Skin Pathology 3 Flashcards
-Explain, using appropriate terminology, the processes of inflammation and how they affect the skin. -List the cardinal signs of inflammation and the macroscopic and microscopic lesions of acute and chronic dermatitis. -Outline the pathogenesis of irritant contact dermatitis with reference to the cell types involved. -Discuss, using examples, the analysis of histological patterns in the diagnosis of skin disease. -Describe the effects of solar radiation on the skin -Explain the process
DERMATITIS
A non-specific cutaneous inflammatory reaction, with concomitant changes in the epidermis AND dermis.
Can be caused by a variety of agents.
Changes are not always visible.
KERATINOCYTES release PRIMARY CYTOKINES (including interleukins, TNFa etc.)
These activate DENDRITIC CELLS, MAST CELLS, Th2 CELLS, EOSINOPHILS, DERMAL FIBROBLASTS, which go on to produce further chemokines and “further reinforce proinflammatory circuits through their massive release of potent cytokines and chemokines”.
Downstream activation cascades are stimulated.
An ‘inflammatory soup’ is produced.
CARDINAL SIGNS OF INFLAMMATION
REDNESS HEAT SWELLING PAIN LOSS OF FUNCTION
NORMAL VS INFLAMED CAPILLARY
Normal- Central axial flow of cells (RBCs, WBCs), zone of plasma around edge. Tight junctions between endothelial cells.
Inflamed- CONGESTION/STASIS, LOSS OF AXIAL FLOW, MARGINATION, PAVEMENTING and EMIGRATION of POLYMORPHONUCLEAR LEUKOCYTES.
If inflammation is severe, RBCs can leak through gaps that form between endothelial cells.
ACUTE INFLAMMATION
eg. Urticaria.
Vasodilation leads to hyperaemia (increased blood flow).
Increased permeability leads to inflammatory oedema
Cell emigration of neutrophils, macrophages (scarce in urticaria).
DERMATITIS- ACUTE MACROSCOPIC LESIONS
Acute dermatitis not often seen in veterinary medicine- most clinical cases have chronic skin disease, and most lesions have been self-traumatised. VESICLES PAPULES ERYTHEMA OEDEMA EXUDATION
DERMATITIS- ACUTE MICROSCOPIC LESIONS
SPONGIOSIS LEUKOCYTE EXOCYTOSIS SUPERFICIAL DERMAL OEDEMA VASODILATION PERIVASCULAR INFLAMMATORY CELLS Not all changes will be present in every case.
DERMATITIS- CHRONIC MACROSCOPIC LESIONS
Chronic cases are most common. Most lesions have been traumatised. SCALE CRUST MILD ERYTHEMA LICHENIFICATION PIGMENT ALTERATION
DERMATITIS- CHRONIC MICROSCOPIC LESIONS
HYPERKERATOSIS EPIDERMAL HYPERPLASIA MILD-MODERATE DERMAL OEDEMA VASODILATION PERIVASCULAR INFLAMMATORY CELLS. Character of cell infiltrate varies with time- in chronic cases, neutrophils and plasma cells can be seen in follicles.
SPONGIOSIS/SPONGIOTIC VESICLES
Widened, fluid filled spaces between keratinocytes in the epidermis.
Intracellular space increases due to oedema.
Mechanism uncertain- increased hyaluron and altered E-cadherin adhesion suggested.
Fluid comes from the dermis, but the change is not explained by hydrostatic pressure alone (little/no spongiosis is seen in urticaria- hives)
SUPERFICIAL DERMAL OEDEMA
Mild reaction.
Minimal erpidermal change.
Some spongiosis and sparse cellular infiltrate seen.
eg. Reaction to folliculitis in adjacent field.
Acute.
CHRONIC DERMATITIS
Results in SCARRING.
Scar tissue is aligned parallel to skin surface.
Hyperplasia, compact hyperkeratosis, hypergranulosis can be seen.
Moderate cell infiltrate.
CONTACT DERMATITIS
An example of physicochemical trauma
eg. Reaction to Tradescantia (spiderworts- certain species).
This is via DIRECT ACTION of the plant chemical.
NOT an allergic reaction- most contacts will be affected.
IRRITANT CONTACT DERMATITIS vs. ALLERGIC CONTACT DERMATITIS
Irritant Contact Dermatitis (ICD) can become Allergic Contact Dermatitis (ACD).
If the animal has been exposed before, a much lower second exposure to the irritant can illicit and allergic response.
INNATE immunity must be activated- irritant contacts skin, which stimulates irritation/inflammation -> leukocyte recruitment, dendritic cell activation.
Activated dendritic cells take up cutaneous haptens (small molecules that can only elicit an allergic response when bound to a larger carrier), then migrate to the draining lymph nodes.
Here, specific T cells are activated and leave the lymph nodes for the circulation.
EFFECTOR T CELLS- CD8+
REGULATORY T CELLS- CD4+
Subsequent contact with the same hapten:
Hapten penetration induces cutaneous irritation, which permits recruitment of EFFECTOR T cells (CD8+).
Effector T cells are activated by presentation of haptenated peptides by MHC I, II on the surface of skin cells.
HISTOLOGICAL PATTERNS
Can be an aid to diagnosis. Consider lesions:
PERIVASCULAR, VESICULAR AND PUSTULAR, INTERFACE, VASCULAR, FOLLICULAR, NODULAR AND DIFFUSE, FIBROSING, PANNICULITIS, ATROPHIC (non-inflammatory dermatosis)
PERIVASCULAR
Perivascular reaction is common. In the abscence of other changes, it provides little clue as to definitive diagnosis.
It just tells us that there IS inflammation.
Subtypes are based on changes in the epidermis and what any cellular infiltrate is based on:
EPIDERMIS- Spongiotic or hyperplastic
CELL INFILTRATE- Neutrophilic, eosinophilic, mononuclear.
May be superficial, deep, or both.
Perivascular dermatitis eg. canine atopic dermatitis. Histologically we can see superficial perivascular dermatitis with epidermal hyperplasia and dermal oedema.
VESICULAR AND PUSTULAR
Vesicles arise by- SPONGIOSIS, ACANTHOLYSIS, HYDROPIC DEGENERATION.
They may evolve in to vesicopustules.
PUSTULES contain INFLAMMATORY CELLS- NEUTROPHILS, EOSINOPHILS.
Pustules may be sterile or indicative of inflammation
lesions are transient and become scale/crust eg. collarettes.
Vesiculopustular dermatitis eg. orthopoxvirus infection- bovine teats become ulcerated and crusted. Histologically, intra-epidermal vesiculation can be seen due to severe ballooning degeneration.
FOLLICULITIS/FURUNCULOSIS
Common reaction pattern, usually indicative of infection (bacterial, parasitic, fungal etc.)
FOLLICULITIS- Inflammation of follicle, wall remains intact.
FURUNCULOSIS- Rupture of follicle wall releases follicle contents.
eg. ‘short haired breed folliculitis’. Bacterial, dog.
NODULAR TO DIFFUSE
Characterised by CELL TYPE- granulomatous/pyogranulomatous, eosinophilic, lymphoplasmacytic, neutrophilic (uncommon).
Granulomatous/pyogranulomatous nodular dermatitis is a common reaction pattern.
In many sterile cases, the cause is idiopathic and thus difficult to determine. Such cases are difficult to treat.
eg. Feline Eosinophilic Granuloma complex- nodular to diffuse dermatitis with oedema and numerous eosinophils. Sterile lesions around the mouth/lips (oral mucosa), inguinal region. Characterised by eosinophilic infiltrate. Lesions can extend deeply.
CAUSES OF INFLAMMATORY SKIN DISEASE
- PHYSICOCHEMICAL TRAUMA- mechanical, thermal, electrical, radiation (UV light), chemical irritants, caustics.
- INFECTIONS- bacterial, fungal, viral, parasitic.
- IMMUNE MEDIATED REACTIONS- allergic dermatitis.
ACTINIC (SOLAR) DERMATITIS
Caused by exposure to UV(B) radiation- physicochemical trauma; has a direct phototoxic effect on cells.
-> photodermatitis (sunburn), inflammation, increased apoptosis, reactive hyperplasia, progressive dysplasia leading to neoplasia.
Structural damage to DNA occurs.
If this is passed on to daughter cells, there will be progressive dysplasia -> neoplasia.
Apoptosed keratinocytes- ‘SUNBURN CELLS.’
eg. Squamous cell carcinoma on the nasal planum of the dog. Similar lesions can be seen on the ears of cats.
Lesions are locally aggressive, but metastasis is uncommon.
PHOTOSENSITISATION
Indirect process, where photodynamic agents in the skin are activated by light.
They then release damaging compounds or react with oxygen to form free radicals:
-Free radicals + singlet oxygen
-Release of inflammatory mediators.
-> erythema, oedema, exudation/crusting and necrosis of sparsely haired, unpigmented skin.
Has been applied to tumour therapy- tumour is injected with photosensitising agent, light is applied, leading to tumour necrosis.
PHOTODYNAMIC AGENTS
These are activated by light, leading to photosensitisation.
- HYPERCIN- primary photosensitisation- ingested preformed eg. St John’s Wort.
- PHYLLOERYTHRIN eg. ragwort. Secondary photosensitisation- animals with liver damage cannot excrete these chlorophyll breakdown products via the liver like normal, so they build up in the skin and cause photosensitisation.
- PORPHYRINS- products of aberrant pigment synthesis. Cause CONGENITAL photosensitisation eg. congenital porphyria in cattle.
PHOTOSENSITISATION IN CATTLE
Unpigmented skin is cold, dry and parchment like, and will eventually slough.
Also seen in sheep- can cause massive oedema- ‘big head’.
BACTERIAL INFECTION
A cause of skin disease; bacteria can infect skin (superficial infection) secondary to physical trauma.
-SKIN FOLD DERMATITIS aka INTERTRIGO- frictional damage and maceration of skin in moist environment can lead to secondary bacterial infection- pus etc.
-ACUTE MOIST DERMATITIS aka PYOTRAUMATIC DERMATITIS- self trauma (scratching, excoriation), associated with flea bite hypersensitivity and sometimes seen with other pruritic disorders.
Trauma is often localised before secondary bacterial infection.
eg. Hotspots- repeated scratching leads to ulceration and necrosis of skin surface, inflammation, then bacterial colonisation of skin surface (visible histologically).
