Case C onference

1. Case Conference 3A Asuncion, Gewelene to Balolong, Joanmarie

2. 1. Diagnostic Approach to Pleural Effusion

3. Pleuropulmonary manifestations of systemic lupus erythematosus • Pleuritis occurs in 17–60% of patients at some point in the course of the disease. • The most common thoracic manifestation of SLE is pleuritis. • Pleuritic pain is present in 45–60% of patients and may occur with or without apleural effusion • Clinically apparent pleural effusions have been reported in up to 50% of patients with SLE3 and may be found in up to 93% of cases at necropsy Keane et al. Pleuropulmonary manifestations of systemic lupus erythematosus. Thorax 2000;55:159-166

5. Evaluation of Pleural Effusion • Hx and Physical Examination • Imaging • Pleural Thoracentesis • Pleural Fluid Analysis • Other Diagnostic Procedures • Summary of Clinical Practice Recommendations

6. History and Physical Examination • Initial clinical assessment with detailed history should be directed at identifying clues to the possible underlying cause of pleural effusion. • Chest examination of a patient with pleural effusion is notable for: • dullness to percussion, decreased or absent tactile fremitus, decreased breath sounds, and no voice transmission.

7. Imaging • Chest radiography • Postero-anterior chest radiography is abnormal when pleural fluid is >200 ml. • Free pleural fluid may blunt the costophrenic angle; form a meniscus laterally; or hide in a subpulmonic location, simulating an elevated hemidiaphragm • Lateral and lateral decubitus

8. Imaging PA View Lateral Decubitus

9. Alternative Imaging Studies • Ultrasonography (US) will detect the presence of as little as 5–50 ml of pleural fluid and is 100% sensitive for effusions; loculated effusion • Chest CT more detailed information about the pleural space in relation to other intrathoracic structures is required, CT is superior to US • MRI

10. Pleural Thoracentesis • Not all patients with pleural effusion should undergo thoracentesis • Indications: • Presence of a clinically significant pleural effusion (> 10 mm thick) with no known cause • Unilateral pleural effusion • Bilateral pleural effusion with fever, pleuritic chest pain, asymmetric effusion or persistent for > 3 days Dr. Bautista Notes – Pleural Disease Lecture. Pulmo/Endo Module. 2009

11. Appearance of Pleural Fluid • Massive and hemorrhagic or sero-hemorrhagic pleural effusions are likely to be malignant. • Pus is characteristicof pleural empyema • A cloudy fluid may be due to parapneumonic pleural effusion and/or to empyema. • A chocolate or gelatinous pleural fluid may be the consequence of paragonimiasis. • A green colored fluid may indicate rheumatoid effusion • A‘milky’ appearance chylothorax. • Classically transudates are limpid, clear yellow-colored fluids. It is also important to smell the pleural fluid because an unpleasant smell suggests infection by anaerobic bacteria. Froudarakis, M. Diagnostic Work-Up of Pleural Effusions. Respiration 2008;75:4–13

12. The first question to be stressed is: is this fluid an exudate? Light’s Criteria Fauci et al. Harrison’s Internal Medicine.16th Edition.

13. Algorithm ctd. Fauci et al. Harrison’s Internal Medicine.16th Edition.

14. Cell Count and Differential Count of Pleural Fluid Blood Cells • RBC > 100,000 /mm3 • Neutrophils > 10,000 / mm3 • Lymphocytes > 50% • Eosinophils > 10% Suggested Diagnosis • Trauma, pulmonary infarction, malignancy • Acute disease process: pyogenic infections, pulmonary infarction, pancreatitis, intra-abdominal abscess or early tuberculosis • Pleural tuberculosis, pleural malignancy • Pleural fluid exposed to air or blood, drug reaction, benign asbestos pleural effusion, paragonimiasis or Churg-Strauss syndrome. Dr. Bautista Notes – Pleural Disease Lecture. Pulmo/Endo Module. 2009

15. Chemical Analysis of Pleural Fluid Chemistry • Pleural fluid glucose < 60 mg/dL • Pleural fluid LDH level • Pleural fluid pH (<7.0) • High amylase • High hyaluronic acid Suggested Diagnosis • Parapneumonic effusion, rheumatoid disease, tb pleurisy, malignant effusion, paragonimiasis, hemothorax or Churg-Strauss syndrome. • Indicates degree of inflammation in the pleural space. • Determine presence of complicated parapneumonic effusion and placement of chest tube. • Pancreatitis, esophageal rupture or malignant pleural effusion. • Mesothelioma Dr. Bautista Notes – Pleural Disease Lecture. Pulmo/Endo Module. 2009

16. Other Examinations of Pleural Fluid Bacteriologic studies • Gram stain and culture • Acid-fast stain and culture • Fungal stain Cytologic tests • Malignant cells in pleural fluid carries a poor prognosis Immunologic studies • Antinuclear antibody titer < 1:160 in SLE • Rheumatoid factor > 1:320 in Rheumatoid arthritis Dr. Bautista Notes – Pleural Disease Lecture. Pulmo/Endo Module. 2009

17. Algorithm ctd. Fauci et al. Harrison’s Internal Medicine.16th Edition.

18. Algorithm ctd. Fauci et al. Harrison’s Internal Medicine.16th Edition. Light, RW. Diagnostic Approach to Pleural Effusion in Adults. Am Fam Physician 2006;73:1211-20.

19. Other Diagnostic Procedures • Needle biopsy of the pleura • INDICATION: • Suspected malignancy or tuberculosis • Pleuroscopy/Thoracoscopy • INDICATION: • Should be considered when less invasive tests have failed to give a diagnosis. Froudarakis, M. Diagnostic Work-Up of Pleural Effusions. Respiration 2008;75:4–13

20. Summary of Clinical Recommendations for Practice Light, RW. Diagnostic Approach to Pleural Effusion in Adults. Am Fam Physician 2006;73:1211-20.

21. 2. Interpret the arterial blood gas.

22. PARTIALLY COMPENSATED METABOLIC ALKALOSIS WITH HYPOXEMIA

23. 3. ACR Criteria for SLE

24. > 4 of the ff will document the diagnosis is likely to be SLE Mnemonic: A RASH POINtsMD AMERICAN COLLEGE of RHEUMATOLOGY Photosensitivity Oral ulcers Immunological disorder (positive LE cell, anti-DNA, anti-Sm, false positive ....serological test for syphilis) Neurological disorders (seizures or psychosis, In the absence of other causes) Malar rash Discoid rash Arthritis Renal disease (proteinuria, cellular casts) ANA (positive antinuclear antibody) Serositis (pleurisy or pericarditis) Haematological disorders (haemolytic anaemia or leucopenia or lymphopenia or thrombocytopenia) Criteria for SLE REFERENCE: Braunwald, et.al Harrison’s Priniciples of Internal Medicine 17th ed. 2006. page 2077 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1753676/pdf/v060p00638a.pdf

25. 4. Reasons for the Immunocompromised state of the patient

26. Prolonged Steroid use (Methylprednisone) • Glucocorticoids are the most effective steroids used for immunosuppression. • Preferentially inhibit T-cell functions • inhibit the entry of cells into the G1 phase • arrest the progression of activated lymphocytes from the G1 to the S phase of the cell cycle. • inhibit the lymphocyte proliferative response to mitogens, antigens, alloantigens and autoantigens. • Corticosteroids inhibit production of IL-1, IL-2, TNFa, IL-4 and IL-6. • Effect on monocyte–macrophage functions • suppress bactericidal activity • interfere with antigen presentation • impair chemotaxis, • decrease response to migration inhibition factor • suppress expression of Fc and complement receptor. Harrisons Manual of Internal Medicine 17th ed

27. Immunosuppresants • Rituximab • Cyclophosphamide • Cyclophosphamide is an alkylating agent that is toxic for cells at all stages of the mitotic cycle, including the intermitotic (G0) phase. • more toxic for cycling than for resting cells (G0). • more cytotoxic for B cells than for T cells Harrisons Manual of Internal Medicine 17th ed

28. 5. Mode of Action, Antimicrobial Coverage & Side Effects of Piperacillin-Tazobactam and Fluconazole

29. Piperacillin/Tazobactam

30. Piperacillin/Tazobactam • Piperacillin • Extended spectrum penicillins • Bactericidal • Binds with PBP-1 and PBP-3 transpeptidation inhibition • Failure of cell wall mucopeptide synthesis • Failure to inactivate inhibitor of autolytic enzymes • Tazobactam • Beta-lactamase inhibitors

31. Coliforms B. fragilis Pneumococcus Mycoplasma Legionella H. influenzae S. aureus C. pneumoniae Actinomycosis P. aeruginosa Streptococcus spp. M. catarrhalis N. meningtidis N. gonorrhea Enterobacteriaceae E. coli Antimicrobial Coverage

32. Common Rash Pruritus Diarrhea Nausea and vomiting Phlebitis Headache Constipation Insomnia Dyspepsia Fever Agitation Hypokalemia Hypotension HTN elevated liver transaminases prolonged INR Serious Reactions anaphylactic/anaphylactoid reaction Hypersensitivity Clostridium difficile associated diarrhea Thrombocytopenia Seizures Interstitial nephritis Renal failure Cholestatic jaundice Hepatitis Erythemamultiforme Stevens-Johnson syndrome Toxic epidermal necrolysis Agranulocytosis Pancytopenia Side Effects

33. Fluconazole

34. Mode of Action inhibit the fungal cytochrome P-450 3-A dependent enzyme 14-alpha demethylase interrupt the synthesis of ergosterol depletion of ergosterol in the cell membrane accumulation of toxic intermediate sterols increased membrane permeability inhibition of fungal growth http://www.doctorfungus.org/thedrugs/antif_pharm.htm

38. Antimicrobial Coverage • Used to treat fungal infections • Effective against broad spectrum of fungi including: • Dermatophytes (Tinea infections) • Yeasts (such as Candida and Malassezia) • Systemic Infections (such as Cryptococcosis and Coccidiodomycosis) Katzung, BG. Basic and Clinical Pharmacology 10th ed. Antifungal Agents, Chap 48 . McGraw – Hill.

39. Fluconazole • Azole of choice in the treatment and secondary prophylaxis of cryptococcal meningitis • The agent most commonly used for tx of mucocutaneouscandidiasis • Prophylaxis of candidiasis in Bone Marrow transplant patients Katzung, BG. Basic and Clinical Pharmacology 10th ed. Antifungal Agents, Chap 48 . McGraw – Hill.

40. Side Effects • More Common Side Effects • mild and short-lived • Diarrhea • Nausea & vomiting • Stomach Pain • Abnormal taste in the mouth • Headache • Acne http://www.mydr.com.au/cmis/ReducedPDFs/CMR09213.pdf

41. Side Effects • Serious Side Effects • rare, may need urgent medical attention • Skin reactions/ rash • Bleeding or bruising more easily than normal • Flaking of the skin • Yellowing of the skin or eye, which may indicate hepatitis • Worsening of your infection, with symptoms such as fever, severe chills http://www.mydr.com.au/cmis/ReducedPDFs/CMR09213.pdf

42. Side Effects • Very Serious Side Effects • very rare; need urgent medical attention or hospitalization • Symptoms of a hypersensitivity reaction • swelling of the face, lips, mouth or throat  difficulty in swallowing or breathing • Seizures • Fast or irregular heartbeat http://www.mydr.com.au/cmis/ReducedPDFs/CMR09213.pdf

43. 6. Criteria and Clinical Manifestations of Antiphospholipid Syndrome

44. Clues from the History… History of any of the following should raise the examiner's suspicion for APS: • Thrombosis (eg, DVT/PE, MI, transient ischemic attack [TIA], or CVA, especially if recurrent, at an earlier age, or in the absence of other known risk factors) • Miscarriage (especially late trimester or recurrent) or premature birth • History of heart murmur or cardiac valvular vegetations • History of hematologic abnormalities, such as thrombocytopenia or hemolytic anemia • History of nephropathy • Nonthrombotic neurologic symptoms, such as migraine headaches, chorea, seizures, transverse myelitis, Guillain-Barré syndrome, or dementia (rare) • Unexplained adrenal insufficiency • Avascular necrosis of bone in the absence of other risk factors • Pulmonary hypertension http://emedicine.medscape.com/article/333221-overview

45. Findings from the Physical Examination • Cutaneous • Livedoreticularis (see image below) • Superficial thrombophlebitis • Leg ulcers • Painful purpura • Splinter hemorrhages • Venous thrombosis • Leg swelling (DVT) • Ascites (Budd-Chiari syndrome) • Tachypnea (PE) • Peripheral edema (renal vein thrombosis) • Abnormal funduscopic examination results (retinal vein thrombosis) • Arterial thrombosis • Abnormal neurologic examination results (eg, CVA) • Digital ulcers • Gangrene of distal extremities (see image below) • Signs of MI • Heart murmur (frequently aortic) or mitral insufficiency (Libman-Sacks endocarditis) • Abnormal funduscopic examination results (retinal artery occlusion) http://emedicine.medscape.com/article/333221-overview

46. Revised Criteria for Diagnosis of APSInternational Consensus Statement • At least one clinical criterion and one laboratory criterion • The clinical criteria are as follows: • Vascular thrombosis • Pregnancy morbidity • Laboratory criteria • Other antiphospholipid (aPL)–associated clinical features recognized by the 2006 consensus statement but not included in the criteria http://emedicine.medscape.com/article/333221-overview

47. Clinical CriteriaVascular Thrombosis • One or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ confirmed by findings from imaging studies, Doppler studies, or histopathology. • Thrombosis may involve the cerebral vascular system, coronary arteries, pulmonary system (emboli or thromboses), arterial or venous system in the extremities, hepatic veins, renal veins, ocular arteries or veins, or adrenal glands. Investigation is warranted if a history of DVT, PE, acute ischemia, MI, or CVA (especially when recurrent) is present in a younger individual (males <55 y; females <65 y) or in the absence of other risk factors. http://emedicine.medscape.com/article/333221-overview

48. Clinical CriteriaPregnancy morbidity • One or more late-term (>10 weeks' gestation) spontaneous abortions • One or more premature births of a morphologically healthy neonate at or before 34 weeks’ gestation because of severe preeclampsia or eclampsia or severe placental insufficiency • Three or more unexplained, consecutive, spontaneous abortions before 10 weeks’ gestation http://emedicine.medscape.com/article/333221-overview

49. Laboratory Criteria and “Extra” • Laboratory criteria: • Patients must have • (1) medium to high levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL), • (2) anti–beta-2 glycoprotein I, or • (3) LA on at least 2 occasions at least 12 weeks apart. • Other antiphospholipid (aPL)–associated clinical features recognized by the 2006 consensus statement but not included in the criteria include: • cardiac valve disease • livedoreticularis • Thrombocytopenia • Nephropathy • neurologic manifestations http://emedicine.medscape.com/article/333221-overview