Dermatitis Herpetiformis Research Articles

Use of IgG4 Immunohistochemistry as a Diagnostic Tool for Pemphigus

Pemphigus belongs to the group of antibody mediated autoimmune vesiculobullous disease (AIBD) of skin and mucous membranes. Antibodies are directed against the desmosomal adhesion proteins and IgG4 is the predominant subclass. It is a rare disease associated with significant mortality and morbidity. DIF is the gold standard test for AIBD. It requires fresh frozen section which is a major technical issue in most centres. The aim of this research was to study the diagnostic accuracy of IgG4 immunohistochemistry in pemphigus. The study was conducted as a diagnostic test evaluation in a tertiary care hospital. Paraffin blocks of histopathologically diagnosed AIBD were used for doing immunohistochemistry. The findings were compared with DIF findings. Statistical analysis was performed using SPSS, version 20.0. 48 paraffin blocks of AIBD were selected, DIF of all cases were already done from outside centre. There were 21 cases of pemphigus, 25 cases of bullous pemphigoid and one case each of epidermolysis bullosa acquisita and dermatitis herpetiformis. The sensitivity of IgG4 IHC was found to be 85.7%, specificity 96.3%, positive predictive value of 94.7% and negative predictive value 89.7%. So, we conclude that IgG4 IHC done on paraffin sections can be used as a diagnostic tool for pemphigus.

Epidemiology of Celiac Disease in Northern Morocco in 2018–2021: A Descriptive Cross-Sectional Study

Celiac disease is an autoimmune disease caused by gluten. This retrospective cross-sectional study with descriptive and analytical aims was conducted over three years, from 2018 to 2021. The participants were 280 patients diagnosed with celiac disease registered in the Gluten Intolerant and Allergic Association of the North in the Tangier-Tetouan-Al Hoceima region. The prevalence and incidence of celiac disease in this region were 1/135 and 1/253, respectively. The average age was 21.18 ± 1.13, and the first symptoms appeared between 10 and 25 years. The data showed a female predominance of 68% versus 32% for males, with a male/female sex ratio of 0.45. The clinical signs of celiac disease manifested more in gastrointestinal symptoms. This study obtained data on 22.6% of microcytic hypochromic anemia patients and 40.7% of Helicobacter pylori infections. In addition to celiac disease, the patients showed other pathologies with different rates: repeated spontaneous abortions (2.14%), type 1 diabetes mellitus (1.42%), autism (1.42%), dermatitis herpetiformis (0.72%), cancer(0.72%), and epilepsy (0.35%). Serologically, anti-transglutaminase antibodies were positive in 47.2% of patients. Analyses of histological data from intestinal biopsies from 141 patients were positive in 50.8% of patients. There was a minor correlation between the serological profile and the degree of atrophy.

Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.

Epidemiological, clinical and therapeutic aspects of dermatitis herpetiformis at Yalgado Ouédraogo University Hospital Centre, Burkina Faso

Background: Dermatitis herpetiformis is a rare autoimmune bullous dermatosis that predominantly affects Caucasians, adults or children, with a sex ratio of 1.8. Materials and Methods: The aim of this study was to document the clinical and epidemiological profiles of dermatitis herpetiformis and to detail its treatment in a hospital setting in order to increase our knowledge about this disease in our context and so to improve its management. We conducted a retrospective, cross-sectional study of the records of all patients seen in consultation or hospitalized at the dermatology department of Yalgado Ouédraogo University Hospital Centre, Ouagadougou, a public hospital in Burkina Faso, from January 2016 to December 2020. Results: We collected 14 cases (0.12%) of dermatitis herpetiformis among 11,456 patients seen. The mean age was 8 years (ranging from 4 to 27 years). The sex ratio was 1.33. The majority of the patients were schoolchildren living in rural areas (8 cases). The duration of the disease ranged from five days to one year (mean duration: 59.35 days). Eight patients had a history of digestive problems such as abdominal pain and diarrhea. Pruritis was the principal functional sign. In all patients, the lesions were polymorphous: disseminated vesicular bullae, papules, erosive, and excoriated lesions, sometimes forming clusters. Mucosal involvement was rare (3 cases). A gluten-free diet and dapsone 2 mg/kg/day were proposed to all patients and resulted in the improvement of the lesions. Conclusion: Our study confirmed that dermatitis herpetiformis is rare in our context. It is more frequent in young children and predominantly affects boys. It is intensely pruritic, and generalized polymorphous lesions were present in all our patients. Treatment is essentially based on a gluten-free diet and dapsone, which is a therapeutic test in the absence of supplementary investigations to establish a definitive diagnosis. Key words: Dermatitis Herpetiformis; Clinical Medicine; Dapsone; Gluten Intolerance

Cutaneous Manifestations in Celiac Disease: An Observational Study

Abstract Background: Cutaneous manifestations associated with celiac disease (CD), other than dermatitis herpetiformis, are poorly known. The aim of the present study was to study the spectrum of dermatological disorders in children with CD. Methodology: A total of 100 cases of biopsy-confirmed CD (both new and old) were recruited after taking written informed consent/assent from the child/guardians. The patient’s demographic details, history, vitals, general physical examination, systemic examination, and cutaneous examination findings were recorded. Relevant investigations were carried out, depending on the clinical findings of the cutaneous examination. Results: A total of 100 patients comprising 62 girls and 38 boys were studied, with the average age being 8.08 ± 3.67 years. Seventy patients showed the presence of dermatological findings. Cutaneous, mucosal, nail, and hair findings were seen in 35%, 7%, 14%, and 14% of patients, respectively. A higher incidence of dermatological findings was found in females (39%) compared to males (18%). The most common cutaneous conditions seen were atopic dermatitis (17%) and xerosis (10%). The most common mucosal finding was oral aphthae (4%). The most common nail changes were leukonychia and ragged cuticles (4% each). There was no statistical correlation between the presence of dermatological findings with the duration of the disease or with the duration of a gluten-free diet. Conclusion: Mucocutaneous manifestations are present in a significant proportion of patients with CD. Further studies with a larger sample size are needed to determine whether these findings are true associations or coincidental.

Risk of vascular diseases in patients with dermatitis herpetiformis and coeliac disease: a long-term cohort study

Introduction Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed. Methods The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR). Results The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91–1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16–1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47–0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07–1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22–2.16) but not in DH. Conclusions The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.

P12 A flare of dermatitis herpetiformis precipitated by etanercept

Abstract We report the case of a 79-year-old man who presented with an acute, intensely pruritic, widespread rash, which, on examination, consisted of symmetrical, haemorrhagic nodules and vesicles with some desquamation affecting the extensor surfaces of the arms, flexor surfaces of the legs and the natal cleft. He had a history of coeliac disease (for which he had adhered to a strict gluten-free diet since 1997) and rheumatoid arthritis. He had his first dose of the anti-tumour necrosis factor (TNF) agent etanercept prior to this episode to manage his arthritis. A punch biopsy for histopathology showed subepidermal blisters with a predominance of neutrophils. Eosinophils were also present to the level of the eccrine coils within the dermis, with eosinophilic flame figures but no eosinophil spongiosis at the edges of the blister. Direct immunofluorescence showed granular IgM and IgA in the dermal papillae, and a similar reaction was seen with fibrinogen. These histological findings were strongly suggestive of dermatitis herpetiformis (DH). Owing to diagnostic uncertainty on presentation, initial treatment was with high-dose topical steroids and emollient. and a yellow card was completed. Since this presentation, he has had no further flares and has not required dapsone. Multidisciplinary team discussion decided that the patient should avoid other anti-TNF treatments, but he has found relief for multiple months with rituximab and has had no cutaneous adverse events on this agent. The aetiology of DH following anti-TNF treatment is not immediately clear. Increased immunogenicity and cytokine release have been hypothesized to be part of the pathology of many adverse reactions to anti-TNF agents. It is conceivable that the cytokine release ordinarily seen in DH is replicated by the administration of anti-TNF agents. There have been many cases of anti-TNF agents leading to worsening eczema and psoriasis. Interestingly, these conditions have been found to upregulate TNF-α, a feature that is also seen in DH. This appears to be the first case described in the literature of etanercept-induced DH. A reaction with infliximab was reported in 2008, with a similar rash and histology consistent with DH, but it differed as the patient had no prior diagnosis of coeliac disease and presented after their second dose (Marakli SS, Uzun S, Ozbek S, Tuncer I. Dermatitis herpetiformis in a patient receiving infliximab for ankylosing spondylitis. Eur J Dermatol 2008; 18:88–9).

Celiac disease: Who should I test, and how?

First-degree relatives of patients with celiac disease and patients with dermatitis herpetiformis, type 1 diabetes mellitus, and autoimmune thyroid disease are among those for whom testing is advisable.

Skin gluten-related disorders: new and old cutaneous manifestations to be considered.

The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a "cutaneous-gluten sensitivity," as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.

Skin Biopsies in Gastrointestinal Diseases: A Single Centre Experience from North India

Skin manifestations have always been alarming to the patient and often warrant complete clinical evaluation. A thorough understanding of relationship between gastrointestinal (GI) disorders and skin diseases can alert the clinician to an underlying occult GI disorder. The aim of the study was to review the cutaneous changes in patients with co-existent, often masked GI diseases and to observe the underlying pathophysiology of such lesions. This was a retrospective, record based observational study. The archived histopathology reports & medical records of patients over a period of 5 years were searched and all patients who underwent skin biopsy with co-existent GI diseases were included. Out of a total of 218 patients of GI diseases who had dermatological manifestations, only 44 were biopsied. Pruritis (n=175), koilonychia (n=52) and erythematous rash (n=35) were the most common clinical features. Psoriasis (n=4), vasculitis (n=4), Dermatitis Herpetiformis (n=3) and pyoderma gangrenosum (n=5) were often seen associated with benign GI diseases like Inflammatory Bowel Diseases, Chronic Liver Disease, Malabsorption syndrome etc. Sweets syndrome (n=2) and cutaneous metastatic nodules (n=3) were associated with underlying malignancy particularly of gall bladder and pancreas.

A transzglutaminázok szerepe dermatitis herpetiformisban

In this review article, after a short introduction, the authors present the pathogenesis and pathomechanism of dermatitis herpetiformis from the perspective of the transglutaminase enzyme family. According to our current knowledge, these isoenzymes consist of nine members in humans, and four of them play a role in the development of the disease. The main autoantigen is probably epidermal transglutaminase, but the role of other isozymes cannot be neglected either. The mechanism of the development of gluten-sensitive enteropathy is presented, followed by the theory of formation of IgA-epidermal transglutaminase immune complexes. The article also briefly covers the associated disorders of the blood coagulation system and neurological conditions.

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study.

Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2-5.5; p < 0.0001) in MMP to 28.7 (CI 3.9-211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2-7.9; p < 0.0001) to 23.3 (CI 17.0-31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

Computer-aided classification of indirect immunofluorescence patterns on esophagus and split skin for the detection of autoimmune dermatoses.

Autoimmune bullous dermatoses (AIBD) are rare diseases that affect human skin and mucous membranes. Clinically, they are characterized by blister formation and/or erosions. Depending on the structures involved and the depth of blister formation, they are grouped into pemphigus diseases, pemphigoid diseases, and dermatitis herpetiformis. Classification of AIBD into their sub-entities is crucial to guide treatment decisions. One of the most sensitive screening methods for initial differentiation of AIBD is the indirect immunofluorescence (IIF) microscopy on tissue sections of monkey esophagus and primate salt-split skin, which are used to detect disease-specific autoantibodies. Interpretation of IIF patterns requires a detailed examination of the image by trained professionals automating this process is a challenging task with these highly complex tissue substrates, but offers the great advantage of an objective result. Here, we present computer-aided classification of esophagus and salt-split skin IIF images. We show how deep networks can be adapted to the specifics and challenges of IIF image analysis by incorporating segmentation of relevant regions into the prediction process, and demonstrate their high accuracy. Using this semi-automatic extension can reduce the workload of professionals when reading tissue sections in IIF testing. Furthermore, these results on highly complex tissue sections show that further integration of semi-automated workflows into the daily workflow of diagnostic laboratories is promising.

Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease.

Dermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous manifestation of celiac disease (CD). The current estimation of DH versus CD is around 1:8 and the affected individuals have a genetic predisposition. Pathogenetically, IgA autoantibodies against the epidermal transglutaminase, an essential constituent of the epidermis, cause DH and are reported to develop through cross-reaction with the tissue transglutaminase, with IgA auto-antibodies causing CD. Immunofluorescence techniques allow for a rapid diagnostics of the disease using patient sera. Evaluation of IgA endomysial deposition with indirect immunofluorescence on monkey oesophagus is highly specific, but moderately sensitive, with some operator-dependent variability. Recently, indirect immunofluorescence with monkey liver as a substrate has been proposed as an alternative, well-functioning diagnostic approach with higher sensitivity in CD. The objective of our study was to evaluate whether monkey oesophagus or liver tissue shows advantage for diagnostics in patients with DH, compared to CD. To that end, sera of 103 patients with DH (n=16), CD (n=67) and 20 controls ere compared by 4 blinded experienced raters. For DH, we found a sensitivity of 94.2% for monkey liver (ML) compared to 96.2% in monkey oesophagus (ME), while specificity in ML was superior (91.6% versus 75%) to ME. In CD, ML had a sensitivity of 76.9% (ME 89.1%) and specificity of 98.3% (ME 94.1%). Our data show that ML substrate is well suitable for DH diagnostics.

Immunopathological Assessment of the Oral Mucosa in Dermatitis Herpetiformis.

Dermatitis herpetiformis (Duhring's disease, DH) is a chronic blistering cutaneous condition with pruritic polymorphic lesions, consisting of vesicles, papules or nodules and erythema, found predominantly on the extensor surfaces of the limbs, buttocks, and neck. Diagnosis is based on characteristic clinical and immunopathological findings. Oral manifestations of DH have rarely been described. The aim of the study was to evaluate IgA, IgG, IgM and C3 complement deposits in the oral mucosa in DH patients. Direct immunofluorescence (DIF) was performed on the oral mucosa specimens collected from 10 DH patients. Biopsy was taken in a local anesthesia from perilesional site from the buccal mucosa and then preserved in a standard procedure using polyclonal rabbit IgG, IgA, IgM and C3 antibodies. Granular IgA and C3 deposits were found in 6 patients (60%), and in 3 subjects (30%) the result was indeterminate. Significant fluorescence of the deposits along the basement membrane was observed in 2 patients, moderate fluorescence in 3 patients, and in 4 cases the result was indeterminate. C3 deposits were found in 5 subjects (50%), 3 of them being moderate and 2 indeterminate. No IgM and IgG deposits were detected in the collected buccal mucosa specimens.

Juvenile idiopathic arthritis in children and adolescents with atopic dermatitis: A Finnish nationwide registry study

Juvenile idiopathic arthritis in children and adolescents with atopic dermatitis: A Finnish nationwide registry study

Perineal cutaneous basal cell carcinomas in patients with familial seronegative celiac disease: Report of three cases

Introduction: Celiac disease (CD) is an autoimmune enteropathy due to hypersensitivity to consumed gluten. Patients can present with gastrointestinal and systemic symptoms. CD often runs in families. Studies have reported multiple subtypes of CD including at least one seronegative variant. The cutaneous manifestations of CD remain to be delineated; some cases of seropositive CD are associated with dermatitis herpetiformis. We report. Cases: In this study, three patients with a longstanding history of personal and/or familial seronegative CD presented withwho developed basal cell carcinoma (BCC) of the perineum. We hope to inform clinical physicians about the possible relationship between CD and cutaneous malignancies. DiscussionResults: We report three adult patients with a diagnosed or suspected personal history of seronegative CD and a family history of CD, who presented with BCC of the perineum. Discussion: The mechanism by which CD causes BCC remains to be defined. Physicians should consider testing evaluating patients with skin cancer located in the perineum for CD.

Rare Complications of Celiac Disease: Clinicopathologic Features

Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation. The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.

Short Course Treatment with Dapsone in a 59-Year-Old Male with Dermatitis Herpetiformis: A Case Report

Dermatitis Herpetiformis is a chronic autoimmune blistering skin condition that is often associated with gluten-sensitive enteropathy. The primary lesion of DH is an erythematous papule, plaque, or, most commonly, a vesicle that can be pruritic.

Celiac Disease: a review

Celiac Disease (CD) is an immune-mediated enteropathy in response to the ingestion of gluten in genetically predisposed individuals, causing a malabsorptive syndrome. This review aims to conceptualize CD, describe its pathophysiology, highlight its epidemiology, detail associated clinical presentations, outline the diagnostic approach, and explain the treatment. To achieve this, works in English, Portuguese, and Spanish from the last five years were sought in the following databases: PubMed, LILACS, and SciELO, using the following keywords: “doença celíaca” and “celiac disease.” The search resulted in 175 articles, with 40 works chosen after screening and evaluation. The results revealed that CD affects approximately 1% of the global population, can be diagnosed at any age, but with more typical symptoms in children and atypical symptoms in adults. The pathogenesis involves the genetic factor HLA DQ2/DQ8, gluten ingestion, the formation of tissue transglutaminase antibodies, and an inflammatory reaction that damages the duodenum, impairing its absorptive function. Typical symptoms include chronic diarrhea, abdominal distension, weight loss, poor growth, and vitamin deficiencies. Atypical symptoms include dermatitis herpetiformis, refractory iron-deficiency anemia, delayed puberty, infertility, and neurological diseases. Diagnosis involves a suspected clinical picture, serologies for autoantibodies, genetic testing, and duodenal biopsy. Treatment is lifelong adherence to a gluten-free diet. Despite being well-characterized, CD remains underdiagnosed, and additional studies are needed.