Claudio Germani

Appendicitis in children less than five years old: A challenge for the general practitioner

Acute appendicitis is one of the most common indications for abdominal surgery in pediatrics with peak incidence in the second decade of life. Acute appendicitis in the first years of life is an uncommon event. The clinical presentation is often varied and the diagnosis may be overshadowed by other medical conditions. Gastroenteritis is the most common misdiagnosis, with a history of diarrhea present in 33% to 41% of patients. Pain is the most common presenting symptom in children less than 5 years old, followed by vomiting, fever, anorexia and diarrhea. The most common physical sign is focal tenderness (61% of the patients) followed by guarding (55%), diffuse tenderness (39%), rebound (32%), and mass (6%). Neonatal appendicitis is a very rare disease with high mortality; presenting symptoms are nonspecific with abdominal distension representing the main clinical presentation. The younger the patient, the earlier perforation occurs: 70% of patients less than 3 years develop a perforation within 48 h of onset of symptoms. A timely diagnosis reduces the risk of complications. We highlight the epidemiology, pathophysiology, clinical signs and laboratory clues of appendicitis in young children and suggest an algorithm for early diagnosis.

Acquired long QT syndrome: a focus for the general pediatrician.

Abstract Acquired long QT syndrome (LQTS) is a disorder of cardiac repolarization most often due to specific drugs, hypokalemia, or hypomagnesemia that may precipitate torsade de pointes and cause sudden cardiac death. Common presentations of the LQTS are palpitations, presyncope, syncope, cardiac arrest, and seizures. An abnormal 12-lead electrocardiogram obtained while the patient is at rest is the key to diagnosis. The occurrence of drug-induced LQTS is unpredictable in any given individual, but a common observation is that most patients have at least 1 identifiable risk factor in addition to drug exposure. The cornerstone of the management of acquired LQTS includes the identification and discontinuation of any precipitating drug and the correction of metabolic abnormalities, such as hypokalemia or hypomagnesemia. Most of the episodes of torsade de pointes are short-lived and terminate spontaneously. We propose a management protocol that could be useful for the daily practice in the emergency pediatric department to reduce the risk of acquired QT prolongation.

Es eficaz el tratamiento con hidroxicloroquina en el déficit de proteína C surfactante

We present the case of two twin brothers with surfactant protein C deficiency who were treated with hydroxychloroquine for three years, with apparent success. The exact physiopathology of this disease is not known and there is no specific treatment for it. There is merely news from a few previous descriptions in the literature about the use of hydroxychloroquine for surfactant protein C deficiency with satisfactory results. Two years after the treatment was withdrawn, the twins were evaluated once again: they presented no new infections, growth and general state were normal and chest CT showed a notable additional reduction in the interstitial pneumopathy. These data seem to cast some doubt on the efficacy of hydroxychloroquine, and they suggest that the clinical improvement was simply the natural evolution of the disease.

A case of Rubinstein‐Taybi syndrome associated with growth hormone deficiency in childhood

Dear Editors, Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disease. Point mutations or deletions of the cAMPresponse element-binding protein-BP (CREBBP) (50–60% of the cases) or the homologous gene E1A-binding protein (EP300) (5%) are involved in RTS. RTS patients show intellectual disability, distinctive clinical characteristics (such as broad and sometimes laterally deviated thumbs and halluces), short stature, and craniospinal and posterior fossa abnormalities. We describe the case of a girl delivered at term with mild perinatal asphyxia. At birth, weight and length were 2630 g ( 1 73 SDS) and 47 5 cm ( 1 34 SDS), respectively. A clinical diagnosis of RTS was performed in the first days of life because of broad thumbs and toes, downslating palpebral fissures and malpositioned ears with dysplastic helices. The molecular analysis showed a frameshift mutation of the CREBBP gene due to a duplication of 20 nucleotides (c.5838_5857dup20). This mutation, never described before, involves the exon 31 of the CREBBP gene and leads to a stop codon (p.Pro1953HisfsX30) with a resulting truncated protein of 1982 aminoacids (the wild-type protein is of 2442 aminoacids). In the following years, she showed growth impairment and development delay. She was referred to our attention at the age of 3 years because of short stature (86 5 cm, 2 1 SDS, 25–50° percentile following RTS growth charts). The growth velocity in the last year was 5 69 cm/year ( 1 67 SDS). The weight was between 10° and 25° percentile (between 25 and 50°pc following RTS growth charts). Tanner pubertal stage was Ph1 B1, and the bone age showed a delay of 2 years. Clinical examination showed features consistent with RTS and cutaneous neuromas. Cortisol levels at 8:00 a.m., thyroid, hepatic and renal functions were normal. Two arginine provocative tests for growth hormone (GH) secretion were performed. GH peak levels were 5 57 lg/l and 6 69 lg/l (n.v. >10 lg/l), respectively, revealing a GH deficiency. The IGF-1 levels were 22 27 nmol/l (n.v. 13 88– 32 75 nmol/l). A brain magnetic resonance (MRI) showed normal pituitary height (3 8 mm with a normal height range for age and sex of 4 25 0 68 mm) and volume, normal anatomy of the stalk, normal position of the posterior pituitary, and normal anatomy of the hypothalamic region. A thinning of the corpus callosum was evident. She started GH therapy (0 033 mg/kg/day) when she was 3 5 years old, with good improvement of growth velocity (the patient’s growth charts are shown in Fig. 1a and b). At last follow-up, the patient was 9 9 years old and her stature was 134 6 cm (+0 58 SDS according Italian charts and 90–97°percentile according RTS growth charts). At the present time, the GH dose is 0 022 mg/kg/day with a growth velocity of 6 95 cm/year (+1 90 SDS). Pubertal stage is Ph1 B1. IGF-1 levels are 49 38 nmol/l (n.v. 16 50–34 19 nmol/l). The bone age shows a retardation of 16 months. The thyroid function is normal. TSH levels are 3 35 mIU/l (n.v. 0 27–4 20 mIU/l), Ft4 levels are 13 64 pmol/l (n.v. 11 9–21 8 pmol/l), and Ft3 levels are 0 059 pmol/l (n.v. 0 027–0 070 pmol/l). She did not presented any side effects to GH therapy. In individuals with RTS, short stature is considered a classic feature of the syndrome and indirect measures of growth hormone secretion have been usually reported as normal. Therefore, these patients do not usually undergone dynamic testing to detect growth hormone deficiency. In literature, we found a single case report of RTS female patient with GH deficiency associated with a CREBBP frameshift mutation. The diagnosis of GH deficiency was performed when she was 11 years old. She was treated with GH therapy for 5 years with good improvement in growth velocity (reaching the 3° percentile of height for the normal population growth chart and the 75° percentile of height for the RTS growth chart) without any side effects. Interestingly, this patient presented also pituitary hypoplasia, Arnold Chiari malformation type 1 and double syringomyelic cavity. This fact underlines the possibility that GH deficiency could play a role in the short stature of RTS patients with CREBBP mutation and that the replacement therapy could lead to improvement of stature. Another RTS patient with GH deficiency and short stature is present in the population of Spena et al. and this patient showed a frameshift CREBBP mutation leading to a stop codon at aminoacid 107. Unfortunately, no more auxological data and information about a possible therapy are available. Herein, we report a precocious diagnosis of GH deficiency (performed when the patient was 3 5 years old) associated with a new CREBBP mutation. Our case report shows a GH replacement therapy started early in life in RTS patients with GH deficiency leading to an important improvement of stature (her height reached the 25° percentile according normal population and 90–97° percentile according RTS growth charts) without any side effects. Unlike the patient previously described, our patient did not present pituitary hypoplasia. The hypothesis of the linkage between short stature and GH deficiency in RTS patients with CREBBP mutations is supported by previous studies in mice and in vitro. cAMP-response element-binding protein (CREB) is one of the first transcription factors that showed an impact on somatic growth. CREB is required for the efficient production of GHRH in hypothalamus and GH in pituitary gland. In fact, CREBmutant mice present reduced postnatal growth consistent with dwarfism caused by GH deficiency. CREBBP, involved in RTS pathogenesis, is a nuclear factor named for its ability to bind CREB. It is possible that CREBBP mutations affect the CREB–CREBBP interaction, determining an impaired CREB-binding protein both at hypothalamic and at pituitary level, with consequent reduction in GH levels. In addition, at pituitary level, CREBBP interacts as cofactor with Pit-1. Pit-1 is an important transcription factor that promotes growth hormone and stimulates somatic growth. Therefore, an impairment of CREBBP/Pit-1 interaction could affect pituitary GH secretion. Considering all the GH secretion steps in whom CREBBP could be implicated, we suppose that in RTS patients without

Acute lobar nephritis in children: Not so easy to recognize and manage

Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.

Still toddler: A clinical clue for acute appendicitis: Still toddler

A previously healthy 30-month-old boy presented to the emergency department with a 2-days history of repeated non-bilious vomiting, low-grade fever and refusal to stand or walk. The day before admission, he had been evaluated by his general practitioner and a viral intestinal infection was suspected. The re-evaluation was prompt by the fact that in the next hours at home he was continuously lying in his bed, refusing to walk or play. On examination, he was alert, vital signs were normal, body temperature was 37.5 C and no signs of dehydration were noted. He was apparently not suffering, calm while lying on the table, trying to limit movements and to keep a still body position. He started crying after palpation of the right lower abdominal quadrant. No guarding or rebound tenderness were noted. Bowel sounds were present. An acute appendicitis was suspected and a diagnostic work-up was performed. Blood tests showed an increased white blood count (20.4 × 10/L) with neutrophilia (17.4 × 10/L) and an elevated C-reactive protein 5.26 mg/dL. Abdominal ultrasonography revealed a hypoanechoic dilated appendix (>1 cm) with peripheral hypervascularity at colour-Doppler analysis with a visible appendicolith (Fig. 1). The patient was admitted to the surgical department and an appendectomy was performed. He recovered without complications.

An adolescent with acute abdominal pain and bowel wall thickening

A 15-year-old girl was admitted with acute crampy abdominal pain and repeated vomiting over the preceding 2 hours; no fever, diarrhoea or abdominal trauma was reported. She had started oestrogen–progestin contraception 3 months ago. She had sought medical advice twice in the previous weeks for self-limiting episodes of right hand swelling, without urticaria. On examination, she was unwell and in pain, with severe tenderness in the right lower quadrant, without guarding or rebound tenderness. Bowel sounds were diminished. Blood tests were unremarkable. Two hours after admission, an abdominal ultrasound scanning showed an impressive wall thickening (>1 cm) of the terminal ileum, caecum and ascending colon (figure 1). Abundant free intraperitoneal fluids in the pelvis and in the hepatorenal recess were present. Figure 1 Marked caecal wall thickening evidenced at the ultrasound scanning. Questions Which of the following is the most likely diagnosis in this patient? Ileocolic intussusception Gastrointestinal manifestation of Henoch-Schönlein purpura Abdominal attack of hereditary angioedema (HAE) Acute pancreatitis Which of the following blood tests may help to confirm the diagnosis? Erythrocyte sedimentation rate C4 Serum amylase: 36 IU/L C1-inhibitor How should this patient be evaluated and treated? Answers are on page ▪▪▪.