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Celiac Disease and Non-Celiac Gluten Sensitivity

Signs, Symptoms, and Associated Conditions

Celiac Disease

Signs, symptoms, and possible manifestations. Symptoms of celiac disease are generally categorized as gastrointestinal (typical) or extraintestinal (atypical) (see Table 2). Other forms of celiac disease include silent, or symptomless celiac disease, as well as potential celiac disease in which autoantibodies are detected but the intestinal lining is undamaged (Sperandeo 2011; Fasano 2001; Di Sabatino 2009; Lionetti 2011). The absence of symptoms in silent celiac disease can be attributed to the ability of the small intestine to compensate for lost function in the damaged area, but only when the damage is minimal. As intestinal damage progresses, symptoms appear (Presutti 2007).

In recent years, more cases of atypical celiac disease and silent celiac disease have been recognized (Telega 2008; Roma 2009; Guandalini 2014; Fasano, Catassi 2012). Many of the signs and symptoms of typical and atypical celiac, as well as the diseases associated with celiac, can be at least partially attributed to the nutrient malabsorption that results from damage to the absorptive surface of the small intestine (Lidums 2015).

Table 2: Possible Presentations of Celiac Disease

Gastrointestinal Presentation (Typical) Extraintestinal Presentation (Atypical)
  • Abdominal pain, bloating
  • Anorexia
  • Bulky stool
  • Constipation
  • Diarrhea
  • Failure to thrive or weight loss
  • Flatulence (gas)
  • Nausea
  • Steatorrhea (fatty stool)
  • Vomiting
  • Asymptomatic
  • Constitutional
    • Fatigue
  • Dermatologic (skin-related)
    • Dermatitis herpetiformis
  • Endocrinologic (related to hormonal system)
    • Short stature
    • Delayed puberty
    • Unexplained infertility in women
    • Miscarriage
  • Hematologic (blood-related)
    • Iron deficiency anemia
  • Hepatic (liver-related)
    • Mildly elevated ALT, AST levels
  • Metabolic
    • Nutritional deficiencies (iron, calcium, vitamin D, B vitamins, among others)
  • Musculoskeletal
    • Arthritis
    • Arthralgia (joint pain)
    • Osteopenia or osteoporosis
    • Fractures
  • Neurologic
    • Cerebellar ataxia
    • Recurring headaches
    • Peripheral neuropathy
    • Seizures
  • Oral
    • Dental enamel defects
    • Aphthous ulcers (oral ulcers; canker sores)
  • Psychiatric disorders
    • Anxiety, panic attacks
    • Depression


(Guandalini 2014; Ferri 2015; Kelly 2014; Nikpour 2012; Lawson 2005; Caruso 2013; Krzywicka 2014; Snyder 2015)

Associated conditions. Celiac disease has been associated with a number of other conditions, especially autoimmune-related conditions such as type 1 diabetes and autoimmune thyroid disease (Barker 2008; Kelly 2014). There is also some evidence that celiac disease may increase risk of certain cancers. A large population study in over 30 000 adult celiac patients corroborated earlier findings of increased risk of certain cancers in celiac patients. In this population, non-Hodgkin lymphoma occurred at a 1.94-fold increased incidence rate, and incidence of small intestinal cancer was increased 4.29-fold, compared with rates expected in the general population. The incidence of colon cancer and basal cell carcinoma were also modestly elevated, by 1.35-fold and 1.13-fold, respectively (Ilus 2014; Green 2003). Table 3 summarizes conditions that may be associated with celiac disease.

Table 3: Diseases and Conditions Associated with Celiac Disease

Strong Association Weak Association
  • Autoimmune thyroid disease
  • Immunoglobulin A (IgA) deficiency
  • Indigestion
  • Type 1 diabetes
  • Addison’s disease
  • Alopecia (loss of hair)
  • Angular cheilitis
  • Asthma
  • Atopic dermatitis (Eczema)
  • Autoimmune liver disease
  • Cataracts
  • Dermatitis herpetiformis
  • Dilated cardiomyopathy
  • Down syndrome, Turner syndrome, Williams syndrome
  • Early atherosclerosis among young adults
  • Easy bruising
  • Endometriosis
  • Hallucinations in adolescents
  • Heartburn/Gastroesophageal reflux disease
  • IgA Nephropathy (Berger’s disease)
  • Inflammatory bowel disease (Crohn’s and Ulcerative colitis)
  • Ischemic heart disease
  • Lack of muscle coordination and balance (gluten ataxia)
  • Multiple sclerosis
  • Myalgia (muscle pain)
  • Nutrient deficiency, including vitamins B12 and folate, calcium, and iron
  • Pancreatitis
  • Primary hyperparathyroidism
  • Poor or absent spleen function (hyposplenia or asplenia)
  • Sjögren’s syndrome
  • Suicidal behavior in adolescents
  • Systemic lupus erythematosus
  • Tooth discoloration or loss of enamel

(Guandalini 2014; Ferri 2015; Kelly 2014; Nikpour 2012; Lawson 2005; Caruso 2013; Krzywicka 2014; Snyder 2015; Elfström 2007)

Non-celiac Gluten Sensitivity

Many symptoms of non-celiac gluten sensitivity are similar to those of celiac disease. As in celiac disease, they include symptoms similar to irritable bowel syndrome such as abdominal pain, bloating, diarrhea, gas, and constipation; and atypical symptoms such as headache, fatigue, joint and muscle pain, dermatitis, depression, and anemia (Eswaran 2013; Sapone 2012; Volta 2013; Lundin 2012). The time interval between gluten exposure and onset of symptoms in celiac disease can be quite long—up to weeks and years—whereas it may be only a matter of a few hours to a few days in non-celiac gluten sensitivity (Catassi 2013; Sapone 2012; Volta, De Giorgio 2012).

There is no evidence that serious, long-term complications occur in non-celiac gluten sensitivity (Catassi 2013).

The Effects of Gluten on the Brain and Nervous System

Among atypical or extraintestinal signs of celiac disease, brain and nervous system problems are prominent (Hu 2006; Bushara 2005; Cascella 2011; Jackson 2012; Briani 2008; Rodrigo 2011; Nikpour 2012).

One mechanism for gluten’s effects on the brain may involve autoimmune antibodies against a subtype of tissue transglutaminase called transglutaminase 6. This enzyme is structurally similar to transglutaminase types involved in intestinal and skin damage in celiac disease, but transglutaminase 6 is found primarily in the brain and nervous system. Antibodies against this enzyme have been identified in patients with gluten ataxia and schizophrenia. Importantly, they do not appear to be present in healthy individuals (Hadjivassiliou 2008; Cascella 2013). Whether antibodies to transglutaminase 6 are involved in other neurological and psychiatric conditions associated with celiac disease is not known, and will require further research. However, there is evidence that transglutaminase 6, and the transglutaminase enzyme family in general, may be important in the development of degenerative diseases of the brain (Thomas 2013; Jeitner 2009; De Vivo 2009; Martin 2011).

Multiple sclerosis is an inflammatory autoimmune disorder that damages the insulating covers of nerve cells in the brain and spinal cord (Compston 2002). Recently, the prevalence of celiac disease was reported to be 5–10 times higher in a study in patients with multiple sclerosis compared to the general population. All the patients in this study had an excellent response to the gluten-free diet in an average of three years, with regard to both digestive and neurological symptoms (Rodrigo 2011).

A 2014 case report showed celiac disease can mimic multiple sclerosis. A 43-year-old male patient with a history of diarrhea and colic since youth and neurological symptoms since age 18 was diagnosed with multiple sclerosis at age 34. Seven years later, though his blood tests did not show any of the typical celiac-related antibodies, he was diagnosed with celiac disease based on neurologic signs and symptoms, positive tests for HLA DQ2 and DQ8, and improvement in both digestive and neurological symptoms on a gluten-free diet (Finsterer 2014).