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- Eosinophilia - 12/1/05 re: Giardia , IgE and allergies My patient, male, 32, chronic patient of year round rhinitis had IgE 1238 IU and Eosinophil 545 with Giardia cysts in his stool. Rest of the tests were normal. He also suffers from unusual type of so-called brain fatigue during teaching sessions. The fatigue remained so severe that he had to quit his teaching job. Treatment with Effexor(SSRI-anti depressant) has shown some improvement in his mental, unusual fatigue. I treated him with Metronidazole 400 mg, Diloxanide furoate 500mg thrice a day for 13 days, than waited for one month and repeated blood test. This time his IgE is 528 and Eosinophil is 400 showing significant drop for these two. Stool test is negative, so far, for Giardia. But he has not shown any improvement in his year round allergy(rhinitis with occasional eczema) and so called brain fatigue. My questions are:
a) Why reduction in IgE and Eosinophils did not reduce his allergy?
b) Will repeating Metronidazole/Diloxanide furoate result in further reduction of IgE and Eosinophils. Is it worth repeating?
c) Is there any link between Extreme, unusual form of mental fatigue and IgE/Eosinophil? In my opinion there may be because the patient does not have psychological stresses in his life. His unusual brain fatigue seem to be Endogenous rather than exogenous.
d) Can Mastocytosis be suspected in this case?Although infection with Giardia involves mainly the G-I tract, products released from large number of such parasites in the G-I tract can stimulate both production of IgE and eosinophilia (see enclosed abstract). Therefore, these findings may not be directly related to the presence of typical IgE-mediated allergies. Indeed, there is debate whether there is an increased incidence of respiratory or food allergies in individuals heavily parasitized. Some groups report a somewhat greater anti-food IgE antibody levels (see enclosed abstract) However, studies from east Africa have suggested a lower incidence of allergies and asthma in children with heavy G-I parasitic infestation. A single study (from South America) of which I am aware found that the incidence of allergies/asthma actually increased in children after they were cleansed of parasites by extensive pharmacotherapy. Therefore, to answer your questions:
1) Reduction of the IgE and eosinophil levels may be due to less stimulation by reduced numbers of Giardia after your treatment but not related to allergies to inhalants and/or foods.
2) Further pharmacotherapy for Giardia should depend on the current studies for the frequency of Giardia organisms in the G-I tract, not on the IgE or eosinophil levels.
3) At very high eosinophil levels, one could have central nervous system manifestations, likely due to local toxic effects of the very cationic components of eosinophils such as eosinophil-derived neurotoxin . However, the eosinophil levels in your patient are not that elevated,-not nearly as high as reported in those hypereosinophilia syndrome patients.
4) Systemic mastocytosis (SM) can cause CNS symptoms. Eosinophilia is common in SM but not increased serum IgE levels. A good screening test for SM would be to measure the total tryptase level in the serum. In about 80% of those with SM and systemic symptoms, the serum tryptase level is over 20. Further investigation would involve biopsy of the bone marrow and ant suspicious skin lesions, with special staining (including immunostaining for tryptase, if available) looking for clumps of mast cells.Arch Med Res. 1994 Summer;25(2):171-7. Related Articles, Links
Evaluation of the immune response in symptomatic and asymptomatic human giardiasis.
Perez O, Lastre M, Bandera F, Diaz M, Domenech I, Fagundo R, Torres D, Finlay C, Campa C, Sierra G.
Finlay Institute, Havana, Cuba.To better understand the common association of Giardia lamblia infection and allergic reactivity, total and specific IgE values were evaluated and different manifestations of symptomatic and asymptomatic infected human hosts were analyzed. The humoral, cellular, and nonspecific immune responses were evaluated in Cuban adults. Increased total serum IgE levels were significantly higher (p < 0.01) in Giardia patients than in negative controls; cure of giardiasis was characterized by a decrease in IgE levels and some patients regained normal IgE values. The skin test was positive in 91% (103/123) of chronic patients and only in 23% (20/123) of negative controls (p < 0.05). A positive test was seen in patients with antecedents of recent giardiasis (< 4 months). Specific IgE was higher in patients than in control sera, and in the former it decreased with sera dilution. During the follow-up period of cured patients, the proportion of IgE decreased and the opposite occurred in noncured patients. The cellular response evaluated by LIF was positive in 92% (11/12) of carriers and significantly higher (p < 0.05) than in symptomatic patients 8% (1/12); the same occurred with IgG and IgA antibody response; titers mainly of IgA were higher in asymptomatic carriers than in patients; all carriers were negative to the skin test. These results indicate the presence of total and specific IgE responses in humans infected with Giardia, but the response in symptomatic cases (patients) is different from that in asymptomatic cases (carriers).
Ann Allergy Asthma Immunol. 1998 Sep;81(3):261-5.
Association between giardiasis and allergy.
Di Prisco MC, Hagel I, Lynch NR, Jimenez JC, Rojas R, Gil M, Mata E.
Institute of Biomedicine, Central University of Venezuela, Caracas.BACKGROUND: Previous studies have indicated that there may be an association between infection by the intestinal protozoan Giardia lamblia and the expression of allergic disease.
OBJECT: We evaluated a group of children who attended the Outpatient Clinic of the Children's Hospital in Caracas, Venezuela, a group in which both allergic disease and giardiasis were common.
METHODS: We performed feces examination and measured total and specific serum IgE (immunoglobulin E) in these children.
RESULTS: We found that 70% of the children infected with G. lamblia presented symptoms of allergy, in contrast to 43% of the non-Giardia parasitized group (P <.05). In addition, the G. lamblia parasitized children showed significantly higher levels of total serum IgE (1194 IU/mL) than the non-Giardia group (822 IU/mL) (P <.005). Children infected with G. lamblia showed higher levels of specific serum IgE antibody against food allergens compared both with the non-parasitized group (P <.0001) and children infected with parasites other than Giardia (P<.05). In contrast, IgE responses against the house dust mite Dermatophagoides pteronyssinus were similar in all the groups studied.
CONCLUSIONS: These results reveal a clear relationship between giardiasis and allergy, possibly because infection by this protozoon enhances sensitization towards food antigens, due to increased antigen penetration through damaged intestinal mucosa
9/30/2005 re: Cause of hypereosinophilia I am writing to ask your opinion regarding a 39 year old woman who was hospitalized in Nov, 2001 for acute chest and flank pain, with a total eosinophil count of 3100, and pulmonary infiltrate Her IgE was 918. Bronchoscopy showed eosinophila, but no infection or malignancy. Since then, her infiltrates have resolved, but she has continued to have eosinophilia. She has had a workup including a bone marrow asp. and biopsy which showed normocellular marrow except for mild eosinophilia and a normocytic anemia with 1% plasma cells. In 2002 a rheumatology evaluation was negative, but in April 2004 she was noted to have nasal septal perforation; biopsy showed no vasculitis or any underlying disease. A hematologist feels that she has idiopathic eosinophilia and irom deficiency, and does not feel repeat bone marrow studies are indicated. He had recommended Gleevec, but it was not covered by her insurance, and he felt hydroxyurea or chronic steroids are not indicated (she also has diabetes). This year, she was noted to have a positive toxocara antibody and was treated with albendazole with no change in her eosinophilia. Her last eosinophil count was 1400, which is still high but trending downward. She has had a normal serum tryptase, a normal bone scan, normal cortrosyn test, and a very elevated urine histamin(1817nmol/g) on two occasions. Her only real complaints now are chronic fatigue and some nonspecific GI symptoms and intermittent diarrhea. Do you think that in spite of the negative marrow study, that this could be mastocytosis, or do you have any other ideas. I will first try to answer your questions then make some other comments:
1) Could this patient have systemic mastocytosis (SM) ?- Dr. Lawrence Schwartz, a mast cell expert in the Medical College of Virginia, has concluded that serum total tryptase levels may be in the "high normal" range (12-20) in up to 1/3 of patients ultimately determined to have SM. However, such individuals usually have abnormal mast cell findings in biopsies of the bone marrow and/or skin lesions. You did not mention whether there were any suggestive skin lesions and/or urtication on vigorous rubbing of the skin. The very high urinary histamine levels on two occasions mentioned by you are highly suggestive of SM provided that the patient was not eating foods that can lead to elevated urinary histamine levels. I would get a skin biopsy with particular staining for mast cells (preferably examined by a dermatopathologist) particularly if there are any suggestive skin lesions (tan, flat papules which may not be all that striking on first exam but urticate when rubbed).
2) However, there are findings described by you which do not fit well with a diagnosis of SM. The quite high serum IgE levels (914) along with eosinophilia in someone with at least one pulmonary infiltrate raise the possibility of allergic bronchopulmonary aspergillosis (ABPA) or the Churg-Strauss syndrome. You did not mention whether your patient had a history of past or present asthma, which is generally present in both these disorders. The nasal septal perforation raises the possibility of vasculitis despite the reportedly negative biopsy findings (assuming that the patient has not been "sniffing" an agent which could cause this). Some migratory parasitic diseases could lead to increases in both serum IgE and eosinophilia. I would recheck the serum IgE, obtain serum ANCA and (if there is any history of asthma) check for serum of IgE anti-Aspergillus antibodies. If there is adenopathy/hepatosplenomegaly, consider the Omenns syndrome or Kimura's disease (if there are subcutaneous swellings). Obtain serum electrophoresis looking for a paraprotein. If the eosinophil counts in your patient continue to decrease, this may not present any potential hazard to her. However, if the levels persist, I would have a careful ECHO study done since cardiac involvement is a major adverse effect of prolonged eosinophilia. If adverse effects are seen and hydroxyurea in usual doses is considered ill-advised, one may consider treatment with a combination of lower dose hydroxyurea and interferon A (see enclosed abstract)
Haematol. 2005;114(1):26-40. Related Articles, Links
Interferon treatment for hypereosinophilic syndromes and systemic mastocytosis.
Butterfield JH.
Divisions of Allergy and Immunology, Mayo Clinic, 200 First Street
SW, Rochester, MN 55905, USAHypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are heterogeneous disorders with clinical symptoms from local and remote effects of excessive proliferation of eosinophils and mast cells, respectively. Interferon alpha (IFN-alpha), alone or in combination with other medications, can be a useful, and at times life-saving, treatment for patients with HES. Receptors for IFN-alpha are present on eosinophils, and clinical benefits are due to its effect on eosinophil proliferation, migration, activation, and survival. These effects are likely mediated through multiple pathways including, but not limited to, inhibition of eosinophil colony-forming cells, upregulation of IFN-gamma synthesis, and inhibition of production of eosinophil-active cytokines by T cells, mast cells, and mononuclear cells. IFN-alpha has been life-saving for patients with intractable HES that were resistant to prednisone, hydroxyurea, and other agents. Resistance to the eosinopenic effect of IFN-alpha does not develop and the dose of IFN-alpha necessary to maintain control of eosinophilia often decreases with time. The combination of IFN-alpha and hydroxyurea is very useful and allows dosage reduction of IFN-alpha and better control of hypereosinophilia than with either agent alone. The efficacy of IFN-alpha for treatment of SMCD has been more difficult to establish, with both favorable and unfavorable results reported. The disparate results may have resulted from the small number of patients with SMCD treated with IFN-alpha, the use of various criteria for a "successful" treatment outcome, short duration of treatment and follow-up, and the use of modest dosages. In reported series, side effects from IFN-alpha have frequently been dose-limiting. IFN-alpha improves many of the clinical symptoms of SMCD including dermatological, hematological, gastrointestinal, and systemic symptoms associated with histamine release. IFN-alpha has a beneficial effect on skeletal symptoms because of its ability to increase bone density and reduce painful episodes from vertebral fractures. No consistent improvement in bone marrow infiltration by mast cells has been demonstrated except in a recent study employing high dosages of IFN-alpha. A beneficial effect from the combination of IFN-alpha and prednisone has been reported for several patients, suggesting that combined use of these two medications may provide synergism in treatment outcomes.
2/10/03 re: Cause of rash, hyper-IgE and eosinophilia 11 year old female from Mexico has had recurrent exfoliating erythroderma since the end of November. Associated with recurrent high fever, marked elevation in eosinophils and IgE near 3,000. IgG has been 2,130, IgA and M are normal. During exacerbations has had severe Coombs negative anemia, thrombocytopenia, elevated BUN and Creatinine, Has progressed to severe respiratory compromise requiring ventilation at one point. Skin Bx: no vasculitis. Blood smear normal. ANA negative, Strep negative, EBV negative, Initial Dx Exfoliative Erythroderma felt to have resulted from medication, but unknown if it was from NSAID, Penicillin or Macrolide. Had been on all three while in Mexico around time of onset.
Responded well to treatment with high dose steroid, now has recurrence of dermatitis as she is being weaned from the steroid, and her creatinine has started rising. Anyone have any good ideas?The case you describe in an 11-year-old child does sound complex. You did not mention whether or not the prominent respiratory symptoms were accompanied by abnormalities seen on plain chest x-ray or high-resolution chest CT exam, or whether the anemia was severe enough to cause respiratory distress on its own. You also did not mention whether a bone marrow exam was carried out during the anemia/thrombopenia and the results if done.
Although adverse reactions to drugs can be manifest as exfoliative rashes and/or a Pulmonary Infiltrate with Eosinophilia (PIE) syndrome, a serum IgE of 3000 (particularly if persistent in subsequent exams) would be most unusual in such drug induced reactions by themselves.
When encountering someone with this clinical picture, serum IgE of 3000 and prominent eosinophilia, I would consider these diagnostic entities.
1) Certain parasitic infections (those with a trans-pulmonary component in the in vivo parasite migration). This is especially true in your patient coming from Mexico. Trichinosis can cause prominent pulmonary symptoms, fever and other systemic symptoms. However, the skin manifestations are usually urticaria/angioedema not exfoliative dermatitis. Nevertheless, appropriate sool for o and p and serum serologic studies are warranted (see enclosed abstract).
2) Allergic broncho-pulmonary aspergillosis (ABPA) cause prominent pulmonary symptoms with migratory infiltrates and fever responsive to steroid therapy. However, the skin manifestations described by you would be very unusual in ABPA. A negative immediate skin test to Aspergillus fumigatus would be strong evidence against this diagnosis.
3) The hyper-IgE (Job-Buckley) syndrome. This rare disorder can include severe skin, systemic and pulmonary manifestations. However, these are generally due to complicating infections and would not be expected to respond promptly to steroid therapy. One would look for evidence of staph infection of the skin and anti-staph IgE antibodies (see enclosed abstract).
4) Atopic dermatitis, generalized with secondary staph infection
5) Cutaneous T cell lymphoma (CTCL) can be manifest by severe exfoliative dermatitis with lesions characterized by abnormally appearing T cells and often prominent eosinophil accumulation. In certain stages of CTCL, there is increased serum IgE levels. However, CTCL would be quite unusual in 11 year old child.
6) Kimura’s disease - rare disorder with prominent dermatitis, hypereosinophilia and often increased serum IgE levels
Of course, it is possible that your patient has 2 disorders, e.g., underlying parasitic infection and a super imposed drug reaction.
Best of luck in your investigation of this complex case. Please send a follow-up note with the definitive diagnosis, if one is made in your patient.Pediatr Allergy Immunol 2000 Aug;11(3):133-41
Hyperimmunoglobulin-E syndrome with recurrent infection: a review of current opinion and treatment.
Erlewyn-Lajeunesse MD.
Allergy and Inflammation Sciences Division (Child Health), School of
Medicine, University of Southampton, Southampton General Hospital
Hyperimmunoglobulin E (hyper-IgE) syndrome with recurrent infection is a rare idiopathic primary immunodeficiency. It consists of a severe dermatitis with recurrent abscess formation, respiratory tract infections and very high titres of serum immunoglobulin E (IgE). Hyper-IgE syndrome is also associated with skeletal abnormalities. Variability of presentation makes it easy to confuse the diagnosis with that of severe atopy or other rare immunodeficiencies. The aim of this article is to review the literature in order to consider the clinical findings, etiology and treatment of this syndrome. Parasite 2001 Jun;8(2 Suppl):S152-7
Class specific antibody responses to newborn larva antigens during Trichinella spiralis human infection.
Mendez-Loredo B, Martinez y Zamora R, Chapa-Ruiz R, Salinas-Tobon R.
Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas, I.P.N. Apdo. Postal CON-238 C.P. 06400, Mexico, D.F. CP 11340, Mexico.
A follow-up study of the class antibody responses to newborn larva (NBL)
antigens in individuals involved in an outbreak of human trichinellosis was carried out by ELISA assays. The data showed that similar kinetics of antibody responses of different magnitude developed in trichinellosis patients; it was low by week 3, a peak raised by week 5 and decreased from week 7 up to the end of the study. The IgA-ELISA assay was the most sensitive and specific while the IgM was the least sensitive and specific. IgA antibodies to NBL antigens were detected in 80% of patients while IgE, IgG and IgM responses were observed in 44, 31 and 19% of the patients by week 3, respectively. From weeks 5 to 7, IgA antibodies were found in 89 to 100% of the patients while lower percentages (0-82%) were found for the other isotypes. Reactivity of IgA, IgE, IgG and IgM to NBL antigens decreased from week 37 to 57 after infection (0-38%). These results suggest that detection of IgA antibodies may be useful for early diagnosis and epidemiological studies in human trichinellosis
6/01 re: Eosinophilic gastroenteritis I am a speech pathologist requesting information on a patient with stage 3 esophagitis, who also had very high white cell count from biopsy. Physician is questioning possible rare allergic reaction. The patient states he said something about eosinacle cell. Can you give me more information? Please excuse the errors in spelling of this as the patient could not clearly recall the name, and I was unable to contact the physician himself. I think that the term that was mentioned to you is eosinophilic esophagitis, which I will call EE for short. EE is a rarely reported form of esophagitis, although it may be more common than recognized (see enclosed abstract). Although an allergic cause for EE has been suspected because of the prominent eosinophil accumulation in the mucosa of the esophagus, the etiology in most cases is still not well-defined. A recent report described an animal model of EE apparently caused by a reaction to inhaled respiratory allergen in sensitized mice (see enclosed abstract). Curr Gastroenterol Rep 1999 Jun; 1(3): 253-8
Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis.
Liacouras CA, Markowitz JE.
University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has Features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.
J Clin Invest 2001 Jan;107(1):83-90
An etiological role for aeroallergens and eosinophils in experimental esophagitis.
Mishra A, Hogan SP, Brandt EB, Rothenberg ME.
Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, USA.Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.
8/10/98 Please advise how to handle the following case: The patient is a well-nourished nine-year-old boy with good general appearance and a history of bronchial asthma. He had had a fever for 20 days. Physical examination showed T:37°C; P:120/min; R:22/min; BP:16/8kpa; skin color is erythema, no cyanosis, edema, eruptions and hemorrhagaic manifestations. There were several subcutaneous lymph nodules in the chest . Breathing sounds are coarse. Dry or moist rales cannot be heard, heart sounds are low, regular rhythm and we could not find any positive signs and symptoms. The neurologic exam was normal. Laboratory findings: chest x-ray finding show a slight infiltration in two lung fields increased bronchovascular shadows. and also we can find a enlargement of pulmonary hilus. Blood routine: WBC:16000/ul; P:30%; E:30%; L:15%; HGB:132g/L; RBC:4.5*109/L. Bone X-ray shows only a little soft tissue swelling in left ankle joint. What's more, we find a slight hydronephrosis by B type ultrasonic. The humoral immunitire function is low. No other abnormality in ultrasonic cardiography, cardiomyoase, urine Rt. etc. LE(-) PPD(-) ANA (-) Cheat CT(-).
We had given the boy antibiotics and anti-anaphylactic treatment. We also had given him an antitubercalotic, but all these had little effect. After six days of treatment he had a sudden cardiac arrest. He was given immediate intubation and sent to the ICU, where he was placed on a ventilator.
The most effective antibiotic(Imipenem) maintained the boy's body temperature for three weeks. As soon as we stopped the antibiotic, the body temperture would increase to 38°C. What's more, now we find a clear splenectasis. The patient still has dyspnea accompanied by pain in his entire body (foot aches, stomach ache, muscle aches, chest ache, etc.) The last blood Rt. show a high eosinophil ratio: 61%; count: 3960/ul.
What can we do?
The degree of blood eosinophilia described by you (up to 60% of the total leukocyte counts) is considerably higher than seen in the usual allergic/anaphylactic reactions. In the presence of fever and pulmonary infiltrates seen in the chest x-rays, I would consider:
- Certain types of parasitic infestations, such as trichinosis, certain fluke-type worms.
- Churg-Strauss syndrome- in these cases, there is almost always a past history of asthma and active wheezing during the current clinical course.
- Pulmonary Infiltrate with Eosinophilia (PIE) Syndrome- this includes Allergic Bronchopulmonary Aspergillosis (ABPA-also almost always seen in those with chronic asthma), certain drug reactions and parasitic infestations. The pulmonary infiltrate seen in Chest X Rays typically is transient in one location, then appearing in another part of the lungs. If the CT exam of the chest was truly normal, this would be evidence
against ABPA.
- Chronic Eosinphilic Pneumonia- here the infiltrate in chest x-rays tends to be concentrated in the periphery of the lungs, sparing the area around the hilum. The diagnosis can be made only by lung biopsy.
It is not clear from your description whether there has been a definite clinical response to antibiotics. If the patient can tolerate it, a transbronchilal lung biopsy through a fiberoptic bronchoscope may give important information. A search for parasitic disease with careful
stool exams, serologic tests for trichinella antodies, etc. should be done.If no evidence of active bacterial infection is found, a trial of corticosteroids, 1 mg/kg/day, may result in significant clinical improvement starting within several days. If the patien responds to this treatment, it should be continued for about 7 days after clearing of the fever and chest symptoms. the dosage of steroids should be gradually reduced over the next several weeks with close observation of the patient.
