Erupsi obat alergi dan peny kulit

berlepuhDr. Encep Kusnandar Sp.KK (K)

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Adverse Cutaneous Drug ReactionsIntroduction- ACDR are common, occurring in 2 % to 3 % of hospitalized patients. - ACDR in an ambulatory practice occurs frequently.- The majority of reactions are mild, accom-panied by pruritus,resolving promptly after the offending drug is discontinued.- However, severe, life-threatening ACDRs do occur and are unpredictable.- Drug eruptions are caused by immunologic or nonimmunologic mecha-nisms & are provoked by systemic or topical administration of a drug. - The majority are based on a hypersensitivity mechanism and may be of types I, II, III, or IV.

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Classification

Type I: Immediate-Type Immunologic Reactions • IgE-mediated. • Drug (penicillin).• Manifested: urticaria & angioedema of skin/mucosa & edema of other organs & fall in blood pressure (anaphylactic shock).• Occur more commonly if drug (antigen) is administered intravenously than by mouth.

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Type II: Cytotoxic Reactions • Drug (penicillin, cephalosporins, sulfonamides, rifampin)

plus cytotoxic antibodies causes lysis of cells such as platelets or leuko-cytes.

• Alternatively, drug (quinine, quinidine, salicylamide, isoniazid, chlorprom-azine, sulfonamides, sulfonyl-ureas) plus antibodies (immune complexes form) causes lysis or phagocytosis.

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Type III: Serum Sickness, Drug-Induced Vasculitis • IgG or, less commonly, IgM antibodies formed against

drug. • Mediated by deposition of immune complexes in

small vessels, activated by complement and recruitment of granulocytes.

• Onset of reaction: 5 to 7 days between introduction of drug and appearance of reaction.

• Manifested by vasculitis, urticaria-like lesions, arthritis, nephritis, alveolitis, hemolytic anemia, thrombocytopenia, agranulocytosis.

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Type IV: Morbilliform (Exanthematous) Reactions

• Cell-mediated immune reaction. • Sensitized lymphocytes react with drug,

liberating cytokines, which trigger cutaneous inflammatory response.

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Immunologic hypersensitivity reactions are manifested by a variety of distinct clinical patterns:Exanthematous reactions Type Ill, IV(?) Urticaria, angioedema Type I, III Fixed drug eruption Type III, IV(?) Bullous eruptions Type IV(?) Stevens-Johnson syndrome/ toxic epidermal necrolysis Type III, IV(?) Vasculitis Type III Lichenoid eruptions Type IV(?) Photoallergic reactions Type IV

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The nonimmunologic drug eruptions are caused by

(1) idiosyncrasy sensu strictiori—reactions due to hereditary enzyme deficiencies;

(2) cumulation, such as melanosis due to gold or amiodarone;

(3) irritancy of a topically applied drug;

(4) an individual idiosyncrasy to a topical or systemic drug

(5) mechanisms not yet known

(6) reactions due to the combination of a drug with ultraviolet irradia-tion (photosensitivity). These may have a toxic (T) or immunologic (allergic) (A) pathology.

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Guidelines for Assessment of Possible Adverse Drug Reactions• Alternative causes should be excluded, especially infections, in that many infections (especially viral) are difficult to distinguish clinically from the adverse effects of drugs used to treat infections.

• The interval between introduction of a drug and onset of the reaction should be examined.

• Any improvement after drug withdrawal should be noted.

• The caregiver should determine whether similar reactions have been associated with the same compound.

• Any reaction on readministration of the drug should be noted.

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Findings Indicating Possible Life-Threatening ACDR* Clinical Findings

CUTANEOUS• Confluent erythema• Facial edema or central facial involvement• Skin pain• Palpable purpura• Skin necrosis• Blisters of epidermal detachment• Positive Nikolsky’s sign (epidermis separates readily from dermis with lateral pressure)• Mucous membrane erosions• Urticaria• Swelling of the tongue

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GENERAL• High fever (temperature >40°C)• Enlarged lymph nodes• Arthralgias or arthritis• Shortness of breath, wheezing, hypotension

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Exanthematous Drug Eruption

An exanthematous drug eruption is an adverse hypersensitivity reaction to an ingested or parenterally administered drug characterized by a cutaneous eruption that mimics a measles-like viral exanthem; systemic involvement is minimal.

Synonyms: Morbilliform drug eruption, maculopapular drug eruption.

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Epidemiology and Etiology• Incidence Most common type of cutaneous drug

reaction• Age Less common in the very young• Etiology

– Drugs with a high probability of reaction (3 % to 5 %): penicillin and related antibiotics, carbamazepine, allopurinol, gold salts (10 % to 20 %).

– Medium probability: sulfonamides (bacteriostatic, antidiabetic, diuretic), NSAIDs, hydantoin derivatives, isoniazid, chloramphenicol, erythromycin, streptomycin.

– Low probabil-ity(1 % or less): barbiturates, benzodiazepines, phenothiazines, tetracyclines.

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Physical Examination• Vital Signs Elevated temperature (drug fever)• Skin Lesions• Macules and/or papules, a few millimeters to 1 cm in size.• Purpura may be seen in lesions of lower legs. • May progress to generalized exfoliative dermatitis, especially if drug not discontinued.• Scaling and/or desquamation may occur with healing

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• Arrangement of multiple lesions macules and papules frequently become confluent.

• Distribution symmetric. Almost always on trunk and extremities.

• Palms and soles variably involved. In children, may be limited to face and extremities.

• Eruption may be accentuated in striae. Reactions to ampicillin usually appear initially on the elbows, knees, and trunk, extending symmetrically to most areas of body.

• Mucous membranes exanthem on buccal mucosa

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Differential diagnosis- Exanthematous eruption viral exanthem- Secondary syphilis- Atypical pityriasis rosea- Early widespread allergic contact dermatitis

DiagnosisClinical diagnosis, at times confirmed by histologic findings

PathophysiologyExact mechanism unknown. Probably delayed hypersensitivity.

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Course and Prognosis• After discontinuation of drug, rash usually fades; In

some cases of exanthematous penicillin reactions, readministration of the drug does not cause the eruption. Duration of ampicillin eruption following discontinuation of drug: 3 to 5 days.

• Of more concern, a morbilliform eruption may be the initial presentation of a more serious eruption – toxic epidermal necrolysis– Stevens-Johnson syndrome– hyper-sensitivity syndrome, or serum sickness.

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Management- The definitive step in management is to identify the offending drug and discontinue it.- Indications for Discontinuation of Drug Urticaria (concern for anaphylaxis), facial edema, blisters, mucosal involvement, ulcers, palpable or extensive purpura, fever, lymphadenopathy- Symptomatic Treatment Oral antihistamine to alleviate pruritus- Corticosteroids Potent topical corticosteroid preparation May help speed resolution of erup-tion, especially if secondary changes of eczematous dermatitis have occurred due to scratching

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Oral or iv corticosteroids

- Usually not indicated or helpful if the offending drug has been discontinued

- If the drug cannot be substituted or omitted, systemic corti-costeroids can be administered to treat the ACDR; also, to induce more rapid remission.

- Prevention The patient must be aware of his or her specific drug hypersensitivity and that other drugs of the same class can crossreact. Although an exanthematous drug eruption may not recur if the drug is given again, readministration is best avoided by using a different agent. Wearing a medical alert bracelet is advised.

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Exanthematous drug eruption:

• ampicillin Symmetrically arranged

• brightly erythematous macules&papules,

• discrete in some areas and confluent in others on the back and extremities.

A

C

B

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Exanthematous drug eruptions.

(A) Numerous pink papules on the trunk due to a cephalosporin

(B) Confluence of lesions on the trunk

(C) annular plaques on the forehead secondary to phenobarbital.

Drug-Induced Acute Urticaria, Angioedema,Edema,and Anaphylaxis

Drug-induced urticaria and angioedema occur due to a variety of mechanisms and are characterized clinically by transient wheals and larger edematous areas that involve the dermis and subcutaneous tissue (angioedema).

In some cases, cutane-ous urticaria/angioedema is associated with systemic anaphylaxis, which is manifested by respiratory distress, vascular collapse, and/or shock.

Synonym: Angioneurotic edema.

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Epidemiology and EtiologyClassification

Immune-mediated (allergic) urticaria/angioedema • IgE-Mediated Antibiotics (especially penicillins), radiographic contrast agents.• Complement-Mediated By way of immune complexes activating complement and releasing anaphylatoxins that induce mast cell degranulation. Serum sick-ness, administration of whole blood, immunoglobulins.• Immune Complex-Mediated Reactions resemble serum sickness, penicillin.

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Nonallergic urticaria (anaphylactoid reactions) • Analgesics/Anti-inflammatory• Drugs (NSAIDs) Drugs inhibit or block cyclooxygenase

enzyme in prostaglandin synthesis. Also associated with rhinosinusitis and asthma.

• Radiographic Contrast Media Most reactions are nonallergic; rarely, allergic.

• Angiotensin-Converting Enzyme (ACE) Inhibitors In 0.1 % to 0.2 % of patients,

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Drugs causing urticaria/angioedema/anaphylaxis1. Antibiotics and chemotherapeutic agents

- Penicillins: ampicillin, amoxicillin,dicloxacillin, mezlocillin, penicillin G, penicillin V, ticarcillin.

- Cephalosporins,including third generation. - Sulfonamides and derivatives.

2. Immunotherapeutics, vaccines antilymphocyte serum, levamisole, horse serum

3. Cytostatic agents l-asparaginase, bleomycin, cisplatin, daunorubicin, 5-fluoro-uracil, procarbazine, thiotepa

4. ACE Inhibitors captopril, enalopril, lininopril

5. Calcium-channel blockers nifedipine, diltiazem, verapramil 25

Drugs releasing histamine Centrally acting drugs (morphine, meperidine, atropine, codeine, papaverine

Incidence - Angioedema occurs in 1 per 10,000 courses of penicillin and leads to death in 1 to 5 per 100,000 courses. - Angioedema associated with angiotensin- converting enzyme (ACE) inhibitors occurs in 2 to 10 per 10,000 new users.

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HistoryTime from Initial Drug Exposure to Appearance of Urticaria

• IGE-MEDIATED Initial sensitization, usually 7 to 14 days urticaria may occur In previously sensitized individuals, usually within minutes or hours.

• IMMUNE COMPLEX-MEDIATED Initial sensitization, usually 7 to 10 days, but as long as 28 days; in previously sensitized individuals, symptoms appear 12 to 36 hours after drug readministered.

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• ANALGESICS/ANTI-INFLAMMATORY DRUGS– Occurs following administration of drug by– 20 to 30 minutes (up to 4 hours).– Prior Drug Exposure

• RADIOGRAPHIC CONTRAST MEDIA – 25 % to 35 % probability of repeat reaction in indi-

viduals with history of prior reaction to contrast media

– Duration of Lesions Hours

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Symptoms - Pruritus, burning of palms/soles, auditory canal.- With airway edema, difficulty breathing.

Constitutional Symptoms IgE-mediated: flushing, sudden fatigue, yawning, headache, weakness, dizzinessnumbness of tongue, sneezing, bronchospasm, substernal pressure, palpitationsnausea, vomiting, crampy abdominal pain,Diarrhea

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Differential Diagnosis• Acute Edematous Red Pruritic Plaque(s) • Allergic contact dermatitis (poison ivy, poison oak

dermatitis)• Cellulitis• insect bite(s)

Diagnosis• Clinical diagnosis, at times confirmed by histologic findings

Course and Prognosis• Drug-induced urticaria/angioedema usually resolves within

hours to days to weeks• after the causative drug is withdrawn.

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ManagementThe offending drug should be identified and withdrawn as soon as possible.

PreventionPreviously sensitized individuals The patient should carry information listing drug sensitivities (wallet card, bracelet).

Radiographic contrast media Avoid use of contrast media known to have caused prior reaction. If not possible, pretreat patient with antihistamine and prednisone (1 mg/kg) 30 to 60 minutes prior to contrast media exposure.

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Treatment of Acute Severe Urticaria/Anaphylaxis• Epinephrine (0.3 to 0.5 mg of a 1 : 1000 dilution)

subcutaneously, repeating in 15 to 20 minutes. Maintain airway. Intravenous access.

• Antihistamines H 1 blockers or H 2 blockers or combination

• Systemic Corticosteroids• Intravenous Hydrocortisone or methylprednisolone for

severe symptoms• Oral Prednisone 70 mg, tapering by 10 or 5 mg daily

over 1 to 2 weeks, is usually adequate.

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Angioedema swellings are deeper than wheals and may affect mucosal sites. They are often pale and poorly defined.

Urticaria secondary to penicillin. Several of the lesions have a figurate appearance.

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Fixed Drug Eruption

• A fixed drug eruption (FDE) is an adverse cutaneous reaction to an ingested drug• characterized by the formation of a solitary, but at times multiple, plaque, bulla, or erosion• if the patient is rechallenged with the offending drug, the FDE occurs repeatedly at the identical skin site (i.e., fixed) within hours of ingestion.

EpidemiologyAge Rare in children

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EtiologyDrugs most commonly implicated:• Phenolphthalein• Antimicrobial agents• Tetracyclines (tetracycline, minocycline)• Sulfonamides, including “nonabsorbable” drugs;

crossreactions with anti-diabetic & diuretic sulfa drug may occur.

• Metronidazole• Nystatin• Anti-inflammatory agents• Salicylates• NSAIDs

Food: peas, beans, lentils have been implicated.Food coloring: in food or medications

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HistoryDrug History Patients frequently give a history of identical lesion(s) occurring at the identical location.

Skin Symptoms Usually asymptomatic. • May be pruritic or burning. • Painful when eroded.• Patients note a residual area of postinflammatory

hyperpigmentation between attacks.

• Time to Onset of Lesion(s) Occur from 30 minutes to 8 hours after ingestion of

drug in previously sensitized individual.

• Duration of Lesion(s) Lesions persist if drug is continued. Resolve days to

few weeks after drug is discontinued.36

Physical Examination Skin Lesions1. TYPE

• The characteristic early lesion is a sharply demarcated macule.

• Within a few hours the lesion becomes edematous, thus forming a plaque, which may evolve to become a bulla and then an erosion.

2. COLOR • Initially, erythema, then dusky red to violaceous.• After healing,dark brown with violet hue

postinflammatory hyperpigmentation.

3. PALPATION • Eroded lesions, especially on genital or oral mucosa,

are quite painful(Figures 22-5 & 22-6).37

4. ARRANGEMENT • Single lesions most common. When multiple,

random. A greatnumber of lesions may simulate toxic epidermal necrolysis (Figure 22-7).

5. DISTRIBUTION • The genital skin is the most commonly involved

site, but any site may be involved. • Face: perioral, periorbital.• Mucous Membranes FDEs may occur within the

mouth or on the conjunctivae.• May simulate herpes simplex, conjunctivitis, or

urethritis.

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Differential Diagnosis• Solitary Genital Erosion Recurrent herpetic lesion• Multiple Erosions Stevens-Johnson syndrome, toxic epidermal necrolysis• Oral Erosion(s) Aphthous stomatitis, primary herpetic gingivostomatitis,• Erythema multiforme

Laboratory and Special Examinations Patch Test The suspected drug can be placed as a patch test at a previously in-volved site; an inflammatory response occurs in 30 % of cases.

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Diagnosis• Made on clinical grounds. Readministration of the drug

confirms diagnosis but should be avoided.

Pathogenesis• Unknown

Course and Prognosis• FDE resolves within a few weeks of withdrawing the

drug. • Recurs within hours following ingestion of a single dose

of the drug.

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ManagementTreatment of Lesion(s) Identify and withhold the offending drug. • Potent topical corticosteroid ointment.• Bacitracin or Silvadene ointment • Postinflammatory hyperpigmentation (dermal melanin) may persist at the site of an FDE for months or years and does not respond to hydroquinone therapy.

• Prevention Identify and withhold the offending drug.• Various types of sulfa drugs may crossreact.

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Fixed drug eruption:• phenolphthalein A violet plaque on the

wrist, eroded plaques on the glans penis and scrotum, associated with extensive intraoral erosions.

• This was the fourth such episode and followed ingestion of a phenolphthalein-containing laxative.

Fixed drug eruption: phenylbutazone A large, oval, red-violet plaque with central bulla formation on the lower abdomen and inguinal region.

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Generalized fixed drug eruption:• tetracycline Multiple, confluent,

violaceous-red, oval erythematous areas, some of which later became bullous.

• The eruption may be difficult to distinguish from toxic epidermal necrolysis.

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Penyakit kulit berlepuh SinonimPeny.vesiko bulosa.

DefinisiYaitu peny2 kulit yg effl terutama vesikel dan bula.

Banyak yang termasuk, diantaranya:1.Pemfigus.2.Dermatitis herpetiformis.3.Pemfigoid bulosa.4.Epidermolisis bulosa hereditaria

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►Pemfigus

Merupakan segol. penyakit yg terdiri dr bbrp type:

1. Pemfigus vulgaris.

2. Pemfigus vegetans.

3. Pemfigus foliaceus.

4. Pemfigus eritematosus.

Penyebab: Termasuk penyakit auto-imum, terdapat auto-antibodi

terhadap jaringan interseluler epidermis.

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Perjalanan penyakit dan gejala klinis.- kronik residif. - Efloresensi yg terpenting : bula seluruh tubuh.- Bula bersifat lembek, berisi cairan jernih kmd jadi

seropurulen bahkan hemoragik- Bula tersebut terdpt pd kulit yg tdk eritema- Bula mudah pecah meninggalkan hiperpigmentasi

tanpa sikatriks.- Tanda Nikolsky positif yg menandakan hilangnya

ikatan antara lapisan2 kulit, yg dpt diperiksa dg terkelupasnya kulit yg tampaknya sehat setelah ditekan dan digesek.

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Diagnosa dan Diagnosa banding: D/ berdasarkan gejala klinis khas yaitu

sifat bula yg lembek dan tanda Nikolsky positif.

Pemeriksaan pembantu:

- Histopatologi/Tzank test

- Imunofluoresenditemukan IgG pd interseluler epidermis

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Tanda diagnostik.a.Bula lembek.b.Tanda Nikolsky positif.c.Tzank test.positif. d.Kronik residif.

Diagnosa banding.a.Dermatitis herpetiformis Duhring.b.Pemfigoid bulosa.c.Sindroma Steven Johnsond.Impetigo vesiko bulosa.e.T.E.N.

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Pengobatan.- Kortikosteroid tinggi jangka panjang,kmd di

tapering off sesuai dg keadaan klinisnya, diberikan prednison 80-120 mg.

- Antibiotika utk infeksi sekunder.- Anabolik. - Diet TKTP.- Pengobatan topikal. Kompres mis dg sol PK

1/10.000, ssd kering beri krem kortikos-teroid.

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►Dermatitis herpetiformis duhringBersifat kronik residif dg efloresensi polimorf tesusun berkelompok disertai rasa gatal dan biasanya simetris.

Gejala klinis- Anak dan dewasa. - Predileksi: punggung, lengan, ketiak bg belakang

dan bokong. - Efloresensi : papula, pustula dan bula, yg menonjol

adalah vesikula berkelompok disertai eritem dan berdinding tegang.

- Pemeriksaan darah tepi ada eosinofilia.- Pada vesikel ada sel2 eosinofil.

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Diagnosa banding :* Pemfigus.* Pemfigoid.* Eritema multiforme.

Pengobatan :* DDS 3x100 mg/hari.* Corticosteroid.* Topical steroid.

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►Pemfigoid bulosa

- Jarang ditemui dengan penyebab belum diketahui.

- Simptomatologi.

- Keadan umum penderita baik.

- Efl berupa: bula yg bedinding tegang.

- Predileksi: ketiak,lengan bg flexor dan lipat paha.

- Pada cairan bula banyak sel eosinofil.

- Percobaan Tzank negatif.

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Histopatologi.• Bula di subepidermis,akantolisis (-)• Diagnosa banding.• Pemfigus.• Dermatitis herpetiformis.

Pengobatan.• Kortikosoeroid.• Antibiotika pd inf sekunder.• Dapson juga efektif.

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►Epidermolisis bulosa hereditaria. Sinonim- Akantolisis bulosa.- Congenital traumatic pemphigus.

• Timbul pada waktu lahir atau segera sesudah lahir,• Bersifat herediter• Disebabkan kekurangan jaringan elastin dari kulit.

Simtomatologi- bayi dan anak-anak.- Tempat predileksi: tempat yang mudah kena trauma punggung dan extensor extremitas

- Timbul bula berisi cairan serosa, purulen/hemoragik.56

Klasifikasi.- Congenital timbul sejak lahir.- Aquiredyang didapat atau timbul kemudian

Bentuk klinik- Benigna atau simpleks apabila bula memecah tdk meninggalkan sikatriks hanya bercak hiperpigmentasi. Bentuk ini diturunkan secara dominan.- Distrofik jika bula memecah meningalkan sikatriks yg atrofi Kalau lebih dalam menyebabkan kontraktur. Pada tangan dapat terjadi ‘claw hand’. Kuku dpt tkena jd atrofi,kdg2 rusak sama sekali. Selain itu dapat juga mengenai selaput lendir. Bntk ini diturunkan secara dominan dan resesif.

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Pengobatan.- Kortikosteorid sistemik dan topikal.- Antibiotika utk inf sekunder.

Diagnosa banding.- Impetigo bulosa pada bayi baru lahir.- Porphyria cutanea tarda.- TEN.

Tanda diagnostik.Suspek pada bayi atau anak yg mudah tbl bula oleh gesekan atau trauma ringan.

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