Hypereosinophilic syndrome has the potential to disrupt every organ in the body and, although it more frequently presents insidiously, sudden and acute deterioration is not uncommon and affects mostly the nervous and cardiovascular system. HES can also be discovered incidentally in up to 12% of patients [11].

Cardiac damage is the major cause of death and pathogenesis generally proceeds along three stages. The first stage is characterized by acute necrosis; clinical manifestations are usually absent. The second stage leads to the formation of thrombi and, in the final stage, there is widespread endomyocardial fibrosis. Patients usually complain of chest pain, dyspnea and orthopnea.

HES can also result in widespread hematologic complications. Anemia associated with the disease can manifest in fatigue and other non-specific symptoms. Thrombosis can result either from cardiac disease or hypercoagulability and targets especially the nervous system. Splenomegaly occurs in 40% of patients and should be suspected in patients complaining of left upper quadrant pain. 

Neurologic involvement manifests with embolic or thrombotic events, which are frequently the initial presenting symptoms of HES. In addition, up to 50% of patients report peripheral neuropathy. The latter has a variable expression and can be symmetric or asymmetric, sensory, pure motor or mixed. 

Lung involvement results from infiltration of eosinophils along the base and periphery and manifests with a nonproductive, chronic and persistent cough. Patients may also develop pleural effusions, secondary to congestive heart failure and can result in dyspnoic symptoms. Other common respiratory complications include angioedema and rhinitis.

Joint and skin involvement are common and patients frequently complain of non-specific skin changes, dermatographism, angioedema, arthralgia and myalgia. Raynaud's phenomenon can also occur, but is uncommon.

Gastrointestinal involvement manifests principally with diarrhea, nausea and abdominal pain. Thrombosis seldom results in small bowel necrosis and some patients develop sclerosing cholangitis.

Finally, patients can develop symptoms that are not organ-specific, such as fever, night sweats, anorexia and weight loss. The latter two seem to occur mostly with cardiac disease although reports are variable.

• Splenomegaly

  We present a 24-year-old-male with left lower quadrant abdominal pain, elevated eosinophil counts and splenomegaly. Molecular analysis was positive for FIP1LI -PDGFRA gene compatible with chronic eosinophilic leukemia. [ncbi.nlm.nih.gov]

• Fever

  […] delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue, nausea, abdominal pain, diarrhea, pruritic rash, fever [accessanesthesiology.mhmedical.com]

  In adults, the frequencies of symptoms found on presentation are: fatigue (26%), cough (24%), dyspnea (16%), rash (12%), and fever (12%). Fever (58.8%), arthralgias (23%), and rash (23.5%) were more common in pediatric cases. [pediatrics.aappublications.org]

  She was admitted in 2008 with fever, headache, confusion and visual loss. Diagnostic workup uncovered an eosinophilia of 3.1×10⁹/L and major ECG abnormalities. [ncbi.nlm.nih.gov]

• Fatigue

  Four years later she re-presented with headache, fatigue and an eosinophilia of 13.4×10⁹/L. This occurred 3 months after cessation of immunosuppression and within 12 months of total colectomy for fulminant ulcerative colitis. [ncbi.nlm.nih.gov]

  Hypereosinophilic syndrome usually presents with fever, weight loss, fatigue, and rash. A rash is present in over 50% of patients, but is non-specific in appearance. Most commonly, red swollen itchy nodules (lumps) have been described. [dermnetnz.org]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019 [patientslikeme.com]

  I have many skin allergies and other symptoms ( severe sinus, been in sugery 2 times) fatigue and short breathing. [inspire.com]

  It usually presents with fever, weight loss, fatigue, and rash. An enlarged liver and spleen and liver is often present. The lungs, kidneys, heart, and nervous system can also be affected. [checkorphan.org]

• Anemia

  Central nervous system (CNS) dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue [accessanesthesiology.mhmedical.com]

  Patients often have Splenomegaly Thrombocytopenia Anemia Elevated serum vitamin B12 levels Hypogranular or vacuolated eosinophils Myelofibrosis Patients with the myeloproliferative subtype often develop endomyocardial fibrosis and may rarely develop acute [merckmanuals.com]

  Refractory neutropenia Refractory thrombocytopenia Refractory anemia with ring sideroblasts Refractory cytopenia with multilineage dysplasia Refractory anemia with excess blasts (RAEB) RAEB-1 RAEB-2 Myelodysplastic syndrome with isolated del(5q) Myelodysplastic [hema-research.or.kr]

• Weight Loss

  Central nervous system (CNS) dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue [accessanesthesiology.mhmedical.com]

  Case Presentation: A 41‐year‐old man with no medical history presented for a second opinion for chest pain, cough, fevers, and an 80‐pound weight loss in 2 months. Previous evaluation revealed peripheral eosinophilia, pericarditis, and pneumonia. [shmabstracts.com]

  Gastrointestinal manifestations include eosinophilic gastritis, enteritis, and/or colitis causing weight loss, abdominal pain, vomiting, and/or severe diarrhea [1]. [hindawi.com]

  Hypereosinophilic syndrome usually presents with fever, weight loss, fatigue, and rash. A rash is present in over 50% of patients, but is non-specific in appearance. Most commonly, red swollen itchy nodules (lumps) have been described. [dermnetnz.org]

  Finally, patients can develop symptoms that are not organ-specific, such as fever, night sweats, anorexia and weight loss. The latter two seem to occur mostly with cardiac disease although reports are variable. [symptoma.com]

• Congestive Heart Failure

  The most serious complication of HES is cardiac involvement (myocardial fibrosis and congestive heart failure); however, hypereosinophilia alone is insufficient to cause cardiac damage. Leukocytosis with eosinophilia. [accessanesthesiology.mhmedical.com]

  Anticoagulant therapy should also be administered as thrombosis and embolous are common complications Symptomatic therapies to treat secondary problems such as congestive heart failure should be treated appropriately Antihistamines may be used to control [healthengine.com.au]

  The five-year survival rate is 80% with congestive heart failure being the most common cause of death. Leukaemic change is a risk in prolonged disease. [patient.info]

  The most dangerous complication involves the heart and involves myocardial fibrosis, congestive heart failure and, ultimately, death. [symptoma.com]

• Cough

  A nonproductive cough, night sweats, and a diffuse pruritic, papular rash developed. His initial absolute eosinophil count was 1890/mm3 (reference: <400/mm3), which increased to 52 000/mm3. [pediatrics.aappublications.org]

  A 43year old food vendor referred to the Haematology Department, University College Hospital, Ibadan on account of a 6-week history of cough productive of mucoid, brownish, foul smelling sputum with associated breathlessness, high grade intermittent fever [ncbi.nlm.nih.gov]

  Case Presentation: A 41‐year‐old man with no medical history presented for a second opinion for chest pain, cough, fevers, and an 80‐pound weight loss in 2 months. Previous evaluation revealed peripheral eosinophilia, pericarditis, and pneumonia. [shmabstracts.com]

• Pneumonia

  The changing pattern of heroin use to inhalation/sniffing leading to an increasing abuse may cause a rise in the prevalence of Heroin induced eosinophilia, as it has been reported in a case of eosinophilic pneumonia associated with heroin inhalation. [ncbi.nlm.nih.gov]

  Previous evaluation revealed peripheral eosinophilia, pericarditis, and pneumonia. On presentation to our facility, his WBC count was 28,000/μL with an eosinophil count of 12,600 cells/μL. [shmabstracts.com]

  Löffler's syndrome ( ICD-10-CM Diagnosis Code J82 Pulmonary eosinophilia, not elsewhere classified 2016 2017 2018 2019 Billable/Specific Code Applicable To Allergic pneumonia Eosinophilic asthma Eosinophilic pneumonia Löffler's pneumonia Tropical (pulmonary [icd10data.com]

  #/EHS# z #. decembra # o spoločnej organizácii trhu s cukrom, najmä na jeho článok # ods en We think it might be eosinophilic pneumonia. sk Z toho istého dôvodu by mal producent, ktorý je členom nejakej medziodvetvovej organizácie a ktorý sa zaviaže dodávať [sk.glosbe.com]

• Dyspnea

  During the hospital stay, the dyspnea worsening and a new thorax CT was performed, which revealed a 7.0 cm diameter cavity in the right hemithorax. [scielo.br]

  The pulmonary infiltration with eosinophilia (PIE) syndrome should also be kept as a differential diagnosis, especially when there is a history of recurrent wheezing or dyspnea. [indianpediatrics.net]

  Common manifestations include brain or lung hypoxia (eg, encephalopathy, dyspnea or respiratory failure). [merckmanuals.com]

  In adults, the frequencies of symptoms found on presentation are: fatigue (26%), cough (24%), dyspnea (16%), rash (12%), and fever (12%). Fever (58.8%), arthralgias (23%), and rash (23.5%) were more common in pediatric cases. [pediatrics.aappublications.org]

• Pleural Effusion

  Cardiac - cardiomyopathy, valve abnormalities, pericardial effusion, thromboembolic disease. Respiratory - pneumonitis, pulmonary emboli, pleural effusion and eosinophilic infiltrates. Skin - dermatitis, urticaria, papular rashes. [patient.info]

  The subsequent diagnosis of HES explained the multiorgan involvement as manifested by the stroke, heart valve, vegetation and pleural effusion. The eosinophilia proved very sensitive to steroids and she tolerated cyclosporin well. [academic.oup.com]

  effusions and/or fibrosis,[6] and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.[6] A proportion of patients have a mutation involving the PDGFRA and FIP1L1 genes on the fourth chromosome, leading to [en.wikipedia.org]

• Rhinitis

  rhinitis with eosinophilia Peritoneal eosinophilia Secondary eosinophilia Traumatic ulcerative granuloma of tongue with stromal eosinophilia Clinical Information Abnormal increase of eosinophils in the blood, tissues or organs Disordered formation of [icd9data.com]

  Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. [ingentaconnect.com]

  […] three months;prednisolone 0.5 mg/kg/day for six months 5 Small Particle Inhaled Steroids in Refractory Steroid-responsive Asthma Completed NCT01171365 Phase 4 Ciclesonide;Placebo 6 Efficacy and Safety of Lectranal® in Treatment of Seasonal Allergic Rhinitis [malacards.org]

  Non-allergic nasal rhinitis with eosinophilia Clinical Information Abnormal increase of eosinophils in the blood, tissues or organs. [icd10data.com]

  Allergic Disorders • Allergic rhinitis Nasal eosinophilia more sensitive than blood eosinophilia • Chronic sinusitis In adult, chronic sinusitis correlates with blood eosinophilia and indicated extensive disease • Asthma blood eosinophilia and sputum [slideshare.net]

• Abdominal Pain

  We present a 24-year-old-male with left lower quadrant abdominal pain, elevated eosinophil counts and splenomegaly. Molecular analysis was positive for FIP1LI -PDGFRA gene compatible with chronic eosinophilic leukemia. [ncbi.nlm.nih.gov]

  Generalised symptoms - fatigue, aches and pains, fever, night sweats and pruritus. Diarrhoea is common, as are abdominal pain and nausea. [patient.info]

  Gastrointestinal manifestations include eosinophilic gastritis, enteritis, and/or colitis causing weight loss, abdominal pain, vomiting, and/or severe diarrhea [1]. [hindawi.com]

• Diarrhea

  Results: A previously healthy 52 year old woman experienced a 10 day history of insidiously progressive confusion with preceding GI upset and diarrhea. On examination, she was afebrile with normal vital signs and a normal neurological examination. [neurology.org]

  Gastrointestinal manifestations include eosinophilic gastritis, enteritis, and/or colitis causing weight loss, abdominal pain, vomiting, and/or severe diarrhea [1]. [hindawi.com]

  […] dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue, nausea, abdominal pain, diarrhea [accessanesthesiology.mhmedical.com]

  The case report involved a 15-year-old male who presented with abdominal pain, diarrhea, and a 10-lb weight loss. Colonoscopy revealed colitis. A nonproductive cough, night sweats, and a diffuse pruritic, papular rash developed. [pediatrics.aappublications.org]

  […] dermatological involvement (urticaria, eczema, angioedema, pruriginous papules, nodules, erythroderma) in more than 50% of cases, followed by involvement of lungs (cough, breathlessness and wheezing) and digestive tract (nausea, vomiting, abdominal pain, diarrhea [orpha.net]

• Nausea

  Alcohol intolerance with abdominal pain, flushing, and nausea. Organ involvement in HES [ 6 ] This can be manifold and the following are some examples: Blood - thrombocytopenia, hypercoagulability. [patient.info]

  Central nervous system (CNS) dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue, nausea [accessanesthesiology.mhmedical.com]

  […] among patients, and consists of dermatological involvement (urticaria, eczema, angioedema, pruriginous papules, nodules, erythroderma) in more than 50% of cases, followed by involvement of lungs (cough, breathlessness and wheezing) and digestive tract (nausea [orpha.net]

• Vomiting

  She also had asymptomatic severe hypokalaemia (1.9mmol/l) likely due to vomiting and reduced dietary intake. [ncbi.nlm.nih.gov]

  Gastrointestinal manifestations include eosinophilic gastritis, enteritis, and/or colitis causing weight loss, abdominal pain, vomiting, and/or severe diarrhea [1]. [hindawi.com]

  […] patients, and consists of dermatological involvement (urticaria, eczema, angioedema, pruriginous papules, nodules, erythroderma) in more than 50% of cases, followed by involvement of lungs (cough, breathlessness and wheezing) and digestive tract (nausea, vomiting [orpha.net]

• Abdominal Cramps

  This past year I was in and out of the hospital several times with pleuritis, pheumonia, food allergies, severe abdominal cramps, veryyy low pressure and cardiac issues (disautonomy) and tachycardia. [inspire.com]

  cramps Diarrhea Nausea Immunologic ≈ 40% Circulating immune complexes with serum sickness Elevated levels of immunoglobulins (especially IgE) Occasionally, patients with very severe eosinophilia (eg, eosinophil counts of > 100,000/mcL [> 100 × 109/L] [merckmanuals.com]

  cramps 3 3 (30) 0 Elevated creatinine 3 3 (30) 0 Pain in hip 3 3 (30) 1 1 (10) Upper respiratory infection 3 3 (30) 1 1 (10) Fever 4 2 (20) 0 Decreased appetite 3 2 (20) 0 Hyponatremia 3 2 (20) 0 Neutrophilia 2 2 (20) 4 3 (30) Hypophosphatemia 2 2 (20 [nejm.org]

• Thrombosis

  A similar case of HES with thrombocytopenia and thrombosis was reported by Sherer and associates. 10 However, their patient had venous thrombosis instead of arterial, and the thrombocytopenia was not as severe (69 × 10 3 /µL). [hematologyandoncology.net]

  The clinical data of a patient with extensive thrombosis in his portal venous system (superior mesenteric, splenic, hepatic, and portal veins), renal artery thrombosis, and mesenteric thrombosis caused by HES with secondary gastrointestinal bleeding and [ncbi.nlm.nih.gov]

  Since in HES patients about half (45%) of thrombosis were arterial,[29] combination of anticoagulants with an antiplatelet agent may still have a role in preventing the recurrence of thrombosis in HES. [journals.lww.com]

• Chest Pain

  We report a 46-year-old female who came to hospital with atypical chest pains and a known history of eosinophilia. After excluding other possible causes of eosinophilia, she underwent further cardiac investigations. [ncbi.nlm.nih.gov]

  Case Presentation: A 41‐year‐old man with no medical history presented for a second opinion for chest pain, cough, fevers, and an 80‐pound weight loss in 2 months. Previous evaluation revealed peripheral eosinophilia, pericarditis, and pneumonia. [shmabstracts.com]

  In the present case, the patient presented with chest pain initially suspected to be having an ACS. [heartindia.net]

  Other symptoms depend on which organ is involved and extent of involvement; for example: Cardiac - chest pain and breathlessness. Respiratory - shortness of breath, and dry cough. Alcohol intolerance with abdominal pain, flushing, and nausea. [patient.info]

  Chest pain, tiredness, general sickness, awful pain in my abdomen, joint pain and hot bruises all over my body, and I couldn’t even walk anymore. I had lost several pounds and now I could barely eat…. my body started to reject all food. [globalgenes.org]

• Hepatosplenomegaly

  nausea, abdominal pain, diarrhea, pruritic rash, fever, night sweats, hepatosplenomegaly, peripheral neuritis, and venous thrombosis. [accessanesthesiology.mhmedical.com]

  Abstract This report concerns three individuals with a similar illness characterized by the following: a striking leukocytosis due primarily to increased numbers of mature eosinophils; cardiac or pulmonary symptoms, or both; and hepatosplenomegaly. [annals.org]

  Among 6 children with idiopathic HES; 2 had pulmonary involvement; 1 had cardiac and pulmonary involvement and splenomegaly; 1 had cardiac involvement and hepatosplenomegaly; 1 had cardiac and central nervous system involvement; and 1 had skin involvement [ncbi.nlm.nih.gov]

• Hepatomegaly

  Idiopathic hypereosinophilic syndrome in a child with fever and hepatomegaly MORINAGA Shingo, TAKAKI Kazutaka, SADA Akiko, MATSUI Toshimitsu Rinsho Ketsueki 53(1) 83-86 2012 Idiopathic hypereosinophilic syndrome (IHES) in children is a rare disorder. [researchmap.jp]

  Gastrointestinal findings are as follows: Hepatomegaly may occur with chronic active hepatitis due to hypereosinophilic syndrome Hepatomegaly may also occur with Budd-Chiari syndrome, which may infrequently be a thrombotic complication of hypereosinophilic [emedicine.medscape.com]

  In NIH series_ hematological involvement was seen in all, pulmonary in 40%, skin in 56%, neurological in 64%, splenomegaly in 45%, hepatomegaly in 35%, cardiovascular in 54% and ocular involvement in 18%(1,8). [indianpediatrics.net]

  […] system Neurologic abnormalities Neurological abnormality [ more ] 0000707 Anemia Low number of red blood cells or hemoglobin 0001903 Autosomal dominant inheritance 0000006 Endocardial fibrosis 0006685 Eosinophilia High blood eosinophil count 0001880 Hepatomegaly [rarediseases.info.nih.gov]

• Blurred Vision

  A 64-year-old man was brought to the emergency department because of sudden-onset blurred vision in both eyes and diplopia, as well as a frontal headache that had begun earlier that day. [doi.org]

  vision Gastrointestinal (GI) tract: weight loss, abdominal pain, vomiting, diarrhea Diagnosis As mentioned above, eosinophils are one of the five types of white blood cells (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). [verywellhealth.com]

  vision and slurred speech have been reported Peripheral neuropathies account for about 50% of all neurologic symptoms in hypereosinophilic syndrome; their etiology is poorly understood, but they may present as symmetric or asymmetric sensory changes, [emedicine.medscape.com]

• Myalgia

  Eosinophilia-Myalgia Syndrome: Multisystemic, chronic, autoimmune disease caused by ingestion of impure l-tryptophan (usually ingested as an amino acid dietary supplement). [accessanesthesiology.mhmedical.com]

  Constitutional symptoms of fever, myalgia and fatigue may occur. Other common complications include central or peripheral nervous system involvement, hepato- and/or splenomegaly, and coagulation disorders. [orpha.net]

  […] reaction 호산구백혈병모양반응 eosinophilic meningoencephalitis 호산구수막뇌염 eosinophilic cellulitis 호산구연조직염 eosinophilic granuloma 호산구육아종 eosinophil stimulation promotor 호산구자극촉진제 eosinophilic pustular folliculitis 호산구잔고름집털집염 eosinophilotactic 호산구주성-, 호산구쏠림- eosinophilia myalgia [kmle.co.kr]

  Manifestations included rash, pruritus, headache, and myalgia. Systemic nonallergic reactions were reported by 2% of subjects who received Nucala and 3% of subjects in the placebo group. Manifestations included rash, flushing, and myalgia. [gsk.com]

• Arthralgia

  Fever (58.8%), arthralgias (23%), and rash (23.5%) were more common in pediatric cases. As with adults, involvement of the cardiovascular system is the major source of morbidity and mortality. [pediatrics.aappublications.org]

  One year after remission she presented malar rash, hair loss, arthralgias, conjuntival redness, dyspnea and thoracic oppression. [ncbi.nlm.nih.gov]

  Joint and skin involvement are common and patients frequently complain of non-specific skin changes, dermatographism, angioedema, arthralgia and myalgia. Raynaud's phenomenon can also occur, but is uncommon. [symptoma.com]

  CHF) Less frequently, pulmonary fibrosis occurs after prolonged disease and often accompanies cardiac fibrosis Bronchospasm and asthmatic symptoms are infrequent Rhinitis is sometimes a presenting symptom Rheumatologic manifestations are as follows: Arthralgias [emedicine.medscape.com]

• Joint Effusion

  […] may also be encountered Angioedema is often a prominent feature associated with pulmonary involvement Rheumatologic findings are as follows: Large joint effusions can occur Digital necrosis is rare but sometimes observed with associated Raynaud phenomenon [emedicine.medscape.com]

• Pruritus

  Pruritus is a frequent occurrence in dermatology, and investigation is often unrevealing. [ncbi.nlm.nih.gov]

  Major symptoms are fatigue, myalgia, cough, breathlessness, sweating, and pruritus. [4] Mucocutaneous manifestations include the following: Common manifestations Pruritus Urticaria Dermatographism Angioedema Erythematous papules, plaques, and nodules [e-ijd.org]

• Angioedema

  Skin and Subcutaneous tissue • Eosinophilic panniculitis - associated with leukocytoclastic vasculitis and erythema nodosum • Angioedema with eosinophilia - recurrent episodes of angioedema, urticaria, pruritis, fever, weight gain, elevated IgM (Gleich [slideshare.net]

  Other hypereosinophilic syndrome variants include chronic eosinophilic leukemia, Gleich syndrome (cyclical eosinophilia and angioedema), familial hypereosinophilic syndrome mapped to 5q 31-33, and other organ-specific syndromes. [merckmanuals.com]

  […] increased serum tryptase, and positive mast cell abnormalities) Familial HES: AD asymptomatic eosinophilia present at birth Benign HES: HE without end-organ damage Complex HES: multisystem organ involvement Episodic HES: Periodic rise in IL-5 leads to angioedema [unboundmedicine.com]

• Dermatitis

  Mepolizumab (trade name Nucala) is a humanized monoclonal antibody that recognizes interleukin-5 (IL-5).Mepolizumab has been investigated or is under investigation for the treatment of severe eosinophilic asthma, atopic dermatitis, hypereosinophilic syndrome [dbpedia.org]

  DISCUSSION WS, or eosinophilic cellulitis, was first described in 1971 by Wells 3 as a recurrent granulomatous dermatitis with eosinophilia. [ncbi.nlm.nih.gov]

  A skin biopsy showed acute neutrophilic folliculitis with perivascular dermatitis with eosinophils. Bone marrow biopsy demonstrated a hypercellular marrow with predominantly eosinophils, which is consistent with idiopathic HES. Methods. [pediatrics.aappublications.org]

  Skin - dermatitis, urticaria, papular rashes. Ear, nose and throat - sinusitis. Central nervous system - acute cerebrovascular event and peripheral neuropathy. [patient.info]

• Urticaria

  Prominent skin findings include erythroderma, plaques, and/or urticaria. [unboundmedicine.com]

  It can also resemble urticaria (hives). An enlarged liver and spleen is often present indicating liver and spleen involvement. The lungs, kidneys, heart and nervous system can be affected. [dermnetnz.org]

  These manifestations include:Skin rashes, for example, urticaria or angioedema, Dizziness, Memory misfortune or disarray, Cough, Shortness of inhale, Fatigue, Fever, Mouth wounds. [omicsonline.org]

  Clinical description Target-organ damage mediated by eosinophils is highly variable among patients, and consists of dermatological involvement (urticaria, eczema, angioedema, pruriginous papules, nodules, erythroderma) in more than 50% of cases, followed [orpha.net]

• Night Sweats

  Finally, patients can develop symptoms that are not organ-specific, such as fever, night sweats, anorexia and weight loss. The latter two seem to occur mostly with cardiac disease although reports are variable. [symptoma.com]

  sweats, hepatosplenomegaly, peripheral neuritis, and venous thrombosis. [accessanesthesiology.mhmedical.com]

  A nonproductive cough, night sweats, and a diffuse pruritic, papular rash developed. His initial absolute eosinophil count was 1890/mm3 (reference: <400/mm3), which increased to 52 000/mm3. [pediatrics.aappublications.org]

  Generalised symptoms - fatigue, aches and pains, fever, night sweats and pruritus. Diarrhoea is common, as are abdominal pain and nausea. [patient.info]

• Stroke

  Conclusions: Hypereosinophilic syndromes can be a rare cause of stroke and should be considered especially in those with undetermined stroke mechanisms. [neurology.org]

  KEYWORDS: Hypereosinophilic syndrome; Neuro-rehabilitation; Stroke [ncbi.nlm.nih.gov]

  Our patient had mild to moderate activity of joint disease and a moderate increase in eosinophil count initially until she developed the stroke. [academic.oup.com]

• Peripheral Neuropathy

  A 36-year-old male with no comorbidities presented progressive erythroderma, pruritus, peripheral neuropathy, and eosinophilia in the previous seven months. No mutations were found in FIP1L1/PDGFRA. [ncbi.nlm.nih.gov]

  Neurological - acute cerebrovascular accident, confusion, ataxia, peripheral neuropathy. Eyes - episcleritis, retinal thrombi. [patient.info]

  Neurologic manifestations are relatively rare in these conditions however encephalopathy, strokes and peripheral neuropathy can occur. [neurology.org]

• Vertigo

  Nervous system - vertigo, paresthesia, speech impairment, and visual disturbances. Heart - congestive heart failure, cardiomyopathy, pericardial effusion, and myocarditis. Blood - deep venous thrombosis, and anemia. [rarediseases.info.nih.gov]

• Paresthesia

  Nervous system - vertigo, paresthesia, speech impairment, and visual disturbances. Heart - congestive heart failure, cardiomyopathy, pericardial effusion, and myocarditis. Blood - deep venous thrombosis, and anemia. [rarediseases.info.nih.gov]

• Dysesthesia

  […] cutaneous diseases Arne Kanig and Rudolf Happle Ichthyoses erythrokeratodermas and related disorders Keratodermas Kro Dariers disease and HaileyHailey disease Daniel Hohl Theodora Mauro and leanPhilippe Gorog Mosaicism and linear lesions Pruritus and dysesthesia [books.google.com]

  Serious adverse events in the placebo group were clinical flares of the hypereosinophilic syndrome, pneumonia, dysesthesia, eosinophilia, nephrotic syndrome, osteonecrosis, and polyneuropathy. [doi.org]

The workup of hypereosinophilic syndrome is broad and extensive, given the range of organs and systems affected. Workup starts with hematologic studies, including a complete blood count, a peripheral smear, a bone marrow aspiration and a biopsy. Leukocytosis above 90,000 cells per microliter is a bad prognostic indication. The peripheral blood smear will generally show mature eosinophils with rare cell precursors, in addition to hypogranularity, hypergranularity and hypersegmentation. Usually, eosinophils with hypogranularity and vacuoles are more common in cardiac disease [12]. Signs of myleoproliferative disorder include leukocyte precursor anemia, thrombocytopenia or thrombocytosis, in addition to tear drops and nucleated red blood cells. 

Serum tryptase levels need to be assessed and elevated levels generally indicate either FIP1LI HES or systemic mastocytosis with chronic eosinophilic leukemia (SM-CEL). Genetic studies can also be done to detect FIP1LI-PDGFRA and C-KIT mutations and help in determining sensitivity to imatinib.

Assessment of organ damage is conducted with computed tomographhy (CT) of the chest, abdomen and pelvis, electrocardiography (ECG), echocardiography and pulmonary function tests. Elevation of troponin levels can signal the presence of cardiomyopathy and a risk of cardiogenic shock with the initiation of imatinib therapy. 

• Pulmonary Infiltrate

  Central nervous system (CNS) dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue [accessanesthesiology.mhmedical.com]

  […] connective tissue disorders ( M30-M36 ) pulmonary infiltrate NOS ( R91.8 ) J82 ) pulmonary eosinophilia ( ICD-10-CM Diagnosis Code J82 Pulmonary eosinophilia, not elsewhere classified 2016 2017 2018 2019 Billable/Specific Code Applicable To Allergic [icd10data.com]

  (itraconazole) EGPA 3 phase : Asthma, Tissue eosinophilia, Vasculitis Diagnostic criteria - Asthma - Peripheral eosinophilia (10% 이상) - Mononeuropathy or polyneuropathy - Nonfixed pulmonary infiltrates - Paranasal sinus abnormality - Biopsy containing [sondoctor.co.kr]

  The pulmonary infiltration with eosinophilia (PIE) syndrome should also be kept as a differential diagnosis, especially when there is a history of recurrent wheezing or dyspnea. [indianpediatrics.net]

  […] cardiomyopathy or mitral or tricuspid regurgitation with cough, dyspnea, heart failure, arrhythmias, endomyocardial disease, pulmonary infiltrates, and pleural effusions Dermatologic > 50% Angioedema Dermatographism Pruritus Rashes (including eczema [merckmanuals.com]

• Neutrophilia

  Blood studies: Eosinophilia (high eosinophil count) is present (more than 1500 cells per microlitre) Neutrophilia may or may not be present ESR (erythrocyte sedimentation rate) is elevated but can be normal Leukocyte alkaline phosphatase levels may be [healthengine.com.au]

  Investigations [ 3, 6 ] FBC - eosinophils >1.5 x 10 9 /L (0.5 x 10 9 /L under the new definition); neutrophilia and anaemia are also common. Platelet counts can be high or low. [patient.info]

  […] prominent eosinophilia AND Presence of a FIP1L1-PDGFRA fusion geneb Diagnostic criteria of MPN associated with ETV6-PDGFRB fusion gene or other rearrangement of PDGFRB A myeloproliferative neoplasm, often with prominent eosinophilia and sometimes with neutrophilia [hema-research.or.kr]

  Romanian Review of Laboratory Medicine 21 (1), 59-65, 2013 1 2013 Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms C Mambet, O Babosova, JP Defour, E Leroy, L Necula, O Stanca, A Tatic [scholar.google.com]

• Thrombocytosis

  […] associated hematological non-mast cell lineage disease (SM-AHNMD) Code Also, if applicable, any associated hematological non-mast cell lineage disease, such as: acute myeloid leukemia ( C92.6-, C92.A- ) chronic myelomonocytic leukemia ( C93.1- ) essential thrombocytosis [icd10data.com]

  Signs of myleoproliferative disorder include leukocyte precursor anemia, thrombocytopenia or thrombocytosis, in addition to tear drops and nucleated red blood cells. [symptoma.com]

  Thrombocytopenia or thrombocytosis are noted in approximately 31% and 16% of HES cases, respectively. 3 Severe thrombocytopenia, as in our patient, is very infrequent, and appears to correlate with disease severity and treatment refractoriness. 3 Approximately [hematologyandoncology.net]

  […] spirogramスパイログラム、呼吸曲線、肺活量曲線 status asthmaticus喘息発作重積状態 steroidステロイド stridor喘鳴 synovium滑膜 systemic lupus erythematosus (SLE）全身性エリテマトーデス、全身性紅斑性狼瘡 systemic steroid全身性ステロイド薬 t Takayasu　disease高安病［症候群］ telangiectasia毛細［血］管拡張、末梢血管拡張 temporal arteritis側頭動脈炎 thrombocytosis [tokyo-med.ac.jp]

  Myelodysplastic syndrome, unclassifiable MDS/MPN Chronic myelomonocytic leukemia CMML-1 CMML-2 Atypical chronic myeloid leukemia, BCR-ABL1 negative Juvenile myelomonocytic leukemia MDS/MPN, unclassifiable Refractory anemia with ring sideroblasts and thrombocytosis [hema-research.or.kr]

• Eosinophils Increased

  However, abnormal CD3-CD4+ T cell clones remained even when the eosinophil count recovered to normal levels. An elevated IL-8 level was observed only when eosinophils increased. [ncbi.nlm.nih.gov]

  Bone marrow biopsy was performed, revealing 21.3% eosinophils and immature eosinophil precursors. Marrow blasts were mildly increased, accounting for 8% of the bone marrow differential count. [austinpublishinggroup.com]

  The increased number of eosinophils can damage the heart, lungs, liver, skin, and nervous system. [msdmanuals.com]

• Pleural Effusion

  Cardiac - cardiomyopathy, valve abnormalities, pericardial effusion, thromboembolic disease. Respiratory - pneumonitis, pulmonary emboli, pleural effusion and eosinophilic infiltrates. Skin - dermatitis, urticaria, papular rashes. [patient.info]

  The subsequent diagnosis of HES explained the multiorgan involvement as manifested by the stroke, heart valve, vegetation and pleural effusion. The eosinophilia proved very sensitive to steroids and she tolerated cyclosporin well. [academic.oup.com]

  effusions and/or fibrosis,[6] and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.[6] A proportion of patients have a mutation involving the PDGFRA and FIP1L1 genes on the fourth chromosome, leading to [en.wikipedia.org]

• Leukocytosis

  Abstract This report concerns three individuals with a similar illness characterized by the following: a striking leukocytosis due primarily to increased numbers of mature eosinophils; cardiac or pulmonary symptoms, or both; and hepatosplenomegaly. [annals.org]

  Other clinical situations with HE: Churg-Strauss syndrome (eosinophilic vasculitis that can affect skin, sinuses, heart, lungs, peripheral nerves), Gleich syndrome (episodic HES with pruritus, urticaria, fever, weight gain, increase serum IgM, and leukocytosis [unboundmedicine.com]

  Abnormal increase of eosinophils in the blood, tissues or organs Disordered formation of eosinophils or an abnormal accumulation or deficiency of these cells 288.3 Excludes Applies To Eosinophilia allergic hereditary idiopathic secondary Eosinophilic leukocytosis [icd9data.com]

  […] associated with a wide range of clinical manifestations reflecting eosinophil-induced tissue/organ damage. [ Orphanet : 168956 ] Synonyms: Idiopathic Hypereosinophilic Syndrome, hypereosinophilic syndrome, hypereosinophilic disorder, HES, eosinophilic leukocytosis [ebi.ac.uk]

Treatment of HES is classified into immediate therapy, definitive therapy directed specifically at the disorder and supportive therapy.

Immediate therapy consists of high doses of IV corticosteroids in the context of severe eosinophilia or complications of hyperleukocytosis. If the patient responds and the eosinophil count decreases by more than 50% after 24 hours, the same dose of corticosteroid can be administered on a routine basis. If the response is negative, an alternative regimen with hydroxyurea can be attempted. Lowering the white blood cell count is critical and treatment targeting eosinophilia should be initiated immediately.

Definitive therapy is dependent on the subtype of HES. Tyrosine kinase inhibitors (TKIs) are particularly effective in patients with a positive FIP1L1/PDGFRA fusion gene. Imatinib is usually the first line drug administered and some studies indicate a response rate approaching 100%. Courses of other TKIs can be attempted in cases where imatinib is not effective or well-tolerated. Corticosteroids are the treatment of choice for patients with cardiac damage. 

On the other hand, symptomatic or asymptomatic patients who are FIP1L1/PDGFRA negative are treated with a 5 day course of corticosteroids, and positive response is usually immediate. Evidence of organ damage necessitates treatment with the same dose for two weeks, followed by a gradual tapering. In case there's no evidence of organ damage, patients are monitored for a period of 6 months. In cases where patients cannot tolerate a tapering of corticosteroids, alternative drugs such as hydroxyurea and interferon-α can be administered [13] [14].

Supportive therapy is mostly targeted at treating the complications and organ damage resulting from HES. Antiplatelet drugs such as clopidogrel, aspirin or ticlodipine are used to prevent thrombosis. Anticoagulation is only indicated in cases of left ventricular thrombosis, as well as transient ischemic attacks that persist after aspirin treatment. On the other hand, cardiac complications, such as inflitrative cardiomyopathy, valvular lesions and heart failure necessitate medical and sometimes surgical intervention. Asymptomatic HES patients do not require any continuous treatment, but need to be followed up for the development of any complications. In particular, serum troponin is measured every 3 to 6 months along with the performance of pulmonary function tests and echocardiography every 6 to 12 months [15]. 

Refractory cases that do not respond to the treatments mentioned above are usually managed with chemotherapeutic drugs such as chlorambuic, etoposide, vincristine, 2-chlorodeoxyadenosine and cytarabine or with hematopoietic stem cell transplantation (HSCT). These treatment modalities are particularly effective in patients resistant to imatinib [16].

Hypereosinophilic syndrome has a variable prognosis, depending on treatment response, severity of organ damage and the possibility to cause a myeloproliferative and neoplastic disorder. It follows a chronic and progressive path and is potentially fatal, especially when the heart is involved. Development into a myeloproliferative disorder can occur after many years and its risk increases when leukocytosis is above 90,000 cells per microliter. Although early studies report a 3 year survival rate of 12%, later studies show a marked improvement in prognosis with a mean of 80% 5-year survival rate and 42% survival rate at 15 years [1] [10].

Studies on tissue from patients diagnosed with HES have so far determined two major causative mechanisms. The first one involves a sporadic mutation in myeloid progenitor cells of the bone marrow, leading to an increase in subpopulations of cells which differentiate into eosinophils. The second mechanism responsible for HES is termed L-HES or the "lymphocytic variant", whereby some lymphocytic T-cells increase their production of eosinophilic cytokines, leading to an expansion of the eosinophil cell line [5]. Granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3 and IL-5 have all been shown to act as eosinophil growth factors, although only IL-5 is specific for eosinophils [3] [4] [8] [9].

HES is a rare disorder and epidemiological reports remain scarce, making it difficult to estimate the exact prevalence. It is known, however, that the disease is more common among men than women, with a ratio of 9:1. All age groups can be affected, although the disease displays a peak in the fourth decade and, in general, has a predilection for patients in the age range of 20 to 50 years old. Studies based on annual hospital discharges and on claims database for outpatient management in the United States have estimated that up to a third of patients with chronic myelogenous leukemia have HES [6]. Improvements in the definition of HES diagnostic criteria, as well as detailed patient registries are required for a more accurate estimation of prevalence.

Normal eosinophils are part of the myeloid cell lineage and play a critical role in the inflammatory cascade. Their cytoplasmic granules contain cationic molecules that are the most important mediators of tissue damage in the body. They also release free radicals and possess a respiratory burst oxidative pathway that further promotes damage in infiltrated tissue.

Organ damage resulting from hypereosinophilia is not directly related to the level of eosinophils in the blood and is thought to be mediated by eosinophilic infiltration of tissue. Eosinophils can also aggregate in blood vessels, particularly when levels are extremely elevated (>100,000 per microliter), resulting in widespread ischemia and tissue microinfractions. The most dangerous complication involves the heart and involves myocardial fibrosis, congestive heart failure and, ultimately, death. The fibrosis is severe and affects mostly the endocardium in either ventricles, leading to significant restrictive cardiomyopathy and inflow obstruction.

Based on pathophysiological mechanisms responsible for hypereosinophilia, HES can be broadly classified into myeloproliferative and lymphoproliferative subtypes. An FIP1L1/PDGFRA fusion gene associated with tyrosine kinase activity and resulting from an interstitial deletion at the CHIC2 site on chromosome 4 is responsible for the myeloproliferative variant. Patients affected by this mutation tend to be predominantly male and respond to a low dose of imatinib. They rarely develop lymphoblastic or acute myeloid leukemia, although they frequently have endomyocardial fibrosis. 

The lymphoproliferative phenotype is characterized by a rearrangement of T-cell receptors, resulting in an aberrant population of T-cells with abnormal eosinophilic cytokine production. Patients with this subtype usually respond to corticosteroids and can develop T-cell lymphoma.

Individuals with HES need to be followed up for early detection and prevention of the complications that can accompany the disease. Periodical assessment of the eosinophil count is recommended, as well as measurements of serum troponin every 3 months, pulmonary function tests and an echocardiogram every 6 months.

Hypereosinophilic syndromes (HES) describe a range of disorders chiefly characterized by persistent and unexplained elevation of eosinophil levels, in the presence of organ damage and absence of any evidence of a known cause, such as parasitic infections or allergic reactions [1] [2].

Because HES can affect almost every organ in the body, patients present with a broad range of symptoms: non-specific ones such as fever, weight loss or night sweats, alongside more organ-specific manifestations such as strokes, heart dysfunction or pleural effusions. Workup is broad and directed at providing evidence for organ involvement as well as hematologic tests to assess possible subtypes of HES. Initial treatment with steroids is targeted at lowering the eosinophil count and is followed by more specific regimens that address subtypes, as well as potential complications. HES can be fatal if not properly treated, but recent advances have significantly improved outcomes.

Hypereosinophilic syndrome is a rare disorder characterized by a significant elevation of eosinophil count above 1,500 cells per microliter in the absence of a well-defined cause. The condition can affect all age groups, but particularly targets men who are 20 to 50 years old. An increase in the number and action of eosinophils can potentially affect all organs including the heart, liver, nervous system, skin and lungs. The heart is especially vulnerable and its involvement can lead to heart failure, heart attacks and damaged heart valves.

Patients with hypereosinophilic syndrome can present with a wide range of symptoms including weight loss, night sweats, fatigue, swelling, rashes, weakness, confusion, coma, chest pain, cough and abdominal pain. Diagnosis is established after blood tests show a persistent elevation of eosinophil count in the presence of symptoms and without evidence of an allergic reaction, a parasitic infection or another definite cause.

Hypereosinophilic syndrome is fatal in patients who are not treated or properly monitored. Recent advances, however, have markedly improved survival among patients and, nowadays, more than 80% survive with adequate treatment. Patients who are asymptomatic are usually treated with a single dose of corticosteroids and then monitored closely for the next 3 to 6 months. Others need to be treated with steroids, hydroxyurea or cancer drugs.

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