drug induced lupus (dil)-drug induced nephrotic sd

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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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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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

drug induced lupus (dil)-drug induced nephrotic sd

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