derm.pyoderma-gangrenosum.core.v1PRODUCTION

derm.pyoderma-gangrenosum.core.v1

Pyoderma gangrenosum (neutrophilic ulcerative dermatosis)

dermatologyacutesubacuteadult

Hard-required inputs

0 / 10

Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame PG as a rapidly progressive, exquisitely painful neutrophilic ulcerative dermatosis that is (a) a DIAGNOSIS OF EXCLUSION confirmed by clinical criteria (Maverakis Delphi / PARACELSUS) with NO confirmatory test — biopsy EXCLUDES mimics, it does not confirm — and (b) governed by PATHERGY: surgical debridement / aggressive surgery enlarges it catastrophically. The dominant error is misdiagnosis as infection and surgical debridement. ~50-70% have an associated systemic disease.

Inputs

Actions

Advance rule

Set

Advance when

exclusion-diagnosis + criteria framing set; pathergy / no-debridement rule flagged; associated-disease mandate noted

Patient inputs (17)

antibiotic_nonresponse_with_sterile_cultures*history • BRANCHING_WORKUP

not present

Failure to respond to adequate antibiotics with negative tissue cultures shifts the prior away from infection toward PG — the dominant misdiagnosis pivot (Shaigany Arch Dermatol Res 2021 PMID 34714405)

ulcer_border_morphology*symptom • CONTEXT

Violaceous, undermined, overhanging, irregular border (present in ~98% of PG) is the single strongest morphologic pointer and anchors the criteria (PARACELSUS PMID 29388188; Maverakis Delphi PMID 29450466)

ulcer_progression_rate*symptom • CONTEXT

Rapid expansion over days is a PARACELSUS major criterion; an indolent ulcer argues a vascular/neoplastic mimic (Jockenhöfer Br J Dermatol 2019 PMID 29388188)

pathergy_or_trauma_localisation*history • CONTEXT

not present

Lesion arising/worsening at a site of trauma/surgery/debridement (pathergy) is a Maverakis minor criterion AND the critical management-safety flag (no debridement) (PMID 29450466; PMID 31498172)

associated_systemic_disease*history • CONTEXT

not present

IBD / inflammatory arthritis / haematologic malignancy or IgA monoclonal gammopathy is present in ~50-70%; a Maverakis minor criterion and drives mandatory associated-disease workup (PMID 29450466; Shaigany PMID 34714405)

ulcer_pain_severity*symptom • ENTRY

Pain markedly out of proportion to ulcer appearance (>4/10 VAS) is a core PG discriminator vs vascular/infective ulcers and a PARACELSUS minor criterion (Jockenhöfer Br J Dermatol 2019 PMID 29388188)

tissue_culture_including_atypicals*lab • INITIAL_WORKUP

Tissue culture (bacterial, mycobacterial, fungal) from the ulcer is required to EXCLUDE infection — a Maverakis minor criterion; sterile cultures support PG (PMID 29450466)

edge_biopsy_to_exclude_mimics*imaging • INITIAL_WORKUP

not present

Biopsy from the ulcer EDGE excludes vasculitis, infection, malignancy (the Maverakis MAJOR criterion is a neutrophilic infiltrate, which is supportive but NON-confirmatory) — biopsy excludes, it does not confirm (PMID 29450466)

necrotising_infection_red_flags*symptom • RED_FLAGS

Crepitus, gas, fulminant sepsis, true rapidly advancing necrotising infection must be excluded BEFORE attributing a non-response to PG — necrotising fasciitis is a surgical emergency (route OUT) (IDSA SSTI; PMID 31498172)

systemic_toxicity_extent_of_disease*symptom • RED_FLAGS

Fulminant/multifocal PG with systemic toxicity or rapidly progressive disease triggers admission + IV immunosuppression (Partridge Br J Dermatol 2018 PMID 29478243; STOP GAP PMID 26071094)

anca_cryoglobulin_antiphospholipidlab • BRANCHING_WORKUP

ANCA / cryoglobulins / antiphospholipid antibodies exclude vasculitic and thrombo-occlusive ulcer mimics on the exclusion pathway (Maverakis Delphi exclusion principle PMID 29450466)

spep_serum_immunofixationlab • BRANCHING_WORKUP

SPEP / immunofixation screens for IgA monoclonal gammopathy and myeloma — a recognised PG association with prognostic weight (Partridge Br J Dermatol 2018 PMID 29478243)

cbc_with_differentiallab • INITIAL_WORKUP

Cytopenias / leukaemic picture screen for an associated haematologic malignancy (worse prognosis) and provide a pre-immunosuppression baseline (Shaigany Arch Dermatol Res 2021 PMID 34714405)

lftlab • INITIAL_WORKUP

Baseline + on-treatment hepatotoxicity monitoring for ciclosporin / azathioprine / methotrexate-class agents (STOP GAP PMID 26071094; Partridge PMID 29478243)

infection_screen_tb_hbv_hcvlab • INITIAL_WORKUP

Latent-TB + hepatitis screen before infliximab / adalimumab or other TNF-class biologic initiation (Brooklyn Gut 2006 PMID 16188920; Partridge PMID 29478243)

creatininelab • TREATMENT

Ciclosporin nephrotoxicity surveillance + immunosuppressant renal dose-adjust; CKD-EPI 2021 race-free eGFR (STOP GAP PMID 26071094; Inker NEJM 2021)

pregnancy_statusdemographic • TREATMENT

Mycophenolate / cyclophosphamide / methotrexate are teratogenic and contraindicated; prednisone or ciclosporin preferred if systemic therapy needed in pregnancy (Partridge Br J Dermatol 2018 PMID 29478243)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement

informationallife_threateningfulminant_or_systemically_toxic_pg
Rapidly progressive / fulminant / multifocal PG with systemic toxicity (fever, malaise, rapid expansion) (Partridge Br J Dermatol 2018 PMID 29478243)
Trigger could not be auto-evaluated — needs clinician judgement.
informationallife_threateningtrue_necrotising_infection_route_out
Genuine necrotising soft-tissue infection features (crepitus, gas, fulminant sepsis, true rapid necrosis) — NOT PG (IDSA SSTI; PMID 31498172)
Trigger could not be auto-evaluated — needs clinician judgement.
informationalseveremisdiagnosed_as_infection_and_debrided_pathergy
Ulcer misdiagnosed as wound/necrotising infection and surgically debrided, now enlarging — pathergy (Flynn Adv Skin Wound Care 2019 PMID 31498172)
Trigger could not be auto-evaluated — needs clinician judgement.
informationalseverepg_with_hematologic_malignancy_or_iga_gammopathy
PG with a newly identified haematologic malignancy / myelodysplasia / IgA monoclonal gammopathy (worse prognosis) (Shaigany Arch Dermatol Res 2021 PMID 34714405; Partridge PMID 29478243)
Trigger could not be auto-evaluated — needs clinician judgement.
informationalmoderateextensive_multifocal_refractory_pg
Extensive or multifocal PG refractory to/dependent on first-line systemic therapy (Partridge Br J Dermatol 2018 PMID 29478243)
Trigger could not be auto-evaluated — needs clinician judgement.
informationalmoderateperi_or_postsurgical_pg_mistaken_for_ssi
Peristomal or postsurgical ulceration mistaken for a stoma complication / surgical-site infection, worsening with manipulation (Flynn Adv Skin Wound Care 2019 PMID 31498172)
Trigger could not be auto-evaluated — needs clinician judgement.
informationalmoderatesevere_uncontrolled_pg_pain
Severe ulcer pain out of proportion to appearance, inadequately controlled (PARACELSUS extreme-pain criterion >4/10 VAS; Jockenhöfer Br J Dermatol 2019 PMID 29388188)
Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

TREATMENToptionalDrives dose adjustment

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Recommended regimen

Pyoderma gangrenosum — exclusion-first immunosuppressive ladder by extent/tempo (Maverakis Delphi PMID 29450466; STOP GAP PMID 26071094; Partridge PMID 29478243)

axis: pg_extent_immunosuppressive_ladderstep 1 - Step 1 — Diagnostic gate + the no-debridement rule (every patient, before any treatment)

Selected step "Step 1 — Diagnostic gate + the no-debridement rule (every patient, before any treatment)" — Any painful rapidly progressive violaceous undermined-border ulcer — confirm exclusion-diagnosis by criteria and enforce pathergy precautions before treatment

avoid_surgical_debridement_and_aggressive_surgery_pathergy
first line
safety_decision_gate
triggers: suspected_pg, wound_misdiagnosed_as_infection, peristomal_or_postsurgical_ulcer
PMID 31498172 — PG is routinely misdiagnosed as wound/necrotising infection and surgically debrided, which enlarges it catastrophically via pathergy. NO debridement / aggressive surgery. This rule precedes all therapy.
exclusion_workup_tissue_culture_edge_biopsy_associated_disease
first line
decision_gate
triggers: no_confirmatory_test, rule_out_infection_vasculitis_malignancy_vascular
Maverakis Delphi (PMID 29450466) — PG has no confirmatory test: 1 major (edge-biopsy neutrophilic infiltrate, supportive only) + 8 minor, ≥4/8 → Sn 86% / Sp 90%. Biopsy EXCLUDES mimics; it does not confirm. Mandatory associated-disease workup (IBD/heme/arthritis).
meticulous_moist_nonadherent_wound_care_and_analgesia
first line
wound_care
triggers: any_pg_ulcer
Partridge Br J Dermatol 2018 (PMID 29478243) — gentle moist non-adherent dressings + adequate analgesia (pain is severe and out of proportion) in parallel with immunosuppression; autolytic, NOT surgical, debridement only.

outpatient playbook — drug actions (4)

1. NO surgical debridement + meticulous moist non-adherent wound care + analgesia
n/a • wound care • continuous
trigger: Any suspected PG ulcer (pathergy precaution precedes therapy) (PMID 31498172)
Debridement enlarges PG catastrophically; autolytic not surgical debridement; treat severe pain
2. clobetasol propionate 0.05% / intralesional triamcinolone (localised PG)
rxcui 21245
0.05% / 10-40 mg/mL • topical / intralesional • daily / q2-4wk
trigger: Localised, limited, slowly progressive PG (Partridge PMID 29478243)
Ultrapotent topical or intralesional steroid to the active border for localised disease
3. prednisone 0.5-1 mg/kg OR ciclosporin 4 mg/kg (moderate-severe / rapidly progressive)
rxcui 8640
0.5-1 mg/kg/day • PO • daily then taper
trigger: Extensive/multifocal/rapidly progressive or topical-refractory PG (STOP GAP PMID 26071094)
STOP GAP — prednisolone = ciclosporin; choose on toxicity profile + preference
4. infliximab 5 mg/kg (refractory / IBD-associated)
rxcui 191831
5 mg/kg • IV • wk0/2/6 then q8wk
trigger: Refractory or IBD-associated PG, steroid-sparing need (Brooklyn Gut 2006 PMID 16188920)
Only placebo-controlled PG RCT; dual benefit when IBD coexists; TB/hepatitis screen first

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Rapidly enlarging, exquisitely painful ulcer with a violaceous, undermined, overhanging border (PARACELSUS — violaceous border in 98% of PG; Jockenhöfer Br J Dermatol 2019 PMID 29388188); A papule/pustule/vesicle that ulcerated within ~4 days of appearing (Maverakis Delphi minor criterion; JAMA Dermatol 2018 PMID 29450466); Ulcer that enlarged after surgical debridement, biopsy, or minor trauma — PATHERGY; commonly misdiagnosed as wound/necrotising infection (PMID 31498172).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Pyoderma gangrenosum (neutrophilic ulcerative dermatosis)** (derm.pyoderma-gangrenosum.core.v1).
Phenotype framing: Terminal exclusion differential with named pivots: PG vs infection/cellulitis/necrotising STI (sterile culture + antibiotic non-response + pathergy pivot — route derm.cellulitis.core.v1 / id.necrotising-fasciitis.core.v1) vs venous ulcer (CEAP/stasis pivot — workup.cvi) vs arterial ulcer (ABI pivot) vs vasculitis (ANCA + biopsy pivot — route rheum.vasculitis.core.v1) vs antiphospholipid/calciphylaxis (thrombo-occlusive + calcium-phosphate/biopsy pivot) vs malignancy/Marjolin (chronicity + edge-biopsy pivot) vs factitial ulcer (geometric/access pivot) vs Sweet syndrome (overlapping neutrophilic, plaques>ulcer pivot) vs ecthyma gangrenosum (Pseudomonas/neutropenia pivot) vs cutaneous Crohn (perianal/biopsy granuloma pivot) vs brown-recluse/loxoscelism (bite history pivot) vs Martorell HYTILU (hypertensive ischaemic supramalleolar pivot). PG remains a diagnosis of exclusion.
Scope: Frame PG as a rapidly progressive, exquisitely painful neutrophilic ulcerative dermatosis that is (a) a DIAGNOSIS OF EXCLUSION confirmed by clinical criteria (Maverakis Delphi / PARACELSUS) with NO confirmatory test — biopsy EXCLUDES mimics, it does not confirm — and (b) governed by PATHERGY: surgical debridement / aggressive surgery enlarges it catastrophically. The dominant error is misdiagnosis as infection and surgical debridement. ~50-70% have an associated systemic disease.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Pyoderma gangrenosum — exclusion-first immunosuppressive ladder by extent/tempo (Maverakis Delphi PMID 29450466; STOP GAP PMID 26071094; Partridge PMID 29478243)** — step "Step 1 — Diagnostic gate + the no-debridement rule (every patient, before any treatment)".
1. avoid_surgical_debridement_and_aggressive_surgery_pathergy (safety_decision_gate, first line) — PMID 31498172 — PG is routinely misdiagnosed as wound/necrotising infection and surgically debrided, which enlarges it catastrophically via pathergy. NO debridement / aggressive surgery. This rule precedes all therapy.
2. exclusion_workup_tissue_culture_edge_biopsy_associated_disease (decision_gate, first line) — Maverakis Delphi (PMID 29450466) — PG has no confirmatory test: 1 major (edge-biopsy neutrophilic infiltrate, supportive only) + 8 minor, ≥4/8 → Sn 86% / Sp 90%. Biopsy EXCLUDES mimics; it does not confirm. Mandatory associated-disease workup (IBD/heme/arthritis).
3. meticulous_moist_nonadherent_wound_care_and_analgesia (wound_care, first line) — Partridge Br J Dermatol 2018 (PMID 29478243) — gentle moist non-adherent dressings + adequate analgesia (pain is severe and out of proportion) in parallel with immunosuppression; autolytic, NOT surgical, debridement only.

Setting playbook (outpatient) — Diagnose PG by clinical criteria as a diagnosis of EXCLUSION (no confirmatory test; biopsy excludes mimics), enforce the no-debridement/pathergy rule, complete the mandatory associated-disease workup, and start an extent-appropriate immunosuppressive + wound-care plan (Maverakis Delphi PMID 29450466; PARACELSUS PMID 29388188; STOP GAP PMID 26071094)
4. NO surgical debridement + meticulous moist non-adherent wound care + analgesia n/a wound care continuous — Any suspected PG ulcer (pathergy precaution precedes therapy) (PMID 31498172) (Debridement enlarges PG catastrophically; autolytic not surgical debridement; treat severe pain)
5. clobetasol propionate 0.05% / intralesional triamcinolone (localised PG) 0.05% / 10-40 mg/mL topical / intralesional daily / q2-4wk — Localised, limited, slowly progressive PG (Partridge PMID 29478243) (Ultrapotent topical or intralesional steroid to the active border for localised disease)
6. prednisone 0.5-1 mg/kg OR ciclosporin 4 mg/kg (moderate-severe / rapidly progressive) 0.5-1 mg/kg/day PO daily then taper — Extensive/multifocal/rapidly progressive or topical-refractory PG (STOP GAP PMID 26071094) (STOP GAP — prednisolone = ciclosporin; choose on toxicity profile + preference)
7. infliximab 5 mg/kg (refractory / IBD-associated) 5 mg/kg IV wk0/2/6 then q8wk — Refractory or IBD-associated PG, steroid-sparing need (Brooklyn Gut 2006 PMID 16188920) (Only placebo-controlled PG RCT; dual benefit when IBD coexists; TB/hepatitis screen first)

Non-pharmacologic actions:
- Flag PG on the record + counsel patient: avoid elective surgery/debridement; tell any future surgeon (pathergy) (PMID 31498172)
- Autolytic moist non-adherent dressings; never sharp/surgical debridement (PMID 29478243)
- Compression for lower-leg PG with venous oedema once arterial disease excluded (PMID 29478243)
- Coordinate associated-disease care by engine_id (gi.ibd.core.v1 / rheum.vasculitis.core.v1 / heme-onc) (Shaigany PMID 34714405)

AVOID / contraindication checks:
- No surgical debridement or aggressive surgery pathergy (PMID 31498172 — PG misdiagnosed as infection and debrided enlarges catastrophically; the single most consequential rule; essential surgery only under immunosuppressive cover)
- Peristomal and postsurgical pg managed conservatively not revised (PMID 31498172 — appliance modification + topical/intralesional + immunosuppression; avoid stoma revision/debridement which is pathergic)
- Tnf biologic latent tb and hbv hcv screen before initiation (Brooklyn Gut 2006 PMID 16188920; Partridge PMID 29478243)
- Long term corticosteroid taper with steroid sparing transition (STOP GAP PMID 26071094 — first line for rapid control then transition off)
- Ciclosporin nephrotoxicity and hypertension monitor bp creatinine (STOP GAP PMID 26071094 — CKD EPI 2021 surveillance)
- Pregnancy avoid mycophenolate cyclophosphamide methotrexate prefer prednisone or ciclosporin (Partridge Br J Dermatol 2018 PMID 29478243)
- Biologic paradoxical pg onset recognise and reconcile drug timeline (PMID 35293377 — rituximab/TNF α associated PG; route derm.drug eruption.core.v1)

Monitoring

Regimen monitoring:
- ulcer size and pain trajectory and healing — response within ~1 month of immunosuppression is a Maverakis minor criterion; STOP GAP benchmark ~47% healed by 6 mo (PMID 29450466; PMID 26071094)
- prednisone: glucose + BP + bone-health on prolonged therapy; slow response-guided taper (STOP GAP PMID 26071094)
- ciclosporin: BP + creatinine (CKD-EPI 2021) during titration and maintenance (STOP GAP PMID 26071094)
- azathioprine/mycophenolate: CBC + LFT periodic; azathioprine TPMT before start (Partridge PMID 29478243)
- TNF biologic: latent-TB/HBV/HCV pre-screen + on-treatment infection vigilance (Brooklyn Gut 2006 PMID 16188920)
- associated-disease activity (IBD/arthritis/heme) tracked as it drives the skin; repeat heme screen if new cytopenia (Shaigany PMID 34714405)

Setting (outpatient) monitoring:
- Ulcer size + pain + healing at intervals; expect immunosuppression response within ~1 month (Maverakis minor; PMID 29450466)
- Drug-class safety labs (ciclosporin BP/Cr; azathioprine/MMF CBC/LFT; biologic infection screen) (STOP GAP PMID 26071094; Partridge PMID 29478243)

Follow-up plan: Chronic surveillance: continued meticulous moist non-adherent wound care + analgesia, slow steroid taper with steroid-sparing maintenance, recurrence vigilance (PG recurs in ~28-30% — STOP GAP), pathergy education (avoid elective surgery/debridement; flag PG to any future surgeon; perioperative immunosuppressive cover if surgery unavoidable), cribriform-scar counselling, and ongoing associated-disease monitoring (repeat heme screen if new cytopenia; IBD/arthritis activity). Dermatology continuity for any systemic agent.
- Close-out criterion: wound-care + taper + pathergy education + recurrence + associated-disease surveillance plan documented

Monitoring phase: Disease: ulcer size + pain trajectory + healing (response within ~1 month of starting immunosuppression is itself a Maverakis minor criterion); STOP GAP benchmark ~47% healed by 6 months on prednisolone OR ciclosporin. Drug safety: prednisone (glucose/BP/bone), ciclosporin (BP + creatinine, CKD-EPI), azathioprine/MMF (CBC/LFT), biologics (infection/TB reactivation). Taper guided by response with transition to a steroid-sparing agent. Track associated-disease activity (IBD/arthritis/heme) as it drives the skin.

Disposition

Current setting: outpatient — Diagnose PG by clinical criteria as a diagnosis of EXCLUSION (no confirmatory test; biopsy excludes mimics), enforce the no-debridement/pathergy rule, complete the mandatory associated-disease workup, and start an extent-appropriate immunosuppressive + wound-care plan (Maverakis Delphi PMID 29450466; PARACELSUS PMID 29388188; STOP GAP PMID 26071094)

Disposition criteria:
- Continue extent-appropriate ladder + wound care + dermatology follow-up if controlled (STOP GAP PMID 26071094)
- Escalate to systemic / biologic per the ladder if topical-refractory or rapidly progressive
- Admit only for fulminant / systemically toxic PG, severe uncontrolled pain, or pathergy-driven enlargement needing multidisciplinary care

Escalation triggers (move to higher acuity):
- Rapidly progressive / fulminant / systemically toxic PG → admit + IV immunosuppression (Partridge PMID 29478243)
- Ulcer enlarging after a debridement/surgery (pathergy) → STOP surgery, immunosuppress, recognise misdiagnosis (PMID 31498172)
- True necrotising soft-tissue infection features (crepitus/gas/sepsis) → route OUT to id.necrotising-fasciitis.core.v1 (surgical emergency)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Rapidly progressive / fulminant / multifocal PG with systemic toxicity (fever, malaise, rapid expansion) (Partridge Br J Dermatol 2018 PMID 29478243)
- [LIFE_THREATENING] Genuine necrotising soft-tissue infection features (crepitus, gas, fulminant sepsis, true rapid necrosis) — NOT PG (IDSA SSTI; PMID 31498172)
- [SEVERE] Ulcer misdiagnosed as wound/necrotising infection and surgically debrided, now enlarging — pathergy (Flynn Adv Skin Wound Care 2019 PMID 31498172)

Citations

- Maverakis et al, Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum — Delphi consensus (JAMA Dermatol 2018; PMID 29450466; DOI 10.1001/jamadermatol.2017.5980) + Jockenhöfer et al PARACELSUS diagnostic score (Br J Dermatol 2019; PMID 29388188; DOI 10.1111/bjd.16401) + Ormerod/Thomas STOP GAP ciclosporin-vs-prednisolone RCT (BMJ 2015; PMID 26071094; DOI 10.1136/bmj.h2958) + Brooklyn et al infliximab RCT (Gut 2006; PMID 16188920; DOI 10.1136/gut.2005.074815) + Partridge et al systematic review of systemic therapy (Br J Dermatol 2018; PMID 29478243; DOI 10.1111/bjd.16485) [PMID:29450466](https://pubmed.ncbi.nlm.nih.gov/29450466/)
- Cited evidence (PMID 29388188) [PMID:29388188](https://pubmed.ncbi.nlm.nih.gov/29388188/)
- Cited evidence (PMID 26071094) [PMID:26071094](https://pubmed.ncbi.nlm.nih.gov/26071094/)
- Cited evidence (PMID 16188920) [PMID:16188920](https://pubmed.ncbi.nlm.nih.gov/16188920/)
- Cited evidence (PMID 29478243) [PMID:29478243](https://pubmed.ncbi.nlm.nih.gov/29478243/)

Last reconciled with current guidelines: 2026-05-22.

References

Maverakis et al, Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum — Delphi consensus (JAMA Dermatol 2018; PMID 29450466; DOI 10.1001/jamadermatol.2017.5980) + Jockenhöfer et al PARACELSUS diagnostic score (Br J Dermatol 2019; PMID 29388188; DOI 10.1111/bjd.16401) + Ormerod/Thomas STOP GAP ciclosporin-vs-prednisolone RCT (BMJ 2015; PMID 26071094; DOI 10.1136/bmj.h2958) + Brooklyn et al infliximab RCT (Gut 2006; PMID 16188920; DOI 10.1136/gut.2005.074815) + Partridge et al systematic review of systemic therapy (Br J Dermatol 2018; PMID 29478243; DOI 10.1111/bjd.16485) — PMID:29450466
Cited evidence (PMID 29388188) — PMID:29388188
Cited evidence (PMID 26071094) — PMID:26071094
Cited evidence (PMID 16188920) — PMID:16188920
Cited evidence (PMID 29478243) — PMID:29478243