The Spectrum of Autoimmune Disorders: When the Immune System Turns Against the Body
What Are Autoimmune Diseases?
Under normal conditions, the immune system differentiates between “self” and “non-self” components using a sophisticated recognition process. However, in autoimmune diseases, this tolerance breaks down. The immune cells begin to produce autoantibodies—antibodies that mistakenly target the body’s own proteins. These autoantibodies trigger inflammation and tissue injury, resulting in disease.
There are over 80 recognized autoimmune diseases, which can be classified into two main types:
Organ-specific autoimmune diseases: affect a single organ or tissue (e.g., Type 1 diabetes affects the pancreas; Hashimoto’s thyroiditis affects the thyroid gland).
Systemic autoimmune diseases: impact multiple organs or systems throughout the body (e.g., Systemic lupus erythematosus and Rheumatoid arthritis).
Celiac Disease
What is Celiac Disease?
Celiac disease (CD), an inflammatory condition of the small intestine, is brought about by the ingestion of gluten, a protein found in wheat and oats. This disease, also called Celiac Sprue or Gluten Sensitive Enteropathy (GSE), may flare up at any time in life, but occurs most often in infancy after gluten has been introduced to the diet and in young adults. The inflammation destroys intestinal villi, resulting in malabsorbtion of nutrients, fluids and electrolytes.
An individual suffering from CD may experience quite severe diarrhea, weakness, and weight loss. However, this disease may present with a broad range of symptoms and severities, making it difficult to diagnose.
Although the response to gluten occurs in the intestines, visible symptoms of gluten sensitivity may not be present or seem unrelated to the digestive tract. Such symptoms include osteoporosis, muscle spasms and autism. Gluten sensitivity can also affect the skin: this condition is called dermatitis herpetiformis.
CD can be diagnosed accurately by gut biopsy or blood test. Individuals diagnosed with CD are advised to go on a gluten-free diet. No food containing gluten (such as breads and cereals made with wheat) should be eaten. Symptoms will gradually subside as intestinal villi regenerate with strict adherence to this diet.
Is CD genetically mediated?
CD is genetically mediated. Family members of patients with this disorder are much more susceptible to this disorder as compared to the general population. Approximately 90% of CD patients have the genetic marker associated with Gluten Sensitive Enteropathy, while it occurs in only 30% of the general population. Individuals without this marker have little likelihood of developing CD.
Why is prompt diagnosis and treatment needed?
In addition to greatly improving quality of life, prompt diagnosis and adherence to a gluten-free diet decrease the risk of life-threatening complications in the course of the disease. The absence of treatment increases the risk of intestinal lymphoma and splenic atrophy.
Group n O EMR O/E
Normal diet 46 7 0.19 36.8***
Reduced gluten 56 5 0.12 41.7***
Strict GFD 108 3 0.46 6.5*
*p<0.05; ***p<0.001
O=Observed; E=Expected; EMR=excess morbidity rate
(Corraza GR et al, Gastroenterology 1993, 16:16-21)
Why is CD so difficult to diagnose?
Patients with CD suffer from a great variety of symptoms. The symptoms may suggest a number of underlying conditions to a doctor. Many patients are initially diagnosed incorrectly before the condition is correctly recognized as CD.
Then how can I be sure I have Celiac Disease?
There are basically two types of tests that could be used in establishing the diagnosis of CD:
Are symptoms alone sufficient for a CD diagnosis?
No! CD is often misdiagnosed when symptoms alone are considered since so many cases are atypical. In addition, in some cases, an unnecessary lifelong gluten free diet might be ordered for a benign or passing condition such as chronic non-specific diarrhea of childhood.
Biopsy Studies
Intestinal biopsies taken from individuals suspected of celiac disease show a spectrum of mucosal abnormalities.
There are however, limitations of the biopsy studies in establishing the diagnosis of celiac disease. Because of these limitations, the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) recommends taking a minimum of three biopsies; one at the initial presentation of clinical symptoms, the second when in remission on a gluten free diet and the third with clinical presentation upon gluten challenge. Though specific for CD, this procedure is time consuming and invasive.
Blood Tests
The following tests are indicated to assist in the diagnosis of CD.
Anti-Reticulin Antibody (IgA)
Anti-Gliadin Antibody (IgG and IgA)
Anti-Tissue Transglutaminase Antibody (IgA)
Anti-Reticulin Antibody (IgA)
A combination of these autoantibody tests provides the most effective method for the serological diagnosis of CD.
Dermatitis Herpetiformis
What is Dermatitis Herpetiformis?
Dermatitis herpetiformis (DH) affects a subset of individuals with Gluten Sensitive Enteropathy. A burning, blistering, itchy rash primarily on the buttocks and extensor surfaces of the body is symptomatic of DH. As with CD, the appropriate treatment is a gluten-free diet with or without Dapsone. Adherence to a strict gluten-free diet will cause the rash to subside.
Is DH genetically mediated?
DH is genetically mediated. Family members of patients with these disorders are much more susceptible to have this disorder as compared to the general population. Individuals without the genetic marker for DH have little likelihood of developing the disease.
Sensorineural Hearing Loss
Sudden SNHL is of great concern and may be caused by various factors. When a distinct cause for SNHL cannot be determined, the condition is usually referred to as “idiopathic SNHL.” Every patient with SNHL should be evaluated thoroughly to determine the underlying disorder contributing to the hearing loss.
Early diagnosis of SNHL is crucial as a significant number of patients with idiopathic SNHL may have an immunological condition causing this loss of hearing. Normally, the immune system protects the body from foreign entities. However, in certain situations, a person’s immune response attacks his or her own body. This condition in referred to as “autoimmune disease.” Hearing can be restored in these patients if proper treatment is instituted in a timely fashion. When someone experiences sudden, or rapidly progressive hearing loss, an early appointment with an Otolaryngologist is essential.
Diagnosis
The diagnostic evaluation for idiopathic progressive SNHL should include a comprehensive patient history, a physical exam-ination, audiometry and laboratory studies. In addition to routine laboratory studies, the workup should include immunological studies for auto-antibodies to 68kD antigen, collagen II antibodies, antinuclear antibodies (ANA), rheumatoid factor (RF), immune complexes and anti-neutrophil cytoplasmic antibodies (ANCA). Autoantibody tests for 68kD antigen by Western Blot Immunoassay have been reported to be specific for a subset of patients with SNHL (Harris et al. Laryngoscope 94:758-767, 1990). In one study, three-fourths of patients positive for antibodies to 68kD antigen responded to steroid treatment (Moscicki et al. JAMA 272:611-616, 1994).
In addition to antibodies to 68kD antigen, patients with idiopathic progressive SNHL may be positive for a number of other autoantibodies, including antinuclear antibodies (ANA), anti-cardiolipin antibodies, anti-collagen antibodies, anti-neutrophil cytoplasmic antibodies (ANCA). The presence of one or more of these autoantibodies can be significant in managing the hearing loss. These autoantibodies occur in patients with various collagen-vascular disorders. Studies have shown that a significant number of patients with such autoimmune collagen-vascular disorders as Systemic Lupus Erythematosus, Rheumatoid Arthritis, Wegener’s Granulo-matosis, Polyarteritis nodosa, Cogan’s syndrome, Relapsing polychondritis, and Sjögren’s syndrome may also have SNHL.
Treatment
The ability to institute prompt and effective treatment is of utmost importance. Patients with autoimmune deafness may benefit from immunosuppressive therapy with gratifying results.
Steroids are generally used to treat patients with SNHL and studies of the efficacy of other immunosuppressive drugs are currently underway. The optimal dosage and duration of treatment varies. The risks of chronic steroid therapy are not trivial and can represent significant morbidity to the patient: they should be carefully monitored under a doctor’s care.