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The Missing Antibody: The Pitfalls of ANCA Testing

Chest computed tomography showing extensive bilateral patchy air space infiltrates and ground-glass changes.
Chest computed tomography showing extensive bilateral patchy air space infiltrates and ground-glass changes.

A 44-year-old white woman presented to the hospital with acute shortness of breath while on a flight back to England from a holiday in Turkey. She denied having a productive cough, hemoptysis, or chest or calf pain. She was asthmatic, and her symptoms were improved by repeated administration of her salbutamol inhaler during the flight.

She had a past medical history of nasal polyps that had required surgical intervention 2 years previously.

One month previously she had been treated with a course of amoxicillin for “chronic” otitis media and was awaiting an ear, nose, and throat (ENT) specialty appointment. She had also developed swollen, tender metacarpophalangeal and ankle joints and was found to have a positive rheumatoid factor. Her symptoms subsequently improved on a short course of prednisolone and she felt well enough to go on holiday.

She worked as a secretary for a law firm, never smoked, and had a long-term partner. She drank a bottle of wine a week. She had no children and had never been pregnant.

Assessment

On presentation she had a temperature of 37.4°C (99.3°F) and a respiratory rate of 20 breaths per minute. Her heart rate was 80 beats per minute and blood pressure was 125/67 mmHg. She required oxygen supplied at 10 L/min to maintain her oxygen saturations above 95%. Auscultation of her chest revealed bilateral crackles, and urine dipstick test revealed 3+ blood, 2+ protein, and was negative for pregnancy. The remainder of her physical examination was unremarkable.

Initial investigation results are shown in Table 1. Thorax computed tomography (Figure 1) demonstrated extensive bilateral patchy air space infiltrates and ground-glass changes but no evidence of embolic disease.

Given the history, elevated C-reactive protein, anemia, and diffuse alveolar infiltration, a diagnosis of pulmonary hemorrhage, secondary to an autoimmune or vasculitic process, and a superimposed chest infection was made.

She was transfused with 2 units of blood and treated with intravenous co-amoxiclav and oral doxycycline; 500 mg intravenous methylprednisolone was given over 3 days, then converted to oral prednisolone at 60 mg per day.

Results of viral serology and immunological testing were available on day 3 of admission (Table 2). Repeated samples remained serologically negative for any specific autoimmune process.

Lung spirometry on day 4 demonstrated a DLCOc (corrected transfer factor) and KCO (transfer coefficient) at 104% and 88% of predicted, respectively.

Given the complexity of the case, a lung biopsy was undertaken on day 12 (Figure 2). This demonstrated foci of organizing pneumonia with evidence of pulmonary hemorrhage but no active vasculitis.

 

To read this article in its entirety please visit our website.

-James Wingfield Digby, MD, MRCP, DTMH, Brendan Tinwell, MD, FRCPath, Joanna Sheldon, PhD, FRCPath, Joe Wang, MD, MRCP, PhD

This article originally appeared in the March 2017 issue of The American Journal of Medicine.

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