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1. IMMUNOBULLOUS
DISEASE – PEMPHIGOID I
DR. HIMANSHU KARMACHARYA
PGY2
DERPARTMENT OF
DERMATOLOGY, NGMCTH

3. SUBEPIDERMAL
IMMUNOBULLOUS DISEASES
• Includes pemphigoid diseases and dermatitis herpetiformis (DH).
• Pemphigoid: Autoantibodies target dermal–epidermal junction (DEJ) structural
proteins.
• Dermatitis herpetiformis: Autoantibodies against epidermal transglutaminase (TG3),
with cross-reactivity to tissue transglutaminase (TG2).
• DEJ links basal keratinocyte cytoskeleton to the dermal extracellular matrix.
• Autoantibody binding → epidermal-dermal separation.
• Shared Clinical Features
• Tense blisters, erosions.
• Negative Nikolsky sign (no epidermal detachment on rubbing).
• Variable: clinical presentation, target antigens, antibody isotypes, and immunopathology.
• Accurate diagnosis is essential due to varying prognosis and treatment.

6. BULLOUS PEMPHIGOID
• Most common subepidermal autoimmune blistering disease.
• Primarily affects elderly, occasionally younger individuals.
• Early signs: pruritus, urticated/red lesions.
• Later: tense blisters on normal or erythematous skin.
• Mucosal involvement is uncommon.
• Histology: subepidermal split.
• Autoantibodies:
• IgG against BP180 (type XVII collagen) – nearly all patients.
• IgG against BP230 – ~50% of patients.

7. EPIDEMIOLOGY
• Incidence: Varies globally: 2.5–76 new cases/million/year.
• Rising trend in developed countries due to:
• Aging population.
• More neurological comorbidities.
• Drug associations (e.g., DPP4-inhibitors, psycholeptics, diuretics).
• Better diagnostic tools.
• Awareness of non-bullous/prodromal BP.
• Prevalence: 26/100,000 in Germany (2014), 48/100,000 in England
(2017).

8. EPIDEMIOLOGY
• Age Distribution
• Primarily a disease of the elderly.
• Mean age at onset: 69–83 years (most regions)
• <50 years: rare (<0.5/million/year).
• Children & adolescents: ~80 cases documented; prevalence ~5/million under 18.
• Infants: Higher rate (23.6/million/year in <1-year-olds in Israel).
• Sex Distribution
• Slight female predominance (52–60%).
• Age-adjusted incidence higher in men (due to higher female life expectancy).
• Ethnicity
• Incidence varies globally – influenced by genetics, environment, diagnostic standards, and healthcare
access.
• UK: Highest incidence in patients of Asian ethnicity.
• New York: Patients with skin of colour presented with disease at younger ages.

9. ASSOCIATED DISEASES
• Neurological & Psychiatric disorders (BP180 and BP230 also expressed in the CNS.) - in ~1/3 to 1/2 of BP
patients.
• Dementia/cognitive decline
• Parkinson’s disease
• Stroke
• Epilepsy
• Multiple sclerosis
• Depression, bipolar disorder
• Malignancy: hematologic malignancies (e.g., lymphoma, leukemia).
• Other Associations
• Cardiovascular disease (especially hypertension).
• Autoimmune diseases:
• Dermatitis herpetiformis
• Coeliac disease
• Ulcerative colitis
• Diabetes mellitus
• Psoriasis
• Allergic asthma

10. PREDISPOSING FACTORS
• Physical trauma
• Burns
• Skin grafting
• Radiotherapy
• UV radiation: sunlight, UVA1, PUVA, photodynamic therapy
• Vaccination: ~20 case reports, especially influenza
• Drugs: (should be discontinued in BP patients)
• Aldosterone antagonists, DPP-4 inhibitors (esp. vildagliptin), Anticholinergics, Dopaminergic drugs, Loop
diuretics, Sulfonamides, Penicillin
• Immune checkpoint inhibitors (PD-1/PD-L1):
• Median onset: 6–9 months
• More pruritus without blisters, less tense blisters
• ↑ peripheral eosinophilia

11. GENETICS
• Most consistent association: DQB1*0301
• Seen in Whites, Chinese Hans, Iranians, Brazilians, Japanese (DPP-4-i-
induced)
• Others:
• Northern China: ↓ DRB108 / DRB108-DQB1*06
• Japan: DRB11101, DQB10302
• GWAS (Germany): Confirmed DQB10301 and DQA105:05 association

12. PATHOPHYSIOLOGY
• BP is an autoimmune subepidermal blistering disease → autoantibodies targeting
BP180 (type XVII collagen) and BP230 (BPAG1e) → inflammation, protease release, and
dermal–epidermal junction (DEJ) splitting.
• Key Antigens
• BP180 (Type XVII Collagen)
• Main antigen; transmembrane hemidesmosomal protein.
• NC16A domain: immunodominant; targeted in 75–90% of patients.
• Antibody classes: IgG (mostly IgG1, IgG4), IgA, and IgE.
• Serum IgG/IgE to NC16A correlates with disease activity.
• BP230
• Intracellular hemidesmosomal protein.
• Antibodies found in 50–70% of BP patients.
• Mainly target the C-terminal domain.
• IgG and IgE responses are observed, but its pathogenic role is less clear.

13. & ROS
Secretion of IL 6 and IL 8 from
‐ ‐
basal keratinocytes as well as
in internalization and
decreased expression of BP180.

14. CYTOKINES & CHEMOKINES
• Elevated levels in
serum/blister fluid:
• IL-1 ,
β IL-4, IL-5, IL-6, IL-8,
IL-10, IL-17, TNF- ,
α CCL2,
eotaxin, etc.
• Correlate with disease
extent.
• Th2 skewing and IL-17A
are prominent features.

15. CELLULAR IMMUNE RESPONSE
• Less studied but crucial.
• CD4+ T cells target BP180, especially in individuals with HLA-DQB1*0301.
• Th1/Th2 mixed cytokine profile in autoreactive T cells.
• Th17 cells and IL-17A implicated in lesion formation.
• T follicular helper (Tfh) cells increased during active disease; aid B-cell activation.
• Role of IgE & Eosinophils
• IgE to BP180 NC16A linked to more severe disease and delayed remission.
• Eosinophils can drive pathology by inducing DEJ separation via protease release.
• Eosinophil infiltration is the hallmark in human disease

17. CLINICAL FEATURES
• Prodromal phase (non-bullous): lasts weeks - months
• Severe pruritus (may precede lesions)
• Lesions: excoriated papules, urticarial, eczematous, hemorrhagic crusts
• Bullous Phase
• Blisters:
• Tense, symmetric, pruritic
• Erythematous or normal background; often hemorrhagic
• Negative Nikolsky sign, Bulla Spread: rounded edge
• Distribution:
• Flexures, limbs, abdomen
• Mucosal (10–20%, esp. oral)
• Mucosal BP → ↓ BP230 autoantibodies, ↓ eosinophils
• Rare: eyes, nose, pharynx, esophagus, genitalia
• Healing:
• No scarring unless infected, PIH ±
• Red macules persist
• Milia rare

18. CLINICAL VARIANTS
• Non-classical Forms
• ~20% initially present with variants
• Types:
• Prurigo nodularis-like
• Eczematous, papular, urticarial, vesicular, erythrodermic
• Vegetating, lymphomatoid papulosis-like, intertrigo-like
• Toxic epidermolysis-like
• Often evolve to classical BP
• Localized BP
• Common sites:
• Pretibial, flexures, palms/soles, genitalia, umbilicus
• Around stoma, dialysis fistulae
• May remain localized or generalize

19. CLINICAL VARIANTS
• Childhood BP
• Two peaks: infancy (<1 yr) and ~8 yrs
• Often linked to vaccination (especially in infants)
• Infants: acral (palms/soles) involvement
• Older children: genital involvement (up to
50%)
• Immunopathology similar to adults
• Autoantibodies: mostly BP180 NC16A
• Prognosis: good with systemic steroids ±
dapsone/sulphapyridine

21. DIFFERENTIAL DIAGNOSIS
• Great imitator particularly because of its pleomorphic presentation
• Pemphigus group: Positive Nikolsky sign; different immunopathology.
• Mucous membrane pemphigoid: Primarily mucosal involvement.
• Linear IgA disease / EBA / anti-p200 pemphigoid: Need DIF and serology for differentiation.
• Dermatitis herpetiformis: DIF and serology (anti-TG1, TG2, gliadin IgA).
• Non-bullous/atypical presentations: May mimic:
• Drug eruptions
• Eczema (contact/allergic dermatitis)
• Urticaria / urticarial vasculitis
• Prurigo
• Scabies
• Ecthyma
• Pityriasis lichenoides
• Diagnosis relies on: history, clinical exam, histopathology, DIF, and serology.

24. CLASSIFICATION OF SEVERITY
• BP Disease Area Index (BPDAI):
• Records:
• Skin (blisters, erosions, urticaria-like lesions)
• Mucosa
• Pruritus
• Cutoffs:
• Mild: <20
• Moderate: 20–57
• Severe: >57
• German Society:
• Mild: <10% BSA
• Moderate: 10–30%
• Severe: >30%

25. COURSE & PROGNOSIS
• Chronic, self-limiting over months to years.
• ~50% relapse, especially with:
• Extensive disease
• High anti-BP180 titers
• Dementia
• Duration: 3–6 years; most remit off-treatment.
• 1-year mortality: 10–40%
• ↑ with age >80, extensive disease, prednisolone >35 mg/day, low albumin (<3.6
g/dL), low Karnofsky score, comorbidities.
• Pooled mortality: ~23.5%
• SMR: 2.93

26. INVESTIGATIONS & DIAGNOSIS
• Triad: Clinical + DIF + serology (BP180/BP230 ELISA or indirect IF).
• Histology: Not always specific—need DIF & serology for definitive dx.
• ~90% diagnosed via clinical + ELISA for BP180/BP230.

27. DIAGNOSTIC CRITERIA
• Classic Criteria (Typical BP)
• Diagnosis is based on a combination of clinical, immunofluorescence, and serological findings:
• Clinical features → ≥3 of 4 must be present:
• Age >70 years
• Absence of atrophic scars
• No mucosal involvement
• No predominant bullous lesions on the neck and head
• Direct Immunofluorescence (DIF):
• Positive DIF showing linear IgG and/or C3 deposition along the basement membrane zone
• Serological markers:
• Presence of circulating IgG autoantibodies binding to the epidermal side of Salt-Split Skin (SSS) by IIF
• ELISA or IIF showing reactivity to:
• BP180
• BP230

29. HISTOPATH
• Early pre-bullous lesions:
subepidermal clefts/eosinophilic
spongiosis/infiltrate of eosinophils in
the upper dermis
• Fresh bulla: subepidermal blister with
a dermal inflammatory infiltrate
composed predominantly of eosinophils
and neutrophils
• Old bulla: may have an artefactual
intraepidermal blister due to re-
epithelialization along the base.

30. IMMUNOFLUORESCENCE
MICROSCOPY
• Direct immunofluorescence (DIF) microscopy
• fine, linear, continuous deposits of IgG and/or C3 (and,
more rarely, other Ig classes) along the epidermal
basement membrane
• Predominant IgG: IgG4 > IgG1
• Essential to further determine:
• Serration pattern: n-serrated (BP and linear IgA bullous
dermatosis) versus u-serrated (epidermolysis bullosa
acquisita)
• Salt-split skin assay
• Indirect immunofluorescence (IIF)
microscopy
• substrate of choice: salt-split normal human skin

31. SALT SPLIT
• Technique involves artificially splitting the
skin at the level of lamina lucida by
incubating it in 1 M solution of sodium
chloride for 24 hr at 4 degree celsius.
• BMZ staining in the split skin may take
either a “roof” pattern (band is seen toward
the epidermal side of the split, eg. BP) or
“floor” pattern (band is seen on the dermal
side of the split, eg. EBA) or a “combined”
pattern (BMZ deposits on either side of the
split).

32. ELISA
• Target antigens: NC16A domain of BP180 and the COOH-terminus (±
the NH2-terminus) of BP230
• Specificity ≥90%
• multivariant ELISA: multiple autoantigens + BIOCHIP technology
• Useful in screening for autoantibodies in patients with autoimmune
blistering diseases (AIBDs).
• These ready-to-use slides are available commercially and contain six
different substrates (monkey esophagus, primate salt-split skin,
recombinant BP180 NC16A, membrane-bound Dsg1 ectodomain, Dsg3
ectodomain, and the C-terminal globular domain of BP230) in a
miniature field.

33. MANAGEMENT OVERVIEW
• Aim: Minimal effective dose due to comorbidities.
• Mainstay: Potent topical steroids ± systemic corticosteroids.
• General measures
• Prick and drain larger bullae
• Raw areas: non-adhesive dressings
• Dietary supplements in malnourished patients
• Long term steroid therapy: supplemental calcium citrate or carbonate and
vitamin D

36. TOPICAL STEROIDS
• Clobetasol Propionate 0.05% Cream
• Initial Dosage
• Mild-to-moderate disease: 20–30g/day
• Extensive disease: 30–40g/day
• Apply once or twice daily over the entire body, including blistered and normal skin
• Sparing the face until Control of Disease Activity (CDA) is achieved
• CDA = No new lesions/pruritus + Healing of existing lesions
• Post-CDA Treatment Strategy
• Continue the same dosage for 15 days
• Then taper over 4 to 12 months
• Tapering schedule (Evidence score: 4.36±0.75):
• 1st month: daily
• 2nd month: every 2 days
• 3rd month: twice weekly
• From 4th month: once weekly
• If CDA not achieved within 1–3 weeks, increase clobetasol dose (up to 40g/day)

37. MAINTENANCE AND
DISCONTINUATION
• Maintenance Treatment Options (after 4 months)
• Option 1: Continue Maintenance for 8 More Months
• Total treatment duration = 12 months
• Recommended maintenance dose: 10g once weekly
• Preferentially apply on previously affected + surrounding areas
• Note: Lower than RCT-tested dose (10g twice weekly) → not validated
• Option 2: Early Discontinuation (within 4 months)
• Suitable if rapid disease control was achieved
• Slightly higher risk of relapse
• Before stopping, consider ELISA for BP180 (if available)

38. RELAPSE MANAGEMENT (FLARE
DEFINITION & DOSE ADJUSTMENT)
• Definition of Relapse/Flare:
• ≥3 new lesions/month (blisters, eczematous, urticarial plaques)
• ≥1 large lesion (≥10cm) unhealed after 1 week
• Extension of existing lesions
• Daily pruritus in patients with previously controlled disease
• Dose Adjustment in Relapse:
• Return to previous dose level during taper
• If relapse occurs after complete withdrawal:
• 10g/day → for localized relapse
• 20g/day → for mild disease
• 30–40g/day → for moderate-to-extensive relapse
• Apply to previously involved areas + surrounding skin

39. SYSTEMIC CORTICOSTEROID
(CS) THERAPY
• Prednisone Use
• High-dose (1mg/kg/day):
• Effective, but associated with higher mortality and side effects
• Not recommended as initial therapy (Score: 4.46±1.10)
• Recommended dose:
• 0.5mg/kg/day prednisone
• Effective in:
• 75% of mild cases (by day 21)
• 69% of moderate cases
• Only 46% of severe cases
• Better tolerated, especially in patients with Karnofsky score ≥70
• (Score: 4.79±0.65)
• Doses <0.5mg/kg/day are not validated and usually ineffective.
• Combination therapy: Can be used with topical CS or other adjuvants

40. TAPERING & DOSE ADJUSTMENT
• Begin tapering 15 days after achieving disease control
• If no control within 1–3 weeks:
• Increase prednisone to 0.75mg/kg/day (Score: 4.62±0.87)
• Or add topical CS (Score: 4.75±0.60)
• Target: Taper to minimal therapy (prednisone 0.1mg/kg/day) within 4–6
months
• If patient maintains complete remission under minimal therapy for 3–6 months:
• Discontinue prednisone if anti-BP180 levels are low/negative
• Total duration (consolidation + maintenance): 9–12 months
• Taper cautiously to prevent HPA axis suppression
• Relapse: Return to previous dose level

41. ADJUVANT IMMUNOSUPPRESSIVE
/ IMMUNOMODULATORY THERAPY
Tetracyclines (Doxycycline ± Nicotinamide)
• Doxycycline 200mg/day ± nicotinamide up to
2g/day
• Initial studies: 74% control with doxycycline +
topical CS
• Only 54% sustained control without switching
to steroids
• Real-world: 72% eventually needed oral steroids
• Best for mild/moderate BP with
contraindications to CS
• Limited benefit in severe BP
No consensus among experts on doxycycline
monotherapy
Dapsone (≤1.5mg/kg/day or max
150mg/day)
• RCT comparing dapsone vs azathioprine (both
with CS):
• Few patients could taper off steroids
• Median cumulative CS dose slightly lower in
dapsone group (p = 0.06)
• Suggests some CS-sparing effect
• Mostly used in Germany with topical CS
• Best for mild/moderate BP in patients with
CS/immunosuppressive contraindications
• Use cautiously in elderly patients with CVS
disease; monitor closely

42. ADJUVANT CONVENTIONAL
IMMUNOSUPPRESSIVE THERAPY
Drug Dose Remarks
Azathioprine 1–3 mg/kg/day TPMT testing needed
MMF 2 g/day (or MPA 1.44 g/day) CS-sparing potential
Methotrexate 5–12.5 mg/week SC/IM
Monitor for renal issues,
leucopenia
Dapsone Up to 1.5 mg/kg/day (max 150 mg)
Used with topical CS, limited CS-
sparing effect
Tetracyclines + Nicotinamide
Doxy 200 mg/day + Nicotinamide
up to 2 g/day
Better safety profile, but lower
efficacy
Ciclosporin 3–5 mg/kg/day
Not recommended (adverse
effects, poor efficacy)

43. BIOLOGICS (IN
REFRACTORY/SEVERE CASES)
Biologic Dose/Protocol Remarks
Rituximab
RA: 2 × 1g IV, 2w apart OR
Lymphoma: 375 mg/m² × 4w
Less effective than in pemphigus
IVIG 2 g/kg total
Trend toward benefit, risk of renal
failure in elderly
Omalizumab N/A
Consider if urticarial lesions + high
serum IgE
Dupilumab N/A
54% clearance in 13 patients (open
series), well tolerated
Others under trial
IL-17, IL-12/23, IL-5R , eotaxin,
α
FcRn, LTB4/C5aR
Experimental

44. MUCOUS MEMBRANE
PEMPHIGOID (MMP)
• MMP is an autoimmune subepidermal blistering disease with
autoantibodies against components of the dermoepidermal junction
(DEJ) and predominant mucosal involvement.
• Previously called cicatricial pemphigoid, now reserved for variants with
scarring skin lesions without mucosal involvement.
• The term benign MMP is outdated and no longer used.
• Subtypes are based on site: ocular MMP, oral MMP, laryngeal MMP, etc.
• MMP can overlap with:
• Linear IgA disease (IgA-predominant)
• Epidermolysis bullosa acquisita (EBA) (anti-type VII collagen antibodies)

45. EPIDEMIOLOGY
• Incidence: ~2/million/year in Germany (2016),
~0.7–0.8/million/year for ocular MMP in Australia/NZ & UK.
• Prevalence: 24.6/million (Germany, 2014).
• Age: Mostly affects 60–70 years; rare in children.
• Sex: Female predominance (1.5–2.3 times).
• Ethnicity: No racial/geographic preference.

46. KEY AUTOANTIGENS IN MMP
Antigen Frequency Notes
BP180 (Type XVII collagen) ~75%
C-terminal epitopes targeted more
than NC16A domain
Laminin 332 10–20%
Linked to malignancy (25–30% of
cases)
BP230 ~25% Often coexists with anti-BP180
Type VII collagen <5% Also a target in EBA
6 4
α β integrin Rare (unconfirmed) Linked with oral and ocular lesions

47. ASSOCIATED CONDITIONS
• Malignancy (esp. solid tumors):
• Seen in 25–30% of patients with anti-laminin 332 antibodies
• 6.8× higher risk of cancer in anti-laminin 332 MMP
• Ocular lesions may be linked to higher internal malignancy risk
• Tumor screening recommended in all patients with anti-laminin 332
• Other autoimmune diseases:
• May co-exist with:
• Thyroid disease
• Rheumatoid arthritis
• SLE
• Polyarteritis nodosa

48. PATHOPHYSIOLOGY
• Autoantibodies target components of the DEJ leading to:
• Subepidermal blistering
• Scarring (especially ocular)
• BP180 Reactivity:
• MMP sera target C-terminal epitopes > NC16A (contrast to bullous pemphigoid)
• Some sera show dual reactivity: C-terminal + intracellular domains
• Monosite lesions ↔ more frequent BP180 NC16A reactivity
• Laminin 332 Reactivity:
• Mainly targets the 3
α chain
• Reactivity to multiple chains possible
• Associated with more severe disease
• 6 4
α β Integrin (less common):
• Anti- 6
α → Oral lesions
• Anti- 4
β → Ocular involvement
• Confirmatory data still limited

49. GENETICS
• HLA associations:
• ↑ HLA-DQB103(01), DRB104, DRB1*11(01)
• ↓ HLA-DRB1*02
• Ocular MMP: Also associated with HLA-B12
• GWAS: Association with GALC gene

50. CLINICAL FEATURES
• Oral cavity (85%) > conjunctivae (65%) >
skin (25–30%)
• Also: nasal cavity, anogenital, pharynx,
larynx, esophagus
• Rare: trachea, urethra, anal canal
• Scarring common in all sites except oral
• Oral Lesions range: mild erosions → painful
ulcers
• Desquamative gingivitis is common

51. CLINICAL FEATURES
• Ocular Lesions
• Start unilaterally: burning, dryness, FB sensation
• Progress to: symblepharon, trichiasis, neovascularization, blindness
• Slit-lamp exam and fornix depth for monitoring
• Bilateral within 2 years in most cases
• 5% yearly risk of ocular involvement in non-ocular cases
• Other Mucosal Sites
• Nasal: hemorrhagic crusts, septal perforation
• Pharynx/larynx: odynophagia, hoarseness
• Esophagus: dysphagia, heartburn
• Genital: erosions → scarring (mimics lichen sclerosus)
• Skin: BP-like or scars with milia formation
• Anti-laminin 332 MMP:
• ↑ risk of solid malignancies (25–30%)
• More frequent oral + pharyngo-laryngeal involvement

53. CLINICAL VARIANTS
• Oral pemphigoid: Confined to oral mucosa;
desquamative gingivitis common
• Ocular pemphigoid: ~20% of cases, often diagnosed
late with scarring
• Vulvar pemphigoid: Young girls, non-scarring,
steroid-responsive
• Cutaneous involvement: 20%–35% of patients
• m/c sites: scalp, face, neck, and upper trunk
• erythematous plaques → recurrent blister formation and
erosions → scars
• Brunsting–Perry variant: skin lesions are localized
predominantly to the head and neck and upper trunk

54. DIFFERENTIAL DIAGNOSIS
• Oral: PV, paraneoplastic pemphigus, Oral LP, Behçet, SJS, bacterial
gingivitis
• Ocular: Conjunctival lichen planus, GVHD, rosacea, SJS/TEN, allergy,
infection
• Direct IF and histopathology help distinguish

55. CLASSIFICATION OF SEVERITY
• S3 Guidelines:
• Mild–Moderate: Oral ± skin involvement
• Severe: Involvement of extraoral sites (eye, airway, esophagus)
• Scoring systems:
• MMP Disease Area Index: 12 skin sites + 10 mucosal + 2 eyes
• Oral Disease Severity Score
• Foster, Mondino, Tauber (ocular; based on fornix depth)

56. COMPLICATIONS AND COURSE
• Blindness (ocular fibrosis)
• Airway stenosis → tracheostomy
• Middle ear involvement → deafness
• Malignancy in anti-laminin 332 subtype
• Carcinoma from chronic mucosal ulcers
• Course & Prognosis
• Chronic, progressive; rare spontaneous remission
• Disease flares → scarring, functional loss
• Dual IgG + IgA autoantibodies = severe disease
• Anti-laminin 332 = aggressive + malignancy risk
• Requires multidisciplinary care & long-term follow-up

57. INVESTIGATIONS
• Histopathology
• subepithelial blister
• Fewer eosinophils vs bullous pemphigoid (BP).
• Direct Immunofluorescence (DIF)
• Gold standard; sensitivity: 70–88%.
• Linear IgG and/or C3 deposition at
dermoepidermal junction (DEJ); IgA also
possible.
• Serration pattern not useful in mucosal biopsies.
• May be negative in 20% with ocular involvement.

58. SITES OF BIOPSY
Scenario Preferred Biopsy Site
Skin involvement Perilesional skin
No skin involvement Normal buccal mucosa (even if no lesions)
Negative first biopsy Repeat from another mucosal site
Ocular suspicion Upper fornix/limbus (avoid anesthesia; 2×3 mm only)

59. INVESTIGATIONS
• Indirect Immunofluorescence (IIF) on Salt-Split Skin
• Sensitivity: 50–80%.
• Staining pattern:
• Epidermal: Anti-BP180, laminin 332, 6 4
α β integrin.
• Dermal: Type VII collagen.
• Low titers (1:10–1:40).
• IgA-only autoantibodies in 10–30%.

60. INVESTIGATIONS
• Antigen-Specific Tests
• Recommended if IIF is negative.
• Commercial assays available for:
• BP180 NC16A, BP230
• Laminin 332 (BIOCHIP™; sensitivity 84%, specificity 100%)
• Type VII collagen
• Significance of anti-laminin 332:
• Associated with 25–30% malignancy risk.
• Should be checked in negative IIF or dermal staining cases.
• Specialized Antibody Tests (in select labs)
• Anti- 6 4
α β integrin (IgG): via immunoblotting
• Anti-BP180 C-terminal: no standard test available
• Other techniques: western blot using gingiva, amniotic membrane, LAD-1, keratinocyte media

61. MANAGEMENT
• Aim: Suppress inflammation early to prevent irreversible scarring.
• Scarring (ocular, laryngeal, esophageal) may progress despite inflammation control.
• Multidisciplinary approach essential: Dermatology, Ophthalmology, ENT, GI, Gyn/Uro.
• Effective agents (site-specific):
• Dapsone, sulphapyridine, sulphamethoxypyridazine: oral, ocular, generalized MMP
• Cyclophosphamide: generalized MMP
• Minocycline: oral MMP
• Mitomycin (topical): ocular MMP
• Methotrexate, mycophenolate mofetil (MMF): ocular MMP
• IVIG: ocular + oral MMP
• Rituximab: generalized, severe/refractory cases
• Colchicine + prednisolone: better than azathioprine, cyclophosphamide, dapsone
• Others: TNF-α inhibitors, bortezomib, baricitinib
• Rituximab Outcomes (n = 100)
• 70% complete healing, though lower than pemphigus.
• Relapse in ~33%.
• Some rituximab failures responded to IVIG.

62. TREATMENT GUIDELINES (S3 +
NATIONAL)
• Mild to Moderate (Oral ± Skin)
• Topical corticosteroids (adhesive paste, mouthwash, spray)
• Combine with: Dapsone, Methotrexate or Doxycycline
• Intralesional triamcinolone: for refractory oral lesions
• Topical antifungals: for candida co-infection
• Periodontal hygiene crucial to reduce inflammation
• Genital MMP (esp. in minors)
• First line: High-potency topical steroids
• Treat superadded infections
• Severe MMP (Extraoral involvement)
• Requires systemic immunosuppressants:
• Prednisolone ± cyclophosphamide/MMF/azathioprine
• Add IVIG, rituximab, or TNF-α inhibitors if needed
• Ocular MMP Management
• Collaborate with ophthalmologist
• Treatments include:
• Topical steroids, tetracyclines, cyclosporine, lubricants
• Surgical intervention for trichiasis/symblepharon

63. THANK YOU