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Monogenic lupus with homozygous C4A deficiency presenting as bronchiectasis and immune-mediated thrombocytopenia

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Abstract

Monogenic lupus is a subset of lupus caused by single-gene disorders, integrating the paradoxical combination of autoimmunity and immunodeficiency. Pulmonary manifestations with recurrent pneumonia and bronchiectasis have rarely been described as the predominant presentation of juvenile lupus and may suggest an alternate differential like primary immunodeficiency, especially in early childhood. We describe a case of 10-year girl who presented with a history of recurrent pneumonia, arthritis, alopecia, and poor weight gain for the past 2 years. On examination, she had respiratory distress, bilateral diffuse crackles and arthritis of the small joints of hands. Lab investigations showed pancytopenia, low complement levels and high titers of ANA and anti-dsDNA antibodies. The patient was diagnosed with juvenile lupus. Imaging studies revealed evidence of multiple lobar collapse and consolidation with bronchiectasis. She was started on steroids, HCQ and supportive measures for bronchiectasis. The child reported relief in initial symptoms of lupus on follow-up but developed recurrent thrombocytopenia requiring IVIG and escalating the doses of oral steroids. The young age and atypical presentation prompted a screening for monogenic lupus, and clinical exome sequencing revealed a novel homozygous missense variation in exon 20 of the C4Agene with clinically reduced C4 levels, consistent with the diagnosis of C4A deficiency.

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Authors and Affiliations

  1. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Asma S. Tak & Jagatshreya Satapathy

  2. Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India

    Manisha Jana

  3. Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Aditi Sinha

  4. Division of Pediatric Pulmonology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Kana Ram Jat

  5. Division of Pediatric Rheumatology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Narendra K. Bagri

Authors
  1. Asma S. Tak
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  2. Jagatshreya Satapathy
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  3. Manisha Jana
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  4. Aditi Sinha
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  5. Kana Ram Jat
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  6. Narendra K. Bagri
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Contributions

Both AST and JS were involved in primary care of the patient and supervised by NKB in making the diagnosis and deciding therapy. AST and NKB conceived the idea. AST collected the data, performed the literature review, and prepared the initial draft with input from all the authors. MJ provided the radiological descriptions of the images for the draft. AS and KRJ helped in patient care and helped in revising the manuscript. NKB made final revisions and supervised the whole process.

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Correspondence to Narendra K. Bagri.

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Tak, A.S., Satapathy, J., Jana, M. et al. Monogenic lupus with homozygous C4A deficiency presenting as bronchiectasis and immune-mediated thrombocytopenia. Rheumatol Int 42, 1477–1482 (2022). https://doi.org/10.1007/s00296-021-04943-y

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  • DOI: https://doi.org/10.1007/s00296-021-04943-y

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