The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy.

OBJECTIVES: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. METHODS: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. RESULTS: Sixty recommendations were provided for suspected allergy to ß-lactam antibiotics (BLAs) and non-ß-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. CONCLUSIONS: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-ß-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency.

BACKGROUND: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. OBJECTIVE: To compare the efficacy of PA and IRT in a randomized crossover trial. METHODS: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. RESULTS: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). CONCLUSION: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. CLINICAL IMPLICATION: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.

Transgenerational occurrence of allergic disease and autoimmunity: general practice-based epidemiological research.

BACKGROUND: Corresponding with the T helper cell type 1/T helper cell type 2 hypothesis, autoimmune and allergic diseases are considered pathologically distinct and mutually exclusive conditions. Co-occurrence of autoimmune disorders and allergy within patients, however, has been reported. Transgenerational co-occurrence of autoimmune and allergic disease has been less often described and may differ from the intra-patient results. AIMS: To test the hypothesis that autoimmune disorders in parents are a risk factor for the development of an allergic disease in their offspring. METHODS: Prospectively registered (by academic general practitioners) International Classifications of Primary Care (ICPC) for diagnoses of autoimmune disorders and allergy within families were evaluated (n=5,604 families) by performing multiple logistic regression analyses. RESULTS: The presence of any ICPC-encoded autoimmune disorder in fathers appeared to be associated with an increased risk in their eldest children of developing an allergy (odds ratio (OR) 1.4, 95% CI 1.042 to 1.794). Psoriasis in fathers was particularly shown to be of influence (OR 1.5, 95% CI 1.061 to 2.117) and, although any ICPC-encoded autoimmune disease in mothers was found not to be of significance, the combined international code for registering rheumatoid arthritis/ankylosing spondylitis in mothers was OR 1.7 (95% CI 1.031 to 2.852). CONCLUSIONS: The occurrence of ICPC-encoded autoimmune disorders in parents, especially psoriasis and rheumatoid arthritis/ankylosing spondylitis, significantly increases the occurrence of allergic disease in their children. After validation in follow-up research in a larger sample, these results may lead to the inclusion of 'parental autoimmune condition' as a risk factor in the general practitioner's diagnostics of allergic disease.

Clinical features of Candidiasis in patients with inherited interleukin 12 receptor ß1 deficiency.

BACKGROUND: Interleukin 12Rß1 (IL-12Rß1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rß1 deficiency. RESULTS: Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. CONCLUSIONS: Patients who are deficient in IL-12Rß1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

Characterization of skin-resident T cells using a crawl-out method and flow cytometry.

A large fraction of the skin-homing T-cell population resides in the skin even under resting, non-inflammatory conditions. Here, we used a crawl-out culture method to retrieve T cells from human skin and characterized them using flow cytometric analysis. On average, 48000 viable, non-proliferating cells were retrieved per biopsy. We found that human skin contains a larger fraction of IL-17-, IL-4-, IL-10- and IL-22-positive T cells as compared with paired blood samples. Our research indicates that it is feasible to use the crawl-out method in combination with flow cytometry to characterize T-cell subpopulations in patient-derived skin biopsies. This method enables further study of the skin immune system and could function as a valuable tool for evaluation of the effects of immunotherapy in skin diseases.

Secondary erythromelalgia involving the ears probably preceding lupus erythematosus.

Secondary erythromelalgia is a rare disease characterized by burning pain, marked erythema, edema, and hyperthermia of the affected limbs. Secondary erythromelalgia can be associated with various systemic diseases. Here, we describe a patient who developed secondary erythromelalgia involving the ears and concomitant clinical and laboratory, probably, indicating the initial stage of a developing lupus erythematosus.