Journal of Ophthalmic Medical Technology

Volume 7, Number 1 September 2011 www.JOMTonline.com

Celiac Disease By Alicia Rogers

Patient History In the fall of 2002, a 15‐year‐old white female presented to the eye clinic with the chief complaint of painful eyes with bitemporal headaches that worsened while wearing glasses. She also complained of a recent nine pound weight loss. She had a history of red and swollen joints with sores and a rash around her mouth. Lab results revealed a positive antinuclear antibody (ANA), increased anti‐cardiolipin antibody, low platelets, and low white blood cell count all which indicated a possible autoimmune disorder such as systemic lupus erythematosus (SLE). Past ocular history was significant for a nasolacrimal duct obstruction which was opened at 17 months of age. She denied using tobacco, alcohol, or illicit drugs. Her current medication was Aspirin 81mg once a day.

Examination Upon examination her visual acuity with correction was 20/200 in both eyes. Her stereo acuity was positive fly, two out of three animals, and zero out of nine circles. The Ishihara color plate test results were seven out of ten in the right eye, and five out of ten in the left eye. All cranial motor and sensory nerves were found to be intact. Confrontational visual fields revealed a right defect. A Humphrey® Visual Field (HVF) 24‐2 and Goldmann Visual Field (GVF) tests were ordered. The results of the HVF (Figure 1) showed a right homonymous with macular sparing OS and cloverleaf pattern OD. The GVF (Figure 2) revealed constriction of the field in both eyes with spiraling and crossing of isopters. The impression at this time was (decreased VA and color VA) vs. L‐sided retrochiasmal disease vs. Functional Visual Loss. An MRI of the brain and orbits with gadolinium was ordered. The test results were normal.

Figure 1: HVF 24‐2, Right homonymous hemianopsia with macular sparing OS and cloverleaf pattern OD.

Figure 2: Goldmann Visual Field, constriction of field in both eyes, with spiraling and crossing isopters.

Five years down the road… In the summer of 2007, the patient was sent for a rheumatology consultation to musculoskeletal pain. The physician found clinical evidence of joint laxity without synovitis or other connective tissue disease. The patient was treated with Aleve® as needed to relieve pain and physical therapy. The complete blood count (CBC) and chemistry panel were normal. In the fall of 2007, the patient was found to have an increased erythrocyte sedimentation rate (ESR) and was diagnosed with polymyalgia rheumatica (PMR). PMR is an inflammatory disorder involving pain and stiffness in the hip or shoulder area. It is a disorder that usually occurs in people over 50 years old. The cause is unknown and may occur before the onset of giant cell arteritis or other disorders. She was also seen by an ophthalmologist at this time due to mild , left eye greater than right eye by 1 mm in dim light. Another visual field test was also ordered (Figure 3). The results showed a bitemporal defect in both eyes.

Figure 3: HVF 30‐2, bitemporal defect in both eyes.

The impression at this time was of a possible pituitary adenoma. The plan was to repeat the HVF and MRI in 6 months. However, shortly after this visit, the patient was admitted to an ER in Northeast Arkansas. MRI and CT of the brain were repeated, and the findings were normal. She was prescribed Diamox® 250mg BID without a lumbar puncture (LP) and discharged. One month later she was admitted to the hospital as a Neurology inpatient for headaches, nausea, weakness, and decreased vision. She presented to neurology with many symptoms including fatigue, weight loss, headaches with vomiting, tonic‐clonic seizures, weakness in upper and lower extremities with the inability to stand, tingling in the lower extremities, ringing in her ears, and slurred speech. Neurology’s work‐up included an LP, MRI of the brain and spine, and general labs; again, the results were normal. The patient was also seen by due to the complaint of tunnel vision upon standing. Her was normal, and another GVF was ordered (Figure 4) which showed constriction of the field in both eyes that was thought to be due to a functional (non‐organic) component.

Figure 4: Goldmann Visual Field, constricted field in both eyes – possible functional component.

The plan at this time was to follow‐up with Ophthalmology. The patient was discharged by Neurology based on the clinical exam, CSF, and MRI results. She was diagnosed with psychogenic paraparesis. She was then sent home with a prescription for antidepressants and pain medicine. After being discharged from the hospital, she was admitted to an ER in Central Arkansas for a blood patch on her LP site due to persistent headaches. She was then referred to a diagnostic clinic. Upon examination, the physician heard a bruit in her chest and ordered a CT of the chest, abdomen, and pelvis and a CT angiogram of the abdomen. The patient was found to have a 50‐60% constriction of the celiac artery of questionable etiology. She started treatment for vasculitis with Aspirin 325mg and Prednisone 20mg three times a day. The patient was to be started on Plaquenil® depending on the lab results for Lupus. She was seen again a few weeks later by Ophthalmology. At this time, she was wheelchair‐bound due to a sudden onset of fatigue and weakness. Upon standing she was still having symptoms of tunnel vision, and her dilated upon physical exertion. The eye examination was normal, and the GVF (Figure 5) was repeated at this time which still showed constriction of the field in both eyes with spiraling of the isopters. The impression at this time was visual field constriction – possible functional component with celiac artery stenosis and possible vasculitis. The plan was to return to the clinic in four months and repeat the GVF.

Figure 5: Goldmann Visual Field tes; visual field constriction in both eyes.

Three years down the road… The patient was not seen again in the eye clinic until February 2010. At this time, she had no visual complaints and her examination was normal. The GVF (Figure 6) was repeated, and the results showed a full and normal visual field.

Figure 6: Goldmann Visual Field test, full normal field in both eyes.

The patient had been diagnosed in 2008 with Celiac Disease (CD) and had been maintaining a Gluten Free Diet (GFD). It should be mentioned that not only was she diagnosed with CD, but there was a remarkable change when she began maintaining a GFD. When she was seen previously, she was in a wheelchair unable to walk on her own, very thin and ill with a sallow complexion and ragged hair, and appeared depressed and angry. When she was seen in 2010, she walked in looking young and vibrant, and she had also just completed college.

Celiac Disease Celiac Disease (CD) is an inherited autoimmune disease that damages the small intestine and interferes with absorption of nutrients from food. People with CD are unable to tolerate gluten, a protein in wheat, rye, and barley. Gluten is found mainly in foods but may also be found in everyday products such as medicines, vitamins, and lip balms. When people with CD eat foods or use products containing gluten, their immune system responds by damaging or destroying villi – the tiny fingerlike protrusions lining the small intestine. Villi normally allow nutrients from food to be absorbed through the walls of the small intestine into the bloodstream. Without healthy villi, a person becomes malnourished, no matter the amount of food one eats.5 Symptoms vary from person to person and may occur in the digestive system or in other parts of the body. Digestive symptoms are more common in infants and young children and may include: abdominal pain, chronic diarrhea, vomiting, constipation, pale, foul‐smelling, or fatty stool, and weight loss. Adults are less likely to have digestive symptoms and may instead have one or more of the following: unexplained iron‐deficiency anemia, fatigue, bone or joint pain, arthritis, bone loss or osteoporosis, depression or anxiety, tingling numbness in the hands and feet, seizures, missed menstrual periods, infertility or recurrent miscarriage, canker sores inside the mouth, and an itchy skin rash called dermatitis herpetiformis.5 Celiac Disease affects people around the world, and it is now known to be a common genetic disorder affecting 1% of the healthy population.5,9 More than two million people in the United States have the disease, or about one in one hundred thirty‐three people. Among people with a first degree relative – a parent, sibling, or child – that has been diagnosed with CD, as many as one in twenty‐two people may have the disease.5

Diagnosis Preliminary diagnosis of Celiac Disease can be measured by a healthcare provider by using specific blood tests that measure certain antibodies. There are three antibodies common in celiac disease: (1) anti‐tissue transglutaminase (tTG‐IgA and IgG), (2) anti‐endomysial (EMA‐ IgA ), and (3) anti‐gliadin (AGA‐IgA and IgG) antibodies. The anti‐tissue transglutaminase (tTg‐ IgA and IgG) antibody test is commonly used with or without the presence of symptoms and is the most sensitive test available. The anti‐gliadin (AGA‐IgA and IgG) antibody test is the most helpful in diagnosing CD in patients with neurological manifestations. The latest test available that has been found to be more specific to CD is the anti‐deamidated gliadin (DGP‐IgA and IgG) antibody test. If the blood tests indicate CD then an intestinal biopsy may be used to confirm the diagnosis. Multiple biopsy specimens are taken from the distal duodenum of the small intestine. The samples are then examined for any damage or inflammation. Changes or inflammation in the small intestine mucosa remain the gold standard for establishing the diagnosis of celiac disease. Diagnostic tests should be performed before the initiation of a Gluten Free Diet. 1, 4, 5 Genetic testing is also available to identify the genetic markers for CD. Negative findings for HLA‐DQ2 and HLA‐DQ8 can essentially rule out current or future celiac disease.4, 5 Because these alleles are common to 40% of the U.S. population it is not considered a diagnostic tool, only a way to rule out CD.4, 5

Treatment The only treatment for celiac disease is a gluten‐free diet. For many, improvement often begins within days of starting the diet. The small intestine usually heals in three to six months in children but may take several years in adults. A healed intestine means a person now has villi that can absorb nutrients from food. To stay well, people with celiac disease must avoid gluten for the rest of their lives. Some people show no improvement on the GFD due largely in part to the fact that their food is contaminated with small amounts of gluten. In rare instances a severely damaged intestine will not heal; this condition is known as refractory celiac disease. Treatment for this condition is still being developed.5

Gluten Free Diet A gluten‐free diet means eliminating foods that contain wheat, rye, and barley which are ingredients found in bread, pasta, cereal, and many processed foods. Potato, rice, soy, amaranth, quinoa, buckwheat, and bean flours may be substituted for wheat flour. “Plain” meat, fish, rice, fruits, and vegetables do not contain gluten and can be freely eaten. Eating out may be a challenge; a person with CD should ask the waiter or chef about ingredients and preparation or if a gluten‐free menu is available. Reading and understanding product labels is important because gluten is sometimes used in unexpected products from drugs to lipstick and playdough.5

The Neurological Connection The term gluten sensitivity describes a spectrum of diseases that have in common an immune response to the ingestion of gluten, but with diverse manifestations such as Enteropathy (Celiac Disease), Dermatopathy (Dermatitis Herpetiforms), and Neurological disorders which include Cerebellar ataxia, Peripheral neuropathy, and Encephalopathy.2, 3 There have been cases reported in which the initial diagnosis was systemic lupus erythematosus (SLE) or polymyalgia rheumatica that were later found to be misdiagnosed cases of gluten sensitivity.7,8 Neuromyelitis optica and celiac disease share the same HLA genetic susceptibility. 60% of patients with gluten ataxia have evidence of cerebellar atrophy on MRI. One‐third of patients with peripheral neuropathy have evidence of enteropathy on duodenal biopsy. With Encephalopathy, symptoms vary from episodic headaches to debilitating headaches, focal neurological deficits and abnormal white matter on MRI. Current evidence suggests that neurological manifestations are immune‐mediated.9

Conclusion Most patients who present with neurological symptoms of gluten sensitivity may have no gastrointestinal symptoms.4 Knowledge of the diverse manifestations of gluten sensitivity is essential for avoiding misdiagnosis. Future studies should focus on the extraintestinal manifestations of gluten sensitivity as they could provide clues and ultimately hold the key to understanding the pathogenesis of gluten sensitivity.

References: 1. AGA Institute. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131:6; 1977‐1980. 2. Hadjivassiliou and Grunewald. The neurology of gluten sensitivity: science vs. conviction. Practical Neurology. 2004; 4; 124‐126. 3. Bushara. Neurologic Presentation of Celiac Disease. Gastroenterology 2005; 128:4; S92‐ S97. 4. Hagjivassiliou, Gruenwald, and Davies‐Jones. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry. 2002; 72; 560‐563. 5. U.S. Department of Health and Human Services: National Institutes of Health. Celiac Disease. National Digestive Diseases Information Clearinghouse. Sept. 2008. NIH Pub. No. 08‐4269. 6. Celiac Disease Awareness Campaign of the National Institutes of Health. Provider Points: Testing for Celiac Disease. April 2009. NIH Pub. No. 09‐7351. 7. Hadjivassiliou, Sanders, Grunewald, Akil. Gluten sensitivity masquerading as systemic lupus erythematosus. Ann Rheum Dis. 2004; 63:1501‐1503. 8. Green, Peter. The Many Faces of Celiac Disease: Clinical Presentation of Celiac Disease in the Adult Population. Gastroenterology. April Supplement 2005; 128: S74‐S78. 9. Hadjivassilou, Sanders, Grunewald, Woodroofe, Boscolo, Aeschlimann. Gluten sensitivity: from gut to brain. Lancet Neurology. 2010; 9: 318‐330.