Inflammatory Back Pain and Gluten Free Diet
Inflammatory Back Pain and Gluten Free Diet
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.