Sequelae of Therapy

Drug Reaction

Definition

Epidemiology

Occurs primarily with chemotherapy agents (in up to 10% of cases), antiarrhythmic agents (amiodarone), and antiseptic agents (nitrofurantoin), etc.

Etiology, pathophysiology, pathogenesis

Purely toxic or immunologic reaction with variable, unspecific manifestation: Diffuse alveolar damage Unspecific pneumonitis Bronchiolitis obliterans with organizing pneumonia Eosinophilic pneumonia.

Imaging Signs

Modality of choice

CT is preferable to plain radiography.

Radiographic and CT findings

– Diffuse alveolar damage: Bilateral ground-glass opacification that may include consolidations Especially busulfan.

– Nonspecific interstitial pneumonitis: Disseminated nodular ground-glass opacities and consolidations in addition to reticular changes, predominantly basal Especially amiodarone, methotrexate, and carmustine.

– Bronchiolitis obliterans with organizing pneumonia: Nodular ground-glass opacities and consolidations, predominantly peripheral Especially bleomycin, methotrexate, cyclophosphamide, amiodarone, nitrofurantoin, etc.

– Eosinophilic pneumonia: Nodular ground-glass opacities and consolidations, predominantly in the peripheral upper lobes Especially nitrofurantoin, penicillamine, antiinflammatory agents, and paraaminosalicylic acid.

Pathognomonic findings

Nonspecific findings Occurrence of symptoms concurrently with therapy is an important diagnostic criterion.

Clinical Aspects

Typical presentation

Nonspecific symptoms such as fever, malaise, nonproductive cough, and dyspnea of variable severity Restrictive ventilation defect.

Therapeutic options

Alternative treatment.

Course and prognosis

Variable.

What does the clinician want to know?

Tentative diagnosis in conjunction with a suggestive constellation of findings.

Fig. 13.1 Sirolimus reaction in a 71-year-old man receiving immunosuppressant macrolide therapy after kidney transplantation. CT shows predominantly basal ground-glass opacities with predominantly interstitial structures similar to findings in nonspecific interstitial pneumonitis.

Fig. 13.2 Pulmonary nitrofurantoin reaction in a 73-year-old man. Both the plain chest radiograph (a) and CT (b) show predominantly basal and peripheral nodular consolidations along with streaky densities similar to findings in bronchiolitis obliterans with organizing pneumonia.

Fig. 13.3 Pulmonary amiodarone reaction in a 70-year-old man.

a The plain chest radiograph shows heterogeneous interstitial shadowing (mixed pattern of streaky reticular shadows and ground-glass confluent opacities) in the right middle and upper lung fields and in the left upper lung field.

b CT also shows a mixed picture—most closely resembling nonspecific interstitial pneumonitis. Areas of normal parenchyma alternate with affected areas. Slight bilateral pleural effusion.

Differential Diagnosis

Pneumonic infiltrates

– Morphologically indistinguishable

– Clinical findings are crucial to the diagnosis

– Biopsy may be indicated

Pneumonitis, radiation reaction

– Limited to the irradiated field

Various forms of idiopathic interstitial pneumonia

– Morphologically indistinguishable

– An initial clinical situation with no history of medication is crucial to the diagnosis

Tips and Pitfalls

Pulmonary changes can be misinterpreted as attributable to causes other than medication, especially when they do not occur concurrently with therapy.

Selected References

Erasmus JJ, McAdams HP, Rossi SE. Drug-induced lung injury. Seminars Roentgenol 2002; 37: 72–81

Erasmus JJ, McAdams HP, Rossi SE. High-resolution CT of drug-induced lung disease. Radiol Clin North Am 2002; 40: 61–72

Radiation Reaction

Definition

Epidemiology

Affects 5–10% of patients receiving radiation therapy in the chest Depends on the irradiated volume, radiation dose and fractionation, and concurrent chemotherapy Rarely occurs at doses < 30 Gy, nearly invariably at doses > 40 Gy.

Etiology, pathophysiology, pathogenesis

Early reaction consists of radiation pneumonitis 1–3 months after therapy and diffuse alveolar damage with an intraalveolar exudate and formation of hyaline membranes Late reaction consists of radiation fibrosis 6–12 months after therapy or complete recovery.

Imaging Signs

Modality of choice

CT is preferable to plain radiography.

Radiographic and CT findings

Changes are essentially limited to the irradiated volume Early reaction consists Late reaction occasionally consists of fibrosis with signs of volume loss and development of traction bronchiectasis.

Pathognomonic findings

Changes not correlating with specific anatomy and limited to the irradiated field occurring in a time frame consistent with sequelae of radiation therapy.

Clinical Aspects

Typical presentation

Often asymptomatic Symptoms may otherwise include cough, subfebrile temperatures, dyspnea with restrictive ventilation defect, elevated erythrocyte sedimentation rate, and leukocytosis.

Therapeutic options

Steroids.

Course and prognosis

Good.

What does the clinician want to know?

Confirmation of the tentative diagnosis. Follow-up examination in symptomatic patients.

Differential Diagnosis

Superinfection

– Not limited to the irradiated field

– Clinical aspects

– Course under therapy

Recurrent tumor

– Volume increase

– New focal lesions

– Peritumoral lymphangitis (can be difficult to distinguish; clinical course is important)

Fig. 13.4 Radiation pneumonitis in a 68-year-old man with bronchial carcinoma in the right lung. CT shows relatively sharply demarcated bandlike ground-glass opacity extending from anterior to posterior. The opacity includes the hilar region and does not respect anatomic boundaries.

Selected References

Choi YW et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics 2004; 24: 985–997

Libshitz HI. Radiation changes in the lung. Semin Roentgenol 1993; 28: 303–320

Reperfusion Edema

Definition

Epidemiology

Direct sequela of lung transplantation, occurring in about 50% of cases.

Etiology, pathophysiology, pathogenesis

Occurs within 48 hours of transplantation Sequela of increased capillary permeability because of ischemia, impaired lymph drainage, and surfactant deficiency Leads to interstitial and alveolar edema.

Imaging Signs

Modality of choice

Radiographs CT is not indicated as primary modality.

Radiographic and CT findings

Canges due to edema include: Increased reticular shadowing Bronchial wall Ground-glass opacity.

Pathognomonic findings

Findings are nonspecific and are distinguishable from acute rejection or infection only by the time of their occurrence and their clinical course (see below).