# SACQ-LUPUS

**Serologically active clinically quiescent lupus risk-context stratification for escalation vs observation**

## What it does

SACQ-LUPUS is a transparent clinical skill for patients with systemic lupus erythematosus who have active serology but little or no overt clinical activity. It estimates whether the current picture is more consistent with:

- stable serologic activity that can be monitored closely,
- smoldering flare risk that deserves tighter follow-up, or
- an evolving clinical flare that should not be treated as SACQ.

## Why it matters

In lupus, anti-dsDNA and complement changes can be meaningful, but they are not a substitute for the bedside picture. The clinical problem is deciding when abnormal serology should lead to closer observation, medication review, or escalation, and when it is safer to avoid reflex steroid intensification because the patient is still clinically quiescent.

## Inputs

- anti-dsDNA status and trend
- complement status (C3/C4)
- recent change in proteinuria
- hematuria or active urine sediment
- new rash, arthritis, serositis, neuro symptoms, cytopenias, or constitutional symptoms
- recent glucocorticoid taper
- hydroxychloroquine use/adherence
- prior lupus nephritis or prior major organ disease
- assay consistency / recent laboratory platform change
- follow-up interval

## Outputs

- serologic activity component
- discordance component
- organ-risk component
- treatment-context component
- total risk score
- risk class: LOW / MODERATE / HIGH / VERY HIGH / ACUTE-FLARE
- recommended action
- explicit limitations

## Clinical method

This is a transparent weighted heuristic, not a fitted prediction model.

1. Serology matters, but it is not enough on its own.
2. Rising anti-dsDNA plus falling complement increases concern more than a single isolated abnormality.
3. New urinary abnormalities, serositis, rash, arthritis, cytopenias, or neurologic symptoms move the case out of the SACQ bucket.
4. Recent steroid taper and prior nephritis increase the need for close follow-up.
5. Hydroxychloroquine exposure is protective and should be visible in the interpretation.
6. Assay drift matters because anti-dsDNA testing is not perfectly interchangeable across platforms.

## Run

```bash
python3 sacq_lupus.py
```

## Demo scenarios

1. Persistent serologic activity with no symptoms, good hydroxychloroquine adherence, and stable urine testing
2. Modified SACQ lupus after steroid taper with prior nephritis, falling complement, and rising proteinuria
3. Active rash, arthritis, hematuria, and proteinuria with abnormal serology, which should be treated as a clinical flare rather than SACQ

## References

1. Steiman AJ, Gladman DD, Ibanez D, Urowitz MB. Prolonged serologically active clinically quiescent systemic lupus erythematosus: frequency and outcome. *J Rheumatol.* 2010;37(9):1822-1827. DOI: 10.3899/jrheum.100007
2. Steiman AJ, Gladman DD, Ibanez D, Urowitz MB. Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period. *Arthritis Care Res (Hoboken).* 2012;64(4):511-518. DOI: 10.1002/acr.21568
3. Steiman AJ, Urowitz MB, Ibañez D, et al. Anti-dsDNA and antichromatin antibody isotypes in serologically active clinically quiescent systemic lupus erythematosus. *J Rheumatol.* 2015;42(5):810-816. DOI: 10.3899/jrheum.140796
4. Huang H, Mu L, Zhang Z, et al. Treatments and outcomes in Chinese patients with serologically active clinically quiescent systemic lupus erythematosus: a retrospective observational study. *Arthritis Res Ther.* 2021;23:275. DOI: 10.1186/s13075-021-02641-5
5. Katsumata Y, Inoue E, Harigai M, et al. Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study. *Ann Rheum Dis.* 2024;83(8):998-1005. DOI: 10.1136/annrheumdis-2023-225369
6. Fanouriakis A, Kostopoulou M, Andersen J, et al. 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus. *Ann Rheum Dis.* 2024;83(1):15-29. DOI: 10.1136/ard-2023-224762

## Limitations

- Not externally validated as a prognostic model.
- Anti-dsDNA assays vary by platform; serial trends are more useful than a single value.
- A clinical flare can coexist with serologic activity, so the tool intentionally stops labeling the case SACQ once organ symptoms appear.
- Not a substitute for nephrology, rheumatology, or urgent flare assessment.

## Authors

Dr. Erick Zamora-Tehozol, DNAI, RheumaAI


## Executable Code

```python
#!/usr/bin/env python3
"""SACQ-LUPUS: serologically active clinically quiescent lupus triage."""

from dataclasses import dataclass
from math import sqrt
from random import Random


@dataclass
class SACQLupusPatient:
    anti_dsdna: str = "positive"  # negative / weak / positive / high / rising
    complement: str = "low"  # normal / borderline / low / very_low / falling
    proteinuria_change: str = "stable"  # stable / mild_rise / marked_rise
    hematuria: bool = False
    active_sediment: bool = False
    new_rash: bool = False
    new_arthritis: bool = False
    serositis: bool = False
    neuro_symptoms: bool = False
    cytopenias: bool = False
    constitutional_symptoms: bool = False
    recent_steroid_taper: bool = False
    hydroxychloroquine_adherent: bool = True
    prior_lupus_nephritis: bool = False
    assay_change: bool = False
    follow_up_weeks: int = 8


def clamp(value, lo=0, hi=100):
    return max(lo, min(hi, value))


def score_serology(p: SACQLupusPatient):
    mapping = {
        "negative": 0,
        "weak": 8,
        "positive": 16,
        "high": 24,
        "rising": 28,
    }
    comp = {
        "normal": 0,
        "borderline": 8,
        "low": 16,
        "very_low": 22,
        "falling": 24,
    }
    score = mapping.get(p.anti_dsdna, 10) + comp.get(p.complement, 10)
    notes = [f"anti-dsDNA={p.anti_dsdna}", f"complement={p.complement}"]
    if p.assay_change:
        score += 6
        notes.append("assay change adds uncertainty")
    return score, notes


def score_discordance(p: SACQLupusPatient):
    score = 0
    if p.follow_up_weeks > 12:
        score += 4
    elif p.follow_up_weeks > 6:
        score += 2
    if p.hydroxychloroquine_adherent:
        score -= 8
    else:
        score += 10
    if p.recent_steroid_taper:
        score += 10
    if p.prior_lupus_nephritis:
        score += 8
    return score, [f"follow-up={p.follow_up_weeks}w", f"HCQ={'yes' if p.hydroxychloroquine_adherent else 'no'}"]


def score_organ_risk(p: SACQLupusPatient):
    score = 0
    details = []
    if p.proteinuria_change == "mild_rise":
        score += 12
        details.append("mild proteinuria rise")
    elif p.proteinuria_change == "marked_rise":
        score += 24
        details.append("marked proteinuria rise")
    if p.hematuria:
        score += 8
        details.append("hematuria")
    if p.active_sediment:
        score += 10
        details.append("active sediment")
    if p.new_rash:
        score += 8
        details.append("rash")
    if p.new_arthritis:
        score += 8
        details.append("arthritis")
    if p.serositis:
        score += 10
        details.append("serositis")
    if p.neuro_symptoms:
        score += 18
        details.append("neuro symptoms")
    if p.cytopenias:
        score += 8
        details.append("cytopenias")
    if p.constitutional_symptoms:
        score += 6
        details.append("constitutional symptoms")
    return score, details


def classify(total, organ, p: SACQLupusPatient):
    if organ >= 28 or p.neuro_symptoms or (p.serositis and p.proteinuria_change == "marked_rise"):
        return "ACUTE-FLARE"
    if total < 18:
        return "LOW"
    if total < 36:
        return "MODERATE"
    if total < 58:
        return "HIGH"
    return "VERY HIGH"


def recommend(risk, p: SACQLupusPatient):
    if risk == "ACUTE-FLARE":
        return "Treat as clinical flare, not SACQ; urgent rheumatology review and organ-directed workup."
    if risk == "LOW":
        return "Continue hydroxychloroquine, avoid reflex steroid escalation, and repeat serology/urine tests on schedule."
    if risk == "MODERATE":
        return "Close follow-up is reasonable; repeat urine, complement, and anti-dsDNA sooner and confirm assay consistency."
    if risk == "HIGH":
        return "Escalate surveillance, review adherence and renal activity carefully, and consider treatment adjustment only if clinical or urinary signals persist."
    return "High concern for smoldering flare; urgent specialist review and low threshold for kidney/organ reassessment."


def uncertainty(total, p: SACQLupusPatient):
    rng = Random(42)
    samples = []
    for _ in range(400):
        jitter = rng.gauss(0, 2.5)
        assay = 4 if p.assay_change else 0
        samples.append(clamp(total + jitter + rng.uniform(-assay, assay)))
    samples.sort()
    return samples[9], samples[-10]


def evaluate(p: SACQLupusPatient):
    serology, serology_notes = score_serology(p)
    discordance, discordance_notes = score_discordance(p)
    organ, organ_notes = score_organ_risk(p)

    total = clamp(serology + discordance + organ)
    risk = classify(total, organ, p)
    lo, hi = uncertainty(total, p)
    return {
        "total_score": total,
        "risk": risk,
        "uncertainty_interval": (lo, hi),
        "components": {
            "serology": serology,
            "discordance": discordance,
            "organ": organ,
        },
        "notes": serology_notes + discordance_notes + organ_notes,
        "recommendation": recommend(risk, p),
    }


def scenario(name, patient):
    result = evaluate(patient)
    print(name)
    print(f"  score={result['total_score']} risk={result['risk']} ci={result['uncertainty_interval']}")
    print(f"  components={result['components']}")
    print(f"  recommendation={result['recommendation']}")
    print(f"  notes={'; '.join(result['notes'])}")
    print()


def main():
    scenario(
        "Scenario 1 - SACQ with stable urine and good HCQ adherence",
        SACQLupusPatient(
            anti_dsdna="positive",
            complement="low",
            proteinuria_change="stable",
            hydroxychloroquine_adherent=True,
            follow_up_weeks=8,
        ),
    )
    scenario(
        "Scenario 2 - mSACQ after steroid taper with prior nephritis and rising proteinuria",
        SACQLupusPatient(
            anti_dsdna="rising",
            complement="falling",
            proteinuria_change="mild_rise",
            recent_steroid_taper=True,
            prior_lupus_nephritis=True,
            hydroxychloroquine_adherent=True,
            follow_up_weeks=6,
        ),
    )
    scenario(
        "Scenario 3 - active rash, arthritis, hematuria and proteinuria",
        SACQLupusPatient(
            anti_dsdna="high",
            complement="very_low",
            proteinuria_change="marked_rise",
            hematuria=True,
            active_sediment=True,
            new_rash=True,
            new_arthritis=True,
            serositis=True,
            cytopenias=True,
            constitutional_symptoms=True,
            hydroxychloroquine_adherent=False,
            recent_steroid_taper=False,
            prior_lupus_nephritis=True,
            assay_change=True,
            follow_up_weeks=4,
        ),
    )


if __name__ == "__main__":
    main()


```

## Demo Output

```
Scenario 1 - SACQ with stable urine and good HCQ adherence
  score=26 risk=MODERATE ci=(20.759163484442116, 31.31637034237609)
  components={'serology': 32, 'discordance': -6, 'organ': 0}
  recommendation=Close follow-up is reasonable; repeat urine, complement, and anti-dsDNA sooner and confirm assay consistency.
  notes=anti-dsDNA=positive; complement=low; follow-up=8w; HCQ=yes

Scenario 2 - mSACQ after steroid taper with prior nephritis and rising proteinuria
  score=74 risk=VERY HIGH ci=(68.75916348444211, 79.31637034237609)
  components={'serology': 52, 'discordance': 10, 'organ': 12}
  recommendation=High concern for smoldering flare; urgent specialist review and low threshold for kidney/organ reassessment.
  notes=anti-dsDNA=rising; complement=falling; follow-up=6w; HCQ=yes; mild proteinuria rise

Scenario 3 - active rash, arthritis, hematuria and proteinuria
  score=100 risk=ACUTE-FLARE ci=(92.95212712518294, 100)
  components={'serology': 52, 'discordance': 18, 'organ': 82}
  recommendation=Treat as clinical flare, not SACQ; urgent rheumatology review and organ-directed workup.
  notes=anti-dsDNA=high; complement=very_low; assay change adds uncertainty; follow-up=4w; HCQ=no; marked proteinuria rise; hematuria; active sediment; rash; arthritis; serositis; cytopenias; constitutional symptoms


```