Psoriasis and Cutaneus Drug Reactions Flashcards
What is psoriasis? Epidemiology?
It is an immune mediated inflammatory disease that affects primarily the skin and to a lesser extent the joints, therefore it is also a rheumatological disorder. 2 to 3 % of the western world is affected, much more than the rest of the world. It can occur at any age but features a bimodal distribution. Type I between 15-25 years of age with more severe course and type II between 50-60 years of age with a less severe course. It occurs in men and women equally.
What is the pathogenesis of psoriasis?
The mechanism of pathogenesis is related to a hyper proliferation of keratinocytes of the epidermis. Usually keratinocytes take 3 to 4 weeks to reach to stratum corneum from the basal layer. In psoriasis they take 5 to 6 days, in other words we have an accelerated turnover of keratinocytes. This causes improper differentiation of the keratinocytes. Keratinocytes in the stratum corneum still have their nucleus called parakeratosis, in normal conditions they should have already lost it. Psoriasis is an immune mediated disease where T lymphocytes and the release of pro inflammatory cytokines like IL23 and IL17 are the cause of the increased turnover of keratinocytes.
What triggers psoriasis?
We don’t know the real cause. It is probably a multi factorial cause. There are as in every autoimmune disease environmental triggers and genetic predisposition. Most of the identified genes relate to the immune system in particulate the MHC and T cells. HLA CW6 has a strong link with type I. Other exogenous triggers might be alcohol, drugs like anti malarials and beta blockers, infections, smoking and obesity.
How does the IL23 and T helper 17 axis work?
Delivery of cytokines from keratinocytes stimulate dendritic cells to release IL23 which stimulates T helper 17 lymphocytes to deliver IL17 to the keratinocytes which increases the turnover.
What is non pustular psoriasis?
It is more frequent and its primary lesion is an erythematous squamous papule that forms psoriatic plaques which are scaly desquamations with with whitish grey color and are itchy. It is subdivided into psoriasis vulgaris characterized by erythematous pruritic plaques and is the most common, nummular where the plaques have a coin like appearance, Inverse where it affect skin folds usually in obese patients and lesions are not scaly but rather erythematous with moist surface, guttate which has a rain drop presentation and is associated to strep infections, seborrheic which manifests as red plaques in areas of higher sebum production like scalp and gentials, universal where the whole body is involved and it progresses slowly, and erythrodermic where almost the whole body is involved with erythematous and inflamed lesions it is the most severe form leading to dehydration, sepsis and heart failure.
What is pustular psoriasis?
It’s primary lesion is a pustule that is aseptic and non infectious. Characterized by raised bumps filled with pus, the skin under and surrounding is red and tender. It is divided in acute generalized which is the worst form as the patient is completely covered, acrodermatitis continua which involves the fingers along with underlying bone, pustolosis palmaris which involves only the palms and soles, and pustular psoriasis of pregnancy characterized by a general acute eruption of erythematous plaques in the 3rd trimester and can cause placental insufficiency, fetal morbidity and mortality.
What is psoriatic arthritis?
It is the most common associated condition with psoriasis. It involves painful inflammation of the joints and can occur anywhere although most frequent in fingers and toes. 30% of plaque type psoriasis involve the joints. The patients have a poor quality of life.
What are some additional comorbidities in psoriatic patients?
Metabolic syndromes like obesity, hyperlidemia, diabetes 2 and cardiovascular diseases. Chronic inflammatory bowel disease, Chrons disease and uveitis.
What are some differential diagnosis of psoriasis?
Plaque type : LRP, seborrheic dermatitis, pityriasis ruba pilaris.
Guttate : Leus, pytiriasis rosea gilbert.
Inverse : Mycosis.
Eritrodermic : Atopic dermatitis, mycosis fungoides.
Pustular type : Reiter syndrome.
Therapy for psoriasis?
Therapy is chosen based on severity, type of psoriasi, lesions, site of lesion. PASI score for severity, >10 is severe. Depending on this we can use topical treatment and phototherapy for mild to moderate cases or biological drugs like anti IL and other systemic therapies for more severe cases.
Ex. Secukinumab is a monoclonal antibody against IL17.
Epidemiology of cutaneous drug reactions? How are they classified?
The skin is the most affected organ. It is more common in women, elderly and immunocompromise patients. Antibiotics, NSAIDs, and anti-epileptic’s are the most commonly associated with cutaneous drug reactions.
- Non- immunological (toxic drug reactions, 70%): dose-dependent, prompt resolution at suspension, it is predictable.
- Immunological (allergic): independent from dose, less common, not predictable and get worse at subsequent exposure.
- Idiosyncratic: not predictable interaction between immunological and genetic-metabolic mechanism.
How are allergic reactions classified?
Type I: IgE-mediated, manifests as urticaria,
angioedema and anaphylaxis (insulin).
• Type II: Cytotoxic reaction produces hemolysis and
purpura. Caused by penicillin, cephalosporins,
sulfonamides and rifampin.
• Type III: Immune-complex reactions, resulting in
vasculitis, serum sickness and urticaria. Caused by
salicylates, chlorpromazine and sulfonamides.
• Type IV: Delayed-type reactions, cell-mediated
hypersensitivity, result in contact dermatitis,
exanthematous reactions and photoallergic
reactions. Most common is not dose-dependent.
Usually, it begins 1-3 weeks after medication is
started. Type IV is the most common reaction
associated with cutaneous drug reactions.
What are angioedemas and urticaria? What are they associated to?
They are one of the most frequent manifestations of drug hypersensitivity reactions that may be IgE mediated or due to direct mast cell activation through non IgE medicated mechanism. Reactions can be immediate or delayed.
Urticaria aka hives is intensely pruritic, circumscribed, raised and erythematous.
Angioedema is the swelling of deeper dermis and subcutaneous tissue than can co exist with hives. It can be disfiguring if it involves the face and can be life threatening if there is involvement of the upper airway. They are associated to antibiotics, NSAIDs, analgesics and ACE inhibitors.
What is the mechanism of action of hypersensitivity of IgE?
IgE is attached to membranes of mast cells, then antigen of the drug comes and it attaches to IgE triggering and activating mast cells. This causes the delivery of vasoactive substances (histamine) that causes edema (to release urticaria).
What are exanthematous drug eruptions?
They are the most common cutaneous reactions accounting for 90% of all drug rashes. Rashes are referred to as exanthematous, morbilliform and maculopapular eruptions. Most commonly occurring after prescribed drugs like antibiotics and follow a type IV delayed reaction. It manifests 4 to 14 days after initial drug administration. It presents no vesicles but pruritus. Resolution in 1 to 2 weeks without complications.
