Sultan Qaboos University Med J, February 2015, Vol. 15, Iss. 1, pp. e124–128, Epub. 21 Jan 15 Submitted 17 Feb 14 Revisions Req. 7 Apr & 1 Jul 14; Revisions Recd. 8 Jun & 17 Jul 14 Accepted 19 Aug 14 ONLINE CASE REPORT Heerfordt’s Syndrome Presenting with Recurrent Facial Nerve Palsy Case report and 10-year literature review Preetam Chappity, *Rajeev Kumar, Anjan K. Sahoo متﻻزمة هريفوردز املصاحبة لتكرار شلل العصب الوجهي تقرير حالة ومراجعة أدبيات عشرة أعوام بريتم �ضابيتي، راجيف كومار، اأجنان كومار �ضاحو abstract: Heerfordt’s syndrome is defined as a combination of facial palsy, parotid swelling, uveitis and fever in sarcoidosis cases. Heerfordt’s syndrome as a cause of facial palsy is very rare. We report a case of alternating facial nerve palsy in a 52-year-old female initially treated for Bell’s palsy. The patient was referred to the All India Institute of Medical Sciences, Bhubaneswar, India, in January 2013 for clinical evaluation. She was found to have a parotid swelling and anterior intermediate uveitis. A pathoradiological evaluation suggested sarcoidosis and a final diagnosis of Heerfordt’s syndrome was made. Steroid treatment was initiated which led to an improvement in the facial palsy and uveitis as well as the disappearance of the parotid swelling with a corresponding decrease in angiotensin-converting enzyme levels. An English literature review was carried out to analyse the varied presentation of this syndrome. The analysis focused on presenting symptoms, biochemical markers and radiological findings of Heerfordt’s syndrome cases. Keywords: Heerfordt Syndrome; Sarcoidosis; Facial Palsy; Case Report; India. امللخ�ص: تعرف متلزمة هريفوردز باأنها مزيج من اﻻأعرا�س التي تتمثل يف �ضلل يف الوجه، تورم الغدة النكافية، التهاب القزحية واحلمى يف حاﻻت ال�ضاركويد. متلزمة هريفورد امل�ضببة لل�ضلل الوجهي حالة نادرة جدا. نقدم هنا حالة �ضلل الع�ضب الوجهي ﻻمراأة تبلغ من العمر 52 عاما عوجلت مبدئيا ل�ضلل بيل. اأحيلت املري�ضة اإىل معهد عموم الهند للعلوم الطبية، بوبان�ضوار، الهند، يف يناير 2013 للتقييم ال�رضيري. وجد عندها تورم يف الغدة النكافية والتهاب العنبية اﻻأمامية املتو�ضطة. اأ�ضار التقييم اإل�ضعاعي ملر�س ال�ضاركويد ومت الت�ضخي�س النهائي ملتلزمة هريفوردز. وقد بداأ العلج بال�ضتريويد والتي اأدت اإىل حت�ضن يف �ضلل الوجه والتهاب القزحية وكذلك اختفاء تورم النكفية مع انخفا�س يف م�ضتويات اأنزمي املحول للأجنيوتن�ضني. مت ا�ضتعرا�س اﻻأدبيات اﻻإجنليزية لتحليل العر�س املتنوع لهذه املتلزمة. وركز التحليل على اﻻأعرا�س، العلمات البيوكيميائية والنتائج اﻻإ�ضعاعية من حاﻻت متلزمة هريفوردز. مفتاح الكلمات: متلزمة هريفوردز؛ مر�س ال�ضاركويد؛ �ضلل الع�ضب الوجهي؛ تقرير حالة؛ الهند. eerfordt’s syndrome is described that do not respond to treatment or are recurrent in as part of the spectrum of sarcoidosis, nature. A review of published literature from 2003 to occurring in approximately 0.3% of 2013 in the MEDLINE database was also carried out, H 1 sarcoidosis cases. It is defined as a combination of based on a search for Heerfordt’s syndrome and its uveitis, parotid gland enlargement, fever and facial clinicopathological presentations. nerve palsy.2 A typical case of Heerfordt’s syndrome is rare and patients usually have atypical presentations. Case Report Unilateral facial nerve palsy without a specific cause is most commonly diagnosed as Bell’s palsy. Although A 52-year-old Indian female was referred for an it is a diagnosis of exclusion, a comprehensive analysis evaluation of her bilateral facial palsy to the All is usually performed only for patients who do not India Institute of Medical Sciences in Bhubaneswar, respond to treatment. Heerfordt’s syndrome as a India. She had a history of right-sided facial palsy cause of unilateral facial palsy is rare, thus invariably dating from January 2013, which was diagnosed as delaying diagnoses and increasing morbidity for Bell’s palsy and treated with short-term oral steroids. 3 patients with this condition. The case presented However, recovery was only partial. In May 2013, she below establishes the need for a comprehensive subsequently developed left-sided facial palsy and was analysis in specific cases of idiopathic facial palsy referred for further evaluation. A history of swelling in Department of Otorhinolaryngology & Head & Neck Surgery, All India Institute of Medical Sciences, Bhubaneswar, India *Corresponding Author e-mail: [email protected] Preetam Chappity, Rajeev Kumar, and Anjan K. Sahoo the parotid region on the left side and undocumented spontaneously or with treatment. Persistence of low-grade fever was elicited. the inflammatory process induces fibrotic changes, 10 On physical examination, the patient had House- resulting in irreversible tissue damage. Nerve root Brackmann grade IV bilateral lower motor neuron and cranial nerve involvement is either caused by facial nerve palsy. A diffuse ill-defined swelling was the compressive effect of an adjacent granuloma or noted in the left parotid region with no palpable because of perivascular and intraneural lymphocytic 11,12 lymphadenopathy, while the right parotid gland was infiltration. The sarcoid granuloma involves the normal. An examination of her chest, lungs and peripheral nerves and is responsible for the varied cardiovascular system was unremarkable. Other cranial clinical presentation of the syndrome. Neurosarcoidosis nerves, motor and sensory physical examinations has no definite modality of treatment. Spontaneous were normal. Cytology from the left parotid gland was remission has been observed, but in progressive or suggestive of non-suppurative chronic granulomatous non-resolving cases, such as the one observed in the disease. Her serum angiotensin-converting enzyme current report, steroid treatment is required. (ACE) levels were significantly elevated (129 U/L; Head and neck manifestations of Heerfordt’s normal range: 8–65 U/L). Serum, urinary calcium levels syndrome are non-specific and a high index of and erythrocyte sedimentation rate were all within suspicion is required to diagnose the condition normal limits. A computed tomography scan of the early. Common otological manifestations thorax revealed mediastinal and hilar lymphadenopathy. include sensorineural hearing loss, facial nerve Except for occasional irritation of the eyes, the patient paralysis, labyrinthine involvement with vestibular 13 had no other significant ophthalmological history. dysfunction and temporal bone involvement. Nasal On a slit-lamp examination, features of anterior symptoms include obstruction, epistaxis, pain and intermediate uveitis were detected. anosmia. The characteristic finding of a yellow- A diagnosis of Heerfordt’s syndrome was made and coloured sub-mucosal nodule is not always found. the patient was initiated on long-term steroid therapy. However, involvement of the airway and salivary 14 After two months of treatment with oral steroids, the gland is frequently noted. Non-caseating epithelioid left facial palsy had completely improved although cell granulomas do not always indicate sarcoidosis; there was still residual palsy on the right side (grade diseases such as tuberculosis, fungal and parasitic III). Her ACE levels were 45 U/L. infections, Wegener’s granulomatosis or leptomeningeal lymphoma may also have such granulomas and should be excluded by the appropriate clinical and Discussion pathoradiological investigations.15 The symptoms of the current case correspond Heerfordt’s syndrome was first described in 1909 with the typical diagnosis for Heerfordt’s syndrome— by the Danish ophthalmologist, Christian Frederick 4 bilateral facial palsy, parotid gland enlargement, Heerfordt. A case of unilateral facial palsy with anterior intermediate uveitis and a low-grade non- no evident cause is usually diagnosed as Bell’s 5 specific fever. Although elevated calcium levels were palsy and treated empirically. The lack of typical not seen, elevated levels of ACE, mediastianal and symptomatology in cases of Heerfordt’s syndrome hilar lymphadenopathy and evidence of non-caseating is a diagnostic hurdle for the treating physician. The granulomas on the cytology of the left parotid gland incidence of cranial nerve palsy in sarcoidosis is about substantiated the diagnosis. The decline in ACE 5%,6 with the facial nerve followed by the optic nerve levels after steroid treatment further confirmed being the most common nerves involved.7 Facial nerve the diagnosis. Unfortunately, the right facial nerve palsy forms an important defining component of palsy still persisted at follow-up, with only partial Heerfordt’s syndrome. The approximate incidence of improvement. facial nerve palsy in this syndrome is 25–50%.8 Sharma To analyse the varied presentation of Heerfordt’s et al. analysed the rare manifestation of sarcoidosis in syndrome, a search of the MEDLINE database of an Indian population and, according to their results, literature published between 2003 and 2013 to Heerfordt’s syndrome was present in 1.2% of cases.9 yielded 31 articles. After excluding articles lacking The aetiology of this syndrome is still ambiguous online abstracts and those not specifically dealing and, as a result, so is the pathogenesis. The pathology with Heerfordt’s syndrome, a total of 14 articles were of neurosarcoidosis is due to a non-caseating 2,3,16–27 reviewed. The findings of these articles have epithelioid granuloma. There is an accumulation been tabulated [Table 1]. The seventh cranial nerve of cluster of differentiation 4 cells at the sites of 16 was most commonly involved, followed by the inflammation. Generally, these granulomas resolve 6 trigeminal nerve. Polyradiculopathy