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Cutaneous manifestations of systemic lupus erythematosus in Pakistani patients.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune process in which cutaneous lesions occur in majority of patients. This study from Karachi, Pakistan was conducted to determine the pattern and prevalence of such lesions in SLE in Pakistani patients. METHODS: One hundred ninety eight patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association were examined between 1986 and 2001 for the presence of cutaneous manifestations. RESULTS: Skin changes noted were: noncicatricial diffuse alopecia (22%), malar rash (31%), mucosal lesions (20%), discoid eruptions (15%), photosensitivity (33%), vascular lesions (20%), pruritus (17%), and pigmentary changes (22%). Peripheral gangrene, chronic ulcers, Raynauds phenomenon, urticaria, chilblains, thrombophlebitis, palmar erythema, and erythema multiform were rare. Anti ANA and anti dsDNA were positive in 93% and 83% patients respectively. CONCLUSION: A different clinical pattern was noted in our patients than reported previously.

Adult↗

Systemic lupus erythematosus causing subglottic stenosis.

Acute lupus erythematosus has manifested itself in many ways. Symptoms most often pertain to polyarthritis, arthralgias, skin lesions and those attributed to lupus nephritis. Recently documented lesions have been seen in the nose and larynx. The following case report shows evidence of subglottic stenosis due to SLE.

Female↗

Lupus erythematosus vegetans.

A 29-year-old woman with known systemic lupus erythematosus presented with exudative and vegetative plaques bilaterally on her groins. The clinical and histological findings indicated a diagnosis of pyodermatitis vegetans. Direct immunofluorescence studies revealed the presence of a definite basement membrane zone band for IgG, IgM and C3, favouring lupus erythematosus. We propose the term lupus erythematosus vegetans for this combination of clinicopathological and immunohistological findings.

Adult↗

Organ-specific antibodies against ovary in patients with systemic lupus erythematosus.

We studied whether patients with systemic lupus erythematosus can have organ-specific antibodies directed against ovaries. With a recently developed enzyme-linked immunosorbent assay system that uses both a soluble and an extractable corpus luteum antigen fraction, we detected both IgG and IgM antibodies in the sera of patients with systemic lupus erythematosus (16 of 19, 84%). The highest levels of IgG antibodies were seen when the extractable organ fraction (ST80) was used as the antigen.

Antibodies↗

UVB-induced leucocyte trafficking in the epidermis of photosensitive lupus erythematosus patients: normal depletion of Langerhans cells.

BACKGROUND: The pathogenic mechanisms of UV-induced skin lesions of lupus erythematosus (LE) are unknown. In a recent study of pathogenic mechanisms of polymorphic light eruption (PLE), significantly more Langerhans cells (LCs) persisted in the epidermis after UVB overexposure than in healthy individuals. Interestingly, the same phenomenon was observed in one subacute cutaneous lupus erythematosus (SCLE) patient. It could therefore be hypothesized that both photodermatoses share a common pathogenic mechanism of photosensitivity. In the present study, we tested this hypothesis by investigating leucocyte trafficking in the initial phase of cutaneous LE after intense UVB exposure. METHODS: In 22 photosensitive LE patients (12 chronic discoid lupus erythematosus, seven systemic lupus erythematosus and three SCLE) and nine age/sex-matched controls, uninvolved buttock skin was exposed to six minimal erythemal dose (MED) UVB radiation. Subsequently, biopsies were taken after 24, 48 and 72 h, and one control biopsy was taken from unirradiated skin. Skin sections were stained for the presence of LCs, neutrophils and macrophages. Areal percentages of positively stained cells within the epidermis were quantified and compared between the patients and controls. RESULTS: A gradual decrease of epidermal LCs and a gradual increase of epidermal neutrophils and macrophages at several timepoints after six MED irradiation was observed equally in both LE patients and controls. CONCLUSION: Immunohistopathology of irradiated uninvolved skin of photosensitive LE patients did not reveal the same pathologic trafficking of LCs and neutrophils as described for PLE patients. We conclude that different mechanisms are operative in the pathogenesis of PLE and photosensitive LE.

Adolescent↗

External ocular findings in lupus erythematosus: a clinical and immunopathological study.

A selected group of 18 patients with systemic lupus erythematosus (SLE) and 30 patients with chronic cutaneous lupus erythematosus (CCLE) showed an unexpectedly high incidence of problems involving the globe or eyelids. Five SLE patients had recurrent episcleritis, two CCLE patients had lower tarsal plaques, and two further CCLE patients had erosion of the lower lid margins associated with conjunctival scarring and symblepharon. This association has not previously been reported. There was an unexpectedly high incidence of deposition of immunoreactants in a linear pattern at the basement membrane zone in normal bulbar conjunctiva, which occurred in both SLE (42%) and CCLE (50%). The significance of these findings is discussed. We believe surface ocular problems in lupus erythematosus to be under-reported and that direct immunofluorescence of bulbar conjunctival biopsy might be helpful in diagnosis.

Adult↗

Histopathologic comparison of the subsets of lupus erythematosus.

A recent study by Bangert et al suggests that there are quantitative histologic differences that distinguish discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Utilizing criteria proposed by these authors, we examined 77 biopsy specimens from 63 patients with various forms of lupus erythematosus, but we were unable to predict the correct clinical subset. Using the clinical diagnosis of DLE as a positive reference standard, the sensitivity and specificity for the overall pathologic diagnosis of DLE were 55% and 42%, respectively. Statistically significant histologic factors favoring the diagnosis of DLE over SCLE in the present study were pilosebaceous atrophy, hyperkeratosis, parakeratosis, basement membrane thickening around the follicles, subepidermal edema, and vascular ectasia. These histologic variables were entered into a forward stepwise multivariate regression analysis to determine distinct predictors of DLE vs SCLE. This analysis showed that pilosebaceous atrophy was the only distinct significant predictor of DLE vs SCLE. These results suggest that the histologic differentiation of clinically defined DLE and SCLE cannot be established from the histologic features examined.

Atrophy↗

Thrombolytic therapy for a patient with systemic lupus erythematosus and acute myocardial infarction.

A young patient with systemic lupus erythematosus was admitted to our hospital because of acute myocardial infarction, and treated by thrombolysis. Coronary angiography revealed a significant stenosis of the left anterior descending artery, together with an intraluminal thrombus. Clotting studies demonstrated an anticoagulant factor suggestive of lupus erythematosus. We conclude that thrombolytic therapy can be useful in patients with systemic lupus erythematosus who present with acute myocardial infarction, although some caution is needed in treatment.

Adult↗

Acute periorbital mucinosis in discoid lupus erythematosus.

Periorbital edema associated with lupus erythematosus is not frequently reported. To our knowledge, periorbital edema from increased dermal mucin has not been reported with any form of lupus. We present a patient with discoid lupus exhibiting periorbital edema from massive mucinosis.

Acute Disease↗

Shingles, allergies, family medical history, oral contraceptives, and other potential risk factors for systemic lupus erythematosus.

The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.

Adult↗

Neonatal lupus erythematosus.

We present a case of neonatal lupus erythematosus (NLE) in a black infant presenting with symmetrical depigmented macules on the face resembling vitiligo. NLE is a rare condition affecting newborn infants of mothers who have connective tissue disease, with or without autoantibodies to extractable nuclear antigens Ro (SS-A), La (SS-B) or ribonucleoproteins. Infants present with cutaneous lesions or congenital heart block or both. The skin lesions are usually annular and erythematous and transient and resemble those of subacute cutaneous lupus erythematosus. The presentation of this patient was therefore striking.

Facial Dermatoses↗

Identification of retroviral DNA sequences in serum of cutaneous forms of lupus erythematosus patients.

Discoid (DLE), discoid disseminated (DDLE) and subacute cutaneous lupus erythematosus (SCLE) are recognised as cutaneous forms of lupus erythematosus (LE). It has been suggested that expression of endogenous retroviral components might induce the biosynthesis of antiDNA antibodies in LE patients. Using the dot blot hybridisation, we detected the greatest correlation between biosynthesis of anti-double stranded DNA (anti-dsDNA), anti-single stranded DNA (anti-ssDNA) antibodies and the presence of human immunodeficiency virus type I (HIV-1) pol sequences in DNA isolated from serum of SCLE (n = 22) patients. The same studies conducted in the groups of DLE (n = 85) and DDLE (n = 51) patients, exhibited a lower correlation between production of anti-dsDNA, anti-ssDNA and the presence of homologous HIV-1 pol sequences than in SCLE patients. Our findings suggest that the presence of endogenous retroviral sequences in patient serum may exhibit a relationship with development of cutaneous forms of LE disease.

Antibodies, Antinuclear↗

[Neonatal lupus erythematosus: 4 cases and clinical review].

Neonatal lupus erythematosus (NLE) is an infrequent disease in newborns caused by the transplacental passage of maternal Anti-Ro/SSA, Anti-La/SSB and/or Anti-U1 RNP antibodies. The most common manifestations are cutaneous and cardiac. We carried out a retrospective study of cases of NLE diagnosed in the last 10 years at the Hospital Universitario Insular in Gran Canaria. Complete data was obtained for 4 patients. Three cases had circulating Anti-Ro antibodies in the mother and in the newborns, while in the fourth case they were Anti-RNP. Two mothers were diagnosed with systemic lupus, one with mixed connective tissue disease and the other with leucocytoclastic vasculitis. The skin lesions consisted of urticaria-like and desquamative lesions. One patient presented with ulceration. The histological study of the urticaria-like lesions showed a non-specific perivascular infiltrate; the desquamative lesions were consistent with subacute lupus erythematosus.

Female↗

The frequent occurrence of neurological disease in patients with late-onset systemic lupus erythematosus.

Ten patients with systemic lupus erythematosus, whose first disease manifestation appeared after age 50 years, have been studied prospectively for up to five years. Neurological manifestations attributable to lupus occurred in nine patients and were multiple and varied. In all nine patients the neurological features appeared within one year of disease onset, and in four were present as an initial manifestation. Clinical recovery was generally satisfactory, and was complete in four. The apparent high incidence of neurological disease observed in late-onset lupus may help to elucidate causative mechanisms.

Adrenal Cortex Hormones↗

[Fatal acute pneumonopathies in disseminated lupus erythematosus].

Two cases of systemic lupus erythematosus (SLE) complicated by pneumonia which resulted in death are reported. The first patient, a 21-year old woman, died of acute diffuse lupus pneumonia; the initial and unusual radiological image of "multiple balloons" progressed within 2 months to terminal interstitial fibrosis. The second patient, a 60-year old woman, died of infection on an interstitial pneumonia which turned into severe fibrosis within 16 months. Acute or chronic lupus pneumonia is uncommon, but it may follow a very serious course. Clinically, true lupus pneumonia must be distinguished from all other types of lung involvement in SLE, such as infection, pulmonary haemorrhage or oedema, iatrogenic pathology, thromboembolic disease, etc. The pathogenetic mechanism of pulmonary lesions directly related to SLE is obscure, although some lung biopsy specimens have shown positive immunofluorescence. Concerning treatment, the initial response to corticosteroid therapy is usually very good, especially in the acute forms of the disease. However, in severe cases immunosuppressive drugs or even plasma exchanges must be added to steroids. For treatment to be rapidly initiated the diagnostic procedures must be completed in the early stages of the disease, involving, when necessary, surgical lung biopsy.

Acute Disease↗

Cyclic adenosine 5'-monophosphate response element modulator is responsible for the decreased expression of c-fos and activator protein-1 binding in T cells from patients with systemic lupus erythematosus.

T cells from patients with systemic lupus erythematosus express increased levels of the cAMP response element modulator (CREM) that has been shown to bind to the IL-2 promoter and suppress its activity. In this study, we demonstrate that CREM binds to the proximal promoter of the c-fos proto-oncogene in live systemic lupus erythematosus T cells and represses its expression following stimulation in vitro. Decreased levels of c-fos protein result in decreased AP-1 activity, as determined in shift assays. Blockade of the translation of CREM mRNA with an antisense CREM vector increases the expression of c-fos and the AP-1 activity. The levels of c-fos mRNA vary with disease activity. We conclude that CREM represses the expression of c-fos and limits the activity of the enhancer AP-1. Thus, CREM is involved indirectly in the modulation of transcriptional regulation of multiple genes including IL-2.

Adult↗

[Oral manifestations in patients with systemic lupus erythematosus].

Forty-six patients with systemic lupus erythematosus underwent thorough dental examination to determine the frequency and severity of oral lesions and periodontal diseases. According to clinical criteria, disease was classified as severe (n = 26) or less severe (n = 20). The overall rate of mucosal involvement in the studied patients was 48%-from 54% in patients with severe disease, 40% in those with less severe disease. Patients with severe disease were found to have a higher rate of tooth loss and an increased rate of gingival inflammation. The severity of periodontal lesions correlated with alterations in the immunoglobulin pattern, particularly with an increase in gamma-immunoglobulins. Thus it is suspected that complex immunodysregulation in combination with immunosuppressive therapy is responsible for the high rate of oral and periodontal lesions in patients with systemic lupus erythematosus.

Adult↗

Mode of inheritance of decreased C3b receptors on erythrocytes of patients with systemic lupus erythematosus.

The erythrocytes of patients with systemic lupus erythematosus have been shown to have a decreased number of receptors for the major cleavage fragment of the third component of complement (C3b). We studied the basis for this decreased number of C3b receptors by measuring the uptake of anti-C3b-receptor antibody on cells from 113 normal subjects, 38 patients with systemic lupus erythematosus, 14 of their spouses, and 47 of their relatives. The normal subjects had 5014 +/- (mean +/- S.E.M.) receptor sites per cell, but the patients and their relatives had significantly fewer sites--2809 +/- 241 and 3167 +/- 196, respectively (P less than 0.0005). The number of sites in the patients' spouses did not differ from normal (P greater than 0.3). Three phenotypes, indicated by the numbers of receptors, occurred in the normal population; a high phenotype (HH, with 5500 to 8500 sites per cell), an intermediate phenotype (HL, with 3000 to 5499), and a low phenotype (LL, less than 3000). These three phenotypes were present in 34, 54, and 12 percent, respectively, of the normal subjects; in contrast, 5, 42, and 53 per cent of patients had these respective phenotypes. Pedigree analyses indicated that these phenotypes were inherited in an autosomal codominant manner. We conclude that the decreased number of C3b receptors in lupus is inherited, not acquired.

Adult↗