Characteristics of Late-Onset Spondyloarthritis: Data from the Moroccan Registry of Biological Therapies in Rheumatic Diseases.

Introduction The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial and peripheral spondyloarthritis (SpA) allow for the classification of patients with an age of onset of disease of less than 45 years. However, SpA can start after this age. This study aimed to assess the characteristics of late-onset SpA (SpA>45 years) in the Moroccan registry of biological therapies in rheumatic diseases (RBSMR). Methods A cross-sectional study was conducted using the baseline data of the RBSMR. The protocol for the original RBSMR study was reviewed and approved by the Ethics Committee for Biomedical Research Mohammed V University - Rabat, Faculty of Medicine and Pharmacy of Rabat (approval number for the study was 958/09/19, and the date of approval was September 11, 2019), and all patients had given their written consent. Patients who met the 2009 ASAS criteria for SpA were included. They were divided into two groups: early-onset SpA (≤ 45 years) and late-onset SpA (>45 years). Clinical, biological, radiological, and therapy data of the two groups were compared. Statistical analysis was performed using SPSS v25 software (IBM Corp. Armonk, NY). Parameters with a p-value ≤0.05 were considered significant. Results Our population consisted of 194 patients. Thirty-one patients (16%) had late-onset SpA. Comparison between patients with early-onset (≤45 years) and late-onset SpA (>45 years) revealed that late-onset SpA had a higher tender joint count (p=0.01), a higher swollen joint count (p=0.02), depression (p=0.00), fibromyalgia (p=0.001), hypercholesterolemia (p=0.01), and a lower frequency of coxitis (p=0.008). Logistic regression analysis confirmed that late-onset SpA was associated with a higher tender joint count (OR=0.93, CI 95%: 0.88-0.98), a higher swollen joint count (OR=0.92, CI 95%: 0.85-0.99), depression ( OR=0.19, CI 95%:0.04-0.38), fibromyalgia (OR=1.75, CI 95%: 1.74-17.85), and a lower frequency of coxitis ( OR=0.29, CI 95%: 0.11-0.75). Conclusion As life expectancy increases, late-onset SpA will become increasingly common. It is therefore imperative to determine its characteristics. In the RBSMR study, late-onset SpA was associated with a high number of tender and swollen joints, depression, fibromyalgia, and a lower frequency of coxitis.

Correction: Characteristics of Late-Onset Spondyloarthritis: Data from the Moroccan Registry of Biological Therapies in Rheumatic Diseases.

[This corrects the article DOI: 10.7759/cureus.39100.].

Extra-Articular Manifestations in Patients with Ankylosing Spondylitis: Baseline Characteristics from the RBSMR Study.

Objectives: To describe and analyse the prevalence of extra-articular manifestations (EAMs) including acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD) in patients with ankylosing spondylitis (AS) in the Moroccan registry of biological therapies in rheumatic diseases RBSMR (Registre des Biothérapies de la Société Marocaine de Rhumatologie). Methods: A cross-sectional, multicentre and analytical study based on the RBSMR database, which included 170 AS. Incidence rates for the development of AAU, psoriasis and IBD were calculated, and risk factors were analysed. Results: Prevalence of EAMs in AS was 13.5%, 4.7% and 11.2% for AAU, psoriasis and IBD respectively. No significant differences were found while establishing a comparison of the prevalence of these EAMs between AS patients with and without peripheral arthritis. Interestingly, AAU was the most common EAM, and was positively associated in multivariable regression with family history of spondyloarthritis (OR= 7.21, CI 95%: 2.23-23.24). Conclusions: AAU was the leading EAM in patients with AS included in the Moroccan biotherapy registry (RBSMR) and it was associated with family history of spondyloarthritis.

Therapeutic Maintenance Level of Methotrexate in Rheumatoid Arthritis: A RBSMR Study.

Objectives: The aim of this study was to determine the therapeutic maintenance level of methotrexate for rheumatoid arthritis patients enrolled in the Moroccan biotherapy registry and to identify predictive factors for discontinuing MTX treatment. Methods: A cross-sectional study was conducted using the baseline data of the Moroccan biotherapy registry for RBSMR (a multicentric study that aims to evaluate tolerance of biological therapy on patients affected with rheumatic diseases). Demographics and disease features were compared using descriptive statistics. Therapeutic maintenance levels were determined according to a Kaplan-Meier survival curve and a univariate Cox proportional hazards regression model was used to compare the strength of potential factors, followed by a multivariate Cox model to identify significant predictors of MTX discontinuation. Statistically significant results were considered for p values less than 0.05. Results: 224 patients with rheumatoid arthritis were included in this study. The mean age of patients was 51.83±11.26 years with a majority of females (87.50%). The median duration of disease was 12 [1.66-41.02] years. The therapeutic maintenance level of MTX was 91.1% at 1 year, 87.1% at 2 years, and 68.3% at 5 years. The median of treatment duration was 2, 02 [0, 46-27,76] years. Causes of treatment interruption were side effects (66/88=75%), inefficiency (12/88=13.63%), and other reasons (10/88=11.36%). Predictive factors for stopping MTX were presence of rheumatoid factor (HR 2.24; 95% CI 1.14-5.15; p=0.02) and the access to education (HR 0.37; 95% CI 0.16-0.88; p=0.02). Conclusion: The therapeutic maintenance level of MTX in our study was satisfactory and comparable to other series, and influenced by many factors such as the occurrence of a side effect. It is necessary to sensitise medical practitioners on symptomatic prevention and management of side effects.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

Background: The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results: In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Prevalence of latent tuberculosis before biotherapy initiation in rheumatoid arthritis and spondyloarthritis: data from the Moroccan biotherapy registry.

Before the initiation of biotherapy in the treatment of rheumatic diseases, it is highly recommended for the patients to be screened for latent tuberculosis infection (LTBI). The objective of this study is to identify the prevalence of LTBI among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) before the initiation of biologic therapy in the Moroccan biotherapy registry (RBSMR). A cross sectional study was conducted using the baseline data of the Moroccan biotherapy registry. Tuberculin skin test or IGRA test or both tests were done before starting anti-TNF treatment for screening LTBI. The comparisons between positive and negative LTBI patients according to rheumatic disease were examined using categorical comparisons. 259 patients were included in this study.94 patients had RA and 165 had SpA. The mean age of the RA patients was 50.49 ± 11.82 years with a majority of females (84%). The mean age for the SpA patients was 36 ± 13.7 years with a majority of males (67.3%). The prevalence of LTBI in the RBSMR was 21.6%. This prevalence was at 24.8% in SpA patients, while it was at 15.9% for RA patients. After the comparison between positive and negative LTBI patients according to rheumatic disease, no demographic, clinical, or therapeutic characteristics were statistically associated with LTBI. This study found that in an endemic TB country like Morocco, a high prevalence of patients with SpA and RA had LTBI, and that RA patients had a lower prevalence than SpA patients.

The first biological choice in patients with rheumatoid arthritis: data from the Moroccan register of biotherapies.

INTRODUCTION: the aim of our study is to determine, from data of the Moroccan register of biotherapies, the factors influencing the choice of the first prescribed biological treatment. METHODS: cross-sectional multicenter study including rheumatoid arthritis patients who were initiated the first biological treatment either: Rituximab, an anti-TNF, or Tocilizumab. The determinants related to the patient and disease have been gathered. A univariate and then multivariate analysis to determine the factors associated with the choice of the first bDMARDs was realized. RESULTS: a total of 225 rheumatoid arthritis patients were included in the Moroccan registry. The mean age was 52 ± 11 years, with female predominance 88% (n = 197). The first prescribed biological treatment was Rituximab 74% (n = 166), the second one was Tocilizumab, 13.6% (n = 31) then comes the anti-TNF in 3rd position with 12.4% (n = 28). The factors associated with the choice of Rituximab as the first line bDMARDs prescribed in univariate analysis were: the insurance type, the positivity of the rheumatoid factor. In multivariate analysis, only the insurance type that remains associated with the choice of Rituximab as the first biological drugs. The Tocilizumab was associated with shorter disease duration and was more prescribed as mono-therapy compared to non Tocilizumab group. TNFi was associated with the insurance type. CONCLUSION: our study suggests that Rituximab and TNFi are associated with the type of insurance and Tocilizumab is the most prescribed biologic mono-therapy in RA patients. Further studies are needed to confirm these results.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

Leflunomide-induced toxic epidermal necrolysis in a patient with rheumatoid arthritis.

INTRODUCTION: Leflunomide is an immunomodulating agent with proven efficacy in rheumatoid arthritis. Although its overall safety profile is good, a few cases of toxic epidermal necrolysis have been reported. CASE REPORT: This 36-year-old woman had rheumatoid arthritis that proved refractory to sulfasalazine and methotrexate, which were used successively in combination with symptomatic drugs. Leflunomide was started. A maculopapular rash and a fever developed 2 weeks later. The skin lesions spread rapidly to most of the body, and ulcers of the ocular and oral mucosa appeared. Leflunomide was stopped. Cholestyramine washout and prednisolone (60 mg/day) were given. The skin lesions healed over the next month. Punctate keratitis with keratinization of the cornea led to complete loss of vision. DISCUSSION: The main adverse effects of leflunomide consist of diarrhea, nausea, liver enzyme elevation, hypertension, alopecia, and allergic skin reactions. A few cases of severe skin reactions such as toxic epidermal necrolysis have been reported. They require immediate discontinuation of the drug and a washout procedure to hasten drug elimination from the body. CONCLUSION: Close monitoring for severe skin reactions is in order when using leflunomide.

Buschke-Ollendorff syndrome.

UNLABELLED: Buschke-Ollendorff syndrome (BOS) is an autosomal dominant disorder characterized by elastin-rich hamartomas and osteopoikilosis. CASE REPORT: In a 21-year-old woman, osteopoikilosis led to the diagnosis of BOS. She had multiple, grouped, buff-colored papules over the thighs and trunk. There was no pain or pruritus associated with the skin lesions. Examination of a biopsy specimen from a papule showed thick uniform collagen fibers and normal numbers of broad interlacing elastic fibers. DISCUSSION: BOS is a rare disease that affects 1/20,000 population. The diagnosis rests on a thorough physical examination and careful examination of radiographs. BOS must be distinguished from other bone abnormalities such as sclerotic bone metastases, particularly when osteopoikilosis is the inaugural manifestation.

Sweet's syndrome in Behçet's disease.

UNLABELLED: Few cases of Sweet's syndrome have been reported in patients with Behçet's disease. CASE REPORT: A 47-year-old woman with five year history of oral and genital ulcers that had not been investigated previously was admitted for an eruption of tender, erythematous, vesicle-like papules over the face, neck, palms, and legs. She reported polyarthralgia and weight loss of 6 kg over the previous month. At admission, she had a fever of 38.5 degrees C and conjunctivitis. Joint tenderness to mobilization without evidence of synovitis was noted. Laboratory tests showed inflammation and leukocytosis (12.5x10(9)/L) with 74% neutrophils. The skin biopsy was typical for Sweet's syndrome, and the pathergy test was positive. Glucocorticoid therapy 40 mg/day and colchicine were effective in alleviating the manifestations. DISCUSSION: Overlap exists between the clinical manifestations of Sweet's syndrome and Behçet's disease. Data from the literature suggest that Behçet's disease may be among the conditions that underlie Sweet's syndrome.

[Pigmented villonodular synovitis]. / Synovite villonodulaire.

OBJECTIVE: To evaluate clinical, radiological and histological characteristics as well as outcome of pigmented villonodular synovitis (PVNS) in 14 patients. METHODS: This retrospective study examined data from 14 cases of pathologically-confirmed PVNS over a 10-year period (1990-1999). RESULTS: All 14 cases (9 women and 5 men) of PVNS involved the knee. Mean age at diagnosis was 32.7 years. The principal functional signs were mechanical pain and disability. All patients had radiographs (normal for 8 patients); 3 had arthrography, which found diffuse cyst formations, 2 had MRI, which showed images characteristic of PVNS, and 4 had arthroscopy. All patients underwent complete surgical excision, and 4 also had osmic acid synoviorthesis. Recurrence occurred in 4 patients, within 10 months on average. CONCLUSION: MRI and arthroscopy improve the early management of pigmented villonodular synovitis.

Hydatid disease of bone. Review of 11 cases.

UNLABELLED: Osseous hydatid disease is defined as development within bone of multiple cysts that are the larval form of the tapeworm Echinococcus granulosus. Bone cysts account for only 0.5-2.5% of all hydatid cysts in humans. We report on our experience. METHODS: This retrospective study included patients managed between 1988 and 1998 for histologically documented hydatid disease of bone. RESULTS: Eleven patients were included, six men and five women, with a mean age of 40.7 +/- 11.04 years (range, 27-60 years). Mean time to diagnosis was 22.7 +/- 18.2 months (range, 5-36). The pelvis was involved in six patients and a long bone in five (the femur in three, the tibia in one, and the fibula in one). Peripheral eosinophil counts were high in four patients and serological tests for hydatid disease were positive in five patients. Surgical treatment was used alone in 10 patients and with albendazole in one patient. The main complications were fistulization (n = 6) and suppuration (n = 4). Five patients experienced recurrences. CONCLUSION: Hydatid disease still occurs in Morocco. The liver and lungs are the most common targets. Bone cysts are uncommon but severe. The behavior of osseous hydatid cysts resembles that of locally malignant lesions. Although immunofluorescent assays are useful, the final diagnosis depends on histology. The treatment rests on surgical excision. Recurrence is common, particularly at sites that are difficult to access.

Vascular involvement in Behçet's disease. Two case reports.

UNLABELLED: Arterial involvement is rare in Behçet's disease but can be at the forefront of the clinical picture and cause life-threatening complications. CASE REPORTS: A 36-year-old man had Behçet's disease with an aortographically documented aneurysm of the abdominal aorta as the inaugural manifestation. He had oral and genital ulcers. Funduscopy showed periphlebitis. In a 38-year-old man with an 8-year history of Behçet's disease, pulmonary and coronary artery aneurysms developed, as well as intracardiac and venous thromboses. DISCUSSION: Arterial involvement occurs in 3-5% of patients with Behçet's disease and usually manifests as multiple spindle-shaped aneurysms. Intracardiac thrombosis and cardiac aneurysm are exceedingly rare. Our patient had an extremely unusual presentation given the low rate of occurrence of arterial lesions in Behçet's disease. CONCLUSION: Arterial involvement in Behçet's disease raises treatment challenges because the lesions tend to recur and can cause life-threatening complications.