DRUG ERUPTIONS

Adverse drug reactions are a common cause of dermatologic consultation. drug eruptions are not simply drug "allergy," but result from variations in drug metabolism immune status coexistent viral disease the patient's racial background the patient's HLA status the inherent chemical structure dosage of the medication itself

Non-allergic drug reactions Overdosage Overdosage accumulation of drugs accumulation of drugs unwanted pharmacological effects (stretch marks from systemic steroids). unwanted pharmacological effects (stretch marks from systemic steroids). idiosyncratic (odd reaction peculiar to one individual) idiosyncratic (odd reaction peculiar to one individual) mouth ulcers cytotoxicity of methotrexate. mouth ulcers cytotoxicity of methotrexate. Silver based preparations, (argyria). Silver based preparations, (argyria). vaginal candidiasis: antibiotics remove resident bacteria vaginal candidiasis: antibiotics remove resident bacteria Dapsone or rifampicin, lepromatous leprosy, may cause erythema nodosum leprosum Dapsone or rifampicin, lepromatous leprosy, may cause erythema nodosum leprosum

Allergic drug reactions appear after the latent period appear after the latent period Chemically related drugs may cross-react. Chemically related drugs may cross-react. majority caused by cell-mediated immune reaction majority caused by cell-mediated immune reaction commonly a maculopapular eruption commonly a maculopapular eruption Helper CD4+ T cells morbilliform eruptions, Helper CD4+ T cells morbilliform eruptions, cytotoxic CD8+ T cells predominate in blistering eruptions ( TEN, Stevens–Johnson syndrome) and fixed drug eruptions. cytotoxic CD8+ T cells predominate in blistering eruptions ( TEN, Stevens–Johnson syndrome) and fixed drug eruptions. urticaria and angioedema, immunoglobulin E (IgE) mediated type I hypersensitivity reactions urticaria and angioedema, immunoglobulin E (IgE) mediated type I hypersensitivity reactions vasculitis type III immune complex-mediated reactions. vasculitis type III immune complex-mediated reactions.

Evaluation 1. Previous general experience with the drug 1. Previous general experience with the drug 2. Alternative etiologic candidates 2. Alternative etiologic candidates 3. Timing of events 3. Timing of events 4. Drug levels and evidence of overdose 4. Drug levels and evidence of overdose 5. Response to discontinuation (dechallenge) 5. Response to discontinuation (dechallenge) 6. Rechallenge 6. Rechallenge

Exanthems

Lesions tend to appear first proximally, in the groin and axilla, generalizing within 1 or 2 days. the face may be spared. Pruritusis usually prominent, helping to distinguish a drug eruption from a viral exanthem. Antibiotics, penicillins and trimethoprim

Urticaria/angioedema Medications may induce urticaria by immunologic and nonimmunologic mechanisms. In either case, clinically there are pruritic wheals or angioedema. Urticaria may be part of a more severe anaphylactic reaction (bronchospasm, laryngospasm, or hypotension).

Aspirin and the NSAIDs common causes of nonimmunologic Immunologic urticaria is most associated with penicillin Angioedema is a known complication of angiotensin- converting enzyme inhibitors. Lisinopril and enalapril more commonly than captopril Lisinopril and enalapril more commonly than captopril Angioedema typically occurs within a week of starting therapy.

Bullous drug reactions (Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN])

S]S and TEN are considered by some as parts of a disease spectrum based on the following: 1.commonly induced by the same medications. 2.Patients initially presenting with S]S may progress to extensive skin loss resembling TEN. 3.The histologic findings are indistinguishable. More than 100 medications have been reported to cause S]S and TEN. S]S has less than 10% body surface area (BSA) involved, cases with 10-30% are S]S- TEN overlap cases, and more than 30% BSA erosion is called TEN.

1. trimethoprim-sulfamethoxazole 2.carbamazepine. 3.Antibiotics (long acting sulfa drugs and penicillins), Fever and influenza-like symptoms precede eruption Fever and influenza-like symptoms precede eruption Skin lesions appear on face and trunk and rapidly spread. macular, followed by desquamation, or may form atypical targets that coalesce, form bullae, then slough. Skin lesions appear on face and trunk and rapidly spread. macular, followed by desquamation, or may form atypical targets that coalesce, form bullae, then slough. In SJS, two or more mucosal surfaces are also eroded, the oral mucosa and conjunctiva being most frequently affected. In SJS, two or more mucosal surfaces are also eroded, the oral mucosa and conjunctiva being most frequently affected. photophobia, difficulty with swallowing, rectal erosions, painful urination, and cough photophobia, difficulty with swallowing, rectal erosions, painful urination, and cough

Fixed drug reactions Fixed drug reactions (FDE) are common. Fixed drug eruptions are so named because they recur at the same site with each exposure to the medication. The time from ingestion of the offending agent to the appearance of symptoms is between 30 minutes and 8 hours, averaging 2 hours.

In most patients, six or fewer lesions occur, and frequently only one. They may present anywhere on the body, but half occur on the oral and genital mucosa. Clinically, an FDE begins as a red patch that soon evolves to an iris or target lesion similar to erythema multiforme, and may eventually blister and erode. Clinically, an FDE begins as a red patch that soon evolves to an iris or target lesion similar to erythema multiforme, and may eventually blister and erode.

Lesions of the genital and oral mucosa usually present as erosions. Most lesions are 1 to several cm in diameter, but larger plaques may occur Characteristically, prolonged or permanent postinflammatory hyperpigmentation results,

Erythema multiformeErythema multiforme Target-like lesions appear mainly on the extensor aspects of the limbs, and bullae may form. Target-like lesions appear mainly on the extensor aspects of the limbs, and bullae may form. Sulphonamides Sulphonamides barbiturates barbiturates lamotrigine lamotrigine phenylbutazone phenylbutazone

Acute generalized exanthematous pustulosis suggests acute pustular psoriasis, with a dramatic generalized eruption of red plaques studded with tiny non-follicular pustules. suggests acute pustular psoriasis, with a dramatic generalized eruption of red plaques studded with tiny non-follicular pustules. Patients have fever and leucocytosis. Patients have fever and leucocytosis. Antibiotics and diltiazem are the most common drugs to induce AGEP, which usually develops after only a few days. Antibiotics and diltiazem are the most common drugs to induce AGEP, which usually develops after only a few days.

Drug rash with eosinophilia and systemic signs syndrome triad of fever, rash (from morbilliform to exfoliative dermatitis) and internal organ involvement (hepatitis, pneumonitis,nephritis and haematological abnormalities). triad of fever, rash (from morbilliform to exfoliative dermatitis) and internal organ involvement (hepatitis, pneumonitis,nephritis and haematological abnormalities). An eosinophilia and lymphadenopathy An eosinophilia and lymphadenopathy develops 3–8 weeks after starting the causative drug. develops 3–8 weeks after starting the causative drug. anticonvulsants anticonvulsants minocycline minocycline allopurinol allopurinol sulphonamides sulphonamides

Hair loss Hair loss Predictable acitretin and cytotoxic agents, Predictable acitretin and cytotoxic agents, an unpredictable anticoagulants, antithyroid drugs. an unpredictable anticoagulants, antithyroid drugs. Diffuse hair loss use of an oral contraceptive. Diffuse hair loss use of an oral contraceptive. Hypertrichosis Hypertrichosis dose-dependent effect of diazoxide, minoxidil and ciclosporin. dose-dependent effect of diazoxide, minoxidil and ciclosporin. Pigmentation Pigmentation Melasma may follow an oral contraceptive Melasma may follow an oral contraceptive phenothiazines blue–grey colour to exposed areas phenothiazines blue–grey colour to exposed areas heavy metals can cause a generalized browning heavy metals can cause a generalized browning clofazimine makes the skin red clofazimine makes the skin red mepacrine turns the skin yellow mepacrine turns the skin yellow minocycline turns areas of leg skin a curious greenish grey colour minocycline turns areas of leg skin a curious greenish grey colour

Photosensitivity reactions (photosensitive drug reactions) most photosensitizing drugs have absorption spectra in the UVA, UVA penetrates into the dermis where the photosensitizing drug is present. Phototoxic reactions are related to dose of both the medication and the UV irradiation. appear from hours to days after exposure. Phototoxic reactions are related to dose of both the medication and the UV irradiation. appear from hours to days after exposure. Photoallergic reactions are typically eczematous and pruritic, and may first appear weeks to months after drug exposure. Photoallergic reactions are typically eczematous and pruritic, and may first appear weeks to months after drug exposure..Treatment may include dose reduction and photoprotection, with a sunblock with strong coverage through the whole UVA spectrum.

Treatment withdraw the suspected drug withdraw the suspected drug In urticaria, antihistamines are helpful. In urticaria, antihistamines are helpful. topical or systemic corticosteroids can be used, and applications of calamine lotion may be soothing. topical or systemic corticosteroids can be used, and applications of calamine lotion may be soothing. Plasmapheresis and dialysis Plasmapheresis and dialysis Anaphylactic reactions require special treatment Anaphylactic reactions require special treatment One or more injections of adrenaline (epinephrine) 0.3–0.5 ml should be given subcutaneously One or more injections of adrenaline (epinephrine) 0.3–0.5 ml should be given subcutaneously slow intravenous injection of chlorphenamine maleate (10–20 mg diluted in syringe with 5–10 mL blood). slow intravenous injection of chlorphenamine maleate (10–20 mg diluted in syringe with 5–10 mL blood). intravenous hydrocortisone (100 mg), it should be given in severely affected patients. intravenous hydrocortisone (100 mg), it should be given in severely affected patients.