Anuläres Erythem bei Sjögren-Syndrom

Annular erythema has been recognised as a cutaneous manifestation of Sjögren’s syndrome in the Asian literature and has been assumed to represent a distinct clinical entity. Since there are common pathophysiologic mechanisms, mainly the presence of anti-Ro/SSA or anti-La/SSB antibodies, it is difficult to separate the annular erythema from subacute cutaneous lupus erythematosus. Histological examination may reveal dermal mucin deposition resembling lupus erythematosus tumidus. We present a Chinese patient with widespread annular erythema, keratoconjunctivitis sicca, and anti-Ro/SSA antibodies. Clinical, histopathological, and immunogenetic findings are discussed reviewing the current literature, and the differences between annular erythema associated with Sjögren’s syndrome and cutaneous lupus erythematosus are emphasized.     

ICAM-1 and LFA-1 Expressions in the Lesional Skin of Annular Erythema Associated with Sjögren Syndrome

ICAM-1 and LFA-1 expression was studied in the lesional skin of ten cases of annular erythema associated with Sjögren syndrome. Most of the infiltrating mononuclear cells around blood vessels expressed LFA-1 in addition to its strong expression on vascular endothelial cells and focal expression on the epidermal basal cell layer in 3 cases. ICAM-1 expression on vascular endothelial cells was similar to LFA-1, although relatively focal and weak expression was observed on mononuclear cells. ICAM-1 expression on keratinocytes was focal and limited to the basal cell layer in annular erythema. These findings suggest that strong expression of ICAM-1 on endothelial cells but not keratinocytes and LFA-1 on mononuclear cells might play some role in the induction of skin lesions in annular erythema associated with Sjögren syndrome.     

Annular Erythema

Abstract: Annular erythema developed in 22 patients with Sjögren syndrome. Clinically, the annular erythema was subdivided into three forms: Sweet disease-like annular erythema with an elevated border (14 cases): subacute cutaneous lupus erythematosus (SCLE)-like marginally scaled erythema (5 cases): and papular erythema (3 cases). Histopathologically, features commonly seen in annular erythema are deep perivascular and/or periappendageal infiltration of the lymphocytes with an admixture of neutrophils or plasma cells and less frequent epidermal changes suggestive of cutaneous lupus erythematosus. Immunoglobulin or complement deposition along the dermoepidermal junction of lesional skin was observed in 8 of 18 cases, and most of the dermal infiltrates consisted of CD4(+), 4B4(+) cells. The appearance of anti-SS-A(Ro) (100%) and anti-SS-B(La) (77%) was significantly higher in patients with annular erythema. These results suggest that patients with Sjögren syndrome might have a distinct annular erythematous lesion that is both clinically and histopathologically different from SCLE, although dose immunologic abnormalities exist in these two diseases.     

SKIN LESIONS ASSOCIATED WITH SJÖGREN'S SYNDROME AND ANTICYTOPLASMIC ANTIBODIES IN SLE PATIENTS

Among forty-two systemic lupus erythematosus patients, three had antibodies against cytoplasmic antigens SSA and SSB. All three patients showed annular nonscarring erythema as a sign of their illness. The most predominant site of skin lesions was the face, but trunk and extremities were involved as well. All of the patients had clinically distinct Sjögren's syndrome following the onset of their skin lesions. These findings suggest that systemic lupus erythematosus patients with anticytoplasmic antibodies might often have accompanying clinical features of nonscarring erythema and Sjögren's syndrome.     

Neonatal lupus erythematosus exacerbated by vaccination

Neonatal lupus erythematosus (LE) is a rare immune-mediated disease caused by placental transport of maternal anti-SSA/Ro, anti-SSB/La and/or anti-U1RNP antibodies. Here, we demonstrate two cases of neonatal LE, in both of which cutaneous LE was exacerbated by inoculation. To our knowledge, cases worsening neonatal LE after administration of vaccines have not been reported. In case 1, not only exacerbation of pre-existing annular erythema but also spreading of new erythematous lesions to the trunk and extremities were induced following vaccination. Of interest, all of the lesions simultaneously improved. By contrast, in case 2, pre-existing facial erythema became prominent without spreading to other sites. The mother of case 1 had Sjögren’s syndrome, whereas in case 2, the mother was diagnosed with Sjögren’s syndrome on this occasion for the first time. Immunohistochemistry in case 1 revealed interleukin (IL)-17-positive cells infiltrating into the papillary dermis, and CD123-positive plasmacytoid dendritic cells in the papillary dermis and the deep reticular dermis. Both innate immune response and IL-17 mediated inflammation following vaccination are speculated as a possible mechanism of the deterioration of LE lesions in our juvenile cases. Caution is necessary since neonatal LE can be worsened following vaccination.     

Neonatal lupus erythematosus in identical twins, showing transient bullous lesions

Abstract: One of identical twin girls was born with ulcers on her leg, and shortly after birth developed a flaccid blister on the leg. Subepidermal blister with vacuolar degeneration of basal cell layer and the heavy infiltration of mononuclear cells in the upper dermis were observed in the blister lesion. She also had generalized livedo. Her identical twin sister did not exhibit ulcers or blisters, but was born with milia on her limbs. Their mother was found to have lupus erythematosus with positive anti‐Ro/SSA antibodies and developed Sjögren syndrome. We emphasize neonatal blistering and congenital milia unique manifestations of neonatal lupus erythematosus.     

Three cases of pigmented cosmetic dermatitis‐like eruptions associated with primary Sjögren's syndrome or anti‐SSA antibody

Pigmented cosmetic dermatitis‐like (Riehl's melanosis‐like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti‐SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle‐aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA‐A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3‐ and few IL17‐positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti‐SSA antibody.     

Lupus miliaris disseminatum faciei in a patient with systemic lupus erythematosus and Sjögren’s syndrome

We herein report a rare case of lupus miliaris disseminatus faciei on the chin and neck in a patient with systemic lupus erythematosus and Sjögren’s syndrome. Histopathological features showed focal aggregates of epithelioid granulomas accompanied by mononuclear cell infiltration in the upper dermis. Immunohistological examination showed enhanced expression of CD68 and CD163. Recent findings have implicated a key role of innate immunity in the pathogenesis of systemic lupus erythematosus, and alteration in M1 and M2 macrophage profile has been suggested. Increased expression of CD163 in the affected skin and other organs, and elevated serum levels of soluble CD163, are reported in systemic lupus erythematosus. Our results may suggest that activated M2 macrophages participated in the induction of lupus miliaris disseminatus faciei in a patient with systemic lupus erythematosus and Sjögren’s syndrome.     

Relevance of complement fixing antinuclear antibodies

Background Connective tissue diseases (CTDs) are a heterogeneous group of disorders defined by the association of a variety of clinical manifestations with immunologic and other laboratory findings. Overlap of syndromes and aberrant findings appear rather frequently. Methods Sera of eight antinuclear antibody (ANA) negative, cases of subacute cutaneous lupus erythematosus (SCLE) with antibodies to Ro (SS-A) and a ninth case with clinical and laboratory signs of Sjögren’s syndrome and systemic lupus erythematosus (SLE) were tested for complement (C′) fixing antinuclear antibodies (C-ANAs). The ninth case was examined in depth by direct immunofluorescence (DIF) and a two-step “C + DIF” test of biopsies for C′ fixation to in vivo bound ANAs, as well as serum tests for C-ANA, ANA, and SCLE markers. Results Sera of five of the eight ANA negative, Ro(SS-A) positive SCLE cases had C-ANAs. The ninth case, a 50-year-old woman with clinical and laboratory signs of Sjögren’s syndrome and SLE, gave a strong positive C + DIF reaction in the skin biopsy for in vivo bound ANAs that fix C′, but negative ANAs and C-ANAs in routine serum tests; they revealed antimitochondrial antibodies. Serum tests on normal skin, however, revealed weak ANA and strong C-ANA reactions with in vitro fixed C′. Conclusions ANA negative cases of SCLE or Sjögren’s syndrome may have C-ANAs. A case with Sjögren’s syndrome and signs of SLE had both in vivo and in vitro C′ fixing ANAs. C-ANA tests can aid in the identification of such cases.     

Hypergammaglobulinaemic purpura of Waldenström and Ro/SSA autoantibodies

Summary Seven out of nine patients (78%). seen over a 13-year period with hypergammaglobulinaemic purpura of Waldenström were found to have antibodies to Ro/SSA. Over this period we saw 175 patients who had antibodies to Ro/SSA. In six of the seven patients. associated diseases were recognized. Five had Sjögren's syndrome, and one had systemic lupus erythematosus with Sjögren's syndrome and thyroiditis (and died 19 years after initial presentation from cerebral infarction). Screening for antibodies to Ro/SSA is important in the diagnosis of patients with hypergammaglobulinaemic purpura. and is helpful in predicting prognosis.     

Giant Mucocele of Oral Cavity as a Mucocutaneous Manifestation of Sjögren Syndrome

Two cases of Sjögren syndrome who developed a giant mucocele on the floor of the oral cavity are reported. Histological analysis revealed the dense infiltration of lymph-plasmacytic infiltration around the dilated salivary duct. Similar findings were observed in the biopsied specimens of the labial salivary gland which were consistent with the grade 4 score proposed by Chisholm and Mason's criteria. Mucocele is a common mucocutaneous disease of unknown etiology except for traumatic origin and Sjögren syndrome might be one of the important underlying disease which causes giant mucocele, especially in elderly female patients.     

Lymphocyte Response to Staphylococcal Enterotoxin B in Patients with Annular Erythema Associated with Sjögren Syndrome

Lymphocyte response to staphylococcal enterotoxin B (SEB) was analysed in 11 cases with Sjögren syndrome (SjS) who developed annular erythema during the course. Increased lymphocyte response against SEB was observed on day 5 in those patients who developed annular erythema at the time of examination. A similar reaction pattern was observed when Con A and PWM, but not protein A, were used as the mitogen. No significant lymphocyte response was observed in the patients in the inactive stage without annular erythema or in normal controls. Furthermore, peripheral blood lymphocytes express LFA-1 after SEB stimulation. These results suggest that lymphocytes from SjS patients react to various types of antigenic or mitogenic stimulation and that they express cell adhesion molecules, especially in patients with active annular erythema.     

Neonatal lupus syndrome and microtubular structure

A female infant, at 6 weeks old, with the clinical manifestation of annular erythemas on the trunk and face, was positive for anti-SS-A and anti-SS-B antibodies. The annular erythema disappeared spontaneously at the age of 7 months when anti-SS-A and anti-SS-B antibodies were negative. Electron microscopic observation of the vascular endothelial cells on the annular erythema revealed microtubular structures. Later microtubular structures were found absent from the vascular endothelial cells of the area where the annular erythema had disappeared. The patient's mother is suffering from Sjögren's syndrome; she has no clinical symptoms but anti-SS-A and anti-SS-B antibodies are positive and a biopsy of small salivary glands of the lip demonstrated a marked periductal mononuclear cell infiltration. Microtubular structures were observed in her vascular endothelial cells in the small salivary gland region. These findings suggest that disappearance of microtubular structure may have some relationship with anti-SS-A and anti-SS-B antibodies.     

Lupus erythematosus associated with erythema multiforme: report of two cases and review of the literature

Rowell's syndrome (RS) is a rare presentation of lupus erythematosus (LE) with erythema multiforme‐like lesions associated with antinuclear, anti‐La (SS‐B)/anti‐Ro (SS‐A) antibodies and rheumatoid factor (RF) positivity. This syndrome is suggested to be a different variant of cutaneous lupus erythematosus by some authors in literature. Here we present a 64‐year‐old woman with LE and a 51‐year‐old woman with LE and Sjögren syndrome (SS) who had erythema multiforme‐like eruptions and discuss the coexistence of lupus erythematosus and erythema multiforme.     

Clinical and Histological Analysis of Labial Lip Biopsy in Sjögren Syndrome

Labial lip biopsy findings from 52 patients with Sjögren syndrome (SjS) and cutaneous manifestations were clinically analyzed. Findings of the labial lip biopsy with more than one focus (a cluster of at least 50 lymphocytes) were positive in 52% (28/52). Sixteen patients who presented with oral dryness had negative labial lip biopsy findings with less than one focus score and five patients without oral dryness had positive results. Cells infiltrating into the salivary gland were categorized as plasma cell rich (Group 1), lymphocyte rich (Group 3), intermediate (Group 2), or no gland in biopsied specimens (Group 4). Sicca complaint and the grade of lip biopsy score were significantly higher in Group 3 than in Group 1; no differences were observed in laboratory findings between Groups 1 and 3. The patterns of age distribution and salivary flow rate were also not statistically significant in these two groups. The patients with plasma cell rich infiltrate presented oral dryness, although their clinical and grade of lip biopsy scores were relatively low; most of these patients have secondary SjS. Some of the patients in Group 4 showed an advanced stage of the disease though their lip biopsy score was grade 1 with atrophic or no gland. These data suggest that labial lip biopsy is a useful screening method for the diagnosis of Sjögren syndrome and that clinical manifestations may differ in parallel with the type of infiltrating cell.     

Recurrent Annular Erythema in a Case of Seronegative Sjögren's Syndrome

We describe a case of Sjögren's syndrome who repeatedly developed annular erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody were all negative. Characteristics of the annular erythema included a tendency to appear on the extremities especially in summer, spontaneous regression after 1–2 weeks, and residual slight pigmentation. The histological findings revealed dermal perivascular lymphocytic infiltration admixed with some neutrophils. Slight exsudative changes were found in the upper dermis. There were no epidermal changes. This case suggests the existence of annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La antibody. Unknown factors other than those antibodies may be involved in the pathogenesis of the annular erythema.     

Guillain-Barré syndrome in a child with systemic lupus erythematosus and anti-Ro/SSA and anti-La/SSB autoantibodies

We report a 9‐year follow‐up of a girl with systemic lupus erythematosus (SLE) and probable Sjögren’s syndrome. At the age of 7 years, the patient developed a chilblain‐like eruption with features of SLE, including leucopenia, oral ulcers, positive rheumatoid and antinuclear antibodies and positive anti‐dsDNA, anti‐Ro/SSA and anti‐La/SSB antibodies. At the age of 13 years she developed Guillain–Barré syndrome, which completely resolved with aggressive treatment, including high‐dose corticosteroids and the use of plasma exchange followed by intravenous gammaglobulin.     

Report of a Turkish child with Sjören-Larsson syndrome associated with peripheral nerve involvement

Sjögren‐Larsson syndrome is a rare hereditary neurocutaneous disorder characterized by ichthyosis, spastic di‐ or tetra‐plegia, and mild to moderate mental retardation. In this article, we present a nine‐year‐old girl with the classical features of the syndrome associated with peripheral nerve involvement because of its rare presentation. To the best of our knowledge, only three cases of Sjögren‐Larsson syndrome with peripheral nerve involvement have been previously reported in the literature. We assume that Sjögren‐Larsson syndrome involves extensive disorders of the ectodermal tissues, including the peripheral nerves as well as the skin and the central nervous system.     

Anti-ribosomal-P antibodies in a Sjögren syndrome patient associated with lupus erythematosus

We describe a 36‐year‐old woman who had Sjögren syndrome with anti‐ribosomal P antibodies and who developed erythema on her back and arms. The histological specimen showed lymphocytic infiltration around the sweat and salivary glands. Her serum reacted with ribosomal‐P0 protein in immunoblotting with HeLa cell extract and P0 recombinant protein. Although autoantibodies to ribosomal‐P proteins appear mainly in patients with systemic lupus erythematosus (SLE), a diagnosis of SLE in this patient could not be supported.     

Neonatal lupus erythematosus infants and their mothers: a 10-year retrospective study

BackgroundNeonatal lupus erythematosus (NLE) is a rare disease associated with transplacental transfer of maternal anti-Ro/anti-Sjögren syndrome A antibodies. The most common manifestations are cutaneous erythema and congenital heart block. Mothers of infants with NLE are either asymptomatic or diagnosed with autoimmune disease. The goal of this study is to investigate the clinical manifestation, prognosis, and association with autoimmune disease in NLE babies and their mothers in Taiwan.MethodsMedical records of newborns with NLE and their mothers from two hospitals in Taiwan between January 1999 and January 2009 were reviewed. Twenty-five newborns (one set of twins) and 24 mothers of infants with NLE were included in the study. Clinical data, including characteristics of skin manifestations, the onset of symptoms, and infants' antibody titers, were collected. A diagnosis of NLE was made if the baby had heart block or characteristic skin lesions and maternal antibodies to Sjögren syndrome A/Ro, Sjögren syndrome B/La, or U1 ribonucleoproteins. Questionnaires were used to determine the mother's health status at the time of delivery and in subsequent years.ResultsOf the infants, 84% had typical cutaneous manifestations of NLE, and 16% presented with congenital heart block without skin changes. The cutaneous lesions appeared on average at 21.7 weeks. Thirteen mothers were initially asymptomatic, and the other 11 remained asymptomatic over a mean follow-up period of 3.9 years. Two mothers developed lupus nephritis.ConclusionThere was a lower incidence of observed congenital heart block compared to previously reported NLE studies among Caucasian populations. Most mothers were asymptomatic before the birth of their NLE child, and few developed autoimmune diseases. However, continued follow-up of asymptomatic NLE mothers is recommended due to the chances of developing a life-threatening, systemic autoimmune disease.