Non-coeliac disease non-wheat allergy wheat sensitivity K90.0

Non-Celiac Wheat Sensitivity (NCWS/NCGS) is a clinical entity that occurs when celiac disease and a wheat allergy are demonstrably excluded and reproducible symptomatic reactions to the consumption of wheat-containing foods are triggered (Losurdo G et al. 2018). In most cases, the symptoms complained of are "vague" and difficult to classify, such as headaches, fatigue, joint and muscle pain and numbness in the legs or arms.

Although this syndrome was originally defined as "non-celiac gluten sensitivity" (NCGS) (Sapone A et al. 2012), the role of gluten could not be proven, so that this form of sensitivity is now generally referred to as "non-celiac wheat sensitivity" (NCWS). According to the Salerno criteria (Catassi C et al. 2015), the diagnosis of NCWS should include a clinical response to a gluten-free diet and a response after a new gluten challenge.

In reality, however, the diagnosis of NCWS is difficult in practice as most patients self-diagnose. Therefore, even scientifically based estimates of prevalence vary widely, ranging from less than 1% to around 10% of the population (Sapone A et al. 2012).

Prevalence rates of 0.49-14.9% are reported for non-celiac wheat sensitivity in survey studies. Due to a lack of epidemiological data, the partial lack of recognition as a disease and the lack of diagnostic biomarkers, the disease is still unknown in many regions of the world (Di Sabatino A et al. 2009).

Women are affected more frequently than men.

The aetiopathogenesis of NCWS symptoms is not yet fully understood. However, they are probably complex in nature, including the role of ATIs, which have been shown to activate receptors in the cell membrane and trigger an innate immune response (Schuppan D et al. 2019). Furthermore, there is convincing evidence that the CD predisposing haplotypes HLA-DQ2 and/or HLA-DQ8 are not important for triggering NCWS. There is also evidence that wheat components other than gluten, such as the amylase trypsin inhibitors (ATIs ), could also be triggers of clinical manifestations, either intestinal or extraintestinal or both (Junker Y et al. 2012). However, given the different effects of ATIs on the lung mucosa in baker's asthma and on the skin in baker's eczema, in vivo studies are warranted to clarify the role of ATIs on the intestinal wall ("the outside in").

However, so-called FODMAPs may also have an important etiopathogenetic significance.

The average age of onset is 36 years (5-69 years) (Bonciolini V et al. 2015)

Clinic similar to coeliac disease: Those affected often experience physical, psychological or even neurological symptoms hours or days after eating gluten-containing foods, such as digestive problems, diarrhea, but also constipation, flatulence, nausea, bone and joint pain, headaches, migraines, fatigue, weakness, muscle weakness, various skin symptoms, depressive moods as well as mood swings, anemia and irritability. The symptoms of non-celiac wheat sensitivity are similar to those that occur after the consumption of so-called FODMAPs (abbreviation for fermentable oligo-, di- and monosaccharides as well as polyols) as classic irritable bowel symptoms.

Autoimmune diseases are associated with 18% of patients in larger collectives (Volta U et al. 2014).

Skin changes are described as itchy, morphologically less specific, psoriasiform, papulo-vesicular, also dermatitis herpetiformis-like, often excoriated lesions, which manifest themselves mainly on the extensor sides of the extremities. Hyperkeratotic, scaly lesions overlying mild erythematous, often also excoriated plaques resembling chronic psoriasis have also been described (Bonciolini V et al. 2015).

The extensor sides of the upper extremities (elbows and back of the hands (94 % and 6 %), extensor sides of the lower extremities (knees) (59 %), buttocks (29 %), chest (18 %), neck (18 %), palms (6 %) and face (6 %) are preferentially affected (Bonciolini V et al. 2015).

However, the relevant specialist literature also repeatedly refers to associated dermatitis herpetiformis Duhring (?).

As there are no reproducible biomarkers for the diagnosis of NCGS, placebo-controlled gluten tests must be carried out for the diagnosis. The gluten controls can be either double-blind or single-blind.

There is no correlation with HLA-DQ2/-DQ8.

Celiac disease serology is negative except for anti-gliadin antibodies IgA and/or IgG which can occur in 25% of patients. Small bowel biopsies showed normal mucosa in 69% of patients. A slight increase in intraepithelial lymphocytes was detected in 31% of cases (Volta U et al. 2014; see also under coeliac disease).

Immunohistologically, granular C3 deposits at the dermato-epidermal junction were detected in 82% of cases in a larger collective, but no IgA deposits (Bonciolini V et al. 2015).

Although there is a large overlap in symptoms, diagnostic markers that are present in wheat allergy (elevated IgE levels) or CD (endoscopic findings, presence of certain genetic markers, coeliac antibodies) are not detected in NCWS. This shows, on the one hand, that it is a diagnosis of exclusion and, on the other hand, that it is an adverse reaction in its own right. There are also certain overlaps between the symptoms of NCWS and irritable bowel syndrome (IBS).

The treatment involves a gluten-free diet. It is not yet clear how long this diet must be followed; however, it is likely that those affected will have to follow a coeliac diet for the rest of their lives.

However, potential disadvantages and risks outweigh any medically unjustified gluten avoidance!

FODMAPs: In a placebo-controlled crossover stress study in people who also met irritable bowel syndrome criteria, no positive clinical effect could be demonstrated by a reduction in gluten, but there was a positive effect when FODMAPs were reduced. The extent to which this is a clinical picture identical to NCGS is still unclear.

At the time of manifest cutaneous symptoms, most patients reported gastrointestinal, irritable bowel syndrome-like symptoms of varying intensity, such as abdominal pain, bloating, flatulence, diarrhea or constipation.

The duration of the skin manifestations was generally one year. Other patients reported a much longer duration of illness with a chronic recurrent course.

The skin symptoms generally improved with the spontaneously assumed GFD.

The term"gluten-related disorder" (GRD) refers to a spectrum of different clinical manifestations that are triggered by the ingestion of gluten in genetically susceptible individuals. This complex of forms includes:

• Celiac disease (CD)
• wheat allergy
• and non-celiac wheat sensitivity (NCWS/Nonceliac Gluten Sensitivity).

Due to frequent self-diagnosis, unclear prevalence and unconfirmed aetiology of NCWS, validated diagnostic criteria and/or reliable biomarkers are required.

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