[Show abstract][Hide abstract] ABSTRACT: A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All
standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation
sequencing allowed fast identification of a new astrovirus strain (HAstV-VA1/HMO-C-PA), which led to tailor the patient's
treatment, with encouraging clinical monitoring over 1 year.
[Show abstract][Hide abstract] ABSTRACT: Background Childhood-onset panniculitides are rare and classically include infectious, connective tissue, malignant, metabolic, and drugs, cold or trauma-induced panniculitis. Some specific types of panniculitis are only seen in neonates and very young infants, and include subcutaneous fat of the newborn, poststeroid panniculitis, sclerema neonatorum, and cold panniculitis. However, no specific discoverable etiology can be identified in many patients.
Objectives To describe the spectrum of clinical and pathological manifestations of childhood-onset panniculitis of unknown cause
Methods A retrospective single-center study of children presenting with panniculitis diagnosed by skin biopsy
Results Eighteen patients were identified. The onset of symptoms occurred within the first two years of life in 15/18 patients (83%). Panniculitis was the revealing manifestation in 15/18 (83%) patients, and relapsed in 13/18 (72%) patients. Associated-non-cutaneous features occurred in 16/18 (89%) patients, especially autoinflammatory manifestations in 13/18 patients (72%), associated with immunodeficiency in 5 patients (low T or B cells count with hypogammaglobulinemia in 4 and 1 patients respectively). Autoinflammatory manifestations consisted in attacks of fever with an elevation of acute phase reactants associated with polyarthritis or polyarthralgia (2 patients), rash (2 patients) or aseptic adenitis (2 patients). Panniculitis was mostly lobular in 10 (55%) patients, septal in 3 (17%) patients or both in 5 patients (28%). Predominant infiltrate consisted of neutrophils, cytophagic histiocytes, lymphocytes, eosinophils in 8 (44%), 5 (28%), 3 (17%), and 1 (5.5%) patients respectively, and included granuloma in 1 patient. No relationship was found between clinical and pathological features. Genomic mutations were identified in 3 of the 4 patients who underwent genetic analysis: mutations in TRNT1, MVK (mevalonate kinase) and LCK genes.
Conclusions This series underlines that auto-inflammatory diseases, possibly associated with inherited immunodeficiency, are a main cause of early-onset panniculitis. The identification of a monogenic cause in 3 patients and the early-onset presentation of the disease suggest that a subset of patients has a genetic predisposition to develop panniculitis, especially early-onset panniculitis.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1222.1-1222. DOI:10.1136/annrheumdis-2015-eular.4745 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: The incidence of invasive fungal diseases (IFD) is currently increasing as a consequence of the growing population of immunocompromised patients. A key to IFD prognosis relies on early diagnosis, allowing early initiation of antifungal therapy. Over past years, the detection of the fungal (1-3)-β-D-glucan (BG) antigen has been increasingly used as an early IFD marker. However, different studies evaluating the performances of the BG assay in different target populations found contradictory results. In the present study, we assessed BG serum concentrations (Fungitell®, Associates of Cape Cod) in patients with documented IFD at time of diagnosis (TOD) and during antifungal treatment.
Methods: We included 118 adults and 23 children with candidemia, invasive aspergillosis (IA) or rare IFD. Patients with two concomitant IFD or a possible cause of false-positive BG results were excluded. For candidemia and IA, serial sera were prospectively collected. The first serum was sampled respectively within [-3;+7] or [-7;+7] days toward mycological diagnosis. The follow-up period was of 2 and 6 months, respectively. Patients with rare IFD were included when at least one BG dosage was available within [-7;+15] days toward diagnosis. Whenever possible, a BG follow-up was performed until the IFD was controlled.
Results: Thirty-three patients with candidemia and 31 with IA (28 probable and 3 proven IA) were included. They were patients with hematological diseases, solid organ transplant or patients hospitalized in ICU. Serum BG at TOD was negative in 44% of patients with candidemia and 52% with IA. No correlation was observed between negative BG at TOD and particular Candida species, catheter use, IA type, category of patients or recent administration of antifungals. Overall, for 18% and 14% of patients with candidemia and IA, BG remained not detected during the entire follow-up period. Among patients with candidemia or IA who had positive BG at TOD, >80% reached their peak value within the subsequent 2 weeks. Afterwards, the decrease of BG concentrations was rapid (half-concentration <1 week) in 50% of patients with candidemia, slow (half-concentration >3 weeks) in 20%, while 30% had persistently high BG. Thirty-three percent of patients with IA had a rapid decrease (half-concentration in <2 weeks) while 67% had very slow decrease (half-concentration >2 months). Regarding rare IFD, we included 77 patients with 26 different infections. While some IFD (scedosporiosis or cryptococcosis) had variable patterns toward BG at TOD, other were associated in all our cases with negative BG (fusariosis, microsporidiosis) or moderate to high (≥ 200 pg/ml) BG (hepatosplenic candidiasis, eumycotic mycetoma, subcutaneous phaehypho- or dermatophytomycosis, trichosporonosis).
Conclusion: Altogether, our results offer valuable information for the clinical use of BG assay in various IFD and highlight the high percentage of patients with documented IFD, mainly candidemia and IA, for whom BG are negative at TOD.
[Show abstract][Hide abstract] ABSTRACT: Thrombotic microangiopathy (TMA) occurring after allogeneic hematopoietic stem cell transplantation (HSCT) has a devastating prognosis. Response rates to current therapies (mainly plasma exchange) are unsatisfactory. Thrombotic microangiopathy after allogeneic HSCT shares similarities with atypical hemolytic uremic syndrome (aHUS) in the underlying pathomechanisms. Eculizumab has been associated with impressive results in aHUS.
We retrospectively analyzed 12 patients who received Eculizumab in France between 2010 and 2013 for severe post-HSCT TMA.
All 12 patients had severe TMA with neurological and/or renal involvement. Fifty-eight percent were refractory to first-line plasma exchange. At the time of TMA diagnosis, infections were present in 50% of the patients and acute graft-versus-host disease in 33%. Patients were treated with Eculizumab according to the aHUS therapeutic scheme. With a median follow-up of 14 months, hematological response and overall survival were 50% and 33%, respectively. Active acute graft-versus-host disease at TMA diagnosis was the only factor associated with worse overall survival (P = 0.009).
Response rate and overall survival after Eculizumab in our cohort compare favorably with previously published data in TMA after allogeneic HSCT. Prospective trials are warranted to confirm these results. Early initiation of Eculizumab may have a favorable effect on long-term renal function and further contribute to the prolongation of survival.
[Show abstract][Hide abstract] ABSTRACT: The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be ‘gold standard’ on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.
Annals of the Rheumatic Diseases 01/2015; 74(5). DOI:10.1136/annrheumdis-2014-206580 · 10.38 Impact Factor