As the inflammation research improves year by year, so does our understanding of the autoinflammatory conditions. Over the past years, the number of monogenic autoinflammatory conditions snowballed ...thanks to our understanding of basic immunology and genetics. Familial Mediterranean Fever (FMF), being the entrance to this fascinating world, still has clinical relevance as it enables us to understand our approach to these patients, treatment modalities, and pathological mechanisms. This review can be used as a tool for clinicians already working with FMF patients to update themselves on recent scientific literature.
Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disease characterized by systemic inflammation and immunodeficiency. Infliximab proved to be favorable in the ...treatment of this condition. This case report is concerned with a DADA2 deficient patient treated with infliximab. This is a rare case of DADA2 in a 32-year-old female patient. The patient was admitted with a clinical presentation of erythema, ulcers, and pruritus on both legs and ankles, accompanied by red ulcerative oral lesions, fatigue, malaise, and dizziness. The patient's genetic analysis was positive for DADA2. Treatment based on TNF-α inhibition was highly effective for this patient. We used laboratory testing and punch biopsy as differential diagnostic tools, where antinuclear antibody positivity, high prolactin levels, and high serum C-reactive protein were observed. The punch biopsy revealed both orthohyperkeratosis and parahyperkeratosis of the dermis, diffuse core fragments, plasma in the stratum corneum, and hypergranulous acanthosis. DADA2 treatment is centered on tumor necrosis factor α suppression. Although high-dose systemic glucocorticoids can reduce inflammation in the initial stages of the disease, most patients have a resistant or relapsing response to tapering attempts. The prevalence of undiagnosed cases of autoinflammatory diseases is anticipated to diminish with the growing awareness of them.
Background:Idiopathic retroperitoneal fibrosis (RPF) is a progressive disorder of the retroperitoneum which is often idiopathic. Although prednisolone is the mainstay approach to treating RPF, the ...remission rates range between 75% to 95% (1-2).Objectives:Here, we report the outcomes and steroid-sparing effect of Rituximab (Rtx) therapy in 14 patients with RPF.Methods:This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with RPF and had at least a course of 0.5-1 mg/kg prednisolone treatment previously. These patients were switched to Rtx due to inadequate response or side effects while on prednisone, tamoxifen, azathioprine or cyclophosphamide therapy. Patients were treated with Rtx in order to be included in this study. Involvement and activation of RPF was shown via PET-CT either before or at least 6 months after the therapy. Daily prednisolone dose was noted before rituximab initiation and 6 months after the therapy. All of the patients reported, except two, were followed for at least 6 months after the Rtx treatment. The final disease status of the three patients were not included in the study.Results:Fourteen patients (7F) received at least 2 cycles (1 gr for each) of Rtx. The age of diagnosis was 54.3 ± 11.0 years, follow-up duration was 46.0 ± 37.2 months. The previous treatments, number of the cycles of Rtx and final disease status were shown in the Table. The Control PET-CT revealed metabolic and radiologic remission in 3 patients. In 6 patients, the disease remained stable. In 2 patients there was disease progression hence they were treated with the second course of Rtx. One of the two patients had the progression two years after the first cycle but then, was lost to follow-up. The mean prednisolone dose decreased from 15.5 ± 12.4 mg to 2.2 ± 2.2 mg/day after 6 months of Rtx initiation. Final prednisolone dose was 2.6 ± 5.5 mg/day (Figure). Rtx treatment was ceased in 6 patients with sustained remission.Conclusion:The present study shows that Rtx could be a therapeutic option after gluocorticoid or DMARD failure. The steroid sparing effect of Rtx is essential and further prospective studies are needed to assess the Rtx efficacy more objectively in RPF treatment.Table.Characteristics and final disease status of the patientsNumberAge of Rituximab InitiationSexPrevious TreatmentsNumber of Rituximab Cycle(s)Final Pet-CT149MPred, Mtx1Stable disease254MPred,Mtx1Stable disease346FPred,Aza,Tmx,Mmf2Progression440MPred,Aza,Mtx4Remission563FPred,Tmx10Stable disease647FPred,Mtx2Stable disease730FPred1Stable disease852MPred,Aza2Progression954MPred1N/A1059MPred,Aza,Mtx1N/A1130FPred, Mtx6Remission1240FPred,Aza,Tmx;Cyc3Stable disease1350MPred2N/A1445FPred,Aza3RemissionPred:Prednisolone, Aza:Azathioprine, Tmx:Tamoxifen,Mtx:Methotrexate,Cyc:cyclophosphamideReferences:1Vaglio A, Palmisano A, Alberici F, Maggiore U, Ferretti S, Cobelli R, Ferrozzi F, Corradi D, Salvarani C, Buzio C: Prednisone versus ta- moxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial. Lancet 378: 338–346, 20112van Bommel EF, Siemes C, Hak LE, van der Veer SJ, Hendriksz TR: Long-term renal and patient outcome in idiopathic retroperito- neal fibrosis treated with prednisone. Am J Kidney Dis 49: 615–625, 2007Disclosure of Interests:None declared
Background:
Familial Mediterranean Fever (FMF) can cause various muscle diseases. Because it is a chronic auto inflammatory disease, painful trigger points may be encountered in the examination due ...to a decrease in the pain threshold (1-3).
Objectives:
The aim of this study was to determine the prevalence of Fibromiyalgia in patients with FMF, at the same time to identify the relationship between fatigue and quality of life.
Methods:
Sixtyseven patients (38 female, 29 male) with FMF were enrolled in the study. They were diagnosed with FMF based on the Livneh diagnostic criteria (4). Fibromyalgia involvement of the patients was evaluated according to the Fibromyalgia Impact Questionnaire (FIQ). Patients with diagnose with other chronic disease were excluded. Fatigue Severity Scale (FSS) was used to evaluate fatigue. Quality of life was evaluated with Short Form-36 (SF-36).
Results:
Respectively, the mean age, disease duration and body mass index were 34.46±12.69 years, 12.66±7.86 years and 24.96±5.42 kg/m
2
. In addition, 65% of the patients had no rheumatic disease in their family history. The mean of scores of FIQ was 38.66±25.14, the mean of FSS was 38.07±17.56, the mean of SF-36-PCS was 45.55±10.54 and SF36-MCS was 30.93±17.39. Patients were categorized as mild (n=28), moderate (n=24) and severe (n=15) affected according to their FİQ score. The relationships of scores of FIQ, FSS and SF-36 were demonstrated Table 1.
Conclusion:
Fibromyalgia symptoms can be seen in FMF. According to our results, it has been shown that patients with moderate and severe symptoms have increased fatigue levels and decreased quality of life. In the light of these results, we can say that also the fibromyalgia symptom of patients with FMF should be considered in the treatment.
References:
1Sari, Ismail; Birlik, Merih; Kasifoglu, Timucin. Familial Mediterranean fever: an updated review. European journal of rheumatology, 2014, 1.1: 21.
2Alayli G, Durmus D, Ozkaya O, Sen HE, Genc G, Kuru O. Frequency of juvenile fibromyalgia syndrome in children with familial Mediterranean fever: effects on depression and quality of life. Clin Exp Rheumatol 2011; 29: S127-32.
3Langevitz P, Buskila D, Finkelstein R, Zaks N, Neuman L, Sukenik S, et al. Fibromyalgia in familial Mediterranean fever. J Rheumatol 1994; 21: 1335-7.
4Bashardoust, Bahman. Familial Mediterranean fever; diagnosis, treatment, and complications. Journal of nephropharmacology, 2015, 4.1: 5.
Table 1.
The correlations of FIQ, FSS and SF-36 scores.
FSS
SF-36 PCS
SF-36 MCS
FIQ-mild
mean±sd
23.78±14.88
53.34±7.01
40.98±13.73
r
0.595
**
-0.014
-0.551
**
p
0.001
0.944
0.002
FIQ-moderate
mean±sd
45.75±10.83
41.09±8.89
38.13±9.19
r
0.053
-0.379
-0.145
p
0.806
0.068
0.498
FIQ-severe
mean±sd
52.46±10.11
38.13±9.19
20.32±15.68
r
0.622
*
-0.548
*
-0.268
p
0.013
0.035
0.333
-Pearson Correlation
Disclosure of Interests:
None declared
Background:
Even though corticosteroids and cDMARDs are effective for inducing remission in patients with Adult-Onset Still Disease (AOSD), relapse is common. Hence, maintaining the clinical ...stability is challenging. Almost all of the patients face side effects because of high dose steroid treatment. Biological DMARDs have been reported to be effective in refractory patients.
Objectives:
We aimed to evaluate the patients’ outcomes who were diagnosed with AOSD and treated with at least one bDMARDs in our tertiary center.
Methods:
Patients with AOSD who were followed in our clinic between 2007 and 2020 were screened retrospectively. For the diagnosis of AOSD, all of the patients fulfilled Yamaguchi criteria. The demographic characteristics, baseline and post-treatment clinical findings and outcomes were reported.
Results:
Twenty-eight patients (21 F, 7 M) were screened (Figure 1). The mean disease duration of the first bDMARD was 21,76 ± 28,05 months (mean ± SD). The mean duration of bDMARD treatment was 37,04 ± 30,75 months. The reasons for starting a bDMARD were systemic symptoms (%80) and chronic arthritis (%20). All of the patients used methotrexate (MTX) except one. This patient had macrophage activation syndrome during diagnosis and was treated with cyclosporine. All of the patients were treated with corticosteroids (34,28 ± 26,70 mg/d) and a cDMARD at initiation (22 of them MTX, 1 of them azathioprine, 2 of them cyclosporine and 1 of them IVIg). Anakinra was the most preferred biologic as a first-line treatment modality (TNF inhibitors=5, tocilizumab=4). The main reason for switching was loss of efficacy (8/22). Tocilizumab was the most used agent in 2
nd
line and canakinumab was in 3
rd
line. Twenty-two patients were in remission at last visit. Also, 15 patients were steroid-free, 14 patients were MTX-free. Patient global visual analogue scale, acute phase reactants and daily steroid dose were reduced significantly at last visit compared to the initial visit (Table 1).
Table 1.
Comparison of important laboratory findings and the mean steroid dose
Clinical finding
At initiation of bDMARD
mean ± SD
At the last visit
mean ± SD
PG-VAS
9.8 ± 0.8
2.3 ± 2.3
ESR (mm/h)
34,28 ± 33,95
18.82 ± 11.60
CRP (mg/l)
70,76 ± 67,80
13.44 ± 27.33
Ferritin (ng/mL)
1662 ± 1239
275.7 ± 381.4
Daily steroid dose (prednisolone, mg/d)
34.28 ± 26.70
5.60 ± 8.60
Figure 1.
Presenting signs and the symptoms of the patients
bDMARD treatment was terminated in 5 patients due to complete remission (n=2) and side effects (1 of them pneumonia, 1 of them EBER (+) Hodgkin Lymphoma and 1 of them tuberculosis). Six patients experienced local injection site reaction, none of them stopped treatment. Also, one patient died while she was in remission under anakinra treatment with an unknown cause.
Conclusion:
The most common presenting symptoms in our cohort were fever and salmon-colored rash. Tocilizumab is an alternative treatment modality in cases with chronic arthritis and IL-1 inhibitors are an alternative for systemic course of disease. bDMARDs, especially IL-1 inhibitors are highly effective for refractory patients with AOSD.
Disclosure of Interests:
None declared
Behçet Syndrome: Is It One Condition? Yazici, H.; Ugurlu, S.; Seyahi, E.
Clinical reviews in allergy & immunology,
12/2012, Letnik:
43, Številka:
3
Journal Article
Recenzirano
Behçet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative ...spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction.
BackgroundApproximately 5 to 10% of FMF patients do not respond to colchicine treatment and/or intolerant to colchicine due to side effects. Several case reports and case series have pointed out the ...efficacy of IL-1 blockade in colchicine resistant FMF subgroup.ObjectivesTo review the patients followed in our centre with FMF who received anakinra, an anti-IL-1 receptor antagonist, because of insufficient colchicine response.MethodsFMF patients who were treated with anakinra were retrospectively reviewed with regard to indication, effect on disease activity and acute phase response, adverse events. Patient global assessment was recorded before and after anakinra treatment.ResultsThere were 48FMF patients with FMF who were treated with anakinra for various indications (colchicine resistant recurrent febrile attacks in 42, colchicine related side effects in 6). The mean age of the group was 31.8±9.2 years. The mean duration of the disease was 12.3±7.9 years. There were various co-existing pathologies among this study group like multiple sclerosis,1 ankylosing spondylitis,1 SLE,1 Behçet’s disease,1 low grade lymphoma,1 psoriasis,2 vasculitis2 and PAN.2 The mean colchicine dose was 2,13±0,51 mg/d. The mean duration of anakinra treatment was 14.47±10.8 months. Twenty seven patients reported no attacks after anakinra treatment whereas 10 patients reported at least 50% decrease in the attack frequency. There are 4 patients who were primarily irresponsive to the therapy, whereas in 5 patients response to therapy ameliorated during the course of the treatment. Mean patient global assessment decreased from 8.58±1.2 to 2.72±3.16 under anakinra treatment (p=0.001).Four patients had severe allergic reactions (severe disseminated rash in 1 patient and severe injection site reaction in 3 patients) and therefore the drug was stopped. Two patients had infections (one had genital warts and urinary tract infection, the other had sinusitis and folliculitis) and the treatment was terminated. One of our patients reported that her psoriatic lesions got worse on anakinra. Forty one patients reported no adverse events during the treatment.Conclusions: Anakinra was effective in controlling the symptoms in colchicine-resistant FMF cases. It was also effective in FMF related amyloidosis. The major cause of treatment termination was injection site reactions. Anakinra seems to be an effective alternative in patients who have insufficient response to colchicine.Disclosure of InterestNone declared
Systemic sclerosis (SSc) represents extremely rare disease with majority of data coming from adults. Studies comparing juvenile- (jSSc) and adult-onset (aSSc) patients are limited. We aimed to ...compare clinical features, treatment modalities and survival rates of jSSc and aSSc patients.
A retrospective study among pediatric and adult Scl patients has been performed. Demographic characteristics, clinical features, autoantibody profiles, and treatment data were retrieved from the databases. Survival analysis was done using Kaplan-Meier plot and factors associated with mortality were identified with multiple regression analysis.
A total of 158 adults and 58 juvenile Scl patients were identified. The mean age at the disease onset was 37±14.7 vs. 8.8 ± 4.1 years, mean age at diagnosis 42±15.2 vs. 10.4 ± 3.8 years and mean follow-up duration was 6.3 ± 4.9 years vs. 6.6 ± 4.9 years for aSSc and jSSc patients, respectively. The frequency of interstitial lung disease (ILD) (50.9% vs 30%, p<0.001) and systemic hypertension (17.9% vs 0, p = 0.009) was significantly higher among aSSc. While aSSc patients had presented mostly with limited cutaneous subset (74.1%), diffuse cutaneous subset was the dominant subset among jSSc (76.7%), (p<0.001). The mortality rate was significantly higher among adults (p = 0.005). The ILD (p = 0.03) and cardiac insufficiency (p = 0.05) were independent risk factors of mortality in both aSSc and jSSc patients.
Juvenile and adult-onset Scl represent rarely seen conditions with different clinical phenotypes. Pediatric patients with LS are more commonly seen by pediatric rheumatologists, in contrary to adults. Diffuse disease subset is the dominant form among juvenile patients, whereas limited form is the main disease subset among adults. On the other hand, juvenile-onset patients have a better survival than those with adult-onset.
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BackgroundDespite methotrexate and steroid treatment, in cases of Adult-onset Still’s disease (AOSD) it is usually difficult to maintain clinic stability. In refractory cases, Anakinra treatment has ...been reported to be efficacious.1 ObjectivesIn this retrospective review, it is aimed to evaluate the AOSD cases treated with anakinra in our centre.MethodsFourteen AOSD patients (11 female,3 male) who were being followed in our outpatient clinic were reviewed retrospectively. The demographic characteristics, pre- and post-treatment clinical findings were reported.ResultsThe mean follow-up period of the patient population was 33.5±30.07 months (mean ±SD). Initial prednisolone dose was 37.3 mg/day. Except for one, all of our patients were exposed to methotrexate before being treated with anakinra. This patient was being treated with cyclosporine instead, since she had concomitant Macrophage Activation Syndrome. The other medications, the patients were previously treated with, were Etanercept (n=2), Tocilizumab (n=3), Infliximab (n=1) and Adalimumab (n=1).All patients were on 100 mgs of Anakinra, daily, except for the one treated with 200 mg/day. The mean duration of Anakinra therapy was 11.4 months. Among 7 patients in whom anakinra therapy was terminated, 1 had drug induced urticaria, 1 was primary irresponsive, 4 were secondary irresponsive and the other had severe pneumonia. Primary irresponsiveness is the lack of response to the therapy since the drug was first introduced, whereas in secondary irresponsiveness the case responds to the medication for a while and starts to flare again after asymptom-free period on the medication. Among 14, 7 of our patients are still on 100 mg/d Anakinra.The mean level of C reactive protein (CRP) measures was reduced from 64.38±61.95 mg/L to 34.3±24.3 mg/L with Anakinra therapy(p=0.003). Similarly, mean Erythrocyte Sedimentation Rate (ESR) was dropped to 33±22 mm/h from 59±35 mm/h by the help of the therapy(p<0.001). Among patients who primarily responded Anakinra therapy the mean Ferritin measures dropped to 427.25 ng/ml from 910 ng/ml (p=0.006). On the other hand, the Ferritin level was not significantly reduced in patients who did not respond Anakinra.The mean Patient reported Global Visual Analogue Scale (PG-VAS) score was also decreased to 3.83±4.7 from 9.5±0.07 following the therapy(p<0.001). Unfortunately, one of our 7 patients who were followed in remission under Anakinra died of an unknown etiology.ConclusionsAdult-onset Still’s disease is a challenging disorder, lacking a sufficient long-time clinical control. In order to obtain a full remission, various efforts have been spent so far. One of these approaches is to treat refractory cases with Anakinra, an IL-1 blocking agent. According to our clinical experience we state that, anakinra has a relatively high efficacy in controlling refractory cases.Reference1 Ortiz-Sanjuán F, et al. Efficacy of Anakinra in RefractoryAdult-OnsetStill’sDisease: MulticenterStudyof 41 PatientsandLiteratureReview. Medicine(Baltimore)2015Sep;94(39):e1554.Disclosure of InterestNone declared
PurposeTo compare quality of life (QoL) in patients with primary open-angle glaucoma (POAG) and dry-type age-related macular degeneration (AMD) with similar best-corrected visual acuity.MethodsAge-, ...sex-, and visual acuity-matched POAG and dry AMD patients were included in the study. Each patient performed 24-2 and 10-2 SITA standard visual field tests. Contrast sensitivity was evaluated with CSV-1000 HGT instrument. The 25 item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was used to analyze QoL. Overall and subscale scores were converted to scores between 0 and 100, the higher scores indicating better vision-related QoL.ResultsOverall NEI-VFQ-25 scores were 86.44 and 84.66 in glaucoma and AMD groups, respectively (P=0.244). The highest scores were obtained in 'vision-related dependency' subgroup in glaucoma and 'color and peripheral vision' in AMD group, whereas the lowest scores were noted 'in peripheral vision' in both glaucoma and AMD patients. Glaucoma patients had significantly lower scores in ocular pain, color vision, and peripheral vision subgroups compared with the AMD group, whereas AMD patients had lower scores in near and distance vision activities, vision-related social activity, and dependency subgroups. Contrast sensitivity results and mean defect values showed correlation with NEI-VFQ-25 scores in both groups.ConclusionsGlaucoma and AMD patients with similar visual acuity experienced similar overall impairment in QoL. However, glaucoma patients described more difficulty with peripheral vision and ocular pain, whereas AMD patients complained more about near and distance vision and dependency items.
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