Pillar 1 Valid Clinical Association: Autoimmune Dermatoses and Genodermatoses
This document constitutes the Pillar 1 Valid Clinical Association (VCA) evidence package for the autoimmune dermatoses and genodermatoses sub-indications. It is intended for inclusion as an appendix to the State of the Art Review (
R-TF-015-011) and for integration into the Clinical Evaluation Report (R-TF-015-003). It does not contain internal engineering references or tool outputs.
How to read this document
This document is organised in five parts: (1) search methodology and appraisal criteria; (2) per-condition evidence summaries and VCA conclusions for autoimmune dermatoses; (3) per-condition evidence summaries and VCA conclusions for genodermatoses; (4) gap coverage tables and limitations; (5) VCA claim statement with scope declaration. The VCA claim statement at the end is the text intended for direct insertion into R-TF-015-003 §VCA. The per-condition sections provide the traceability trail linking each named condition to its VCA anchor(s). The search block structure, Boolean search strings for supplementary searches S2–S6, record counts per block, and condition-by-condition coverage decisions are documented in the companion search strategy report. Boolean queries for primary blocks A1–D6 are documented in the search result PDFs held by the manufacturer. Full appraisal records including excluded-paper rationale are available for audit on request.
Purpose
This evidence review establishes that image-based clinical recognition of autoimmune dermatoses and genodermatoses is an accepted clinical practice with published diagnostic standards. This satisfies the association-existence element of the Pillar 1 Valid Clinical Association (VCA) requirement under MDCG 2020-1 §4.2: that the scientific link between the device's input (clinical and dermoscopic images) and the device's Top-5 prioritised differential-diagnosis view presented to the healthcare professional is corroborated by the established medical literature.
Scope of this document. This review establishes the first element of the Pillar 1 VCA — that image-based clinical recognition of the covered conditions is an accepted standard. It does not, and is not intended to, establish the downstream link from improved diagnostic recognition to patient-level clinical outcome. That surrogate-endpoint-to-outcome link is addressed in a separate structured literature review of surrogate-endpoint validity for dermatology decision-support systems, which forms the complementary component of the Pillar 1 VCA package for the Class IIb indirect clinical-benefit claim. The device's technical analytical performance (Pillar 2) and its effect on healthcare professional decision-making (Pillar 3) are established in the respective dedicated evidence packages.
The review addresses the device's intended use for two sub-indication categories:
- Autoimmune dermatoses (approximately 3% of the device's real-world use cases, based on the legacy report corpus): discoid lupus erythematosus, lichen planus (skin, nail, and mucosal), dermatomyositis, pemphigus vulgaris, bullous pemphigoid, mucous membrane pemphigoid, morphea, and cutaneous vasculitis.
- Genodermatoses (approximately 1% of the device's real-world use cases): ichthyoses, neurofibromatosis type 1 and type 2, tuberous sclerosis complex, and epidermolysis bullosa.
Search Methodology
A systematic targeted literature search was conducted across four thematic blocks, each comprising two to three sub-searches in PubMed (MEDLINE) using controlled vocabulary (MeSH) and free-text terms. Supplementary searches were conducted for six conditions identified as unaddressed in the initial block results: epidermolysis bullosa, tuberous sclerosis complex, dermatomyositis, morphea, pemphigus/bullous pemphigoid, and cutaneous vasculitis. Authoritative reference works (GeneReviews, international consensus guidelines) were retrieved by direct author or title search when systematic search did not return them. Searches were restricted to English-language, human-subject studies; no publication date limit was applied. Search execution date: 19–20 April 2026.
Databases searched. PubMed (MEDLINE) was the primary database. Embase and Cochrane Library were not searched in the current iteration, which is acknowledged as a limitation; the supplementary guideline-retrieval strategy (direct named-paper searches for professional-society guidelines) partially compensates for this gap for the autoimmune blistering disease and classification-criteria anchors. An expanded multi-database search is planned for the state-of-the-art section of R-TF-015-011.
Protocol documentation. The companion search strategy report (held by the manufacturer) documents the search block structure, record counts per block, Boolean search strings for supplementary searches S2–S6, and condition-by-condition coverage decisions. Boolean queries for primary blocks A1–D6 are documented in the search result PDFs held by the manufacturer; those PDFs also serve as the primary traceability record for those blocks. A formal PICO framework and PRISMA flow diagram were not produced for this targeted review; a full PRISMA-compliant systematic search is planned for the state-of-the-art section of R-TF-015-011. Full appraisal records including excluded-paper rationale are available for audit on request.
Titles and abstracts were screened against seven appraisal criteria (CRIT 1–7; see Appendix). Papers scoring ≥15/21 were retained as load-bearing VCA anchors; papers scoring 12–14/21 were retained as supporting context references; papers below 12/21 were excluded. All papers appraised from abstract only are noted as such; cited performance metrics for those papers are derived from the published abstract. Papers at the load-bearing threshold (15/21) appraised from abstract only are flagged for priority full-text retrieval and re-scoring before final incorporation into R-TF-015-011 and R-TF-015-003.
Appraisal Criteria Summary
| Criterion | Focus |
|---|---|
| CRIT1 | Relevance to the device's indication (image-based recognition of a condition in scope) |
| CRIT2 | Study design quality |
| CRIT3 | Reporting completeness (performance metrics, confidence intervals, external validation) |
| CRIT4 | Applicability to image-based clinical practice (clinical photography, dermoscopy) |
| CRIT5 | Evidence hierarchy (systematic review, multi-centre study, international consensus) |
| CRIT6 | Risk of bias |
| CRIT7 | Direct contribution to VCA claim (benchmarks image-based diagnostic accuracy) |
Maximum score: 21. Load-bearing threshold: ≥15. Inclusion threshold: ≥12.
The CRIT 1–7 appraisal rubric is the evaluation instrument applied in this review. Each criterion maps to corresponding items in the IMDRF MDCE WG/N56 Appendix F appraisal framework: CRIT1 and CRIT4 map to relevance/applicability; CRIT2 and CRIT6 map to methodological quality and bias; CRIT3 maps to reporting completeness; CRIT5 maps to evidence hierarchy; CRIT7 is a VCA-specific contribution criterion. A criterion-level mapping table is held in the internal search strategy documentation.
Autoimmune Dermatoses
Rationale for image-based recognition
Autoimmune dermatoses present with characteristic cutaneous morphologies that are the established basis for clinical suspicion and initial management decisions. Dermoscopy has been systematically validated as a tool that improves clinical recognition of these conditions over naked-eye examination alone. Definitive diagnosis for most autoimmune dermatoses requires confirmatory laboratory investigations (direct immunofluorescence, serology, histopathology); however, clinical and dermoscopic recognition at the point of care is the established first step that triggers the diagnostic workup. The device provides image-based differential-diagnosis support at this initial-recognition step; it does not perform or replace the confirmatory investigations.
Discoid lupus erythematosus and lichen planus
Evidence summary
Fathy et al. 2022 (Indian J Dermatol Venereol Leprol): Prospective study of 28 patients with histopathologically confirmed DLE. Dermoscopy features assessed against histopathological ground truth. Overall dermoscopic sensitivity 88.6%, specificity 71.2%, accuracy 83.5%. Follicular plugging showed the highest discriminatory value: sensitivity 95.8%, specificity 100%, accuracy 96.4%, κ=0.868. Perifollicular whitish halo: κ=0.652. Linear blood vessels: sensitivity 95.8%, specificity 75.0%, accuracy 89.3%, κ=0.71. Novel starburst pattern identified in 39.3% of cases, predominantly in early facial DLE. Score: 17/21 (full text).
Sadhukhan et al. 2025 (Indian J Dermatol Venereol Leprol): Prospective dermoscopy study of 503 patients with lichen planus, lichen sclerosus, and psoriasis. Establishes dermoscopic criteria for lichen planus in a large prospective clinical series. Score: 15/21 (full text).
Lim et al. 2021 (Acta Derm Venereol): Review of dermoscopic and onychoscopic features of inflammatory nail disorders, including nail lichen planus, nail psoriasis, and trachyonychia. Establishes onychoscopy criteria for nail LP as standard clinical practice. Score: 18/21 (full text).
Tordjman et al. 2025 (Int J Dermatol): Systematic review (PRISMA-compliant) of nail lichen planus and nail psoriasis dermoscopy across Fitzpatrick phototypes IV–VI; 60 studies, 12,743 cases. Confirms onychoscopy criteria for nail LP are validated across darker phototypes. Score: 20/21 (full text).
Supporting context — Bazzacco et al. 2024 (Ital J Dermatol Venerol; DOI: 10.23736/S2784-8671.24.07825-3): Dermoscopy review covering 12 differential scenarios in which neoplastic and inflammatory lesions present similarly in clinical practice. DLE appears as the inflammatory differential from actinic keratosis; lichen planus appears as the inflammatory differential from squamous cell carcinoma. Supports the position that dermoscopy reliably differentiates DLE and LP from their neoplastic mimics. Score: 14/21 (full text) — supporting context, not load-bearing VCA anchor (CRIT7: differentiates-from-mimics contribution, which is adjacent to but not identical to the image-recognition-standard claim).
VCA conclusion — DLE and LP
Dermoscopic criteria for discoid lupus erythematosus (follicular plugging, perifollicular whitish halo, scaling, dyspigmentation) and lichen planus (Wickham striae, violaceous papules, perilesional hyperpigmentation, nail onychoscopy features) are established clinical standards supported by multicenter studies, systematic reviews, and prospective clinical series. Image-based recognition of DLE and LP using clinical photography and dermoscopy is an accepted component of the standard clinical workup for these conditions.
Autoimmune blistering diseases
Evidence summary
Hertl et al. 2015 (J Eur Acad Dermatol Venereol 29:405–414): European Dermatology Forum / European Academy of Dermatology and Venereology S2 guideline for pemphigus (pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus). Establishes the visual clinical phenotype — flaccid blisters and erosions (PV), superficial crusted erosions (PF), Nikolsky sign — as the basis for clinical suspicion that triggers confirmatory direct immunofluorescence and anti-desmoglein serology. Score: 19/21 (full text).
Borradori et al. 2022 (J Eur Acad Dermatol Venereol 36:1689–1704): Updated EADV S2K guideline for bullous pemphigoid diagnosis and treatment. Establishes the clinical visual phenotype — tense blisters on urticarial base, preferentially on the limbs and trunk — as the recognition standard that initiates the confirmatory workup. Score: 19/21 (full text).
Venning et al. 2012 (Br J Dermatol 167:1200–1214): British Association of Dermatologists guideline for management of bullous pemphigoid, NHS Evidence accredited. Establishes clinical recognition criteria consistent with the EADV guideline; provides national-level guideline confirmation. Score: 19/21 (full text).
Schmidt et al. 2021 (J Eur Acad Dermatol Venereol 35:1926–1948): EADV S3 guideline for mucous membrane pemphigoid (MMP), Part II: diagnosis and management. Establishes scarring mucosal blistering disease, subepidermal blisters, and skin involvement patterns as the clinical recognition features for MMP. Score: 17/21 (full text).
VCA conclusion — autoimmune blistering diseases
The visual clinical presentation of pemphigus group (flaccid blisters, erosions, Nikolsky sign), bullous pemphigoid (tense blisters on urticarial base), and mucous membrane pemphigoid (scarring mucosal disease, subepidermal blisters) is established as the recognised basis for initial clinical suspicion in four professional-society guidelines (EDF/EADV S2, EADV S2K, BAD, EADV S3). Definitive confirmation by direct immunofluorescence and serology is not part of the device's intended output.
Dermatomyositis
Evidence summary
Lundberg et al. 2017 (Ann Rheum Dis 76:1955–1964): 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies, developed in a multi-centre international cohort. Cutaneous DM features (Gottron's papules, heliotrope rash, V-sign, shawl sign, mechanic's hands, periungual changes) are assigned explicit probability weights against a validated reference standard. Gottron's papules are treated as pathognomonic. Score: 20/21 (full text).
Ali et al. 2025 (Semin Immunopathol 47:32): Review focused on cutaneous manifestations of dermatomyositis, including Gottron's papules, heliotrope erythema, mechanic's hands, and nail fold capillaroscopy changes, as the primary clinical recognition features. Score: 17/21 (full text).
Didona et al. 2023 (Ital J Dermatol Venerol 158:84–98): Comprehensive review of dermatomyositis with emphasis on cutaneous manifestations and their diagnostic significance. Score: 15/21 (full text).
Chong and Werth 2022 (J Invest Dermatol 142:936–943): Validation and clinical use of the Cutaneous Dermatomyositis Activity and Severity Index (CDASI), a standardised visual scoring tool for assessing DM cutaneous disease. Confirms that DM cutaneous features can be reliably scored by visual assessment in clinical practice. Score: 15/21 (full text).
VCA conclusion — dermatomyositis
Cutaneous features of dermatomyositis — Gottron's papules, heliotrope rash, V-sign, shawl sign, mechanic's hands — have formally validated probability weights in an international multi-centre classification study (EULAR/ACR 2017) and are used as the primary clinical recognition trigger. The CDASI confirms these features are reliably assessed by visual examination. Image-based recognition of DM cutaneous features is an established standard of clinical practice.
Morphea (localised scleroderma)
Evidence summary
Mertens et al. 2017 (Am J Clin Dermatol 18:491–512): Clinical update on morphea and eosinophilic fasciitis. Describes the characteristic image-recognisable clinical features of morphea — indurated ivory-white or violaceous plaques with a lilac ring at the active border, shiny surface, skin tethering — as the basis for clinical recognition before biopsy confirmation. Score: 15/21 (full text).
VCA conclusion — morphea
Morphea has characteristic image-recognisable clinical features described in the standard dermatology literature. Dermoscopy-specific criteria for morphea (crystalline structures, fibrosis patterns, loss of follicular openings) are documented in the observational literature but were not captured in the current search strategy owing to publication-type filters applied; these observations strengthen but are not required for the VCA claim at the clinical-photography level. Definitive diagnosis requires histopathological confirmation; the device supports clinical recognition at the initial-suspicion level. The morphea VCA anchor reaches the load-bearing threshold on a single reviewed source; the single-anchor dependency for this condition is noted in the limitations.
Cutaneous vasculitis
Evidence summary
Fraticelli et al. 2021 (Intern Emerg Med 16:831–841): Diagnosis and management of leucocytoclastic vasculitis (LCV). Establishes palpable purpura as the "leading clinical presentation" of LCV — an image-recognisable skin finding that triggers the diagnostic workup including histopathology. Score: 15/21 (full text).
Chen et al. 2024 (J Dermatol 51:150–159): Classification of cutaneous vasculitis skin patterns in autoinflammatory diseases (FMF, DADA2, VEXAS). Provides a dermatology-level classification of cutaneous vasculitis morphologies — palpable purpura, petechiae, livedo racemosa, urticarial wheals — as clinical recognition criteria. Score: 16/21 (full text).
VCA conclusion — cutaneous vasculitis
Palpable purpura, petechiae, livedo racemosa, and urticarial wheals are established image-recognisable clinical features that constitute the recognised basis for clinical suspicion of cutaneous vasculitis. Dermoscopy-specific literature on vasculitis morphology (dermal vascular structures in purpuric lesions) exists in small observational studies and is noted as a state-of-the-art supplement; it is not required for the VCA argument at the clinical-photography level.
Genodermatoses
Rationale for image-based recognition
Genodermatoses are rare hereditary skin disorders. Their low prevalence makes large prospective device performance studies impractical within reasonable timescales; MDCG 2020-6 §6.3 permits the clinical evidence base to be weighted toward alternative evidence sources when design constraints are justified. The clinical phenotype of genodermatoses — defined by international consensus diagnostic criteria and large phenotyping cohorts — is established in the literature, and clinical photography is the standard method for phenotype assessment and documentation in these conditions.
Ichthyoses
Evidence summary
Sun et al. 2021 (JAMA Dermatol. 2021;158(1):1–11; PMID 34851365): Prospective cohort study of 1,000 kindreds with suspected ichthyosis over 10 years (Yale Ichthyosis Registry). Standardised clinical photographs were used as the primary method for phenotype assessment and genotype-phenotype correlation across 32 ichthyosis-associated genes (869/1000 kindreds had confirmed pathogenic variants; 266 novel variants identified). Demonstrates that clinical photography is the accepted standard method for phenotyping autosomal recessive congenital ichthyosis (ARCI), lamellar ichthyosis, and related disorders. Score: 20/21 (full text).
VCA conclusion — ichthyoses
Standardised clinical photography is the established method for phenotypic characterisation of ichthyosis. Sun et al. 2021 is a landmark multi-centre cohort demonstrating that genotype-phenotype associations in 32 ichthyosis genes are mapped using clinical photographs, confirming image-based recognition as the standard clinical practice for this condition group.
Neurofibromatosis type 1 and type 2
Evidence summary
Legius et al. 2021 (Genet Med): International NF Diagnostic Criteria Consensus Group (I-NF-DC) revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome. Developed by Delphi consensus with global experts and patient representatives. Café-au-lait macules (CALMs), axillary/inguinal freckling, Lisch nodules, and cutaneous/subcutaneous neurofibromas are defined as major diagnostic criteria — each is image-recognisable in clinical photographs or slit-lamp examination. Score: 20/21 (full text).
Plotkin et al. 2022 (Genet Med): I-NF-DC updated diagnostic criteria for neurofibromatosis type 2 and schwannomatosis. Establishes image-recognisable cutaneous features (subcutaneous schwannomas, cutaneous neurofibromas, CALMs in NF2) as part of the revised criteria. Score: 17/21 (full text).
VCA conclusion — NF1 and NF2
The I-NF-DC international consensus establishes that café-au-lait macules, axillary freckling, and cutaneous neurofibromas — all image-recognisable in clinical photographs — are the primary diagnostic criteria for NF1. The device's differential-diagnosis support for NF1 is based on recognition of these visual features, consistent with the established diagnostic standard.
Tuberous sclerosis complex
Evidence summary
Portocarrero et al. 2018 (An Bras Dermatol 93:323–331): Review of TSC based on the 2012 International Tuberous Sclerosis Complex Consensus Conference revised diagnostic criteria (Northrup/Krueger criteria). Describes the major cutaneous criteria — hypomelanotic macules (ash-leaf spots), facial angiofibromas, fibrous cephalic plaque, shagreen patches, ungual fibromas — as formal major diagnostic criteria for TSC. These are image-recognisable features that alert clinicians to the diagnosis before neuroimaging or genetic confirmation. Score: 16/21 (full text).
VCA conclusion — tuberous sclerosis complex
TSC cutaneous features (angiofibromas, hypomelanotic macules, shagreen patch, ungual fibromas) are formal major diagnostic criteria per the 2012 International Consensus; they are image-recognisable and are the features that typically bring TSC to clinical attention.
Epidermolysis bullosa
Evidence summary
Has et al. 2020 (Br J Dermatol 183:614–627): International consensus reclassification of inherited epidermolysis bullosa. Classifies inherited EB types (EB simplex, junctional EB, dystrophic EB, Kindler EB) by clinical morphology — blistering patterns, healing characteristics, associated features — that are visible in clinical photographs. Cited by 292 publications at time of appraisal; the primary reference for EB clinical taxonomy. Score: 19/21 (full text).
Pfendner and Lucky 2018 (GeneReviews [NBK1125]): Authoritative reference chapter for junctional epidermolysis bullosa. Establishes clinical features — blistering from minimal trauma, granulation tissue formation, nail dystrophy, extensive mucosal involvement — as the basis for clinical recognition of JEB before molecular confirmation. Score: 16/21 (full text).
Lucky et al. 2025 (GeneReviews [NBK1304]): Authoritative reference chapter for dystrophic epidermolysis bullosa. Establishes clinical features — scarring blisters, pseudosyndactyly of hands and feet, milia formation — as the basis for clinical recognition of RDEB and DDEB before molecular confirmation. Score: 16/21 (full text).
VCA conclusion — epidermolysis bullosa
Inherited EB types have distinct, clinically recognisable morphologies described by the 2020 international consensus reclassification and confirmed in authoritative reference sources. Clinical photography is the standard method for documenting EB phenotype; the Has 2020 consensus classification is based on clinical features observable in photographs.
Evidence Gap Coverage Summary
Autoimmune dermatoses
| Condition | Load-bearing VCA anchor(s) | Gap status |
|---|---|---|
| Discoid lupus erythematosus | Fathy 2022 | Closed |
| Lichen planus (skin) | Sadhukhan 2025 | Closed |
| Nail lichen planus | Lim 2021; Tordjman 2025 SR | Closed |
| Oral lichen planus | None | Gap — no load-bearing VCA anchor retrieved (Jha 2022 excluded: full text not publicly available) |
| Dermatomyositis | Lundberg 2017 EULAR/ACR; Ali 2025; Didona 2023; Chong & Werth 2022 | Closed |
| Pemphigus group | Hertl 2015 EDF/EADV S2 | Closed |
| Bullous pemphigoid | Borradori 2022 EADV S2K; Venning 2012 BAD | Closed |
| Mucous membrane pemphigoid | Schmidt 2021 EADV S3 | Closed |
| Morphea | Mertens 2017 | Partially closed (clinical features standard established; single anchor at 15/21 threshold; dermoscopy-specific evidence not captured by publication-type filter) |
| Cutaneous vasculitis | Fraticelli 2021; Chen 2024 | Partially closed (clinical features standard established; dermoscopy-specific evidence not captured by publication-type filter; flagged for SotA supplementary search) |
Genodermatoses
| Condition | Load-bearing VCA anchor(s) | Gap status |
|---|---|---|
| Ichthyoses (ARCI, lamellar) | Sun 2021 JAMA Dermatol (1,000 kindreds) | Closed |
| Neurofibromatosis type 1 | Legius 2021 I-NF-DC consensus | Closed |
| Neurofibromatosis type 2 | Plotkin 2022 I-NF-DC consensus | Closed |
| Tuberous sclerosis complex | Portocarrero 2018 (2012 International Consensus) | Closed |
| Epidermolysis bullosa (JEB, DEB) | Has 2020 international consensus; Pfendner & Lucky 2018; Lucky 2025 | Closed |
| Netherton syndrome | Bittencourt 2015 trichoscopy (context only) | Partial — no cohort or guideline VCA anchor identified |
| Monilethrix | Baltazard 2017 trichoscopy (context only) | Partial — no cohort or guideline VCA anchor identified |
| Gorlin syndrome (BCNS) | None identified | Gap — no disease-specific VCA anchor retrieved |
Limitations and Residual Gaps
Morphea and cutaneous vasculitis (autoimmune): the VCA argument for these two conditions is partially established (clinical-recognition phenotype described in the literature; load-bearing anchors at the 15/21 threshold). For both conditions, dermoscopy-specific evidence was not captured by the publication-type filters applied; this is noted as a state-of-the-art supplement for R-TF-015-011 and is not required for the Pillar 1 VCA argument at the clinical-photography level.
Oral lichen planus (autoimmune): no load-bearing VCA anchor was retained. Jha et al. 2022 (IDS multicenter dermoscopy of DLE/LP at mucosal sites) was appraised at 17/21 from abstract and would have served as the primary mucosal-site anchor, but the full text was not publicly available and the paper has been excluded from the evidence package. Dedicated oral dermoscopy consensus literature is available but was not retrieved in the current searches. Oral LP is therefore treated as a residual gap (Tier 3) in the VCA Claim Statement below.
Netherton syndrome and monilethrix: trichoscopy case reports (Bittencourt 2015; Baltazard 2017) confirm pathognomonic trichoscopy patterns but do not establish a clinical recognition standard accepted by the broad medical community. Cohort-level evidence or a professional-society guideline would strengthen this VCA claim.
Gorlin syndrome (basal cell naevus syndrome): no dedicated VCA anchor was identified. The cutaneous features of Gorlin syndrome (multiple early-onset BCCs, palmar/plantar pits, jaw keratocysts) are described in standard dermatology reference sources, but a disease-level image-based recognition study specific to Gorlin syndrome as a genodermatosis has not been retrieved. This is an acknowledged residual gap.
The partial and absent anchors for morphea, cutaneous vasculitis, oral LP, Netherton, monilethrix, and Gorlin syndrome do not materially weaken the overall VCA argument for either category. The principal autoimmune dermatoses and genodermatoses — DLE, LP, nail LP, DM, the autoimmune blistering diseases, ichthyoses, NF1, TSC, and the major EB subtypes — account for the large majority of presentations in both sub-indications and are well-anchored. The residual uncertainties are acknowledged and will be confirmed and strengthened by the post-market clinical follow-up activity for these sub-indications, which pre-specifies enrolment targets and diagnostic-accuracy thresholds per condition group (Ingredient 5, PMCF specification). The PMCF activity strengthens an adequately-evidenced base; it does not substitute for pre-certification evidence.
VCA Claim Statement
The following statement summarises the Pillar 1 VCA established by this evidence review. It is tiered to reflect the gap-status distinctions declared in the evidence sections above.
Tier 1 — Fully closed VCA (load-bearing anchors confirmed from full text or from abstract-appraised high-quality consensus sources)
Image-based clinical recognition of the following autoimmune dermatoses — discoid lupus erythematosus, lichen planus (skin), nail lichen planus, dermatomyositis, pemphigus vulgaris, bullous pemphigoid, and mucous membrane pemphigoid — and the following genodermatoses — ichthyoses, neurofibromatosis type 1, neurofibromatosis type 2, tuberous sclerosis complex, and epidermolysis bullosa — is an established diagnostic standard, evidenced by: international expert consensus diagnostic criteria and clinical guidelines (Legius 2021 I-NF-DC; Plotkin 2022 I-NF-DC; Hertl 2015 EDF/EADV S2 pemphigus guideline; Borradori 2022 EADV S2K BP guideline; Venning 2012 BAD BP guideline; Schmidt 2021 EADV S3 MMP guideline; Lundberg 2017 EULAR/ACR IIM classification criteria; Has 2020 international EB consensus reclassification); published dermoscopy criteria studies and systematic reviews (Fathy 2022 sens 88.6% / spec 71.2%; Sadhukhan 2025 503 patients; Lim 2021 onychoscopy review; Tordjman 2025 SR 12,743 cases; Ali 2025; Chong & Werth 2022 CDASI); and large clinical phenotyping cohorts and authoritative reference sources (Sun 2021 JAMA Dermatol 1,000 kindreds; Portocarrero 2018 TSC 2012 criteria; GeneReviews JEB/DEB chapters).
Tier 2 — Partially closed VCA (clinical-recognition phenotype established; dermoscopy-specific or full-text confirmation pending)
For morphea and cutaneous vasculitis, the clinical-recognition phenotype is described in the standard dermatology literature (Mertens 2017; Fraticelli 2021; Chen 2024), confirming that image-recognisable features are the basis for initial clinical suspicion. Dermoscopy-specific evidence for these conditions was not captured by the publication-type search filters; this gap is noted as a state-of-the-art supplement recommendation and does not affect the VCA argument at the clinical-photography level.
Tier 3 — Residual gaps (context references only; VCA anchor not yet load-bearing)
For Netherton syndrome, monilethrix, Gorlin syndrome, and oral lichen planus (mucosal site), the clinical-recognition phenotype is described in reference sources but load-bearing VCA anchors have not been retrieved. These conditions account for a small minority of presentations within the genodermatoses and autoimmune sub-indications. The PMCF activity will confirm and strengthen the evidence base for these conditions post-certification.
Scope of this Pillar 1 VCA review
This review establishes the scientific association between the device's input modality (clinical and dermoscopic images) and the Top-5 prioritised differential-diagnosis view presented to the healthcare professional, for the autoimmune dermatoses and genodermatoses sub-indications. It does not establish the downstream causal link from accurate image-based recognition to patient-level clinical outcome. That surrogate-endpoint-to-outcome link is addressed in a separate structured literature review that forms the complementary component of the Pillar 1 VCA package for the Class IIb indirect clinical-benefit claim. The device's technical analytical performance (Pillar 2) and its effect on healthcare professional decision-making (Pillar 3) are established in the respective dedicated evidence packages.
Reference List
Autoimmune dermatoses — load-bearing VCA anchors (score ≥15/21)
- Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 guideline for diagnosis and treatment — guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2015;29(3):405–414.
- Borradori L, Van Beek N, Feliciani C, et al. Updated S2K European guidelines (EuroGuiDerm) on the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2022;36(10):1689–1704.
- Venning VA, Taghipour K, Mohd Mustapa MF, et al. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. Br J Dermatol. 2012;167(6):1200–1214.
- Schmidt E, Rashid H, Marzano AV, et al. S3 guidelines on diagnosis and management of mucous membrane pemphigoid initiated by the European Academy of Dermatology and Venereology — Part II. J Eur Acad Dermatol Venereol. 2021;35(9):1926–1948.
- Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76(12):1955–1964.
- Fathy W, Gouda HM, Ismail N, et al. Dermoscopic features and their correlation with clinical and histopathological findings in discoid lupus erythematosus. Indian J Dermatol Venereol Leprol. 2022;88(5):607–614.
- Lim JNL, Dissanayake M, Tey HL. Dermoscopy of inflammatory nail disorders: a review. Acta Derm Venereol. 2021;101(4):adv00432.
- Tordjman M, Wortsman X, Monteagudo C, et al. Nail lichen planus and nail psoriasis in Fitzpatrick phototypes IV–VI: a systematic review. Int J Dermatol. 2025.
- Sadhukhan M, Mandal A, Mondal D, et al. Dermoscopy of lichen planus, lichen sclerosus, and psoriasis. Indian J Dermatol Venereol Leprol. 2025;91(1):47–55.
- Ali MM, Sabbah HA, Abdulkadir NF, et al. Dermatomyositis: focus on cutaneous manifestations and their diagnostic utility. Semin Immunopathol. 2025;47:32.
- Didona D, Caposiena Caro RD, Sequeira Santos AM, et al. Dermatomyositis: comprehensive review of cutaneous manifestations and management. Ital J Dermatol Venerol. 2023;158(2):84–98.
- Chong BF, Werth VP. Assessing cutaneous disease activity in dermatomyositis: clinical tools and laboratory markers. J Invest Dermatol. 2022;142(4):936–943.
- Fraticelli P, Rivera R, Gabrielli A. Leucocytoclastic vasculitis: diagnosis, treatment and prognosis. Intern Emerg Med. 2021;16(4):831–841.
- Chen X, Zhao Y, Wang X, et al. Cutaneous manifestations in autoinflammatory diseases: from phenotype to classification. J Dermatol. 2024;51(2):150–159.
- Mertens JS, Seyger MM, Thurlings RM, et al. Morphea and eosinophilic fasciitis: an update. Am J Clin Dermatol. 2017;18(4):491–512.
Autoimmune dermatoses — supporting context (score 12–14/21)
- Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043–1046.
- Bazzacco G, Mazzetto R, Micali G, et al. Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions. Ital J Dermatol Venerol. 2024. DOI: 10.23736/S2784-8671.24.07825-3.
Genodermatoses — load-bearing VCA anchors (score ≥15/21)
- Sun Q, Burgren NM, Cheraghlou S, Paller AS, Larralde M, Bercovitch L, Levinsohn J, Ren I, Hu RH, Zhou J, Zaki T, Fan R, Tian C, Saraceni C, Nelson-Williams CJ, Loring E, Craiglow BG, Milstone LM, Lifton RP, Boyden LM, Choate KA. Genotype-phenotype correlations in 1000 individuals with pathogenic ARCI variants. JAMA Dermatol. 2021;158(1):1–11. PMID 34851365.
- Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med. 2021;23(8):1506–1513.
- Plotkin SR, Messiaen L, Legius E, et al. Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis. Genet Med. 2022;24(9):1967–1977.
- Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614–627.
- Pfendner EG, Lucky AW. Junctional epidermolysis bullosa. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [NBK1125]. Seattle (WA): University of Washington; 1993–2025. Updated 2018.
- Lucky AW, Pfendner EG, Pillay E. Dystrophic epidermolysis bullosa. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [NBK1304]. Seattle (WA): University of Washington; 1993–2025. Updated 2025.
- Portocarrero LKL, Quental KN, Samorano LP, Oliveira ZNP de, Rivitti-Machado EA. Tuberous sclerosis complex: review based on new diagnostic criteria. An Bras Dermatol. 2018;93(3):323–331.
Genodermatoses — supporting context (score 12–14/21)
- Bittencourt MJ dos S, Moure ERD, Pies OT de C, et al. Trichoscopy as a diagnostic tool in trichorrhexis invaginata and Netherton syndrome. An Bras Dermatol. 2015;90(1):114–116.
- Baltazard T, Dhaille F, Delos M, et al. A case of monilethrix revealed by trichoscopy. Dermatol Online J. 2017;23(11).
Appendix: Appraisal Criteria Detail
| Criterion | Score 1 | Score 2 | Score 3 |
|---|---|---|---|
| CRIT1 (Relevance) | Irrelevant | Partially relevant | Directly relevant (image-based recognition, condition in scope) |
| CRIT2 (Design) | Case report / expert opinion | Retrospective observational | Prospective multi-centre / SR / meta-analysis |
| CRIT3 (Reporting) | Abstract only, no metrics | Metrics without CI or validation | Full metrics with external validation |
| CRIT4 (Applicability) | Non-image (genomics, blood test) | Histology / limited dermoscopy | Clinical photography / routine dermoscopy |
| CRIT5 (Hierarchy) | Case report / small series | Cohort / observational | SR / meta-analysis / multi-site landmark |
| CRIT6 (Bias) | High | Moderate | Low (external validation, prospective, blinded) |
| CRIT7 (VCA contribution) | None | Indirect (disease burden, AI benchmark) | Direct (image-based diagnostic accuracy with sens/spec/AUC) |