Articular involvement is the most frequent extra-intestinal manifestation of inflammatory bowel diseases (IBD). IBD-related spondyloarthropathy is mainly characterised by axial involvement (including inflammatory back pain, isolated sacroiliitis and ankylosing spondylitis) but may also be associated with peripheral symptoms (i.e peripheral arthritis, dactylitis and enthesopathy, such as Achilles tendinitis, plantar fasciitis, and chest wall pain). In particular, inflammatory back pain (IBP) is characterised by an insidious onset, improves after exercise but not with rest, and is associated with morning stiffness. Up to now, several criteria sets have been proposed to define IBP. Studies conducted in various populations have confirmed a high sensitivity and specificity for the Berlin criteria. Celiac disease (CD) is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases. Recently, it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS) or Non-celic Wheat Sensitivity (NCWS). The clinical picture of NCWS is characterized by combined gastrointestinal and extra-intestinal or systemic manifestations. Many patients affected with CD and NCWS complain of IBP-like symptoms, which generally improve, together with the other clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore, the aims of the present study are to investigate 1) the effect of a GFD in IBP patients, randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.

Articular involvement is the most frequent extra-intestinal manifestation of inflammatory bowel diseases (IBD), frequently follows a course that is independent of the course of intestinal involvement, and its diagnosis mainly relies on clinical evidence and imaging data, because laboratory assessments are rarely useful. More in details, IBD-related arthropathy is one of a group of inflammatory arthritides, known as seronegative spondyloarthropathies, that also includes idiopathic ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and undifferentiated seronegative spondyloarthropathies, all of which are classified on the basis of peripheral arthritis (asymmetrical, predominantly in the lower extremities) and/or inflammatory spinal involvement in IBD patients using the well-known criteria of the European Spondyloarthropathy Study Group. IBD-related spondyloarthropathy is mainly characterised by axial involvement (including inflammatory back pain, isolated sacroiliitis and ankylosing spondylitis) but may also be associated with peripheral symptoms (i.e peripheral arthritis, dactylitis and enthesopathy, such as Achilles tendinitis, plantar fasciitis, and chest wall pain). In particular, inflammatory back pain (IBP) is characterised by an insidious onset, improves after exercise but not with rest, and is associated with morning stiffness. It may also present as pain during the second half of the night and/or alternating buttock pain. Up to now, several criteria sets have been proposed to define IBP. Firstly, the Calin criteria set was developed in 1977 and has since then been most widely used for defining IBP. The Calin criteria set has no entry criteria and is not based on standardized questions. Studies conducted in various populations have confirmed a high sensitivity for the Calin criteria, but shown much lower specificity than that reported in the original study. Berlin criteria for IBP were derived from a controlled study, including patients with ankylosing spondylitis and mechanical low back pain, who all had chronic low back pain. Berlin criteria are applicable only to those patients with chronic low back pain (>3 months) and age younger than <50 years old. This criteria set yielded a sensitivity of 70% and a specificity of 81% if at least two of the four following criteria were met: morning stiffness of >30-min duration, improvement in back pain with exercise but not with rest, awakening because of back pain during the second half of the night only, and alternating buttock pain. Assessment of Spondyloarthritis International Society (ASAS) has just recently published new criteria for classification of IBP. These were based on the expert judgment of the rheumatologist as the "gold standard" for diagnosing IBP in patients with chronic back pain of unknown origin. These new candidate IBP criteria administered by the interviewing clinician included the domains "improvement with exercise," "nocturnal pain," "age at onset <40 years," and "no improvement with rest." They were then validated in a distinct cohort of patients presenting to the rheumatologist with new-onset back pain and were shown to have a sensitivity of 79.6% and specificity of 72.4%. Celiac disease (CD) is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases, such as musculoskeletal pain, asthenia, and cognitive fatigue. Recently, it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). NCWS lacks of specific diagnostic tests, being its diagnosis essentially of exclusion. Many patients affected with CD and NCWS complain of IBP-like symptoms, which significantly affect the patients' quality of life and generally improve, together with the other clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore, the aims of the present study are to investigate 1) the effect of a GFD in IBP patients, randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.

Inclusion Criteria:

To diagnose IBP the standard Berlin Criteria will be adopted. IBP is defined by at least 2 positive responses among four items:

• morning stiffness >30 min of duration
• improvement in back pain with exercise but not with rest
• awakening because of back pain during the second half of the night only
• alternating buttock pain.

To diagnose CD the standard criteria will be adopted. All the patients will meet the following criteria:

• positive serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies
• presence of intestinal villous atrophy.

To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet the following criteria:

• negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies
• absence of intestinal villous atrophy
• negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum specific IgE detection)
• resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms
• symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As the investigators previously described in other studies, DBPC cow's milk protein challenge and other "open" food challenges will be performed too.

Exclusion Criteria:

Exclusion criteria for NCWS diagnosis will be:

• positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa
• self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study
• other previously diagnosed gastrointestinal disorders
• other previously diagnosed rheumatic diseases
• nervous system disease and/or major psychiatric disorder
• physical impairment limiting physical activity.