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Dietary Approach to Mild-to-moderate Psoriasis

Primary Purpose

Psoriasis, Gluten Sensitivity

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Open wheat challenge
Placebo challenge
Sponsored by
University of Palermo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis focused on measuring psoriasis, gluten sensitivity, gluten-free diet

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria of psoriasis patients age >18 and <65 years; no systemic therapy for psoriasis for at least 3 months before inclusion in the study; negativity of anti-deamidated gliadin protein (anti-DGP) immunoglobulins (Ig) class A (IgA) and immunoglobulins (Ig)G, anti-tissue transglutaminase (anti-tTG) class IgA and IgG, and Endomysium antibodies (EmA); absence of WA (negative prick-test and/or specific serum immunoglobulins (Ig)E assay for wheat, gluten, and gliadin). Exclusion criteria of psoriasis patients age <18 and >65 years; severe chronic plaque-type psoriasis (based on BSA); self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study; pregnancy; alcohol and/or drug abuse; Helicobacter pylori and other bacterial and/or parasitic infections; diagnosis of chronic inflammatory bowel disease and other organic pathology affecting the digestive system (e.g., severe liver disease), nervous system diseases, major psychiatric disorders, immunological deficits, and impairments that limit physical activity; diagnosis of cancer treatment with steroids and/or immunological therapies; patients undergoing chemotherapy and/or radiotherapy.

Sites / Locations

  • Internal Medicine Division of the "Cervello-Villa Sofia" HospitalRecruiting
  • Dermatology Department of the University Hospital 'P. Giaccone' of Palermo, Italy,Recruiting
  • Internal Medicine Department of the University Hospital of PalermoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Open wheat challenge group

Placebo group

Arm Description

Before starting the elimination diet (time 0, T0), intervention patients will be evaluated by experienced dermatologists, as well as by physicians with expertise in the field of food intolerance about GI and extraintestinal symptoms related to foods intake. Moreover, all these subjects will be subjected to blood, urine, and stools collections, and to a dietary consult, and a food and symptom's diary will be provided to all patients, which must be filled-in daily. After 2 months of elimination diet (time 1, T1), intervention patients will be evaluated again both clinically and by laboratory techniques, identically to T0. At this time-point, intervention patients will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify (T2int), patients will be valued again both clinically and by laboratory techniques, identically to T0 and T1, and then will end the study.

Before starting the elimination diet (time 0, T0), control patients will be evaluated by experienced dermatologists, as well as by physicians with expertise in food intolerance. Moreover, patients will be subjected to blood, urine, and stools collections, and to a dietary consult, and a food and symptom's diary will be provided. After 2 months of elimination diet (time 1, T1), patients will be evaluated, identically to T0. Then, control patients will be asked to repeat the elimination diet, this time removing wheat and all cow's milk products for further 2 months (T2con). Then, patients will be valued again both clinically and by laboratory techniques, identically to T0 and T1. Then, patients will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify (T3con), patients will be valued again, identically to T0, T1 and T2con, and then will end the study.

Outcomes

Primary Outcome Measures

Self-perceived non-celiac wheat sensitivity (NCWS) questionnaire in psoriasis patients
To identify psoriasis patients reporting a self-perceived NCWS; all patients will be asked to answer, consecutively, to a validated questionnaire for the self-assessment of wheat and other foods' intolerance. This is a questionnaire self-compiled by patients consisting of three sections: 1) general information (eg. age, sex, highest completed education level, etc.) 2) wheat-related symptoms (sore 0 = no symptoms, score = 1, symptoms after wheat intake; if score = 1 other question qualitatively inquire the symptoms evoked by wheat intake, eg. what kind of symptoms, how long patient perceive this problem, etc.); 3) other foods-related symptoms (score 0 = no symptoms, score 1 = symptoms after intake of other foods; if score = 1 other question qualitatively inquire the symptoms evoked by the intake of the specific food reported by the patients, eg. what kind of symptoms, how long patient perceive this problem, etc.)
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by BSA
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Body Surface Area (BSA), representing the percentage of cutaneous area affected by psoriasis.
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by Psoriasis Area Severity Index
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Psoriasis Area Severity Index (PASI), a composite evaluation for psoriasis severity, subscoring for erythema, induration, scaling, and percentage of body-surface area affected. The rating scale includes 4 levels: No Psoriasis, Mild Psoriasis, Moderate Psoriasis, and Severe Psoriasis.
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by IGA
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Investigator's Global Assessment (IGA), a 5-point instrument for rating the clinician's impression of the overall severity of the psoriasis, from 0, clear skin, to 4, severe disease.
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by GSRS
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Gastrointestinal Symptom Rating Scale (GSRS), assessment scale for irritable bowel syndrome-like and functional dyspepsia-like symptoms, providing for a score ranging from 15 to 60).
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by Extraintestinal symptoms rating scale.
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Extraintestinal symptoms rating scale, a scoring system based on the symptoms most frequently observed in NCWS patients, providing for a score ranging from 9 to 34.
Effect of WFD plus CMPFD in changing Quality of Life (QoL) of psoriasis patients.
To assess the effect that a WFD plus CMPFD determines in QoL of patients affected with psoriasis, both of the intervention and the control group. The following score will be used: Dermatology Life Quality Index (DLQI, a validated instrument to evaluate quality of life for skin disease, providing for a score ranging from 0 to 30 points, with higher scores indicating a greater effect on quality of life).

Secondary Outcome Measures

Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by BSA
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Body Surface Area (BSA), representing the percentage of cutaneous area affected by psoriasis.
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by Psoriasis Area Severity Index
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). the following score will be used: Psoriasis Area Severity Index (PASI), a composite evaluation for psoriasis severity, subscoring for erythema, induration, scaling, and percentage of body-surface area affected. The rating scale includes 4 levels: No Psoriasis, Mild Psoriasis, Moderate Psoriasis, and Severe Psoriasis.
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by IGA.
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Investigator's Global Assessment (IGA), a 5-point instrument for rating the clinician's impression of the overall severity of the psoriasis, from 0, clear skin, to 4, severe disease.
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by GSRS.
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con).The following score will be used: Gastrointestinal Symptom Rating Scale (GSRS), assessment scale for irritable bowel syndrome-like and functional dyspepsia-like symptoms, providing for a score ranging from 15 to 60).
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by Extraintestinal symptoms rating scale.
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Extraintestinal symptoms rating scale, a scoring system based on the symptoms most frequently observed in NCWS patients, providing for a score ranging from 9 to 34.
Effect of open wheat challenge in Quality of Life (QoL) changing of psoriasis patients.
To assess the effect that an open wheat challenge determines in QoL of patients affected with psoriasis, both of the intervention (T2int) and the control group (T3con). The following score will be used: DLQI (a validated instrument to evaluate quality of life for skin disease, providing for a score ranging from 0 to 30 points, with higher scores indicating a greater effect on quality of life).
Erythrocyte sedimentation rate (ESR) changing in psoriasis and NCWS patients.
Laboratory blood analysis will be performed to assess erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP) changing in psoriasis and NCWS patients.
Laboratory blood analysis will be performed to assess C-reactive protein (CRP)
Complete blood count changing in psoriasis and NCWS patients.
Laboratory blood analysis will be performed to assess complete blood count
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-1β
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-2
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-4
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-5
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-6
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-8
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-10
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-17A
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-22
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-23,
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: Tumor Necrosis Factor (TNF)-α
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interferon (IFN)-γ
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: Toll-Like Receptor (TLR)-4.
Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of psoriasis
Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of psoriasis pathogenetic pattern [i.e., T helper (Th)17, and T cytotoxic (Tc)17].
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: zonulin
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: F-Actin
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: intestinal fatty acid-binding protein (i-FABP)
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: lipopolysaccharide (LPS)
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: LPS-binding protein (LBP)
Lactulose(LA)/Mannitol(MA) test changing in psoriasis and NCWS patients.
LA/MA test will be performed to assess in vivo intestinal permeability.
Fecal ELISA analysis of inflammatory gut marker changing in psoriasis and NCWS patients.
Fecal ELISA analysis of inflammatory gut marker will be performed to assess fecal calprotectin.
Gut microbiota changing in psoriasis and NCWS patients.
Gut microbiota assessment will be performed by analysis and quantification of gut microbioma on stools samples. After fecal collection, bacterial DNA will be extracted by cetyltrimethyl ammonium bromide. A simple and inexpensive physical lysis method for DNA and RNA extraction from freshwater microalgae and 16S ribosomal ribonucleic acid (rRNA) sequencing will be performed by polymerase chain reaction (PCR) methods, using universal primers. The resulting fragments will be then sequenced by pyrosequencing. Each reading will be compared with a database of known 16S rRNA sequences, using the BLAT program by phylogenetically assigning the most specific and reliable nodes. This method of assigning the obtained data leads to a "weighted" phylogenetic tree that characterizes well the bacterial content of the sample.

Full Information

First Posted
October 27, 2022
Last Updated
May 9, 2023
Sponsor
University of Palermo
Collaborators
Aurelio Seidita
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1. Study Identification

Unique Protocol Identification Number
NCT05644782
Brief Title
Dietary Approach to Mild-to-moderate Psoriasis
Official Title
The Role of Gut-skin Axis in Psoriasis: a Randomized Placebo-controlled Dietary Approach to Assess Clinical Efficacy in Mild-to-moderate Psoriasis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
July 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Palermo
Collaborators
Aurelio Seidita

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Psoriasis is a systemic chronic inflammatory immune-mediated disease whose etiopathogenetic mechanisms involve genetic predisposition, and immunological and environmental factors. Its prevalence is about 3% in adults, and it is characterized by well-demarcated, erythematous plaques, covered by silvery-white scales, in elbows, knees, trunk, and scalp. However, psoriasis is far from being considered just a dermatologic condition because the cytokine's cascade, which lays behind its inflammatory and immune-mediated pathogenesis, can determine multiple systemic manifestations. In addition, several patients with psoriasis often complains of gastrointestinal (GI) symptoms. Therefore, authors focused their attention over the gut-skin axis and its possible pathogenetic and immunoregulatory role in psoriasis (i.e., altered gut barrier, increased blood concentration of gut microbiota-derived metabolites, systemic inflammation). In this context, several dietetic approaches (e.g., Mediterranean, low calories, protein-restricted, vegetarian diets, and gluten-free diet, GFD) have shown a certain efficacy in improve psoriasis cutaneous and systemic manifestations. In recent years, the existence of a wheat-related disorder in patients who do not suffer from CD or wheat allergy (WA) has been definitively ascertained and defined as Non-Celiac Wheat Sensitivity (NCWS). Its prevalence in the general population is unknown, but self-reported NCWS is around 10%. This condition is characterized by both GI and extraintestinal symptoms, which are triggered by wheat ingestion. In these patients, wheat ingestion might lead to alteration in intestinal permeability and gut microbiota and to systemic immune activation and inflammation. Based on the evidence of gut involvement in the pathogenesis and clinical manifestation of psoriasis, as well as on the ability of gluten/wheat to increase intestinal permeability, it could be hypothesized that gluten/wheat may represents one of the pathogenetic environmental factors of psoriasis and that its intake may be able to worsen symptoms in affected patients. The investigators hypothesize that a wheat-free diet (WFD) can reduce the inflammatory state and ameliorate the clinical symptoms in psoriasis patients. The successive clinical and immunologic reaction to the re-exposure to wheat ingestion, performed by an open challenge, will be also evaluated to confirm a wheat-dependent mechanism and to understand the underlining physiopathology.
Detailed Description
Psoriasis is a systemic chronic inflammatory immune-mediated disease whose etiopathogenetic mechanisms involve genetic predisposition, as well as immunological and environmental factors. Its prevalence is about 3% in adults, and it is characterized by well-demarcated, erythematous plaques, covered by silvery-white scales, in elbows, knees, trunk, and scalp, with a typical pair distribution. However, psoriasis is far from being considered just a dermatologic condition because the cytokine's cascade [including interleukin (IL)-1β, IL-17, IL-22, IL-23, Interferon (IFN)-γ, and Tumor Necrosis Factor (TNF)-α], which lays behind its inflammatory and immune-mediated pathogenesis, can determine multiple systemic manifestations. Several reports assess that, especially in moderate-to-severe psoriasis, the same inflammatory cytokines, found in cutaneous plaques, can be found in blood, and should be considered the enhancers of a chronic inflammatory condition, which, in long-term, will flow in systemic comorbidities, such as psoriatic arthritis, cardiovascular diseases, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and inflammatory bowel disease. In addition, a variable percentage of psoriatic patients (0.2-4.3%) may present with concomitant celiac disease (CD), a well-known immune-mediated bowel disease, as well as patients suffering from CD have an increased risk of psoriasis development, and, finally, several patients with psoriasis often complains of gastrointestinal (GI) symptoms. These evidences have recently induced authors to focus their attention over the gut-skin axis and its possible pathogenetic and immunoregulatory role in psoriasis. In this context, some studies analyzed the role of intestinal permeability and, more specifically, of the gut barrier integrity, proving that an altered gut barrier is associated with GI symptoms, systemic inflammation, and increased blood concentration of gut microbiota-derived metabolites (e.g., trimethylamine N-oxide). Confirming a strict relationship between psoriasis and gut, from a clinical point of view, several dietetic approaches (e.g., Mediterranean, low calories, protein-restricted, and vegetarian diets) have shown a certain efficacy in improve psoriasis cutaneous and systemic manifestations. Moreover, some authors showed a positive effect of a gluten-free diet (GFD) over Psoriasis Area and Severity Index (PASI) score, even if contrasting data are reported, and, to date, no large randomized controlled trials have been performed. In recent years, the existence of a wheat-related disorder in patients who do not suffer from CD or wheat allergy (WA) has been definitively ascertained and defined as Non-Celiac Wheat Sensitivity (NCWS). Its prevalence in the general population is unknown, but self-reported NCWS is around 10%. This condition, initially named as Non-Celiac Gluten Sensitivity, assuming that, as in CD, gluten was the main culprit, is characterized by both GI [irritable bowel syndrome (IBS)-like and functional dyspepsia-like] and extraintestinal (e.g., fatigue, neuropsychiatric disorders, dermatitis, gynecological alterations, etc.) symptoms, which are triggered by wheat ingestion. Moreover, an increasing number of data have shown that patients with NCWS could have an association with autoimmune diseases, including thyroiditis, Sjogren's syndrome, undifferentiated connective tissue disease, and psoriatic arthritis. Conflicting data have been reported about the underlying physiopathology and possible symptom's triggers. Some authors identified a prevalent role for fermentable oligosaccharides-disaccharides-monosaccharides and polyols (FODMAPs), other the activation of both innate and acquired immunity. More recently, it has been shown that wheat has high concentrations of wheat amylase-trypsin inhibitors (ATIs), proteins able to activate innate immunity via toll-like receptor-4 (TLR-4) on myeloid cells. Orally ingested ATIs increase intestinal inflammation by activating gut and mesenteric lymphnode myeloid cells. A possible role in this fragmented and articulated context has been attributed to alteration of intestinal permeability. It has been known for years how exposure to gliadin, both in CD and in healthy patients (albeit with reduced levels in the latter), is able to alter intestinal permeability acting on zonulin release and signaling mechanisms. When the integrity of the intestinal barrier is compromised, penetration of toxic wheat peptides into the intestinal lamina propria could be favored, determining the onset of an inflammatory response activated by local immune system through the intervention of antigen presenting cells (APC), particularly dendritic ones. Finally, both psoriatic and NCWS patients seems to have quantitative and qualitative disbalances of gut microbiota, which could influence severity and course of these diseases. However, data on this point are conflicting and this correlation is far from being unanimously accepted. Based on the evidence of gut involvement (i.e., influence of GFD on symptoms, increased intestinal permeability, altered microbiota) in pathogenesis and clinical manifestation of psoriasis, as well as on the ability of gluten/wheat to increase intestinal permeability, altering zonulin mechanisms of regulation and signaling, and the ability of some of its components (ATIs, but not only) to activate a local inflammatory response, it could be hypothesized that gluten/wheat may represents one of the pathogenetic environmental factors of psoriasis and that its intake may be able to worsen symptoms in affected patients. In the investigators' hypothesis, exposure to gluten/wheat would cause a release of zonulin, which, binding to the surface of the intestinal epithelial cells, is able to modify cell cytoskeleton and cause the loss of normal occludins function, ultimately leading to an increased intestinal monolayer permeability. This increase in permeability would result in greater exposure of the immune system cells to gluten/wheat molecules via activation of TLR-4, with an increase in the infiltration and activation of myeloid cells in the intestinal mucosa and an augmented activity of lymphnode dendritic and myeloid cells. Such local inflammatory response, associated with an increase of circulating antigens coming from the gut's modified permeability, would have systemic repercussions, with alteration of normal cytokine pattern (e.g., increase of IL-1β, IL-22, IL-23, and TNF-α) and activation of plasmacytoid dendritic cells, as well as of other innate immune cells, in the skin. This background, in predisposed patients, represents the trigger for activation of myeloid dendritic cells and macrophages, IL-12, IL-23, and TNF-α-mediated recruitment of T helper type 17 (Th17) and T cytotoxic type 17 (Tc17) lymphocytes, and production of a new cytokines pattern (mainly IL-17A, and IFN-γ), which can stimulate keratinocytes to proliferate and produce antimicrobial peptides and other proinflammatory cytokines. Such complex cytokine's pattern produced by immune cells and keratinocytes, creates a positive feedback loop, perpetuating the inflammatory response which leads to clinical manifestation of psoriasis. Therefore, the investigators hypothesize that a wheat-free diet (WFD) can reduce the inflammatory state and ameliorate the clinical symptoms in psoriatic patients. The successive clinical and immunologic reaction to the re-exposure to wheat ingestion, performed by an open challenge, will be also evaluated to confirm a wheat-dependent mechanism and to understand the underlining physiopathology. Overall, the project results might provide data about a possible therapeutic role of a WFD in psoriasis, improve the knowledges about the relationship between intestinal permeability and systemic inflammation in psoriasis, and reveal, at least in part, the pathogenic mechanisms underlying NCWS. Starting from the hypothesis of an altered gut-skin axis, based on altered intestinal permeability and systemic response, the investigators aim to: identify the prevalence of self-reported NCWS in psoriatic patients; assess the overall effect that a WFD plus cow's milk products free diet (CMPFD) determines in symptoms control and quality of life (QoL) of the patients affected with psoriasis; the investigators decided to include a CMPFD in association with a WFD because, according to several authors, including our previous studies, NCWS, and more generally gluten-related disorders, are often associated with multiple foods intolerance, first of all cow's milk products intolerance; evaluate, by an open wheat challenge, the real frequency of a coexistent NCWS condition; assess the possible role played by wheat ingestion in the pathogenesis and molecular mechanisms of psoriasis and NCWS by analyzing the variation of intestinal permeability and gut microbiota, in association with cytokine pattern typical of psoriasis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis, Gluten Sensitivity
Keywords
psoriasis, gluten sensitivity, gluten-free diet

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective, randomized, placebo-controlled, cross-over, single center clinical trials.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open wheat challenge group
Arm Type
Active Comparator
Arm Description
Before starting the elimination diet (time 0, T0), intervention patients will be evaluated by experienced dermatologists, as well as by physicians with expertise in the field of food intolerance about GI and extraintestinal symptoms related to foods intake. Moreover, all these subjects will be subjected to blood, urine, and stools collections, and to a dietary consult, and a food and symptom's diary will be provided to all patients, which must be filled-in daily. After 2 months of elimination diet (time 1, T1), intervention patients will be evaluated again both clinically and by laboratory techniques, identically to T0. At this time-point, intervention patients will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify (T2int), patients will be valued again both clinically and by laboratory techniques, identically to T0 and T1, and then will end the study.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Before starting the elimination diet (time 0, T0), control patients will be evaluated by experienced dermatologists, as well as by physicians with expertise in food intolerance. Moreover, patients will be subjected to blood, urine, and stools collections, and to a dietary consult, and a food and symptom's diary will be provided. After 2 months of elimination diet (time 1, T1), patients will be evaluated, identically to T0. Then, control patients will be asked to repeat the elimination diet, this time removing wheat and all cow's milk products for further 2 months (T2con). Then, patients will be valued again both clinically and by laboratory techniques, identically to T0 and T1. Then, patients will go to an open challenge, with reintroduction of wheat. After 2 weeks of open diet or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify (T3con), patients will be valued again, identically to T0, T1 and T2con, and then will end the study.
Intervention Type
Other
Intervention Name(s)
Open wheat challenge
Other Intervention Name(s)
Wheat
Intervention Description
Patients randomized to intervention diet group will have to follow a diet with elimination of wheat and cow's milk products for 2 months; after that they will be exposed to an open wheat challenge, with reintroduction of wheat. After 2 weeks of open diet, or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify, all patients will be revaluated and will end the study.
Intervention Type
Other
Intervention Name(s)
Placebo challenge
Other Intervention Name(s)
Placebo
Intervention Description
Patients randomized to control diet group will have to follow a diet with elimination of rice and turkey's meat products for 2 months; after that they will crossover to a wheat and cow's milk products free diet and, finally, after 2 months, they will be exposed to an open wheat challenge, with reintroduction of wheat. After 2 weeks of open diet, or whenever dermatologic, intestinal and/or extraintestinal symptoms should return or intensify, all patients will be revaluated and will end the study.
Primary Outcome Measure Information:
Title
Self-perceived non-celiac wheat sensitivity (NCWS) questionnaire in psoriasis patients
Description
To identify psoriasis patients reporting a self-perceived NCWS; all patients will be asked to answer, consecutively, to a validated questionnaire for the self-assessment of wheat and other foods' intolerance. This is a questionnaire self-compiled by patients consisting of three sections: 1) general information (eg. age, sex, highest completed education level, etc.) 2) wheat-related symptoms (sore 0 = no symptoms, score = 1, symptoms after wheat intake; if score = 1 other question qualitatively inquire the symptoms evoked by wheat intake, eg. what kind of symptoms, how long patient perceive this problem, etc.); 3) other foods-related symptoms (score 0 = no symptoms, score 1 = symptoms after intake of other foods; if score = 1 other question qualitatively inquire the symptoms evoked by the intake of the specific food reported by the patients, eg. what kind of symptoms, how long patient perceive this problem, etc.)
Time Frame
Before enter the study.
Title
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by BSA
Description
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Body Surface Area (BSA), representing the percentage of cutaneous area affected by psoriasis.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Title
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by Psoriasis Area Severity Index
Description
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Psoriasis Area Severity Index (PASI), a composite evaluation for psoriasis severity, subscoring for erythema, induration, scaling, and percentage of body-surface area affected. The rating scale includes 4 levels: No Psoriasis, Mild Psoriasis, Moderate Psoriasis, and Severe Psoriasis.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Title
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by IGA
Description
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Investigator's Global Assessment (IGA), a 5-point instrument for rating the clinician's impression of the overall severity of the psoriasis, from 0, clear skin, to 4, severe disease.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Title
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by GSRS
Description
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Gastrointestinal Symptom Rating Scale (GSRS), assessment scale for irritable bowel syndrome-like and functional dyspepsia-like symptoms, providing for a score ranging from 15 to 60).
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Title
Effect of WFD plus CMPFD in changing symptoms of psoriasis patients as assessed by Extraintestinal symptoms rating scale.
Description
To assess the effect that a WFD plus CMPFD determines in symptoms of patients affected with psoriasis the following score will be used: Extraintestinal symptoms rating scale, a scoring system based on the symptoms most frequently observed in NCWS patients, providing for a score ranging from 9 to 34.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Title
Effect of WFD plus CMPFD in changing Quality of Life (QoL) of psoriasis patients.
Description
To assess the effect that a WFD plus CMPFD determines in QoL of patients affected with psoriasis, both of the intervention and the control group. The following score will be used: Dermatology Life Quality Index (DLQI, a validated instrument to evaluate quality of life for skin disease, providing for a score ranging from 0 to 30 points, with higher scores indicating a greater effect on quality of life).
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60).
Secondary Outcome Measure Information:
Title
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by BSA
Description
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Body Surface Area (BSA), representing the percentage of cutaneous area affected by psoriasis.
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by Psoriasis Area Severity Index
Description
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). the following score will be used: Psoriasis Area Severity Index (PASI), a composite evaluation for psoriasis severity, subscoring for erythema, induration, scaling, and percentage of body-surface area affected. The rating scale includes 4 levels: No Psoriasis, Mild Psoriasis, Moderate Psoriasis, and Severe Psoriasis.
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by IGA.
Description
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Investigator's Global Assessment (IGA), a 5-point instrument for rating the clinician's impression of the overall severity of the psoriasis, from 0, clear skin, to 4, severe disease.
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by GSRS.
Description
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con).The following score will be used: Gastrointestinal Symptom Rating Scale (GSRS), assessment scale for irritable bowel syndrome-like and functional dyspepsia-like symptoms, providing for a score ranging from 15 to 60).
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Effect of open wheat challenge in symptoms changing of psoriasis patients as assessed by Extraintestinal symptoms rating scale.
Description
To evaluate, by an open wheat challenge, the frequency of a coexistent NCWS condition in psoriasis patients, both of the intervention group (T2int) and the control group (T3con). The following score will be used: Extraintestinal symptoms rating scale, a scoring system based on the symptoms most frequently observed in NCWS patients, providing for a score ranging from 9 to 34.
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Effect of open wheat challenge in Quality of Life (QoL) changing of psoriasis patients.
Description
To assess the effect that an open wheat challenge determines in QoL of patients affected with psoriasis, both of the intervention (T2int) and the control group (T3con). The following score will be used: DLQI (a validated instrument to evaluate quality of life for skin disease, providing for a score ranging from 0 to 30 points, with higher scores indicating a greater effect on quality of life).
Time Frame
Day 60; 2 weeks of open wheat challenge (Day 75).
Title
Erythrocyte sedimentation rate (ESR) changing in psoriasis and NCWS patients.
Description
Laboratory blood analysis will be performed to assess erythrocyte sedimentation rate (ESR)
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
C-reactive protein (CRP) changing in psoriasis and NCWS patients.
Description
Laboratory blood analysis will be performed to assess C-reactive protein (CRP)
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Complete blood count changing in psoriasis and NCWS patients.
Description
Laboratory blood analysis will be performed to assess complete blood count
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-1β
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-2
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-4
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-5
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-6
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-8
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-10
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-17A
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-22
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interleukin (IL)-23,
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: Tumor Necrosis Factor (TNF)-α
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: interferon (IFN)-γ
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of inflammatory cytokines changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of inflammatory cytokines pattern will be performed to assess: Toll-Like Receptor (TLR)-4.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood cytofluorimetric analysis to evaluate expression of lymphocytes typical of psoriasis
Description
Peripheral blood cytofluorimetric analysis will be performed to assess expression of lymphocytes typical of psoriasis pathogenetic pattern [i.e., T helper (Th)17, and T cytotoxic (Tc)17].
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: zonulin
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: F-Actin
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: intestinal fatty acid-binding protein (i-FABP)
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: lipopolysaccharide (LPS)
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Peripheral blood ELISA analysis of intestinal permeability markers changing in psoriasis and NCWS patients.
Description
Peripheral blood ELISA analysis of intestinal permeability markers will be performed to assess: LPS-binding protein (LBP)
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Lactulose(LA)/Mannitol(MA) test changing in psoriasis and NCWS patients.
Description
LA/MA test will be performed to assess in vivo intestinal permeability.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Fecal ELISA analysis of inflammatory gut marker changing in psoriasis and NCWS patients.
Description
Fecal ELISA analysis of inflammatory gut marker will be performed to assess fecal calprotectin.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)
Title
Gut microbiota changing in psoriasis and NCWS patients.
Description
Gut microbiota assessment will be performed by analysis and quantification of gut microbioma on stools samples. After fecal collection, bacterial DNA will be extracted by cetyltrimethyl ammonium bromide. A simple and inexpensive physical lysis method for DNA and RNA extraction from freshwater microalgae and 16S ribosomal ribonucleic acid (rRNA) sequencing will be performed by polymerase chain reaction (PCR) methods, using universal primers. The resulting fragments will be then sequenced by pyrosequencing. Each reading will be compared with a database of known 16S rRNA sequences, using the BLAT program by phylogenetically assigning the most specific and reliable nodes. This method of assigning the obtained data leads to a "weighted" phylogenetic tree that characterizes well the bacterial content of the sample.
Time Frame
Start of the study (Day 0); 2 months of wheat elimination diet (Day 60); 2 weeks of open wheat challenge (Day 75)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria of psoriasis patients age >18 and <65 years; no systemic therapy for psoriasis for at least 3 months before inclusion in the study; negativity of anti-deamidated gliadin protein (anti-DGP) immunoglobulins (Ig) class A (IgA) and immunoglobulins (Ig)G, anti-tissue transglutaminase (anti-tTG) class IgA and IgG, and Endomysium antibodies (EmA); absence of WA (negative prick-test and/or specific serum immunoglobulins (Ig)E assay for wheat, gluten, and gliadin). Exclusion criteria of psoriasis patients age <18 and >65 years; severe chronic plaque-type psoriasis (based on BSA); self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study; pregnancy; alcohol and/or drug abuse; Helicobacter pylori and other bacterial and/or parasitic infections; diagnosis of chronic inflammatory bowel disease and other organic pathology affecting the digestive system (e.g., severe liver disease), nervous system diseases, major psychiatric disorders, immunological deficits, and impairments that limit physical activity; diagnosis of cancer treatment with steroids and/or immunological therapies; patients undergoing chemotherapy and/or radiotherapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pasquale Mansueto, MD
Phone
+393477279879
Email
pasquale.mansueto@unipa.it
First Name & Middle Initial & Last Name or Official Title & Degree
Aurelio Seidita, MD
Phone
+393209150370
Email
aurelio.seidita@unipa.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Carroccio, MD
Organizational Affiliation
University of Palermo
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Maria R. Bongiorno, MD
Organizational Affiliation
University of Palermo
Official's Role
Study Chair
Facility Information:
Facility Name
Internal Medicine Division of the "Cervello-Villa Sofia" Hospital
City
Palermo
State/Province
PA
ZIP/Postal Code
90146
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Carroccio, MD
Phone
+390916554815
Email
acarroccio@hotmail.com
Facility Name
Dermatology Department of the University Hospital 'P. Giaccone' of Palermo, Italy,
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MARIA R. BONGIORNO, MD
Email
mariarita.bongiorno@unipa.it
First Name & Middle Initial & Last Name & Degree
GIUSEPPE PISTONE, MD
Email
giuseppe.pistone@unipa.it
Facility Name
Internal Medicine Department of the University Hospital of Palermo
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pasquale Mansueto, MD
Phone
+39-091-6552884
Email
pasquale.mansueto@unipa.it
First Name & Middle Initial & Last Name & Degree
Pasquale Mansueto, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32349568
Citation
Marsili F, Travaglini M, Stinco G, Manzoni R, Tiberio R, Prignano F, Mazzotta A, Cannavo SP, Cuccia A, Germino M, Bongiorno MR, Persechino S, Florio T, Pettinato M, Tabanelli M, Sarkar R, Aloisi E, Bartezaghi M, Orsenigo R. Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study. J Dermatolog Treat. 2022 Feb;33(1):401-407. doi: 10.1080/09546634.2020.1757017. Epub 2020 Apr 30.
Results Reference
result
PubMed Identifier
31306540
Citation
Pistone G, Gurreri R, Tilotta G, Caruso P, Curiale S, Bongiorno MR. Timing of quality of life improvements in psoriatic patients treated with different systemic therapies. Dermatol Ther. 2019 Sep;32(5):e13021. doi: 10.1111/dth.13021. Epub 2019 Jul 31.
Results Reference
result
PubMed Identifier
28753927
Citation
Carroccio A, Giambalvo O, Blasca F, Iacobucci R, D'Alcamo A, Mansueto P. Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics. Nutrients. 2017 Jul 19;9(7):771. doi: 10.3390/nu9070771.
Results Reference
result
PubMed Identifier
24275240
Citation
Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.
Results Reference
result
PubMed Identifier
22825366
Citation
Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.
Results Reference
result

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Dietary Approach to Mild-to-moderate Psoriasis

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