1.gif (1892 bytes)

Brief Reports

Indian Pediatrics 2000;37: 1098-1101

Role of Cetirizine in Treatment of Eosinophilia


Tribhuvan Pal Yadav
Rajpal Singh
Rajbala Yadav*
Minakshi Bhardwaj*
L. Satyanarayana**

From the Departments of Pediatrics and Pathology*, Dr. Ram Manohar Lohia Hospital, New Delhi 110 011, India and **Institute of Cytology and Preventive Oncology, Maulana Azad Medical College Campus, New Delhi 110 002, India.

Reprint requests: Dr. Tribhuvan Pal Yadav, 16 LF, Tansen Marg, Bengali Market, New Delhi 110 001, India.

Manuscript received: September 25, 1999;
Initial review completed: December 7, 1999;
Revision accepted: April 13, 2000

Eosinophilia has been defined as an absolute eosiophil count (AEC) of greater than 0.45 ´ 109/L or an eosinophil count of more than 6%(1). It is arbitrarily classified as mild (<1500 cells per cubic millimeter), moderate (1500-5000 cells per cubic milimeter) or severe (>5000 cells per cubic milimeter)(2). It occurs in a variety of disorders like helminthic infestations, allergic conditions, collagen disorders, drug reactions and lymphomas(2-5). The most common cause of eosinophilia worldwide is helmithic infestations and the most common cause in an industrialzed nation is atopic disease(2,4). Eosinophilia may occur as a result of increased differentiation and proliferation of eosinophils and its precursors in bone marrow by interleukin-5, interleukin-3 and granulocyte macrophage colony stimulat-ing factor; or increased chemo-attraction and rolling over endothelial cells; or increased survival and decreased destruction of eosinophils in tissues(2,3).

Although, many drugs inhibit the produc-tion of eosinophils or the production or action of their products in vitro(2), how much effect does each one of them has in decreasing peripheral eosinophil count, is not known. Hence, this study was undertaken to evaluate the role of cetirizine in the treatment of eosinophilia.

 Subject and Methods

All the hemograms done in children over a period of one year in the hematology laboratory of outpatient department of the hospital were screened daily for eosinophilia.

Inclusion Criteria

All the patients in whom the eosinophil count was found to be more than 0.5 ´ 109/L were included in the study after taking an informed consent from the attendant of each patient. Four thousand four hundred and sixty three hemograms were done in the year and eighty-five of them had eosinophilia. They formed the study subjects.

Exclusion Criteria

Patients with clinically relevant cardiac disease, known hypersensitivity to cetirizine or related compounds, malabsorption states or those on immunosuppressants were excluded from the study.

Each patient was subjected to a detailed history taking and systemic examination. Relevant information obtained included history of allergy, atopy or asthma in the patient and the family, drug intake, contact with tuberculosis patient, joint pains, rash and passage of worms in stools.

Investigations

Stool, urine and hematological examina-tion, Mantoux test, chest X-ray, immuno-globulin E, complement, CRP and ANF level estimation was done in all patients. The stool examination was performed on fresh specimen on three consecutive days. Eosinophil count of the parrents and bone marrow examination of the patient was also part of the protocol in case of suspicion of familial eosinophilia and malignancy. Eosinophil count was performed by the method described by Dacey(1).

Those patients in whom a cause for eosinophilia could be ascertained were given specific treatment. The rest of the patients were randomly allocated in an alternating even and odd manner into two groups - treatment group and placebo group. Subjects in the treatment group were given cetirizine tablet/syrup 5 mg/day, once a day if body weight was less than 30 kg and 10 mg/day if body weight was more than 30 kg, for two weeks empirically. Patients in the placebo group were given similar looking tablet/syrup but not containing cetirizine. Neither the doctor nor the patient knew to which group the patient belonged. Only the nurse knew the codes. The nature of treatment was disclosed at the end of therapy.

Eosinophil count was repreated in each patient at the end of therapy and two weeks later. The response was judged by eosinophil count. If the absolute eosinophil count was less than 450/cu mm at the end of therapy or two weeks after therapy, it was taken as response to medication.

The patients were asked to report in case of any side effects like excessive sedation. The statistical analysis was done using chi-square test and Student ‘t’ test.

 Results

A total of 4463 hemograms were performed. of these, 85 patients (1.9%) had eosinophilia. The maximum number of patients (forty-two, 49.4%) were in the age group 1-5 years. Thirty one (36.5%) patients were in the age group 6-10 years. A male preponderance was observed. Forty-four patients (51.76%) were found to have mild eosinophilia, thirty seven (43.52%) moderate and only four patients (4.7%) had severe or hyper-eosinophilia. Out of these 85 patients with eosinophilia, a cause could be ascertained in 24 and in 61 no cause was found.

Of the twenty-four patients (28%) in whom a cause could be ascertained, 14 (16.5%) had parasite infestation. viz., Ascaris lumbricoides in 9, hook worm in one, Entamoeba histolytica and Giardia lamblia in 2 each. Pulmonary tuberculosis was responsible for eosinophilia in four (4.7%) patients and bronchial asthma in six (7.15%) patients. The diagnosis of pulmonary tuberculosis was based on clinical symptoms, positive Mantoux test, suggestive X-ray picture and isolation of Mycobacterium tuberculosis from gastric aspirate/sputum.

All patients infested with ascaris and hook-worm were given mebendazole and those with E. histolytica and giardiasis were given metronidazole. In all these AEC decreased to normal in one month. Of the patients with pulmonary tuberculosis, only in two, the AEC returned to normal after two months of therapy. However, in all the patients of bronchial asthma, the eosinophil count countinued to remain high.

Of the sixty one patients in whom no cause was found, the results are based on thirty patients in the treatment group and thiry one in the placebo group. The baseline characteristics of both the groups were comparable (Table I).

Table IBaseline Characteristics of the Treatment Group (TG) and Placebo Group (PG)

Characteristics TG
No. (%)
PG
No. (%)
I. Age (yr)    
<1 0 1 (3.2)
1-5 16 (53.3) 14 (45.16)
6-10 9 (30) 12 (38.7)
>10 5 (16.6) 4 (12.9)
Mean age ± SD 5.8±3.71 5.92±3.19
II. Sex    
M 21 20
F 9 11
III. Eosinophilia    
Mild 15 (50) 16 (51.6)
Moderate 13 (43.3) 13 (41.93)
Severe 2 (6.45) 2 (6.45)
None of the differences between the two groups were statistically significant.

Fall in the eosinophil count below 450/cu mm was observed in 7 (23.3%) patients out of 30 in the treatment group as compared to 6 (19.4%) out of 31 in the placebo group (p >0.05). None of the patients in the treatment group complained of side effects.

 Discussion

In our study of patients with eosinophilia, a male preponderance was observed, a finding similar to that of other workers(4,5). The most frequent cause was parasitic infestation similar to reports from South East Asian countries(4,6). However, in a series reported from the West, allergic conditions accounted for eosinophilia in 52% of patients(4). Most of the cause specific eosinophilia patients responded to specific therapy except patients with bronchial asthma.

Cetirizine is potent, third generation selective H blocker, used extensively in both children and adults(7). It inhibits eosinophil accumulation and migration(8,10). It also inhibits eosinophilic vacuolisation by decreas-ing T lymphocytic recuritment(9). It inhibits in vivo intercellular adhesion molecule-I expression in nasal and conjunctival epithe-lium during allergic inflammation(11,12) and eosinophilic recruitment in the skin, nose, eyes and lungs(9,13). It has also been shown to prevent asthma in infants with atopic dermatitis with evidence of sensitivity to either grass pollen or house dust mite(14).

There has been no study to indicate whether cetirizine has a role in decreasing peripheral blood eosinophilia and to draw comparison with the present study. In our study, only seven patients out of thirty responded to cetirizine therapy compared to six in the placebo group. Since the difference was not significant it can be concluded that cetirizine does not have a role in decreasing eosinophilia in peripheral blood.

Contributors: TPY designed and co-ordinated the study, was responsible for analysis and interpretation of data and drafted the paper. He will act as guarantor for the paper, RPS co-ordinated the study and collected and analysed the data. RY co-ordinated the study and collected the data. MB had intellectual contribution towards drafting the paper. LS was responsible for analysis and interpretation of data and intellectual contribution towards drafting.

Funding: Nil.
Competing interests: None stated.

Key Messages

  • Parasitic infestation was the most common cause of eosinophilia

  • Eosinophil count in these patients reduced to normal range with specific treatment

  • Cetirizine had no role in decreasing peripheral eosinophil count in patients in whom no cause could be ascertained.

  References
  1. Dacie YV, Lewis SM. Basic hematologic techniques In: Practial Hematology, 7th edn. Edinburg, Churchill Livingstone 1991; pp 37-68.

  2. Epstein FH. Eosinophilia. N Engl J Med 1998, 338: 1592-1600.

  3. Sanderson CJ. Control of eosinophilia. Int Arch Allergy Appl Immunol 1991; 94: 122-126.

  4. Brigden M, Graydon C. Eosinophilia detected by automated blood cell counting in Ambulatory North American outpatients - Incidence and clinical significance. Arch Pathol Lab Med 1997; 121: 963-967.

  5. Nutman TB, Ottesan EA, Iengs, Samuels J, Kimball E, Lutkoshki M, et al. Eosinophilia in Southeast Asian refugees: Evaluation at a referral center. J Inf Dis 1987; 155: 309-313.

  6. Gopinathan VP, Dutta PK. Eosinophilia in South-East Asia. Trans Roy Soc Trop Med Hyg 1988; 82: 175.

  7. Compoli-Richards DM, Buckley MM, Fitton A. Cetirizine. A review of its pharmacological properties and clinical potential in allergic rhinitis, pollen induced asthma and chronic urticaria. Drugs 1990; 40: 762-781.

  8. Synmann JR, Sommer’s Dek, Gregorowoski MD, Boraine H. Effect of cetirizine, ketotifen and chlorpheniramine on the dynamics of the cutaneous hypersensitivity reaction: A comprative study. Eur J Clin Pharmacol 1992; 42: 359-362.

  9. Redier H, Chanez P, Devos C, Rifal N, Caluzel AM, Michel FB et al. Inhibiting effect of cetirizine on the bronchial eosinophil recruitment induced by allergen inhalation challenge in allergic patients with asthma. J Allergy Clin Immunol 1992; 90: 215-224.

  10. Martins MA, Pasquale CP. Desilva PMR, Pires ALA, Ruffie C, Rihoux JP, et al. Interference of cetirizine with the late eosinophil accumula-tion induced by either PAF or compound 48/80. Br J Pharmacol 1992; 105: 176-180.

  11. Fasce L, Ciprandi G, Pronzato C, Cozzani S, Tosca MA, Gialdi I, et al. Cetirizine reduces ICAM-1 on epithelial cells during nasal minimal persistent inflammation in asympto-matic children with mite allergic asthma. Int Arch Allergy Immunol 1996; 109: 272-276.

  12. Ciprandi G, Buscaglia S, Pesco G, Passalacqua G, Rihoux JP, Bagnosco M, et al. Cetirizine reduces inflammatory cell recruitment and ICAM-1 (CD54) expression of conjunctival epithelium in both early and late phase reaction after allergen specific challenge. J Allergy Clin Immunol 1995; 95: 612-621.

  13. Charlesworth E, Massey WA, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Effects of H receptor blockade on the early and late response to cutaneous allergen challenge. J Pharmacol Exp Ther 1992; 262: 964-970.

  14. ETAC study group, Allergic factors associated with development of asthma and the influence of cetirizine in a double blind, randomized, placebo controlled trial. First results of ETAC. Ped Allergy Immunol 1998; 9: 116-124.

Home

Past Issue

About IP

About IAP

Feedback

Links

 Author Info.

  Subscription