Unexplained Eosinophilia Research Articles

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

A tale of two studies: is peripheral eosinophilia associated with Dientamoeba fragilis detection in adult stool samples?

The protozoan parasite Dientamoeba fragilis is a frequently isolated stool organism and postulated cause of gastrointestinal symptoms. Peripheral blood eosinophilia has been described. This is the first study amongst the Australasian adult population to assess the relationship between organism detection and eosinophilia. A case-control study took place over 7 years at a single Sydney laboratory site, evaluating patients with D.fragilis identified on stool using real-time PCR with a recent full blood count, to control groups with Giardia spp. and sequential negatives with neither organism. A nested study compared those with microscopic evidence of D.fragilis as a marker of disease burden, to molecular diagnosis alone. Sixty-four D.fragilis, 30 Giardia spp., and 94 sequential controls were enrolled. Only 60.1% of samples were preserved in sodium acetate-acetic acid formalin (SAF) fixative, indication mostly not documented. The major co-organism detected amongst all participants was Blastocystis sp., particularly in the D.fragilis cohort (37.2%). The most common pathogen amongst sequential controls was Campylobacter spp. (7.4%). Patients with D.fragilis were more likely (12.5%) to have a clinically significant eosinophilia (>0.5×109/L) compared to those with Giardia spp. (3.3%) or sequential controls (4.3%) (p=0.03). A significant difference was also noted in the overall median eosinophil count of those with D.fragilis versus all controls (0.2 vs 0.1×109/L, p=0.01); however, this was within the reference interval (where up to >0.5×109/L is accepted in healthy individuals within a typical population). No eosinophil difference was found between those with molecular versus additional microscopic detection of D.fragilis (0.1 vs 0.1×109/L). These results support an association between the identification of clinically significant peripheral blood eosinophilia and D.fragilis presence, which may impact the diagnostic approach to the patient with unexplained eosinophilia. Further prospective trials may help assess any significance further and the implication of co-carriage with other enteric organisms. The importance of clinical indication and need for appropriate fixative media in diagnostic parasitology are also highlighted.

Evidence of helminthic infestation and efficacy of anthelminthic treatment in children investigated for eosinophilia

Background/Aim. The cause of eosinophilia often remains unelucidated. The aim of the study was to analyze causes and treatment approaches in children with eosinophilia in pediatric tertiary care hospital. Methods. The medical records of children investigated for eosinophilia (based on the International Classification of Diseases code D72.1) were retrospectively reviewed in the University Children?s Hospital, Belgrade, Serbia, from December 2011 to December 2022. A total of 105 children (62 boys; male:female ratio was 1:4) aged one month to 16.5 years (median 7.7 years) were diagnosed with eosinophilia. After excluding 15 of them due to incorrectly assigned diagnosis based on relative eosinophil number only, the remaining 90 children were grouped according to the severity of eosinophilia (mild, moderate or severe). Results. Serological analysis confirmed toxocariasis in six (6.7%) patients, while two (2.2%) had a confirmed nematode infestation (Ascaris lumbricoides and Enterobius vermicularis, respectively). Thirty-two (35.6%) children with eosinophilia and three with no true eosinophilia were diagnosed with helminthiasis ex juvantibus. Eosinophilia was ultimately explained by allergic/atopic conditions [19 (21.1%)], drug reactions [four (4.4%)], bacterial infections [nine (8.9%)], hematological problems [five (5.5%)], autoimmune disorders [three (3.3%)], unrelated congenital disorders (one), or as an isolated finding [seven (7.8%)]. In addition, one of the children without an increased absolute eosinophil number was diagnosed with eosinophilic esophagitis. A total of 56 (53.3%) children received anthelminthic treatment: 9 (90.0%) with severe eosinophilia, 19 (51.4%) with moderate, 23 (53.5%) with mild, and 5 (33.3%) children with no true eosinophilia. Most (42) of the children were given mebendazole only, while the remaining 14 (eight with severe, three with moderate, and three with mild) were also initially treated with mebendazole but subsequently shifted to albendazole due to the persistence of eosinophilia. In all treated children, eosinophilia and other relevant findings (if any) subsided in a matter of a few days to a few weeks after initializing treatment. Conclusion. Our results support the recommendation that unexplained eosinophilia of all levels of severity requires a standardized diagnostic approach. The results also provide some support for a potential rational basis for ex juvantibus administration of anthelminthic drugs in a fraction of children with eosinophilia without an obvious etiological explanation.

Worm globalization

We report the first case of eosinophilic pleural effusion due to Anisakis spp. infection in a 39-years-old European subject hospitalized for worsening dyspnoea and abdominal and thoracic pain. Lung CT scan showed bilateral pleural effusion; thoracentesis revealed significant eosinophilia (45%), with normal eosinophils in the blood. Microbiological tests on pleural effusion were negative for bacteria, SARS-CoV-2, tuberculosis, fungi and parasites. The patient used to eat raw fish; Western blot was positive for Anisakis spp. in blood and pleural effusion. In the era of globalization, unusual parasitic infections should be considered also in nonendemic countries, especially in patients with unexplained eosinophilia.

P017 Prescription trends and reasons for discontinuation amongst at-home biological therapies

Abstract Background/Aims Our unit currently follows the 2019 British Society of Rheumatology Guidelines in the prescribing and monitoring of bDMARDs which advocates 3-6 monthly monitoring blood tests in patients prescribed a biologic without a concomitant csDMARD. The guideline acknowledges “there is no evidence on the optimal monitoring requirements for patients receiving biologics”. In particular there is lack of evidence on the extent to which routine blood monitoring in such patients results in the discontinuation of the biologic. Given the costs associated with complying with this aspect of the guideline we devised this project to describe at-home biologic prescribing trends at our unit over the previous 5 years and to identify the rate of biologic discontinuation due to dyscrasias. Methods We retrospectively analysed all at-home biologic prescriptions issued at our unit between 2017 and 2021 to describe temporal trends in biologic prescribing habits. We used this data to identify patients that discontinued biological therapies and then performed a detailed retrospective analysis of electronic case records of patients who discontinued an at-home anti-TNF biologic (adalimumab, etanercept, golimumab, and certolizumab) between 01/01/2017 and 31/12/2018 to describe the reasons for discontinuation of anti-TNF biologics. Blood dyscrasia was defined as: white cell count <3.5 × 109/l; neutrophils <1.6 × 109/l; creatinine increase >30% over 12 months and/or calculated GFR <60 ml/min; unexplained eosinophilia >0.5 × 109/l; ALT and/or AST >100 U/l; platelet count <140 × 109/l; unexplained reduction in albumin <30 g/l. Results Between 2017 and 2021 our unit issued a total of 39,298 prescriptions for at-home biologics. During this timeframe the total number of annual prescriptions at our unit increased by 76.6% (2017: 5240, 2021: 9265) and the number of unique patients prescribed a biological therapy increased by 72.4% (2017: 1018, 2021: 1755). The total number of anti-TNF biologic prescriptions increased by 49.8%, and the number of adalimumab prescriptions increased by 89.8%. Between 1/1/2017 and 31/12/2018 295 patients discontinued an anti-TNF biologic. Reasons for discontinuation included: drug inefficacy: n = 156 (52.9%), treatment de-escalation: n = 15 (5.1%), adverse event (e.g. infection, side effect, intolerance): n = 36 (12.2%), blood dyscrasia: n = 4 (1.4%), patient lost to follow up: n = 43 (14.6%), pregnancy: n = 8 (2.7%), other (e.g. malignancy, heart failure, interstitial lung disease): n = 33 (11.2%). Conclusion Our data suggests that prescription of at-home biological therapies has increased significantly between 2017-2021. Amongst patients taking anti-TNF therapies the number of patients discontinuing therapy due to blood dyscrasia was very low. In view of the increasing number of biologic prescriptions and the associated costs of 3-6 monthly blood monitoring, further data to determine the optimal monitoring requirements for patients on biological therapies is needed. Disclosure M.D.J. Gibson: None. J. Wells: None. S. Subesinghe: None.

The role of flexible bronchoscopy in the diagnostic pathway of children with unexplained peripheral eosinophilia.

Many possible underlying causes can be seen in children with unexplained peripheral eosinophilia (UPE) with suspected pulmonary involvement. Here, we aimed to demonstrate the clinical characteristics and diagnoses of children evaluated for UPE who underwent diagnostic bronchoscopy. Thirty-one children who underwent diagnostic bronchoscopy for UPE between 2006-2018 were included. Demographic characteristics, bronchoscopy findings and final diagnosis, and treatments were evaluated. The median age at the time of diagnosis was 5 (0.25-17.5) years. The final diagnoses of 26 patients were as follows: immunodeficiency (n=6); hyper-IgE syndromes (n=4), DOCK8 deficiency + HES (idiopathic hypereosinophilic syndrome; n=1), and severe combined immunodeficiency (n=1), HES (n=3), idiopathic chronic eosinophilic pneumonia (ICEP; n=3), idiopathic pulmonary hemosiderosis (n=1), B cell lymphoma (n=1). In one child, an integrin α3 mutation + cytomegalovirus (CMV) pneumonia was detected. Congenital pneumonia was found in one patient, and parasitic infection in another. In two, eosinophilia was attributed to underlying asthma and atopy. In four, the underlying reasons could not be elucidated. Two children with HES and one with ICEP were lost to follow-up. There was no significant relationship between the peripheral eosinophil count at the time of diagnosis and the percentage of bronchoalveolar lavage eosinophils (BAL). Bronchoscopy contributed to the management of 14 (53.9%) patients. Bronchoscopy has potential diagnostic contribution in patients with UPE suspected of having pulmonary involvement. Numerous various underlying causes may be present in this patient group. There is no relation between peripheral eosinophil count and BAL eosinophil percentage.

UNRECOGNIZED PARASITIC INFECTION AS A CAUSE OF PERSISTENT EOSINOPHILIA IN AN INNER-CITY ALLERGY CLINIC POPULATION

<h3>Introduction</h3> Persistent peripheral blood eosinophilia (absolute eosinophil count (AEC)> 500 cells/mL) is frequently a manifestation of a serious medical problem. Nevertheless, previous studies have shown that patients with persistent eosinophilia are often not adequately evaluated for possible underlying causes. <h3>Methods</h3> Patients from an inner-city Allergy clinic from 2020-2022 with AEC>500 cells/mL at least on 2 occasions and no established cause were evaluated. <h3>Results</h3> A total of 82 patients were enrolled. Patients were predominantly female (72%), with mean age of 50 years (range 15-97), of Hispanic (42%) and African- American (32.5%) race. Hypereosinophilia (AEC>1500 cells/mL) was found in 17% (14/82) patients, with the highest AEC of 40,000 cells/mL. Co-morbid conditions included allergic rhinitis [(80.4% (66/82)], asthma [(53.6% (44/82)], nasal polyposis [(12% (10/82)], and eczema [(8.5% (7/82)]. Overall, 30% (24/75) of the study population tested positive for some parasitic infection: <i>T. canis</i> (25.3% (16/63)); <i>S. stercoralis</i> [10.9% (8/73), 6% (4/63) had both infections]; <i>B. hominis</i> (4% (1/23). One had <i>W. bancrofti</i> and one had <i>S. mansoni</i>. 18 of 24 patients received anti-parasite therapy. Post-treatment AEC was measured in 9 of the treated patients and eosinophilia resolved in all of them. 23% (12/52) of the study population had elevated IgG4(>86 mg/dL) but none had evidence of IgG4- related disease. 7% (4/56) of study population had elevated IL-5 levels (>3 pg/mL). 3 of these 4 patients had parasitic infections. <h3>Conclusion</h3> Parasitic infection is a common cause of unexplained persistent eosinophilia in inner-city patients. Role of elevated IL-5 in different causes of eosinophilia needs further investigation.

A SERIES OF GENETIC EVENTS: FIP1L1/PDGFR REARRANGEMENT LEADING TO EOSINOPHILIC MYOCARDITIS

A SERIES OF GENETIC EVENTS: FIP1L1/PDGFR REARRANGEMENT LEADING TO EOSINOPHILIC MYOCARDITIS

Dress Syndrome Without Cutaneous Manifestations

DRESS Syndrome without cutaneous manifestation is a rare drug hypersensitivity reaction to memantine. This paper presents a case of drug hypersensitivity reaction to a drug rarely associated with such reactions, followed by a reminder to maintain elevated suspicion for hypersensitivity reactions in unexplained eosinophilia.

Activating Dormant Strongyloidiasis Secondary to COVID-19 Treatment

The SARS-CoV-2 pandemic has grown into a major global concern with huge efforts to combat the spread. Exaggerated inflammatory response plays a major role in which was the rationale to use corticosteroids as a treatment option. However, multiple studies showed an association between of opportunistic and bacterial infections in patients under corticosteroid therapy. We report a case of a 76-year old patient diagnosed with COVID-19 pneumonia, treated with 10 days Dexamethasone and Remdesivir who presented with abdominal symptoms with eosinophilia. Biopsy and stool studies revealed strongyloides stercoralis larvae. The patient was treated with 2 doses of Ivermectin with significant clinical resolution. Clinician should have high clinical suspicion for Strongloydiasis in patients who have lived or visited Strongyloides stercoralis endemic areas and for patients with unexplained eosinophilia. Prompt treatment with Ivermectin is crucial for confirmed cases and should be also implemented empirical in high risk groups, where obtaining a diagnosis is unfeasible.

Hypereosinophilic\xa0syndrome presenting as coagulopathy

BackgroundHypereosinophilic syndrome (HES) is an extremely uncommon group of disorders. It rarely presents with coagulopathy without cardiac involvement.Case presentationA 33-year-old previously healthy male with no history of atopic disease presented with abdominal pain, hematochezia, peripheral eosinophilia as high as 10,000 eos/µL, right and left portal vein, mesenteric, and splenic vein thrombi with ischemic colitis resulting in hemicolectomy and small bowel resection. Despite an extensive workup for primary and secondary etiologies of hypereosinophilia by hematology/oncology, infectious disease, rheumatology and allergy/immunology, no other clear causes were identified, and the patient was diagnosed with idiopathic HES. His eosinophilia was successfully treated with high-dose oral corticosteroids (OCS) and subsequently transitioned to anti-IL-5-receptor therapy with benralizumab. He has continued this treatment for over a year with no recurrence of eosinophilia or thrombosis while on benralizumab.ConclusionIn patients with an unexplained coagulopathy and eosinophilia, eosinophilic disorders such as HES should be considered. Corticosteroid-sparing agents, such as benralizumab show promise for successfully treating these patients.

Activating dormant strongyloidiasis secondary to COVID-19 treatment

The SARS-CoV-2 pandemic has grown into a major global concern with huge efforts to combat the spread. Exaggerated inflammatory response plays a major role in which was the rationale to use corticosteroids to treat patients. However, multiple studies showed an association between opportunistic and bacterial infections with corticosteroid therapy. We report a case of a 76 year old patient diagnosed with COVID-19 treated with 10 days Dexamethasone and Remdesivir who presented with abdominal symptoms with eosinophilia. Biopsy and stool studies revealed Strongyloides stercoralis larvae. The patient was treated with 2 doses of Ivermectin with significant clinical resolution. Clinician should have high clinical suspicion for Strongloydiasis in patients who have lived or visited endemic areas and for patients with unexplained eosinophilia. Prompt treatment with Ivermectin is crucial for confirmed cases and high risk cases where obtaining a diagnosis is unfeasible.

Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review

BackgroundEosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy.Case presentationA 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease.ConclusionMontelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.

The causes of a peripheral blood eosinophilia in a secondary care setting.

A peripheral blood eosinophilia of greater than 1.0×109 /L is relatively unusual and offers a clue to the underlying diagnosis. In 2003, we established a specialist service to diagnose unexplained eosinophilia. To describe the causes of an eosinophilia in our service and the diagnostic algorithm we developed. Subjects were referred by physician colleagues across a range of specialties and undertook standard investigations following a semi-structured protocol. Data were extracted from a bespoke database. Three hundred and eighty two subjects were referred over a 17-year period. Average age was 54years and 183 (48%) of subjects were female, with 21 of 25 (84%) females in the idiopathic eosinophilic pneumonia group (p<0001), 22 of 30 (73%) females in the gastrointestinal disease group (p<.008), but 11 of 37 (30%) females in the eosinophilic granulomatosis with polyangiitis group (p<.04). A diagnosis was assigned after systematic evaluation using a pre-defined algorithm in 361 (94.5%) of cases. Fungal allergy (82 subjects: 21%), parasitic infection (61 subjects: 16%) and severe eosinophilic asthma (50 subjects: 13%) were the three commonest individual diagnoses. Hypereosinophilic syndrome (HES) disease including eosinophilic granulomatosis with polyangiitis (EGPA) accounted for 85 subjects (20%) of which seven subjects (2%) had myeloproliferative disease (M-HES). A high IgE was common, and 79 (91%) of subjects with complete data who had an IgE of ≥1000IU/L had fungal allergy or parasite infection. The serum tryptase was raised in 44 of 302 (14.5%) of individuals across all diagnostic groups, though none had mastocytosis. A diagnosis of an unexplained eosinophilia can usually be determined using as semi-structured algorithm. Parasitic infection and fungal allergy often with severe eosinophilic asthma were common causes, whereas HES, particularly myeloproliferative, disease was relatively rare.

Venous thrombosis and predictors of relapse in eosinophil-related diseases

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Hookworm infection in infants: a case report and review of literature

BackgroundHookworm infections (Necator americanus, Ancylostoma duodenale) are common in rural areas of tropical and subtropical countries. Human acquisition results from direct percutaneous invasion of infective larvae from contaminated soil.Overall, almost 472 million people in developing rural countries are infected. According to simulation models, hookworm disease has a global financial impact of over US$100 billion a year. Hookworm infection in newborn or infancy is rare, and most of the cases reported in literature are from endemic countries.Here, we describe the case of an infant with an Ancylostoma duodenale infection and review the literature currently available on this topic.Case presentationAn Italian 2-month-old infant presented with vomit and weight loss. Her blood exams showed anemia and eosinophilia and stool analysis resulted positive for hookworms’ eggs, identified as Ancylostoma duodenale with real time-PCR. Parasite research on parents’ stools resulted negative, and since the mother travelled to Vietnam and Thailand during pregnancy, we assumed a transplacental transmission of the infection. The patient was treated successfully with oral Mebendazole and discharged in good conditions.DiscussionHookworm helminthiasis is a major cause of morbidity in children in the tropics and subtropics, but rare in developed countries.Despite most of the patients is usually asymptomatic, children are highly exposed to negative sequelae such as malnutrition, retarded growth and impaired cognitive development. In infants and newborns, the mechanism of infection remains unclear. Although infrequent, vertical transmission of larvae can occur through breastfeeding and transplacentally. Hookworm infection should be taken into account in children with abdominal symptoms and unexplained persistent eosinophilia. The treatment of infants infected by hookworm has potential benefit, but further studies are needed to define the best clinical management of these cases.

A report of an unusual case of pediatric eosinophilia associated with platelet-derived growth factor receptor-beta rearrangement

AbstractEosinophilia is a common finding in the pediatric age group. While the majority of mild eosinophilia cases are benign and due to reactive causes, persistent hypereosinophilia is uncommon and requires prompt clinical evaluation because of the potential risk of end-organ damage associated with it. Given the broad differential diagnoses of eosinophilia, it is essential to have a systematic approach to the evaluation of unexplained eosinophilia in children. Here, we discuss the case of a 2-year-old child who presented with very high eosinophil counts. A systematic workup of the case helped us in arriving at a rare diagnosis of platelet-derived growth factor receptor-beta (PDGFRB)-rearranged clonal eosinophilia. Identification of such an entity is important as it has therapeutic implications, and early recognition helps in preventing associated end-organ damage by instituting appropriate therapy. Such cases of eosinophilia associated with platelet-derived growth factor receptor-alpha and PDGFRB rearrangement respond dramatically to imatinib.

EP44 Taking eosinophilia more seriously

Abstract Background Asymptomatic eosinophilia is common in migrants and travellers returning from the tropics, and helminth infection is the most common identifiable cause. Most helminth infections have a benign course, but some carry a risk of serious disease which is relevant to the rheumatologist as administration of immunosuppression can trigger severe reactions such as the potentially fatal hyper infection syndrome in strongyloidiasis. Helminth infections are of increasing relevance in an era of growing migration from endemic regions. A recent audit performed at a central London hospital in HIV outpatients found that of those patients with asymptomatic eosinophilia that were investigated, 28.6% had serological evidence of strongyloidiasis. Unexplained eosinophilia should be evaluated prior to starting immunosuppressive medications, especially in those who have lived in regions endemic for helminth infections. In 2010 the British Infection Society (BIS) published guidelines on the investigation of migrants and returning travellers with asymptomatic eosinophilia. We set out to establish how often our unit investigated unexplained eosinophilia prior to initiating immunosuppressive medication. Methods All patients attending rheumatology outpatients at our centre were screened and included if they had a recorded eosinophilia of ≥ 0.8 X109/L between December 2016 to December 2018. Patients were excluded if they did not have a sustained eosinophilia ≥0.8 X109/L &amp;gt; 1 year or if another documented diagnosis was recognised as the cause of eosinophilia. Investigation of asymptomatic eosinophilia was compared to the best practice set out in British Infection Society guideline. Results 109 patients fulfilled the inclusion criteria. 64 patients did not have a sustained eosinophilia &amp;gt; 1 year and 16 had an alternate diagnosis to explain eosinophilia and so were excluded. The remaining 29 patients were included. 13 patients were male and 16 female. 16 (55%) had a diagnosis of rheumatoid arthritis. 19 (66%) had an eosinophil count &amp;gt; 1 X109/L and 7 (24%) &amp;gt; 2 X109/L. Despite this, eosinophilia was only noted in documentation for 4 (14%) patients. Five (17%) patients had a travel history documented and 4 of them had travelled to the tropics. 3 (10%) patients were investigated for eosinophilia and only 1 (3%) was investigated fully according to the BIS guideline. 14 (48%) patients were on bDMARDs and a further 6 (21%) were on cDMARDs. Of the 14 (48%) on bDMARDS, 7 had ethnic origin in the tropics. Median eosinophil count was 1.2 x109/L. One had travel history taken. All had a negative HIV test. None of the patients on biological therapy had investigations for eosinophilia. Conclusion This study confirms the local lack of awareness of eosinophilia. Most patients with unexplained eosinophilia were not identified or investigated, even prior to administration of immunosuppressive medication. With a growing migrant population, the likelihood of serious consequences of ignoring eosinophilia are rising. Disclosures: Z. Rutter-Locher: None. J. Galloway: None. B. Menon: None. A. Goodman: None.

Painless lymphadenopathy, eosinophilia and nephrotic syndrome: a diagnostic challenge in an era of increased migration.

Kimura’s disease is a rare chronic inflammatory condition of unknown cause that most frequently affects Asian adults. It is characterized by painless lymphadenopathy in the head and neck region and eosinophilia, often associated with nephrotic syndrome. Α young Asian male presented to our Department with œdema at the lower limbs and scrotum, retroauricular masses, eosinophilia and proteinuria. Diagnosis was reached by a combination of the clinical picture, the patient’s origin and a histological examination, which revealed well-developed lymph follicles with increased numbers of eosinophils and fibrosis, a finding typical of Kimura’s disease. In case of a young Asian male who is otherwise healthy, but presents head/neck masses and/or unexplained eosinophilia associated with nephrotic syndrome, consider Kimura’s disease in the differential diagnosis.

JAK2ex13InDel drives oncogenic transformation and is associated with chronic eosinophilic leukemia and polycythemia vera

AbstractThe V617F mutation in the JH2 domain of Janus kinase 2 (JAK2) is an oncogenic driver in several myeloproliferative neoplasms (MPNs), including essential thrombocythemia, myelofibrosis, and polycythemia vera (PV). Other mutations in JAK2 have been identified in MPNs, most notably exon 12 mutations in PV. Here, we describe a novel recurrent mutation characterized by a common 4-amino-acid deletion and variable 1-amino-acid insertion (Leu583-Ala586DelInsSer/Gln/Pro) within the JH2 domain of JAK2. All 4 affected patients had eosinophilia, and both patients with Leu583-Ala586DelInsSer fulfilled diagnostic criteria of both PV and chronic eosinophilic leukemia (CEL). Computational and functional studies revealed that Leu583-Ala586DelInsSer (herein referred to as JAK2ex13InDel) deregulates JAK2 through a mechanism similar to JAK2V617F, activates signal transducer and activator of transcription 5 and extracellular signal-regulated kinase, and transforms parental Ba/F3 cells to growth factor independence. In contrast to JAK2V617F, JAK2ex13InDel does not require an exogenous homodimeric type 1 cytokine receptor to transform Ba/F3 cells and is capable of activating β common chain family cytokine receptor (interleukin-3 receptor [IL-3R], IL-5R, and granulocyte-macrophage colony stimulating factor receptor) signaling in the absence of ligand, with the maximum effect observed for IL-5R, consistent with the clinical phenotype of eosinophilia. Recognizing this new PV/CEL-overlap MPN has significant clinical implications, as both PV and CEL patients are at high risk for thrombosis, and concomitant cytoreduction of red cells, neutrophils, and eosinophils may be required for prevention of thromboembolic events. Targeted next-generation sequencing for genes recurrently mutated in myeloid malignancies in patients with unexplained eosinophilia may reveal additional cases of Leu583-Ala586DelInsSer/Gln/Pro, allowing for complete characterization of this unique MPN.