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derm.bullous-pemphigoid.core.v1PRODUCTION
derm.bullous-pemphigoid.core.v1

Bullous pemphigoid

dermatologysubacutechronicadultgeriatric
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12/12 authored

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

Current phase

Frame

Detailed

Frame as the COMMONEST autoimmune subepidermal blistering disease of the ELDERLY — anti-hemidesmosome (BP180/BP230) autoimmunity, chronic-relapsing, managed on a severity-tiered ladder with TOPICAL clobetasol as the survival-superior mainstay. The non-bullous prodrome (itch ± urticarial/eczematous, no blisters) is the diagnostic trap. Drug-induced BP (gliptin/checkpoint/diuretic) is reconciled here. Infection/sepsis from eroded skin is the leading cause of death and is escalated/routed.

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chronic autoimmune-bullous framing set; non-bullous-prodrome + drug-induced + infection escape routes noted

Patient inputs (20)

Limited mild oral involvement may occur in BP, but predominant/scarring mucosal disease (esp. ocular) shifts the diagnosis to mucous-membrane pemphigoid and mandates ophthalmology/ENT (EADV MMP 2021 PMID 34309078)

Tense subepidermal bullae on erythematous/urticarial base (BP) vs flaccid easily-rupturing bullae with positive Nikolsky (pemphigus, intraepidermal) is a top discriminator (EADV 2022 PMID 35766904)

Eczematous/urticarial/prurigo-like itch without blisters is the prodromal non-bullous phase — recognising it ends months of diagnostic delay and triggers biopsy+serology (EADV 2022 PMID 35766904)

DPP-4 inhibitors (gliptins), immune-checkpoint inhibitors, and loop diuretics/spironolactone can induce BP; identifying and withdrawing the culprit is disease-modifying (Tasanen Front Immunol 2019 PMID 31275298; Sibaud Am J Clin Dermatol 2018 PMID 29256113)

BP overwhelmingly affects the elderly (peak >70 y); age + frailty drive the topical-first mortality-avoidance strategy and 1-yr-mortality counselling (Joly NEJM 2002 PMID 11821508)

Intractable itch is the cardinal and often the FIRST (pre-bullous) symptom of BP and the primary patient-reported activity measure that drives recognition and step-up (EADV 2022 PMID 35766904)

Direct immunofluorescence of PERILESIONAL skin showing linear C3 ± IgG along the basement-membrane zone is the diagnostic gold standard and the pivot vs pemphigus (intercellular) and EBA (also linear — needs salt-split) (EADV 2022 PMID 35766904)

Serum anti-BP180-NC16A (± anti-BP230) ELISA confirms the diagnosis and its titre correlates with disease activity for monitoring/relapse prediction (Schmidt Arch Dermatol 2000 PMID 10677092)

Eroded denuded skin superinfects; sepsis is the leading cause of death in BP — pustules/purulent crust/fever/systemic toxicity force admission + infection pathway (EADV 2022 PMID 35766904)

Localised/moderate vs extensive disease (BLISTER strata: 3–9 mild, 10–30 moderate, >30 severe blisters) gates topical-vs-systemic escalation and admission (Williams BLISTER Lancet 2017 PMID 28279484)

BP is elderly-predominant; frailty/dementia raises systemic-steroid mortality and constrains topical-clobetasol whole-body application (caregiver burden) — drives the topical-first vs systemic decision (Joly NEJM 2002 PMID 11821508)

Indirect IF on 1 mol/L NaCl salt-split skin localises circulating antibody to the epidermal roof (BP) vs the dermal floor (EBA / anti-p200 pemphigoid) — the EBA/anti-p200 pivot (EADV 2022 PMID 35766904)

Stroke/dementia/Parkinson disease are independent BP associations and worsen prognosis + application capacity (Tasanen Front Immunol 2019 PMID 31275298)

Tissue + peripheral eosinophilia supports BP and is a baseline for steroid-sparing immunosuppressant safety monitoring (EADV 2022 PMID 35766904)

Baseline + on-treatment hepatotoxicity monitoring for azathioprine / methotrexate / MMF and doxycycline (EADV 2022 PMID 35766904)

Pre-rituximab/immunosuppressant latent-TB + hepatitis B/C screen before B-cell-depleting or immunosuppressive therapy (EADV 2022 PMID 35766904)

Systemic-steroid hyperglycaemia surveillance, and the gliptin-BP link makes diabetic status decision-relevant (drug reconciliation) (Tasanen Front Immunol 2019 PMID 31275298)

BP in pregnancy is rare; pemphigoid gestationis (gestational pemphigoid) is a distinct peri-/post-partum anti-BP180 entity to differentiate, and it gates immunosuppressant choice (EADV 2022 PMID 35766904)

TPMT enzyme activity/genotype before azathioprine prevents life-threatening myelosuppression in low/absent-activity patients (EADV 2022 PMID 35766904)

Renal function for methotrexate dosing/contraindication and CKD-EPI 2021 race-free eGFR in the elderly multimorbid BP population (EADV 2022 PMID 35766904; Inker NEJM 2021)

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Severity triggers (7)

7 need judgement
  • informationallife_threateningextensive_bp_with_secondary_infection_or_sepsis
    Extensive eroded/denuded BP with secondary skin infection, purulent crust/pustules, fever, or systemic toxicity / sepsis physiology
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereerythrodermic_or_very_extensive_bp
    Very extensive / near-erythrodermic BP with impaired thermoregulation, fluid/electrolyte loss, or haemodynamic stress
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_mucosal_involvement_reassess_mmp
    Predominant or scarring mucosal involvement, especially ocular (symblepharon/conjunctival scarring) or oral/laryngeal/oesophageal erosions
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererapidly_progressive_or_refractory_bp
    Rapidly progressive widespread blistering, or BP refractory to/intolerant of systemic corticosteroid + a steroid-sparing immunosuppressant
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresteroid_related_decompensation_in_frail_elderly
    Systemic-corticosteroid complication in a frail elderly BP patient — hyperglycaemic crisis, serious infection, fracture, delirium, or GI bleed
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatecheckpoint_inhibitor_induced_bp
    BP arising during immune-checkpoint-inhibitor (anti-PD-1/PD-L1/CTLA-4) therapy in an oncology patient
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateunrecognised_non_bullous_prodrome_diagnostic_delay
    Elderly patient with months of intractable pruritus ± urticarial/eczematous/prurigo-like lesions and NO blisters, repeatedly treated as eczema/urticaria/scabies
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Bullous pemphigoid — severity-tiered ladder, topical-clobetasol-first (EADV 2022 / Joly NEJM 2002 / BLISTER 2017)
axis: bp_severity_tiered_topical_first_ladderstep 1 - Step 1 — Withdraw culprit drug + skin/blister care (every patient)
Selected step "Step 1 — Withdraw culprit drug + skin/blister care (every patient)" — All patients at presentation — reconcile and withdraw drug-induced BP triggers; supportive skin care throughout
  • withdraw_offending_drug_dpp4i_checkpoint_loop_diuretic
    first line
    culprit_withdrawal
    triggers: recent_gliptin_or_checkpoint_inhibitor_or_loop_diuretic
    Tasanen Front Immunol 2019 (PMID 31275298) + Sibaud Am J Clin Dermatol 2018 (PMID 29256113) — DPP-4 inhibitors (esp. vildagliptin), immune-checkpoint inhibitors and loop diuretics induce BP; withdrawing the culprit is disease-modifying and may obviate immunosuppression. Coordinate checkpoint-inhibitor hold with oncology.
  • gentle_wound_blister_care_and_infection_surveillance
    first line
    supportive_skin_care
    EADV 2022 (PMID 35766904) — non-adherent dressings, blister decompression with roof preservation, emollients, and active surveillance for secondary infection (the leading cause of BP death).

outpatient playbook — drug actions (5)

  1. 1. withdraw culprit drug (gliptin/checkpoint/loop diuretic) + supportive blister/wound care
    n/a • n/a • immediate
    trigger: Drug-induced BP suspected (Tasanen PMID 31275298; Sibaud PMID 29256113)
    Culprit withdrawal is disease-modifying; coordinate checkpoint-inhibitor hold with oncology
  2. 2. clobetasol propionate 0.05% whole-body (mainstay first line)
    rxcui 21245
    ~20–40 g/day • topical • once–twice daily then taper
    trigger: Localised/moderate or extensive BP where application feasible (Joly NEJM 2002 PMID 11821508)
    Survival-superior + fewer severe complications vs oral prednisone in extensive BP
  3. 3. doxycycline 200 mg/day (steroid-sparing; preferred if oral steroid contraindicated)
    rxcui 3640
    200 mg • PO • once daily
    trigger: Moderate BP or oral-steroid contraindicated (Williams BLISTER Lancet 2017 PMID 28279484)
    Non-inferior short-term blister control, significantly safer long-term
  4. 4. prednisone 0.5 mg/kg/day + steroid-sparing agent (azathioprine [TPMT] / MMF / methotrexate)
    rxcui 8640
    0.5 mg/kg/day • PO • once daily, taper
    trigger: Extensive BP, topical not feasible/failed (EADV 2022 PMID 35766904)
    Lowest-effective steroid + steroid-sparing immunosuppressant to limit cumulative steroid harm
  5. 5. rituximab / omalizumab / dupilumab / IVIG (refractory)
    rxcui 121191
    per protocol • IV/SC • per agent
    trigger: Refractory to steroid + steroid-sparing immunosuppressant (EADV 2022 PMID 35766904; Zhao JAMA Dermatol 2023 PMID 37531116)
    B-cell depletion / anti-IgE / anti-IL-4Rα / IVIG for treatment-resistant disease; reassess diagnosis

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Tense bullae on erythematous/urticarial skin with intense pruritus in an elderly patient — the classic bullous phase (EADV S2k BP guideline, JEADV 2022; PMID 35766904); Months of intractable pruritus ± urticarial/eczematous/prurigo-like lesions WITHOUT blisters in the elderly — the non-bullous prodrome (commonly mis-labelled eczema/urticaria/scabies for months) (EADV 2022; PMID 35766904); New DPP-4 inhibitor (gliptin, esp. vildagliptin) / immune-checkpoint inhibitor / loop diuretic preceding a pruritic-bullous eruption → drug-induced BP (Tasanen, Front Immunol 2019; PMID 31275298; Sibaud, Am J Clin Dermatol 2018; PMID 29256113).

Objective

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

Assessment

**Bullous pemphigoid** (derm.bullous-pemphigoid.core.v1).
Phenotype framing: Terminal autoimmune/blistering differential with named pivots: BP vs pemphigus vulgaris (intraepidermal, flaccid, mucosal, Nikolsky+, intercellular DIF, anti-Dsg pivot) vs mucous-membrane pemphigoid (predominant/scarring mucosa, ocular/oral pivot) vs epidermolysis bullosa acquisita (trauma-site, dermal-floor salt-split pivot) vs dermatitis herpetiformis (grouped intensely itchy, granular IgA, celiac pivot) vs linear IgA bullous dermatosis (linear IgA pivot) vs bullous drug eruption / SJS-TEN (drug latency, DIF-negative necrosis pivot — route derm.sjs-ten.core.v1) vs bullous arthropod/contact/diabetic bullae (distribution/exposure pivot) vs urticaria (non-bullous-phase mimic — route derm.urticaria.core.v1) vs scabies/eczema (non-bullous mimic — route derm.atopic-dermatitis.core.v1). Drug-induced BP is a within-BP modifier, not an alternative.
Scope: Frame as the COMMONEST autoimmune subepidermal blistering disease of the ELDERLY — anti-hemidesmosome (BP180/BP230) autoimmunity, chronic-relapsing, managed on a severity-tiered ladder with TOPICAL clobetasol as the survival-superior mainstay. The non-bullous prodrome (itch ± urticarial/eczematous, no blisters) is the diagnostic trap. Drug-induced BP (gliptin/checkpoint/diuretic) is reconciled here. Infection/sepsis from eroded skin is the leading cause of death and is escalated/routed.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Bullous pemphigoid — severity-tiered ladder, topical-clobetasol-first (EADV 2022 / Joly NEJM 2002 / BLISTER 2017)** — step "Step 1 — Withdraw culprit drug + skin/blister care (every patient)".
1. withdraw_offending_drug_dpp4i_checkpoint_loop_diuretic (culprit_withdrawal, first line) — Tasanen Front Immunol 2019 (PMID 31275298) + Sibaud Am J Clin Dermatol 2018 (PMID 29256113) — DPP-4 inhibitors (esp. vildagliptin), immune-checkpoint inhibitors and loop diuretics induce BP; withdrawing the culprit is disease-modifying and may obviate immunosuppression. Coordinate checkpoint-inhibitor hold with oncology.
2. gentle_wound_blister_care_and_infection_surveillance (supportive_skin_care, first line) — EADV 2022 (PMID 35766904) — non-adherent dressings, blister decompression with roof preservation, emollients, and active surveillance for secondary infection (the leading cause of BP death).

Setting playbook (outpatient) — Confirm BP (perilesional DIF + lesional H&E + anti-BP180/BP230 ELISA + salt-split IIF), recognise the non-bullous prodrome, reconcile/withdraw any culprit drug, and treat topical-clobetasol-first with severity-tiered escalation and anti-BP180-titre-guided monitoring (EADV 2022 PMID 35766904; Joly NEJM 2002 PMID 11821508)
3. withdraw culprit drug (gliptin/checkpoint/loop diuretic) + supportive blister/wound care n/a n/a immediate — Drug-induced BP suspected (Tasanen PMID 31275298; Sibaud PMID 29256113) (Culprit withdrawal is disease-modifying; coordinate checkpoint-inhibitor hold with oncology)
4. clobetasol propionate 0.05% whole-body (mainstay first line) ~20–40 g/day topical once–twice daily then taper — Localised/moderate or extensive BP where application feasible (Joly NEJM 2002 PMID 11821508) (Survival-superior + fewer severe complications vs oral prednisone in extensive BP)
5. doxycycline 200 mg/day (steroid-sparing; preferred if oral steroid contraindicated) 200 mg PO once daily — Moderate BP or oral-steroid contraindicated (Williams BLISTER Lancet 2017 PMID 28279484) (Non-inferior short-term blister control, significantly safer long-term)
6. prednisone 0.5 mg/kg/day + steroid-sparing agent (azathioprine [TPMT] / MMF / methotrexate) 0.5 mg/kg/day PO once daily, taper — Extensive BP, topical not feasible/failed (EADV 2022 PMID 35766904) (Lowest-effective steroid + steroid-sparing immunosuppressant to limit cumulative steroid harm)
7. rituximab / omalizumab / dupilumab / IVIG (refractory) per protocol IV/SC per agent — Refractory to steroid + steroid-sparing immunosuppressant (EADV 2022 PMID 35766904; Zhao JAMA Dermatol 2023 PMID 37531116) (B-cell depletion / anti-IgE / anti-IL-4Rα / IVIG for treatment-resistant disease; reassess diagnosis)

Non-pharmacologic actions:
- Non-adherent dressings + blister decompression with roof preservation + emollients (EADV 2022 PMID 35766904)
- Relapse-recognition education (itch, new blisters) + anti-BP180 titre trend counselling (Schmidt Arch Dermatol 2000 PMID 10677092)
- Permanent culprit-drug avoidance flag + alternative-antidiabetic plan if gliptin-induced (Tasanen Front Immunol 2019 PMID 31275298)
- Caregiver training for whole-body topical clobetasol application in frail/demented patients (Joly NEJM 2002 PMID 11821508)

AVOID / contraindication checks:
- Avoid prolonged high dose systemic corticosteroid in frail elderly (Joly NEJM 2002 PMID 11821508 — prefer whole body topical clobetasol [survival superior] / doxycycline [BLISTER PMID 28279484])
- Azathioprine check tpmt activity or genotype before starting (EADV 2022 PMID 35766904 — absent/low TPMT → severe myelosuppression; use MMF instead)
- Dapsone check g6pd before starting monitor haemolysis methaemoglobinaemia (EADV 2022 PMID 35766904)
- Methotrexate mycophenolate contraindicated in pregnancy and conception (EADV 2022 PMID 35766904)
- Pre rituximab immunosuppressant screen latent tb and hbv hcv avoid live vaccines (EADV 2022 PMID 35766904)
- Withdraw culprit drug first gliptin checkpoint inhibitor loop diuretic (Tasanen Front Immunol 2019 PMID 31275298; Sibaud Am J Clin Dermatol 2018 PMID 29256113 — coordinate checkpoint hold with oncology)
- Secondary infection and sepsis from eroded skin is the leading cause of death treat do not only escalate immunosuppression (EADV 2022 PMID 35766904)
- Pemphigoid gestationis is a distinct pregnancy entity not managed as classic bp (EADV 2022 PMID 35766904)

Monitoring

Regimen monitoring:
- anti BP180 NC16A titre tracks disease activity rising titre predicts relapse (Schmidt Arch Dermatol 2000 PMID 10677092)
- itch plus new blister count plus BSA at each visit (EADV 2022 PMID 35766904; BLISTER strata PMID 28279484)
- systemic steroid: glucose/BP/bone/infection surveillance + taper to lowest effective (Joly NEJM 2002 PMID 11821508)
- azathioprine/MMF/methotrexate: CBC + LFT periodic; TPMT-guided azathioprine; folic acid with methotrexate (EADV 2022 PMID 35766904)
- doxycycline: photosensitivity + GI tolerance; dapsone: CBC + methaemoglobin (EADV 2022 PMID 35766904)
- rituximab: infusion reactions, hypogammaglobulinaemia, infection (rare PML) — periodic immunoglobulins + infection vigilance (Thomas Clin Dermatol 2019 PMID 32563354)
- infection surveillance throughout leading cause of death (EADV 2022 PMID 35766904)

Setting (outpatient) monitoring:
- Itch + new-blister count + BSA + anti-BP180-NC16A titre each visit (EADV 2022 PMID 35766904; Schmidt PMID 10677092)
- Drug-class safety labs on schedule (steroid glucose/BP/bone; azathioprine/MMF/MTX CBC/LFT; doxycycline photosensitivity) (EADV 2022 PMID 35766904)

Follow-up plan: Chronic relapsing-remitting maintenance: taper to lowest effective therapy (ideally topical/intermittent), relapse-recognition education (itch/new blisters), anti-BP180 titre trend for relapse prediction, periodic steroid/immunosuppressant safety surveillance, infection precautions, and — for drug-induced BP — a permanent culprit-avoidance flag (and an alternative-antidiabetic plan if gliptin-induced). Dermatology continuity for any systemic agent; reassess the diagnosis (repeat biopsy/serology) if the course is atypical or treatment-refractory.
- Close-out criterion: taper plan + relapse education + titre surveillance + culprit-avoidance flag + safety monitoring documented

Monitoring phase: Disease: itch + new-blister count + BSA + anti-BP180-NC16A titre at follow-up — the ELISA titre tracks disease activity and rising titre predicts relapse (Schmidt 2000). Drug safety: systemic steroid → glucose/BP/bone/infection; azathioprine/MMF/methotrexate → CBC + LFT (and TPMT-guided azathioprine dosing); doxycycline → photosensitivity/GI; rituximab → infusion reactions, hypogammaglobulinaemia, infection (PML — rare). Infection vigilance throughout (leading cause of death). Taper systemic therapy to the lowest effective dose/topical maintenance.

Disposition

Current setting: outpatient — Confirm BP (perilesional DIF + lesional H&E + anti-BP180/BP230 ELISA + salt-split IIF), recognise the non-bullous prodrome, reconcile/withdraw any culprit drug, and treat topical-clobetasol-first with severity-tiered escalation and anti-BP180-titre-guided monitoring (EADV 2022 PMID 35766904; Joly NEJM 2002 PMID 11821508)

Disposition criteria:
- Continue topical-first ladder + anti-BP180-titre-guided monitoring + derm follow-up if responding (EADV 2022 PMID 35766904)
- Step up the ladder if an adequate trial fails after adherence/application optimisation
- Admit only for infection/sepsis, erythroderma, application-incapacity in extensive disease, or steroid decompensation

Escalation triggers (move to higher acuity):
- Extensive BP with secondary infection / sepsis or erythroderma → admit + infection/sepsis pathway (EADV 2022 PMID 35766904)
- Severe/scarring mucosal (esp. ocular) involvement → reassess for MMP + emergent ophthalmology/ENT (EADV MMP 2021 PMID 34309078)
- Frail elderly unable to apply whole-body topical therapy + extensive disease → admit for supervised therapy

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Extensive eroded/denuded BP with secondary skin infection, purulent crust/pustules, fever, or systemic toxicity / sepsis physiology
- [SEVERE] Very extensive / near-erythrodermic BP with impaired thermoregulation, fluid/electrolyte loss, or haemodynamic stress
- [SEVERE] Predominant or scarring mucosal involvement, especially ocular (symblepharon/conjunctival scarring) or oral/laryngeal/oesophageal erosions

Citations

- EADV updated S2k guideline for the management of bullous pemphigoid (Borradori et al, JEADV 2022; PMID 35766904) — high-potency topical corticosteroid is the mainstay first line; oral prednisone 0.5 mg/kg/day alternative; azathioprine/MMF/methotrexate steroid-sparing; doxycycline/dapsone when steroids contraindicated; rituximab/IVIG for resistant disease; omalizumab/dupilumab promising. Diagnosis per EADV autoimmune-bullous canon (perilesional DIF + lesional H&E + anti-BP180-NC16A/anti-BP230 ELISA + salt-split-skin IIF). Mucous-membrane-pemphigoid differential per EADV MMP S3 guideline Parts I+II (Rashid/Schmidt, JEADV 2021; PMID 34245180 / 34309078). Cornerstone trials: Joly NEJM 2002 topical-clobetasol superiority (PMID 11821508); Williams BLISTER Lancet 2017 doxycycline non-inferiority/safety (PMID 28279484). [PMID:35766904](https://pubmed.ncbi.nlm.nih.gov/35766904/)
- Cited evidence (PMID 11821508) [PMID:11821508](https://pubmed.ncbi.nlm.nih.gov/11821508/)
- Cited evidence (PMID 16038572) [PMID:16038572](https://pubmed.ncbi.nlm.nih.gov/16038572/)
- Cited evidence (PMID 28279484) [PMID:28279484](https://pubmed.ncbi.nlm.nih.gov/28279484/)
- Cited evidence (PMID 10677092) [PMID:10677092](https://pubmed.ncbi.nlm.nih.gov/10677092/)

Last reconciled with current guidelines: 2026-05-22.
References
  • EADV updated S2k guideline for the management of bullous pemphigoid (Borradori et al, JEADV 2022; PMID 35766904) — high-potency topical corticosteroid is the mainstay first line; oral prednisone 0.5 mg/kg/day alternative; azathioprine/MMF/methotrexate steroid-sparing; doxycycline/dapsone when steroids contraindicated; rituximab/IVIG for resistant disease; omalizumab/dupilumab promising. Diagnosis per EADV autoimmune-bullous canon (perilesional DIF + lesional H&E + anti-BP180-NC16A/anti-BP230 ELISA + salt-split-skin IIF). Mucous-membrane-pemphigoid differential per EADV MMP S3 guideline Parts I+II (Rashid/Schmidt, JEADV 2021; PMID 34245180 / 34309078). Cornerstone trials: Joly NEJM 2002 topical-clobetasol superiority (PMID 11821508); Williams BLISTER Lancet 2017 doxycycline non-inferiority/safety (PMID 28279484). — PMID:35766904
  • Cited evidence (PMID 11821508) — PMID:11821508
  • Cited evidence (PMID 16038572) — PMID:16038572
  • Cited evidence (PMID 28279484) — PMID:28279484
  • Cited evidence (PMID 10677092) — PMID:10677092