Parry-Romberg syndrome

Historical Perspective

Parry–Romberg syndrome (PRS) is a rare condition first described in 1825 by Caleb Parry and in 1846 Moritz Romberg provided a detailed description of the disease Due to diseases feature such as gradual shrinkage of the facial tissue Albert Eulenburg in 1871 named it as progressive hemifacial atrophy. Some evidence suggests that the condition has historical roots, as it is found in 2 out of 200 ancient mummy portraits.

Pathophysiology:

PRS also known as progressive hemifacial atrophy is a neurocutaneous disorder characterized by unilateral facial atrophy affecting skin, tissues, muscles, and even bone on one side of the face the pathophysiology of the disease is unclear but literature suggests that issue in some specific parts of the brain play a significant role. These areas include regions around the upper sympathetic ganglion, certain areas of the spinal cord, and fluid-filled cysts in spinal cord conditions known as syringomyelia . These problems can affect involuntary function on one side of the face and can impact the brainstem.

Additionally, many people have a dormant form of the varicella-zoster virus in nerve cells associated with the trigeminal nerve. If this virus becomes active again, it can spread to the trigeminal nerve, leading to an immune response where lymphocytes attack the nerve and the nearby blood vessels, potentially contributing to the development of PRS

Presenting symptoms:

The symptoms of PRS are similar to linear scleroderma en coup de saber, which makes the diagnosis of PRS challenging. In this condition, the eye and the region around the eye are affected, leading to symptoms such as a sunken eye, changes in the eyelid, eye socket, cornea, and retina as well as issues with the optical nerve and eye moments. The skin of the affected side becomes lighter or darker and the shrinking of muscles sometimes extends to the other body parts such as the neck arms and even the opposite side. It can cause hair loss, tongue shrinking, vision problems, and differences in eye color these are the sign of Horner-Bernard syndrome the changes in the skin is resemble scleroderma which is accompanied by neurological problems such as seizures, migraines, trigeminal neuralgia

Causes:

The cause of the diseases is not clear however literature has suggested several potential factors that contribute to the development of the diseases such as autoimmune, trauma,neurovascular, infection, genetics, Sympathetic nervous system dysfunction, and others.

Autoimmune:

PRS is hypothetically considered autoimmune, with some studies suggesting an association with autoimmune disorders. The evidence supporting this hypothesis includes symptoms such as trigeminal neuralgia and other neurological manifestations. Additionally, immunological abnormalities reported in PRS patients indicate a possible dysregulation of the immune system

Trauma:

Approximately 24-34% of patients had a history of trauma before the onset of the symptoms of (PRS) which may occur due to tooth extraction, surgery procedures, or gynecological interventions. Additionally, development of the diseases has also been associated with trauma resulting from accidents.

Neurovascular:

The inflammation of blood vessels specifically lymphocytic neuro-vasculitis is a cause of PRS in this condition the immune system attacks on the blood vessels and damages them effect nerves particularly the trigeminal nerve a major nerve in the face.

Infection:

PRS may be caused by infections such as Lyme disease, herpes, tuberculosis, tooth infection,and diphtheria and some others can also cause disease but still the association between PRS and infection is not clear

Genetics:

Research on the genetic causes of the disease has not provided clear evidence that it is hereditary. However, patients have shown increased activity in specific genes that promote inflammation, such as GFCSF3, ADAMTS4, and IL24 were more active in PRS patients.

Epidemiology and Demographics:

PRS is a rare disease and the incidence of the disease is reported at 1 in 70000 to 1 in 250000 individual this diseases affect 1,000,000 worldwide

Age:

The age at which the disease begins can vary, but it is most commonly observed around 10 years old or within the first 20 years of life.

Gender:

Investigations suggest that the disease is predominant in females.

Diagnosis:

At the time of diagnosis during physical examination and history taking some clinical symptoms related to Facial, Ophthalmic, Neuro-ophthalmological, Neurologic, Maxillofacial, Cardiac and Endocrine is looking out for favoring the diagnosis of PRS over scleroderma. After this some diagnostic workup will be done.

Physical examination:

It includes an examination of the eye, dental, skin Rheumatology, and neurology

Orbital Ultrasound/ultrasound biomicroscopy:

To look at the back part of the eye and if it is blocked due to cataracts or corneal opacity then orbital ultrasound is used to observe changes in the ciliary part of the brain ultrasound biomicroscopy is used

CT scan:

To see any changes in the eye socket (orbital) the bone around the eyes, and the skull

Electroencephalogram:

Epilepsy seizures are also observed in this disease there for EEG is performed to find out the area of the brain that is causing seizures in epilepsy cases

Cerebrospinal fluid (CSF) analysis

During neurological examination, it usually shows normal results but in some cases, specific protein band oligoclonal bands and increased IGg index appear which are linked to certain brain lesion visible on MRI

MRI:

To evaluate this disease MRI 1 is performed to identify the area in the brain where tissue is shrunk or thinned out and MRI2 sequence highlights the unusual bright spot in brain

MR Angiogram:

It shows where and how much number of blood vessels in the brain are abnormal

Brain SPECT Scan:

It detects small brain problems that might be not visible on regular scan

Orthopantomograms:

Regular X rays and photos are used to detect the changes in jaw bone and teeth

Skin biopsy:

It is not mostly done but it is used to differentiate PRS from its similar condition

Anti-nuclear antibody (ANA)

ANA shows positive results in 25-50% of PRS cases

Other serology tests:

These tests are not useful in diagnosing PRS

Treatment:

There are various treatment options are available to overcome the disease and improvement of appearance is also considered the available treatment options are

Medication/radiation/eye drops

This treatment is effective for suppressing the immune system it includes Methotrexate (MTX) it prevent the diseases from coming back the dose range of the medication is 0.3 to 1 milligram per kilogram of body weight per week and it is combined with another medication that could be Corticosteroids such as prednisolone or methylprednisolone and if the disease do not respond to this medication then other will be used such as mycophenolate mofetil, cyclophosphamide, hydroxychloroquine, and cyclosporine. And Psoralen and Ultraviolet a (PUVA) light is used to stop diseases from progressing. For management of eye related issues eye drops are used to reduce inflammation and steroids are also used as a drop or in the form of pills this treatment is continued until the eye becomes normal and to protect the eye surface from damage, the eyelids may be gently taped shut, and lubricating eye drops be used to protect eye from damage and trabeculectomy is used to protect the eye from damage due to high pressure and misalignment of the eye is treated with surgery or glasses and in case of neurological management like seizures medications are used to control this problem

Surgery:

It is important for the management of appearance as well as for the eyes which are effect due to disease like if the white part of the eye becomes thin or melts the scleral patch graft is considered as best treatment option the surgery option is also available for the cosmetic treatment after the diseases stop progressing and eye related cosmetic treatments include frontalis sling surgery, browpexy or Z-plasty, and other options are also available to treat sunken eye, contracted eye socket, Drooping Eyelid PMID: 30851754, plastic surgery option include Synthetic Tissue Fillers to correct uneven facial features, Autologous Fat Grafting, orthognathic surgery and Free Soft Tissue Transplantation are done to provide good cosmetic results