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8/22/2019 Drug Induced Lupus (DIL)-Drug Induced Nephrotic Sd
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DRUG INDUCED LUPUS (DIL)
DRUG INDUCED NEPHROTIC
Mara Vernica Castillo Higgins
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Adverse Drug Reactions
We define an adverse drug reaction as a harmful or
unpleasant reaction, resulting from the use of a medicinal
product
It can be divided in 2 groups:
Type A: Augmented pharmacologic effects - dose dependent and
predictable
Type B: Bizarre effects (or idiosyncratic) - dose independent andunpredictable
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Type B adverse drug reaction
Cannot be predicted from the know pharmacology of the
drug.
Do not show a simple dose-response relationship.
Affect a minority of patients taking the drug The predisponding factors for these reactions are
unknown.
The proposed mechanism is immune mediated toxicity .
Genetics factors also play an important role.
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DRUG INDUCED LUPUS
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Introduction
Drug-induced lupus (DIL) is a lupus-like syndrome
Is a rare type B adverse reaction to a large variety of
drugs
Related to continuous drug exposure. Resolves upon drug discontinuation.
Drug-induced autoimmunity is idiosyncratic belonging to
the category
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Epidemiology
15,00030,000 cases of DIL in the United States every
year.
Less predilection for females and African Americans than
LES
The age of onset of DIL is generally older
Female to male distribution 1:1
Whites may be affected up to six times more frequently
than african americans and may have more severemanifestations.
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Etiology
Over 80 drugs have been implicated in DIL, and the
number is increasing constantly .
The drugs differ widely in their pharmacological and
chemical characteristics and therapeutic indications.
Their belonging to at least 10 major categories of drugs
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Etiology
Drugs can be divided into three main groups according
to the likelihood of causing DIL
Group I: Definite association based on controlled studies
confirming its pathogenic role in inducing DIL.
Group II: Probable association based on large series or cohorts
consistently reported.
Group III: Possible association with a few case reports.
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Etiology-Drugs
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Etiology-Drugs
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Clinical Signs and Symptoms of DIL
Usually milder than those seen in idiopathic SLE
Onset of symptoms can be abrupt, but more typicallythere are only a few mild symptoms initially, with gradual
worsening over a period of weeks or even months
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Clinical Signs and Symptoms of DIL
The most frequent clinical signs and symptoms of DIL are:
Arthralgia
Myalgia
Fever
Malaise
Anorexia and weight loss.
Cutaneous manifestations are less common than in SLEdepending on the inducing agent.
Other manifestations include pleuritis/pleural effusion,
pericarditis, and hepatosplenomegaly.
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CONTRASTING DIL & SLE
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Clinical Signs and Symptoms of DIL
Major organ involvement is rare, although cases of
glomerulonephritis have been reported after treatment
with:
Hydralazine
Sulfasalazine,
Propylthiouracil
Anti-TNF- therapy
Nephrotoxicity seems to be particularly frequent in D-
penicillamine induced lupus
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Diagnosis
Specific criteria for diagnosing drug-induced lupus havenot been formally established. However, some symptomsoverlap with those of SLE. These include:
Arthritis Serositis
Flu-like symptoms of fatigue and fever
Laboratory test abnormalities : antinuclearantibodies [ANA] , anti-histone antibodies;
In addition the symptoms: Must have begun after initiation of the drug treatment
Must resolve after drug discontinuation
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Treatment
DIL resolves spontaneously and completely within weeks
or months after withdrawal of causative agent.
Time required for resolution is variable, Depend on theagent and the patient disease characteristics
Irreversibility is an indication of drug unmasked underlying
idiopathic SLE
Severe cases may require corticosteroids or other
immunosuppressive therapy
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DRUG INDUCED NEPHROTIC SYNDROME
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Introduction
Medications that alter glomerular histology and
permeability often cause proteinuria in the nephrotic
range
Toxic lymphokines of interstitial inflammation might be
implicated
Humoral factors might also be involved, given the
presence of eosinophils and lymphocytes in the interstitial
infiltrate.
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DRUGS MECHANISM
N SAIDS
Mefenamate
Fenoprofen
Minimal change lesions
Gold
Penicillamine
ACE inhibitors
Foscarnet
Membranous lesions
interferon Minimal change, focal segmental
hyalinosis with crescenticglomerulonephritis and membranous
nephropathy
Bisphosphonate
Pamidronate
Focal segmental sclerosis
Lithium focal glomerulosclerosis of the collapsing
type.
Other
propiltiouracilo
infliximab
Bevacizumab
Heroin
Heavy metals - mercurium
Nefrotic range proteinuria
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Treatment
Discontinuation of medication usually reverses the clinical
findings.
Severe cases may require corticosteroids or otherimmunosuppressive therapy
Resolution can, however, be delayed for months or years,
specially that of gold-induced nephropathy