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Cross-provider research synthesis

Psoriatic Arthritis

MONDO:0011849 Curated 2026-07-04T00:00:00Z 9 harmonized findings
falcon · 17 citations asta · 19 citations perplexity · 56 citations
Concordant asserts the finding Partial supports a weaker/qualified form Contradictory conflicts with it Silent does not address it

Harmonized findings

The IL-23/IL-17 cytokine axis is the dominant/central inflammatory pathway driving psoriatic arthritis, with IL-23-driven Th17 (and innate-like) IL-17 production amplified by TNF and other cytokines in skin and synovium.

MAJORITY INTEGRATED
pathophysiology
ProviderStanceScoreEvidence
falcon CONCORDANT 95% driven principally by the IL‑23/IL‑17 axis and amplified by TNF and other cytokines
Falcon centers PsA pathophysiology on the IL-23/IL-17 axis amplified by TNF.
DOI:10.46497/archrheumatol.2025.10934
perplexity CONCORDANT 97% The interleukin-23 and interleukin-17 signaling axis has emerged as the dominant cytokine pathway driving PsA pathogenesis
Perplexity explicitly names the IL-23/IL-17 axis as the dominant driver.
asta PARTIAL 55% Both PsO and PsA share similar Th1- and Th17-driven inflammation, with increased production of inflammatory cytokines, including TNFα, IFN-γ, IL-17, IL-22, IL-23 in the skin and the synovial membrane
Asta's retrieved snippets list the IL-17/IL-23 axis among key PsA cytokines but, being retrieval-only, do not assert it as the single dominant pathway.
PMID:36159785

Enthesitis and the synovio-entheseal complex are a primary/initiating lesion in PsA, with mechanical stress at tendon/ligament insertions triggering local immune activation that can extend to adjacent synovium.

MAJORITY INTEGRATED
pathophysiologyphenotype
ProviderStanceScoreEvidence
falcon CONCORDANT 90% enthesitis is a primary lesion and that inflammation at the enthesis initiates the musculoskeletal symptoms of psoriatic arthritis
Falcon foregrounds the enthesitis-first hypothesis and synovio-entheseal complex.
DOI:10.3899/jrheum.2024-0593
perplexity CONCORDANT 85% The enthesis experiences substantial mechanical stress during normal movements, generating forces that exceed those experienced by synovial joints
Perplexity describes the enthesis as a mechanically stressed site of vulnerability.
asta PARTIAL 55% Inflammation is considered to develop adjacent to bone insertions, affecting the enthesis and the synovium, and being associated with both processes of bone destruction and new bone formation
Asta retrieves the enthesis-adjacent inflammation concept but not the explicit enthesitis-as-primary-lesion framing.
PMID:35847785

PsA shows a paradoxical bone phenotype of simultaneous osteoclast-driven bone erosion and new bone formation (osteoproliferation), reflecting RANKL-driven osteoclastogenesis alongside Wnt-antagonist (DKK1/sclerostin) modulation.

MAJORITY INTEGRATED
pathophysiologyphenotype
ProviderStanceScoreEvidence
falcon CONCORDANT 90% RANKL‑driven osteoclastogenesis (erosion) occurs alongside Wnt pathway modulation by DKK1/SOST, enabling paradoxical osteoproliferation
Falcon states the RANKL-erosion / Wnt-DKK1/SOST new-bone paradox directly.
DOI:10.46497/archrheumatol.2025.10934
perplexity CONCORDANT 92% A pathognomonic feature of PsA distinguishing it from rheumatoid arthritis is the simultaneous occurrence of bone erosion and new bone formation, often within the same joint or even the same digit
Perplexity gives a detailed osteoclast/osteoblast account of the erosion-plus-formation pattern.
asta PARTIAL 45% the concentration of IL 17A and other cytokines was correlated with markers of bone remodeling, identifying the molecular pathways involved in psoriatic arthropathy
Asta links cytokines to bone remodeling but does not articulate the erosion/new-bone paradox.
PMID:37298466

PsA susceptibility involves HLA class I / antigen-processing genes (notably HLA-B27) together with non-MHC IL-23/Th17-pathway loci (IL23R, IL12B, TYK2) and other inflammatory-signaling genes.

MAJORITY INTEGRATED
genetic_factor
ProviderStanceScoreEvidence
falcon CONCORDANT 90% Genetic susceptibility implicates HLA class I and antigen processing/presentation (HLA‑B27, ERAP1/2) alongside IL‑23/Th17 and interferon/JAK signaling genes (IL23R, IL12B, TYK2, TRAF3IP2)
Falcon enumerates HLA class I, ERAP1/2, and IL-23/Th17/JAK pathway genes.
DOI:10.3899/jrheum.2025-0273
perplexity CONCORDANT 90% HLA-B*27 displays stronger association with PsA, particularly in patients with axial skeletal involvement, though at substantially lower frequency than observed in ankylosing spondylitis
Perplexity details HLA class I associations and non-MHC loci (IL23R, IL12B, TYK2, REL).
asta PARTIAL 60% It is associated to type I major histocompatibility complex (MHC) alleles, with risk polymorphisms in genes related to interleukins (IL) 23 and 12, nuclear factor κB and tumor necrosis factor (TNF)
Asta retrieves the MHC class I + IL-23/IL-12/NF-kB/TNF risk-polymorphism claim but does not resolve individual PsA-specific loci such as HLA-B27.
PMID:35847785

Psoriatic arthritis develops in roughly 30% of patients with psoriasis, typically years after the onset of skin disease.

UNANIMOUS INTEGRATED
epidemiology
ProviderStanceScoreEvidence
perplexity CONCORDANT 90% The disease emerges in approximately thirty percent of patients with psoriasis vulgaris, typically between five to twelve years following initial skin manifestations
Perplexity gives the ~30% figure plus the typical 5-12 year skin-to-joint latency.
asta CONCORDANT 85% Around 30% of patients with PsO develop arthritis with axial and/or peripheral manifestations
Asta retrieves the same ~30% psoriasis-to-arthritis conversion figure.
PMID:36159785
falcon SILENT —
Falcon's mechanism-focused report does not state the ~30% psoriasis-to-PsA figure.

JAK/STAT signaling is a convergence hub integrating multiple PsA-relevant cytokines (including IL-23 via JAK2/TYK2/STAT3) and is a validated therapeutic axis (JAK/TYK2 inhibitors).

MAJORITY INTEGRATED
pathophysiologygene_functiontreatment
ProviderStanceScoreEvidence
falcon CONCORDANT 90% 2024 reviews synthesize how IL‑23 and other cytokines signal through JAK2/TYK2/STAT3, aligning with clinical success of JAK/TYK2 inhibitors
Falcon frames JAK/STAT (JAK2/TYK2/STAT3) as a unifying intracellular hub and drug target.
DOI:10.1007/s11926-024-01144-x
perplexity CONCORDANT 92% The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway integrates signals from multiple cytokines including IL-6, IL-17, IL-23, interferons, and type I interferons, serving as a crucial convergence point for inflammatory signaling in PsA
Perplexity describes JAK/STAT as a cytokine convergence point and cites JAK inhibitor therapy.
asta PARTIAL 50% Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways) in T cells is of concern in the last few years
Asta retrieves JAK/STAT as a druggable T-cell pathway in psoriatic disease but without the PsA synovial-convergence detail.
PMID:37251381

TNF-alpha is a central pro-inflammatory driver of tissue destruction in PsA and a clinically validated therapeutic target (anti-TNF biologics).

UNANIMOUS INTEGRATED
pathophysiologytreatment
ProviderStanceScoreEvidence
perplexity CONCORDANT 90% Tumor necrosis factor-alpha, a prototypical pro-inflammatory cytokine, reaches elevated concentrations in PsA serum, synovial fluid, and synovial tissue, where it drives multiple aspects of inflammatory joint disease
Perplexity dedicates a section to TNF-alpha amplification/tissue destruction and anti-TNF therapy.
falcon CONCORDANT 75% anti‑IL‑17A/F, anti‑IL‑23p19, anti‑IL‑12/23p40, and anti‑TNF biologics validate the central axes
Falcon lists anti-TNF among the biologics that mechanistically validate the central cytokine axes.
DOI:10.46497/archrheumatol.2025.10934
asta CONCORDANT 70% Cytokine pathways, especially those involving TNF-α, IL-23/IL-17, and IL-22 [36,42], play crucial roles in the pathogenesis of PsA, as these cytokines are found at elevated levels in affected tissues
Asta retrieves TNF-alpha as a crucial elevated cytokine in PsA pathogenesis.
DOI:10.3390/biologics5010001

Psoriatic disease carries a high burden of cardiometabolic comorbidity (hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome, cardiovascular disease) linked to shared systemic inflammation.

SINGLE LEAD
comorbidity
ProviderStanceScoreEvidence
asta CONCORDANT 85% PsD is associated with a high burden of cardiometabolic diseases such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular (CV) complications as compared to the general population
Asta retrieves multiple papers quantifying the cardiometabolic comorbidity burden of psoriatic disease.
PMID:36159785
perplexity SILENT —
Perplexity focuses on joint/skin mechanism and does not cover cardiometabolic comorbidity.
falcon SILENT —
Falcon's pathophysiology report does not address systemic cardiometabolic comorbidity.

Mast cells are enriched in PsA synovium relative to rheumatoid arthritis and are a prominent local source of IL-17A, contributing to innate IL-17 supply.

MAJORITY LEAD
pathophysiologyphenotype
ProviderStanceScoreEvidence
asta CONCORDANT 85% synovial IL-17+ mast cells are significantly increased in PsA and produce more IL-17A compared with RA
Asta retrieves synovial-biopsy evidence that IL-17+ mast cells are increased in PsA vs RA.
PMID:30805340
perplexity CONCORDANT 90% Mast cells represent a previously underappreciated cellular component particularly enriched in PsA synovium compared with rheumatoid arthritis
Perplexity describes mast cells as PsA-synovium-enriched and a major IL-17A source.
falcon PARTIAL 45% Provide IL-1, TNF, IL-6 and extrafollicular IL-17 (e.g., from neutrophil NETs/mast cells)
Falcon lists mast cells among innate myeloid IL-17 sources but without the PsA-vs-RA enrichment claim.
DOI:10.3390/nu17081323

Narrative

Overview

All three providers frame psoriatic arthritis as a complex, immune-mediated inflammatory musculoskeletal disease of psoriatic disease, converging on a genetic-susceptibility-plus-environmental-trigger model in which dysregulated innate and adaptive immunity target the synovium, the enthesis, the skin, and bone. Falcon and perplexity both used the mechanism-focused pathophysiology template and produced narrative, mechanistic accounts; asta is a retrieval-only corpus dump whose 19 papers and 20 snippets supply supporting evidence rather than a synthesized argument. Falcon organizes the disease around an enthesis-initiated, cytokine-amplified process integrated through JAK/STAT signaling; perplexity is the broadest and most granular, walking through genetics, the IL-23/IL-17 axis, TNF, JAK/STAT, individual innate and adaptive cell populations, bone remodeling, the enthesis, metabolism, epigenetics, angiogenesis, and clinical phenotypes; asta's retrieved literature adds histopathology, cytokine profiling, and a strong cardiometabolic-comorbidity thread.

Agreement

The providers agree on the core mechanistic backbone. The IL-23/IL-17 axis is treated as the dominant/central inflammatory pathway, amplified by TNF, with Th17 and innate-like cells producing IL-17 that acts on stromal and skeletal cells. Enthesitis and the synovio-entheseal complex are recognized as a primary/initiating lesion driven in part by mechanical stress. The paradoxical bone phenotype — simultaneous osteoclast-driven erosion and new bone formation via RANKL and Wnt-antagonist (DKK1/sclerostin) modulation — is a shared, PsA-distinguishing feature. Genetic susceptibility is anchored in HLA class I / antigen processing (notably HLA-B27) plus non-MHC IL-23-pathway loci (IL23R, IL12B, TYK2). JAK/STAT is described as a cytokine convergence hub and validated drug target, and TNF-alpha as a central destructive driver and anti-TNF target.

Divergence

Divergence is coverage-driven, not contradictory — no direct conflicts were found. Falcon uniquely commits to the enthesitis-first (GRAPPA) framing and the JAK2/TYK2/STAT3 unifying-hub argument, and it is the only provider foregrounding the DKK1/SOST Wnt-antagonist bone axis by name, but it is silent on the ~30% psoriasis-to-PsA epidemiology and on comorbidity. Perplexity contributes by far the most detail and several elements the others omit entirely — CD8+ tissue-resident memory T cells with shared skin/joint clones, metabolic reprogramming/glycolysis, epigenetics, angiogenesis, complement, Toll-like receptors, and quantified clinical phenotypes (oligo/polyarticular, dactylitis, axial). Asta's distinctive value is the retrieved evidence base: the ~30% conversion figure, the cardiometabolic comorbidity burden, and synovial histopathology (IL-17+ mast cells increased in PsA vs RA). As a retrieval-only provider, asta supports mechanistic claims only partially, earning mostly PARTIAL stances where falcon/perplexity are CONCORDANT.

Integration

The concordant mechanistic backbone is ready for promotion into the disorder YAML: the IL-23/IL-17 axis as the central pathway, enthesitis / synovio-entheseal complex as an initiating lesion, the RANKL-erosion / Wnt-DKK1/sclerostin new-bone paradox, HLA class I (HLA-B27) plus IL23R/IL12B/TYK2 genetics, the JAK/STAT convergence hub with JAK/TYK2 inhibitors, and TNF-alpha with anti-TNF therapy. The ~30% psoriasis-to-PsA epidemiology (perplexity + asta) is a clean, two-provider prevalence claim suitable for the prevalence/description block. Each promoted claim should be re-grounded on verified primary literature (fetch-reference on the underlying PMIDs/DOIs) before it enters kb/disorders.

Not integrated (leads)

Two findings are retained as leads rather than promoted. The cardiometabolic comorbidity burden (finding 8) rests on a single provider (asta) and belongs in a comorbidity entry with its own verified evidence rather than in the core pathophysiology. The mast-cell finding (finding 9) — IL-17+ mast cells enriched in PsA synovium versus RA — is supported by asta and perplexity but is a finer-grained cellular claim best held as a lead pending confirmation of the synovial-biopsy evidence. Perplexity-only threads (CD8+ Trm skin-joint clonal sharing, glycolytic reprogramming, epigenetics, angiogenesis, complement, TLRs) were not elevated to harmonized findings and remain research leads.

Cross-provider synthesis of three independent PsA deep-research reports: falcon (mechanism/pathophysiology-focused, IL-23/IL-17 + enthesitis + genetics), asta (retrieval-only snippet corpus, strong on histopathology, cytokine profiling, and cardiometabolic comorbidity), and perplexity (broad, deeply detailed mechanism and phenotype coverage). Providers were concordant on the core mechanistic backbone (IL-23/IL-17 axis, enthesitis, bone-remodeling paradox, HLA/IL-23-pathway genetics, JAK/STAT hub, TNF). Divergence is coverage-driven, not contradictory: falcon is silent on the ~30% psoriasis-to-PsA epidemiology and on cardiometabolic comorbidity (asta's strength), while asta's retrieval-only snippets support mechanisms only partially. No direct contradictions were found. best_matching_text values are verbatim excerpts from the cited report files; falcon quotes preserve its non-breaking hyphen characters.