Heerfordt's Syndrome

Synonyms: Heerfordt syndrome (USA form), Heerfordt's disease, Heerfordt-Mylius syndrome, Heerfordt-Waldenstrom syndrome, Waldenstrom's uveoparotitis, uveoparotid fever, febris uveoparotidae, neuro-uveoparotitis syndrome, uveoparotitic paralysis, uveomeningitic syndrome

See also: Sarcoidosis.
An acute syndromal presentation of sarcoidosis. Several physicians were involved in its discovery and characterisation,¹ hence its plethora of eponymous names. It forms a small proportion (<5%) of sarcoidosis cases, with variation in its likelihood between ethnic groups. Its classical combination of features is virtually pathognomonic of sarcoidosis.

The overall US prevalence of sarcoidosis is estimated at 10–40 cases per 100,000 population but its prevalence in Irish- Scandinavian- and Caribbean-origin populations appears to be highest in the US. The lifetime prevalence of sarcoidosis for North Americans is 2.4% in the black population, and 0.85% in whites.

Heerfordt's syndrome is relatively rare and accounts for <5% of presentations of the parent disease. Parotid gland involvement in UK sarcoidosis sufferers had a prevalence of 6% in one series, but not all of these cases could be classified as Heerfordt's syndrome.³ In a series of 147 patients with ocular sarcoidosis, facial palsy occurred in 12% and parotid gland enlargement in 10%.⁴

Risk factors

It appears to be a more common presentation in white patients, particularly those of Scandinavian origin. There is an appreciable low-level incidence in the Japanese population.⁵

Presents most commonly in young adults, usually aged 20–40 years.³ Other features of sarcoidosis may appear alongside the syndrome. For full details of sarcoidosis presentations see the separate article on sarcoidosis.

Symptoms

• Fever and constitutional upset:
  • The patient may have experienced episodes of fever or night sweats.
  • Other symptoms such as headache and weight loss may occur.⁶
• Ocular symptoms:
  • Acute uveitis presents with ocular discomfort, photophobia, blurred vision, seeing floaters and a red eye.
  • The lacrimal glands may be involved, causing puffy eyelids.⁶
• Parotid swelling:
  • Unilateral or bilateral (affects both sides in 73% of cases of parotid sarcoidosis).³
  • Diffuse, painless swelling of the parotid ± other salivary glands/lacrimal glands.
  • May cause a dry mouth.
• Cranial Nerve Palsy:
  • Strictly speaking must affect Facial Nerve (CN VII).
  • Abrupt onset within short period of parotid swelling.
  • Nerve thought to be entrapped/infiltrated by granulomatous inflammation in parotid gland or facial canal, but site still uncertain.
  • May be accompanying disturbance of taste (chorda tympani dysfunction – supporting presumed site of lesion).
  • Other cranial nerves can be involved.
  • Symptoms of other cranial neuropathies commonly involved in neurosarcoidosis include disturbance of smell, blurred vision/diplopia/blindness, speech or swallowing difficulty, vertigo/deafness/tinnitus, weakness of trapezius/neck muscles and tongue deviation or atrophy.⁷

Signs

• General/observation:
  • Pyrexia, possibly evidence of weight loss, facial swelling around the cheeks, maybe swollen eyes.
  • Patient has inflamed eyes and may squint in light.
  • May be visible facial nerve palsy with drooping of features on one side (can be bilateral when facial symmetry may be preserved).
• Cranial nerve palsy:
  • Lower-motor-neurone VIIth CN lesion, affecting the whole face including forehead and eyelids.
  • Bell's phenomenon may be seen – upward, outward turning of the eyeball as the patient attempts to close the eyelids.
  • Examine other cranial nerves as other palsies may be found.
  • If alternative cranial nerve palsy found in place of Facial Nerve paralysis, most would still define the syndrome as Heerfordt's, where all other classical features of the syndrome are present.
  • Bilateral lower-motor-neurone facial nerve palsy of abrupt onset in young adults is virtually always due to sarcoidosis.
  • There may be accompanying signs of meningism.
• Eyes:
  • Anterior uveitis is painful and presents with miosis, pupillary irregularity and injected conjunctivae next to the cornea (so-called perilimbal flush).
  • Fundoscopy may show retinal detachment or vasculitis and papilloedema if there is posterior uveitis.
  • Severe cases may show hypopyon – a collection of yellowish inflammatory exudate and cells at the bottom of the anterior chamber.
  • Slit lamp examination may reveal cells, flare and precipitates in the anterior chamber/vitreous humour.
  • See internet section below for link to image of uveitic eye.
• Salivary/lacrimal glands:
  • Diffuse, firm swelling which is not tender to palpation.

The syndrome is a fairly distinct clinical entity and once recognised is not likely to be confused with illnesses other than sarcoidosis, being virtually pathognomonic for the disease. Sarcoidosis has a vast differential diagnosis, depending on its mode of presentation. See separate article. The differential diagnoses of uveitis and facial nerve palsy are discussed in separate articles.

Sarcoidosis tends to undergo spontaneous remission in 50–60% of cases and does not always require active management. The disease course is very variable and difficult to predict. See separate article for full details.

Medical

The most troublesome aspect of the syndrome to manage is uveitis which may be sight-threatening and requires expert ophthalmological assessment and monitoring. Topical or systemic corticosteroids are the mainstays of management of ocular sarcoidosis. Other immunomodulatory drugs may be used as steroid-sparing or disease-modifying agents.⁹ Systemic steroids are used to treat the facial nerve palsy if it is troublesome enough and does not resolve, usually successfully.

Surgical

Surgical intervention may be used to treat the complications of cataracts or vitreous opacification, once active disease has been controlled. Uveitis increases the risk of glaucoma, so a significant proportion of patients may require trabeculectomy or other glaucoma-drainage devices.⁹

• Ocular sarcoidosis:
  • Ocular sicca syndrome
  • Band keratopathy
  • Cataracts
  • Glaucoma
  • Vitreous haemorrhage
  • Retinal detachment
  • Cystoid macular oedema
  • Blindness due to macular disease
  • Diplopia
  • Optic atrophy
• Neurosarcoidosis:
  • Seizures
  • Hydrocephalus
  • Deafness
  • Spinal cord lesions causing motor/sensory paresis
  • Pituitary dysfunction
  • Sterile meningitis
• Parotid sarcoidosis:
  • Xerostomia
  • Oral infections/dental caries due to reduced saliva secretion

Very variable. Facial paralysis tend to recover or respond to steroids. Of the acute presentations of sarcoidosis, it carries a relatively poorer outlook in terms of severity of disease, but permanent complications can be avoided or ameliorated by adequate management in many cases. Heerfordt's syndrome is not thought to relapse once it has remitted or responded to therapy, but other patterns of sarcoidosis may follow it. The degree of involvement of sarcoidosis at other sites will influence the overall prognosis. Overall long-term mortality in sarcoidosis is about 5-8%.¹⁰

The cause of sarcoidosis is not really understood so primary preventive strategies do not exist. Patients with sarcoidosis are prone to relapse and may benefit from long-term specialist follow up. Patients should be advised to seek early help if they experience symptoms potentially attributable to sarcoidosis.