharyngeal soft tissue mass. A computed tomography (CT) scan with contrast of the neck further demonstrated a large, predominantly right-sided, sharply demarcated and homogenous lesion that extended inferiorly to the thyroid gland. A magnetic resonance imaging (MRI) with contrast of the neck was performed to characterize the cystic nature of the mass and established a diagnosis of macrocystic LM due to
1614
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
Fig. 1. Pre-treatment MRI of the neck.
Fig. 2. Doxycycline sclerotherapy under fluoroscopy.
Fig. 3. Post-treatment MRI of the neck.
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
visualization of a large, well-circumscribed, lobulated, approximately 4.8 cm 3.8 cm 2.0 cm mass centered in the right retropharyngeal space and superiorly extending into the right parapharyngeal and carotid spaces, with an enhancing thin wall and a few enhancing thin septations within the mass (Fig. 1). Sclerotherapy with doxycycline was then performed with three treatments over three days. At a concentration of 10 mg/ml, a total of 80 mg of doxycycline was administered during each of the three treatments using an indwelling pigtail catheter with a two hour indwelling time (Fig. 2). No leakage or extravasation of contrast was observed in each treatment. Direct laryngoscopy with telescopic visualization after the third day of sclerotherapy revealed improved hypopharyngeal airway and a diminished LM. One day after complete treatment, the patient was extubated to high flow nasal cannula and showed improvement in secretion handling and respiration over the next few days. One week following treatment, the patient was observed to have Horner’s syndrome, displaying right sided ptosis and miosis. Difficulties with oral feeding prompted a video fluoroscopic swallow study (VFSS) which revealed silent aspiration. Patient was discharged home with 100% NG feeding, speech therapy, and pulse oximetry. VFSS at one month follow-up demonstrated significant improvement in swallow function with only a trace amount of silent aspiration. MRI of the neck without contrast at two month follow-up revealed greater than 70% volumetric reduction in mass size at 2.5 cm 2.2 cm 1.9 cm, and likely 80–90% reduction in functional size due to irregular residual margins (Fig. 3). The patient’s NG tube was also removed at this time due to return of adequate oral feeding. Follow-up at 2.5 months revealed the patient to be doing well, respiring without difficulty, gaining weight, and showing no need for further sclerotherapy, with improved, but continuing slight right-sided ptosis and miosis. Follow-up at four months revealed further improvement in miosis and a mild ptotic right lid, and follow-up at one year revealed only mild ptosis. 3. Discussion Lymphatic malformations are congenital, vascular lesions, of which 90% are diagnosed by 2 years of age [1,3,4]. Although benign in nature, they can grow in size and lead to complications from mass effects on surrounding structures [1–3,5]. This is especially true in the head and neck, where more than 50% of LM occur [2,3,6]. Our patient had a large LM compressing the pharynx that led to respiratory distress. Although the LM was not appreciable on physical exam, a retropharyngeal soft tissue mass was visualized during bedside flexible laryngoscopy and confirmed to be LM by MRI. Historically, surgery has been the standard of care, but with
1615
the extension of the LM to the skull base, complete excision would have been difficult, if not impossible without secondary sequelae [2,3,6]. Over the years, sclerotherapy has emerged as a viable treatment option for LM [1–7]. A number of different sclerosants have been used and described in the literature, including bleomycin, OK432 (Picibanil), sodium tetradecyl sulfate, alcohol, acetic acid, hypertonic saline, and doxycycline [1–7]. Doxycycline has been shown in the literature to be an effective sclerosant with an excellent safety profile [1–7]. The exact mechanism by which doxycycline acts as a sclerosant is not fully understood but presumed to involve an inflammatory response within the LM resulting in angiogenesis inhibition and fibrosis [2,5,7]. In the interventional radiology suite, use of three instillations of 10 mg/ml of doxycycline sclerosant is consistent with protocols used in other studies [1,5,7]. After treatment, our patient obtained an 80–90% reduction in functional volume of their LM and complete resolution of their respiratory distress. Complications arising from doxycycline sclerotherapy can include pain, local inflammation, fever, infection, anemia, acidosis, blistering, and scarring [1,3–7]. A limited number of neurological complications, including Horner’s syndrome, have been documented in larger studies (Table 1) [1,5,7,8]. However, the details of these cases, including presentation, imaging, management, and resolution have not been described. None have documented aspiration as a complication of doxycycline sclerotherapy. Our patient suffered from post-treatment Horner’s syndrome and silent aspiration. Horner’s syndrome is a sympathetic neuropathy that is classically manifested by unilateral ptosis, miosis, with or without anhidrosis of the forehead [9,10]. It results from damage or compression of the ipsilateral ascending sympathetic chain [9,10]. Prognosis of Horner’s syndrome depends on the underlying cause, which can include trauma, tumors, and iatrogenic processes [10]. Horner’s syndrome as a complication from doxycycline sclerotherapy has only been documented in the literature in three studies, with a total number of six cases [1,5,7]. All but one case showed resolution of symptoms, with the remaining case requiring surgery for persistent ptosis [1,5,7]. Over the course of one year, our patient also showed significant improvement in her symptoms, with only mild ptosis remaining at one year. Our patient also had silent aspiration following sclerotherapy treatment that was not evident prior to surgery. Her vocal cord function was normal post-treatment. Silent aspiration is aspiration without signs of distress [11]. Based on a number of studies showing injury to the superior laryngeal nerve injury to be involved in the pathogenesis of silent aspiration, we would assume this to be the etiology of our patient’s complication [11–13]. This complication was transient and resolved at two months posttreatment.
Table 1 Previous studies with neurologic complications from doxycycline sclerotherapy to the head and neck. Authors
Number of patients
Cahill et al. [1]
17 (all with head and neck LM)
Number of procedures 49
Shergill et al. [5]
50 (19 with head and neck LM)
146
Burrows et al. [7]
41 (27 with head and neck LM)
60
Kirse et al. [8]
1 (chylous fistula of the neck)
2
Neurologic complications
Non-neurologic complications
4/49: Horner’s syndrome 1/49: right facial nerve palsy 1/49: transient left lip weakness 1/49: transient left hemi-diaphragm paralysis
3/49: 2/49: 1/49: 1/49:
1/146: Horner’s syndrome
1/146: severe pain 1/146: skin blister 1/146: post-op ileus
1/60: Horner’s syndrome
3/60: prolonged pain and swelling 2/60: skin blisters 1/60: hair loss
1/1: permanent phrenic nerve paralysis
metabolic acidosis hemolytic anemia transient hypotension skin excoriation
1616
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
The exact mechanism by which doxycycline sclerotherapy causes Horner’s syndrome and silent aspiration is unclear. Location of LM and secondary inflammation from treatment have been attributed by the authors of the previous studies who have observed Horner’s syndrome in their patients [1,5,7]. Our patient’s aspiration may have also occurred in this way. However, Kirse et al. have also shown that topical doxycycline causes histologic nerve damage, and doxycycline injected into nerves causes decreased impulse and conduction velocity [14,15]. During our patient’s treatments, no leakage or extravasation of contrast was observed. While the doxycycline did not extravasate during our patient’s injections, it is possible that there was diffusion of the agent to the surrounding tissue leading to the neurologic injury. Thus, doxycycline’s ability to damage surrounding nervous tissue either directly or through secondary inflammation should be taken into consideration.
4. Conclusion Lymphatic malformations are common in the pediatric head and neck. While doxycycline sclerotherapy is an effective treatment in some cases, it does carry possible risks such as neuropathy as seen in our case study. Further studies may be needed to elucidate the exact mechanism by which doxycycline sclerotherapy causes neuropathy. Until then, we recommend doxycycline sclerotherapy for appropriately selected patients where awareness of potential complications is taken into account.
Conflicts of interest There are no conflicts of interest or financial disclosures of the authors in regards to this manuscript.
Acknowledgements All authors have contributed to, reviewed, and approved the manuscript for submission.
The material contained in this manuscript was presented at the 2013 American Society of Pediatric Otolaryngology (ASPO) Spring Meeting in Arlington, VA on April 25–28, 2013. References [1] A.M. Cahill, E. Nijs, D. Ballah, D. Rabinowitz, L. Thompson, N. Rintoul, et al., Percutaneous sclerotherapy in neonatal and infant head and neck lymphatic malformations: a single center experience, J. Pediatr. Surg. 46 (November (11)) (2011) 2083–2095. [2] N. Jamal, S. Ahmed, T. Miller, J. Bent, A. Brook, S. Parikh, et al., Doxycycline sclerotherapy for pediatric head and neck macrocystic lymphatic malformations: a case series and review of the literature, Int. J. Pediatr. Otorhinolaryngol. 76 (August (8)) (2012) 1127–1131. [3] D. Nehra, L. Jacobson, P. Barnes, B. Mallory, C.T. Albanese, K.G. Sylvester, Doxycycline sclerotherapy as primary treatment of head and neck lymphatic malformations in children, J. Pediatr. Surg. 43 (March (3)) (2008) 451–460. [4] W.E. Shiels 2nd, D.R. Kang, J.W. Murakami, M.J. Hogan, G.J. Wiet, Percutaneous treatment of lymphatic malformations, Otolaryngology – Head Neck Surg.: Off. J. Am. Acad. Otolaryngol. – Head Neck Surg. 141 (August (2)) (2009) 219–224. [5] A. Shergill, P. John, J.G. Amaral, Doxycycline sclerotherapy in children with lymphatic malformations: outcomes, complications and clinical efficacy, Pediatr. Radiol. 42 (September (9)) (2012) 1080–1088. [6] J.A. Perkins, S.C. Manning, R.M. Tempero, M.J. Cunningham, J.L. Edmonds Jr., F.A. Hoffer, et al., Lymphatic malformations: review of current treatment, Otolaryngology – Head Neck Surg.: Off. J. Am. Acad. Otolaryngol. – Head Neck Surg. 142 (June (6)) (2010) 795–803, 803 e791. [7] P.E. Burrows, R.K. Mitri, A. Alomari, H.M. Padua, D.J. Lord, M.B. Sylvia, et al., Percutaneous sclerotherapy of lymphatic malformations with doxycycline, Lymph. Res. Biol. 6 (3–4) (2008) 209–216. [8] D.J. Kirse, J.Y. Suen, S.J. Stern, Phrenic nerve paralysis after doxycycline sclerotherapy for chylous fistula, Otolaryngology – Head Neck Surg.: Off. J. Am. Acad. Otolaryngol. – Head Neck Surg. 116 (June (6 Pt 1)) (1997) 680–683. [9] A.Y. Allen, D.R. Meyer, Neck procedures resulting in Horner syndrome, Ophthal. Plast. Reconstruct. Surg. 25 (January–February (1)) (2009) 16–18. [10] I. Lazar, Y. Cavari, E. Rosenberg, B. Knyazer, Horner’s syndrome in patients admitted to the paediatric intensive care unit: epidemiology, diagnosis and clinical practice, Anaesth. Intensive Care 41 (January (1)) (2013) 20–23. [11] D. Ramsey, D. Smithard, L. Kalra, Silent aspiration: what do we know? Dysphagia 20 (Summer (3)) (2005) 218–225. [12] P. Ding, R. Campbell-Malone, S.D. Holman, S.L. Lukasik, T. Fukuhara, E.M. GierboliniNorat, et al., Unilateral superior laryngeal nerve lesion in an animal model of dysphagia and its effect on sucking and swallowing, Dysphagia (February) (2013). [13] S. Jafari, R.A. Prince, D.Y. Kim, D. Paydarfar, Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans, J. Physiol. 550 (July (Pt 1)) (2003) 287–304. [14] D.J. Kirse, S.J. Stern, J.Y. Suen, S. Rudnicki, P.K. Roberson, R.F. Schaefer, Neurotic effects of doxycycline sclerotherapy, Otolaryngology – Head Neck Surg.: Off. J. Am. Acad. Otolaryngol. – Head Neck Surg. 118 (March (3 Pt 1)) (1998) 356–362. [15] D.J. Kirse, J.Y. Suen, S.J. Stern, R.F. Schaefer, P.K. Roberson, Histologic effect of doxycycline sclerotherapy on rat femoral nerve, Head Neck 18 (November– December (6)) (1996) 506–511.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case report
Sympathetic neuropathy and dysphagia following doxycycline sclerotherapy Kevin L. Wang, Robert H. Chun *, Joseph E. Kerschner, Cecille G. Sulman Medical College of Wisconsin, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 May 2013 Accepted 3 July 2013 Available online 6 August 2013
This case report demonstrates neurologic sequela following treatment with doxycycline sclerotherapy. A six-week-old child presented with respiratory distress from a macrocystic lymphatic malformation, extending from the skull base to the anterior mediastinum. Following doxycycline sclerotherapy, the airway symptoms resolved; however, the child developed silent aspiration and Horner’s syndrome. Two months following treatment the patient resumed oral diet and at one year post-intervention there has been no recurrence of symptoms, with only mild ptosis remaining. While neuropathies following doxycycline sclerotherapy have been described, aspiration has never been documented. This case demonstrates a single patient’s clinical course and resolution of their neuropathies. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Doxycycline sclerotherapy Lymphatic malformation Complication Aspiration Horner’s syndrome
1. Introduction Lymphatic malformations (LM) are common, benign head and neck tumors seen in children [1–4]. They are the result of errors in embryonic development leading to abnormal lymphatic capillaries that become cystic [1–5]. These cystic spaces can enlarge, especially from infection or an inflammatory response, and compress surrounding structures, including the airway and esophagus [1–3,5]. There exist several different interventions for LM including sclerotherapy and surgical excision [2–6]. Multiple studies have shown the effectiveness and excellent safety profile of doxycycline as a sclerosant used in sclerotherapy [1–7]. Potential complications from doxycycline sclerotherapy typically include pain, fever, infection, and skin irritation [1,3–7]. Neurologic complications, including Horner’s syndrome (unilateral miosis, ptosis, with or without anhidrosis), have proven to be rare with only a limited number of documented cases in larger studies [1,5,7,8]. There have been no documented cases of aspiration following doxycycline sclerotherapy. Furthermore, none have detailed the individual presentation and imaging of LM, course of doxycycline sclerotherapy treatment, resulting complications of Horner’s syndrome and aspiration, and resolution. We are reporting the case of a six-week-old child who underwent doxycycline sclerotherapy for a macrocystic LM compressing on the
* Corresponding author at: 9000 West Wisconsin Avenue, PO Box 1997, Suite 550, Children’s Hospital Clinics Building, Pediatric Otolaryngology Offices, Milwaukee, WI 53226, United States. Tel.: +1 414 266 8383; fax: +1 414 266 2693. E-mail address: [email protected] (R.H. Chun). 0165-5876/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2013.07.005
airway, resulting in complications of Horner’s syndrome and silent aspiration. 2. Case report A six-week-old female infant presented to the Children’s Hospital of Wisconsin from an outside hospital (OSH) with a four-day history of respiratory distress. The patient was born full term via cesarean section due to maternal tachycardia. No other complications during pregnancy or following birth. Over the previous four days, the patient experienced respiratory distress, cough, rhinorrhea, sneeze, and decreased enteral intake without aspiration symptoms. On the fourth day, the patient was admitted to the pediatric intensive care unit (PICU) of an OSH due to continued respiratory distress, including tracheal tugging and intercostal retractions. The patient received Decadron, nebulized epinephrine, and was placed on continuous positive airway pressure (CPAP). She continued to have signs of respiratory distress, which necessitated intubation after transfer to the Children’s Hospital of Wisconsin. Workup for infection, including lumbar puncture, blood culture, and urine culture, was negative. Following failure of extubation trials, flexible and rigid bronchoscopies were performed and showed no evidence of tracheal disease, but demonstrated a retropharyngeal soft tissue mass. A computed tomography (CT) scan with contrast of the neck further demonstrated a large, predominantly right-sided, sharply demarcated and homogenous lesion that extended inferiorly to the thyroid gland. A magnetic resonance imaging (MRI) with contrast of the neck was performed to characterize the cystic nature of the mass and established a diagnosis of macrocystic LM due to
1614
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
Fig. 1. Pre-treatment MRI of the neck.
Fig. 2. Doxycycline sclerotherapy under fluoroscopy.
Fig. 3. Post-treatment MRI of the neck.
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
visualization of a large, well-circumscribed, lobulated, approximately 4.8 cm 3.8 cm 2.0 cm mass centered in the right retropharyngeal space and superiorly extending into the right parapharyngeal and carotid spaces, with an enhancing thin wall and a few enhancing thin septations within the mass (Fig. 1). Sclerotherapy with doxycycline was then performed with three treatments over three days. At a concentration of 10 mg/ml, a total of 80 mg of doxycycline was administered during each of the three treatments using an indwelling pigtail catheter with a two hour indwelling time (Fig. 2). No leakage or extravasation of contrast was observed in each treatment. Direct laryngoscopy with telescopic visualization after the third day of sclerotherapy revealed improved hypopharyngeal airway and a diminished LM. One day after complete treatment, the patient was extubated to high flow nasal cannula and showed improvement in secretion handling and respiration over the next few days. One week following treatment, the patient was observed to have Horner’s syndrome, displaying right sided ptosis and miosis. Difficulties with oral feeding prompted a video fluoroscopic swallow study (VFSS) which revealed silent aspiration. Patient was discharged home with 100% NG feeding, speech therapy, and pulse oximetry. VFSS at one month follow-up demonstrated significant improvement in swallow function with only a trace amount of silent aspiration. MRI of the neck without contrast at two month follow-up revealed greater than 70% volumetric reduction in mass size at 2.5 cm 2.2 cm 1.9 cm, and likely 80–90% reduction in functional size due to irregular residual margins (Fig. 3). The patient’s NG tube was also removed at this time due to return of adequate oral feeding. Follow-up at 2.5 months revealed the patient to be doing well, respiring without difficulty, gaining weight, and showing no need for further sclerotherapy, with improved, but continuing slight right-sided ptosis and miosis. Follow-up at four months revealed further improvement in miosis and a mild ptotic right lid, and follow-up at one year revealed only mild ptosis. 3. Discussion Lymphatic malformations are congenital, vascular lesions, of which 90% are diagnosed by 2 years of age [1,3,4]. Although benign in nature, they can grow in size and lead to complications from mass effects on surrounding structures [1–3,5]. This is especially true in the head and neck, where more than 50% of LM occur [2,3,6]. Our patient had a large LM compressing the pharynx that led to respiratory distress. Although the LM was not appreciable on physical exam, a retropharyngeal soft tissue mass was visualized during bedside flexible laryngoscopy and confirmed to be LM by MRI. Historically, surgery has been the standard of care, but with
1615
the extension of the LM to the skull base, complete excision would have been difficult, if not impossible without secondary sequelae [2,3,6]. Over the years, sclerotherapy has emerged as a viable treatment option for LM [1–7]. A number of different sclerosants have been used and described in the literature, including bleomycin, OK432 (Picibanil), sodium tetradecyl sulfate, alcohol, acetic acid, hypertonic saline, and doxycycline [1–7]. Doxycycline has been shown in the literature to be an effective sclerosant with an excellent safety profile [1–7]. The exact mechanism by which doxycycline acts as a sclerosant is not fully understood but presumed to involve an inflammatory response within the LM resulting in angiogenesis inhibition and fibrosis [2,5,7]. In the interventional radiology suite, use of three instillations of 10 mg/ml of doxycycline sclerosant is consistent with protocols used in other studies [1,5,7]. After treatment, our patient obtained an 80–90% reduction in functional volume of their LM and complete resolution of their respiratory distress. Complications arising from doxycycline sclerotherapy can include pain, local inflammation, fever, infection, anemia, acidosis, blistering, and scarring [1,3–7]. A limited number of neurological complications, including Horner’s syndrome, have been documented in larger studies (Table 1) [1,5,7,8]. However, the details of these cases, including presentation, imaging, management, and resolution have not been described. None have documented aspiration as a complication of doxycycline sclerotherapy. Our patient suffered from post-treatment Horner’s syndrome and silent aspiration. Horner’s syndrome is a sympathetic neuropathy that is classically manifested by unilateral ptosis, miosis, with or without anhidrosis of the forehead [9,10]. It results from damage or compression of the ipsilateral ascending sympathetic chain [9,10]. Prognosis of Horner’s syndrome depends on the underlying cause, which can include trauma, tumors, and iatrogenic processes [10]. Horner’s syndrome as a complication from doxycycline sclerotherapy has only been documented in the literature in three studies, with a total number of six cases [1,5,7]. All but one case showed resolution of symptoms, with the remaining case requiring surgery for persistent ptosis [1,5,7]. Over the course of one year, our patient also showed significant improvement in her symptoms, with only mild ptosis remaining at one year. Our patient also had silent aspiration following sclerotherapy treatment that was not evident prior to surgery. Her vocal cord function was normal post-treatment. Silent aspiration is aspiration without signs of distress [11]. Based on a number of studies showing injury to the superior laryngeal nerve injury to be involved in the pathogenesis of silent aspiration, we would assume this to be the etiology of our patient’s complication [11–13]. This complication was transient and resolved at two months posttreatment.
Table 1 Previous studies with neurologic complications from doxycycline sclerotherapy to the head and neck. Authors
Number of patients
Cahill et al. [1]
17 (all with head and neck LM)
Number of procedures 49
Shergill et al. [5]
50 (19 with head and neck LM)
146
Burrows et al. [7]
41 (27 with head and neck LM)
60
Kirse et al. [8]
1 (chylous fistula of the neck)
2
Neurologic complications
Non-neurologic complications
4/49: Horner’s syndrome 1/49: right facial nerve palsy 1/49: transient left lip weakness 1/49: transient left hemi-diaphragm paralysis
3/49: 2/49: 1/49: 1/49:
1/146: Horner’s syndrome
1/146: severe pain 1/146: skin blister 1/146: post-op ileus
1/60: Horner’s syndrome
3/60: prolonged pain and swelling 2/60: skin blisters 1/60: hair loss
1/1: permanent phrenic nerve paralysis
metabolic acidosis hemolytic anemia transient hypotension skin excoriation
1616
K.L. Wang et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1613–1616
The exact mechanism by which doxycycline sclerotherapy causes Horner’s syndrome and silent aspiration is unclear. Location of LM and secondary inflammation from treatment have been attributed by the authors of the previous studies who have observed Horner’s syndrome in their patients [1,5,7]. Our patient’s aspiration may have also occurred in this way. However, Kirse et al. have also shown that topical doxycycline causes histologic nerve damage, and doxycycline injected into nerves causes decreased impulse and conduction velocity [14,15]. During our patient’s treatments, no leakage or extravasation of contrast was observed. While the doxycycline did not extravasate during our patient’s injections, it is possible that there was diffusion of the agent to the surrounding tissue leading to the neurologic injury. Thus, doxycycline’s ability to damage surrounding nervous tissue either directly or through secondary inflammation should be taken into consideration.
4. Conclusion Lymphatic malformations are common in the pediatric head and neck. While doxycycline sclerotherapy is an effective treatment in some cases, it does carry possible risks such as neuropathy as seen in our case study. Further studies may be needed to elucidate the exact mechanism by which doxycycline sclerotherapy causes neuropathy. Until then, we recommend doxycycline sclerotherapy for appropriately selected patients where awareness of potential complications is taken into account.
Conflicts of interest There are no conflicts of interest or financial disclosures of the authors in regards to this manuscript.
Acknowledgements All authors have contributed to, reviewed, and approved the manuscript for submission.
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