Polymicrobial Acute Suppurative Parotitis in a 33-Day-Old Infant: A Case Report and Review of the Literature.

BACKGROUND: Acute suppurative parotitis (ASP) of neonates is a rare condition characterized by irritability, erythema, and tenderness of the affected gland. METHODS/RESULTS: Only few cases have been reported in Engilsh literature, mostly in male neonates, in a unilateral fashion. In our case, a polymicrobial etiology (Klebsiella pneumoniae, Staphylococcus aureus, Acinetobacter ursingii, and Acinetobacter junii) was found. Based on the review of the microbiological findings of cases of ASP in English literature for the years 1970 to 2020, S. aureus is the most commonly isolated microorganism (47% of the total 65 patients). Our patient was born with a C-section procedure and was not breast-fed, making dysbiosis along with the usage of the feeding bottle, possible risk factors for the development of ASP. CONCLUSIONS: ASP may be due to polymicrobial etiology. Initial presentation in neonates may not include typical signs and symptoms, like fever. Aseptic technique of oral procedures is of utmost importance also in immune-competent neonates.

Recommendations for the Management of Uveitis Associated With Juvenile Idiopathic Arthritis: The Czech and Slovak adaptation of SHARE Initiative.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.

Happle-Tinschert, Curry-Jones and segmental basal cell naevus syndromes, overlapping disorders caused by somatic mutations in hedgehog signalling genes: the mosaic hedgehog spectrum.

Happle-Tinschert syndrome (HTS) and Curry-Jones syndrome (CJS; OMIM 601707) are rare, sporadic, multisystem disorders characterized by hypo- and hyperpigmented skin patches following Blaschko's lines, plus acral skeletal and other abnormalities. The blaschkoid pattern implies mosaicism, and indeed CJS was found in 2016 to be caused by a recurrent postzygotic mutation in a gene of the hedgehog signalling pathway, namely SMO, c.1234C>T, p.Leu412Phe. More recently the original case of HTS was found to carry the same somatic mutation. Despite this genetic and phenotypic overlap, two significant differences remained between the two syndromes. The histological hallmark of HTS, basaloid follicular hamartomas, is not a feature of CJS. Meanwhile, the severe gastrointestinal manifestations regularly reported in CJS had not been described in HTS. We report a patient whose phenotype was entirely consistent with HTS apart from intractable constipation, and a second patient with classic features of CJS plus early-onset medulloblastoma, a feature of basal cell naevus syndrome (BCNS). Both had the same recurrent SMO mutation. This prompted a literature review that revealed a case with the same somatic mutation, with basaloid follicular hamartomas and other features of both CJS and BCNS. Segmental BCNS can also be caused by a somatic mutation in PTCH1. We thus demonstrate for the first time phenotypic and genetic overlap between HTS, CJS and segmental BCNS. All of these conditions are caused by somatic mutations in genes of the hedgehog signalling pathway and we therefore propose the unifying term 'mosaic hedgehog spectrum'. What's already known about this topic? Happle-Tinschert syndrome (HTS) and Curry-Jones syndrome (CJS) are rare mosaic multisystem disorders with linear skin lesions. CJS is characterized by severe constipation, which has not previously been reported in HTS. HTS is characterized by basaloid follicular hamartomas, which are not a recognized feature of CJS. The recurrent mosaic SMO mutation found in CJS was recently reported in a patient with HTS. What does this study add? We describe a patient with HTS and intractable constipation, and a case of CJS with medulloblastoma. Both patients had the same recurrent somatic SMO mutation also found in a case reported as segmental basal cell naevus syndrome. SMO functions in the hedgehog pathway, explaining phenotypic overlap between HTS, CJS and mosaic basal cell naevus syndrome. We propose the term 'mosaic hedgehog spectrum' for these overlapping conditions.

[Pachydermodactyly]. / Pachydermodaktylie.

The differential diagnosis of swelling of the small finger joints is broad. We report on two young men presenting with progressive painless swelling of the proximal interphalangeal (PIP) joints where the physical examination was otherwise inconspicuous. Laboratory investigations including auto- antibodies were all normal, x-rays and magnetic resonance imaging (MRI) revealed no joint pathologies but only increased skin thickening. Skin biopsy demonstrated hyperkeratosis and acanthosis without tissue inflammation. We thus diagnosed pachydermodactyly in both cases. This rare disease predominantly affects young males, can affect one or both hands and is often associated with mechanical stress due to repetitive movements in patients with obsessive-compulsive disorders. Occupational exposure by monotonous actions (e.g. poultry processing) may also be a cause. A specific therapy is unnecessary in most cases but may include intralesional steroid administration or surgical resection. Cessation of mechanical stress can significantly improve pachydermodactyly.

[Osteoarthritis in hereditary metabolic diseases]. / Arthrosen bei hereditären Stoffwechselerkrankungen.

Primary osteoarthritis (OA) of peripheral joints is a common disease mainly occurring after the age of 50. It is important to distinguish primary from secondary OA. Younger age at disease onset, rapid progression, unusual disease manifestations and co-morbidities are signs of secondary OA. This review outlines an important group of secondary OA. Hereditary metabolic diseases can exhibit joint involvement. For some of these diseases, correct diagnosis is critical, since appropriate therapy influences not only joint function and quality of life, but can also prevent relevant end-organ damage.

[Osteoarthritis in hereditary metabolic diseases]. / Arthrosen bei hereditären Stoffwechselerkrankungen.

Primary osteoarthritis (OA) of peripheral joints is a common disease mainly occurring after the age of 50. It is important to distinguish primary from secondary OA. Younger age at disease onset, rapid progression, unusual disease manifestations and co-morbidities are signs of secondary OA. This review outlines an important group of secondary OA. Hereditary metabolic diseases can exhibit joint involvement. For some of these diseases, correct diagnosis is critical, since appropriate therapy influences not only joint function and quality of life, but can also prevent relevant end-organ damage.

BAFF from bone marrow-derived mesenchymal stromal cells of rheumatoid arthritis patients improves their B-cell viability-supporting properties.

Mesenchymal stromal cells (MSCs) represent a unique cell type with anti-proliferative effects on activated T and B cells. Based on our observation of differences between rheumatoid arthritis and osteoarthritis bone marrow B cells we hypothesized that rheumatoid arthritis bone marrow MSCs may enhance B-cell survival. We aimed to compare the effect of rheumatoid arthritis and osteoarthritis bone marrow-derived MSCs (rheumatoid arthritis MSCs, osteoarthritis MSCs) on the survival of healthy donor purified B cells. Rheumatoid arthritis and osteoarthritis MSCs were isolated from patients undergoing hip replacement surgery, and cultured in vitro for 2-5 passages. Washed cells were co-cultured with CD20+ B cells for 30-90 hours. Cell survival was analysed using 7-amino-actinomycin D labelling by flow cytometry. Expression of mRNA and protein was determined by RT-PCR and flow cytomery. Co-culture with both rheumatoid arthritis MSCs and osteoarthritis MSCs significantly enhanced B-cell survival, the effect being more prominent in rheumatoid arthritis MSCs. Both types of MSCs displayed expression of B cell-activating factor mRNA and protein. Blocking B cell-activating factor signalling from MSCs by specific anti-B cell-activating factor and anti-B cell-activating factor receptor antibodies weakly reversed the effect of MSCs on B-cell survival mainly in rheumatoid arthritis MSCs. MSC interaction with B cells provides stimuli for B-cell survival and therefore may contribute to the pathogenesis of rheumatoid arthritis. MSC-derived factors other than B cell-activating factor are likely to contribute to this effect. This feature is more prominent in rheumatoid arthritis MSCs, possibly due to the B cell-activating factor.

B cell activating factor, its role in autoimmunity, and targeting in autoimmune diseases.

B cell activation factor (BAFF), a recently identified member of the tumour necrosis factor (TNF) family, is a key survival factor during B cell maturation and is essential for the development of B cell tolerance. Breakdown of the regulation of BAFF expression results in excessive BAFF production that impairs B cell tolerance and leads to autoimmune phenomena. Consistent with this, BAFF levels are elevated in plasma of patients with various autoimmune diseases. BAFF is considered to be one of the principal factors that regulate the size and composition of B cell compartment. BAFF acts as an important driving factor for B cell hyperplasia and autoantibody production in autoimmune processes. Thus BAFF has become a very attractive target for the treatment of autoimmune diseases with an altered B cell function. Results of clinical trials have confirmed a crucial role of BAFF in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). BAFF inhibitors in the treatment of RA, SLE and other autoimmune diseases are under intensive investigation. However, BAFF biology remains poorly understood. Nonetheless, results of the ongoing studies may enable the development of a new generation of BAFF inhibitors with more selective efficacy and increased safety (Fig. 2, Ref. 92). Full Text (Free, PDF) www.bmj.sk.

CTLA-4 and the genetic predisposition to autoimmunity.

Due to the wide spectrum of clinical manifestations and their epidemiological dimensions, autoimmune diseases represent an important medical issue. They are the consequence of the loss of immune tolerance to autoantigens, which in turn is a result of the interaction of environmental, as well as genetic factors. The predisposing role of HLA antigens is widely accepted; nonetheless, it does not fully explain the occurrence of autoimmune disorders. In this topical review, we present the current knowledge on the role of some non-HLA genes (ICOS, CD28 and CTLA-4 in particular) in the development of autoimmunity. (Fig. 1, Ref: 106.)