Eosinophilic Lung Disease PPT-2024 latest

Eosinophilic lung disease

1. EOSINOPHILIC LUNG DISEASE BY- DR.TANUSHREE SANGHI 2 ND YEAR PG RESIDENT Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

2. TOPICS DISCUSSED: INTRODUCTION CLASSIFICATION PARASITIC EOSINOPHILIC PNEUMONIA: TPE,LOFFLER’S, STRONGYLOIDES, PARAGONIMIASIS AEP CEP DRUG INDUCED EGPA HES Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

3. INTRODUCTION REPRESENTS HETROGENOUS GROUP OF DISEASE CHARACTERIZED BY EXCESSIVE EOSINOPHILIC INFILTERATES INTO LUNGS AND CAUSE TISSUE DAMAGE MANIFESTING INTO DIFFERENT SYMPTOMS Eosinophils appear brick red in colour when stained with eosin. Bilobed nucleus with eosinophilic granules. Eosinophilic granules consists of- Eosinophilic peroxidase : Produces free radicals against parasite. Eosinophilic cation protein & eosinophil derived neurotoxin : Contain ribonuclease activity against viruses. Major basic protein: Stimulate basophils resulting in its degranulation. Eosinophils are produced from bone marrow & constitue 2-3% of WBC in blood Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

4. IL-5 Receptors: -expressed on eosinophils and IL-5 help in eosinophil differentiation and lung recruitment. - Excessive recruitment in lung leads to damage GM-CSF,IL-3 and IL-33 also activate eosinophils. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

5. PATHOPHYSIOLOGY OF EOSINOPHILIC LUNG DISEASE Due to some trigger there will be excess production of IL-5,lung recruitment and activation of eosinophils. Activated circulating eosinophils migrate to tissue and bind to endothelium & causes lung damage by releasing granule proteins, cytokines, superoxide anions and other mediators. Lead to lung tissue and vessel damage, bronchial hyperresponsiveness. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

6. WHAT’S NORMAL The normal AEC- <500/mm 3 Mild-500 to 1500/mm^3 M oderate-1500 to 5000/mm3 Severe- > 5000/mm^3 BAL eosinophils % Normal <2% Increased >5% Primary Pulmonary eosinophilic syndromes >20%  Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

7. Disease associated with Pulmonary infiltrates and Eosinophilia PULMONARY EOSINOPHILIC SYNDROMES OF KNOWN CAUSE Parasitic induced eosinophilic pneumonia Drug or Toxin induced eosinophilic pneumonias Tropical pulmonary eosinophilia ABPA Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate PULMONARY EOSINOPHILIC SYNDROMES OF UNKNOWN CAUSE Idiopathic acute eosinophilic pneumonia Chronic eosinophilic pneumonia EGPA Idiopathic hypereosinophilic syndrome

8. Other Lung diseases variably associated with eosinophilia Asthma/Allergy(Allergic rhinitis,atopic dermatitis) Bronchocentric granulomatosis Bronchiolitis obliterans organising pneumonia(BOOP) Infections-Viral, Fungal,Tuberculosis ILD-IPF,CTD related, Sarcoidosis, HP, Pulmonary histiocytosis Malignancy-Non small cell cancer of lung,NHL , Myeloblastic leukemia , Metastatic disease Miscellaneous- lung transplantation,UC , Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

9. PARASITIC INDUCED EOSINOPHILIC PNEUMONIA Helminths parasites Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate INTESTINAL NEMATODES Ascaris lumbricoides Ancyclostoma duodenale Necator americanus Strongyloides stercoralis Toxocara canis / Toxocara cati Trichinella spiralis FILARIA WORMS Wuchereria bancrofti Brugia malayi Dirofilaria immitis

10. LOEFFLER SYNDROME (Transpulmonary migration of helminth Larvae) Triad of- Self limiting respiratory illness Immune response to nematode Ascaris lumbricoides( human roundworm) due to transpulmonary migration of helminth larvae. Simple Pulmonary eosinophilia Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Uncooked food containing ova of Ascaris Ova reaches and hatches in Small Intestine Cross wall of SI to enter splanchnic circulation Reaches Pulmonary circulation and to alveoli(leads to acute inflammation resulting eosinophilia) and then reaches airway and ingested back to reach intestine

11. Ancyclostoma Soil contaminated by stool from infected animal Penetrates human skin mostly through feet Creeping eruptions (raised erythematous, serpiginous, tunnel like and often itchy lesions on exposed area) Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

12. Clinical Features: Low grade fever Non productive cough Dyspnoea (mild to severe) Chest discomfort with coughing or deep breathing Wheezing Occasionally hemoptysis Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Lab findings: Self limited usually resolves in 1-2 weeks Peripheral blood eosinophilia: peak levels as respiratory symptoms resolve and resolves over weeks Expectorated sputum: eosinophils and/or Charcot-Leyden crystals Parasite identification from sputum, BAL or gastric lavage(can be recovered during pneumonic stage of the illness) Stool examination for ova and parasite: Negative for 8 weeks after the onset of respiratory symptoms due to complete cycle of ascaris.

13. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Chest X-Ray U sually shows abnormal shadows that can be unilateral or bilateral. Generally peripheral or pleural based Present with both interstitial and alveolar pattern (at the same time). Usually a few centimeters in diameter, but larger areas of consolidation are possible Generally transient, migratory, and disappear completely within 2-4 weeks. Pleural effusions is not common in Loeffler syndrome TREATMENT: Bronchodilators and rarely OCS may be used for aggravated pulmonary symptoms Oral Mebendazole(100mg twice a day for 3 days or a single dose of 500mg) should be given to prevent GI manifestations. Alternate options: Pyrantel pamoate, albendazole, ivermectin

14. Caused by Paragonimus westermani (lung fluke) Follows a migratory path Uncooked food containing ova Ova reaches small intestine Reaches peritoneum after piercing wall of intestine Pierces diaphragm and reaches pleura and lung parenchyma Reaches pulmonary circulation to goes to alveoli and is ingested back to reach intestine Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate PARAGONIMIASIS

15. Symptoms Pleuritic chest pain Cough Dyspnea ’ Fatigue Chest tightness Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Investigations and findings Identify egg in sputum or stool Blood tests show elevated eosinophils and high levels of serum IgE . Serology tests done by ELISA. Chest X-ray: nodules, peripheral consolidation, pleural effusion, pneumothorax Pathology reveals eosinophilic inflammation( microabscesses and vasculitis) , cystic spaces(adults are found), eggs may be found in lung parenchyma. P’S in PARAGONIMUS: PLEURITIC PAIN PLEURAL EFFUSION PNEUMOTHORAX PERIPHERAL CONSOLIDATION PERIPHERAL EOSINOPHILIA PRAZIQUANTEL

16. Rare manifestation of human filarial infections (<1%) caused by wuchereria bancrofti and brugia malayi . Male> Female 25-40 years Symptoms resembles asthma Nocturnal worsening of cough, dyspnea , wheeze, mild fever, malaise, anorexia Most common distinguishing symptom of TPE is spasmodic cough usually occurring at night Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate TROPICAL PULMONARY EOSINOPHILIA

17. PATHOLOGY Filarial larva reaches lymphatics through mosquito bite and remains inhabitant for many months or years. Pregnant females discharge microfilariae, some of which enter into bloodstream and trapped in pulmonary vasculature. The release of antigens from degenerating microfilariae in pulmonary vessels cause intense pulmonary and systemic inflammatory response characterized by parasite specific antibodies and eosinophilia. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

18. INVESTIGATIONS & LAB FINDINGS: Marked eosinophilia: >3000 or >90% of Differential Eosinophils high in sputum, BAL and pleural fluid. Elevated total IgE >1000 IU/L Microfilariae are not detected in blood or sputum & filarial ova are not detected in stool. Microfilariae have been identified in tissue from lung and lymph nodes. High titres of filarial specific IgE , IgG confirm diagnosis. Negative serology rules out TPE. PFT usually shows obstructive pattern. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

19. HISTOLOGY OF LUNG Histiocytic inflammation in alveolar, interstitial, peribronchial , perivascular spaces with preserved lung architecture. 1-3 months after symptom onset eosinophilic infiltrates with eosinophilic bronchopneumonia & microabscesses (with degenerating microfilariae in the centre) is present in untreated patients. Long standing untreated disease is associated with chronic inflammation in nodular pattern and later pulmonary fibrosis.Foreign body type granulomatous lesions are often present. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

20. RADIOLOGY Bilateral diffuse reticulonodular opacities B ilateral  miliary nodules, pleural effusions G lobal reduction in lung transparency, better demonstrated when compared to normal radiographs obtained after treatment The CT is more sensitive and can demonstrate in more detail the radiological abnormalities centrilobular nodules smooth  interlobular septal thickening ground-glass opacities mosaic attenuation air trapping interstitial  pulmonary fibrosis  in untreated cases mediastinal lymphadenopathy Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

21. DIAGNOSTIC CRITERIA FOR TPE: Relevant exposure in endemic area Paroxysmal nocturnal cough, dyspnea Infiltrate on chest radiograph Leukocytosis with eosinophilia Elevated serum IgE Elevated serum antifilarial IgE , IgG Clinical improvement with DEC treatment Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate TREATMENT: DOC: Diethycarbamazine 6mg/kg/day in 3 doses for 14 to 21 days Directly filaricidal to both adult worms and microfilariae. Mostly curative but relapse occurs in 20% cases.

22. PATHWAY Enters through the bare skin and reaches circulation. From the circulation reaches intestine and finally to lungs In intestine, larvae initiate repeated cycles of endogenous infection called autoinfection. Can cause GI symptoms and Loeffler syndrome. Repeated cycles of reinfection and migration of larvae through lungs is mistaken as recurrent pneumonias. Chronic strongyloidiasis mimics frequent asthma exacerbations. Immunosuppression with systemic steroids to treat asthma has potential risk of worsening of non disseminated infections. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate STRONGYLOIDIASIS

23. Hyperinfection Syndrome: Accelerated autoinfection leading to widespread dissemination of parasite in immumocompromised patients. Respiratory manifestation: cough, dyspnea , chronic bronchitis, wheezing, hemoptysis , patchy pulmonary infiltrates. In severe cases,ARDS is reported. GI manifestation: pain, constipation, diarrhea , paralytic ileus, nausea vomiting, bowel perforation leading to sepsis from Gram negative (mortality 80%). Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

24. Investigations: Peripheral eosinophilia and elevated serum IgE . Direct identification in stool or body fluids:less sensitive PCR (more sensitive) Serological assays to detect anti Strongyloides IgG. Radiology: GGO Septal thickening Consolidations Patchy migratory infiltrates Miliary pulmonary micronodules Diffuse bilateral infiltrates (in case of ARDS) Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate DOC:IVERMECTIN(200UG/KG FOR 2 DAYS,IN HYPERINFECTION SHOULD BE CONTINUED FOR 2 WEEKS AFTER STOOL SAMPLE TESTS NEGATIVE FOR LARVAE.

25. Systemic infection with intestinal roundworm of dog ( toxocara canis ) Toxocara catis and ascaris suum are less common cause. Children are more affected H/O geophagia or ingestion of raw animal parts. GI and lung symptoms seen. Clinical findings and investigations: Peripheral blood and BAL eosinophilia and elevated IgE . Treatment: albendazole 400mg X 5 days. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate VISCERAL LARVA MIGRANS

26. ACUTE EOSINOPHILIC PNEUMONIA Acute inflammatory reaction to an inhaled agent. More in Men of age group 20-40 years Commonly occur in previously healthy individuals after exposure to tobacco smoke (70% cases),smoking/vaping, inhalation of heroin/cocaine. Reported among persons after unusual exposures: Firefighters Cave exploration Gasoline & Petroleum tank cleaners Dust exposure H/O CML, Hemopoietic stem cell transplantation, HIV infection Reported in treatment history of Venlafaxine, Minocycline, Daptomycin. No h/o atopy/asthma Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

27. Pathogenesis: Exposure triggers inflammatory response. Type 1 Hypersensitivity reaction: IgE mediated mast cell degranulation and activation of innate and adaptive immune response There is activation of type 2 cytokines including IL-5,IL-4,IL-13. Mediators like CCL4/CCL24 enhance eosinophil migration to lung and lead to damage. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

28. Clinical features Acute presentation with symptoms <7 days usually. Dyspnea , fever, non productive cough, tachypnea , pleuritic chest pain and can rapidly progress to respiratory failure. Mistaken for CAP. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Lab findings Leucocytosis Eosinophilia may be absent in early stage of disease but is present during late phase. Raised serum IgE Elevated ESR,CRP Eosinophilia in BAL fluid and pleural fluid.

29. Radiology: Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

30. Lung Biopsy: Diffuse alveolar damage with hyaline membrane. Eosinophilic infiltrates in alveolar space and interstitium . Type 2 pneumocyte hyperplasia. Lymphocytic infiltration of interstitum Intra alveolar fibrinous exudate Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Diagnostic Criteria: Acute respiratory illness <1month duration. Pulmonary infiltrates on chest Xray or CT chest. Pulmonary eosinophilia >25% eosinophilia in BAL fluid or eosinophilic pneumonia on lung biopsy. Absence of known causes of pulmonary eosinophilia. AEP should be considered in a patient who presents with an acute febrile illness,ARDS withot typical antecedent illness, Its ia a diagnosis of exclusion.

31. Treatment: Avoid exposure to offending agent. Steroids: Methyprednisolone 60 to 125mg 6 hourly iv. Responds to systemic steroids in 24-48 hours. After resolution of respiratory failure, oral prednisolone (in doses of 40-60 mg/day) continued for 2-4 weeks. In contrast to CEP,AEP does not typically relapse after therapy is completed. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

32. Affects women twice more than men Age group 30-45 years. Association with Asthma (asthma is usually severe) Most have prior atopy, allergic rhinitis, nasal polys. Majority of patients with CEP are non smokers. ETIOLOGY: Exact cause:unknown No genetic predisposition Type 2 helper cells and type 2 cytokines are involved in pathogenesis which activate IL-4,IL-5 and IL-13. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate CHRONIC EOSINOPHILIC PNEUMONIA AEP CEP HISTORY: <1 MONTH >1 MONTH GENDER: MEN FEMALE AFFECTS HEALTHY INDIVIDUALS PRIOR HISTORY OF ATOPY , ASTHMA EXPOSURE TO SMOKE NO EXPOSURE

33. Clinical features and Lab Findings: Subacute presentation. Dyspnea : Progressive and on exertion. Dry cough. Fever,fatigue Peripheral blood eosinophilia (>1000/mm3) Lack of peripheral blood eosinophilia does not rule out CEP Normocytic normochromic anemia and thrombocytosis. Elevated ESR,CRP. Raised serum IgE in 50% cases. BAL eosinophilia. Negative result for other infectious agents like TB Rapid resolution of infiltrates following steroid with recurrence at identical locations Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

34. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Figure 1 A-E, High-resolution computed tomography of the chest demonstrating bilateral patchy peripheral regions of consolidation predominantly involving the upper and mid-lung zones, with D, relative sparing of lower-lung zones.  F. Extensive bilateral mixed interstitial alveolar processes localized to the mid-upper lung zones are seen on x-ray Appearance of “ Photographic – ve of Pulmoanry Edema ” is pathognomic for CEP

35. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Lung Biopsy: Eosinophilic infiltrates in alveolar space and microabscesses . Type 2 epithelial cell hyperplasia. Focal edema of the capillary endothelium. fibrinous alveolar exudates. Diagnostic Criteria: Clinical characteristics Radiologic features BAL eosinophilia Absence of other cause of eosinophilic lung disease Transbronchial lung biopsy: May show eosinophilic infiltrates . PFT: obstructive pattern due to prior asthma,but as disease progress show restrictive pattern

36. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate D/d(if not responding to steroids): Adenocarcinoma lung Viral, fungal, parasitic infections Churg Strauss Syndrome Idiopathic HES Drug induced eosinophilia Sarcoidosis Lymphoma Treatment: Rarely resolves spontaneously: If not treated may progress to fibrosis Systemic steroids(Oral prednisolone 0.5mg/kg/day for 2 week) Clinical improvement occurs with steroids by 24-48 hours. Radiological response:2-4 weeks. Role of ICS:Asthma control and symptomatic relief. Relapse:Occur in 50-80% on tapering/stopping steroid. Infiltrates can occur in same site or different sites. Relapse more if steroid duration is <6 months and is treated with increased dose of steroid. Antibodies against IL-5 to control CEP: Mepolizumab: Anti IL-5 antibody Benralizumab -Anti IL-5R antibody Omalizumab:Anti IgE antibody

37. DRUG INDUCED EOSINOPHILIC DISEASE Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

38. Diagnosis: Diagnosis is based on careful history and review of medications and other drugs and exposure. Other causes of eosinophilic lung disease must be excluded. A concurrent skin rash and pleural effusion supports the diagnosis of drug induced eosinophilic pneumonia. Onset is subacute Clinical improvement after cessation of drug/toxin. Recurrence with re challenge to the drug. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Lab findings and radiological features: Peripheral eosinophilia may be present. M/c Radiologic finding:Bilateral airspace consolidations and GGO in an asymmetric and peripheral distribution. Prognosis is good. Elimination of exposure to the drug is key for treatment.

39. Previously called as Churg Strauss Syndrome No gender predisposition Age group:38-50 years Rarely after 65 years Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate EOSINOPHILIC GRANULOMATOSIS WITH POLYANGITIS ETIOPATHOGENESIS: ANCA causes tissue injury by activating inflammatory cells, proteolytic enzymes and by oxidative stress. Augmented Th2 immunity: Association with allergy, eosinophilia, elevated levels of type 2 cytokines and IgE . Eosinophils also contribute significantly to tissue injury. Heightened humoral immunity with immune complex disease also play role. Association with LTRA, ICS and omalizumab (not conclusively proven)

40. THREE PHASES: PRODROMAL: Characterized by symptoms of allergic rhinitis, rhinorrhoea, nasal obstruction, asthma, sinusitis. EOSNIOPHILIC: marked peripheral eosinophilia and eosinophilic infiltration of Lung, GI Tract and skin. VASCULITIS: Characterized by vasculitis of small and medium vessels with vascular and extravascular granulomas. Onset of vasculitis phase is marked constitutional symptoms like fever, loss of appetite, fatigue, arthralgia. Usually occurs after years of allergic symptoms, but interval can be short(a few months). Overlap of each phase can also occur. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

41. CLINICAL FEATURES: Respiratory system involvement in almost all cases. Necrotising granulomas involving upper airway are unusual in EGPA unlike GPA. MCC of death:Cardiac involvement Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

42. RADIOLOGICAL FEATURES Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate CHEST X RAY- homogenous infiltrates along with interstitial shadows. CT chest-findings are due to infiltration of eosinophils. -Scattered nodules/Ground glassing/consolidation. -Interlobular septal thickening. -Bronchial wall thickening.

43. LAB FINDINGS AND INVESTIGATIONS: Peripheral eosinophilia (20-90% of TC) Elevated Serum IgE . ANCA:40-60% cases pANCA positive against MPO Absence of ANCA does not exclude the diagnosis. ANA: Negative BAL shows increased % of eosinophils Pleural fluid: exudative, eosinophil predominant Gold standard for tissue diagnosis: Open lung Biopsy Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

44. American college of rheumatology criteria for EGPA Asthma Peripheral eosinophilia >10% Mono or poly neuropathy Migratory or transient pulmonary infiltrates: Cavitations are rare in EGPA, effusions are seen and there is no zonal predominance. Paranasal sinus abnormality Extravascular eosinophils in a blood vessel on a biopsy sample Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate D/D : Microscopic polyangitis , GPA Chronic eosinophilic pneumonia,ABPA , HES, Asthma, drug induced vasculitis TREATMENT: Prednisone 1-1.5mg/kg/day for 3-12 weeks. Once vasculitis phase is controlled steroids may be tapered. Low dose prednisone is usually given daily or alternate day for 1 year. Severe systemic involvement: Highdose IV Methyprednisolone or IV cyclophosphamide Maintenance therapy: Azathiprine for 1-2 years Traials : IVIG,IFN- Alpha,Plasma exchange,Rituximab

45. Occurs in 3 variants: Myeloproliferative (primary/neoplastic HES): Stem cells, myeloid or eosinophil neoplasms causing clonal expansion of eosinophils m/c genetic change: Deletion 4q12 Anemia and hepatosplenomegaly can occur Lymphocytic variant (secondary/reactive HES): 30% cases Increased levels of IL-5,IL-13 & IL-4. Skin and soft tissue involvement are characteristic. 3. Idiopathic variant (50%) Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate HYPEREOSINOPHILIC SYNDROME (HES) HES is defined as the presence of hypereosinophilia with eosinophilic tissue infiltration and organ damage .

46. CLINICAL FEATURES Men> Female m/c symptoms: cough,dyspnea MCC of mortality: Cardiac disease Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate Memory loss, gait disturbances, visual changes and hemiparesis Peripheral neuropathy with sensory or motor axonal loss is common in HES. Bone marrow is universally affected in HES and eosinophils make up to 25-75%. Anemia,venous arterial thromboembolism,HSM , lymphadenopathy Progressive CHF d/t eosinophilic myocarditis and endocarditis. Endocardial fibrosis leading to restricted cardiomyopathy Urticaria, angioedema, nodular or papular lesions. More common in lymphatic variant

47. LAB FINDINGS AND INVESTIGATIONS: Peripheral blood eosinophilia. Elevated total serum IgE . Fungal,parasitic serologies and analysis of body fluids for ova and parasites are negative. Blood & BAL eosinophilia are predominant with pulmonary involvement. Histology of lung: reveals intense interstitial infiltration with eosinophils. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate DIAGNOSTIC CRITERIA: Blood eosinophils >1500/mm3 on two examinations separated by >/= 1 month and/or tissue eosinophilia (>20% of cells in a bone marrow specimen, tissue infiltration defined by a pathologist). Other causes of hyper eosinophilia and organ damage should be excluded Diagnosis of exclusion. TREATMENT: Systemic steroids: mainstay of therapy

48. Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate

49. THANK YOU Reference:Fishman's pulmonary diseases and disorders:6th edition,Harrisons rinciple of inernal medicine 21st edition,Pubmed,Uptodate