bluuebunny/crossref_metadata_2025 huggingface dataset:
44 Pediatric onset systemic lupus erythematosus (p-SLE)
Authors: Maher Sheren
Published: October 2022

Background

Pediatric onset Systemic lupus erythematosus (p-SLE) is multisystem autoimmune disease with disease onset before the 18th birthday. It is a highly complex disease with marked heterogeneity between patients, causing anything from mild to life-threatening disease.

Objective

To assess thrombomodulin (TM) and D-dimer levels in pediatric systemic lupus erythematosus patients and their correlation to disease activity.

Methods

This study included 40 children diagnosed with systemic lupus erythematosus. They were grouped according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score into group (A) [Mild activity] included 20 children with SLEDAI score less than or equal to 4, group (B) [Moderate-high activity] included 20 children with SLEDAI score >4. Also, 40 apparently healthy children were included as a control group. They were age and sex matched, with the children having SLE.

Results

The two studied groups had significantly higher TM level than controls, furthermore group B had significantly higher TM level than group A (p< 0.008 in all). The two studied groups had significantly higher frequency of abnormally high TM level than controls, furthermore group B significantly had higher frequency of abnormally high TM level than group A (p< 0.02 in all). SLE children had significantly higher D dimer level than controls, furthermore group B had significantly higher D dimer level than group A (p≤ 0.006 in all). The two studied groups had significantly higher frequency of abnormally high D dimer level than controls, furthermore group B had significantly higher frequency of abnormally high D dimer level than group A (p≤ 0.03 in all). TM had a significant positive correlation with SLEDAI score as r = 0.342 and p = 0.031. D dimer had a significant positive correlation with SLEDAI score as r = 0.42 and p = 0.007.

Conclusion

Thrombomodulin and D dimer are potentially valuable markers of the disease activity and thrombotic tendency in p SLE patients. Thus, regular evaluation may be useful for early detection of thrombotic complications.
45 Juvenile systemic lupus erythematosus: about a series of 35 cases
Authors: El Qadiry R , Nassih H , Bourrahouat A , Ait Sab I
Published: October 2022

Background

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system with a wide range of disease manifestations, and can lead to significant morbidity and even mortality.

Objectives

To describe the epidemiology, common clinical features, complications, and management of SLE in children.

Methods

A single center retrospective descriptive study of 35 children with SLE.

Results

There were 27 (77%) girls and 8 (22.9%) boys. The mean age at diagnosis was 9 ± 2 years, with extremes of 3 and 15 years. Systemic involvement was in the form of protracted fever in 62.8%, nephrotic syndrome in 37%, nephritic syndrome in 40%, thrombotic microangiopathy in 8.6%, isolated proteinuria in 25.7%, acute kidney injury in 25.7%, malar rash in 48.6%, arthritis in 57%, neurolupus in 17%, serositis in 11.4%, and hemolytic anaemia in 28.6%. Coexisting autoimmune conditions were systemic sclerosis, antiphospholipid antibodies syndrome and Gujerat-Sjogren syndrome. Two cases had severe pancreatitis as a revealing pattern. Posterior uveitis was present in one case. Meanwhile, pulmonary involvement was seen in two cases (interstitial lung disease and recurrent pneumonia). Proliferative lupus nephritis was found in kidney biopsy in 48.6%. Four cases had end stage kidney disease and had hemodialysis sessions. Management consisted of hydroxychloroquine at 5 mg/kg/day and oral steroids at a starting dose of 2 mg/kg/day in all cases, while pulses of methylprednisolone were prescribed in 57%. Other immunomodulatory treatments used were IV cyclophosphamide in 34.4%, mycophenolate mofetil in 51.4%, azathioprine in 8.6%, tacrolimus in 5.7%, rituximab in 11.4%, and methotrexate in 2.8%. Evolution was marked by stabilization in 42.8% and recurrent flares in 28.6%. Meanwhile six cases were lost to follow-up and four cases died. The reasons for mortality were severe disease activity (seen in two cases), infection and macrophage activation syndrome (in one case each).

Conclusion

Management of juvenile SLE can be challenging especially when there is severe systemic involvement. Disease damage, side effects of drugs and frequent hospitalization have major effect on the quality of life of pediatric patients.
49 Autoimmune hemolytic anemia revealing a familial systemic lupus erythematosus
Authors: Hatem Rouag , Seif Zayani , Alaa Akid , Emna Sfar , Tesnime Ghedira , Radhia Hadj Salem , Chokri Chouchane , Farah Thabet , Slah Chouchane
Published: October 2022

Background

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease; whose pathogenesis remains poorly understood. The genetic susceptibility to lupus is supported by the high concordance rate of the disease in monozygotic twins (29–57%) compared with dizygotic twins (2%), and by the existence of familial lupus (10–12%). Furthermore, SLE shares genetic and environmental risk factors, as well as pathophysiologic mechanisms with autoimmune hemolytic anaemia (AIHA), which is clearly over-represented in patients with SLE and often occurs before the diagnosis of the underlying disease.

Objective

We report a case of familial SLE in two siblings, in whom, the main symptom was AIHA.

Case report

A twelve-year-old girl was referred to our Pediatric department for polyarthralgia, asthenia and anorexia developing over the previous 4–6 months. Regarding family history, she is born of a non-consanguineous marriage and has a 7-year-old brother who has been followed for 2 years for AIHA of undetermined aetiology. The examination upon admission objectified a splenomegaly and jaundice. The laboratory workup revealed an autoimmune hemolytic anaemia: haemoglobin: 7.2 g/dl, positive Coombs' test with specific anti globulin IgG and C3d; unconjugated bilirubin (45 µmol/l) and reduced haptoglobin (0.01 g/l). These findings being very evocative of SLE, an antinuclear antibody (AAN) assay was positive at 1/400. The formal SLE diagnosis was established according to the EULAR/ACR 2019 criteria; with a score of 12 (AIHA: 4; positive antiphospholipid antibodies: 2; positive anti-Sm antibodies: 6). The therapeutic management based on corticosteroids at a dose of 1 mg/kg/day, with a favorable clinical and biological outcome. In light of this diagnosis, the case of the aforementioned brother was reviewed, and a familial lupus was suspected. A physical examination and a several biological explorations were done, the results of which allowing to retain the diagnosis of SLE with EULAR/ACR 2019 score of 10 (ANA > 1/80, AIHA : 4, positive anti-phospholipid antibodies: 2, proteinuria: 4)

Conclusion

Since the new criteria EULAR/ACR 2019 have made it possible to diagnose incomplete forms of lupus, the challenge remains to detect autoimmune thyroiditis, antiphospholipid syndrome, complement deficiencies and other entities that are associated with familial lupus according to scientific literature.
56 Prevalence and severity of infections in patients with systemic autoimmune diseases on biotherapy
Authors: Hiba Ben Ayed , Sarra Ben Yacoub , Manel Boudokhane , Rym Bourguiba , Zeineb Teyeb , Mariem Ayari , Taieb Jomni , Imen Abdelaali , Syrine Belakhal , Hedi Dougui Mohamed
Published: October 2022

Introduction

The prognosis of chronic inflammatory diseases has been transformed by the use of biologic drugs. However, there is evidence of an increased risk of infection in patients undergoing biotherapy. The objective of our study was to investigate the frequency and the severity of infections in patients on biotherapy.

Methods

We conducted a retrospective descriptive study including all patients followed in the internal medicine department of the ISF hospital and treated with biotherapy over a period of 14 years [2009–2022].

Results

We identified 50 patients treated with biologic therapy among 76 patients. The patient’s mean age was 48 years± 12.5 [23–76] and male to female ratio (M: F) was 1 :6. The mean age at initiation of biotherapy was 41.3 ± 11.6 [17–68] years. The molecules used were TNFα inhibitors in 82% of cases, rituximab in 14% of cases and tocilizumab in 4%. Infectious complications were identified in 20 patients. Infections occurred after a mean duration of 12 months [0.5–36] after the initiation of biotherapy. They affected the skin in nine cases, the bronchopulmonary tract in seven cases, the central nervous system in four cases, the gastrointestinal tract in three cases, and the upper respiratory tract in two cases. The infection was bacterial in 16 cases (64%), viral in five cases (20%) and fungal in four cases (16%). We report five cases of tuberculosis (TB), including four cases of pulmonary TB and one case of neuro-meningeal TB. The infection was severe, requiring hospitalization in only eight cases (32%). The median duration of hospitalization was 12 days [2–58]. The infectious episode led to temporary interruption of biotherapy in six cases and definitive interruption in two cases. No deaths were noted.

Conclusion

Our study confirms the increased susceptibility to infections in patients treated with biologics. These infections, often bacterial, are in the majority of cases benign. However, tuberculosis remains frequent.
57 Ocular tuberculosis: a differential for chronic panuveitis
Authors: Thakkar Monali , Migowa Angela
Published: October 2022

Background

Mycobacterium tuberculosis is an organism responsible for causing chronic granulomatous inflammation leading to active or latent tuberculosis (TB). Both pulmonary and extrapulmonary infections; including the skin, the eye, the cardiovascular, genitourinary and gastrointestinal systems can occur. Within the eye, it can cause global disease ranging from anterior or posterior uveitis to retinal TB. Within this abstract we demonstrate a case of chronic panuveitis with a diagnosis of ocular TB.

Methodology

Retrospective chart review

Results

We reviewed a 9-year-old- male in the rheumatology outpatient clinic who was on treatment for ocular TB with methotrexate 2.5 mg once a week, prednisone 5 mg once a day, maxitrol eye drops once a day and prednisolone eye drops twice a day.

He presented with a red, painless left eye with deteriorating vision 2 years ago. Functional enquiry was unremarkable. He was noted to have a fixed dilated left pupil at 3-4mm but other examinations were normal. Extensive investigations were carried out, including an Interferon-gamma release assay (IGRA)- which was positive. Toxoplasma antibody test, Treponema pallidum Haemagglutination test, and chest X-ray were all negative. He was then started on the above-mentioned therapies with marked improvement.

A decision on increasing the methotrexate dose if steroid tapering showed no improvement was undertaken and a plan on reassessing the patient with ANA, ACE and HLA B51 was made, to ensure complete workup.

Discussion and conclusion

Intra or extra ocular TB (OTB) manifestations may result as a direct inoculation of the organism in ocular fluid or as a systemic immune response initiated by an infection from a distant site. There is a myriad of ocular manifestations of OTB which make forming a clinical diagnostic criterion difficult. The gold standard for diagnosis is an ocular fluid culture showing organisms but the yield may be low and the risk of damage to surrounding structures may be high. PCR tests done on the sample may yield clinical information but non ocular tests, such as the IGRA and tuberculin tests may also be employed. Therapy depends on active vs latent disease and mainly involves anti-inflammatory agents and anti-TBs.

Ocular TB may lead to sudden and irreversible blindness with high socioeconomic implications and hence, an index of suspicion in areas with a high disease burden should be kept as diagnosis poses a challenge.
58 Comparison of the 2015 pediatric diagnostic criteria for Behcet’s disease with the 2014 and 1990 International Study Group Diagnostic Criteria
Authors: El Ouassifi K , Sakhi A , Bouayed K , Zoukal S , Nani S
Published: October 2022

Background

Behçet's disease is a multisystem vasculitis whose pathogenesis remains unclear. Although usually described in young adults, it may begin in childhood. The diagnosis is clinical, based on international criteria. The limitations of early diagnosis are related to the progressive onset of symptoms and the variety of differential diagnoses at this age in the absence of a pathognomonic diagnostic test.

Objectives

To report the epidemiological features of our series and to compare the 2015 pediatric criteria with the 2014 and 1990 international criteria.

Materials and Methods

This is a monocentric, retrospective study of 31 children over an 11-year period from January 2011 to December 2021. All patients suspected with Behcet's disease by a pediatric rheumatologist were included in the study, the 2014 international criteria “ISG 2014” being the gold standard classification criteria used in our center.

Results

31 cases of Behcet's were collected. The mean age was 10 years (5.5–16) ± 2.87 years. A female predominance is noted with a sex ratio F/M of 1.21. A quarter of the patients were from a consanguineous marriage and 38.7% had a family history of Behcet disease. Mucocutaneous manifestations were represented by recurrent oral aphthosis 87.1%, genital aphthosis 29%, pseudofolliculitis 48.4%, erythema nodosum 6.5% and acne lesions 3.2%. The pathergy test was positive in 1 case. Ocular involvement was reported in 29% and joint involvement in 45.2%. Thromboembolic complication was seen in 9.6% and neurobehcet in one patient. The HLA B51 antigen was present in 45.2% of cases. In our series 38.7% respond the pediatric criteria, while 61.3% met the 2014 international criteria and 35.5% met the 1990 international criteria. The 2015 pediatric criteria have respectively a sensitivity and specificity of 63.2% and 100% (p = 0.002) compared with the 2014 international criteria taken as gold standard, as well as the 1990 international criteria with a respective sensitivity and specificity of 52.6% and 91.7% (p = 0.034).

Conclusion

Our study highlights a female predominance, a high rate of consanguinity and familial Behcet. The sensitivity and specificity of the 1990 pediatric and international criteria appear to be better than those of 2014, with a more significant trend for the 2015 pediatric criteria (p = 0.002).
59 Behçet disease with CNS thrombophlebitis
Authors: Boutrid N , Rahmoune H , Bioud B , Amrane M
Published: October 2022

Background

Behçet's disease is a peculiar vasculitis that affects both small and large vessels of the arterial and venous circulations.

Objectives

We present the case of two school-aged boys who presented with acute cerebral venous thrombosis, leading to the diagnosis of Behçet’s disease.

Case presentation

- An 8-year-old boy is admitted for severe headaches with nausea. The clinical examination notes a febrile child with marked aphtosis (with a history of genital “burns”). ESR and CRP are slightly elevated, while cerebral CT angiography reveals superior sagittal sinus occlusion. Angio-MRI confirms thrombophlebitis.

- Another 9-year-old boy is referred for abdominal and spinal pain with intense headaches; accompanied with a subacute fever for >15 days. CT angiography revealed (reveals) stenosis of the longitudinal sinuses.

For both children, the pathergy test, skin biopsy, and ophthalmic examination completed the whole picture of the Behçet disease.

Discussion

Major vascular manifestations of Behçet's disease include venous and/or arterial occlusion and aneurysm.

Cerebral venous thrombosis (CVT) is very particular and might lead to an intracranial hyper-pressure, as in our cases.

Steroids remain the initial reference treatment, with particular attention to anticoagulation and the addition/relay with colchicine.

Conclusion

Cerebral venous thrombosis may reveal Behçet's disease, especially in the pediatric population.

The prognosis is poor and requires a rigorous, multidisciplinary follow-up.
62 Rachialgia of difficult diagnosis: an unusual clinical form!
Authors: Yettou S , Hafirassou N , Dahou-Makhloufi C
Published: October 2022

Background

Spinal pain is a frequent symptom whose aetiology can be extremely varied. It is not only the prerogative of adults; it is frequent in children and particularly in adolescents.

Inflammatory spinal pain is a warning sign that should prompt further investigations to rule out an underlying pathology such as infectious spondylodiscitis, malignant pathology, ankylosing spondylitis or SAPHO syndrome.

In this case, we report on a 15-year-old child with uncommon inflammatory spinal pain that caused diagnostic difficulties.

Observation

The child B.A., aged 15 years, with no previous history, consulted for inflammatory back pain that had been evolving for >3 months in a context of apyrexia and conservation of the general state, associated with pain of the anterior thoracic wall. The clinical examination revealed an exaggerated dorsal kyphosis, a lumbar spinal syndrome. The rest of the joint examination was without abnormalities and the somatic examination revealed a retention acne. Biologically, there was no inflammatory syndrom, brucella serology and tubeculin TST were negative.

An X-ray and a CT scan of the dorsal-lumbar spine showed multiple bone erosions of the vertebral plates and a fracture of the T6 and T7 vertebrae with global disc pinching, without recession of the posterior wall or damage to the soft tissues and with exaggeration of the dorsal cyphosis at this level. The spinal MRI revealed a spondylodiscitis with hypo T1 hyper T2 signal at the T6-T7 level without any collection. An osteolytic lesion of the sternal manubrium lateralized to the left with blurred contours was objectified by the CT scan of the anterior chest wall. Bone scans revealed intense hyper fixation foci at the T6-T7 level and the sternal manubrium. MRI of the sacroiliac joints was normal. A scan-guided biopsy of the T6-T7 level did not show any specific lesion. In view of the inflammatory spinal pain, the anterior chest wall pain, the negativity of the biological tests and the imaging data, the diagnosis of incomplete SAPHO syndrome was retained after having ruled out other etiologies. SAPHO syndrome is a rare entity that refers to the association of a heterogeneous set of cutaneous and osteoarticular manifestations with a common denominator of an aseptic inflammatory process. It remains a diagnosis of elimination.

Conclusion

Spinal pain in children can be a symptom of multiple etiologies and sometimes poses a diagnostic problem. This is a particular observation and deserves to be reported because unusual clinical forms of SAPHO syndrome exist and should not be ignored.
63 Dental aspects in osteogenesis imperfecta type IV
Authors: Boutrid N , Rahmoune H , Bioud B , Amrane M
Published: October 2022

Background

The term “dentinogenesis imperfecta” includes dental anomalies quite similar to hereditary opalescent dentin and osteogenesis imperfecta.

We present dental findings in a boy with osteogenesis imperfecta type IV

Case Presentation

A young boy was referred to the pediatric department for management of vertebral compression and a recurrent femoral fracture without obvious trauma.

The appearance of his teeth with the overall assessment of this patient reveals dentinogenesis imperfecta compatible with osteogenesis imperfecta type IV, associated with major vertebral involvement

Discussion

Osteogenesis imperfecta (OI), also known as also known as « brittle bone disease » is a heterogeneous group of rare genetic diseases involving connective tissue.

A reduction in the amount of normal collagen leads to Type I, while qualitative and quantitative abnormalities in collagen synthesis lead to Types II, III and IV of OI.

This type IV is subdivided into groups A and B: the group B depicting the characteristic dentinogenesis imperfecta like in our patient.

Conclusion

Dentinogenesis imperfecta is a major sign of osteogenesis imperfecta. Skeletal phenotype, scleral colour and deafness complete the picture allowing the final classification of this inherited disorder

The peculiar bone lesions with normal dental aspects are highly suggestive of the extreme rare osteogenesis imperfecta type IV.
64 Conical teeth? Think outside the box!
Authors: Boutrid N , Rahmoune H , Bioud B , Amrane M
Published: October 2022

Background

Ectodermal dysplasias (ED) are inherited disorders involving congenital abnormalities of different ectodermal structures, the most prominent presentation being adontia/hypodontia

In this article, we present a brief overview of several pediatric cases of ED with a short review of the odontological manifestations.

2. Case reports

We report several cases of children consulting in the pediatric department for abnormal teeth, with or without systemic manifestations.

The clinical examination of these patients revealed insufficient and abnormal dentition, with rare beveled teeth and thin and rare hair, as well as eyelashes and eyebrows.

Also, parents reported episodes of hyperthermia without sweating from an early age.

Dental radiography confirmed the diagnosis of ectodermal dysplasia.

3. Discussion

Ectodermal dysplasias (EDs) are a group of various inherited disorders involving abnormal congenital development of at least two ectodermal structures (hair, nails, teeth, and sweat glands). The management of these rare disabling conditions is still mainly symptomatic. The traditional removable prosthesis can be an option to replace missing teeth. However, implants provide the best long-term results and prognosis. In particular, dental implants are commonly used in oral reconstruction of ED patients, but long-term data on bone augmentation and bone resorption, aesthetic outcomes, and implant success are needed.

4. Conclusion

EDs are a myriad of heterogeneous conditions encompassing several inherited embryopathies affecting teeth and other ectoderm-derived structures in utero.

Diagnosis is essentially clinical, confirmed by radiology and genetics which can specify the causal mutation; treatment is mainly conservative.
65 First francophone e-learning of pediatric rheumatology in Africa: the trainers’ opinion
Authors: Ines Cherif , Hanene Ferjani , Ichrak Khamessi , Kaouther Maatallah , Rahma Guedri , Saoussen Miladi , Monia Ben Khaled , Alia Fazaa , Manel Jallouli , Kaouther Ben Abdelghani , Monia Khemiri , Zohra Fitouri , Wafa Hamdi
Published: October 2022

Background

Pediatric Rheumatology is currently gaining importance across Africa. Initiatives such as the creation of the paediatric society of the African league against rheumatism (PAFLAR) proved the efforts made to bridge the insufficiency. In the same line, training in pediatric rheumatology remains the main challenge of this orphan subspecialty. For this purpose, a post-graduate certification in Pediatric Rheumatology was created in 2021 in the Faculty of Medicine of Tunis—Tunis-El Manar University. It is the first online certification dedicated to French speakers in Africa. The certification is entitled “musculoskeletal diseases of children and adolescents”.

Objective

To assess the learners' perceptions and views of this certification.

Methods

We established an online survey targeting the participants. The questionnaire was divided into three main sections: the first section examined the participant characteristics: their specialty, the use of the Moodle platform of the Virtual University of Tunis (UVT), their previous participation in an online post-graduation course, etc.). The second section focused on platform acceptability. The third and final section evaluated the content of the course. The Likert scale was used in most questions.

Results

Fifteen participants responded to the survey. Among them, one is specialized in family medicine, 1 in orthopedics, 5 in pediatrics, and 8 in rheumatology. Fifty-three percent have never used the platform of the virtual university of Tunis (UVT) before, and 26.7% have never attended an online course. Most participants found the platform easy to access and easy to use with a mean Likert scale of 2.2 and 2.13, respectively. In the third section of the questionnaire, the course met the expectations of the candidates with a mean Likert scale of 2.1. Most of them found the post-test useful to their learning experience, and only two found it to be the opposite. This can be explained by the pressure that it may generate. Eighty-six percent of the candidates had an interactive experience with the educator and enjoyed the interactions and the discussions between the participants. Most participants were pleased with the seminar organization and with the number of h devoted to each seminar (mean Likert Scale = 2.1). Eighty-six percent of the participants have found that the course improved their medical practice and 93.3% confessed that they were satisfied with the online nature of the certification and did not wish it to be physical.

Conclusion

Overall, the post-graduate “musculoskeletal diseases of children and adolescents” course was beneficial and enriching/rewarding for the participants.

Developing this training program helps to promote pediatric rheumatology in Africa and to provide children with rheumatic diseases access to healthcare.
72 Distinguishing features of MIS-C to other paediatric febrile diseases in the acute setting
Authors: Butters Claire , Spracklen Timothy , Stander Raphaella , Day Jonathan , Facey-Thomas Heidi , Zuhlke Liesl , Scott Christiaan , Webb Kate
Published: October 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, shock, rash, abdominal pain and raised inflammatory markers, as well as common features of inflammatory childhood illnesses. In the acute setting, especially in countries where infectious diseases are common differential diagnoses, it is challenging to diagnose MIS-C. Therefore, data differentiating MIS-C from other inflammatory and/or febrile diseases at presentation is needed.

Methods

Prospective data was collected from children admitted to the Red Cross War Memorial Children’s Hospital in Cape Town, South Africa from May 2020 to end November 2021 where MIS-C was part of their differential diagnoses. Clinical features on the day of admission were compared between children with confirmed MIS-C (MIS-C+) and those with alternate diagnoses (MIS-C-).

Results

In this time period, 60 children were MIS-C+ and 34 were MIS-C-. There was no significant difference in age (p = 0.321), sex (p = 0.525), ethnicity (p = 0.279), or in the frequency of comorbidities (p = 0.151) between the two groups. The presence of conjunctivitis (OR = 8.12), rash (OR = 8.67), tachycardia (OR = 2.8) and oral mucositis (OR = 3.75) was associated with MIS-C+ while abdominal pain and hypotension were not. MIS-C+ had statistically higher median C-reactive protein (CRP), pro-brain natriuretic protein (pro-BNP) and ferritin, and lower median lymphocyte count, platelet count and sodium levels than MIS-C-. Ferritin discriminated MIS-C+ well (AUC = 0.86) with a 94% sensitivity and 60% specificity at a cut off of > 195ng/l. Sodium had an AUC of 0.72, with a 70% sensitivity and 71% specificity at a cut off of < 132.5 mmol/l. CRP did not distinguish MIS-C well (AUC = 0.52) and although they had good AUC, platelet count and pro-BNP had cut off values in the normal range decreasing clinical utility.

Conclusion

We provide evidence for the use of accessible clinical and laboratory variables for the diagnosis of MIS-C in diverse settings.

Implications

These data will aid clinicians to do a rapid diagnosis (and ultimately treat earlier) of patients with MIS-C in the acute setting, especially those in under-resourced settings.
73 Joint pains revealing a dysautonomic syndrome
Authors: Boutrid N , Rahmoune H , Boutrid H , Bioud B , Amrane M , Chehad A.S
Published: October 2022

Background

Primary dysautonomia is a disorder of the autonomic nervous system with nonspecific manifestations, mainly affecting blood pressure and heart rate.

Objective

We report the diagnostic odyssey in an 11-year-old girl starting with arthralgia and leading to the final diagnosis of a rare dysautonomia.

Methods

A 13-year-old girl, with no pathologic history, was admitted to pediatrics for diffuse arthralgia without clinical inflammatory signs.

Biological exploration unmasked a morning proteinuria without hypoalbuminemia and with a normal electrophoretic profile, microcytic anaemia and orthostatic hypotension authenticated during his hospitalization.

Exhaustive explorations were undertaken (including autoimmune panel, ophthalomological examination, full metabolic screen and even renal biopsy), without any conclusive result.

Results

The development—after one year of follow up—of arterial hypertension, associated with orthostatic hypotension and proteinuria, points toward the extremely rare defect in baroreceptors.

The management, in collaboration with the cardiology department, enhanced the patient’s quality of life with a reduction in hypertensive peaks. An appropriate lifestyle also amended the intensity of orthostatic hypotension.

The close multidisciplinary follow-up over >48 months is reassuring.

Conclusion

The peculiar baroreceptor defect in a context of dysautonomia should be kept in mind in the (long) list of differential diagnosis of arthralgias, as joint pain can be triggered by dysautonomia. Management is mainly symptomatic.
74 Hereditary angioedema revealed by compartment syndrome
Authors: Boutrid N , Rahmoune H , Boutrid H , Bioud B , Chehad A.S , Amrane M
Published: October 2022

Background

Hereditary angioedema (HAE) can present with a wide spectrum of clinical symptoms, including articular features like the compartment syndrome.

Objective

We present the peculiar case of a young female patient suffering from this rare complement system disorder and presenting as a « wrist oedema ».

Methods

A 14-year-old girl was admitted in the emergency room during a night shift. She presented with acute compartment (wrist) syndrome due to edematous compression of the median nerve, associated with a typical personal history of HAE. It resolved within 6 h with IV steroids and hyperhydration.

The quantitative and qualitative C1 INH esterase returning negative, the diagnosis of HAE type III was made.

The patient was treated with long-term treatment based on Danazol, (the most frequently prescribed attenuated androgen to treat HAE).

Results

HAE is due to the deficiency or dysfunction of the C1 inhibitor protein (quantitative or qualitative deficiency). A new nomenclature has replaced the initial use of denominations HAE type 1, 2 or 3; to speak rather of HAE with a deficient C1 inhibitor (type 1), with a dysfunctional C1 inhibitor (type 2) or with a normal C1 inhibitor (type 3)

Type 3 HAE is rare and difficult to treat. It may respond to anti-estrogenic drugs such as progestins and especially to androgens; specific (very expensive) molecules do exist and act directly on the bradykinin pathways

Conclusion

A compartment syndrome may reveal extremely rare conditions such as hereditary angioedema.

Early recognition and management are the guarantee of a preserved functional prognosis.
78 Transient neonatal Behçet’s disease: a case report
Authors: Hatem Rouag , Marwa El-Ouaer , Salma Dhouib , Zaineb Ben Mohamed , Ghofrane Bedoui , Siwar Abdelmoula , Hayet Ben Hmida , Kamel Monastiri
Published: October 2022

Background

Behçet’s disease (BD) is a systemic vasculitis of unknown aetiology. The disease usually affects patients in the 3rd life decade and is rare in pediatrics. A very rare clinical form of Behçet's disease occurs during neonatal period.

Observation

We report a case of a term neonate presenting with oral and genital ulcerations appeared at the age of 7 days. The mother had a history of Behçet’s disease and antiphospholipid antibody syndrome (APLS) diagnosed at the age of 20 years, characterized by severe recurrent orogenital ulceration and complicated by thrombophlebitis and mycocarditis. She was treated with colchicine, corticoids during the attacks and an antiplatelet treatment. Also, the siblings of the neonate (2 sisters and one brother) had the same symptoms in the neonatal period and developed disfiguring scars since they were treated as herpes by antiviral therapy. Family history, clinical course and negative laboratory results, suggest the diagnosis of transient neonatal BD. The treatment with systemic and local corticoids was effective. The neonate didn’t develop scars, neurological or vascular symptoms. The antibodies anti-nuclear and HLAB51 were negative.

Conclusion

Transient neonatal Behçet’s disease (BD) is a rare secondary neonatal autoimmune condition. The transmission from mother to fetus is still unclear. It is thought to be transmitted by an immune mechanism. However, the causative antibodies for neonatal BD have not been identified. Corticosteroid is recommended after diagnosis in order to avoid scars
82 Juvenile dermatomyositis with early-onset anti-MDA 5 antibodies: a case report
Authors: Ayad N , Gherbi M , Gacem O , Falek H , Labboun L , Amirat L , Chouli M , Abba K , Benmakhlouf H , Achir M , Ladj M. S
Published: October 2022

Background

Juvenile dermatomyositis (JDM) is a very rare inflammatory myopathy with an approximate incidence of 2–4 per million. The discovery of specific circulating autoantibodies present in about 60% of cases has allowed them to be classified according to their clinical and immunological expressions and their therapeutic response. Anti-Melanoma differentiation associated gene5 (MDA5) antibodies seem to be correlated with a particular clinical phenotype associating cutaneous, respiratory, and articular involvement and most often sparing the muscles.

Observation

We report the case of an early-onset anti-MDA 5 JDM in a 27-month-old girl. The first symptoms appeared at the age of 18 months and consisted of a skin rash and muscle weakness complicated 6 months later by generalized oedema. The child received symptomatic treatments without improvement. At 27 months of age, the child worsened and was admitted for respiratory distress. On clinical examination, she presented with fever and general deterioration, respiratory impairment with swallowing problems, skin damage with specific ulcerations, very significant generalized oedema, and severe muscle damage with axial hypotonia and myogenic EMG tracing. The inflammatory workup was positive and the autoimmune workup revealed 1/320 speckled antinuclear antibody (ANA) and positive anti-MDA5 anti bodies. Chest CT scan showed right interstitial lung disease. The diagnosis of anti-MDA5 JDM was retained and the child was treated with corticosteroids pulses associated with immunoglobulins and methotrexate (MTX) leading to a clear improvement. Corticosteroids and MTX were maintained on a long-term basis.

Discussion

The prevalence of anti-MDA5 anti bodies is variable and depends on ethnic origin (7% in an English cohort vs 38% in the Japanese cohort). These antibodies seem to be specific to a particular phenotype of DM associating skin involvement, interstitial lung disease with little or no muscle involvement. The originality of this observation lies in the early age of onset of JDM and in the fact that it expresses the anti-MDA5 antibodies. The skin and muscle involvement was prominent in our patient, while the pulmonary involvement, although not rapidly progressive, justified the combination of bolus methylprednisolone, MTX and immunoglobulins. Despite the delay in diagnosis, we noted a good therapeutic response and stabilization of the disease.

Conclusion

Anti-MDA 5 antibodies must be identified as soon as JDM is diagnosed; their presence is a risk factor for severe lung damage, which must be systematically investigated and treated to improve the prognosis.
89 Association of brucellosis and ankylosing spondylitis: a pediatric case report
Authors: Hadef Djohra , Mansouri Oum Keltoum , Behamma Hayat , Benbouzid Nourelhouda , Boukhalfa Imane , Bougherara Hind , Rouichi Hadda , Gourmat Khaoula , Bezziou Khadidja , Serhane Kamel
Published: October 2022

Introduction

Ankylosing spondylitis is a common chronic rheumatic disease in male young adults. Brucellosis is a worldwide zoonosis and remains endemic in several Mediterranean countries, which may have features similar to other diseases, leading to serious problems of differential diagnosis. This case report described a case of a 14-year-old male diagnosed with ankylosing spondylitis whose exploration reveals associated subacute brucellosis.

Methods and results

A 14- years- old boy from Batna, born of a first degree consanguineous marriage, and the 2nd of a sibling of 05 children. He had no relevant past medical history. He complained of chronic polyarthritis of three years, affecting the large joints: hip, knees, ankles, elbows and wrists as well as the cervico-dorsolumbar spine. Pain on palpation of the tendon insertion zones without fever. Delayed growth in weight and height was found. He was misdiagnosed at disease onset as Rheumatic fever treated by Extencillin with vitamin D3 supplementation but no improvement was noticed.

The Ultrasound examination of the joints revealed moderate effusion with synovial thickening of the hip (hip synovitis). CT scan of the cervical-dorsal-lumbosacral spine revealed a bilateral erosive sacroiliitis with cervical ankylosis of the posterior apophyseal joints at C2-C3, C3-C4, and C4-C5 levels. A biological inflammatory syndrome was found. Brucellosis serology (Rose Bengal and Wright) was positive twice (IgM and IgG). Quantiferon test was negative.

The treatment of the Brucellosis was started (Doxicyclines, Gentamycin, and Rifampicin). Non-steroidal anti-inflammatory drugs were also prescribed.

Conclusion

Brucellosis is a differential diagnosis of spondyloarthritis. However, an association of both diseases might exist and should be adequately managed.

Disclosure of Interest

None declared
91 Systemic lupus erythematosus and infectious complications: a pediatric case report
Authors: Hadef Djohra , Salhi Badereddine , Haddadi Meriem , Benbrahim Khaoula , Belaala Rimah , Bouderdaben Leila , Bensacia Norhane , Kahlane Ibtissam , Abdallaoui Abdarahmane , Khenferi Yacine , Khernane Nacer
Published: October 2022

Introduction

Infection is one of the leading causes of morbidity and mortality in Systemic Lupus Erythematosus (SLE). Bacterial infections are the most frequent, followed by viral and fungal infections. Therapeutic factors as well as disease- and genetic related factors, all contribute to a lupus patient's increased susceptibility to infections.

This report describes a case of a 12-year-old female who presented with features of systemic lupus erythematosus with inaugural infectious joint involvement.

Methods and results

An 11- year- old girl, from Biskra (Algeria), from a non-consanguineous marriage and the 7th of eight children. She had no relevant past medical history. She was referred to our department for the diagnostic and therapeutic management of a suspected systemic lupus erythematosus.

The girl had a fever with a malar erythema and oral ulcerations. Arthralgia of the right hip was reported. Laboratory tests showed a positive CRP (C-reactive protein) and a positive Procalcitonin. The immunological assessment revealed Anti DNA, Anti Sm and Anti RNP positive.

Ultrasound of the hip showed a very large arthro-synovial cyst of the anterior face of the right hip of 07 cm compressing the psoas muscle. The cyst was drained and antibiotic therapy initiated. Hydroxychloroquine was started while waiting for the rest of the exploration.

Conclusion

Joint involvement in systemic lupus erythematosus is frequent but an infectious complication is possible even at the disease onset and should not be missed.

No conflicts of interest to declare.
TNF‐α‐dependent lung inflammation upregulates PD‐L1 in monocyte‐derived macrophages to contribute to lung tumorigenesis
Authors: Wen Yue , Wang Xiuqing , Meng Wei , Guo Wenli , Duan Chenyang , Cao Jingjing , Kang Lifei , Guo Ningfei , Lin Qiang , Lv Ping , Zhang Rong , Xing Lingxiao , Zhang Xianghong , Shen Haitao
Published: October 2022

Chronic inflammation, which is dominated by macrophage‐involved inflammatory responses, is an instigator of cancer initiation. Macrophages are the most abundant immune cells in healthy lungs, and associated with lung tumor development and promotion. PD‐L1 is a negative molecule in macrophages and correlated with an immunosuppressive function in tumor environment. Macrophages expressing PD‐L1, rather than tumor cells, exhibits a critical role in tumor growth and progression. However, whether and how PD‐L1 in macrophages contributes to inflammation‐induced lung tumorigenesis requires further elucidation. Here, we found that higher expression of PD‐L1 in CD11b+CD206+ macrophages was positively correlated with tumor progression and PD‐1+CD8+ T cells population in human adenocarcinoma patients. In the urethane‐induced inflammation‐driven lung adenocarcinoma (IDLA) mouse model, the infiltration of circulating CD11bhighF4/80+ monocyte‐derived macrophages (MoMs) was increased in pro‐tumor inflamed lung tissues and lung adenocarcinoma. PD‐L1 was mainly upregulated in MoMs associated with enhanced T cells exhaustion in lung tissues. Anti‐PD‐L1 treatment can reduce T cells exhaustion at pro‐tumor inflammatory stage, and then inhibit tumorigenesis in IDLA. The pro‐tumor lung inflammation depended on TNF‐α to upregulate PD‐L1 and CSN6 expression in MoMs, and induced cytokines production by alveolar type‐II cells (AT‐II). Furthermore, inflammatory AT‐II cells could secret TNF‐α to upregulate PD‐L1 expression in bone‐marrow driven macrophages (BM‐M0). Inhibition of CSN6 decreased PD‐L1 expression in TNF‐α‐activated macrophage in vitro, suggesting a critical role of CSN6 in PD‐L1 upregulation. Thus, pro‐tumor inflammation can depend on TNF‐α to upregulate PD‐L1 in recruited MoMs, which may be essential for lung tumorigenesis.
LncRNA MYMLR promotes pituitary adenoma development by upregulating carbonyl reductase 1 via sponging miR-197-3p
Authors: Wang Tuo , Mao Ping , Zhang Yan , Cui Bo , Wang Mao-De , Li Ya , Gao Ke
Published: October 2022

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in various biological processes and play key roles in tumorigenesis and metastasis. Pituitary adenoma (PA) is one of the most common malignancies in central nervous system. Recently, multiple lncRNAs have been identified to regulate PA initiation, progression and metastasis. we aimed to elucidate the expression pattern and function of lncRNA MYMLR in PA development. The expression of lncRNA MYMLR in PA tissues and cells was examined by real-time quantitative PCR. Knockdown of MYMLR expression was achieved by using shRNA. The function of MYMLR and regulatory network were analyzed using CCK-8 assay, wound-healing assay, migration assay and Annexin V/PI staining. Xenograft tumor model was used to explore the function of MYMLR in vivo. Bioinformatics analysis and luciferase reporter assay were conducted to investigate the interaction between MYMLR and its regulatory network. LncRNA MYMLR was highly expressed in PA tissues compared with that in normal tissues. Knockdown of MYMLR suppressed cell proliferation, migration and invasion, while promoting PA cell apoptosis. Mechanistically, MYMLR functioned as a competing endogenous RNA (ceRNA) sponging microRNA miR-197-3p. Furthermore, miR-197-3p exerted its tumor inhibitory role via negatively regulating carbonyl reductase 1 (CBR1). Overexpression of CBR1 antagonized the inhibitory effect of lncRNA MYMLR knockdown or miR-197-3p overexpression. In addition, xenograft tumor model revealed that knockdown of lncRNA MYMLR suppressed PA tumor development in vivo via regulating CBR1. Our findings suggest a regulatory network of lncRNA MYMLR/miR-197-3p/CBR1, which benefits the understanding of PA development and provides a promising lncRNA-direct therapeutic strategy against PA.
Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis
Authors: Yang Gang , Tan Jie , Guo Jian , Wu Zhiwei , Zhan Qiong
Published: October 2022

Exosomes are critical mediators of intercellular communication. Exosomal circular RNAs (circRNAs) have been reported to play critical roles in the development of chemoresistance in various tumors, including gastric cancer. However, the role of exosomal circ_0063526 in cisplatin (CDDP) resistance of gastric cancer is still unclear. The expression of circ_0063526, microRNA-449a (miR-449a) and serine hydroxymethyltransferase 2 (SHMT2) mRNA was determined by quantitative real-time PCR (qRT-PCR). Cell viability was assessed by the Cell Counting Kit-8 assay. Cell migration and invasion were evaluated by the transwell assay and wound healing assay. Western blot assay was used to measure the protein expression of light Chain 3 (LC3) I/II, p62 and SHMT2. Exosomes were detected using transmission electron microscopy. The size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-449a and circ_0063526 or SHMT2 was confirmed by a dual-luciferase reporter and RNA pull-down assays. Circ_0063526 expression was increased in gastric cancer tissues and cells and CDDP-resistant cells. Extracellular circ_0063526 could be packaged into exosomes and transmitted to sensitive cells, thus disseminating CDDP resistance. Knockdown of exosomal circ_0063526 inhibited CDDP resistance via suppressing migration, invasion and autophagy in gastric cancer cells. Moreover, circ_0063526 was identified as a molecular sponge of miR-449a to upregulate SHMT2 expression. Further, exosomal circ_0063526 regulated SHMT2 expression to enhance CDDP resistance of gastric cancer cells. Additionally, high expression of exosomal circ_0063526 in serum was associated with poor response to CDDP treatment in gastric cancer patients. Exosomal circ_0063526 facilitated CDDP resistance in gastric cancer via regulating the miR-449a/SHMT2 axis.