Lupus Tumidus Research Articles

Éruption cutanée atypique au cours d’un syndrome des antiphospholipides

Antiphospholipid syndrome (APS) is characterised by arterial or venous thrombosis combined with the presence of specific antibodies known as antiphospholipids. It is commonly associated with cutaneous signs. Herein we report a case of atypical cutaneous eruption occurring during the course of APS and we discuss the possible mechanism. A 45-year-old woman consulted twice within six months for an erythematosus papular eruption around the neckline. She was being followed-up for antiphospholipid syndrome treated with fluindione (Préviscan®), and her International Normalized Ratio (INR) was consistent with the prescribed anticoagulation target. Blood tests confirmed the presence of anticardiolipin and antiphospholipid antibodies, but no laboratory evidence of lupus was seen. Histopathological examination of a skin biopsy demonstrated the presence within the vascular lumen of a weakly eosinophilic anhistic substance positive for PAS stain. The patient was given acetone salicylic acid (Kardégic®) combined with fluindione, and four years later, she had presented no relapses. Despite a clinically evocative appearance, the diagnosis of lupus tumidus was ruled out in our patient by histopathological features, and associated systemic lupus erythematosus was repeatedly refuted on the basis of clinical and laboratory data. We suggest that the specific histological images of intraluminal deposits within the dermal vessels seen in this patient, although not typical of thrombosis, are associated with APS. The clinical remission seen from the start of antiplatelet treatment could be due to the action of these drugs against the obstruction of small-calibre dermal vessels.

Successful Use of Interleukin 6 Antagonist Tocilizumab in a Patient With Refractory Cutaneous Lupus and Urticarial Vasculitis

Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6). It is a humanized monoclonal immunoglobulin G1 antibody against the α-chain of the IL-6 receptor that prevents the binding of IL-6 to membrane-bound and -soluble IL-6 receptor. It was approved by the US Food and Drug Administration in January 2010 for rheumatoid arthritis refractory to other approved therapies and in April 2011 for systemic juvenile idiopathic arthritis. It has been used as an off-label treatment in many autoimmune diseases, where IL-6 plays a major role in pathogenesis. We report a case of refractory systemic lupus erythematosus in a 22-year-old woman with recurrent high-grade fever, polyarthritis, diffuse rash with urticarial vasculitis, and tumid lupus who did not respond to topical corticosteroids, photoprotection, antimalarials, methotrexate, anakinra, mycophenolate mofetil, etanercept, and intravenous immunoglobulin therapy. Symptoms recurred after corticosteroid tapers below 10 mg. She was noted to have an elevated IL-6 level, and tocilizumab was started. She responded favorably with remission of fever, arthritis, and skin manifestations and was able to taper corticosteroid therapy successfully.

Pulsed dye laser as an excellent choice of treatment for lupus tumidus: a prospective study

Clinical manifestations of cutaneous lupus erythematosus (CLE) vary widely, and different subtypes of this autoimmune disease exist. Tumidus subtype (LT) has been recently separated from the chronic subtypes and is now considered an independent entity due to its particular clinical and histological features. Different treatments are usually prescribed for CLE. Our group has experience of CLE effectively treated with pulsed dye laser (PDL). It was our impression that better responses were achieved in the LT subtype, but no controlled prospective studies with PDL have been specifically performed. A prospective study was performed on 10 patients with histologically confirmed LT treated with PDL. All patients were treated with 595 nm PDL using the 10 mm spot size at 0.5 ms pulse width and a fluence of 8 J/cm(2). Biopsies were taken before and 4 weeks after treatment and were stained with haematoxylin-eosin. Evaluation after PDL treatment showed clinical improvement in all of them without side-effects and reduction of the dermal lymphocytic infiltrate in 9/10 of the patients. Epidermal changes were absent in all patients. Mucin deposition persisted only in one patient. However, 50% of the patients developed new lesions nearby or distant to the treated zones. PDL therapy is an effective and fast treatment option for acute flares of LT; however, it does not prevent recurrences. A histological improvement has been confirmed in this study. Purpura seems to be necessary to achieve a good response.

Lupus erythematodes

The typical clinical forms of cutaneous lupus erythematosus (LE) are the butterfly rash, acute, subacute and chronic cutaneous lupus, intermediate lupus (lupus tumidus), chilblain- and bullous lupus, lupus profundus, and ulcerating lesions on the mucous membrane. Besides the typical lupus forms, nonspecific skin lesions are also observed such as dermal mucinosis, acneiform skin lesions, different variants of livedo, necrotizing vasculitis with ulcers, purpura, urticaria vasculitis, neutrophilic dermatosis, hyperpigmentation, hair and nail changes as well as overlap syndromes with erythema multiforme, scleroderma, Sjögren syndrome, Raynaud phenomenon, lichen planus, bullous pemphigoid und psoriasis. There are lupus imitators which create differential diagnostic challenges, such as infections with atypical mycobacteria or subcutaneous T-cell lymphoma both of which are similar to lupus profundus. All these skin lesions can present as maximal pathological findings seen in lupus or be caused by a variety of pathological laboratory findings such as the anti-phospholipid antibodies or a deficiency of complement factors. In the latter situation severe lupus often with complications can be expected.

Lupus erythematosus tumidus as a separate subtype of cutaneous lupus erythematosus: reply from authors

Conflicts of interest: none declared. Madam, We thank Dr Mutasim for his valuable comments and are grateful for the opportunity to clarify certain aspects of our study investigating lupus erythematosus tumidus (LET) as a separate subtype of cutaneous lupus erythematosus (CLE).1 Dr Mutasim remarks that the study ‘did not add anything new to what is already known about tumid lupus’, that it did not ‘accomplish a resolution to the objectives stated by the authors’, and that the objective of the paper, to evaluate ‘whether LET can be distinguished as a separate entity in the classification system of the disease, … seems to be ill conceived’. He further notes that the ‘results could not have been otherwise as the authors have preselected patients whom they have identified as having LET prior to their entry into the study’. The of concern Dr Mutasim is comprehensible if our objective would have been to define LET as its own entity; however, this has already been shown by several groups.2 In our study, we sought to investigate if this existing entity of LET can be considered a separate subtype in the classification of CLE and be distinguished from other forms of CLE.1 Therefore, it was necessary to include patients with LET that had been diagnosed prior to inclusion in the study and to compare with other disease subtypes, such as subacute CLE (SCLE) and discoid lupus erythematosus (DLE) as the most common form of chronic CLE (CCLE).

Lupus erythematosus tumidus as a separate subtype of cutaneous lupus erythematosus

Conflicts of interest: none declared. Madam, I read with interest the article by Schmitt et al.1 in a recent issue of the BJD. The article continues the previous legacy of the authors who should be highly commended for their efforts in studying cutaneous lupus erythematosus (CLE), especially lupus erythematosus tumidus (LET). My problem with the paper is that it did not add anything new to what is already known about tumid lupus, neither did it accomplish a resolution to the objectives stated by the authors, namely ‘whether LET can be distinguished as a separate entity in the classification system of the disease’. This objective seems to be ill conceived in view of having at least 25 papers in the reference list (from a total of 46) that have the words ‘lupus tumidus’ in their title. It is difficult to accept such an objective in the first place. Another objective of the authors (as written in the summary) is ‘to compare characteristic features of different subtypes of CLE’. If the authors start with the widely accepted premise that there are different subtypes of CLE that are clearly based on characteristic features of each, what does it mean when the authors say they wanted to compare characteristic features of different subtypes of CLE?

Lupus tumidus induced by bortezomib not requiring discontinuation of the drug

Lupus tumidus induced by bortezomib not requiring discontinuation of the drug

Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.

Traitement par photochimiothérapie extracorporelle de quatre cas de lupus érythémateux cutané réfractaires aux traitements conventionnels

Photopheresis is a leucopheresis procedure in which cells are photoactivated by psoralen and then irradiated by ultraviolet A. We report four cases of women with refractory cutaneous lupus erythematosus (LE) who responded to this treatment. We treated one patient with subacute LE having a contraindication to antimalarials and to thalidomide and three patients with chronic LE (lupus panniculitis, lupus tumidus and disseminated discoid LE) refractory to treatment with hydroxychloroquine, chloroquine, thalidomide and dapsone, and also, in some cases, to oral and intravenous corticosteroids, methotrexate, colchicine, acitretine, sulfasalazine, mycophenolate mofetil and intravenous immunoglobulin. Treatment consisted of two 4-hour sessions fortnightly. Only antimalarials were continued during photopheresis. Photopheresis had a positive effect on all four patients. We noticed complete remission in two patients and interruption of progression followed by partial remission in the other two after a mean delay of two to three months of treatment. All treatments other than antimalarials were stopped. Photopheresis appears to be an effective treatment option in patients with cutaneous LE. Due to its high cost, it should nevertheless remain an exceptional therapeutic option restricted to patients with cutaneous LE resistant to standard therapy.

Drug-induced lupus: an update on its dermatologic aspects

Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)-alpha antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF-alpha antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.

Medikamenteninduzierter Lupus erythematodes tumidus unter Adalimumab-Therapie

Patients treated with TNF-alpha inhibitors frequently have serum autoantibodies, but only a few develop clinically apparent lupus erythematosus. The TNF-alpha inhibitor adalimumab is a fully humanized antibody and seems to induce autoantibodies less frequently than other drugs of this group. We report on a patient with rheumatoid arthritis, who developed anti-histone antibodies and lupus tumidus after eight months on adalimumab therapy.

Coexistence of Tumid Lupus Erythematosus With Systemic Lupus Erythematosus and Discoid Lupus Erythematosus

Tumid lupus erythematosus (LE) is a rare variant of chronic cutaneous LE that is characterized clinically by smooth, nonscarring, pink to violaceous papules or plaques without evidence of surface change. Histopathologic features include superficial and deep lymphocytic infiltration in a perivascular and periadnexal distribution, with dermal interstitial mucin deposition and focal or absent dermoepidermal junction involvement. These clinical and histopathologic features can be challenging to differentiate from other cutaneous diseases. This is particularly true because patients with tumid LE usually do not have other manifestations of systemic LE or cutaneous LE. We present 2 cases of tumid LE, one associated with concomitant systemic LE and the other occurring concurrently with discoid LE. Furthermore, we demonstrate the rare occurrence of a patient with tumid LE occurring below the waist at a photo-protected site.

Cicatricial alopecia: discoid lupus erythematosus

Chronic cutaneous lupus erythematosus consists of three major dermatologic diseases: discoid lupus erythematosus (DLE), lupus panniculitis/lupus profundus, and lupus tumidus (Table 1). DLE is estimated to be responsible for 50-85% of patients with chronic cutaneous lupus erythematosus. Scalp involvement is most often the presenting symptom. The clinical features and diagnosis of DLE, its pathophysiology and treatment, are reviewed.

Manifestations dermatologiques du lupus

Various dermatologic manifestations are observed in the different lupus subsets. Lupus lesions are most frequently characterized by a dermoepidermal dermatitis. Other lesions, vascular or nonvascular, are essentially present in association with systemic lupus erythematosus. Acute, subacute and chronic lupus erythematosus are distinguishable according to their clinical aspects, pathological features and their evolution. Acute lesions are either localized to the midface or widespread. Subacute lesions may be annular or psoriasiform. Chronic lupus erythematosus includes localized or widespread discoid lupus, lupus tumidus, chilblain lupus and panniculitis. Therapy of cutaneous lupus is mainly based on antimalarials and avoidance of sun exposure. In refractory cutaneous lupus, no universal guidelines are available. Except for acrosyndromes and urticaria-like lesions, vascular lesions may be due to vasculitis or thrombosis. An accurate diagnosis is necessary, since therapeutic management is quite different in these two conditions. Nonvascular and nonlupus lesions are numerous and some of them require specific treatment, such as dapsone for bullous lupus.

Tumid Lupus Erythematosus: An Unusual Scleredema‐Like Presentation

A 43-year-old white man presented with an 8-month history of redness and swelling on the back of the neck. He also noted a decrease in range of motion of his upper body. There was no improvement with a 4-week course of topical corticosteroids. Review of systems was negative for polydipsia, polyuria, polyphagia, and bone pain. His medical history included depression, gastroesophageal reflux disease, and microdiscectomy. His medications included sertraline and omeprazole. Physical examination revealed a 20-cm erythematous, indurated plaque on the posterior part of the upper back and neck (Figure 1). A lack of skin wrinkling was noted with lateral pressure. Biopsy revealed a periadnexal and mild interface dermatitis with an increase in connective tissue mucin as demonstrated with colloidal iron (Figures 2A and 2B). Serum protein electrophoresis, hemoglobin A1C, and antinuclear antibody titer were within normal limits. A diagnosis of tumid lupus erythematosus mimicking scleredema was made. Hydroxychloroquine therapy was started at a dose of 200 mg and, at 2 months' follow-up, the patient's symptoms and appearance were improved.

Monolateral severe eyelid erythema and edema as unique manifestation of lupus tumidus

Monolateral severe eyelid erythema and edema as unique manifestation of lupus tumidus

Lupus Tumidus Qualifies as Cutaneous LE Subtype

Lupus Tumidus Qualifies as Cutaneous LE Subtype

Tumid lupus erythematosus occurring following highly active antiretroviral therapy for HIV infection: A manifestation of immune restoration

Tumid lupus erythematosus (LE) is a relatively rare and only recently recognized subset of chronic cutaneous lupus. We report a case occurring in a male with HIV infection whereby his rash was only unmasked by immune restoration following highly active antiretroviral therapy (HAART). The phenomenon of latent inflammatory or autoimmune disease appearing following HAART is now recognized as the "immune restoration syndrome" and tumid LE has not been reported in this setting previously. Fortunately this variant of lupus does not result in scarring and is responsive to anti-malarials, allowing continuation of HAART in this patient.

Photosensitivity in lupus erythematosus.

Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide synthase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor alpha also seems to play a role in the development of photosensitivity. The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor alpha polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sine qua non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity.

Erythema annulare centrifugum: results of a clinicopathologic study of 73 patients.

Erythema annulare centrifugum is classified generally into a superficial and a deep type. Whether those types are variants of the same process or unrelated to one another, and whether they represent non-specific patterns or specific clinico-pathologic entities, is controversial. To answer those questions, we analyzed 82 biopsy specimens from 73 patients with a clinical and histopathologic diagnosis of erythema annulare centrifugum, gyrate erythema, or figurate erythema regarding a variety of clinical and histopathologic findings. We found substantial differences between cases with a wholly superficial type and cases with a superficial and deep infiltrate. Clinically, a collarette of scales was seen only in the superficial type. Histopathologically, some findings were much more common in the superficial type (eg, spongiosis, parakeratosis, crusts, edema of the papillary dermis, epidermal hyperplasia) and others in the deep type (eg, sleeve-like arrangement of the infiltrate, melanophages, subtle vacuolar changes at the dermo-epidermal junction, individual necrotic keratinocytes). Whereas cases of the superficial type could be distinguished from differential diagnoses by a variety of clinical and histopathologic findings, most cases of the deep type showed subtle signs of lupus erythematosus. Neither type was associated consistently with any other systemic disease. Because the superficial and the deep type of erythema annulare centrifugum seem to be unrelated to one another, they should not be referred to by the same name. We believe that the term should be reserved for the superficial type because the latter seems to be a specific clinico-pathologic entity. By contrast, most cases of the deep type seem to be annular examples of tumid lupus erythematosus and should be diagnosed that way. If findings militate against the diagnosis of lupus erythematosus, we suggest using a descriptive term that signals non-specificity-namely, deep figurate erythema.