Incomplete Clinical Presentation Research Articles

Juvenile Behçet syndrome: a contemporary view and differential diagnosis in pediatric practice.

This review aims to provide a comprehensive and contemporary overview of juvenile Behçet syndrome (jBS), highlighting its clinical manifestations, diagnostic challenges, and treatment strategies. Behçet syndrome, with its intricate etiopathogenesis and diverse clinical phenotypes, is more aptly classified as a syndrome than a single disease. Its heterogeneous nature requires a broad diagnostic approach and sophisticated differential diagnosis capabilities. The relatively rare occurrence of Behçet syndrome, combined with incomplete clinical presentations and overlapping differential diagnoses, presents significant diagnostic challenges, particularly in pediatric cases. Nevertheless, substantial progress has been made in treatment, especially in managing inflammatory components and preventing complications. Juvenile patients, given their developmental stage, require distinct therapeutic strategies compared to adults, with careful consideration of treatment side effects on growth and psychosocial development. To ensure early identification of jBS, it is imperative to refine and develop diagnostic criteria specifically tailored to pediatric populations. With a deeper understanding of the disease mechanisms, treatment protocols should be designed to address the developmental, psychosocial, and individual needs of patients, aiming to minimize long-term side effects. Additionally, comprehensive studies considering age, sex, and ethnic differences are necessary to fill gaps in the literature and resolve existing inconsistencies.

Clinical features and eosinophilia in pityriasis rubra pilaris: A multicenter cohort

Clinical features and eosinophilia in pityriasis rubra pilaris: A multicenter cohort

Kawasaki disease in infants under one year of age. A challenge for the diagnosis and treatment of patients. Experience in a hospital center in Mexico

Frequency of Kawasaki disease (KD) in infants is low in almost all countries. These patients are at higher risk of developing cardiac complications. To evaluate the clinical features, treatment used and cardiac outcome in infants under one year of age attending for KD in a third level pediatric hospital in Mexico City, Mexico. A cross-sectional study was conducted in our hospital from August 1995 to August 2019. We analyzed the clinical features, laboratory results, treatment used and cardiac outcomes in infants younger than one year of age and compared them with older patients. We included 687 patients, 152 were younger than one year of age (22.1%). There was a delayed diagnosis in younger patients with an increased frequency of incomplete clinical presentations. Coronary artery abnormalities were most common in younger infants who also had an increased frequency of giant coronary artery aneurysms. Two patients in the younger group died in the acute phase of KD of myocardial infarction. Diagnosis of KD in infants younger than 1 year of age is a clinical challenge with an increased rate of incomplete clinical presentations and also an increased risk of development of severe cardiac complications.

Clinical spectrum of the pentanucleotide repeat expansion in the RFC1 gene in ataxia syndromes.

To determine the clinical significance of an intronic biallelic pentanucleotide repeat expansion in the gene encoding replication factor C subunit 1 (RFC1) in patients with late-onset cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), in patients with other ataxias, and in healthy controls by comprehensive genetic analyses. In this case-control study, we included 457 individuals comprising 26 patients with complete or incomplete CANVAS, 70 patients with late-onset cerebellar ataxia, 208 healthy controls, and 153 individuals from 39 multigenerational families without ataxia to determine repeat stability. All 96 patients were screened for the repeat expansion by duplex PCR. To further characterize the repeat type and lengths, we used fragment length analysis, repeat-primed PCR, Sanger sequencing, and Southern blotting. Expression of RFC1 and the neighboring gene WDR19 were determined by quantitative PCR. Massive biallelic pentanucleotide expansions were found in 15/17 patients with complete CANVAS (88%), in 2/9 patients with incomplete CANVAS (22%), in 4/70 patients with unspecified, late-onset cerebellar ataxia (6%), but not in controls. In patients, the expansion comprised 800-1,000 mostly AAGGG repeats. Nonmassively expanded repeat numbers were in the range of 7-137 repeats and relatively stable during transmission. Expression of RFC1 and WDR19 were unchanged and RFC1 intron retention was not found. A biallelic pentanucleotide repeat expansion is a frequent cause of CANVAS and found in a considerable number of patients with an incomplete clinical presentation or other forms of cerebellar ataxia. The mechanism by which the repeat expansions are causing disease remains unclear and warrants further investigations.

Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait macules.

Children with neurofibromatosis type 1 (NF1) may exhibit an incomplete clinical presentation, making difficult to reach a clinical diagnosis. A phenotypic overlap may exist in children with other RASopathies or with other genetic conditions if only multiple café-au-lait macules (CALMs) are present. The syndromes that can converge in these inconclusive phenotypes have different clinical courses. In this context, an early genetic testing has been proposed to be clinically useful to manage these patients. We present the validation and implementation into diagnostics of a custom NGS panel (I2HCP, ICO-IMPPC Hereditary Cancer Panel) for testing patients with a clinical suspicion of a RASopathy (n = 48) and children presenting multiple CALMs (n = 102). We describe the mutational spectrum and the detection rates identified in these two groups of individuals. We identified pathogenic variants in 21 out of 48 patients with clinical suspicion of RASopathy, with mutations in NF1 accounting for 10% of cases. Furthermore, we identified pathogenic mutations mainly in the NF1 gene, but also in SPRED1, in more than 50% of children with multiple CALMs, exhibiting an NF1 mutational spectrum different from a group of clinically diagnosed NF1 patients (n = 80). An NGS panel strategy for the genetic testing of these two phenotype-defined groups outperforms previous strategies.

Neuromyelitis optica spectrum disorders in South of Tunisia: A rare entity with low seroprevalence of anti-aquaporin 4 autoantibodies

IntroductionScreening for anti-aquaporin 4 (anti-AQP4) antibodies, a specific marker of neuromyelitis optica spectrum disorders (NMOSD), is part of the immunological investigation performed in a context of central nervous system (CNS) inflammation with optic neuritis and/or myelitis. The aim of our study was to evaluate the prevalence and the diagnostic value of anti-AQP4 antibodies in Tunisian patients with such inflammatory neurological conditions. MethodsDuring 3years, 170 consecutive serum samples of Tunisian patients with CNS inflammatory disorders and optico-spinal involvement were tested in our laboratory for anti-AQP4 antibodies using indirect immunofluorescence on transfected cells. ResultsThe global seroprevalence of anti-AQP4 in our study was 4.1% (7 cases/170). The diagnosis of NMOSD was made for the 7 seropositive patients and for 2 seronegative patients, which leads to a seroprevalence of 77.7% in our NMOSD subgroup. The detection of anti-AQP4 allowed the diagnosis of NMOSD in 4 patients with incomplete clinical presentation and 5 patients with positive antinuclear antibodies. In one case, seropositivity was detected in a second sample, one year after an initial seronegativity. ConclusionNMOSD seem to represent a rare etiology of optic neuritis and/or myelitis in Tunisian patients. Despite its low global seroprevalence in our study population, anti-AQP4 appears to be a very clinically relevant marker for NMOSD diagnosis. Repeating the screening in case of initial negativity could be interesting in clinical practice.

Onset of Kawasaki disease immediately after birth

Abstract Kawasaki disease (KD) is one of the most common causes of childhood systemic vasculitis, with the potential to cause significant cardiovascular complications, especially if undiagnosed. An investigation of coronary artery abnormalities with the application of appropriate therapeutic measures can improve the prognosis in these infants, decreasing the risk of coronary artery aneurysms. Neonatal KD is a rare event, often characterized only by few of the clinical features observed in older children. In this case report, we describe a newborn male who presented an incomplete clinical presentation of KD, where symptoms of the disease erupted immediately after birth. The objective of this report is to draw the attention of pediatricians and neonatologists to the possible presence of KD in an asymptomatic newborn during the immediate postnatal period, even in the absence of the classic features of KD, such as fever.

Differentiating Vogt-Koyanagi-Harada syndrome from recurrent optic neuritis: a case report and review of the literature concerning Hispanic patients

BackgroundFirst recognized at the beginning of twentieth century and named after three authors who independently described some affected patients, Vogt-Koyanagi-Harada syndrome is a rare multisystemic autoimmune disease targeting melanin-containing tissues of the eye, meninges, inner ear and skin. It predominantly affects Asian people, but also people with darker skin pigmentation such as Native Americans and Hispanics (Mestizos), whose ancestors moved from Asia across the Bering strait to North America and further down to Central and South America. Heterogenous presentation is observed, especially among different ethnic groups. Here we describe the case of an Hispanic South American patient presenting with multiple visual relapses and thus mimicking recurrent optic neuritis; we provide insights into the differential diagnosis and a brief review of the literature concerning the epidemiology of Vogt-Koyanagi-Harada syndrome in Hispanic patients compared with other ethnic groups.Case presentationA 34-year-old Ecuadorian woman presented over years with multiple relapses involving the visual system. She was investigated in both neurologic and ophthalmic clinical settings. Brain Magnetic Resonance Imaging, cerebrospinal fluid examination, Spectral Domain Optical Coherence Tomography and Fluorescein Angiography were performed. She was misdiagnosed first as an optic neuritis pointing to a demyelinating disorder, then as a posterior scleritis. Due to the protean manifestations of Vogt-Koyanagi-Harada syndrome and the incomplete clinical presentation at the beginning, the right diagnosis was made only at a later disease stage using retrospective criteria.ConclusionsHispanic patients often present without extraocular symptoms in early phases of the disease and they have globally lower rates of intertegumentary signs compared to Asian patients. The diagnosis of a multisystemic disease such as Vogt-Koyanagi-Harada syndrome is a challenge involving specialists operating in different medical fields; especially in urban multiethnic populations, rare etiologies of common symptoms have to be taken into account when performing a differential diagnosis.

Microangiopatía trombótica secundaria y eculizumab: una opción terapéutica razonable

Understanding the role of the complement system in the pathogenesis of atypical haemolytic uraemic syndrome and other thrombotic microangiopathies (TMA) has led to the use of anti-complement therapy with eculizumab in these diseases, in addition to its original use in patients with paroxysmal nocturnal haemoglobinuria andatypical haemolytic uraemic syndrome. Scientific evidence shows that both primary and secondary TMAs with underlying complement activation are closely related. For this reasons, control over the complement system is a therapeutic target. There are 2scenarios in which eculizumab is used in patients with TMA: primary or secondary TMA that is difficult to differentiate (including incomplete clinical presentations) and complement-mediated damage in various processes in which eculizumab proves to be efficacious. This review summarises the evidence on the role of the complement activation in the pathophysiology of secondary TMAs and the efficacy of anti-complement therapy in TMAs secondary to pregnancy, drugs, transplant, humoral rejection, systemic diseases and glomerulonephritis. Although experience is scarce, a good response to eculizumab has been reported in patients with severe secondary TMAs refractory to conventional treatment. Thus, the role of the anti-complement therapy as a new treatment option in these patients should be investigated.

Secondary thrombotic microangiopathy and eculizumab: A reasonable therapeutic option

Understanding the role of the complement system in the pathogenesis of atypical haemolytic uraemic syndrome and other thrombotic microangiopathies (TMA) has led to the use of anti-complement therapy with eculizumab in these diseases, in addition to its original use in patients with paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome. Scientific evidence shows that both primary and secondary TMAs with underlying complement activation are closely related. For this reasons, control over the complement system is a therapeutic target. There are 2 scenarios in which eculizumab is used in patients with TMA: primary or secondary TMA that is difficult to differentiate (including incomplete clinical presentations) and complement-mediated damage in various processes in which eculizumab proves to be efficacious. This review summarises the evidence on the role of the complement activation in the pathophysiology of secondary TMAs and the efficacy of anti-complement therapy in TMAs secondary to pregnancy, drugs, transplant, humoral rejection, systemic diseases and glomerulonephritis. Although experience is scarce, a good response to eculizumab has been reported in patients with severe secondary TMAs refractory to conventional treatment. Thus, the role of the anti-complement therapy as a new treatment option in these patients should be investigated.

The Clinical Diagnosis and Management of Kawasaki Disease: a Review and Update.

Kawasaki disease is an acute, self-limited vasculitis of childhood and has become the leading cause of acquired pediatric heart disease in the USA. Prompt treatment is essential in reducing cardiac-related morbidity and mortality. The underlying etiology remains unknown. The disease itself may be the characteristic manifestation of a common pathway of immune-mediated vascular inflammation in susceptible hosts. The characteristic clinical features of fever for at least 5 days with bilateral nonpurulent conjunctivitis, rash, changes in lips and oral cavity, changes in peripheral extremities, and cervical lymphadenopathy remain the mainstay of diagnosis. Supplementary laboratory criteria can aid in the diagnosis, particularly in cases of incomplete clinical presentation. Diagnosis of Kawasaki disease can be challenging as the clinical presentation can be mistaken for a variety of other pediatric illnesses. Standard of care consists of intravenous immune globulin and aspirin. Corticosteroids, infliximab, and cyclosporine A have been used as adjunct therapy for Kawasaki disease refractory to initial treatment. There is ongoing research into the use of these agents in the initial therapy of Kawasaki disease.

Indocyanine green angiography findings in patients with nonfamilial amyloidosis

PurposeThe purpose of this study is to assess indocyanine green angiographic findings in patients with nonfamilial amyloidosis.MethodsThe method used was a prospective study including seven patients (14 eyes) with nonfamilial amyloidosis. All patients underwent detailed ophthalmic clinical examination, fundus photography, and indocyanine green angiography (ICGA). Fluorescein angiography (FA) was performed in four patients.ResultsOf the seven patients, four (57.1 %) were male. Mean age was 49.5 years. Six patients had renal amyloidosis and one patient had systemic amyloidosis. Mean best-corrected visual acuity was 20/25. Fundus and FA findings included cotton-wool spots (28.5 %), retinal hemorrhages (14.3 %), retinal pigment epithelial changes (21.4 %), serous retinal detachment (7.1 %), optic disk edema or staining (7.1 %), area of peripheral retinal capillary non-perfusion (7.1 %), disseminated peripheral punctiform hyperfluorescence (21.4 %), and subretinal pooling (7.1 %). Fundus examination results were unremarkable in eight eyes (57.1 %). ICGA showed abnormal findings in all eyes. These included diffuse or focal/multifocal choroidal vascular staining appearing at the late phase and prevailing in peripheral fundus (100 %), hyperfluorescent fleecy lesions appearing at the late phase and also prevailing in peripheral fundus (28.5 %), hypofluoresent areas of variable sizes (85.7 %), and pinpoints (71.4 %).ConclusionsOur results show that a subclinical, fairly typical choroidal involvement, detectable only by ICGA, is common in patients with nonfamilial amyloidosis. ICGA may be useful in better understanding the pathogenesis of amyloidosis choroidopathy and in establishing a diagnosis of amyloidosis in atypical or incomplete clinical presentations.

Complete and incomplete Kawasaki disease: two sides of the same coin

We sought to determine differences in clinical presentation, treatment response and coronary artery outcomes between complete and incomplete KD. All patients treated for KD between January 1990 and April 2007 were reviewed. Patients were classified as having an incomplete presentation if presenting with fever ≥ 5 days and <4 "classic" KD clinical signs. A total of 955 patients were included. Incomplete clinical presentation was seen in 217 cases (23%). Patient's demographic, clinical and laboratory characteristics were similar between groups with few exceptions. Patients presenting with incomplete KD had a longer median interval from symptom onset to diagnosis (7 [4-17] versus 6 [6-13] days, p < 0.001) and were less likely to be treated with intravenous immunoglobulin (86% versus 96%, p < 0.001). No significant difference between groups were seen in regard to coronary artery abnormalities (incomplete 13% versus complete 11%, p = 0.58). Complete and incomplete KD appear to be different sides of the same coin, differing only in the number of signs and symptoms at presentation. Similar laboratory findings and coronary artery outcomes between the two groups support this conclusion.

Travel‐Related Cerebro‐Meningeal Infections: The 8‐Year Experience of a French Infectious Diseases Unit

The etiological spectrum of cerebro-meningeal infections (CMI) in travelers has never been specifically analyzed. To assess the etiologies of CMI in hospitalized travelers and to propose a diagnostic approach to travel-related CMI. During an 8-year period, we retrospectively collected data on all travelers hospitalized in our department for a CMI occurring during travel or in the month after their return. Fifty-six patients (35 men and 21 women; mean age 29 years (16-83); 44.6% tourists, 26.8% military, 16% immigrants, 12.5% expatriates) were included. The main destinations were Africa (57.2%), Europe (19.5%), and Asia (12.5%). The median duration of travel was 24 days (5-550). Symptoms occurred during travel in 20 patients (11 of which required a medical evacuation). In the remaining 36 patients, the median duration between return and clinical onset was 10 days. The median time from clinical onset to hospitalization was 4 days (0.5-96). Twenty-four patients presented with a meningeal syndrome and 20 others with encephalitic features. The remaining 12 patients had an incomplete clinical presentation (headaches or fever). The etiology was confirmed in 42 cases (75%) of which tropical diseases (n = 14) were less common than cosmopolitan ones (n = 28). Sub-Saharan Plasmodium falciparum malaria (n = 12) was the leading tropical infection, whereas viral infections (enterovirus, herpesviridae, HIV) were the main cosmopolitan etiologies. Only four bacterial infections were reported (Neisseria meningitidis, Mycoplasma pneumoniae, Brucella melitensis, Salmonella typhi). Sixteen patients were admitted to intensive care for a median time of 9.5 days (1-63). The average duration of hospitalization was 14 days (3-63). One death by herpes simplex virus 1 encephalitis was recorded. Four patients (7%) had neurological sequelae. Among the diversified etiological spectrum of CMI, cosmopolitan infections are widely predominant, particularly viral infections, followed by tropical causes, of which malaria is the leading disease in returnees from endemic areas. The diagnostic approach should be driven by history and physical examination. Key investigations include: blood smear, cerebrospinal fluid polymerase chain reaction and culture as well as neuroimaging. Management should focus on curable causes.

Characteristics of Kawasaki Disease in Infants Younger than Six Months of Age

Kawasaki disease is the leading cause of acquired heart disease in childhood. However, there are only a few reports in infants younger than 6 months. The objective of this study is to investigate the clinical and laboratory characteristics of Kawasaki disease in infants younger than 6 months. From 1994 to 2003, 120 patients with Kawasaki disease diagnosed at our institution were included. Group 1 consisted of 20 (17%) patients younger than 6 months, and group 2 consisted of 100 (83%) patients older than 6 months. Clinical manifestations, laboratory results, echocardiographic findings, treatment and outcome were compared between these 2 groups. Clinical manifestations (hydrops of gallbladder: 0% versus 16%, P < 0.001) and laboratory results (white blood cell count 21,740 +/- 11,706 versus 11,830 +/- 4390/mm3, P < 0.001; hemoglobin 9.98 +/- 1.25 versus 10.8 +/- 1.37 g/dL, P = 0.015; platelet 483 +/- 393 versus 355 +/- 138 x 1000/mm3, P = 0.011; triglyceride 138 +/- 77.5 versus 107 +/- 17 mg/dL, P < 0.001) were different between patients with Kawasaki disease younger and older than 6 months, respectively. Younger infants were more likely to have incomplete presentation (35% versus 12%, P = 0.025), coronary involvement (65% versus 19%, P < 0.001), late intravenous immunoglobulin treatment and relatively poor outcome. Infants younger than 6 months with prolonged unexplained febrile illnesses should be suspected as having Kawasaki disease, despite the incomplete clinical presentation. Because early diagnosis and timely treatment are difficult in younger infants with Kawasaki disease because of delayed and incomplete clinical presentations, echocardiogram becomes an important implement for diagnosis. Early intravenous immunoglobulin treatment is required in view of the highest risk of coronary involvement in them.

Formes pauci-symptomatiques du syndrome respiratoire aigu sévère (sras)

IntroductionUne épidémie de pneumopathies atypiques est apparue en novembre 2002 dans la région Chinoise de Guangdong. Elle a ensuite été décrite sous le nom de syndrome respiratoire aigu sévère (SRAS) à partir de nouveaux foyers survenus à Hanoi et à Hong Kong en février 2003. En France, 5 cas reliés au même patient source ont été rapportés.ObservationNous rapportons l’observation d’un patient de 52 ans contact direct avec un cas probable de SRAS. À l’admission, le patient présente une hyperthermie isolée sans symptomatologie respiratoire associée à une lymphopénie et une cytolyse hépatique. La radiographie thoracique est normale. La tomodensitométrie thoracique objective l’existence d’un aspect en verre dépoli sous pleural. L’étude par PCR des prélèvements naso-pharyngés précoces (36e heure) à la recherche du coronavirus associé au SARS sera négative. La confirmation du cas sera obtenue par l’étude sérologique.ConclusionsCette observation illustre l’existence de présentations cliniques frustres du syndrome respiratoire aigu sévère. La contagiosité des formes pauci symptomatiques n’est pas connue. Des analyses sérologiques permettront de mieux les préciser. Le danger actuel d’une recrudescence saisonnière particulièrement hivernale ne peut être écarté. Dans ce contexte, l’existence et la reconnaissance des formes pauci symptomatiques pour lesquelles la contagiosité ne peut être écartée est primordiale.