Krzysztof Rutkowski

Infection with Babesia microti in humans with non-specific symptoms in North East Poland

Abstract Aim: The aim of the study was to evaluate the clinical course and effectiveness of diagnostics tools for Babesia spp. infection in patients bitten by ticks. Materials and methods: Five hundred and forty-eight patients hospitalised or seen in outpatients department because of various symptoms after a tick bite were included in the study. PCR, nucleotide sequencing of Babesia 18S rRNA gene fragment, blood smears and serological tests for Babesia spp., TBEV, A. phagocytophilum and B. burgdorferi were performed in all patients. Six patients infected with Babesia were included in the final analysis. They had PCR, Babesia 18S rRNA gene fragment nucleotide sequencing, blood smears and serological tests for Babesia spp., TBEV, A. phagocytophilum and B. burgdorferi performed twice. Results: Tick-borne infection with Babesia microti in six immunocompetent patients with non-specific symptoms was confirmed for the first time in Poland. No severe course of the disease was seen. No piroplasm forms were noticed within erythrocytes on blood smear. Three patients developed a serological response. Conclusions: Immunocompetent patients may be unaware of infection with Babesia microti after a tick bite. It must be included in the differential diagnosis after the tick bite. In patients with low parasitaemia PCR and serology seem useful when blood smear is negative. Self-elimination of Babesia spp. is possible, especially in cases with low parasitaemia.

Tick-borne infections and co-infections in patients with non-specific symptoms in Poland

AIM The aim of the study was the evaluation of the frequency of infections and co-infections among patients hospitalized because of non-specific symptoms after a tick bite. MATERIALS AND METHODS Whole blood, serum and cerebrospinal fluid samples from 118 patients hospitalised for non-specific symptoms up to 8 weeks after tick bite from 2010 to 2013 were examined for tick-borne infections. ELISA, Western blot and/or molecular biology (PCR; fla gene; 16S rRNA; sequencing) and thin blood smears (MDD) were used. Control group included 50 healthy blood donors. All controls were tested with PCR and serology according to the same procedure as in patients. RESULTS Out of 118 patients 85 (72%) experienced headaches, 15 (13%) vertigo, 32 (27%) nausea, 17 (14%) vomiting, 37 (31%) muscle pain, 73 (62%) fever and 26 (22%) meningeal signs. 47.5% were infected with at least one tick-borne pathogen. Borrelia burgdorferi sensu lato infection was confirmed with ELISA, Western blot in serum and/or (PCR (fla gene) in whole blood in 29.7% cases. In blood of 11.9% patients Anaplasma phagocytophilum DNA (16S rRNA gene) was detected; in 0.9% patients 1/118 Babesia spp. DNA (18S rRNA gene) was also detected. Co-infections were observed in 5.1% of patients with non-specific symptoms. B. burgdorferi s.l. - A. phagocytophilum co-infection (5/118; 4.2%) was most common. In 1/118 (0.8%) A. phagocytophilum - Babesia spp. co-infection was detected. All controls were negative for examined pathogens. CONCLUSIONS Non-specific symptoms after tick bite may be caused by uncommon pathogens or co-infection, therefore it should be considered in differential diagnosis after tick bite.

HLA B62 as a possible risk factor for drug reaction with eosinophilia and systemic symptoms to piperacillin/tazobactam

Unpredictable adverse drug reactions (ADRs) (World Health Organization type B [bizarre]) make up 5% to 20% of all ADRs. Severe cutaneous reactions are very rare at 0.4 to 1.2 cases/ million but more common in inpatients (1:1000). Drug reaction with eosinophilia and systemic symptoms (DRESS) carries a mortality of 10% and is one of a spectrum of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis. Carbamazepine seems to be the most common trigger, but more than 44 drugs have been associated with DRESS. The diagnosis can be made using the European Registry of SCAR (RegiScar) clinical and laboratory scoring criteria to rate cases as negative, possible, probable, or definite. Three of 4 criteria need to be met: an acute rash, temperature of more than 38 C, lymphadenopathy at 2 sites, involvement of more than 1 organ, and abnormalities in lymphocyte and eosinophil counts. Additional criteria include hospitalization and that the reaction is suspected to be drugrelated. Japanese criteria overlap with RegiScar and include evidence of viral reactivation, for example, Herpesviridae. The underlying pathophysiology is only partially understood and may involve detoxification defects, viral reactivation, and a T-celledependent immune response. Activation of T cells is dependent on the presentation of antigen as MHC-associated peptides to T-cell receptors. In the case of carbamazepine and abacavir, specific alleles (HLA-B*15:02 and 57:01, respectively) carry a greatly increased risk of such an activation and SCARs. This has led to the recommendation of HLA typing of patients before administering these drugs. Beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs account for the majority of all ADRs and have been described as the cause of SCARs. In the last 12 months, 3175 doses of piperacillin/tazobactam (PT) were administered at Cambridge University Hospital. Over the last 7 years, this antibiotic was the probable cause of 74% of SCARs investigated in the local Department of Allergy (15 out of a total of 20 cases). Therefore, the ability to predict the risk of DRESS to PT would be of major benefit to patient safety. Between 2009 and 2016, 3 definite and 3 probable cases of DRESS to PT (Tazocin, Pfizer Ltd, UK) were diagnosed in the Department of Allergy in Cambridge. RegiScar score, skin testing, and HLA typing were undertaken (Table I). Skin prick test with stock concentrations of benzylpenicilloyl octa-L-lysine, bencilpeniciloate sodium, amoxicillin, benzylpenicillin, flucloxacillin, and PT were negative in all patients at 15 minutes. Intradermal tests with a 1:10 dilution of the antibiotics in 0.9% NaCl were read at 15 minutes and 24 (48) hours. In all patients, they were negative at 15 minutes. In 4 patients, there was a positive delayed intradermal test result to PT only; in 1 patient, to all penicillins with the strongest reaction (central blister) to PT. The result was not documented in 1 patient (Table I). RegiScar criteria do not recommend routine tests for viral reactivation. However, patients 4 and 6 had a negative cytomegalovirus, EBV, herpes simplex, hepatitis A, B, and C, and adenovirus serology. Low-resolution (first field) HLA-A, HLA-B, HLA-C, HLADRB1, HLA-DRB3/4/5, HLA-DQB1 typing was performed using PCR sequence-specific primers (PCR-SSO, LABType SSO, One Lambda, Canoga Park, Calif) and results converted to serological equivalents for the purposes of presentation (Table II). Three of the 6 white patients (50%) were HLA-B62 positive. Our own data calculated using HLA types of 10,000 consecutive deceased organ donors confirm a 12% frequency of B62 in the UK whites. The patient cohort sample size was however too small to perform meaningful statistical comparison. All patients required topical steroids (bethamethasone, clobetasol, or mometasone) and oral (fexofenadine) or intravenous antihistamines (chlorphenamine). Only patient 3 received 5 days of 100 mg intravenous hydrocortisone twice a day followed by 5 days of 30 mg prednisolone once a day. The understanding of the pathophysiology of the immune response inDRESS has improved since its first description in 1950 (phenytoin). It is a Gell-Coombs type IV (T-cellemediated) reaction. Activation of T cells requires binding of MHCassociated peptides to specific T-cell receptors. In delayed drug hypersensitivity, novel HLA-binding peptides are derived from drug-hapten protein adducts or direct binding of a drug to the peptide sequences displayed by theMHCmolecules, altering their specificity. Specific alleles seem to predispose to this. So far most associations have been identified within the HLA class I and more specifically the HLA B locus. For carbamazepine and abacavir, there is a clear association with HLA-B*15:02 and HLA-B*57:01, respectively. Indeed, absence of these has a 100% negative predictive value for a severe hypersensitivity reaction, allowing patient selection before treatment. However, their presence has only a 50% positive predictive value. Other risk or protective factors may play a role in addition to the immunological response. Identifying predictive factors for the development of DRESS to PT faces a number of difficulties. There is no simple diagnostic test due to the heterogeneity of the patient group. Although piperacillin is thought to be the allergenic moiety in PT, tazobactam-specific immune response cannot be ruled out. Moreover, commercially, these 2 agents are not separately available for testing. In addition, in vitro experiments suggest that under certain circumstances, for example, high concentration of the drug, a less restricted and more promiscuous T-cell response

Sesame allergy in adults: Investigation and outcomes of oral food challenges

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A multicenter evaluation of diagnosis and management of omega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) in 132 adults

BACKGROUND Omega-5 gliadin allergy (also known as wheat-dependent exercise-induced anaphylaxis) is a rare allergy to wheat that often presents with intermittent severe anaphylaxis in the context of a cofactor, such as exercise. OBJECTIVE To undertake a detailed clinical characterization of the largest cohort of patients with omega-5 gliadin allergy to date. METHODS We retrospectively analyzed the demographic characteristics, presentation, investigation, and management of 132 patients presenting with omega-5 gliadin allergy in 4 UK centers. RESULTS There were significant delays in diagnosis of 1 to 5 years (40% of patients) and more than 5 years (29% of patients). The commonest cofactors were exercise (80%), alcohol (25%), and nonsteroidal anti-inflammatory drugs (9%). A minority of patients (11%) had no identifiable cofactor. The level of specific IgE to omega-5 gliadin does not predict the severity of allergic reactions. Patients who adhered to a gluten-free diet and those who avoided wheat in combination with exercise achieved the largest reductions in subsequent allergic reactions of 67% and 69%, respectively. CONCLUSION Omega-5 gliadin allergy is a rare wheat allergy that presents with severe anaphylaxis. The diagnosis is frequently delayed, and therefore we recommend that all adult patients presenting with anaphylaxis of unclear cause should have omega-5 gliadin specific IgE tested. A gluten-free diet or avoidance of wheat-based meals in combination with exercise (if the cofactor is exercise) helps to significantly decrease the risk of future allergic reactions. However, antihistamines and an epinephrine autoinjector must always be prescribed because one-third of patients continue to have allergic reactions despite dietary advice.

Anaphylaxis: clinical features and GP's role in management

Anaphylaxis can be fatal if not treated promptly and it is important to identify likely triggers and educate patients on the proper use of adrenaline autoinjector. Here, the authors outline the clinical features, acute and long‐term treatment and the GPs role in management.