IRF8 in Conjunction With CD123 and CD20 to Distinguish Lupus Erythematosus Panniculitis From Subcutaneous Panniculitis-like T-Cell Lymphoma.

Distinguishing lupus erythematosus panniculitis (LEP) from subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a diagnostic challenge with important clinical implications. Immunohistochemical expression of interferon regulatory factor 8 (IRF8) has been shown to highlight cells with plasmacytoid dendritic cell differentiation. Considering that the presence of plasmacytoid dendritic cells highlighted by CD123 immunolabeling is a well-described feature that supports LEP over SPTCL, we hypothesized that IRF8 immunohistochemistry can be used as a diagnostic test to improve accuracy in differentiating LEP from SPTCL. In this study, we assessed the expression of IRF8, CD123, and CD20 in 35 cutaneous biopsies from 31 distinct patients, which included 22 cases of LEP and 13 cases of SPTCL. We found that clusters of IRF8-positive cells within the dermis, and away from subcutaneous fat, could discriminate LEP from SPTCL ( P =0.005). Similarly, CD123-positive clusters in any location were observed in LEP but absent in all cases of SPTCL. In addition, we found that dermal CD20-predominant lymphoid aggregates could help discriminate LEP from SPTCL ( P =0.022). As individual assays, IRF8, CD123, and CD20 were highly specific (100%, 100%, and 92%, respectively) though poorly sensitive (45%, 29%, and 50%, respectively). However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.

Apoptosis in chronic cutaneous lupus erythematosus, discoid lupus, and lupus profundus.

INTRODUCTION: Lupus erythematosus is a multisystemic disease that is characterized by autoantibody production and immune complex deposition in such tissues as the mucosa, joints, the central nervous system, and skin. Cutaneous lupus erythematosus is categorized as acute, subacute, and chronic. Chronic cutaneous lupus erythematosus comprises discoid lupus erythematosus (DLE) and lupus profundus (LP). AIM: To analyze the expression of proapoptotic molecules in patients with lupus erythematosus discoid and lupus profundus. MATERIAL AND METHODS: Descriptive study, the study groups comprised 10 cases of LP and 10 cases of DLE, and a control. Skin samples of cases and controls were processed for immunohistochemistry and by TUNEL technique. The database and statistical analysis was performed (statistical test X(2)) SPSS (Chicago, IL, USA). RESULTS: Apoptotic features were broadly distributed along the skin biopsies in epidermal keratinocytes as well as at dermis. By immunohistochemistry the expression of Fas receptor and Fas-L was higher in the skin of lupus patients compared with controls. We also noted differences in Fas-L, -Fas, and -Bax proteins expression intensity in discoid lupus erythematosus patients in the epidermis, and hair follicles. CONCLUSIONS: Fas and Fas-L are expressed similarly in LP and DLE.

Magnetic resonance imaging findings are useful for evaluating the three-dimensional development and follow-up of linear lupus erythematosus profundus.

Lupus erythematosus profundus (LEP), which is a variant of chronic cutaneous lupus erythematosus (CLE), is seen in approximately 2∼3% of CLE patients, and only 10% to 20% of LEP patients present with systemic LE (SLE). LEP shows subcutaneous nodules with or without discoid LE (DLE). Linear LEP, a very rare variant of LEP, was first reported in 1991 in Japanese and in 1998 in English. Since LEP sometimes leaves skin depressions or scars as a result of atrophy of adipose tissue, early and adequate treatments are necessary. Here, we introduce an LEP case in which magnetic resonance imaging (MRI) was quite effective in evaluating a lesion that had been considered to be linear DLE.

The involvement of T regulatory lymphocytes in a cohort of lupus nephritis patients: a pilot study.

T regulator lymphocytes (Tregs) play a key role in the maintenance of immune tolerance and in the development of autoimmune diseases. Expression of Foxp3 is specific for Tregs, and can be used for the identification of these cells. This study investigated the variations of Tregs Foxp3+ in the kidney biopsies inflammatory infiltrate of different lupus nephritis classes compared to that of ANCA glomerulonephritis, acute tubulointerstitial nephritis and nephroangiosclerosis. Sections of paraffin-embedded tissue have been stained by immunohistochemistry with anti-CD3 and anti-FoxP3 antibodies. We find that the ratio of FoxP3+/CD3+ cells is significantly lower in patients with lupus nephritis class IV and in patients with vasculitides than in the course of nephroangiosclerosis, tubulointerstitial nephritis and lupus nephritis class V. The data presented herein demonstrate a decrease of FoxP3+ Treg cells in the inflammatory infiltrate of lupus nephritis, particularly during the most active phases of lupus nephritis, as observed in the course of a IV class nephritis.

The proportion of lymphocytic inflammation with CD123-positive cells in lupus erythematous profundus predict a clinical response to treatment.

Lupus erythematosus profundus is a rare inflammatory disorder of subcutaneous fat in patients with lupus ery-thematosus. Previous reports suggested that plasmacytoid dendritic cells, which expressed CD123 and CD303 antigens, play a central proinflammatory role in the patho-genesis of lupus erythematosus. To find the factors that determine the response to treatment, we analysed 23 skin specimens from the patients with lupus erythematosus profundus. The patients with considerable lymphocytic inflammation with high percentages of CD123+ cells in dermis and subcutaneous fat significantly responded to the systemic corticosteroid therapies. On the other hand, the patients with minor lymphocytic inflammation with low percentages of CD123+ cells showed poor response to treatments. The mean percentage of CD123+ cells in patients who showed good response to therapy was significantly higher than those that showed poor response (p = 0.027). These results suggest that the clinical response to treatment of lupus erythematosus profundus could be predicted from the histological features.

Human myxovirus resistance protein 1 (MxA) as a useful marker in the differential diagnosis of subcutaneous lymphoma vs. lupus erythematosus profundus.

BACKGROUND: Substantial clinicohistologic overlap exists between lupus erythematosus profundus (LEP) and lymphomas involving the subcutis, including subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma/delta T-cell lymphoma (GDTCL). Unequivocal markers separating the entities are not established. OBJECTIVES: To explore the usefulness of interferon alpha (INF-α)-induced protein, myxovirus resistance protein 1 (MxA), in the differential diagnosis of these entities, as studies show that the expression pattern of MxA follows the distribution of the inflammatory infiltrate in cutaneous lupus, while INF- α is not known to operate in lymphoma. MATERIALS AND METHODS: MxA immunohistochemistry was performed on skin biopsies from 5 patients with a clinical and histological diagnosis of SPTCL, 9 patients with GDTCL and 9 patients with LEP. RESULTS: In SPTCL and GDTCL, MxA was primarily seen in macrophages and generally did not exceed 20% of the infiltrate. In contrast, a significant portion of the subcutaneous infiltrate was positive for MxA in LEP, with 50% of the infiltrate staining on average. A greater number of macrophages and lymphocytes stained with a greater intensity as well (P<0.001). Moreover, endothelial cell staining was uniquely identified in LEP but not in lymphoma. CONCLUSION: Although specificity is not 100%, minimal staining of MxA is a predictor for SPTCL or GDTCL. Conversely, extensive staining for MxA both qualitatively and quantitatively is a feature of LEP. Endothelial staining also appears to be specific for LEP.

Alterations in the dynamics of inflammation, proliferation and apoptosis in subcutaneous implants of lupus-prone mice.

Wound repair is a complex process that involves inflammation, proliferation, extracellular matrix deposition/remodeling and apoptosis. Autoimmune diseases profoundly affect the healing process. We have used histological parameters to characterize the recruitment of mast cells and the proliferative activity and apoptosis in the fibrovascular tissue induced by subcutaneous polyether-polyurethane sponge implants in lupus-prone New Zealand White (NZW) and in control Balb/c mouse strains at days 10 and 21 post implantation. Fibrovascular tissue infiltration (hematoxylin and eosin staining), mast cell number (Dominici staining) and cellular proliferation (AgNOR staining) peaked early (day 10) but collagen deposition (picrosirius red staining) and apoptosis remained high in implants of NZW mice during the experimental period. In contrast, implants of Balb/c animals showed a progressive increase in mast cell recruitment and cellular proliferation but apoptosis fell from day 10 to 21 post-implantation. This divergent response early mast cells recruitment, excessive collagen deposition and disturbed removal of apoptotic cells from the site of injury in NZW mice implies that the genotype trait of NZW mice is a determining factor in abnormal healing response.

A case of lupus erythematosus profundus with unusual manifestations.

We describe a 16-year old female with lupus erythematosus panniculitis with unusual manifestations. She had noted to have developed erythematous nodules and plaques in the right axilla and inguinal region at the age of one year. These lesions resolved gradually with scar formation. However, new lesions were noted at the same locations in the following years. Some of her lesions at the scalp and the left axillary regions developing within the last two years slowly enlarged showing an annular configuration and subsequently resulted in hair loss. The erythematous border of her lesion in the left axilla consisted of two parallel red lines. Histopathological and direct immunofluorescent findings were consistent with lupus erythematosus panniculitis. Similar clinical findings in the same locations were also observed in the mother.

Lupus erythematosus panniculitis (lupus profundus): clinical, histopathological, and molecular analysis of nine cases.

BACKGROUND: The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL). METHODS: We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20-71 years). RESULTS: Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of alpha/beta-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-gamma gene showed a polyclonal smear in all cases. CONCLUSIONS: Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.

Panniculitis mimicking lupus erythematosus profundus: a new histopathologic finding in malignant atrophic papulosis (Degos disease).

We present the case of a 57-year-old woman with a 1-year history of a cutaneous eruption clinically and histopathologically characteristic of Degos disease. In one of the two cutaneous biopsy specimens taken from the trunk lesions, the histopathology consisted of necrosis and sclerosis of the subcutaneous lobules, a finding that to our knowledge has not been previously described in the cutaneous lesions of Degos disease. Two months after cutaneous biopsies were taken, the patient developed ptosis and an episode of acute abdominal pain; intestinal perforation and many characteristic lesions of visceral Degos disease involving the entire small bowel were noted at laparotomy.