Changes at the dermal/epidermal junction- Interface pattern
The Interface pattern is composed of 2 subgroups 1. The Lichenoid pattern characterised by a well defined lymphocytic infiltrate which hugs the dermo epidermal junction with basal layer damage and 2. the Vacuolar pattern where the lymphocytic infiltrate is less well defined but the basal layer vacuolar damage can be quite extensive.
Clinical Correlation - Histological changes at the dermal/epidermal junction can involve the epidermis and for this reason disorders that are primarily due to an immune attack of lymphocytes at the dermal/epidermal junction may give an epidermal reaction with scale.
Classic conditions in this category include lichen planus, lupus erythematosis and erythema multiforme. There are variants on this such as fixed drug reaction, graft versus host reaction and some of the other collagen diseases that also are associated with damage to the dermal/epidermal junction and the greater that degree of damage the more it influences the clinical picture.
Pigmentation Changes - Damage at the dermal/epidermal junction often has collateral damage to melanocytes. This means that melanin may be found in melanophages beneath the dermal/epidermal junction. This will give rise to grey dots on dermatoscopic images and will give rise to perilesional hyperpigmentation in conditions such as lichen planus and in lupus erythematosis and also certainly in fixed drug reactions. Severe damage to melanocytes can lead to hypopigmentation centrally in lesions.
Alopecia - The changes in lupus, because they also involve the sides of the hair follicles can cause damage to the hair follicle and hence it can be associated with alopecia. There is also the phenomenon of plugging of the hair follicles, but whether this can be directly attributed to the damage at the dermal/epidermal junction is another issue.
Blisters - There are various other clinical manifestations of lupus which are again associated with a degree of damage to the dermal/epidermal junction. If it is severe you can actually get blister formation (Bullous Lupus Erythematosus) with a split occurring at the dermal/epidermal junction. This gives rise to the very rare condition of bullous lupus. There is also a bullous variant of lichen planus, again a reflection of the degree of basal layer damage. In erythema multiforme the typical lesions are the target lesions, where there is a surrounding area of erythema and a central area that is much darker. Sometimes this central area can be bullous, again a reflection of the degree of damage that is occurring to the epidermis at certain points. Fixed drug reaction can also give rise to a bullous lesion usually with very little in the way of surrounding erythema but there is often post-inflammatory hyperpigmentation and this may be the feature with melanin melanophages which is most apparent histologically depending on the stage at which you are viewing the specimen.
Clinical Correlation - Histological changes at the dermal/epidermal junction can involve the epidermis and for this reason disorders that are primarily due to an immune attack of lymphocytes at the dermal/epidermal junction may give an epidermal reaction with scale.
Classic conditions in this category include lichen planus, lupus erythematosis and erythema multiforme. There are variants on this such as fixed drug reaction, graft versus host reaction and some of the other collagen diseases that also are associated with damage to the dermal/epidermal junction and the greater that degree of damage the more it influences the clinical picture.
Pigmentation Changes - Damage at the dermal/epidermal junction often has collateral damage to melanocytes. This means that melanin may be found in melanophages beneath the dermal/epidermal junction. This will give rise to grey dots on dermatoscopic images and will give rise to perilesional hyperpigmentation in conditions such as lichen planus and in lupus erythematosis and also certainly in fixed drug reactions. Severe damage to melanocytes can lead to hypopigmentation centrally in lesions.
Alopecia - The changes in lupus, because they also involve the sides of the hair follicles can cause damage to the hair follicle and hence it can be associated with alopecia. There is also the phenomenon of plugging of the hair follicles, but whether this can be directly attributed to the damage at the dermal/epidermal junction is another issue.
Blisters - There are various other clinical manifestations of lupus which are again associated with a degree of damage to the dermal/epidermal junction. If it is severe you can actually get blister formation (Bullous Lupus Erythematosus) with a split occurring at the dermal/epidermal junction. This gives rise to the very rare condition of bullous lupus. There is also a bullous variant of lichen planus, again a reflection of the degree of basal layer damage. In erythema multiforme the typical lesions are the target lesions, where there is a surrounding area of erythema and a central area that is much darker. Sometimes this central area can be bullous, again a reflection of the degree of damage that is occurring to the epidermis at certain points. Fixed drug reaction can also give rise to a bullous lesion usually with very little in the way of surrounding erythema but there is often post-inflammatory hyperpigmentation and this may be the feature with melanin melanophages which is most apparent histologically depending on the stage at which you are viewing the specimen.
True Lichenoid Reaction Pattern
Other conditions with a strong lichenoid element include lichen nitidus, but it characteristically has a ball and claw appearance where there is a much more focal, circumscribed infiltrate of lymphocytes and there is surrounding acanthosis of the epidermis holding it in.
Other rarer conditions with this lichenoid pattern include lichen striatus which tends to occur in younger children, particularly on the limbs, as a linear eruption. Sometimes the overlying epidermis may show a little bit of spongiosis as well and there may be involvement of sweat glands, and wherever lymphocytes have invaded into the epidermis and knocked out some of the epidermal cells, you may see what are called dyskeratotic cells. This is different from apoptosis. Apoptosis is programmed cell death that occurs without inflammation, whereas dyskeratotic cells are typically the result of T cell damage. Other similar conditions can include lichen planus like keratosis (LPLK) where there is an immune reaction to perhaps an underlying solar lentigo or perhaps even to a seborrhoeic keratosis. In these circumstances you also get parakeratosis overlying the area of inflammation and melanin in melanophages in the dermis.
View video below on LPLK Histology
In lichenoid drug eruptions you will get the same sort of response as in lichen planus like keratosis but you will also get eosinophils and it is the presence of the eosinophils in the dermal infiltrate, in amongst the lymphocytes, that makes a lichenoid drug eruption more likely.
Other disorders with significant lichenoid reaction patterns include pityriasis lichenoides, especially the more acute form where again there will be basal layer damage, but there is usually some degree of overlying epidermal thickening and parakeratosis corresponding to the scale that is seen in this disorder. There is also dyskeratosis of the keratinocytes as well and a characteristic feature of the dermal infiltrate of lymphocytes is it's wedge shaped distribution. There is a chronic form of this condition where the dyskeratotic cells won't be as prominent, but there is still a degree of parakeratosis and the lichenoid infiltrate won't be as prominent as well.
In late secondary syphilis you can get quite a marked lichenoid pattern but this time as well as the lymphocytes you will see a lot of plasma cells and you should not see much in the way of eosinophils.
The Vacuolar Reaction Pattern
A fixed drug reaction has a very similar picture, again for the same immunological reasons, but here the drug is probably attached to a keratinocytic protein and is acting as a hapten and it is a Type 2 immune reaction that can give very extensive damage to the epidermis. If it is extensive enough you will actually get blisters. Otherwise you can almost get complete necrosis of the epidermis and the latter is a feature of the condition toxic epidermal necrolysis where not just localised areas as in fixed drug but generalised areas of the skin can be subject to this immunological attack. In a fixed drug, depending on the stage at which it is biopsied, you may see a lot less of this vacuolar change at the dermal/epidermal junction and more melanin continence with melanin in melanophages. The prominence of eosinophils in this area of infiltrate is much more in favour of a fixed drug eruption.
Graft versus host disease is also a lichenoid infiltrate but it is often much more sparse than in lichen planus and again, though there can be significant vacuolar damage at the dermal/epidermal junction, it is seldom full thickness. It is similar to a mild form of erythema multiforme and it may show the phenomenon of what is called satellite cell necrosis where you have a lymphocyte next to a dead keratinocyte.
Lupus erythematosis can give both a lichenoid and an interface vacuolar pattern and the degree of one or the other determines to some extent the clinical appearance. The three major clinical variants of lupus are discoid lupus, subacute lupus and systemic lupus. In discoid lupus a lot of the damage is centred round hair follicles, also at the dermal/epidermal junction and with a superficial and deep perivascular infiltrate in the dermis. There is often thickening of the basement membrane and a few scattered Civatte bodies or dyskeratotic cells. A degree of hyperkeratosis and follicular plugging is also seen.
In subacute lupus you have much more damage at the dermal/epidermal junction with basal vacuolar change and you may in fact get epidermal atrophy. There can be a bit of mucin also in the dermis in conjunction with thickening of the dermal/epidermal junction. In a condition called tumid lupus there is even more mucin in the dermis but there is not as much epidermal involvement and there is still a superficial and deep perivascular infiltrate.
In systemic lupus you have much more basal vacuolar damage but the infiltrate of lymphocytes can be a lot less than you might expect. The damage is more centred on the keratinocytes in the epidermis itself and you may also see sub papillary oedema and extensive mucin in the dermis. There are usually much fewer dyskeratotic cells in the epidermis, so there is less epidermal reactivity and hence less epidermal scaling and the like. Typically systemic lupus shows mainly skin erythema. There is also sometimes vascular damage with fibrin in the blood vessels.
In lupus panniculitis the main area of damage is in the fat layer and here you have a lobular panniculitis with lymphocytes invading and destroying the fat lobules. There may be some overlying epidermal changes of discoid lupus as well.
Bullous lupus will have a subepidermal blister and surprisingly there are often neutrophils in the dermal papillae with lymphocytes in the perivascular area, but this is a rare condition.
In subacute lupus you have much more damage at the dermal/epidermal junction with basal vacuolar change and you may in fact get epidermal atrophy. There can be a bit of mucin also in the dermis in conjunction with thickening of the dermal/epidermal junction. In a condition called tumid lupus there is even more mucin in the dermis but there is not as much epidermal involvement and there is still a superficial and deep perivascular infiltrate.
In systemic lupus you have much more basal vacuolar damage but the infiltrate of lymphocytes can be a lot less than you might expect. The damage is more centred on the keratinocytes in the epidermis itself and you may also see sub papillary oedema and extensive mucin in the dermis. There are usually much fewer dyskeratotic cells in the epidermis, so there is less epidermal reactivity and hence less epidermal scaling and the like. Typically systemic lupus shows mainly skin erythema. There is also sometimes vascular damage with fibrin in the blood vessels.
In lupus panniculitis the main area of damage is in the fat layer and here you have a lobular panniculitis with lymphocytes invading and destroying the fat lobules. There may be some overlying epidermal changes of discoid lupus as well.
Bullous lupus will have a subepidermal blister and surprisingly there are often neutrophils in the dermal papillae with lymphocytes in the perivascular area, but this is a rare condition.
The other collagen diseases such as dermatomyositis are similar to lupus, more perhaps to the subacute lupus variant than any of the others. The perivascular infiltrate is usually superficial rather than superficial and deep and the degree of basal vacuolar damage is not as great, neither is the amount of mucin that is deposited in the dermis. However there may be a little bit more epidermal atrophy than you will see in some cases of lupus.
The only other lichenoid interface condition that perhaps we should mention is lichen sclerosus et atrophicus. Again it depends on the stage of the illness that is biopsied. In the late stage there will be quite marked collagen deposition in the upper dermis and this band of collagen is quite a prominent feature. It is usually relatively acellular and there is usually atrophy of the overlying epidermis. Of course if you see this at an earlier stage there may be a more superficial dermal infiltrate of lymphocytes with perivascular prominence and damage to the basal layer. The sclerotic changes only occur as a later feature. There also may be follicular plugging in this condition, again because of the early epidermal involvement.
