[Cutaneous lupus erythematosus. Part 1: clinical manifestations and classification]. / Kutaner Lupus erythematodes. Teil 1: Klinik und Klassifikation.

Cutaneous lupus erythematosus (CLE) is a heterogenous disorder with a wide range of skin manifestations. Therefore, it has been difficult to develop a unifying concept for classifying CLE from the dermatologic perspective in the past. In 2004, the classification system was updated and includes now acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Additional rarely described variants are not listed as separate entities but are included in the classical forms. Diagnosis of the different subtypes of CLE is made by considering genetic, clinical, histopathologic, and immunoserologic findings, with a systematic analysis of individual criteria. In the past years, the etiology and pathogenesis of CLE has been subject of intensive research and it has been shown by several groups that exogenous factors, such as ultraviolet light and drugs, can induce CLE. The first part of this review will enable the reader to identify the various clinical manifestations of CLE and to employ characteristic criteria to assess differential diagnostic considerations.

Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.

INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients). OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome. METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses. RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features. CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.

Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?

Sixteen patients with histologically confirmed lupus erythematosus profundus were followed for a decade (on average). At the initial examination, two of 16 (12%) patients fulfilled the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). During the period of observation, SLE developed in another two (12%) patients, both of whom developed a malar rash. The remaining 12 (75%) patients never met the criteria for SLE. Four of the 16 (25%) had no extracutaneous manifestation. In conclusion, most patients with lupus erythematosus profundus have a relatively mild disease course, although a few develop systemic abnormalities and have abnormal laboratory findings.