Drug-Induced Glomerular Disease: Immune-Mediated Injury

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Figure 1.
A glomerulus from a patient who used cocaine that contained levamisole and presented with rapidly progressive GN and high-titer anti-myeloperoxidase ANCA. The glomerulus exhibits fibrinoid necrosis, multifocal rupture of the glomerular basement membrane, and an overlying, circumferential cellular crescent. Jones methenamine silver, ×400.
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Figure 2.
Digital cutaneous vasculitis of a patient with levamisole-associated, ANCA-associated vasculitis. Reprinted from Joan Von Feldt and Robert Michelleti, with permission.
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Figure 3.
A glomerulus from a patient who developed nephrotic syndrome while receiving a nonsteroidal anti-inflammatory drug for arthritis. The glomerulus exhibits global thickening of the glomerular basement with spike formation, which is characteristic of stage 2 membranous changes. Jones methenamine silver, ×400.

Table 1.

Drugs commonly implicated in ANCA-associated vasculitis

Drug	Evidence	Renal Involvement	Comments
Cocaine and levamisole	Multiple case series and case reports	44%^a	Skin manifestations in 61%^a
Cocaine and levamisole	Multiple case series and case reports	44%^a	Neutropenia in 28%^a
Hydralazine	Case series and case reports	80%–90%^b	Combined pulmonary-renal syndrome is rare (15 patients to date)
Hydralazine	Case series and case reports	80%–90%^b	Lupus-like syndrome is common
Antithyroid medications	PTU: multiple case series and case reports	May be common	Animal models also support association with PTU
Antithyroid medications	Carbimazole and methimazole: case reports	May be common	Animal models also support association with PTU
Minocycline	Small case series and case reports	No reported cases of renal involvement with small-vessel vasculitis	Conflicting data on ANCA seroconversion with minocycline use (45,46)
Minocycline	Small case series and case reports	PAN with p-ANCA positivity and renal involvement reported
Allopurinol	Case reports	Reported	Pulmonary-renal syndrome rarely reported
Penicillamine	Case reports	Reported	No seroconversion noted in analysis of scleroderma trial (46)
Sulfasalazine	Case reports	Reported	Pulmonary-renal syndrome also reported
Sulfasalazine	Case reports	Reported	No seroconversion noted in analysis of the CSSRD Trial (46)

PTU, propylthiouracil; PAN, polyarteritis nodosa; p-ANCA, perinuclear ANCA; CSSRD, Cooperative Systematic Studies of the Rheumatic Diseases.
↵a Data from the largest case series of cocaine- and levamisole-associated, ANCA-associated vasculitis (21).
↵b Data from the largest series of hydralazine-associated, ANCA-associated vasculitis (5,38).

Table 2.

Drugs and risk for developing drug-induced lupus

Drug Category	Risk for Drug-Induced Lupus
Drug Category	High	Moderate	Low	Very Low
Antiarrhythmics	Procainamide	Quinidine		Disopyramide, propafenone, amiodarone
Antihypertensives	Hydralazine		Methyldopa, captopril, acebutolol	Enalapril, lisinopril, clonidine, atenolol, labetalol, pindolol, minoxidil, prazosin
Antipsychotics			Chlorpromazine	Phenelzine, chlorprothixene, lithium
Antibiotics			Isoniazid, minocycline	Nalidixic acid, sulfamethoxazole, quinine
Anticonvulsants			Carbamazepine	Clobazam, phenytoin, trimethadione, primidone, ethosuximide, valproic acid
Antithyroid			Propylthiouracil
Diuretics				Chlorthalidone, hydrochlorothiazide
Biologics			TNF-α inhibitors	IFN-α
Miscellaneous				Statins, levodopa, aminoglutethimide, timolol drops, ticlodipine

Table 3.

Comparison of clinical and laboratory features of three drugs associated with drug-induced lupus

Drug	Clinical Features	Laboratory Features	Positive Antibody Tests
Hydralazine	Rash, fever, myalgias, pleuritis, polyarthritis nephritis <10%	Anemia, leukopenia	ANA, anti-dsDNA, ANCA, antihistone
Procainamide	Polyarthritis, polyarthralgias serositis nephritis <10%	Anemia	Anti-dsDNA, antihistone, anticardiolipin
TNF-α inhibitors	Systemic symptoms predominant (nephritis in 7%); skin manifestations dominate	Thrombocytopenia, hypocomplementemia	ANA, anti-dsDNA, antinucleosome, anticardiolipin