Esophageal lichen planus: Current knowledge, challenges and future perspectives

Table 1 Inflammatory diseases of the esophagus

Chemical or physical damages

Reflux esophagitis

Chemical esophagitis (acids, leach)

Radiation induced esophagitis

Drug-induced esophagitis e.g. NSAID, bisphosphonates, tetracyclines, KCl, ferric sulfate, ascorbinic acid

Infectious esophagitis

Candida spp.

Viruses, e.g. Cytomegalovirus, Herpes simplex, HIV

Immune-mediated esophagitis

EoE

Crohn’s disease

GVHD

Behçet’s disease

Systemic sclerosis

Lymphocytic esophagitis

Lichen planus

Mucus membrane pemphigoid

Pemphigus

Congenital skin disease

Esophageal involvement in epidermolysis bullosa

Others

EIPD

Sloughing esophagitis

NSAIR: Non-steroidal anti-inflammatory drug; KCl: Kalium chloride; HIV: Human immunodeficiency virus; GVHD: Graft-versus-host disease; EIPD: Esophageal intramural pseudodiverticulosis; EoE: Eosinophilic esophagitis.

Table 2 Studies on esophageal lichen planus (numbers in braces indicate number/percentage of patients from the cohort to which the criterion applies)

Ref.	Study design	Number of ELP cases	Further manifestation sites of LP	Macroscopic findings as described in the manuscript	Histologic findings as described in the manuscript	Signs and symptoms	Therapy
Keate et al[53], 2003	Case series	3 (all)	Cutaneous oral genital	Mucosal sloughing stenosis	Band-like infiltrate hyperkeratosis acanthosis	Dysphagia	Tacrolimus intralesional Pred. Response 3/3; Etretinate (no effect)
Donnellan et al[116], 2011	Case series	5 (all)	Oral (all), genital (2), cutaneous (1)	Ulcerations, strictures	Band-like lymphocytic infiltrate, civatte bodies	Dysphagia (all)	Dilation (4) Flut; Response 3/5
Franco et al[69], 2015	Case series	6 (83%)	Cutaneous and oral (4)	Ulcerations, strictures (5)	Band-like lymph infiltrate, civatte bodies, fibrinogen + in DIF	Dysphagia (all), food impaction (2)	Dilation (3) Flut/Pred/Triam. Response 5/5
Dickens et al[74], 1990	19 LP patients	5	Cutaneous (19), oral (4)	Papular lesions, mucosal detachment on biopsy, erosions	Submucosal lymphocytic infiltrate	Dysphagia (1)
Harewood et al[65], 1999	Retrospective search in patient register	6 (100%)	Oral (5), genital (3), cutaneous (2), ELP as initial manifestation (5)	Proximal strictures (4)	Lymphocytic infiltration (4)	Dysphagia (6); odynophagia (2)	Dilation of strictures (6); Prednisone (40-60mg). Response 3/4
Quispel et al[16], 2009	24 LP patients	12	Oral and/or cutaneous (all)	Whitish papules (10), hyperemic lesions (3), mucosal detachment (2), submucosal plaques (3)	Lymphohistiocytic infiltrations para-/hyperkeratosis, hyperplasia, civatte bodies, glycogen akanthosis	Dysphagia (4), odynophagia (3), heart burn (3), regurgitation (2)
Katzka et al[17], 2010	Retrospecitve review (10 years) of data base/ esophageal biopsies from patients with dysphagia	27 (92%)	Oral (19), genital (13), cutaneous (3), ELP as initial manifestation (13)	Strictures (18): Proximal (11), distal (3), both (4), mucosal detachment (11), erythema, plaques, whitish mucosa, superficial ulcerations, Koebner effect after dilat	Lichenoid lymphocytic infiltration, damage of ephithelial basal layer civatte bodies squamous cell carcinoma (1)	Dysphagia (27); odynophagia (2)	Dilation of strictures (17). Dilation + Fluticasone Response 10/11. No dilation plus intralesional corticosteroids (2) or swallowed Futicason/ Budesonide (2). Response 6/6
Fox et al[77], 2011	Review of published ELP cases until 2009 (including 4 own cases)	72 (87%)	Oral (89%), genital (42%), cutaneous (38%), scalp (7%); nails (3%), eyes (1%), ELP as initial manifestation (14)	Pseudomembranes, bleeding, fragility, inflammation; proximal (64%); distal (11%); Both (26%); Stenosis (47%)	Lichenoid lymphocytic infiltrates; dysplasia/squamous cell carcinoma (6%)	Dysphagia (81%); odynophagia (24%); weight loss (14%); heart burn (8%); regurgitation (3%); hoarseness (1%); asymptomatic (17%)
Linton et al[66], 2013	Retrospective analysis of esophageal biopsies from 273 patients out of a large cohort	1 typical ELP; 6 possible ELP	No data	Inflammation (7); stricture (5); trachealization (4) mucosal fragility (1); ulcerations (3); nodules (3)	Lymphocytic infiltration (7); Civatte bodies (1); parakeratosis (6); mixed infiltration (6) elongation of lamina propria papillae (7) hyperplasia of basal cells (4); widened intercellular space (3); neutrophilic inflamm (1)	Dysphagia (7); odynophagia (4)	Dilation of stenosis (3). Topical Fluticasone (2). Response 2/2. Proton pump inhibitors (7). Sucralfate (2). 5-HT4-RA (1)
Podboy et al[19], 2017	Retrospective analysis of a cohort of ELP-patients	40 (80%)	Cutaneous (4), oral (19), genital (15), ELP as only; manifestation (13)	Strictures (29), ring formation (29), ulcerations (8), mucosal detachment (6), other mucosal, lesions (14), squameous cell carcinoma (2)	Common findings (> 5): Esophagitis (20), focal ulcerations (13), mucosal hyperplasia (10), intraepithelial lymphocytic infiltrate (13), eosinophilia < 5 (13) dyskeratosis (11). DIF positive: Lichenoid (2) equivocal (5) not evaluable because of mucosal detachment (13)	Dysphagia for solid food (32) even for fluids (8); odynophagia (6); reflux (1)	Topical corticosteroids: Budesonide in honey 2 x 3mg (32). Fluticasone spray 880 µg 2x/d (8). Response rate: Endoscopic (72,5%), clinical (62%)
Ravi et al[101], 2019	Retrospective analysis of ELP patients	132 (80%)		Clinical diagnosis (77)	“Specific histology” (55); Esophageal carcinoma (8)		Response to topical steroids 84/132 63.6%. Immunosuppressive; therapy necessary 38/132. Response: No data
Kern et al[18], 2016; Schauer et al[20], 2019	52 patients.with proven LP on other site (75%)	34mild (18); severe (16)	Oral 78-100% (vs 78% in non-ELP), genital 44-61% (vs 6% non-ELP). Cutaneous 25-44% (vs 28% non-ELP)	Mucosal detachment iatrogenic (12); spontaneous (16); hyperkeratosis (7); trachealization (10); stenosis/strictures (7)	Epithelial detachment, lymphocytic infiltration, Civatte bodies, dyskeratosis; DIF: Fibrinogen deposits (17); (85% in severe ELP)	Dysphagia. severe ELP: 15; mild ELP: 8	Topical corticosteroids (12). Budesonide gel 3x0.5mg. Fluticasone. Response 11/12. Stenosis: Topical corticosteroids dilation

LP: Lichen planus; ELP: Esophageal lichen planus;DIF: Direct immunofluorescence; Flut: Fluticasone; Bud: Budesonide; Pred: Prednisolone; Triam: Triamcinolone.

Table 3 Diagnostic criteria to establish diagnosis and assess disease severity (modified from Schauer et al[20])

Macroscopic-endoscopic criteria
Specific signs
D	Denudation/sloughing of the mucosa
D1	Iatrogenic denudation (caused by biopsies)
D2	Spontaneous localized denudation < 1 cm2
D3	Spontaneous spacious denudation > 1 cm2
Possible signs
S	Stenosis/stricture
S1	Passable with standard endoscope
S2	Not passable with standard endoscope
H	Hyperkeratosis (whitish, rough mucosa)
T	Trachealization
N	None of the criteria fulfilled
Microscopic criteria- histopathology and direct immunofluorescence
HP	Sloughing of the epithelia (subepithelial, intraepithelial)
	Lymphocytic infiltrate, mainly T-lymphocytes subepithelial, intraepithelial, junctional (region of the basal membrane)
	Intraepithelial apoptosis of keratinocytes (Civatte bodies)
	Dyskeratosis
HP0	Negative
HP1	Weakly positive
HP2	Positive
HP3	Strong positive
F	Fibrinogen deposition along the basal membrane
F0	No visible reaction
F1	Weak positive, discrete depositions visible
F2	Marked fibrinogen depositions along the basal membrane
Severity grading
Severe ELP	≥ D2 and HP ≥ 1 and/or F ≥ 1
Mild ELP	D1 and HP ≥ 1 and/or F ≥ 1; S, H, T, N and HP ≥ 1 and F ≥ 1
No ELP	Criteria not fulfilled in a patient with LP on other localization

HP: Histopathology; F: Immunofluorescence; ELP: Esophageal lichen planus.