Chilblain Lupus Erythematosus Research Articles

The Spectrum of Cutaneous Manifestations in Lupus Erythematosus: A Comprehensive Review.

Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited solely to the skin. Cutaneous LE (CLE) manifests with a wide range of skin lesions divided into acute, subacute and chronic subtypes. Despite classic forms of CLE, such as malar rash or discoid LE, little-known variants may occur, for instance hypertrophic LE, chilblain LE and lupus panniculitis. There are also numerous non-specific manifestations including vascular abnormalities, alopecia, pigmentation and nail abnormalities or rheumatoid nodules. Particular cutaneous manifestations correlate with disease activity and thus have great diagnostic value. However, diversity of the clinical picture and resemblance to certain entities delay making an accurate diagnosis The aim of this review is to discuss the variety of cutaneous manifestations and indicate the clinical features of particular CLE types which facilitate differential diagnosis with other dermatoses. Although in diagnostically difficult cases histopathological examination plays a key role in the differential diagnosis of LE, quick and accurate diagnosis ensures adequate therapy implementation and high quality of life for patients. Cooperation between physicians of various specialties is therefore crucial in the management of patients with uncommon and photosensitive skin lesions.

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

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.

Panoramic view of clinical features of lupus erythematosus: a cross-sectional multicentre study from China

ObjectiveLupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the...

Characterization of B cells in lupus erythematosus skin biopsies in the context of different immune cell infiltration patterns.

Cutaneous lesions in lupus erythematosus (LE) subtypes are heterogenous. In line with the heterogeneity of the clinical presentation, the underlying lesional inflammation in LE skin samples is defined by different immune cell infiltrates. Pathophysiologically, lesional inflammation is driven by autoreactive cytotoxic T cells, targeting keratinocytes; plasmacytoid dendritic cells (pDCs), producing large amounts of interferon (IFN); and B cells, whose function in cutaneous LE is still unclear. This study aims to (a) classify inflammatory patterns with regard to the dominating cell type or cytokine expression and (b) investigating the specific role of B cells in LE skin lesions. Therefore, the immunohistological expression of inflammatory surrogates (CD20, CD123, MXA) in skin samples of n = 119 LE (subtypes: subacute cutaneous LE, chronic discoid LE, chilblain LE, LE tumidus, other LE) and n = 17 patients with inflammatory skin diseases (atopic dermatitis, psoriasis) were assessed. Samples were classified with regard to inflammatory groups. In addition multiplex-immunohistochemical analyses of n = 17 LE skin samples focusing on lesional B cells were conducted. In this study, we show that cutaneous lesions present with eight different inflammatory groups dominated by B cells, pDCs, a strong IFN expression, or overlapping patterns. Altogether, LE subtypes show heterogenous infiltration regardless of LE subtype, certain subtypes display a preference for infiltration groups. Furthermore, lesional B cells either form diffuse infiltrates or pseudofollicular structures, wherein they show antigen-presenting and T cell-activating properties. Altogether, in the light of emerging targeted therapeutic options, we suggest histological assessment in regard to B-cell or pDC preponderance to allow tailored treatment decisions.

Chronic Cutaneous Lupus Erythematosus in a White Population: Dermoscopic Characteristics by Clinical Subtype, Lesion Location and Disease Duration.

IntroductionChronic cutaneous lupus erythematosus (CCLE) comprises three major clinical variants: discoid lupus erythematosus (DLE), chilblain lupus erythematosus (CHLE), and lupus erythematosus profundus, also referred to as lupus erythematosus panniculitis (LEP). The aim of the current study was to systematically describe the dermoscopic features of CCLE in Polish patients with Fitzpatrick skin phototypes I–III.MethodsThe videodermoscopic images from patients with various clinical variants of CCLE (DLE, CHLE and LEP) were reviewed. Predefined parameters for dermoscopic evaluation in general dermatology were used to describe the findings in lesions located beyond the scalp. In the analysis of trichoscopic findings in lesions located on the scalp, dermoscopic features of follicular openings, hair shafts, the perifollicular surface, the interfollicular surface and vessel morphology were considered. Based on personal experience, several additional dermoscopic and trichoscopic characteristics were included in the analysis.ResultsA total of 85 lesions from 26 patients (16 women and 10 men; mean age 40.8 ± 11.2 years) were assessed. DLE on glabrous skin showed polymorphous vessels (89.1%), pink-red background (70.9%), follicular plugs (67.3%) and white scaling (58.2%), while scalp DLE was characterized by polymorphous vessels (83.3%), yellow dots (66.7%), follicular plugs (55.6%) and a reduced number of follicles (55.6%). Labial DLE (n = 2) showed linear branched and linear curved vessels, white structureless areas, red structureless (hemorrhagic) areas and red dots/globules. White scaling (61.1% vs. 34.1%; p = 0.042), gray-brown dots/globules (44.4% vs. 12.2%; p = 0.015) and peripheral pigmentation (100.0% vs. 46.2%; p = 0.036) were significantly more common in long-lasting (> 1 year) DLE lesions. CHLE (n = 5) presented with polymorphous vessels, white scales, pink-red background, red structureless areas and red dots/globules. LEP showed polymorphous vessels, white-yellow scales, follicular plugs, white structureless areas and red hemorrhagic areas.ConclusionsDermoscopy might be useful in the preliminary diagnosis of DLE, and its role in the diagnosis of CHLE and LEP needs further elucidation.

Severe Ulcerative Perniosis Treated With Abobotulium Toxin.

Perniosis (also known as pernio or chilblains), is a condition characterized by the development of pruritic, painful erythrocyanotic skin lesions induced by exposure to cold temperatures.2 When perniosis occurs in conjunction with clinical or laboratory features of systemic lupus erythematosus, the condition is further classified as chilblain lupus erythematosus (CHLE). CHLE is a rare condition with limited treatment options especially in refractory cases.3 Here we discuss the utility of therapeutic botulinum toxin injections in the treatment of severe, ulcerative CHLE. J Drugs Dermatol. 2021;20(12):1350-1351. doi:10.36849/JDD.6176.

British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective. provide guideline recommendations and if appropriate research recommendations.

187 Photosensitivity and cGAS-dependent type I IFN activation in lupus patients with TREX1 deficiency

The exonuclease three prime repair exonuclease 1 (TREX1) safeguards the cell against DNA accumulation in the cytosol and thereby prevents innate immune activation and autoimmunity. TREX1 mutations lead to chronic DNA damage and a cell-intrinsic type I interferon (IFN) response. Associated disease phenotypes include Aicardi-Goutières syndrome, familial chilblain lupus and systemic lupus erythematosus. Given the role of ultraviolet (UV) light in lupus pathogenesis, we assessed sensitivity to UV light in lupus patients with TREX1 mutation by phototesting which revealed an enhanced photosensitivity compared to healthy controls.

Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

Early onset chilblain lupus erythematosus with atypical presentation in an Indian girl

&lt;p&gt;Chilblain lupus erythematosus (Chilblain LE) is a rare form of lupus erythematosus with only 70 cases reported worldwide with most of the patients in middle age and very few cases in adolescent age group.&lt;strong&gt; &lt;/strong&gt;Herein, we are reporting a 16 years old girl presented with an early age of onset at 10 years with atypical presentation who fulfilled Mayo clinic diagnostic criteria for Chilblain LE.&lt;/p&gt;

New insights in COVID-19–associated chilblains: A comparative study with chilblain lupus erythematosus

New insights in COVID-19–associated chilblains: A comparative study with chilblain lupus erythematosus

A Case Report of Chilblain Lupus Erythematosus in a Young Male with Literature Review

Chilblain lupus erythematosus (CHLE), also known as Hutchinson lupus, is rare form of chronic cutaneous lupus erythematosus. The diagnosis is made in patients with clinical findings of chilblains in conjunction with the clinical or laboratory features of cutaneous or systemic lupus erythematosus (SLE). Similar to idiopathic chilblains (or perniosis), CHLE presents with tender, reddish-blue papules, nodules, or plaques on the toes, fingers, nose, or ears which are precipitated by cold exposure. There is a variation in lab findings that become positive in these patients ranging from a positive Antinuclear antibody (ANA), Rheumatoid factor (RF), SSA/Ro autoantibodies. Anemia, hypocomplementemia, other autoantibodies and elevated ESR have also been described in numerous patients Sporadic disease commonly affects middle-aged women whilst familial disease manifests in childhood. We report herein, a case of CHLE in a young male with no family history of lupus and a negative ANA on initial evaluation. There is little in the published literature on CHLE. This case report serves to revisit the diagnosis of CHLE and review the existing literature. Clinicians should understand the importance of early diagnosis and prompt treatment initiation in order to reduce associated morbidity and possible disfigurement.

TREX1 variants in Sjogren's syndrome related lymphomagenesis

Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. We aimed to explore whether TREX1 common variants could influence the risk of primary Sjogren’s syndrome (SS) and SS-related lymphoma. Three single nucleotide polymorphisms (SNPs) of the TREX1 gene (rs11797, rs3135941 and rs3135945) were evaluated in 229 SS, 89 SS-lymphoma (70 SS-MALT and 19 SS non-MALT) and 240 healthy controls by PCR-based assays. In available 52 peripheral blood and 26 minor salivary gland tissues from our SS cohort, mRNA expression of type I interferon (IFN) related genes and TREX1 was determined by real-time PCR. Significantly decreased prevalence of rs11797 A minor allele was detected in SS patients complicated by non-MALT lymphoma compared to controls (ΟR [95% CI]: 0.4 [0.2–0.9], p-value: 0.02). SS patients carrying the rs11797 AA genotype had increased type I IFN related gene mRNA expression in minor salivary gland tissues. These data support genetically related dampened type I IFN production as an additional mechanism for SS-related lymphomagenesis.

An unusual variant of perniosis: A case series of “cold-associated perniosis of the thighs” without equestrian activity

The role of cold exposure in the etiology of perniosis was clearly identified among susceptible individuals. However, few authors have newly reported purple-red “equestrian-type lesions” localized on thighs in patients without equestrian activity and suggested to use the reputation; “cold-induced perniosis of thighs.” We conducted a retrospective chart review of patients who have presented to our department with cold perniosis-like lesions exclusively localized on the thighs. Clinical and histopathological features of five female patients aged 16–31 years without equestrian activity indicated the diagnosis of cold-induced perniosis of the thighs. Cold-associated perniosis may be appropriate diagnosis for the patients presenting with symmetrically distributed painful, itching, or burning violaceous plaques and patches on the thighs for several weeks. The condition primarily affects overweight women and does not require outdoor activity. Microscopic presentation of the disorder is variable and very similar to acral idiopathic perniosis and chilblain lupus erythematosus.

TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia.

Cryofibrinogenemia is a rare cryopathy presenting as acrocyanosis following exposure to cold. Familial presentation has been described but the underlying molecular cause remained undetermined. Forty (40) members from a large family with an initial diagnosis of familial cryofibrinogenemia were interviewed and examined to determine affected status and collect DNA. Exome sequencing was performed on three affected individuals from distinct branches of the pedigree. Seventeen (17) family members reported a history of acrocyanosis with cold exposure. None reported symptoms were suggestive of lupus. Exome sequencing of three subjects identified the heterozygous mutation D18N in the TREX1 gene which was then confirmed by Sanger sequencing in all affected as well as 2 unaffected family members. The mutation is already being associated with familial chilblain lupus erythematosus (CHLE), and a systematic review of literature was undertaken to compare reports of familial CHLE and cryofibrinogenemia. Both entities were found to share highly similar clinical presentations suggesting they are part of a same syndrome in which cryofibrinogenemia and lupus manifestations have variable penetrance. Familial cryofibrinogenemia without lupus should be added to the spectrum of TREX1-related disease.

286 Chilblain lupus erythematosus - clinical and histologic characterization of an institutional cohort

286 Chilblain lupus erythematosus - clinical and histologic characterization of an institutional cohort

Chilblain lupus erythematosus treated successfully with mycophenolate mofetil

Chilblain lupus erythematosus treated successfully with mycophenolate mofetil

Cold-Associated Perniosis of the Thighs ("Equestrian-Type" Chilblain): A Reappraisal Based on a Clinicopathologic and Immunohistochemical Study of 6 Cases.

Cold-associated perniosis of the thighs ("equestrian cold panniculitis") is an unusual and still enigmatic entity. The authors retrieved 6 cases for a re-evaluation of their clinicopathologic features and for an immunohistochemical assessment with antibodies anti-CD3, anti-CD20, and anti-CD123. All patients were women, aged 17-45 years. One of them had elevated antinuclear antibody titers. Available anamnestic data confirmed the triggering role of prolonged/intermittent exposure to cold (not necessarily for equestrian activities). The lesions affected the thighs, with a preferential, although not exclusive involvement of the upper lateral surface. The histopathological pattern was perivascular, superficial, and deep, extending toward the superficial fat lobules, with lymphocytic vasculitis and mucin deposition; clumps of CD123 cells were found in 4 of 6 cases. Cold-associated perniosis of the thighs cannot be considered as a panniculitis. The histopathological features considerably overlap with perniosis at other sites of the body and with chilblain lupus erythematosus.