Question shared with ENT. Amyloidosis is a localized or systemic deposition of fibrillar proteins. It can be primary or secondary. The most frequently affected organs are the kidneys and the heart. Sometimes amyloid deposits appear on the tongue which can produce macroglossia.

If a patient reports having for months now enlargement of the tongue, with no other alterations of the tongue causing constant biting, which disease would you think of the following:

Orofacial granulomatosis

The enlargement of the tissues of the mouth, lips and face seen in OFG is painless. Melkersson–Rosenthal syndrome is where OFG occurs with fissured tongue and paralysis of the facial nerve. The cause of the facial paralysis is thought to be caused by the formation of granulomas in the facial nerve, which supplies the muscles of facial expression. Causes The cause of the condition is unknown. The disease is characterized by non-caseating granulomatous inflammation. That is, the granulomas do not undergo the caseating ("cheese-like") necrosis typical of the granulomas of tuberculosis.

Amyloidoma of the Tongue: Case Report, Surgical Management, and Review of the Literature.

Localized amyloidosis of the tongue is a benign condition in which surgical management may be considered. The aim of the study was to review the current literature and report a case. We searched the PubMed database for all relevant articles reporting cases of localized tongue amyloidosis published between 1980 and February 2020. In addition, we updated 1 case diagnosed and treated in our department. A 49-year-old male patient presented with an asymptomatic tongue nodule of the dorsum mimicking median rhomboid glossitis. The results of an incisional biopsy showed an amyloid on Congo red staining and positive findings for the κ light chain by immunohistochemical analysis. The findings of the systemic workup were negative. Therefore, a diagnosis of localized κ light-chain amyloidosis was made. The patient underwent a resection of the lesion, and no recurrence or progression was observed during a period of 18 months. The literature review showed 12 reports describing 21 patients (11 men, 52.3%) with localized tongue amyloidosis. The most common clinical presentation was nodular with a single lesion of the tongue dorsum (15 patients, 71.4%). All cases showed positive findings on Congo red staining. Immunohistochemical analysis findings were available for only 9 patients (42.8%) and showed light-chain amyloidosis. No case showed any systemic involvement or the development of systemic disease. Surgical excision was performed in 9 cases, with recurrence at the site of operation in 2 cases. Localized amyloidosis of the tongue is a rare disease in which surgical excision may be therapeutic when a multidisciplinary evaluation does not show any systemic disease. We recommend an excision when the lesion is persistent or shows an enlargement or when discomfort is reported. In the case of any further local recurrence, resection may be repeated.

A foreign body embedded in the mobile tongue masquerading as a neoplasm.

Foreign bodies in a mobile tongue are rarely presented to the laryngologist, because such bodies are commonly lodged superficially and are easily removed by the patients themselves or by general practitioners. Thus, it is rare that a foreign body totally embedded in the mobile part of the tongue presents as an enlarged tongue mass. We have described a 64-year-old female with a 3-month history of an enlarged mass in the anterior right tongue. Physical examination showed a mass located in the anterior right tongue, with intact mucosa and normal color. A benign tongue neoplasm was considered first. However, a fish bone totally embedded in the mobile tongue with granuloma formation was encountered during the incisional biopsy operation. Complete removal of the foreign body with granuloma was achieved under local anesthesia. There was no neuromuscular or neurosensory deficit of the tongue in the follow-up period of 2 years. Although an embedded foreign body in the mobile tongue is a rare condition, it should be considered in the work-up of a patient with an enlarged tongue mass, with or without a history of swallowing a foreign body.

First_Aid_Step1

B . Ataxic GAAit. CN V motor lesion Jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle. CN X lesion Uvula deviates away from side of lesion. Weak side collapses and uvula points away. CN XI lesion Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion (trapezius). The left SCM contracts to help turn the head to the right. CN XII lesion LMN lesion. Tongue deviates toward side of lesion (“lick your wounds”) due to weakened tongue muscles on affected side. Facial nerve lesions Bell palsy is the most common cause of peripheral facial palsy A . Usually develops after HSV reactivation. Treatment: corticosteroids +/– acyclovir. Most patients gradually recover function, but aberrant regeneration can occur. Other causes of peripheral facial palsy include Lyme disease, herpes zoster (Ramsay Hunt syndrome), sarcoidosis, tumors (eg, parotid gland), diabetes mellitus.

[Melkersson Rosenthal syndrome. Presentation of a case].

This a case report of a 24 year old black woman who referred to her physician recurrent episodes of inferior lip enlargement for a period of two years. Remission periods were incomplete, unrelated to any apparent cause and plicate tongue. No improvement was seen with medication, including the use of steroids. Complementary exams were negative except the biopsy which reported granulomatous cheilitis. We conclude that the Melkersson Rosenthal Syndrome must be considered when confronted with a patient who suffers from lip enlargement and pleated tongue, with or without neurological alterations as for example, facial paralysis.

Ultrasonography of the tongue in macroglossia - a case report.

This paper is an attempt to assess the usefulness of ultrasonography in the diagnosis of the enlargement of the tongue (macroglossia). The role of sonography in diagnosing local pathologies of the tongue, such as neoplasms, abscesses or granulomas, has been well-established for 20 years. Rarely is its usefulness considered with respect to diagnosing macroglossia with concomitant systemic diseases. The starting point of these considerations was the presented case of a 59-year-old patient with considerably enlarged tongue. The patient had difficulty speaking and ingesting meals. Moreover, he complained about swelling and pain in the carpal and proximal interphalangeal joints. Tongue ultrasound examination revealed blurred lingual structure with evident, irregular vascular pattern in the color Doppler. The obtained image helped to rule out local pathology of the tongue and directed our diagnostic considerations towards immunoglobulin-related diseases (deposition diseases). We believe that the presented ultrasound image of the tongue was helpful in the diagnostic process. Establishing the final, correct diagnosis was a particularly strenuous process. The suspicion of a deposition disease had been rejected during two previous stays in two hospitals. This was the consequence of a negative diagnostic test of staining tissue deposits with Congo red. An accurate diagnosis occurred to be a rare form of a deposition disease: lambda light chain disease with symptoms of amyloidosis. Such a diagnosis was based on a thorough hematological analysis. A high level of free lambda light chains in the serum was detected and the bone marrow biopsy showed 13% of plasma cells. The patient underwent chemotherapy.

Lingual thyroid--a lesson to learn.

We present a case of a middle-aged woman with a mass in the posterior third of the tongue which was diagnosed as a tongue haemangioma. The tumour was successfully excised via a midline mandibular osteotomy and tongue splitting approach. The histopathology examination, however, revealed the 5x4 cms mass to be a lingual thyroid. The salient features of this unusual presentation of a thyroid enlargement will be discussed.

Orofacial granulomatosis

"Full width" gingivitis (compare with marginal gingivitis). Gingival enlargement (swelling of the gums). Fissured tongue (grooves in the tongue). Enlargement of the mucous membrane of the mouth, which may be associated with cobblestoning and mucosal tags (similar lesions often occur on the intestinal mucosa in Crohn disease). Enlargement of the perioral and periorbital soft tissues (the tissues of the face around the mouth and the eyes). The facial skin may be dry, exfoliative (flaking) or erythematous. Cervical lymphadenopathy (enlarged lymph nodes in the neck). Facial palsy (weakness and altered sensation of the face).

Hemihypoglossal nerve transfer for acute facial paralysis.

The authors have developed a technique for the treatment of facial paralysis that utilizes anastomosis of the split hypoglossal and facial nerve. Here, they document improvements in the procedure and experimental evidence supporting the approach. They analyzed outcomes in 36 patients who underwent the procedure, all of whom had suffered from facial paralysis following the removal of large vestibular schwannomas. The average period of paralysis was 6.2 months. The authors used 5 different variations of a procedure for selecting the split nerve, including evaluation of the split nerve using recordings of evoked potentials in the tongue. Successful facial reanimation was achieved in 16 of 17 patients using the cephalad side of the split hypoglossal nerve and in 15 of 15 patients using the caudal side. The single unsuccessful case using the cephalad side of the split nerve resulted from severe infection of the cheek. Procedures using the ansa cervicalis branch yielded poor success rates (2 of 4 cases). Some tongue atrophy was observed in all variants of the procedure, with 17 cases of minimal atrophy and 14 cases of moderate atrophy. No procedure led to severe atrophy causing functional deficits of the tongue. The split hypoglossal-facial nerve anastomosis procedure consistently leads to good facial reanimation, and the use of either half of the split hypoglossal nerve results in facial reanimation and moderate tongue atrophy.

Craniofacial regeneration

Following facial injury it is also critical to restore nerve function to avoid facial paralysis. Often, patients who received surgery following injury or tumor resection suffer extensive nerve damage. This is a serious problem given the importance of facial expressions and speech for communicating in human society. For many who endure such nerve damage, they recover after 12 months; however, others may never fully recover. While there is not currently much modern medicine can do for these patients, the cutting edge of care is now nerve grafting. These grafts are taken from the masseter muscle, which controls mouth movement, or the hypoglossal nerve which controls the tongue. To avoid denervation caused by lack of stimulus, surgery should be done as soon as possible; however, it is often difficult to determine if a patient will recover naturally or whether nerve grafting is required. Generally this distinction can be made by 6 months post injury and grafting occurs soon after. Nerve

Ancient schwannoma of the tongue: a case report.

A 45-year-old male patient had left sided submucosal swelling extending backwards from the tip of the tongue disturbing articulation and swallowing. Submucosally located lesion was 3 x 2 x 1.5 cm in size and totally excised under local anesthesia. In this article, we present a case of ancient schwannoma of tongue. Although a very rare entity, ancient schwannoma should be considered in differential diagnosis of tongue lesions.

[Successful reanimation of facial paralysis with an indirect anastomosis between hypoglossal nerve and facial nerve, without loss of function of the tongue].

To describe the surgical procedure and the results of the indirect hypoglossal-facial nerve anastomosis using a free nerve graft in patients with facial nerve paralysis. This technique leaves the tongue function intact. Prospective study. Tongue function was assessed in 39 consecutive patients who underwent this procedure and facial reanimation was assessed in 29 of these patients who had completed at least 24 months follow-up. Facial nerve function was judged using the House-Brackmann (HB) facial nerve grading system. Tongue movements were normal in all operated patients; one patient had mild homolateral atrophy. Initial facial movements occurred on average 7.5 months postoperatively (range 4 to 18 months) in all but one patient. The results were graded HB II in 6 patients (20.9%), HB III in 13 (44.6%), HB IV in 7 (24.1%), HB V in 2 (6.8%) and HB VI in 1 patient (3.4%). Hemifacial synkineses were noticeable but no mass movements or gross hypertonia were observed (as are often present in direct hypoglossal-facial anastomosis). The results of facial reanimation were significantly better in young patients and when a short time interval between paralysis and surgery existed. HB grade II was achieved only if the duration of paralysis was less than 12 months. Indirect hypoglossal-facial anastomosis with interposition of a nerve graft allows preservation of tongue function together with good overall facial reanimation, and is therefore to be preferred to the classical direct hypoglossal-facial anastomosis.

Rare amyloidoma of the tongue base: A case report and review of the literature.

Localized amyloidosis is a rare condition characterized by the deposition of misfolding protein in a tissue, without other systemic manifestations. Only a small number of cases of localized amyloidosis of the tongue have been reported to date, in contrast to systemic amyloidosis, in which localization on the tongue is common. This study presents a rare case of localized amyloidosis of the tongue (amyloidoma) and provides a summary of the known literature of localized amyloidosis. This study describes the case of a 36-year-old female who presented with a swelling of the tongue base. The diagnosis of amyloidoma was made based on the findings of the physical examination, head and neck MRI findings and the histopathological examination with Congo red stain under polarized light. The histopathological diagnosis was as follows: Localized lambda light-chain amyloidosis. A thorough physical examination was performed by the ENT and Hematology/Oncology departments, without revealing signs of systemic disease. A series of hematological and imaging tests were also performed to verify that there was no sign of systemic involvement. The patient declined surgical excision and the 2-year follow-up did not reveal any changes in tumor dimension. Although the etiology of localized amyloidosis is yet not clear, the prolonged reaction of tissue plasma cells to environmental antigens may be a causative factor for the initiation of the neoplastic process.

Global assessment of outcomes after varying reinnervation techniques for patients with facial paralysis subsequent to acoustic neuroma excision.

To determine whether there are objective and/or subjective differences in facial function, tongue function and quality of life in patients who have undergone 1) direct facial-to-facial (Primary, 4 patients), 2) direct facial-to-hypoglossal (End-to-End, 7 patients), 3) end-to-side facial-to-hypoglossal nerve anastomoses with sural nerve/greater auricular nerve interposition (End-to-Side with Interposition Graft, 7 patients), and 4) end-to-side facial-to-hypoglossal nerve anastomoses (End-to-Side, 7 patients) after acoustic neuroma excision. Tertiary university referral center. Case series. Twenty-five patients with complete facial paralysis after acoustic neuroma surgery who have also undergone 1 of 4 types of facial musculature reinnervation volunteered for the study. The mean duration of follow-up was 11.5 years (range, 1-25 yr). Each patient was globally assessed using the Sunnybrook Facial Grading scale (objective), Facial Disability Index (subjective), Oral-Pharyngeal Disability Index (subjective), Tongue Movement/Muscle symmetry (objective), and short-form SF-36 quality-of-life index (subjective). Patients who underwent direct facial-to-hypoglossal anastomosis had generally poorer outcomes some of which were statistically significant (p < 0.05) in some components of the Oral-Pharyngeal Disability Index. All of these patients had reduced lateral tongue movement as well as ipsilateral tongue atrophy. There was no significant difference in the Sunnybrook Facial Grading scale scores in those patients in whom end-to-side interposition reinnervation surgery was performed compared with those in whom direct end-to-side anastomosis surgery was performed. Complete sacrifice of the ipsilateral hypoglossal nerve does present with clinically and statistically significant morbidity in patients. Facial function is statistically similar in patients who underwent an end-to-side anastomosis with or without an interposition graft. These findings suggest thatin the setting of the posttranslabryinthine approach, the technicallyeasier interposition graft procedure is not acompromise.

A fast-growing schwannoma of the tongue in a 15-year-old Iranian male: Review of literature and case report.

Schwannoma can be included in the list of differential diagnoses of tongue masses but seems to be a rare finding in the Iranian population. The current case was presented as an exophytic nodular sessile mass which was growing fast.

Split hypoglossal-facial nerve neurorrhaphy for treatment of the paralyzed face.

Several methods of neural rehabilitation for facial paralysis using 12-7 transfers have been described. The purpose of this study is to report on a series for dynamic reinnervation of the paralyzed face by using a split 12-7 nerve transposition. The goals of this procedure are to minimize tongue morbidity and to provide good facial reinnervation. Prospective case series. Melolabial crease discursion, overall facial movement, and degree of tongue atrophy and mobility were recorded. Thirteen patients underwent facial reanimation using a split hypoglossal-facial nerve transfer with postoperative follow-up to 58 months (range, 6-58 months). All patients achieved excellent rest symmetry and facial tone. Of 13 patients, 10 had measurable coordinated movement and discursion of their melolabial crease. Of 13 patients, 12 had mild to moderate ipsilateral tongue atrophy. The mean time to onset of visible reinnervation was 3 months. Split hypoglossal-facial nerve transposition provides good rehabilitation of facial nerve paralysis with reduced lingual morbidity. Long-term rest symmetry and potential learned movement can be achieved. This technique may provide a favorable alternative to the traditional method of complete hypoglossal sacrifice or jump grafting.

Tuberculosis of the tongue clinically masquerading as a neoplasm: a case report and literature review.

Tuberculosis of the tongue is a very rare event even in areas and countries in which tuberculosis is endemic. The disease can present itself in a variety of clinical appearances, most of which may mimic malignant lingual neoplasms clinically. In this case, we present a patient who initially complained of an ulcerated lingual swelling, which was suspected to be a squamous cell carcinoma on clinical examination. In addition, the diagnosis was missed on the first and initial biopsy as it was not representative of the lesion. The diagnosis of lingual tuberculosis was made by histopathology on a second biopsy. In this article, we described the clinicopathological features of tuberculous glossitis with a comparison between our case and other similar reported cases in addition to a literature review.

Facial nerve reconstruction using a split hypoglossal nerve with preservation of tongue function.

A prospective study conducted on 13 patients suffering from complete facial nerve injury (for 4 months up to 2 years) aimed to show that using the split hypoglossal nerve allows for reconstruction of the facial nerve with preservation of tongue function. The hypoglossal nerve was split longitudinally. For each half, a split of the hypoglossal nerve's response was measured intraoperatively by recording the compound muscle action potential of the tongue muscle. The half that showed the least response was selected for anastomosis. The facial nerve was transected at the stylomastoid foramen, and its distal part underwent a direct anastomosis with the selected half of the hypoglossal nerve. The six grades of the House-Brackman grading system were used to analyze the results. The average postoperative follow-up period was 3 years. Before surgery, 12 patients in this study were graded VI, with total paralysis, and 1 was graded V. After surgery, 2 of the 13 patients showed mild dysfunction (grade II), 7 patients showed moderate dysfunction (grade III), 3 patients showed moderately severe dysfunction (grade IV), and 1 patient showed a severe dysfunction (grade V). Microsurgical facial nerve reconstruction using a split hypoglossal nerve results in functional facial nerve improvement with preservation of tongue function.

Abrikossoff's tumor of tongue: Report of an uncommon lesion.

Granular cell tumor, an uncommon neoplasm, can occur at any site in the body, but they are more commonly observed in the head and neck region, especially the oral cavity. A lesion of controversial origin, this entity has to be considered in the differential diagnosis of swellings of the tongue. Immunohistochemical findings obtained in the present case also render support for the neural histogenetic origin for this tumor. Though commonly observed in the fourth to sixth decades of life, we present this case in a 9-year-old female patient.

Distal spinal muscular atrophy type 1

Pathophysiology The pathology underlying the observable characteristics of DSMA1 is cell body degeneration of motor nerves. Specifically, the anterior horn α-motorneurons degenerate within the first six months of life leading to a variety of symptoms. Muscle deterioration increases at around 1–2 years of age, resulting in reduced motor function. The most severely affected muscles include facial muscles and the tongue (which may develop a twitch due to hypoglossal nerve paralysis). Reduced pain sensation and excessive sweating are sometimes observed. Non-ambulant patients may develop pressure ulcers, severe constipation, urinary incontinence, and (rarely) reflux nephropathy in the advanced stages of the disease.

Granular cell tumour of tongue: A case report.

Granular cell tumour, also known as Abrikossoff tumour, is a relatively uncommon benign neoplasm, which is more commonly found in females in the 4th to 6th decades of life even though it can occur in all ages. It occurs in all areas of the body but about 45-65% of all lesions are reported in the head and neck region. Intraoral lesions represent about 70% of the granular cell tumours of the head and neck, and account for 1/3 of all cases affecting the whole body. Most of the intraoral lesions occur on the tongue, usually on the lateral aspect, followed by the buccal mucosa and hard palate. Although majority of granular cell tumours are benign, some are clinically aggressive and a few frankly malignant forms have been reported. Some benign lesions exhibit surface ulcerations and this clinical appearance, combined with the overlying pseudoepitheliomatous hyperplasia, seen histologically, may lead to misdiagnosis of malignancy if adequate biopsy material was not taken. A case of granular cell tumour which occurred on the midline area of the dorsum of the posterior 1/3 of the tongue is reported in a 20-year-old female patient. It is interesting because the patient was younger than the average age of occurrence and the tumour occurred in a similar site to that of a lingual thyroid.

[Hypoglossal-facial nerve cross-over for rehabilitation of the paralyzed face (author's transl)].

Ten patients with unilateral facial nerve paralysis had been treated by hypoglossal-facial nerve approximation in the years 1971-1979. The proximal part of the facial nerve inside the petrous bone and at the inner ear entrance had been destroyed by tumor or accident without chance for repair. Therefore the hypoglossal nerve had been used to contact the intact main tunk and its intact peripheral nerve and mimic muscle system. 3 to 4 epineural nerve sutures had been placed with 8/0 vicryl suture material for approximation. In one patient anastomosis could be obtained by splitting the hypoglossal nerve with remarkable result to the mimic function, while the muscular atrophy of the tongue was minimal. With regard to the results the achieved mimic reinnervation took place in 3,5 to 5 months, but was found to be refined up to 2 years. Oral discomfort, swallowing, and speech disorders lasted 2 1/2 to 6 weeks postoperatively, depending upon the age and the patients mental activity, since the patient has to learn by using his tongue for mimical expressions. The final result obtained a balanced closure of the mouth and eyes, a complete movement of the lips and cheeks, a rarely delayed innervation of the frontal muscles. Due to reinnervation the denervated half of the tongue had developed a marked increase of activity from nerve fiber ingrowth of the intact side. The patient finally feels little to complain about the favourable facial result.

Large mass on base of tongue. Diagnosis: lingual thyroid.

Our patient's tongue mass hadn't bothered her until she became pregnant; that's when it got larger and caused problems swallowing and breathing. A simple test confirmed our suspicions.

Amyloidosis

Oral cavity Amyloid deposits in tissue can cause enlargement of structures. Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste. Tongue enlargement does not occur in ATTR or AA amyloidosis. Deposition of amyloid in the throat can cause hoarseness. Pathogenesis

Outcomes and complications of direct end-to-side facial-hypoglossal nerve anastomosis according to the modified May technique.

The aim of this study was to address the efficiency and safety of direct end-to-side facial-hypoglossal nerve anastomosis for facial palsy rehabilitation. The authors conducted a retrospective study of 12 consecutive procedures performed between December 2000 and February 2006. Facial palsies were caused by the surgical removal of tumors in the brainstem, cerebellopontine angle, or mastoid process. Direct end-to-side facial-hypoglossal anastomosis was performed in each case. Facial function (evaluated using the overall percentage of facial function and House-Brackmann scale grades), as well as tongue trophicity and mobility, were assessed at 6, 12, and 24 months after surgery. Postoperative early and late complications were systematically reviewed. The mean delay between tumoral and reparative surgery was 15.9 +/- 4 months (median 11 months). Preoperatively, the mean percentage facial function score was 11.6 +/- 1.7% (45% of patients with House-Brackmann Grade 5 facial palsy and 55% of patients with House-Brackmann Grade 6). Mean facial function scores increased to 19.3, 32.2, and 43.8% at 6, 12, and 24 months after surgery, respectively. Twenty-four months after surgery, 50% of cases had House-Brackmann Grade 3 facial palsy and 50% had Grade 4. A significantly better recovery at 24 months was observed postoperatively for neural lesions occurring in the mastoid or the brainstem compared with those in the cerebellopontine angle. Tongue hemiparesis was observed in 5 patients (41.7%), 2 of whom had tongue hypotrophy (16.7%). No patient complained of swallowing or speech disturbance. Facial synkinesis was noted in 1 patient (8.3%). Facial recovery after direct end-to-side facial-hypoglossal nerve anastomosis is similar to results observed with end-to-end or end-to-side facial-hypoglossal nerve anastomosis with an interpositional graft. Tongue hypotrophy and palsy were observed in a small number of cases. This procedure allows one to minimize, although not fully prevent, facial synkinesis. The site of the neural lesion appears to be an important factor in the prognosis of recovery.

Oral and maxillofacial pathology

Acquired Causes Carcinoma Lingual Thyroid Myxedema Amyloidosis Consequences Noisy breaths, obstructs airway if severe Drooling Difficult in eating Lisping speech Open-bite Protruding tongue, may ulcerate and undergo necrosis Treatments For mild cases, surgical treatment is not mandatory but if speech is affected, speech therapy may be useful. Reduction glossectomy may be required for severe cases. Ankyloglossia Stafne defect Torus palatinus Torus mandibularis

Ramsay Hunt syndrome type 2

Ramsay Hunt Syndrome Type 2 is estimated to account for 12% of all facial nerve paralysis. It occurs in both immunocompetent and immunocompromised individuals with immunocompromised patients often having more severe disease presentation. RHS may occur in any age group with cases reported in patients ranging in age from 3 months to 82 years. The affected ganglion is responsible for the movements of facial muscles, the touch sensation of a part of ear and ear canal, the taste function of the frontal two-thirds of the tongue, and the moisturization of the eyes and the mouth. The syndrome specifically refers to the combination of this entity with weakness of the muscles activated by the facial nerve. In isolation, the latter is called Bell's palsy. However, as with shingles, the lack of lesions does not definitely exclude the existence of a herpes infection. Even before the eruption of vesicles, varicella zoster virus can be detected from the skin of the ear.

[Benign tumor of the oral cavity: idiopathic granuloma of the tongue].

The diagnosis of granuloma of the oral cavity can favour the detection of several diseases such as sarcoidosis, Crohn's disease, tuberculosis, syphilis and malignant tumors. In Melkerson Rosenthal syndrome it has an idiopathic origin. In this regard, we here report an original case of idiopathic granuloma of the tongue not secondary to Melkerson Rosenthal syndrome and being part of benign tumors of the oral cavity. The study involved a 60-year old female patient, with no particular past medical history, presenting with discomfort during mastication secondary to a swelling on the free edge of the tongue which had occurred one month before her admission. Physical examination showed overgrowth at the level of the right edge of the tongue measuring 15 mm along its longer axis. The tongue was not plicated and there was no cervical adenopathy. The remainder of the physical examination was normal. MRI of the oral cavity showed suspected necrotizing tissue lesion on the right free edge of the mobile tongue measuring 15x12x19 mm without signs of extension to the ipsilateral lingual pedicle or to the floor of the oral cavity and without cervical adenomegalies. Biopsy of tongue lesion showed gigantocellular epithelioid granulomas without caseous necrosis or histological signs of malignancy. Biologically, there was no inflammatory syndrome, leukopenia or lymphopenia. The assessment of an underlying cause was negative: syphilis serology, evaluation of phosphocalcic profile, dosing of the angiotensin-converting enzyme, intradermo tuberculin reaction, chest radiograph, thoracoabdominopelvic CT scan and ophthalmological examination. Finally, the diagnosis of idiopathic granuloma was retained in the absence of arguments in favor of its secondary nature.

Neurology_Adams

neck including carotid endarterectomy. Goodman and coworkers showed a dissecting aneurysm of the carotid artery to have compressed the hypoglossal nerve, with resultant weakness and atrophy of the tongue. Rare instances of temporal arteritis and Takayasu arteritis affecting the carotid artery and adjacent twelfth nerve have been described. Lance and Anthony have described the simultaneous occurrence of nuchal-occipital pain and ipsilateral numbness of the tongue, provoked by the sudden, sharp turning of the head and termed it the neck–tongue syndrome. The phenomenon has been attributed to compression in the atlantoaxial space of the second cervical root, which carries some of the sensory fibers from the tongue, via the hypoglossal nerve, to the C2 segment of the spinal cord.

Transposition of the Intratemporal Facial to Hypoglossal Nerve for Reanimation of the Paralyzed Face: The VII to XII TranspositionTechnique.

The hypoglossal nerve has long been an axonal source for reinnervation of the paralyzed face. In this study, we report our experience with transposition of the intratemporal facial nerve to the hypoglossal nerve for facial reanimation. To determine the feasibility and outcomes of the transposition of the infratemeporal facial nerve for end-to-side coaptation to the hypoglossal nerve for facial reanimation. A case series of 20 patients with facial paralysis who underwent mobilization and transposition of the intratemporal segment of the facial nerve for an end-to-side coaptation to the hypoglossal nerve (the VII to XII technique). Participants were treated between January 2007 and December 2014 at a tertiary care center. Outcome measures include paralysis duration, facial tone, facial symmetry at rest, and with smile, oral commissure excursion, post-reanimation volitional smile, and synkinesis. Demographic data, the effects of this technique on facial tone, symmetry, oral commissure excursion and smile recovery were evaluated. Preoperative and postoperative photography and videography were reviewed. Facial symmetry was assessed with a facial asymmetry index. Smile outcomes were evaluated with a visual smile recovery scale, and lip excursion was assessed with the MEEI-SMILE system. All 20 patients had adequate length of facial nerve mobilized for direct end-to-side coaptation to the hypoglossal nerve. The median duration of facial paralysis prior to treatment was 11.4 months. Median follow-up time was 29 months. Three patients were excluded from functional analysis due to lack of follow-up. Facial symmetry at rest and during animation improved in 16 of 17 patients. The median (range) time for return of facial muscle tone was 7.3 (2.0-12.0) months. A significant reduction in facial asymmetry index occurred at rest and with movement. The MEEI FACE-gram software detected a significant increase in horizontal, vertical, overall lip excursion and smile angle. No patient developed significant tongue atrophy, impaired tongue mobility, or speech or swallow dysfunction. Mobilization of the intratemporal segment of the facial nerve provides adequate length for direct end-to-end coaptation to the hypoglossal nerve and is effective in restoring facial tone and symmetry after facial paralysis. The resulting smile is symmetric or nearly symmetric in the majority of patients with varying degree of dental show. The additional length provided by utilizing the intratemporal segment of the facial nerve reduces the deficits associated with complete hypoglossal division/splitting, and avoids the need for interposition grafts and multiple coaptation sites. 4.

Tongue in cheek.

Apyogenic granuloma is an innocent lesion commonly found on the gingiva, but can occur at other oral sites. A case is reported of a tongue lesion which had been present for 20 years and is unusually large.

Isolated bilateral hypoglossal nerve paralysis following an atlanto-occipital dislocation: A case report.

The present report highlights a case of successful treatment of an 11-year-old male patient who presented with an atlanto-occipital dislocation and multiple fractures of the forearm, pelvis, and lower leg because of a fall. The patient experienced dysarthria and paralysis of the tongue, which became completely immobile and could not be moved from side to side, impeding speech. The patient also experienced dysphagia due to the inability to propel food toward the pharynx and chewing attempts resulted in scattering of food residue throughout the oral cavity. The lack of tongue mobility led to saliva accumulation, forcing the patient to swallow frequently, which was possible as larynx movement was unaffected. The other cranial and motor sensory nerves appeared normal. Our diagnostic examinations confirmed the presence of isolated bilateral paralysis of the hypoglossal nerve secondary to traction at the base of the skull. The patient was still unable to protrude his tongue and tongue gradually atrophied two weeks after admission. Electromyography revealed denervation of the tongue and minimal active contraction of the single motor units. Immobilization therapy and rehabilitation therapy were initiated to improve tongue movement, but this was unsuccessful and one month after the accident, the patient's tongue was still atrophied. The patient was placed on a soft food diet and experienced no difficulty in swallowing either saliva or food three months after admission. Tongue mobility was deemed normal. Electromyography six months after the initial episode revealed normal motor unit potentials during contractions. We postulate that compression and stretching of the bilateral hypoglossal nerves against the greater horn of the hyoid bone was a probable cause of the hypoglossal palsy. The use of immobilization and rehabilitation therapy likely supported the recovery of functionality and resulted in a good prognosis.


Middle-aged male with iron deficiency anemia and increased number of stools, a colonoscopy should be done to rule out colorectal cancer!!! If the HLA is negative it is very unlikely to be celiac disease (high negative predictive value).

Middle-aged male with iron deficiency anemia and increased number of stools, a colonoscopy should be done to rule out colorectal cancer!!! If the HLA is negative it is [HIDDEN] (high negative predictive value).

A 55-year-old man, father of a celiac child, with iron-deficiency anemia and a recent increase in the stool rhythm, has been tested negative for HLA-DQ2 and HLA-DQ8 alleles. Which diagnostic test is the most appropriate in this case?

Determination of anti-transglutaminase IgA antibodies.

Prudence is necessary in the application of the new ESPGHAN criteria for celiac disease omitting duodenal biopsy: a case report.

New guidelines for celiac disease (CD) diagnosis from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) propose the option to omit the duodenal biopsy in the diagnosis of CD. For this option, all four of the following criteria have to apply in children and adolescents: signs and symptoms suggestive of CD, anti-transglutaminase type 2 antibody (anti-TG2) levels more than 10 times the upper limit of normal, positive confirmation tests of anti-endomysium-IgA antibodies (EMA), and at-risk HLA-DQ2 or HLA-DQ8. Here, we report the case of a female patient, 2 years old, with chronic diarrhea that started after an acute viral gastroenteritis. The patient had anti-TG2 levels of more than 10 times the upper limit of normal, positivity for EMA, antigliadin IgA, and IgG (AGA-IgA, AGA-IgG, respectively), and the at-risk HLA-DRB1*0301, DQB1*0201/DRB1*10, DQB1*0501 genotype, thus fulfilling all criteria for the diagnosis of CD. Although the diarrhea disappeared after about 5 weeks, anti-TG2, EMA, and AGA-IgG remained positive. Therefore, a duodenal biopsy was performed and evidenced a normal mucosa (Marsh 0). After about 18 months, the antibody titer for AGA-IgG, anti-TG2, and EMA became negative. The patient was all the time on a normal, gluten-containing diet. This clinical case represents an exception to the new ESPGHAN guidelines for CD diagnosis. During 5 weeks, the new ESPGHAN criteria were all fulfilled, allowing to propose for this patient the diagnosis of CD without performing a duodenal biopsy. Therefore, a prudent approach is suggested when the pediatric gastroenterologist makes a diagnosis of CD without duodenal biopsy.

AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review.

The purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents. The recommendations outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management. Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase-immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing. Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis. Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis. Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended. Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency. Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD). Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future. Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing. Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA. Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology. Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter. Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA.

[Celiac disease:a case report detailing clinical and pathological improvement with a gluten-free diet].

Celiac disease has a morbidity of 0.2 to 1% in Europe and the United States (US), but appears to be extremely rare in Japan with only a few case reports. This report details a Japanese woman with celiac disease diagnosed by histopathological findings and the improvement of her clinical symptoms on a gluten-free diet. The woman was in her 60s and presented with diarrhea, abdominal pain, and vomiting which were repeatedly exacerbated over several weeks. Therefore, she was referred to our hospital for a detailed examination and treatment. Upper gastrointestinal endoscopy revealed a crude granular mucosa with an erythematous color in the duodenum. No special findings were noted on colonoscopy or capsular endoscopy. Histopathological ﬁndings of the duodenum noted villous atrophy, crypt hyperplasia, and lymphocytic inﬁltration within the surface epithelium, which were suspicious for celiac disease. A gluten-free diet was started which resulted in improved clinical symptoms. Repeat endoscopic imaging and histopathological ﬁndings after initiation of the gluten-free diet demonstrated improved small bowel villous atrophy. In this case, appropriate testing had ruled out inflammatory bowel disease, amyloidosis, infectious enteritis, parasitic disease, and allergies. Although anti-gliadin antibody (AGA) and anti-tissue transglutaminase antibody (ATTGA) were serologically negative, and HLA typing was HLA-DQ6, the patient was ultimately diagnosed as having celiac disease based on the characteristic pathological findings and clinical course. In many cases of celiac disease reported in Japan, serum antibodies such as AGA and ATTGA have not been detected, and HLA testing has been negative for DQ2 or DQ8. Therefore, it is possible that celiac disease in Japan might have different genetic and immunological characteristics than the disease in the US and Europe. In the future, additional cases with histology and molecular biological analysis are necessary to test this hypothesis.

Controversies in the laboratory diagnosis of celiac disease in children; new haplotypes discovered.

The latest consensus on celiac disease in 2008, under the auspices of the International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, shows that HLA DQ2/DQ8 typing indicates the highest negative predictive value for celiac disease, which would exclude the diagnosis of celiac disease. In Romania, there are no studies on the implication of HLA-DQ2/DQ8 in celiac disease in children. The aim of our study was to analyze the significance of genetic tests, with a focus on negative HLA-DQ2/DQ8 cases, as well as to determine the main haplotypes involved in celiac disease in children. We tested in 37 children with old celiac disease, confirmed based on the presence of intestinal villi changes on duodenal biopsy, the IgA anti-tissue transglutaminase antibodies (TgA-IgA) by ELISA and the IgA anti-endomysium antibodies (EmA-IgA) by indirect immunofluorescence, compared to HLA-DQ2/DQ8 typing by polymerase chain reaction (PCR). In 25 children, the determined HLA haplotypes predominantly belonged to DQ2, and in 3 children we report the presence of a new haplotype, DR3-DQ2/DR4-DQ8, formed by pattern 1, DR3-DQ2-the DQA1*0501 and DQB1*0201 alleles, and pattern 5, DR4-DQ8-the DQA1*0301 and DQB1*0302 alleles. In 9 children, genetic tests were negative for celiac disease. The identification of HLA-DQ2/DQ8 provides additional data in the diagnosis of celiac disease, but a rigid algorithm in the diagnosis of celiac disease has no practical applicability.

What a practitioner needs to know about celiac disease?

Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and is characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes and enteropathy. CD is triggered by wheat gluten and related prolamines in barley and rye. Worldwide, the disease affects approximately 1 % of the general population. Clinical features of CD vary considerably. Intestinal symptoms are more common in young children. In older children extra intestinal manifestations affecting almost all organs are seen. IgA tTG antibody, upper GI endoscopy with histological analysis of multiple biopsies of the duodenum and in selected cases HLA DQ2 and DQ8 positivity and endomysial antibodies (EMA) are needed for diagnosis. Currently, the only treatment for CD is a life-long gluten-free diet (GFD). Strict avoidance of wheat, rye, barley and their derivatives will result in intestinal healing and relief of symptoms for the majority of individuals with CD. The GFD is simple in principle, however, completely eliminating all foods and ingredients containing wheat, rye, barley, and most commercial oats can be very challenging. Newly diagnosed CD children should undergo testing and treatment for micronutrient deficiencies specially iron, folic acid, vitamin D, and vitamin B12. Long-term monitoring and follow up of patients with CD is necessary.

Gluten-related disorders

Eliminating the possibility of CD can generally also be done by adding HLA-DQ typing. The absence of HLA-DQ2 and HLA-DQ8 has a very high negative predictive value for CD, and the predictive value can be further enhanced by including HLA-DQ7.5 (HLA-DQ2 and HLA-DQ8 are found in coeliac disease 98% of the time in Caucasians, HLA-DQ7.5 present in the remaining 1.6% and only 0.4% of Caucasians are missed with the combination of these three). Without serological or HLA-DQ2/8 positivity, celiac disease is likely not present. HLA-DQ typing has a practical advantage in that it is the only diagnostic test that allows to exclude CD when a person is already on a gluten-free diet; however, as not only celiacs are HLA-DQ2/HLA-DQ8 positive, this method has a higher false positive rate than anti-TG2 and EMA antibody testing.

Celiac disease: the new proposed ESPGHAN diagnostic criteria do work well in a selected population.

The need for an early and accurate diagnosis in celiac disease (CD) has focused attention on new diagnostic approaches, based on the efficiency of serological markers and the high negative predictive value of human leukocyte antigen (HLA) non-DQ2/8. We performed a retrospective review of all of the patients suspected of having CD who had undergone a small bowel biopsy in our gastroenterology unit. All symptomatic children with serological marker at time of biopsy (immunoglobulin A-tissue transglutaminase antibody, endomysial antibody, and HLA genotype) were included. The triple test (TT) was positive if immunoglobulin A-tissue transglutaminase antibody was 10 times the upper limit of normal, plus positive endomysial antibody plus human leukocyte antigen-DQ2/DQ8. A total of 150 patients met the inclusion criteria and were enrolled in the study. One hundred sixteen were positive for the TT; 113 of 116 (97.4%) had a Marsh 2/3 histological lesion and had been considered to have CD. Thus, positive predictive value of the TT was 97.4%. The other 3 cases (2.6%) had Marsh 0/1 lesion, so we consider them to be false-positives for the TT; however, on follow-up, all 3 children developed histological damage after a gluten challenge. Finally, the positive predictive value of the TT was 100%. Thirty-four patients were negative for the TT: 22 patients are celiac, 3 are celiac but challenge gluten diet is pending, and the 9 patients left have other gastrointestinal disorder. Our study supports the view that in selected children who are symptomatic and positive for the TT, CD diagnosis could be established independent of histological findings.

Non-celiac gluten sensitivity

Many people remove gluten from their diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them to be suffering from irritable bowel syndrome, and some may eliminate gluten before seeking medical attention. This fact can diminish the CD serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies. In these cases, patients should be tested for the presence of HLA-DQ2/DQ8 genetic markers because a negative HLA-DQ2 and HLA-DQ8 result has a high negative predictive value for celiac disease. If these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies. However, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients. Gluten challenge is also

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

Coeliac disease

Other antibodies such as anti–Saccharomyces cerevisiae antibodies occur in some people with coeliac disease but also occur in other autoimmune disorders and about 5% of those who donate blood. Antibody testing may be combined with HLA testing if the diagnosis is unclear. TGA and EMA testing are the most sensitive serum antibody tests, but as a negative HLA-DQ type excludes the diagnosis of coeliac disease, testing also for HLA-DQ2 or DQ8 maximises sensitivity and negative predictive values. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) does not (as of 2015) recommend the use of HLA typing to rule out coeliac disease outside of a specialist setting, for example, in children who are not having a biopsy, or in patients who already have limited gluten ingestion and opt not to have a gluten challenge. Endoscopy

Clinical utility of celiac disease-associated HLA testing.

Negative predictive value (NPV) of celiac disease (CD)-related human leukocyte antigens (HLA) DQ2 and DQ8 approaches 100 % in individual patients. However, studies evaluating its exclusionary utility in patient groups are lacking. We aim to assess the performance of HLA testing when applied to patient groups with varying characteristics and propose evidence-based recommendations for its clinical use. Demographic and clinical information was recorded in patients undergoing HLA testing. Using predetermined criteria, patients were classified as CD, non-CD, or indeterminate. Diagnostic yield of HLA testing was defined as the percentage of patients in whom CD could be excluded based on negative HLA test. Two hundred and fifty-six patients underwent testing for CD-related HLA DQ2 and DQ8. 102 (100 non-CD, 2 CD) patients tested HLA negative for a 98 % NPV and 39 % diagnostic yield. Diagnostic yield was highest (60 %) in patients with intraepithelial lymphocytosis plus normal IgA tissue transglutaminase antibody (IgA-tTG) and lowest in patients with positive IgA-tTG plus villous atrophy (0 %). CD was diagnosed in two HLA-negative patients, who carried half of DQ2.5 trans genotype. Diagnostic yield of CD-related HLA testing varies widely depending on clinical indication. HLA testing is a practical and valuable test for most patients in whom initial evaluation for CD is inconclusive. A negative HLA result usually obviates the need for further celiac testing including endoscopy and gluten challenge. Rarely, in patients reported as HLA negative, half of HLA DQ2.5 (cis or trans) is sufficient for development of CD.

Duodenal lymphocytosis

Antibodies associated with coeliac disease were reported in around 11% of cases. These IgA endomysial antibodies and anti-transglutaminase antibodies are very sensitive and specific for coeliac disease implying that this proportion of duodenal lymphocytosis cases has definite coeliac disease. Around 33% of cases have the HLA-DQ2 allele, which is found in over 90% of people with coeliac disease. Absence of HLA-DQ2 (and the rarer HLA-DQ8) makes coeliac disease most unlikely. As antibody-negative coeliac disease is recognised, HLA status, persistence or progression of the duodenal IEL numbers following a gluten challenge, followed by symptomatic improvement on a gluten-free diet, has been used to be more certain about the diagnosis, which was made in 22% of one series of over 200 adult cases.

SERONEGATIVE CELIAC DISEASE IN BRAZILIAN PATIENTS: A SERIES OF CASES.

Celiac disease (CD) is an autoimmune disease characterized by immune reaction mostly to wheat gluten. The diagnosis is based on clinical, serological and histological findings in patients ingesting gluten. Cases that the clinical profile indicates CD and the autoantibodies are negative bring so a dilemma for the professional, as the risk of missed the diagnosis or a delay at the same. To show the importance of correct diagnosis of cases with seronegative celiac disease (SNCD). Ten cases of SNCD Brazilian patients were retrospectively studied (2013 to 2019). Data of clinical complaints, autoantibodies, IgA serum levels, histological findings and HLA-DQ2/DQ-8 were compiled. Dual-X densitometry, delay at diagnosis, previous autoimmune diseases and family history of CD were also checked. All SNCD patients presented clinical symptoms of CD, with confirmed diagnosis by histological findings of the duodenal mucosa and HLA-DQ2 and/or HLA-DQ8 positivity. All patients had normal IgA levels and negative autoantibodies (IgA-anti-transglutaminase and anti-endomysial). Dual-X densitometry detected osteopenia in two women and osteoporosis in two males, all with low levels of vitamin D. Delay diagnostic ranged from 1 to 19 years. Familiar occurrence of CD was reported in 40% of the cases. After one year of gluten-free diet, eight patients refer improve of symptoms, while duodenal biopsies, done in five cases, showed histological improvement. Patients who demonstrate the clinical profile of celiac disease with negative serology and normal levels of IgA, especially those who have family members with celiac disease, should be submitted to duodenal biopsies to look for histological findings.

Gluten-related disorders

A four-of-five rule was proposed 2010 for confirming celiac disease, with the disease confirmed if at least four of the following five criteria are satisfied: typical symptoms of celiac disease; positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer; human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes; celiac enteropathy at the small bowel biopsy; and response to the gluten-free diet. For diagnosis of wheat allergy, allergy tests are available. Treatment For people with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date; For people diagnosed with non-celiac gluten sensitivity, there are still open questions concerning for example the duration of such a diet. The results of a 2017 study suggest that non-celiac gluten sensitivity may be a chronic disorder, as is the case with celiac disease.

Non-celiac gluten sensitivity

To evaluate the possible presence of celiac disease, specific serology and duodenal biopsies are required while the person is still on a diet that includes gluten. Serological markers Serological CD markers (IgA tissue transglutaminase , IgA endomysial [EmA] and IgG deamidated gliadin peptide [DGP] antibodies) are always negative in those with NCGS; in addition to specific IgA autoantibody levels, it is necessary to determine total IgA levels. IgG antibodies should be checked in selective IgA deficiency, which can be associated with celiac disease and occurs in as many as one in 40 celiac patients.

Coeliac disease

If all these antibodies are negative, then anti-DGP antibodies (antibodies against deamidated gliadin peptides) should be determined. IgG class anti-DGP antibodies may be useful in people with IgA deficiency. In children younger than two years, anti-DGP antibodies perform better than anti-endomysial and anti-transglutaminase antibodies tests. Because of the major implications of a diagnosis of coeliac disease, professional guidelines recommend that a positive blood test is still followed by an endoscopy/gastroscopy and biopsy. A negative serology test may still be followed by a recommendation for endoscopy and duodenal biopsy if clinical suspicion remains high.

Gluten-related disorders

Diagnosis A literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (CD) and wheat allergy. Persons suspected of having celiac disease may undergo serological testing for IgA anti-tissue transglutaminase antibodies (abbreviated anti-tTG antibodies or anti-TG2 antibodies) and anti-endomysial antibodies (abbreviated EMA) provided the IgA-level is high, and if IgA is low, testing for certain IgG antibodies; in case of positive serological indication, a duodenal biopsy may confirm active celiac disease.

Non-celiac gluten sensitivity

The prevalence of undiagnosed celiac disease has increased fourfold during the past half-century, with most cases remaining unrecognized, undiagnosed and untreated, leaving celiac patients with the risk of long-term complications. Some people with NCGS may indeed have celiac disease. A 2015 systematic review found that 20% of people with NCGS presenting with HLA-DQ2 and/or HLA-DQ8 haplotypes, negative serology, and normal histology or duodenal lymphocytosis had celiac disease. The presence of autoimmune symptoms in people with NCGS suggests the possibility of undiagnosed celiac disease. Autoimmune diseases typically associated with celiac disease are diabetes mellitus type 1, thyroiditis, gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and others. To evaluate the possible presence of celiac disease, specific serology and duodenal biopsies are required while the person is still on a diet that includes gluten.

Indolent T cell lymphoproliferative disorder of the gastrointestinal tract

Celiac disease: A high proportion of patients with CD4+ ITCLD-GT and rare cases of CD8+ ITCLD-GT have been misdiagnosed as having celiac disease. Unlike celiac disease, ITCLD-GT: a) is unresponsive to gluten-free diets: b) is negative for antigens detected in standard celiac disease serology blood tests such as anti-transglutaminase antibodies; c) has infiltrating clonal T cells which do not express HLA-DQ2 or HLA-DQ8 human leukocyte antigens; and d) have lesions populated by mature, slowly proliferating clonal T cells which are CD56- and either CD4+, CD8+, CD4+/CD8+, or CD4-/CD8-. However, rare patients have been inflicted with both celiac disease and ITCLD-GT.

Is routine duodenal biopsy necessary for the detection of celiac disease in patients presenting with iron deficiency anemia?

Iron deficiency anemia (IDA) is one of the well recognized presentations of celiac disease (CD). According to the lack of data from our population in this regard, we determined the prevalence of CD in patients presenting with IDA to see if it is worthwhile to do a precise screening for CD in such patients. This cross-sectional study was conducted on patients referred with IDA to Poursina Hakim Gastroenterology Clinic, Isfahan (IRAN). All included patients underwent upper gastrointestinal endoscopy and duodenal biopsy. Histopathological changes were assessed according to the Marsh classification. Also, patients were evaluated for IgA anti-tissue transglutaminase (t-TG) antibody with enzyme-linked immunosorbent assay (ELISA) technique. CD was defined as having Marsh II or above histopathology or being seropositive with Marsh I histopathology and having a good response to gluten free diet (GFD). During the study, 130 patients with the mean age of 35.5±13.7 (67.7% female [20.4% post-menopausal]) were undergone seropathological studies. According to histopathological study and a clinical response to GFD, 13 patients (10%) were ultimately diagnosed with CD. Nine patients (6.9%) were seropositive, from which, five patients (3.8%) were ultimately diagnosed as CD cases. IgA anti-tTG became negative in all of these patients after six months of GFD. CD should be considered in any adult patient presenting with unexplained IDA, even if not accompanied with gastrointestinal symptoms. Routine duodenal biopsy performed during diagnostic upper gastrointestinal endoscopy is worthwhile in order to investigate for CD as an underlying cause of IDA in adult patients.

Gluten-Associated Medical Problems -- Evaluation -- CD

Positive serology and a high probability of celiac (regardless of serology) will necessitate a small bowel biopsy. Pathology is varied, and staining methods can identify areas of villous atrophy. Video capsules sometimes reveal classic features of the disease and alleviate the need for biopsy. This is especially true in more distal disease. The disease is confirmed when serology and pathology are compatible, and there is the resolution of symptoms and pathology with a gluten-free diet. In case there is still a diagnostic dilemma after all these steps, genetic testing for susceptibility with HLA DQ2/DQ8 check is required. A negative test will rule out celiac. Occasionally a gluten challenge is needed, and serology/pathology response to gluten challenge will yield the diagnosis. [24]

Prevalence, human leukocyte antigen typing and strategy for screening among Asian first-degree relatives of children with celiac disease.

Data on prevalence, human leukocyte antigen (HLA) typing and small bowel histology among first-degree relatives of subjects with celiac disease (CD) is scarce. This prospective study evaluated the prevalence and role of HLA DQ2/8 testing in screening of first-degree relatives of children with CD. Thirty confirmed children with CD and 91/94 first-degree relatives (parents and siblings) were enrolled. HLA DQ2/8 testing was carried out in all index CD cases. Clinical evaluation with a questionnaire, total serum immunoglobulin A (IgA), human IgA-tissue transglutaminase (IgA-tTGA) and HLA DQ2/8 testing was carried out in all first-degree relatives. Subjects who were positive for IgA-tTGA were recommended endoscopic duodenal biopsy to document histological changes of CD. Nine first-degree relatives were positive for IgA-tTGA, seven underwent duodenal biopsy and four subjects had Marsh IIIa changes suggestive of CD. The prevalence of histologically confirmed CD in first-degree relatives was 4.4%. The prevalence of potential CD was 9.8%. IgA-tTGA-positive subjects (4/9) were significantly more often symptomatic than IgA-tTGA-negative first-degree relatives (2/82). Twenty-nine (96.6%) index cases of CD and all IgA-tTGA-positive first-degree relatives were positive for HLA DQ2. None of the index CD cases or first-degree relatives were HLA DQ8-positive. A total of 85% of the first-degree relatives were positive for HLA DQ2 and thus at risk of developing CD. In this first Asian study on a limited number of families of children with CD, 4.4% of the first-degree relatives had CD. Only 15% of the first-degree relatives were negative for HLA DQ2/DQ8. Initial evaluation with HLA and serology followed by only serial serology in HLA-positive relatives is recommended.

Non-celiac gluten sensitivity

In people with duodenal lymphocytosis – following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) – a high count of celiac disease cells (or CD/CD3 ratio) in immunohistochemical assessment of biopsies, or the presence of IgA anti-TG2 and/or anti-endomysial intestinal deposits, might be specific markers for celiac disease. Catassi and Fasano proposed in 2010 that in patients without celiac disease antibodies, either lymphocytic infiltration associated with IgA subepithelial deposits or a histological response to a gluten-free diet, could support a diagnosis of celiac disease. Wheat allergy The clinical presentation may be sufficient in most cases to distinguish a wheat allergy from other entities. It is excluded when there are normal levels of serum IgE antibodies to gluten proteins and wheat fractions, and no skin reaction to prick tests for wheat allergy. Nevertheless, these tests are not always completely reliable.

Dermatitis herpetiformis

The diagnosis may be confirmed by a simple blood test for IgA antibodies against tissue transglutaminase (which cross-react with epidermal transglutaminase), and by a skin biopsy in which the pattern of IgA deposits in the dermal papillae, revealed by direct immunofluorescence, distinguishes it from linear IgA bullous dermatosis and other forms of dermatitis. Additionally, the concomitant diagnosis of Celiac disease can be made without the need for a small-intenstinal biopsy if an individual has biopsy-confirmed dermatitis herpetiformis as well as supporting serologic studies (elevated levels of IgA tissue transglutaminase antibodies, IgA epidermal transglutaminase antibodies, or IgA endomysial antibodies). These tests should be performed before the patient starts on a gluten-free diet, otherwise they might produce false negatives.

Non-celiac gluten sensitivity

Celiac disease The main goal in diagnosing NCGS is to exclude celiac disease. NCGS and celiac disease cannot be separated in diagnosis because many gastrointestinal and non-gastrointestinal symptoms are similar in both diseases, and there are people with celiac disease having negative serology (absence of specific celiac disease antibodies in serum) or without villus atrophy. There is no test capable of eliminating a diagnosis of a celiac disease, but such a diagnosis is unlikely without confirming HLA-DQ2 and/or HLA-DQ8 haplotypes.

Duodenal lymphocytosis

Helicobacter infection is a common finding at endoscopy and although duodenal IEL counts were found to be slightly higher with this infection, this was not considered to be a meaningful cause in children. Other infections, including Cryptosporidiosis and Giardiasis can also be associated with an increase in IELs. Management The management is that of any identified associated disorder such as a gluten free diet for cases with coeliac disease or treatment of associated infections. Prognosis When duodenal lymphocytosis is associated with other features of coeliac disease, in particular positive antibodies, or HLA-DQ2/8 and a family history, treatment with a gluten-free diet produces an improvement in IEL numbers. Diarrhoea, thyroiditis, weakness and folate deficiency were other predictors of the development of gluten sensitivity and coeliac disease, which developed in 23 of 85 patients over 2 years in one series. References Gastrointestinal tract disorders Inflammations Pathology

Fingertip rapid point-of-care test in adult case-finding in coeliac disease.

Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose. As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects. In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive. The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.

The prevalence of celiac disease among family members of celiac disease patients.

Celiac disease (CD) is more common in certain risk groups. Family members of known celiac patients represent the most important group. Serological screening enables us to detect patients before they develop serious complications. HLA typing has also proven to be a valuable diagnostic tool, especially in excluding the disease. To assess the prevalence of CD among family members, we screened 106 first-degree relatives (73 parents, 33 siblings; mean age 27.9 years) of 45 celiac patients in NE Slovenia. We analysed antigliadin (AGA) and antiendomysium (EMA) antibodies. Levels of IgG and IgAAGA were determined using the ELISA method, and EMA using indirect immunofluorescence. Serologically positive patients were recalled for intestinal biopsy and were HLA typed. Intestinal biopsy was performed by peroral aspiration capsule or during upper GI endoscopy. Biopsy specimens were examined histologically. Six family members (5.67%) were both AGA IgG and EMA positive, and one (0.94%) was only EMA positive. All were either HLA DQ2 or DQ8 positive. Nine family members (8.49%) were only AGA IgG positive, two of them lacked the HLA DQ susceptibility alleles. Intestinal biopsy was performed in six family members, and the diagnosis of CD confirmed in five. All were both AGA IgG and EMA positive. They were either symptom-free or had only mild gastrointestinal symptoms, and carried the known HLA DQ risk alleles. The minimum prevalence of CD among family members in NE Slovenia can therefore be estimated at 4.72%. The prevalence of CD among first-degree relatives is much higher than the prevalence of the disease in the general population. Most of these patients have an atypical form of the disease and would therefore be overlooked without an active search. Serological testing is recommended for all first-degree relatives of CD patients; they should also undergo HLA typing to detect those whose HLA phenotype is consistent with CD. This approach can also help in excluding individuals who do not need further diagnostic procedures for CD.

Cost-effectiveness analysis of strategies for diagnosing celiac disease.

To compare strategies for diagnosing celiac disease (CD). A decision analytic model was used to compare five strategies on diagnostic performance and costs. First, tTG screening alone is the least costly strategy ($22/individual). While the NPV is high (99.8%), the PPV is low (63.4%). Second, if tTG-positive patients undergo esophagogastroduodenoscopy (EGD) to confirm CD, the PPV increases to 100% ($2,237/false-positive diagnosis avoided). Third, if EGDs are restricted to only those who are both tTG and HLA DQ2/8 positive, costs are slightly reduced ($59 vs. $63/individual), while PPV and NPV remain unchanged. Fourth, screening tTG-negative patients for IgA deficiency increases the NPV to 99.9% ($32,605/false-negative diagnosis avoided). Sensitivity analyses revealed that as the prevalence of CD increases, the cost of avoiding a false-positive diagnosis by adding EGD to the tTG alone strategy increases considerably. When the pre-test probability of CD is low, patients with positive tTG serology should undergo EGD with biopsy-either directly or after positive screening for HLA DQ2/8-to confirm CD. As the pre-test probability of CD increases, the added cost of EGD should be weighed against the consequences of a false-positive diagnosis. Routinely screening for IgA deficiency in order to avoid a false-negative diagnosis is quite costly.

Gluten-related disorders

Antibodies to α-gliadin have been significantly increased in non-celiacs individuals with oral ulceration. Anti-α-gliadin antibodies are frequently found in celiac disease (CD), to a lesser degree subclinical CD, but are also found in a subset who do not have the disease. Of people with pseudo-exfoliation syndrome, 25% showed increased levels of anti-gliadin IgA. Other people that are also at risk are those taking gluten despite having the disorder, or whose family members have CD. In addition people with autoimmune conditions are also at risk for CD. It has just been found that there is a risk of death in CD. Therefore, gluten intake should be limited before or even after the diagnosis. One-fourth of people with Sjögren's syndrome had responses to gluten; of five that had positive response to gluten, only one could be confirmed as CD and another was potentially , the remaining three appeared to be gluten-sensitive. All were HLA-DQ2 and/or DQ8-positive.

Non-celiac gluten sensitivity

Duodenal biopsies in people with NCGS are always almost normal – an essential parameter for diagnosis of NCGS, although is generally accepted that a subgroup of people with NGCS may have an increased number of duodenal intraepithelial lymphocytes (IELs) ( ≥25/100 enterocytes), which represent Marsh I lesions. Nevertheless, Marsh I is considered compatible with celiac disease and the most frequent cause of these findings, especially in people positive for HLA DQ2 and/or DQ8 haplotypes, is celiac disease, with a prevalence of 16-43%.

Gluten challenge test

Today, with serological testing (determination of coeliac disease-specific antibodies in the blood) and duodenal biopsy with histological testing being available for diagnosing coeliac disease, patients with suspected coeliac disease are strongly advised to undergo both serological and biopsy testing before undertaking a gluten-free diet. People who present minor damage of the small intestine often have negative blood antibodies titers and many patients with coeliac disease are missed when a duodenal biopsy is not performed. Serologic tests have a high capacity to detect coeliac disease only in patients with total villous atrophy and have very low capacity to detect cases with partial villous atrophy or minor intestinal lesions with normal villi. Currently, gluten challenge is no longer required to confirm the diagnosis in patients with intestinal lesions compatible with coeliac disease and a positive response to a gluten-free diet. Nevertheless, in some cases, a gluten challenge with