hello welcome to pathology central key concepts the topic of this video is inflammatory dermatosis now if you've watched my cutaneous malignancy and bullish disorders videos you may be thinking that the skin is pretty straightforward the inflammatory dermatosis are anything but that and in part that's because they have to deal with immune dysregulation and whenever you bring in the immune system things get complicated now when you think about it the skin like the gastrointestinal tract is our interface with the outside world and the skin is exposed to variety of antigens and pathogens and is tasked with mounting an appropriate immune response the inflammatory dermatosis arise when we have immune dysregulation i'm going to begin by reviewing the patterns of inflammation of the skin this is a somewhat more sophisticated approach to looking at these diseases and i'm doing this not because i'm trying to train you to be dermatopathologists but because i think some sort of framework is necessary or else this just becomes a laundry list of diseases and you just memorize so i'm trying to provide some context once we have set up that context i'm going to go through six different diseases that fall into one of the three patterns of inflammation of the skin the spongiotic dermatitis interphase dermatitis and the psoriasis form dermatitis let's begin first by remembering what the skin looks like so here we see the stratum corneum which is you can see that right here beneath that we have our granular layer and then the spinous layer and the very bottom of the epidermis we have our basal layer and we have our superficial dermis now there's some terms i'm going to be using throughout this talk and i'm going to introduce them here so here we have a healthy stratum corneum this basket we have appearance when we get some of these diseases we will get hyperkeratosis which will be significant thickening of the stratum corneum and loss of this basket weave appearance it'll be a thickened uh strip now if we lose our nuclear features that will be called hyperkeratosis if we retain the nuclei it is called perikeratosis and you'll see examples of both of these another term i will be using is acanthosis which is when we get expansion of the spinous layer we'll sometimes use this interchangeably with epidermal hyperplasia because epidermal hyperplasia is typically due to acanthosis this is the area that expands and then another term i'll be using uh will be a spongiosis that's when you see edema in the epidermis which is going to pull apart and splay the um the keratinocytes making the intracellular junctions more apparent all right so let's begin first by thinking about the clinical presentation of the inflammatory dermatosis they can have an acute onset so arising over days to weeks and in these instances we will see an inflammatory infiltrate composed predominantly of lymphocytes and macrophages neutrophils are not a significant component of this infiltrate when we have injury we can get edema and i send you back to the acute inflammation lectures this edema may be in the epidermis the dermis or both now injury can occur to the epidermis the vasculature or to the subcutaneous tissue i'll be focusing on the epidermal and dermal epidermal junction in this talk now you can also have inflammatory dermatosis that evolve over months to years and in these circumstances what the characteristic findings will be will be changes in epidermal growth so either atrophy or hyperplasia and because of the chronicity and the secretion of cytokines we're going to get dermal fibrosis okay so here are the different patterns of inflammation in the skin and again not trying to turn you into dramatic pathologists just trying to provide a framework so spongiotic dermatitis refers to epidermal edema spongiosis examples of this include allergic contact dermatitis and atopic dermatitis in spongiosis this fluid is going to splay apart our keratinocytes causing prominent intracellular bridges as that fluid builds up you get vesicle formation that can go on all the way to form bola that are visible also we tend to see dermal edema and a superficial mixed inflammatory perivascular infiltrate the second pattern is interface dermatitis this is going to be an inflammatory infiltrate at the dermal epidermal junction there are two patterns we can see one is where we see vacuolar degeneration of basal keratinocytes the the example this will be erythema multiforming and the other pattern is a dense band of inflammatory infiltrate a lycanoid reaction an example of this is lycan planus the final pattern is psoriasis form dermatitis not surprisingly associated with psoriasis but also with lichen simplex chronicus what we see here is epidermal hyperplasia due to acanthosis remember expansion of the stratum spinosum we get elongation of the reedy ridges hyperkeratosis and or perikeratosis so these are the six entities i will be looking at in their categories so spongiotic dermatitis encompasses the acute examines dermatitis of which there are multiple examples the two i will focus on are allergic contact dermatitis and atopic dermatitis the next pattern is interphase dermatitis erythema multiforma which shows the vacuolar pattern like in planus with that lycanoid pattern and finally psoriasis form dermatitis with psoriasis and lichen simplex chronicus so let's begin with our spongiotic dermatitis example of acute examinus dermatitis so this is one of the most common skin disorders the name eczema comes from the ancient greek meaning to boil over and there are multiple clinical subtypes so the first that i'll mention is allergic contact dermatitis and for me personally what this invokes is poison ivy this is a delayed type hypersensitivity that is cell mediated so type four the second category to look at is atopic dermatitis this is due to defects in epidermal barrier function which increases skin permeability to antigens this is similar to what we see in inflammatory bowel disease and i encourage you to take a look at uh at that video the next three entities i'm not going to go into in much detail other than to say that drug related extremities dermatitis is due to hypersensitivity reaction to a drug this is why it's important when a patient presents to you with acute examines dermatitis to ask if they've just started a new medication because if you stop that medication you can abrogate this reaction next we have photoexemitis dermatitis which is in atypical reaction to ultraviolet or visible light and then primary irritant dermatitis where there's some sort of substance that either chemically physically or mechanically damages the skin now all of these will have in common this type of progression okay so this is showing uh this is from robinson cotron pathologic basis of disease we have here progression over time this would be that initial onset so this is where right here you brush up against that poison ivy you'll get mast cell degranulation immediate edema here in the dermis and this perivascular mixed inflammatory infiltrate this is when that first spongiosis is going to begin right here at the outset over the next day to two you're going to get increasing edema fluid building up in the epidermis as well as a little bit of thickening here in our stratum corneum edema will continue to build up as well as mast cell degranulation occurring over time you can get these uh these increased numbers of vesicles but the edema is going to resolve as we move towards chronicity chronicity is going to bring increased fibrosis which you can see here in these brown lines but because we still have some interaction so for example an atopic dermatitis which can go on for months to years we're going to maintain this perivascular infiltrate and because of the stimulus we're going to have this parakeratosis or hyperkeratosis here with elongation of our reedy ridges all right let's now look at two entities allergic contact dermatitis as i mentioned t-cell mediated inflammatory reaction type 4 hypersensitivity what happens here is that some sort of topical chemical acts as a haptin so it's going to react with self-proteins creating a neo-antigen and the longer han cells are going to present that new antigen to naive cd4 positive t cells and activate them and they'll develop into effector memory t cells so that first time you brush up against poison ivy you might not even notice but the second time you're going to notice because on that re-exposure memory t cells are going to migrate to that cutaneous site because that antigen has now been deposited there it's going to release chemokines and cytokines recruit additional inflammatory cells erythema and intense pruritus the second type i want to mention is atopic dermatitis and if you hear someone say oh i have eczema even though exemitus dermatitis is what all of these are typically that is what it refers to as atopic dermatitis now there's something called the atopic triad which is asthma allergic rhinitis and eczema and it tends to run in families in fact about 70 percent of patients who have atopic dermatitis have someone in their family with some form of atopy so either asthma allergic rhinitis or eczema it is an inherited susceptibility so we see about 80 concordance in identical twins a topic dermatitis most commonly presents in early childhood but as the patient ages will remit spontaneously laboratory values will show elevated serum ige and experiments looking at susceptibility genes have found defects in keratinocyte barrier function innate immunity and t cell function and this like all of the dermatitis i've mentioned so far are intensely proritic and we'll see why when we get to the end when we talk about like and simplex chronicus that something that is peritic can cause secondary lesions so what does this look like clinically it can be erythematous to hyperpigmented with papules and vesicles as i mentioned we have that spongiosis fluid building up in the uh in the epidermis that can then exude through the surface of the skin causing weeping crusted lesions over time as you'll recall the edema will resolve and the lesions will become dry but because of that hyperkeratosis that we see we get scaly thickened skin with again acanthosis thickening of our stratum spinosum so let's look at two examples here here's an allergic contact dermatitis uh this was to a necklace that this woman wore you can see this erythema the lesions are slightly raised due to edema in this individual with atopic dermatitis again a chronic issue you can see a range of hyperpigmentation across the neck there's thickening of the skin and a little bit of scale which is uh present here and then you can see these lesions here from excoriation this can be intensely proritic okay so what do we see histologically you should be ready because we've already looked at a cartoon spongiosis superficial lymphocytic perivascular infiltrate mast cell degranulation can be hard to see but when you see it it's always a treat and edema of the dermal papillae this reactive acanthosis to this inflammation the thickening of the stratum spinosum and hyperkeratosis and or perikeratosis we can get intraepithelial vesicles due to fluid accumulation or mechanical shearing now if we have a drug associated uh dermatitis we'll tend to see eosinophils in the superficial or deep dermis by contrast examines dermatitis from contact antigens is going to show a mononuclear infiltrate in the superficial dermis without eosinophils okay here is a beautiful histologic example here we have our stratum corneum our stratum granulosum and here are our intra-epidermal vesicles and you can appreciate some spongiosis around these vesicles so this is where the fluid is accumulated most profoundly but it's leaking throughout and it looks like these keratinocytes are floating in a little sea of white that white is where fluid was pulling it apart from its companions you can also appreciate here this uh edema at the dermal papilla all right that brings us to the end of our spongiotic dermatitis discussion we're now going to move on to our interface dermatitis beginning with erythema multiforming this is basal cell injury which is mediated by skin homing cd8 positive t cells it's very similar to what you see in graft versus host disease it's uncommon and it's a usually self-limited response to infections such as herpes simplex medications cancer or autoimmune diseases like systemic lupus erythematosus or polyarteritis nerdosa now even though it is usually self-limited it can rarely be a medical emergency so you can see stevens johnson syndrome usually in children who are febrile and are having a response to a medication that and toxic epidermal necrolysis are characterized by extensive skin sloughing in fact it can mimic what you would see in a patient who has extensive burns you get loss of skin which is going to cause fluid loss and risk of infection so erythema multiforma erythema means reddish multiforma means many shapes so you're going to think we're going to see reddish multiple apparent lesions and you're right so in this individual with lightly pigmented skin you can appreciate the erythematous appearance this targatoid appearance is classic where you have a red circle with central pallor these are macules so they're flat lesion papules are raised but you can also get vesicles or even bullei which we see in this individual here these lesions are more hyperpigmented and erythematous and here we can see some central necrosis of that epidermis we'll look at how that happens let's begin first with some histology of an early lesion or one that's not quite so severe again our stratum corneum here granular cell layer we can see some spongiosis here so a little bit of splaying a part of our keratinocytes but the thing to draw your eye here is going to be these degenerating and necrotic individual keratinocytes this is where the cd8 positive t cells are attacking these individual cells and killing them the other thing that you'll notice here is that this basal keratinocyte has this vacuolar change so remember that is one of the two patterns we see in interface dermatitis you might appreciate it's a little busy here the dermal epidermal junction that's due to t lymphocytes to confirm that you'd want to do immunohistochemistry and there's a mild uh perivascular lymphocytic infiltrate we'll see that in clearer image in the next picture all right so let's look there this is a more uh significant lesion where right away you can appreciate this intense perivascular um mixed inflammatory infiltrate the next thing you'll notice is that as opposed to those individual dead care tennocytes we see a lot of death going on here and in fact in stephen johnson syndrome you can see full thickness necrosis this damage here is sufficient to cause sloughing off of the skin and this uh bolus bullet formation all right so that brings us then to the end of this type of interface dermatitis we're now going to look at the next pattern which is lycan planus which is going to have that lycanoid inflammation this is a disorder of the skin and mucosa and tends to affect middle aged adults there's a mnemonic proridic so itchy purple pink so velacious polygonal so not round or linear and planar which means flat on top and they can be papules or plaques the other thing you'll notice clinically will be surface white dots or lines these are called wickham's tree eye and i'll show you an image in a moment typically these are multiple symmetric self-limited cutaneous lesions that will resolve in one to two years however about 70 percent of patients have oral lesions and these can persist much longer and can be so significant that is difficult for patients to get adequate nutrition because of mouth pain we don't know the pathogenesis of this it's thought to be a cd8 positive t cell response to unknown antigens either those expressed by basal keratinocytes or something that's deposited at the dermal epidermal junction histologically we'll see an interface dermatitis but unlike that difficult to discern interface dermatitis of our previous lesion this is going to be a thick band of lymphocytes at that dermal epidermal junction and the injury that's being caused there is going to cause sawtoothing so we're going to lose that smooth interface between the dermis and epidermis we'll see epidermal hyperplasia hyperkeratosis and hypergranulosis so let's see what we get clinically this matches everything we were expecting to see this is a classic image so first of all we're purple or velacious we're polygonal we're a plaque and we have these uh white uh striaes so wickham's tree eye so this is a classic example of this entity now here we can see it uh in an individual here we can see it in an individual with a lighter skin where we have erythematous to uh to tan raised lesions again polygonal except for this interesting linear one here and this gives me the opportunity to mention for you the kobner phenomenon so what we see in the codemar phenomenon is that individuals who are predisposed to multiple different types of dermatologic diseases uh if they cause some sort of trauma so scratching that lesion will arise in that area of trauma so if this individual were to scratch right here they would get a linear plaque that arose in that area let's look at the histology uh and we can see here this is a beautiful classic example right so so absolutely patho mnemonic we see here this dense band of mixed inflammation of mononuclear cells so lymphocytes you can even get a little bit of bonus perivascular lymphocytic infiltrate uh you can see that the epidermis is is quite thickened and we have the sawtooth appearance at the dermal epidermal junction we have our hyperkeratosis and even at this power you can appreciate the hypergranulosis look how prominent this dark purple is but you don't need to stick with low power let's go on high power and you can see again the sawtoothing the band of mixed inflammation and here that hypergranulosis and you can see here that this is in fact hyperkeratosis we don't have uh the nuclear features so this is not perikeratosis okay so this brings us now to our final pattern the psoriasis form dermatitis and the classic example will of course be psoriasis psoriasis is a chronic t-cell-mediated inflammatory dermatosis that's thought to be autoimmune and in part because of its response to immune modulating medications it's believed to be due to genetic and environmental factors some combination of self and environmental antigens and it's believed that a sensitized population of t cells cd4 positive th17 th1 cd8 positive home to the dermis accumulate in the epidermis and there they secrete cytokines and growth factors and this is going to cause keratinocyte hyperproliferation which is going to lead us to the histologic features individuals of psoriasis also have the codename phenomenon so if they get trauma to an area they can get a psoriatic lesion and about 10 of patients develop arthritis which can be quite severe and because we have this background chronic inflammation these patients are at increased risk of cardiovascular disease and i encourage you to watch the video on atherosclerosis to remember how chronic inflammation has an impact on cardiovascular disease so clinically what we're going to see will be plaques at the elbows knees scalp lumbosacral areas intergluteal cleft glands penis and depending on the patient's skin we can get a variety of different appearances so it can be pink to salmon colored hyper pigmented in individuals with light lighter skin tones will have a pink to salmon colored appearance with loosely adherent silver white scale in individuals with darker skin it will be hyperpigmented with grayscale about 30 patients 30 of patients will have nail changes so a yellow brown discoloration with pitting or oncolysis histologically remember we have increased uh proliferation so we're going to see epidermal hyperplasia due to acanthosis so expansion of our stratum spinosum elongation of our radio ridges that can give a test tube like appearance because we're proliferating we'll get mitotic figures above the basal cell layer so unlike the mitotic figures that we see above the basal cell layer in neoplasia we're seeing it due to all of the growth factors that are being secreted and because we're growing quickly we don't have time to develop our stratum granulosum so it'll be thinned or absent we also have time for our nuclei to resorb so our overlying scale is typically going to be parakeratic another feature that we'll see in psoriasis is neutrophilic aggregates in the superficial epidermis and perikeratotic stratum corneum so let's see what we've got here clinically here we have in lightly pigmented skin the salmon-colored plaques with that loosely adherent silver scale here is where the patient has perhaps picked off an area this can cause bleeding pinpoint bleeding and i'll show you why when we review the histology in individuals with darker skin types the lesions may appear hyperpigmented and the scale will have more of a grayish appearance on microscopic examination we see epidermal thickening right so quite apparent here uh due to acanthosis so thickening of our stratum spinosum there's elongation of the reedy ridges looking here like uh test tubes and uh if we looked at a higher magnification we can find mitotic figures above the basal layer and even at this power you can see loss of the stratum granulosum now that's not absolutely patho mnemonic there are some instances of psoriasis where you'll see the stratum granulosum it all depends on that individual's extent of disease and the treatment they're receiving the scale tends to be parakeratic so let's go ahead and look here at higher magnification absence of our stratum granulosum we have perikeratosis with our nuclear features here and you can see our microabscesses here in the stratum corneum this brings us to our final entity and after the excitement of psoriasis lycan simplex chronicus seems like a little bit of a letdown although it is also psoriasis form dermatitis and will have similar histologic features lichen simplex chronicus is due to local repetitive trauma which results in roughening of the skin so you can create this for yourself at home just pick an area of skin and start scratching and keep it up for days weeks months even and you will get lycan simplex chronicus and if you go the next step and you go ahead and do a punch biopsy you'll see epithelial hyperplasia due to acanthosis hyperkeratosis hypergranulosis elongation of the reedy ridges a chronic dermal inflammatory infiltrate and because of this chronicity dermal scarring not recommended that you do this by the way what do we see histologically it looks at first blush somewhat similar to psoriasis which is not surprising since this is a psoriasis form dermatitis we see our elongation of the reedy ridges we have this chronic dermal inflammatory infiltrate some scarring below the scale here is going to be hyperkeratotic not parakeratic and if you were to look on higher magnification uh you would not see those neutrophilic microabscesses and of course the clinical presentation is completely different for lichen simplex chronicus uh compared to um psoriasis so i'd like to leave you with a few questions uh just to review what it is you've learned i encourage you to see if you can recall the three patterns as well as which diseases you see with each i think that having that framework is useful but it's also just a couple of questions how does acute examines dermatitis evolve clinically and histologically over time and then just finish up with what are the classic find in psoriasis and how they differ from like and simplex chronicus all right and as always thank you very much for your time and attention i hope you find this useful thank you very much