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.
Subject(s)
Arthritis , Bronchiectasis , Lupus Erythematosus, Systemic , Thrombocytopenia , Antibodies, Antinuclear , Bronchiectasis/drug therapy , Bronchiectasis/genetics , Child , Child, Preschool , Complement C4a/deficiency , Female , Hereditary Complement Deficiency Diseases , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Steroids , Thrombocytopenia/etiology , Thrombocytopenia/geneticsABSTRACT
To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.
