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When th e treatment becomes the problem

When th e treatment becomes the problem. Sonia M. Castillo MD Mark Hamblin MD , FCCP Department of Internal Medicine University of Kansas Medical Center, Kansas City. Background. Melanoma: 5th most prevalent cancer 1 First line treatment: local excision

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When th e treatment becomes the problem

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  1. When the treatment becomes the problem Sonia M. CastilloMD Mark Hamblin MD, FCCP Department of Internal Medicine University of Kansas Medical Center, Kansas City

  2. Background • Melanoma: 5th most prevalent cancer1 • First line treatment: local excision • Interferon (IFN)alfa therapy: indicated as adjuvant treatment2 • Kim KB, Davies MA, Rapini RP, Hwu P, Bedikian AY. Chapter 39. Malignant Melanoma. In: Kantarjian HM, Wolff RA, Koller CA, eds. The MD Anderson Manual of Medical Oncology. 2nd ed. New York: McGraw-Hill; 2011. • Ascierto PA, Gogas HJ, Grob JJ et al. Adjuvant interferon alfa in malignant melanoma: an interdisciplinary and multinational expert review. Critial Reviews in Oncology/Hematology. 2013;85:149-161

  3. Case presentation 80 year old male with malignant melanoma • 09/2011  Shave biopsy of scalp lesion • 11/2011  Excision and nodal dissection • 01/2012  Peginterferonalpha 2b • 12/2012  Shortness of breath for 6 weeks

  4. Past Medical History • Malignant Melanoma • Hypertension Social History • Nonsmoker • No pets • No sick contacts Medications • Peginteron alfa-2b • Amlodipine

  5. Physical exam Temp=38.2C HR=102 BP=122/58 RR=24 SO2=88% on room air • General: Well-developed male in mild respiratory distress • Cardiovascular: Tachycardic • Respiratory: Bibasilar fine crackles • Extremities: no clubbing

  6. Chest X-ray

  7. Initial laboratory testing • White blood cell count: 6.2 • Neutrophils: 54% • Lymphocytes: 34% • Monocytes: 12% • Arterial blood gas: 7.49/30/55/23 • B-type natriuretic peptide: 39

  8. Chest CT Angiography Apices Mid-lung fields Lung bases

  9. Infectious work-up • Bacterial and AFB smear and culture • Legionella urine antigen • Mycoplasma IgG and IgM • Aspergillus galactomannan • Fungitell • Histoplasma and coccidioides urine antigens • Cryptococcal serum antigen • Respiratory viral panel Negative

  10. Autoimmune work-up • ANA • C-ANCA, P-ANCA • Anti GBM Antibody Negative

  11. Bronchoalveolar lavage • Cell count: • Red blood cells: 1450/uL • White blood cells: 360/uL • Monocytes: 55% (Normal>85%1) • Lymphocytes: 29% (Normal=10-15%1) • Neutrophils: 16% (Normal<3%1) • Other studies: • Bacterial, mycobacterial and fungal stain and culture • Respiratory viral panel • PJP PCR • Cytology  NEGATIVE 1. Meyer K, Raghu G, Baughman R et al. An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of BronchoalveolarLavage Cellular Analysis in Interstitial Lung Disease. Am J Respir Crit Care Med Vol 185, Iss. 9, pp 1004–1014, May 1, 2012

  12. Hospital course • Antibiotics and trial of diuresis • Non-invasive positive pressure ventilation • Unrevealing infectious work-up • Methylprednisolone 125mg IV q6hrs • No response •  Discontinuation of antibiotics  Clinical improvement

  13. Follow-up CT chest 2 months later

  14. Discussion Why did we suspect IFN-induced interstitial lung disease (ILD) on this patient? • Negative work-upfor infectious, autoimmune and malignant processes • Findings on Chest CT • Lymphocytosis on BAL cell count • Clinical deterioration despite empiric antibiotics

  15. IFN-inducedILD • Uncommon complication (0.01-0.3%)1 • Presenting symptoms:dyspnea, dry cough,fever, fatigue, anorexia, myalgias2 • Average time of presentation: 12 weeks • Solsky J, Liu J, Peng M, Schaerer M, Tietz A. Rate of interstitial pneumonitis among hepatitis virus C infected patients treated with pegylated infeterferon. J Hepatol. 2009; 50 Suppl 1: S238. • Ji FP, Li ZX, Deng H et al. Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C. World Journal of Gastroenterology. 2010;16(35):4394.

  16. Case reports

  17. Diagnosis of IFN-induced ILD1 • Exclusion of other etiologies • Compatible chest CT • Lymphocytosis on BAL cell count • Resolution of symptoms and infiltrates after cessation of therapy 1. Ji F-P. Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C. World Journal of Gastroenterology. 2010;16(35):4394.

  18. Treatment of IFN-induced ILD • Discontinuation of IFN • Corticosteroids1 • Puente Vazquez J, Moreno Anton F, Grande Pulido E, Lopez Tarruella-Cobo S, Perez Segura P, Diaz-Rubio E. Interstitial pneumonitis and lung fibrosis during adjuvant treatment of melanoma with interferon alpha according to the Kirkwood schedule. Dermatology. 2005;210(3):247-249.

  19. Key points IFN-induced Interstitial Lung Disease: • Uncommon complication of IFN-alfa 2b therapy, but potentially life threatening • Should be a diagnosis of exclusion

  20. Acknowledgements • Mark Hamblin MD, FCCP Division of Pulmonary and Critical Care Department of Internal Medicine University of Kansas Medical Center, Kansas City, Kansas • Gary DoolittleMD Division of Hematology and Oncology Department of Internal Medicine University of Kansas Medical Center, Kansas City, Kansas

  21. Questions? Thank you!

  22. Case reports

  23. IFN-related pulmonary toxicity • Interstitial pneumonitis • BOOP • ARDS • Pleural effusion • Asthma exacerbation

  24. Cases with other malignancies • Melanoma. Puente Vasquez et al. Dermatology 2005 • Hemangioendotelioma. Wolf et al. Clinical Toxicology 1997 • CML. Yufu et al. American Journal of Hematology 1994

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