Idiopathic Hypereosinophilic Syndrome

V.K. Anand

From the Departments of Pediatrics and *Pathology, Lady Hardinge Medical College and Associated, Kalawati Saran Children Hospital, New Delhi 110 001, India.

Revision Accepted: March 18, 1999

Idiopathic hypereosinophilic syndrome (HES) represents a heterogenous group of leukoproliferative disorders associated with prolonged eosinophilia of an undetectable cause with multi-organ system dysfunction. The eosinophil count exceeds 1500 cells/mm³ and persists for atleast 6 months unless death intervenes. It is a rare disorder in children; most cases are reported in women aged between 20 and 50 years(1-3). The clinical presentation is generally insidious but may be acute with sudden cardiac or neurological complications. We report a young child with this uncommon condition.

Case Report

A two-year-old male child presented with complaints of continuous moderate grade fever, cough and fast respiration for one month and puffiness over face for 15 days. There was no history of dyspnea, orthopnea or wheezing. The child was initially treated for similar complaints and became asymptomatic. The facial puffiness, abdominal distension and fever recurred within a week. There was no history of oliguria, joint pains, hematuria, anuria or dysuria, jaundice, skin maifestations, worm infestation, bronchial asthma, allergic dis- orders or bleeding tendencies. There was no history of tuberculous contact. The child was on a normal vegeterian diet. There was no history of pica or geophiga. At admission, the child appeared sick with a pulse rate of 112/min and respiratory rate of 56/min. He looked pale and had pitting edema over feet with puffiness of face. There was no lymph-adenopathy, sternal tenderness, joint pain or other skin lesions. The anthropometry was normal. Auscultation of chest revealed bilateral crepitations. The liver was palpable 2 cm below costal margin in the midclavicular line. The hepatic span was 7 cm and the spleen was just palpable. The systemic examination was normal.

Investigations revealed: Hb-7.8g/dl, TLC-48,100 cells/mm³ (polymorhs 11%, lymphocytes 17%, eosinophils 72%) and platelet count of 1.7 lac/mm³. MCV was 59 f1 and ESR was 45 mm at the end of one hour. Peripheral blood smear examination showed marked eosinophilia with absolute eosinophil count (AEC) of 3456/mm³. The bone marrow examination showed myeloid hyperplasia with increased eosinophils and its precursors. There was suppression of the erythroid series but the megakaryocytes were normal. No abnormal cells or parasites were seen. Chest radiograph revealed bilateal interstitial infiltrations. There was no biochemical evidence of hepatic or renal dysfunction. The mantoux test was negative. Ultrasound examination of the abdomen revealed mild hepatospleno-megaly. Buffy coat preparations for micro- filariae and serology for filaria antigen were negative. The heart was normal on echo- cardiographic examination. IgE levels were 250 IU/ml. Rheumatoid factor and antinuclear antibodies were negative. Karyotyping was normal and Philadelphia chromosome was negative. Hematological parameters of parents were normal. Repeated stool examinations for ova and cysts were negative for common parasitic infections. Toxocariasis, Trichnella spiralis and Clonorchis sinesis infections were excluded on the basis of history. Though there were bilateral infiltrations on X-ray chest, the symptoms attributable to pulmonary eosinophilia were absent. Since no cause attributable to hypereosinophilia was found; a diagnosis of idiopathic HES was made.

The child was given a course of diethylcarbazine for 21 days with no clinical or hematological improvement. The child was then put on prednisolone (1mg/kg/day) and followed up with complete hemogram including peripheral blood smear examination. There was only a partial improvement. Prednisolone was tapered off after 4 weeks as the patient had developed steroid-induced hypertension. The blood pressure settled on follow up. The child remained asymptomatic, although with elevated AEC. At follow up 8 months later the hemoglobin concentration increased from 7.8 to 9.6 g/dl, TLC declined from 48,100/mm³ to 3848/mm³, AEC decreased from 3456/mm³ to 500/mm³. The child is still under a regular follow up and recent hemogram has shown Hb concentration of 9.6 g/dl, TLC-3848/mm³ and AEC-500/mm³. The organomegaly is, however, persisting.

Discussion

A case of HES was first reported in 1968 by Hard and Anderson but no details were available(1,4). Chusid and coworkers later used restricted definition and criteria for the diagnosis of HES as persistant eosinophilia of more then 1500 cells/mm³ for alteast 6 months or death before 6 months with signs or symptoms of HES; lack of evidence for any recognized cause of eosinophilia; and signs of symptoms of multi-organ system involvement(1-5). HES can occur at any age, most cases occur in women aged between 20-50 years(2,6). Fewer than 30 cases have been reported in children below 12 years of age(3). The presentations are vivid: weakness, fatigue, cough, dyspnea, myalgia, angioedema, rashes, fever, rhinitis and may include symptoms due to specific organ system involvement(1,6,7). Any organ may be involved. The characteristic feature of HES is the eosinophilic tissue damage related to the release of major basic proteins, eosinophil peroxidase, eosinophil cationic protein and eosinophil- derived neurotoxin(4). 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). In our case the bone marrow, liver, spleen and lungs were involved with no peripheral organ damage. The organ involvement was consistent with other case reports(2).

Acute eosinophilic leukemia is of special concern as a differential diagnosis. There are no specific markers to identify clonal nature of cells. Despite the lack of markers, there are similarities between HES and myeloproli-ferative or myelodysplastic syndrome(1,6). Characteristics of lymphopro-liferative diseases with associated hypereosinophilia include male sex, hypereosinophilic response to chemotherapeutic agents, presence of hypo-granular and/or vacoulated eosinophils, high incidence of cardiovascular disorder, presence of Philadelphia chromosome and decreased alkaline phosphatase(1,5-7). Hence, these patients should be kept under close follow up with complete hemograms repeated every 3 months. Malignancy is unlikely in the absence of immature cells in the peripheral smear or bone marrow aspirates and with normal myeloid series wihtout hyperplasia of the remaining marrow elements(1,6,8). The conversion of idiopathic HES to acute leukemia is rare. 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.

A patient with HES who has no organ dysfunction or symptoms despite high AEC needs no treatment except for a close follow up at 3 to 6 monthly intervals(2,4,6). The symptomatic patient should be treated with prednisolone therapy (1 mg/kg/d) until clinical improvement occurs; followed by alternate day therapy. If clinical improvement occurs the dose should be tapered off gradually(1,4,5,9). Response to steroid therapy was good in 38% cases (NIH series) and additional 31% patients showed a partial response. A very low dose steroid can also be used with good results. Symptomatic patients non- responsive to steroids should be offered chemotherapeutic agents. Common chemotherapeutic drugs used include hydroxyurea, vincristine (VCR), 6-mercaptopurine (6-MP), busulphan and chlorambucil. Hydroxyurea, because of its absence of leukemogenic effect and convenience of oral administration is used frequently. Hematological remission can be achieved and maintained with vincristine alone or in combination with 6 MP and 6 Thioguanine. Interferon alpha and cyclospo-rine have also been found to be useful in HES(10).

Although mortality of HES is high, aggressive medical aid and surgical treatment can result in significant clinical improvement. The most common cause of mortality in HES is damage to heart and CNS by eosinophilic infiltration. Thrombectomy in thrombo- embolism, endocardial resection in endo-cardial fibrosis and valve replacement in severe regurgitation of mitral and tricuspid valve can be life saving(2,3). NIH published a follow up of 50 patients diagnosed and treated over 11 years, with variable survival rates depending on the major organ involved. Patients with cardiovascular complications had a low survival rate. Our case highlights the importance of thorough screening in a symptomatic patient with marked eosinophilia.

References

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9. Bass DA. Eosinophilic syndrome. In: Cecil Text Book of Medicine, 17th edn. Eds. Wyngaarden JB, Smith LK. Philadelphia, W.B. Saunders Co, 1985; pp 1011-1022.

10. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Int Med 1978; 89: 167-173.