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Background: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. Objectives: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. Methods: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. Results: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red‐brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma‐like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia‐telangiectasia (52%), combined immunodeficiency (24%), cartilage‐hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. Conclusion: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID. [ABSTRACT FROM AUTHOR]

Purpose of review: We aimed to review invasive fungal infections complicating primary immunodeficiencies (PID). Recent findings: Several PID predisposing to fungal infections were recently deciphered. CARD9 deficiency selectively predisposes to fungal infections including candidiasis, aspergillosis, deep dermatophytosis, and phaeohyphomycosis, with frequent central nervous system location, especially after Candida infection. Patients with heterozygous STAT1 gain-of-function mutations are mostly predisposed to chronic mucocutaneous candidiasis but may also display, even though less frequently, invasive fungal infections. Aspergillosis complicating STAT3 deficiency is also a major concern in patients with lung cavities. Antifungal prophylaxis is recommended in this first group of patients. Previously well-reported PID are known to predispose to fungal infections, such as genetic defects impairing the IL-12/IFN-γ axis can predispose to cryptococcosis, and dimorphic fungal infections. Summary: Patients developing invasive fungal infections including candidiasis, aspergillosis, cryptococcosis, phaeohyphomycosis, pneumocystosis, or disseminated infections caused by dimorphic fungi, without known underlying risk factors, should be explored immunogenetically in order to diagnose primary immunodeficiencies, even in the absence of previous other infectious episodes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which focuses on the study on ichthyosis as the dermatological phenotype associated with tetratricopeptide repeat domain 7A gene (Ttc7) mutations.

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 (HAstVVA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year. [ABSTRACT FROM AUTHOR]

Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [18F]fluorodeoxyglucose ([18F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [18F]FDG ([18F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [18F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [18F]FDG was observed in all areas previously identified by computed tomography and/ or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [18F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [18F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [18F]FDG-PET was performed to assess the evolution of the disease. [18F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [18F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study. [ABSTRACT FROM AUTHOR]

Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth. [ABSTRACT FROM AUTHOR]

Pyomyositis is a primary purulent infection of skeletal muscles mostly described in tropical areas. Staphylococcus aureus is by far the main causative microorganisms. In temperate areas, pyomyositis more frequently affects male adults with immunodeficiency. Gram-negative bacilli pyomyositis are uncommon and occur mainly in this context of immunodeficiency. Only one case of Enterobacter cloacae pyomyositis has been reported so far. Chronic Granulomatous Disease (CGD) is a rare inherited immunodeficiency characterized by a loss of NADPH oxidase activity in phagocytic cells that favors infections due to catalase-positive microorganisms. Pyomyositis has only been described once as a complication of CGD. We report here a case of Enterobacter cloacae-associated pyomyositis of the left thigh in a patient with CGD, and review the literature on Gram-negative pyomyositis. [ABSTRACT FROM AUTHOR]

Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective. Because both methods of administration provide similar efficacies, a cost-minimization analysis was performed. First, costs were calculated through a simulation testing different hypothesis on costs drivers. Secondly, costs were estimated on the basis of field data collected by a questionnaire completed by a population of patients suffering from agammaglobulinaemia and hyper-immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented. Results of the simulation showed that direct medical costs ranged from &U20AC;19 484 for home-based IVIG to &U20AC;25 583 for hospital-based IVIG, with home-based SCIG in between at &U20AC;24 952 per year. Estimations made from field data were found to be different, with significantly higher costs for IVIG. This result was explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While the theoretical model showed very little difference between SCIG and hospital-based IVIG costs, SCIG appears to be 25% less expensive with field data because of lower doses used in SCIG patients. The reality of the dose difference between both routes of administration needs to be confirmed by further and more specific studies. [ABSTRACT FROM AUTHOR]

Primary immunodeficiencies (PID) are rare diseases; therefore transnational studies are essential to maximize the scientific outcome and to improve diagnosis and therapy. In order to estimate the prevalence of PID in Europe as well as to establish and evaluate harmonized guidelines for the diagnosis and treatment of PID, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Within 4 years, 7430 patients from 39 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity, with 1540 patients or 20·7% of all entries, followed by isolated immunoglobulin (Ig)G subclass deficiency (546 patients, 7·4%). Evaluations show that the average life expectancy for PID patients varies from 1 to 49 years (median), depending on the type of PID. The prevalence and incidence of PID remains a key question to be answered. As the registration progress is far from finished we can only calculate minimum values for PID, with e.g. France currently showing a minimum prevalence of 3·72 patients per 100 000 inhabitants. The most frequently documented permanent treatment is immunoglobulin replacement; 2819 patients (42% of all patients alive) currently receive this form of treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Fusion of ZMIZ1 to ABL1 in a B-cell Acute Lymphoblastic Leukaemia With a t(9;10)(q34;q22.3) Translocation," in the November 15, 2007 issue.