Variant Of Cutaneous Lupus Erythematosus Research Articles

OA14 Subcutaneous panniculitis-like T-cell lymphoma: a mimic of lupus erythematous panniculitis

Abstract Background/Aims Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus characterised by tender, erythematous subcutaneous nodules or plaques on the face, trunk and proximal extremities. Without treatment, profound lipoatrophy frequently occurs, which often has a devastating psychosocial impact. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous T-cell lymphoma, which may appear in a similar manner. SPTCL initially preferentially infiltrates the subcutaneous adipose tissue and symptoms vary widely depending on the stage of the disease. Early-stage disease presents as painless self-resolving subcutaneous nodules on limbs and trunk. Methods We present the case of a young woman who presented with progressively developing, widespread painful cutaneous lesions, pyrexia of unknown origin and general malaise for one month. She had a history of hurthle cell neoplasm and a strong family history of malignancy. Initial examination revealed 1-2 cm firm, skin-coloured subcutaneous nodules over her lower back, chest and thigh, with groin and axillary lymphadenopathy. Further lesions progressively developed over a three-month period, with lesions turning increasingly erythematous and with associated ulceration. Of note, a significant periorbital lesion appeared, associated with an ipsilateral facial palsy. Results Initial bloods revealed an elevated LDH with cholestatic liver function tests. PET-CT imaging showed an enlarged axillary node with extensive pathology throughout the subcutaneous fat of unknown aetiology. Due to the family history, underlying haematological malignancy and atypical Sweet’s were considered for this unusual presentation. Seropositivity for anti-Ro and ENA, alongside raised angiotensin converting enzyme, broadened the differentials to include LEP, mixed atypical connective tissue disease and cutaneous sarcoid. Notably, complement, myositis panel and creatine kinase were normal. Lupus vulgaris was considered due to high local prevalence and excluded with T-SPOT testing. Histopathological analysis of lesional skin from the upper arm found predominantly subcutaneous infiltrates of atypical lymphoid cells with irregular hyperchromatic nuclei and rimming of individual fat cells. T-cell clonality analysis detected clonal T-cell receptor beta (V-J and D-J) gene rearrangements consistent with SPTCL. Her orbital and cutaneous lesions responded well to six cycles of CHOEP (cyclophosphamide, hydroxydaunorubicin, oncovin, etoposide, prednisone) and the patient returned to functional baseline. Conclusion This case demonstrates the diagnostic difficulties when managing a patient with relapsing remitting panniculitis. Whilst the initial presentation of SPTCL here was classical, with widespread multifocal subcutaneous nodules, the appearance of facial symptoms in SPTCL is rare. Diagnostic uncertainty is frequent in both LEP and SPTCL due to the initial non-specific cutaneous presentation. This case emphasises the importance of clinicopathological correlation for accurate diagnosis. Interestingly, up to 20% of SPTCL patients have concomitant autoimmune diseases, and there is evidence suggesting a potential association between LEP and subcutaneous SPTCL beyond chance, leading some researchers to propose that these two entities exist along a spectrum. Disclosure D. Li: None. L. Spencer: None.

Chilblain lupus erythematous- A rare encounter

Chilblain lupus erythematosus is a rare, chronic variant of cutaneous lupus erythematosus that occurs during cold or damp periods on the hands, fingers, or feet

Identification of Significant Genes and Pathways for the Chronic and Subacute Cutaneous Lupus Erythematosus via Bioinformatics Analysis.

Background Chronic cutaneous lupus erythematosus (CCLE) and subacute cutaneous lupus erythematosus (SCLE) are both common variants of cutaneous lupus erythematosus (CLE) that mainly involve the skin and mucous membrane. Oral mucosal involvement is frequently observed in patients of CLE. Despite that they have different clinicopathological features, whether there is a significant difference in pathogenesis between them remains unclear. Herein, we investigated specific genes and pathways of SCLE and CCLE via bioinformatics analysis. Methods Microarray expression datasets of GSE109248 and GSE112943 were both retrieved from the GEO database. Differentially expressed genes (DEGs) between CCLE or SCLE skin tissues and health controls were selected by GEO2R. Common DEGs were picked out via the Venn diagram software. Then, functional enrichment and PPI network analysis were conducted, and the top 10 key genes were identified via Cytohubba. Results Totally, 176 DEGs of SCLE and 287 DEGs of CCLE were identified. The GO enrichment and KEGG analysis of DEGs of SCLE is significantly enriched in the response to virus, defense response to virus, response to IFN-gamma, cellular response to IFN-γ, type I IFN signaling pathway, chemokine activity, chemokine receptor binding, NOD-like receptor signaling pathway, etc. The GO enrichment and KEGG analysis of DEGs of CCLE is significantly enriched in the response to virus, regulation of multiorganism process, negative regulation of viral process, regulation of lymphocyte activation, chemokine receptor binding, CCR chemokine receptor binding, NOD-like receptor signaling pathway, etc. The top 10 hub genes of SCLE and CCLE, respectively, include STAT1, CXCL10, IRF7, ISG15, and RSAD2 and CXCL10, IRF7, IFIT3, CTLA4, and ISG15. Conclusion Our finding suggests that SCLE and CCLE have the similar potential key genes and pathways and majority of them belong to IFN signatures and IFN signaling pathway. Besides, the NOD-like receptor signaling pathway might also have an essential role in the pathogenesis of SCLE and CCLE. Together, the identified genes and signaling pathways have enhanced our understanding of the mechanism underlying the occurrence and development of both SCLE and CCLE.

Histology of Skin Alterations in Lupus Erythematosus

Abstract Lupus erythematosus is an autoimmune connective tissue disorder showing a broad spectrum of clinical manifestations. The aim of this study was to assess the correlation of skin histology and different types of lupus erythematosus. Materials and methods: Fifty-one skin specimens were assessed from 39 female and 12 male patients with acute, subcutaneous and chronic lupus erythematosus, diagnosed and treated in the Department of Dermatology and Venereology, Alexandrovska University Hospital for a 4-year period. Results: Follicular hyperkeratosis, epidermal atrophy, vacuolar degeneration and interface dermatitis were the most frequently observed lesions in chronic cutaneous lupus erythematosus while diffuse hyperkeratosis, epidermal atrophy and indistinct interface dermatitis in the dermis were predominant in subacute cutaneous lupus erythematosus. Lupus tumidus, a rare intermittent variant of cutaneous lupus erythematosus, showed almost no epidermal involvement and mucin deposition in the dermis. However, in one of our lupus tumidus patients the disease progressed to a systemic form with histological changes of acute cutaneous lupus erythematosus including atrophy, dermal-epidermal smoothing and lymphocytic infiltration in the dermis. Of note, a few patients showed histological changes of urticarial vasculitis-like and rheumatic-like patterns. Conclusion: The correlation of clinical course, histopathological findings and immunological tests are of vital importance for the correct diagnosis and follow up of patients with lupus erythematodes, thus preventing complications and improving their quality of life.

Recent Insight on the Management of Lupus Erythematosus Alopecia.

Lupus erythematosus (LE) is a chronic autoimmune condition with a wide spectrum of clinical presentations. Alopecias, both non-scarring and scarring, frequently occur in the context of LE and can assume several different patterns. Furthermore, alopecia occurring with LE may be considered LE-specific if LE-specific features are present on histology; otherwise, alopecia is considered non-LE-specific. Non-scarring alopecia is highly specific to systemic LE (SLE), and therefore has been regarded as a criterion for the diagnosis of SLE. Variants of cutaneous LE (CLE), including acute, subacute, and chronic forms, are also capable of causing hair loss, and chronic CLE is an important cause of primary cicatricial alopecia. Other types of hair loss not specific to LE, including telogen effluvium, alopecia areata, and anagen effluvium, may also occur in a patient with lupus. Lupus alopecia may be difficult to treat, particularly in cases that have progressed to scarring. The article summarizes the types of lupus alopecia and recent insight regarding their management. Data regarding the management of lupus alopecia are sparse and limited to case reports, and therefore, many studies including in this review report the efficacy of treatments on CLE as a broader entity. In general, for patients with non-scarring alopecia in SLE, management is aimed at controlling SLE activity with subsequent hair regrowth. Topical medications can be used to expedite recovery. Prompt treatment is crucial in the case of chronic CLE due to potential for scarring and irreversible damage. First-line therapies for CLE include topical corticosteroids and oral antimalarials, with or without oral corticosteroids as bridging therapy. Second and third-line systemic treatments for CLE include methotrexate, retinoids, dapsone, mycophenolate mofetil, and mycophenolate acid. Additional topical and systemic medications as well as physical modalities used for the treatment of lupus alopecia and CLE are discussed herein.

A Rare Case of Tumid Lupus Erythematosus with Unilateral Linear Distribution in A Young Child

Tumid lupus erythematosus (TLE) as a rare variant of cutaneous lupus erythematosus (CLE) is characterized by edematous, urticarial-like annular papules and plaques. TLE has similar histopathologic findings to CLE such as periadnexal lymphocytic infiltration and interstitial mucin deposition. Although TLE develops on sun-exposed areas at any age, it is rarely distributed along the Blaschko lines and develops in infancy and childhood. Unlike CLE, skin lesion of TLE heals without leaving scarring or dyspigmentation. Here, we report a rare case of unilateral linear TLE in a 4-year-old girl, which was improved by intralesional corticosteroid injection and oral antimalarial drug with leaving postinflammatory hyperpigmentation.

Toxic Epidermal Necrolysis-like Subacute Cutaneous Lupus Erythematosus: A Case Report

Toxic epidermal necrolysis (TEN)-like lesions have been described in the setting of lupus erythematosus, and have been considered as a specific hyperacute variant of cutaneous lupus erythematosus, with features different from classical drugrelated toxic epidermal necrolysis. This is a report of a case of subacute cutaneous lupus erythematosus in a 62-year old Caucasian woman, which evolved into a TEN-like presentation over the course of 4 weeks. The patient responded rapidly to treatment with high doses of prednisone

A rare case of tumid lupus erythematosus with unilateral linear distribution in a young child

Tumid lupus erythematosus (TLE) as a rare variant of cutaneous lupus erythematosus (CLE) is characterized by edematous, urticarial-like annular papules and plaques. TLE has similar histopathologic findings to CLE such as periadnexal lymphocytic infiltration and interstitial mucin deposition. Although TLE develops on sun-exposed areas at any age, it is rarely distributed along the Blaschko lines and develops in infancy and childhood. Unlike CLE, skin lesion of TLE heals without leaving scarring or dyspigmentation. Here, we report a rare case of unilateral linear TLE in a 4-year-old girl, which was improved by intralesional corticosteroid injection and oral antimalarial drug with leaving postinflammatory hyperpigmentation.

Pediatric Tumid Lupus Erythematosus: Two Case Reports

Tumid lupus erythematosus (TLE) is a rare variant of cutaneous lupus erythematosus. The clinical diagnosis can be difficult to ascertain as it often presents with negative serology and without associated systemic symptoms. We present two pediatric cases of TLE: a young girl with erythematous facial papules and a second with purple and grey facial plaques. Biopsies displayed a lymphocytic infiltrate consisted with TLE and both improved on antimalarials. These cases highlight the varied morphologies and bring greater awareness of TLE and its treatments.

Lupus erythematosus tumidus: a clinical and histological study of 25 cases.

Lupus erythematosus tumidus (LET) is a subtype of cutaneous lupus erythematosus (CLE) that has been well characterized in recent years. However, some controversy still remains concerning the histological features of epidermal involvement. The objective of this report is to describe the clinical and microscopic features of LET in patients diagnosed at Hospital Universitari Germans Trias i Pujol, Spain. We conducted a retrospective study of 25 patients with a diagnosis of LET. All patients presented with typical LET lesions (smooth, erythematous plaques without macroscopic epidermal changes, such as follicular plugs or scale, that resolved without residual scarring or hypopigmentation). None of the patients fulfilled the criteria for systemic lupus erythematosus during follow-up. Test results for antinuclear antibodies were positive in five patients (20%), with titres below one of 320 in all cases. Twenty-two patients (88%) required antimalarial therapy; response was good in 70% and moderate response in 30%. Minor epidermal alterations were observed in 52% of biopsy specimens, with focal basal vacuolization being the most frequent. LET is a variant of CLE that has distinctive clinical, histologic and prognostic features. Unlike the patients in the case series previously described in the literature, most of our patients required treatment with antimalarials. Histology revealed mild epidermal alterations in a significant percentage of patients. Thus, in our opinion, the absence of microscopic epidermal alterations is not constant in LET.

Nonbullous neutrophilic lupus erythematosus: A newly recognized variant of cutaneous lupus erythematosus

Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. This study was limited by the small number of cases. Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil-mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease.

Lupus erythematosus tumidus with discoid lupus erythematosus-induced alopecia of the scalp

Lupus erythematosus tumidus (LET) is an uncommon variant of cutaneous lupus erythematosus. Lupus erythematodes tumidus is characterized by smooth, erythematous plaques on sun-exposed areas without surface changes, such as follicular plugs, atrophy, or scale. Histopathologic features include a lymphocytic, perivascular and periadnexal infiltrate with abundant interstitial, superficial, and deep dermal mucin without appreciable epidermal and vacuolar changes. Typically, LET is responsive to treatment with systemic antimalarials. We present a unique case of alopecia associated with LET, which was partially responsive to hydroxychloroquine. We also note that the plaque of LET is adjacent to the plaque of discoid lupus erythematosus.

Toxic Epidermal Necrolysis-like Cutaneous Lupus Erythematosus: A Series of Three Patients

Toxic epidermal necrolysis-like lesions have been described in the setting of lupus erythematosus, and have been considered as a specific hyperacute variant of cutaneous lupus erythematosus, with features different from classical drug-related toxic epidermal necrolysis. We report here a series of three patients with lupus erythematosus who presented with severe worsening of their cutaneous disease in a toxic epidermal necrolysis-like fashion. We compared these cases with cases reported previously. Based on this discussion, we speculate that some of these patients may have classical drug-related toxic epidermal necrolysis rather than lupus erythematosus-related toxic epidermal necrolysis.

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.

Immunopathology of vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog: a canine homologue of subacute cutaneous lupus erythematosus in humans.

Clinical and histological features of an erosive disease in the rough collie and Shetland sheepdog are most consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). This paper reports the immunopathological findings of canine VCLE using samples from 17 affected dogs. Lesional skin sections were stained with monoclonal antibodies specific for CD3 (11 dogs) or a panel of monoclonal antibodies specific for leukocyte antigens (two dogs). Apoptotic cells were detected using the TUNEL method in 12 cases. Direct (14 dogs) and indirect immunofluorescence tests (five dogs) were also performed. Circulating antibodies to extractable nuclear antigens (ENA) were surveyed in 11 dogs by immunoblotting and ELISA. The predominant cells at the dermal-epidermal interface were identified as CD3(+) T lymphocytes expressing CD4 or CD8 and CD1(+) dendritic antigen presenting cells. In 7/12 dogs (58%), apoptosis of basal keratinocyte nuclei was present. Up-regulation of MHCII and ICAM-1 was observed on basal keratinocytes from the two dogs examined. Direct immunofluorescence revealed deposition of immunoglobulins bound to the cytoplasm of keratinocytes (6/14 dogs; 43%), to the dermal-epidermal junction (7/14 dogs; 50%), or to superficial dermal venules (13/14 dogs; 93%). Circulating IgG auto-antibodies targeting one or more ENA were detected in nine (82%) and eight (73%) of 11 dogs by immunoblotting and ELISA, respectively. These auto-antibodies recognized Ro/SSA and/or La/SSB in four (36%) and six (55%) of 11 dogs respectively by these two methods. Altogether, results of these studies provide evidence supporting the hypothesis that canine VCLE is an immunological homologue of subacute cutaneous lupus erythematosus in humans.

Lupus erythematosus tumidus

Lupus erythematosus tumidus (LET) is a rare form of chronic cutaneous lupus erythematosus that characteristically presents as a succulent, erythematous plaques on sun-exposed areas. The histopathological change that primarily distinguishes LET from other variants of cutaneous lupus erythematosus is the lack of alterations of the dermo-epidermal junction and epidermis. Our purpose was to describe 15 cases of LET from Thailand. The records of 15 patients diagnosed with LET at Srinagarind Hospital Medical School between 1995 and 2002 were reviewed on the following aspects: clinical manifestation, laboratory investigation, direct immunofluorescence study, phototesting, histopathological findings, clinical course, and treatment. All 15 patients consisted of 10 females and five males. The mean age at onset was 38.8 years. The lesions more commonly affect the face and trunk. One patient had concomitant discoid lupus erythematosus and two developed systemic involvement 4 and 6 months after LET. Direct immunofluorescence studies all showed negative results. Positive phototest reactions were detected in five of 10 tested patients: four with ultraviolet A and B and one with ultraviolet A only. Most patients responded well to chloroquine phosphate and the remainder successfully improved with methotrexate, topical and systemic corticosteroids. Our data demonstrate the features of LET that are repeatable and characteristic. Lupus erythematosus tumidus in this study was more common in women, and photosensitivity reactions of the patients were seen less frequently compared with those in the earlier report of Kuhn et al. Furthermore, two of 15 patients exhibited systemic involvement in the course of their disease.

Eleven cases of vesicular cutaneous lupus erythematosus in Shetland sheepdogs and rough collies: clinical management and prognosis.

A cutaneous ulcerative disease is recognized to affect the adult Shetland sheepdog and rough collie. This has a distinct clinical and histological appearance consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). Retrospective information on the clinical outcome and response to therapy was collected from 11 cases of histologically confirmed VCLE. In 8/11 dogs the onset of disease was in the summer; in three dogs recrudescence occurred in subsequent summers. In eight dogs the skin disease was judged to be 75-100% controlled with therapy after a minimum follow-up of 9 months. Successful treatment in seven of these cases comprised immunosuppressive doses of oral glucocorticoids, alone (one dog), in combination with azathioprine (five dogs) and doxycycline (one dog). One case responded to topical fluocinolone. Three dogs were euthanised for reasons directly related to the disease, one prior to initiating any therapy. Vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog can be a debilitating skin disease which is best managed with aggressive immunosuppressive therapy. Sun avoidance or the use of sunscreens is an important additional management recommendation.

Histopathologic findings in lupus erythematosus tumidus: Review of 80 patients

Background: In a recent study, we demonstrated that lupus erythematosus (LE) tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas. Objective: Our purpose was to analyze skin biopsy specimens from 80 patients with this disease and to determine whether it could be differentiated from other variants of CLE on histopathologic grounds. Methods: Skin biopsy specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients with LET were examined and compared with skin biopsy specimens from patients with discoid LE (DLE) and subacute CLE (SCLE). Results: Specimens from LET lesions showed a characteristic and diagnostic pattern of perivascular and periadnexal cellular infiltrates in the papillary and reticular dermis composed almost entirely of lymphocytes. In some cases, few scattered neutrophils were present. Furthermore, interstitial mucin deposition was observed in all specimens, as confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE lesions, epidermal atrophy or alteration at the dermoepidermal junction was not detected. Conclusion: Skin lesions of patients with LET present with specific histopathologic features, and the differences compared with subacute CLE and discoid LE further support the concept to consider LET as a separate entity of CLE. (J Am Acad Dermatol 2003;48:901-8.)

Upregulation of epidermal surface molecule expression in primary and ultraviolet-induced lesions of lupus erythematosus tumidus.

Lupus erythematosus tumidus (LET), a photosensitive skin disorder with characteristic clinical and histological features, has not been generally accepted as a subset of cutaneous lupus erythematosus (CLE). To analyse the expression of epidermal surface molecules in skin biopsy specimens from patients with LET and to relate the results to other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute CLE (SCLE). In total, 45 patients with different subtypes of CLE were included in the study, and cryostat sections from primary and ultraviolet (UV) A- and UVB-induced skin lesions were investigated using immunohistochemical methods. In contrast to healthy controls, skin lesions of LET showed upregulation of intercellular adhesion molecule-1 (ICAM-1) and histocompatibility class II molecules (HLA-DR), with an expression pattern resembling that seen in DLE and SCLE. Furthermore, staining with a monoclonal antibody against 27E10, a distinct marker for cell activation and differentiation, revealed intense focal or band-like labelling of all epidermal layers independent of the type of lesion. Expression of epidermal surface molecules such as ICAM-1, HLA-DR and 27E10 is equally upregulated in primary and UV-induced lesions of patients with LET, DLE and SCLE. These results support our recent clinical findings that LET represents a distinct subset of CLE with a similar immunopathomechanism rather than a different disease.

Generalized lupus erythematosus profundus in a patient with genetic partial deficiency of C4

Lupus erythematosus profundus (LEP) is an unusual variant of cutaneous lupus erythematosus (CLE)that is characterized by chronic, recurrent inflammation of the subcutaneous tissue leading to fibrosis. It is found in the settings of both discoid and systemic lupus erythematosus. Generalized forms are extremely rare. We present a case of generalized LEP associated with genetic partial C4-deficiency. (J Am Acad Dermatol 1999;41:362-4.)