Diagnosis is established on the basis of biopsy. In adults biopsy taken from descending duodenum distal to the papilla of Vater within gastroscopy is sufficient. The histological finding of intestinal mucosa includes a varying degree of mucosal atrophy, lymphoplasmocytary infiltration, crypt hypertrophia, and increased number of intraepithelial lymphocytes (Marsh classification I–IIIc). Histochemical examination proves enzymatic disorders [17]. Biopsy is indicated on the basis of evaluation of clinical and laboratory signs of malabsorption and evidence of serum antibodies typical of celiac disease: antigliadin (AGA), anti-endomysial (EMA), tissue transglutaminase (anti-tTG), and anti-reticulin antibodies (ARA [3, 10, 15]). Antigliadin antibodies are not specific enough for celiac disease. In terms of both specificity and sensitivity, the dominating method is evidence of anti-endomysial antibodies and antibodies against tissue transglutaminase. The most efficient single serologic test for the detection of celiac disease is the IgA tTGA (ELISA). Specificity of these antibodies is more than 95 % and sensitivity 90–96 %. EMA antibodies (examined by indirect immunofluorescence) have only slightly less sensitivity, but their specificity is also high (99.6 %) [3].

In addition to these conventional tests, new kits are available for determination of antigliadin antibodies targeted only against specific epitopes of gliadin peptides. Examination of ARA antibodies is currently used quite rarely, as these antibodies, although highly specific, have a low sensitivity [15].

It has to be taken into account that celiac patients who are, for instance, IgA immunodeficient will not produce IgA anti-tTG recommended in the screening, or only in insignificant amount, and therefore patients with a high suspicion of celiac disease should be examined for IgA immunoglobulin levels even in case of negative IgA AGA [3].

Prevalence of celiac disease in the highest risk groups is shown in Table 22.1.

In 2013, the Czech Gastroenterological Society published a methodological guideline for celiac disease screening, which recommends, in addition to the high-risk groups included in the table, to perform screening by IgA antibodies against tissue transglutaminase and total IgA also in individuals with therapeutically resistant diarrhea associated with the irritable bowel syndrome, polyneuropathy, myopathy and ataxia of unclear etiology; unexplained weight loss, with depression, retarded psychosomatic development, recurrent aphthous stomatitis, and enamel hypoplasia; and associated autoimmune disorders, such as systemic lupus erythematosus, primary sclerosing cholangitis, and IgA nephropathy.

In addition to screening, examination of AGA, EMA, and anti-tTG antibodies is used to observe the therapeutic effect. With a good therapeutic effect of gluten-free diet and the patient’s compliance, titers of these antibodies decrease down to the normal values not quite correlating with the histological finding [14]. A sudden evident increase in total IgA levels may signal development of a malignant lymphoma.

If celiac disease is clinically suspected despite negative serologic test results, genetic examination may be useful. Except for DQ2 and DQ8 antigen carriers, celiac disease may be reliably excluded and there is no need for biopsy [3, 10].

In newly diagnosed patients with celiac disease, osteoporosis is found by densitometry in 28 % of cases in the region of the lumbar spine and in 15 % of cases in the region of the proximal femur [2].

Studies dealing with prevalence of celiac disease in patients with low BMD report that 0.9 up to 3.4 % of patients with osteoporosis have celiac disease. Screening of celiac disease in children with low BMD proved the diagnosis of this disease in 5 % of cases. In a study of 978 patients with low BMD, performed in the Great Britain, biopsy proved celiac disease in 2.1 % of patients with osteoporosis and in 1.2 % of patients with osteopenia. Where the screening covered only selected patients with decreased BMD and minimal gastrointestinal manifestations or with anemia, prevalence of celiac disease in osteoporotic patients amounted to 3.9 % and in osteopenic patients to 2.6 %.

It is not recommended to perform screening in all patients with osteoporosis; it is more efficient to select those with gastrointestinal disorders and unclear iron deficiency anemia [27].

Pathogenesis of osteoporosis and osteomalacia in patients with celiac disease is associated not only with disorder of intestinal calcium absorption because of reduced resorption surface and steatorrhea with decreased absorption of fat-soluble vitamin D but also other mechanisms, such as low calcium intake due to lactose intolerance, secondary hyperparathyreosis, and impact of pro-inflammatory cytokines activating osteoclasts through increased production of RANKL (receptor activator of nuclear factor kB ligand) by stromal cells and osteoblasts.

In celiac patients, osteoporosis may develop also without diarrhea, skeletal pain, and biochemical abnormalities as well as during a gluten-free diet (in case of lactose intolerance [18]). Decreased BMD can be found mainly in the peripheral skeleton; it is caused by hyperparathyreosis that relatively spares the axial skeleton. Decreased bone density in the peripheral skeleton persists even with good response to treatment of BMD in the spine and its returning back to normal [19, 28].

The basis of treatment of osteoporosis in celiac disease is in addition to gluten-free diet also calcium and vitamin D substitution [2, 19, 24]. After introduction of gluten-free diet, it takes minimally one year (depending on the degree of intestinal mucosa damage) before the structure of intestinal mucosa is restored and intestinal absorption of Ca and vitamin D gets back to normal and at least 2 years before the bone tissue is remineralized. Patients with celiac disease diagnosed and treated since childhood reach the BMD values comparable with the general population [25]. Osteomalacia occurs in celiac patients less frequently.

Celiac disease should be considered in examination of patients with joint pain of unclear origin, accompanied by fatigue, muscle weakness, and digestion and neurological disorders (polyneuropathy), particularly in individuals suffering from depression. In the course of several years, arthralgia may progress to arthritis. Special attention should be paid to patients with the primary Sjögren’s syndrome, as prevalence of celiac disease in these patients is the highest of all systemic connective tissue diseases [6, 30].

Similarly as Crohn’s disease and ulcerative colitis, celiac disease may be the cause of enteropathic arthritis. Enteropathic arthritis is a seronegative, nonerosive condition, although sometimes erosions may occur [12]. This form of arthritis is classified as one of the group of seronegative spondyloarthropathies [35]. Joint involvement in enteropathic arthritis includes typically both peripheral and axial joint disorders – sacroiliitis with or without spondylitis, as well as tendinitis and enthesopathy. Peripheral joint involvement is divided into two types. In HLA-B27-positive patients, it is first of all type 1 – pauciarticular (affecting less than five joints), asymmetrical, affecting mostly lower limbs, acute course associated with intestinal inflammation relapse, and self-limiting (spontaneously resolving within about 10 weeks). Type 2 with polyarticular involvement, developing independently of the activity of bowel inflammation, persists over months or years. The latter type occurs typically in celiac patients. Association with HLA-B27 in this type of involvement has not been proved.