See general separate article on Eosinophilia.

Introduction

Hypereosinophilic syndrome (HES) is characterised by a blood eosinophil count >1.5 x 10⁹/L (for more than 6 months) and associated organ damage, it is categorised under the idiopathic group of eosinophilias.^1,2 It is unclear whether this is a distinct entity or represents an underlying myeloid neoplasia. Patients may be asymptomatic or severely unwell and can present in a variety of ways.¹

Epidemiology

• Hypereosinophilic syndrome (HES) is rare with only 50 cases between 1971 and 1982, being even rarer in children.^3,4,5
• HES can present anywhere from the age of 20 to 70 years, with a mean age of presentation of 33 years.³
• HES has a preponderance in males (9:1).⁶

History and examination

Hypereosinophilic syndrome (HES) can only be diagnosed once secondary causes and clonal eosinophilias have been ruled out.^1,6 Document all medications, including herbal remedies and over-the-counter medicines and any recent travel. A full and thorough examination is needed as the list of potential organs involved and the pathologies in each system are numerous.

Diagnosis

The diagnosis of hypereosinophilic syndrome (HES) is not always straightforward, e.g. differentiating between idiopathic eosinophilia with organ involvement from eosinophilia associated with a systemic vasculitis. In order to diagnose HES, clonal eosinophilia, i.e. neoplastic proliferation of eosinophils which can be seen in a number of myeloid malignancies or as an eosinophilic leukaemia, need to be excluded. This will usually require investigations similar to any suspected bone marrow (BM) neoplasia, e.g. peripheral blood smear, BM examination and cytogenetic studies.

If all of these tests are negative, then idiopathic eosinophilia is the likely diagnosis - the most important subcategory of which is HES.

Presentation^1,6

The history and examination needs to be very thorough due to the multisystem nature of hypereosinophilic syndrome (HES).

• Generalised symptoms - fatigue, aches and pains, fever, night sweats and pruritus.
• Diarrhoea is common, as is abdominal pain and nausea.
• 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.

Organ involvement in HES^1,6

This can be manifold and the following are some examples:

• Blood - thrombocytopenia, hypercoagulability.
• Cardiac - cardiomyopathy, valve abnormalities, pericardial effusion, thromboembolic disease.
• Respiratory - pneumonitis, pulmonary emboli, pleural effusion and eosinophilic infiltrates.
• Skin - dermatitis, urticaria, papular rashes.
• Ear, nose and throat - sinusitis.
• Central nervous system - acute cerebrovascular event and peripheral neuropathy.
• Gastrointestinal tract - tract inflammation, infarction of the gut secondary to emboli, splenomegaly, ascites, hepatitis, pancreatitis.
• Neurological - acute cerebrovascular accident, confusion, ataxia, peripheral neuropathy.
• Eyes - episcleritis, retinal thrombi.

Investigations

• FBC - eosinophils >1.5 x 10⁹/L; neutrophilia and anaemia are also common. Platelet counts can be high or low.
• Peripheral smear - eosinophils may have cytoplasmic vacuolisation and nuclear hypersegmentation and there may also be nucleated erythrocytes.
• Erythrocyte sedimentation rate (ESR) - usually raised.
• U&E and LFTs may both be abnormal.
• 12-lead ECG - may show conduction defects or inverted T waves.
• CXR - look for pleural effusions.

Further tests should be tailored towards the presenting symptoms and signs, e.g. echocardiogram, further lung imaging, biopsy of endocardium, skin or BM..

Management¹

• The rarity of hypereosinophilic syndrome (HES) means there are no evidence-based guidelines on management. Management is aimed at reducing tissue and blood eosinophils and monitoring and restricting organ damage, e.g. regular echocardiographic monitoring.
• Corticosteroids are first-line, e.g. prednisolone with hydroxyurea or interferon alpha as second-line agents. If these also fail, imatinib mesylate or the monoclonal antibodies, such as mepolizumab (not licensed yet) and alemtuzumab, may be useful.⁷
• Allogeneic hematopoietic cell transplant may be a treatment option in refractory HES.

Other generic measures may include anticoagulants, symptomatic relief agents, e.g. histamines and opiates. Other treatment will depend upon the organs involved, e.g. diuretics in cardiac failure.

Prognosis in hypereosinophilic syndrome^1,6

• Good prognostic factors include response to prednisolone and lack of systemic symptoms.
• Poor prognosis is associated with anaemia, thrombocytopenia and organ involvement at time of presentation.
• 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.

Document references

1. Tefferi A, Gotlib J, Pardanani A; Hypereosinophilic syndrome and clonal eosinophilia: point-of-care diagnostic Mayo Clin Proc. 2010 Feb;85(2):158-64. Epub 2010 Jan 6. [abstract]
2. Freeman HJ; Adult eosinophilic gastroenteritis and hypereosinophilic syndromes. World J Gastroenterol. 2008 Nov 28;14(44):6771-3. [abstract]
3. Fauci AS, Harley JB, Roberts WC, et al; NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations.; Ann Intern Med. 1982 Jul;97(1):78-92. [abstract]
4. Alfaham MA, Ferguson SD, Sihra B, et al; The idiopathic hypereosinophilic syndrome.; Arch Dis Child. 1987 Jun;62(6):601-13. [abstract]
5. Katz HT, Haque SJ, Hsieh FH; Pediatric hypereosinophilic syndrome (HES) differs from adult HES.; J Pediatr. 2005 Jan;146(1):134-6. [abstract]
6. Scheinfeld NS et al; Hypereosinophilia Syndrome, eMedicine, Sep 2010
7. Coutre S, Gotlib J; Targeted treatment of hypereosinophilic syndromes and chronic eosinophilic leukemias with imatinib mesylate.; Semin Cancer Biol. 2004 Aug;14(4):307-15. [abstract]

Internet and further reading

• Hypereosinophilic syndrome, DermNet NZ; Includes some good pictures

Acknowledgements