The skin in Systemic disease Flashcards
LO:
- The aim of this guided online session is to introduce the underlying systemic disorders associated with dermatological presentations and understand the systemic complications of skin conditions.
The Skin In Systemic Disease-why is this important?
It’s important to remember that rashes may be more than skin deep, comprehensive assessment, coupled with dermatological diagnostic skills, can help facilitate early detection of internal organ involvement, thereby preventing or reducing internal organ damage. It may also allow detection of internal malignancy.
In this talk, I’m also going to be advocating a systematic approach towards reaching a diagnosis and avoiding the temptation to rush to a spot diagnosis, which is often impossible or inappropriate.
The Skin In Systemic Disease-systemic disease:
The ways that the skin can be involved in systemic disease are highly variable. The skin may be targeted as one of many organs in the multi or systemic disease, such as sarcoidosis as seen here.
The skin may simply display a sign of an internal disorder, such as flushing in carcinoid syndrome, while not being directly involved in the process.
There may be a so-called telltale skin condition, such as Pyoderma gangrenosum, which may be associated with underlying inflammatory bowel disease, or rheumatoid arthritis or malignancy.
Conversely, the skin may cause secondary internal organ involvement, such as high output cardiac failure, which may occur in erythroderma.
Session plan
Case
Her bloods show:
Pancytopenia- a condition that occurs when a person has low counts for all three types of blood cells: red blood cells, white blood cells, and platelets.
Urinalysis shows proteinuria
Increased inflammatory markers
Positive autoantibody profile including double stranded DNA antibody, and a high titre of antinucleotide antibody.
Differential diagnosis and investigation:
When approaching a diagnosis, it’s important to consider all possibilities and categorising the different possibilities is helpful. Think BMI SS.
This also influences your diagnostic tests, and in considering the different possibilities you choose appropriately, for example, when considering neoplasia as a possibility you may consider imaging to examine for internal organ involvement ,or a biopsy of the infected tissue, in this case, a skin biopsy.
When considering an infectious etiology, you may consider a viral or a bacterial serology, swabs for bacterial or viral studies, or a tissue for culture or PCR.
Autoimmune serology may also be helpful. A thorough history will detect any possible drugs.
Skin biopsy:
Briefly, about skin biopsy, this is a type of skin biopsy called a punch biopsy, which uses a cookie cutter like technique to take a small amount of tissue. This tissue can be sent for different types of studies, such as culture or PCR for microbes or histology, where the type of inflammatory process and the type of cells involved are identified.
Here we see vacuoles, little white spaces and lymphocytes all along the dermal epidermal junction. This is called an interface pattern of inflammation and as seen in lupus as well as other conditions. At the bottom right, we see a type of test called immunofluorescence, which is used to detect antibodies. Here we see a line along the dermal epidermal junction, indicating the presence of autoantibodies there.
Lupus Erythematosus-2 main groups:
The patient’s presentation is suggestive of lupus erythematosus.
There are two main groups of lupus: systemic lupus erythematosus, involving multiple organ or cutaneous limited lupus.
There is, however, some overlap
Systemic Lupus Erythematosus – diagnostic criteria
There are diagnostic criteria that are required to make the diagnosis of systemic lupus, and a minimum amount of them must be fulfilled. These can be broadly categorised by organ.
In terms of the mucocutaneous manifestations, there are manifestations of acute lupus, such as this photo distributed rash where chronic cutaneous lupus, which we’ll talk about in a second, as well as non-specific manifestations such as oral ulcers or alopecia. Here we see chilblains. And the photo distributed rash, meaning a sun exposed stress.
Other diagnostic criteria include synovitis, serositis (including pericarditis or pleuritis), renal involvement or neurological involvement, as well as haematological involvement such as leukopenia, haemolytic anaemia or thrombocytopenia.
Also forming part of the diagnositic criteria are immunological criteria, such as auto antibodies as seen here, or low complement.
Two main groups: symptoms and pictures
In terms of systemic lupus erythematosus cutaneous manifestations, these include alopecia, chilblains, livido reticularis, which is this net like pattern of redness, cutaneous vasculitis, as we see in the top right, manifesting as palpable purpura, or subacute cutaneous lupus, where we see annular or semi-annular (which means ring-like) scaley erythema, in the photo distribution.
And in terms of cutaneous lupus, subacute cutaneous lupus as seen on the bottom right may be a manifestation of that or it may be discoid lupus.
Two main groups: symptoms and pictures
Discoid lupus has characteristically causes scarring, which is particularly noticeable when it’s present on the scalp where it results in alopecia, as the hair follicle unit is totally replaced by scar tissue. It causes scarring wherever it appears however.
Here again, we see an example of subacute cutaneous lupus, which may be present in systemic lupus or may be present as skin limited disease, manifesting a photo-distributed annular or semi-annular erythematosus scaley rash.
Case
This newborn infant has an annular rash affecting the forehead and zygomatic prominences.
In some cases, a characteristic rash can facilitate a rapid diagnosis. Even in those cases, it’s always important to consider other possibilities.
In this case, an annular rash in a newborn raises a suspicion for neonatal lupus, which is often associated with Ro antibodies. The test that needs to be performed is an ECG, because there’s a 50 percent risk of heart block. And if that goes undetected, it can lead to complications such as heart failure.
Case
As part of approaching any rash, a comprehensive systems review is important. And here she informs us of weakness, particularly when climbing stairs along with weight loss and fatigue.
These are the different categories that we must always consider, as well as different diagnostic tests to consider.
Dermatomyositis
The history of a photo-distributed rash, along with weakness, raises suspicion of dermatomyositis. And indeed, she has manifested some of the pathognomonic features, such as Gottron’s papules, which are these pink to violet rashes of the metacarpophalangeal joints and interphalangeal joints, and also ragged cuticles, erythema along the upper trunk in a shawl like distribution, as well as this so-called heliotrope rash.
Dermatomyositis is classically associated with the proximal extensor inflammatory myopathy. There are additional features and associations that can be predicted by an auto antibody profile.
Dermatomyositis-autoantibodies:
So amongst these on autoantibodies are SRP, which can predict a very severe muscle involvement causing necrosis, or Mi-2, which is associated with mild muscle disease. SAE may suggest that muscles are completely spared. Amyopathic dermatomyositis is a form of dermatomyositis characterized by the presence of typical skin findings without muscle weakness. Some of the skin changes that suggest dermatomyositis include a pink rash on the face, neck, forearms and upper chest; Gottron’s papules and heliotrope eyelids.
Presence of p155 antibodies suggest the likelihood of a malignancy when in adults. The MDA5 antibody is suggestive of the involvement of the lungs, specifically interstitial lung disease, as well digital ulcers as illustrated here. (think MDL5 and replace L with A)
At the picture on the top right, we again see Gottron’s papules, which are erythema of the metacarpophalangeal and interphalangeal joints. And then the bottom right, we see the upper trunk shawl sign.
Dermatomyositis-diagnostic test
The diagnostic tests to undertake when considering this diagnosis are an autoantibody profile, including ANA and ENA with extended dermatomyositis auto antibody profile. The ANA tests for the presence or absence of autoantibodies, while the ENA panel evaluates which proteins in the cell nucleus the autoantibodies recognize. The ENA panel helps diagnosis, distinguish between, and monitor the progression of autoimmune diseases and is performed with a simple blood draw.
Muscle involvement may be detected by either detection of CK, EMG or MRI.
Skin biopsy may also show an interface dermatitis, liver function tests are often increased.
And when this diagnosis is being suspected, it’s important to screen for internal malignancy.
Case
Urinanalysis is abnormal as showed 50-100 RBCs!
Review of systems and physical exam (ROS and PE)
Again, we must think in terms of the systematic approach of neoplastic, infectioous, inflammatory, drug induced, and autoimmune categories.
What do you do about this case?
A biopsy was taken for immunofluorescence that showed an IgA antibody targeting the blood vessels. This thereby indicated a condition called Henoch-Schonlein purpura-HSP. (Hehe think schon!)
So this patient presented with a gastrointestinal bleed, which was part of this condition. He also had red blood cells in his urine. And in this particular case, the patient actually developed severe kidney failure as a result.
key symptoms-purpura on legs and butt, joint pain, abdominal pain, kidney disease
occurs mainly in children under 10.
Vasculitis-classifications:
So vasculitis can affect different sizes of blood vessels, so small vessel vasculitis may be simply a drug reaction or associated with an infection elsewhere in the body, or it may be a manifestation of a connective tissue disease such as lupus, a non-specific manifestation of lupus, as we saw. It may indicate a specific condition such as Henoch-Scholein Purpura.
Where you have both small and medium vessel involvement, it may be an ANCA-associated vasculitis, such microscopic polyangitis or granulomatosus with polyangitis or Cryoglobulinemia (Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis), characterized by destruction and inflammation of small vessels.
Where it affects medium blood vessels only it may be Polyarteritis nodosa.
And large vessels include Takayasu arteritis and temporal arteritis. (think Ts!)
Vasculitis-images of manifestations:
The manifestations of vasculitis in the skin really depend on the size of the blood vessel involved. So small vessel vasculitis typically manifests in Purpura, such as we see in the picture in the left. Whereas medium vessel manifestations include digital necrosis, this ratchet form or net like Purpura, along with linear ulcers.
In the bottom right, there are a subcutaneous nodules along blood vessels. Or you may again see another example of ratchet form Purpura with ulceration in medium vessel vasculitis.
IgA Vasculitis
So it’s important to always bear in mind, because IgA vasculitis doesn’t look like any other small vessel vasculitis, and it can cause progressive renal failure. So it really needs to be followed up and communicated with the renal physicians.
Case
What do they have? Explain
This manifests in different symptoms reflecting the different organ systems including lung involvement, such as cough, shortness of breath, and chest pain. On the skin, we see both small and medium vessel involvement, or one or the other. If we remember the small vessel manifestations were macular or popular purpura, whereas medium vessel manifestations include retiform or net like purpura, digital necrosis, or subcutaneous nodules distributed along blood vessels or ulcers.
Case
Comprehensive review of systems indicates a long centime, dry cough, but also joint pains
So, again, we take a step back and think, could this be neoplastic, in which case we should do a biopsy?
Could this be infectious? Then maybe we should check some serology or maybe we should send the tissue for a culture or PCR.
Could it be drug induced? No, he hasn’t taken any new drugs.
Could it be inflammatory? Yes.
Could it be auto immune? Should we check some auto immune serology?
So at the tests we take depend on the clinical signs.
Sarcoidosis
So here we see the clinical signs are quite suggestive of sarcoidosis, you have these plaques which look quite kind of grainy and rough. And sarcoidosis is quite an interesting condition because, first of all, it can affect multiple different organs, particularly the lungs. Secondly, we don’t know why it happens. And thirdly, even though sometimes you do see characteristic clinical manifestations such as those rough plaques, it can look like anything at all.
It can look like these red to violaceous papules on the face lips or upper back or neck. You can got this manifestation on the face, called lupus Pernio. Important to remember that that’s not anything to do with lupus erythematosus. It’s just a similar name. Or you can get ulcers or you can get inflammation of the subcutaneous fat in the legs, which is known as erythema nodosum.
The histology shows granulomas. It’s a diagnosis of exclusion. So you need to exclude the possibility that this could be infectious. And you do that with the tissue for culture or PCR.
Sarcoidosis pics
So when you make this diagnosis, you really should evaluate for underlying lung involvement, and part of that is undertaking a chest x ray and discussing with respiratory colleagues, whether any further at diagnostics are necessary, such as, for example, pulmonary function tests or high resolution CTs of the thorax.
So you can see how heterogenous it is. On the left, we just see some erythematosus macules, which are flat lesions and papules which are elevated. On the right we see a kind of redy purple involvement to the face, which is called lupus pernio, and we see some plaques on the face as well, which are raised red areas.
Lupus pernio is a chronic raised indurated (hardened) lesion of the skin, often purplish in color. It is seen on the nose, ears, cheeks, lips, and forehead. It is pathognomonic of sarcoidosis.
We also see involvement around the opening of the nose, which is Lupus pernio. And sometimes you just see hypo pigmentation, which is pale areas on different parts of the skin.
So a case in point of skin being targeted in a condition which targets multiple organs.
Case
So again, we have to take a step back and think of…
Are we going to look for neoplasm? We already know he has multiple myeloma.
Is it an infection, yes could be an infection. So blood cultures, serology,
Drug induced. Yes. Strong possibility. Multiple new drugs.
Auto immune-a possibility.
What does he have? And what are the features of this?
=So this is actually Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), which is where you have a multi systemic drug reaction, which causes skin, solid organ and haematological disturbances.
And the features include a rash. And the rash may be a very characteristic one, such swelling of the face, facial oedema, or it could be a wide spread rash such as erythroderma.
Other signs include fever, lymphadenopathy, peripheral eosinophilia. You can also get atypical lymphocytes on a blood film. And many different organs can be involved, the liver, the kidneys, the heart, the brain. And this can be fatal in about 10 percent of cases (fulminant hepatic failure is the usual cause of that).
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Internal organ involvement
This can be fatal in about 10 percent of cases.
In the liver, fulminant hepatic failure, is the usual cause of that. The specific ways in which other organs involved are interstitial nephritis, in the case of the kidneys. Myocarditis in the case of the heart and thyroiditis- altered cognition in the brain and interstitial pneumonitis in the lungs.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Diagnosis
So there are criteria and when you have a patient and you suspect they may have this condition, you undertake a number of aspects of clinical examination and as well as serology, you score them up to determine if they meet the criteria for this condition.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Nobody knows what causes the condition, the drug which is responsible for triggering it may have been given up to six weeks before the onset. And as we mentioned, liver involvement is the most common cause of fatality. And amongst the drugs, certain causes are anti epileptics, sulphonamides, allopurinol, antibiotics, and nonsteroidal anti-inflammatory drugs.
And usually it starts at the face and the upper trunk and the extremities and then spreads downwards and inwards. And you can see how different it looks in these pictures alone. In the top right, you can see that kind of so-called bull’s eye pattern, which we call a targetoid pattern. In the bottom, it’s a morbilliform rash (a rose-red flat (macular) or slightly elevated (maculopapular) eruption, showing circular or elliptical lesions varying in diameter from 1 to 3 mm, with healthy-looking skin intervening).
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Rash morphologies and treatment:
So the targetoid-like appearance we call that a erythema multiforme-like rash.
You can also get an urticated papular exanthem, which basically means a raised rash that looks a little bit like a nettle rash.
The treatment for this is to obviously stop the drug and then suppress the inflammatory response with corticosteroids.
Case-what does she have?
Urticarial rash=nettle like rash
Always important to remember Urticaria is not a diagnosis. You can get Urticaria as an allergy, you can also get it due to an underlying infection. You can even get it as a manifestation of vasculitis, it can be a chronic autoimmune disease, it can be related to lupus, it can also be related to these autoinflammatory syndromes eg…
…Schnitzler’s syndrome
Schnitzler syndrome is a rare disorder characterized by a chronic reddish rash that resembles hives (urticaria) and elevated levels of a specific protein in the blood (monoclonal IgM gammopathy).
=A condition that is associated with the monoclonal gammopathy and the other manifestations include fever, bone and joint pains, swollen lymph nodes, splenomegaly, hepatomegaly and increased inflammatory markers and abnormalities on imaging of the bone.
An urticaria doesn’t typically leave pigmentation behind. So that’s a small clue.
Schnitzler Syndrome-treatment:
This condition is extremely rare and it’s something that would be monitored in a very specialised centre. It’s an example of how you always have to take a step back and do a comprehensive systems review to think, OK is this just uticaria or is there something else going on?
Case
macules-flat areas of redness
papules-raised areas of redness (think PLs are bigger)
Confluence means they join together, and they cover 60% of his body surface area
Scleral icterus, also known as conjunctival icterus, refers to the yellowish pigmentation of the sclera, which is the normally white area of the eye. This yellowish pigmentation arises due to the buildup of bilirubin in blood.
So he has had an allogeneic haematopoietic stem cell transplant, so we have to consider here not just the categories that we considered before, but also the category not just autoimmune, but alloimmune. So. This is actually graft versus host disease.
Autologous: Auto means self. The stem cells in autologous transplants come from the same person who will get the transplant, so the patient is their own donor.
Allogeneic: Allo means other. The stem cells in allogeneic transplants are from a person other than the patient, either a matched related or unrelated donor
Graft versus Host Disease:
How can you tell if a rash is caused by a drug or GvHD?
acral involvement=Peripheral body parts ie distal limbs
If have these 3, then GvHD is likely, the other thing we can do is take a skin biopsy which can sometimes help us make the distinction.
The treatment is obviously going to vary quite a lot if it’s a drug rash or graft versus host disease. Because the drug rash will require withdrawal of a drug, whereas graft versus host disease is treated with suppression of the immunity.
Graft versus Host Disease-what is it?
So it does affect up to 10 to 80 percent of patients who’ve had allogeneic haematopoietic stem cell transplant. And it’s the donor’s T lymphocytes which are attacking the host, and it can affect many different organs and it can be chronic.
Self test: MCQ 1
Case
Polycythaemia=means haemaglobin is high
He undergoes a scan and you see this in his kidney.
What do they have?
So itching without a rash is suggestive of an internal cause. So there are different causes such as lymphoma, so night sweats, weight loss, fever. Polycythaemia, renal failure can cause it, cholestasis, iron deficiency or overload, HIV, hepatitis A, B and C, Internal cancers, drugs such as opiates or opioids, it may be psychogenic or sometimes that happens simply because of old age because the connections between the keratinocytes become more fragile and frayed.
Pruritus- investigations
So when we’re approaching a patient like this, in addition to a history and checking all their lymph nodes and looking for any skin signs that may indicate a cause, we also do some diagnostic tests, such as the FBC, LDH, which are looking at haematological causes, liver function tests to look for cholestasis, Ferritin, to look for iron deficiency or overload, an X-ray of the chest as a general screen for lymphadenopathy and thoracic masses and viral serology.
So when someone experiences a severe, prolonged itch, the skin can change into these kind of nodules, which are a sign of nodular Prurigo and nodular Prurigo is not really a condition in itself, it’s kind of the end result of scratching. it’s simply the skin trying to mend the defence. So learning point is itch without a rash, look for an underlying cause.
Case
What do they have?
Systemic Amyloidosis is a manifestation of plasma cell dyscrasia. And the amyloid is composed of AL protein, which itself is composed of immunoglobulin light chains, and the manifestation is really varied and non-specific, so it’s not necessarily an easy diagnosis to make.
Amongst the symptoms you can get, as this man had: Weight loss, fatigue, parathesia, shortness of breath and syncope. So where you suspect that this can be the condition you need to do very specific investigations, such as a biopsy of the abdominal fat or the rectal mucosa or imaging such as Serum Amyloid protein Scintigraphy. And the treatment of this condition treats the underlying plasma cell dyscrasia, and those, treatment options are listed at the bottom. You only see skin features in about a quarter of patients with systemic amyloidosis, but they can be quite subtle or non-specific.
Systemic Amyloidosis: Cutaneous Features
You only see skin features in about a quarter of patients with systemic amyloidosis, but they can be quite subtle or non-specific.
So he had some bruising around his eyes, some purpura, and that’s the so-called racoon sign and that can be quite dramatic or it can be quite subtle. But you may also see these waxy, translucent or purpuric papules anywhere they could be in the face, neck or anogenital region, or on the digits.
Case
Denies any trauma or abuse
What do they have?
So here we see that the hair looks like an unusual shape, and we see a kind of purplish hue around the hair follicles, and you can see the poor dentition there. So these changes are scurvy, which is Vitamin C deficiency, it was historically seen in sailors who didn’t have access to fruit for long periods of time.
And the features in the mouth are spongy gums with bleeding and erosions, and on the skin you see petechiae, which are tiny, tiny little pinprick bruising, ecchymoses, which is just bruising, and follicular hyperkeratosis, so where the hair follicles are quite bumpy, almost like goose bumps. And then you get these corkscrew hairs with haemorrhage around the rim of the hair follicle. So these are very characteristic signs of scurvy.
Other Nutritional Deficiencies
k…
So there are other nutritional deficiencies which also manifest in the skin, so kwashiorkor manifests with sparse, dry hair, thin, soft, fragile nails, Cheilitis (inflammation of the lips), and you can get this small erosive changes or large areas of desquamation (skin peeling) and erosion. And the systemic features include infections, diarrhoea, loss of muscle mass and organomegaly.
Other Nutritional Deficiencies: zinc
So zinc deficiency also manifests in the skin, and it particularly manifests in peroneal, perioral and acral sites as redness, erosion, scale and crusts and hair loss and conjunctivitis and stomatitis, and systemic manifestations include diarrhoea and a decreased affect. Because zinc has so many different roles in so many different processes in the body.
Other Nutritional Deficiencies: Vitamin B3
So vitamin B3 deficiency manifests as pellagra. So the 4 Ds of pellagra are dermatitis, diarrhoea, dementia and death. And there are some quite characteristic dermatological manifestations, so you can get photodistributed erythema and this so-called casal’s necklace of changes around the neck. You can get an inflammation of the perianal and vaginal and perioral skin.
It’s a diagnosis that even despite how dramatic its manifestations can be, does require an index of suspicion. So it’s another item to add to your differential for photo-distributed. Erythema.
Case
What does he have?
So this is carcinoid syndrome. So carcinoid reflects a metastasis of a malignant carcinoid tumor, resulting in 5-HT secretion into the bloodstream. In about a quarter of cases this causes flushing, which can be very dramatic. Other symptoms include bronchospasm causing wheezing, hypotension, which may cause collapse and diarrhoea. But only 25 percent people will will develop flushing.
Self test: MCQ 2
Case-what do they have?
His skin progresses from this to this very quickly, and this is what we call denudation of the skin where the epidermis falls off.
Blisters merge - sheet like skin loss
Nikolsky +ve – slight skin rub = exfoliation of epidermis
Distinct entitity from EM – mainly drug cause
This is Stevens-Johnson syndrome/ toxic epidermal necrolysis. Stevens Johnson syndrome and toxic epidermal necrolysis are the same process, but I’ll explain the difference in a second.
So generally, this is one of the really rare conditions where you have a dermatological emergency, and it’s preceded by flu like symptoms, followed by the abrupt onset of lesions.
The Nikolsky’s sign means when you push your finger on the effect skin and move it to the right or the left or up or down it spreads the problem. You get extensive full thickness necrosis of the epidermis within days.
Notes from slide:
Nikolsky – exfoliation of epidermis on slight skin rub
Atypical targetoid – x2 circles of colour (vs 3 in EM erythema multiforme?)
See SJS/TEN as same condition = just difference in severity
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
What’s the difference?
They’re the same process. The only difference is Stevens Johnson syndrome affects less than 10 percent of the body surface area. Whereas Toxic Epidermal Necrolysis affects more than 30 percent of the body surface area. Anywhere inbetween 10 percent and 30 percent involvement is the so-called overlap syndrome.
Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis
Cause:
So it’s caused by a cell mediated cyto toxic reaction against the epidermal cells. And drugs cause the vast majority of cases and they may have been started up to three weeks before the rash.
And it can resemble cutaneous graft versus host disease or staphylococcal scalded skin syndrome, or burns.
Notes from slide:
>200 meds reported!
Graft vs host is a big mimec of SJS/TEN
Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis
Criteria for diagnosis and complications
In terms of predicting prognosis, we add on a bunch of different criteria, such as people’s age, their heart rate, the presence of malignancy, their glucose level, et cetera. And that helps inform us about their outcome.
Unfortunately, 30 percent of patients die. And in those that don’t die, there are complications such as blindness, hypothermia/hyperthermia, renal tubular necrosis, spread into the gastrointestinal tract or the lungs, causing interstitial pneumonitis or liver or heart failure.
Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Pics
And this is a patient in the midst of Stevens Johnson syndrome.
And on the right you can see him after he’s recovered. So that’s an example of how patients internal organs can be affected by a skin disease.
Case-what does he have?
So he became erythrodermic, and the systemic manifestations of this reflect the impairment and skin function. So you lose your ability to thermoregulate, so you can get hypothermia. You lose your fluid barrier, so you lose fluid and proteins, and that in turn can cause tachycardia and oedema. The loss of your barrier protection also means that you are vulnerable to microbes and any rash can basically cause this, but it’s usually drugs or psoriasis or eczema. You can also get a type of lymphoma called Sezary Syndrome that causes it. In a lot of cases. There is no explanation. So idiopathic.
Erythroderma management:
And the way it’s managed is by supporting people’s barrier, by applying widespread emollients and then treating any infection, maintaining their fluids, their electrolytes and managing their body temperature in special rooms.
And if you know the cause, if they have underlying psoriasis, you can treat that with psoriasis treatments. This is true regarding the disease.
Self test: MCQ 3
Cutaneous Signs of Systemic Disease
So now we’re going to talk about his manifestations associated with specific organs or conditions. So here we have Excoriations and Prurigo, which means itch. Xerosis, which means dryness, you can see the skin looks like it has some fine scale and a little bit of a cobblestoned pattern on top. Half and half nails. And here we retiform (netlike) Purpura, as well as ulcers, and that suggests a condition called calciphylaxis, where calcium blocks the arteries.
Here we see nephrogenic systemic fibrosis, although that’s best appreciated on palpation.
Here we see perforation of the skin, a perforating disorder. Viral warts and pallor of the ocular mucosa. So these are all manifestations of chronic kidney disease.
Chronic Kidney Disease
So these are all manifestations of chronic kidney disease. The warts are actually more related to immunosuppression used to treat renal transplant recipients. But the others are manifestations of kidney disease. So in chronic kidney disease, you get anaemia which can cause mucosal pallor, hair thinning, may cause an itch in itself.
The higher urea in the blood, causes an itch resulting in excoriations, so they may develop nodular prurigo. Calciphylaxis may occur, Half and half nails are commonly seen, where you have half of the nail pale white and the distal half red. You may see manifestations of the underlying cause of their kidney disease, such as Lupus. Lupus often involves the kidney. So you may see photo distributed erythema such as in the lady we met earlier, or ANKA-associated vasculitis, causing ulcers, retiform purpura or a small vessel vasculitis palpable purpura.
Cutaneous Signs of Systemic Disease
So this patient has some pale transverse white bands known as Muehrcke’s Lines in his nails, jaundice, spider telagiectasia, Terry’s nails where the nail is mostly white, with a distal dark band, palmar Erythema, Porphyria cutaneous tarda, which are blisters and skin fragility in a sun distribution, and clubbing.
So put together all of these indicates chronic liver disease.
Chronic Liver Disease
So those nails with the distal dark band, but mostly white are called Terry’s nails and the paired white bands are muehrcke’s nails.
Case
What do they have?
So this is Necrobiosis lipoidica. So where you have a kind of reddy Brown mark on your legs with a pale, atrophic or thin centre, that’s quite characteristic. But we usually take a skin biopsy to confirm this. This prompts us to look for underlying diabetes, because between a fifth and two thirds of patients have diabetes melitus with this condition.
Other Cutaneous Manifestations of Diabetes Mellitus
There are other manifestations of diabetes. Remember, Terry’s nails from liver disease. We also see them in diabetes. You can get this annular condition called granuloma annulare, neuropathic ulcers, this velvety thickening of the skin in the armpits called acanthosis nigricans. You can get dryness (xerosis) in diabetes as well. Xanthelesma and Xanthomata. And you can also get infections such as the fungal infection we see here.
Hyperlipidemia
Hyperlipidaemia, which we saw in Xanthelesma.
You can also get eruptive xanthomas.
Cutaneous Manifestations of Other Endocrinological Disorders
There are other endocrine disorders also manifest in the skin, such as graves’ disease, as pretibial myxoedema, where you’ve get these waxy pretibial plaques.
Hyper pigmentation of the skin and gums, which we see in Addison’s disease.
Acne is a sign of acromegaly, Cushing syndrome and polycystic ovarian syndrome, although you don’t obviously have to have any of those conditions.
And cutis gyrata verticis has these thickened skin on the scalp with a kind of a brain-like appearance which can be a sign of acromegaly.
Cutaneous Signs of Systemic Disease
So another constellation of signs, seborrhoeic dermatitis, also known as seborrhoeic eczema-these greasy scales on a background of erythema around hair bearing sites. Extensive viral warts. Scabies, Norwegian’s scabies is when it’s scaly. Severe psoriasis. Ulceration closed by cytomegalovirus-CMV, folliculitis of the eosinophilic variant, bacillary angiomatosis. So these are signs of immunosuppression.
This is penicillininosis, an opportunistic infection. Tinea Corporis, which is much more extensive than usual. Cryptococcosis, Kaposi sarcoma.
HIV
So HIV has different manifestations at different stages of the disease.
So in the seroconversion phase, you may get a morbilliform rash, you may get uticaria-the nettle rash, you mya get the targetoid rash called erythema multiforme, or you may get an oral or genital ulceration.
So it’s one of those things that whenever we see a rash of any of those descriptions, we check for HIV. Some people that have some severe forms of psoriasis or severe seborrheic dermatitis, that also merits a HIV test.
Opportunistic infections can be a sign of AIDS. Persistent or infections or atypical manifestations such as chronic ulceration due to herpes, that’s an unusual manifestation, so we check for HIV. We saw earlier that HIV can cause an itch wihtout a rash. Eosinophilic folliculitis is very unusual and it’s often seen in the context of HIV, so that would also prompt a HIV test.
I think if there’s one Take-Home message from this slide, it’s pretty much always just check for HIV in any skin condition.
Cutaneous Signs of Systemic Disease
Hidradenitis suppuritiva
So here we see some panniculitis, the specific type here is erythema Nodosum, that’s inflammation of the subcutaneous fat. This is painful, extending ulceration due to neutrophilic inflammation, this is pyoderma gangrenosum.
Dermatitis herpetiformis, which manifests as itchy blisters of the extensor surfaces. You almost never see the blisters, because it’s so itchy that people scratch them away, leaving these erosions. Apthous ulceration. Swelling of the lips is oro facial granulomatosis. These are cutaneous signs of. Of different internal organ manifestations.
This is hidradenitis suppuritiva, which is where you get inflamed nodules, sterile abscesses, sinus tracts and fistulae, that favour the intertriginous zones, such as the auxilla and the anogenital area and the inframammary area.
Pyoderma gangrenosum
It often starts it’s a pustule on a red base that ulcerates and extends with the necrotic undermined border.
It’s very painful. Can be associated with inflammatory bowel disease leukaemia or seronegative arthritis.
The skin in Gastrointestinal Disorders
pemphigoid-blistering condition
So it dermatitis herpetiformis is not associated with inflammatory bowel disease it is associated with coeliac disease.
Cutaneous Signs of Systemic Disease
So here we have P’eau d’orange breast carcinoma, groin metastases in prostatic carcinoma. This is metastatic bronchial carcinoma. This is leukaemia cutis. This is metastatic oesophageal carcinoma.
So I think in several of these, they look so floridly abnormal that they could be neoplastic or an atypical opportunistic infections. So, again, we think back to our diagnostics and we think of imaging for internal malignancy and tissue for biopsy and for culture and PCR.
And other signs of internal malignancy include haemorrhagic nodules, extra mammary Paget’s disease, which is associated with internal malignancy while being a malignancy in itself. Paget’s disease of the nipple. Acanthosis nigricans can also be a manifestation of internal malignancy, as well as being associated with diabetes.
Cutaneous Signs of Systemic Disease
You also have some conditions such as erythema gyratum repens, which is supposedly a geographic looking condition. Paraneoplastic Pemphigus, an auto immune blistering condition brought on by a malignancy.
So here we have chilblains-like lesion, urticaria, vasculitis, and itching these can also be a manifestation of malignancy.
Cutaneous Signs of Systemic Disease
You also may have specific signs, such as Mucosal Melanosis indicating a genetic cancer predisposition syndrome. Leiomyomas may indicate a predisposition to renal cancer if they’re part of the HLRCC syndrome. Facial angiofibromas are seen in tuberous sclerosis, which can cause both benign and rarely malignant tumours.
Cutaneous Signs of Internal Malignancy
Self test: MCQ 4
The Skin In Systemic Disease-take home message
