Parry-Romberg syndrome

What is Parry-Romberg syndrome?

Parry-Romberg syndrome (PRS) is a rare acquired disorder characterised by the progressive atrophy of skin, fat, muscle, bone, and cartilage typically on one side of the face. Systemic manifestations may occur, particularly with neurologic and ophthalmic involvement.

This disorder is considered by some to be a rare, severe variant of linear morphoea (localised scleroderma).

Other names for Parry-Romberg syndrome include:

• Progressive facial hemiatrophy
• Progressive hemifacial atrophy
• Idiopathic hemifacial atrophy
• Romberg syndrome.

There are overlapping features of morphoea and PRS

Hemiatrophy of the tongue in addition to facial changes of fat and muscle atrophy (PRS-patient2)

Dermal sclerosis is evident in morphoea, but there was also cerebral and lingual changes more in keeping with PRS (PRS-patient1)

Who gets Parry-Romberg syndrome?

Parry-Romberg syndrome classically presents within the first two decades of life, however cases have also been reported in older adults. PRS can affect both genders, but is more commonly seen in females. PRS does not appear to show any racial predilection.

What causes Parry-Romberg syndrome?

The cause of PRS is unknown (idiopathic). Several factors have been proposed to play a role in the pathogenesis of PRS.

Common etiological theories include:

• Autoimmune-driven: Parry-Romberg syndrome is often considered an autoimmune condition due to its similarities with localised scleroderma. This is further supported by findings of improvement following immunosuppressive therapy, positive serum auto-antibodies, and reports of co-occurring autoimmune disease eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease.
• Trauma-induced: 30% of cases report a history of trauma, including tooth extraction.
• Infection-driven: There have been documented associations between PRS and infection with Borrelia burgdorferi (Lyme disease); however, a causal link has not been proven.
• Neurovasculitis: Chronic inflammation of nerves/vessels, leading to arterial wall fragility, may explain the presence of cerebrovascular malformations in some PRS patients; this is supported by histopathology revealing proliferative interstitial neurovasculitis on facial specimens.
• Autonomic dysregulation: Dysregulation of the sympathetic nervous system may affect the nerves supplying fat and skin, leading to atrophy; cervical sympathectomy in animal models was able to produce hemifacial atrophy and other findings similar to PRS.
• Genetic predisposition: The vast majority of reported cases have been sporadic. That said, there has been a case report of two first cousins, both presenting with the syndrome, highlighting a possible genetic link. Moreover, a study conducted in Shanghai, based on whole exome sequencing, revealed two potentially implicated genes: MTOR and DHX37.

What are the clinical features of Parry-Romberg syndrome?

Parry-Romberg syndrome is characterised by the unilateral wasting of facial skin, fat, muscles, cartilage, bones, or even glands. This creates a sunken, indented appearance of one side of the face. The severity and speed of atrophy vary greatly from patient to patient.

In rare cases, bilateral facial involvement can occur, or other parts of the body can be affected (eg, torso and extremities).

Additional facial features:

• Tends to affect the lower face, with sparing of the forehead
• Minimal cutaneous involvement; skin appears soft and not sclerotic
• Co-occurring morphoea en coup de sabre — a shiny, atrophic linear depression of the head/scalp, resembling the ‘blow of a sword’
• Ipsilateral atrophy of the tongue, gingiva, and hard palate
• Skin discolouration on affected areas.

Parry-Romberg syndrome can also cause extracutaneous manifestations; an estimated 15% of patients have neurologic involvement, and up to 35% have ophthalmic involvement.

Neurologic features:

• Epilepsy — may be refractory to medical treatment
• Headache and facial pain
• Neuropsychiatric symptoms eg, cognitive disturbances, intellectual disability, hallucinations
• Cerebrovascular malformations eg, aneurysms, cavernomas, carotid-jugular fistula, hypoplastic or stenotic arteries
• Movement disorders eg, dystonia, torticollis, spasms.

Ophthalmic features:

• Enophthalmos (sunken eye)
• Ocular motor dysfunction (difficulty controlling eye movements) and double vision
• Glaucoma
• Retinal vasculitis
• Optic neuritis.

How do clinical features vary in differing types of skin?

There are no notable differences in presentation based on skin type.

What are the complications of Parry-Romberg syndrome?

• Psychosocial distress due to disfigurement
• Nasal or lingual deviation
• Ocular complications eg, glaucoma, retinal detachment, enophthalmos, ptosis, uveitis
• Dental complications eg, smaller teeth with shorter roots
• Severe facial pain (trigeminal neuralgia) and recurrent migraines
• Status epilepticus
• Cerebrovascular accidents eg, subarachnoid haemorrhage from cerebral aneurysm rupture, ischemic stroke, carotid dissection
• Intellectual disability and psychiatric disorders

How is Parry-Romberg syndrome diagnosed?

There are currently no universally accepted diagnostic criteria. Parry-Romberg syndrome is primarily a clinical diagnosis, based on the history of a slowly progressive, localised, hemifacial atrophy, and the exclusion of other causes.

Neuroimaging with CT/MRI should be performed if patients have neurological symptoms; they may also aid the diagnosis by demonstrating changes such as lipoatrophy. Seizures should prompt evaluation with electroencephalogram studies.

Although histopathology is not required for diagnosis, skin biopsy reveals minimal sclerosis, extensive dermal fat atrophy, preservation of dermal elastic tissue, and a decrease in adnexal structures.

What is the differential diagnosis for Parry-Romberg syndrome?

• Rasmussen encephalitis
  • An autoimmune disorder affecting one side of the brain and shares neurological manifestations with PRS (eg, hemicerebral atrophy).
  • Intracranial neuroimaging may be indistinguishable from PRS and the two diseases can co-occur.
  • PRS is distinguished by its cutaneous features.
• Multiple sclerosis (MS)
  • On MRI, the white matter lesions of PRS overlap with those in MS patients.

Other causes of acquired localised lipoatrophy:

• Morphoea en coup de sabre (ECDS; variant of morphoea/localised scleroderma)
  • Frequently coexists with PRS and shares overlapping features
  • Ongoing debate whether the two are distinct entities or exist along the same disease spectrum
  • Some authors distinguish PRS and morphoea ECDS through certain features eg, lack of cutaneous sclerosis and induration, lack of cicatricial alopecia, relative forehead sparing, greater severity of atrophy, and preservation of dermal elastic tissue in PRS.
• Barraquer-Simon syndrome (acquired partial lipodystrophy) – a rare disorder characterised by bilateral, symmetrical lipodystrophy of the upper body, with renal involvement.
• Lupus profundus
• Repeated trauma or pressure
• Drug injections
• Antiretroviral therapy for HIV.

What is the treatment for Parry-Romberg syndrome?

Currently, there is no known cure or standardised treatment for Parry-Romberg syndrome. Instead, efforts are aimed at halting disease progression and treating acute complications. Once the disease has stabilised, aesthetic rehabilitation may be initiated.

Treatment of Parry-Romberg syndrome requires a multidisciplinary approach and may involve dermatologists, neurologists, ophthalmologists, plastic surgeons, maxillofacial surgeons, and dentists.

Disease treatment

Treatments to halt disease activity are similar to those employed for scleroderma and involve immunosuppression or immunomodulation:

• Systemic corticosteroids
• Disease-modifying antirheumatic drugs (DMARDs) eg, methotrexate, mycophenolate mofetil, ciclosporin, hydroxychloroquine
• Biologics eg, secukinumab, tocilizumab
• Psoralen and ultraviolet A (PUVA).

Cosmetic treatment

• Cosmetic camouflage
• Prosthetic devices
• Dental work
• Dermal fillers
• Autologous fat transfers
• Facial reconstruction (eg, bone augmentation)

How do you prevent Parry-Romberg syndrome?

There is no known way of preventing Parry-Romberg syndrome.

What is the outcome for Parry-Romberg syndrome?

Parry-Romberg syndrome is an incurable disease that tends to slowly progress over a 2 to 20-year period, before spontaneously entering a stable phase where disease progression halts. Prognosis is favourable and patients are expected to have a normal life expectancy.

Mild cases of Parry-Romberg syndrome usually do not cause disability other than cosmetic effects.