Vitamin B12 Hypersensitivity: A Retrospective Multicenter Study.

BACKGROUND: Vitamin B12 (Vit B12) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes. OBJECTIVE: To investigate a cohort of patients with Vit B12 hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H. METHODS: A total of 29 patients seen between 2014 and 2022 underwent skin prick testing (1 mg/mL) with cyanocobalamin (CC) and hydroxycobalamin (HC) and intradermal testing (0.1 and 0.01 mg/mL). Patients with negative skin tests underwent a Vit B12 drug provocation test (DPT) with either the index or the alternative drug. RESULTS: Of 29 patients, 18 (62%) presented with immediate VB12H. Eight experienced anaphylaxis (4 to HC and 4 to CC) and had positive skin tests to the index drug. One patient reacted to oral and 7 patients to injectable Vit B12. Seven patients sensitized to one form of Vit B12-tolerated DPT with an alternative Vit B12. One patient with immediate VB12H reacted to polyethylene glycol (PEG) in oral cobalamin. Of 29 patients, 8 presented with delayed hypersensitivity reaction; 4 patients tolerated the intramuscular index formulation, whereas 2 patients tolerated the per oral formulation. One patient presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema. Three patients were referred because of cobalt allergy. CONCLUSION: Confirmed VB12H is rare. We propose a comprehensive evaluation protocol that includes Vit B12 skin tests and considers PEG allergy in patients presenting with VB12H.

Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections.

PURPOSE: Ticks transmit several pathogens and seem implicated in the production of specific IgE antibodies to alpha-1,3-galactose (α-gal sIgE). They cause delayed and immediate allergy to mammalian meat and medication including antivenoms, vaccines and monoclonal antibodies. METHODS: We assessed the prevalence of α-gal sIgE in forest workers and healthy controls in the Podlasie voivodeship, north-eastern Poland; the relationship between α-gal sIgE and allergy to α-gal-containing products; the correlation between α-gal sIgE and anti-Borrelia burgdorferi and anti-tick-borne encephalitis virus (TBEV) antibodies; the relationship between α-gal sIgE and markers of infection with lesser-known pathogens transmitted by ticks such as Anaplasma phagocytophilum. RESULTS: Production of α-gal sIgE was closely related to tick bites. The odds ratio for detectable α-gal sIgE was 9.31 times higher among people with a history of tick bites (OR 9.3; p < .05). There was no correlation with the history of TBE, Lyme disease or human granulocytic anaplasmosis. However, serum α-gal sIgE correlated with anti-TBEV IgM antibodies in CSF. There was a strong correlation between α-gal sIgE and total IgE and sIgE to pork and beef. CONCLUSIONS: Our data support the link between I.ricinus ticks and the production of α-gal sIgE and confirm that the pathogens carried by ticks we examined for do not seem implicated in this immune response.

Adverse reactions to COVID-19 vaccines: A practical approach.

COVID-19-related mortality in high-risk individuals is substantial and current treatment options are limited. There is convincing evidence that the COVID-19 vaccines reduce the severity of infection and prevent deaths. Three COVID-19 vaccines are approved in the United Kingdom with many more in development. There are limited data on the triggers and mechanisms of anaphylaxis to these vaccines. We review the potential allergenic compounds in the COVID-19 vaccines and describe an innovative allergy support model for the vaccination hubs that allows most patients with severe allergy be immunized. Finally, we propose a practical algorithm for the investigations of anaphylaxis to these vaccines.

Immediate hypersensitivity reactions to steroids and steroid containing medications.

PURPOSE OF REVIEW: Although rare and counterintuitive, hypersensitivity reactions to corticosteroids have been reported since the 1950s. Delayed hypersensitivity reactions following cutaneous exposure (contact allergy) are well understood and principles of testing, as well as cross-reactivity patterns, have been established. In contrast, understanding of immediate hypersensitivity reactions and delayed hypersensitivity reactions after systemic exposure is evolving more slowly. However, progress has been made in the delineating of underlying pathogenic mechanisms and in the development of testing. RECENT FINDINGS: IgE-mediated hypersensitivity reactions to corticosteroids have been described. It has been recognized that some, if not all of them, may be due to excipients in steroid formulations. Two excipients, polyethylene glycol and carboxymethylcellulose, seem of particular importance, but cases of reactions to polysorbate 80 and lactose have also been reported. The use of skin testing but also, increasingly, in-vitro methods such as basophil activation test is improving diagnostic accuracy. SUMMARY: The recognition of the role of excipients is leading to a paradigm shift in our approach to immediate hypersensitivity to corticosteroids. Improved access to in-vivo and in-vitro testing will enhance our understanding of true corticosteroid immediate allergy.

Alpha-gal syndrome: An emerging cause of food and drug allergy.

Alpha-gal syndrome (AGS) describes a wide spectrum of hypersensitivity reactions mediated by specific IgE to the α-gal epitope (galactose-α-1,3-galactose) ubiquitously expressed on glycolipids/glycoproteins of most mammals. This fascinating new entity has completely changed the paradigms of allergy as allergic response is directed against an oligosaccharide and the reactions can be both immediate and delayed. They appear to be stimulated only by tick bites which induce production of α-gal specific IgE antibodies that lead to (at times fatal) hypersensitivity response. AGS is completely different to previously described anaphylaxis to tick saliva. It provides unique insight into the interplay between different arms of the immune system and the role of ectoparasites in the development of anaphylaxis to food and medication in patients at risk of tick bites including travellers. This review summarises recent advances in our understanding of its clinical presentation, pathomechanism and role of various tick species in the development of AGS.

Steroid Allergy: Clinical Features and the Importance of Excipient Testing in a Diagnostic Algorithm.

BACKGROUND: True corticosteroid (CS) allergy is rare. Instead, many patients may be allergic to excipients found in various CS preparations. Excipient testing is frequently overlooked. It might lead to unnecessary CS avoidance or dangerous re-exposure. OBJECTIVE: The objective of this study was to evaluate the clinical characteristics and frequency of excipient allergy in patients with confirmed type I hypersensitivity to systemic CS preparations. METHODS: Patients with a confirmed diagnosis of allergy (positive skin test or drug provocation test [DPT]) or tolerance (negative DPT to CS) over the past 10 years were studied. Patient characteristics, index CS, route of administration, clinical indications, symptoms of index reaction, and outcomes of CS/excipient allergy testing were analyzed. RESULTS: Sixty-four patients underwent CS allergy testing. True CS allergy was confirmed in 9 of 64 (14%) patients. The majority (5/9, 56%) with positive skin tests or DPT were actually allergic to the excipients (2 to carboxymethylcellulose and 3 to polyethylene glycol) rather than the CS. Respiratory manifestations were significantly associated with confirmed allergy (odds ratio = 6.79 [95% confidence interval = 1.36-34.03], P = .02). CONCLUSIONS: Patients with respiratory manifestations were significantly more likely to be truly allergic. CS allergies are rare and may be overdiagnosed without excipient testing. We suggest the use of Carmellose eye drops as a readily available source of carboxymethylcellulose for testing and propose a comprehensive diagnostic algorithm for suspected CS allergy.

Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing.

BACKGROUND: True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized. OBJECTIVE: The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT. METHODS: Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity. RESULTS: Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P = .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P = .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P = .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR: 0.27; 95% CI: 0.08-0.86; P = .008). CONCLUSIONS: Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols.

Evaluation of NF-κB concentration in patients with tick-borne encephalitis, neuroborreliosis, anaplasmosis and Anaplasma phagocythophilum with tick-borne encephalitis virus co-infection.

OBJECTIVES: The aim of the study was the evaluation of NF-κB concentration in serum and cerebrospinal fluid (CSF) of patients with diagnosis of tick-borne diseases: tick-borne encephalitis (TBE), neuroborreliosis (NB), anaplasmosis (ANA) and patients co-infected with tick-borne encephalitis virus and Anaplasma phagocythophilum (TBE+ANA). Additionally NF-κB concentration during acute and convalescent period was compared. METHODS: Sixty-seven patients with diagnosis of tick-borne diseases were included in the study. The control group (CG) consisted of 18 patients hospitalized because of headaches and had lumbar puncture performed. The NF-κB was measured by human inhibitory subunit of NF-κB ELISA Kit during acute and convalescent period. RESULTS: In serum the significant differences were observed only in patients with TBE+ANA co-infection. In CSF the concentration of NF-κB was significantly higher in patients with TBE, TBE+ANA co-infection, and patients with NB than in CG. Receiver operating characteristic (ROC) curves analysis showed that NF-κB concentration in CSF differentiated patients with NB with CG; patients co-infected with TBE and ANA with CG and patients with TBE with CG. NF-κB concentration in serum differentiated patients co-infected with TBE and ANA with NB and with ANA, with TBE and with CG. In TBE group the serum NF-κB concentration significantly decreased in convalescent period, while in NB and TBE groups significant CSF decrease of NF-κB concentration was observed.

Meningitis, clinical presentation of tetanus.

Background. Tetanus is an acute disease caused by a neurotoxin produced by Clostridium tetani. Tetanus immunization has been available since the late 1930s but sporadic cases still occur, usually in incompletely vaccinated or unvaccinated individuals. Case Report. An elderly previously vaccinated female contracted tetanus following foot injury. Clinically she presented with meningitis causing diagnostic and therapeutic delays. Why Should Physician Be Aware of This? Even in developed countries the differential diagnosis of meningitis, especially in the elderly, should include tetanus. Treatment in intensive care unit is required. General population might benefit from vaccine boosters and education on this potentially fatal disease.

Visual assessment of voice disorders in patients with occupational dysphonia.

INTRODUCTION: In a group of persons using the voice occupationally, the frequent symptoms are hoarseness, voice fatigability and aphonia. Pathological changes in the larynx may have organic or functional character which require different methods of treatment and rehabilitation. Visualization of vibrations of the vocal folds is an essential condition for an appropriate assessment of the causes of dysphonia. OBJECTIVE: The purpose of the study is assessment of the usefulness of a high-speed imaging (HSI) system in the diagnosis of functional and organic dysphonia of occupational character, compared with digital kymography (DKG) and digital stroboscopy (DS) with a high resolution module. MATERIAL AND METHODS: The study group consisted of 64 patients with voice quality disorders with features of occupational dysphonia. The control group consisted of 15 patients with euphonic voice. Analysis of the voice quality parameters during phonation of the 'e' vowel was performed using HSI, DKG and stroboscopy of high resolution, by means of a digital HS camera (HRES Endocam, Richard Wolf GmbH, Knittlingen, Germany). Vocal folds vibrations were registered at the rate of 4,000 frames per second. RESULTS: HSI is the most reliable diagnostic tool giving the possibility of an analysis of the true vibrations of the vocal folds. It also enables an observation of the aperiodicity of vibrations of the vocal folds, while DS with high resolution allows diagnosis of the periodicity of the vibrations. CONCLUSIONS: HSI is particularly useful in the diagnosis of neurologically-based pathology of the voice (paralytic dysphonia) and organic dysphonia. The quickest method of diagnosing the phonatory paresis of the glottis is DKG. The advantage of both HSI and DKG is the non-invasiveness of examinations; however, their limitations are time-consuming and the high cost of equipment.

Allergic diseases: the price of civilisational progress.

Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between host's immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon.

Dehydroepiandrosterone (DHEA): hypes and hopes.

Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a 'superhormone' and an 'anti-aging' panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25(hi) and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.

Optical radiation in modern medicine.

Optical radiation extends between microwaves and X-rays of the electromagnetic radiation and includes ultraviolet (UV), visible light (VL) and infrared (IR) components. The dose of radiation that reaches the skin is influenced by the ozone layer, position of the Sun, latitude, altitude, cloud cover and ground reflections. The photobiological effects of UV, VL and IR bands depend on their wavelength, frequency and mechanism of action. They are modified by the thickness, structure, vasculature and pigmentation of skin's stratum corneum, epidermis and dermis. Following absorption, IR affects the body mainly through transfer of thermal energy to tissues. Visible light and skin interact either thermally or photochemically, whereas UV acts mainly photochemically. Optical radiation in the form of sunlight therapy had been used already in ancient times. Nowadays IR, VL and UV are widely applied in the therapy of allergic, dermatological, cardiovascular, respiratory, rheumatic, neonatal, pediatric and psychiatric disorders.

[Gap junction intercellular communication in carcinogenesis of endometrial cancer]. / Komunikacja miedzykomórkowa z udzialem polaczen typu gap w karcinogenezie blony sluzowej trzonu macicy.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.

[Assessment of speech and linguistic disorders in patients with cochlear implant--preliminary results]. / Ocena mowy i zaburzen jezykowych u chorych z implantem slimakowym--doniesienie wstepne.

UNLABELLED: Cochlear Implant (CI) is the most advanced technical solution in the treatment of profound hearing loss and deafness in patients of all age groups. The aim of the study was to analyse the speech and linguistic disorders in adults with pre- and postlingual deafness rehabilitated with Cochlear implant (CI). MATERIAL AND METHODS: 21 adults with pre- (I group) and postlingual (II group) deafness deriving no benefit from hearing aids participated in this study. Phonatory organ was examined by endoscopy (VLS) and stroboscopy (VLSS). Test of Auditory Perception (TSS) was conducted directly after the activation of speech processor and after rehabilitation. The logopedic assessment before and after CI was based on the examination of motoric activity of articulatory organs, type of respiration, loudness of speech and the assessment of articulation. The linguistic assessment of grammatical and lexical aspect was carried out. The prosodic elements of speech were also analysed. RESULTS: Stroboscopic examination pointed to hypofunction of larynx in patients with prelingual deafness and hyperfunction--in postlingual deafness. The values of TSS were improved after CI, especially in patients with postlingual deafness. The most severe disorders of the efficiency of articulatory organs were observed in patients with prelingual deafness before CI. In the group of prelingually deaf patients disorders of the articulation of vowels and consonants as well as the lexical and grammatical aspect of speech were improved after CI. The correctness of syntax and inflection, development of active vocabulary, improvement of prosodic elements of speech were noticed in patients with postlingual deafness after CI. CONCLUSIONS. Patients with postlingual deafness achieved better results of rehabilitation in auditory perception than prelingually deaf patients. The linguistic improvement of grammatical and lexical aspect was noticed especially in prelingually deaf patients after implantation. This group of patients achieved also the significant progress in prosodic elements of speech in comparison with the results before implantation.