When we talk about immunity we usually mean infectious disease and we can get immunity through natural exposure to the disease or artificially through, for example, vaccination. This was one of the great breakthroughs in early twentieth century medicine. This implied that the defensive mechanisms in the body could distinguish between what was self and not self.
But in the 1960s it began to be found that these same defense mechanisms, the immune response, was sometimes directed against the body itself, and this is autoimmunity. Everyone has some degree of natural autoimmunity and it can be harmless. But in some cases autoimmunity may cause damage to the body. Autoimmune disease involves immune reactions in which something triggers the immune system to react against the body's own tissues and to produce abnormal antibodies, auto-antibodies, which attack these tissues.
Triggers: We do not know in PSC what this trigger or triggers are. Immune reactions are characterized by inflammation. This is normally part of the process of repair and the inflammation subsides once the repair is made. But in our case both with PSC and IBD, the inflammation is chronic and normal tissues are damaged. In bone disease, to which we may be prone, such as osteoporosis or rheumatoid arthritis, chronic inflammation damages the cartilage. Inflammation is thought to be a major factor in causing some cancers and therefore our higher risk of cancers of the colon and bile ducts.
In the case of PSC, and also IBD, as long as we don't know the causes we're continuing to work in the dark. What we're doing is to treat the symptoms. In the case of IBD we have drugs, which may effectively keep colitis and Crohn's under control but until we know the causes we can't find a cure.
Genes: The evidence available continues to indicate that PSC is an immunologically mediated disease that occurs in genetically susceptible people, possibly triggered by an infectious or toxic agent. The fact that about three quarters of us also have IBD means that it's possible that these agents can gain access to the portal circulation from the diseased bowel. But because a quarter of us do not have IBD this cannot be the only cause.
The fact that most of the diseases, in addition to PSC, which we may suffer from, are also autoimmune diseases gives added weight to the belief that PSC is of autoimmune origin. In addition PSC is linked with the inheritance of the HLA Haplotype A1 B8 DRWQ 52A, (Haplotype is a set of closely linked genes inherited as a unit), which is also found in some other organ-specific autoimmune diseases, but not in PBC, indicating that this is a different disease. The presence of the specific HLABB antigen suggests the importance of genetic factors.
While it's very rare to find more than one case of PSC in a family, it's not unusual to find more than one member of that family suffering from other autoimmune diseases. We're dealing with vulnerability or susceptibility in that family to such diseases.
If we're genetically susceptible to PSC it's possible that we're susceptible to other autoimmune related diseases, which is why most of us are suffering from more than one such disease. The list is long and you're not likely to have heard of many of these illnesses. If your symptoms are mild you may even have one of these diseases without knowing it. The following list of autoimmune diseases comes from chapter 15, "Primary Sclerosing Cholangitis" by Russell H. Wiesner in L.S. Friedman and E.B. Keefe, Handbook of Liver Diseases, (Churchill Livingston), 2004.
Other autoimmune diseases associated with PSC include:
Autoimmune Chronic Hepatitis: Inflammation of the liver with accompanying damage to liver cells.
Hemolytic Anemia: A form of anemia caused by premature destruction of red blood cells (hemolysis) The red cells are destroyed by the immune system. May be controlled by immunosuppressant drugs.
Bronchiectasis: A lung disorder. Bronchi (the air passages leading from the trachea) are abnormally distorted. Continuous production of phlegm and shortage of breath. It results in pockets of chronic infection in the airways. Symptoms can be controlled with antibiotics and drainage.
Celiac Sprue: An allergic intolerance to gluten causing changes in the intestine, which results in malabsorption. It's an inherited disorder. All gluten must be excluded from the diet.
Chronic Pancreatitis: Chronic inflammation of the pancreas. Severe upper abdominal pain, which may spread to the back. Nausea, vomiting. Treatment is with painkillers, insulin, pancreatic enzymes and sometimes removal of all or part of the pancreas.
Cystic Fibrosis: Chronic lung infection, inability to absorb fats and other nutrients. Main feature is secretion sticky mucous which blocks nose, throat, airways, and intestines. Prompt treatment with intensive physiotherapy and antibiotics helps prevent lung damage from chest infections. A genetic disorder.
Eosinophils Syndromes: a complex and chronic group of gastrointestinal disorders (EGID). These disorders are characterized by having an abnormal amount of eosinopohils, (a type of white blood cell) in the digestive system. Symptoms include vomiting, nausea, diarrhea, abdominal pain. None of these is specific to EDID. No cure but treatment of symptoms can prevent damage to the GI tract.
Histiocytosis: A rare childhood disease but one type affects adults. Affects bones, skill, ribs, etc., causing swelling pain.
Immune Thrombocytopenic Purpura: A reduction in the number of platelets in the blood resulting in a tendency to bleed. . . Purpura is abnormal bleeding into the skin. Unknown cause but it may be an autoimmune disorder. Treatment is by corticosteroid drugs and sometimes removal of the spleen.
Lupus Erythematosus: An autoimmune disorder causing inflammation of the connective tissue. Usually only affects exposed areas of the skin. Starts as a rash. Much more common in PBC. Treatment is with corticosteroid drugs and immunosuppressant. Cause unknown.
Membranous Nephropathy: Nephropathy is a term for any disease or damage to the kidneys. A kidney disorder resulting in disruption of kidney function because of inflammation of the glomerulus. (the inner structures of the kidney). Often is treated with corticosteroids and immunosuppressants. Cause unknown.
Peyronie's Disease: A disorder of the penis. Part of the sheath of fibrous connective tissue thickens causing the penis to bend during erection. Intercourse may be painful. Unknown cause. Treatment is with corticosteroids or surgical removal of the thickened area.
Retroperitoneal Fibrosis: Affects the urinary system. A fibrous mass blocks the ureters. Pain in abdomen later becoming severe. Reduction in urine output. Stents surgery, corticosteroids. Men more than twice as likely to be affected than women. Cause unknown.
Rheumatoid Arthritis: A common type of arthritis. The joints in the fingers, wrists, toes, etc. become painful swollen and stiff. An autoimmune disorder usually starting in early adulthood or middle age, non-steroidal anti-inflammatory drugs, immunosuppressants such as azathioprine, physiotherapy.
Osteoporosis: This bone disease can be caused by certain medicines as well as older age, most specifically in post-menopausal women, although men can be affected, as well.
IBD (Inflammatory Bowel Disease), Ulcerative Colitis and Crohn's Disease: Suffered by around 70 percent of people with PSC.
Sarcoidosis: A rare disease of unknown cause. Inflammation of tissue throughout the body, especially lymph nodes, eyes, skin, lungs and liver. Often asymptomatic. Treatment is not always necessary. Most patients recover within two years with or without treatment.
Sjogren's Syndrome (pronounced Show-grins): Characterized by dry eyes and mouth. Nasal cavity, throat, and vagina can also be affected. Tends to occur with other autoimmune disorders, such as rheumatoid arthritis and lupus. Mostly suffered by middle-aged women. Much more common in PBC. Eye drops can be used and drugs can stimulate the salivary glands, etc. There is no cure but usually the disease is mild and easy to manage. Thought to be an autoimmune disorder. In more severe cases prednisolone may be used.
Thryroiditis: Inflammation of the thyroid gland.
Vasculitis: Inflammation of the blood vessels leading to damage to the lining of vessels. This is the basic condition in a number of disorders.
Prepared by Ivor S., Chairman of PSC Support, UK
Cancer is not an autoimmune disease but it is another disease to be aware of in relation to PSC.
There are mainly two types of cancer that occur with increased frequency in PSC patients: colon cancer and bile duct cancer. The increased risk in colon cancer is mainly in PSC patients who also have underlying IBD. Frequent screening with colonoscopy is recommended.
Click here for the National Institutes of Health web site on colon cancer.
Click here to go to the American Cancer Society site on colon cancer.
All PSC patients are at greater risk for cholangiocarcinoma (CCA), irrespective of bowel disease. Risk factors are poorly identified, although smoking seems to increase the PSCer's risk. Cholangiocarcinoma may be difficult to diagnose. Despite MRI, CT, serum cancer markers, and ERCP, many remain undiagnosed until the very late stages of tumor growth. Cholangiocarcinoma may be treated by resection or transplantation, but often the tumor is too advanced when diagnosed to consider these options. Palliative procedures include RFA (radio frequency ablation) of liver tumors, chemoembolization of the hepatic tumor, or chemotherapy.
The Mayo Clinic pioneered a treatment for CCA, which is now available at selected transplant centers. The Mayo Protocol involves treatment with chemotherapy and later liver transplant. Success is promising, although qualifications for the protocol are stringent, with respect to tumor size, stage (not above stage 2), metastasis, and related criteria. Another name for the protocol is neoadjuvant chemo/radiation followed by liver transplant.
Several members of PSC Partners have undergone the procedure and have written about their experiences on the discussion group. Click here to join the group.
The Cholangiocarcinoma Foundation offers background information and an active discussion board, which you can go to by clicking here.
The website lists major cholangiocarcinoma cancer treatment/research facilities, but does not endorse specific centers. Click here for the list of cancer centers.