Dengue Literature Review

Velazqueza2017 - SLE vs Dengue Case Series

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Velazqueza2017 - SLE vs Dengue Case Series

Full citation: Luevanos-Velázquez A, Vega-Cornejo G, Monteón-Galván D. What are we looking for? Systemic lupus erythematosus vs. dengue infection: A case series report. Rev Colomb Reumatol. 2018;xxx(xx):xxx–xxx. https://doi.org/10.1016/j.rcreu.2017.05.006

Raw file: [[raw/Velazqueza2017.pdf]]

Summary

This case series from the Pediatric Rheumatology Service at Hospital General de Occidente, Guadalajara, Jalisco, Mexico, reports two pediatric female patients presenting with confirmed dengue virus infection who were subsequently diagnosed with systemic lupus erythematosus (SLE) based on the 1997 ACR classification criteria. Mexico is a dengue-endemic country, and the authors note that the clinical diversity of SLE demands diagnostic suspicion even when serological dengue testing is positive.

Case 1 (6-year-old female) presented with fever, arthralgias, mucocutaneous ulcers, generalised erythematous maculopapular lesions, polyarthritis (right elbow, both hands, knees, and ankles), and hepatomegaly. Dengue serology was positive, and the patient was diagnosed with severe dengue. During her admission she developed pericardial effusion, anemia, thrombocytopenia, leukopenia, transaminasemia, elevated CRP and LDH, proteinuria, and haematuria. Rheumatology was consulted and found ANA 1:1280 (homogeneous + cytoplasmic pattern), anti-native DNA 1:10 positive, antinucleosome antibodies 52 U/ml, and hypocomplementemia — meeting ≥4 ACR criteria for both severe dengue and SLE. She was treated with chloroquine, azathioprine, prednisone, and naproxen, with adequate treatment response.

Case 2 (3-year-old female) was hospitalised with fever and convulsive crisis, plus thrombocytopenia, facial oedema, and proteinuria (nephrotic syndrome), with dengue confirmed by positive epidemiological study. She deteriorated into ICU with cardiovascular decompensation, managed with furosemide, hydralazine, prednisone, calcium, levetiracetam, and phenobarbital. Two months after discharge she re-presented with malar erythema, alopecia, bilateral periorbital and facial oedema, anemia, thrombocytopenia, proteinuria, and haematuria. Rheumatology found ANA 1:1280 (fine speckled), anti-dsDNA 31 IU/ml, and antinucleosome antibodies 258 IU/ml — SLE diagnosed by ACR criteria. She was discharged on intravenous gammaglobulin, hydroxychloroquine, mycophenolic acid, enalapril, and vitamin D. One week later she died from pulmonary haemorrhage and cardiorespiratory arrest.

Study Design

  • Type: Case series
  • Sample size: n=2
  • Setting: Hospital General de Occidente, Guadalajara, Jalisco, Mexico; Pediatric Rheumatology Service; dengue-endemic region
  • Population: Pediatric female patients, ages 3 and 6; both with confirmed dengue infection and subsequently diagnosed SLE

Key Findings

  • Both pediatric patients fulfilled ≥4 ACR 1997 SLE classification criteria in the context of confirmed dengue virus infection
  • ANA titres were markedly elevated in both cases: 1:1280 — far above the 1:80 mandatory SLE entry criterion; patterns were homogeneous + cytoplasmic (Case 1) and fine speckled (Case 2)
  • Antinucleosome antibodies positive in both cases: 52 U/ml (Case 1) and 258 IU/ml (Case 2) — a canonical SLE-specific autoantibody targeting the nucleosome (histone-DNA complex)
  • Anti-dsDNA positive in both cases: 1:10 (Case 1) and 31 IU/ml (Case 2)
  • Case 1: concurrent dengue + SLE diagnosis; responded to immunosuppressive management; survived
  • Case 2: dengue was the acute presentation; SLE diagnosed 2 months later — temporally consistent with dengue preceding SLE onset; died from pulmonary haemorrhage
  • Key lab findings (Case 1 / Case 2): Hgb 9.2 / 10.3 g/dl; WBC 2.59 / 4.39 K/μl; platelets 143 / 42 K/μl; AST 590 / 102 U/l; albumin 2.42 / 2.5 IU; ESR 102 / 85 mm/h; CRP 0.97 / 2.15 mg/l
  • Authors note chronology between dengue and SLE cannot be definitively determined: “infection processes can trigger autoimmunity”
  • Proposed mechanisms: molecular mimicry, T cell superantigen activation, FC receptor polymorphism contributing to inadequate immune complex clearance → autoimmune disease; anti-dengue NS1 antibodies cross-reactivity with endothelial cells and plasminogen inhibition via molecular mimicry

Methods Used

Entities Mentioned

  • NS1 Protein (NS1 antibody cross-reactivity with endothelial cells and plasminogen inhibition cited as mechanism)
  • FcγRIIa Receptor (FC receptor polymorphism cited as contributor to inadequate immune complex clearance → autoimmune disease)

Concepts Addressed

Relevance & Notes

Velazqueza2017 is the first directly reported pediatric SLE-dengue case series from Mexico in this wiki, adding geographic breadth (Latin American endemic setting) to the SLE-dengue literature alongside Morel2014 (Paraguay, ANA-negative MAS) and the Talib 2013 case referenced via Palacios2016. The critical distinction from Morel2014 is serological: both Velazqueza2017 cases had the complete SLE autoantibody signature (ANA 1:1280, anti-dsDNA, antinucleosome, hypocomplementemia) — the opposite phenotype from Morel2014’s ANA-negative macrophage-driven MAS. Together, these papers confirm that dengue-associated immune complications span from ANA-negative macrophage hyperactivation to full ANA-positive SLE.

The antinucleosome antibody specificity in both cases deserves attention in the context of Vo2020’s finding that nuclear antigen IgGs (including histone H3/H4 and nucleosome antigens) are positively correlated with platelet counts in DHF — interpreted as consumption via immune complex formation. Whether the very high antinucleosome titres in active SLE (production-dominant state) and the Vo2020 DHF consumption signal represent different phases or different pathophysiological pathways cannot be resolved from n=2 case reports.

Methodological caution: n=2 case series — lowest evidence level; not generalizable. No dengue serotype data reported. The temporal relationship between dengue and SLE is ambiguous for Case 1 (concurrent diagnosis — either dengue triggered SLE or pre-existing subclinical SLE was revealed during dengue workup) and only partially resolved for Case 2 (SLE 2 months after dengue). The 1997 ACR criteria used have been superseded by 2019 EULAR/ACR criteria (see Aringer2019 - 2019 EULAR ACR SLE Classification Criteria).

Questions Raised

  • Can the temporal sequence between dengue infection and SLE autoantibody appearance be established prospectively in a pediatric endemic-population cohort from Mexico?
  • Do dengue patients who develop high-titer antinucleosome antibodies (as in these SLE cases) show the same nuclear antigen IgG consumption pattern described by Vo2020 in DHF, or does active SLE-level production override the consumption signal?
  • What is the seroprevalence of anti-dsDNA and antinucleosome antibodies in dengue-infected children without a prior SLE diagnosis, in a large prospective endemic-region study?

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