Vasculitis and Panniculitis

Question 1

Leukocytoclastic vasculitis

Answer 1

• Can be a manifestation of several underlying disezSes that can manifest clinically as palpable purpuric lesions

Common causes:
IgA vasculitis (Henoch-Schonlein purpura)
* Necrotising vasculitus of small vessels
* Children
* Palpable purpuric rash
* Arthritis
* Haematuria
* Bowel angina/Ischaemia
* Post strep throat infection

Polyarteritis Nodosa
* Necrotising vasculitis of medium vessels
* Middle aged men
* Renal failure
* Cardiac involvement
* Subcut nodules
* Livedo Reticularis
* P-ANCA and ANA negative
* Common post Hep B

Wegener’s Granulomatosis
* Granulomatous vasculitis
* URT and LRT
* Arthritis
* c-ANCA positive

• Connective tissue diseases
• Autoimmune diseases
• Drug-induced
• Infectious

Micro:
* Neutrophillic small-vessel vasculitis –> post-capillary venules in the superficial dermis
* Leukocytoclasis (fragmentation of neutrophilic nuclei into dust)
* Fibrin deposits around vessel walls
* Best seen in a lesion of 18 to 24 hours duration
* Eosinophils seen in older lesions

Direct immunofluorescence:\
* Predominantly IgA1 deposits in the postcapillary venules (Henoch-Schönlein purpura)
* Depending on the age of the lesions, skin biopsies of leukocytoclastic vasculitis can show deposition of IgG, IgA, IgM or complement C3
* Fully developed –> fibrinogen and IgG
* Late lesions –> fibrinogen +/- C3 in vessel walls

Question 2

Erythema nodosum

Answer 2

• Panniculitis with tender red nodules, usually on both shins
• Erythema nodosum migrans (subacute nodular migratory panniculitis, migratory panniculitis): asymmetrical, unilateral and distributed solely on the legs; marked female predominance; older age group
• Chronic erythema nodosum: nodules appear over months / years; otherwise indistinguishable from typical condition

Clinic:
* Red, painful, bilateral, symmetrical nodules, elevated above the skin surface
* On anterior surface of legs, arms, face, calves and trunk
* Usually involutes in days / weeks, leaving depressed, pigmented lesions
* No ulceration
* Immune mediated but precise mechanism is unknown

Causes:
NODOSUM - Mnemonic

• NO cause found in 60%
• Drugs –> sulphamides, amoxicillin
• Oral contraceptives
• Sarcoidosis or Lofgren’s
• Ulcerative colitis, Crohns, Bechet’s
• Microbes –>
  Viral: HSV, EBV, HIV, HepB, HepC,
  Bacterial: Campylo, Rickettsiae, Salmonella, Psittacosis, Bartonella, Syphillis
  Parasitic: Smoebiasis, Giardiasis

Micro:
* Marked septal fibrosis, infiltrated by lymphocytes, neutrophils, histiocytes and granulomas with giant cells
* Septal infiltrate spills over to affect the fat lobules
* Dermis shows perivascular and periadnexal chronic inflammatory cell infiltrate
* Early, the septal inflammation is acute and characterized by neutrophils, soon replaced by lymphocytes and histiocytes
* Variable eosinophils

• Miescher radial granuloma: characteristic finding of erythema nodosum; septal collection of histiocytes surrounding a cleft (appear to look like spaces); reported in Sweet syndrome, nodular vasculitis and necrobiotic lipodica

Question 3

Acute febrile neutrophilic dermatosis
(Sweet syndrome)

Answer 3

• Abrupt onset of tender or painful erythematous plaques and nodules on the face and extremities and less commonly on the trunk
• Association with fever (usually), malaise
• Neutrophil leukocytosis
• Associated with AML, less often with solid malignancies
• Often females, any age but rare in childhood
• Unknown etiology, but may represent immunological hypersensitivity reaction
• Most cases respond to oral corticosteroids

Micro:
* Intense neutrophilic dermal infiltrate in reticular dermis
* May be perivascular, diffuse and surround sweat glands; edema with marked leukocytoclasia; marked papillary edema
* Occasional presence of dermal papillary microabscesses can result in confusion with dermatitis herpetiformis
* Epidermis is normal, occasionally slight spongiosis, vesiculation with spongioform pustule
* Necrotic keratinocytes may be present
* Variable eosinophils, lymphocytes and histiocytes
* Blood vessels are dilated and show endothelial swelling

Diagnostic Criteria:
* Abrupt onset of painful erythematous plaques or nodules
* Histo evidence of dense neutrophilic infiltrate without evidence of leukoclastic vasculitis
* Pyrexia >38C
* Association with underlying haematological or visceral malignancy, inflammatory disease, pregnancy, or preceeded by upper respiratory or GI infection
* Excellent response to corticosteroids or potassium iodide
* Abnormal labs –> ESR >20 mm/hr, CRP, >8000 leukocytes, >70% neutrophils

Question 4

Eosinophilic cellulitis
(Wells syndrome)

Answer 4

• Idiopathic inflammatory dermatitis with eosinophilic infiltration
• Also known as eosinophilic cellulitis

Clinical:
* Recurrent bouts of edematous nodules and plaques, often preceded by prodromal itching or pain
* Usually a limited course over weeks to month but often recur
* May resemble cellulitis clinically but not warm or tender
* Erythematous papules, plaques or nodules that may be painful or pruritic
* Sometimes annular configuration, can blister
* May be single or multiple
* Peripheral blood eosinophilia common (found in 67% of cases)
* Leukocytosis (found in 41% of cases)

Micro:
* Diffuse dermal infiltrate of perivascular and interstitial eosinophils throughout superficial and deep dermis, often with extension into subcutis
* Admixed histiocytes and lymphocytes
* Old lesions may show granulomas
* Flame figures often present (deposition of eosinophil basic protein on collagen bundles)
* Can have subepidermal edema, sometimes with blister formation
* May have eosinophilic spongiosis
* No vasculitis

Question 5

Morphea/Scleroderma

Answer 5

• Connective tissue disease of unknown etiology
• Characterised by thickening and sclerosis of skin
• Morphea –> Cutaneous form od scleroderma without associated systemic involvement
• Lesions –> plaque like, linear, segmental, or generalised in distribution
• Tend to have predilection for face, distal extremities and trunk

Micro:
Early lesions
* pandermal mild homogenisation of dermal collagen
* Perivascular and interstitial infiltrate of lymphocytes with admixed plasma cells

Established lesions
* Pandermal mild homogenisation of dermal collagen (square silhouette)
* Well-defined demarcation of deep dermis from the underlying subcutis (almost a straight line)
* Septal thickening
* Loss og peri-eccrine adipocytes
* Minimal inflammatory cell infiltrate

Antibodies:
* Antinuclear antibody (ANA) - present in up to 90% with systemic scleroderma, 50% with localised scleroderma
* Anticentromere antibody - >90% and believed to correlate with morphea/limited cutaneous systemic sclerosis or CREST syndrome

Question 6

Molluscum contagiosum

Answer 6

• Infectious dermatosis most commonly affecting children and immunocompromised patients
• Majority of infections are caused by MCV1 (98% of cases)
• In contrast to most double stranded DNA viruses, poxvirus replicates in the cytoplasm
• Most common in children aged 2 - 5
• Self limited
• Firm, white to flesh colored, dome shaped, pearly, umbilicated papules
• Spares palms and soles

Micro:
* Cup shaped lesion with inverted lobules of hyperplastic squamous epithelium which expand into the underlying dermis
* Henderson-Paterson or molluscum bodies: large (up to 35 microns) intracytoplasmic eosinophilic inclusion bodies
* At the granular layer, the bodies become increasingly hematoxyphilic and occupy the entire cell
* Chronic inflammatory infiltrate seen in regressing lesions