Alpha-Gal Syndrome in Children: Peculiarities of a “Tick-Borne” Allergic Disease

The alpha-gal syndrome is an allergic syndrome that comprises two clinical pictures: an immediate hypersensitivity to drugs containing alpha-gal and a delayed hypersensitivity to the ingestion of red mammalian meat. This allergic syndrome is often under-recognized, and patients are mislabeled with diagnosis as spontaneous urticaria or idiopathic anaphylaxis. Even though less frequently, children could also be of interest, especially in tick-endemic areas. In most cases, a positive anamnesis for tick bites months before the onset of symptoms is recorded. The clinical manifestations could range from asymptomatic cases to severe anaphylaxis. The most frequently used diagnostic test is the determination of specific IgE for alpha-gal. Oral provocation test is usually reserved to unclear cases or to verify tolerance after diet. No long-term follow-up studies have been published, although an elimination diet could lead to a decrease of specific IgE for alpha-gal and a possible reintroduction of some avoided foods. This paper provides a literature review, focused on pediatric age, and an evaluation of available diagnostic tests. We analyze the correlation between tick bites and symptom onset and unfold the different clinical pictures to help clinicians to promptly recognized this syndrome. Lastly, we address unmet needs in this specific allergy.

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Case Report: Eosinophilic Myenteric Ganglionitis in a Child With Hirschsprung's Disease: A Challenge in Pseudo-Obstruction

Frontiers in Pediatrics ◽

10.3389/fped.2020.617309 ◽

2021 ◽

Vol 8 ◽

Author(s):

Enza D'Auria ◽

Valeria Calcaterra ◽

Luciano Maestri ◽

Milena Meroni ◽

Giorgio Giuseppe Orlando Selvaggio ◽

...

Keyword(s):

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Clinical Symptoms ◽

Abdominal Distension ◽

Specific Ige ◽

Elimination Diet ◽

Long Term Follow Up ◽

Functional Intestinal Obstruction ◽

Infectious Enterocolitis

Introduction: The presentation of eosinophilic myenteric ganglionitis (EMG) can be similar to that of Hirschsprung's disease (HD). In a limited number of cases of pediatric patients, the diagnosis of both EMG and HD are reported. A case of pseudo-obstruction in EMG occurring in a child with HD diagnosis is discussed with literature review.Case Presentation: A boy aged 2 years and 6 months presented with intractable constipation and abdominal distension. Histological HD diagnosis was carried out and transanal Soave pullthrough was performed. At the age of 3 years and 2 months, an infectious enterocolitis occurred. One month later, he presented with constipation, marked abdominal distension and melena. Full thickness colonic biopsies revealed eosinophilic myenteric ganglionitis. Specific IgE tests were positive for several foods. Dietary exclusion was adopted with resolution of clinical symptoms and histologic remission.Conclusion: EMD may occur in patients with HD. At the onset, EMD may be associated with functional intestinal obstruction. The use of an elimination diet proved effective for the relief of symptoms. Long term follow-up is mandatory to define the timing of the reintroduction of foods.

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КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ПИЩЕВЫХ АЛЛЕРГЕНОВ ЖИВОТНОГО ПРОИСХОЖДЕНИЯ

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/raj.2019.1-1.53221 ◽

2019 ◽

Author(s):

A.N. Pampura ◽

E.E. Varlamov

Keyword(s):

Clinical Manifestations ◽

Red Meat ◽

Cross Reactivity ◽

Allergic Reactions ◽

Essential Nutrients ◽

Animal Products ◽

Food Animal ◽

Mammalian Meat

Продукты животного происхождения обладают наиболее сбалансированным комплексом необходимых нутриентов, поэтому их включение в пищевой рацион оправданно в различные возрастные периоды. Клинические проявления аллергии к данным продуктам крайне разнообразны. Одним из ключевых аспектов обозначенной проблемы является диагностика и оценка вероятности развития перекрестной реактивности. К пищевым продуктам животного происхождения, наиболее часто индуцирующим симптомы, относятся коровье молоко, куриное яйцо, рыба, моллюски, ракообразные, мясо млекопитающих. В представленной статье изложены данные об основных классах пищевых аллергенов животного происхождения, индуцирующих развитие перекрестных аллергических реакций. Описаны синдромы, связанные с перекрестной реактивностью: птица-яйцо , кошка-свинина , рыба-курица и -Gal-синдром/ синдром красного мяса .Animal foods products contain the most balanced complex of essential nutrients. The clinical manifestations of allergy to these products are varied. Key aspect of this problem is diagnostics and assessment of cross-reactivity. The food animal products that more often induce symptoms include cows milk, hens egg, fish, mollusks, crustaceans, mammalian meat. Data on the main classes of food animal allergens inducing the development of cross-allergic reactions as well as syndromes associated with cross-reactivity like bird-egg , cat-pork , fish-chicken and a-Gal-syndrome/ red meat syndrome are described in this article.

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POS0083 USEFUL EXPERIENCE OF RHEUMATOLOGISTS FOR UNDERSTANDING OF THE DISEASE ORIGIN AND APPROACHES TO THERAPY IN FIBRODYSPLASIA OSSIFICANS PROGRESSIVA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4307 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 249.2-250

Author(s):

I. Nikishina ◽

S. Arsenyeva ◽

V. Matkava ◽

A. Arefieva ◽

M. Kaleda ◽

...

Keyword(s):

Heterotopic Ossification ◽

Kinase Inhibitor ◽

Inflammatory Diseases ◽

Clinical Manifestations ◽

Fibrodysplasia Ossificans Progressiva ◽

Rapid Progression ◽

Time Duration ◽

Long Term Follow Up ◽

Vertebral Bodies ◽

The One

Background:Many monogenic genetic conditions, such as auto-inflammatory diseases (AIDs), have similar clinical manifestations and immunopathogenesis to “classic” rheumatic diseases (RD). Such cases may include Fibrodysplasia ossificans progressiva (FOP), an extremely rare genetic disease, which, according to our previous study and data from other authors1, may represent an example of AID with catastrophic heterotopic ossification due to a mutation in the ACVR1 gene. it seems that the experience of rheumatologists, especially children’s ones, will be useful in the treatment of FOP.Objectives:To analyzed the dynamics of clinical manifestations and to therapy approaches including target anti-inflammatory drug Tofacitinib (TOFA) in the one of the world’s largest groups of patients (pts) with FOP.Methods:The study was based on the analysis retrospective and prospective observation of the 35 pts (17 males and 18 females) with a verified diagnosis of FOP for the period from 1998 to 2020. In 9 pts with severe course of FOP TOFA administration were evaluated.Results:In all 35 pts the diagnosis was verified by “classic” FOP phenotype: malformed great toes in 33 pts (94,3%); short malformed thumbs-8 (22.8%); peripheral osteochondromas-20 (57.1%); abnormalities of the cervical spine-32 (91.4%), multiple heterotopic ossifications-32 (91,4%). Genetic tests were done in 26, it confirmed mutation in the ACVR1 gene in 100%. Long term follow-up detected a lot of spondyloarthritis-like signs similar to the manifestation of RD: ankylosis of the facet joints and vertebral bodies (by the type of syndesmophytes) in most pts, sacroiliitis, confirmed by radiological methods (X-ray, CT, MRI), gradual ankylosis in the peripheral joints in 18 (56.4%), synovitis in large joints in 8 (25%) pts (knee and hip mostly). In 9 pts with the most difficult course with rapid progression of ossification due to continuous flares despite the NSAIDs and steroids intake, we tried to use TOFA after the approval of the local Ethic Committee. We use the similar dose to randomized trial for JIA (up to 5 mg twice a day). The first patient was 16 y.o. at the time of TOFA administration in December 2019, the age of the other pts was from 2 to 12 y.o. By present time duration of TOFA therapy is from 6 to 15 mo. For the previous 6 months before TOFA initiation the number of flares was in average 8 per patient. After 6 months of TOFA treatment the number of new flares decreased to 0-1, except youngest patient of 2 y.o. in whom the number of flares decreased from 10 to 4 per the same period. In all 9 pts we minimize the dose or completely stop the steroids. New nodes formation stopped immediately in most pts and also the significant motion improvement of large (shoulder) joints were established. Drug tolerance was good in all pts, no AE were registered. But despite the good clinical effect without new heterotopic ossification in our first patient, we found continuous intraskeletal ossification between vertebral bodies, facet and sacroiliac joints in MRI.Conclusion:We are confident that the processes of heterotopic ossification in FOP are very similar to new born formation phenomenon in spondyloarthritis and reliable suppression of inflammation can interrupt the progression of the disease. We used similar justifications to our colleagues for the use of anti-cytokine drugs, but used a JAK-kinase inhibitor, it was extremely important the oral rout of drug administration and possibility to escape any injections in FOP. TOFA demonstrated positive effect and safety in children with severe course of FOP. It showed their advantages over the use of steroids and possibility to inhibit the rate of progression.References:[1]R.Haviv et al. Is fibrodysplasia ossificans progressiva aninterleukin-1 driven auto-inflammatory syndrome? Pediatric Rheumatology (2019) 17:84 //doi.org/10.1186/s12969-019-0386-6Disclosure of Interests:None declared.

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Food antigen-specific IgE in dogs with suspected food hypersensitivity

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.1055/a-1274-9210 ◽

2020 ◽

Vol 48 (06) ◽

pp. 395-402

Author(s):

Sandra A. Baumann ◽

Cornelius Fritz ◽

Ralf S. Mueller

Keyword(s):

Clinical Relevance ◽

Specific Ige ◽

Elimination Diet ◽

Cross Reactivity ◽

Food Hypersensitivity ◽

Strong Correlations ◽

Odds Ratios ◽

Cross Reactions ◽

Ige Reactivity ◽

Food Specific Ige

Abstract Objective Knowledge of cross-reactions in food-sensitive dogs will influence the choice of elimination diets and the long-term management of those patients. The objective of this study was to evaluate food allergen-specific IgE tests of suspected allergic dogs for concurrent positive reactions as possible evidence for cross reactions between allergens. Material and methods Results of serum IgE tests from 760 suspected allergic dogs submitted to 2 laboratories were evaluated statistically. After the tested allergens were grouped by their phylogenetic relationship, odds ratios as well as a sensitivity analysis of the odds ratios were performed to evaluate if concurrent positive IgE results to 2 allergens occurred more often than expected. Results Within related allergen pairs 27% (laboratory 1) and 72% (laboratory 2) of the pairs could be considered as associated. For the unrelated allergen pairs only 6.8% and 10.6% of the analyzed pairs were considered associated respectively. Strong correlations were shown in the group of ruminant allergens, especially beef and lamb, and grain allergens. High rates of concurrent reactions were also detected in the poultry group, especially between chicken and duck, as well as between pork and ruminant allergens, and soy and grain allergens. Conclusion As our results showed not only correlations within related but also between non-related allergens, the possible relevance of carbohydrate moieties as well as panallergens for canine hypersensitivities warrants further study. Further investigations are necessary to distinguish co-sensitization from cross-reactions and determine the clinical relevance of food-specific IgE reactivity. Clinical relevance Due to possible cross reactivity related allergens, especially beef and lamb as well as grain allergens, should not be used for an elimination diet to avoid false results.

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Minimally invasive debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis: a long‐term follow‐up study

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-03988-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jianbiao Xu ◽

Leiming Zhang ◽

Rongqiang Bu ◽

Yankang Liu ◽

Kai-Uwe Lewandrowski ◽

...

Keyword(s):

Minimally Invasive ◽

Clinical Manifestations ◽

Operation Time ◽

Intervertebral Discs ◽

Intraoperative Ct ◽

Long Term Follow Up ◽

Invasive Method ◽

Vertebral Bodies ◽

Adjacent Segments

Abstract Background Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. Methods From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. Results Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. Conclusions Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.

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Prospective study of 5-day challenge with penicillins in children

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000734 ◽

2020 ◽

Vol 4 (1) ◽

pp. e000734

Author(s):

Birgitte Tusgaard Petersen ◽

Josefine Gradman

Keyword(s):

Prospective Study ◽

Children And Adolescents ◽

Provocation Test ◽

Specific Ige ◽

Hypersensitivity Reactions ◽

Skin Reactions ◽

Full Dose ◽

Culprit Drug ◽

Drug Provocation Test ◽

Registration Number

ObjectivesTo examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions.DesignSubjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home.ParticipantsChildren and adolescents aged 0–18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included.ResultsA total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1–8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3–6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT.ConclusionIn children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE.Trial registration numberNCT04331522

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Total thymectomy for thymic lymphoepithelioma-like carcinoma—report of two cases

Surgical Case Reports ◽

10.1186/s40792-019-0706-6 ◽

2019 ◽

Vol 5 (1) ◽

Author(s):

Sachi Kawagishi ◽

Naoko Ose ◽

Masato Minami ◽

Soichiro Funaki ◽

Takashi Kanou ◽

...

Keyword(s):

Surgical Resection ◽

Thymic Carcinoma ◽

Clinical Manifestations ◽

Staging System ◽

Early Recurrence ◽

Anterior Mediastinum ◽

Total Resection ◽

Distant Lymph Node Metastasis ◽

Long Term Follow Up

Abstract Background Thymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized. Case presentation Two patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease. Conclusion We report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.

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P208 A case of double positivity

Rheumatology ◽

10.1093/rheumatology/keab247.203 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Salema Khalid ◽

Jordan Li ◽

Steven Young Min

Keyword(s):

Clinical Manifestations ◽

Kidney Injury ◽

Position Sense ◽

Joint Position Sense ◽

Small Vessel Vasculitis ◽

Double Positive ◽

Vasculitic Neuropathy ◽

Antibody Titres ◽

Long Term Follow Up ◽

Dominant Disease

Abstract Background/Aims In the absence of renal or lung involvement, the investigation of small vessel vasculitis does not routinely include checking of anti-glomerular basement membrane (GBM) antibodies. We present a patient with an MPO-ANCA positive vasculitic neuropathy who later developed anti-GBM positive glomerulonephritis. We review the literature on patients who are “double-positive” for ANCA and GBM antibodies and speculate on the utility of routinely screening all vasculitis patients for GBM antibodies in the absence of manifestations of Goodpasture’s syndrome. Methods We describe a 70 year old female who presented feeling generally unwell with reduced mobility due to discomfort in her feet. Examination was unremarkable, except for reduced temperature and joint position sense in the feet. CRP was elevated and she was found to have a weakly positive MPO titre of 32. She was treated as an MPO-ANCA positive vasculitis and neuropathy with steroids and Mycophenolate Mofetil, with a good clinical and biochemical response. Fifteen months into her treatment, routine monitoring revealed an acute kidney injury with a creatinine of 459 umol/l from a baseline of 88. Anti GBM titres were requested for the first time as part of the renal screen. MPO antibody titres were only 9, but GBM antibody titres were markedly elevated (>200). Renal biopsy showed focal necrotising glomerulonephritis, in keeping with anti-GBM disease. She was treated with steroids, cyclophosphamide and plasma exchange by the renal physicians. She remains dialysis dependant. Results In our patient, GBM antibodies were only requested once she developed relevant clinical manifestations of anti-GBM disease. This in contrast to nephrology practise, where ANCA and GBM antibodies are routinely requested simultaneously in the context of nephritis. It could be speculated that if the GBM antibody status had been detected sooner, we may have altered her management and possibly improved her disease course. Anti-GBM disease and ANCA-associated vasculitis are both rare conditions. However, co-existence of the two uncommon diseases in individual patients is well-described and more than chance occurrence. A study showed that 5% of ANCA-positive cases were also positive for anti-GBM antibodies, while one-third of anti-GBM positive samples had detectable ANCA. Multiple studies have shown that low level ANCA antibodies develop months to years before onset of anti-GBM disease, as seen in our patient as well.The dominant disease phenotype in double positive patients is anti-GBM disease rather than vasculitis. It is very rare for isolated anti-GBM disease to relapse. In contrast, half of double positive patients experience disease relapse and therefore, require long-term follow-up and maintenance immunosuppression. Conclusion Awareness of this double positive phenomenon is important. Rheumatologists do not routinely check anti-GBM in all vasculitis. This case highlights the importance of doing so, especially in atypical presentation of vasculitis or in relapse and refractory disease. Disclosure S. Khalid: None. J. Li: None. S. Young Min: None.

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Current Diagnosis and Management of Cervical Spondylotic Myelopathy

Global Spine Journal ◽

10.1177/2192568217699208 ◽

2017 ◽

Vol 7 (6) ◽

pp. 572-586 ◽

Cited By ~ 45

Author(s):

Joshua Bakhsheshian ◽

Vivek A. Mehta ◽

John C. Liu

Keyword(s):

Natural History ◽

Cervical Spondylotic Myelopathy ◽

Early Recognition ◽

Clinical Manifestations ◽

High Quality ◽

Diagnosis And Management ◽

Imaging Characteristics ◽

Cervical Sagittal Alignment ◽

Long Term Follow Up ◽

The Cost

Study Design: Review. Objectives: Cervical spondylotic myelopathy (CSM) is a major cause of disability, particular in elderly patients. Awareness and understanding of CSM is imperative to facilitate early diagnosis and management. This review article addresses CSM with regard to its epidemiology, anatomical considerations, pathophysiology, clinical manifestations, imaging characteristics, treatment approaches and outcomes, and the cost-effectiveness of surgical options. Methods: The authors performed an extensive review of the peer-reviewed literature addressing the aforementioned objectives. Results: The clinical presentation and natural history of CSM is variable, alternating between quiescent and insidious to stepwise decline or rapid neurological deterioration. For mild CSM, conservative options could be employed with careful observation. However, surgical intervention has shown to be superior for moderate to severe CSM. The success of operative or conservative management of CSM is multifactorial and high-quality studies are lacking. The optimal surgical approach is still under debate, and can vary depending on the number of levels involved, location of the pathology and baseline cervical sagittal alignment. Conclusions: Early recognition and treatment of CSM, before the onset of spinal cord damage, is essential for optimal outcomes. The goal of surgery is to decompress the cord with expansion of the spinal canal, while restoring cervical lordosis, and stabilizing when the risk of cervical kyphosis is high. Further high-quality randomized clinical studies with long-term follow up are still needed to further define the natural history and help predict the ideal surgical strategy.

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