Key findings to expedite the diagnosis of hyper-IgE syndromes in infants and young children.

BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8. METHODS: Here, we assess the clinical and immunologic phenotype of DOCK8- and STAT3-HIES patients including the cell activation, proliferation, and cytokine release after stimulation. RESULTS: Existing HIES scoring systems are helpful to identify HIES patients. However, those scores may fail in infants and young children due to the age-related lack of clinical symptoms. Furthermore, our long-term observations showed a striking variation of laboratory results over time in the individual patient. Reduced memory B-cell counts in concert with low specific antibody production are the most consistent findings likely contributing to the high susceptibility to bacterial and fungal infection. In DOCK8-HIES, T-cell lymphopenia and low IFN-gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT3-HIES, DOCK8-HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers (HLA-DR, CD69, CD86, and CD154), and significantly increased inflammatory cytokines (IL1-beta, IL4, IL6, and IFN-gamma). CONCLUSION: Differentiating HIES from other diseases such as atopic dermatitis early in life is essential for patients because treatment modalities differ. To expedite the diagnosis process, we propose here a diagnostic workflow.

Antibiotic concentrations in saliva: a systematic review of the literature, with clinical implications for the treatment of sialadenitis.

PURPOSE: The current recommendations for the treatment of bacterial salivary gland infections are mainly empirical. Therefore, an evidence-based literature review was conducted to identify antibiotics with favorable pharmacokinetics in saliva and to establish recommendations for the antibiotic treatment of sialadenitis. MATERIALS AND METHODS: The authors performed a systematic review of the pertinent literature published from 1985 to 2013. If the predefined inclusion criteria were met, the articles were screened for various variables: antibiotic type, mode of administration, type of examined saliva, peak salivary antibiotic concentrations, biochemical methodology, and minimal inhibitory concentrations of bacteria implicated in sialadenitis (Staphylococcus aureus, Viridans streptococci, various gram-negative strains, and anaerobes). RESULTS: The review included 18 studies. The systematic analysis of the reported results concurred that intravenously administered cephalosporins achieve the highest concentrations in saliva, followed by orally administered cephalosporins and fluoroquinolones. These concentrations exceed the minimal inhibitory concentrations of the bacteria of interest. Phenoxymethylpenicillin and tetracyclines are not secreted in the saliva at bactericidal levels. The antibiotic peak salivary levels depended on the type of saliva examined (parotid vs submandibular vs minor salivary gland) and the biochemical method of measurement (high-performance liquid chromatography vs bioassay). CONCLUSION: Cephalosporins and fluoroquinolones display superior pharmacokinetics in saliva and cover the spectrum of all bacteria implicated in sialadenitis. Within the limitations of this review, they can be recommended for the treatment of bacterial salivary gland infections.

Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study.

INTRODUCTION: The delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ. PATIENTS AND METHODS: 54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100 mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow-up. RESULTS: The study included a total of 54 patients (32 female and 22 male, mean age 71.4 ± 9.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence-guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. CONCLUSION: The study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab.

Etiology and clinical characteristics of symptomatic unilateral maxillary sinusitis: A review of 174 cases.

The purpose of the study was to analyze the causative pathology associated with symptomatic unilateral maxillary sinusitis requiring surgical treatment. A retrospective review of all patients that have been treated surgically for unilateral symptomatic maxillary sinusitis between 2006 and 2013 at a single institution was performed. Demographic, anamnesis, clinical, radiological, microbiological and histological data were gathered and analyzed. The patients were allocated into groups depending on the underlying cause of the disease. Descriptive and inferential statistics were computed (level of significance: p ≤ 0.05). The study sample was composed of 174 patients (72 female; 102 male) with a mean age of 52.7 years (SD 16.9). Most cases (130; 75%) were triggered by odontogenic pathology following dentoalveolar surgical interventions (83/130 patients; 64%). Other etiological factors for odontogenic unilateral sinusitis were periapical (23/130 cases; 18%) and periodontal pathology (13/130 cases; 10%). Rhinogenic factors for sinusitis were detected in 13 patients (7.5%) and dental implant-associated unilateral maxillary sinusitis was diagnosed in nine patients (5.2%). Four patients (2.3%) had undergone previous sinus augmentation surgery. A leading cause for the sinus infection could not be identified in 18 patients (10%) who all had a history of midfacial surgery. Medication-related osteonecrosis of the jaw (8) and squamous cell carcinoma (2) were incidental findings. There were no differences in the clinical appearance of the disease with respect to its etiology. Odontogenic causes for maxillary sinusitis must be considered especially in unilateral cases. Maxillary dental implants may induce symptomatic unilateral maxillary sinusitis.