RX Patient Tools
Use these quick guides before reading the article, or return to them when you need help preparing questions for a doctor.
Tropical Pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">Eosinophilia (TPE) is a hyperresponsive pulmonary syndrome in response to trapped microfilariae within the lung tissue. TPE is a clinical manifestation of lymphatic filariasis caused by filarial nematodes. Weingarten first described the term tropical pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">eosinophilia (TPE) in 1943. It was previously described as “pseudotuberculosis with eosinophilia.”[rx][rx]
Tropical Pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">Eosinophilia or TPE, is characterized by coughing, asthmatic attacks, and an enlarged spleen, and is caused by Wuchereria bancrofti, a filarial infection. It occurs most frequently in India and Southeast Asia. Tropical allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">eosinophilia is considered a manifestation of a species of microfilaria. This disease can be confused with tuberculosis,[rx] asthma, or coughs related to roundworms.[rx]
Pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">Eosinophilia (PE) is defined as infiltration of eosinophils into the lung compartments constituting airways, interstitium, and alveoli. Various infections, drugs, parasites, autoimmune processes, malignancies and obstructive lung diseases have been associated with increased eosinophils in the lungs.[rx][rx][rx]
Synonyms of Simple Pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">Eosinophilia
- Loeffler syndrome
- Löffler syndrome
Types of Pulmonary allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।" data-rx-term="eosinophil" data-rx-definition="Eosinophil is a white blood cell involved in allergy, parasites, and some inflammation. সহজ বাংলা: অ্যালার্জি/পরজীবী সংক্রমণে জড়িত রক্তকণিকা।">eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।" data-rx-term="eosinophilia" data-rx-definition="Eosinophilia means high eosinophil count, often linked with allergy, parasites, inflammation, or blood disease. সহজ বাংলা: ইওসিনোফিল বেশি হওয়া।">Eosinophilia
- Acute eosinophilic pneumonia (AEP) – usually is acute onset within days to weeks of symptoms with dyspnea, cough, and fever. No other causes of eosinophilic pneumonia can be elicited from the history such as inciting drugs. AEP occurs predominantly in males, and they have no prior history of asthma. Cigarette smoking is believed to have a causative role in this disease as the majority of the cases reported have either recently started smoking or have had an alteration in their smoking habits. Findings on examination are tachypnea, tachycardia, crackles, and wheezing; many have an acute respiratory failure, with around 70% of the patients needing mechanical ventilation.
- Chronic eosinophilic pneumonia (CEP) – occurs predominantly in women and nonsmokers. Though the etiology is not known, it is more frequently seen in asthmatics and those with a history of atopic disease. Usually, it presents with few months of dyspnea, cough, or chest pain and may have associated constitutional symptoms.
- Eosinophilic granulomatosis with polyangiitis (EGPA) – presents at a mean age of 35, with a history of severe corticosteroid-dependent asthma that usually precedes the onset by a few years. Up to 75% of patients have associated rhinitis and sinusitis. These patients have multisystem vasculitis and can have constitutional symptoms, arthralgias/myalgias, signs and symptoms of heart failure, renal failure, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।" data-rx-term="neuropathy" data-rx-definition="Neuropathy means nerve damage or irritation causing pain, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।">neuropathy, and palpable purpura.
- HES – symptoms are nonspecific such as a cough and dyspnea, which are seen in the only one-quarter to one-half of all cases. They often will present with signs and symptoms of heart failure, central nervous system complaints, peripheral neuropathies, and cutaneous changes such as urticaria and angioedema.
- ABPA – usually have a history of poorly controlled asthma or cystic fibrosis with a productive cough, occasionally with brownish sputum and wheezing.
Pathophysiology
Eosinophils are one of the main cells of allergic inflammation. They develop from hematopoietic stem cells and undergo maturation and activation by the IL-5 secreted by TH-2 lymphocytes. IL-3 and granulocyte macrophage colony-stimulating factor (GM-CSF) are also involved in the eosinophil maturational pathway.
EP is characterized by the prominent infiltration of the lung parenchyma by eosinophils, along with other inflammatory cells such as lymphocytes, plasma cells, and polymorphonuclear neutrophils. Macrophages and scattered multinucleated giant cells may be present in the infiltrate and may contain eosinophilic granules or Charcot–Leyden crystals. Activated eosinophils release pro-inflammatory cytokines, reactive oxygen species, and cationic proteins, such as major basic protein and eosinophil cationic protein, which lead to tissue pathology. The release of platelet-activating factor and leukotrienes contributes to bronchospasm. Local tissue injury due to these mediators causes respiratory tract damage and can lead to respiratory failure. The distribution of EP depends on the underlying etiology; it can be diffuse or focal.
In EP due to Ascaris, the transmission is through the fecal-oral route. In Strongyloidiasis, the entry is through the skin. They both settle in the intestine and release eggs, which form larvae that penetrate into the venous circulation to the lungs. In the lungs, they migrate through the bronchi and trachea and are swallowed into the small intestine again. The pulmonary symptoms mainly occur during the migration in the lungs.
ABPA results from colonization of Aspergillus forming mucus plugs in the bronchi with an inflammatory response.
Causes of Tropical Pulmonary Eosinophilia
Tropical pulmonary eosinophilia (TPE) is a type 1 hypersensitivity reaction to the microfilariae trapped within the lung parenchyma. The species causing filariasis in humans are Wuchereria bancrofti, Brugia malayi, and Brugia timori. These nematodes reside in the lymphatic system and bloodstream of the humans. Filariasis spreads from person to person by mosquito bites, which serve as a vector. The vectors of W. bancrofti are Culex, Anopheles, and Aedes mosquitoes.[rx][rx]
The finding of pulmonary eosinophilia is not specific to a certain disease. However, it breaks the differential down into a handful of diseases that the physician can narrow their differential towards. Pulmonary eosinophilia may be broadly categorized into primary/idiopathic and secondary/extrinsic from external factors.[rx][rx][rx][rx]
Primary pulmonary eosinophilia occurs due to unknown causes, such as acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES). Secondary pulmonary eosinophilia occurs due to known causes, such as allergic bronchopulmonary aspergillosis (ABPA), parasites, medications, radiation effects, and malignancies.
Mildly increased levels of eosinophils may be found in the bronchoalveolar lavage (BAL) differential cell count in the idiopathic interstitial pneumonia, sarcoidosis, and Langerhans cell histiocytosis; however, in these diseases, they are just a mere association and have no causal effects.
All drugs taken in the weeks or months preceding the syndrome of eosinophilic pneumonia (EP) must be thoroughly investigated, including illicit drugs. Medications that are commonly known to cause drug-induced EP include nonsteroidal anti-inflammatory drugs, antibiotics such as trimethoprim-sulfamethoxazole, penicillin, nitrofurantoin, minocycline, angiotensin converting enzyme-inhibitors, sulfa drugs, and ethambutol.
Parasitic infestation is the most common cause of EP worldwide. Simple pulmonary eosinophilia, also termed Loeffler syndrome, refers to the acute, transient pulmonary radiographic opacities and peripheral blood eosinophilia associated with intestinal parasites, commonly described with Ascariasis and Strongyloidiasis.
Symptoms of Tropical Pulmonary Eosinophilia
Symptoms may include any of the following:
A persistent or recurrent cough that gets aggravated at night, weakness, weight loss and a low fever raises the possible diagnosis of this disease. Some children with this disease may also have enlarged lymph nodes in the neck and elsewhere. Others may cough up a little blood and may also have a wheeze.[rx]
- Chest pain
- Dry cough
- Fever
- General ill feeling
- Rapid breathing
- Rash
- Shortness of breath
- Wheezing
Symptoms can range from none at all to severe. They may go away without treatment.
Occasionally, patients with very severe eosinophilia (eg, eosinophil counts of > 100,000/mcL [> 100 × 109/L]) develop complications of hyperleukocytosis, such as manifestations of brain or lung hypoxia (eg, encephalopathy, dyspnea, respiratory failure). Other thrombotic manifestations (eg, cardiac mural thrombi) may also occur.
Diagnosis of Tropical Pulmonary Eosinophilia
The major histopathological changes in tropical pulmonary eosinophilia with time are as follows:
-
Histiocyte infiltration in the lung parenchyma is the earliest finding resulting in symptoms like cough, dyspnea, and wheezing.
-
Eosinophilic interstitial infiltration occurs shortly after histiocyte infiltration, which may further progress to eosinophilic abscesses, eosinophilic granulomas, or eosinophilic bronchopneumonia.
-
At 6 months to 2 years from onset, mixed cell reaction is seen (histiocytes, eosinophils, epithelioid cells, and lymphocytes).
-
If still untreated, the patient may show pulmonary fibrosis.[rx]
History
The patient gives a history of residence or travel to a filarial endemic region. History of medications and foods should be asked to rule out other causes of pulmonary eosinophilia. Loeffler syndrome is precipitated by infections, food, or medications.
Characteristic symptoms of tropical pulmonary eosinophilia include:
-
Dry cough which is paroxysmal and nocturnal
-
Cough associated with dyspnea
-
Systemic manifestations such as fever, malaise, anorexia, and weight loss
-
Peripheral blood eosinophilia >3,000/mm3
-
Extrapulmonary manifestations like lymphadenopathy and hepatosplenomegaly may be seen in a few cases.
Physical Findings
-
Chest auscultation may reveal wheezing and crepitations.
-
Organomegaly on abdominal palpation in a few cases
-
Enlarged lymph nodes
Evaluation
Evaluation of a suspected patient with tropical pulmonary eosinophilia includes blood work-up, stool test, chest radiography, and pulmonary function test.
-
Complete blood count – Leukocytosis with eosinophilia >3,000/mm3 is the cardinal finding in a patient with TPE.
-
Stool examination – To rule out other parasites causing the pulmonary eosinophilia syndrome
-
Quantitative serum immunoglobulin test – Elevated immunoglobulin E level is frequently seen in a patient with TPE.
-
Indirect ELISA test – Diagnosis is confirmed by a rise in filarial antibody titers.[rx]
-
Chest x-ray – May show reticulonodular opacities or miliary mottling in the middle or lower lung zones. About 20-30% of patients with TPE may have normal lungs. Fibrosis may be seen in advanced disease.
-
Chest CT scan – May show bronchiectasis, lymphadenopathy, and pleural effusion. It is done in cases where the diagnosis is not established.
-
Pulmonary function tests (PFTs) – Typically shows a mixed pattern with a predominant restrictive and mild to a moderate obstructive pattern.
- The diagnostic criteria for TPE – (a) history of residence or travel to a filarial endemic region, (b) paroxysmal and nocturnal cough with dyspnea, (c) leukocytosis with peripheral blood eosinophilia >3,000/mm3, (d) elevated serum IgE and filarial antibody titers, (e) pulmonary infiltrations in chest x-ray, and (f) clinical improvement with DEC.
The patient presenting with TPE like syndrome due to other infectious causes may have serological tests that cross-react with filarial antigens. So, to differentiate TPE like syndrome according to causes, there is a need for more specific tests.[rx]
Treatment of Tropical Pulmonary Eosinophilia
The treatment of EP depends on the underlying etiology and is directed towards the alleviation of the underlying etiology. [rx][rx]
In a patient with risk factors and positive serology for parasites, an empiric trial of mebendazole can be given.
- In acute EP, intravenous corticosteroids – are started with rapid improvement, as early as 12 hours and within 48 hours in almost all cases, which is then followed by switching to oral steroids which are tapered over 2-4 weeks.
- Chronic EP responds very well to corticosteroids – with an improvement in symptoms and the radiological opacities within days to weeks. There is no established dose of corticosteroids. However, prednisone can be started at 0.5mg/kg/day with most patients requiring prolonged treatment (greater than 6 months) because of relapse while decreasing below a daily dose of 10 to 15 mg/day of prednisone. Of note, only around 30% of the patients can be weaned off prednisone therapy in their lifetime.
- In EGPA, corticosteroids – are also the mainstay of therapy. Depending on severity, patients can be given either pulse dose methylprednisolone or prednisone 1 mg/kg/day and tapered slowly over months. In severe disease or with multisystem involvement such as heart, kidneys and gastrointestinal tract, cyclophosphamide can be used as steroid-sparing therapy.
- In hypereosinophilic syndrome, Imatinib is first-line therapy – in patients with the myeloproliferative variant of HES. Corticosteroids may be used, especially in the “lymphocytic variant” of HES (with response in only about half of the patients). The anti-IL-5 antibody mepolizumab has recently been shown to be beneficial as a corticosteroid-sparing agent
- For ABPA, oral corticosteroids – are the mainstay of treatment, with recent evidence showing itraconazole giving added benefit. Steroids are tapered over a few months.
- Diethylcarbamazine – is the drug of choice for tropical pulmonary eosinophilia.
- Ascariasis is treated with oral mebendazole or albendazole – Strongyloides is treated with ivermectin, even if only antibodies are found to be positive, due to the risk of hyperinflation in the future.
Immediate therapy
For patients with very severe eosinophilia, complications of hyperleukocytosis, or both (usually patients with eosinophilic leukemia), high-dose IV corticosteroids (eg, prednisone 1 mg/kg or equivalent) should be initiated as soon as possible. If the eosinophil count is much lower (eg, by ≥ 50%) after 24 hours, corticosteroid dose can be repeated daily; if not, an alternative treatment (eg, hydroxyurea) is begun. Once the eosinophil count begins to decline and is under better control, additional drugs may be started.
Definitive therapy
Patients with the FIP1L1/PDGFRA-associated fusion gene (or similar fusion genes) are usually treated with imatinib (2) and, particularly if heart damage is suspected, corticosteroids. If imatinib is ineffective or poorly tolerated, another tyrosine kinase inhibitor (eg, dasatinib, nilotinib, sorafenib) can be used, or allogeneic hematopoietic stem cell transplantation can be used.
Patients without the FIP1L1/PDGFRA-associated fusion gene, even if asymptomatic, are often given one dose of prednisone 60 mg (or 1 mg/kg) orally to determine corticosteroid responsiveness (ie, a decrease in the eosinophil count). In patients with symptoms or organ damage, prednisone is continued at the same dose for 2 weeks, then tapered. Patients without symptoms and organ damage are monitored for at least 6 months for these complications. If corticosteroids cannot be easily tapered, a corticosteroid-sparing drug (eg, hydroxyurea, interferon alfa) can be used.
Supportive care
Supportive drug therapy and surgery may be required for cardiac manifestations (eg, infiltrative cardiomyopathy, valvular lesions, heart failure). Thrombotic complications may require the use of antiplatelet drugs (eg, aspirin, clopidogrel, ticlopidine); anticoagulation is indicated if a left ventricular mural thrombus is present or if transient ischemic attacks persist despite use of aspirin.
Investigational therapy
Mepolizumab and other anti‐interleukin‐5 antibodies are investigational treatments for hypereosinophilic syndrome. Mepolizumab is a fully human monoclonal antibody against interleukin 5 (a regulator of eosinophil production). Mepolizumab decreases eosinophilia and need for high-dose corticosteroid therapy (3) and is currently available for compassionate use in the US for patients with refractory hypereosinophilic syndrome.
References
- https://www.ncbi.nlm.nih.gov/books/NBK537169/
- https://www.ncbi.nlm.nih.gov/books/NBK470600/
- https://www.ncbi.nlm.nih.gov/books/NBK547729/
- https://www.ncbi.nlm.nih.gov/books/NBK560929/
- https://www.ncbi.nlm.nih.gov/books/NBK532294/
- https://www.ncbi.nlm.nih.gov/books/NBK459297/
- https://www.ncbi.nlm.nih.gov/books/NBK557524/
- https://www.ncbi.nlm.nih.gov/books/NBK557618/
- https://www.ncbi.nlm.nih.gov/books/NBK513313/
- https://www.ncbi.nlm.nih.gov/books/NBK534850/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708180/
- https://en.wikipedia.org/wiki/Tropical_eosinophilia
