Time to progression from discoid lupus erythematosus to systemic lupus erythematosus: a retrospective cohort study.

Determining the risk of progression to systemic lupus erythematosus (SLE) among patients diagnosed with discoid lupus erythematosus (DLE), and the time frame of this risk, are important clinical questions. Past reports have demonstrated a wide time frame of progression from DLE to SLE, with mean time to progression of approximately 8 years. Using data obtained from an academic lupus centre, we identified 32 patients who progressed from DLE to SLE. In our cohort, we found that the median time to progression from DLE to SLE was 453 days, much sooner than previously reported. We believe this information can help inform clinicians on monitoring visit intervals and how best to counsel patients on SLE progression.

Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort.

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

The natural history of pediatric-onset discoid lupus erythematosus.

BACKGROUND: Pediatric discoid lupus erythematosus (DLE) is rare. The risk of progression to systemic lupus erythematosus (SLE) is uncertain. OBJECTIVE: We sought to determine the risk of progression of pediatric DLE to SLE and to characterize its phenotype. METHODS: This was a retrospective review of 40 patients with DLE. RESULTS: Six (15%) of 40 patients presented with DLE as a manifestation of concurrent SLE. Of the remaining 34, 9 (26%) eventually met SLE criteria and 15 (44%) developed laboratory abnormalities without meeting SLE criteria. Only 10 (29%) maintained skin-limited disease. The average age at progression to SLE was 11 years, with greatest risk in the first year after DLE diagnosis. Most (89%) patients with SLE met diagnostic criteria with mucocutaneous disease (discoid lesions, malar rash, oral and nasal ulcers, photosensitivity), positive antibodies, and/or cytopenia without developing end-organ damage over 5 years of median follow-up. LIMITATIONS: The study was retrospective. CONCLUSIONS: In pediatric patients, DLE carries a significant risk of progression to SLE but may predict a milder phenotype of systemic disease. All patients require careful monitoring for SLE, particularly within the first year of diagnosis.

Acute lumbosacral polyradiculoneuropathy heralding transformation to systemic lupus erythematosus in a patient with discoid lupus.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with which a variety of neuropathic disorders have been associated. Among these, the acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barré syndrome has been well established. However, acute axonal lumbosacral polyradiculoneuropathy accompanied by albuminocytological dissociation in the cerebrospinal fluid has been extremely rarely reported in SLE. We report on a 47-year-old woman with discoid lupus presenting with acute onset of flaccid paraplegia. Extensive investigations suggested the diagnoses of axonal lumbosacral polyradiculoneuropathy and SLE. Treatment with intravenous methylprednisolone and cyclophosphamide resulted in clinical recovery. Development of immune-mediated polyneuropathy in a patient with discoid lupus should forewarn the clinician regarding transformation into the systemic form of the disease.

Squamous cell carcinoma arising in a recent plaque of discoid lupus erythematous, in a sun-protected area.

Squamous cell carcinoma is a known complication reported to occur in chronic discoid lupus erythematosus in sun-exposed areas. We report a patient with systemic lupus erythematosus who developed a squamous cell carcinoma in a recent plaque of discoid lupus erythematosus in a sun-protected area. This article emphasizes the need for a very high index of suspicion for squamous cell carcinoma and repeated biopsies when discoid lupus erythematosus fails to respond to conventional therapy or there is unexplained exacerbation.

Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus.

The prevalence and prognostic value of cutaneous manifestations in patients with systemic lupus erythematosus (SLE) is not clear due to a lack of distinct criteria. Our aim was to investigate the prevalence of cutaneous manifestations in SLE patients according to strict dermatological classification, compare the results with other studies and to assess differences in serological markers between patients with and without cutaneous lupus erythematosus (CLE). Secondary aims were to investigate the validity of the criteria 'malar rash' and 'photosensitivity' for SLE diagnosis. We included 260 consecutive SLE patients, and 164 with skin complaints were examined by a dermatologist. CLE was found in 23% of the 260 SLE patients. There was agreement on the presence of malar rash in only 60% of patients seen by both rheumatologists and dermatologists. A history of polymorphous light eruption (PLE) was found in 42% of patients. Raynaud's phenomenon was significantly more common in patients with CLE. In addition, four malignant melanomas were found. Based on our findings, we suggest that the American College of Rheumatology (ACR) criteria for SLE diagnosis include histopathologically confirmed CLE as one criterion, and that the criteria photosensitivity and malar rash should be re-defined. Regular examination by a dermatologist is called for in SLE patients.

Discoid lupus erythematosus in a patient with scleroderma and hepatitis C virus infection.

A 49-year-old Japanese woman presented with discoid lupus erythematosus (DLE) on the face. The presence of Raynaud's phenomenon, swollen fingers, a high anti-nuclear antibody titer, and the results of a biopsy revealed limited-type systemic sclerosis (lSSc). The association of SSc with DLE is rare, although some single case reports have been published in Japan. Our patient was positive for hepatitis C virus infection. Racial predisposition and immune imbalance are proposed to have played a role in the development of these lesions in our case.

Dramatic response of scarring scalp discoid lupus erythematosus (DLE) to intravenous methylprednisolone, oral corticosteroids, and hydroxychloroquine in a 5-year-old child.

Discoid lupus erythematosus (DLE) is rare in childhood. We report the case of a 5-year-old girl who presented with erythematous scaly plaques, with scarring alopecia, involving approximately 40% of her scalp. Histopathology confirmed the diagnosis of DLE. Treatment with intravenous methylprednisolone, hydroxychloroquine, oral prednisone, topical corticosteroids, and sunscreen lead to reversal of scarring alopecia and re-growth of hair.

Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus.

Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus- and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+ T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.

Instrumentation and action spectra in light-associated diseases.

Instrumentation for studying action spectra in controls and various light-associated diseases is described. This study summarizes tests performed with a prism grating monochromator during the last 10 yr. There were 68 photodermatoses studied: xeroderma pigmentosum (XP) (1), lupus erythematosus (LE) (12), polymorphous light eruption (PLE) (23), solar urticaria (4), actinic reticuloid (2), halogenated salicylanilide photosensitivity and persistent light reactors (11), psoralen photosensitivity (6), and porphyria (9). A normal minimal erythema dose in the UVB (below 320 nm) was generally observed in polymorphous light eruption and lupus erythematosus. The most exquisite photosensitivity for delayed erythema was observed in actinic reticuloid, which in one case was 25-35 times more sensitive in the UVB range which was also observed but to a lesser extent in XP and in persistent light reactors. Persistence of erythema and edema at test sites was observed in XP, PLE, LE, and actinic reticuloid. A delay in development of erythema reaching a maximum at 72 hr was observed in XP and psoralen phototoxicity. Maximum photosensitivity occurred in solar urticaria. Three patients had peak sensitivity in the range of 310-313 nm and the 4th at 460 nm. Photosensitivity in the visible range was detected in 2 patients with solar urticaria, one with actinic reticuloid, and confirmed in 9 patients with porphyria (405 nm). Photosensitivity in the UVA (above 320 nm) occurred to some degree in all groups.

Collagen vascular diseases.

Collagen vascular diseases are multisystem disorders that frequently affect the skin. At times, cutaneous disease is the initial manifestation. This article focuses on lupus erythematosus, dermatomyositis, and sclerodermoid syndromes.

Light-induced skin lesions in lupus erythematosus: photobiological studies.

To investigate the light sensitivity to various wavelength regions in lupus erythematosus (LE), phototests were performed in 24 LE patients with clinical photosensitivity (7 had systemic LE, 9 discoid LE, and 8 subacute cutaneous LE). Skin areas (measuring 40-60 cm2) were irradiated daily, maximally six times. With all three light sources used (emitting UVB, UVA, and visible light respectively) abnormal papular or papulosquamous reactions could be induced. In four of the 20 patients reacting abnormally, lesions occurred 10 or more days after cessation of the phototests; this indicates that the problem of photosensitivity in LE may be greater than appreciated so far.

Analysis of 70 KD heat shock protein (HSP70) expression in the lesional skin of lupus erythematosus (LE) and LE related diseases.

Biopsied specimens from skin lesions of SLE were studied for expression of 70 KD heat shock protein (HSP70). The pattern of HSP70 expression in SLE was diffuse in whole epidermis, hair follicles, and sweat gland cells and rather more intense than that in other control groups or normal skin. No significant differences in HSP70 expression were observed between sun-exposed and protected areas of SLE skin lesions. Unlike SLE, reduced or no expression of HSP70 was observed in skin lesions of DLE. In tissue culture, UVB radiation in vitro induced relatively intense expression of HSP70 in the nuclear area of keratinocytes. A few gamma delta T cell receptor positive cells which might respond to HSP70 expressing cells were detected in the basal layer of skin lesions of diseases. These studies suggest that aberrant expression of HSP70 in skin lesions of SLE might contribute to both skin lesions and antibody formation in SLE.

Cutaneous lupus erythematosus--a study of clinical and laboratory prognostic factors in 65 patients.

An eleven year review of patients presenting with cutaneous lupus erythematosus (LE) was made in order to determine the frequency of change from discoid LE (DLE) to systemic LE (SLE) and to identify clinical and laboratory prognostic factors. Three of fifty-six (5.4%) patients with DLE progressed to SLE after 1, 13 and 34 years respectively. They had a progressive rash and persistent abnormalities in their full blood count, erythrocyte sedimentation rate, antinuclear antibody and serum immunoglobulins prior to the development of SLE. We recommend that regular longterm monitoring of these indices should be carried out in patients presenting with DLE.

Cutaneous manifestations of connective tissue disease.

There is evidence that early treatment of connective tissue in adolescence improves clinical outcomes; thus, recognition of the cutaneous manifestation of CTD is critical. This review summarizes the clinical features that are unique to children and adolescents in cutaneous (CLE) and systemic lupus erythematosus (SLE), juvenile dermatomyositis (JDM), juvenile systemic scleroderma (JSS), juvenile localized scleroderma (JLS), and juvenile inflammatory arthritis (JIA).