# Drug-Induced Pathology > Drug-induced pathology for MBBS Pathology: type A and B reactions, paracetamol and ATT liver injury, SJS, TEN, DRESS and marrow aplasia. - Canonical URL: https://prepelephant.com/topics/mbbs/pathology/drug-induced-pathology - Exam / course: MBBS · Subject: Pathology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Drug-Induced Pathology", PrepElephant, https://prepelephant.com/topics/mbbs/pathology/drug-induced-pathology ## Direct answer No organ escapes adverse drug reactions, and pathology sorts them into two families: type A — dose-dependent augmentation of the drug's known pharmacology, predictable and common — and type B, idiosyncratic reactions that are dose-independent, unpredictable and often immune-mediated, allergy being the paradigm. The liver bears the heaviest burden: paracetamol produces dose-related centrilobular necrosis through NAPQI glutathione depletion, reversible within a window by N-acetylcysteine, while anti-tubercular therapy causes idiosyncratic hepatotoxicity — isoniazid, rifampicin and pyrazinamide together — a daily clinical event in India, where national programme guidance hinges on monitoring and timely drug withdrawal. The skin contributes Stevens-Johnson syndrome and toxic epidermal necrolysis, the marrow aplasia, and the kidneys interstitial nephritis and crystal injury — each with named culprit drugs the exam expects verbatim. ## What you must remember - **Paracetamol mechanism to recite:** metabolised to the toxic NAPQI, which is detoxified by glutathione; overdose floods the pathway, NAPQI covalently binds centrilobular hepatocytes, and N-acetylcysteine (within roughly 8-24 hours, best early) repletes glutathione — the antidote logic examiners reward. - **ATT hepatotoxicity, the Indian standard:** baseline and periodic liver function testing under the national programme; the usual working rule is withdrawal when transaminases exceed three times the upper limit with symptoms, or a substantially higher asymptomatic threshold per current guidance — learn it as "jaundice or symptoms plus enzymes", and rechallenge cautiously. - **SJS/TEN continuum:** epidermal necrosis with mucosal involvement — under 10 per cent body-surface detachment is SJS, over 30 per cent is TEN, between lies the overlap; culprit drugs are sulphonamides, aromatic anticonvulsants (carbamazepine, phenytoin), allopurinol, nevirapine and NSAIDs; keratinocyte apoptosis via Fas-Fas ligand and granulysin; mortality is scored by SCORTEN. - **DRESS syndrome:** drug reaction with eosinophilia and systemic symptoms — rash, fever, eosinophilia, hepatitis, onset two to eight weeks after the culprit (which distinguishes it from SJS timing), with HHV-6 reactivation implicated; treated by drug withdrawal and systemic steroids. - **HLA-pharmacogenomics pairs to quote:** abacavir with HLA-B*57:01 (hypersensitivity) and carbamazepine with HLA-B*15:02 (SJS) — the clearest proof that idiosyncrasy has genetic structure. - **Marrow and blood:** chloramphenicol aplasia, methotrexate mucositis and myelosuppression, heparin-induced thrombocytopenia (paradoxical thrombosis), clopidogrel-associated TTP — and linezolid's lactic acidosis with prolonged use. - **Renal patterns:** acute interstitial nephritis (NSAIDs, beta-lactams — with the classic trial of fever, rash and eosinophilia), aminoglycoside proximal tubular injury, tenofovir Fanconi syndrome, and crystal nephropathy from aciclovir or indinavir. - **Timing is diagnosis:** type A follows dose and time-on-drug predictably; immune reactions cluster at one to eight weeks; idiosyncratic DILI has no safe window — a drug started years ago can still be the culprit. ## Rash and fever three weeks into a new drug A 34-year-old started on carbamazepine for focal seizures three weeks ago presents with fever, a spreading maculopapular rash on the trunk, facial oedema, tender cervical lymphadenopathy and eosinophilia on the smear; transaminases are three times normal. The differential now runs SJS/TEN versus DRESS versus a simple exanthem, and three questions decide it. Are mucosae involved — conjunctivitis, oral erosions, genital ulceration? SJS/TEN yes, DRESS minimal. Is the skin blistering or detaching with lateral pressure (Nikolsky sign)? That settles TEN. How far does the rash go — DRESS is a spreading infiltrated eruption with systemic organ involvement, at times desquamating late? The patient has mucosal sparing, no blisters, marked eosinophilia and hepatitis: DRESS. Management: stop carbamazepine immediately, never rechallenge, switch to a structurally unrelated anticonvulsant (levetiracetam is the usual choice), supportive care with steroid judgement, and observe hepatic function over weeks. Had the answer been TEN, the patient would go to a burns-style unit, fluids and wound care; the two pathways diverge completely from one bedside examination. ## Where students slip Type A versus type B is a guaranteed one-mark question answered wrongly by assuming all drug toxicity is allergic — paracetamol is type A, penicillin anaphylaxis type B. Do not call every DILI pattern "hepatitis": cholestatic (amoxicillin-clavulanate, anabolic steroids) and mixed patterns exist, and the R-ratio (ALT/ALP multiples of normal) sorts them. Students forget that N-acetylcysteine works beyond the classic eight-hour window — late is still better than never. And the nevirapine SJS signal matters in Indian HIV practice: escalating dose, women with higher CD4 counts, and the first six weeks carry the risk. ## Frequently asked questions ### How does paracetamol kill hepatocytes? Its reactive metabolite NAPQI, normally detoxified by glutathione, accumulates in overdose and covalently binds centrilobular hepatocyte proteins, causing necrosis. ### Which drugs are the commonest causes of SJS/TEN? Sulphonamides, aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbitone), allopurinol, nevirapine and oxicam NSAIDs, typically one to three weeks after starting. ### What distinguishes DRESS from SJS? DRESS shows eosinophilia, systemic organ involvement and onset two to eight weeks after the drug, with minimal mucosal involvement; SJS/TEN is mucosa-eroding epidermal necrosis. ### When should anti-tubercular drugs be stopped for liver injury? Per national programme practice, when jaundice appears or transaminases exceed three times the upper limit with symptoms — with rechallenge and alternative regimens thereafter. ### Which HLA allele predicts abacavir hypersensitivity? HLA-B*57:01 — screening before prescription has essentially eliminated the hypersensitivity reaction in carriers.