Drug induced skin disorders, Assignments of Clinical Medicine

Download Drug induced skin disorders and more Assignments Clinical Medicine in PDF only on Docsity! | [ -INDUCED 33 SKIN eee Izzatullah Khan é Basresssses: a 6  ADRs are an inevitable consequence of modern drug therapy. They are an important cause of iatrogenic illness in terms of morbidity and mortality.  Fortunately, only about 2% of all drug-induced skin reaction are sever and very few are fetal.  However, all drug-induced skin eruption can cause morbidity, affect the patient’s confidence in the prescriber and future adherence with medication  Therefore, all drug-induced rashes should be carefully evaluated and documented.  Phototoxic reactions, which are more common resemble severe sunburn and progress to blistering.  They dose dependent for both drug and sunlight, occur within 5-15hrs of taking the drug and subside quickly on drug withdrawal.  Photoallergic rashes are usually eczematous but may be lichenoid, urticarial, bullous or purpuric.  They are not e dose dependent and occur following exposure to normal amount of sunlight exposure.  The onset can be delayed by weeks or months, while recovery is often slow following drug withdrawal  Rarely, a photoallergic state can persist for years after the drug responsible has been discontinued.  Patients receiving known photosensitizing drug should be advised to avoid strong sunlight.  They should also be advised to use a broad-spectrum topical sunscreen, providing both UVA protection and UVB cover. DRUGS CAUSING LIGHT- INDUCED ERUPTION  Topical preparation  Topical NSAIDs  Component of sunscreen such as para-aminobenzoic acid, benzophenone  Systemic drugs  Phototoxic reaction  Amiodarone  Nalidixic acid  NSAIDs  Chlorpromazine  Tetracyclines  Photoallergic reaction  Grisofulvin  Sulphonamides  Suphonylureas  Thiazise diuretics  The purpose pathogenic mechanisms are: 1. Drug or drug metabolite deposition in the dermis and epidermis. E.g. agyria, in which topical silver sulphadiazine, causes a slate grey discolouration of the skin. 2. Enhanced melanin production with or without an increase in the number of active melanocytes . iii. Nail changes  The growth and colour of finger and toenails can be modified by drugs. Abnormalities of texture and architecture of the nail unit can also be drug-induced.  Blue discoloration of the nail can result from therapy with mepacrine, while a blue black pigmentation may occur due the minocycline and certain cytotoxic drugs.  Potassium permanganate solution will dye nails brown. White nails(leuconychia) can be result from treatment with chemotherapy agents, especially cyclophosphamide, doxorubicin, vincristine.  Onycholysis is characterized by separation of the nail plate from the underlying nail bed. Any cytotoxic agnent may induce onycholysis by direct toxicity to the matrix. iv. Hair changes  Drug may exert an effect on the hair follicle or on growth cycle of hair. The cycle of hair growth involve anagen ( the growth phase of the hair), catagen (the resting phase) and telogen (the shedding phase).  Loss of hair.  Drug induced alopecia may be partial or complete. The relationship between the introduction of drug and hair loss depend on the part of the hair cycle with which the drug interfere. ii. Mild drug-induced skin disorders  Drug-induced exanthems  A drug-induced exanthem(widespread rash) is the most common type of drug reaction in the skin.  Exanthems are characterized by erythema (redness) and may be morbilliform (resembling measles) or maculopapular (a mixture of flat and raised area).  Less frequently there may be blister, which may be small (vesicle ) or large (bullae), and the skin may feel hot, burning or itchy.  The proportion of the body surface area (BSA) involved varies from case to case but when severe, involving more than 90% of the BSA, the presentation is referred to as ‘erythroderma’ maculopapular (a mixture of flat and raised area) morbilliform (resembling meales)  The common cause of drug-induced exanthems include antibiotics(e.g. sulphonamides, ampicillin, isoniazide), antconvulsants and malarilas.  Most drug-induced exanthems begin within 7 days of comencing a drug, the mechanism being a delayed (type iv) hypersensitivity.  If the drug can be identified, it should be stopped, appropriate symptomatic relief instituted with antihistamin, and topical steroids. A clear record of the reaction should be made in the patient’s notes.  Pruritus  Pruritus (itching) can accompany a drug rash, or may be an isolated symptoms provoked by a medication.  The most common example trigger of drug-induced pruritus is the administration opiate analgesics and their related synthetic derivatives such tramadol.  Opiate induced pruritus is centrally mediated rather than by the peripheral nerves; therefore antihistamines do not, in general ameliorate the itch.  This can pose a particular problem in the palliative care setting where opiate analgesic are required regularly.  Fixed drug eruption  Fixed drug eruption is characterized by one or more inflammatory patches the recur at the same cutaneous or mucosal sites each time the patient is exposed to the offending drug.  The eruption usually involve the torso, hands, feet, face or genitalia, and is characterized by a deep red, circular, well-demarcated patches.  They take between 2 and 24hrs to develop following drug ingestion. On the first exposure, there is usually only one lesion, but subsiquent exposure can result in multiple lesion.  Drugs causing fixed drug eruption include, ampicillin, aspirin, barbiturates, metronidazole, NSAIDs, oral contraceptives. Fixed drug eruption Hyperpigmentation fixed drug eruption Psoriasiform eruption  Psoriasiform eruption  Drugs can either induced psoriasis in predisposed patients or induced psoriasiform rashes in previously unaffected patients.  It is characterized by itchy, scaly red patches on the elbows, forearm, knee and sclap,  Drugs responsible for psoriasiform include beta blockers, lithium, antimalarial, and ACE inhibitors  Lichenoid eruption Drug induced linchenoid eruption resemble lichen planus, occurring as flat mauve lesion. The lesion can be seen at any site, but are found mainly on the forearm, neck and on the inner surface of the thighs The eruption resolves with drug withdrawal, with or without topical steroid, but post inflammatory hyperpigmentation is often long lasting. Drug causing lichenoid eruption include antimalarials, aspirin, CCB,ACE Inhibitors, etc.  Eczematous eruption and contact dermtitis  Retinoid drugs and statins having drying on the skin, and can induce pre-existing eczema or precipitate eczema in susceptible individual.  Irritant contact dermattitis may be seen in preparation with an alcohol base, such as topical antiboitics, benzoyl peroxide, tar,  Allergic cntact dermititis is a delayed hypersensitivity reaction which can be developed to any topical prepartion.  Most commonly, this will be to excipient contained in preparation e.g. preservative sodium bmetacisulphite  EM is triggered by the drug include Allopurinol, barbiturates, antiretroviral (e.g. nevirapine), carbamazepine,macrolide antibiotics, NSAIDs,phenytoin etc.  Drug induced EM will usually present within 2 weeks of starting a new medication.  Once the responsible drug has been stopped, treatment is symptomatic with paracetamol, topical steroids and appropriate topical therapy for the mouth and other involved mucosal surface.  Stevens-Johson syndrome (SJS) and toxic epidermal necrolysis (TEN)  Stevens-Johson syndrome (SJS) and toxic epidermal necrolysis (TEN) are terms used to describe a life- threatening mucocutaneous drug hypersensitivity syndrome characterized by blistering and epidermal sloughing.  In SJS, there is epidermal detachment of <10% BSA, in TEN there is detachment of >30% of the BSA, while cases with 10-30% involvement are labeled SJS/TEN overlap.  Nearly all cases are caused by a reaction to a drug, most often sulfa antibiotics; barbiturates; anticonvulsants, such as phenytoin and carbamazepine; certain nonsteroidal anti-inflammatory drugs (NSAIDs); or allopurinol. Some cases are caused by a bacterial infection.  Occasionally, a cause cannot be identified. The disorder occurs in all age groups but is more common among older people, probably because older people tend to use more drugs. The disorder is also more likely to occur in people with AIDS.  Symptoms  Stevens-Johnson syndrome and toxic epidermal necrolysis usually begin with fever, headache, cough, and body aches. Then a flat red rash breaks out on the face and trunk, often spreading later to the rest of the body in an irregular pattern.  The areas of rash enlarge and spread, often forming blisters in their center. The skin of the blisters is very loose and easy to rub off.  In Stevens-Johnson syndrome, less than 10% of the body surface is affected. In toxic epidermal necrolysis, large areas of skin peel off, often with just a gentle touch or pull. In many people with toxic epidermal necrolysis, 30% or more of the body surface peels away.  Treatment  People with Stevens-Johnson syndrome or toxic epidermal necrolysis are hospitalized. Any drugs suspected of causing the disorder are immediately discontinued. When possible, people are treated in a burn unit and given scrupulous care to avoid infection. If the person survives, the skin grows back on its own, and unlike burns, skin grafts are not needed. Fluids and salts, which are lost through the damaged skin, are replaced intravenously.  Use of corticosteroids to treat the disorder is controversial. Some doctors believe that giving large doses within the first few days is beneficial, whereas others believe that corticosteroids should not be used. These drugs suppress the immune system, which increases the potential for serious infection. If infection develops, doctors give antibiotics immediately.  In many cases, intravenous human immunoglobulin prefer to treat toxic epidermal necrolysis. This substance helps to prevent further immune damage to the skin and further progression of blistering.  Drug Reaction with Eosinophilia & Systemic Symptoms (DRESS)/Drug-induced Hypersensitivity Syndrome  The DRESS/drug-induced hypersensitivity syndrome (DIHS), is used to describe a severe drug hypersensitivity eruption associated with constitutional symptoms, such as fever, malaise, lymphadenopathy, hepatitis, myocarditis, interstitial nephritis and pneumonitis.  To meet the diagnostic criteria, there will also be a haematological abnormality either a raised eosinophil count (>1.5×109 /L) or the presence of atypical lymphocytes in the blood film.  DRESS is characterized by its long latency of onset with syndrome usually presenting between 2-8 weeks of commencement of the causative drug.  The important point is the medication history, as often the drug responsible may be overlooked if it is considered to have started too long ago.  Morbidity and mortality has been estimated at 10%.  Systemic steroids are usually administered, and may be beneficial.  Management involving the suspected drug, and supportive care dictated by extent of involvement.