Dermatology Online Journal

Systemic lupus erythematosus with generalized chronic cutaneous (discoid) lupus erythematosus
Chicky Dadlani MD, Melissa Pulitzer MD, and Stephen D Prystowsky MD
Dermatology Online Journal 14 (5): 5

Department of Dermatology, New York University

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Abstract

A 24-year-old pregnant African-American woman had a 3-4 year history of chronic, scarring, hyperpigmented plaques on her scalp, face, trunk, and extremities. She complained of joint pain and fatigue. Clinical presentation, laboratory data, and histopathologic features were consistent with systemic lupus erythematosus in a patient with generalized chronic discoid lupus erythematosus. This subtype is a distinct lupus erythematosus subset that rarely develops renal disease and has a relatively benign but chronic course.

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Clinical synopsis

A 24-year-old African-American woman, who is 6 months pregnant, presented to the Dermatology Clinic at Bellevue Hospital Center in March, 2007, for treatment of multiple plaques that had involved her scalp, ears, face, trunk, and extremities for the last 4 years. At the time of onset, she reported joint pain and pruritic, discolored lesions that began on her arms, face, and scalp. At that time, she was hospitalized for pruritus and arthralgias. Hydroxychloroquine and prednisone were administered and she was followed up in a rheumatology clinic. Although she kept her follow up appointments, she was not compliant with her medications. Within 1 year, similar lesions developed in other areas of her body. She denied a history of headaches, seizures, fever, weight loss, cough, shortness of breath, and Raynaud phenomenon. She had not received any treatment for the previous year. The skin lesions have remained stable with no new skin lesions noted over the last year. She experiences mild pruritus of her skin lesions, arthralgias, fatigue, and myalgias. Medications include multivitamins. Medical history is otherwise unremarkable. The patient denies smoking, alcohol consumption, and drug use. A punch biopsy was obtained from her right upper arm in March, 2007.

Physical examination

There were no oral lesions. Bilateral, diffuse, well-demarcated, papules and plaques with irregular borders and thick, adherent, white scale were present on the flanks, sacrum, thighs, abdomen, arms, scalp, face, and ears. Most lesions had a hyperpigmented periphery and an atrophic, hypopigmented center. The plaques on the arms, abdomen, flanks, and buttocks had coalesced with adjacent plaques to form larger disfiguring lesions. Lesions on posterior thighs appeared smaller and predominantly round. Lesions in the scalp were associated with areas of scarring alopecia. On the soles, palms, and volar aspects of the fingers were a few, scattered, fading, hyperpigmented, poorly-marginated macules. Fingernail abnormalities could not be assessed due to acrylic nails.

Figure 1	Figure 2

Laboratory data

In February, 2004, the sedimentation rate was normal. Antinuclear antibody (ANA) was detected at < 1:40. In February - March, 2007, the white-cell count was 5.3 x 109/L, hemoglobin 11.9 g/dl, hematocrit 36.2 percent, and platelets 211 x 109/L with a normal differential analysis. The sedimentation rate was 44 mm/hr. Basic metabolic and hepatic function panels were normal. ANA was detected at 1:1280 with a homogenous pattern. Anti-smith antibody (>6.0), anti-RNP (>6.0), anti-Ro/SS-A (>6.0), and anti-double-stranded DNA (dsDNA) antibodies (76) were positive. Anti-La/SS-B, anti-fl-2 glycoprotein, lupus anticoagulant, and anti-cardiolipin antibody were absent. Human immunodeficiency virus was negative. A 24-hour urine protein level was elevated at 147 mg.; C3 and C4 were normal.

Histopathology

Figure 3

There is compact orthokeratosis, hypergranulosis, and irregular acanthosis of the epidermis. There are interface changes of the dermoepidermal junction with necrotic keratinocytes and a thickened basement membrane. Within the papillary dermis are dilated blood vessels, numerous melanophages, and perivascular and interstitial lymphocytes.

Comment

Lupus erythematosus (LE) is manifested in several forms and may involve any organ in the body. Systemic lupus erythematosus (SLE) affects the skin, joints, kidneys, lungs, nervous system, serous membranes, and other systems [1]. Musculoskeletal manifestations are the most common feature of SLE. In some patients, arthralgia or arthritis may precede the onset of multisystem disease by many years [1]. There are three major forms of cutaneous lupus erythematosus as follows: chronic cutaneous (discoid) LE (CCDLE), subacute cutaneous LE (SCLE), and acute cutaneous LE. Chronic cutaneous DLE affects twice as many women as it does men and usually appears in early-to-mid-adulthood [2]. Chronic cutaneous DLE begins as red-purple macules, papules, or small plaques, with adherent scale that extends into patulous follicles. The lesions tend to heal centrally with atrophy, scars, dyspigmentation, and telangiectases [3]. Patients with localized CCDLE have lesions on the head, neck, or both. However, in the generalized variant, lesions can be found on the trunk, upper extremities, palms, and soles [2, 3, 4]. Patients with CCDLE generally have no extracutaneous disease and less than 10 percent of them will develop SLE [3]. Patients with CCDLE who tend to develop SLE are characterized by generalized DLE, the presence of periungual telangiectases, persistent elevated erythrocyte sedimentation rates, leucopenia, and positive ANA [5]. Patients may have CCDLE alone at the onset or CCDLE with other symptoms or signs [5]. When systemic symptoms develop, they are frequently milder than are those found in patients with SLE who do not have CCDLE.

The systemic symptoms usually consist of arthritis, arthralgia, and Raynaud phenomenon [2]. No single test can reliably detect those CCDLE patients who will have systemic manifestations [2]. The time frame is variable, but most patients develop the criteria for SLE within 1-3 years [5]. Simultaneous occurrence of severe systemic LE with nephritis is rare in this subset of patients; if renal disease does occur, it is often transient and mild [3]. This group of patients is a distinct subtype of SLE and the course is relatively benign but chronic [5]. Although there is considerable heterogeneity among patients with this subtype, there are a few important generalizations as follows [2, 6, 7]: patients rarely will have diffuse proliferative glomerulonephritis and renal insufficiency; greater than 90 percent of patients have serum antinuclear antibodies, but the peripheral immunoflourescence staining pattern is seldom present in high titer; persistent elevations in anti-dsDNA antibody occur infrequently; one-half of these patients have depression of serum complement levels; patients with Raynaud phenomenon frequently have antibodies either to ribonucleoprotein or to nucleolar ribonucleic acid; and severe CNS disease and systemic vasculitis may occur in this group.

Histopathologic findings in active CCDLE show hyperkeratosis and follicular dilatation with keratin plugs, an atrophic or flattened epidermis, liquefactive degeneration of the basal layer of the epidermis, basement-membrane thickening, and a perivascular and periadnexal inflammatory cell-infiltrate of lymphocytes with variable numbers of macrophages [8].

Antimalarials are the standard treatment of CCDLE. The mechanism of action is unknown but is thought to be related to systemic photoprotection or to immunomodulation. Patients with the CCDLE-SLE subtype respond more poorly to antimalarials than do those without systemic manifestations. Many other systemic agents have been reported as treatment for CCDLE, including azathioprine, methotrexate, cyclophosphamide, oral gold, cytarabine, cyclosporin, mycophenolate mofetil, retinoids, dapsone, and thalidomide [5]. Despite their effect on systemic manifestations, systemic glucocorticoids are rarely effective for CCDLE.

Our patient is also being followed by a rheumatologist. Hydroxychloroquine 200 mg twice a day has been reinstituted. Early reports of in utero chloroquine toxicity have caused some concern about the use of hydroxychloroquine in pregnancy. However, more recent studies have suggested its safety. A prospective study of hydroxychloroquine use in pregnancy found that the rates of miscarriage, stillbirths, and congenital abnormalities were not statistically different from those of women who were not exposed to hydroxychloroquine [9]. The cessation of hydroxychloroquine activity increases the degree of activity of lupus erythematosus in pregnancy, which can be detrimental because disease activity in patients with SLE predicts a poor pregnancy outcome [10]. Systemic LE per se increases the risk of a reduced birth weight and preterm delivery [10, 11].

References

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6. Prystowsky SD, et al. Discoid lupus erythematosus as part of a larger disease spectrum. Arch Dermatol 1975;111:1448

7. Prystowsky SD. Mixed connective tissue disease. West J Med 1980;132:288

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11. Dhar PJ, et al. Pregnancy outcomes before and after a diagnosis of systemic lupus erythematosus. Am J Obstet Gynecol 2005;193:444

12. Prystowsky SD, et al. Chronic cutaneous lupus erythematosus (DLE): a clinical and laboratory investigation of 80 patients. Medicine 1976;55:183

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