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Arthritis Treatment with Photochemotherapy

photochemotherapy arthritis treatment UVA lightA paper published in the Journal of Clinical Rheumatology last month details the case of a patient with ankylosing spondylitis successfully treated with photochemotherapy (Akay, et al, 2011). The authors of the paper suggest that this anti-cancer therapy may be of benefit to other types of autoimmune arthritis such as psoriatic arthritis and rheumatoid arthritis due to the effect of such treatment on the immune system. Arthritic conditions such as ankylosing spondylitis can cause severe spinal stenosis as the structure of the spinal column changes with joint degeneration. Pronounced curvature of the spine is a significant feature of ankylosing spondylitis, particularly in the cervical spine, which may then create problems of radiculopathy and even myelopathy as spinal nerves and the spinal cord are compressed. In psoriatic arthritis and rheumatoid arthritis the spine is not always affected, with the larger joints, such as the knees, more common sites of inflammation and pain. However, some patients with these inflammatory diseases may develop significant problems in the spine, particularly where other injuries, such as whiplash, predispose the bones and ligaments in the spine to become inflamed and degenerate under stress.


The patient in the particular case reported by Akar, et al, had cutaneous T-cell lymphoma, in addition to ankylosing spondylitis, and underwent three cycles of extracorporeal photochemotherapy (ECP) to treat the lymphoma. The combination of these two conditions is quite rare but complicated the treatment of the patient as medication for the lymphoma (intreferon gamma) aggravated the arthritic condition. Instead, the patient received this specialized form of chemotherapy which involves the removal of blood then treated with 8-methoxypsoralen and UVA before being infused back into the patient. Following treatment, the patient’s scores on the Bath AS Disease Activity Index and Bath AS Functional Index improved, along with reductions in both pain and inflammation.

arthritis treatment extracorporeal photochemotherapyThe idea of using extracorporeal photochemotherapy for arthritic conditions is not new, but there has been little investigation into the effectiveness of the treatment as so many other disease modifying agents exist to manage these diseases which can cause spinal stenosis. A paper published back in 1994, in the Annals of the Rheumatic Diseases, discussed the ‘future for extracorporeal photochemotherapy in the treatment of the rheumatological diseases’, and listed the therapy amongst other experimental treatments for rheumatoid arthritis. Along with methotrexate and cyclosporin, other therapies included anti-tumour necrosis factor, cytokine toxic fusion proteins, and cytokine receptor antagonists. Stem cell treatment for autoimmune diseases is also being investigated with researchers earlier this year demonstrating a positive effect on rheumatoid arthritis following bone marrow stem cell transplant in some patients.

How ECP Works for Arthritis

Patients receiving extracorporeal photochemotherapy are given a dose of oral methoxypsoralen two hours before blood is drawn. The blood is then treated outside of the body (extracorporeally) with ultraviolet A light at room temperature, before being infused back into the patient. In some cases this treatment is done as a continuous flow, with other patients treated with a concentrated lymphocyte bolus reinfused on two consecutive days each month. The treatment works due to methoxypsoralen’s photoreactive nature as it is temporarily transformed into its active form as it is exposed to UVA light before returning to its inactive state after a fraction of a second. Less than 10% of the blood lymphocytes are treated during ECP meaning that actual cell death is unlikely to be the mechanism behind the effectiveness of the treatment for either lymphoma or rheumatic conditions. Instead, researchers think that the leucocyte cell membranes may undergo an alteration in their DNA and that these modifications in DNA are taken up by other cells. In addition, certain enzymes are thought inactivated by methoxypsoralen’s effect on some amino acid residues.


Despite such speculation, it remains unclear as to how extracorporeal photochemotherapy works its magic on patients with cutaneous T-cell lymphoma. Another theory is that the expression of human leukocyte antigen class I increases with photoactivation of methoxypsoralen at room temperature and that this may then trigger an increased CD8+ antilymphoma response. The temperature of the ECP process is likely important in the effectiveness of the therapy as this response by the immune system differs when the blood is at body temperature rather than room temperature. A 1991 study (Malawista, et al) of ECP for rheumatoid arthritis patients saw seven patients given the treatment on two consecutive days every month for three months, then either monthly or biweekly ECP for the next three months. Four out of seven patients saw improvements in joint health after the three months and some reported improvements in grip strength, walking time, and morning stiffness. Unfortunately, the patients appear to have deteriorated again two to three months after ECP finished.

Other autoimmune diseases have been the focus of pilot studies with ECP, including systemic lupus erythematosus (SLE). The same two-day consecutive treatment strategy was used in one such study, with ten patients treated for six months before bimonthly treatments were given for six more months. Only eight patients completed the study and seven of these had significant improvements including a lessening of arthritis symptoms of SLE. Research into the use of ECP for psoriatic arthritis also found that patients improved as a general rule, with the benefits for joint symptoms lasting for over a year in some cases, having commenced within the first three months of treatment (Vahlquist, et al, 1996).

Despite all of these positive indications the use of ECP in the treatment of arthritis remains experimental with little research having occurred in recent years. Each ECP session was estimated to cost around £1000 ($1600) in 1997 which may have contributed to the resistance to developing clinical trials for autoimmune conditions affecting the joints when other treatments were available and generally effective. With the publication of this new paper detailing a case of ankylosing spondylitis treated with extracorporeal photochemotherapy, in addition to a 2003 case of a patient with seronegative polyarthritis enjoying complete remission from the disease following ECP, it may be that the therapy enjoys renewed interest from the scientific community. Extracorporeal photochemotherapy may, therefore, offer hope to those suffering from spinal stenosis due to autoimmune arthritis.


References

Akay BN, Sanli H, Kutlay S., Treatment of ankylosing spondylitis by extracorporeal photochemotherapy given for mycosis fungoides: a potential treatment option? J Clin Rheumatol. 2011 Aug;17(5):278-80.

Leaders, Is there a future for extracorporeal photochemotherapy in the treatment of the rheumatological diseases? Annals of the Rheumatic Diseases 1997;56:339–342

Malawista SE, Trock DH, Edelson RL. Treatment of rheumatoid arthritis by extracorporeal photochemotherapy: a pilot study. Arthritis Rheum 1991;34:646-54.

Vahlquist C, Larsson M, Ernerudh J, Berlin G, Skogh T, Vahlquist A. Treatment of psoriatic arthritis with extracorporeal photochemotherapy and conventional psoralen-ultraviolet A irradiation. Arthritis Rheum 1996; 39:1519-23.

Macheiner W, Jantschitsch C, Graninger W, Pálóczy K, Bálint G, Marschalkó M, Kainberger F, Breier F, Knobler RM., Sézary syndrome and seronegative polyarthritis: treatment with extracorporeal photochemotherapy. J Am Acad Dermatol. 2003 Feb;48(2):220-6.

2 replies
  1. Pain Diseases
    Pain Diseases says:

    Well, ECP is definitely a boon for the long-suffering patients of the disease. However, natural pain relief solutions work wonders too! 🙂

    Reply

Trackbacks & Pingbacks

  1. […] by lmatthews on September 8, 2011 Tweet Lyme arthritis affects thousands of people each year in the US and can begin within weeks of being infected with Borrelia. Lyme arthritis treatment should be commenced as soon as possible as untreated Lyme disease can lead to permanent joint problems. Most people with arthritis caused by Lyme disease will have their symptoms resolved when the bacterial infection is eradicated but for others it can lead to a lifetime of joint problems with seemingly no cure. One treatment strategy that is rarely used but shows some promise is extracorporeal photochemotherapy (ECP), which has also been in the spotlight recently for its potential to treat ankylosing spondylitis. […]

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