Progressive hemifacial atrophy (ORPHA:1214)
Progressive hemifacial atrophy (PHA) is a rare acquired disorder, characterized by unilateral slowly progressive atrophy of the skin and soft tissues of half of the face leading to a sunken appearance. Muscles, cartilage and the underlying bony structures may also be involved.
Epidemiology
The prevalence is estimated to be at least 1/700,000 individuals, women being slightly more affected than men.
Clinical description
PHA usually presents during the first 20 years of life, characterized by slowly progressive unilateral atrophy of various tissues (skin, connective tissue, fat, muscle and rarely, underlying bony structures) in the territory of the 5th cranial nerve. PHA may start with alopecia, hair hypopigmentation, and atrophy may be preceded by cutaneous induration and hypo- or hyperpigmentation. PHA may extend to the upper lip and/or one side of the tongue and the masticatory muscles, resulting in deviation of the nose/mouth toward the affected side, unusual twisted or raised appearance of the upper lip, micrognathia, difficulty opening/closing the jaws and chewing/smiling/speaking, trismus, abnormal exposition of certain teeth, late eruption and/or atrophic roots and malocclusion. Rarely both sides of the face and the skin on the arms/trunk/leg or the entire body may be involved. Seizures and headaches are the most common neurologic symptoms. Ophthalmologic anomalies (enophthalmos, globe retraction, ptosis, iris heterochromia, uveitis, retinal vasculitis, glaucoma and eyelid atrophy) may result in visual impairment or blindness. Ear involvement (ipsilateral misshaping of the ear, abnormal small appearance and protrusion from the head) may also be observed. Anxiety and depression are common. A significant overlap between clinical and histological features of PHA and localized scleroderma ''en coup de sabre'' is reported.
Etiology
The exact etiology of PHA is unknown. Due to the presence of autoimmune diseases in several cases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis), autoimmunity may be a cause of PHA, along with facial or head trauma, meningoencephalitis, abnormal development or hyperactivity of the sympathetic nervous system, neuro-vasculitis, angiogenesis anomalies, and slow viral infections.
Diagnostic methods
PHA diagnosis is based on clinical and histopathology features. The skin biopsy reveals homogenized dermal sclerosis, fat atrophy, decrease in adnexal structures, and perivascular plasma cells and lymphocytes. Computerized tomography (CT) and magnetic resonance imaging (MRI) may display infarction, hemorrhage and white matter hyper-density. Ultrasounds, ocular/dental imaging and photographs allow the monitoring of disease activity and progression.
Differential diagnosis
Differential diagnosis includes localized scleroderma, Rasmussen syndrome, hemifacial microsomia, Goldenhar syndrome, idiopathic facial palsy, Berardinelli-Seip congenital lipodystrophy and partial acquired lipodystrophy. Patients with face injuries (e.g. burns), fat necrosis and congenital deformities (e.g. wry neck) should also be considered.
Genetic counseling
PHA is sporadic in most cases, but rare familial cases have been reported. The effective transmission of the disease has not yet been reported. Genetic counseling is not recommended at this time.
Management and treatment
PHA management is symptomatic, requiring a multidisciplinary approach (pediatricians or internists, plastic surgeons, dentists, ophthalmologists, dermatologists, neurologists). Surgical management (fat/silicone injections, flap/pedicle grafts or bone implants) is usually not advised until the progression of PHA is stabilized. Patients with cerebral involvement may be considered for immunosuppressive therapy.
Prognosis
In some cases, the atrophy stops before the entire face is affected, with rare recurrence and no disability other than the cosmetic effects in the mild cases. Occasionally, PHA course may be accelerated, secondary to stress, surgery and pregnancy or shortly after childbirth.

                            Last update: 
                            July 2015


                            - Expert reviewer(s): 
                            Dr Nirav PATEL  - Dr Stanislav TOLKACHJOV  - Dr Megha TOLLEFSON