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.

The overall UK incidence of sarcoidosis is estimated at approximately 5/100,000 per annum.
About 3000 new cases are diagnosed each year.³ Prevalence amongst different ethnic groups varies widely: in London, there was a prevalence of 97/100,000 amongst Irish males and 200,000 amongst West Indian males.⁴ 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.⁵ In a series of 147 patients with ocular sarcoidosis, facial palsy occurred in 12% and parotid gland enlargement in 10%.⁶

Risk factors

• Young adulthood - more frequent in those aged between 20-40 years.⁵
• More common presentation in women than men.⁵
• More common presentation in white patients, particularly those of Scandinavian origin. There is an appreciable low-level incidence in the Japanese population.⁷

Note, additional features of sarcoidosis may appear alongside the core syndrome.

Symptoms

Fever and constitutional upset

• The patient may have experienced paroxysmal episodes of fever or night sweats.
• Other symptoms such as headache and weight loss may occur.⁸

Ocular symptoms

• Acute uveitis presents with:
  • Ocular discomfort
  • Photophobia
  • Blurred vision
  • Seeing 'floaters'
  • Red eye
• The lacrimal glands may be involved, causing puffy eyelids.⁸

Parotid swelling

• May be unilateral or bilateral - bilateral in 73% of cases of parotid sarcoidosis.⁵
• Diffuse, painless swelling of the parotid ± other salivary glands/lacrimal glands.
• May cause a dry mouth.

Cranial nerve palsy

• Strictly speaking must affect the facial nerve (CN VII).
• Abrupt onset within a short period of the parotid swelling.
• Nerve thought to be entrapped/infiltrated by granulomatous inflammation in the parotid gland or facial canal, but exact site remains 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:⁴
  • Disturbance of smell
  • Blurred vision/diplopia/blindness
  • Speech or swallowing difficulty
  • Vertigo/deafness/tinnitus
  • Weakness of trapezius/neck muscles
  • Tongue deviation or atrophy

Signs

General

May include:

• Pyrexia
• Evidence of recent weight loss
• Facial swelling around the cheeks
• Swollen eyelids
• Inflamed eyes, squinting in light
• Visible facial nerve palsy with drooping of features on one side (note, if bilateral, facial symmetry may be preserved)

Cranial nerve palsy

• Lower motor neurone CN VII lesion - affects 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 present.
• If an alternative cranial nerve palsy is found in place of facial nerve paralysis, most would still define the syndrome as Heerfordt's, provided 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
  • 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.
• For image of uveitic eye, see Ref.⁹

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. The differential diagnoses of Uveitis and Facial Nerve Palsy are discussed in separate articles.

The two most useful specific diagnostic tests for this presentation of sarcoidosis are:

1. Serum Angiotensin Converting Enzyme (ACE) - which is usually elevated.
2. Scintigraphy using Gallium 67 - which shows increased uptake in the parotid gland, signifying active sarcoidosis. Scintigraphy may reveal other sites of active sarcoidosis.

These 2 tests combined have a specificity of 99%.¹⁰
Biopsy of the parotid gland or other sites of disease may be required in some cases which should reveal characteristic non-caseating epithelioid granulomata.

Additional investigations may include:

• CXR - to look for evidence of hilar adenopathy or pulmonary involvement.
• Basic screening bloods such as ESR, FBC, U&E/LFTs are usually performed as baseline investigations but are fairly non-specific.
• Autoantibodies if there is any suspicion of a connective tissue disease.
• Lumbar puncture may be needed where there is suspicion of meningitis - in sarcoidosis, it shows a sterile pleomorphic inflammatory picture.

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.

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.¹¹
• 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.¹¹

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

Prognosis is very variable:

• 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.
• Facial paralysis tend to recover or respond to steroids.
• 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%.¹²

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.