Pines City Colleges 2.02 Vesiculobullous Disorders PDF

DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble...

DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 OVERVIEW: MANEUVERS  Pemphigus NIKOLSKY SIGN ASBOE HANSEN SIGN a.Pemphigus foliaceus b.Pemphigus vulgaris  Pemphigoid a.Bullous pemphigoid b.Epidermal bullosa  Others a.Linear IgA Disease b.CBDC  Differentials Lateral pressure on a.Bullous impetigo Lateral extension of a unblistered skin with b.Viral diseases blister with downward resulting shearing of the c. Dermatitis pressure epidermis LET’S RECALL Nikolsky: (+) SSSS, (+) SJS/TEN Vesicle < 1cm Bullae >1cm See appendix BULLAE  Thorough history and physical examination  Tests - Skin biopsy for routine hematoxylin and eosin histology - Second biopsy juxtaposed to a lesion but on normal-appearing skin for DIF - Blood draw to test for antibodies against the  Patients with acquired immunobullous diseases have basement membrane zone (BMZ) and/or Type autoantibodies directed against components of the VII collagen by indirect immunofluorescence (IIF) epidermis (e.g. in pemphigus) or epidermal or enzyme-linked immunosorbent assay (ELISA). basement membrane (e.g. in various forms of pemphigoid). I. PEMPHIGUS  A group of autoimmune mucocutaneous blistering diseases  Histologically: Intraepidermal blisters - Acantholysis: separation of epidermal cells from each other - In vivo bound and circulating immunoglobulin directed against the cell surface of keratinocytes.  Usually above 40 years old 1 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 A. PEMPHIGUS VULGARIS B. PEMPHIGUS FOLIACEUS  Cutaneous findings  Aka Superficial Pemphigus Pruritic or painful  CUTANEOUS FINDINGS Primary lesion: flaccid blister Scaly, crusted erosions on an erythematous base - Observed: large erosions Early/ localized disease: well demarcated and Location: anywhere, spares palms and soles scattered in a seborrheic distribution, Pain and burning Mucous membrane involvement is rare Frequently initially diagnosed as impetigo for several consults When widespread, may lead to exfoliative erythroderma Because the vesicle is so superficial and fragile, often only the resultant crust and scale are seen  Because PV blisters are fragile, the most common skin lesions observed in patients are erosions resulting from broken blisters. These erosions are often quite large, as they have a tendency to spread at their periphery  Mucous membrane lesions Most common: oropharyngeal and nasal mucosa. Painful mucous membrane erosions are the presenting sign of PV and may be the only sign for an average of 5 months before skin lesions develop. Others: GI tract, vulvovaginal and ocular epithelia 2 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023  Diagnosis of Pemphigus Disease  TREATMENT Clinical  Corticosteroids ELISA - Mainstay of treatment - Pemphigus Vulgaris: Desmoglein 1 and 3 - PV, even in limited extent, should be treated at its (Dsg 3- usually oral mucosa) onset, because prognosis without therapy is very - Pemphigus Foliaceus: Desmoglein 1 only poor. - Localized PF prognosis without systemic therapy may be good, topical steroid only - Generalized PF: similar to that for PV  Rituximab  Oral Immunosuppressive agents - Azathioprine, Mycophenolate mofetil, Methotrexate PEMPHIGUS VULGARIS PEMPHIGUS FOLIACEUS II. PEMPHIGOID  Suprabasal Acantholysis-  also called superficial blister occurs in the pemphigus A. BULLOUS PEMPHIGOID deeper part of the  Acantholysis in the granular  Most common autoimmune bullous disease epidermis, just above layer- blister is in the (AIBD) in adults the basal layer granular layer  Pruritic, tense blisters on urticarial plaques  Row of Tombstones(fatal)  Location: flexural surfaces, the lower abdomen, and the thighs  Non-bullous lesions are the first manifestation  Mucous membrane lesions occur in approximately 10% of patients and are almost always limited to the oral mucosa  Waxing and waning course with occasional spontaneous remission in the absence of treatment  Heals without scarring  Another frequent finding is subcorneal pustules, with neutrophils and acantholytic epidermal cells in the blister cavity: often indistinguishable from those seen in bullous impetigo/staphylococcal scalded skin syndrome, because blisters in these latter diseases also result from dysfunction of desmoglein 1. Therefore, immunochemical studies are essential to confirm a diagnosis of PF, as these would be negative in Staphylococcal- mediated skin blisters.  DIF- IgG  Via autoantibodies directed against hemidesmosomal proteins BP180 and BP230, which trigger an inflammatory cascade that ultimately leads to blister formation. Pemphigus Vulgaris Pemphigus Foliaceus 3 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023  Diagnosis of Bullous pemphigoid  Treatment options are limited and often difficult.  Clinical  Heal with: hypo- and hyperpigmentation, skin  ELISA mottling, nail loss, milia formation, scarring, and - BP180 fibrosis  Histopathology with Immunofluorescence  Diagnosis Subepidermal blister with eosinophilic inflammatory  Clinical infiltrate  ELISA - Anti- type VII collagen DIF: Linear IgG and C3 in the DEJ  Histopathology and Immunofluorescence Diagnostic Criteria  A bullous disorder within the clinical spectrum  No family history of a bullous disorder  Histology showing a subepidermal blister.  Deposition of immunoglobulin G deposits within IgG C3 the dermal– epidermal junction (ie, a positive direct immunofluorescence of perilesional skin).  Treatment  Mainstay: Corticosteroids  Localized: topical corticosteroids  Extensive: oral prednisone + potent topical steroids  Others: - Dapsone and Sulfapyridine - Immunosupressive: Azathioprine, Mycophenolate mofetil, Methotrexate - Rituximab B. EPIDERMOLYSIS BULLOSA ACQUISITA  Rare, autoimmune subepidermal bullous disease due to immunoglobulin G autoantibodies to Type VII  Routine histologic examination of lesional skin collagen. obtained from EBA patients shows a subepidermal  Skin fragility, subepidermal blisters, residual scarring, blister and a clean separation between the epidermis and milia formation. and dermis. The degree of inflammatory infiltrate  Common sites are trauma-prone areas (hands, feet, within the dermis usually reflects the degree of elbows, knees, sacrum, nails, and mouth) inflam- mation of the lesion observed by the clinician.  Related underlying systemic disease: inflammatory Lesions that are reminiscent of recessive dystrophic bowel disease. EB or PCT usually have a notable scarcity of  May have erosions of the mucosa and esophageal inflammatory cells within the dermis. Lesions that stenosis/ strictures are clinically reminis- cent of BP usually have 4 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 significantly more inflamma- tory cells within the dermis, and these cells may be a mixture of lymphocytes, monocytes, neutrophils, and eosinophils. The histology of EBA skin specimens obtained from BP-like lesions may be difficult to dis- tinguish from BP itself. EBA  Floor(ebaba)  Collagen 7  IgG antibodies from epidermolysis bullosa acquisita (EBA) serum binds to the dermal side (floor) of the split (collagen VII of anchoring fib DIF: Linear IgG depositson the DEJ  TREATMENT Salt Split Skin Smear  EBA usually responds poorly to treatment - Often refractory to high doses of systemic Indirect immunofluorescence on normal skin previously glucocorticoids, azathioprine, methotrexate, and incubated in 1-M NaCl to induce a split through the cyclophosphamide lamina lucida of the dermal epidermal junction  Supportive management  Colchicine: often used as a first-line drug because its side effects are relatively benign compared with other therapeutic choices - Other options: Dapsone, Cyclosporine, Infliximab and Rituximab  Colchicine is a well- known microtubule inhibitor, but it also appears to have properties that have the potential to inhibit anti-gen presentation to T cells, which could downregulate autoimmunity  The anti–TNF-α biologics (such as infliximab) have been tried in EBA with some success in uncontrolled open trials. Rituximab, a monoclonal antibody against the CD20 protein on the surface of B lymphocytes induces markedly decreased B-cell lymphocytes in the patients and has shown efficacy in recalcitrant EBA patients Bullous Pemphigoid  Roof(bubong)  BP180. BP230  Immunoglobulin (Ig) G antibodies from bullous pemphigoid serum binds to the epidermal side (roof) of the artificial blister (BP180 and BP230 of hemidesmosomes) 5 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 III. OTHER AIBD vesicles and bullae arising on normal A. LINEAR IgA DERMATOSIS appearing skin grouped urticarial papules  Rare  Onset: typically after fourth decade of life  Annular or grouped papules, vesicles, and bullae distributed symmetrically on extensor surfaces B. CHRONIC BULLOUS DISEASE OF CHILDHOOD  Very pruritic  Oral lesions in up to 70%  Possible association with ulcerative colitis  Ultraviolet light is the chief physical trigger  Treatment: - Dapsone, sulfapyridine (response within 24-48 h) -Low-dose prednisone may suppress blister formation crusted erosions, papules and vesicles -annular and herpetiform vesicles arising on an inflammatory base  Children less than 5 years old  Tense bullae on an inflammatory base most frequently in the perineum and perioral region  Occur in clusters, giving a “cluster of jewels”  New lesions sometimes appear around the periphery of previous lesions, with a resulting “collarette” of blisters.  (+) significant pruritus and/or a burning of the skin  Spontaneous remissions, often within 2 years  Possible association with infectious mononucleosis and Paecilomyces lung infection 6 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023  Treatment IV. COMMON VESICULOBULLOUS CONDITIONS Dapsone, sulfapyridine small doses of prednisone mycophenolate mofetil as a steroid-sparing agent topical tacrolimus  CBDC differs from linear IgA bullous dermatosis of adults in its typical clinical appearance, relative paucity of serious mucosal involvement, and good prognosis Linear IgA Dermatosis and CBDC BULLOUS IMPETIGO Bacterial infection caused by Staph aureus. Blisters are flaccid, with noted honey colored crusting IRRITANT CONTACT DERMATITIS VARICELLA Subepidermal bulla with collections of neutrophils along the basement membrane, often accumulating at the papillary tips. A mild neutrophilic infiltrate may be present around the superficial dermal blood vessels without any evidence of neutrophilic vasculitis. 7 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 HERPES ZOSTER OROLABIAL HRPES ZOSTER ECZEMA HERPETICUM GENITAL HERPES SIMPLEX 8 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 9 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 10 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 11 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 12 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.02 VESICULOBULLOUS DISORDERS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 13 | Page TRANSCRIBERS: Jay-G