MANAJEMEN REAKSI ALERGI

PADA PENDERITA HIV

 Pendahuluan.

Penyakit alergi seperti : sinusitis, eksim, asma bronkial,

hipersensitivitas terhadap obat, sering dijumpai pada
penderita hiv.

Pada beberapa penelitian klinis atopi seperti sinusitis,

hipesensitivitas terhadap obat, dihubungkan dengan
peyakit HIV yang dideritanya.

Kekacauan sistem imun pada penderita HIV ditenggarai

sebagai penyebab timbulnya klinis Alergi.
 Pendahuluan.

Sebagian besar penderita HIV mengalami

peningkatan Ig E meskipun dalam berbagai penelitian
mendapatkan adanya hubungan dengan klinis atopi
yang timbul dan sebagian penelitian mengatakan
tidak adanya hubungan dengan klinis atopi yang
timbul.
Tatalaksana reaksi alergi pada penderita HIV tidak
berbeda dengan non HIV yaitu pemberian obat
simtomatik dari klinis atopinya dan penghindaran
allergen.
 Pendahuluan.

Hipersensitivitas obat merupakan kejadian yang

cukup sering pada penderita HIV.

Terdapat sedikit catatan pada tatalaksana

penggantian ARV (antiretroviral) , terutama
Nevirapin(NVP) dan Efavirenz (EFV) dalam
hipersentivitas obat ARV.
 Adverse drug reaction

Adverse drug reaction are common and can cause

serious health problems.

Allergic drug reactions account for 5 to 10% of all

adverse drug reactions.
 Definition : Drug allergy

A drug allergy is the abnormal reaction of your immune

system to a medication.

Any medication over-the-counter, prescription or

herbal is capable of inducing a drug allergy.

A drug allergy is not the same as drug side effects, and

also distinct from drug toxicity caused by an overdose
of medication.

By Mayo Clinic Staff

 Classification of Drug Reaction2

Drug Allergy

Immunologic reaction Pseudoallergic

(Gell and Coombs classification) reaction

Type I Type II Type III Type IV

Reaction Reaction Reaction Reaction

IgE mediated Antibody Immune T-cell-

Anaphylactic dependent complex mediated
Urticaria cytotoxicity damage damage
Angioedema IgG/IgM bind Antibody
Bronchopasm to antigens bindings
Hypotension on cells To antigens
Complement in large
Phagocyte quantities
German DF. MGH Lange, 2008
 Drug Allergy Symptoms

Erythema multiforme-Red, raised and itchy patches on the

skin that sometimes look like bull's-eye targets and which
may occur together with swelling of the face or tongue.

Fever
Muscle and joint aches
Lymph node swelling
Inflammation of the kidney
Drug allergy may cause serious reactions, including
anaphylaxis, a life-threatening condition that affects
multiple body systems.
 Erythematous maculopapular eruption due to penicillin: rashes of this kind are by far the
most common reactions to drugs.

Vervloet D , Durham S BMJ 1998;316:1511-1514

1998 by British Medical Journal Publishing Group

 Manifestasi alergi obat
Stevens-Johnson syndrome and toxic epidermal necrolysis: Patho... http://www.uptodate.com/contents/stevens-

Eritema multiforme

Lesi target
Angioedema
Urticarial
 Exfoliative dermatitisa severe complication in this case due to co-trimoxazole.

Vervloet D , Durham S BMJ 1998;316:1511-1514

1998 by British Medical Journal Publishing Group

 Manifestasi alergi obat

Fixed drug eruption

 Manifestasi alergi obat

Toxic epidermal necrolysis

Stevens-Johnson syndrome
Stevens-Johnson syndrome and toxic epidermal necrolysis: Patho... http://www.uptodate.com/contents/stevens-johnson-syndrome-and...
 Manifestasi alergi obat

Vasculitis
 What is an antiretroviral medication allergy?

An antiretroviral (ARV) medication allergy is a harmful

reaction to an ARV medicine.

An allergic reaction may happen when you start a new ARV

medicine or after you take the medicine for a few weeks.
 What are the signs and symptoms of an allergic
reaction to an ARV medicine ?
Mild reactions include hot, red, itchy, or swollen skin, or a hard
lump where the shot was given. You may have a flat, red area on
your skin that is covered with small bumps, headache, feel tired or
dizzy, or have muscle pain.

Severe symptoms include skin that blisters or peels, vision

problems, and severe swelling or itching. You may also have
yellowing of your skin or whites of your eyes, abdominal pain, or
dark urine. Severe reactions include conditions such as toxic
epidermal necrolysis (TEN). TEN can cause serious skin damage. Ask
your healthcare provider for more information on TEN and other
serious conditions.

Anaphylaxis symptoms include throat tightness, trouble breathing,

tingling, dizziness, and wheezing. Anaphylaxis is a sudden, life-
threatening reaction that needs immediate treatment.
 What increases my risk for an ARV medication
allergy?

HIV or AIDS

A history of other infections, such as hepatitis B, hepatitis C,

or Epstein-Barr virus (EBV)

A family history of ARV medicine reaction

A CD4 or CD8 cell (white blood cell) count above a certain

level when you start the medicine

A CD4 cell count below a certain level when you start the
medicine
 When clinical symtoms begin

Most begin one to three weeks after the introduction of

the medication, while recurrences after re-challenge begin
within 2 days.

This timing suggests sensitization and a specific

immunologic memory rather than direct toxicity, which
should occur when a dose related threshold is reached.

It is not yet understood why mild eruptions usually occur 9

5 days after initiation of the medication, when most
severe reactions often begin later: 14 7 days for Stevens-
Johnson syndrome(SJS)or Toxic Epidermal Necrolysis(TEN).

Allergology International Vol 55, No1, 2006 http://www.jsaweb.jp

 When clinical symtoms begin

28 14 days fordrug hypersensitivity syndrome(DHS)also

called drug reaction with eosinophilia and systemic
symptoms(DRESS).

Some eruptions occur much sooner : minutes to hours for

urticaria and anaphylaxis,

1 to 3 days for acute generalized exanthematous

pustulosis(AGEP) and fixed drug eruption(FDE). It is usually
proposed that AGEP and FDE are recall reactions after prior
overt or latent sensitization

Allergology International Vol 55, No1, 2006 http://www.jsaweb.jp

Patofisilogi
Medical Treatment
 Medical Treatment for Drug Allergies

Generally, treatment of a drug allergy falls into three categories:

Mild allergy (localized hives and itching)

Treatment is aimed at caring for the symptoms and stopping the
reaction caused by the drug.
Medications prescribed may include a sedating antihistamine, such as
diphenhydramine (Benadryl) or a non-sedating one, loratadine (Claritin).
You may be advised to stop taking the drug that caused the allergy.

Moderately severe allergy (all-over hives and itching)

Treatment is aimed at caring for the symptoms and stopping the
reaction.
Usually the offending medication is stopped.
Drugs prescribed may include antihistamines such as diphenhydramine
(Benadryl)), oral steroids (prednisone), or histamine blockers such as
cimetidine (Tagamet), famotidine (Pepcid), or ranitidine (Zantac).
 Medical Treatment for Drug Allergies

Severe allergy (shortness of breath, throat tightness, faintness, severe

hives, involvement of many organ systems)
Treatment includes strong medications to quickly reverse the
dangerous chain of events.
The offending drug is stopped immediately.
Medications prescribed may include antihistamines, oral or
intravenous steroids such as prednisone or methylprednisolone
(Solu-Medrol), or histamine (H2) blockers such as cimetidine
(Tagamet), famotidine (Pepcid), or ranitidine (Zantac).
Bronchodilators such as albuterol to reduce asthma-like symptoms
(moderate wheezing or cough)
Depending on the severity of other symptoms, other medications
may be used including epinephrine (also called adrenaline), which is
inhaled or injected into a vein or under the skin.
 Tata laksana Anafilaksis
I. Kecepatan penanganan sangat penting:
A. Airway, Breathing, Circulation, dan kesadaran
B. Epinefrin, IM anterolateral paha;
Epinefrin 1:1000, 0.3 - 0.5 mL , ulang tiap 5-15 jika
dibutuhkan.

C. Berbaring rata/ tinggikan posisi kaki bila mungkin

D. Oksigen 6 - 8 liter/menit
E. Infus NaCl fisiologis bolus atau infus 20 mL/kg diberikan
secepatnya bila perlu dengan tekanan ; atau koloid pada
hipotensi berat. (Pada anafilaksis berat, kehilangan 35 %
dari volume darah dalam waktu 10 menit pertama)
F. pertahankan airway (endotracheal tube atau
cricothyrotomy)
Kemp S and Lockey R. J Allergy Clin Immunol 2002;110:341-8
Simons FER et al. J Allergy Clin Immunol 2001;108:871-3
 Tata laksana Anafilaksis
Hipotensi
Ulangi infus NaCl fisiologis 10-20 ml/kg dapat mencapai 50 ml/kg dalam 30
menit pertama.
i.v. atropine 0.02 mg/kg bila bradikardi berat dosis minimum 0.1 mg
i.v vasopresor untuk mengatasi vasodilatasi.
i.v. glucagon pada pasien yang memakai obat penyekat beta.
Bronkospasme
Inhalasi salbutamol secara kontinyu
Hidrokortison iv
Obstruksi saluran napas bagian atas
Adrenalin inhalasi mungkin membantu.
Persiapkan krikotiroidektomi

Kemp S and Lockey R. J Allergy Clin Immunol 2002;110:341-8

Simons FER et al. J Allergy Clin Immunol 2001;108:871-3
 Stevens-Johnson syndrome

Requires hospitalization, often in an intensive care unit or burn unit.

Stopping nonessential medications

The first and most important step in treating Stevens-Johnson
syndrome is to discontinue any medications that may be causing it.
Because it's difficult to determine exactly which drug may be
causing the problem, your doctor may recommend that you stop
taking all nonessential medications.
Supportive care
Supportive care you're likely to receive while hospitalized includes:
Fluid replacement and nutrition. Because skin loss can result in
significant loss of fluid from your body, replacing fluids is an
important part of treatment. You may receive fluids and nutrients
through a tube placed through your nose and advanced into your
stomach (nasogastric tube).
 Stevens-Johnson syndrome

Wound care. Cool, wet compresses will help soothe blisters while
they heal. Your health care team may gently remove any dead skin
and place a medicated dressing over the affected areas.

Eye care. You may also see an eye specialist (ophthalmologist).

Medications
Medications commonly used in the treatment of Stevens-Johnson
syndrome include:
Pain medication to reduce discomfort
Medication to relieve itching (antihistamines)
Antibiotics to control infection, when needed
Medication to reduce skin inflammation (topical steroids
 Skema Pencegahan Reaksi Alergi Obat
Adakah obat alternatif yang efektif

Ada Tidak Ada

Obati dengan obat Uji kulit atau laboratorium

alternatif (tersedia dan dapat dipercaya)

Ya Tidak

Uji Uji Provokasi

Negatif Positif Negatif

Berikan obat Desensitisasi Teruskan

hati-hati atau pengobatan
pikirkan kembali
alternatif yang lain
 Efek samping NNRTI

Keluhan NVP (%) EFV (%)

Rash, total 17-24 5-10
Stevens-Johnson syndrome 0,5
Demam 5-10
Peningkatan transaminase 3-8 2
Efek CNS 52
Nausea 7-11
Substitusi ARV akibat efek samping
Obat ARV Toksisitas yang Sering Terjadi Anjuran Substitusi
AZT Anemia berat atau netropenia TDF
Intoleransi GI yang persisten
d4T Asidosis laktat TDF, AZT
Lipoatrofi/ sindrom metabolik,
neuropati perifer
TDF Toksisitas renal (disfungsi tubuler) AZT
EFV Toksisitas SSP persisten dan berat NVP atau TDF
Potensi teratogenik (pada NVP atau ABC
kehamilan trimester pertama atau
perempuan tanpa kontrasepsi yang
memadai)
NVP Hepatitis EFV
Reaksi hipersensitif tidak berat Jika memburuk dengan
(derajat 1- 2) diteruskannya NVP, substitusi
dengan EFV
Ruam kulit berat yang mengancam Hentikan NVP dahulu, lalu NRTI
jiwa (Stevens-Johnson syndrome) dihentikan 7 hari kemudian.
Substitusi dengan EFV
Pedoman Nasional Terapi Antiretroviral, 2011
Nevirapine

Efektivitas sama, dapat ditukar

NVP pada perempuan CD4 250-350 sel/mm3
berisiko lebih tinggi hepatotoksisitas dan alergi
limited evidence monitoring ketat
EFV dianjurkan digunakan bersama rifampisin,
dapat diganti setelah rifampisin selesai
EFV -> NVP: langsung dosis penuh (2 x 200 mg)