BMJ 2014;349:g7572 doi: 10.1136/bmj.g7572 (Published 10 December 2014)
Page 1 of 3
Endgames
ENDGAMES PICTURE QUIZ
Ear pain, vesicular rash, and facial palsy 1
2
Ali Al-Hussaini ear, nose, and throat specialist registrar , Farah Latif core medical trainee , Sandeep 1 Berry ear, nose, and throat consultant Department of Otolaryngology, Head and Neck Surgery, Royal Glamorgan Hospital, Llantrisant CF72 8XR, UK; 2Nephrology Department, University Hospital of Wales, Cardiff, UK 1
A 76 year old man presented to the emergency department with a three day history of a painful rash on his right cheek, associated with right sided otalgia and sore throat. He had noticed a right sided facial droop over the past 24 hours. He had no history of other neurological disturbances, otological symptoms, or head trauma.
Ten years earlier he had received a right cochlear implant, which was still functioning, and he also had benign prostatic hypertrophy. He was on aspirin 75 mg once daily and tamsulosin 400 µg once daily and had no known allergies. He was afebrile and had partial right facial nerve palsy with incomplete eye closure; his forehead muscles were also affected. Neurological examination was otherwise normal. Examination of the right ear identified vesicles on the external auditory canal; the right tympanic membrane was normal. The left ear was normal. A rash comprising lentil sized vesicles, in part confluent and pustular with surrounding erythema, was noted in the dermatomal distribution of the maxillary branch of the right trigeminal nerve. A vesicular rash was noted on the right side of the hard palate (figure); the oropharynx was normal. Examination of the neck showed no parotid swelling or cervical lymphadenopathy.
Vesicular rash on the right side of the hard palate
Questions 1. On the basis of the history and clinical findings, what is the likely diagnosis? 2. What system is usually used to grade facial nerve palsy? 3. How is this condition managed?
Answers
1. On the basis of the history and examination findings, what is the likely diagnosis? Short answer
Ramsay Hunt syndrome, which is caused by reactivation of the varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. Clinically, it usually comprises a painful vesicular rash on the external ear (herpes zoster oticus) associated with ipsilateral lower motor neurone facial nerve palsy. Because it is a cranial polyneuritis, other cranial nerves—most often the vestibular, cochlear, and trigeminal nerves—can also be affected.
Long answer
Ramsay Hunt syndrome refers to reactivation of VZV, usually in the geniculate ganglion of the facial nerve. It was initially described to comprise the clinical features of lower motor neurone facial nerve palsy and painful vesicular rash in the ipsilateral ear (herpes zoster oticus) and palate.1 Other possible features include hyperacusis and vesicular rash on the anterior two thirds of the tongue, taste disturbance, and reduced lacrimation owing to impaired functioning of the facial nerves. Hearing loss, tinnitus, vertigo, nausea, and vomiting can occur if the neighbouring cochlear and vestibular nerves are inflamed. The virus is thought to enter the geniculate ganglion during the initial chickenpox infection through the sensory branches of the facial nerve located on the ear and tongue.2 The associated dermatological signs and symptoms can be explained by viral infection of further cranial nerves or spinal
Correspondence to: A Al-Hussaini [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
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BMJ 2014;349:g7572 doi: 10.1136/bmj.g7572 (Published 10 December 2014)
Page 2 of 3
ENDGAMES
ganglia. This occurs through anastomoses of the facial nerve and its branches with sensory fibres of other cranial or cervical nerves, or as a result of infection of multiple ganglia. This can include the spinal ganglia of C2-C4, the trigeminal nerve, and the lingual nerve, with infection of the last two nerves causing the dermatomal herpetiform rash on the face and oral mucosa, respectively.3 4
The diagnosis of Ramsay Hunt syndrome is made primarily on clinical grounds. The gold standard of laboratory diagnosis comprises a positive polymerase chain reaction result and direct identification of VZV in cell cultures from vesicle swabs. The detection of IgM and IgA anti-VZV antibodies is useful, particularly in immunocompromised patients, who may present atypically.5 Ramsay Hunt syndrome is the second most common cause of lower motor neurone facial paralysis not caused by trauma. A prospective cohort study of 1507 consecutive patients presenting with unilateral facial palsy identified Ramsay Hunt syndrome in 185 (12%) patients. Compared with Bell’s palsy (idiopathic facial paralysis) found in 772 patients (51%), patients with Ramsay Hunt syndrome had more severe paralysis at onset and were less likely to recover completely.6 A retrospective study of 102 patients with Ramsay Hunt syndrome found that complete facial paralysis and age over 50 years were significantly related to poor prognosis.7 Another retrospective study of 101 patients with the syndrome found that facial nerve function was less likely to recover after one year in patients with incomplete eye closure and a dry eye.8
2. What system is usually used to grade facial nerve palsy? Short answer The House-Brackmann grading system.
Long answer
The House-Brackmann system is commonly used by clinicians to assess the severity of facial nerve palsy (box).9 It is also used by clinicians to assess recovery of function at different time points. However, because of the potential subjectivity of this scale, many other grading systems have been developed.10 11 Nonetheless, clinicians rarely use these other grading systems to evaluate facial symmetry.
3. How is this condition managed? Short answer
Ramsay Hunt syndrome is typically managed with oral aciclovir and oral prednisolone for seven days; adequate analgesia is also essential. It is imperative to start combined treatment with aciclovir-corticosteroid as early as possible because this is associated with better outcomes. Patients with incomplete eye closure also require eye protection in the form of artificial tear drops, lubricating eye ointment, and taping of the affected eye to keep it shut when they sleep.
Long answer
In adults Ramsay Hunt syndrome is typically managed with oral aciclovir at a dose of 400-800 mg five times a day for seven days. In severe cases, aciclovir may be given intravenously. Oral prednisolone is also given, with the typical dose for an adult being 40-60 mg once daily for seven days or a tapering regimen over 10-14 days,12 although dosage regimens vary greatly in the literature. Eye care is needed to prevent the affected eye from drying, which can lead to corneal ulceration. For personal use only: See rights and reprints http://www.bmj.com/permissions
Liquid tears should be used during the day and ophthalmic ointment at night. The eyelids may need to be taped during sleep if the affected eye does not fully close on blinking. Ophthalmology review should be requested if there is any concern about the state of the eye.
Studies suggest that early treatment with prednisolone and aciclovir can improve the outcome, although no high quality prospective, double blind, randomised controlled trials have been undertaken. A Cochrane systematic review, which included only one randomised controlled study of just 15 patients, found no significant difference between combined aciclovir and corticosteroid versus treatment with corticosteroids alone.13
The largest retrospective study of treatment to date analysed outcomes in 80 patients according to when treatment was started. Treatment was a combination of oral prednisolone (1 mg/kg/day for five days followed by a 10 day taper) and aciclovir (intravenous 250 mg three times daily, or oral 800 mg five times daily, for five days). In 28 patients treatment was started within three days of the onset of facial nerve paralysis; in 29 patients it was started after four to seven days and in the remaining 23 patients on the eighth day or later. In the first group, where treatment was started within three days¸ 75% of patients had complete remission of facial nerve paralysis, compared with 48% in the second group and only 30% in the third group, and the differences were significant.12 No significant differences were noted among patients treated with intravenous or oral aciclovir. Valaciclovir is a pro-drug of aciclovir and offers a more convenient oral dosage regimen of three times a day.
Post-herpetic neuralgia is a chronically debilitating consequence of Ramsay Hunt syndrome, and herpes zoster infection in general. It affects about 20% of patients with herpes zoster infection and is defined as pain that persists for longer than four weeks or that occurs four weeks after a pain-free interval.5 Patients with post-herpetic neuralgia should be managed according to the analgesic ladder and often require specific analgesia for neuropathic pain, such as amitriptyline, gabapentin, or pregabalin.14 If these measures do not relieve the patient’s pain, referral to a specialist pain clinic is indicated.
Patient outcome The patient was assessed by the otolaryngology team and discharged home with a one week course of prednisolone (60 mg once daily) and oral aciclovir (800 mg five times a day). He also received analgesia and eye care comprising liquid tears eye drops, eye ointment, and taping of his right eye shut at night. He was followed up in the ear, nose, and throat department as an outpatient and notably did not develop post-herpetic neuralgia. His facial nerve function improved from House-Brackmann grade IV to grade II before he was discharged from the clinic. Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests. Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent obtained. 1 2 3 4 5
Hunt JR. On herpetic inflammations of the geniculate ganglion: a new syndrome and its complications. J Nerv Ment Dis 1907;34:73-96. Grose C, Bonthius D, Afifi AK. Chickenpox and the geniculate ganglion: facial nerve palsy, Ramsay Hunt syndrome and acyclovir treatment. Pediatr Infect Dis J 2002;21:615-7. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry 2001;71:149-54. Wagner G, Klinge H, Sachse MM. Ramsay Hunt syndrome. J Dtsch Dermatol Ges 2012;10:238-44. Gross G, Schöfer H, Wassilew S, Friese K, Timm A, Guthoff R, et al. Herpes zoster guideline of the German Dermatology Society (DDG). J Clin Virol 2003;26:277-89.
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BMJ 2014;349:g7572 doi: 10.1136/bmj.g7572 (Published 10 December 2014)
Page 3 of 3
ENDGAMES
House-Brackmann facial nerve grading system Grade I: Normal facial appearance and function in all areas Grade II: Slight dysfunction—normal symmetry and tone at rest; slight weakness noticeable on close inspection; complete eye closure Grade III: Moderate dysfunction—normal symmetry and tone at rest; obvious weakness but not disfiguring difference between the two sides; complete eye closure Grade IV: Moderately severe dysfunction—normal symmetry and tone at rest; obvious and disfiguring weakness; incomplete eye closure Grade V: Severe dysfunction—asymmetry at rest; only minimally perceptible motion Grade VI: Total paralysis 6 7 8 9 10 11
Robillard RB, Hilsinger RL Jr, Adour KK. Ramsay Hunt facial paralysis: clinical analyses of 185 patients. Otolaryngol Head Neck Surg 1986;95:292-7. Devriese PP, Moesker WH. The natural history of facial paralysis in herpes zoster. Clin Otolaryngol 1988;13:289-98. Coulson S, Croxson GR, Adams R, Oey V. Prognostic factors in herpes zoster oticus (Ramsay Hunt syndrome). Otol Neurotol 2011;32:1025-30. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146-7. Kang TS, Vrabec JT, Giddings N, Terris DJ. Facial nerve grading systems (1985-2002): beyond the House-Brackmann scale. Otol Neurotol 2002;23:767-71. Burres S, Fisch U. The comparison of facial grading systems. Arch Otolaryngol Head Neck Surg 1986;112:755-8.
For personal use only: See rights and reprints http://www.bmj.com/permissions
12 13 14
Murakami S, Hato N, Horiuchi J, Honda N, Gyo K, Yanagihara N. Treatment of Ramsay Hunt syndrome with acyclovir-prednisone: significance of early diagnosis and treatment. Ann Neurol 1997;41:353-7. Uscategui T, Dorée C, Chamberlain IJ, Burton MJ. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev 2008;4:CD006851. Whitley RJ, Volpi A, McKendrick M, Wijck Av, Oaklander AL. Management of herpes zoster and post-herpetic neuralgia now and in the future. J Clin Virol 2010;48:S20-8.
Cite this as: BMJ 2014;349:g7572 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
Page 1 of 3
Endgames
ENDGAMES PICTURE QUIZ
Ear pain, vesicular rash, and facial palsy 1
2
Ali Al-Hussaini ear, nose, and throat specialist registrar , Farah Latif core medical trainee , Sandeep 1 Berry ear, nose, and throat consultant Department of Otolaryngology, Head and Neck Surgery, Royal Glamorgan Hospital, Llantrisant CF72 8XR, UK; 2Nephrology Department, University Hospital of Wales, Cardiff, UK 1
A 76 year old man presented to the emergency department with a three day history of a painful rash on his right cheek, associated with right sided otalgia and sore throat. He had noticed a right sided facial droop over the past 24 hours. He had no history of other neurological disturbances, otological symptoms, or head trauma.
Ten years earlier he had received a right cochlear implant, which was still functioning, and he also had benign prostatic hypertrophy. He was on aspirin 75 mg once daily and tamsulosin 400 µg once daily and had no known allergies. He was afebrile and had partial right facial nerve palsy with incomplete eye closure; his forehead muscles were also affected. Neurological examination was otherwise normal. Examination of the right ear identified vesicles on the external auditory canal; the right tympanic membrane was normal. The left ear was normal. A rash comprising lentil sized vesicles, in part confluent and pustular with surrounding erythema, was noted in the dermatomal distribution of the maxillary branch of the right trigeminal nerve. A vesicular rash was noted on the right side of the hard palate (figure); the oropharynx was normal. Examination of the neck showed no parotid swelling or cervical lymphadenopathy.
Vesicular rash on the right side of the hard palate
Questions 1. On the basis of the history and clinical findings, what is the likely diagnosis? 2. What system is usually used to grade facial nerve palsy? 3. How is this condition managed?
Answers
1. On the basis of the history and examination findings, what is the likely diagnosis? Short answer
Ramsay Hunt syndrome, which is caused by reactivation of the varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. Clinically, it usually comprises a painful vesicular rash on the external ear (herpes zoster oticus) associated with ipsilateral lower motor neurone facial nerve palsy. Because it is a cranial polyneuritis, other cranial nerves—most often the vestibular, cochlear, and trigeminal nerves—can also be affected.
Long answer
Ramsay Hunt syndrome refers to reactivation of VZV, usually in the geniculate ganglion of the facial nerve. It was initially described to comprise the clinical features of lower motor neurone facial nerve palsy and painful vesicular rash in the ipsilateral ear (herpes zoster oticus) and palate.1 Other possible features include hyperacusis and vesicular rash on the anterior two thirds of the tongue, taste disturbance, and reduced lacrimation owing to impaired functioning of the facial nerves. Hearing loss, tinnitus, vertigo, nausea, and vomiting can occur if the neighbouring cochlear and vestibular nerves are inflamed. The virus is thought to enter the geniculate ganglion during the initial chickenpox infection through the sensory branches of the facial nerve located on the ear and tongue.2 The associated dermatological signs and symptoms can be explained by viral infection of further cranial nerves or spinal
Correspondence to: A Al-Hussaini [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;349:g7572 doi: 10.1136/bmj.g7572 (Published 10 December 2014)
Page 2 of 3
ENDGAMES
ganglia. This occurs through anastomoses of the facial nerve and its branches with sensory fibres of other cranial or cervical nerves, or as a result of infection of multiple ganglia. This can include the spinal ganglia of C2-C4, the trigeminal nerve, and the lingual nerve, with infection of the last two nerves causing the dermatomal herpetiform rash on the face and oral mucosa, respectively.3 4
The diagnosis of Ramsay Hunt syndrome is made primarily on clinical grounds. The gold standard of laboratory diagnosis comprises a positive polymerase chain reaction result and direct identification of VZV in cell cultures from vesicle swabs. The detection of IgM and IgA anti-VZV antibodies is useful, particularly in immunocompromised patients, who may present atypically.5 Ramsay Hunt syndrome is the second most common cause of lower motor neurone facial paralysis not caused by trauma. A prospective cohort study of 1507 consecutive patients presenting with unilateral facial palsy identified Ramsay Hunt syndrome in 185 (12%) patients. Compared with Bell’s palsy (idiopathic facial paralysis) found in 772 patients (51%), patients with Ramsay Hunt syndrome had more severe paralysis at onset and were less likely to recover completely.6 A retrospective study of 102 patients with Ramsay Hunt syndrome found that complete facial paralysis and age over 50 years were significantly related to poor prognosis.7 Another retrospective study of 101 patients with the syndrome found that facial nerve function was less likely to recover after one year in patients with incomplete eye closure and a dry eye.8
2. What system is usually used to grade facial nerve palsy? Short answer The House-Brackmann grading system.
Long answer
The House-Brackmann system is commonly used by clinicians to assess the severity of facial nerve palsy (box).9 It is also used by clinicians to assess recovery of function at different time points. However, because of the potential subjectivity of this scale, many other grading systems have been developed.10 11 Nonetheless, clinicians rarely use these other grading systems to evaluate facial symmetry.
3. How is this condition managed? Short answer
Ramsay Hunt syndrome is typically managed with oral aciclovir and oral prednisolone for seven days; adequate analgesia is also essential. It is imperative to start combined treatment with aciclovir-corticosteroid as early as possible because this is associated with better outcomes. Patients with incomplete eye closure also require eye protection in the form of artificial tear drops, lubricating eye ointment, and taping of the affected eye to keep it shut when they sleep.
Long answer
In adults Ramsay Hunt syndrome is typically managed with oral aciclovir at a dose of 400-800 mg five times a day for seven days. In severe cases, aciclovir may be given intravenously. Oral prednisolone is also given, with the typical dose for an adult being 40-60 mg once daily for seven days or a tapering regimen over 10-14 days,12 although dosage regimens vary greatly in the literature. Eye care is needed to prevent the affected eye from drying, which can lead to corneal ulceration. For personal use only: See rights and reprints http://www.bmj.com/permissions
Liquid tears should be used during the day and ophthalmic ointment at night. The eyelids may need to be taped during sleep if the affected eye does not fully close on blinking. Ophthalmology review should be requested if there is any concern about the state of the eye.
Studies suggest that early treatment with prednisolone and aciclovir can improve the outcome, although no high quality prospective, double blind, randomised controlled trials have been undertaken. A Cochrane systematic review, which included only one randomised controlled study of just 15 patients, found no significant difference between combined aciclovir and corticosteroid versus treatment with corticosteroids alone.13
The largest retrospective study of treatment to date analysed outcomes in 80 patients according to when treatment was started. Treatment was a combination of oral prednisolone (1 mg/kg/day for five days followed by a 10 day taper) and aciclovir (intravenous 250 mg three times daily, or oral 800 mg five times daily, for five days). In 28 patients treatment was started within three days of the onset of facial nerve paralysis; in 29 patients it was started after four to seven days and in the remaining 23 patients on the eighth day or later. In the first group, where treatment was started within three days¸ 75% of patients had complete remission of facial nerve paralysis, compared with 48% in the second group and only 30% in the third group, and the differences were significant.12 No significant differences were noted among patients treated with intravenous or oral aciclovir. Valaciclovir is a pro-drug of aciclovir and offers a more convenient oral dosage regimen of three times a day.
Post-herpetic neuralgia is a chronically debilitating consequence of Ramsay Hunt syndrome, and herpes zoster infection in general. It affects about 20% of patients with herpes zoster infection and is defined as pain that persists for longer than four weeks or that occurs four weeks after a pain-free interval.5 Patients with post-herpetic neuralgia should be managed according to the analgesic ladder and often require specific analgesia for neuropathic pain, such as amitriptyline, gabapentin, or pregabalin.14 If these measures do not relieve the patient’s pain, referral to a specialist pain clinic is indicated.
Patient outcome The patient was assessed by the otolaryngology team and discharged home with a one week course of prednisolone (60 mg once daily) and oral aciclovir (800 mg five times a day). He also received analgesia and eye care comprising liquid tears eye drops, eye ointment, and taping of his right eye shut at night. He was followed up in the ear, nose, and throat department as an outpatient and notably did not develop post-herpetic neuralgia. His facial nerve function improved from House-Brackmann grade IV to grade II before he was discharged from the clinic. Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests. Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent obtained. 1 2 3 4 5
Hunt JR. On herpetic inflammations of the geniculate ganglion: a new syndrome and its complications. J Nerv Ment Dis 1907;34:73-96. Grose C, Bonthius D, Afifi AK. Chickenpox and the geniculate ganglion: facial nerve palsy, Ramsay Hunt syndrome and acyclovir treatment. Pediatr Infect Dis J 2002;21:615-7. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry 2001;71:149-54. Wagner G, Klinge H, Sachse MM. Ramsay Hunt syndrome. J Dtsch Dermatol Ges 2012;10:238-44. Gross G, Schöfer H, Wassilew S, Friese K, Timm A, Guthoff R, et al. Herpes zoster guideline of the German Dermatology Society (DDG). J Clin Virol 2003;26:277-89.
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;349:g7572 doi: 10.1136/bmj.g7572 (Published 10 December 2014)
Page 3 of 3
ENDGAMES
House-Brackmann facial nerve grading system Grade I: Normal facial appearance and function in all areas Grade II: Slight dysfunction—normal symmetry and tone at rest; slight weakness noticeable on close inspection; complete eye closure Grade III: Moderate dysfunction—normal symmetry and tone at rest; obvious weakness but not disfiguring difference between the two sides; complete eye closure Grade IV: Moderately severe dysfunction—normal symmetry and tone at rest; obvious and disfiguring weakness; incomplete eye closure Grade V: Severe dysfunction—asymmetry at rest; only minimally perceptible motion Grade VI: Total paralysis 6 7 8 9 10 11
Robillard RB, Hilsinger RL Jr, Adour KK. Ramsay Hunt facial paralysis: clinical analyses of 185 patients. Otolaryngol Head Neck Surg 1986;95:292-7. Devriese PP, Moesker WH. The natural history of facial paralysis in herpes zoster. Clin Otolaryngol 1988;13:289-98. Coulson S, Croxson GR, Adams R, Oey V. Prognostic factors in herpes zoster oticus (Ramsay Hunt syndrome). Otol Neurotol 2011;32:1025-30. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146-7. Kang TS, Vrabec JT, Giddings N, Terris DJ. Facial nerve grading systems (1985-2002): beyond the House-Brackmann scale. Otol Neurotol 2002;23:767-71. Burres S, Fisch U. The comparison of facial grading systems. Arch Otolaryngol Head Neck Surg 1986;112:755-8.
For personal use only: See rights and reprints http://www.bmj.com/permissions
12 13 14
Murakami S, Hato N, Horiuchi J, Honda N, Gyo K, Yanagihara N. Treatment of Ramsay Hunt syndrome with acyclovir-prednisone: significance of early diagnosis and treatment. Ann Neurol 1997;41:353-7. Uscategui T, Dorée C, Chamberlain IJ, Burton MJ. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev 2008;4:CD006851. Whitley RJ, Volpi A, McKendrick M, Wijck Av, Oaklander AL. Management of herpes zoster and post-herpetic neuralgia now and in the future. J Clin Virol 2010;48:S20-8.
Cite this as: BMJ 2014;349:g7572 © BMJ Publishing Group Ltd 2014
Subscribe: http://www.bmj.com/subscribe
