|Autoimmune Disease Overlap Syndromes|
|Wednesday, 21 September 2011 00:49|
Because of their variable features, overlapping autoimmune connective tissue, thyroid and liver disorders can be difficult to diagnose.
It’s not unusual for several years to go by before overlapping autoimmune conditions are properly diagnosed. One reason is that the autoantibodies that help diagnose these conditions may only show up during disease flares. In addition, test results may not fall into the patterns that hallmark a specific disorder. Also, symptoms of overlapping autoimmune disorders can be confusing when they stray from the established criteria required for a clear-cut diagnosis. For instance a patient with suspected systemic lupus erythematosus (SLE) may present with signs of vasculitis and antineutrophil cytoplasmic antibodies (ANCA). Although vasculitis can occur in SLE, the presence of ANCA can indicate other ANCA-associated diseases such as glomerulonephritis or an overlap syndrome such as SLE/ANCA-associated vasculitis.
Autoimmune Disease Diagnostic Criteria
The diagnosis of autoimmune diseases is based on clinical signs and symptoms and laboratory test results. Specific diagnostic criteria are established for autoimmune disorders. A specific number of criteria must be present for diagnosis. Other symptoms and abnormal test results suggest a coexisting autoimmune disorder, an autoimmune disease variant, or an overlap syndrome.
Overlap Syndromes and Multiple Autoimmune Diseases
Individuals with an autoimmune disorder are at increased risk of developing a second autoimmune disorder. One reason is genetic susceptibility. HLA antigens that predispose people to autoimmune diseases cause an increased risk for several different autoimmune disorders. For instance, a positive blood test for HLA B27 is associated with ankylosing spondylitis, reactive arthritis, uveitis, and Reiter’s syndrome.
In multiple autoimmune syndrome (MAS) and in the polyglandular (polyendocrine) autoimmune syndromes, patients have two or more autoimmune disorders that tend to coexist. For example, in type 1 MAS patients may have conditions that include myasthenia gravis, thymoma, giant cell myocarditis, and myositis. Patients with type 1 MAS may also have coexisting autoimmune thyroid, pancreatic, ovarian, and adrenal disorders.
Two types of overlap syndromes have been observed: the crossover, in which the diagnosis of one disorder is fairly typical but the patient also has some features of a second disorder; and the true overlap, in which the patient has features of two distinct autoimmune disorders as well as additional features such as the presence of Ku and Pm/Scl antibodies in patients with polymyositis/scleroderma overlap syndrome.
Overlapping Connective Tissue Disorders
Mixed connective tissue disease (MCTD) is a classic overlap syndrome. It combines features of SLE, systemic sclerosis, and polymyositis along with antibodies to U1-RNP. Symptoms are variable and can include Raynaud’s phenomenon, arthritis, arthralgia, malar rash, calcinosis, photosensitivity, pulmonary symptoms associated with fibrosing alveolitis, and polymyositis. MCTD can lead to the potentially fatal condition of pulmonary hypertension and is considered to be a more serious disorder than SLE. Treatment depends on the specific organ involvement and on the most serious signs and symptoms.
Overlapping connective tissue disorders include SLE/systemic sclerosis, SLE/lichen planus, SLE/Sjögren’s syndrome, polymyositis/systemic scleroderma, and SLE/polymyositis. Autoantibody tests help diagnose the overlapping connective tissue disorders. For instance, PM-Scl antibodies are found almost exclusively in patients with polymyositis or dermatomyositis/scleroderma overlap syndromes.
Overlapping Autoimmune Thyroid Diseases
Patients with autoimmune thyroid disease (AITD) may have features of both Hashimoto’s thyroiditis and Graves’ disease in a condition known as Hashitoxicosis. In Hashitoxicosis, patients are primarily hypothyroid and have the stimulating TSH receptor antibodies characteristic of Graves’ disease, which causes transient symptoms of hyperthyroidism. Conditions of Hashimoto’s encephalopathy may overlap with other autoimmune thyroid disorders.
Overlapping Autoimmune Liver Disorders
Autoimmune liver disorders include autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune cholangitis (AIC).
PBC is a disorder most often seen in middle-aged women caused by autoimmune destruction of bile ducts. In PSC, which primarily occurs in men, the bile ducts are destroyed by fibrosis and cirrhosis. According to the London liver specialist Jeremy Woodward, about 70% of cases of PSC have an association with inflammatory bowel disease.
Most coexisting autoimmune liver diseases occur as overlap syndromes. Often, changes are seen in laboratory test results and imaging studies before symptoms become apparent. Immunological abnormalities make diagnosis challenging. While antimitochondrial antibodies (AMA) are diagnostic for PBC, they also rarely occur in AIH, and while antinuclear antibodies (ANA) are always seen in AIH, they’re rarely seen in PBC. AIC is similar to PBC except that patients with AIC do not have AMA. AIC is sometimes referred to as AMA-negative PBC.
In overlapping liver diseases, one disorder, usually AIH, is typically diagnosed first. Features of an overlapping disorder later emerge. Immunological changes are often the first sign. For instance, AIH patients may experience a total reduction of ANA in AIH/PBC and a positive AMA result. Although it is not as common as AIH/PBC, cases of AIH/PSC and AIH/AIC occur sporadically.
Diagnosis is especially important for the overlapping liver disorders because proper treatment is different for AIH than it is for the cholestatic disorders. AIH is treated with corticosteroids and immunosuppressant drugs such as azathioprine, whereas bile acids are used to reduce symptoms and help treat the biliary disorders.
Source: Moore, E. (2011), "Autoimmune Disease Overlap Syndromes", General Medicine At Suite101; orignal article can be viewed here.