Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Development and validation of a patient-reported outcome in systemic sclerosis: the Hand scleroDerma lived Experience (HAnDE) scale.

BACKGROUND: Hand involvement in systemic sclerosis (SSc) is at the core of the disease, with a substantial impact on both functional aspects and quality of life. There is no patient-reported outcome (PRO) scale globally assessing hand involvement in SSc. OBJECTIVES: To develop and validate a PRO scale, the Hand scleroDerma lived Experience (HAnDE) scale, to assess the lived experience of hand involvement in patients with SSc. METHODS: This was an exploratory sequential mixed-methods study with two phases: (i) PRO development through an inductive process to analyse the structure of lived experience, involving 21 patients with SSc; and (ii) PRO validation by assessing the psychometric properties of the scale among 105 patients with SSc. RESULTS: Phase 1 enabled us to generate the 18-item provisional scale. From Phase 2, the mean (SD) total score of the scale was 29·16 (16·15). The item reduction process retained 16 items with five levels of answers (range 0-64). Internal consistency of the 16-item version was excellent (Cronbach's alpha = 0·946). Construct validity was very good, principal component analysis pointing towards a unidimensional instrument, with one factor explaining 56% of the variance, and concurrent validity being confirmed: Cochin Hand Function Scale r = 0·66; Health Assessment Questionnaire - Disability index r = 0·58; Hospital Anxiety and Depression Scale, anxiety r = 0·51, depression r = 0·4; Mouth Handicap in Systemic Sclerosis scale r = 0·61; 36-Item Short Form Health Survey, physical component r = -0·48, mental component r = -0·46; and Kapandji score r = -0·46. The correlations were statistically significant (P < 0·05). CONCLUSIONS: We propose, for future trials and clinical practice in SSc, a new PRO, the HAnDE scale, that assesses all the dimensions - functional, aesthetic, relational, existential and emotional - of the lived experience of hand involvement in SSc.

Development of a new patient-reported outcome measure to assess activities and participation in people with systemic sclerosis: the Cochin 17-item Scleroderma Functional scale.

BACKGROUND: Patient-reported outcome measures (PROMs) aimed at assessing people with systemic sclerosis (SSc) have rarely involved the target population in the item- and domain-generation stage of the instrument construction. OBJECTIVES: To develop a new PROM assessing activities and participation in people with SSc. METHODS: A provisional International Classification of Functioning, Disability and Health (ICF)-based 65-item questionnaire previously developed from interviews of people with SSc was sent by email to all patients followed in the internal medicine department of Cochin hospital (n = 184) and enrolled in the Scleroderma Patient-centered Intervention Network Cohort. Items were reduced according to their metric properties. Dimensional structure of the questionnaire was assessed by principal component analysis, convergent and divergent validities by Spearman's rank correlation coefficient, internal consistency by Cronbach's α, and reliability by a test-retest method using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Overall, 113 of 184 patients (61·4%) completed the provisional questionnaire. The item-reduction process resulted in a 17-item questionnaire, the Cochin 17-item Scleroderma Functional scale (CSF-17). Principal component analysis extracted two dimensions: 10 items related to mobility (CSF-17 section A) and seven items related to general tasks (CSF-17 section B). We observed convergent validity of the CSF-17 total score with global activity limitation, pain, depression and aesthetic burden, and divergent validity with anxiety. Cronbach's α was 0·94 for section A and 0·95 for section B. ICC (n = 25 patients) was 0·92 for the CSF-17 total score. Bland-Altman analysis did not reveal a systematic trend for the test-retest. CONCLUSIONS: The CSF-17 is a new PROM assessing activities and participation specifically in people with SSc. Its content and construct validities are very high. What is already known about this topic? In the earliest stages of construction patient-reported outcomes (PROMs) for people with systemic sclerosis (SSc) rarely involve the target population. Instruments able to capture the specific needs of people with SSc in terms of activities and participation are lacking. What does this study add? The Cochin 17-item Scleroderma Functional Scale (CSF-17) is a new PROM assessing global activities and participation specifically in people with SSc. Patients' perspectives were prioritized at all stages of construction. What are the clinical implications of this work? The CSF-17 could be used in clinical practice and research to assess the efficacy of complex multidisciplinary interventions targeting activity limitations and participation restriction in people with SSc. Linked Comment: Clark and Denton. Br J Dermatol 2020; 183:610.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance.

BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.

[Pansclerotic morphea with a rapidly fatal outcome in an 11-year-old girl]. / Morphée pansclérotique d'évolution rapidement létale chez une jeune fille de 11ans.

BACKGROUND: Pansclerotic morphea is a poorly described but extremely debilitating variant of localized scleroderma. We report a case with a rapidly fatal outcome in an 11-year-old girl. PATIENTS AND METHODS: An 11-year-old girl with a 2-year history of morphea presented at our institution in April 2012. The sclerosis had started on her trunk and progressed rapidly to involve her entire skin. Initial treatment with corticosteroids was ineffective and she presented extremely painful ulcerations of the lower limbs. The outcome was rapidly fatal, in early 2014, due to cachexia and sepsis after two amputations and several failed treatments including methotrexate. DISCUSSION: Pansclerotic morphea is characterized by rapidly progressing sclerosis involving the entire skin, trophic cutaneous ulcers, painful contraction and limited joint mobility. The prognosis is poor since the disease has an incapacitating and potentially fatal outcome. No reliably effective treatment has yet been established. CONCLUSION: Our case highlights the clinical characteristics of this uncommon form of localized scleroderma, the extremely severe prognosis, and the therapeutic challenge involved.

Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

OBJECTIVES: Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. METHODS: Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. RESULTS: We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. CONCLUSIONS: Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up.

The economic burden and health-related quality of life associated with systemic sclerosis in France.

OBJECTIVES: To provide data on the economic burden and health-related quality of life (HRQoL) associated with systemic sclerosis (SSc) in France and to raise awareness of the repercussions of this disease for patients and caregivers and on the health and social care system. METHOD: A cross-sectional study was carried out on 147 patients recruited through the Association des Sclérodermiques de France (ASF), the French association for SSc patients. Data on the patients' use of resources were obtained retrospectively from an online questionnaire and costs were estimated by a bottom-up approach. The HRQoL patients and caregivers was assessed with the five-level EURQol-5 Dimension (EQ-5D-5L) health questionnaire. RESULTS: The average annual cost of SSc was estimated at EUR 22,459 per patient. Direct healthcare costs amounted to EUR 8452, direct non-healthcare formal costs to EUR 1606, direct non-healthcare informal costs to EUR 1875, and indirect costs resulting from patients' absence from the labour market to EUR 10,526. The main contributors to SSc costs were hospitalizations and early retirement. Mean EQ-5D utility scores were 0.49 for patients and 0.66 for caregivers. CONCLUSIONS: Although SSc is a rare disease, its economic burden from a societal perspective is substantial and the consequences for HRQoL are significant for both patients and caregivers in France, underscoring the need to develop tailored policies targeted at improving patients' care and reducing the long-term impact of SSc.

Tobacco differentially affects the clinical-biological phenotypes of ANCA-associated vasculitides.

OBJECTIVES: To describe the clinical-biological phenotype of ANCA-associated vasculitides (AAV) according to tobacco consumption. METHODS: We conducted a descriptive study to describe that phenotype at diagnosis according to tobacco use. AAV patients entered in the French Vasculitis Study Group database with data on smoking habits were analysed. The clinical-biological phenotypes at diagnosis were compared according to current tobacco use (current smokers) or not (including previous and never smokers). RESULTS: AAV diagnoses were: granulomatosis with polyangiitis (GPA) for 583 (50%), eosinophilic granulomatosis with polyangiitis (EGPA) for 326 (28%) and microscopic polyangiitis (MPA) for 256 (22%). Among them, 973 patients (84%) never smoked, 116 (10%) were previous smokers and only 76 (6%) were current smokers. Current smokers were younger age (p=0.01), male gender (p=0.004), less frequently EGPA (p=0.017) and MPA (p=0.036), and had less frequent kidney involvement (p=0.10). Among GPA patients, current smokers, compared to non-current smokers, were younger age (p=0.02), male gender (p=0.08), more frequent skin involvement (p=0.03) and less frequent ENT involvement (p=0.06). Among EGPA patients, current smokers, compared to non-current smokers, were also younger (p=0.028) and had less frequent constitutional symptoms (p=0.02), arthralgias (p=0.04), renal involvement (p=0.025) and MPO-ANCA (p=0.02). Finally, analysis of MPA patients was impossible because only 6 (2%) were current smokers. CONCLUSIONS: These results suggest that tobacco use could differentially affect GPA and EGPA clinical-biological phenotypes, and support the role of environmental exposures in AAV development and its phenotype.

Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts.

OBJECTIVES: To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. METHODS: The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥ 1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). RESULTS: 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6 ± 13.9 vs. 46.8 ± 17.3 years), had higher Birmingham vasculitis activity score (19.5 ± 9.1 vs. 16.9 ± 7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). CONCLUSIONS: Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations.

[What's new in internal medicine?]. / Quoi de neuf en médecine interne?

Taking advantage of the French annual dermatologic conference "Journées Dermatologiques de Paris" that took place in December 2015, this article highlights the latest clinical advances, which occurred in autoimmune, inflammatory and systemic diseases during the past year. Evaluations of new classifications, new prognostic factors, and significant results of clinical trials in such diseases are underlined. A special attention is given to the classifications of systemic lupus erythematosus and systemic sclerosis as well as the use of rituximab in idiopathic thrombocytopenic purpura or in the maintenance treatment of patients with anti-neutrophil cytoplasmic antibodies-associated vasculitis.

Use of bosentan for digital ulcers related to systemic sclerosis: a real-life retrospective French study of 89 patients treated since specific approval.

OBJECTIVES: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. METHOD: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. RESULTS: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. CONCLUSIONS: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

[Autologous peripheral stem cell transplantation in systemic sclerosis: An important step forward, but we must temper our enthusiasm!] / Autogreffe de cellules souches périphériques dans la sclérodermie systémique : un progrès important, mais il faut tempérer notre enthousiasme !

Three prospective randomized studies have demonstrated the efficacy of autologous hematopoietic stem cell (HSC) transplantation in systemic sclerosis (SSc) on survival. These results encourage us to offer this therapy to patients who have a rapidly progressive disease and who have early symptoms but no advanced visceral involvement. HSC autograft can thus be discussed in patients with diffuse cutaneous SSc with a duration of the disease since the first visceral manifestations (cutaneous, cardiac, digestive, pulmonary, or renal) excluding Raynaud's phenomenon of less than 5 years. However, the indications for HSC autograft in SSc validated at European level and in the national diagnostic and care protocol (PNDS) are broader and some of these indications are debatable, in particular in patients with worsening diffuse interstitial lung disease. These indications are discussed in a reasoned way, taking into account the level of evidence and the toxicity of the HSC autograft.

[Update on targeted biopharmaceuticals in systemic sclerosis!] / Biothérapies ciblées : nouveautés dans la sclérodermie systémique !

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by inflammation, fibrosis, and autoimmunity. Despite few clinical trials when compared to other autoimmune diseases, SSc has benefited from renewed interest over the past ten years and a large number of clinical trials have been performed or are underway. We present here the results of the trials published in the last 5 years in ScS according to the chosen endpoint criteria and describe the trials in progress or expected in the years to come.

[Messages from the estates general on French internal medicine]. / Que retenir des états généraux de la médecine interne française ?

Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice.

In vitro and in vivo properties differ among liquid intravenous immunoglobulin preparations.

OBJECTIVE: To compare in vitro and in vivo biological and biochemical properties of five liquid intravenous immunoglobulin (IVIg) preparations licensed for therapeutic use in Europe. METHODS: ClairYg(®) was compared in a blinded manner to four other liquid IVIg preparations licensed in Europe (Octagam(®) , Kiovig(®) , Gamunex(®) , Privigen(®) ). Three batches of each preparation were tested, except for the IgG repertoires and the animal model. RESULTS: Levels of anti-A and anti-B antibodies were lower in ClairYg(®) (0·11/0·11) relative to a positive EDQM standard and Octagam(®) (0·11/0·08) than in other preparations (0·33-0·69/0·42-0·46). IgG in ClairYg(®) recognized 365 and 416 protein spots in HEp-2 cell and Escherichia coli protein extracts vs. 230-330 and 402-842 protein spots, respectively, for IgG in other preparations. IgA content (301 vs. 165-820 ng/mg of IgG), Factor XI and Factor XII antigen (0·46 vs. 0·85-2·40 mU/mg of IgG and 7·8 vs. 20·0-46·2 lU/mg of IgG) C1q binding (0·42 vs. 0·67-1·89 arbitrary units) and C5a uptake (0·41 vs. 0·45-0·66% of activation) were lower in ClairYg(®) than in other preparations. Finally, intravenous infusion of ClairYg(®) , Gamunex(®) and Privigen(®) had no major effect on arterial blood pressure in spontaneously hypertensive rats. CONCLUSIONS: Our results evidence some differences in the biological and biochemical properties among licensed liquid IVIg preparations.

Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension.

OBJECTIVE: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by obstruction of small pulmonary veins. Pulmonary venous involvement has been reported in pathologic assessment of patients with systemic sclerosis (SSc) presenting with precapillary PH. High-resolution computed tomography (HRCT) of the chest is a noninvasive diagnostic tool used to screen for PVOD. No HRCT data are available on SSc patients with precapillary PH. We undertook this study to evaluate the frequency and effect on prognosis of HRCT signs of PVOD in SSc patients with precapillary PH. METHODS: We reviewed chest HRCT data from 26 SSc patients with precapillary PH and 28 SSc patients without pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD). RESULTS: The radiographic triad of HRCT signs of PVOD (lymph node enlargement [57.7% versus 3.6%], centrilobular ground-glass opacities [46.2% versus 10.7%], and septal lines [88.5% versus 7.1%]) was significantly more frequent in SSc patients with precapillary PH than in SSc patients without PAH or ILD (all P < 0.005). Indeed, 61.5% of SSc patients with precapillary PH had ≥ 2 of these signs. Cardiomegaly (P < 0.0001), pulmonary artery enlargement (P < 0.0001), and pericardial effusion (P < 0.0005) were also significantly more frequent in SSc patients with precapillary PH. Pulmonary venous involvement was histologically confirmed in 2 patients with radiographic signs of PVOD. The presence of ≥ 2 radiographic signs of PVOD was associated with the occurrence of pulmonary edema after initiation of PAH-specific therapy (in 8 of 16 patients) and with more rapid progression from diagnosis of PH to death. CONCLUSION: HRCT signs of PVOD are frequently observed in SSc patients with precapillary PH, correlated with histologic assessment, and were associated with a high risk of pulmonary edema.