Chemotherapy as Treatment for Autoimmune Diseases

           As most of you may know, I was diagnosed with a rare autoimmune connective tissue disease this past July. To make a long story short, it is a small vessel vasculitis called Wegener’s Granulomatosis in which small vessels in organs like the kidneys and lungs become inflamed due to the accumulation of immune cells responding to auto-antibodies. Modern medicine and recent studies have shown the most effective treatments consist of a heavy dose of gluco or corticosteroids and cyclophosphamide, commonly known as Cytoxan, and/or rituximab (Beimler & Andrassy 2004). We are all we aware of that chemotherapy is used in treating all forms of cancer and can vary widely depending on the person, drug, or particular type of cancer. However, I was completely unaware that it could also be used as therapy for autoimmune diseases that affect connective tissues like lupus and general glomerulonephritis. Therefore, I did some research to figure out just how chemotherapeutic agents work to bring about remission in connective tissue disorders.

            For the sake of time and brevity, I decided to focus specifically on Cytoxan and how it affects these disorders. According to an article published in the British Journal of Pharmacology, cyclophosphamide functions as an alkylating agent that is converted to an active state by the cytochrome P450. The active metabolite form, 4-hydroxycyclophosphamide, alkylates guanidine residues on DNA and can have varying toxicity on an individual depending on that person’s genetics, environment, and disease state given that nephritises have wide spread effects on serum protein concentrations, urine protein excretion, and overall kidney function (Joy et al. 2012). Thus, urine protein/ creatinine ratios can give clinicians significant insight into the overall exposure to 4-hydroxycyclophosphamide an individual may experience. Furthermore, Cytoxan is only twenty percent bound in plasma, but can increase to fifty to sixty percent as it is broken down into its metabolite forms. These metabolites increase protein clearance (Joy et al. 2012). Therefore, to answer my original inquiry, it would appear that Cytoxan effectively attacks DNA in target cells so as to decrease cell counts whether that be with tumor cells or an individual’s own, mistaken, immune cells.

REFERENCES:

Beimler JHM, Andrassy K. Cyclophosphamide Treatment in Systemic Necrotizing Vasculitis

and Lupus Nephritis. How Long? How Much? Pediatric Nephrology 19.9: 949-955, Sep.

2004.

Joy MS, La M, Wang J, Bridges AS, Hu Y, Hogan SL, Frye RF, Blaisdell J, Goldstein JA,

Dooley MA, Brouwer KLR, Falk RJ. Cyclophosphamide and 4-Hydroxycyclophosphamide Pharmacokinetics in Patients with Glomerulonephritis Secondary to Lupus and Small Vessel Vasculitis. British Journal of Clinical Pharmacology 74.3: 445-455, March 2012.

Kallenberg CG. Could We Abandon Cyclophosphamide in Systemic Vasculitis and Lupus Nephritis?Annals of the Rheumatic Diseases: The                      Eular Journal 72.2: 62-65, April 2013.