Abstract
Antiglomerular basement membrane disease is a small vessel vasculitis
which affects the lungs and kidneys, causing diffuse alveolar
haemorrhage and rapidly progressive glomerulonephritis respectively. It
is extremely uncommon in children. Diagnosis requires the presence of
specific anti-GBM autoantibodies. Presentation with renal involvement is
much more common than pulmonary involvement. However, a small proportion
of cases might have isolated pulmonary involvement. Minimal changes on
renal biopsy culd still be present in these patients. Treatment of
antglomerular basement membrane disease includes plasmapheresis and
immunosuppression. We present a case where a 7 year old boy presented
with a long history suggestive of pulmonary haemorrhage but no renal
manifestations and was diagnosed on the basis of anti-GBM autoantibodies
and renal biopsy. He responded well to immunosuppressive therapy alone.
To the Editor,
Goodpasture’s disease or antiglomerular basement membrane (anti-GBM)
disease is a small vessel vasculitis which presents as pulmonary-renal
syndrome, causing rapidly progressive glomerulonephritis (RPGN) and
diffuse alveolar haemorrhage (DAH). Goodpasture’s syndrome is a
non-specific term for any pulmonary-renal presentation, which is
labelled as Goodpasture’s disease in presence of anti-GBM
autoantibodies. It has a bimodal age distribution and is rare in
children1.
Majority of the patients present with RPGN, 40 to 60% of patients have
simultaneous alveolar haemorrhage. Isolated pulmonary involvement at
presentation is found in less than 10% patients. Diagnosis requires DAH
and/or glomerulonephritis (GN) along with characteristic anti-GBM
antibodies directed against the non-collagenous domain of α-3 chain of
type IV collagen, either in circulation or in tissue. Treatment usually
involves plasmapheresis and immune-suppression and prognosis depends
upon the extent of disease at diagnosis. We present a case of anti-GBM
disease in a child who had long standing pulmonary involvement but no
renal symptoms and was managed without plasmapheresis.
A 7 year old boy presented to our institution with history of recurrent
episodes of pallor and generalized weakness, since the age of 3 years.
He had previously received blood transfusion on four occasions. The
lowest haemoglobin level (Hb) documented was 3.5 g/dL. Most episodes
were preceded by fever and dry cough but no breathlessness. In the most
recent episode, he had been symptomatic for 3 months with intermittent
fever, cough and 5-6 bouts of haemoptysis with small amounts of bright
red blood. There was no history of dietary allergy, bleeding from any
other site, haematuria or passage of cola coloured urine, rash, oral
ulcers, joint or eye symptoms, or contact with active tuberculosis. On
examination, growth was preserved, there was no hypertension, oedema or
clubbing. There was mild pallor. Systemic examination including
respiratory and cardiovascular systems was normal.
Hemoglobin was 8.4 g/dL with hypochromia and microcytosis.
Investigations confirmed iron deficiency. Chest xray from 1 year back
showed bilateral infiltrates, predominantly involving right middle and
lower and left lower zones (Figure 1A). However, fresh chest xray did
not show these infiltrates. In view of chronic pulmonary symptoms with
haemoptysis, iron deficiency anaemia and alveolar infiltrates on
previous imaging, diffuse alveolar haemorrhage was considered.
CT angiography of the chest showed ill-defined alveolar opacities,
consolidation and ground glassing involving the left upper lobe (Figure
1B). A flexible fibreoptic bronchoscopy was done under conscious
sedation using oral triclofos and intravenous midazolam. No focal
bleeding was observed. Bronchoalveolar lavage (BAL) analysis showed
haemosiderin laden macrophages. Renal function tests were normal, urine
microscopy done twice did not show any red blood cells and there was no
proteinuria. Ophthalmic fundus examination did not show any changes
suggestive of vasculitis. Serum ANA, ANCA and anti ds-DNA were negative.
However, anti-GBM antibodies were positive (25 IU/ml). Therefore, a
renal biopsy was done to look for glomerulonephritis associated with
anti-GBM disease. It showed normal glomerular morphology on light
microscopy (Figure 1C) on multiple serial sections, however direct
immunofluorescence (repeated twice) showed 3+ linear positivity for IgG
along the glomerular capillary walls (Figure 1D).
Within a few days, the child developed new onset fever, cough and
haemoptysis. There was tachypnoea, tachycardia and hypoxia in room air.
Auscultation revealed bilateral coarse crackles. Chest xray showed
bilateral infiltrates. He received oxygen by nasal prongs and
antibiotics, during which the symptoms resolved and xray infiltrates
cleared. Again, there was no proteinuria or haematuria. The anti-GBM
antibody level was 11 IU/ml.
The child was administered methylprednisolone pulses for 3 days followed
by oral prednisolone (1 mg/kg/day) and cyclophosphamide (2.5 mg/kg/day).
He was discharged on the same therapy and had no further episodes of
haemoptysis or anaemia. Anti-GBM antibody levels done 2 months after
starting therapy were negative (2.6 IU/ml). Follow-up over 6 months
confirmed that the child remained well, with no requirement for further
transfusions. He will continue to be closely monitored as the risk
factors that determine prognosis in this particular subgroup of
Goodpasture’s disease have not been well studied.
Anti-GBM disease is extremely uncommon in children. In a retrospective
review of more than 2000 renal biopsies and autopsies conducted over a
period of 25 years at a tertiary centre in the USA, there were 4 cases
of anti-GBM disease in children less than 18 years of
age2. Another review over a 30 year period identified
a total of 24 cases younger than 16 years, with either Goodpasture’s
disease or syndrome3.
Haematuria, proteinuria and anaemia are the commonest symptoms in
children with anti-GBM disease3. The unusual feature
in the index case was the absence of symptoms or signs of renal
dysfunction despite the long history. There are very few reports of
children with only pulmonary symptoms. The terms ‘Early Goodpasture
syndrome’ or ‘Goodpasture variant’ have been used for patients with
pulmonary haemorrhage and anti-GBM antibodies without renal disease.
Renal problems are said to develop within two to three years in most
cases in this group. In these patients, light and electron microscopy of
renal biopsy may be normal or show minimal changes4.
It is unclear whether this group differs from that with renal
presentation in terms of treatment and prognosis.
Most of the current treatment regimens for anti-GBM disease use
plasmapheresis to rapidly remove circulating autoantibodies along with
immune-suppression using cyclophosphamide and steroids. This is based on
observational studies showing better outcomes with
plasmapheresis1. The same studies reported using only
steroids with cyclophosphamide in patients with lower antibody
levels5. In our patient, the levels were not very high
to start with. Therefore, we chose to go ahead with immunosuppression
alone with close monitoring of the renal status.
Anti-GBM disease is a treatable condition and should be looked for in
children with diffuse alveolar haemorrhage, even if renal involvement is
not clinically apparent as happened in the index child. Factors
predicting outcome include severity of renal dysfunction, requirement
for dialysis, proportion of glomeruli with crescents and presence of
interstitial infiltrate5. None of these risk factors
were present in the index case.