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 Table of Contents  
Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 141-144

Helicobacter pylori infection presenting as a hypereosinophilic syndrome and secondary immune thrombocytopenia

Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission16-Apr-2020
Date of Decision26-Apr-2020
Date of Acceptance08-May-2020
Date of Web Publication16-Sep-2020

Correspondence Address:
Dr. Vishal Mangal
Department of Internal Medicine, Armed Forces Medical College, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_44_20

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Eosinophilia is seen in patients with parasitic infections, various inflammatory and allergic diseases, as well as hematologic malignancies and autoimmune conditions. The bacterial infections as a cause of hypereosinophilia (HE) are rare. In the following article, we report a case of HE with rare etiology. Sixty-six-year-old male, presented with symptomatic thrombocytopenia and pain abdomen of 6 months duration. The evaluation revealed HE on the peripheral blood smear, and bone marrow studies, without atypical cells. During workup for complications, eosinophilic duodenitis was present with a positive rapid urease test, without the involvement of other systems. Etiological workup was negative for other secondary causes of hypereosinophilic syndrome (HES) and immune thrombocytopenia (ITP). The patient responded to anti-Helicobacter pylori treatment, with clinical and hematological improvement. Hence, the final diagnosis of H. pylori-associated HES and secondary ITP was made. The clinicians should bear in mind that H. pylori is an established cause of secondary ITP. However, it has never been reported to cause HES. Anti H. pylori treatment can reverse all the changes without the need for corticosteroids and other therapies. Hence, in an Indian setting, it should always be considered.

Keywords: Case report, Helicobacter pylori, hypereosinophilic syndrome, secondary immune thrombocytopenia

How to cite this article:
Mangal V, Hasvi J, Kumar A. Helicobacter pylori infection presenting as a hypereosinophilic syndrome and secondary immune thrombocytopenia. J Appl Hematol 2020;11:141-4

How to cite this URL:
Mangal V, Hasvi J, Kumar A. Helicobacter pylori infection presenting as a hypereosinophilic syndrome and secondary immune thrombocytopenia. J Appl Hematol [serial online] 2020 [cited 2020 Oct 22];11:141-4. Available from: https://www.jahjournal.org/text.asp?2020/11/3/141/295122

  Introduction Top

Hypereosinophilia (HE) is defined as an absolute eosinophil count >1.5 × 109/L on two occasions at least 1 month apart and/or pathologic confirmation of tissue HE.[1] Hypereosinophilic syndrome (HES) is defined as the presence of HE and eosinophil-mediated end-organ damage, provided other potential causes of damage have been ruled out. The most common organs involved in HES are the skin, gastrointestinal tract, and lungs. The heart and brain are less commonly involved. HES is caused by the overproduction of eosinophils in the bone marrow.[2] HES is an uncommon disorder with an annual prevalence of 0.36–6.3/100,000.[3] HES can be further classified as primary HES, secondary HES, and idiopathic HES. In primary HES, there is a clonal eosinophilic expansion in the setting of myeloid, stem cell, or eosinophilic neoplasm. In secondary HES, the eosinophilic expansion is polyclonal and is driven by eosinopoietic cytokines such as interleukin-5. The most common causes of secondary HES are parasitic infections such as ancylostoma, toxocara, trichiura, trichinella, certain solid neoplasms, and T-cell lymphoma. Helicobactor pylori has never been documented to cause HES in literature. Eosinophilic gastroenteritis is characterized by the infiltration of eosinophils into the stomach and/or duodenum. It is diagnosed on the basis of demonstration of infiltration by eosinophils into the gastrointestinal tract on biopsy, demonstration of eosinophils in the ascitic fluid, lack of the involvement of other organs, and history of food allergy or intolerance. The diagnosis can be established by demonstrating ≥30 eosinophils per high power field in the duodenal biopsy.[4] It could be challenging to differentiate between HES related gastrointestinal involvement from eosinophilic gastroenteritis. Immune thrombocytopenia (ITP) is an acquired disorder characterized by platelet count <100 × 109/L and caused by the destruction of platelets by antiplatelet antibodies, impaired platelet production, and T-cell–mediated destruction of platelets, with each mechanism playing a different role in different patients.[5],[6] The primary ITP occurs at the rate of 3.3/100,000 adults per year, whereas of secondary ITP accounts for 20% of all ITP diagnosis. The most common causes of secondary ITP are autoimmune disorders such as systemic lupus erythematosus, Evans syndrome, infections such as HIV, hepatitis C, and Helicobacter pylori. Patients with secondary ITP due to H. pylori are older as compared to primary ITP and other causes of secondary ITP. We present a case of a 66-year-old male presenting with ecchymosis and pain abdomen, which was diagnosed with H. pylori infection-related HES and secondary ITP and achieved clinical and hematological remission with anti-H.pylori therapy without the use of glucocorticoids or diet restriction within 1 week.

  Case Report Top

A 66-year-old male with no significant medical history, presented with easy fatigability, generalized weakness, epigastric pain, and spontaneous ecchymosis of 6 months duration. There was no history suggestive of orthopnea, paroxysmal nocturnal dyspnea, and chest pain. He did not have any history of wheeze, urticarial rash, nausea, vomiting, and dysphagia. He denied any history of photosensitivity or oral ulcers. General physical examination revealed pallor with ecchymotic patches over the abdomen and limbs. However, there was no urticarial rash or lymphadenopathy. On examination of the abdomen, it was soft in consistency with normal bowel sounds and no hepatosplenomegaly. Initial complete blood count revealed a total leukocyte count of 35.5 × 109/L, with 71% eosinophils, an absolute eosinophil count of 24.8 × 109/L, a hemoglobin level of 123 g/L, and a platelet count of 8 × 109/L. Biochemical parameters, including liver function test and kidney function tests, were in normal limits. Stool routine examination and microscopic examination were negative for the ova and cyst. He was evaluated further for the complications and tissue involvement as part of the HES evaluation. There was no evidence of cardiac involvement in echocardiography. His chest radiograph and ultrasonography of the abdomen were normal. However, on esophagogastroduodenoscopy patient had features of duodenitis with a positive rapid urease test (RUT). A biopsy was taken from the second part of the duodenum. The histopathological examination of duodenal biopsy revealed eosinophilic duodenitis [Figure 1].
Figure 1: Duodenal biopsy H and E stain 40x - The red arrow showing eosinophilic infiltrates in epithelial lining and lamina propria with no granuloma, parasite, or dysplasia

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On etiological workup, for primary HES, the patient tested negative for FIP1-like 1 platelet-derived growth factor receptor A (FIP1 L1-PDGFRa) mutation by reverse transcriptase-polymerase chain reaction and gel electrophoresis. He also tested negative for JAK2V617F mutation and Break point cluster - Abelson tyrosine kinase chimeric oncogene (BCR-ABL) mutation. He underwent bone marrow aspiration and biopsy studies, which showed M:E ratio of 2.91:1 with myeloid preponderance and an increase in eosinophils (38%) and their precursors, megakaryocytes were adequately seen with no increase in blasts or atypical cells [Figure 2]. He was also evaluated for the other secondary causes of ITP. He was negative for HIV, hepatitis B, and hepatitis C. His anti-nuclear antibody by indirect immunofluorescence was negative. In view of positive RUT, the diagnosis of H. pylori was considered, and the patient was started on anti-H. pylori regimen including capsule amoxicillin 1 g, tablet clarithromycin 500 mg, and tablet pantoprazole 40 mg all to be taken twice a day along with component support for thrombocytopenia. There was a significant reduction in the absolute eosinophil count from 24.8 × 109/L to 0.4 × 109/L and an increase in platelet count from 8 × 109/L to 30 × 109/L after 7 days of therapy. On follow-up after 2 weeks, the complete blood count revealed hemoglobin concentration of 12.3 g/L, a total leukocyte count of 5.3 × 109/L, and a platelet count of 30 × 109/L and there was no further rise in eosinophil count or fall in platelet count. Hence, the final diagnosis of H. pylori-related secondary HES and secondary ITP was made.
Figure 2: Bone marrow aspirate smear H and E stain, 10x - The red arrows showing severe eosinophilia

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  Discussion Top

HES is an uncommon disease characterized by peripheral blood eosinophilia and multiple target organ involvement by eosinophil infiltrates.[2],[7] In HES, the level of peripheral eosinophilia or the duration of eosinophilia does not correlate with the severity of target organ damage.[2],[5] Usually, different patients present with different clinical features depending on the organ involved by eosinophils. HES can involve multiple organ systems; however, the involvement of the heart is the cause of death in the majority of the patients.

Myeloid HES or primary HES patients present with chromosomal abnormalities, increased serum Vitamin B12 levels, anemia, thrombocytopenia, hepatomegaly, splenomegaly, and circulating leukocyte precursors.[8] The recent WHO classification system of hematopoietic and lymphoid tissues describes a separate category for myeloid and lymphoid disorders with eosinophilia and abnormalities such as interstitial deletion on chromosome 4q12, resulting in a FIP1 L1-PDGFRA fusion, mutation in the gene for tyrosine kinase receptor PDGFR beta, fibroblast growth factor receptor 1 translocation with the zinc finger and MYM2 gene on chromosome 13q12. Clonal eosinophilia has also been noted in patients with D816V KIT-positive systemic mastocytosis.[9] The prevalence of FIP1 L1-PDGFRA fusion in patients fulfilling the criteria for HES is estimated to be 10%–14%. In practice, once classical causes of HE have been ruled out such as parasitic infection and drugs, the underlying mechanism, resulting in HE remains unknown despite thorough investigations in 70%–80% of the patients.

Lymphocytic variant HES (L-HES) is characterized by a predominance of skin and soft-tissue involvement. However, other clinical manifestations of HES, including cardiovascular, pulmonary, and rheumatological/articular involvement, are also present. In this variant, which is classified as a sub variant of secondary/reactive HES, interleukin-5-producing T-cell subsets have been identified in the peripheral blood. L-HES commonly presents with raised immunoglobulin E level, skin involvement, and lymphadenopathy. Our patient had thrombocytopenia, anemia and severe HE so we evaluated him for primary causes of HES after ruling out all the known secondary causes. However, FIP1 L1-PDGFRA fusion gene, JAK2V617F mutation, and BCR-ABL mutation were not detected. Hence, we were able to rule out primary HES.

HES may be confused with eosinophilic gastroenteritis. The etiology of eosinophilic gastroenteritis is not well established, and the distinction from HES must be made on the clinical presentation, laboratory parameters, and response to therapy. Eosinophilic gastroenteritis is usually restricted to the stomach and/or duodenum.[10] Hence, it does not affect multiple organ systems, which is a feature of HES, and at the same time, it does not cause cardiac damage due to eosinophil infiltration. Thus, eosinophilic gastroenteritis can generally be differentiated from HES after clinical and laboratory evaluation; however, in some patients with overlapping features, it might be challenging to establish the exact diagnosis.

In our patient, establishing the diagnosis of secondary HES was challenging as he presented with eosinophilic duodenitis, severe HE in peripheral blood as well as bone marrow, thrombocytopenia, and RUT positive for H. pylori. The differential diagnosis considered at that point was ITP, idiopathic HE (after ruling out all the possible primary and secondary causes), H. pylori-related duodenitis, or eosinophilic gastroenteritis. However, when the patient responded to anti-H. pylori therapy within 1 week with a drastic fall in the absolute eosinophil count and rise in platelet levels, diagnosis of HES secondary to H. pylori was made. The basis of the diagnosis was severe HE, the involvement of gastrointestinal tract (which was not typical of eosinophilic gastroenteritis), the involvement of bone marrow causing thrombocytopenia, which cannot be explained by any other cause, and response to anti-H. pylori therapy signifies that all the manifestations were related to H. pylori. The diagnosis of HES requires that the other causes leading to target organ damage in the absence of eosinophils must be excluded. In our patient gastrointestinal involvement could be explained by H. pylori infection; however, there was no identifiable cause of thrombocytopenia other than bone marrow involvement by eosinophils (38%). In patients with HE who do not have evidence of target organ damage, specific treatment is not required.[2] However, patients with vital organ involvement requires treatment.[2] Tyrosine kinase inhibitor imatinib can be used for myeloid HES. The natural history and disease course of eosinophilic gastroenteritis are not well defined; however, some patients with the untreated disease can occasionally remit spontaneously, whereas the majority of the patients have progressive disease.[10] The initial treatment of eosinophilic gastroenteritis is an empiric six food elimination diets or elemental diet. If dietary measures fail to improve the symptoms, the next line of treatment is the trial of glucocorticoids. However, in our patient, neither dietary restriction was advised nor the glucocorticoids were used, and he responded only to anti-H. pylori therapy. Similarly, previous studies have demonstrated that H. pylori-associated secondary ITP responds within 1 week of therapy.[11] Our patient also had the same course. In conclusion, we report the first case of H. pylori infection presenting with HES and secondary ITP. The final diagnosis in this patient was HES and secondary ITP due to H. pylori infection. Clinicians should bear in mind that H. pylori is a known cause of secondary ITP. However, it has never been reported to cause HES. Treatment with anti-H. pylori therapy can reverse all the changes without the need for corticosteroids and other therapies. Hence in an Indian setting, it should always be considered.

Informed consent

Written informed consent was obtained from the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Ethical approval

Ethical approval is not required from the institutional ethical committee for individual case reports.


We are thankful to the paramedical staff for helping in managing this patient.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Valent P, Klion AD, Horny HP, Roufosse F, Gotlib J, Weller PF, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 2012;130:607-12.e9.  Back to cited text no. 1
Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759-79.  Back to cited text no. 2
Crane MM, Chang CM, Kobayashi MG, Weller PF. Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 2010;126:179-81.  Back to cited text no. 3
Collins MH. Histopathologic features of eosinophilic esophagitis and eosinophilic gastrointestinal diseases. Gastroenterol Clin North Am 2014;43:257-68.  Back to cited text no. 4
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: Report from an international working group. Blood 2009;113:2386-93.  Back to cited text no. 5
Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood 2017;129:2829-35.  Back to cited text no. 6
Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med 1982;97:78-92.  Back to cited text no. 7
Roufosse F, Cogan E, Goldman M. The hypereosinophilic syndrome revisited. Annu Rev Med 2003;54:169-84.  Back to cited text no. 8
Florian S, Esterbauer H, Binder T, Müllauer L, Haas OA, Sperr WR, et al. Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): Detection of FIP1L1/PDGFR alpha, classification by WHO criteria, and response to therapy with imatinib. Leuk Res 2006;30:1201-5.  Back to cited text no. 9
Lee M, Hodges WG, Huggins TL, Lee EL. Eosinophilic gastroenteritis. South Med J 1996;89:189.  Back to cited text no. 10
Kuwana M. Helicobacter pylori – Associated immune thrombocytopenia: Clinical features and pathogenic mechanisms. World J Gastroenterol 2014;20:714-23.  Back to cited text no. 11


  [Figure 1], [Figure 2]


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