Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine.

VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.

Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis.

CASE REPORT: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. DISCUSSION: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.

Characterization of three adults and an adolescent with Osteogenesis Imperfecta type VI and a novel founder SERPINF1 variant.

Osteogenesis imperfecta (OI) type VI is an extremely rare form of OI caused by biallelic variants in the SERPINF1 gene, which codes for the pigment-epithelium derived factor (PEDF). We report on four patients (three adults and one adolescent) with a severe deforming form of OI. All patients presented no abnormalities at birth, frequent long bone and vertebrae fractures (mainly during childhood), marked short stature, severe bone deformities, chronic mild to moderate pain, and severe limitation of mobility, with three being completely wheelchair bound. Blue sclera and dentinogenesis imperfecta were absent, although some patients presented tooth, ophthalmological, and/or cardiac features. Radiographic findings included, among others, thin diaphysis and popcorn calcifications, both of which are non-specific to this type of OI. The novel homozygous variants c.816_819del (p.Met272Ilefs*8) and c.283+2T > G in SERPINF1 were identified in three and one patient, respectively. The three patients carrying the frameshift variant were born in nearby regions suggesting a founder effect. Describing the long-term outcomes of four patients with OI type VI, this cohort adds relevant data on the clinical features and prognosis of this type of OI.

Oral antiviral treatments for COVID-19 during severe connective tissue disease flares: report of two cases.

Antiviral therapies targeting SARS-CoV-2 replication change the course of COVID-19. The European Medicines Agency (EMA) has approved a nirmatrelvir/ritonavir combination that inhibits the main protease of the virus. Molnupiravir, an RNA polymerase misdirector, is proposed by EMA in selected cases, despite still without marketing authorisation. Both are for use in mild disease with a high risk of progression to severe COVID. Patients with inflammatory rheumatic diseases under immunosuppression, mainly high-dose glucocorticoids, are at higher risk of developing severe COVID. We report two clinical cases in which nirmatrelvir/ritonavir and molnupiravir were successfully used to treat COVID-19 in immunosuppressed patients during severe flares of connective tissue diseases, namely systemic lupus erythematosus and dermatomyositis. No significant adverse events attributable to these drugs were noted.

Osteoporosis management during the COVID-19 pandemic - Position paper.

COVID-19 pandemic significantly increased the already large number of victims of osteoporosis in Portugal. Osteoporosis outpatient clinics were either closed or had limited presential appointments. Many hospitals reduced orthopaedic services to make space for patients with COVID-19. In addition, the volunteer or forced sedentarism, as imposed by the pandemic, increased the risk of falls and fractures drastically. It urges to intensify the current efforts to improve the management of bone health and to prioritize fragility fracture care and prevention. This paper addresses the challenges in osteoporosis management during the COVID-19 pandemic and provides guidance on osteoporosis management. This position paper is a joint initiative of several health professionals and patients dedicated to osteoporosis.

A COVID-19 Outbreak in a Rheumatology Department Upon the Early Days of the Pandemic.

Objectives: To describe our experience with a coronavirus disease 2019 (COVID-19) outbreak within a large rheumatology department early in the pandemic. Methods: Symptomatic and asymptomatic healthcare workers (HCWs) had a naso-oropharyngeal swab for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were followed clinically. Reverse transcription polymerase-chain reaction (RT-PCR) was repeated to document cure, and serological response was assessed. Patients with risk contacts within the department in the 14 days preceding the outbreak were screened for COVID-19 symptoms. Results: 14/34 HCWs (41%; 40 ± 14 years, 71% female) tested positive for SARS-CoV-2, and 11/34 (32%) developed symptoms but were RT-PCR-negative. Half of RT-PCR-positive HCWs did not report fever, cough, or dyspnea before testing, which were absent in 3/14 cases (21%). Mild disease prevailed (79%), but 3 HCWs had moderate disease requiring further assessment, which excluded severe complications. Nevertheless, symptom duration (28 ± 18 days), viral shedding (31 ± 10 days post-symptom onset, range 15-51), and work absence (29 ± 28 days) were prolonged. 13/14 (93%) of RT-PCR-positive and none of the RT-PCR-negative HCWs had a positive humoral response Higher IgG indexes were observed in individuals over 50 years of age (14.5 ± 7.7 vs. 5.0 ± 4.4, p = 0.012). Of 617 rheumatic patients, 8 (1.3%) developed COVID-19 symptoms (1/8 hospitalization, 8/8 complete recovery), following a consultation/procedure with an asymptomatic (7/8) or mildly symptomatic (1/8) HCW. Conclusions: A COVID-19 outbreak can occur among HCWs and rheumatic patients, swiftly spreading over the presymptomatic stage. Mild disease without typical symptoms should be recognized and may evolve with delayed viral shedding, prolonged recovery, and adequate immune response in most individuals.

Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view.

The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novel status quo and assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

A doença de Still do adulto é uma entidade pouco comum que se caracteriza por manifestações clínicas muito variadas. A pneumonite, menos frequente, merece particular destaque dado a necessidade do seu diagnóstico diferencial e pela possível progressão para insuficiência respiratória grave. Com o objetivo de destacar a relevância do envolvimento do parênquima pulmonar na doença de Still do adulto, descrevemos um caso clinico que cursou com pneumonite.

Erythema elevatum diutinum in Crohn's disease-associated Spondyloarthritis - a rare vasculitis, an unusual association.

Erythema elevatum diutinum is a rare neutrophilic dermatoses with vasculitis, which presents as persistent, symmetrical, purple or brownish papules and nodules, mainly in the extensor surface of the limbs. We describe a case of erythema elevatum diutinum and polyarthritis as initial manifestations of Crohn's disease associated spondyloarthritis. A 51-year-old man, from São Tomé e Príncipe, with previous history of treated tuberculosis and chronic hepatitis B infection, was admitted due to 4 months history of polyarthritis, hyperpigmented papules on the extensor surfaces, occasional episodes of bloody mucous diarrhea and significant weight loss. Histology of the skin showed neutrophilic granulocytes with marked fibrosis and moderate karyorrhexis, consistent with erythema elevatum diutinum. Colonoscopy showed erosions in sigmoid and rectum. Diagnosis of erythema elevatum diutinum secondary to Crohn's disease with associated peripheral spondyloarthritis was assumed. The patient was treated with prednisolone, sulphasalazine, metronidazole, azathioprine and tenofovir with good clinical response. As erythema elevatum diutinum can be secondary to multiple systemic diseases, including rheumatic diseases and inflammatory bowel disease, being aware and recognizing this entity can be of great importance for rheumatologists.

Multidisciplinary Portuguese recommendations on DXA request and indication to treat in the prevention of fragility fractures.

OBJECTIVE: To establish Portuguese recommendations regarding the indication to perform DXA and to initiate medication aimed at the prevention of fragility fractures. METHODS: A multidisciplinary panel, representing the full spectrum of medical specialties and patient associations devoted to osteoporosis, as well as national experts in this field and in health economics, was gathered to developed recommendations based on available evidence and expert consensus. Recently obtained data on the Portuguese epidemiologic, economic and quality-of-life aspects of fragility fractures were used to support decisions. RESULTS: 10 recommendations were developed covering the issues of whom to investigate with DXA and whom to treat with antifracture medications. Thresholds for assessment and intervention are based on the cost-effectiveness analysis of interventions at different thresholds of ten-year probability of osteoporotic fracture, calculated with the Portuguese version of FRAX® (FRAX®Port), and taking into account Portuguese epidemiologic and economic data. Limitations of FRAX® are highlighted and guidance for appropriate adjustment is provided, when possible. CONCLUSIONS: Cost-effectiveness thresholds for DXA examination and drug intervention aiming at fragility fracture prevention are now provided for the Portuguese population. These are practical, based on national epidemiological and economic data, evidence-based and supported by a wide scope multidisciplinary panel of experts and scientific societies. Implementation of these recommendations holds great promise in assuring the most effective use of health resources in the prevention of osteoporotic fractures in Portugal.

A FRAX model for the estimation of osteoporotic fracture probability in Portugal.

INTRODUCTION: The objective of this study was to develop a Portuguese version of the World Health Organization fracture risk assessment tool (FRAX®). METHODS: All cases of hip fracture occurred at or after 40 years of age were extracted from the Portuguese National Hospital Discharge Register from 2006 to 2010. Age and sex-ranked population estimates and mortality rates were obtained from National Statistics. Age- and gender stratified incidences were computed and the average of the five years under consideration was taken. Rates for other major fractures were imputed from the epidemiology of Sweden, as undertaken for most national FRAX® models. All methodological aspects and results were submitted to critical appraisal by a wide panel of national experts and representatives of the different stakeholders, including patients. RESULTS: Hip fracture incidence rates were higher in women than in men and increased with age. The lowest incidence was observed in 40-44 years group (14.1 and 4.0 per 100,000 inhabitants for men and women, respectively). The highest rate was observed among the 95-100 age-group (2,577.6 and 3,551.8/100,000 inhabitants, for men and women, respectively). The estimated ten-year probability for major osteoporotic fracture or hip fracture increased with decreasing T-score and with increasing age. CONCLUSIONS: Portugal has one of the lowest fracture incidences among European countries. The FRAX® tool has been successfully calibrated to the Portuguese population, and can now be used to estimate the ten-year risk of osteoporotic fractures in this country. All major stakeholders officially endorsed the Portuguese FRAX® model and co-authored this paper.