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

When the 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
cancer1
 First line treatment: local
excision
 Interferon (IFN) alfa therapy:
indicated as adjuvant
treatment2
1.
2.
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
Case presentation
80 year old male with malignant melanoma
 09/2011  Shave biopsy of scalp lesion
 11/2011  Excision and nodal dissection
 01/2012  Peginterferon alpha 2b
 12/2012  Shortness of breath for 6 weeks
Past Medical History
Malignant Melanoma
Hypertension
Medications
Peginteron alfa-2b
Amlodipine
Social History
Nonsmoker
No pets
No sick contacts
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
Chest X-ray
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
Chest CT Angiography
Apices
Mid-lung fields
Lung bases
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
Autoimmune work-up
ANA
C-ANCA, P-ANCA
Anti GBM Antibody
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%
 Other studies:  NEGATIVE
 Bacterial, mycobacterial
and fungal stain and
culture
Respiratory viral panel
PJP PCR
Cytology
(Normal<3%1)
1. Meyer K, Raghu G, Baughman R et al. An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular
Analysis in Interstitial Lung Disease. Am J Respir Crit Care Med Vol 185, Iss. 9, pp 1004–1014, May 1, 2012
Hospital course
Antibiotics and trial of diuresis  No response
Non-invasive positive pressure ventilation
Unrevealing infectious work-up  Discontinuation
of antibiotics
Methylprednisolone 125mg IV q6hrs  Clinical
improvement
Follow-up CT chest
2 months later
Discussion
Why did we suspect IFN-induced interstitial
lung disease (ILD) on this patient?
1. Negative work-up for infectious,
autoimmune and malignant processes
2. Findings on Chest CT
3. Lymphocytosis on BAL cell count
4. Clinical deterioration despite empiric
antibiotics
IFN-induced ILD
 Uncommon complication (0.01-0.3%)1
 Presenting symptoms: dyspnea, dry cough,
fever, fatigue, anorexia, myalgias2
 Average time of presentation: 12 weeks
1.
2.
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.
Case reports
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.
Treatment of IFN-induced ILD
 Discontinuation of IFN
 Corticosteroids1
1.
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.
Key points
IFN-induced Interstitial Lung Disease:
 Uncommon complication of IFN-alfa 2b
therapy, but potentially life threatening
 Should be a diagnosis of exclusion
Acknowledgements
 Mark Hamblin MD, FCCP
Division of Pulmonary and Critical Care
Department of Internal Medicine
University of Kansas Medical Center, Kansas City, Kansas
 Gary Doolittle MD
Division of Hematology and Oncology
Department of Internal Medicine
University of Kansas Medical Center, Kansas City, Kansas
Thank you!
Questions?
Case reports
IFN-related pulmonary toxicity
Interstitial pneumonitis
BOOP
ARDS
Pleural effusion
Asthma exacerbation
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