March 24, 2023

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In this video we’re gonna talk about dress syndrome which stands for drug reaction with eason ophelia and systemic symptoms it’s a potentially life-threatening drug-induced hypersensitivity reaction that occurs two to six weeks of commencing a new drug it is characterized by skin eruption looking like a more billa form rash hematological abnormalities such as

Atypical lymphocytosis eason ophelia hence the name and internal organ involvement including the lungs liver kidneys as well as other organs not mentioned the pathogenesis involves a delayed hypersensitivity reaction to a drug and is more characteristic of a type 4 hypersensitivity reaction where the t cells the immune cells play an important role there is also

Evidence of reactivation of dormant viruses during the infection such as epstein-barr virus ebv and human herpes virus 6 and human herpes virus 7 the latency between drug exposure and onset of symptoms is considerably longer and rest that in most drug eruptions the clinical presentation includes fever malaise lymph adenopathy all around the body and eruption of a

More billa form rash that evolves differently but occupies more than 50% of the body surface area and here is an example of someone with a more beautiful and rash people with dress can also develop swelling of the face called facial edema and so a dress is sometimes mistaken for an allergic reaction like anaphylaxis other features depend on organ involvement so we

Have lung involvement in dress and this is quite nonspecific but can include pleural effusion as well as pneumonitis liver involvement is common and is usually asymptomatic with some liver derangement however other features can include jaundice and hepatomegaly and worse liver failure kidney involvement can also include acute interstitial nephritis the cause and

Culprit is usually a new drug comments two to six weeks prior to the manifestation of symptoms any drug can really cause dress but the most common drugs known to cause it include anti-epileptics such as carbamazepine lamotrigine phenytoin as well as allopurinol other drugs include antipsychotics sulfonamides such as sulfasalazine as well as vancomycin now let’s

Talk about the the physiology of dressed in a bit more detail now there’s a lot of theories behind this and different causes etiology z’ as to how it how the immune system responds to a drug there’s a metabolism to help the genic form theory and it’s where a drug is known as a pro hapten and when it’s metabolized by the liver it becomes a hapten now the hapten

Which is usually safe does not do much but it may bind to certain proteins termed carrier proteins from different parts of our body now when they bind they form a hapten carrier protein complex and this complex can now be detected by antigen presenting cells such as macrophages the antigen presenting cells will express or pick pick this complex up and then express

A component of this protein housing complex on an mhc class 2 molecule similarly circulating b cells which are also antigen presenting cells can bind and detect this hapten carrier protein complex take it in process it and then express its component on a mhc class 2 molecule as well antigen-presenting cells travel to the lymph nodes where they then activate t

Helper cells now a helper cells are cd4 cells because they contain the cd4 receptor which together with the t cell receptor help identify the mhc class 2 molecule as well as the component of the drug peptide the t helper cells are activated by interleukin 12 telling it to become t helper one cells the t-helper one cells are triggered by interleukin twelve and their

Further differentiation and activity by interleukin 2 which are released by the t helper cells themselves t upper one cells stimulate the cell mediated immune response by activating macrophages with interferon gamma and tnf alpha macrophages which are activated are primed to attack the hapten protein complex presented by the antigen presenting cell initially now

This hapten carrier protein complex can be anywhere in the body regardless the activated macrophage will attack and as a side effect causes tissue inflammation in various areas of the body via tnf alpha interleukin 1 and interleukin 6 t helper 1 cells promote the cell mediated immune response by also stimulating t killer cells also known as cd8 t-cells cd8 t-cells

Target cells which have interacted with the drug peptide and will kill it essentially further causing inflammation tissue inflammation as a side effect this mounting of immune response is what happens in dress syndrome the first theory we looked at was one called the metabolism of haptic genic form there’s also another theory called the direct hapten theory whereby

The drug is not metabolized but it’s carried by a carrier protein directly the carrier protein drug complex is identified again by antigen presenting cells mentioned earlier such as a circulating b-cells the monocytes the macrophages and this will again trigger the cascade of events we talked about leading to t helper one cell activation the final theory is the p

I theory standing for the pharmacological interaction with immune receptors theory the p eye theory or concept postulates that some drugs that lack hapten characteristic can bind directly and reversibly to immune receptors and thereby stimulate the cells here you can see that a drug binds directly onto the t-cell receptor the t helper cell can then be stimulated

Or the drug binds to mhc class 2 receptors directly which in turn will stimulate t helper cells via interleukin 12 the immune response mounted from the drug will cause tissue inflammation to different areas of the body including organs such as the liver kidneys and lungs unique to dress is that the immune response amounted can trigger the reactivation of dormant

Viruses such as epstein-barr virus and human herpes virus the theory here is that the cytokines produced in the inflammatory response such as tnf alpha interleukin 1 and interleukin 6 will stimulate the immune response some viruses actually stay dormant in these immune cells so when the immune cells get stimulated the virus becomes reactivated the other idea is at

Antigen presenting cells such as b cells can have latent viruses inside them chilling out the hapten carrier protein complex we learned about earlier is recognized by the antigen presenting cell the antigen presenting cell is actively stimulated and the virus particles that were latent inside them can be reactivated thus the antigen presenting cell will incorporate

Part of the virus particles with it expressing it on an mhc class 1 molecule together with a drug peptide the stimulated antigen presenting cells such as the b cell will activate the latent epstein-barr virus and human herpes virus the b cell that is expressing the mhc class 1 molecule will be recognized by the t killer cell via the cd8 t cell receptor and thus

The t killer cell will be stimulated and will attack this v cell and also will cause further tissue inflammation one of the clinical features of dress we have learned is lymphocytosis elevated lymphocytes in the blood lymphocytes specifically t lymphocytes as we have learned play a key role in the pathophysiology of dress the t-helper cells and t killer cells

Are known to produce a special interleukin interleukin 5 and interleukin 5 is a key cytokine for isa novel survival proliferation and activation so a lot of interleukin 5 secreted by these lymphocytes will cause e sinha philia a hallmark of dress and plays a key role in the pathophysiology as well easterner fills our circulating granulocytes involved in the host

Defense normally against parasites bacteria viruses as well as in allergic reactions in dress east’s inner fills infiltrate different organs because of chemokines which attract them into these sites here the inner fills release their granules which cause damage to the tissue thus in the liver hopera sites it can lead to hepatitis or worse liver failure in their

Cardiomyocytes of the heart it can lead to myocarditis and the most dangerous involvement in dress patients is caused by hot east and a fuel damage in the pulmonary system the release of these granules can lead to interstitial pneumonitis in the kidneys interstitial nephritis and in the skin you get the development of a more billa form rash again the escena fills

Infiltrates these organs because these organs release chemokines such as zio taxon and talk which attract the center fills to the area so that was the overall pathophysiology of dress and the different theories as to how the immune response become activated and mounted the most important challenge in dress syndrome is early recognition of the condition and immediate

Withdrawal of the offending drug failing to do so often proves crucial leading to unwarranted morbidity and mortality treatment also involves steroids topical steroids for mild skin manifestations or more commonly high dose oral or intravenous steroids with oregon involvement or critically ill people intravenous immunoglobulin is a possible alternative steroids

Are usually weaned over course six to eight weeks so in summary dress is a delayed hypersensitivity reaction to a drug that it was commenced two to six weeks prior to symptomology treatment involves steroids you

Transcribed from video
DRESS Syndrome (drug related eosinophilia) – causes, pathophysiology, signs and symptoms, treatment By Armando Hasudungan