Case
A 16 month old female with history of prematurity at 36 weeks gestation
presented to the emergency department with a 2 week history of
rhinorrhea, congestion, cough, and decreased activity with a recent ED
visit for vomiting and diarrhea that had since resolved. There were no
reports of obvious blood loss with hematemesis, hematochezia or
hemoptysis. She attended daycare where there were multiple sick
contacts. Her family history included severe SLE, rheumatoid arthritis
and fibromyalgia in her mother and severe SLE and scleroderma in her
maternal aunt. A CBC and CMP were obtained as part of her initial
work-up and were notable for severe anemia with hemoglobin of 2.9 and a
normal CMP. A repeat CBC again demonstrated severe anemia with a
hemoglobin of 2.7 and a reticulocyte count of 11.6%. Additional initial
lab studies revealed signs of iron deficiency anemia and were otherwise
unremarkable. Pertinent findings on her physical exam included a female
toddler who was tired-appearing and fussy, a flow murmur, tachycardia,
clear lungs, and a soft abdomen.
The patient was admitted to the PICU for pRBC transfusion, further
work-up and care. Her initial chest X-ray done on Day 2 of hospital
admission showed bilateral diffuse alveolar airspace disease. She was
given successive small (5 ml/kg) aliquots of PRBC’s. Her chest CT
(obtained about 12 days after admission, Figure 1 ) showed
bilateral patchy parenchymal opacities throughout the lungs with most
pronounced areas of dense opacification in the periphery. A flexible
bronchoscopy was done 13 days after admission and showed bloody
secretions in the lower lobes. The cytopathology from the
bronchoalveolar lavage fluid showed predominantly red blood cells,
macrophages (many hemosiderin- laden), neutrophils and foci of fibrin.
Oil-red-O also showed occasional lipid-laden machrophages. All cultures
(viral, bacterial, fungal and mycobacterial) were negative. Lab work-up
for autoimmune diseases and other infectious etiology was negative. A
left lung biopsy obtained on day 19 of admission showed acute and
chronic pulmonary hemorrhage syndrome with features consistent with
resolving acute capillaritis (see Figure 2 ). Within the tissue,
there were few EBV-positive cells but EBV infection did not appear to be
the cause of pulmonary bleeding. Direct immunofluorescence microscopy
showed a granular deposition of IgA and C3 in the alveolar walls.
Throughout her hospital stay, the patient was treated with Bipap and
oxygen (for intermittent hypoxia and respiratory distress), diuretics,
multiple blood transfusions and oral steroids (prednisone, 2 mg/kg/day).
Her hemoglobin levels gradually stabilized and she no longer required
respiratory support. She was hospitalized for a total of 23 days and was
discharged with a hemoglobin of 8.5, Hct of 35.1, and a reticulocyte
count 4.7%. Her discharge medications included prednisone 2 mg/kg/day,
ranitidine and iron supplementation. Her CXR prior to discharge showed
improved pulmonary opacities.
Following discharge from the hospital she was followed by pulmonology,
rheumatology and nephrology due to the IgA deposition noted on lung
biopsy. IgA nephropathy was eventually ruled out due to normal kidney
function and ultrasound.
At about 2.5 months following her initial admission while continuing
oral corticosteroids, a surveillance bronchoscopy showed continued
alveolar hemorrhage and the patient was again admitted to the hospital
for observation despite a stable Hb and CXR. She was started on
methotrexate 0.3 ml SQ weekly and continued prednisone 2 mg/k/day. Other
daily medications included ranitidine and atovaqone. Her immune
modulators were then changed from methotrexate to mycophenolate mefotil
20 mg/kg twice daily due to the possibility of improved pulmonary
penetration and IgA deposition noted on her biopsy. About 2 months
later, she had a surveillance bronchoscopy that showed continued lower
airway bleeding. Her Hb at that time was stable at 12.3 g/dl, however
the decision was made to change her immune modulator to a monthly
cyclophosphamide infusion at a dose of 45 mg/kg following a 3 day course
of pulse steroids (30 mg/kg/dose). She received 6 total doses of
cyclophosphamide. Following the completion of these infusions during
which time her prednisone was weaned to 0.5 mg/kg/day, a surveillance
CXR showed signs of continued pulmonary hemorrhage that was verified by
chest CT. She also had a dip in Hb to 9.8 g/dl and an elevated
Reticulocyte count to 5.3% and did not show signs of acute illness.
She then began a new long-term treatment regimen that included rituximab
infusions of 500 mg/m2 on days 0 and 14 and at 6 months, IV solumedrol
at a dose of 30 mg/kg IV (weekly for the first 3 months, then bi-weekly
for 3 months, then monthly for 2 months) and IVIG at 2 grams monthly for
3 months. Following that, she was then given oral azathioprine (approx.
2 mg/kg) for 3 years and her oral steroids were slowly weaned. About 10
months after starting the second phase, she was admitted to the hospital
for a week for multifocal pneumonia, gastroenteritis and relapse in her
capillaritis. Her Hb at that time dropped to 8.4 and was 9.8 g/dl prior
to discharge. At the time of that illness, she was getting azathioprine
daily and her steroids had been weaned to 2.5 ml every other day. During
the admission and following discharge, an antibiotic course was
completed, her azathioprine continued at 2 mg/ kg/day and her steroid
dose was increased back to 2 mg/ kg/ day. Her subsequent lab testing at
hospital follow up revealed a Hb of 13.1 g/dl. Her prednisone dose was
gradually weaned again to a final dose of 1 ml every other day and her
azathioprine dose was continued at 2 mg/kg/ day. After about 2 years of
continued therapy following the clinical relapse, her Hb has remained in
the normal range. She had a subsequent surveillance bronchoscopy that
did not show evidence of alveolar hemorrhage. Since that time, she is
not receiving medications and is an active 6 year old.