Helicobacter pylori-Related Extraintestinal Manifestations-Myth or Reality.

It is well documented that Helicobacter pylori (H. pylori) can cause both gastrointestinal and extraintestinal manifestations. The latter one represents a major burden in terms of diagnosis and treatment. H. pylori-associated systemic subclinical inflammation is mostly responsible for the development of extraintestinal manifestations, and its early eradication might result in preventing all adverse events related to their occurrence. Thus, it was suggested that H. pylori might be associated with iron deficiency anemia, thrombocytopenia (immune thrombocytopenic purpura), Schonlein Henoch purpura, failure to thrive, vitamin B12 deficiency, diabetes mellitus, body mass index, cardiovascular diseases, as well as certain neurological conditions. Nevertheless, studies showed both pros and cons in terms of the role of H. pylori in the development of previously mentioned clinical entity underlining the crucial need for further studies on these topics. Although most of these extraintestinal manifestations occur during adulthood, we must not forget that H. pylori infection is acquired mainly during childhood, and thus its early diagnosis and eradication might represent the cornerstone in the prevention of H. pylori-induced inflammatory status and consequently of all related extraintestinal conditions.

The Peculiar Trialogue between Pediatric Obesity, Systemic Inflammatory Status, and Immunity.

Pediatric obesity is not only an energetic imbalance, but also a chronic complex multisystem disorder that might impair both the life length and quality. Its pandemic status should increase worldwide awareness regarding the long-term life-threatening associated complications. Obesity related complications, such as cardiovascular, metabolic, or hepatic ones, affect both short and long-term wellbeing, and they do not spare pediatric subjects, defined as life-threatening consequences of the systemic inflammatory status triggered by the adipose tissue. The energetic imbalance of obesity clearly results in adipocytes hypertrophy and hyperplasia expressing different degrees of chronic inflammation. Adipose tissue might be considered an immune organ due to its rich content in a complex array of immune cells, among which the formerly mentioned macrophages, neutrophils, mast cells, but also eosinophils along with T and B cells, acting together to maintain the tissue homeostasis in normal weight individuals. Adipokines belong to the class of innate immunity humoral effectors, and they play a crucial role in amplifying the immune responses with a subsequent trigger effect on leukocyte activation. The usefulness of complete cellular blood count parameters, such as leukocytes, lymphocytes, neutrophils, erythrocytes, and platelets as predictors of obesity-triggered inflammation, was also proved in pediatric patients with overweight or obesity. The dogma that adipose tissue is a simple energy storage tissue is no longer accepted since it has been proved that it also has an incontestable multifunctional role acting like a true standalone organ resembling to endocrine or immune organs.

Neonatal polycystic kidney disease, a potential life-threatening condition at this age: A case report.

RATIONALE: Autosomal recessive polycystic kidney disease (ARPKD) is a severe rare genetic condition, with high mortality rates and autosomal recessive pattern of transmission similar to most early onset cystic kidney diseases. The mortality rates can reach up to 30% during the neonatal period. PATIENT CONCERNS: We report a case of a 27-day-old male neonate admitted in our clinic for fever, foul-smelling urine, and diarrhea. A previous abdominal ultrasound at the age of 2 weeks revealed enlarged, hyperechoic kidneys, no abnormalities of the urinary exam. Clinical examination revealed poor general status, ill-looking face, diminished cutaneous turgor, distended abdomen, and palpable kidneys. Laboratory tests pointed out leukopenia, anemia, border-line platelet count, elevated inflammatory biomarker level, hyponatremia, hypoalbuminemia, proteinuria, leukocyturia, and hematuria. Both urine and blood cultures were positive for E. coli. DIAGNOSES: Abdominal ultrasound revealed bilateral nephromegaly, diminished parenchymatous index, with the absence of differentiation between the cortex and medulla. Abdominal MRI described bilateral nephromegaly, the hypertrophy comprising especially the structures of Malpighi pyramids, with multiple cystic lesions disseminated within both kidneys, projected also in Malpighi pyramids, their diameters ranging between 2 and 7 mm. Thus, our final diagnoses were polycystic kidney disease and sepsis due to urinary tract infection with E. coli. INTERVENTIONS: After treating the infection, the patient was referred to a more experienced center for appropriate management of polycystic kidney disease. OUTCOMES: The progress of the patient until the age of 1 year and 2 months has been remarkably favorable, presenting first-degree chronic kidney disease, with normal blood parameters and controlled blood pressure values, no other episodes of urinary infection, and without supplementary pathological changes in ultrasound. LESSONS: Despite the poor prognosis of PKD reported in the literature, our case had an outstandingly favorable evolution during the first 2 years of life most-likely due to the early diagnosis and treatment, but also proper monitoring.

An uncommon case of herpetic esophagitis in a small child with allergic rhinitis: A case report and literature review (CARE compliant).

RATIONALE: Herpetic esophagitis (HE) is a common condition in immunosuppressed patients, but a rare entity in immunocompetent patients affecting especially male teenagers and young adults. PATIENT CONCERNS: We report the case of a 5-year-old male patient, with a history of allergic rhinitis admitted in our clinic for acute onset fever refractory to antipyretics, chest pain, anorexia, refusal of solid food, accepting only small amounts of fluids, odynophagia, and epigastric pain. The clinical exam revealed severe malaise, pallor, decreased skin turgor, abdominal epigastric tenderness, heartburn at palpation within the epigastric area. The laboratory tests showed leukocytosis, monocytosis, hypoglycaemia, and elevated inflammatory biomarkers. DIAGNOSES: The serology tests for human immunodeficiency virus (HIV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV) were negative, except for immunoglobulin G (IgG) anti-EBV which was positive. The chest radiography was normal, and the abdominal ultrasound showed abdominal bloating. The upper digestive endoscopy revealed friable esophageal mucosa, with multiple ulceration on the entire esophagus, and whitish exudates especially on the middle and lower part of the esophagus suggesting a possible eosinophilic esophagitis or caused by Candida. Despite the empirical initiated treatment, the patient's evolution was only slowly favorable. The histological exam established the diagnosis of HE. INTERVENTIONS: We initiated acyclovir therapy with an outstandingly favorable evolution. OUTCOMES: After 1 month, we detected the seroconversion of IgG anti-HSV. The patient's follow-up revealed no additional complaints. LESSONS: Despite its rarity in immunocompetent individuals, HE must be taken into account even in otherwise healthy small children. Allergic conditions might represent a predisposing factor for HE.

Pediatric ovarian tumors, a challenge for pediatrician and gynecologist: Three case reports (CARE compliant).

RATIONALE: Ovarian or adnexal tumors are very rare in patients below the age of 18 years, most of them being functional cysts, only 10% being malignant. We report 3 cases of ovarian tumors with the aim of revealing the particularities regarding the diagnosis and management of benign and malignant ovarian tumors in pediatric patients. PATIENT CONCERNS: The 1st case, a 9-year-old girl presented for diffuse abdominal pain, distended abdomen and rapid increase in abdominal volume. The 2nd case describes a 13-year-old female patient admitted for acute abdominal pain and nausea, and the 3rd one was an 18-year-old female teenager who presented for distended abdomen, intermittent diffuse abdominal pain and rapid increase in abdomen volume. DIAGNOSES: The abdominal ultrasound revealed in all 3 patients suggestive signs for ovarian tumors. INTERVENTIONS: The 1st patient underwent laparotomy with adnexectomy, and the histopathological exam showed the diagnosis of dysgerminoma. The 2nd patient underwent laparoscopy with adnexectomy, and the histopathological exam revealed a borderline tumor. The 3rd patient benefited by a laparotomy with left ovariectomy, and the histopathological exam pointed out a mature teratoma. OUTCOMES: The outcome was favorable in all 3 cases, but the patients with dysgerminoma and mature teratoma were further referred to the oncologist for proper assessment. LESSONS: Laparoscopy may represent the first choice for uncomplicated ovarian masses. The diagnosis and the therapeutic plan must be based on symptoms, pelvic ultrasound, the time of menarche and the potential serum markers.

The Relationship between Toll-like Receptors and Helicobacter pylori-Related Gastropathies: Still a Controversial Topic.

Innate immunity represents the first barrier against bacterial invasion. Toll-like receptors (TLRs) belong to the large family of pattern recognition receptors (PRRs), and their activation leads to the induction of inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. Recent studies have focused on identifying the association between TLRs and Helicobacter pylori- (H. pylori-) related diseases. Therefore, this minireview focuses on assessing the role of these TLRs in the development of H. pylori-related gastropathies. Both TLR2 and TLR were found to be involved in H. pylori LPS recognition, with contradictory results most likely due to both the inability to obtain pure LPS in experimental studies and the heterogeneity of the bacterial LPS. In addition, TLR2 was found to be the most extensively expressed gene among all the TLRs in gastric tumors. High levels of TLR4 were also associated with a higher risk of gastric cancer. TLR5 was initially associated with the recognition of H. pylori flagellin, but it seems that this bacterium has developed mechanisms to escape this recognition representing an important factor involved in the persistence of this infection and subsequent carcinogenesis. TLR9, the only TLR with both anti- and proinflammatory roles, was involved in the recognition of H. pylori DNA. The dichotomous role of TLR9, promoting or suppressing the infection, depends on the gastric environment. Recently, TLR7 and TLR8 were shown to recognize purified H. pylori RNA, thereby inducing proinflammatory cytokines. TLR1 and TLR10 gene polymorphisms were associated with a higher risk for gastric cancer in H. pylori-infected individuals. Different gene polymorphisms of these TLRs were found to be associated with gastric cancer depending mostly on ethnicity. Further studies are required in order to develop preventive and therapeutic strategies against H. pylori infections based on the functions of TLRs.

An incidental diagnosis of a giant paraovarian cyst in a female teenager: A case report.

RATIONALE: Paraovarian cysts (PCs) are cystic tumors that can be encountered between the ovarian hilum and the ovarian fimbria located within the mesosalpinx and broad ligament, being usually diagnosed within the 3rd and 4th decade of life. PATIENT CONCERNS: We report the case of a 15-year-old female admitted in our clinic for consciousness loss, who was incidentally diagnosed with a giant pelvic cystic at ultrasound. DIAGNOSES: The magnetic resonance image showed a cystic mass of 170/140/85 mm, suggesting an origin from the left ovary, reaching the subhepatic area. INTERVENTIONS AND OUTCOMES: The surgical intervention revealed 3 PCs, a giant one and 2 smaller ones within the large ligament. The cysts were removed by laparoscopic approach, and the histologic examination did not reveal any signs of neoplasia. LESSONS: In addition to their rarity, giant PCs can be an incidental diagnosis in patients presenting unrelated symptoms resulting in increased difficulties related to the diagnosis. Moreover, the imagistic tools might not establish precisely the origin of these cysts, and therefore, the final diagnosis and treatment approach could be determined sometimes only during the surgical intervention.

Atypical onset of total colonic Hirschsprung disease in a small female infant: A case report.

RATIONALE: Hirschsprung disease (HD) or colonic aganglionosis is a congenital disorder, which results from the abnormal migration of neuronal cells of the neural crest leading to a disorder of the enteric nervous system consisting in the absence of ganglion cells within the submucosal and myenteric plexus. PATIENT CONCERNS: We report the case of a 7-month-old female infant admitted in our clinic for constipation and failure to thrive. At the age of 6 months, she was examined in our clinic for the same reasons, and we recommended symptomatic treatment without improvements. The clinical examination revealed pallor of the skin and mucosa, distended abdomen, and abdominal tenderness at palpation. DIAGNOSES: The abdominal ultrasound showed abdominal bloating, and the barium enema was normal. The patient's evolution worsened progressively within the following 3 days after admission associating sings of toxic megacolon. INTERVENTIONS: She underwent a surgical intervention with total colectomy and ileostomy, and the final diagnosis confirmed by the histological examination was of total colonic aganglionosis (TCA). OUTCOMES: The evolution immediately after the surgery and the follow-up examination after approximately 3 months pointed out normal weight gain and the laboratory tests were within normal limits. LESSONS: TCA can also manifest in older infants. Barium enemas can guide the diagnosis in most cases of HD. Nevertheless, in patients with TCA, it can be normal. Moreover, it could represent a trigger for toxic megacolon.

Incomplete Refractory Kawasaki Disease in an Infant-A Case Report and a Review of the Literature.

Kawasaki disease (KD) is a febrile vasculitis, which is commonly defined by fever and at least four specific clinical symptoms. Incomplete KD is defined by suggestive echocardiographic findings with an incomplete clinical picture. Refractory KD is diagnosed in patients resistant to intravenous immunoglobulin (IVIG). We report the case of a 6-month-old male infant admitted to our clinic for persistent fever and onset of a generalized polymorphous rash, accompanied by high fever, rhinorrhea, and cough for the past 7 days. The laboratory tests, on the day of admission, revealed leukocytosis with neutrophilia, anemia, thrombocytosis, hypernatremia, hypoalbuminemia, elevated C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Echocardiography showed dilation of the left anterior descending coronary artery (LAD). Based on all these findings, we established the diagnosis of KD, and we initiated IVIG and intravenous pulsed methylprednisolone, with an initial favorable outcome. However, the symptoms reappeared, and we administered a second higher single dose of IVIG, but without any clinical improvement. Moreover, the laboratory parameters and echocardiographic findings worsened. We reinitiated a longer course of intravenous methylprednisolone in a smaller dose, which had a favorable impact on the clinical, laboratory, and echocardiographic parameters. Multiple uncertainties exist related to the management of refractory KD despite the wide spectrum of therapeutic options that have been proposed. Our case demonstrates that in patients refractory to aggressive initial therapy, low or moderate doses of steroid given daily may be helpful.

Diagnostic challenges of celiac disease in a young child: A case report and a review of the literature.

RATIONALE: Celiac disease is a chronic, immune-mediated, multiorgan disorder that affects susceptible individuals, and it is triggered by gluten and other prolamins. PATIENT CONCERNS: We present the case of a 1-year-old male child, with a history of idiopathic pericardial effusion, admitted in our clinic for severe abdominal bloating, irritability, loss of appetite and intermittent diarrheic stools. The clinical findings were: influenced general status, irritability, distended abdomen, and diffuse abdominal tenderness. DIAGNOSES: The initial laboratory tests revealed anemia, leukocytosis, increased inflammatory biomarkers, high levels of transaminases, and hypoalbuminemia. The stool culture identified an enterocolitis with enteropathogenic Escherichia coli (E. coli). INTERVENTIONS: We initiated antibiotic treatment, substitution therapy with human albumin and probiotics with initial favorable evolution, but after 1 month, the patient was re-admitted for the persistence of intermittent diarrheic stools and abdominal bloating, when we established the diagnosis of cow's milk protein allergy. We initiated diary-free diet. OUTCOMES: Unfortunately, the patient was re-admitted after another 8 months, presenting the same clinical and laboratory findings as during the initial admission. We repeated the serology for celiac disease and we performed an upper gastrointestinal endoscopy with duodenal biopsies, which established the diagnosis of celiac disease. After 1 month of gluten-free diet, the patient's evolution improved considerably. LESSONS: Enterocolitis with E. coli could be considered as trigger for CD in our case. The diagnosis of CD in small children can be hindered by an insufficient gluten-exposure, and can lead to a delay in the diagnosis as in the case presented above.