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Drug-Induced Lupus Erythematosus Workup

  • Author: Ivan D Camacho, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 14, 2016

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.[5]

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.

Contributor Information and Disclosures

Ivan D Camacho, MD Dermatologist, Private Practice; Voluntary Assistant Professor of Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine

Ivan D Camacho, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Florida Medical Association, International Society of Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.


Catharine Lisa Kauffman, MD, FACP Georgetown Dermatology and Georgetown Dermpath

Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, Royal Society of Medicine, Women's Dermatologic Society, American Medical Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Arden E Fredeking Georgetown University School of Medicine

Arden E Fredeking is a member of the following medical societies: American Medical Student Association/Foundation

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Craig A Elmets, MD Professor and Chair, Department of Dermatology, Director, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine

Craig A Elmets, MD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, American College of Physicians, American Federation for Medical Research, and Society for Investigative Dermatology

Disclosure: Palomar Medical Technologies Stock None; Astellas Consulting fee Review panel membership; Massachusetts Medical Society Salary Employment; Abbott Laboratories Grant/research funds Independent contractor; UpToDate Salary Employment; Biogen Grant/research funds Independent contractor; Clinuvel Independent contractor; Covan Basilea Pharmaceutical Grant/research funds Independent contractor; ISDIN None Consulting; TenX BIopharma Grant/research funds Independent contractor

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

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Erythematous macules and papules are seen on face, upper chest, and arms in photodistribution.
Dermis contains interface and superficial and deep perivascular lymphohistiocytic infiltrate (×100, hematoxylin-eosin).
Parakeratosis, apoptosis, and basal vacuolization (×200, hematoxylin-eosin).
Table. Comparison of Findings Between Drug-Induced Lupus Erythematosus and Systemic Lupus Erythematosus
Findings SLE DILE
Clinical Average age of onset of 20-30 y

Affects blacks more than whites

Female-to-male ratio of 9:1

Average age of onset of 50-70 y

Affects whites more than blacks

Female-to-male ratio of 1:1

Laboratory Antihistone antibodies in 50%

Anti-dsDNA present in 80%

C3/C4 levels decrease

Cutaneous findings in >75%

Raynaud phenomenon in 50%

Antinuclear antibodies in >95%

Antihistone antibodies in >95%

Anti-ssDNA present

Anti-dsDNA rare C3/C4 levels normal

Cutaneous findings in ~25%

Raynaud phenomenon in 25%

Antinuclear antibodies in >95%

Immunofluorescence Histopathology Direct immunofluorescence reveals granular deposition of IgG at dermoepidermal junction

Lymphohistiocytic interface dermatitis

Apoptosis basal vacuolization

Same as SLE

Same as SLE

DILE = drug-induced lupus erythematosus, IgG = immunoglobulin G; SLE = systemic lupus erythematosus.
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