Stevens-Johnson syndrome (SJS) is a severe skin and mucosal bullous disease. When complicated with Hemophagocytic lymphohistiocytosis (HLH), the condition is especially life-threatening.
Here we report the case of a 4-year-old boy suffering from SJS with extensive erythema multiforme and bulla. Despite active intervention and supportive care, the boy experienced increased skin lesions and a higher fever. Meanwhile, decreases in white blood cell count and hemoglobin were observed. Hyperferritinemia, increased soluble CD25 level, decreased NK cell activity and hemophagocytosis in the boy’s bone marrow confirmed the diagnosis of HLH. After high-dose intravenous immunoglobulin and methylprednisone pulse therapy, the boy was discharged in good condition.
Simultaneous occurrence of HLH and SJS is very uncommon and the condition is life-threatening. Pancytopenia can be a precocious indicator and enables to start a prompt diagnosis and treatment.
Pancytopenia; Early diagnosis; Stevens-Johnson syndrome (SJS); Hemophagocytic lymphohistiocytosis (HLH)
In term newborns meconium ileus is frequently associated with cystic fibrosis. Reports on meconium ileus in preterm infants being diagnosed with cystic fibrosis early after birth are very scarce. Associations between genotype and phenotype in cystic fibrosis and its particular comorbidities have been reported.
Two extremely preterm twin infants (26 weeks of gestation) born from a Malaysian mother and a Caucasian father were presented with typical signs of meconium ileus. Despite immediate surgery both displayed a unique and finally lethal course. Mutation analysis revealed a novel, probably pathogenic cystic fibrosis mutation, p.Cys524Tyr. The novel mutation might explain the severity of disease next to typical sequelae of prematurity.
Preterm neonates with meconium ileus have to be evaluated for cystic fibrosis beyond ethnical boundaries, but may take devastating clinical courses despite early treatment. The novel, potentially pathogenic CF mutation p.Cys524Tyr might be associated with severe meconium ileus in neonates. Disease-modifying loci are important targets for intestinal comorbidity of cystic fibrosis.
Preterm infant; Meconium ileus; Cystic fibrosis; Mutation; Disease modifying gene locus; Surgery
Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children.
We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus.
Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.
Bronchial casts; Plastic bronchitis; Atelectasis; Children; Respiratory tract infection; Human bocavirus
Arthrogryposis multiplex congenita is an etiopathogenetically heterogeneous disorder characterised by non-progressive multiple intra-articular contractures, which can be recognised at birth. The frequency is estimated at 1 in 3,000 newborns. Etiopathogenesis of arthrogryposis is multifactorial.
We report first 26 weeks of life of a boy with severe arthrogryposis. Owing to the integrated rehabilitation approach and orthopaedic treatment a visible improvement in the range of motion as well as the functionality of the child was achieved. This article proposes a cooperation of various specialists: paediatrician, orthopaedist, specialist of medical rehabilitation and physiotherapist.
Rehabilitation of a child with arthrogryposis should be early, comprehensive and multidisciplinary. Corrective treatment of knee and hip joints in infants with arthrogryposis should be preceded by the ultrasound control. There are no reports in the literature on the ultrasound imaging techniques which can be used prior to the planned orthopaedic and rehabilitative treatment in infants with arthrogryposis. The experience of our team indicates that such an approach allows to minimise the diagnostic errors and to maintain an effective treatment without the risk of joint destabilisation.
Infant; Arthrogryposis; Rehabilitation
Systemic lupus erythematosus (SLE) is known to present with a wide variety of clinical manifestations. Lymphadenopathy is frequently observed in children with SLE and may occasionally be the presenting feature. SLE presenting with granulomatous changes in lymph node biopsy is rare. These features may also cause diagnostic confusion with other causes of granulomatous lymphadenopathy.
We report 12 year-old female who presented with generalized lymphadenopathy associated with intermittent fever as well as weight loss for three years. She also had developed anasarca two years prior to presentation. On presentation, she had growth failure and delayed puberty. Lymph node biopsy revealed granulomatous features. She developed a malar rash, arthritis and positive ANA antibodies over the course of next two months and showed WHO class II lupus nephritis on renal biopsy, which confirmed the final diagnosis of SLE. She was started on oral prednisolone and hydroxychloroquine with which her clinical condition improved, and she is currently much better under regular follow up.
Generalized lymphadenopathy may be the presenting feature of SLE and it may preceed the other symptoms of SLE by many years as illustrated by this patient. Granulomatous changes may rarely be seen in lupus lymphadenitis. Although uncommon, in children who present with generalized lymphadenopathy along with prolonged fever and constitutional symptoms, non-infectious causes like SLE should also be considered as a diagnostic possibility.
Granulomatous; Lymphadenopathy; SLE
Idiopathic intracranial hypertension is a condition typically characterised by headache, normal level of consciousness, papilloedema and raised cerebrospinal fluid pressure. Children often present with visual loss and atypical features of raised pressure, posing a diagnostic and management challenge. A range of renal disorders can predispose to developing this raised intracranial pressure syndrome. We present a case of severe visual failure in a child with nephrotic syndrome, with no headache when elevated pressure was proven. In nephrotic syndrome, visual failure related to elevated intracranial pressures without concurrent headache symptoms has not been reported previously.
We discuss a 5-year-old Caucasian girl with steroid sensitive nephrotic syndrome who went on to become a late non-responder and presented with intracranial hypertension. Following initial response to steroids, she had a relapse of her nephrotic syndrome; her proteinuria did not resolve on steroid treatment, requiring addition of cyclosporine therapy to manage her nephrotic syndrome. Three months following this, she presented with visual failure in the right eye with bilateral central scotoma and papilloedema. At the time of presentation of visual impairment, she was otherwise well, with no symptoms of a raised intracranial pressure syndrome or associated systemic illness. Medical management was initiated following confirmation of a raised intracranial pressure. Her intracranial pressure remained elevated requiring serial therapeutic lumbar punctures before some improvement in visual acuity was observed. Later in the clinical course, she presented with worsening of her visual impairment with further deterioration of the vision in the left eye, again associated with elevated intracranial pressure. An urgent surgical cerebrospinal fluid diversion procedure was performed. At review, three years after presentation our patient has severe visual impairment with no perception of light in her right eye and 6/36 Snellen acuity in the left secondary to optic atrophy.
Our case demonstrates the occurrence of intracranial hypertension in nephrotic syndrome, highlighting the atypical presentation of severe visual failure without concurrent headache at presentation. This demonstrates the management complexities and the need for clear guidelines for ophthalmological surveillance to aim to reduce permanent visual impairment.
Pseudotumour cerebri; Benign intracranial hypertension; Idiopathic intracranial hypertension; Optic atrophy; Papilloedema; Cyclosporine
X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton’s tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant.
We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted.
We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.
X-linked agammaglobulinaemia; Bruton’s tyrosine kinase; Proteinuria; Haematuria; Immunoglobulin
Cytomegalovirus is the most common pathogen causing congenital infection and can result in significant neurodevelopmental adverse outcomes. For this reason, it is the standard of care in many regions to treat congenital cytomegalovirus infection involving the brain with six weeks of ganciclovir. There have been no reports in the published literature of significant cytomegalovirus neonatal infection in infants previously treated for congenital infection.
A preterm male infant with congenital symptomatic cytomegalovirus infection was initially treated with over 8 weeks of ganciclovir between the ages of 3 and 14 weeks. At four months chronologic age, just prior to planned discharge, he developed an episode of life-threatening multisystem cytomegalovirus disease notable for severe pneumonitis, encephalitis, hepatitis, and disseminated intravascular coagulation. This disease resolved after re-treatment with a prolonged course of intravenous ganciclovir and oral valganciclovir.
Clinicians should be aware of the possibility of recurrence of congenital cytomegalovirus infection, especially in preterm infants. Serial plasma cytomegalovirus viral load monitoring may have a role in the management of premature infants treated with ganciclovir; had the diagnosis of recrudescent cytomegalovirus infection been considered sooner, specific therapy might have been more quickly initiated and perhaps further morbidity would have been prevented.
Cytomegalovirus; Congenital infection; Ganciclovir
Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use.
A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved.
Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child.
Gynecomastia; HIV; Efavirenz; Child; Prepubertal
Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disorder, characterized by wide spread calcifications in arterial walls, leading to vaso-occlusive ischaemia of multiple organs. Mortality is high, and there is no definitive treatment.
A male neonate, 36+5 weeks gestation, 2.81 kg, was admitted to NICU for respiratory distress. At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary oedema. An echocardiogram (ECHO) indicated moderate persistent pulmonary hypertension (PPHN) of unclear etiology. A diagnosis of Idiopathic infantile arterial calcification was made and a trial of Editronate therapy was given without success.
IIAC is a rare disorder, it should be considered whenever a neonate presents with unexplainable cardiac failure, PPHN, echogenic vessels on X-ray/ultrasound and, or concentric hypertrophic ventricles on ECHO. Serial antenatal ultrasound findings of echogenic cardiac foci should raise the suspicion of IIAC. Further studies to determine the long term effects of Editronate on vascular calcifications, disease outcome, and other treatment options are needed.
Neonate; Infantile arterial calcification; Pulmonary hypertension; Biphosphonate
Benign hyperplastic thymus is a rare but important differential diagnosis of anterior mediastinal lesions. Histological and radiological criteria are used to distinguish this benign condition from other malignant diseases but have their limitations, and biopsy of mediastinal masses can be risky. We report for the first time the diagnostic value of fluorodeoxyglucose 18 F positron emission tomography for patients with incidentally identified anterior mediastinal masses to avoid biopsy in some cases.
A 2 year old girl presented with new onset of emesis and constipation leading to the incidental discovery of an anterior mediastinal mass on radiograph. Chest computed tomography revealed cystic components within the mass concerning for a malignancy. Biopsy of the lesion and bone marrow aspiration and biopsy were negative but there was concern that the mediastinal biopsy may have missed the malignant component of the lesion. Hence, a positron emission tomography scan was obtained that showed mild homogeneous fluorodeoxyglucose 18 F avidity within the mass similar to that of normal thymus. The diagnosis of benign hyperplastic thymus was made.
The differential diagnosis of an incidentally found anterior mediastinal mass includes malignancy, but benign lesions such as benign hyperplastic thymus must also be considered, particularly when the complete blood count and biochemical profile are normal. Fluorodeoxyglucose 18 F positron emission tomography can help guide a clinician’s decision for further interventions and treatment.
Mediastinal disease; Mediastinum; Positron-emission tomography; Thymus hyperplasia
Prune belly syndrome is a rare congenital malformation of unknown aetiology and is characterised by abnormalities of the urinary tract, a deficiency of abdominal musculature and bilateral cryptorchidism in males. We report a case of prune belly syndrome from Papua New Guinea, which was suspected on pregnancy ultrasound scan and confirmed upon delivery.
A 26-year-old married woman, Gravida 3 Para 2, presented to antenatal clinic in Madang, Papua New Guinea, at 21+5 weeks’ gestation by dates. She was well with no past medical or family history of note. She gave consent to participate in a clinical trial on prevention of malaria in pregnancy and underwent repeated ultrasound examinations which revealed a live fetus with persistent megacystis and anhydramnios. Both mother and clinicians agreed on conservative management of the congenital abnormality. The mother spontaneously delivered a male fetus weighing 2010 grams at 34 weeks’ gestation with grossly abnormal genitalia including cryptorchidism, penile aplasia and an absent urethral meatus, absent abdominal muscles and hypoplastic lungs. The infant passed away two hours after delivery. This report discusses the implications of prenatal detection of severe congenital abnormalities in PNG.
This first, formally reported, case of prune belly syndrome from a resource-limited setting in the Oceania region highlights the importance of identifying and documenting congenital abnormalities. Women undergoing antenatal ultrasound examinations must be carefully counseled on the purpose and the limitations of the scan. The increasing use of obstetric ultrasound in PNG will inevitably result in a rise in prenatal detection of congenital abnormalities. This will need to be met with adequate training, referral mechanisms and better knowledge of women’s attitudes and beliefs on birth defects and ultrasound. National medicolegal guidance regarding induced abortion and resuscitation of a fetus with severe congenital abnormalities may be required.
Congenital abnormality; Eagle-Barrett syndrome; Management; Papua New Guinea; Prenatal diagnosis; Prune belly syndrome; Ultrasound
Kearns-Sayre Syndrome (KSS) is a multisystem disorder caused by a dysfunction of the oxidative phosphorylation system within mitochondria. Mitochondrial DNA (mtDNA) rearrangements are a key molecular feature of this disease, which manifest a broad phenotypic spectrum.
Here, we present a boy with KSS whose symptoms included cardiac conduction deficit, cardiomyopathy and growth hormone (GH) deficiency. The patient showed typical symptoms for KSS from early childhood (chronic progressive external ophthalmoplegia, retinopathy, short stature). Long-range PCR analysis disclosed a 7663-base pair heteroplasmic deletion in the mtDNA encompassing nucleotides 6340–14003. At 12 years of age, GH deficiency was recognized and recombinant growth hormone (rGH) therapy was started. At 15 years of age, a complete atrioventicular block was diagnosed and the patient received a pacemaker. During the following 6 months, progressive deterioration of the left ventricle was observed and an echocardiogram showed features of dilated cardiomyopathy. The rGH treatment was then discontinued at a final height of 163 cm. Unfortunately, due to multi-organ insufficiency and inflammation, the patient died at the age of 18 years.
The response to rGH therapy in the patient was very satisfactory. The large mtDNA deletion had no apparent impact on the response to rGH. Cardiac disturbances occurred as part of the syndrome and were not related to rGH therapy; however, the progression of the disease led to death.
Growth hormone treatment; Mitochondrial disease; Atrio-ventricular block; Cardiomyopathy; Short stature
Long-term complications of sympathomimetic drug overdosing have not been adequately investigated in infants and young children. Despite reports discouraging their use in children, these formulations are frequently administered for “cold-like symptoms”. Their frequent adverse events are different forms of arrhythmias, including multifocal atrial tachycardia.
A 3-year-old toddler developed multifocal atrial tachycardia following an iatrogenic overdose of epinephrine accidentally administered intravenously. His ECG showed wandering atrial pacemaker (p-waves with different origins and configurations) that persisted for at least one year. This event demonstrated the sensitivity of young children to the sympathomimetic drugs, especially overdosing.
Health care providers and parents should be warned of toxicities associated with sympathomimetic drug overdosing. Future studies are needed to determine whether wandering atrial pacemaker is a potential long-term complication of high-dose sympathomimetics.
Epinephrine; Iatrogenic; Supraventricular tachycardia; Sympathomimetic toxicity; Wandering pacemaker; Arrhythmia
Evaluation of palpable neck masses may be a diagnostic problem in pediatric patients, with differential diagnosis including congenital, inflammatory, tumoral and traumatic lesions. Ultrasonography is usually a satisfactory method to make a correct pre-operative evaluation of neck masses, although diagnosis is often challenging for the surgeon and the radiologist and sometimes only possible after a histopathological examination of the resected lesion.
We report an 8-month-old patient with a cervical, anterior midline mass. Ultrasonographic images showed features suggesting a partly cystic lesion, with a preoperative suspect of thyroglossal duct cyst. Histological examination, performed after surgical removal of the mass, led to a diagnosis of lymph node angiomyomatous hamartoma (AH).
AH, a rarely occurring benign lymph node lesion, has been reported in the neck lateral region only twice. This case, presenting as a palpable neck midline mass, is the first reported case occurring in infancy. Although rare, AH should be included in the differential diagnosis of head and neck masses.
Angiomyomatous hamartoma; Pediatric neck mass; Ultrasonography; Lymph node
Intestinal spirochetosis is an unusual infection in children and its clinical significance in humans is uncertain. The presence of these microorganisms in humans is well-known since the late 1800’s and was first described in 1967 by Harland and Lee by electron microscopy.
This article reports the findings of one pediatric case, review of the current literature, and an overview of therapeutic options.
A high degree of suspicion is required in cases presenting with abdominal pain, chronic diarrhoea and/or hematochezia associated with a normal endoscopic examination, thus emphasizing the importance of multiple biopsies throughout the colon.
Intestinal spirochetosis; Brachyspira aalborgi; Brachyspira pilosicoli; Inflammatory bowel disease
The ATP7A gene encodes the ATP7A protein, which is a trans-Golgi network copper transporter expressed in the brain and other organs. Mutations in this gene cause disorders of copper metabolism, such as Menkes disease. Here we describe the novel and unusual mutation (p.T1048I) in the ATP7A gene of a child with Menkes disease. The mutation affects a conserved DKTGT1048 phosphorylation motif that is involved in the catalytic activity of ATP7A. We also describe the clinical course and the response to copper treatment in this patient.
An 11-month-old male Caucasian infant was studied because of hypotonia, ataxia and global developmental delay. The patient presented low levels of serum copper and ceruloplasmin, and was shown to be hemizygous for the p.T1048I mutation in ATP7A. The diagnosis was confirmed when the patient was 18 months old, and treatment with copper-histidinate (Cu-His) was started immediately. The patient showed some neurological improvement and he is currently 8 years old. Because the p.T1048I mutation affects its catalytic site, we expected a complete loss of functional ATP7A and a classical Menkes disease presentation. However, the clinical course of the patient was mild, and he responded to Cu-His treatment, which suggests that this mutation leads to partial conservation of the activity of ATP7A.
This case emphasizes the important correlation between genotype and phenotype in patients with Menkes disease. The prognosis in Menkes disease is associated with early detection, early initiation of treatment and with the preservation of some ATP7A activity, which is necessary for Cu-His treatment response. The description of this new mutation and the response of the patient to Cu-His treatment will contribute to the growing body of knowledge about treatment response in Menkes disease.
ATP7A; Menkes disease; Copper transporter; Cu-His treatment
The association of achondroplasia and Klinefelter syndrome is extremely rare. To date, five cases have been previously reported, all of them diagnosed beyond the postnatal period, and only one was molecularly characterized. We describe the first case of this unusual association diagnosed in the neonatal period, the clinical findings and the molecular studies undertaken.
The boy was born at term with clinical and radiological features indicating the diagnosis of achondroplasia or hypochondroplasia combined with the prenatal karyotype of Klinefelter syndrome (47,XXY). Neonatal FGFR3 mutation screening showed that the newborn was heterozygous for the classic achondroplasia G340R mutation. Microsatellite marker analysis showed that the sex chromosome aneuploidy had arisen from a non-disjunction error in paternal meiosis I, with a recombination event in the pseudoautosomal region 1 (PAR1).
Specific mutation analysis is appropriate to confirm the clinical diagnosis of achondroplasia for appropriate diagnosis, prognosis, and genetic counseling, especially when the karyotype does not explain the abnormal prenatal sonographic findings. In the present case, a recombination event was observed in the PAR1 region, although recombinational events in paternally derived Klinefelter syndrome cases are much rarer than expected.
Klinefelter syndrome; Achondroplasia; Mutation; Karyotype; Prenatal diagnosis