Buxton: Rashes Flashcards
What are the more common cutaneous drug reactions?
cumulative toxicity
overdose
photosensitivity
drug-drug interactions
when the immune response to a drug results in an increased or exaggerated response
hypersensitivity
Drugs and their metabolites act as (blank) making some proteins immunogenic inducing either a cell-mediated or humoral response.
haptens
A drug substance that is capable of reacting with a specific antibody but cannot induce the formation of antibodies unless bound to a carrier protein or other molecule.
Also called incomplete antigen, partial antigen.
haptens
(blank) reactions are caused by the formation of drug/antigen-specific IgE that cross-links with receptors on mast cells and basophils leading to immediate release of chemical mediators, including histamine and leukotrienes.
Type 1
Clinical features of Type 1 hypersensitivity reactions?
pruritus urticaria angio-oedema bronchoconstriction anaphylaxis
Drugs most commonly responsible for type 1 hypersensitivity reactions?
aspirin
opioids
penicillins
These reactions are based on IgG or IgM-mediated mechanisms.
These involve binding of antibody to cells with subsequent binding of complement and cell rupture.
Type II hypersensitivity
Clinical features of type II sensitivity reactions?
blood cell dyscrasias
ex: haemolytic anemia and thrombocytopenia
These reactions are mediated by intravascular immune complexes that arise when drug antigen and antibodies, usually of IgG or IgM class, are both present in the circulation, with the antigen present in excess.
Slow removal of immune complexes by phagocytes leads to their deposition in the skin and the microcirculation of the kidneys, joints and gastrointestinal system
Type III hypersensitivity
Examples of type III hypersensitivity reactions
serum sickness
vasculitis
These reactions are mediated by T cells causing ‘delayed’ hypersensitivity reactions
Type 4 hypersensitivity
Examples of type 4 hypersensitivity reactions
contact dermatitis
delayed skin tests to TB
The clinical manifestations of drug hypersensitivity depend on various factors, including…
the chemical or structural features of the drug
the genetic background of the affected individual
the specificity and function of the drug-induced immune response
the classic drugs acting as haptens, but are reported to cause type 1 IgE mediated (immediate-type) hypersensitivity reactions as well as non-IgE mediated reactions, including morbilliform eruptions, erythema multiforme and Stevens–Johnson syndrome.
Penicillins
There is a high incidence of hypersensitivity reactions in patients with altered immune status, for example due to viral infections (Epstein–Barr virus or HIV). Give an example.
increased risk of trimethoprim/sulfamethoxazole hypersensitivity in HIV patients
T/F: Many drug reactions cannot be distinguished from naturally occurring eruptions.
True, misdiagnosis is very common
What are some examples of diagnostic uncertainty when it comes to rashes
A morbilliform rash may be due to viral infection or an antibiotics, and may limit the use of a particular medication
Patients may be taking multiple medications, making it difficult to establish which is responsible
If a patient is taking two drugs, one of the drugs might be more likely to cause the particular type of cutaneous eruption than the other
How can timing be used to determine what drug is responsible for causing a skin reaction?
in general, the onset occurs soon after the introduction of the causative drug
**When examining a list of medicines taken by a patient with a rash, new drugs taken within the previous month are the most likely cause.
What are two exceptions to the timing rule?
hypersensitivity reactions to penicillins can occur several weeks after the drug has been discontinued
gold can cause late reactions, too
Drugs suspected of causing skin reactions should usually be (blank) and not used again in that patient, although the risk–benefit potential needs to be considered before discontinuing any necessary medicines.
withdrawn
What are these?
mucous membrane involvement blisters or skin detachment high fever angio-edema or tongue swelling facial edema skin necrosis lymphadenopathy dyspnoea.
signs suggestive of a severe reaction
In most cases drug eruptions are (blank), resolving gradually after the causative drug is withdrawn.
Knowledge of the (blank) of the implicated drugs can be important; for medications with long (blank), the time to resolution may be several weeks or more.
reversible; half-lives; half-lives
What are these?
Acetaminophen Allopurinol Antimicrobials: cephalosporins, penicillins, chloramphenicol, erythromycin, gentamicin, amphotericin, antituberculous drugs, nalidixic acid, nitrofurantoin, sulfonamides Antifungals (allylamine type: Terbinafine) Barbiturates Captopril Carbamazepine Furosemide Gold salts Lithium Phenothiazines Phenylbutazone Phenytoin Thiazides
Drugs commonly causing exanthematous reactions
This drug usually is well tolerated at recommended therapeutic doses.
Rash and other allergic reactions occur occasionally. The rash usually is erythematous or urticarial, but sometimes it is more serious and may be accompanied by drug fever and mucosal lesions. Patients who show hypersensitivity reactions to the salicylates only rarely exhibit sensitivity
Acetaminophen
The use of (blank) has been associated anecdotally with neutropenia, thrombocytopenia, pancytopenia, hemolytic anemia, and methemoglobinemia.
Kidney damage has been reported, and liver damage is a prominent feature of overdose.
acetaminophen
What causes a fixed drug eruption? How does a fixed drug eruption present? What might the patient complain of? Where does the eruption occur?
drugs or chemicals alone;
erythematous round or oval lesion of a reddish, dusky purple or brown color, sometimes with blisters; initially, one lesion appears but many others may follow; pt may complain or itching or burning; can occur on any part of the skin or mucous membranes (hands, feet, tongue, penis, perianal areas)
What does it mean that a drug eruption is “fixed?”
whenever the pt takes the causative drug, the eruption will occur at exactly the same site
**healing will occur over 7-10 days after the drug is stopped
3 drugs frequently implicated in fixed drug eruptions?
sulfonamides
tetracyclines
NSAIDs
the second most common form of cutaneous drug reaction after exanthematous reactions.
drug-induced urticaria
How do urticarial lesions present?
raished, itchy, red blotches or wheals that are pale in the center and red around the outside
Drug-induced urticaria may occur after the first exposure to a drug or after many previously (blank) exposures.
The onset is more (blank) than with other drug eruptions; lesions usually develop within 36 hours of initial drug exposure.
Individual lesions rarely persist for more than 24 hours. On rechallenge, lesions may develop within (blank)
well-tolerated; rapid; minutes
a vascular reaction resulting in increased permeability and fluid leakage, leading to edema of the deep dermis, subcutaneous tissue or submucosal areas
angioedema
Is angioedema more or less common than urticaria? What areas are usu affected?
less common; tongue, lips, eyelids, genitalia
**unilateral or bilateral
one of the most common causes of angioedema
ACE inhibitors
T/F: It has been shown that continuing use of ACE inhibitors after the first episode of angioedema results in a markedly increased rate of recurrence, with serious morbidity.
ACE inhibitors should therefore be withdrawn immediately in any patient who presents with angioedema, and they are contraindicated in patients with a history of idiopathic angioedema.
True
In what two ways do ACE inhibitors cause angioedema?
- block renin-angiotensin mediated vasoconstriction
2. prevent breakdown of bradykinin leading to formation of NO and prostacyclin
What are these:
Drugs acting thru IgE receptors to the drug on mast cells triggering degranulation
Drugs that cause mast cell degranulation
Drugs that pharmacologically promote/exacerbate urticaria
Immune complex formation precipitation and activation of complement
Excpients in the medication that provoke allergic or pseudoallergic reactions
drugs causing urticaria/angioedema
Some drugs can cause or exacerbate acne. Name a few.
ACTH corticosteroids androgens (in females) oral contraceptives isoniazid phenytoin lithium
can unveil psoriasis in susceptible patients or aggravate existing psoriasis
Lithium
List some drugs that may cause psoriasiform eruptions or exacerbate psoriasis
ACE inhibitors beta-blockers chloroquine digoxin G-CSF gold lithium interferons NSAIDs
small cutaneous extravasations of blood. It is an occasional feature of drug-induced skin eruptions, and in some cases it is the main characteristic
purpura
Purpura is often caused by thrombocytopenia or platelet dysfunction, but drugs can also cause damage to small blood vessels and cause changes in vascular permeability. Give some examples of such drugs.
aspirin quinine sulfonamides atropine penicillin
refers to inflammation of the blood vessels leading to raised purpuric lesions mainly on the legs
vasculitis
2 types of vasculitis that can be induced by drugs
systemic vasculitis
cutaneous vasculitis
What is the mechanism behind vasculitis?
type III hypersensitivity reaction with immune complex deposition in postcapillary blood vessels
This drug is associated with a hypersensitivity syndrome that typically manifests as a vasculitis involving one or more organ systems.
propylthiouracil
3 diseases with a continuous spectrum of disease:
pts present with fever and flu-like symptoms before skin eruption
skin eruption affects hands, feet, limbs the most
may present with blisters, papular lesions, erythematous areas
involvement of the mucosa is common
erythema multiforme
Stevens-Johnson syndrome
toxic epidermal necrolysis
When do the severe non-urticarial drug eruptions like Stevens-Johnson typically occur?
1-2 weeks after treatment
What is the major precipitating cause of toxic epidermal necrolysis?
medications
This syndrome comprises fever, malaise, myalgia, arthralgia, and extensive erythema multiforme of the trunk and face.
It is frequently drug induced. There may be skin blistering and mucosal erosion covering up to 10% of the body surface area.
This syndrome is distinct from TEN, but there is a degree of overlap
Stevens-Johnson Syndrome
Denotes a reaction occurring when a photosensitising agent in or on the skin reacts to normally harmless doses of ultraviolet or visible light.
photosensitivity
A widespread eruption suggests exposure to a (blank) photosensitizing agent, whereas a localized eruption indicates a reaction to a (blank) topical photosensitizer
systemic; locally applied
This drug is associated with a 30–50% incidence of photosensitivity.
Symptoms develop within 2 hours of sun exposure, as a burning sensation followed by erythema. A small number of affected patients develop slate-grey pigmentation on light-exposed areas.
Light sensitivity may persist for up to 4 months after the drug is stopped.
Amiodarone
This drug may cause a phototoxic response when given in high doses.
The reaction is characterized by a burning, painful erythema within minutes of exposure to sunlight, either directly or through windows.
Erythema may persist for more than 24 hours.
Occasionally, a golden-brown or slate-grey pigmentation, predominantly of exposed sites, may be seen
Chlorpromazine
Many skin diseases are followed by changes in skin (blank).
In particular, after fixed drug eruptions there may be residual (blank)
color; pigmentation
This drug can cause a brown patchy pigmentation on light-exposed areas
Phenytoin
How are drugs that induce hair loss classified?
by the phase of the hair follicle cycle that is affected
In anagen effluvium, what cycle of hair growth is interrupted?
cessation of active anagen growth - hairs are shed within days or weeks with tapered or broken roots
(blank) is associated with alkylating agents such as cyclophosphamide, cytotoxic antibiotics such as bleomycin, vinca alkaloids, and platinum compounds.
alopecia
(blank) may be useful to partially prevent hair loss in patients undergoing chemotherapy.
scalp hypothermia
an excessive growth of coarse hair with masculine characteristics in a female.
This is a consequence of androgenic stimulation of hormone sensitive hair follicles.
hirsutism
Drugs that commonly cause hirsutism
testosterone danazol corticotropin anabolic steroids glucocorticoids
Patients with drug-induced hirsutism may also present with other dermatological signs of virilization, such as (blank)
acne
the growth of terminal and/or vellus hair on areas of the body where the hair is usually short, such as the forehead and cheeks.
hypertrichosis
(blank) may produce hypertrichosis in 50% of transplant recipients, with the excess growth being most marked on the face and upper back.
Cyclosporin
Drugs that can cause hypertrichosis?
androgens cyclosporin diazoxide methoxsalen minoxidil nifefipine penicillamine phenytoin verapamil
T/F: In phototoxic drug eruptions it is always necessary to stop the medication, even if protection from the sun is possible.
false, if sun protection is possible, it may be best OK to remain on the drug
A known cause of photosensitivity reactions
NSAIDs
