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DRUG ERUPTION

(IN HIV/AIDS PATIENT)

Indah Febrini Triana J. C 111 08 148 Ashari Mohpul C 111 08 319

CASE REPORT

Name : Mrs. O Age : 26 years old Address : Kampung Melawang, Sudiang Marital status : Married Admission date : 25th August 2012

ANAMNESIS
Chief complaint : itchiness and red spot all over the body Brief anamnesis: Patient came to hospital with a complain of itchiness and red spot all over the body since 4 days ago. The itchiness began after the patient consumed a few drugs. Then appears red spot from the arms to the entire body. The patient felt itchy on her mouth, neck, and forehead too. This patient has history of taking ARV, Piracetam, and Amoxicillin since a month ago. Family history (). History of drugs and foods allergy not known.

PRESENT STATUS
General

status: Moderately ill Consciousness: Composmentis Nutritional status: Good Vital signs:

BP HR RR Temp

: 100/70mmHg : 80x/minute : 20x/minute : 36,8C

DERMATOLOGY STATUS
Location: Region generalized Efflorescence: erythema macula

LABORATORY RESULTS
SGOT : 12 U/L SGPT : 12 U/L Albumin : 4.0 g/dl Ureum : 8 mg/dl Creatinine : 0.62 mg/dl Total bilirubine : 0.26 mg/dl Bilirubin direct : 0.07 mg/dl CD4 absolut : 127 sel/ Ul VCT : reaktif

RESUME
A 26 years old woman came to hospital with a complain itchiness and red spot all over the body since 4 days ago. The itchiness began after the patient consumed a few drugs. Then appears red spot from the arms to the entire body. The patient felt itchy on her mouth, neck, and forehead too. This patient has history of taking ARV, Piracetam, and Amoxicillin since a month ago. Patient is treated for her underlying disease which is Human Immunodeficiency Virus(HIV). Family history (-). History of drugs and foods allergy not known.

RESUME (2)
Internal status in normal range. Dermatology status: regio location generalized, erhytema macula efflourescene. Vital status in normal range. Obstetry status: pregnancy (22-24 weeks) Diagnosis : Drug eruption : type IV ( based on Immunological Mechanisms)

TREATMENT
Systemic

: Chlorpheniramine maleate (CTM) 3x1 Metil prednisolon 4mg 3x1 Topical : Salicylic powder for neck area

PROGNOSTIC : The prognosis of this patient is dubia

DISCUSSION

DRUG ERUPTIONS
Introduce :
ADR ( Adverse Drug Reaction) = an undesirable clinical manifestation resulting from administration of a particular drug; this includes reactions due to overdose, predictable side effects and unanticipated adverse manifestations ACDRs (adverse cutaneous drug reactions) = ADRs in Cutaneous = DRUG ERUPTIONS

INCIDENCE
USA (1969 2002) = about 2.3 million case reports ADRs Drug eruptions = 24% of all ADRs ( other study : 29%) A survey of ACDRs among in-patients :
In

one-third were xed drug reactions o one-third were exanthematous o 20% were urticaria or angio-oedema ACDRs : Antimicrobial agents (42%); antipyretic/antiinammatory analgesics (27%); drugs acting on the central nervous system accounting for 10% of reactions. ACDRs : Amoxicillin (51 cases/ 1000 exposed), trimethoprimsulfamethoxazole (33 cases/1000 exposed) and ampicillin (33 cases/1000 exposed.
o

MECHANISMS

Drug reactions may arise as a result of immunological allergy directed against the drug itself, a reactive metabolite or some contaminant of the drug or, more commonly, by non-immunological mechanisms, such as pseudoallergic reactions caused by nonimmune-mediated degranulation of mast cells and basophils.

CLASSIFICATION (1)
Type A : Drug reactions may be predictable Type B : Drug reactions unpredictable Type C : reactions include those associated with prolonged therapy (e.g. analgesic nephropathy) Type D : reactions consist of delayed reactions (e.g. carcinogenesis and teratogenicity).

CLASSIFICATION (2)

Non-immunological :
Predictable :
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Overdosage Side effects Cumulation Delayed toxicity Facultative effects Drug interactions Metabolic alterations Teratogenicity Non-immunological activation of effector pathway Exacerbation of disease Drug-induced chromosomal damage Intolerance Idiosyncrasy

Unpredictable :
1. 2.

CLASSIFICATION (3)
Immunological (unpredictable) : IgE-dependent drug reactions Immune complex-dependent drug reactions Cytotoxic drug-induced reactions Cell-mediated reactions Miscellaneous : JarischHerxheimer reactions Infectious mononucleosisampicillin reaction

IMMUNOLOGICAL MECHANISMS
IgE-dependent (type I) drug reactions: pruritus, urticaria, bronchospasm and laryngeal oedema, and in severe cases anaphylactic shock with hypotension and possibly death.

Antibody-mediated (type II) drug reactions : fever, arthritis, nephritis, neuritis, oedema, and an urticarial or papular rash. Immune complex-dependent (type :Urticaria and anaphylaxis, III) drug reactions

Serum sickness,

Vasculitis, Arthus reaction.

Cell-mediated (type IV) reactions : morbilliform and bullous ACDRs, xed drug reactions, lichenoid reactions, LE-like reactions, dress syndrome and erythema multiforme, Stevens Johnson syndrome and TEN, involve T-lymphocyte responses to altered self.

TYPES OF CLINICAL REACTION


Exanthematic (maculopapular) reactions Purpura Annular erythema Pityriasis rosea-like reactions Exfoliative dermatitis/ erythroderma : thickening of skin resulting in increased skin folds, universal redness, a fine brawny scaling. Psoriasiform eruptions Anaphylaxis and anaphylactoid reactions Urticaria OTHER CLINICALS: Fixed drug eruptions. LE-like syndrome induced by drugs. Erythema multiforme StevensJohnson syndrome TEN. Lichenoid drug eruptions Drug-induced pemphigus

DRUGS CAUSING ERYTHRODERMA AND EXFOLIATIVE DERMATITIS


Allopurinol p-Aminosalicylic acid Ampicillin Barbiturates Captopril Carbamazepine Cefoxitin Chloroquine Chlorpromazine Cimetidine Diltiazem Gold Griseofulvin

HydantoinsIsoniazid Lithium Nitrofurantoin Penicillamine Penicillin Phenylbutazone Quinidine Streptomycin Sulphonamides Sulphonylureas Thioacetazone (thiacetazone) Zidovudin

ACDRS VS AIDS
Patients with AIDS : increased risk for ADRs Patients with AIDS : more likely to have particularly severe reactions, ranging from erythema multiforme to toxic epidermal necrolysis (TEN) (especially with sulphonamides, clindamycin, phenobarbital (phenobarbitone) and chlormezanone) and to demonstrate multiple cutaneous drug reactions. Antiretroviral therapy (including abacavir, non-nucleoside reverse transcriptase inhibitors such as nevirapine, and protease inhibitors such as amprenavir) : implicated hypersensitivity

STAGING OF HIV/AIDS

Stage I asymptomatic or Persistent generalized lymphadenopathy (PGL) Stage II - mild disease Stage III - moderate disease Stage IV - advanced immunocompromise

COMMON DERMATOLOGICAL CONDITIONS IN HIV INFECTION.


Pruritus/xerosis/ichthyosis Viral warts Mollusca Oral and vaginal candidosis Tinea (including onychomycosis) Scabies Basal cell carcinom Squamous cell carcinoma Kaposis sarcoma

Nodular prurigo Folliculitis Eosinophilic folliculitis Pruritic papular eruption Seborrhoeic dermatitis Psoriasis Drug eruptions Herpes simplex Herpes zoster

PRINCIPAL CUTANEOUS SIDE EFFECTS OF ARV DRUGS


Nucleoside

reverse transcriptase inhibitors

(NRTIs) :
o

o
o o o o o o o

All NRTIs: Pruritus, xanthem, urticaria Abacavir : HLA B5701 hypersensitivity syndrome, SJS, TEN, Kawasaki syndrome, anaphylaxis, lipodystrophy Didanosine (ddI, DDI) : Vasculitis, purpura, SJS, anaphylaxis, Ofujis papuloerythroderma, gynaecomastia, lipodystrophy, acral erythema, diaphoresis Emtricitabine (FTC) : Hyperpigmentation Lamivudine (3TC) : Vasculitis, anaphylaxis, angio-oedema, allergic contact dermatitis, gynaecomastia, lipodystrophy, diaphoresis Stavudine (d4T) : Lipodystrophy, gynaecomastia, neutrophilic eccrine hidradenitis, tendon xanthomas, diaphoresis Tenofovir : Maculopapular toxic erythema, diaphoresis Zalcitabine* (ddC, DDC) : Anaphylaxis, angio-oedema, acne, photosensitivity, erythroderma, granuloma annulare, bullous eruption, diaphoresis Zidovudine (AZT, ZDV) : Exanthem, erythema multiforme and SJS, polymyositis, erythroderma, porphyria cutanea tarda, purpura, vasculitis, insect bite reaction, discoloration of the skin (also mucosa and nails) especially in dark-skinned individuals), neutrophilic eccrine hidradenitis, acne, bullous eruption, lipodystrophy, bromhidrosis, diaphoresis

PRINCIPAL CUTANEOUS SIDE EFFECTS OF ARV DRUGS (2)


Non-nucleoside

reverse transcriptase inhibitors (NRTIs) :


All NNRTIs : Pruritus, exanthem, SJS/TEN Delavirdine : Xerosis, urticaria, angio-oedema, dermatitis, vesicobullous eruption, purpura, vasculitis, seborrhoea, gynaecomastia, diaphoresis Efavirenz : Eczema, photosensitivity, gynaecomastia, leukocytoclastic vasculitis, urticaria, ushing, folliculitis Nevirapine : DRESS, angioedema, anaphylaxis, lipodystrophy

Fusion

inhibitors

Enfuvirtide : Injection site reactions, xerosis, pruritus, exanthem, acne, herpes simplex, papillomas, ecchymosis, paraesthesia

PRINCIPAL CUTANEOUS SIDE EFFECTS OF ARV DRUGS (3)


Protease

inhibitors (PIs):

All Pis : Exanthem, SJS/TEN, pruritus, xerosis, hypersensitivity syndrome, anaphylaxis, panniculitis, toxic pustoloderma, tendon xanthomas, lipodystrophy, acanthosis nigricans Amprenavir :Signicant incidence of rash (2030%) Atazanavir : Eczema, photosensitivity, seborrhoea, urticaria, vesicobullous eruption, purpura, gynaecomastia, diaphoresis Darunavir : Hyperhidrosis (with ritonavir), sulphonamide therefore incidence of rash high (7%) Fosamprenavir (pro-drug of amprenavir) : Signicant incidence of rash (20%) Indinavir : Erythroderma dermatitis, folliculitis, pigmentation (skin, nail and hair), seborrhoea, urticaria, vasculitis, paronychia/pyogenic granuloma, striae, lipomatosis, porphyria, gynaecomastia, paraesthesia, diaphoresis, bromhidrosis Nelnavir : Urticaria, dermatitis, lichenoid reaction, palmar erythema, vasculitis, gynaecomastia Ritonavir : Urticaria, IgA-mediated hypersensitivity, acne, seborrhoea, bullous eruption, dermatitis, folliculitis, granulomas, ecchymosis, haematoma, paraesthesia, diaphoresis Saquinavir : Photosensitivity, urticaria, acne, bullous eruption, dermatitis, seborrhoeic dermatitis, folliculitis, papulovesicular eruptions, furunculosis, herpes simplex, herpes zoster, candidosis, hyperpigmentation, psoriasis, warts, xed drug eruption, gynaecomastia, paraesthesia, diaphoresis Tipranavir :Photosensitivity

ACDRS VS PREGNANCY

The fetus is particularly at risk from drug-induced developmental malformations during the period of organogenesis (the third to the tenth week of gestation)

Sex

hormones, psychotropic drugs, benzodiazepines, tetracycline, rifampicin, penicillamine and the folate antagonist pyrimethamine are possibly teratogenic and should be avoided in the rst trimester of pregnancy.

RECOMMENDED EXAMINATION
Provocation tests : Provoking the lesion with the suspected drug confirms the diagnosis, prevents recurrences, and allays the anxiety of the patient regarding venereal origin of the disease. Patch tests are performed on the patient's normal and prelesional skin with the drug in a petrolatum base. A biopsy shows hydropic degeneration of the epidermal basal cells and pigmentary incontinence.

DIFFERENTIAL DIAGNOSIS

Erytroderma : Pityriasis rubra pilaris, psoariasis and cutaneous T-cell lymphoma

Psoariasis

Pityriasis rubra pilaris

Cutaneous T-cell lymphoma

MANAGEMENT
Systemic : o Kortikosteroid : 3x10 mg till 4 x 10 mg for a day o Histamint agent for itchness Topycal : Ianolin Zalp 10 %.

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