Interstitial Lung Diseases(ILD) By : Dr. Shaher M. Samrah Done by : Ibrahim M. sun. 26.11.11 Introduction Interstitial Lung Diseases (ILD) are group of diseases that affect the interstitium of the lungs, it includes a long list of diseases with different prognosis and different management; so we should learn about the presentation of the patients with ILD, and how to make approach for Dx. In this lecture the doctor concentrates on four diseases of ILD: Sarcoidosis, Idiopathic Pulmonary Fibrosis, Eosinophilic Granuloma and Lymphangioleiomyomatosis. The classical presentation for ILD is Idiopathic Pulmonary Fibrosis(IPF), also known as "Usual interstitial pneumonitis", or as known in the past "cryptogenic pneumonitis", which has fibrotic impact on the interstitium of the lung. The patient comes to the hospital hypoxic with severe SOB, the SOB is chronic and progressive. This disease has a poor prognosis, so we have to rule out all other causes of ILD carefully. The other example is Sarcoidosis: it's a multi-systemic disease; start in the interstitium of the lung, unlike IPF which purely affects the Lung; there is no fibrosis at the early stages, in contrast they have "noncaseating granulomas", but may end up as fibrosis in the late stages. Interstitium The interstitium of the Lung is : the space between basement membrane of the capillary endothelium and alveolar cell epithelium, it contains fibroblast, collagen and elastic fibers, interstitial matrix, inflammatory cells like macrophages; B & T lymphocytes, and proteins like 1 antitrypsin which assists in elasticity of the lung and causes early onset COPD if deficient.
Mechanisms of Injury Inflammation : due to proteases of Neutrophils, oxidants like "H2O2, OH", chemotactic factors or Immunologically mediated by antibodies. Mesenchymal cells chemotaxis like PDAF, Fibronectin. Locally produced injurious products like O2 toxicity. Drugs : usually chemotherapy drugs like Bleomycin, Busulfan, Methotrexate. Extracellular molecules deposits Like Amyloidosis. Vasculitis : like Goodpasture syndrome. Remember that : Bleomycin : is an antibiotic used in testicular carcinoma. Methotrexate : immunosuppressant agent, used in rheumatoid arthritis. Pathological Classification Granulomatous reaction: Sarcoidosis. Fibrosis: Silicosis & Asbestoses Exudative: Vasculitis. Mix. Functional consequences of ILD Mechanical: Stiff lungs -decreased compliance- followed by shrinkage of the lung, also restrictive lung disease changes; like decrease Vital capacity 'VC', decrease total lung capacity ' TLC ', also there is decreased Diffusion capacity 'Dlco' because the O2 has to go through diseased and thick interstitium from alveoli to blood capillaries. Dyspnea: because of lung stiffness and the need for using the accessory muscles even when not hypoxic, the work of breathing increase and dyspnea results. Tachypnea: because of activation of J-receptors. Hypoxia: due to the increased Alveolar-arterial gradient.
Pulmonary hypertension : as a consequence of blood vessels destruction and distortion, and the vasoconstriction induced by hypoxia. Remember!! Hypoxia in general causes vasodilatation; except in the lung where it causes vasoconstriction. So in ILD the hypoxia causes vasoconstriction and then vasoconstriction worsen the hypoxia itself and so on. In ILD we have two elements that increase O2 requirement; ILD itself and pulmonary HTN that's caused by hypoxia. ILD Classification Known causes: Occupational: Asbestosis, Silicosis. Hypersensitivity Pneumonitis: Farmer s lung. Drug induced: Chemotherapy, Antibiotics. Poison induced. Radiation induced: like breast cancer or lymphoma radiation therapy. There is fibrosis and even hypoxia, but to consider it as radiation induced it must be localized at the radiation beam site. Unknown causes: Sarcoidosis. Idiopathic Pulmonary Fibrosis (IPF). Connective tissue disease: like SLE, Scleroderma, Rheumatoid arthritis, ankylosing spondylitis, those are known diseases with unknown etiology.
Langerhans cell Histiocytosis (Eosinophilic Granuloma). Alveolar hemorrhage syndromes/ Vasculitis : Goodpasture Syndrome, wegener's granuloma. Chronic Eosinophilic Pneumonia (CEP). There is a long list of ILD classification the doctor didn't read them, please refer to the slides #( 11-14) if you're interested. X-Ray Findings Reticular / Reticulo-nodular diffuse infiltration. Increase lung markings. Lymphadenopathy, like in Sarcoidosis. Fibrosis: Honeycomb changes like in IPF. Granulomatous diseases like Sarcoidosis and Ankylosing Spondylitis: mainly show upper lobe lesion on CXR. Connective tissue diseases: mainly show Lower lobes lesions on CXR. Note!! Inhalation injury like TB affect upper lobes more!! Circulation and antibodies related diseases : affect Lower lobes!!
This is reticular diffuse lung infiltration on CXR, indicate marked diffuse interstitial fibrosis, we can also see normal sized heart, the other differential diagnosis we should put in mind is pulmonary edema but usually is accompanied with congestive heart failure. This is a CT- scan shows honeycomb changes detected in cross section.
Approach to diagnose ILD We start by history taking and Physical examination : Assess symptoms severity. Detect extra pulmonary manifestation in systemic diseases like sarcoidosis; and rule out secondary causes like rheumatoid arthritis in which joint pain associated, or scleroderma which is presented by deformities and esophagitis. Pulmonary Function Test 'PFT': We have restrictive lung findings on spirometry; like decrease TLC and VC, also we detect decrease Diffusion capacity 'Dlco'. Labs : We screen for Connective Tissue diseases like rheumatoid arthritis; and SLE where we ask for canca in case of Vasculitis suspicion. Kidney Function Test 'KFT' is also helpful in Vasculitis and as a routine test. X-RAY : To assess the severity of ILD we ask for Chest X-Ray 'CXR', High resolution CT "HRCT" which is similar to the classical CT scan with thicker slices to observe lung parenchyma better; but without contrast. Biopsy : We do either Bronchoscopy and get TBBx "Trans bronchial biopsy", or we do Open lung biopsy which is invasive and has a risk for pneumothorax. Nowadays, studies showed that in IPF the fibrosis is very characteristic; so we don't need invasive procedure like biopsy to confirm Dx; the characteristic CT scan findings are enough to diagnose idiopathic pulmonary fibrosis 'IPF'.
Sarcoidosis Idiopathic, multi-systemic disease characterized histologically by Noncaseating Granuloma. Noncaseating Granuloma 'NCG' is not specific for sarcoidosis : so remember that the caseating granuloma is always TB, but Noncaseating is either sarcoidosis, "early stage TB", Fungal infection,vasculitis,, Beryllium, Silicosis and maybe malignant lesion like lymphoma. We should differentiate between them; because management is different; imagine treating misdiagnosed fungal infection as sarcoidosis with IV steroids; this will worsen the situation and could kill the patient. It affects Young (20-40), Females more than males, and more in Blacks. There is high Dx rate in TB community, because in any patient if we find lymph node we call it TB then upon biopsy we find it sarcoidosis, so there is a higher diagnosing rate in TB community. Symptoms : Mostly asymptomatic; diagnosed accidently by enlarged lymph nodes on CXR, then Noncaseating granuloma upon biopsy; here we don't need treatment when we rule out other causes. Acute Symptoms: Fever, LÖfgren s syndrome which is "Triad of Skin lesion (Erythema Nodosum), Polyarthritis and bilateral Hilar Lymphadenopathy". In Chronic sarcoidosis we have: Pulmonary symptoms like; Cough, SOB, chest pain, or we have extra-pulmonary symptoms. Extra-Pulmonary symptoms ENT: Hoarseness of the voice, Xerostomia (dryness mouth), hearing loss. Eye: Uveitis and impaired vision, enlarged Lacrimal glands which is characteristic for sarcoidosis because no other similar disease can cause it.
Skin: Erythema Nodosum seen in many diseases include sarcoidosis in the shin of the lower extremities, Lupus Pernio "see Figure below"; it is redness involve the nose saddle and the cheeks; it differs from SLE as it is more diffused. Heart: Heart Block, Arrhythmias, cardiomyopathy. Nervous System: Bell s palsy, Meningeal signs. Parotid gland: Heerfordt s syndrome or Uveoparotid fever which is "Parotid gland enlargement + Fever + Facial palsy+ Ant. Uveitis" Liver: Hepatomegaly Joints: Arthritis. Blood: leucopenia, anemia; so we should be careful when treating with steroids because of infection. Endocrine: Hypercalcemia & Hypercalciuria, increase vitamin D activity, so we pay attention to steroid induced osteoporosis, Sarcoidosis may also cause pituitary Diabetes insipidus which cause dehydration and hypernatremia. Lupus Pernio SLE
Diagnosis of Sarcoidosis As usual we start by Hx and physical examination. Labs: In the past they used to measure Angiotensin Converting Enzyme level (ACE), but because it increases in any case of inflammation and it's not specific, this is only helpful in assessing the responding for treatment, or measuring disease activity. Pulmonary Function Test: indicates restrictive changes, and decreased Diffusion capacity as any ILD. Chest X-ray is used for staging: see the figure next page. Stage I: bilateral Hilar lymph nodes on CXR but no ILD. Stage II: bilateral Hilar lymph nodes with ILD. Stage III: ILD without fibrosis but no lymph nodes on CXR. Stage IV: Fibrotic changes also without lymph nodes on CXR. So sarcoidosis starts as lymph nodes on CXR; and ends up as fibrosis. Remember also that those stages may be skipped; so stage I may all of a sudden goes to stage IV skipping stage II and III. Keep in mind also that it's irreversible progression; it can't back off to an earlier stage if it progresses to an advanced stage. Biopsy: here the biopsy is important: we might use Transbronchial biopsy or mediastinoscopy, the later one is more helpful than open lung biopsy; because it goes more medially in the mediastinum to the lymph nodes to take a biopsy. Bronchoalveolar lavage also helpful; it reveals increase in CD4+ T-lymphocyte. Gallium scan: not important, because it's expensive, inconvenient, difficult, and not used any more.
Those are the stages of sarcoidosis Prognosis Good prognosis. Most cases are self-limiting, (85%) of cases resolve in within 2 years. 10-15% of cases: have chronic and progressive course. Mortality rate is 1-6%.
Causes of death Pulmonary: respiratory failure, infection, mycetomas, hemoptysis. - Mycetomas : is a fungus inside a cavity with destruction of lung parenchyma, that commonly affect blood vessels and cause severe hemorrhage. Cardiac: heart block, arrhythmias, cardiomyopathies, congestive heart failure. Kidney may also be involved with renal failure. Sarcoidosis treatment In the 85% of self limiting cases; we don't need treatment, but we treat in those cases: Pulmonary Indications for treatments: Moderate or severe lung disease; we can't wait, we should treat before fibrosis takes place. Progressive lung disease. Extra-Pulmonary Indications: Threatened organ failure like heart, CNS, Eye...etc Persistent Hypercalcemia. Disfiguring skin lesion like lupus Pernio. Severe constitutional symptoms; like generalized weakness, fatigue, fever, insomnia..etc Management includes: Steroids, Immunosuppressive, cytotoxic agents; or Lung transplantation, Single lung is enough.
Idiopathic Pulmonary Fibrosis (IPF) Specific clinical syndrome of unknown etiology. Affects middle aged or elderly (>40). More in Males (2:1); unlike sarcoidosis which is more common in females. Clinical presentation: insidious Progressive SOB; exertional than at rest, with nonproductive Cough, and Cyanosis. weight loss, fatigue, anorexia. On examination: Chest: Velcro-inspiratory crackles; which is an early inspiratory crackles; it results from taking breath that opens fibrotic alveoli; it differs from congestive heart failure crackles as these are end inspiratory phase. Clubbing : is not a specific sign, has Long list of DDx. IPF diagnosis We start with Hx, and Physical examination. Labs: we should rule out secondary causes of ILD like connective tissue diseases; because this disease has a bad prognosis and high mortality so we should carefully rule out all other treatable possibilities. PFT: Restrictive changes TLV, VC, and decreased DLco "diffusion capacity".
ABG: Hypoxia. CXR: changes are more prominent in the lower lobes and the periphery; subpleurally. HRCT-Chest: findings range from ground glass to Honeycomb changes or mix; depending on the stage of the disease. This HRCT distribution is diagnostic and characteristic, and no need for biopsy if founded. We can't do Transbronchial biopsy; because we need large biopsy to diagnose IPF, so we need open lung biopsy. We see fibrotic changes in the lower lobes and peripherally, we don't see effusion because it's rare in IPF, no mediastinal deviation because fibrosis is bilateral, note that upper lobes are spared. If we do Bronchoalveolar lavage we found neutrophiles unlike sarcoidosis where we found CD4+ T-lymphocytes, the normal limit for neutrophiles is 1%, more than this is pathological and contributed by IPF in this case. Histopathological classification: not important Usual interstitial pneumonia (UIP) most common. Desquamative interstitial pneumonia (DIP) better prognosis than UIP. Nonspecific interstitial pneumonia (NSIP).
IPF management Because the disease is not treatable we give nonspecific treatment : Indication for treatment: Deteriorating or significant Symptoms + inflammatory changes (ground-glass opacities) on HRCT. Steroids. Immunosuppressive or Cytotoxic agents: Azathioprine, Cyclophosphamide. Antifibrotic agents: Colchicine, D-Penicillamine, γ-interferon (not used in sarcoidosis). Lung transplantation: single When we have a disease that has a long list of medications; the response is very poor because the disease is untreatable. Prognosis: Poor Causes of death: Cor pulmonale. Respiratory failure (3-8 years after onset of Symptoms). Malignancy (Adenocarcinoma) is more common and hard to diagnose in this case because the whole lung is fibrotic. Eosinophilic Granuloma : Langerhans cell granulomatosis. Smokers, M>F. They have Lytic bone lesion, pituitary Diabetes insipidus like that in sarcoidosis.
Causes pneumothorax in up to 50%. Chest HRCT: diffuse centrilobular nodules and cysts formation. See figure below We take lung Biopsy. Bronchoalveolar lavage: reveals increase Langerhans cell. Management: Stop smoking + sometimes Steroids. HRCT image from a patient with pulmonary Langerhans cell Histiocytosis showing diffuse centrilobular nodulation and cyst formation.
Lymphangioleiomyomatosis (LAM) Exclusively premenopausal women Immature smooth muscle proliferation in the lymphatic, vascular and alveolar wall. HRCT-Chest: Diffuse thin walled cystic lesion. Recurrent Pneumothorax, hemoptysis, Chylothorax because it affects the lymph. Management.: No Estrogen, and advice against pregnancy. Anti-Estrogen (progesterone), Oophorectomy. HRCT image from a patient with lymphangioleiomyomatosis showing characteristic thin-walled cysts throughout the parenchyma
The END Done By : Ibrahim Mahmoud