Recurrent Autoimmune Haemolytic Anaemia or Diffuse Alveolar Haemorrhage? A Diagnostic Dilemma in a Case of Childhood SLE

A 10-year-old boy presented to us with unremitting fever, mild dry cough and breathlessness for two months. He had a significant past history of being treated elsewhere for autoimmune haemolytic anaemia (AIHA) from six months of age with intermittent tapering doses of steroid and a year of being on mycophenolate mofetil. His parents had stopped his treatment since he was relatively doing well. In the current visit, his investigations in the paediatric department were unrevealing for an infectious aetiology and hence a rheumatology consultation was taken. On examination, he had a malar rash and pallor. On evaluation, he had mild microcytic hypochromic anaemia with normal platelet count, normal lactate dehydrogenase (LDH) levels and negative Coombs test. The chest radiograph was normal. Anti-nuclear antibody (ANA) by indirect immunofluorescence was 4+ coarse speckled; anti dsDNA along with anti-Smith titres were significantly elevated and complement levels were normal. His previous records however showed a positive Coombs test. Patient was negative for antiphospholipid antibodies and also for anti-myeloperoxidase and anti-proteinase 3. His symptoms resolved on correction of anaemia and on starting steroids. He was hence diagnosed with a case of childhood SLE and with a history of being previously coombs positive for AIHA and on being steroids for the same, it was decided to start him on azathioprine as a steroid-sparing drug. The dose of steroid and azathioprine were being optimized in the lockdown period through telemedicine and he was stable for around nine months with a normal haemoglobin. Later, he returned with the recurrence of fever, cough and increased breathlessness. Examination was suggestive of tachypnea and end-inspiratory crepitations with normal saturation. sHe was admitted with a case of pneumonia and worked up for same. There was a fall in haemoglobin, with raised inflammatory markers and normal arterial blood gas. A chest radiograph done at that time seemed normal. However, his high-resolution computed tomography (HRCT) images were suggestive of extensive ground glass opacities (GGO) bilaterally with subpleural cystic areas. A bronchoscopic alveolar lavage (BAL) was done which was haemorrhagic and revealed hemosiderin-laden macrophages with a negative workup for infective aetiology. The findings were hence corroborative of diffuse alveolar haemorrhage (DAH). In retrospect, the recurrent episodes of fever, breathlessness and anaemia seemed possible due to DAH itself, giving rise to the chronic changes seen on HRCT thorax. His previous roentgenograms were as unrevealing as the current one, hence a call of HRCT was not taken previously. A magnetic resonance imaging (MRI) brain done for his headache was also suggestive of small vasculitic infarcts. Considering the young age of onset of features suggestive of SLE, autoimmune lymphoproliferative syndrome and common variable immunodeficiency were ruled out on the basis of clinical features and immunoglobulin measurements.

In a multisystemic disease such as SLE where both AIHA and DAH can manifest, a sudden drop in haemoglobin with breathlessness combined with a normal appearing roentgenogram, may perplex physicians. For a patient to be diagnosed as AIHA, there have to be suggestive clinical (paleness, jaundice, splenomegaly, dark coloured urine, fever, breathlessness) and laboratory features (anaemia with raised mean corpuscular volume, reticulocytosis, raised LDH levels and positive coombs test). ¹ Our patient was diagnosed as AIHA in a paediatric department of another institute on the basis of recurrent falls in haemoglobin with a single report of Coombs test being positive, with fever and breathlessness which responded well to steroids. His older chest radiographs were not available for re-evaluation, and the chest radiograph when the child first presented to us with fever and breathlessness one year back was also unrevealing. Serological features along with response to steroids and azathioprine convinced us of his diagnosis of childhood SLE presenting with AIHA, malar rash and photosensitivity. However, HRCT thorax and subsequent BAL done for recurrence of symptoms despite being on treatment revealed DAH.

Diffuse alveolar haemorrhage is one of the rare yet devastating complications of SLE occurring in 0.6%–5.4% cases.^{2, 3} It can be acute, recurrent or chronic and is postulated to be due to either due to bland haemorrhage or immune complex-mediated capillaritis. ³ Diagnosis is based on the presence of three major components: signs or symptoms of pulmonary haemorrhage, new drop in haemoglobin (typically 1.5–2 g/dL) and new, diffuse infiltrates on chest imaging. Haemoptysis may not always be present in DAH especially if the patient is a child or very frail unable to cough out. There have been rare instances where the chest radiograph was normal in patients of DAH. ³ Our case also represents one such instance and re-iterates the necessity of getting HRCT done when in doubt. The presence of cystic subpleural areas along with diffuse ground glass opacities bilaterally indicates that the child was having chronic recurrent DAH which responded to steroids and recurred as it was tapered off. He was hence given rituximab which will work for his CNS vasculitis and lung capillaritis as well.^4–6 The patient is on maintenance rituximab therapy and still doing well on two years of follow-up.

Figure 1.

A and B Depicts High Resolution Computed Tomography Images of Thorax Showing Diffuse Ground Glass Opacities in all Lung Fields and also Cystic Changes Indicating Chronic Changes or Recurrent Diffuse Alveolar Haemorrhage While C Shows a Absolutely Normal Looking Radiograph of Same Patient and D & E Shows Acute Tiny Infarcts From Vasculitic Activity.