This is just a little something I would check. This will be my first time at posting an immunologic add via AMIE attempting to first agree, but second to look into the immunologic manifestations of freckles. Beauty like this makes me only have more power in my cathexis of matters of the heart eg immunologic research. In any event if you can believe that she is 50, I may buy the bridge with you, but if she is , freckles may be a sign of longevity. Lets look into this. Let us try to begin at Google and quiz the wiz!The following is an article which lumped senile keratosis with freckles in an investigation into the known cytokines which stimulate freckle development. Let me give thanks ahead of time to the model and to the author and his company.
Title: Prevention of Pigment Spots: Strategy for Future Prevention with Respect to Cellular Actions.
Abstract; Recently, paracrine cytokine linkage plays an essential role in the accentuated pigmentation in the epidermis by secreting by keratinocytes or fibroblasts and responding by melanocytes to various melanogenic cytokines. In UVB or UVA-induced pigmentation as well as in non-UV-associated epidermal pigmentary disorders such as senile freckles, seborrhoeic keratosis and dermato-fibroma, specific melanogenic cytokines have been shown to be intrinsic cytokines responsible for stimulating melanocyte function leading to each hyperpigmentation. Furthermore, it has been reported that there are several crosstalks between melanogenic cytokines in intracellular signalling pathways for eliciting a synergistic stimulatory effect on melanocytes. Therefore, it will be an ideal strategy to interrupt the signalling pathways at specific sites by which the ability of melanocytes to proliferate and to synthesize melanin is abolished to a normal control level, resulting in the prevention of the pigmentation.
Journal of Japanese Cosmetic Science Society,VOL.24;NO.1;PAGE.29-34, 2000
Author:IMOKAWA GENJI
And from Dar Clark's review. I like it!
Melanocytes
Intercalated in among the basal cells; the basement membrane is beneath "all these guys." Each melanocyte reaches out to about 36 keratnocytes. The melanocytes make the pigment but they then transfer that pigment to the keratnocytes. It is then the keratnocytes which contain the pigment to give you skin color.
Vitiligo
Melanocytes are destroyed by t-cells (autoimmune disease). It is associated with other autoimmune diseases such as hypothyroidism, Addison's disease and pernicious anemia, all of which give you syndrome complexes. Total drop out of melanocytes within a lesion of vilitiligo is quite different from that in albinism.
Albinism
Melanocytes are there but they do not make pigment for all kinds of reasons. It exists in just about every animal species (see Robbins, "One of those little boxes").
Lentigo
Proliferation of melanocytes singly disposed along basement membrane in a young child. These are not freckles. Biopsies of freckles show nothing really abnormal. Same number of melanocytes seemingly making the same amount of melanin. No one know what causes freckles.
Moles
Not a furry little animal. Moles are proliferations of melanocytic nevi but in nests at the basement membrane. They give you a junctional nevus and with time they migrate down into the dermis and make a compound nevus and finally and they form finally an interdermal nevus. As they migrate down they lose their ability to make pigment and thus get lighter in color: this is the normal life of a "mole." They make nice even cords. In melanoma, regardless of the layer of skin it is in, the nests are very bizarre looking
Langerhans cells
These are the macrophages of the skin. They are antigen presenting cells and are the basis of contact dermatitis. Langerhans cells capture antigens in epidermis and then travel down through the dermis, up the lymphatics and into the local lymph nodes where they present antigens. They do not live in the epidermis forever; they migrate on.
When you get exposed to something like poison ivy, lymph cells, which are always percolating around, recognize and release a set of cytokines which call in more lymphocytes and turns on keratnocytes. These keratnocytes are very important in this process for they are responsible for releasing cytokines. These released cytokines stimulate the epithelium which then express aggresin so that the lymphocytes know where to go. This doesn't just happen in the skin; the skin is just one example for lymphocyte homing.
Desmosomes
Desmosomes link the keratnocytes together. It is mostly the linkage between the cells in the spinous layer which give you the real strength of the epidermis. If there are no desmosomes, like in pemphigus, it all just falls apart. In this disease the patients make antibodies to the desmosomes in which case the desmosomes fall apart and so does the skin.
Images were shown of the proteins linking half a desmosome of one cell to half a desmosome of another to make a full desmosome. Shown on EM we can see the keratin filaments on the cytoplasmic face of the desmosome. We can see how the keratin filaments inside the cell act as clotheslines to add strength to the epidermis. You can see the spaces between adjacent keratin filaments. The proteins linking the desmosomes together are desmogleans and desmocollins. The antigen in pemphigus is almost always desmoglean III (sometimes desmoglean I).
Immunofluoroesence of skin was shown of a patient with pemphigus. In it was shown basal cells still attached because there is no rupture of the basal cells off of the basement membrane. Pathologists call these "tombstones" (friggin' pathologists). In acantholysis the keratnocytes are "rounded up" in the stratum corneum.
As the keratnocytes mature up into the granular cell layer they still have desmosomes but now they start to make granules (lamellar bodies and keratohyalin granules). Through electromicroscopy, lamellar bodies appear to be very similar to lamellar bodies found in the synovium, lung, cornea. They have bilayers of different types of lipid. Lipids contained in the lamellar bodies of the skin are cholesterol sulfate, free fatty acid and ceramides. Alternatively, the major of the lung is surfactant.
When keratnocytes mature into corneocytes the lamellar bodies are released upon which the cholesterol sulfates, free fatty acids and ceramides come together to make one gigantic complex of cholesterol, fatty acids and ceramides. There are no free fatty acids nor cholesterol sulfate in these complexes. In excallen icthiosis patients do not make cholesterol sulfatase and so they can't take the sulfate off of the cholesterol which inhibits the big complex from being made. As a result, scales form because the permeability barrier does not form well and the ability of the stratum corneum to shed is disrupted as well.
The other component which allows epidermis to shed properly is a natural moisturizing factor. It is a breakdown product of fillangrin made in the keratohyalin granules. This factor is hydroscopic and thus pulls in water. Without this factor, the enzymes which break down desmosomes do not work properly and because of all of this, scales form. During winter seasons, the combined effects of low humidity, wind and low temperatures will inhibit these same enzymes.
Xeroderma
There are lots of causes of xeroderma, including soaps and detergents.
Ichthyosis
We are not responsible to know the types of ichtyposis but he wants us to understand that there are a set of genodermatoses that lead to lots of scales and dry skin because they lock up the skin's ability to make this permeability barrier and natural moisturizing factor.
Test answer note:
we will not see excallen icthiosis nor will we need to know the specific names of these enzymes just discussed.
Psoriasis
In psoriasis the skin turns over really fast (normal: 28 days; psoriasis: 1/wk) and they leave trails of scales (sounds like a new song title). They make stratum corneum so fast that the enzymes which break down the desmosomes simply cannot keep up. As a result, the skin does not mature properly. This is why patients with psoriasis and excema have scales. Eczema is a hyperproliferative disease, also probably due to an autoimmune (T-cell) problem. Psoriasis is a reaction to cytokines which get released when t-cells attack the epidermis.
Excema
There are a variety of excemas. In contact dermatitis the skin is an innocent bystander. The lymphocytes get through the epidermis and beat up the keratnocytes along with the antigens they are after. Allergic contact dermatitis is not a direct assault on the epidermis, its just an allergic reaction that hits the epidermis. The same is true for atopic dermatitis. In atopic dermatitis, the whole protein antigen is present as opposed to allergic contact dermatitic which is a response to haptens. Whole proteins include things like pollen, mite feces and animal dandruffs.
Suberyp dermatitis
With the aids epidemic it became clear that the inciting agent there turned out to be an inflammatory reaction (probably an immune response) to pitiform ovale, a fungus that normally lives on the skin. In patients with AIDS this fungus overgrows from which they get an antibody complement mediated response (t-cell).
Even very severe dry skin can cause eczema just because it is irritating to have very dry skin.
Epidermal-dermal junction/interface
The epidermis is attached to the dermis through a basement membrane called the epidermal-dermal junction/interface. This is made up of a bunch of proteins (mostly bullous pemphigoid antigen- there are two of these but we don't need to know them separately). The others are lamannin, Type 4 collagen, and heparinsulfate proteoglycans. Note to remember: the fibrillar collagens (types 1-3) are like link-enlogs which make big strong bundles. Type 4 collagen is very different, it makes a sort of basket-weave. Type 4 collagen runs parallel with the skin making a net-like basket weave.
Bullous pemphigoid
Patients with this disease make an antibody to the bullous pemphigoid antigen proteins. This reaction causes a lot of inflammation and a split under the epidermis right through the basement membrane. This leaves tense bullae. I did not get this part straight: This is different from flaccid bullae which are a result of pemphigus because in pemphigus the whole skin is falling apart…sorry. Anyway, there is a difference between 'pemphigus' and 'pemphigoid.' An immunofluoresence image was shown illustrating the linear appearance of bullous pemphigoid.
Basal cell carcinomas
YOU MUST KNOW WHAT A PEARLY PAPULE BASAL CELL CARCINOMA LOOKS LIKE. "There is nothin' else that looks like this."
Sometimes a basal cell carcinoma can be pretty subtle. The pearliness is due to light reflection. The light reflection results from a total effacement of all the skin markings. The skin markings are gone because the tumor has replaced them. Sometimes specs of pigment can be seen within the borders of the tumor and this may through you off track but, if you "erase" the pigment you have a shiny, pearly plaque left. All of the markings have been effaced. Basal cell carcinomas are the most common cancer…period. They are fairly harmless if you catch and treat them. Of course if the patient never comes in, she may lose her entire upper lip on Thanks Giving day. So, these tumors are invasive and can even get as far as the brain. But, BASAL CELL CARCINOMAS DO NOT METASTASIZE and if treated they have no effect locally. Basal cell carcinomas are VERY well organized tumors.
Squamous cell carcinoma of the skin
SQUAMOUS CELL CARCINOMAs OF THE SKIN TEND NOT TO METASTASIZE with the major exceptions being those which appear on the lip or in a scar: these have a much greater chance of metastasizing. The abnormal cells usually span the entire depth of the epidermis but there is still a basement membrane.
Actinic keratosis
These are precursor lesions to nothing or, to squamous cell carcinoma: 1/25 of these just go away whereas 1/100 progress to squamous cell carcinoma. In places like good 'ole L.I., Florida and Hawaii, people will have hundreds of these actinic keratosis lesions. They can be all over the sun exposed areas of skin. They are treated with either topical 5-fluorouracil or they get frozen. Those that are not clear are biopsied. The abnormal cells don't quite make it through the entire depth of the epidermis. They tend to be localized more towards the bottom of the epidermis: very characteristic.
'actinic' » sun
'keratosis' » "rough spot"
Melanoma
Appear with scalloped boarders and with irregular variations in color. The image he showed included the 'sign of regression.' There may also be a nodular component which would appear raised. Melanomas grow in bizarre, "helter-skelter" arranged nests and as singly disposed melanocytes "all over the place," not just along the basement membrane like in lentigo "helter-skelter is a red flag for cancer." The cells and nests vary from one to the next. Dermal nevi (not melanomas) growth in nice little cords, not in a mess like with melanomas. Two growth phases are described the first being radial and the second, vertical. The melanomas which start the vertical growth phases early become nodular melanomas and are deadly. Most grow radially for weeks, months or years before they begin to grow vertically. If caught early, these patients with "superficial spreading melanoma" can be cured by simple excision.
Dermatomyositis
One of the more unusual kinds of connective tissue diseases. It is characterized by some unusual rheumatologic features and symmetric proximal muscle weakness. Diagnosis includes myocytal enzymes, EMG changes and inflammation.
A heliotrope was shown (???)
Scaly erythematous plaques and papules are characteristic: neutron papules. When these same kinds of lesions exist between the joints then it is a sign of lupus and then are not called neutron papules either instead, they are called discoid lupus lesions. Thus, the placement is very important when it comes to these scaly papules on patient's hands who you think have connective tissue disease.
Periungal telangiectasia due to capillary drop out and compensatory dilatation of residual capillaries. Periungal telangiectasia can be seen in dermatomyositis, scleroderma and lupus. It sign a good sign to tell of a connective tissue disease but it is a terrible sign to tell you what kind of connective tissue disease it is.
In scleroderma, the sclerosis is throughout the entire skin including the subcutaneous tissue. This is why it is so bound down. They have lost all of their padding and they get ulcers easily over their knuckles and finger tips.
Diffuse cutaneous sclerosis and limited sclerosis are symmetric diseases. The localized sclerosis is asymmetric. They can be down arms and legs. One patient will usually have it only on one side. They too have joint contracture and limited mobility in the involved joints because the sclerosis goes right through the skin and into muscle (I AM NOT SURE THAT I GOT THIS RIGHT!!!)
Palpable purpura
First, you need to know if there is any underlying disease like lupus or another connective tissue disease like rheumatoid arthritis or others or, if it is drug related. If this were a drug related vasculitis, the most common would be cutaneous lymphcytoplastic vasculitis. Always get a urinalysis for RBCs and always get a stool for occult blood. These tests will help to rule out two big organs that get hit with other diseases: microangiitis and micropolyarteritis. The differentiation between cutaneous lymphcytoplastic vasculitis and microscopic angiitis (microscopic polyarteriitis) is not well written in Robbins at all. Robbins may lead you to think that the microangiitis commonly affects all the organs and that is "clearly not the case."
Palpable purpura is associated with wide spread disease in all body organs resulting in bleeding in the bowel, hemoptysis, and glomerular nephritis. These are not blanchable. Palpable purpura is a primary vasiculitis with secondary inflammation of the fat.
polyarteritis nodosa
Next up was an image showing the deeper lesions of polyarteritis nodosa which aren't blanchable either. There is a big differential with erythema nodosa. It is a piniculitis in response to a ___?____ and you will see mostly beta strep throat; this is a very common thing.
Patients with polyarteritis nodosa do not get glomerular nephritis like those with micropolyarteritis do. Again, it is in Robbins. These patients (PAN) get renal hypertension. Polyarteritis nodosa is one of the most confusing diseases you will ever run into. It often doesn't even have any skin signs at all. Patients will just present with some bizarre complaints. In polyarteritis nodosa there is a primary inflammation of the fat with secondary vasculitis.
Henloch-Schloen Purpura
In younger people with red cells in their urine or stools be sure to consider Henloch-Schloen Purpura and do immunoflouresence either on the early lesion on the skin looking for immune complexes (the biopsy must be done on an early lesion to see the IgA) or do a kidney biopsy and again, look for the IgA immune complexes. Most people with Henloch-Schloen Purpura also do fine.
http://www.epicrecords.com/epiccenter/custom/1173/audio/absolutely.wav
And from too much in a spot to too little all over.........
Vitiligo: A Manifestation of Apoptosis?
Current Opinion American Journal of Clinical Dermatology. 3(5):301-308, 2002.Huang, Carol L.; Nordlund, James J.; Boissy, Raymond
Abstract: Vitiligo is a common cutaneous disorder that has significant biological and social consequences for those affected. It is characterized by a loss of melanocytes from the epidermis, which results in the absence of melanin, i.e. depigmentation. There are numerous hypotheses about the etiology of vitiligo, but no data to definitively prove one theory over another. It is likely that there are numerous causes for the loss of these melanocytes.
One way to approach the identification of the etiology is to determine the mechanism by which the melanocytes are destroyed. The two known mechanisms for the destruction of cells are necrosis and apoptosis. One purpose of this paper is to review the extant data that might suggest which of the two mechanisms is operative against melanocytes in patients with vitiligo. The histological data, and some laboratory data, support apoptosis, rather than necrosis, as the mechanism for removal of melanocytes. Apoptosis can be induced by a variety of factors, including immune cytokines, some environmental chemicals (for example substituted hydroquinones such as monobenzone) or other molecular mechanisms. Current therapies, such as corticosteroids and ultraviolet light, do affect apoptosis in a variety of ways.
Confirmation of apoptosis as a mechanism, and identification of how apoptosis is initiated to produce vitiligo, can serve as a basis for devising medications that might stop the progression of the disorder. The problem of vitiligo would be essentially solved if there was a medication that is well tolerated in children, adults and pregnant women, and that would halt the progression of the depigmentation. The study of apoptosis, mechanisms of its induction, and the ways to block apoptosis, is one possible way to find both the causes of depigmentation and medications to prevent its progression.
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