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Anaphylaxis is a rare side-effect of COVID-19 vaccines. To (a) provide direct advice and reassurance to certain persons with a history of anaphylaxis/complex allergy, in addition to that available in national guidelines, and (b) to provide a medically supervised vaccination, a specialist regional vaccine allergy clinic was established. The main objective was to determine if risk stratification through history can lead to safe COVID-19 vaccination for maximum population coverage. A focused history was taken to establish contraindications to giving COVID-19 vaccines. People who reported a high-risk allergy history were given a vaccine not containing the excipient thought to have directly caused previous anaphylaxis. All vaccines were monitored for 30 min after administration. A total of 206 people were vaccinated between 6 July 2021 and 31 August 2021; Comirnaty (Pfizer-BioNTech) (n = 34), and Janssen (n = 172). In total, 78% were women. Ninety-two people (45%) reported a high-risk allergy history. There were no cases of anaphylaxis. Three people developed urticaria and one of these also developed transient tachycardia. One vaccinee developed a pseudoseizure. Two of 208 people (

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4−CD8−) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion:: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

Pathology is important in training to become a medical doctor but as curricula become more integrated, there is a risk that key aspects of pathology may be excluded. Following a survey of the current delivery of teaching in Ireland under the auspices of the Faculty of Pathology at the Royal College of Physicians of Ireland, suggested components of a core curriculum in pathology have been developed to be delivered at some stage during the medical course. These have been based on key principles and themes required by the Medical Council in Ireland. Professionalism is one of the core principles emphasised by the Medical Council. It includes the role of the pathologist in patient care and other professional values such as patient-centred care, clinical competencies and skills, e.g. explaining results, and knowledge under the various sub-disciplines, i.e. histopathology (including neuropathology), clinical microbiology, haematology, chemical pathology and immunology. In each of these, we suggest key aspects and activities that the medical graduate should be comfortable in carrying out. The methods of delivery of teaching and assessment across pathology disciplines have evolved and adapted to recent circumstances. Lessons have been learned and insights gained during the COVID-19 pandemic as educators have risen to the challenge of continuing to educate medical students. Integrated and multi-disciplinary teaching is recommended to reflect best the professional environment of the medical graduate who works as an integral part of a multi-disciplinary team, with the minimum dependence on the traditional lecture, where at all possible. Finally, options on assessment are discussed, e.g. multiple-choice questions, including their respective advantages and disadvantages. Supplementary information The online version contains supplementary material available at 10.1007/s11845-021-02774-1.

BACKGROUND: α‐synuclein aggregates in the form of Lewy bodies and Lewy neurites are the pathological hallmark of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Autopsy studies suggest that α‐synuclein aggregates appear in localized areas of the central nervous system before spreading in a sequential pattern from the brainstem to the cerebral cortex, known as the Braak hypothesis. Increased prevalence of peripheral neuropathy in PD is recognized, with multiple hypothesized mechanisms including α‐synuclein deposition. METHOD: We describe a patient who developed a peripheral sensory neuropathy at age 60, which progressed insidiously over the following decade. RESULTS: During the patient's eighth decade, the patient developed a fluctuant cognitive disturbance with hallucinations before becoming overtly parkinsonian at age 78 years leading to a diagnosis of DLB. At this point, histology slides from a sural nerve biopsy taken at age 72 were re‐evaluated and immunohistochemistry demonstrated α‐synuclein deposition. CONCLUSION: This case provides important in vivo clinical correlation for the Braak hypothesis, extending its scope beyond idiopathic PD. A growing body of evidence supports the α‐synuclein spreading hypothesis that posits the pathologic process begins in the peripheral nerves and spreads trans‐synaptically to the CNS in an ascending pattern.

Summary Despite over 140 million SARS‐CoV‐2 infections worldwide since the beginning of the pandemic, relatively few confirmed cases of SARS‐CoV‐2 reinfection have been reported. While immunity from SARS‐CoV‐2 infection is probable, at least in the short term, few studies have quantified the reinfection risk. To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS‐CoV‐2 reinfection over time. A standardised protocol was employed, based on Cochrane methodology. Electronic databases and preprint servers were searched from 1 January 2020 to 19 February 2021. Eleven large cohort studies were identified that estimated the risk of SARS‐CoV‐2 reinfection over time, including three that enrolled healthcare workers and two that enrolled residents and staff of elderly care homes. Across studies, the total number of PCR‐positive or antibody‐positive participants at baseline was 615,777, and the maximum duration of follow‐up was more than 10 months in three studies. Reinfection was an uncommon event (absolute rate 0%–1.1%), with no study reporting an increase in the risk of reinfection over time. Only one study estimated the population‐level risk of reinfection based on whole genome sequencing in a subset of patients; the estimated risk was low (0.1% [95% CI: 0.08–0.11%]) with no evidence of waning immunity for up to 7 months following primary infection. These data suggest that naturally acquired SARS‐CoV‐2 immunity does not wane for at least 10 months post‐infection. However, the applicability of these studies to new variants or to vaccine‐induced immunity remains uncertain.

Learning Point Point 1 - This case illustrates auto-antibody testing as an essential diagnostic tool in patients with idiopathic ILD. It is the first reported case of isolated anti-Ku-related ILD without clinical manifestation of CTD. This may represent an independent pathology or a diagnosis of ILD that precedes development of clinical manifestations of a CTD.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

The European Society for Immunodeficiencies (ESID) Primary Immunodeficiencies Care in Development Working Party was founded in order to improve diagnosis and care of patients with primary immunodeficiencies (PIDs).

Phelan PJ, O’Kelly P, O’Neill D, Little D, Hickey D, Keogan M, Walshe J, Magee C, Conlon PJ. Analysis of waiting times on Irish renal transplant list. Clin Transplant 2010: 24: 381–385. © 2009 John Wiley & Sons A/S. Abstract: Introduction: A number of recipient variables have been identified which influence waiting list times for a renal allograft. The aim of this study was to evaluate these factors in the Irish population. Methods: We examined patients accepted onto the transplant list from January 1, 2000 until December 31, 2005. Inclusion criteria were adults listed for kidney only, deceased donor transplants. We included patients previously transplanted. Patients were censored, but still included in the analysis, if they died while on the list, permanently withdrew from the list or if they were not transplanted at the time of the study. Results: There were a total of 984 patients accepted onto the waiting list during the study period, of which 745 of these were transplanted. Factors significantly associated with longer waiting times included age above 50 yr, blood group O and high peak panel reactive antibodies level. Gender and patient body mass index were not associated with longer waiting times. Conclusion: We have identified factors associated with a longer waiting time on the Irish cadaveric renal transplant list. This information can help our patients make informed decisions regarding likely waiting times and the merits of living related transplantation.

Background Living donation is not only a method to increase access to kidney transplantation but can also offer superior outcomes. We report the experience of the living donor (LD) program in the Republic of Ireland and explore reasons why potential donors do not proceed to live donation. Methods Retrospective cohort study of all potential donors from January 2000 to March 2014 who presented wishing to undergo donor work-up and their subsequent outcomes. Results A total of 956 donors for 496 recipients contacted the live kidney donation program of which 883 potential donors proceeded to the initial stage of assessment. The donor dropout rate at this stage was 64.2% (614/956 potential donors did not proceed to further evaluation). Thereafter, 269 (28.1%) donors underwent further assessment by the multidisciplinary team. In total, 93 (9.7%) donors were declined following this assessment with 176 (18.4%) donors ultimately proceeding to live kidney donation. The major reason for declining a donor was a medical contraindication (n = 63, 67.7%). In term of recipients, 54.2% (n = 269/496) had a potential donor proceed for further assessment of which 65.4% (n = 176/269) ultimately proceeding to live donation. Conclusion Further evaluation of the declined donor group is warranted to allow for expansion of the LD program.

A 65-year-old man presented with headache, weight loss, occasional scalp tenderness, and visual loss in his left eye, which worsened over a number of weeks to bare light perception. There was a left relative afferent papillary defect with a swollen disc and a small amount of associated hemorrhage. Erythrocyte sedimentation rate (ESR) was 16 mm/1st h, C-reactive protein (CRP) was 3.3 mg/l (normal \7). Temporal artery biopsy demonstrated no evidence of arteritis. On initiation of corticosteroids, his vision improved dramatically and the corticosteroids were subsequently weaned to zero over a period of 6–8 weeks. Three months later, he re-presented with left-sided ptosis and worsening headache. There had been weight loss (7 kg within the prior 6 months). Examination revealed a complete left-sided ptosis, with normal eye movements. Visual acuity was measured at 6/5 on the right and 6/9 on the left. Slit-lamp examination was unremarkable. Laboratory investigations revealed mild eosinophilia (0.78, range 0.04–0.4 9 10/l), an ESR of 9 mm/1st h, and a CRP of 13 mg/l. Serum complement levels were reduced: C3 \0.04 g/l (range 0.75–1.88), C4 \0.01 g/l (range 0.14–0.61). Dipstick urine testing was negative for blood and protein. Urinalysis was negative for casts and red cells. Serum anti-nuclear antibody, extractable nuclear antigen, anti-neutrophil cytoplasmic antibody (ANCA), PR3 and MPO antibodies were negative. Chest radiograph was normal. Dedicated gadolinium-enhanced magnetic resonance imaging (MRI) of the orbits and brain revealed dural enhancement and thickening over the left and right temporal lobes (Fig. 1), with normal orbits. Cerebrospinal fluid (CSF) examination demonstrated an absence of cells with normal glucose and protein concentrations. CSF bacterial and TB cultures and CSF ANCA were negative. The patient was commenced on high-dose corticosteroids (1 mg/kg/day), with resolution of his headache over the following days. The CRP level and eosinophilia normalized quickly. The ptosis improved significantly but not completely. Biopsy of the fronto-temporal dura mater demonstrated thickened dura (Fig. 2a), with multifocal infiltration by cellular aggregates comprised of an admixture of mature lymphocytes, plasma cells, and multinucleate giant cells (Fig. 2c). Foci of necrosis were present (Fig. 2b), and characterized by accumulation of polymorphonuclear A. McCarthy T. Lynch K. O’Rourke (&) Dublin Neurological Institute at the Mater Misericordiae University Hospital, 57 Eccles St, Dublin 7, Ireland e-mail: killian.orourke@gmail.com

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P = .0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function. J. Clin. Apheresis 18:103–110, 2003. © 2003 Wiley-Liss, Inc.

Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT.In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS).PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients.WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease.

Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies.We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data.Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013).These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.

They showed convincing evidence that with a negativepenicillin skin test, a course of b-lactam is safe 2hours after a negative challenge. However, we advisecaution in generalizing these data to the outpatientsetting where resensitization is a possibility. One studyshowed that 4.9% of patients who had negative skintests and drug challenges reacted on rechallenges 3weeks later.

Background We examined, through genome-wide association studies (GWAS), the correlation between recipient genetic variation and renal function at five yr. Methods Our cohort contained 326 Irish, first time, kidney-only, deceased donor, transplant recipients on calcineurin inhibitors (263 had a functioning graft at five yr) between 1993 and 2002. Outcomes were creatinine at five yr and long-term graft function. Results Two variants were identified showing borderline genome-wide significance – one on chromosome 18 (p = 4.048e-08, rs6565887) and another on chromosome 14 (p = 7.631e-08, rs3811321). Individually, the two SNPs explained up to 8.8% and 11.29% of five-yr creatinine variance, respectively, while together they explained up to 17.4% of trait variance. Both variants were predictors of long-term allograft function (p = 0.004, 70% vs 30% survival at 10 yr). The chromosome 14 variant is located in the intergenic region of the T-Cell Receptor Alpha locus. Conclusions Using a genome-wide approach, we have identified two associations with five-yr creatinine levels in renal transplant recipients treated with calcineurin inhibitors. Independent replication is now warranted to clarify the clinical significance of these results.

Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg) but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.

Publisher Summary Autoantibodies directed against specific nuclear antigens (proteins and DNA) are central to the pathogenesis of systemic lupus erythematosus (SLE). Anti-extractable nuclear antigens (ENA) antibodies are detected to varying degrees in SLE patients. Knowledge regarding the genetic susceptibility towards developing SLE and the etiology of autoantibody development has greatly increased in recent years and it is now widely accepted that defective clearance of apoptotic bodies, viral infection, and molecular mimicry all contribute to the activation of autoreactive B cells and autoantibody production. Anti-ENA antibodies develop a number of years prior to disease onset and, with the exception of Anti-Ro and anti-Sm, are not directly implicated in tissue pathogenesis. The role of the IFN system in the pathophysiology of SLE is well recognized. The anti-ENA immune complexes, by virtue of their being bound to RNA, act as potent stimulators of TLR7 and help drive IFN-α production by plasmacytoid dendritic cells and promote the autoimmune cycle. Recent research findings have suggested that a subset of ENA autoantigens, associated with the Ro/La autoantigen complex, is potentially involved in regulating IFN responses and innate immune detection mechanisms. The possibility that autoantibody generation not only mediates inflammation associated with the recognition of autoantigens but might also result in the inappropriate sequestering of Ro52 and Ro60 is being probed into.

Introduction The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. Materials and methods Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of ‘elevated tumour marker’ in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. Results Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41–91] y), were imaged to evaluate: ‘elevated tumour marker’. They underwent 29 imaging studies (mean [±standard deviation (SD)] per patient = 1.2 [±0.4]), and had 42 elevated tumour marker serology tests (mean [±SD] per patient = 1.7 [±0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. Conclusion The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of ‘elevated tumour marker’. ‘Elevated tumour marker’, in the absence of a known underlying malignancy, should not be considered an independent indication for imaging.

The characteristic clinical features of constitutional trisomy 8 include varying degrees of developmental delay, joint contractures and deep palmar and plantar creases. There is an established literature, which describes features of Behcet syndrome occurring in phenotypically normal individuals with myelodysplastic syndromes and trisomy 8 in their bone marrow. In this article, we describe four patients with constitutional trisomy 8, all with varying clinical phenotypes, who developed features of Behcet, in particular but not exclusively mucocutaneous ulceration. In addition, we examined gene copy numbers of the variable-number neutrophil defensin genes DEFA1A3 in one of the cases (case 1) and her parents, together with 14 cases of Behcet syndrome in comparison with 121 normal controls. The gene copy number was highest in case 1 (copy number 14) and was also increased in her parents (both copy number 9). However the mean copy number for DEFA1A3 among the 14 Behcet syndrome patients was actually lower (5.1) than among the controls (mean of 6.8 copies). Thus, we conclude that patients with constitutional trisomy 8 and those with trisomy 8 confined to the bone marrow are both at increased risk of developing features of Behcet syndrome. The mechanism may relate to increased chromosome 8 gene dosage with further analysis of candidate genes on chromosome 8 required.

Dear Editor, An 18-month-old female infant presented to the paediatric haematology service in 1985 with lymphadenopathy, hepatosplenomegaly, anaemia (Hb 6.3 g/dL, range 11.7– 14 g/dL) and thrombocytopenia (17×10, range 150– 400×10). Bone marrow and lymph node examinations were reported as ‘reactive’. Karyotyping was normal. Viral, autoimmune and metabolic screens were negative. Following a period of observation and external review, during which time her marrow blast count rose to 9 %, the decision was made to proceed with Medical Research Council protocol for acute lymphoblastic leukaemia, with complete normalisation of peripheral blood counts and regression of spleen size for the duration of treatment (1986–1988). Her subsequent disease course included recurrent sinus and respiratory tract infections, fluctuating cytopenias, chronic lymphadenopathy and an elective splenectomy in the setting of massive splenomegaly. She developed severe autoimmune haemolytic anaemia, requiring intense immunosuppression and ultimately plasma exchange followed by recurrent invasive pneumococcal septicaemia on ages 14, 16 and 18 years. She was referred for immunological assessment in 2009 when a biopsy of an epitrochlear lymph node revealed paracortical T cell zone expansion with evidence of clonal T cell rearrangements, subsequently confirmed on bone marrow biopsy. CT images of thorax, abdomen and pelvis showed no evidence of lymphoma. On review, it emerged that her father, paternal aunt and first cousin all had a previous diagnosis of lymphoma. Screening for autoimmune lymphoproliferative syndrome (ALPS) confirmed the presence of double negative (DN) αβT cells (18 %, normal

SummaryWe present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.

The prevalence of Clostridium difficile infection (CDI) is increasing worldwide. Oral vancomycin is an effective and frequently used treatment. However, patients with CDI who are allergic to intravenous vancomycin cannot receive oral vancomycin due to the risk of anaphylaxis if given the oral form.We present a case where oral vancomycin desensitisation was used to successfully treat a vancomycin allergic patient with recurrent CDI. Keywords: Allergy, Anaphylaxis, Desensitisation, Vancomycin, Clostridium difficile

A syndrome of sensory ataxia has been associated with immunoglobulin (Ig) M antibodies to NeuNAc (alpha2–8), NeuNAc (alpha2–3), and disialylated gangliosides, including GD1b, GD3, GD2, GT1a, GT1b, and GQ1b.1-3⇓⇓ In some patients, cold agglutinins have also been present.4 The acronym CANOMAD encompasses the clinical phenotype of c hronic a taxic n europathy with o phthalmoplegia, M -protein, a gglutination, and anti d isialosyl antibodies.1,4⇓ This condition is distinguished from the Miller Fisher variant of Guillain–Barre syndrome by the presence of cold agglutinins and occasionally cryoglobulins and by the chronic and progressive nature of the phenotype. A 53-year-old man developed slowly progressive unsteadiness and painful paraesthesias in his extremities during a 5-month period. His examination revealed marked gait disturbance, sensory ataxia, and weakness in the distal extremities. The remainder of his neurologic examination was normal. Lumbar puncture yielded an elevated CSF protein (85 mg%). Neurophysiologic studies revealed temporal dispersion and prolonged distal latencies that were more marked in the sensory nerves than in the motor nerves. Denervation activity was …

The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels.

Background: Membranoproliferative glomerulonephritis (MPGN) is a relatively uncommon cause of progressive renal disease characterized by immune complex deposition resulting in mesangial proliferation and endocapillary inflammation with capillary wall thickening and double contour formation. Although a familial linkage has been reported in MPGN type II disease and less often in type I disease, a familial linkage in type III disease has not been reported previously. Methods: We identified a family in which MPGN type III developed in a living-related donor 12 years later and recurred in the renal allograft of his son, whose primary disease was MPGN type III. We screened the members of the extended family, looking for evidence of hematuria and proteinuria. Renal biopsy specimens exhibited the findings of subendothelial deposits, subepithelial deposits, and complex glomerular basement membrane changes with C3 but not IgG seen on immunofluoresence. Results: Screening identified eight affected family members (six biopsy proven) over three generations. The condition is inherited in an apparent autosomal dominant fashion. Conclusion: This is the first description of familial MPGN type III. We hope that by studying the disease in this family group, we may learn more about the pathogenesis of the condition. © 2002 by the National Kidney Foundation, Inc.