Dermal Inflammation Lecture PDF

Dermal inflammation Suteeraporn Chaowattanapanit MD. Division of Dermatology Khon Kaen University  Scope Vesiculobullous disease Panniculitis Skin signs in connective tissue disease – Cutaneous lupus erythematosus – Scleroderma – Raynau...

Dermal inflammation Suteeraporn Chaowattanapanit MD. Division of Dermatology Khon Kaen University  Scope Vesiculobullous disease Panniculitis Skin signs in connective tissue disease – Cutaneous lupus erythematosus – Scleroderma – Raynaud phenomenon – Vasculitis Vesiculobullous disease Vesiculobullous lesions Clinics in Dermatology Y 2001;19:598-606 Autoimmune Blistering Disease Intraepidermal 1. Pemphigus vulgaris 2. Pemphigus foliaceus Subepidermal 1. Bullous Pemphigoid 2. Dermatitis herpetiformis Autoimmune Blistering Disease Intraepidermal 1. Pemphigus vulgaris 2. Pemphigus foliaceus Subepidermal 1. Bullous Pemphigoid 2. Dermatitis herpetiformis Localization of target adhesion sites and cleft formation of bullous diseases  Pemphigus Vulgaris Middle-aged HLA-DR4 & DQ1 haplotype IgG autoAb against desmoglein 3 and/or 1 Loss of cohesion between epidermal cells “ Acantholysis “ formation of intraepidermal blisters  Pemphigus Vulgaris Typically, flaccid blisters on both normal and erythematous skin Blister rupture easily à denuded area Nikolsky’s sign : positive Asboe –Hensen sign (bullous spreading sign) : positive  Pemphigus Vulgaris Typically on oral mucosa, scalp, face, neck, axilla, trunk lesion begins in mouth, other mucosa pruritus in early heal without scar except 2nd infection post inflammatory hyperpigmentation  Tzanck smear: acantholytic cells round homogenous cells containing hyperchromatic nuclei and perinuclear halo  Pemphigus Vulgaris Biopsy : intraepidermal vesicle (suprabasal) blister contain acantholytic epidermal cells ( round homogenous cells containing hyperchromatic nuclei and perinuclear halo ) Suprabasal blister Acantholytic cell  Pemphigus Vulgaris Direct immunofluorescence (DIF): Deposition of IgG and/or C3 on surface of keratinocyte in perilesional skin Indirect immunofluorescence (IIF): titer correlates to disease activity DIF: intercellular deposition of IgG and/or C3 (chicken- wire pattern)  Bullous Pemphigoid Autoimmune subepidermal blistering disease Elderly MHC class II allele HLA-DQ B1*0301  Bollous Pemphigoid Circulating Ab : 230 and 180 kDa hemidesmosome-asso. protein “ BPAG1 & BPAG2 “ mast cell degranultion complement Eo, PMN infiltrate tissue damage blister formation  Bullous pemphigoid Tense bullae on normal or erythematous skin Blister rupture & replaced by flaccid lesion or erosion with or without surmouting crust Distributed : lower abdomen, groin ,flexor surface of extremities  Bullous Pemphigoid Oral mucosa 10-40% Pruritus not severe, urticarial stage Heal without scarring Not increase incidence of malignancy  Bollous Pemphigoid Biopsy : subepidermal blister with eosinophil- rich infiltrate within the papillary dermis at sites of vesicle formation Subepidermal blister with eosinophils  Bollous Pemphigoid DIF :linear deposition of IgG and/or C3 in the epidermal basement membrane ( EBM ) IIF: no correlation of titer and disease activity DIF: IgG and/or C3 deposition at dermo-epidermal junction Panniculitis  Definition : Inflammatory process that predominantly affects subcutaneous fat presenting with subcutaneous tender nodules Anatomy & Histology Septa lobule Clinical caused panniculitis CNT associated panniculitis Vascular panniculitis Systemic disease associated panniculitis Noninfectious granuloma panniculitis Infectious associated panniculitis Others Histologic approach Septal eg. erythema nodosum Lobular eg. lupus profundus  Erythema nodosum The most common type of paniculitis Etiology & pathogenesis Reactive dermatosis occur in myriad of Condition, hypersensitivity reaction to antigenic stimuli Antigens: Streptococcus – children Drug / Sarcoidosis / IBD – Adult Idiopathic Causes of Erythema nodosum  Erythema nodosum Clinical manifestation - symmetry, non-ulcerated, nodules - common affecting knees, shins, ankles - associated systemic symptom : pyrexia, malaise, headache, arthralgia  Erythema nodosum Lab investigation - CBC, ESR, CXR, ASO titer Pathology: predominantly septal panniculitis without vasculitis Septal panniculitis Skin signs in connective tissue disease Cutaneous lupus erythematosus Acute CLE 1. Localized (malar rash, butterfly rash) 2. Generalized (MP lupus rash, photosensitive lupus dermatitis, urticaria-like, EM-like, TEN-like, bullous LE) Subacute CLE 1. Annular 2. Papulosquamous Chronic CLE 1. Classic DLE (localized or generalized) 2. Hypertrophic or verrucous DLE 3. Lupus profundus or panniculitis 4. Mucosal DLE (oral or conjunctival) 5. Lupus tumidus (urticarial plaque) 6. Chilblain LE 7. Lichenoid DLE Cutaneous lupus erythematosus ACLE(malar rash) almost always associated with visceral involvement SCLE: 50% meet SLE criteria ACLE and SCLE: highly photosensitive, typically precipitated by UV, post- inflammatory pigmentary, no scarring CCLE: often have skin only DLE: scarring and disfiguring  Subacute CLE Annular/polycyclic or papulosquamous or mixed Resolve with vitiligo-like leukoderma Variants: erythema multiforme, vesiculobullous, pityriasis rosea-like, exfoliative erythroderma Anti-Ro/SS-A strongly supports Dx SCLE but not required for diagnosis of SCLE Neonatal LE: transient, photosensitive, non- scarring LE-specific skin, IgG anti-Ro SCLE+ACLE or SCLE+DLE  Chronic CLE Localized DLE (5% develop SLE) and generalized DLE (risk SLE > localized) Early lesion: erythematous plaques covered by adherent scale Late lesion: white atrophic scar surrounding with hyperpigmentation and telangiectasia Palm and sole: painful Scalp: scarring alopecia Lupus panniculitis/profundus (Kaposi-Irgang disease) Tumid LE: no epidermal involvement  Thickened basement membrane Superificial and deep and periadnexal lymphocytic infiltrate  Drug-induced CLE Drug-induced SLE (anti-histone Ab): procainamide, hydralazine, INH, chlorpromazine, phenytoin, minocycline, anti-TNF: manifests similarly to SLE but without cutaneous involvement Drug-induced SCLE: HCTZ, Ca channel blocker, ACEI, cinarizine, terbinafine, piroxicam, D-penicillamine, sulfonylurea, gold, griseofulvin, PTU, leflunomide Drug-induced SCLE and DLE: anti-TNF  Raynaud phenomenon Digital ischemia from vasospasm (abnormal vasomotor tone) White - blue - red Numbness, pain Precipitating factors: cold, stress, smoking Primary/ secondary Common causes: connective tissue disease ( systemic scleroderma 85%, SLE)  Scleroderma Localized: morphea (plaque, linear, generalized) Systemic sclerosis (SSc): Limited SSc, diffuse SSc, SSc sine scleroderma Scleroderma-like: 1. infiltrative disorders: amyloidosis, scleromyxedema, scleredema of Buschke 2. metabolic disorders: myxedema, PCT, acromegaly, phenylketonuria 3. inflammatory: eosinophilic fasciitis (Shulmann syndrome), chronic GVHD, sarcoidosis Thickened and homogenized collagen  Scleroderma Systemic sclerosis (SSc): American College of Rheumatology diagnostic criteria Major criterion: symmetric cutaneous sclerosis proximal to the metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints Minor criteria: sclerodactyly, digital pitted scars or loss of substance from finger pads, bibasilar pulmonary fibrosis Limited (distal to elbow and knee), diffuse (proximal to elbow and knee) SSc, SSc sine scleroderma  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Scleroderma 3 phases 1. Edematous phase 2. Indurated phase 3. Atrophic phase (bound-down) Matted telangiectasia Round finger pad sign Sclerodactyly Digital pitting scar Salt and pepper appearance Raynaud phenomenon  Limited cutaneous SSc Long pre-existing Hx of Raynaud phenomenon Skin sclerosis spares proximal sites CREST (calcinosis cutis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome High frequency of visceral disease including pulmonary arterial hypertension Pulmonary fibrosis and GI involvement: common Low frequency of renal crisis Often anti-centromere positive  Diffuse cutaneous SSc Proximal skin sclerosis Close temporal relationship between onset of Raynaud and skin sclerosis Prominent inflammatory features (swelling of the extremities) during first 24 months of disease High frequency of pulmonary fibrosis, cardiac involvement, renal crisis Often antiScl-70 or anti-RNAPIII positive Vasculitis  Vasculitis Manifestation: Small-sized vessel: palpable purpura, hemorrhagic blister, necrosis, ulcer, pyoderma Medium-sized vessel: subcutaneous nodule, ulcerative nodule Small-sized vasculitis  Vasculitis Manifestation: Small-sized vessel: palpable purpura, hemorrhagic blister, necrosis, ulcer, pyoderma Medium-sized vessel: subcutaneous nodule, ulcerative nodule Histology: neutrophils, nuclear dust infiltrate with extravasated RBC, fibrin within vessel wall, ± granulomatous inflammation Small vessel Medium vessel vasculitis  Henoch-Schonlein purpura Palpable purpura Age at onset less than 20 yr Arthritis or arthralgia Bowel angina Renal involvement Dx: leukocytoclastic vasculitis, IgA deposit within vessel wall  Polyarteritis nodosa 30-50% asso. With HBV Subcutaneous nodules (ulcer) with livedo reticularis (star-burst) Renal impairment, hypertension Neuropathy, myopathy Classic: spares the lungs Testicular pain Abnormal arteriography  Granulomatosis with polyangiitis Wegener’s granulomatosis Nasal or oral inflammation CXR: nodules, infiltration (fixed) or cavities Microscopic hematuria or red cell casts in urine Granulomatous inflammation on biopsy (within vessel wall or perivascular from organ involvement) C-ANCA or anti-proteinase-3 positivity Eosinophilic granulomatosis with polyangiitis Churg-Strauss syndrome Asthma eosinophilia (more than 10%) Neuropathy Pulmonary infiltrates (nonfixed) Sinusitis Extravascular eosinophils on biopsy P-ANCA or anti-myeloperoxidase positivity  Giant-cell (temporal) arteritis Age>50 yr at onset New type of headache Abnormal temporal artery (tenderness to palpation or decreased pulsation) Elevated ESR Temporal artery biopsy showing vasculitis  Takayasu’s arteritis Age 10 mmHg difference between 2 arms Bruits Arteriogram abnormal