Limited Skin Involvement Research Articles

Expert consensus on systemic therapy for plaque psoriasis with limited skin involvement in JAPAN: Results from a DELPHI study.

Our objective was to establish consensus on (1) which patients with plaque psoriasis and limited skin involvement (body surface area [BSA] <10%) are suitable for systemic treatment, and (2) a definition of 'topical therapy failure'. A steering committee refined 13 statements drawn from literature related to the study objectives. An independent panel of 45 clinical experts from Japan indicated their agreement to each statement using a 10-point Likert scale (Round 1; strong consensus, ≥70% of responses = 7-10 and median value ≥8). The steering committee reviewed Round 1 results and refined the statements for Round 2, as necessary. In Round 2, the panel indicated their agreement to each statement using a 3-point scale (strong consensus, ≥70% of responses and median value of 3) and were shown Round 1 responses before voting. Forty-five clinicians participated in Round 1 and 41 of those (91%) participated in Round 2. Consensus was achieved on the criteria of eligibility for systemic treatment among patients with limited skin involvement as disease involvement at special or difficult to treat areas, psoriasis-induced psychological distress, uncontrolled symptoms (e.g., scaling, bleeding, pruritus, insomnia) affecting their social life, psoriatic arthritis, or failure of topical therapy. Consensus on criteria for topical failure were persistent symptoms (e.g., itchiness, pain) and plaques, poor patient satisfaction with treatment, a need to increase medication quantity or application time after treatment with two topicals for 4 weeks; or if the Psoriasis Area Severity Index score of >3 or Physician Global Assessment Score of ≥2 after 8 weeks treatment. Our Delphi panel proposes criteria to help physicians identify patients with psoriasis and limited skin involvement who would benefit from systemic therapy and suggests a definition for topical therapy 'failure' which could indicate a move to systemic treatment is warranted.

S2k guideline: Diagnosis and therapy of localized scleroderma.

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoSrepresents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoScan be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.

The relationship between peripheral T follicular helper cells and disease severity in systemic sclerosis

We aimed to investigate the association between follicular T helper cells (Tfh) and disease severity in systemic sclerosis (SSc), a chronic connective tissue disease characterized by progressive fibrosis. While Tfh cells have been extensively studied in other autoimmune diseases, their role in SSc remains poorly understood. A cohort of 50 SSc patients, diagnosed based on the ACR/EULAR 2013 classification criteria, was included in the study. Patient data, including demographic information, comorbidities, treatment history and organ involvement, were collected. Disease severity was assessed using the modified Rodnan skin score and Medsger disease severity index. Statistical analyses were performed, considering a p value of < 0.05 as statistically significant. 38% had SSc with limited skin involvement, while 62% had SSc with extensive skin involvement. However, there were no statistically significant differences observed in the levels of CD4+ CXCR5+ , CD4+ ICOS+ , CD4+ CD40L+ and CD4+ PD+ lymphocytes between the two groups. Notably, SSc patients with Raynaud’s phenomenon, digital ulcer and lung involvement exhibited higher levels of CD4+ CXCR5+ lymphocytes compared to those without these manifestations. Furthermore, a significant positive correlation was observed between CD4+ CXCR5+ lymphocyte levels and the severity of lung disease according to the Medsger disease severity index. Based on these findings, we conclude that elevated levels of Tfh cells are associated with lung involvement in SSc and there is a significant correlation between Tfh cell levels and the severity of lung disease. These observations suggest a potential role for Tfh cells in the pathogenesis of lung involvement in SSc and may guide the development of targeted therapies for this aspect of the disease.

Patient and Physician Perceptions of Psoriatic Disease in the United States: Results from the UPLIFT Survey.

The Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey study was conducted globally in 2020 to understand how disease perceptions, including disease severity, treatment goals, and quality of life (QoL), have evolved recently, especially for mild-to-moderate psoriatic disease. Here, key findings from the UPLIFT survey based on respondents located in the US are presented. Leveraging results from the UPLIFT survey could lead to more effective interactions between patients and physicians and greater patient satisfaction. UPLIFT was a multinational web-based survey of dermatologists, rheumatologists, and patients who self-reported a healthcare provider diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) conducted from March 2, 2020, to June 3, 2020. US respondents included 1006 patients (26.4% of global population; PsO only, n = 535; PsA only, n = 72; PsO and PsA, n = 399) and 216 physicians (dermatologists, n = 115; rheumatologists, n = 101). Most patients (66.4%) reported a body surface area (BSA; assessed by number of palms) of ≤ 3; of these, 56.2% rated their disease as moderate or severe. Most patients with PsO felt they were somewhat (40.1%) or very (49.3%) closely aligned with their dermatologists regarding treatment goals. Alternately, most patients with PsA felt that they were not too closely (32.1%) or not at all (59.3%) aligned with their rheumatologists. Most patients reported either a moderate (PsO, 35.5%; PsA, 31.8%) or strong (PsO, 47.7%; PsA, 53.9%) need for better treatments. Across BSA subgroups, most patients (60.8% to 86.1%) had a Dermatology Life Quality Index score ≥ 6, indicating at least a moderately impacted QoL. Despite more treatment options, management of psoriatic disease remains suboptimal, with many patients reporting moderate-to-severe disease and impaired QoL, even with limited skin involvement. Results further suggest an unmet need for alignment between patients and physicians in the US to optimize the management of PsO and PsA.

Efficacy and safety of apremilast in patients with mild-to-moderate psoriasis up to 32 weeks: Results from the extension phase of the randomized, phase 3 ADVANCE trial

To the Editor: Mild-to-moderate psoriasis often involves special areas such as the scalp.1 Patients can experience substantial quality-of-life impairment despite limited overall skin involvement.1 In the phase 3 ADVANCE study (NCT03721172), apremilast demonstrated efficacy and tolerability in adults with mild-to-moderate psoriasis (static Physician's Global Assessment [sPGA] 2-3, psoriasis-involved body surface area [BSA] 2%-15%, and Psoriasis Area and Severity Index 2-15) inadequately controlled with/intolerant to ≥1 topical therapy.

Survival in Patients with Systemic Sclerosis: A Single Center Cohort

Sistemik sklerozis (SSk), oto-antikor pozitifliği, vaskülopati, deride ve iç organlarda progresif fibrozis ile karakterize olan kronik bir hastalıktır. Hastalığın tutulumuna bağlı olan veya hastalıkla ilişkili olmayan sebeplerle SSk’de yaşam beklentisi azalmıştır. SSk’a bağlı ölüm oranları yıllar içerisinde azalma göstermiş olsa da, genel popülasyona oranla hala yüksek seyretmektedir. Çalışmamızda, merkezimizde takip ettiğimiz SSk hastalarının başlıca ölüm sebeplerini ve ilişkili klinik, laboratuvar ve demografik özelliklerini bildirmeyi amaçladık. Kocaeli Üniversitesi Tıp Fakültesi Romatoloji Polikliniği’nde 2007-2022 arasında SSk tanısı ile takip edilen 168 hasta arasından 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) sınıflama kriterlerini dolduran 157 hasta dahil edildi. Hastaların çoğu (%66,4) sınırlı cilt tutulumlu, hastalık süresi 10,3 (±6,3) yıl olan kadınlardan (%88) oluşmaktaydı. 15 yıllık takip sırasında 23’ü (%14,6) hayatını kaybedildi. Ölen hastaların tanı sırasındaki yaşları daha ileri, dijital ülserleri (aktif ve inaktif) ve malignite sıklığı daha fazla saptandı. İki hasta grubu arasında oto-antikor ve major organ tutulumu açısından fark görülmedi. Kohortumuzdaki en sık ölüm sebebi enfeksiyon (n=5, %21,7) olup bu hastaların 3’ü (%13) COVID19 ve 2’si (%8,7) başka enfeksiyöz etkenlere bağlı pnömoni sebebiyle kaybedildi. Enfeksiyondan sonra en sık ikinci ölüm sebebi malignite (n=4, %17,4) olarak saptandı. Cox regresyon analizi sonucunda tanı sırasındaki yaşta yaklaşık 1 yıl artış ölüm riskinde 10 kat artış (hazard oranı (HR)= 10,93; %95 GA=10,51-11,37) ile ilişkili bulundu. Sonuç olarak, çalışmamız ülkemizde dikkatli takip edilen SSk kohortlarından bildirilmiş az sayıdaki sağ kalım verilerine katkı sağlamaktadır. Sonuçlarımız yorumlanırken SSk hastalarının klinik özelliklerinin coğrafi ve etnik farklılıklar gösterebileceği göz önünde bulundurulmalıdır.

Development of Pulmonary Hypertension in Over One-Third of Patients With Th/To Antibody-Positive Scleroderma in Long-Term Follow-Up.

This study was undertaken to describe clinical manifestations in patients with Th/To antibody-positive systemic sclerosis (SSc) during long-term follow-up. We performed a case-control study involving anti-Th/To antibody-positive patients with SSc who were newly referred to the University of Pittsburgh Medical Center and the Pittsburgh Scleroderma Center from 1980 to 2015. For every case, 2 anti-Th/To antibody-negative SSc patients (the first 2 consecutively seen after a case) were used as controls. Long-term disease manifestations and survival were then compared between cases and controls. A total of 204 anti-Th/To antibody-positive SSc patients and 408 controls were identified. The cohort had a mean ± SD age of 52 ± 12.9 years, and 76% of individuals were women. Anti-Th/To antibody-positive patients more often presented without skin thickening (P < 0.0001) and had a higher rate of pulmonary hypertension (PH) (P < 0.0001) and interstitial lung disease (P=0.05) compared to anti-Th/To antibody-negative SSc controls. Anti-Th/To antibody-positive SSc patients also had less frequent muscle and joint involvement than anti-Th/To antibody-negative SSc controls (P < 0.0001). After a median clinical follow-up period of 6.1 years (interquartile range 2.4-12.7), 38% of anti-Th/To-positive patients had developed PH compared to 15% of anti-Th/To antibody-negative SSc controls (P < 0.0001). The rate of PH classified as World Health Organization (WHO) Group 1 pulmonary arterial hypertension [PAH] was 23% in anti-Th/To-positive patients compared to 9% in anti-Th/To antibody-negative SSc controls (P < 0.0001). After adjusting for age and sex, anti-Th/To antibody positivity was associated with a hazard ratio (HR) of 3.3 (95% confidence interval 2.3-4.9) for increased risk of developing PH at 10 years of follow-up from the first scleroderma center visit. This is the largest cohort of patients with anti-Th/To antibody-positive SSc with long-term follow-up data. The very high rate (38%) and associated independent risk of anti-Th/To antibody-positive patients developing PH in follow-up, particularly in WHO Group 1 PAH patients, is striking. Patients presenting with limited skin involvement should be tested for Th/To antibodies, and if present, careful monitoring for PH is warranted.

Dermoscopy of Gottron's papules and other inflammatory dermatoses involving the dorsa of the hands.

Several inflammatory dermatoses, including dermatomyositis (DM), may present as erythematous papules or plaques on the dorsal aspects of the hands over the joints. Limited skin involvement in these entities may pose a diagnostic challenge. (Video)dermoscopy is being utilized more frequently to aid in the differential diagnosis of inflammatory skin conditions. To describe the dermoscopic findings in Gottron's papules and compare them with dermoscopic features of other dermatoses involving the dorsal aspects of the hands. Videodermoscopic images from patients presenting with erythematous papules or plaques on the dorsal surface of the hands were retrospectively analysed for the presence of standardized dermoscopic parameters. Dermoscopic images from patients with DM (n = 12), psoriasis (n = 19), chronic dermatitis (n = 16), mycosis fungoides (n = 7), lichen planus (n = 5) and pityriasis rubra pilaris (n = 3) were included. Gottron's papules were characterized by pleomorphic vessels (dotted vessels accompanied by thick or thin linear vessels with branches or linear curved vessels) in 66.7% of cases, arranged in an unspecified pattern (91.7%), and accompanied by white or pink structureless areas (75.0%). Psoriatic plaques were characterized by dotted vessels arranged in a uniform pattern (94.7%). Vessels arranged in a ring pattern were nearly exclusively observed in psoriasis, while yellow structureless areas and erosions were more frequently present in chronic dermatitis. White lines, corresponding to Wickham striae, were specific for lichen planus. Videodermoscopy might be of value in differentiating Gottron's papules from other dermatoses involving dorsa of the hands.

Evolution of Patient Perceptions of Psoriatic Disease: Results from the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) Survey.

IntroductionSince the 2012 Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, several systemic treatments for psoriasis (PsO) and/or psoriatic arthritis (PsA) have been approved. The population-based UPLIFT survey was conducted to understand how perceptions of treatment-related outcomes have evolved, particularly for patients with mild to moderate PsO and/or PsA and their dermatologists.MethodsThis population- and web-based survey was conducted from 2 March to 3 June 2020, in North America, Europe, and Japan. Adults with self-reported healthcare practitioner (HCP)-diagnosed PsO and/or PsA and dermatologists who spent > 50% of time treating patients and treated ≥ 20 patients with PsO, including plaque PsO, per month were included. Patient participants were recruited at random from online panels; dermatologists were recruited randomly from representative physician panels.ResultsOf 264,054 patient responses, 3806 who self-reported an HCP diagnosis of PsO and/or PsA were included in the final sample; 67% had PsO alone, 28% had PsO and PsA, and 5% had PsA alone. The estimated population prevalence of psoriatic disease was 7% (PsO only: 4%; PsO and PsA: 2%; PsA only: 1%). Most patients (78%) reported PsO-involved body surface area (BSA) ≤ 3 palms, and ~ 90% or more reported itching, redness, flaking, and scales. Many PsO patients without diagnosed PsA reported musculoskeletal symptoms suggestive of PsA (63%). Across BSA categories, approximately one in four patients was not currently receiving treatment and > 50% had Dermatology Life Quality Index score > 5. Patients and dermatologists had different perceptions of PsO severity, office visit discussions, treatment goals, and treatment satisfaction. The survey was conducted during the coronavirus disease 2019 (COVID-19) pandemic, which could have affected assessments of patient-reported outcomes and ability to have in-person HCP visits.ConclusionsPatients with PsO and PsA in UPLIFT reported high disease burden, including patients with limited skin involvement. An opportunity exists to align patient and dermatologist perceptions to optimize management of PsO and PsA.Infographic Digital featureThis article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article go to 10.6084/m9.figshare.17104586.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00635-4.

Bio-P-04 - Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma

<h3>Background:</h3> In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20–30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood. <h3>Methods:</h3> In patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, in order to characterize markers of lesion progression. <h3>Results:</h3> Despite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of a combination of tissue residency markers, heat shock proteins, tumor suppressor genes and chemokine receptors in the malignant clone. By contrast, collateral benign infiltrating immune cells within the lesions did not show consistent changes at the mRNA level. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a mechanism across MF subtypes. Markers of disease progression were reverted upon successful topical treatment with chlormethine. <h3>Conclusions:</h3> Our data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF.

Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma

BackgroundIn early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20–30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood.MethodsIn patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, and compared results with early-stage MF as well as nonlesional MF and healthy control skin.ResultsDespite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of the tissue residency markers CXCR4 and CD69, the heat shock protein HSPA1A, the tumor suppressors and immunoregulatory mediators ZFP36 and TXNIP, and the interleukin 7 receptor (IL7R) within the malignant clone, but not in benign T cells. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a common mechanism across MF subtypes. Conversely, malignant cells in clinically unaffected skin from MF patients showed upregulation of these markers.ConclusionsOur data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF.

26698 Characteristics and disease burden in patients with mild to moderate vs severe plaque psoriasis in real-world settings: Results from the Corrona Psoriasis Registry

Background: Mild-to-moderate psoriasis may present with high disease burden despite limited skin involvement, particularly when psoriasis involves special areas (eg, scalp, nails, palms/soles). We compared characteristics of adults with mild-to-moderate vs severe psoriasis who initiated systemic treatment at enrollment in the real-world Corrona Psoriasis Registry (4/2015-6/2020).

Esclerosis sistémica

Systemic sclerosis, also known as scleroderma, is a systemic autoimmune disease characterised by fibrosing involvement of the skin and internal organs. It is a disease of unknown cause, and its aetiopathogenesis involves genetic and environmental factors and three fundamental processes: vascular involvement, immune system intervention and fibrosis. It predominates in females and peaks in middle age. Skin involvement is divided into two types according to extent: limited skin involvement and diffuse skin involvement. It is a very heterogeneous disease, with a wide spectrum of manifestations, which can present with mild and stable forms over time or rapidly progressive severe forms. Raynaud's phenomenon, digestive tract involvement, especially the oesophagus, pulmonary hypertension, interstitial pulmonary, musculoskeletal, and cardiac involvement are characteristic of the disease. Diagnosis of the disease is medical, based on symptoms, examination, and complementary tests. Some involvement may be asymptomatic on onset, and therefore early detection and treatment is important since many of its manifestations entail significant morbimortality.

Primary cutaneous T-cell lymphomas in childhood and adolescence.

Primary cutaneous lymphomas are extranodal non-Hodgkin lymphomas of T- or B- cell origin, that predominantly affect older patients but have been reported in all age groups and as early as in the first years of life. Diagnosis of cutaneous lymphomas is challenging and requires high clinical suspicion and close collaboration between dermatologists, pediatric oncologists and pathologists. Skin involvement of non-Hodgkin lymphomas in children or adolescents can either be primary cutaneous or secondary due to an underlying nodal lymphoma. The most common primary cutaneous lymphomas encountered in children are of T-cell origin, with mycosis fungoides being the most prevalent cutaneous T-cell lymphoma, followed by CD30+ lymphoproliferative disorders. While cutaneous lymphomas share clinicopathologic characteristics between juvenile and adult forms, there are important differences in terms of clinical presentation, diagnosis and treatment. The hypopigmented variant of mycosis fungoides seems to be overrepresented in the pediatric age group. Prognosis and treatment of mycosis fungoides are stage dependent. The majority of children present with early-stage disease and respond well to topical corticosteroids and phototherapy.

Characterization of Hidradenitis Suppurativa Phenotypes: A Multidimensional Latent Class Analysis of the National Italian Registry IRHIS

In spite of the large heterogeneity, limited data exist on hidradenitis suppurativa (HS) phenotypes. To identify the HS phenotypes that best explain the disease heterogeneity, a cross-sectional study using latent class (LC) analysis was conducted on a cohort of patients examined at 17 dermatological centers participating in the Italian Registry of Hidradenitis Suppurativa and being enrolled between January 2015 and January 2020. Overall, 965 patients aged 32.0 ± 12.4 years (mean ± SD) were evaluated. A three-class model in LC analysis best fitted the data. Patients in LC1 (20.1%) were females, mostly obese, with a high probability of axillary‒groin (0.85) and mammary (0.59) lesions and the highest HS severity. Patients in LC2 (29.6%) were nonobese males, with moderate disease severity; with a high probability of gluteal (0.50) and genital (0.17) lesions, besides axillary‒groin involvement; and with acne and pilonidal cysts. Patients in LC3 (50%) were nonobese females with a milder disease mostly limited to axillary (0.52) and groin (0.66) areas. The stratification of patients with HS into a severe axillary‒mammary‒groin phenotype with predominantly anterior body involvement in females, an axillary‒gluteal‒groin phenotype of intermediate severity mainly affecting males in the posterior body areas, and an axillary‒groin phenotype with mildest clinical symptoms and limited skin involvement may help in optimizing HS management.

Retrospective analysis of a cohort of 16 patients with drug reaction with eosinophilia and systemic symptoms

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug-induced reaction characterized by a triad of fever, skin rash, and symptomatic or asymptomatic internal organ involvement. Aims: The aim of this study is to determine the study of varied clinical manifestations and their therapeutic outcome in patients with DRESS. Materials and Methods: A hospital-based retrospective case series was conducted in the department of dermatology. The medical records of patients with DRESS syndrome, drug reaction with eosinophilia, and drug hypersensitivity syndrome within 3 years were reviewed and were entered into a specially prepared pro forma. Results: A total of 16 patients fulfilled the criteria and were studied with equal involvement in males and females. The latency period of 4–6 weeks was the most common duration for drug exposure. Anticonvulsants were associated with more than 50% of the cases. Other than skin, hematological and hepatic involvement was noted. The topical steroids with moisturizers reduced scaling and erythema in 62.5% of the patients. Conclusion: The manifestations in DRESS can be diverse ranging from cutaneous lesions such as maculopapular rash to systemic involvement. Anticonvulsants are the most commonly implicated drug. Topical steroids are effective in patients with limited skin involvement.

Revisiting Imiquimod for Treatment of Folliculotropic Mycosis Fungoides: A Case Report and Review of the Literature.

Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) characterized by infiltration of the hair follicle epithelium by neoplastic T cells. FMF demonstrates poor response rates to standard skin-directed therapies such as phototherapy and topical corticosteroids. Imiquimod, an immunomodulatory agent that stimulates the antitumor immune response, has been used successfully in treatment of early-stage MF. We report a 21-year-old patient with unilesional FMF who achieved clinical remission with imiquimod application. This case highlights a potential for use of imiquimod as a treatment option for patients with FMF and limited skin involvement.

Positive Antinucleolar Antibodies on Direct Immunofluorescence of Lesional Skin of a Patient With Limited Systemic Sclerosis

To the Editor: Limited systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Circulant anticentromere antibody is usually positive.1 Antinucleolar antibodies are positive less frequently (15%–40%),2 having prognostic significance on the overall course of the patients. We present a case of limited SSc with negative serologic test for extractable nuclear antigens in which direct immunofluorescence revealed positive antinuclear antibodies (ANA) with nucleolar pattern. A 54-year-old man was referred to the dermatology department because of a 5-year history of multiple asymptomatic telangiectasias on the face and neckline. Clinical examination revealed the presence of sclerodactyly and multiple scars of ulcers in the fingertips that appeared when the patient worked in a frigorific chamber. Capillaroscopy showed predominance of areas of angiogenesis and some small avascular areas. The patient complained about mild interphalangeal arthralgias without inflammatory changes. Unspecific gastrointestinal symptoms and dyspnea were also present. High-resolution chest computed tomography showed mild pulmonary fibrosis predominantly in peripheral areas and bases of the lungs. Echocardiography confirmed the clinical suspicion of pulmonary hypertension, and bosentan therapy was initiated. Circulant ANA resulted positive at 1:1280 dilution. The determinations of extractable nuclear antigens, antibodies against parietal cells, against smooth muscle, and against double-stranded DNA were all negative. A skin biopsy of the neckline area with telangiectasia revealed lymphocytic perifolliculitis, with no other alterations. Direct immunofluorescence study (DIF) performed on lesional skin showed the presence of IgG ANA with a nucleolar pattern (Fig. 1).FIGURE 1.: Direct immunofluorescence on a skin biopsy from an area with telangiectasia in the patient's neckline. IgG resulted positive with a nucleolar pattern (×100).Circulating autoantibodies are found in as many as 95% of patients with SSc and carry greater weight in the newly proposed ACR/EULAR classification system. Centromere (CEN) proteins (P), topoisomerase I, and RNA polymerase III autoantibodies closely reflect patterns of organ involvement and disease progression.3 Circulating anti-Th/To type antinucleolar antibodies are detectable mainly by immunoprecipitation, which is not performed routinely in most clinical laboratories. Its positivity is related to limited skin involvement and frequent fibrosis of internal organs (interstitial lung disease, pericarditis, and renal involvement). Frequency of negative circulating antibodies with positive DIF findings is largely unknown because the last is not routinely performed. In the study by Kulthanan et al,4 a subgroup of patients with SSc presented positive DIF findings in 77% of the cases with the dermoepidermal junction and epidermal nuclei as the most common site, and of these patients, 45% presented negative serum ANA. Shibeshi et al5 reported a DIF positivity rate of 25,7% in 63 patients with SSc, with only one case with no circulating autoantibodies at all, and another with positive serum ANA but no characteristic antibodies of SSc. Antinucleolar pattern has been rarely reported in DIF of patients with SSc. Only 6 cases were found in the literature, all of them with high ANA titles. As these cases date from the 1980s, only circulating anti-ribonucleoprotein was performed, resulting positive in one of the patients.6,7 Our patient had ANA in peripheral blood, but more specific antibodies were not detected (antinucleolar, Scl70, or anticentromere). However, a skin biopsy with DIF was allowed to demonstrate the fixation of antibodies with a nucleolar pattern. Nucleolar pattern ANA in DIF of a skin biopsy is an unusual finding. We believe this technique can help to confirm clinical diagnosis and assess prognosis on individual patients.

Free light chains of immunoglobulins in patients with systemic sclerosis: correlations with lung involvement and inflammatory milieu

AimHumoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is...

Evaluation of Surgical Outcomes of Oncoplasty Breast Surgery in Locally Advanced Breast Cancer and Comparison with Conventional Breast Conservation Surgery.

The purpose of this study was to compare early oncologic outcomes of oncoplastic breast surgery and conventional breast conservation surgery in patients of locally advanced breast cancer. A single-center, prospective, non-randomized study enrolled select cases of locally advanced breast cancer (TNM T3/T4, N0/1/2) who after neoadjuvant chemotherapy, were considered for breast conservation surgery with oncoplasty techniques. The specimen volume resected, the mean margins and mean closest margin obtained were noted. The re-surgery rates, complication rates, and incidence of locoregional recurrence were also noted. Variables were compared with a retrospective cohort of similar patients who had undergone conventional breast conservation surgery. Fifty-seven patients underwent OBS (group 1) and were compared with 43 cases that had undergone conventional BCS (group 2). Majority of the patients in group 1 (73%) had cT3 with N0 or N+ and a minority (17%) were with limited skin involvement (cT4 and N0/N+). Relatively larger sized, post-NACT tumors could undergo OBS(4.4 vs 2.3cm). Relatively greater proportion of tumors in central and lower quadrants were addressed by oncoplasty than traditional BCS (17/57, 29% vs 4/43, 9%, p=0.04). The mean specimen volume excised in group 1 was more than that in group 2. (187.54 vs 125.19; p=0.01). The mean of the margins were obtained more in group 1 (1.04 vs 0.69cm); p<0.01) as also the mean closest margin (0.86 vs 0.49cm; p<0.01). The incidence of close or involved margins was lesser in the OBS group (8vs 24%). Overall incidence of complications was similar in both groups (8/57, 14% vs 4/43, 9%; p=0.34 NS). The median follow-up period of group 1 is 18months (range 06-30months) while group 2 is 34months (14-44months. There was no recurrence in group 1, but there were 5 cases (11%) in group 2. Oncoplasty breast surgery offers more opportunity for breast conservation and oncologic safety than conventional breast conserving surgery.