Neutrophilic Dermatoses Flashcards

Question

Bullous PG (Atypical PG, PG subtype)

Answer 1

Assoc with myeloproliferative disorders Rapidly arising Superficial haemorrhagic bullae Often located on the arms Shares clinical and histological findings with Sweet syndrome but Typically ulcerates Heals with scarring ASSOCIATED DISEASES Myeloproliferative disorders —> PG can precede the onset of malignancy —> should be investigated with high index of suspicion for haem malignancy

Answer 2

Superficial lesions of PG With a granulomatous histology Begins with single superficial ulcer with granulations and elevated edge Most often on trunk Lower incidence of associated conditions (idiopathic) More responsive to Rx than other variants - TCS - ILCS - systemic CS - minocycline - Dapsone

Answer 3

Aseptic abscessus ``` Lungs (most common) Bones Liver Heart Brain GIT Muscle ```

Answer 4

Vascular occlusive or venous disease Vasculitis Malignancy Primary infection —> Bx and tissue culture - Fungi - atypical mycobacteria - Sporotrichosis - Mucormycosis - Histoplasmosis - Blastomycosis Drug-induced - Nicorandil Exogenous tissue injury

Answer 5

Mortality ? from secondary infection, immunosuppressive Rx, or combo ``` PG COMPLICATIONS/CO-MORBIDITIES (either predispose to PG or a result from PG) Diabetes (long term pred) Peripheral vascular disease Obesity Depression Anaemia Renal impairment Thyroid disease ```

Answer 6

Chronic condition Takes many months or years to completely resolve May be recurrent —> consider long term systemic preventive Rx

Answer 7

EXAM Lymphadenopathy (malignancy) SKIN BX Not diagnostic, but performed in all (except classical Ulcerative PG) to exclude other conditions that may minic PG particularly infection Bx for H&E, and Bx for tissue culture (bacterial, mycobacterial, fungal, viral) BLOODS FBC (haem malignancy) ELFT Blood culture (infection) IMAGING CXR (TB, malignancy) CT scan (malignancy) OTHER Endoscopy (IBD, malignancy) BMAT (malignancy)

Answer 8

No typical histology Skin bx taken to exclude other causes of ulceration esp infection that mimic PG clinically Neutrophilic pustules (early lesions) Features generally non-specific Presence of vasculitis debatable —> may be secondary to ulceration If vasculitis is present —> exclude vasculitides and infective causes —> tissue culture, special stains of tissue for fungi, mycobcteria TYPICAL FINDINGS Central necrosis Ulceration of the epidermis + dermis Surrounded by intense mixed to chronic inflammatory cell infiltrate CLASSIC ULCERATIVE SUBTYPE Massive dermal epidermal neutrophilic infiltrate with suppurative/abscess formation PUSTULAR SUBTYPE Perifollicular neutrophilic infiltrate with subcorneal pustule formation BULLOUS SUBTYPE Neutrophilic infiltrate with intraepidermal vesicle formation ``` SUPERFICIAL GRANULOMATOUS (VEGETATIVE) SUBTYPE Granulomatous reaction with peripheral palisading histiocytes and giant cells ```

Answer 9

FIRST LINE Analgesia Supportive Rx to promote wound healing - Dressings - Topicals for cleansing and debriding and keeping wound moist - Compression Potent TCS (small lesions) ILCS (small lesions) Topical tacrolimus ointment (small lesions) SECOND LINE (more severe dosease, or PG not responding to simple measures) * Systemic CS (mainstay Rx) - Oral prednisolone 0.5 - 1mg/kg/day * CSA 5mg/kg * Combined oral prednisolone + CSA Pulsed oral prednisolone 1mg/kg/day for 5 days MTX MMF Dapsone Others - Tetracyclines - Thalidomide - Tacrolimus - Cyclophosphamide - Chlorambucil - AZA - Colchicine THIRD LINE mainly d/t cost (Biological Rx) Anti-TNF (should be comsidered more often as 1st line esp those with IBD) - Infliximab** - Adalimumab —> risk of paradoxical onset of PG - Etanercept —> risk of paradoxical onset of PG IL12/23 - Ustekinumab Anti- IL1 - Anakinra (successful for PAPA, PASH syndrome) IVIg Topical platelet derived growth factor ``` ALTERNATIVE RX Skin graft (although surgery should be avoided in the inflammatory stage and can grequently induce PG, skin graft can be successful if inflammation has already resolved following systemic Rx with oral CS) ``` Granulocyte apheresis Topical sodium cromoglycate Topical nicotine Hyperbaric oxygen

Answer 10

DEFINITION Pustular vasculitic lesions Assoc with blind loops of bowel Or other causes of stasis of bowel content CLINICAL FEATURES Begins as small macular lesions Progress into papules —> pustules on an erythematous purpuric base Arms, other areas on upper body Pustules typically occur in crops Each crop lasts ~ 2 weeks Recurring at intervals of several months Other lesion types - larger erythema nodosum-like lesions - larger PG-like pustular lesions Pathergy Lesions May be preceded by constitutional symptoms - - Fever - Flu-like symptoms - Myalgia - GIT upset Arthralgia or non-erosive polyarthritis —> acute inflammatory with tenderness, swelling - Hands - Wrists - Other peripheral joints Ocular - Episcleritis GUT - Haematuria - Proteinuria ``` DDX Behcet disease (oral aphthae, lesions of pustular vasculitis) ``` PATHOGENESIS Proliferation of bowel flora antigen (peptidoglycans) —> circulating immune complexes —> immune complex-mediated blood vessel damage ``` PREDISPOSING FACTORS causing blind loops of bowel or stasis of bowel contents Jejuno-ileal bypass surgery Gastric resection Blind loops of bowel Defunctioning ileo-anal pouch Bilio-pancreatic diversion ``` IBD - Crohn disease - Ulcerative colitis Diverticulitis of the colon Jejunal diverticula Appendicitis Achalasia of the gastric cardia Combined causes i.e. surgery for IBD DX Requires clinicopathologic correlation IX Swab MCS of pustules Urinalysis (haematuria, proteinuria —> immune complex initiated glomerulonephritis) HISTO Pustular vasculitis —> similar to Sweet syndrome MX Surgical correction of bowel anatomy (for patients following bowel bypass surgery) —> often eliminates signs and symptoms Surgical correction difficult for patients with blind loops of bowel —> resolution of sumptoms less likely ``` SYSTEMIC RX (first line —> antibacterials —> suggests role of bacterial colonisation in trigerring systemic response in BADAS) Oral tetracycline Oral metronidazole Oral ciprofloxacin Oral erythromycin ``` SYSTEMIC RX (second line) —> may need to be combined with appropriate AB Oral prednisolone - usually unnecessary - but may be justified depending on degree of skin, joint, systemic symptoms, or manage IBD) Oral colchicine Oral dapsone Oral MMF

Answer 11

DEFINITION Sterile subcorneal pustules Affecting flexural areas of trunk and proximal extremities CLINICAL FEATURES Sterile oval pea-sized pustules on a normal or erythematous base May see characteristic fluid level - Pus lower half - Clear fluid upper half Pustules may be isolated or grouped, coalescing to form annular or serpiginous patterns Successive waves may pass ofer the same area Pustules may rupture in the flexures —> becomes indistinct Acute flares lasts several days or weeks Flexures of the trunk, proximal limbs (axillae, groin, submammary, neck, apron) Spares face, mucous membrane ``` ASSOCIATED DISEASES Benign monoclonal gammopathy (more commonly IgA) Multiple myeloma Lymphomas IBD PG RA Connective tissue disease incl. SLE ``` ``` PATHOGENESIS Obscure Linked to - excessive production of TNF-alpha - Neutrophil activation —> in common with other neutrophilic dermatosis ``` ? Overlap with pemphigus (but most cases DIF megative) —> a subset has IgA deposited in the upper dermis directed against desmocollin 1 —> IgA pemphigus —> relationship between IgA pemphigus and classic subcorneal pustular dermatosis unclear DDX Impetigo Pustular psoriasis (spongiform pustules, unlike subcorneal pustular dermatosis) AGEP (fevers, recent drug exposure) Pemphigus foliaceus IgA Pemphigus (DIF intercellular IgA) Dermatitis herpetiformis (this is usually on extensor surfaces, rather than flexures) IX Skin swab MCS (exclude impetigo) Skin biopsy of early pustules (most recent pustules) Skin bx of perilesional skin for DIF (DDx IgA pemphigus) Anti-skin antibodies (Pemphigus) FBC + diff, SPEP, UPEP + immunofixation, serum free light chains (Exclude multiple myeloma) Rh factor, anti-CCP (Exclude RA) —> only if indicated by hx ANA (exclude autoimmunity) —> only if indicated by hx Faecal calprotectin (exclude IBD) —> only if indicated by hx HISTO Perivascular inflammatory infiltrate with occasional EOSINOPHILS Pustules sit on the surface of the viable epidermois No spongiosis No spongiotic pustules IHC neg (positive in intercellular IgA pemphigus) MX Rx underlying associated disease Rx condition FIRST LINE RX Dapsone 50-150mg daily —> partial or complete response ``` SECOND LINE RX Potent TCS —> not really effective Oral CS —> not really effective Acitretin Tacalcitol NbUVB PUVA Oral retinoids + PUVA CSA + oral pred ``` THIRD LINE RX Oral ketoconazole Anti-TNF (case reports) - Etanercept - Adalimumab (combined with other immunosuppressant i.e. MMF) - Infliximab (combined with other immunosuppressants i.e. pred, AZA) COURSE/PROGNOSIS Benign but chronic

Answer 12

Some consider this the oral mucosal form of pustular PG CLINICAL FEATURES Oral mucosal thickening with multiple pustules, Snail track superficial ulceration on an erythematous base Any site of oral mucosa But tongue less affected Skin lesions may be present - often flexural - Clinically suggestive of pemphigus vegetans with verrucous plaques studded with pustules - may be assoc dorsal hand lesions morphologically similar to neutrophilic dermatosis and rash resembling Sweet syndrome - May display pathergy ``` ASSOCIATED DISEASES IBD esp ulcerative colitis (strongest assoc) Leukaemias Lymphomas Follicular occlusion syndromes - Acne conglobata - HS - Dissecting cellulitis Immunosuppression Malnutrition ``` PATHOGENESIS Unknown Suggested immunological and microbial factors May represent abnormal response to infection (various bcteria reported as causative) IX Total IgE (raised) FBC (peripheral eosinophilia) HISTO ORAL MUCOSAL LESIONS Intraepithelial and/or subepithelial abscesses containing large numbers of EOSINOPHILS Deeper tissue have mixed infiltrate of neuts, eos Often assoc peripheral blood EOSINOPHILIA ``` HISTO SKIN LESIONS (IF PRESENT) —> verrucous plaques studded with pustules Pseudoepitheliomatous hyperplasia Neutrophilic abscesses Negative DIF —> unlike pemphigus vegetans ``` MX Antimicrobials (if cause uncertain) ``` RX FOR ORAL DISEASE First line - TCS - TCI (tacrolimus) - Oral pred when topicals fail ``` Second line - Dapsone - Oral pred +/- AZA - CSA - Adalimumab - MTX + infliximab (Crohn assoc cases)

Answer 13

Most cases occur in patients with SLE CLINICAL FEATURES Rapidly evolving small semi-confluent pustules Pustules —> erosions, crusts Predominatly affect flexures —> 1 major (axilla, inguinal) + 1 minor skin fold (face, scalp) affected Alopecia if affects scalp ``` ASSOCIATED DISEASES (mainly autoimmune conditions) SLE (most cases) Coeliac disease Autoimmune thyroid disease Autoimmune hepatic disease Crohn disease Sjogren disease IgA nephropathy ``` DIAGNOSTIC CRITERIA Major criteria - Pustulosis involving 1 or more major skin fold - Pustulosis involving 1mor more minor skin folds in the anogenital area - Histo pattern with intraepidermal spongiform pustules + mainly neutrophilic dermal infiltrate - Negative culture from unopened non-ruptured pustule Minor criteria - Assoc with 1or more autoimmune disorders - Positive ANA 1:160 or higher - Autoantibodies ENA, anti-dsDNA, anti-smooth muscle, anti-mitochondrial, antiendomesial DDX Subcorneal pustular dermatosis Pustular psoriasis Erosive pustular dermatosis of the scalp (if involves scalp) IX Neutrophilic epidermal and ostial exocytosis Spongiform pustules Neutrophilic dermal infiltrate Variable DIF positivity for IgM, C3, IgG (endothelium or lupus band) FIRST LINE RX Oral pred ``` SECOND LINE RX Dapsone CSA Oral zinc TCS Colchicine Cimetidine Ascorbic acid Anakinra (if IL-1 demonstrated to be involved) ```