Introduction

What is parry-romberg syndrome?

Parry-Romberg Syndrome (PRS) is a rare and acquired disease where one side of a person' s face slowly wastes away (known as atrophy), affecting skin, fat, muscles and bones.¹ This condition affecting only 1 in 250,000² can develop from childhood or adolescence and usually progresses for several years before stabilising. In addition to facial changes, patients also may experience neurological symptoms such as migraines and seizures.³

Why immunosuppressive therapy?

The cause of PRS is still not yet fully understood. However some factors suggest that some factors contributing to this disease are: viral and bacterial infections- such as meningitis and lyme disease and autoimmune diseases- where the persons own antibodies start attacking healthy organs and tissues.² The latter of these factors is why immunosuppressive therapy is considered in the management of PRS, and immunosuppressants are given to calm down the overreactive immune system and prevent the disease from spreading. 

Why is treatment important?

PRS often develops over the years, either from childhood or adolescence and causes atrophy to one side of the face, nerve pain, epilepsy, headaches and muscle deterioration.^{1, 3} Early treatment is critical because the loss of facial tissues cannot naturally be restored. Immunosuppressants are therefore used to reduce the progression and symptoms of PRS as well as a step forward to ensure a better quality of life for those living with this condition which currently has no cure.⁴ 

Main immunosuppressive therapies

Methotrexate (MTX)

Methotrexate (MTX) is an immunosuppressant used to treat inflammatory conditions, an example being rheumatoid arthritis.⁵ It is typically the first-line treatment for PRS and works by inhibiting dihydrofolate reductase, reducing the activity of immune cells. Often, MTX is combined with corticosteroids (as they have a slow onset of action of about 1-3 months) with a dosage of 0.3–1 mg/kg/week given orally or as an injection and has been shown to be effective in halting the progression of PRS.^6,7

Corticosteroids (e.g., prednisone, methylprednisolone)

Corticosteroids (such as prednisone and methylprednisolone) are steroids used for anti-inflammatory purposes for diseases such as lupus.⁸ They are combined with MTX to combat inflammation caused by PRS as MTX initially works slowly to control the immune system and does not affect the body immediately.^{6 7} After a few weeks, when MTX has started to work, the dose of the steroids is reduced due to the harmful side effects of corticosteroids, such as high blood pressure.⁸

Mycophenolate Mofetil (MMF)

Another immunosuppressant is Mycophenolate Mofetil (MMF), which is an alternative for those who cannot tolerate MTX.^1,9 MMF works by blocking certain enzymes that make DNA in white blood cells (lymphocytes) involved in immune responses, leading to fewer immune cells actively attacking healthy tissues. In PRS, this reduces inflammation and atrophy, allowing facial tissues to stablise and slow progression of disease. As it is an immunosuppressant,⁴ once on this medication, side effects include increased infections and increased bloating in arms and legs. 

Cyclophosphamide

Cyclophosphamide is a powerful immunosuppressant that destroys lymphocytes’ DNA and is used to treat conditions such as lupus and rheumatoid arthritis. It is only considered for the most aggressive cases of PRS, when the first-line treatment of MTX and corticosteroids is not effective, though there are not many recorded cases of the drug being used for PRS.^1,10 This could be due to side effects such as infertility and bone marrow suppression.¹¹

Other medicines (less common)

Less common medicines such as Azathioprine and biologics (such as Rituximab) have also been reportedly used for the management and treatment of PRS.¹⁰ These medications are used to treat rheumatoid arthritis and other inflammatory conditions. Azathioprine’s mechanism of action is largely unclear, but it is thought to inhibit B and T cells, which reduces the chance of antibodies attacking healthy tissues, as seen in PRS.¹² Rituxamab, which is given intravenously (via injection) is also a possible way to combat the effects of PRS where a man-made antibody targets a protein on the surface on white blood cells called CD20, ultimately destroying them which in turns reduces inflammation.¹³ 

What does research show?

PRS remains a rare disease with no large clinical trials taking place to study for a universal treatment, however there are smaller case studies where we can draw our evidence from.^1,3 These smaller case studies indicate that the best outcome to slow the progression of PRS is when treatment starts early. Kormaz et al’s⁴ research suggests that before immunosuppressants, in one particular patient, the disease was active, with brain lesions worsening, which were visible on an MRI. After treatment, clinical improvement was evident in the patient, with symptoms being better controlled and an MRI scan indicating no new progression in the disease or any worsening damage. Studies show Methotrexate combined with corticosteroids remains the most effective combination for patients.^{6 7} It is important to note that while these treatments slow progression and stabilises many patients, it will not reverse any damage already caused. 

Risks and monitoring

One of the main side effects of immunosuppressants is the increased risk of infections and organ toxicity. This is due to the immune system being repressed by these medications and antibodies cannot fight off infections, meaning even the smallest of illnesses could escalate to something huge. Therefore, patients with PRS who are on immunosuppressants are also given vaccinations as also given as a preventive before starting treatment. They are also subjected to regular blood tests, which are done to check the liver, kidney and blood cells’ health and function.¹⁴ As each medication has its own particular side effect, for example, MTX may have a negative effect on the liver⁵, doctors will carefully balance the benefit of each drug with its long-term risks. 

Challenges and limitations

As mentioned before, PRS is an extremely rare disease, only affecting 1 in 250,000 people.² Hence, no large-scale clinical trials have been undertaken to find a definite cause or treatment for this disease,¹⁰ meaning no universal treatment guidelines are in place. Secondly, every person’s body is unique and reacts differently. Some patients stabilise more quickly, while in others PRS continues, despite ongoing therapy. Finally, immunosuppressive therapy aims to slow down progression, not reverse damage or eradicate the disease altogether. This poses the question as to how long one will have to continue treatment of drugs which can have detrimental side effects and long-term risks.^5,6,7

Other supportive options

Alongside immunosuppressive therapy, there are other options that PRS patients can explore. For example, when there has been a halt in progression in the disease, facial implants and reconstructive surgery can be considered for facial appearance.^{2 10} Alloplastic implants have been used in the past and these effectively restore facial symmetry after being affected by atrophy.¹⁵ Additionally, if muscle function has deteriorated, physical therapy is also recommended to help improve jaw function. Most importantly, for the people living with PRS, sometimes they may need emotional and psychological support, so counselling will always be available for them if they contact the right people, such as their local GP.² 

Future directions

One of the main future directions is research. This future research should focus on developing a more universal treatment for PRS, to ensure the best outcome for patients.¹ Biologics, such as rituximab, which have not been fully explored yet, could in the future provide a safer, more effective option, so research regarding them could be carried out.¹² Furthermore, a reliable biomarker (a measurable indicator in the body) could be identified so more specific, targeted treatments can be carried out.³ Collectively, these ideas can help in better advancement in understanding PRS.

Summary 

PRS is a rare and acquired disease, which is characterised by atrophy on one side of the face. The exact cause as to why this occurs is still unknown, and PRS’s symptoms are largely controlled by immunosuppressive therapies, such as Methotrexate (MTX), Corticosteroids, Mycophenolate Mofetil (MMF), Cyclophosphamide and other less explored options such as biologics, and the small amount of research conducted has shown that early treatment has a more desirable outcome. Due to the nature of immunosuppressants, close monitoring of the patients is required to ensure low rates of infections and organ damage. Apart from immunosuppressive therapy, facial surgery, muscle therapy and psychological counselling is also undertaken by patients living with PRS. In the future, suitable biomarkers for PRS can be established and larger clinical trials and research can be carried out, so a universal treatment for PRS can be acknowledged.