OMPR lec 2

• Autoimmune Oral Vesiculo-bullous Disorders

  Pemphigus Vulgaris, Mucous Membrane Pemphigoid
• Autoimmune Vesiculo-bullous Disorders


  • 80-100% of patients develop ORAL lesions FIRST, and 24% remain Exclusively Oral
  • They are among the few LETHAL disorders that a dentist can and should diagnose
  • Dentists are the best qualified to detect these oral manifestations
• Early diagnosis and effective treatment improves outcomes: Control, Remission, Cure
• Pemphigus Vulgaris and Mucous Membrane Pemphigoid


  Mucocutaneous autoimmune bullous diseases characterized by multiple, chronic blisters (bullae) which rupture to form large, non-healing ulcerations
• Onset usually in 5th and 6th decades; but can affect all ages
• Ultra orphan illnesses


  • Each affecting <50,000 people in the U.S.
  • Lack of awareness
  • Diagnostic delays
  • Lack of knowledge
  • Ineffective treatment
  • Lack of attention
  • Slow discovery for cure and lack of advocacy among payors and policymakers
• IPPF


  • International Pemphigus & Pemphigoid Foundation
  • Premier patient advocacy organization dedicated to individuals affected by pemphigus and pemphigoid
  • Provide educational and referral resources to clinicians
  • Provide education, counseling, support, referral services to patients and clinicians
  • Connects patient, doctor, research and health care communities
  • Sponsor annual patient-doctor meetings
  • Peer Health Coaches
  • Manage rare-disease registry

  
• Despite ORAL presentation being the MOST COMMON, it is the LEAST RECOGNIZED: On average a patient will see 5 clinicians over 10 months in search of a diagnosis, One third of patients with oral lesions still in search of a diagnosis after ONE YEAR! (vs >95% patients w skin lesions diagnosed < 6 months), Takes more clinician contacts to recognize oral lesions than it does skin, Dentists are often the first clinician the patient seeks help from
• Rare: minimal curricular time and very little clinical experience, Serious: People die if untreated; & even w treatment there is significant morbidity
• Patient Evaluation Process: History (CC, detailed HxCC), Examination, Clinical tests (palpation, percussion, vital stains, imaging, etc… (as needed)), Differential or Presumptive Diagnosis, Further Diagnostic / Assessment depending on differential: Histopathology (routine H&E, DIF, other tissue-based tests), Hematology, Chemistry, Serology etc…, Outcome to Empirical treatment, Definitive Diagnosis
• History: 90% of the story!!!

  Prior occurrence, Duration, Frequency, Number, Location (intra / extra oral), Size, Associated events, Changes in size or behavior, Pain, Other (constitutional) symptoms
• KEY H&P FINDINGS supporting Bullous AI disorders in DDX

  • Shallow, non-specific ulcers (rarely see bullae), Multiple, bilateral / general, Chronic, non-healing, Minor trauma can lead to lesions (Nikolsky Sign), w or wo extraoral lesions (skin, nasal, GI, ocular, vaginal)

  
• KEY features VB lesions

  • multiple, chronic / non-healing, shallow mucosal ulcers w/wo skin/EO lesions
• Assessing Skin and Mucosal Disorders: Traumatic / reactive, Immunologic, Infectious, Malignant, But NOT very helpful for establishing a clinical diagnosis.... For this, the HISTORY & APPEARANCE are KEY!

  
• For Any Lesion...


  How Many?, How Long?, Had it before?, Anywhere else?
• Pemphigus Vulgaris and Mucous Membrane Pemphigoid: Multiple, Chronic, Primary, Local (oral) or General (skin, mucosa)
• The answer to those 4 simple questions can help narrow the differential diagnosis into a limited number of conditions according to pathological process
• Differential Diagnosis


  • Trauma, Malignancy, Hematologic, Infectious, Fungal, Bacterial, Leukopenia, Viral, Immunologic, Major Aphthous, Chronic, Ulcerative Lichen Planus, Pemphigus, Pemphigoid

  
• Chronic, multiple, mucosa / skin ulceration: ulcerative lichen planus, pemphigus, pemphigoid
• The step(s) you take next (when properly executed) will result in a definitive diagnosis
• Lichen Planus, Lichenoid Lesions, Lichenoid Dysplasia: very often will include Ulcerative Lichen Planus
• Oral Lichen Planus


  Idiopathic oral lichen planus, oral lichenoid lesions not readily attributable to any defined cause, and with highly characteristic clinical and histopathological findings, includes the unique clinical phenotype of desquamative gingivitis
• Oral Lichenoid Contact Lesions


  Direct topographic relationship to dental restorative materials, most commonly amalgam
• Oral Lichenoid Mucositis / Drug Reactions


  Oral or cutaneous lesions occur, temporally associated with the use of certain medications (such as oral hypoglycaemic drugs, angiotensin converting enzyme (ACE) inhibitors, and non-steroidal anti-inflammatory agents (NSAIDS))
• Oral Lichenoid Lesions of Graft versus Host Disease

  In the setting of patients with acute, but predominantly chronic graft versus host disease (GVHD)

  
• Lichenoid Dysplasia


  Chronic, solitary, unilateral, ulceration, erythroleukoplakia
• Classic appearance of LP: Wickham striae erythroleukoplakia
• The ulcerative features of LP can be nearly identical in appearance to PV and MMP, Desquamative gingivitis can appear identical in LP, PV and MMP, But the presence of Wickham Striae aids in identifying LP

  
• Pemphigus and Pemphigoid


  Ultra orphan illnesses, Each affecting <50,000 people (in U.S.), Lack of awareness, Diagnostic delays, Lack of knowledge, Ineffective treatment, Lack of attention, Slow discovery for cure
• Pemphigus Vulgaris


  Multiple, chronic mucocutaneous ulcers, mucocutaneous autoimmune disease characterized by intra-epithelial bullae (acantholysis) which rupture to form multiple, large, non-healing superficial ulcerations, onset usually in fifth and sixth decades
• Pemphigus vulgaris detachment "between the bricks": anti-Dsg1,3, Mucous membrane pemphigoid detachment "along the foundation": anti-BPA2
• Pemphigus Subtypes


  Pemphigus Vulgaris (most common, any mucosal or skin surface), Pemphigus foliaceous (superficial, skin only), Paraneoplastic pemphigus (associated with cancer), Drug-induced

  
• Pemphigus Vulgaris: Clinical Phenoptypes


  Approximately 1 in 4 PV patients experience only mucosal lesions throughout their illness (mucosal dominant, AntiDsg3 IgG only), Majority eventually have mixed mucosal and skin lesions (AntiDsg 1 & 3 IgG), The desmoglein autoantibody profile can identify / predict the lesion distribution (clinical phenotype)

  
• Epitope Spreading in Pemphigus: diversification of B and/or T-cell response from the initial dominant epitope (mucosal) to a secondary epitope (mucosal AND skin) over time. Early treatment can reduce / prevent spreading of lesion activity from local to mixed / widespread
• Knowing the autoantibody profile (Dsg 1 v Dsg3) by indirect immunofluorescence (IIF) early on can influence your aggressiveness in supressing autoantibody production to prevent the progression from limited to widespread lesions (epitope spreading)

  
• Shallow multiple chronic / non-healing ulcers on any surface
• PV skin lesions: early bullae, persistent ulcerations, and post-inflammatory melanosis often appears at sites of past lesions

  
• Lesion activity can be unpredictable, explosive and severe. Even with effective treatments PV has a ~2% mortality rate
• PV lesions can affect virtually any mucosal surface (oral, nasal, ocular, pharyngeal, esophageal, genital)
• Shallow, multiple chronic / non-healing mucosal and skin ulcerations (often don't see the bulla phase due to fragility), ALWAYS consider PV!