Drug-Induced Lupus Erythematosus Clinical Presentation

  • Author: Ivan D Camacho, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 27, 2012
 

History

Most patients with drug-induced lupus erythematosus (DILE) have 1 or more clinical symptoms of systemic lupus erythematous (SLE), such as arthralgias, lymphadenopathy, rash, and fever, and have no prior history of autoimmune disease. If a rash is present, it often manifests as a polycyclic, scaling, erythematous rash in sun-exposed areas.

Approximately 50% of patients have constitutional symptoms of fever, weight loss, and fatigue. As many as 90% of patients with DILE have severe but usually noninflammatory joint pain; however, synovitis may be present. Arthralgia is often the only clinical manifestation of DILE. As many as 50% of patients with DILE experience muscle pain (myalgia).

The drug will have been taken anywhere from 3 weeks to 2 years before the appearance of symptoms. Note that drug-associated exacerbations of SLE and typical drug hypersensitivities can also be temporally related to drug exposure. Clinical improvement is usually rapid when the drug is discontinued, whereas antinuclear antibodies and other serologic markers slowly decrease toward more normal levels.

Generally, the absence of central nervous system (CNS) and renal involvement is more suggestive of DILE than of SLE. High rates (ie, 5-10%) of glomerulonephritis, however, occur in hydralazine-induced DILE, and rare cases of death from renal involvement in DILE have been reported.

DISCLE differs from idiopathic SCLE by virtue of distinctive cutaneous features, particularly the common widespread presentation (82% vs 6%) and the frequent occurrence of malar rash (45% vs 6%), vasculitic manifestations (45% vs 3%), and bullous and erythema multiforme–like lesions (45% vs 1%). Visceral manifestations are not seen in DISCLE.[29]

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Physical Examination

Extracutaneous physical findings in DILE can include the following:

  • Splenomegaly
  • Hepatomegaly
  • Inflammation of the serous membranes that surround the lungs and pleural cavity walls (pleurisy)
  • Fever
  • Inflammation of the fibroserous membranes that cover the heart and the initial part of the great vessels (ie, pericarditis)
  • Cerebritis (rarely)
  • Episcleritis (rarely)[30]
  • Nephritis (rarely)

Skin findings are apparent in approximately 25% of all patients diagnosed with DILE. Note, however, that certain manifestations typical in persons with SLE are not usually observed in persons with DILE. Patients with DILE (unlike patients with SLE) typically do not have the following:

  • Mucosal ulcers
  • Hair loss (alopecia)
  • Circular (discoid) plaques
  • Photosensitivity (with the exception of thiazide-induced subacute lupuslike syndrome)

Compared with patients who have SLE, patients with DILE present with a higher prevalence of the following:

  • Purpura
  • Erythema nodosum (painful nodules, usually on the extremities)
  • Erythematous papules (typically on sun-exposed areas; see the image belowErythematous macules and papules are seen on face,Erythematous macules and papules are seen on face, upper chest, and arms in photodistribution.

Lymphadenopathy or Raynaud phenomenon is present in approximately 35-50% of patients with SLE but in fewer than 25% of those with DILE.

More than 75% of patients with SLE also have cutaneous findings, versus an average of less than 25% in patients with DILE. However, in both SLE and DILE, approximately 75% of patients have arthritis or arthralgia.

Patients with DILE less commonly present as drug-induced SCLE, exhibiting skin findings that are analogous to those manifested in patients with SCLE, such as erythematous annular polycyclic or papulosquamous lesions, but malar rash, vasculitic manifestations, blisters, or targetoid lesions mimicking erythema multiforme may also be observed.[31]

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Complications

Although both SLE and DILE can affect multiple organ systems, including the skin, joints, kidneys, eyes, and CNS, complications of DILE that affect the kidneys and CNS are generally considered rare. In DILE induced by certain drugs, however, the rate of kidney involvement can be significant. For example, the rate of glomerulonephritis in hydralazine-induced DILE is 5-10%. In rare instances, patients may die of renal involvement.

Penicillamine is also more likely to be associated with renal disease. Rare cases of death associated with DILE have been reported as a direct result of renal complications. Thus, a renal biopsy may be necessary to rule out membranous proliferative and necrotizing glomerulonephritis. Hepatic necrosis is another potential serious complication of DILE and has been documented in cases of minocycline-induced DILE.

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Contributor Information and Disclosures
Author

Ivan D Camacho, MD  Assistant Professor of Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine; Medical Director of Dermatology Clinic, Jackson Memorial Hospital

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, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

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, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society

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  Director, Ackerman Academy of Dermatopathology, New York

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

Disclosure: Nothing to disclose.

Additional Contributors

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 1. Comparison of Findings Between Drug-Induced Lupus Erythematosus and Systemic Lupus Erythematosus
FindingsSLEDILE
ClinicalAverage 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 HistopathologyDirect 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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