Non-classical Presentations Research Articles

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

Q1291H-CFTR molecular dynamics simulations and ex vivo theratyping in nasal epithelial models and clinical response to elexacaftor/tezacaftor/ivacaftor in a Q1291H/F508del patient.

Background: Cystic fibrosis (CF) is caused by a wide spectrum of mutations in the CF transmembrane conductance regulator (CFTR) gene, with some leading to non-classical clinical presentations. We present an integrated in vivo, in silico and in vitro investigation of an individual with CF carrying the rare Q1291H-CFTR allele and the common F508del allele. At age 56years, the participant had obstructive lung disease and bronchiectasis, qualifying for Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTR modulator treatment due to their F508del allele. Q1291H CFTR incurs a splicing defect, producing both a normally spliced but mutant mRNA isoform and a misspliced isoform with a premature termination codon, causing nonsense mediated decay. The effectiveness of ETI in restoring Q1291H-CFTR is largely unknown. Methods: We collected clinical endpoint measurements, including forced expiratory volume in 1s percent predicted (FEV1pp) and body mass index (BMI), and examined medical history. In silico simulations of the Q1291H-CFTR were compared to Q1291R, G551D, and wild-type (WT)-CFTR. We quantified relative Q1291H CFTR mRNA isoform abundance in patient-derived nasal epithelial cells. Differentiated pseudostratified airway epithelial cell models at air liquid interface were created and ETI treatment impact on CFTR was assessed by electrophysiology assays and Western blot. Results: The participant ceased ETI treatment after 3months due to adverse events and no improvement in FEV1pp or BMI. In silico simulations of Q1291H-CFTR identified impairment of ATP binding similar to known gating mutants Q1291R and G551D-CFTR. Q1291H and F508del mRNA transcripts composed 32.91% and 67.09% of total mRNA respectively, indicating 50.94% of Q1291H mRNA was misspliced and degraded. Mature Q1291H-CFTR protein expression was reduced (3.18% ± 0.60% of WT/WT) and remained unchanged with ETI. Baseline CFTR activity was minimal (3.45 ± 0.25μA/cm2) and not enhanced with ETI (5.73 ± 0.48μA/cm2), aligning with the individual's clinical evaluation as a non-responder to ETI. Conclusion: The combination of in silico simulations and in vitro theratyping in patient-derived cell models can effectively assess CFTR modulator efficacy for individuals with non-classical CF manifestations or rare CFTR mutations, guiding personalized treatment strategies and optimizing clinical outcomes.

Abstract #1412436: Nonclassical Presentation of Hypophosphatasia

Hypophosphatasia (HPP) is a rare genetic disorder characterized by impaired mineralization (calcification of bones and teeth). The signs and symptoms of HPP vary widely and can appear from birth to adulthood. We report a case of delayed bone fracture healing in the setting of hypophosphatasia. A 48-year-old male patient with a past medical history of vitamin D deficiency was seen in the outpatient clinic for low ALP levels. He had delayed wound healing involving the left clavicular and multiple rib fractures after a motor vehicle accident that occurred in 2012, which ultimately needed multiple surgeries requiring 1.5 years to fully heal/fuse. This involved placing and removing multiple plates and screws as well as bone grafts. He denied other fractures, skeletal deformities, or dental problems. He does have normal development and does not have short stature. He has a history of vitamin D deficiency and is on vitamin D 2000 units daily. He was found to have a family history remarkable with two sons with low ALP and vitamin D beginning in childhood. The older son was noted to have lost his teeth early at age 3-4 years, with no history of fractures. Musculoskeletal examination: no swelling noted, and no tenderness was noted but the patient did have a bone spur on the elbow, knee, and heel. He is able to ambulate without assistance and was found to have no other skeletal deformity. Laboratory findings: ALP 31 U/L (Normal 34-122). Bone-specific alkaline phosphatase: 5.6 ug/L (Normal 6.5-20.1). Vitamin D 25 OH level: 84 (on replacement therapy). Calcium: 9.2 mg/dl, phosphorus 3.5 mg/dl, iPTH levels 23 pg/ml. DXA scan: shows T values on the lumbar spine of -1.8, right hip of -1.4, and right neck of -1.9, consistent with osteopenia. We checked vitamin B6 level: 1087.7 nmol/L, consistent with hypophosphatasia. The patient then underwent genetic testing and is positive for ALPL gene mutation (heterozygous). Both his 2 sons are positive for ALPL gene mutation. We present a case of hypophosphatasia with nonclassical presentations, his mild symptoms likely from incomplete penetration. HPP causes pathogenic variants in ALPL gene. This gene provides instruction for making an enzyme called tissue non-specific alkaline phosphatase (TNSALP) which plays an essential role in the mineralization of the skeleton and teeth. Mutation in the ALP gene leads to the production of an abnormal version of TNSALP that cannot participate effectively in the mineralization process. There is currently no cure for hypophosphatasia, however human recombinant enzyme replacement therapy called asfotase alfa is now available.

Comprehensive Review of Reported Nonclassical Spindle Cell Lipoma Presentations and a Unique Case Report.

Introduction:Spindle cell lipoma (SCL) is a rare subset of benign lipomatous neoplasms, making up approximately 1.5% of all adipocytic neoplasms. Since SCLs were first described in 1975, numerous nonclassical cases have been reported in the literature, with variation in location, cytologic composition, patient demographic, and progression. Although some previous reports review related cases of specific rare presentations or institution-based summaries, no comprehensive summary of published nonclassical SCL case reports has been done.Methods:PubMed was queried for nonclassical presentations of SCL from 1978 to 2018. The nonclassical characteristics were analyzed and described. Those with multiple nonclassical features were studied for common characteristics. The Fisher exact test was used, and a P value of 0.05 was determined to be statistically significant.Results:We present the first case of a patient with six nonclassical findings: a fast-growing, infiltrating into skeletal muscle, located in two positions on the chin of an 18-year-old African American woman. In this review of the existing nonclassical SCL, we evaluate 125 cases for demographics, location, size, erosion/infiltration, multiple lesions in one individual, and the number of nonclassical findings in one individual. Women and younger than 40-year-old patients significantly present with more than one nonclassical finding.Conclusions:Thorough characterization of the rare nonclassical cases of this benign condition could guide diagnostic decision-making and identify trends in disease presentation over time as well as alert the clinician to the increased risk of rapid regrowth or invasion in an individual with nonclassical findings especially young age and female gender.

Atypical Transmissible Venereal Tumor in Dogs

Background: The Transmissible Venereal Tumor (TVT), classified as a round cell tumor, is considered one of the oldest existing tumors. It affects dogs all over the world and has a contagious characteristic. Despite the good response to clinical treatment in most cases, it can sometimes have non-classical presentations and even different behavior. Thus, the present study aims to report 3 cases of atypical TVT treated at the Veterinary Medical Teaching Hospital of the State University of Maringá (UEM) in Umuarama, Paraná, aiming to describe the epidemiology and clinical-pathological aspects, focusing on the diagnostic method used, the treatment of choice and the clinical follow-up of each case.Cases: Case records of 3 intact male mongrel dogs with atypical Transmissible Venereal Tumor (case 1: intranasal; case 2: intra-abdominal and case 3: cutaneous with lymph node metastasis) were reviewed regarding history, clinical signs, duration of clinical signs, examination findings, results and findings of complementary exams (hematological, biochemical, radiographic, ultrasonographic and cytological), treatment, follow-up and final result. Case 1: had an ulcerated mass in the nasal plane causing significant airway obstruction and respiratory difficulty. Case 2: had a lesion in a typical location (penile mucosa in the glans area) but with a large intra-abdominal mass in the lumbar paravertebral region, causing compression of important structures. Case 3: on the other hand, had cutaneous TVT with several ulcerated plaque lesions all over the skin, in addition to popliteal lymph node enlargement due to metastasis later confirmed by microscopy. All dogs reported were mixed breed, intact males with free access to the street. Despite the fact that each patient had their own anatomical tumor characteristics, they were all diagnosed through cytological examination and all classified as lymphocytic TVT. The standard treatment for this neoplasm was instituted; the chosen chemotherapy was vincristine sulfate at a dose of 0.75 mg/m2 intravenously every 7 days for 5-7 weeks. In addition, all 3 animals needed supportive treatment due to anorexia, bacterial contamination secondary to injuries, dehydration and pain.Discussion: Usually, TVT is not considered malignant, not causing metastasis, however it is now known that its behavior has changed a lot and more and more cases of metastatic or highly infiltrative TVT have been reported. The 3 cases presented in this report had epidemiological characteristics as mentioned in the literature, but the location, macroscopic and radiographic characteristics are uncommon for this neoplasm, that is, with an atypical tumor presentation. This demonstrates the importance of a good clinical evaluation and, especially, of the cytological exam, which was essential for the definitive diagnosis for the three cases presented. It is speculated that more “aggressive” cases of TVT may be correlated with the plasmacytic cytological type, however none of the patients described here had this cytological presentation. Thus, the clinician must be aware of the risk factors associated with this neoplasia, because even in non-classical presentations, the lymphocytic cell morphological characteristic was present and the patients responded well to the classic treatment, not requiring a change in chemotherapy protocols, however a special attention must be paid to the particularities involved in each presentation of the same tumor in different patients. Keywords: TVT, canine, neoplasm, metastasis, cytology.

Paired Tumor-Normal Sequencing Provides Insights Into the TP53-Related Cancer Spectrum in Patients With Li-Fraumeni Syndrome.

Genetic testing for Li-Fraumeni syndrome (LFS) is performed by using blood specimens from patients selected based on phenotype-dependent guidelines. This approach is problematic for understanding the LFS clinical spectrum because patients with nonclassical presentations are missed, clonal hematopoiesis-related somatic blood alterations cannot be distinguished from germline variants, and unrelated tumors cannot be differentiated from those driven by germline TP53 defects. To provide insights into the LFS-related cancer spectrum, we analyzed paired tumor-blood DNA sequencing results in 17 922 patients with cancer and distinguished clonal hematopoiesis-related, mosaic, and germline TP53 variants. Loss of heterozygosity and TP53 mutational status were assessed in tumors, followed by immunohistochemistry for p53 expression on a subset to identify those lacking biallelic TP53 inactivation. Pathogenic/likely pathogenic TP53 variants were identified in 50 patients, 12 (24.0%) of which were clonal hematopoiesis related and 4 (8.0%) of which were mosaic. Twelve (35.3%) of 34 patients with germline TP53 variants did not meet LFS testing criteria. Loss of heterozygosity of germline TP53 variant was observed in 96.0% (95% confidence interval [CI] = 79.7% to 99.9%) of core LFS spectrum-type tumors vs 45.5% (95% CI = 16.8% to 76.6%) of other tumors and 91.3% (95% CI = 72.0% to 98.9%) of tumors from patients who met LFS testing criteria vs 61.5% (95% CI = 31.6% to 86.1%) of tumors from patients who did not. Tumors retaining the wild-type TP53 allele exhibited wild-type p53 expression. Our results indicate that some TP53 variants identified in blood-only sequencing are not germline and a substantial proportion of patients with LFS are missed based on current testing guidelines. Additionally, a subset of tumors from patients with LFS do not have biallelic TP53 inactivation and may represent cancers unrelated to their germline TP53 defect.

Alpha-Synuclein as a Biomarker of Parkinson's Disease: Good, but Not Good Enough.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

Lobular capillary haemangioma of nasal septum with remodelling of bony lateral wall

The diagnosis of intranasal masses can often be confusing due to the diversity of inflammatory and neoplastic lesions affecting the sinonasal tract, and the ambiguity of symptoms. Haemangiomas have been described in head and neck. However, uncommon findings such as bony remodelling and unusual clinical appearance of mass were noted in the present case. The description of such non-classical presentations is essential in deciding further management and preventing plausible hemodynamic imbalance.

Clinical features and psychological impact of celiac disease at diagnosis

Background and aimWe aimed to describe the socio-demographic, behavioral and clinical profiles of adult patients with newly diagnosed celiac disease (CeD) and their possible association with QoL and psychological symptoms. MethodsAdults newly diagnosed with CeD and residents in the Veneto region were included. Their sociodemographic characteristics, clinical presentation, mode of diagnosis, duration of symptoms before diagnosis and comorbidities were recorded. All patients completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) and Short Form Health Survey (SF-36) questionnaires. ResultsBetween 2016 and 2019, 110 CeD patients (81% females, mean age 37.5) were recruited. At diagnosis, patients were categorized into classical (n = 56), nonclassical CeD (n = 49) and asymptomatic (n = 5) groups. Patients with classical presentation had a lower QoL than nonclassical patients, who were found to be more depressed. We observed a diagnosis delay of more than 7 months in more than 60% of patients with both classical and nonclassical presentations and we found that a longer duration of GI symptoms decreased the self-reported SF36 scores in the physical health (p = 0.002), social functioning (p = 0.03) and general health (p = 0.009) domains. Women had an overall lower self-perceived QoL. ConclusionsSymptomatic presentation at CeD diagnosis, diagnostic delay and sex may affect QoL and psychological disorders.

Plasma C3d levels as a diagnostic marker for complete complement factor I deficiency

Plasma C3d levels as a diagnostic marker for complete complement factor I deficiency

Systematic Review of Methemoglobinemia in Acetaminophen Poisoning.

Acetaminophen (N-acetyl-para-aminophenol, paracetamol, (APAP) toxicity is one of the commonly encountered poisonings by emergency physicians. Methemoglobinemia is an uncommon association and rarely seen in APAP poisoning. Retrospective analysis of all the published reports on APAP induced methemoglobinemia from 1968 to 2019. In total there were 14 cases with 9 females and 6 males. The median age of the study cohort was 59 years. The most common presenting feature was altered mentation (9 patients) followed by cyanosis (3 patients). The intent of consumption was therapeutic (7 cases) versus suicidal (5 cases) attempt.In most cases, the dose of APAP consumption was not known. Aspirin, sulfasalazine, benzocaine spray, nitrate preservative, contaminated water, detergents, etc. where the other agents consumed by the patients in addition to APAP before developing methemoglobinemia. The median MethHb level of the study cohort was 15.85% Patients were treated with NAC, hemodialysis, methylene blue, and ascorbic acid and CRRT in various combinations. Full recovery was seen in 9 patients while 4 patients died. APAP toxicity is a well-known and common entity with multiple sequelae that presents with a variable spectrum of mild to fulminant multiorgan failure. Awareness of non-classical presentations like methemoglobinemia is essential to ensure timely intervention.

Mitochondrial disease in children.

Mitochondrial disease presenting in childhood is characterized by clinical, biochemical and genetic complexity. Some children are affected by canonical syndromes, but the majority have nonclassical multisystemic disease presentations involving virtually any organ in the body. Each child has a unique constellation of clinical features and disease trajectory, leading to enormous challenges in diagnosis and management of these heterogeneous disorders. This review discusses the classical mitochondrial syndromes presenting most frequently in childhood and then presents an organ-based perspective including systems less frequently linked to mitochondrial disease, such as skin and hair abnormalities and immune dysfunction. An approach to diagnosis is then presented, encompassing clinical evaluation and biochemical, neuroimaging and genetic investigations, and emphasizing the problem of phenocopies. The impact of next-generation sequencing is discussed, together with the importance of functional validation of novel genetic variants never previously linked to mitochondrial disease. The review concludes with a brief discussion of currently available and emerging therapies. The field of mitochondrial medicine has made enormous strides in the last 30years, with approaching 400 different genes across two genomes now linked to primary mitochondrial disease. However, many important questions remain unanswered, including the reasons for tissue specificity and variability of clinical presentation of individuals sharing identical gene defects, and a lack of disease-modifying therapies and biomarkers to monitor disease progression and/or response to treatment.

High number of hospitalisations and non-classical presentations: lessons learned from a measles outbreak in 2017, Belgium.

We describe and analyse an outbreak of measles that affected Belgium early 2017. In total, 289 cases were reported, mostly (53%) in people 15 years or older. For 133 (46%) vaccination status was unknown and a further 117 (41%) were not vaccinated. According to national guidelines, 83 of the unvaccinated cases (29% of total cases) should have received minimum one dose of vaccine, but did not. One in five cases (21%) did not present with the classical triad of fever, rash and any of coryza, conjunctivitis or cough. Rash was the most sensitive symptom, being absent in only six cases. A large proportion of cases (125/289, 43%) required hospitalisation. In hospitalised patients, the most commonly observed complications were hepatic disorders (present in 58/125 hospitalised patients, 46%). Thirty-six of the cases (12%) were in healthcare workers and nosocomial spread contributed importantly to the outbreak. Older age at presentation, altered clinical presentations and presence of complications like hepatitis can delay the correct diagnosis of measles. Clinicians should maintain a high index of suspicion in any individual presenting with rash. If the elimination target is to be reached, catch-up vaccination campaigns should be intensified and target young adults and health care workers.

Effect of a Gluten-free Diet on Quality of Life in Patients With Nonclassical Versus Classical Presentations of Celiac Disease.

Celiac disease (CD) often presents with symptoms of diarrhea and malabsorption, termed classical CD. However, it can also present as nonclassical CD, which is commonly associated with nongastrointestinal symptoms. Studies suggest that nonclassical CD tends to have less severe symptoms than classical CD, which may affect both adherence to a gluten-free diet (GFD) and psychological stress. Therefore, we compared adherence to a GFD and psychological measures, including quality of life (QOL) and somatization, between patients with nonclassical and classical presentations of CD. Patients at a tertiary care center with biopsy-proven CD, who completed a Talley Bowel Disease Questionnaire and the Short Form-36 at diagnosis and who had been on a GFD for at least 1 year, were included in this study. Patients were further surveyed to assess gastrointestinal symptoms, QOL, Somatization Symptom Checklist (SSC), and adherence to a GFD. Results were compared between patients with classical versus nonclassical CD presentation. Among 122 patients included in this study, 62 had classical CD and 60 had nonclassical CD. At diagnosis, health-related QOL was lower in the classical CD group than in the nonclassical CD group. After following a GFD, both groups had improved QOL after following a GFD, and body mass index significantly increased in both groups. Most subscales of QOL, SSC scores, and adherence to the GFD were similar between the groups, except the Short Form-36 Mental Component summary scores that were still lower in the classical CD (48.4 vs. 52.6 nonclassical CD group; P=0.03). Despite QOL at diagnosis being higher in those with nonclassical CD versus lower in those with classical CD, both groups had improved QOL and achieved a similar QOL after following a GFD.

Non-Classical Presentation of Complete Gonadal Dysgenesis in Adolescents

Disorders of sex development (DSD) commonly result from testicular dysfunction either due to developmental defect resulting in complete gonadal dysgenesis (CGD) or androgen synthesis/action causing congenital adrenal hyperplasia (CAH) or androgen insensitivity syndrome (AIS) and are phenotypically females with diverse clinical presentation. CGD is typically associated with absent breast development, streak gonads and hypoplastic mullerian structures. We report two cases of CGD with non-classical presentations highlighting the heterogeneous presentation this diagnosis can have.

Scabies presenting as cutaneous nodules or malar erythema: reports of patients with scabies surrepticius masquerading as prurigo nodularis or systemic lupus erythematosus

Scabies surrepticius is a unifying term that represents non-classical presentations of scabies mite infestation. A patient with scabies surrepticius is described: a man with scabies masquerading as prurigo nodularis. The 91-year-old man had metastatic prostate cancer and presented with diffuse pruritic nodules. Prurigo nodularis was suspected; however, the biopsy revealed scabies mites in the stratum corneum. He was successfully treated with topical permethrin 5% cream and oral ivermectin. In addition, the features of a woman with scabies mimicking systemic lupus erythematosus are summarized. The 47-year-old woman had idiopathic thrombocytopenic purpura and presented with malar erythema and a positive antinuclear antibody (titer 1:320). A diagnosis of systemic lupus erythematous was entertained until skin scraping and mineral oil preparation revealed scabies mites; she was successfully treated with oral ivermectin. In conclusion, Sarcoptes scabiei infestation can present with atypical clinical morphology and an absence of classical lesions such as burrows conventionally distributed in the interdigital web spaces, volar wrists, periumbilical area, or genitalia. Scabies surrepticius is a term that has been designated to describe these unusual presentations. Prurigo nodularis and systemic lupus erythematosus can be added to the litany of conditions masquerading as scabies and are included amongst the guises of scabies surrepticius.

Celiac disease in Saudi children. Evaluation of clinical features and diagnosis.

Objectives:To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease.Methods:All children (<18 years) with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh, Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading.Results:A total of 59 children had confirmed celiac disease. Thirty (50.8%) were male. Median age was 8 years (range 1 to 16 years). The mean duration of symptoms before diagnosis was 2.3 (±1.5) years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease.Conclusion:Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

Celiac Disease in South Jordan.

PurposeCeliac disease, an autoimmune enteropathy triggered by exposure to gluten, is not uncommon in South Jordan. However, its prevalence is underestimated due to lack of physician awareness of the diversity of disease presentation. The clinical spectrum includes classic gastrointestinal manifestations, as well as rickets, iron-deficiency anemia, short stature, elevated liver enzymes, and edema. Our goal was to evaluate celiac disease presentation in clinically diagnosed children.MethodsRetrospective study included all children diagnosed with celiac disease between September 2009 and September 2015. Hospital charts were reviewed. Demographic data, clinical characteristics, and follow-up were recorded.ResultsThirty-five children were diagnosed with celiac disease during the study period. Mean age±standard deviation was 6.7±3.8 years (range, 2.0–14 years). There were 17 (48.6%) female patients. The average duration between onset of symptoms and diagnosis was 16.3±18.7 months. Fifteen (42.9%) patients presented with classic malabsorption symptoms, whereas 7 (20.0%) patients presented with short stature. Positive tissue transglutaminase antibodies (tTg)-immunoglobulin A (IgA) was seen in 34 (97.1%) patients. The one patient with negative tTg-IgA had IgA deficiency. Although tTG-IgA values were not available for objective documentation of compliance, clinical data (resolution of presenting abnormalities and growth improvement) assured acceptable compliance in 22 (62.9%) patients.ConclusionCD in children may present with diverse picture. Although of the small number, the non-classical presentations are not uncommon in our rural community. Gluten-free diet is the main strategy for treatment and associated with usually correction of laboratory abnormalities and improvement of growth.

Non-classical Celiac Disease: Often Missed

Celiac disease (CeD) is an immune-mediated enteropathy triggered by ingestion of gluten in genetically susceptible individuals. CeD is a global disease and estimated to affect approximately one percent of the global population. With advent of simple serological tests for the diagnosis, the number of individuals diagnosed with CeD is increasing exponentially. It was initially thought that gluten hypersensitivity in CeD is limited to small intestine only and all other features are secondary to malabsorption, but it is now recognized that the hypersensitivity to gluten is not limited to small intestine alone and may affect other organs such as skin, brain, and bones independent of intestinal involvement. CeD is now considered a multi-system disorder and their clinical presentation may be with gastrointestinal symptoms, called “classical CeD” or more often with non-gastrointestinal symptoms called “non-classical CeD”. These patients may present with short stature, anemia, liver dysfunction (asymptomatic increase in transaminases, chronic liver disease, autoimmune hepatitis), cutaneous manifestations (dermatitis herpetiformis, oral ulcers), reproductive diseases (infertility, recurrent abortions), neurological manifestations (ataxia, peripheral neuropathy), and metabolic disorders (osteopenia/osteoporosis). What determines these variable phenotypes remain unclear but likely is a result of genetic as well as environmental factors. Many of these patients with non-classical CeD are likely to report to specialists other than gastroenterologists such as hematologists, endocrinologists, rheumatologists or gynecologists. Unfortunately, the awareness about non-classical presentations of CeD amongst health care professionals remains low. There is an urgent need to increase awareness among health care professionals about varied manifestations of CeD in order to decrease the burden of undiagnosed CeD.

Tu1384 The Effect of a Gluten-Free Diet in Celiac Disease Patients With Nonclassical Presentations on Quality of Life, Compared to Celiac Disease Patients With Classical Presentation

Tu1384 The Effect of a Gluten-Free Diet in Celiac Disease Patients With Nonclassical Presentations on Quality of Life, Compared to Celiac Disease Patients With Classical Presentation