PULMONARY BOARD REVIEW:

EOSINOPHILIC LUNG DISEASE and PARASITES

Eosinophilic Lung Disease: Allen and Davis. AJRCCM 1994; 150: 1423-1438.

  1. Classification:
  2. Primary:
  3. Simple Eosinophilic Pneumonia: migratory, peripheral eosinophilic infiltrates, peripheral eosinophilia, spontaneously resolves
  4. Chronic Eosinophilic Pneumonia: insidious, peripheral eosinophilic infiltrates, peripheral eosinophilia, steroid responsive, relapses
  5. Acute Eosinophilic Pneumonia: diffuse eosinophilic infiltrates, no peripheral eosinophilia, steroid responsive, no relapses
  6. Secondary:
  7. Asthma: ABPA, Churgg-Strauss
  8. Infections: Parasites, Fungal, PCP
  9. Drug induced: ampicillin, bleomycin, nitrofurantoin, cocaine, nickel
  10. Other: Idiopathic Hypereosinophilic Syndrome, IPF, Eosinophilic Granuloma, HP, Sarcoidosis, Malignancy (NSCC, Lymphoma)
  1. Simple Pulmonary Eosinophilic = Lofflers syndrome:
  2. Migratory pulmonary infiltrate accompanied by peripheral eosinophil and minimal to no pulmonary symptoms
  3. CXR: peripheral infiltrate, migratory
  4. Most probably have Ascaris infection or Drug reaction
  5. No cause found in 1/3
  6. Excellent prognosis – usually resolves spontaneously and rarely require steroids à search for underlying cause!
  1. Chronic Eosinophilic Pneumonia:
  2. Serious disease
  3. Onset insidious – cough, fever, dyspnea, wt loss, wheeze (asthma in 50%), night sweats
  4. Peripheral eosinophilia, increased IgE, increased ESR
  5. PFTs: restriction with reduced DLCO, obstruction if concomitant asthma
  6. CXR: peripheral infiltrate, negative image of pulmonary edema, may have LAN
  7. Histo: eosinophil and lymphocyte accumulation in alveoli and interstitium, eosinophilic abscesses, BOOP
  8. BAL: high eosinophils (>25%)
  9. Tx: Prednisone 40 mg/day – dramatic clinical resolution in 1-2 days and radiographic resolution in 10 days
  10. Px: most patients have relapse if prednisone discontinued within first 6 months, treat relapse with less steroids, minority require long term steroids
  1. Acute Eosinophilic Pneumonia:
  2. Unclear etiology – acute hypersensitivity reaction?, must R/O infection (bacterial – atypicals, fungal - aspergillus/cocci)
  3. Diagnostic criteria:
  4. Acute febrile illness < 5 days
  5. Hypoxemic respiratory failure
  6. Diffuse infiltrate (not peripheral)
  7. BAL eosinophils > 25%
  8. Absence of parasitic, fungal, other infections
  9. Prompt and complete response to steroids
  10. Failure to relapse after discontinuation of steroids
  11. Effusions are common – bilateral
  12. Peripheral eosinophils are usually normal, despite BAL eosinophils strikingly high
  13. Histo: eosinophils and edema within alveoli, bronchial walls and less interstitium, no vasculitis
  14. Tx: rapid response to steroids – Solumedrol 60-125 mg Q6 until respiratory failure resolves and then 40-60 mg/day for 2-4 weeks and then taper over 2-4 weeks
  1. Idiopathic Hypereosinophilic Syndrome:
  2. Blood eosinophilia for > 6 months and signs of end organ damage related to increased eosinophils
  3. Abnormal clonal proliferation of T-helper lymphocytes
  4. Cardiac involvement – fibrosis, restriction, valvular damage, mural thrombus – major cause of morbidity
  5. 40% with pulmonary involvement – infiltrate, effusions, long standing disease can cause fibrosis
  6. Other organs: thromboembolic, peripheral neuropathy, GIT, renal, joints, skin, muscle
  7. Tx: Prednisone 60 mg/day tapering over 3 months
  1. ABPA: done already
  1. Bronchocentric Granulomatosis: done already
  1. Churgg-Strauss: done already
  1. Parasitic infections:
  2. Strongyloides: vector – none, host – dog, monkey
  3. Peripheral blood Eosinophilia, rash, transient pulmonary infiltrate
  4. Larvae enter thru skin à migrate to lung à crawl up airway à swallowed à develop into adult worms in intestinal tract
  5. Gut infection is usually asymptomatic
  6. Capable of perpetuating its life cycle in humans indefinitely à can have transient migratory infiltrate decades after initial infection
  7. Hyperinfection syndrome: in patients with cell mediated immunity, massive numbers of larvae penetrate the intestinal wall and migrate to lungs carrying gram negative bacteria à diffuse pulmonary infiltrates, gram negative sepsis, respiratory failure
  8. Tx: Ivermectin 2 days (treat for disseminated - hyperinfection syn – 2 wks)
  1. Ascaris: vector – none, host - none
  2. Round worm – most frequent cause of eosinophilia and pulmonary infiltrate in developing countries
  3. Probably responsible agent in Lofflers syndrome
  4. Eggs ingested à larvae hatch in small intestine à thru intestinal wall and migrate to lungs à adult worms à crawl up airway à swallowed into intestines
  5. Fever, cough, chest pain, peripheral eosinophilia, skin rash, no LAN
  6. CXR: perihilar infiltrate
  7. Stool exam may be negative for 8 weeks after onset of respiratory symptoms à may isolate from sputum or gastric aspirates
  8. Tx: Mebendazole, pulmonary symptoms resolve spont over 7-10 days
  1. Toxocara: dog roundworm, vector – none, host – cat/dog
  2. Eggs ingested à hatch in intestine à migrate thru blood to organs
  3. Mature worms do not develop in humans – do not check stool
  4. Associated with Pica (mentally retarded)
  5. Cough, wheezing, infiltrate on CXR, peripheral eosinophilia, high IgE
  6. Dx: serologically
  7. Tx: Mebendazole
  1. Ancylostoma: dog hookworm, vector – none, host - humans
  2. “Creeping eruption” – pulmonary infiltrate, peripheral eosinophilia, red rash
  3. Infect humans by skin contact à rash
  4. May develop CXR infiltrate – usually asymptomatic
  5. Organism not found in sputum or stool – clinical diagnosis
  6. Tx: Thiabendazole
  1. Wucheria bancrofti = Tropical Pulmonary Eosinophilia

vector – mosquitos, host - humans

  1. Transmitted by mosquitoes à lymphaticsà release microfilariae à lungs and create intense inflammatory reaction
  2. Nocturnal cough, dyspnea, wheezing, weight loss, peripheral eosinophilia
  3. High IgG and IgE in blood and BAL correlate with disease activity
  4. PFTs: early - restr or obstr, later can develop decreased DLCO
  5. CXR: normal to reticulonodular pattern (lower lung fields)
  6. Histo: histiocytes to alveoli à eosinophils à eosinophilic abscesses
  7. Dx: demonstration of microfiliariae in lung or affected organ, can check serologies (Ab) – not in blood
  8. Tx: Diethylcarbazine for 1-3 weeks
  9. Px: may develop chronic ILD with continued symptoms, CXR changes, and reduced DLCO
  1. Schistosoma: vector – none, host - snails
  2. Pulmonary hypertension caused by chronic embolization of the lungs by blood borne eggs (see granulomas around eggs) – from Snails!
  3. Treatment (Praziquantel) can result in syndrome of increased IgE, peripheral eosinophilia, restrictive vent defects, and diffuse reticulonodular infiltrate due to antigens released after anti-helmintic therapy
  1. Paragonimus: host - crustacean
  2. lung fluke, from crayfish and freshwater crabs – endemic in Asia
  3. ingested à thru duodenum to peritoneal and then pleural cavity and then lungs à cause hemorrhage and necrosis and then cyst formation
  4. right > left lung
  5. hemoptysis, PNA, bronchiectasis, peripheral eosinophilia, pleural effusions (exudates and eosinophilic) à diagnosed by ova in sputum or stool
  6. Early – 2 months before egg production - chest pain, effusion, cough, hemoptysis, blood eosinophilia
  7. Late – egg production – decades later – hemoptysis, cysts, less blood eosinophilia
  8. may get cerebral infections as well, Treat with praziquantel
  1. Other: IPF (BAL usually < 20% eosinophils, may have peripheral eosinophilia), EG (eosinophils seen on tissue – less so for BAL, no peripheral eosinophilia), HP, Sarcoidosis (uncommon and not very high BAL eosinophils), Malignancy (NSCC, Lymphoma), Fungal infections (cocci, asperg, PCP), BOOP
  1. Work Up:
  2. History, exam ,stool exam, PFTs, BAL, OLBx
  3. Obstructed:
  4. Only lungs involved: Asthma, ABPA, Bronchocentric Granulomatosis
  5. Multi-organ: Churgg-Strauss
  6. Restricted:
  7. BAL:
  8. R/O infection: parasite, fungus, PCP
  9. <20% eosinophils: ILD, drug reaction
  10. >20% eosinophils:
  11. high peripheral eosinophils: HES
  12. moderate peripheral eosinophils: CEP, SEP
  13. low/normal peripheral eosinophils: AEP

12.  Other Bugs:

  1. Chagas (Trypanasoma): reduviid bugs, see myocarditis, meningitis, bronchiectasis, esophageal dilation with recurrent aspiration à atypical mycobacterium in the lungs!!!
  2. Amebiasis: vector- none, host - none
  3. dysentery, liver abscesses
  4. Pleuro-pulmonary disease in 20-30%
  5. Sterile sympathetic effusions, may rupture into pleural space with need for surgical drainage
  6. Dx: anchovie paste, chocolate sauce color, trophozoites in pleural space
  7. Eosinophilia is rare
  8. Serology may be positive for two years after effective treatment
  9. Rx: Flagyl
  10. Malaria: plasmodium – vector – mosquito, host - man
  11. ranges from cough to respiratory failure (ARDS – indicates high parasite load accompanied by cerebral changes and ATN)
  12. Rx: Quinidine, exchange transfusion if >5% parasitemia
  13. Giardia: vector – none, host – beaver/dog

PARASITES – HELPFUL TABLES AND DIAGRAMS

TABLES FROM CHESTNET.ORG = TROPICAL LUNG DISEASE

Table 1—Parasites Causing Lung Diseases in Humans
Nematodes (roundworms)
Löffler's syndrome / Ascaris lumbricoides
Ancylostoma braziliense (cutaneous larva migrans)
Ancylostoma duodenale (hookworm)
Necator americanus (hookworm)
Strongyloides stercoralis
Trichinella spiralis
Toxocara canis, Toxocara cati (visceral larva migrans)
Chronic cough / Mammomonogamus spp
Capillaria spp
Gnathostoma spinigerum
Tropical eosinophilia / Wuchereria bancrofti (lymphatic filariasis)
Brugia malayi
Solitary nodule on radiograph / Dirofilaria immitis (dog heartworm)
Cestodes (tapeworms)
Tapeworm / Echinococcus granulosus (hydatid disease)
Lung mass / Echinococcus multilocularis
Calcification of intercostal muscle / Cysticercus cellulosae
Trematodes (flatworm)
Pleural effusion / Paragonimus westermani
Pulmonary infiltrates / Schistosoma mansoni
Pulmonary hypertension / Schistosoma haematobium
Löffler-like syndrome / Clonorchis sinensis
Fasciola hepatica
Protozoa
Pleural effusion / Entamoeba histolytica
Respiratory failure / Plasmodium falciparum
Pulmonary infiltrate / Toxoplasma gondii
Kala-azar / Leishmania donovani
Bronchiectasis / Trypanosoma cruzi
Table 3—Drugs for Treatment of Parasitic Infections
Infection / Drug / Adult Dosage
Systemic amebiasis (hepatic abscess, lung) / Metronidazole
or / 750 mg tid for 10 d
Tinidazole* / 600 mg bid or 800 mg tid for 5 d
Ascariasis / Mebendazole
or / 100 mg bid for 3 d or 500 mg once
Pyrantel palmoate†
or / 11 mg/kg once (maximum, 1 g)
Albendazole† / 400 mg once
Filariasis (TPE) / Diethylcarbamazine / 6 mg/kg/d in 3 doses for 14 d
Paragonimus westermani / Praziquantel
or / 75 mg/kg/d in 3 doses for 2 d
Bithionol / 30–50 mg/kg on alternate days for 10–15 doses
Hookworm (Ancylostoma duodenale) / Mebendazole
or / 100 mg bid for 3 d or 500 mg once
Pyrantel palmoate†
or / 11 mg/kg (maximum, 1 g) for 3 d
Albendazole† / 400 mg once
Schistosoma mansoni / Praziquantel / 40 mg/kg in 2 doses for 1 d
Schistosoma haematobium / Praziquantel / 40 mg/kg in 2 doses for 1 d
Schistosoma japonicum / Praziquantel / 60 mg/kg in 3 doses for 1 d
Strongyloidiasis / Ivermectin
and / 200 mg/kg/d for 1–2 d
Thiabendazole / 50 mg/kg/d in 2 doses for 2 days (maximum, 3 g/d)
Echinococcus granulosus / Albendazole / 400 mg bid for 28 d; repeat as necessary
Severe malaria / Quinidine gluconate
or / 10 mg/kg loading dose (maximum, 600 mg) in normal saline slowly over 1–2 h followed by continuous infusion of 0.02 mg/kg/min until oral therapy can be started
Quinine dihydrochloride / 20 mg/kg loading dose IV in 5% dextrose over 4 h followed by 10 mg/kg over 2–4 hrs q8h (maximum, 1,800 mg/d) until oral therapy can be started
*Not marketed in the United States.
†An approved drug, but considered investigational for this condition by the US Food and Drug Administration.

STRONGYLOIDES REVIEW

The Strongyloides life cycle is more complex than that of most nematodes with its alternation between free-living and parasitic cycles, and its potential for autoinfection and multiplication within the host. Two types of cycles exist:
Free-living cycle: The rhabditiform larvae passed in the stool (see "Parasitic cycle" below) can either molt twice and become infective filariform larvae (direct development) or molt four times and become free living adult males and females that mate and produce eggs from which rhabditiform larvae hatch . The latter in turn can either develop into a new generation of free-living adults (as represented in ), or into infective filariform larvae . The filariform larvae penetrate the human host skin to initiate the parasitic cycle (see below) .
Parasitic cycle: Filariform larvae in contaminated soil penetrate the human skin , and are transported to the lungs where they penetrate the alveolar spaces; they are carried through the bronchial tree to the pharynx, are swallowed and then reach the small intestine . In the small intestine they molt twice and become adult female worms . The females live threaded in the epithelium of the small intestine and by parthenogenesis produce eggs , which yield rhabditiform larvae. The rhabditiform larvae can either be passed in the stool (see "Free-living cycle" above), or can cause autoinfection . In autoinfection, the rhabditiform larvae become infective filariform larvae, which can penetrate either the intestinal mucosa (internal autoinfection) or the skin of the perianal area (external autoinfection); in either case, the filariform larvae may follow the previously described route, being carried successively to the lungs, the bronchial tree, the pharynx, and the small intestine where they mature into adults; or they may disseminate widely in the body. To date, occurrence of autoinfection in humans with helminthic infections is recognized only in Strongyloides stercoralis and Capillaria philippinensis infections. In the case of Strongyloides, autoinfection may explain the possibility of persistent infections for many years in persons who have not been in an endemic area and of hyperinfections in immunodepressed individuals.

TROPICAL PULMONARY EOSINPOHILIA = WUCHERIA = FILIARIASIS

The vector for Loa loa filariasis are flies from two species of the genus Chrysops, C. silacea and C. dimidiata. During a blood meal, an infected fly (genus Chrysops, day-biting flies) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound . The larvae develop into adults that commonly reside in subcutaneous tissue . The female worms measure 40 to 70 mm in length and 0.5 mm in diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43 mm in diameter. Adults produce microfilariae measuring 250 to 300 μm by 6 to 8 μm, which are sheathed and have diurnal periodicity. Microfilariae have been recovered from spinal fluids, urine, and sputum. During the day they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs . The fly ingests microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and migrate from the fly's midgut through the hemocoel to the thoracic muscles of the arthropod . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate to the fly's proboscis and can infect another human when the fly takes a blood meal .