Gluten and the skin: Celiac disease and gluten sensitivity for the dermatologist

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1 2/10/18 Gluten and the skin: Celiac disease and gluten sensitivity for the dermatologist 76th Annual American Academy of Dermatology Meeting February 16th, 2017 Matthew Goldberg, MD Assistant Professor, Dermatology and Pathology Icahn School of Medicine at Mount Sinai New York, NY Disclosures I have no conflicts of interest No discussion of experimental or off label use of medications Learning objectives Review screening approach and diagnosis of celiac disease and dermatitis herpetiformis Gluten free diet counseling basics and pearls Introduction to expanding cutaneous manifestations of celiac disease and non-celiac gluten sensitivity 1

2 What is Celiac Disease (CD)? CD is a systemic immune mediated disorder triggered by dietary gluten in genetically susceptible individuals Over 95% have HLA DQ2 or DQ8 From Fasano, NEJM 2012 and Green NEJM 2007 What is Celiac Disease (CD)? Adapted from Green, NEJM 2007 CD is more common than expected - Worldwide prevalence is % - United States prevalence: 1:133 in general population 1:22 in first degree relatives From Gujral, WJG 2012 and Fasano Arch Intern Med,

3 Classic CD is no longer most common Less than 50% present classically - Abdominal pain, diarrhea, weight loss From University of Chicago Celiac disease center, 2009 CD associations are increasing Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of CD Patients with DH can have active, silent or latent CD Adapted from Farrell, NEJM 2002 and Smecuol E et.al. Clin Gastroenterol and Hepatol 2005 Gluten-related disorders in Dermatology Gluten related disorders Celiac Disease (CD) Dermatitis Herpetiformis (DH) 3

4 Gluten-related disorders in Dermatology Gluten related disorders CD Non-celiac gluten sensitivity DH Other cutaneous manifestations Skin Rash NOS 3 cases seen over 3 months at UCSF #1) Classic dermatitis herpetiformis #2) Atypical presentation of celiac disease #3) Gluten sensitivity and atopic dermatitis Case #1 Clinical presentation 15 yo F with known CD Recent trip to France with lapse in gluten-free diet Acute onset of extremely pruritic papulovesicles below knees 4

5 2/10/18 Case #1 Biopsy recommendations Lesional biopsy for H & E Perilesional biopsy for DIF Case #1 Histopathology confirms DH Neutrophils in the dermal papillae with vesicle formation Granular IgA in the dermal papillae Courtesy of Laura Pincus, M.D. and from Bolotin, 2011 Case #1 Serology recommendations Total serum IgA + IgA anti-ttg Ab From Fasano, NEJM

6 2/10/18 Case #1 Serology recommendations IgA anti-tge levels correlate with DH severity - IgA anti-tge test not yet commercially available Sardy, Exp Med 2002, Bolotin, JAAD 2011, and Boroni, JEADV 2012 JAAD algorithm for DH From Bolotin, JAAD 2011 Why recommend gluten free diet? Proven effective treatment for CD and DH Untreated CD leads to systemic manifestations - Restores intestinal barrier function Decreased absolute risk of rare enteropathy associated T-cell lymphoma Gluten free diet is now more possible to maintain 6

7 Gluten Free is a booming industry Wheat free gluten free Gluten containing grains Wheat Heirloom Wheat (spelt, semolina, kamut, triticale) Rye Barley Conventional Oats* Gluten is a protein found in wheat, rye, and barley Gluten-free oats and flours are readily available New FDA Standard for Gluten Free Foods FDA defined Gluten-Free packaged foods in <20 parts per million (ppm) gluten by ELISA Independent 3 rd party testing is also available 7

8 Surprising sources of gluten Gluten-full Soy sauce Malt vinegar Beer Cross contamination Dietary supplements Gluten-free alternatives Tamari All other vinegars Gluten-free beer, cider, wine Dedicated prep space, inquire at restaurants Check ingredients and seek therapeutic alternatives My gluten free diet approach Refer patients to a knowledgeable nutritionist Turn to experts for advice - Columbia University, University of Chicago, Mass General CD, UC San Diego centers My gluten free diet approach Refer patients to a knowledgeable nutritionist Turn to experts for advice - Columbia University, University of Chicago, Mass General CD, UC San Diego centers Focus on the positive - Less, so many foods to avoid - More, discover new gluten-free foods - Support groups, selected blogs and guides 8

9 3 cases seen over 3 months at UCSF #1) Classic dermatitis herpetiformis #2) Atypical presentation of celiac disease #3) Gluten sensitivity and atopic dermatitis Case #2 Clinical presentation 69yo M with 15 year h/o severe chronic pruritus Lichen simplex chronicus (LSC) and prurigo nodularis (PN) Failed a wide range of topicals, phototherapy, antipruritics and immunomodulatory therapies Case #2 - Histopathology - Marked acanthosis - Slight spongiosis - Negative DIF - Positive IgA anti-ttg - Upper endoscopy + duodenal biopsy suggestive of CD Courtesy of Thaddeus Mully, M.D. 9

10 Case #2 PN and CD PN + CD Acanthosis + Spongiosis Atypical DH? Courtesy of Thaddeus Mully, M.D., Laura Pincus, M.D. and Bolotin, 2011 Case #2 PN and CD PN + CD Acanthosis + Spongiosis Atypical cutaneous CD? Courtesy of Thaddeus Mully, M.D., Laura Pincus, M.D. and Bolotin, 2011 Role for gluten-free diet in PN? Atypical cutaneous CD Gluten- Free Diet Anecdotal responses 5 reported cases reported with PN + CD All responded to gluten-free diets Adapted from Humber, Eur J Dermatol

11 Case #2 PN and CD PN + CD Gluten- Free Diet Improved after several months 5 reported cases reported with PN + CD All responded to gluten-free diets Patient started on gluten-free diet and significantly improved with dietary intervention CD linked to many skin findings Conflicting case reports/series Non-standard case definitions Humbert, Eur J Dermatol, 2006 CD in patients with psoriasis Increased risk of developing psoriasis before and after CD diagnosis Case control study- 29,000 Swedish patients with CD PASI reduction after 3-month gluten free diet Case-control study- 34 patients Worsening psoriasis after restarting regular diet Ludvigsson, JF et.al. JID 2011, Bhatia, BK et.al. JAAD 2014, and Michaelsson, BJD

12 Clinical implications remain uncertain Total serum IgA Psoriasis or PN. +.. IgA anti-ttg Gluten-free diet Gluten-free diet may be beneficial for subset of patients with a range of inflammatory skin conditions Recommend clinical screening for family history and functional GI symptoms Bhatia, BK et.al. JAAD cases seen over 3 months at UCSF #1) Classic dermatitis herpetiformis #2) Atypical presentation of celiac disease #3) Gluten sensitivity and atopic dermatitis Case #3 Clinical presentation 2yo M with 6-month h/o refractory atopic dermatitis Father has non-celiac gluten sensitivity (NCGS) Parents report that child also has a gluten sensitivity 12

13 Case #3 Gluten sensitivity + AD Is there a relationship between my son s gluten sensitivity and his rash? What is non-celiac gluten sensitivity (NCGS)? Patients with functional GI and extra-intestinal symptoms triggered by dietary gluten Negative for CD and distinct from irritable bowel syndrome May be more common than CD - estimates from 1-6% From Aziz, Proc nutr soc 2012, Volta U, Cell Mol Immunol 2013, and Biesiekierski, Am J Gastroenterol, 2011 What is non-celiac gluten sensitivity (NCGS)? Reproducible symptoms in double blinded placebo controlled gluten ingestion studies From Biesiekierski, Am J Gastroenterol, 2011 and Caroccio, Am J Gastroenterol,

14 2/10/18 NCGS linked with atopy and skin rash Significantly increased rates of atopy compared to CD Skin rash is among most common extra-intestinal symptoms 33 40% in largest studies Dermatologic studies are now emerging Volta, Gastroenterology and Hepatol 2012, Caroccio, Am J Gastroenterol, 2012 and Sapone, BMC Medicine 2012 Clinicopathologic correlation in NCGS Clinical Eczematous/psoriasiform pruritic papules + plaques Histology Superficial perivascular + spongiosis, acanthosis, or hyper/parakeratosis DIF Granular C3 at DEJ Adapted from Bonciolini V et.al. Nutrients, 2015 and D'Alcamo, A et.al. Nutrients, 2017 Clinicopathologic correlation in NCGS Clinical Higher rates of nickel contact allergy compared to patients with IBS Adapted from Bonciolini V et.al. Nutrients, 2015 and D'Alcamo, A et.al. Nutrients,

15 Case #3 Gluten sensitivity + AD Atopic Dermatitis and NCGS Biopsy, DIF, serologic testing Gluten free diet Is there a relationship between my son s gluten sensitivity and his rash? Await larger studies to guide recommendations Take Home Points Approach to CD and DH screening Lesional punch biopsy and perilesional DIF Total Serum IgA + anti-ttg antibodies Range of cutaneous manifestations in patients with CD and NCGS Gluten may be an inflammatory trigger for a larger subset of patients Gluten-free diet may have wider application in dermatology Provide patients with basic dietary recs and resources Acknowledgements UCSF Faculty and Dermatopathologists Dr. Thaddeus Mully Dr. Laura Pincus Dr. Erin Mathes Dr. Kelly Cordoro - Dr. Kanade Shinkai - Dr. Timothy Berger Dr. John Zone, University of Utah Colombia Celiac Disease Center 15

16 Gluten free literacy 101 Support groups Restaurants Yelp, Zagat Celiac disease centers Blogs/Guides What is gluten? A protein found in wheat, rye, and barley Jabri, Immunological reviews, 2005 Gluten sensitivity is distinct from CD Pathogenesis CD Autoimmunity, gut permeability NCGS Unknown, possibly innate immunity HLA HLA-DQ2/DQ8 No specific HLA Autoantibodies Always present Always absent Enteropathy Always present Always absent Symptoms GI + extra-intestinal Adapted from Fasano, NEJM 2012 and Caroccio, Am J Gastroenterol,

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