Systemic LE Research Articles

Prospects for UV-A1 therapy as a treatment modality in cutaneous and systemic LE.

Prospects for UV-A1 therapy as a treatment modality in cutaneous and systemic LE.

Annular erythema associated with lupus erythematosus/Sjögren's syndrome

Background: Annular-polycyclic and papulosquamous lesions are associated with subacute cutaneous lupus erythematosus (SCLE). In some Asian cases, annular erythema has been associated with Sjögren's syndrome (SS). However, the relation between the two is unclear. Objective: Our purpose was to clarify the clinical manifestations and immunologic features of patients with annular erythema. Methods: This study included 15 patients with annular erythema. Systemic, serologic, and genetic findings were analyzed. Results: Histologic examination showed perivascular and periappendageal lymphocytic infiltrates in all patients. However, LE-specific epidermal changes were observed in only three (20%). Although all patients at least partially demonstrated features of LE or SS, eight (53%) fulfilled the American Rheumatism Association criteria for systemic LE (SLE) and five (33%) were diagnosed with SS. Renal (20%) and central nervous system (7%) involvement was observed. Anti-Ro(SS-A) and anti-La(SS-B) antibodies were detected in nine (60%) and seven (47%) patients, respectively. There were no histocompatibility antigen (HLA) haplotype differences. Conclusion: Annular erythema in Asian patients is the counterpart of subacute skin lesions of LE in whites, except for the paucity of LE-specific histopathologic findings and HLA-DR3 tissue type. (J Am Acad Dermatol 1997;36:214-8.)

Failure to detect paramyxovirus RNA in the skin of connective tissue disease

Etiology of connective tissue disease is unknown. The association of infectious agents has been suspected serologically, ultrastructurally and recently by means of molecular biological techniques. We extracted RNA from lesions of 25 discoid lupus erythematosus, 9 systemic LE, and 3 systemic sclerosis biopsies, and reverse transcription-polymerase chain reaction was performed for all paramyxoviruses known to infect human beings. None of the samples yielded positive signal for any of the viruses. The existence of paramyxovirus in the skin of connective tissue disease is very unlikely.

Preliminary, dermatologic first step criteria for lupus erythematosus and second step criteria for systemic lupus erythematosus.

Comparisons of cases of systemic lupus erythematosus (SLE) with cases of rheumatoid arthritis and other rheumatologic disorders affords the basis of the 1982 revised criteria of the American Rheumatism Association (ARA) for classifying SLE cases. We address three questions: Do comparisons of LE cases with non-LE cases that have suggestive skin lesions yield criteria for use in dermatology clinics for primary classification of cases with photo distributions of skin lesions? Do comparisons of SLE with cutaneous LE cases yield the same or similar criteria to the revised ARA criteria for SLE? How should subacute cutaneous LE cases be evaluated for signs of significant systemic involvement? Discriminant analyses on 168 cases with skin lesions suggestive of LE were performed using data based on the ARA criteria for SLE and study factors for cutaneous LE suggested by the European Academy of Dermatology and Venereology. These yielded two sets of criteria: (1) The 11 preliminary, dermatologic first step criteria (10 plus 1 for discoid lesions and histology) serve to classify cases as LE or non-LE. (2) The 11 preliminary, dermatologic second step criteria classify LE cases as cutaneous LE or systemic LE. Interestingly, 5 of 11 of these second step criteria differ from the 11 ARA criteria for systemic LE. These second step criteria afford a useful means of distinguishing between subacute cutaneous LE cases with or without significant systemic involvement. The study factors included in both the first and the second step criteria fall into three groups, notably clinical criteria, laboratory criteria, and "added study factors." The latter factors distinguish between the groups compared (LE vs. non-LE and cutaneous vs. systemic LE) but not as well as the study factors included as "criteria."

Subacute Cutaneous Lupus Erythematosus: A Decade’s Perspective

Based upon the rather large worldwide experience that has been published recently, it would appear that the concept of subacute cutaneous LE as presented in our original reports starting 10 years ago is still a viable one. However, we must now also consider the possibility that these patients will occasionally develop other types of autoimmune disorders such as rheumatoid arthritis and Sjögren's syndrome and, on occasion, have their skin disease triggered by drugs such as hydrochlorothiazide. However, the majority of these patients will have recurrent skin disease activity and musculoskeletal symptoms as the major manifestations of their illness. Although most of these patients do have a relatively mild disease course, a small percentage seem to be at risk for developing potentially life-threatening complications of systemic LE. The future challenge in this area lies in identifying prognostic features that may correlate with this more aggressive disease course so that this subgroup of patients can be more efficiently managed. Our preliminary studies have suggested several candidates for further study: the papulosquamous/psoriasiform subacute cutaneous LE lesional subtype; development of acute cutaneous LE; resistance to antimalarials alone; leukopenia; high titer ANA; and the presence of circulating double-stranded DNA antibodies. Another possibility may include the rate of systemic disease onset. Discoid LE patients who have not developed clinically significant SLE manifestations within the first 2 years of the appearance of their skin lesions have a very low risk for suffering from severe SLE complications later in their disease course. The same question might be asked of subacute cutaneous LE. In addition, some subacute cutaneous LE patients have a single episode of disease activity followed by long-term, if not permanent, remission. More needs to be learned about this more benign pattern of illness in the hope of identifying favorable prognostic signs. Our impressions regarding subacute cutaneous LE disease outcome have mostly come from retrospective or point-prevalence types of clinical analyses; more prospective examinations of large groups of patients will be required to better address the issue of prognosis in subacute cutaneous LE. The data published to date suggest that this is a relatively homogeneous group of patients immunogenetically: they frequently have circulating anti-Ro auto-antibodies and often possess the HLA-DR3 phenotype. Much circumstantial evidence indicates that this particular genetically determined autoimmune response might be directly participating in pathogenesis of this form of LE-specific skin injury.(ABSTRACT TRUNCATED AT 400 WORDS)

The History of Lupus Erythematosus: From Hippocrates to Osler

Hippocrates (460-375 BC) was the first to describe cutaneous ulcers under the heading of herpes esthiomenos. From what we can tell, Herbernus of Tours was the first to apply the term lupus to a skin disease in 916 AD. Following this, a number of terms including lupus, noli me tangere, and herpes esthiomenos were used to describe cutaneous ulcers. Willan (1757-1812) expanded the classification of skin diseases using the term herpes for vesicular diseases and lupus for destructive and ulcerative diseases of the face. The first clear description of lupus erythematosus was by Biett and was reported by his student Cazenave under the term erythema centrifugum in 1833. In 1846 Hebra, under the name of Seborrhea Congestiva described disc-shaped patches and introduced the butterfly simile for the malar rash. In 1851 Cazenave renamed erythema centrifugum, calling it lupus erythematosus and gave a classic description of discoid lupus erythematosus. In 1872 Kaposi subdivided lupus into the discoid and systemic forms and introduced the concept of systemic disease with a potentially fatal outcome. Hutchinson alluded to the photosensitive nature of the rash and may have provided the earliest description of what is now called annular subacute cutaneous lupus. In 1894 Payne used quinine in the treatment of patients with LE and postulated the presence of a vascular disturbance. In 1902, Sequira and Balean published a large series of patients with discoid and systemic LE and provided clinical and pathologic details of a young woman who died of glomerulonephritis. In 1904, Jadassohn published an exhaustive review of discoid and systemic LE, including clinical features and pathologic findings. Between 1895 and 1904 Sir William Osler published 29 cases of what was termed the erythema group of diseases. Perhaps his major contribution was to show that skin diseases could be accompanied by a variety of systemic manifestations. In retrospect most of his patients suffered from diseases other than SLE and it was only in his 1904 paper that two cases with SLE were described. He did not acknowledge this diagnosis in his cases and we share the viewpoint that his contribution to the study of SLE has been overemphasized.

Lupus erythematosus in small animals

In veterinary medicine, lupus erythematosus has been classically divided into systemic lupus erythematosus (SLE) and discoid (cutaneous) lupus erythematosus (DLE). These two subdivisions vary markedly in presenting clinical signs, laboratory evaluation, immunologic testing, aggressiveness of therapy and prognosis, and, therefore, will be discussed separately. Systemic LE has been reported in dogs, 1–15 cats, 16–19 and mice. 8 Discoid LE has been reported in dogs. 20–23 SLE is a rare disease in dogs and has been estimated to affect approximately one of every 4000. 24 Epidemiologic studies have shown no increased risk of SLE in human contacts of SLE dogs or dogs with high-titer antinuclear antibody tests. 25,26 Human contacts and controls showed no difference in antinuclear, anti-DNA, anti-RNA, and anti-lymphocyte antibody titers, lymphocytotoxic activity, rheumatoid factors, or elevation of serum immunoglobulins. Prior to these studies, one unfortunate clinical brief erroneously implied a possible correlation between human and canine SLE based on DNA binding studies. 27

Chronic cutaneous lupus erythematosus. Clinical, laboratory, therapeutic, and prognostic examination of 62 patients.

Chronic discoid lupus erythematosus (DLE) is a common condition. Sixty-two patients with biopsy-proved, active DLE were observed and their conditions were analyzed for clinical, laboratory, and therapeutic data. Fifty-six patients had disease limited to the skin-26 localized and 30 widespread (above and below the neck). At the time of follow-up examination, active disease was present in 32 patients, 28 of whom had widespread DLE. Six patients had DLE as a manifestation of systemic LE (SLE). In four patients, the DLE preceded the development of SLE. Laboratory abnormalities were substantially more common in patients with widespread DLE than in patients with localized DLE. An analysis of therapeutic results in this series confirmed the beneficial effects of intralesional corticosteroids and antimalarial agents and demonstrated relatively poor responsiveness to topical or oral corticosteroids.

Chronic Cutaneous Lupus Erythematosus

• Chronic discoid lupus erythematosus (DLE) is a common condition. Sixty-two patients with biopsy-proved, active DLE were observed and their conditions were analyzed for clinical, laboratory, and therapeutic data. Fifty-six patients had disease limited to the skin—2 localized and 30 widespread (above and below the neck). At the time of follow-up examination, active disease was present in 32 patients, 28 of whom had widespread DLE. Six patients had DLE as a manifestation of systemic LE (SLE). In four patients, the DLE preceded the development of SLE. Laboratory abnormalities were substantially more common in patients with widespread DLE than in patients with localized DLE. An analysis of therapeutic results in this series confirmed the beneficial effects of intralesional corticosteroids and antimalarial agents and demonstrated relatively poor responsiveness to topical or oral corticosteroids. (<i>Arch Dermatol</i>1982;118:412-416)

Studies on fibronectin in the skin. IV. Indirect immunofluorescence studies in lupus erythematosus.

Fibronectin is an important constituent of normal human skin, mediating cell/cell and cell/fibre interactions. In affected skin in discoid and systemic LE, changes in the distribution of fibronectin in the dermo-epidermal junction and in the papillary dermis are observed with homogenization and degenerative changes, IF negative gaps and slit formation in the dermo-epidermal region, together with IF positive globular bodies and transport of fibronectin into the epidermis. Unaffected skin in LE demonstrates the pattern of fibronectin as found in normal human skin.

Isomorphic skin reaction with DNCB in SLE and DLE.

DNCB sensitization was studied in 76 cases of systemic and 44 of discoid lupus erythematosus and in 101 immunosuppressed and tumor patients as controls, as well as in 40 contact-sensitized eczematous and 115 unselected patients. Sensitization of patients with discoid LE and that of mixed patients are of the same order, while it is lower in the systemic LE group. The highest incidence was found in the polysensitized positive control group; the lowest in the immunosuppressed and tumor patients. DNCB sensitization showed clear age dependency in the different groups. At the site of the DNCB exposure, isomorphic reactions were found in 43% of discoid and 25% of systemic LE patients. Histological and immunofluorescence studies supported the findings of the clinical picture, i. e. the appearance of isomorphic reactions at the site of the exposure cannot be related either to the intensity of the early reaction or with the developing intensity.