Consideration Of Alternative Diagnoses Research Articles

Real-world challenges in the diagnosis of primary progressive multiple sclerosis.

Despite the 2017 revisions to the McDonald criteria, diagnosing primary progressive multiple sclerosis (PPMS) remains challenging. To improve clinical practice, we aimed to identify frequent diagnostic challenges in a real-world setting and associate these with the performance of the 2010 and 2017 PPMS diagnostic McDonald criteria. We retrospectively recorded clinical, radiological and laboratory characteristics at time of diagnosis from designated PPMS patient files. Possible complicating factors were recorded such as confounding comorbidity, signs indicative of alternative diagnoses, possible earlier relapses, and/or incomplete diagnostic workup (no cerebrospinal fluid examination and/or MRI brain and spinal cord). We calculated the percentages of patients fulfilling the 2010 and 2017 McDonald criteria after censoring patients with these complicating factors. A total of 322 designated PPMS patients were included. Of all participants, we found that n=28/322 had confounding comorbidity and/or signs indicative of alternative diagnoses, n=103/294 had possible initial relapsing and/or uncertainly progressive phenotypes, and n=73/191 received an incomplete diagnostic work-up. When applying the 2010 and 2017 diagnostic PPMS McDonald criteria on n=118 cases with a full diagnostic workup and a primary progressive disease course without a better alternative explanation, these were met by 104/118 (88.1%) and 98/118 remaining patients (83.1%), respectively (p=0.15). Accurate interpretation of the initial clinical course, consideration of alternative diagnoses, and a full diagnostic workup are the cornerstones of a PPMS diagnosis. When these conditions are met, the 2010 and 2017 McDonald criteria for PPMS perform similarly, emphasizing the importance of their appropriate application in clinical practice.

Esclerosis múltiple: diagnóstico diferencial y tratamiento

The diagnostic criteria for multiple sclerosis(MS) are based on the identification of a typical syndrome attributable to the central nervous system, the demonstration of dissemination in space and time, and the absence of a better explanation than MS. This article includes some of the demographic, clinical or paraclinical criteria that should prompt consideration of alternative diagnoses. In addition, the usage of the 18 disease-modifying drugs currently employed is reviewed, including the latest additions (diroximel fumarate, siponimod, ozanimod, ponensimod and ofatumumab), the recent indications in clinical courses other than relapsing-remitting and the symptomatic treatment of the disease.

URTICARIAL VASCULITIS MASQUERADING AS TYPICAL ACUTE URTICARIA

<h3>Introduction</h3> Urticaria is a common condition which has clinical overlap with urticarial vasculitis, a rare entity affecting <1% of the population. We report a case of typical acute urticaria evolving into urticarial vasculitis. <h3>Case Description</h3> A 58-year-old female with a history of endometrial hyperplasia, Hashimoto's thyroiditis, and asthma was initially seen in Allergy and Immunology clinic following an episode of severe perioperative anaphylaxis, determined to be due to cefazolin. Two months later, she presented with new-onset urticaria and angioedema following a mild self-resolving viral illness. The rash was pruritic, with migratory lesions lasting for <24 hours, and not associated with ecchymoses upon resolution. Initial physical examination was notable for erythematous wheals with blanching. She was started on high dose second-generation antihistamines and received multiple steroid tapers with transient improvement. Four weeks after initiation of the rash, she developed a new-onset burning sensation at its site and subsequently developed painful hyperpigmented purpuric lesions in prior areas of urticaria. She had no associated fever, ocular involvement, abdominal pain, or joint pains. Laboratory values were significant for negative CBC, CMP, ESR, TSH, tryptase, c-KIT mutation analysis, ANA, C1q, C3, C4, and SARS-CoV-2 nucleocapsid antibodies. Extensive autoimmune workup was negative. Skin biopsy revealed leukocytoclastic vasculitis consistent with urticarial vasculitis. Patient was started on omalizumab with initial improvement. <h3>Discussion</h3> Although initially presenting with acute urticaria, the progression of atypical urticarial symptoms warranted consideration of alternative diagnoses, including urticarial vasculitis. This case highlights the clinical overlap between acute/chronic urticaria and urticarial vasculitis which may result in a delay in diagnosis.

Description of neurological mimics presented to the neurology service of a small animal referral hospital.

Clinicians observe that cats and dogs referred to neurology services often do not have an underlying neurological disorder. There has been no analysis of the frequency or categorisation of these neurological mimics. Retrospective study of 520 cases was carried out. Data on signalment, presenting clinical signs, neurological examination findings and final diagnosis were collected. Final diagnoses were classified as primary neurological, non-neurological in origin but with neurological clinical manifestation, completely non-neurological (neurological mimics) or undiagnosed. Presenting clinical signs and neurological examination results were compared between neurological mimics and primary neurological cases using Chi-square or Fischer exact test. Relative risk (RR) was calculated for significant associations. A total of 74% were primary neurological conditions, 8% neurological mimics, 3% non-neurological with neurological manifestation and 15% undiagnosed. An animal referred for lameness was approximately five times more likely to be diagnosed as a neurological mimic than as a primary neurological disorder (RR=5.42, p<0.001). Cases with a normal neurological examination were approximately 15 times more likely to be a neurological mimic (RR=14.97, p<0.001). Thorough examination with consideration of alternative diagnoses is important when a neurological condition is suspected in an animal that presents with lameness or normal neurological examination.

The multidisciplinary team severe asthma day case assessment and its impact on patient care

People with severe and difficult to control asthma can be a complex and heterogenous group of patients often with multiple comorbidities. Living with this disease imposes a huge physical and psychological burden upon the patient which requires a comprehensive, systematic and patient-focused assessment, using a wide range of clinical expertise from within the multidisciplinary team. This article describes a severe asthma systematic and multidimensional day case assessment, and the positive benefits that the authors perceive it offers for patient care. These benefits include a confirmed diagnosis, consideration of alternative diagnosis, enhanced adherence, medication optimisation, access to and gatekeeping of high-cost specialist medications, improved patient self-management skills and signposting to appropriate therapies. As a consequence, they believe that this facilitates better patient outcomes through a reduction in corticosteroid exposure, exacerbations and hospitalisation. This severe asthma multidisciplinary team day case approach offers more than just physical benefits when compared with the traditional medical model. Patient feedback reports an excellent patient experience, feeling listened to, understood, empowered and hopeful for the future.

A215 MDR3 DEFICIENCY MIMICKING WILSON DISEASE

Abstract Background The chronic phenotype of ALF includes a broad differential diagnosis. Class III multi-drug resistance P-glycoprotein 3 (MDR3) deficiency, also referred to as progressive familial intrahepatic cholestasis type 3, is an autosomal recessive genetic disorder. It is caused by a defect on the ABCB4 gene located on chromosome 7, which encodes MDR3. MDR3 is responsible for transporting phosphatidylcholine across the canalicular membrane, thereby allowing it to be incorporated into bile micelles. MDR3 deficiency results in increased levels of free bile acids and detergent bile. Progressive cholangiopathy ensues from this detergent bile and indirectly leads to cholestasis and liver failure in severe cases. Significantly increased urinary and hepatic copper (Cu), which are hallmarks of Wilson disease, have also been reported in patients with acute hepatitis and cholestasis including patients with MDR3 deficiency Aims We report a case of a girl who presented with a chronic phenotype of PALF, who had multiple features of Wilson disease and so was treated as such until genetic analysis confirmed MDR3 deficiency Methods Results A 6 year old girl presented to the ED with a 1mth history of epistaxis and a 1wk history of abdominal pain and distension, facial edema, pallor and fever. Her family history was significant for parental consanguinity and maternal itch during pregnancy. On examination she had clubbing, scleral icterus and a distended abdomen with hepatosplenomegaly. Her bloodwork showed bicytopenia (HGB 53 &amp; Plts 63) along with liver dysfunction (INR 2.9, albumin 25, conjugated bilirubin 9) and raised liver enzymes (transaminases &amp; GGT &amp;gt;10xULN). Her total serum bile acids were raised at 134. An US showed hepatosplenomegaly with multiple hyperechoic nodules and perisplenic varices. She was extensively worked up for malignancy, autoimmune and metabolic disease. Serum ceruloplasmin was reduced, ophthalmology examination showed no KF rings and her 24hr urinary Cu was 10xULN. Liver Cu quantification was markedly raised at 40xULN. Liver biopsy showed cirrhosis with fibrosis related minimal non-specific portal and septal inflammation. Additionally, complete loss of canalicular staining on immunohistochemistry for MDR3 protein was noted, suggestive of MDR3 deficiency. Based on the Cu levels, a provisional diagnosis of Wilson disease was made and Cu chelation therapy was commenced pending genetic testing. A cholestatic gene panel subsequently showed homozygous pathogenic variant for the ABCB4 gene. Trientine was stopped and she was commenced on ursodeoxycholic acid. Though biochemically she remains largely unchanged, she is clinically stable whilst awaiting a liver transplant Conclusions This case highlights the diagnostic difficulties associated with Cu test result interpretation in patients with chronic cholestatic liver disease and urges a thorough consideration of alternative diagnoses of PALF Funding Agencies None

Evolving Immunologic Perspectives in Chronic Inflammatory Demyelinating Polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest chronic idiopathic dysimmune neuropathy. Pathophysiologic processes involve both cellular and humoral immunity. There are various known forms of CIDP, likely caused by varying mechanisms. CIDP in its different forms is a treatable disorder in the majority of patients. The diagnosis of CIDP is clinical, supported routinely by electrophysiology. Cerebrospinal fluid analysis may be helpful. Routine immunology currently rarely adds to the diagnostic process but may contribute to the identification of an associated monoclonal gammopathy with or without hematologic malignancy and the consideration of alternative diagnoses, such as POEMS syndrome, anti-myelin associated glycoprotein (MAG) neuropathy or chronic ataxic neuropathy, with ophthalmoplegia, M-protein, cold aglutinins and disialosyl antibodies (CANOMAD). The search for antibodies specific to CIDP has been unsuccessful for many years. Recently, antibodies to paranodal proteins have been identified in a minority of patients with severe CIDP phenotypes, often unresponsive to first-line therapies. In conjunction with reports of high rates of antibody responses to neural structures in CIDP, this entertains the hope that more discoveries are to come. Although still arguably for only a small minority of patients, in view of current knowledge, such progress will enable earlier accurate diagnosis with direct management implications but only if the important, unfortunately and infrequently discussed issues of immunologic technique, test reliability and reproducibility are adequately tackled.

Functional cognitive disorder: dementia's blind spot.

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional cognitive disorder (FCD). FCD is likely very common in clinical practice but may be under-diagnosed. Clinicians in many settings make liberal use of the descriptive term mild cognitive impairment (MCI) for those with cognitive difficulties not impairing enough to qualify as dementia. However, MCI is an aetiology-neutral description, which therefore includes patients with a wide range of underlying causes. Consequently, a proportion of MCI cases are due to non-neurodegenerative processes, including FCD. Indeed, significant numbers of patients diagnosed with MCI do not 'convert' to dementia. The lack of diagnostic specificity for MCI 'non-progressors' is a weakness inherent in framing MCI primarily within a deterministic neurodegenerative pathway. It is recognized that depression, anxiety and behavioural changes can represent a prodrome to neurodegeneration; empirical data are required to explore whether the same might hold for subsets of individuals with FCD. Clinicians and researchers can improve study efficacy and patient outcomes by viewing MCI as a descriptive term with a wide differential diagnosis, including potentially reversible components such as FCD. We present a preliminary definition of functional neurological disorder-cognitive subtype, explain its position in relation to other cognitive diagnoses and emerging biomarkers, highlight clinical features that can lead to positive diagnosis (as opposed to a diagnosis of exclusion), and red flags that should prompt consideration of alternative diagnoses. In the research setting, positive identifiers of FCD will enhance our recognition of individuals who are not in a neurodegenerative prodrome, while greater use of this diagnosis in clinical practice will facilitate personalized interventions.

Patient pathways of tuberculosis care-seeking and treatment: an individual-level analysis of National Health Insurance data in Taiwan

IntroductionPatients with tuberculosis (TB) often experience difficulties in accessing diagnosis and treatment. Patient pathway analysis identifies mismatches between TB patient care-seeking patterns and service coverage, but to date, studies have...

P51 Serious pathology mimicking GCA: two cases of carcinoma tongue

Abstract Background Jaw and tongue pain with constitutional symptoms and raised inflammatory markers are considered pathognomonic ischemic features of giant cell arteritis (GCA). Temporal artery ultrasound (US) (or biopsy) available in GCA fast-track clinics (FTC) for a rapid assessment of patients with suspected GCA. Atypical presentation and negative US or biopsy require further workup to look for an alternative diagnosis. ENT pathology can occur as a mimic of GCA. Herein we discuss two clinical cases of squamous cell cancer tongue presenting with signs and symptoms that resemble GCA. Methods We have put together a case report. Results Case-1: A 58-year-old male with a recent presumed diagnosis of relapsing GCA was referred with worsening visual symptoms and right eye pain despite ongoing steroid treatment (60mg), for consideration of Tocilizumab (TCZ). His initial presentation was 5 months ago with a right parietal and retro-orbital headache and blurred vision. He had a normal eye examination. His C-reactive protein (CRP) was raised (24). He was started on prednisolone 40 mg for GCA with complete resolution of symptoms with normalised CRP within weeks. Several weeks later, symptoms reoccurred. CT brain, abdomen and pelvis was normal and temporal artery biopsy negative. His prednisolone was increased to 60 mg. 6 months later, his jaw and tongue pain worsened, and he was treated with pulsed methylprednisolone. Due to partial response to steroids, he was referred to consider TCZ. He had tender left TMJ with normal temporal artery US. Urgent MRI head and neck revealed a left posterior tongue mass with the histology confirmed poorly differentiated squamous cell carcinoma. He was managed with chemo and radiotherapy. Case-2: A 75 years old female, presented with right scalp pain, tongue pain, painful swallowing and chewing. Her blood investigations were normal except a raised ESR (48) and presumed GCA she was started on steroids (60 mg). she had initially good response but, within a few weeks, her symptoms returned. She was then referred to our FTC. Temporal artery US and biopsy were normal. MRI of the head and neck showed a large mass seen in the right half of the posterior tongue extending into the deep aspect of the anterior tongue. Histology confirmed poorly differentiated Squamous cell carcinoma. She was treated with a combination of chemotherapy and radiotherapy. Conclusion GCA mimics represent a major diagnostic dilemma. FTC helps to stratify the GCA from mimics. Careful evaluation of the history, examination as well as a temporal artery US helps to exclude GCA and aids prompt requesting of appropriate tests to find an alternative diagnosis such as tongue cancers as in our cases. We have now introduced negative weightage for consideration of alternative diagnoses in our GCA probability score. Disclosures A. Kayani None. A. Sebastian None. L. Borukhson None. M. Whitlock None. B. Dasgupta Consultancies; Roche, Sanofi. Grants/research support; Roche.

Patient Pathways of Tuberculosis Care-Seeking and Treatment: An Individual-Level Analysis of National Health Insurance Data

Background: Tuberculosis patients often experience difficulties in accessing diagnosis and treatment. Patient Pathway Analysis provides a tool to identify mismatches between provision of, and patient demand for, tuberculosis care, but was developed using cross-sectional, aggregate data. Methods: We developed an algorithmic approach to analyse and interpret patient-level routine data on healthcare utilisation and construct patients' pathways from initial care-seeking to treatment outcome. We applied this to tuberculosis patients in a simple random sample of one million patients' records in the Taiwan National Health Insurance database. We analysed heterogeneity in pathway patterns, delays, service coverage, and patient flows between different health system levels. Findings: We constructed 7,255 pathways for 6,258 patients. Patients most commonly initially sought care at the primary clinic level, where the capacity for diagnosing tuberculosis was 12%, before eventually initiating treatment at higher levels. Patient pathways are extremely heterogeneous prior to diagnosis, with the 10% most complex pathways accounting for 48% of all clinical encounters, and 55% of those pathways yet to initiate treatment after a year. Extended consideration of alternative diagnoses was more common for patients aged 65 or older and for patients with chronic lung disease. Interpretation: Patient-level routine healthcare data can be analysed to generate individual patient tuberculosis care-seeking pathways. Improving tuberculosis awareness and specimen-handling capacity at primary care level may improve patient experience of accessing tuberculosis care in Taiwan. Funding Statement: PJD was supported by a fellowship from the UK MRC (MR/P022081/1). HHL was supported by the Taiwan MoST, (101-2314-B-002-124) and the Taiwan NHRI (NHRI-EX105- 10228PC). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was approved by the ethics committee of the University of Sheffield (Reference Number 017693).

CHEST PAIN AND NEUROLOGIC DEFICIT: A POTENTIALLY FATAL COMBINATION

Clinical presentation of acute aortic dissection can be subtle and hemodynamic instability may not always be present, often leading to consideration of alternative diagnosis. 51 year old male with no significant medical history presented with chest pain, syncope and left arm weakness. Chest x-ray,

Methods to improve the noninvasive diagnosis and assessment of disease severity in children with suspected nonalcoholic fatty liver disease (NAFLD): Study design

BackgroundNonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is the most common liver disease in the developed world. In children with suspected NAFLD, present guidelines suggest consideration of alternative diagnoses via extensive blood testing, though the yield of this work up is unknown. Furthermore, the gold standard diagnostic test for NAFLD remains liver biopsy, making the development of non-invasive tests critically important. ObjectivesOur objectives are: 1) to determine the accuracy of elastography and multiple serum biomarkers – each assessed individually and as algorithms (including those previously tested in adults) – for the diagnosis of nonalcoholic steatohepatitis (NASH) and early fibrosis in children and (2) to examine the utility of extensive testing for rare alternative diagnoses in overweight or obese children with elevated alanine aminotransferase (ALT) suspected to have NAFLD. DesignThis is an ongoing, cross-sectional study in children 2–18 years of age with up to 2 years of prospective follow up. Eligible patients are asymptomatic, overweight or obese, and have an ALT ≥35 U/L upon enrollment. Two forms of elastography are obtained serially along with anthropometric data and routine laboratory tests. Elastography and serum biomarkers are also performed immediately prior to any clinically-indicated biopsy. MethodsBetween April 2015 and April 2018, 193 children have been enrolled in this ongoing study and 71 have undergone liver biopsy. Here we carefully report the rationale, methodology, and preliminary data for this study.

Life-course exposure and physical activity impact on genomic biomarkers of a group of older adults

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is the most common liver disease in the developed world. In children with suspected NAFLD, present guidelines suggest consideration of alternative diagnoses via extensive blood testing, though the yield of this work up is unknown. Furthermore, the gold standard diagnostic test for NAFLD remains liver biopsy, making the development of non-invasive tests critically important.Our objectives are: 1) to determine the accuracy of elastography and multiple serum biomarkers – each assessed individually and as algorithms (including those previously tested in adults) – for the diagnosis of nonalcoholic steatohepatitis (NASH) and early fibrosis in children and (2) to examine the utility of extensive testing for rare alternative diagnoses in overweight or obese children with elevated alanine aminotransferase (ALT) suspected to have NAFLD.This is an ongoing, cross-sectional study in children 2–18 years of age with up to 2 years of prospective follow up. Eligible patients are asymptomatic, overweight or obese, and have an ALT ≥35 U/L upon enrollment. Two forms of elastography are obtained serially along with anthropometric data and routine laboratory tests. Elastography and serum biomarkers are also performed immediately prior to any clinically-indicated biopsy.Between April 2015 and April 2018, 193 children have been enrolled in this ongoing study and 71 have undergone liver biopsy. Here we carefully report the rationale, methodology, and preliminary data for this study.

IgG4-related orbital disease masquerading as thyroid eye disease, vice versa, or both?

ABSTRACTA 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses. Inferior oblique biopsy stained positive for IgG4 with histologic features atypical of TED. The patient received rituximab for presumed IgG4-related orbital disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near complete resolution of EOM restriction, and improved proptosis, the latter two of which are not routinely anticipated in advanced TED. The possible role for B-cell depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying immune-related pathophysiology that is yet to be defined.

Diagnosis of adverse local tissue reactions following metal-on-metal hip arthroplasty.

Metal-on-metal (MOM) bearing surfaces in hip arthroplasty have distinct advantages that led to the increase in popularity in North America in the early 2000s. However, with their increased use, concerns such as local cytotoxicity and hypersensitivity reactions leading to soft tissue damage and cystic mass formation (known collectively as adverse local tissue reactions (ALTR)) became apparent. The clinical presentation of ALTR is highly variable. The diagnosis of ALTR in MOM articulations in hip arthroplasty can be challenging and a combination of clinical presentation, physical examination, implant track record, component positioning, serum metal ion levels, cross-sectional imaging, histopathologic analysis, and consideration of alternative diagnoses are essential.

Lyme disease: authentic imitator or wishful imitation?

Lyme disease: authentic imitator or wishful imitation?

Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87 children in Papua New Guinea participating in a detailed longitudinal observational study who had undergone lumbar puncture for further investigation of altered consciousness and/or convulsions. After rigorous exclusion of non-malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF leukocytosis, which was unrelated to prior, including complex, seizures. There were eight children with a CSF leukocyte density > 10 cells/μL (9.2% of the total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal fluid leukocytosis is infrequent in severe pediatric malaria, especially in children with P. vivax infections, and it is generally mild. Its presence in a blood slide-positive child should prompt consideration of alternative diagnoses and empiric antibiotic therapy.

Polymyalgia rheumatica: pathogenesis and management

#### Key points Polymyalgia rheumatica (PMR) is a treatable, inflammatory musculoskeletal disease mostly affecting those over 50 years of age Diagnosis of PMR can be difficult and is primarily based on the history of the patient plus consideration of alternative diagnoses including infection,

Neutrophilic Infiltration in Gluten-sensitive Enteropathy Is Neither Uncommon Nor Insignificant

The histologic findings of celiac disease, that is, gluten-sensitive enteropathy (GSE), are dominated by increased intraepithelial lymphocytes, villous blunting, lymphoplasmacytic infiltration of lamina propria, and crypt hyperplasia. To date, neutrophils have not been thought to constitute a significant cell type in GSE, and their presence often invokes consideration of alternative diagnoses. Thus, we sought to determine the prevalence and severity of neutrophilic infiltration in duodenal biopsies from patients with GSE. The degree of neutrophilic infiltration and features characteristic of GSE were assessed in duodenal biopsies from 267 clinically confirmed GSE patients (116 adults and 151 children). These specimens were graded by the disease activity score (DAS) and the neutrophilic activity score (NAS). Gastric antral biopsies obtained from 195 patients were also evaluated for lymphocytic gastritis. NAS was correlated with DAS and other clinicopathologic features. We found that 56% of pediatric and 28% of adult GSE patients had significant duodenal neutrophilia. NAS was higher in children than in adults (2.3 vs. 1.2, P<0.001). Multivariate regression showed that DAS, eosinophilic infiltration, and foveolar metaplasia correlated positively, and age correlated negatively with NAS. Lymphocytic gastritis was seen in 21.5% of the gastric biopsies. The presence of lymphocytic gastritis correlated positively with NAS and DAS, and in the pediatric population it correlated negatively with age. Significant duodenal neutrophilia is often found in patients with celiac disease, especially in the pediatric population, and is associated with more active disease. Thus, the findings of duodenal neutrophilia in biopsies, otherwise consistent with GSE, should not preclude the diagnosis of GSE.