Chronic Cutaneous Lupus Erythematosus Research Articles

Hypertrophic Lupus Erythematosus Treated Successfully with Acitretin as Monotherapy

Hypertrophic lupus erythematosus (HLE) is a distinct and rare subset of chronic cutaneous lupus erythematosus characterized by verrucous lesions which are chronic in course and resistant to treatment (1). We describe the successful use of acitretin in a patient with HLE who had multiple hyperkeratotic verrucous plaques over the dorsa of his hands, feet, and legs and who failed to respond to local steroids and antimalarials.

Lupus erythematosus tumidus: a series of 26 cases

To study 26 cases of lupus erythematosus tumidus (LET), a subset of chronic cutaneous lupus erythematosus (CCLE), referred to in the literature as a rare entity. A retrospective study was conducted of 26 patients diagnosed with LET between 1996 and 2002. The clinical characteristics, histopathologic and laboratory findings, response to treatment, association with other subsets of lupus, course, and diagnostic criteria were analyzed. The incidence by sex was similar. The mean age of presentation was 49.19 years. The clinical presentation usually involved erythematous, edematous plaques located on the face, chest, back, or extremities, related to sun exposure. A dermal lymphocytic infiltrate with a perivascular disposition and differing degrees of mucin deposition was observed in all cases. Minimal epidermal changes were present in 18 cases, and 11 of these also showed minimal dermal-epidermal changes. Only one case showed dermal-epidermal changes without any epidermal alteration. Direct immunofluorescence test was performed in 15 patients, and 11 were negative. All cases showed a benign course without systemic manifestations. The response to topical steroids or antimalarial treatment was excellent, but a seasonal recurrence was usually observed. Discussion No defined criteria for LET are universally accepted. The main controversies are the acceptance of LET as a separate subset of CCLE, and the histopathologic diagnostic features, mainly the presence or absence of epidermal and dermal-epidermal changes in these lesions. No inflexible histologic criteria should be employed for the diagnosis of LET. This subset of lupus erythematosus is characterized by intense photosensitivity, definite clinical lesions, a benign course, the absence of systemic disease, good response to antimalarial treatment, and a tendency to recur. More studies should be performed in order to establish the true incidence of LET because this subset of CCLE is probably underestimated.

Recurrence of palmar hypertrophic chronic cutaneous LE after surgical excision

Recurrence of palmar hypertrophic chronic cutaneous LE after surgical excision

Photoprotection by thalidomide in patients with chronic cutaneous and systemic lupus erythematosus: discordant effects on minimal erythema dose and sunburn cell formation.

Thalidomide is an anti-inflammatory and immunomodulatory agent with proven efficacy in several refractory inflammatory skin conditions including photoexacerbated skin diseases. The effects of thalidomide on ultraviolet (UV)-induced cutaneous damage in humans have not been extensively studied. We describe the results of minimal erythema dose (MED) testing in nonlesional skin of three patients with chronic cutaneous lupus erythematosus (CCLE) before and after treatment with thalidomide. To determine whether thalidomide treatment provides clinical and histological evidence of photoprotection from acute UV injury. MED testing was performed in nonlesional skin of three patients with CCLE before and after treatment with thalidomide. Skin biopsy specimens were taken from MED sites for in situ immunochemistry. In each patient, the MED to UVB irradiation was significantly higher while the patient was receiving thalidomide treatment than in the absence of thalidomide, suggesting a systemic photoprotective effect. Thalidomide treatment had no significant effect on markers of apoptosis including sunburn cell formation and terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labelling, which identifies single-strand breaks in DNA. Thalidomide inhibits acute UVB erythema at 24 h after exposure, as a 100-mg daily dose of this drug for 4 weeks conveyed a sun protection factor of 1.56 to > 4.0. We conclude that inhibition of UVB-induced inflammation may, in part, explain the therapeutic benefits of this agent on photosensitive diseases.

Susceptibility of T cell receptor-alpha chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus.

The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-alpha(-/-) mice and B6 TCR-delta(-/-) mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-alpha(-/-) mice with low FU (0.2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2.0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-delta(-/-) mice at a very low incidence. Specifically, the skin lesions of TCR-alpha(-/-) mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.

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.

Erythema elevatum diutinum associated with lupus panniculitis in a patient with discoid lesions of chronic cutaneous lupus erythematosus

Erythema elevatum diutinum (EED) is a rare variant of cutaneous leukocytoclastic vasculitis that normally presents with symmetrical violaceous or red papules, plaques, and nodules of the extremities.1 We report a case of EED with an associated lupus panniculitis presenting as large verrucous tumors on the arms in a patient who also had discoid lesions of cutaneous lupus.

Subcutaneous panniculitis-like T-cell lymphoma with vacuolar interface dermatitis resembling lupus erythematosus panniculitis

Lupus erythematosus (LE) panniculitis (LEP) is a form of chronic cutaneous LE most often characterized by erythematous subcutaneous nodules. The histopathology of LEP may be distinctive, allowing a diagnosis even in the absence of any other LE features. Lymphocytic infiltration of the panniculus is termed lymphocytic lobular panniculitis. This entity has been reported in both LEP and subcutaneous panniculitis-like T-cell lymphoma. We describe a 67-year-old woman who presented with multiple dermal and subcutaneous nodules on her legs and hips. Biopsy specimens of roughly 15 lesions were interpreted as being diagnostic of LEP, however, with each subsequent biopsy specimen more atypical cells were observed. The patient responded only to moderate doses of oral prednisone, and failed intralesional triamcinolone acetonide, oral immunosuppressive agents, oral antimalarial agents, and oral thalidomide. Three years after the onset of her disease, ulcerated plaques and nodules developed. At this time a T-cell receptor gene rearrangement was present and subcutaneous panniculitis-like T-cell lymphoma was diagnosed. Despite multiple doses of chemotherapy she died approximately 1 year after diagnosis. Patients with apparent LEP that have atypical lymphocytes in their biopsy specimens should be followed up closely for the development of T-cell malignancy.

Lúpus eritematoso cutâneo crônico: estudo de 290 pacientes

FUNDAMENTO: Lúpus eritematoso cutâneo crônico é uma doença inflamatória crônica relativamente freqüente, mas pouco estudada entre nós. OBJETIVO: Caracterizar epidemiologia e clínica de pacientes com lúpus eritematoso cutâneo crônico, visando comparar dados obtidos com literatura mundial. PACIENTES E MÉTODOS: Foram estudados retrospectivamente 290 pacientes com lúpus eritematoso cutâneo crônico no período de 1982 a 1996, na Clínica de Dermatologia da Santa Casa de São Paulo. RESULTADOS: A média de idade da instalação da doença foi de 32,3 anos, houve predomínio do sexo feminino em relação ao masculino (3,4:1), a maior parte dos pacientes teve lesões localizadas no segmento cefálico (58,3%). Quanto às variedades clínicas, houve predomínio da placa discóide típica em 90,4% dos casos, seguida das variantes verrucosa ou hipertrófica (7,9%), lúpus eritematso pérnio (1,4%), e túmida (0,3%). Lesões em mucosas ou epitélios de transição ocorreram em 27,2% dos pacientes. CONCLUSÕES: Lúpus eritematoso cutâneo crônico é doença mais comum em mulher adulta, sendo a placa discóide típica a lesão mais comum. Lesões mucosas ocorreram em aproximadamente em um quarto dos casos.

A rare case of autoimmune polyglandular syndrome type 3

A 57-year-old female was admitted to our hospital suffering from a lower lip tumor, small ulcers in the arms and alopecia of the head. Because she had type 2 diabetes mellitus (DM) for the past 3 years, she was referred to our department of internal medicine for its treatment. Her endogenous insulin secretion was much decreased despite the short duration of diabetes. Glutamic acid decarboxylase antibodies (GADA) and islet cell antibodies (ICA) were both positive. Therefore, she was diagnosed as having slowly progressive form of type 1 DM. Type 1 DM is sometimes complicated with autoimmune disorders. After further examinations, she was diagnosed as having Sjögren's syndrome, Graves’ disease and autoimmune neutropenia (AIN). According to the histological examinations of the lip tumor and peripheral site of the skin ulcer, the patient was diagnosed as having carcinoma spinocellulare and chronic cutaneous lupus erythematosus. The examination also showed positive anti-intrinsic factor and anti-ribonucleoprotein (RNP) antibodies. She is a rare case of an autoimmune polyglandullar syndrome (APS) type 3 simultaneously manifesting these seven diseases with multiple autoimmune antibodies.

Discoid Lupus Erythematosus in Children

Chronic cutaneous lupus erythematosus, or discoid lupus erythematosus (DLE), is rare in children. Only 29 pediatric cases have previously been reported

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62

Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26–56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow‐up period was 8,6 months (range 2–18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory‐motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, “zoster‐like” thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow‐up and the study of more patients are needed to confirm the results.

Cutaneous lupus erythematosus: diagnosis and management.

Cutaneous lupus erythematosus (CLE) includes a variety of lupus erythematosus (LE)-specific skin lesions that are subdivided into three categories - chronic CLE (CCLE), subacute CLE (SCLE) and acute CLE (ACLE) - based on clinical morphology, average duration of skin lesions and routine histopathologic examination. This paper describes our personal experience in the management of CLE over the last 30 years, with details on preferential therapeutic options related to clinical, histologic and immunopathologic aspects of each clinical subset of the disease. Effective sunscreening and sun protection are considered the first rule in the management of CLE because of the high degree of photosensitivity of the disease. Antimalarial agents are crucial in the treatment of CLE and are the first-line systemic agents, particularly in discoid LE (DLE) and SCLE. Dapsone is the drug of choice for bullous systemic LE (BSLE) as well as for LE in small dermal vessels (e.g. leukocytoclastic vasculitis). Retinoids, known as second-line drugs for systemic therapy, are sometimes used to treat chronic forms of CLE and are particularly successful in treating hypertrophic LE. Systemic immunosuppressive agents are required to manage the underlying systemic LE disease activity in patients with ACLE. These drugs, especially azathioprine, methotrexate, cyclophosphamide and cyclosporine, together with corticosteroids, constitute third-line systemic therapy of CLE. In our experience, oral prednisone or parenteral 'pulsed' methylprednisolone are useful in exacerbations of disease activity. Thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, although its distribution is limited to a few countries because of the risk of teratogenicity and polyneuropathy. However, medical treatment with local corticosteroids remains the mainstay of CLE treatment, especially for DLE. Patient education regarding the disease is also important in the management of CLE, because it helps relieve undue anxiety and to recruit the patient as an active participant in the treatment regimen.

Scarring alopecias

The irreversibility and the possible important cosmetic consequences of scarring alopecia demand special diagnostic attention in order to promptly attain a precise diagnosis and specific treatment. Scarring alopecias are either due to permanent damage to essential parts of the hair follicle or destruction of the entire hair follicle. They are classified into the categories of primary scarring alopecias, where the hair follicle is the primary target of destruction, and secondary scarring alopecias, where the follicular damage results incidentally from events around impinging on the follicular unit. The differential diagnosis of the more common primary scarring alopecias, e.g. follicular lichen planus, chronic cutaneous lupus erythematosus and folliculitis decalvans, can be difficult when based only on anamnestic and clinical findings. The scalp biopsy is essential for appropriate nosologic classification and has prognostic relevance. The primary therapeutic goal is to halt progression of the irreversible process as early as possible by means of immunomodulatory, immunosuppressive or antiinfectious agents, respectively.

Thalidomide: an antineoplastic agent.

It has been more than three decades since the withdrawal of thalidomide from the marketplace. Thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor-alpha by accelerating the degradation of its messenger RNA. Thalidomide inhibits angiogenesis. Recently, thalidomide was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. Thalidomide has been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behcet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with HIV infection, in which this drug is an efficacious agent against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. Only in the last several years has thalidomide been aggressively investigated for its antiangiogenic potential and immunomodulatory properties in various tumor types. Current research on thalidomide in oncology covers investigation in a wide range of both solid tumors and hematologic malignancies.

Cutaneous lupus erythematosus.

Lupus erythematosus (LE) has many different clinical manifestations including a variety of cutaneous findings. Some of the cutaneous manifestations are not specific for LE, such as photosensitivity reactions, oral ulcers, alopecia, urticaria, vasculitis, vesiculo-bullous lesions, acral changes, cutaneous mucinoses, and cutaneous calcinosis. Other findings are specific for LE in that they are found only in patients who have lupus erythematosus. These LE-specific disorders include acute cutaneous LE, subacute cutaneous LE, and several forms of chronic cutaneous LE, including discoid LE. Skin biopsies are often helpful in differentiating LE-specific skin lesions from other disorders that can mimic them. Photoprotective measures and a number of drugs are useful in treating cutaneous LE.

Lymphocyctes Tgammadelta in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity.

Human Tgammadelta lymphocytes constitute from 1 to 15% of all peripheral blood lymphocytes. Recent work has demonstrated that this population plays a major role in the pathogenesis of infectious and immune diseases. Increased numbers of gammadelta T cells have been found in affected skin from systemic sclerosis and chronic cutaneous lupus erythematosus patients. In our study, we have determined the numbers of Tgammadelta lymphocytes and their subpopulations in peripheral blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy volunteers using flow cytometry and specific monoclonal antibodies. The same cells in uninvolved skin from SLE patients and human controls using immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain gene rearrangement was identified with primers for Vdelta1, Vdelta2 and Vdelta3 by the polymerase chain reaction. Statistical analysis showed a significantly decreased number of gammadelta T cells in SLE patients (26.4+/-16.9/microl) compared with the control group (55.3+/-20.6/microl (p < 0.001). The number of Vdelta2 TCR+ and Vgamma9 TCR+ subpopulations was also lower in SLE patients than in healthy persons. No statistical correlation between disease activity and the number of gammadelta T cells was demonstrated. The percentage of Tgammadelta lymphocytes in clinically normal skin from SLE patients was twice (22.0+/-9.4%) that found in the skin from healthy persons (11.1+/-5.5%) (p < 0.002). Higher percentages of the Vdelta2 TCR+ and Vgamma9 TCR+ subpopulation of lymphocytes were found in the skin from SLE patients. We have also found positive correlation between the percentage of Tgammadelta lymphocytes in skin and the activity of SLE (r=0.594, p < 0.001), and between subpopulation Vdelta3 TCR+ and disease activity (r=0.659, p< 0.001). In conclusion, the results of our studies demonstrate that, in patients with SLE, accumulation of Tgammadelta lymphocytes can be seen in clinically normal skin, and the percentage of these cells correlates with the activity of the disease.

The spectrum of cutaneous manifestations in lupus erythematosus--the Italian experience.

We have evaluated the incidence of lupus erythematosus (LE)-specific skin disease in 186 patients with LE, seen retrospectively over a 10-year period at our Dermatology Department and determined the correlation of LE-nonspecific skin disease in patients with systemic involvement. Chronic cutaneous LE (CCLE) with classical discoid lesions (localized, 70%; generalized, 30%) was the most common cutaneous manifestation (72.5%). Subacute cutaneous LE (SCLE) represented only 8% of LE skin disease (annular-polycyclic type, 73%; papulo-squamous type, 27%). Acute cutaneous LE (ACLE) was detected in 15% of our patients: the butterfly erythema was the most frequent skin lesion (96%) while only one case of bullous LE and one case of widespread maculo-papular eruption in association with malar erythema were demonstrated. In 8 patients no LE-specific skin lesions (lupus sine lupo) were found. LE-nonspecific skin lesions were found in 31% of our patients with systemic LE (SLE): Raynaud's phenomenon was found in 23/58 (39.6%), cutaneous small vessel leukocytoclastic vasculitis in 8/58 (13.7%), nonscarring alopecia in 18/58 (31%), lupus pernio in 6/58 (10.3%), hemorrhagic lesions in 4/58 (6.8%), livedo reticularis in 5/58 (8.6%), mucosal ulcers in 3/58 (5.1%) and periungual telangiectasia in 12/58 (20.6%) SLE patients. LE-nonspecific skin lesions are detected only in patients with SLE and usually in the active phases of the disease.

Lupus tumidus

Lupus tumidus is a rare subtype of chronic cutaneous lupus erythematosus that was first described by Gougerot and Bournier in 1930. Clinically, lupus tumidus presents as smooth, shiny, red-violet plaques of the head and neck that may be pruritic and have a fine scale. These lesions characteristically clear without scarring and recur in their original distribution. Histologic features include superficial and deep lymphohistiocytic infiltrates and abundant dermal deposits of mucin. We describe lupus tumidus as a distinct form of cutaneous lupus erythematosus and report 4 cases. (J Am Acad Dermatol 1999;41:250-3.)

Antinuclear antibody seropositivity in patients with cutaneous T-cell lymphoma

Background: We attempted to determine the frequency and clinical relevance of antinuclear antibody (ANA) testing and positive ANA test results in patients with cutaneous T-cell lymphoma (CTCL). Methods: A retrospective chart and computer record review was conducted to determine the frequency of ANA testing in CTCL patients and the rate of seropositivity. Patients with a positive ANA were further examined to define possible explanations of the positive test. Results: Of 381 patients with CTCL, 66 (17%) had ANA tests; 8 of these (12.1%) were found to have an ANA titer greater than or equal to 1:40. Of patients with a positive ANA test, one was found to have chronic cutaneous lupus erythematosus histologically and clinically mimicking CTCL. Others were found to have a comorbid connective tissue disorder, some had apparent drug-induced antinuclear antibodies, and some had no identifiable reason for a positive ANA test. Conclusion: ANA seropositivity does not appear to be increased in CTCL patients, and the ANA test remains a useful screening tool for differentiating between CTCL and connective tissue disorders. (J Am Acad Dermatol 1998;39:434-8.)