Paniculitis lúpica: características clínico-patológicas de una serie de 12 pacientes / Lupus panniculitis: Clinicopathological features of a series of 12 patients

Antecedentes y objetivo: La paniculitis lúpica (PL) es una forma infrecuente de lupus eritematoso cutáneo crónico, cuyo diagnóstico requiere una adecuada correlación clínico-patológica, especialmente si constituye la primera manifestación de lupus eritematoso (LE). Dependiendo del estado evolutivo de las lesiones, la biopsia puede mostrar cambios poco específicos que dificultan el diagnóstico. Existen pocas series publicadas sobre esta entidad. Aportamos la experiencia de nuestro centro en su diagnóstico y manejo. Materiales y métodos: Estudio clínico-patológico retrospectivo descriptivo de 12 casos diagnosticados de PL en nuestro servicio. Resultados: Todos los pacientes tenían placas y/o nódulos dolorosos recurrentes, característicamente localizados en la zona proximal de las extremidades, la cara y el cuero cabelludo. En la biopsia había paniculitis de predominio lobulillar con infiltrados linfoplasmocitarios. Esto, junto con la coexistencia de otras manifestaciones clínicas de LE y el estudio de expresión de CD123, permitió establecer el diagnóstico de PL. En 3 pacientes la PL fue la primera manifestación de LE. Conclusiones: La PL es una entidad de difícil diagnóstico. La presencia de otras manifestaciones clínicas y/o histológicas de lupus y la utilización de técnicas inmunohistoquímicas pueden ser útiles para el diagnóstico diferencial con otras paniculitis

Background and objective: Lupus panniculitis (LP) is a rare variant of chronic cutaneous lupus erythematosus, which diagnosis requires clinicopathological correlation, especially in those patients without any other manifestation of lupus erythematosus (LE). According to the phase when the biopsy is performed, histological findings can be non-specific. Few series have been published to date. Hence, we report our own experience in the diagnosis and management of this disease. Materials and methods: We conducted a retrospective descriptive clinicopathological study of 12 patients diagnosed in our centre. Results: All the patients had painful and recurrent plaques and/or nodules, with a predilection for proximal extremities, face and scalp. Histopathologic examination showed mostly lobular panniculitis and lymphoplasmacytic infiltrate. For the diagnosis, we also considered the coexistence of other clinical manifestations of LE as well as the expression of CD123 by immunohistochemistry. In 3 patients, LP was the first manifestation of LE. Conclusions: The diagnosis of LP can be difficult. The presence of other clinical and/or histological manifestations of LE along with immunohistochemistry techniques could help in the differential diagnosis with other panniculitis

Analysis of possible structures of inducible skin-associated lymphoid tissue in lupus erythematosus profundus.

Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin-associated lymphoid tissues (iSALT). We subsequently reported structures analogous to iSALT in human secondary syphilis, suggesting that iSALT can also exist in humans. Here, we studied ectopic lymphoid tissues in the lesions of LEP by immunohistochemistry and compared their characteristics with those of TLO. We demonstrated that LF of LEP were composed of B-cell follicles intermingled with CXCL13-expressing cells, distinct aggregations of T cells, and some blood vessels expressing peripheral node addressin. These findings indicate that LF of LEP can be considered as a type of iSALT.

Lupus eritematoso sistémico masculino / Systemic male lupus erythematosus

El Lupus Eritematosos Sistémico es el paradigma del síndrome autoinmune sistémico, cuya etiología está lejos de ser aclarada, aunque el conocimiento de su patogenia ha avanzado en estos últimos años inexorablemente, como el de los secretos más ocultos del funcionamiento del sistema autoinmune. Es mucho más frecuente en mujeres (10:1) y suele presentarse en la adolescencia tardía y a los 50 años, también es más frecuente y grave en algunos grupos étnicos, en especial afroamericanos e hispanos; su carácter crónico, su gran variedad clínica, sus episodios de activaciones y remisiones, la presencia de numerosos anticuerpos y la respuesta al tratamiento inmunosupresor son muestra de su naturaleza autoinmune. Presentamos el caso de un paciente de sexo masculino, de 38 años de edad, de origen hispano, que debutó con serositis, y que respondió de forma adecuada al tratamiento inmunosupresor instaurado.

Systemic Lupus Erythematosus is the paradigm of systemic autoimmune syndrome, whose etiologyis farfrom being clarified, although the knowledge of its pathogenesis has inexorably advanced in recent years, such as the most hidden secrets of the functioning of the autoimmune system. It is much more common in women (10: 1) and usually occurs in late adolescence and at age 50, is also more frequent and severe in some ethnic groups, especially African American and Hispanic; its chronic nature, its great clinical variety, its episodes of activation and remission, the presence of numerous antibodies and the response to immunosuppressive treatment are indicative of its autoimmune nature. We present the case of a 38-year-old male patient of Hispanic origin, who debuted with serositis, and who responded adequately to the immunosuppressive treatment instituted.

Linear Sclerodermoid Lupus Erythematosus Profundus in a Child.

Lupus erythematosus panniculitis, also known as lupus profundus, is a variant in the clinicopathological spectrum of lupus erythematosus (LE) affecting about 2%-3% of LE patients. A linear configuration of LE panniculitis has been reported rarely with rare reports describing the coexistence of different forms of cutaneous LE and localized morphea. In this study, the authors present a 9-year-old girl with linear arrangement of subcutaneous nodules on her left forearm. Microscopic findings from 2 biopsies included lymphocytes at the dermoepidermal junction with mild interface dermatitis, a dense lymphocytic infiltrate that was concentrated around adnexae and subcutaneous fat in concert with thickened collagen bundles and mild widening of fibrous septae surrounding fat lobules. Although the clinical differential diagnosis included panniculitis or a sporotrichoid infection, 1 biopsy showed a dense lymphocytic infiltrate histologically bordered on that of cutaneous lymphoid hyperplasia or a late stage of Lyme disease, and a second also demonstrated more prominent sclerodermoid collagen bundles rendering the diagnosis of linear sclerodermoid LE profundus.

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.

Prominent mucoid degeneration of the parotid gland in a patient with systemic lupus erythematosus.

Lupus erythematosus (LE) can cause various cutaneous lesions including panniculitis (LE profundus), but salivary gland involvement has been extremely rare in patients with LE. Herein, we report the first documented case of systemic LE with prominent mucoid degeneration and lymphoplasmacytic infiltration in the parotid gland. A 38-year-old Japanese male with histories of autoimmune hemolytic anemia and systemic LE presented with a swelling of the bilateral cervical region. A physical examination revealed a swelling of the bilateral parotid gland and erythema of the right cheek. A biopsy specimen of the cheek demonstrated LE profundus with mucoid material deposition in the dermis. A biopsy specimen of the parotid gland showed lymphoplasmacytic infiltration and prominent mucoid material deposition within the parotid gland as well as mild lymphoplasmacytic infiltration and hyaline fat necrosis in the perisalivary tissue. Mucoid material deposition is one of the characteristic features of LE, however, this is the first case demonstrating mucoid material deposition in the salivary gland. Moreover, albeit extremely rare, lymphoplasmacytic infiltration within the lobules of the salivary gland has also been reported in patients with LE. Therefore, it is important that both lymphoplasmacytic infiltration and mucoid material deposition must be included in the differential diagnostic considerations for salivary gland tumors in patients who had been previously diagnosed as systemic or discoid LE.

The presence of clusters of plasmacytoid dendritic cells is a helpful feature for differentiating lupus panniculitis from subcutaneous panniculitis-like T-cell lymphoma.

AIMS: Both lupus panniculitis (LP) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are characterized by subcutaneous lobular lymphocytic infiltrates, and they are sometimes difficult to differentiate. Recently, plasmacytoid dendritic cells (PDCs) were found to be present in various types of cutaneous lupus erythematosus lesions, including LP, and are supposed to play important pathogenetic roles. The aim of this study was to investigate whether PDCs are differentially present in these two diseases and can be utilized to differentiate them. Conventional histopathological features were also compared. METHODS AND RESULTS: Initial biopsies from 21 LP and 11 SPTCL patients were analysed. Our results showed that the presence of lymphoid follicles, dermal mucin deposition and lack of moderate to marked nuclear atypia or adipocyte rimming were more suggestive of LP. Several distinct patterns of fat necrosis, i.e. hyaline/lipomembranous and fibrinoid/coagulative in LP and SPTCL, respectively, were also diagnostically useful. Also, clusters of PDCs were characteristically seen in LP lesions (17/21, 81%) but not in SPTCL lesions (2/11, 18.2%). In LP lesions, but not in SPTCL lesions, the presence of epidermal interface change correlated perfectly with the presence of PDCs in the papillary dermis. CONCLUSIONS: We conclude that the presence of clusters of PDCs and certain histological features are helpful for the differential diagnosis.

CCL5 expression in panniculitic T-cell dyscrasias and its potential role in adipocyte tropism.

Subcutaneous panniculitis-like T-cell lymphoma and gamma/delta T-cell lymphoma involving fat are unique among the hematologic dyscrasias because of their almost exclusive involvement of the subcutaneous fat with little tendency toward extracutaneous dissemination. The systemic manifestations associated with this lymphoma are largely the sequelae of cytokine production by neoplastic T cells found within the subcutaneous fat. We hypothesized that the basis of this localization could be due to an interactive microenvironment between the neoplastic cells and the adipocytes. Given the expression of CCR5 in adipocytes, we explored the expression of its ligand CCL5 in the subcutaneous infiltrates in subcutaneous panniculitis-like T-cell lymphoma, gamma/delta T-cell lymphoma and compared it with those in lupus erythematosus profundus (LEP). We found that CCL5 was expressed in a significantly higher percentage of lymphocytes in lymphomas compared with those in LEP (P < 0.01). Additionally, the upregulation of CCL5 in areas of necrosis involved by lymphoma contrasted with the minimal staining in the zones of degeneration/necrosis in the setting of LEP. We observed direct internalization of CCL5-positive lymphocytes within adipocytes based on ultrastructural studies. This study shows that the basis of the adipocyte tropism may reflect a unique interaction between CCL5-positive lymphocytes and CCR5 positive adipocytes. Given the known pharmacologic inhibitors of CCR5-expression one might propose that using such inhibitors (ie, anti-CCR5) could be of therapeutic value in select cases.

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus.

BACKGROUND: Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon. CASE REPORT: We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.

Expression of interleukin-17 is correlated with interferon-α expression in cutaneous lesions of lupus erythematosus.

BACKGROUND: Type I interferon (IFN) has been reported to have an important role in the development of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). A new subset of CD4+ T cells, T helper (Th)17 cells, also plays a role in the development of autoimmunity. AIM: To investigate expression of interleukin (IL)-17 and IFN-α in different CLE subsets, and their associations with the pathogenesis of LE. METHODS: Skin tissue samples from 33 cases, including chronic discoid LE (n = 24), acute (A)CLE (n = 4), subacute CLE (n = 1) and lupus panniculitis (n = 4) were collected for immunohistochemistry. Expression of IL-6, IL-17A, IFN-α, IFN-γ, myxovirus protein (Mx)A and transforming growth factor (TGF)-ß was assessed in these samples. RESULTS: All LE specimens had staining for IL-6 and TGF-ß in the infiltrated inflammatory cells. IL-17A staining was seen in 84.8% of specimens, and IFN-α or MxA was seen in 93.9%. TGF-ß expression in ACLE was significantly greater than that in both chronic cutaneous (CC)LE and in lupus panniculitis (P = 0.02 for both). Expression of IL-17A was positively associated with expression of IFN-α and MxA (Spearman's ρ = 0.56 and 0.39, respectively). In addition, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) correlated positively with expression of IFN-α and MxA (ρ = 0.40 for both), whereas there was no correlation with IL-17A expression. CONCLUSIONS: Two major cytokines, IL-17A and IFN-α, may play roles in the pathogenesis of CLE. Their patterns of expression positively correlated with each other.

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.

Manifestaciones cutáneas del lupus eritematoso / Cutaneous manifestations of lupus erythematosus

Las lesiones en la piel producidas por el LE constituyen una de lasmanifestaciones más visibles y frecuentes de esta enfermedad. Estas lesiones muestran una gran variabilidad, tanto en su expresión clínica comomicroscópica, lo que dificulta su comprensión y estudio. Los pacientes queexpresan enfermedad en la piel no tienen, en su mayoría, complicacionessistémicas graves pero sí importante morbilidad dada la extensión, cronicidad, riesgo de cicatrices y desfiguramiento de la apariencia física quelas lesiones cutáneas pueden ocasionar. Los mecanismos patogénicos exactos que conducen al desarrollo de lesiones cutáneas en el LE no se conocenpero probablemente la radiación ultravioleta juega un papel importante.La apoptosis de los queratinocitos inducida por esta radiación y los estí-mulos proinflamatorios que se desencadenan como consecuencia del déficit en la eliminación de estas células apoptóticas constituyen probablementelos pilares en los que se basa la etiopatogenia de esta enfermedad en la piel.Sin embargo, restan múltiples interrogantes aún por dilucidar. El tratamiento se basa en la fotoprotección, la aplicación tópica de corticoides yla administración oral de antipalúdicos (AU)

Skin lesions are the most visible and frequent symptoms in lupuserythromatosus (LE). These lesions vary greatly in their clinical as well asmicroscopic features, which difficults the understanding and study of LE.Most of the patients that express skin disease do not suffer from serioussystemic complications, but from important morbidity given the extension, chronicity, chances of scarring and disfigurement that skin lesionsmay cause. The exact pathogenic mechanisms that induce the development of skin lesions in LE are unknown at present; however, ultraviolet(UV) radiation could play an important role. UV- induced keratinocyteapoptosis as well as proinflammatory stimuli release because of uncomplete apoptotic cell clearance may be the pillars of the etiology of this skindisease. Nonetheless, there are still many questions to answer. The treatment consists of photoprotection, topical administration of corticoids aswell as oral administration of antimalarial drugs (AU)

Lupus erythematosus panniculitis: clinicopathological, immunophenotypic, and molecular studies.

Lupus erythematosus panniculitis (LEP) is an inflammatory disorder of the subcutaneous fat in patients with lupus erythematosus (LE). It is a rare variant of the disease, which occurs approximately in 1%-3% of patients with cutaneous LE. The purpose of this study was to investigate the clinical, histopathologic, immunophenotypical, and molecular profiles of LEP. We performed a retrospective study of 19 biopsy specimens from 17 patients with LEP. We reviewed their clinical data and reexamined the histopathology. Immunophenotyping and molecular studies were done using sections from paraffin-embedded formalin-fixed tissue. The most common clinical manifestation was a depressed patch on upper arm. Patients showed good response to variable treatment modalities, but, generally, relapse of panniculitis was noted when treatment was discontinued. Histopathologically, most specimens revealed lymphoplasmacytic lobular panniculitis with epidermal and dermal changes of LE, hyaline fat necrosis, and lymphoid follicles. Immunohistochemistry showed a mixture of T and B cells in dermis and subcutis with a slight preponderance of T cell. Although the polymerase chain reaction analysis of the T-cell receptor-gamma gene rearrangement showed a polyclonal smear in 89.5% of cases, a small portion of specimens demonstrated monoclonality. LEP is a chronic recurrent disease with characteristic features. Its diagnosis is often challenging, and a precise diagnosis is achievable only upon elaborate clinicopathologic correlation and integrated interpretation of all diagnostic criteria.

Clinical entity of Lupus erythematosus panniculitis/lupus erythematosus profundus.

We reviewed the clinical and histological characteristics of the 44 cases of lupus erythematosus profundus (LEP) that have been encountered in our department. The female to male ratio was 4.5:1. The mean age of the females was 36 years, and the mean age of the males was 34 years. The most common sites were the face (38.4%) and upper limbs (26.0%). Even among the patients with LEP alone many of the positive patients had low antibody titers of 1:40 or 1:80. In 18 of the 44 cases SLE was complicated by LEP, and in those cases there was a tendency for LEP to develop during the course of SLE (11 cases). The important histological findings were lobular panniculitis associated with mucin deposition (32 cases) and a tendency to be associated with damage to the basal cell layer. In addition, the direct immunofluorescence test was positive in both the basement membrane (90.5%) and blood vessels (85.7%) in a high percentage of even the cases of LEP alone. Based on the above findings, LEP is a cutaneous variant of erythematosus, and the importance of the histological findings when making the diagnosis of LEP was reconfirmed.