Immunology - Lecture Note

Immunology • • • • Anaphylaxis Uriticaria Angioedema Eczema 2 3 4 5 Immuno 1 of 9 Anaphylaxis A massive Type I, IgE mediated mast cell hypersensitivity reaction NB: anaphylactoid response is clinically the same but doesn’t involve antibodies (usually drug reactions) Clinical features Angio-oedema à warm peripheries Laryngeal oedema & bronchial spasm Urticaria Difficulty breathing Hypotension due to hypovolaemia Rhinitis Conjunctivitis Abdominal pain, vomiting, diarrhoea. Cardiovascular collapse is common, especially in response to intravenous drugs or stings, and is caused by vasodilatation and loss of plasma from the vascular compartment. If not treated swiftly cardiac arrest may occur. Treatment Consider when compatible history of severe allergic-type reaction with respiratory difficulty and/or hypotension especially if skin changes present Oxygen Stridor, wheeze, respiratory distress or clinical signs of shock EPINEPHRINE (adrenaline) 1:1000 solution 0.5 ml (500 micrograms) i.m. Repeat in 5 minutes if no clinical improvement Antihistamine (chlorpheniramine) 10-20 mg slow i.v. For all severe or recurrent reactions and patients with asthma give hydrocortisone 100-500 mg i.m./or slowly i.v. If clinical manifestations of shock do not respond to drug treatment give 1-2 litres i.v. fluid. Rapid infusion may be necessary Adrenaline’s A receptor actions reverse peripheral vasodilation and reduce oedema. Its b receptor activity dilates the airways, increases the force of myocardial contraction, and suppresses histamine and leukotriene release. Antihistamines should be used routinely in the management of the anaphylactic reactions to help encounter histamine mediated vasodilatation. Their use alone, is however, unlikely to be lifesaving. Corticosteriods are slow acting drugs (4-6 hours for effect) even given IV. They may, however, help in the emergency treatment of an acute attack, and they also have a role in preventing or shortening protracted reactions. Follow up Take bloods for tryptase level to confirm the diagnosis Avoid skin prick allergy tests in future (use specific IgE tests instead) Immuno 2 of 9 Urticaria Itchy red wheal (nettle rash) which blanches with pressure Due to degranulation of mast cells à leaky capillaries à Oedema, vasodilatation and cellular infiltrate of lymphocytes, polymorphs and histiocytes May preceed - vasculitis, pemphigoid, dermatitis herpetiformis Can be physical urticaria Dermatographism – due to histamine release on light pressure Cold/heat urticaria Solar urticaria – reaction to sunlight exposure Cholinergic – after exertion, stress or exposure to heat Aquagenic – occurs on contact with water Non physical urticaria Food – fish, dairy, eggs, chocolate, nuts, strawberry, pork, tomato Food additives – dyes, sodium benzoates Salicylates – in medicines and foods Infection – bacterial, viral and protozoal Systemic – autoimmune, collagen, carcinoma Contact – may occur with many things Papular – insect bites Inhalants – house dust, animal danders Management Eliminate all possible causes Antihistamines & H2 blockers (e.g. cimetidine) Adrenaline –for acute attacks, esp if angioedema of resp tract Systemic corticosteroids only in acute cases Toxic epidermal necrolysis Rapidly evolving mucocutaneous reaction Widespread erythema, necrosis, and bullous detachment of the epidermis resembling scalding Complications Epithelial loss results in vulnerability to bacterial and fungal infections and predisposes to septicemia. Mucosal membranes are affected to a varying extent and can cause GI hemorrhage, respiratory failure, ocular abnormalities, and genitourinary lesions. Significant fluid loss from extensive skin lesions as well as an inability to tolerate oral intake can lead to hypovolemia, acute tubular necrosis, and shock. Causes Sulfonamide antibiotics Anticonvulsants (phenobarbital, phenytoin, carbamazepine, valproic acid) Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) Allopurinol Antiretroviral medications Corticosteroids Immuno 3 of 9 Angioedema Subcutaenous non-pitting soft tissue swelling (eyes, lips, hands, mouth) When in the abdomen à Recurrent abdominal pain (intestinal oedema) Due to mast cell degranulation (spontaneous or IgE mediated) May occur alone or with urticaria Causes: Most commonly part of an IgE mediated response Can be assoc with changes in temperature or pressure on skin (dermatographism) Drugs include ACEi’s, aspirin, NSAIDs, radiocontrast media, opiates and Abx Hereditary angioedema involves recurrent, self limiting attacks involving the skin, sub cut tissues and upper resp tract. Will not respond to antihistamines Diagnosis based on Hx Rx – avoid triggers, give oral H1 antihistamines prophylactic or just with sx, steroids Immuno 4 of 9 Eczema 10% of the population affected Vasodilatation à erythema & heat Exudate of plasma & inflammatory cells à oedema Release of inflammatory mediators à pain & itch • Develop a rational method for classifying eczema Acute Dermal vessels v/d à erythema Epidermal oedema à separation of keratinocytes (spongiosis) Inflammatory cells invade dermis/epidermis à oedema Appearance is modified by scratching Sub acute Less spongiosis à less vesicles Epidermal cell malfunction Thickening (acanthosis) Increased keratin (hyper/parakeratosis) à scaling Chronic Marked acanthosis, hyper & parakeratosis à thickened rough “lichenification” with dry, scaly & fissures Persistent vasodilatation & inflammatory cells à erythema • Name the main types of endogenous and exogenous eczema Endogenous Atopic Seborrheic Asteatotic Gravitational Discoid Exogenous Irritant – most people’s skin would respond if in contact for long enough Infective Allergic contact – due to a hypersensitivity – normal skin wouldn’t response • List the main side effects of topical steroids and the measures needed to safeguard against these Tachyphylaxis Tolerance to the vasoconstrictive action of topical steroids à capillaries do not constrict With high potency can occur within 4 days, Takes 4 days to return after stopping therapy. Steroid rosacea In fair-skinned people who already have rosacea Occurs on reducing from prolonged steroid use. Skin Atrophy Thinning of the epidermis and changes in the connective tissue of the dermis. The skin becomes lax, wrinkled, and shiny, visible telangiectasias, hypopigmentation, and prominence of underlying veins. Reversible in most cases but may take months to recover Striae - Stretch Marks In areas where skin touches skin such as the groin and armpits Permanent and irreversible, may be itchy (requiring low dose steroid to relieve. Alteration of Infection Alters the immune response and so the appearance of fungal infections à tinea incognito. Topical Steroid Allergy To a component of the topical steroid base. High risk in those with multiple prescriptions Glaucoma Isolated cases reports of people developing glaucoma after long-term use of topical steroids around the eyes. • Know how to apply topical treatments correctly and familiar with the finger tips unit Immuno 5 of 9 Should be applied in the direction of the hair 1 finger tip unit is the amount in a single line along the distal phalange of the index finger 1 finger tip unit should be sufficient for one hand area – body plans are available to show how many finger tip units each area requires • Describe the distribution and morphology of atopic, discoid, varicose, pompholyx and seborrhoeic eczema Atopic Due to – selective activation of TH2 CD4 lymphocytes in the skin 15-20% prevalence, improves with age Infants – face & exposed surfaces Children – flexures Itchy erythematous scaly patches (esp in flexor surfaces) – vesicles if acute Scratching à thickening Increased IgE antibodies, skin prick tests often +ve Diagnosis Itchy skin for the last 12 months + 3 of the following Personal / family history of atopy Visible flexural dermatitis (cheeks < 10yrs) Dry skin in last yr Hx of flexural involvement Early onset (<2yrs) Treatment Education, advise carers, keep nails short (reduce excoriation) Avoid allergens & irritants Use soap substitute Creams (aq), ointments (soft paraffin) bath oils (oilatum) Steroids – v/c and inactivate inflammatory mediators Mild – 1% hydrocortisone bd (sparingly) Mod – hydrocortisone butyrate Potent – betamethasone bd (4-7 days only) Occlusive bandaging (with tar, zinc paste or wet wraps) Antihistamines (if poor sleep) Antibiotics (if bright red with pustules & exudates) – fluclox / erythromycin Topical tacroliums – similar to potent steroid but don’t think skin If all else fails Oral steroids – short term to bring under control UV light Cyclosporin A (check BP, resp function, increased malignancy risk) ? Diet, ? Chinese herbs? Psychological intervention? Complications Of bacteria – staph / strep Viral – molluscum, HSV, Warts, herpeticum Of Treatment – skin thinning, striae, adrenal suppression Eczema herpeticum – virus colonisied eczematous & normal skin à painful puctuate erosions à Rx with oral / IV acyclovir = emergency Seborrheoic eczema Abnormal response to commensal yeast (pityrosporum ovale) Adults - Most common in young men Features Affects areas rich in sebaceous glands (face, scalp, upper trunk) Erythema, scaling, dandruff Folliculitis and flexural variants Treatment Ketoconazole shampoo, imidazole +/- 1% hydrocortisone Immuno 6 of 9 Often recurs Children First few weeks of life Features Moist shiny erythema in folds Scalp has yellow scales Treatment Emollients, 1% hydrocortisone, +/- antifungal, aq salicylic acid & olive oil for scalp Asteatotic Eczema (without fat) Common in elderly when skin fat is decreased Surface dries out à craquale (like crazy paving) Rx – topical steroids f.b. long term emollients, avoid excessive washing Graviational (static / varices) On lower legs, assoc with poor venous return Rx – emollients + mild-mod topical steroids, compression hosiery. NB – risk of ulceration if severe Discoid Caused by substances affecting skin integrity (chemical damage – alkalia, detergent, water) Most often on hands (hair dressers, nurses, young mums) Most common form of industrial dermatitis Atopic individuals are more susceptible Rx – avoid irritants, wear cotton gloves where possible, emollients & topical steroids Contact dermatitis (allergic) Idiosyncratic type IV hypersensitivity reaction to exogenous substance Usually occurs in industry – nickel is most common, look for distribution pattern, also seen with chromates (builders), epoxy (engineers), rubber (drs), can be a big problem in leg ulcer patients Ix - Patch testing à identify allergens Rx – avoid allergens, emollients, topical steroids Hand dermatitis May be endogenous, irritant or contact (often mixed) Women : men = 2:1 Morphology very variable but if unilateral think fungus Ix – patch testing Rx – v.difficult, often hard to avoid triggers, can à loss of employment Acute – KMnO4 soaks, emollients, topical steroids Chronic – avoid irritants if possible, emollients, steroids, retinoids, attention to hand care Immuno 7 of 9 Miscellaneous • Describe the indications for and interpretation of the following investigations: C-reactive protein & ESR Acute phase response Macrophage detects problem à releases enzymes to prevent haemorrhage / sepsis à cytokine release Acts on bone marrow à inhibits RBC release (limit Fe for bacteria), increases releae of platelets & neutrophils Acts of brain à resets hypothalamus to higher body temp to fight infection Acts on Liver à increased acute phase proteins (inc CRP & fibrinogen) à opsonisation, haemostatsis & protease inhibition Protein aggregation (and/or immunoglobulins)à Increased ESR (max 200) Overall acute phase à Pyrexia Normochromic, Normocytic anaemia Reactive thrombocytosis Raised ESR Raised CRP (NB: If ESR is elevated and CRP isn’t à send Ig levels to check for myeloma) Serum Ig Total Ig levels – if suspected abnormal immune system Serum and urine electrophoresis Separates the Ig down by mass to IgA, IgE etc Use to look mainly for paraproteins (most commonly due to haem malignancy) Can have benign paraproteinaemia in the elderly Complement levels Involved in Opsonisation, inflammatory response and cell membrane lysis Deficiency seen in hereditary angioedema, some nephritis and paroxysmal nocturnal haematuria Abnormal levels seen in autoimmune diseases Autoantibodies (including the autoimmune screen) Aid in diagnosis of SLE, autoimmune hepatitis etc Total and specific IgE levels Used for assessing allergies Skin prick and patch testing For dermatological response to allergens • Describe the ways in which the immune system may be manipulated therapeutically. Increased – by marrow stimulation Decreased – by steroids, immunosupressants (e.g. azothioprine etc) New antigen responses – by vaccination • List the organs that are commonly transplanted and outline the main indications for transplantation. Outline the main immunological barrier to successful transplantation and how this may be overcome by tissue typing and immunosuppressive therapy. Immuno 8 of 9 Organs Cornea Heart - cardiomyopathy Lungs - CF Liver – end stage failure, metabolic disease, hepatoma Kidney – end stage renal failure Skin - burns Marrow – malignancy, immune deficiency Barriers Rejection (graft V host disease) Avoid by good donor tissue typing and appropriate immunosupression therapy Immuno 9 of 9