Inflammatory Skin Flashcards
Spongiotic Dermatitis
- Presence of epithelial intercellular oedema
- Lymphocytes predominate
- With Eosinophils –> allergic contact dermatitis
- With Plasma Cells –> Syphilitis
- With Neutrophils –> Seborrhaic dermatitis
Acute Spongiotic Dermatitis:
* Epidermal spongiosis
* Vesicle formation –> proteinaceous fluid with lymphocytes and histiocytes
* No acanthosis or parakeratosis
* Contact dermatitis –> Eosinophils
Subacute Spongiotic Dermatitis:
* Most frequent
* Irregular acanthosis and parakeratosis
* Superficial dermal perivascular lymphohistiocytic inflammatoruy infiltrate
Chronic Spongiotic Dermatitis:
* Spongiosis is mild to absent
* Pronounced irregular acanthosis, hyperkeratosis and parakeratosis
* PAS stain essential
Spongiotic Dermatitis with dermal eosinophils DDx:
DID A CAN
* Dermatophytes
* ID reaction
* Drug reaction
* Arthropod bite
* Contact dermatitis
* Atopic dermatitis
* Nummular dermatitis
Lichen planus
- Clinical: the “6 Ps”: purple, pruritic, planar (flat), polygonal papules and plaques
- Skin (flexor, wrists and forearms, dorsal hands, shins, presacral area)
- Mucous membranes (oral mucosa, genitalia)
- Hair, nails,
- Esophagus (rare)
- Association with Hep C
- Possible delayed hypersensitivity reaction
- Cytotoxic CD8+ lymphocytes lead to apoptosis of basal keratinocytes
- Features may overlap with drug induced lichenoid eruptions; clinical history is key
- Koebner phenomenon: new lesions at trauma sites (e.g. scratching)
- Wickham striae: fine white lines on surface of lesions corresponding to areas of hypergranulosis
Micro:
* Hyperkeratosis
* Acanthosis
* Wedge shaped hypergranulosis
* Sawtoothing of rete ridges
* Band-like lymphohistiocytic infiltrate obscuring the dermoepidermal junction
* Civatte / cytoid bodies (apoptotic basal keratinocytes, PAS+)
* Basal cell squamatization (flattening of cells)
* Parakeratosis: generally absent, think twice before diagnosing lichen planus
* Artifactual cleft formation between epidermis and papillary dermis (Max Joseph space)
* Melanin pigment within macrophages of the dermis (pigment incontinence)
* Occasional subepidermal bullae
Oral Lichen Planus:
* Subtle/absent granular layer
* Parakeratosis
* Lichenoid infiltrate less prominent
* Saw tooth not usually present
Lichen nitidus
- Papular eruption most commonly seen in the young
- Skin of upper limbs, dorsal hands, trunk and genitalia
- Typically asymptomatic but occasionally pruritic
- Sometimes onychodystrophy
Micro:
* Discrete inflammatory cell infiltrate obscuring the dermoepidermal junction
* Lichenoid infiltrate expands 1 - 4 dermal papillae
* Epidermal collarette gives a ball and claw appearance
* Variable admixture of lymphocytes and histiocytes with occasional giant cells
* Basal layer vacuolation and colloid bodies may be prominent
* Overlying hyperkeratosis with or without parakeratosis frequent
Erythema multiforme
- Acute, self limited, hypersensitivity reaction to:
Infections:
* coccidioidomycosis
* herpes simplex
* histoplasmosis
* leprosy
* mycoplasma
* typhoid
Drugs:
* penicillin
* phenylbutazone
* phenytoin
* salicylates
Malignancy:
* Carcinoma
* Lymphoma,
Collagen vascular disorders
Macro:
* Variable (multiform) lesions, including papules, macules, vesicles, bullae, target lesions
* Commonly in mucous membranes; also elbows, knees, extensor surface of extremities
Micro:
* Subepidermal bullae with basement membrane in bullae roof due to dermal edema
* Severe dermal inflammatory infiltrate (includes lymphocytes, histiocytes)
* Eosinophils may be present, but neutrophils are sparse or absent
* Overlying epidermis often demonstrates liquefactive necrosis and degeneration, dyskeratotic keratinocytes
IHC:
* Granular C3 and IgM at basement membrane and in vessels
Stevens-Johnson syndrome
- Historically there has been controversy as to whether Stevens-Johnson syndrome (SJS) is a distinct entity or at the center of the disease spectrum that includes erythema multiforme (EM) and toxic epidermal necrolysis (TEN)
- Currently, there is an increasing trend for SJS and TEN as representing the ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions
- Increased incidence with HIV
- Lesions usually begin on trunk and spread centrifugally
- Mechanism unknown but appears to be CD8+ T cell mediated immune reaction
- SJS: keratinocyte necrosis; epidermal detachment < 10% body surface area; the beginning of the spectrum
- SJS / TEN: considered point of overlap of two diseases in patients with 10 - 30% body surface area epidermal detachment
- TEN: severe disease state and the end of a spectrum of epidermolytic adverse cutaneous drug reactions; full thickness epidermal necrosis; epidermal detachment > 30% body surface area
Causes:
Cases in children are usually associated with infection, especially
* Mycoplasma pneumonia
* Herpes simplex virus
In adults, most cases are due to medications, including:
* Allopurinol (most common cause of SJS and TEN)
* Antibiotics: sulfonamides, cephalosporins, quinolones, aminopenicillins
* Nonsteroidal anti inflammatory drugs (NSAIDs)
* Anticonvulsants: carbamazepine, phenytoin, phenobarbital
* Corticosteroids
Clinical:
* Drug associated cases typically present one to three weeks following initiation of therapy with the offending drug; occurs more rapidly with re-challenge
* Fever, malaise, cutaneous and mucosal eruption
* Cutaneous and mucosal lesions are tender
* Nikolsky sign positive for epidermal detachment with application of tangential mechanical pressure
Micro:
* Early lesions: apoptotic keratinocytes scattered in basal epidermis
* Later lesions: numerous necrotic keratinocytes, full thickness epidermal necrosis and subepidermal bullae
* Epidermal changes are often accompanied by a moderate or dense lymphocyte predominant dermal infiltrate
* Less common findings are red blood cell extravasation, pigment incontinence, regenerating epidermis, parakeratosis and necrosis of hair follicle
* Clinical correlation is essential to distinguish erythema multiforme, SJS and TEN, as they may look nearly identical histologically
Staphylococcal Scalded Skin Syndrome (SSSS)
- Caused by certain strains of Staphylococcus aureus bacteria, which produce exfoliative toxins –> A and B
- Toxins bind to a specific desmosome –> desmoglein 1
- Split in the granular layer
Graft versus host disease
- Graft versus host disease (GVHD) is a multisystem immunologic disorder following an allogenic hematopoietic cell transplant (bone marrow) and rarely after solid organ transplant or transfusion
- It can be acute or chronic and can affect many organ systems, including the skin, gastrointestinal tract, liver and lungs
- Donor (graft) T cells attack and destroy recipient (host) cells
Acute
* Triad of –> Skin lesions, hepatic dysfunction, diarrhoea
* 3 months after transplant
* Acute GVHD usually affects skin: ears, palms, soles, lateral neck, cheeks and upper back
* Acute extracutaneous GVHD involves liver, gastrointestinal tract, lungs and lymphoid tissue
There are 3 pathophysiologic phases of acute GVHD
* Host tissue damage from the radiation and chemotherapy that precede the transplant
* Activation and multiplication of donor T cells as a result of interaction with antigens from the host
* These activated T cells lead to tissue damage once target organs are reached
Chronic
* Occurs >3 months to a year after transplant
* Early lichenoid stage
* Late sclerotic stage
* Chronic GVHD affects primarily the skin; however, nearly all organ systems can be involved (mucous membranes, liver, lung, eye, joints and fascia, gastrointestinal tract, genitalia)
There are also 3 pathophysiologic phases of chronic GVHD
* Activation of innate immune cells, endothelial cells and fibroblasts resulting from tissue cytotoxic injury, infections and acute GVHD
* Increased response of the adaptive immune system and decrease in immune cell regulators (upregulation of Th1, Th2 and Th17 cells and downregulation of T regulatory cells)
* Activation of macrophages resulting in production of transforming factor b and platelet derived growth factor, which activate fibroblasts leading to abnormal tissue repair
Micro:
**Acute GVHD **
* Grade 1 –> Vacuolar alteration of the basal layer, may be focal or diffuse
* Grade 2 –> Intraepidermal necrotic keratinocytes, occassionally surrounded by lymphocytes (satellite necrosis)
* Grade 3 –> Widespread necrosis of keratinocytes with separation at the dermo-epidermal junction.
* Grade 4 –> Full-thickness necrosis and loss of epidermis
Chronic Phase
Chronic lichenoid GVHD
* Acanthosis, orthohyperkeratosis, parakeratosis with hypergranulosis
* Underlying band-like lymphocytic infiltrate with basal layer vacuolization and apoptotic keratinocytes
* May be difficult to distinguish from lichen planus without clinicopathologic correlation; satellite cell necrosis is the most helpful clue in GVHD biopsies to distinguish it from lichen planus
Chronic sclerodermoid GVHD
* Dermal sclerosis (thickened compact collagen with loss of periadnexal fat)
* Epidermal atrophy
Cutaneous lupus erythematosus
- Lupus erythematosus is an autoimmune disease that involves a pathological spectrum ranging from a skin limited disease to a severe multisystemic illness
- Skin lesions can be classified as specific (eruptions diagnostic of or unique to lupus erythematosus) and nonspecific (commonly seen in but not unique to lupus erythematosus)
- Specific skin lesions include acute, subacute and chronic cutaneous lupus erythematosus
- Subacute cutaneous lupus erythematosus (SCLE) presents clinically as a photosensitive, nonscarring, nonatrophy producing eruption
- Sun exposed skin: face, V area of the neck, extensor surfaces of the arms and upper back
- ANA positive in 50 - 80% of patients with SCLE
- Anti-Ro / SSA (40 - 100%)
- anti-La / SSB (15%)
- others: anti-dsDNA (5 - 24%), anti-Sm (7 - 18%)
Micro:
* Interface dermatitis with variable degrees of basal layer vacuolization and scattered cytoid bodies
* Occasionally, basal layer vacuolation and keratinocyte apoptosis may be so severe that full thickness epidermal necrosis may result, generating a differential diagnosis of erythema multiforme
* Erythema multiforme-like lesions may occur, showing exuberant interface tissue reaction (Rowell syndrome)
* Dyskeratotic keratinocytes extending into upper spinous layers is a very characteristic but rare finding of SCLE
* Hyperkeratosis / parakeratosis may be present
* Sometimes focal hypergranulosis
* Superficial and sometimes superficial and deep perivascular lymphocytic infiltrate
* Dermal mucin, which may be highlighted with Alcian blue or colloidal iron
IHC:
* Immunofluorescence is not regularly used to confirm the diagnosis; however, it might help when a clinicopathological correlation is lacking
* Direct immunofluorescence: continuous granular deposition of IgG, IgM and C3 along the dermal epidermal junction
Cutaneous mastocytosis
- Most cutaneous mast cell disorders have a good prognosis
- Mastocytosis: monomorphic population of mast cells with rare eosinophils
- Telangiectasia macularis eruptive perstans (TMEP): telangiectatic light or dark brown macules
- Urticaria pigmentosa: common form of mastocytosis, numerous small yellow brown papules, become hives when rubbed –» To confirm the diagnosis, the chloracetate esterase stain is used.
- CD117 mutations in patients with mastocytosis
Clinical:
* At birth or during the first 3 months of life
* May present with flushing attacks due to high histamine content
* Urticaria pigmentosa: most common form of mastocytosis of skin; usually childhood onset of multiple brown macules
* Systemic variant is malignant and involves liver, spleen, bone marrow, lymph nodes and occasionally peripheral blood (mast cell leukemia)
* Darier’s sign: stroking skin releases histamine, causing hives
* Dermatographism: dermal edema resembling hives due to stroking with pointed instrument
Micro:
* Within the macules and plaque, mast cells are predominantly in papillary dermis
* Mast cells are round or spindle shaped with abundant eosinophilic cytoplasm, distinct cytoplasmic boundaries, large pale nuclei (toluidine blue, giemsa)
* Eosinophils are often present
* Also edema of papillary dermis, subepidermal vesiculation
* Bullous mastocytosis may be diagnosed by Tzank smear; infiltrate may be slight and perivascular
Pityriasis rosea
- Pityriasis rosea is a viral exanthem, commonly caused by reactivation of human herpesvirus 6 and human herpesvirus 7
- Clinically presents with the herald patch manifesting first, followed by disseminated similar patches on the upper trunk
- Usually happens in young patients, with the peak incidence in the 20 - 24 year old age groups
Clinical:
* Large, scaly patch with slightly raised margins appears first on the trunk in most cases or more rarely on the extremities (herald patch)
* Rarely, multiple herald patches may appear
* Prodrome symptoms with malaise, fever, arthralgias or headaches may precede the development of skin lesions
* Disseminated lesions are slightly oval in shape and follow Langer lines, forming a so called Christmas tree pattern on the back
* Face, palms and soles are usually but not always spared
* Disease is usually self limiting and resolves in a few weeks; some durations of several months have been reported
Micro:
* Subacute spongiotic dermatitis with perivascular lymphocytic infiltrate
* Mild acanthosis of the epidermis may be present, especially in herald patch
* Foci of parakeratosis overlying spongiosis
* Granular layer may be diminished or absent under area of parakeratosis
* Erythrocyte extravasates may be focally present in the superficial dermis
* Rare presence of dyskeratotic cells and eosinophils may be observed
Psoriasis
- Psoriasis is a chronic relapsing condition affecting skin, nails and joints
- Most commonly presents with well demarcated erythematous papules and plaques with silvery white scales
- T cell (Th1) activation and release of cytokines (TNFα, IFγ, IL12, etc.)
- Koebner Phenomenon: New psoriasis papules at sites of trauma
- Auspitz sign: pinpoint bleeding when scales are removed
- Woronoff ring: area of blanching surrounding resolving psoriatic plaques
Micro:
* Regular acanthosis, often with elongated rete (psoriasiform)
* Alternating zones of hypo and hypergranulosis in the epidermis
* Thinning of the suprapapillary plates
* Areas of parakeratosis in the stratum corneum with mounds of neutrophils (Munro microabscesses)
* Perivascular, predominantly lymphocytic infiltrate in the upper and middle portions of the dermis; few neutrophils or eosinophils may be seen
* Collections of neutrophils in the spinosum (spongiosiform pustules of Kogoj)
* Dilated and tortuous vessels in the dermal papillae
* Focal spongiosis may be present in the evolving lesions, intertriginous, acral and scalp variants
* Subcorneal pustules in the pustular forms of psoriasis
Molecular:
* PSOR1 locus map on chromosome 6 is the most important genetic region responsible for the disease
* HLA-Cw6 is associated with early onset of psoriasis
* Additional associations include HLA-B27 (pustular psoriasis, psoriatic arthritis), HLA-B13, HLA-B17 and HLA-DR7
Lichen simplex chronicus
- Chronic dermatitis characterized by localized areas of thickened, hyperkeratotic skin resulting from chronic rubbing or scratching
- Absence of underlying dermatologic condition
- Itch / scratch cycle perpetuates the condition
Micro:
* Early lesions may demonstrate spongiosis
* Compact orthokeratosis with focal parakeratosis
* Hypergranulosis
* Occasional pseudoepitheliomatous hyperplasia
* Prominent irregular acanthosis with curvilinear, blunt rete ridges
* Papillary dermal fibrosis, with vertically oriented collagen bundles
* Superficial chronic perivascular inflammatory infiltrate
Prurigo nodularis:
* Same findings as in lichen simplex chronicus but in nodular configuration rather than plaque-like
Granuloma annulare
- Benign, self limited dermatosis characterized by erythematous papules and plaques, classically in an arciform or annular configuration
- Dermal plaques with central clearing and raised erythematous borders
2 classic morphologic patterns
* Palisaded granulomas with central necrobiosis (collagen degradation) with peripheral histiocytes and admixed lymphocytes
* Histiocytes intercalating among collagen bundles with interstitial mucin
- Associations with hyperlipidemia and diabetes mellitus
- No proven treatment for this recurring, idiopathic disease
Etiology
Numerous inciting factors reported
* Viral infections
* Arthropod bites
* Ultraviolet radiation
* Borrelia infection
* HIV
* Medications (e.g. TNFα inhibitors)
* Paraneoplastic
Micro:
* Palisaded or interstitial granulomatous inflammation with mucin unites all forms
* Typically involves upper or middle dermis
* Necrobiotic (collagenolytic) granulomas
* Granulomas characterized by central areas of degraded collagen surrounded by lymphocytes and histiocytes, occasionally palisaded, are present in dermis
* Occasional multinucleate giant cells
* Perivascular infiltrates of lymphocytes
* Eosinophils may be present
IHC:
Highlight mucin:
* Colloidal iron stain
* Alcian blue
Necrobiosis lipoidica
- Atrophic, yellow depressed plaques, usually on legs of diabetic patients
- Also associated with hypo and hyperthyroidism, inflammatory bowel disease and vasculitis
- Atrophic, yellow depressed plaques, telangiectasia and active inflammatory edge
- Chronic lesions may show ulceration and crusting
- Solitary or multiple, often symmetrical in lower extremities in pretibial area
- Rarely, squamous cell carcinoma may arise in chronic lesions
Micro:
* Palisading, necrobiotic granuloma consist of a large confluent area of necrobiosis centered in the superficial dermis and subcutaneous fat
* Usually epithelioid histiocytes, giant cells and sometimes a well formed granuloma
* Eosinophilic, swollen or degenerate collagen appears hyalinised with surrounding infiltrate of lymphocytes and histiocytes
* Layer cake pattern –> necrobiotic collagen with palasading granulomas
* Linear infiltrate of histiocytes between collagen bundles; occasionally lipomemebranous fat necrosis
* Blood vessel wall thickening with intimal proliferation and narrowing of the lumen; also mild to moderate perivascular lymphocytic infiltrate
Plasma cells are almost always present
IHC:
Lysozyme and mucin negative differentates from granuloma annulare
Granuloma faciale
- Chronic fibrosing vasculitis with eosinophils
- Facial plaque or plaques
- Persistent and refractory to treatment
- Mixed infiltrate with neutrophils, plasma cells and eosinophils
- Immune complex mediated vasculitis
- IL5 production by clonal CD4+ T cells leads to eosinophil recruitment
Micro:
* Grenz zone
* Diffuse, polymorphous inflammatory infiltrate involves the upper half of the dermis
* Neutrophils, plasma cells, eosinophils, lymphocytes and histiocytes
* Leukocytoclasia (karryorrhexis), extravasated red blood cells and hemosiderin
* Fibrinoid necrosis of small vessels is variable
* Perivascular fibrosis with clefting between collagen bundles results in storiform fibrosis
IHC:
Granular IgG at dermal-epidermal junction.
Also outlines the hair follicles and walls of blood vessels
