Drug-Induced Lupus Erythematosus Workup

Updated: Jun 23, 2020
  • Author: Catharine Lisa Kauffman, MD, FACP; Chief Editor: Dirk M Elston, MD  more...
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Antibody Assays

Test for the presence of antinuclear antibodies, which can appear in a homogeneous pattern in as many as 90% of patients with lupus erythematosus. In drug-induced lupus erythematosus (DILE), when anti-ssDNA and anti-dsDNA are measured, the prevalence of anti-ssDNA is higher. This is a major difference from systemic lupus erythematosus (SLE); in SLE, antibodies tend to attack double-stranded DNA.

Antinuclear antibodies with homogeneous patterns are produced by procainamide, isoniazid, timolol, hydralazine, and phenytoin. In contrast, speckled antinuclear antibody patterns are associated with anti-SSA/Ro antibodies, which can be produced in response to thiazide diuretics such as hydrochlorothiazide. A systematic review evidenced that anti-SSA/Ro antibodies are found in most patient with DISCLE (about 80% of cases), in whom antihistone antibodies are uncommonly found, and most remained positive after resolution of SCLE skin disease activity. [7]

In persons with DILE, the antibodies also tend to attack histones (proteins typically found in cell nuclei). Antihistone antibodies are indicated by a homogeneous pattern of antinuclear antibodies. They are present in more than 75% of patients with DILE induced by hydralazine and procainamide. An example of an antihistone antibody that is often implicated in DILE is immunoglobulin G (IgG; anti-[H2A-H2B] DNA). Antihistone antibodies are much more likely to indicate DILE; however, they can also appear in as many as 50% of patients with SLE.

In persons with DILE, anti-Sm antibodies are rare. Complement levels are within the reference range, which is not usually the case in persons with SLE.


Other Tests

Further tests in the workup of a patient with possible DILE are as follows.

A complete blood count (CBC) should be performed to evaluate for anemia, which is present in most patients with SLE but is rare in those with DILE. Blood urea nitrogen (BUN) and creatinine should be assessed. C3 and C4 levels should be measured. Complement levels are often reduced in persons with SLE, whereas they tend to not be reduced in persons with DILE.

Liver function tests to can be performed to evaluate for hepatic involvement. Urinalysis can be performed to evaluate for hematuria and proteinuria.

Use chest radiography to rule out pulmonary infiltrates. Use echocardiography, if indicated, to rule out pericarditis.


Tissue Analysis and Histologic Findings

Skin biopsy may be indicated, as well as renal biopsy if renal involvement is suggested. Skin biopsy and direct immunofluorescence typically reveal findings that are indistinguishable from those seen in SLE.

Histologic examination reveals variable epidermal atrophy, basal vacuolar degeneration, apoptotic or dyskeratotic keratinocytes, and lymphocytic interface dermatitis (see the images below).

Dermis contains interface and superficial and deep Dermis contains interface and superficial and deep perivascular lymphohistiocytic infiltrate (×100, hematoxylin-eosin).
Parakeratosis, apoptosis, and basal vacuolization Parakeratosis, apoptosis, and basal vacuolization (×200, hematoxylin-eosin).

Direct immunofluorescence may reveal granular deposition of IgG along the dermoepidermal junction.