A 75-year-old Sudanese male presented with acute myocardial infarction and was treated including with amiodarone due to frequent PVCs on ECG. He was discharged after improvement but returned two weeks later with shortness of breath, dry cough, and fever. Examination found signs of bilateral lung fibrosis. He was diagnosed with amiodarone-induced interstitial pneumonitis-fibrosis based on radiological findings and improved after stopping amiodarone and receiving steroids and supportive care. Literature review discussed amiodarone-induced pulmonary toxicity as a serious adverse effect, with interstitial pneumonitis-fibrosis being common, and management involving discontinuing amiodarone and considering steroids

1. بسم الله الرحمن الرحيم Elshaab Teaching Hospital Unit Of Dr .Nawal Kordofani Case Presentation By Ahmed Hassan

2. Personal Data: Name: Age:75 year Sex:Male Res: Toti Tribe: Mahas Occ:Tailor D.O.A: 23/10/2003 C/O : Chest pain /7 hrs

3. H.P.I: This pt is a known case of HTN for the last 20 years but not on regular treatment.Presented with retrosternal ,constricting chest pain , radiated to the Lt shoulder and Lt arm associated with nausea and vomiting ,also there was sweating and restlessness.There was no cough,S.O.B,palpitations or syncopal attack.

4. Systemic Review : G.U.S: M.S.S: Un remarkable C.N.S: P.M.H: No P.H of similar condition. The Pt is not known to be diabetic or asthmatic No PH of chronic cough

5. F.H: No FH of similar condition, HTN ,DM ,or asthma No FH of sudden death. S.H :He is of moderate socioeconomic status, married with 5 daughters . Not smoker or alcohol consumer. D.H : He was on diltiazem 60 mg b.d but not regularly. Not known to be hypersensitive to any known drug.

6. O/E: He looks unwell not P,J or C J.V.P not raised Thyroid not enlarged L.N:not palpable Pulse was 100 /b.p.m regular of small and normal character, no R.F.D, peripheral pulses were intact. BP :110/75 C.V.S: Chest: Abdomen: N.A.D C.N.S:

7. Investigations done at that time showed: Hb:13.5 g/dl T.W.B.C: 6800 E.S.R: 45mm/h B. urea:52mg/ dl S.k+: 3.6 meq/L S.Na+: 133 meq/L R.B.S : 102 mg/dl C.X.R : not done E.C.G: showed extensive ant- M.I with unifocal P.V.Cs (SHOW) .

8. According to this presentation he was admitted to the CCU , received :morphia ,nitrates , streptokinase and lignocaine. On the 2 nd day his general condition was improved and also his E.C.G (SHOW). In addition to nitrates he received,aspirin captopril ,and amiodarone After one week he discharged in a good condition.(SHOW E.C.G on discharge):.

9. .Two weeks later he presented to the casualty again C/O : S.O.B even at rest and dry cough which was increased at night for 2 days.There was no chest pain , palpitations or syncopal attack . No orthopnea ,P.N.D ,and no haemoptysis, but the condition was associated with intermittent ,low grade fever not associated with sweating or rigor.

10. O/E : The Pt looks unwell, dyspnoic,not P,J or C. J.V.P not raised. Thyroid not enlarged. L.N : not palpable Pulse was 110 b.p m, irregular of small volume and normal character ,no R.F.D ,peripheral pulses were intact. B .P 80/50. Hands :N.A.D. C.V.S : Apex at 6 th i.c.s , lateral to the m.c.l, normal in character .No palpable thrill, no L.P.H and no palpable 2 nd H.S .Muffled S1,and S2 ,no added sound and no murmurs.

11. Chest: There is pectus exacavatum deformity . R.R 20/min. Chest moves equally . Trachea is central TVF : Decreased in the upper zones on both sides Impaired percussion note in the upper zones on both sides Decrease air entry on both upper and middle zones bilaterally There is bilateral coarse crepitations Abdomen CNS N.A.D.

12. SUMMARY: 75 Year-old Sudanese male presented to the casualty with acute MI,Received the treatment accordingly plus amiodarone due to the presence of frequent P.V.Cs on E.C.G, and discharged after showing remarkable improvement.Two weeks later he was readmitted again C/O S.O.B , dry cough and fever for with no P.H of lung disease, with signs suggesting bilateral lung fibrosis

13. ∆ /∆ : 1) Amiodarone-induced pulmonary toxicity 2)Cryptogenic F.A 3)Extrinsic allergic alveolitis 4) Sarcoidosis

14. Investigations: *C.B.C: Hb 14.1 g/dl E.S.R:55mm/h T.W.B.C 8500 Neut: 53% Lymph: 42% Mono: 2% Eos : 3% Platelets : 300000 R.B.Cs:Normochromic, normocytic. W.B.C :Of normal morphology.

15. *B.urea:68 mg/dl *S.K+ 2.5 meq/L *S .Na+ 134meq/L *S. creatinene 0.9 mg/dl *S. Ca++9.3 mg/dl *R.B.S: 96 mg/dl  E.C.G :( SHOW) C.X.R: showed diffuse reticulonodular shadowing mainly in the upper and mid zones. Also there is enlarged cardiac shadow (SHOW) *Old C.X.R (SHOW)

16.  Echo: Dilated poorly contracting LV with aneurysm of the LV and amural thrombus.There is dyskinesia of the IVS (Ischaemic cardiomyopathy)  C.T scan of the chest :There is reticular shadowing and peripheral honey combing affecting mainly the mid and upper zone. Also there is marked parenchymal distortion in the upper zones. A few small lymph nodes seen in the aorto-pulmonary pre-tracheal regions. All these features are in favor of sarcoidosis .(SHOW)

17. Hospital course: The Pt was admitted to the I CC U. Received oxygen, dopamine and dobutamine. Nitrates, captopril and amiodarone were stopped. Heparin and warfarin are given His general condition was improved: all symptoms subsided, and BP became 100/70. After 2 weeks C.X.R was repeated (SHOW).

18. Diagnosis: Amiodarone-induced interstitial pneumonitis-fibrosis

19. So the Pt was discharged in a good condition. On discharge he was on: Isosorbide dinitrate 10 mg b.d Captopril 12.5 mg /day and aspirin 100 mg/day

20. Literature Review Amiodarone-induced pulmonary toxicity

21. Amiodarone hydrochloride is commonly administered due to its effectiveness against both supraventricular and ventricular tachyarrhythmias and its lack of association with increased mortality. Amiodarone-induced pulmonary toxicity (AIPT) is one of the most serious adverse effects of amiodarone therapy and can be fatal.

22. Estimates of AIPT vary widely in the literature, likely due to lack of standard diagnostic criteria and administration of high dosages of amiodarone in earlier studies .Recent estimates suggest a frequency of 3% or less. Several forms of pulmonary toxicity have been described with amiodarone, the most common of which is (1)interstitial pneumonitis-fibrosis (2) acute respiratory distress syndrome, (3) BOOP, (4) and a solitary pulmonary mass

23. *Mechanisms ofAIPT . (1) A direct toxic reaction in which cell injury occurs due to accumulation of cellular phospholipids secondary to inhibition of lysosomal phospholipases by the drug. (2) S econd is an indirect immunologic mechanism with CD8 T cell lymphocytosis

24. Onset of AIPT May be rapid, occurring within days, or, more commonly, insidious, occurring after several months of therapy . Risk factors for AIPT include dose and, potentially, duration of treatment with the drug, and abnormal baseline pulmonary function. Dosages of 400 mg/day or less are believed to be associated with a lower frequency of AIPT ] Duration of therapy is thought to pose a risk due to the high cumulative amount of amiodarone to which the person is exposed

25. Symptoms of AIPT include fever, nonproductive cough, pleuritic chest pain, and dyspnea . Physical findings may include diffuse rales and a pleural rub Since the signs and symptoms are nonspecific and often similar to those in patients with heart failure, pulmonary emboli, and pneumonia, the diagnosis is one of exclusion

26. Management of AIPT ideally involves(1)discontinuation of amiodarone. (2)corticosteroids were documented to be effective in case reports and should be considered.Although specific steroid regimens often are not reported, prednisone 40-60 mg/day with tapering over 2-6 months was suggested .

27. If the patient's presentation is not life threatening and amiodarone cannot be withdrawn because it is the only or optimal therapy available for a patient, lowering the dosage and administering concurrent low-dose steroids may be effective. Supportive therapy to manage respiratory distress should be started as necessary.

28. The prognosis of patients with AIPT is generally good as pulmonary toxicity is often reversible. Mortality rates vary widely because death may be due to the underlying cardiac disease, amiodarone toxicity, or both. In patients who develop acute respiratory failure and require mechanical ventilation, mortality ranges from 50-100%. However, death due to AIPT itself was 5-10% in earlier studies that gave dosages of more than 400 mg/day .

29. The lowest effective dosage of amiodarone should be given. A simple and important screening method for AIPT involves patient self-reporting of pulmonary symptoms such as nonproductive cough, dyspnea, and pleuritic chest pain. Patients should be instructed to report development of such symptoms promptly, as this is often the earliest indication of AIPT and early detection is vital.

30. . In addition, baseline chest radiograph and pulmonary function tests, with repeat chest films every 3 months, are suggested for monitoring. However, as AIPTcan present rapidly, the value of serial chest radiograph monitoring is questionable .

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