PRESENTATION OF CASE

 A 61 year-old woman was admitted to this hospital because of respiratory failure.

She had been well until 4 years before admission, when a diagnosis of granulomatous

polyangiitis was made, characterized by uveitis and pulmonary hemorrhage with respiratory

failure and requiring intubation.

Treatment with azathioprine, the titer of antimyeloperoxidase antibodies normalized within 5

months after the start of treatment and remained normal.Patient had a history of Poland

syndrome (agenesis of the right breast, pectoralis muscle, and the third and fourth costal

cartilages) and had received a silicone implant in the right breast 28 years earlier.

Nine months before admission, the patient reported pain associated with the right breast

implant; it was removed and replaced with a saline implant at another hospital. For 6 weeks

after the procedure, there was drainage of sanguinous fluid and local induration at the site.

Laboratory-test results are shown in TABLE 1Laboratory Data.. The dose of azathioprine was

decreased from 75 mg to 50 mg daily. Because of persistent pain at the site, the implant was

replaced 7 months before admission and again 3 weeks before admission, with

reconstruction of the right chest wall. Five weeks before admission, the patient began to

have dyspnea on exertion and intermittent back pain. The platelet count reportedly

decreased to 16,000 per cubic millimeter. A specimen from a bone marrow biopsy reportedly

revealed an increased number of megakaryocytes, which was suggestive of peripheral

destruction of platelets. Azathioprine and trimethoprim –sulfamethoxazole were stopped, and

prednisone (40 mg daily) and narcotic analgesia were administered. During the 2 weeks

before admission, intravenous immune globulin and a dose of romiplostim were given,

without improvement. Testing for antineutrophil cytoplasmic antibodies (ANCA) was

negative. The dose of prednisone was tapered to 20 mg daily. The day before admission,

dyspnea worsened. The patient came to the emergency department at this hospital.

The patient reported a nonproductive cough, pain in the right upper back, but no other chest-

wall or breast pain; she reported no fevers, chills, sweats, hemoptysis, urinary or bowel

symptoms, or edema. She had a history of hypothyroidism, hypertension, supraventricular 

tachycardia, hyperlipidemia, and herpes zoster in a thoracic dermatome (2 years earlier);

she also had a remote history of cholecystectomy and tonsillectomy. Medications included

prednisone, atenolol, levothyroxine, simvastatin, estrogen (vaginal), multivitamins, and iron.

She had no known allergies. She was married, had no children, and worked in an office. She

had stopped smoking 25 years earlier and drank alcohol rarely. Her mother had had

hypertension and died of heart failure, and her father died of emphysema.

 

On examination, the blood pressure was 119/56 mm Hg, the pulse 58 beats per minute, the

temperature 35.6°C, the respiratory rate 20 breaths per minute, and the oxygen saturation

93% while she was breathing 3 liters of oxygen per minute through a nasal cannula. There

were fine inspiratory crackles in both lungs, and there was an implant in the right breast, with

well-healed scars on the right chest wall and breast without erythema, tenderness,

fluctuance, crepitance, or drainage; there was no axillary lymphadenopathy. The remainder 

of the examination was normal.

Serum levels of electrolytes, protein, albumin, globulin, bilirubin, alanine aminotransferase,

aspartate aminotransferase, calcium, phosphorus, magnesium, troponin T, troponin I, and

creatine kinase isoenzymes were normal, as were results of tests of coagulation; other test

results are shown in table 1. An electrocardiogram was normal.

Computed tomography (CT) of the chest, after the administration of intravenous contrast

material, performed according to pulmonary embolism protocol, revealed no evidence of 

pulmonary embolism. There were multifocal areas of ill-defined ground-glass opacities and

consolidation in all lobes of the lungs and scattered discrete nodules, some with a

surrounding ground-glass halo; there was layering of a small pleural effusion on the left side

and a loculated pleural effusion within the right major fissure, and there were multiple pleural

or pleural-based nodules. There was a right breast implant with a surrounding minimally

enhancing soft-tissue mass containing foci of gas superiorly, which extended through the

chest wall into the anterior mediastinum.

 A nasal specimen showed no evidence of respiratory viruses or methicillin-resistant

staphylococcus. Blood cultures were sterile; urinalysis revealed trace ketones and protein

and was otherwise normal. Vancomycin, cefepime, piperacillin –tazobactam, levofloxacin,

trimethoprim –sulfamethoxazole, metronidazole, oseltamivir, and methylprednisolone were

administered, and levothyroxine, simvastatin, atenolol, and iron sulfate were continued.

Oxygen supplementation was increased to 4 liters at rest and 6 liters when walking, to

maintain oxygen saturation between 92 and 94%.

Early on the third hospital day, the respiratory rate increased to 28 breaths per minute,

oxygen saturation decreased to 87%, and diffuse crackles were heard on auscultation.

Serum levels of vitamin B12, folate, iron, iron-binding capacity, IgG and IgA were normal.

Testing was negative for ANCA, lupus anticoagulant, antiphospholipid IgM and IgG

antibodies, and urinary legionella antigen; other test results are shown in table 1. A chest

radiograph showed persistent diffuse bilateral air-space opacities with multiple coalescing

pulmonary nodules. Red cells and platelets were transfused.

Later that day, the patient was transferred to the intensive care unit for elective intubation.

Bronchoscopic examination with bronchoalveolar lavage of the right middle lobe revealed

diffuse alveolar hemorrhage. The lavage fluid was red, with a hematocrit of less than 3.0%

 

(reference range, 0) and a white-cell count of 463 per cubic millimeter (72% neutrophils, 2%

band forms, 3% lymphocytes, 6% monocytes, 1% eosinophils, and 16% macrophages).

Hemosiderin-laden macrophages were present. There was no evidence of respiratory

viruses, fungi (including Pneumocystis jirovecii ), bacteria, or acid-fast bacilli. After the

procedure, hypotension developed and pressors were begun. Trimethoprim –

sulfamethoxazole was stopped, and liposomal amphotericin B and atovaquone were added.

Pathological examination of a specimen from a bone marrow biopsy revealed trilineage

hematopoiesis and no abnormal lymphocyte populations or cytogenetic abnormalities. On

the fourth day, cultures remained negative, and antimicrobial agents except for atovaquone

were stopped.

During the next week, the patient remained dependent on the ventilator and pressors; large

ecchymoses developed on the skin. Pulmonary suctioning produced thick, bloody sputum,

and transfusions of platelets and fresh-frozen plasma were administered. Transthoracic

echocardiography revealed right ventricular hypertrophy and a left ventricular ejection

fraction of 74%. Aminocaproic acid, immune globulin, and romiplostim were administered,

and parenteral nutrition was begun. On the ninth day, cyclophosphamide, mesna, and

ganciclovir were begun.

On the 10th day, testing for antibodies to Borrelia burgdorferi, ehrlichia, and anaplasma was

negative. The galactomannan antigen index of the bronchoalveolar-lavage fluid from the

third day was 1.03 (negative test, <0.5). Repeat bronchoscopy revealed blood-tinged

secretions in all segments of the lungs, without focal lesions or evidence of active bleeding.

Examination of bronchial washings showed a moderate number of leukocytes, with no

microorganisms, and testing for respiratory viruses was negative. The administration of 

doxycycline was begun.

On the 13th day, cultures of the bronchoalveolar-lavage fluid grew aspergillus. Doxycycline

was stopped, voriconazole was begun, and ganciclovir was continued. On the 14th day,

oxygen saturation decreased, and acidosis and renal failure developed (table 1). In

consultation with the patient's family, a decision was made to continue care, without

escalation for further deterioration. The next day, the patient died.

 An autopsy was performed.