A case of Satoyoshi syndrome: a multisystem disorder

A 14-year-old boy with Satoyoshi syndrome is reported. Less than 50 patients with Satoyoshi syndrome have been reported in the world literature. This patient had alopecia, muscle spasms, and skeletal abnormalities, which are three of the most common clinical features of Satoyoshi syndrome. Despite extensive laboratory evaluation, an alternate explanation was not documented for the cluster of clinical findings in this patient. Immune dysregulation is believed to be an underlying mechanism for the development of Satoyoshi syndrome. In contrast to some reports, this patient failed to respond to intravenous immunoglobulin therapy. However, he responded dramatically to steroids.     

The spectrum of Evans' syndrome

Eleven patients (10 boys, one girl) with Evans'' syndrome with a median follow up time of 8.0 years were evaluated retrospectively. Six patients had either persistent hepatosplenomegaly or generalised lymphadenopathy, or both. In five patients, an increase in lymph node and/or spleen size was observed during the exacerbations of cytopenias. Seven patients had quantitative serum immunoglobulin abnormalities at the time of presentation. There were associated systemic manifestations in nine patients. Various forms of treatment were used with mixed results. Four patients died from sepsis and haemorrhage; four had complete recovery—two after splenectomy. These findings show that Evans'' syndrome is a heterogeneous disorder with significant morbidity and mortality. High incidence of quantitative serum immunoglobulin abnormalities, lymphoid hyperplasia, and associated systemic manifestations suggest that Evans'' syndrome may represent a stage of a more broad spectrum, generalised immune dysregulation.

     

Bladder wall telangiectasis causing life-threatening haematuria in ataxia-telangiectasia: a new observation

We report two cases of life-threatening haemorrhage from bladder telangiectasia in children with ataxia-telangiectasia (A-T) who had been treated for lymphoma earlier in life. Whilst oculocutaneous telangiectasiae are an almost universal finding in this syndrome, bladder wall telangiectasis has not been reported previously. Both teenagers presented with recurrent severe haematuria due to extensive bladder telangiectasis. Recurrent haemorrhage was controlled with cystoscopic diathermy treatment. As A-T is a DNA repair disorder, it is possible that chemotherapy-mediated damage to the bladder mucosa prompted the development of clinically significant telangiectasis in these patients. Conclusion: We advocate early cystoscopy for A-T patients who develop haematuria to investigate the cause, and cystodiathermy to pre-emptively treat developing lesions prior to haemodynamically significant haemorrhage.     

WISKOTT-ALDRICH SYNDROME A Study of 6 Cases with Determination of the Immunoglobulins A, D, G, M and ND

Six cases with Aldrich syndrome are presented, one of them splenectomized at the age of 3, died at the age of 6 years of adrenal haemorrhage. Another patient died at the age of 6 years of pneumonia with empyema and meningitis. The other 4 patients (1/2–6 years) are alive in a fairly good condition. Bleeding tendency dominates the symptoms in 2 cases, in the other 2, susceptibility to infections and/or eczema are the main symptoms. The bleeding tendency does not seem to be correlated to the number of platelets. Immunological studies in 5 of the patients have revealed a normal or high content of IgG in 4 of 5 cases and an increase of IgA in all. In 3 of 4 investigated patients elevated concentrations were demonstrated of a new immunoglobulin class, IgND. The immune response is changed; antibody production by vaccinations against viral diseases was poor, tuberculin reactions after BCG vaccination were negative, the pharyngeal lymphoid tissue was absent, and in 4 of the 5 investigated cases low titers of isoagglutinins were demonstrated.     

The Cockayne syndrome: an evaluation of hypertension and studies of renal pathology

Three children with renal disease, hypertension, and the Cockayne syndrome were evaluated. All patients had severe hypertension; peripheral vein renin was elevated in two patients. Renal biopsy specimens from two patients were studied by light microscopy, electron microscopy, and immunofluoresence. Immunohistologic studies demonstrated deposits of immunoglobulin and complement in the vessels and glomeruli of the first patient; deposits of immunoglobulin and complement were seen in the glomeruli of the third patient. Also electron-dense deposits were seen in the glomerular basement membrane of the third patient. Circulating immune complexes were detected by the Raji cell and Clq binding techniques in this child as well. Both hypertension and renal disease are frequent complications of the Cockayne syndrome.     

Hodgkin lymphoma developing in a 4.5-year-old girl with hyper-IgE syndrome

The authors report a case of Hodgkin lymphoma developing in a 4.5-year-old female child with hyper-IgE syndrome. This is one of the few cases of malignancy reported in this syndrome. The patient had severe atopic dermatitis, asthma, recurrent pneumonia, recurrent skin infections, and growth retardation. Immunologic evaluation revealed a high level of immunoglobulin E (7000 IU/mL) and peripheral eosinophilia. She was found to have normal values for serum IgG, IgM, IgA, WBC chemotaxis, serum complement function and normal sweat chloride test. The development of fatal Hodgkin lymphoma in this patient with hyper-IgE syndrome may suggest an increased risk for developing premature malignancies in hyper-IgE syndrome, although the precise immunologic defect is still unknown.     

Nasal and intrapulmonary haemorrhage in sudden infant death syndrome.

BACKGROUND: Fresh intrapulmonary and oronasal haemorrhages in cases of sudden infant death syndrome (SIDS) might be markers for accidental or intentional smothering inappropriately diagnosed as SIDS. AIM: To compare the incidence, epidemiological association, and inter-relation of nasal haemorrhage, intrapulmonary haemorrhage, and intrathoracic petechiae in infant deaths certified as SIDS. METHODS: In SIDS cases from a large nationwide case-control study, a wide range of variables were compared in cases with and without reported nasal haemorrhage and, in a subgroup of cases, in those with and without pathologically significant intrapulmonary haemorrhage. RESULTS: Nasal haemorrhage was reported in 60 of 385 cases (15%) whose parents were interviewed. Pathologically significant intra-alveolar pulmonary haemorrhage was found in 47% of 115 cases studied, but was severe in only 7%. Infants with nasal haemorrhage had more haemorrhage into alveoli and air passages than age matched cases without nasal haemorrhage. In multivariate analysis, nasal haemorrhage was associated with younger infant age, bed sharing, and the infant being placed non-prone to sleep. Intrapulmonary haemorrhage was associated with the same three factors in univariate analysis, but in multivariate analysis only younger infant age remained statistically significant. There was no significant association between nasal or intra-alveolar haemorrhages and intrathoracic petechiae. CONCLUSIONS: Nasal and intrapulmonary haemorrhages have common associations not shared with intrathoracic petechiae. Smothering is a possible common factor, although is unlikely to be the cause in most cases presenting as SIDS.     

MRI findings in Caffey's disease

A patient with infantile cortical hyperostosis (ICH) is presented. Common features in all reported patients include: onset in the early part of the 1st year, tender swellings in more than one site and multiple scattered hyperostoses, shown by radiography, but no previous study has determined the cause or origin of ICH. Biopsy of bony lesions only reveals hyperplasia of the lamellar cortical bone, without inflammation or subperiosteal haemorrhage. Although MRI resulted in excellent images for differentiation between bony and soft tissue structures and for evaluation of the extent of soft tissue involvement, it had no additional value in the management of the patient. Only in questionable cases can MRI provide additional information about the presence of a subperiosteal haemorrhage. Radiographic examination, in addition to clinical history and physical examination, is considered sufficient with regard to differential diagnosis and follow up of ICH.     

Nasal and intrapulmonary haemorrhage in sudden infant death syndrome

BACKGROUND—Fresh intrapulmonary and oronasal haemorrhages in cases of sudden infant death syndrome (SIDS) might be markers for accidental or intentional smothering inappropriately diagnosed as SIDS.AIM—To compare the incidence, epidemiological association, and inter-relation of nasal haemorrhage, intrapulmonary haemorrhage, and intrathoracic petechiae in infant deaths certified as SIDS.METHODS—In SIDS cases from a large nationwide case-control study, a wide range of variables were compared in cases with and without reported nasal haemorrhage and, in a subgroup of cases, in those with and without pathologically significant intrapulmonary haemorrhage.RESULTS—Nasal haemorrhage was reported in 60 of 385 cases (15%) whose parents were interviewed. Pathologically significant intra-alveolar pulmonary haemorrhage was found in 47% of 115 cases studied, but was severe in only 7%. Infants with nasal haemorrhage had more haemorrhage into alveoli and air passages than age matched cases without nasal haemorrhage. In multivariate analysis, nasal haemorrhage was associated with younger infant age, bed sharing, and the infant being placed non-prone to sleep. Intrapulmonary haemorrhage was associated with the same three factors in univariate analysis, but in multivariate analysis only younger infant age remained statistically significant. There was no significant association between nasal or intra-alveolar haemorrhages and intrathoracic petechiae.CONCLUSIONS—Nasal and intrapulmonary haemorrhages have common associations not shared with intrathoracic petechiae. Smothering is a possible common factor, although is unlikely to be the cause in most cases presenting as SIDS.     

Is pericerebral hemorrhage a cause of severe malaise in infants?]

The authors report 7 cases of infants presenting with an apparent life-threatening event associated with acute pericerebral haemorrhage (subarachnoid haemorrhage and/or subdural hematoma) without evidence of traumatism, abuse, or shaking. Clinical characteristics were the same in all cases, including limpness, severe dysautonomic disorders, and pallor; all infants had retinal and pre-retinal haemorrhages. Two infants died; the five survivors have severe neurologic sequelae. The symptoms revealing an infant's pericerebral haemorrhage are usually axial hypotonia and pallor. Traumatism remains the most common aetiology and must be searched for. Non-traumatic aetiologies are unusual and were excluded in these reported cases. The 'shaken baby' syndrome is not the sole aetiology of an apparent spontaneous pericerebral haemorrhage: a slight bump associated with predisposing vascular factors particular to infancy could be involved. When confronted with an apparent life-threatening event associating limpness and pallor, one must consider the diagnosis of pericerebral haemorrhage.     

Development of Kawasaki disease in a patient with PFAPA

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) is one of the autoinflammatory diseases of unknown etiology characterized by regularly recurrent fever episodes with attacks lasting 3–6 days every 3–8 weeks associated with at least one of the three cardinal clinical signs: aphthous stomatitis, pharyngitis, and cervical adenitis. Kawasaki disease (KD) is an acute, self‐limited systemic vasculitis that occurs predominantly in infants and young children. In most KD patients, i.v. immunoglobulin leads to a rapid amelioration of clinical symptoms and significantly decreases the risk of coronary artery aneurysms. Although the etiology of KD is still unknown, it was reported that innate immunity was activated in the patients. Described herein is a patient with PFAPA who developed KD. This is the first report of KD development in a PFAPA patient. The association between KD and PFAPA may represent a genetic predisposition to dysregulated innate immune response.     

Massive gastrointestinal haemorrhage in isolated intestinal Henoch-Schonlein purpura with response to intravenous immunoglobulin infusion

There is increasing recognition that Henoch-Schonlein purpura may present in an atypical form in which gastrointestinal symptoms may predominate, and classic cutaneous changes may be delayed or absent. This may lead to significant diagnostic delay. We report the case of a 9-year-old girl who presented acutely with life-threatening gastrointestinal haemorrhage from multiple intestinal sites, with no skin rash and only mild evidence of renal involvement. Henoch-Schonlein purpura was confirmed by finding IgA deposition on vessels within gastric and duodenal mucosa, while immunohistochemistry also identified dense focal T cell infiltration in gastric mucosa and within duodenal epithelium. After initial stabilisation, the patient became shocked due to further gastrointestinal haemorrhage. Isotope bleeding scan identified multiple bleeding sites. Her endoscopically confirmed gastritis was sufficiently severe to preclude corticosteroids, and she was thus treated with intravenous immunoglobulin. This therapy induced prompt and sustained resolution of symptoms, and she has remained well since. Our patient's response concords with previous reports in corticosteroid-resistant cases to suggest that severe intestinal Henoch-Schonlein purpura may respond preferentially to intravenous immunoglobulin (IVIG) therapy. In severe cases where there is significant gastritis, IVIG provides an effective alternative to corticosteroids that may be employed as first-line therapy.     

Clinical practice: immune thrombocytopenia in paediatrics

Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A “watch and wait” strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents.     

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome in a Swiss child

Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a rare neurodegenerative syndrome first reported in 1991. Most patients described are of Finnish descent and very few patients have been reported in other countries. We report the first Swiss patient who fulfils the criteria of the PEHO syndrome. The course of the epilepsy is less severe than previously reported. Our patient developed a severe dystonic state after a febrile gastrointestinal infection, with a hypotonic state that may have been a dysregulation of brainstem origin. The diagnosis was made because of marked cerebellar atrophy in the repeated MRI. In patients with infantile spasms and severe developmental delay PEHO syndrome should be considered; it is not confined to Finnish heritage. Optic atrophy should be looked for and repeat MRI is indicated.     

IMMUNOGLOBULINS IN 13–15 TRISOMY SYNDROME DUE TO A TRANSLOCATION

A case of 13–15 trisomy syndrome, due to a translocation between two chromosomes of the 13–15 group, is described. The parents' karyotypes were normal. The child showed typical features of the syndrome except for the absence of harelip, cleft palate and four-finger lines. Despite numerous infections the immunoglobulin concentrations were very low, although not significantly lower than those found in normal, non-infected infants of the same age. At present the boy is 27 months old. Thus, he has survived longer than most other patients with this syndrome reported in the literature.     

Recombinase-activating gene 1 immunodeficiency: different immunological phenotypes in three siblings

We report different immunological phenotypes in three siblings from consanguineous family with recombinase-activating gene 1 ( RAG1 ) gene mutations. Null mutations of RAG genes result in severe combined immunodeficiency (SCID) with absent T and B cells. Hypomorphic mutations with retained activity of RAG genes may lead to a 'leaky' SCID with some features of Omenn syndrome (OS) or typical OS. In our three patients, homozygous, hypomorphic RAG1 gene mutation (g.368–369delAA) was detected. Two patients presented with T−B−SCID phenotype while the youngest patient developed T+B+NK+SCID phenotype with expansion of autologous T-cell receptor (TCR) γδ-positive T cells, increased immunoglobulin levels and retained ability for antibody production. Similar to originally reported patients with this newly recognized immune phenotype, our patient developed disseminated cytomegalovirus (CMV) infection and autoimmune cytopenia.
Conclusion: In infants with disseminated cytomegalovirus infection and autoimmune cytopenia, even if basic immunologic investigation appears normal, RAG1 immunodeficiency should be considered.     

Autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura in pediatric solid organ transplant recipients, report of five cases and review of the literature

Cytopenias are common among pediatric SOT; however, autoimmune cytopenias are infrequently reported. We report five cases of autoimmune cytopenias in pediatric LT patients: two with isolated IgG-mediated AIHA, two with ITP, and one with Evans syndrome (ITP and AIHA). All patients were maintained on tacrolimus as immunosuppression. Viral illness commonly preceded the autoimmune cytopenias. All patients responded well to medical therapy (steroids, intravenous immunoglobulin, and rituximab) and lowering tacrolimus serum level. Prognosis appears to be worse when more than one cell line (e.g., Evans syndrome) is affected, and/or there is no preceding viral illness. A critical literature review of autoimmune cytopenias in children following SOT is conducted. Autoimmune cytopenias are a rarely reported complication of pediatric SOT, but clinicians taking care of pediatric transplant recipients need to be aware of this complication.     

High-dose iv human immunoglobulin in a case with infantile opsoclonus polymyoclonia syndrome

We report a 14-month-old male with infantile opsoclonus polymyoclonia syndrome. His clinical disabilities responded favorably to high-dose human immunoglobulin therapy. High dose immunoglobulin therapy is one of the therapies for patients with this syndrome.     

Dose related growth response to indometacin in Gitelman syndrome.

Growth failure is a recognised feature of Gitelman syndrome, although it is not as frequent as in Bartter syndrome. Indometacin is reported to improve growth in Bartter syndrome, but not in Gitelman syndrome, where magnesium supplements are recommended. This paper presents 3 sisters with Gitelman syndrome who could not tolerate magnesium supplements, and whose hypotension and polyuria were eliminated by taking 2 mg/kg/day indometacin, but who grew poorly. However, increasing the indometacin dose to 4 mg/kg/day improved their growth significantly, without changing their symptoms or biochemistry. Gastrointestinal haemorrhage necessitated the use of misoprostol.     

Dose related growth response to indometacin in Gitelman syndrome

Growth failure is a recognised feature of Gitelman syndrome, although it is not as frequent as in Bartter syndrome. Indometacin is reported to improve growth in Bartter syndrome, but not in Gitelman syndrome, where magnesium supplements are recommended. This paper presents 3 sisters with Gitelman syndrome who could not tolerate magnesium supplements, and whose hypotension and polyuria were eliminated by taking 2 mg/kg/day indometacin, but who grew poorly. However, increasing the indometacin dose to 4 mg/kg/day improved their growth significantly, without changing their symptoms or biochemistry. Gastrointestinal haemorrhage necessitated the use of misoprostol.