DRUG INDUCED DERMATOLOGICAL DISEASES

ByM.Vinay Kumar Chakravarthy.B.Pharmacy 4th Year 2nd Sem

010760

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INTRODUCTION:

Skin is the organ most frequently affected by the adverse drug reactions.

Virtually all drugs may induce skin reactions.Although most drug related skin eruptions are not serious, some are severe and potentially life threatening, such as Steven’s Johnson Syndrome and Toxic epidermal Necrolysis.

Drug eruptions can also occur as part of a spectrum of multiorgan involvement, for example in drug induced systemic Lupus Erythematosus.Apr 12, 2023 2

Etiology:

The cause of skin reactions is often unknown. Although many have an allergic or toxic basis.

Allergic reactions may be independent of dose and can persist long after the causative drug has been withdrawn.In penicillin hypersensitivity reactions, for example, the skin condition may worsen for seven to 10 days after the drug is withdrawn.

In contrast, toxic reactions are dose-dependent and skin symptoms generally resolve fairly soon after the causative agent is withdrawn.

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Genetic factors may be an important influence; for example, acetylator status may predispose to sulphonamide reactions.

Hepatic disease, renal disease, systemic lupus erythematosus and AIDS are some of the disease states associated with an increased risk of skin reactions.

The route of administration can influence drug allergy; in general, topical application has the greatest propensity to induce allergy, followed by parenteral then oral administration.

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Cutaneous drug reactions may be classified with respect to pathogenesis and clinical morphology.

They may be mediated by immunologic and nonimmunologic mechanisms.

Immunologic reactions require host immune response and may result from IgE-dependent, immune complex-initiated, cytotoxic, or cellular immune mechanisms.

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Nonimmunologic reactions may result from nonimmunologic activation of effector pathways, overdosage, cumulative toxicity, side effects, ecologic disturbance, interactions between drugs, metabolic alterations, or exacerbation of preexisting dermatologic conditions.

Common Drug Rashes

• Exanthematous • Urticaria• Fixed-drug eruption• Phototoxic reactions• Acne

Serious Drug Rashes• Toxic epidermal

necrolysis• Stevens-Johnson

syndrome

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Diagnosis

It can be difficult to diagnose a drug eruption confidently.

Many reactions cannot be distinguished from naturally occurring eruptions so misdiagnosis is common and this may unnecessarily limit the future use of a particular medication.

Furthermore, patients are often taking more than one drug, making it more difficult to confirm the cause.

Drugs suspected of causing skin reactions should usually be withdrawn and not used again in that patient.

Symptomatic treatment with calamine lotion or systemic antihistamines may be required. For more serious reactions, systemic corticosteroids may be indicated.

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Pencillins and sulfonamides frequently cause these eruptions.

• DRUGS THAT COMMONLY CAUSE EXANTHEMATOUS REACTIONS Antituberculous drugs Barbiturates Carbamazepine Cephalosporins Erythromycin Frusemide Gold Gentamicin Isoniazid Nitrofurantoin Penicillins Phenothiazines Phenylbutazone Phenytoin Sulphonamides Thiazides

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FIXED DRUG ERUPTION:

The site of eruption is fixed, i.e, when the individual takes the causative drug again the eruption generally recurs within 8 hrs at exactly same site as was previously affected.

PATHOGENESISFDEs are caused by the activation of cytotoxic T lymphocytesin the basal layer by drugs. Common causative drugs areNSAIDs, tetracyclines, sulfa drugs, phenacetin, food additives etc.,

SYMPTOMSThe sites mainly affected are the hands, feet and perianal areas. It consists of erytematous round or oval lesions of a dusky brown colour sometimes featuring blisters or vesicles.

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TREATMENTHealing occurs over 7 to 10 days after the causative drug is stopped.Topical corticosteroids may help to reduce the intensity of the reaction.

DRUGS THAT CAUSE FIXED DRUG ERUPTION Barbiturates Carbamazepine ChlordiazepoxideNSAIDsPhenolphthaleinPhenylbutazoneQuinineSalicylatesTetracyclinesTrimethoprim

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URTICARIA (nettle-rash or hives )

Medically, urticaria may be defined as skin eruption, which is allergic (or non-allergic) in origin and is characterized by profound itching, red circular or irregularly shaped eruptions on any part of the body

SYMPTOMSUrticaria lesions present as raised, itchy, red blotches or weals that are pale in the centre and red around the outside. Drug-induced urticaria may occur after the first exposure to a drug or after many previously well-tolerated exposures.

Urticaria is characterized as acute when it lasts 6 weeks or less and chronic when it persists beyond this.

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TREATMENT It is essential to take a detailed medication history when a patient presents with urticaria, remembering that pharmaceutical excipients may be a trigger.Management of urticarial reactions involves stopping the causative agent and treatment with an oral antihistamine.

DRUGS THAT MAY CAUSE URTICARIAACE inhibitors Anaesthetics (local and general)AntibioticsDextransEnzymes (eg, streptokinase)HydralazineInsulinMuscle relaxantsNSAIDsOpioidsRadiocontrast mediaSalicylates

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Psoriasis and Psoriasiform Eruptions:

Psoriasis is a chronic disorder, which means it can last a long time and can come back frequently.

SYMPTOMSPsoriasis most commonly appears as thick, flaky patches of skin that may be silver or red.

A number of drugs can induce psoriasis in patients with no previous history or can worsen pre-existing psoriasis.

In patients with pre-existing psoriasis, symptoms usually developed within the first month of treatment but in those with no previous history they developed after at least two months’ treatment.

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CAUSEIn psoriasis, skin cells reproduce many times faster than normal and live only three to four days. The dead cells build up on the skin, forming thick, flaky patches.

Practolol was withdrawn as it causes a serious syndrome termed the oculomucocutaneous syndrome, featuring a psoriasiform rash, xerophthalmia due to lachrymal gland fibrosis, otitis media, sclerosing peritonitis and a lupus-like syndrome.

TREATMENTTopical treatments such as corticosteroids or calcipotriol may accelerate resolution.

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• SOME DRUGS THAT MAY CAUSE PSORIASIFORM ERUPTIONS OR EXACERBATE PSORIASIS

• Interferon'sLithium ACE inhibitors

• Beta-blockersChloroquine and hydroxychloroquineNSAIDsTetracyclines

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VASCULITIS:

Vasculitis is an extreme reaction to a drug, infection, or foreign substance that leads to inflammation and damage to blood vessels of the skin.

Several drugs can induce both systemic vasculitis with cutaneous manifestations and cutaneous vasculitis without other organ involvement.

About 10% of cases of acute cutaneous vasculitis are believed to be drug induced.

SymptomsPurple-colored spots and patches, which get pale when pressure is placed on them (purpura), Skin lesions usually located on the legs, buttocks, or trunk, Blisters on the skin.

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The skin lesions may persist for up to 4 weeks or longer, and in some cases become yellow-brown upon healing.

TREATMENTDrug therapy should be stopped at the first suspicion and the condition usually subsides thereafter.Systemic corticosteroids and immunosuppressants may be of some benefit in severe cases.

SOME DRUGS FREQUENTLY IMPLICATED IN VASCULITISPropylthiouracil Allopurinol AmpicillinCimetidineFrusemideHydralazineNSAIDsPhenytoinSulphonamidesThiazides

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ERYTHEMA MULTIFORME:

As the name implies, it can present with a variety of patterns.Erythema multiforme (EM) is a cutaneous response triggered by various infections and drugs.

SYMPTOMSThere may be blisters, papular lesions or erythematous areas. A characteristic lesion is one of concentric rings, variously described as target, iris or bullseye shaped.

The classic pattern affects the hands, feet and limbs.

CAUSEErythema multiforme may be due to vaccination, a variety of topical medications, and some environmental substances (eg, nickel).

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TREATMENTWhen the condition is suspected, all drugs, especially those introduced within the past month, should be discontinued, since there is a risk of progression to Stevens Johnson syndrome or toxic epidermal necrolysis.

SOME DRUGS THAT MAY CAUSE ERYTHEMA MULTIFORME.Barbiturates CarbamazepineCimetidineCo-trimoxazoleChlorpropamideLamotrigineNSAIDsPenicillinsPhenothiazinesPhenytoinSulphonamidesTetracyclines

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STEVEN JOHNSON SYNDROME:

It is the most severe form of erythema multiforme and is characterized by ulcerated lesions on the skin and mucous membranes. It is a serious, sometimes fatal inflammatory disease.

SYMPTOMSInvolvement of the mucosa is common, so the mouth, eyes and genitalia may be affected.A painful conjunctivitis may occur in the eye frequently with a pus discharge and may lead to loss of vision.

CAUSEStevens Johnson Syndrome is frequently drug induced. A large number of drugs have been implicated as a cause of SJS.Penicillins, tetracyclines, sulfonamides and NSAIDs are among the most common.

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This syndrome is distinct from Toxic Epidermal Necrolysis(TEN), but there is a degree of overlap as severe forms of SJS can evolve into TEN and several drugs can produce both entities.

The estimated incidence of SJS ranges between 1.2 and 6 per million population per year. In about 50 % of cases the cause is not known. The fatality rate is believed to be about 5 per cent.

TREATMENTDrugs that may be responsible for the reaction should be stopped immediately. Treatment involves systemic corticosteroids, fluid replacement and antibiotics, if required.

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DRUGS THAT MAY CAUSE

STEVENS JOHNSON SYNDROME.Barbiturates CarbamazepineCimetidineCo-trimoxazoleChlorpropamideLamotrigineNSAIDsPenicillinsPhenothiazinesPhenytoinRifampicinSulphonamidesTetracyclinesThiazides

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TOXIC EPIDERMAL NECROLYSIS:

Toxic epidermal necrolysis (TEN), or Lyell’s syndrome, is a rare variety of erythema with acute epithelial necrosis affecting all areas of the skin.

SYMPTOMSThe disorder is characterised by widespread full-thickness epidermal necrosis with involvement of more than 30% of the body surface area.Commonly, there is severe involvement of the mucous membranes (oropharynx, eyes and genitalia).

The estimated incidence ranges from 0.4 to 1.2 per million population per year. It has a high associated mortality approaching 40%.

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The conjunctivae are commonly affected 1–3 days before the appearance of skin lesions. Buccal, nasopharyngeal and pulmonary tract desquamation and erosion may be present.

CAUSEIdentification of the causative drug is often difficult. In general, most drugs causing TEN have been given in the previous 1–3 weeks.

Phenytoin-induced TEN can occur at any time between 2 and8 weeks after initiation of therapy, and may progress despite discontinuation of the drug.

The antiepileptic lamotrigine causes serious skin reactions. About 1:1000 adults treated develop Toxic epidermal necrolysis.

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TREATMENT Involves the careful protection of exposed dermis and eroded mucosal surfaces, managing fluid and electrolyte balance, nutritional support, and close monitoring for evidence of infection.

Antibiotic therapy should be given at the first sign of sepsis, rather than prophylactically.

Immunosuppressive agents such as cyclophosphamide have also been given to some patients, with claimed benefits.

The place of systemic corticosteroids in the management of TEN is controversial.

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• DRUGS THAT MAY CAUSE TOXIC EPIDERMAL NECROLYSIS Allopurinol BarbituratesCarbamazepineGoldGriseofulvinLamotrigineNitrofurantoinNSAIDs (especially oxicam derivatives)PenicillinsPhenytoinSalicylatesSulphonamidesTertacyclines

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PHOTOSENSITIVITY:

Two types include phototoxic eruptions and photoallergic eruptions.

Phototoxic eruptions are due to absorption of UV light (usually UVA) by the drug, which causes a release of energy and damage to cells. Looks like a bad sunburn, which may blister.

Photoallergic eruptions are a lymphocyte-mediated reaction caused by exposure to UVA, which converts the drug to an immunologically active compound that activates lymphocytes, causing an eczematous reaction in a photodistribution.

Usually due to topical agents including fragrances and biocides in soaps.

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Both types can be caused by phenothiazines, chlorpromazine, sulfa, and NSAIDS, although phototoxic reactions are more common with these agents.

DRUGS ASSOCIATED WITH PHOTOSENSITIVITY Frequent Amiodarone NSAIDsPhenothiazines (particularly   chlorpromazine)RetinoidsSulphonamidesTetracyclines (particularly   demeclocycline)ThiazidesLess frequent Antidepressants CarbamazepineGriseofulvinQuinolonesQuinineSulphonylureas

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Management points to be considered when a patient have experienced a Drug Eruption.

• Take an accurate medication history. Note details of all current and recent medication, including over-the-counter medicines, herbal and homoeopathic preparations, and injections, including vaccines or contrast media.

• Note the times when each medicine was first taken relative to the onset of the reaction, and check whether the patient has taken these medicines previously.

• Some skin reactions, particularly urticaria, may be due to sensitivity to pharmaceutical excipients. If this type of reaction is present, it is worth noting the proprietary (brand) names of medicines taken as well as the generic name.

• Ask the patient if they have a previous history of drug sensitivity, contact dermatitis, connective tissue disease or atopic disease with asthma or eczema.

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• Examine the rash to determine what type it is and whether it appears to be a drug eruption.

• Record clearly in the patient’s notes any known or suspected ADR, with details of the presumed cause. Tell the patient or relatives, and preferably give a written note so that future exposure can be avoided.

• Take great care in prescribing for the patient subsequently. Clarify that compound preparations do not contain potentially harmful constituents.

• Notify suspected ADRs to the relevant regulatory authority. This information is essential for identifying new drug safety hazards and enables the study of factors associated with ADRs.

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REFERENCES:

www.ncbi.nlm.nih.gov › Journal List › Br Med J › v.1(6168); Apr 7, 1979

http://www.nlm.nih.gov/medlineplus/ency/article/000874.htm

http://emedicine.medscape.com/dermatology

www.pharmpress.com/shop/samples/ADRe2Ch05.pdf

http://www.stevensjohnsonsyndrome.org/ivig-Stevens-Johnson-Syndrome.php

http://www.healthscout.com/ency/68/698/main.html

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THANK YOU!!

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