What rheumatologist should know about Fabry disease

Moiseev, Sergey; Karovaikina, Ekaterina; Novikov, Pavel; Ismailova, D S; Moiseev, Alexey; Bulanov, Nikolai

doi:10.1136/annrheumdis-2019-215476

Cited by 14 publications

(10 citation statements)

References 4 publications

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“…Data from the medical literature have repeatedly shown that many of those patients present unspecific signs and symptoms, but nevertheless require specialized assessment [1,2]. Our results show that almost 65% of patients were diagnosed with one or more rheumatological conditions before the correct diagnosis, the higher incidence reported in the literature [3,13,34]. Gender did not seem to impact in the occurrence of wrong diagnoses.…”

Section: Discussionsupporting

confidence: 41%

“…FD patients are commonly misdiagnosed [3,4]. Incorrect diagnoses are often related to rheumatologic conditions, since patients may present with different rheumatic and immune-mediated manifestations [5][6][7][8][9][10][11][12][13]. Inappropriate diagnosis may lead to improper therapies and delay in FD recognition and adequate treatment initiation, thus hampering prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

Neto¹,

Bento²,

Pereira³

2020

Adv Rheumatol

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Background: Fabry disease (FD) is an X-linked lysosomal disorder due to mutations in the GLA gene resulting in defective enzyme alpha-galactosidase A. FD patients are frequently misdiagnosed, commonly for rheumatic diseases. Determining pathogenicity of a mutation depends of in silico predictions but mostly on available clinical information and interpretation may change in light of evolving knowledge. Similar signs and symptoms in carriers of GLA gene genetic variants of unknown significance or of benign variants may hamper diagnosis. This study reviews rheumatic and immune-mediated manifestations in a cohort of Brazilian FD patients with classic mutations and also in subjects with GLA gene A143T and R118C mutations. Misdiagnoses, time to correct diagnosis or determination of GLA gene status, time to treatment initiation and reasons for treatment prescription in A143T and R118C subjects are reviewed. Methods: Genotype confirmed classic FD patients (n = 37) and subjects with GLA gene mutations A143T and R118C (n = 19) were referred for assessment. Subjects with R118C and A143T mutations had been previously identified during screening procedures at hemodialysis units. All patients were interviewed and examined by a rheumatologist with previous knowledge of disease and/or mutation status. A structured tool developed by the authors was used to cover all aspects of FD and of common rheumatic conditions. All available laboratory and imaging data were reviewed. Results: Thirty-seven consecutive FD patients were interviewed-16 male / 21 female (mean age: 43.1 years) and 19 consecutive subjects with GLA gene mutations R118C and A143T were evaluated-8 male / 11 female (mean age: 39.6 years); 15 [R118C] / 4 [A143T]. Misdiagnosis in FD patients occurred in 11 males (68.8%) and 13 females (61.9%) of which 10 males and 9 females were previously diagnosed with one or more rheumatic conditions, most frequently rheumatic fever or "rheumatism" (unspecified rheumatic disorder). Median time for diagnosis after symptom onset was 16 years (range, 0-52 years). Twenty-two patients were treated with enzyme replacement therapy (ERT)-13 male and 9 female. Median time to ERT initiation after FD diagnosis was 0.5 years (range, 0-15 years). Rheumatic manifestations occurred in 68.4% of R118C and A143T subjects. Two subjects had been prescribed ERT because of renal disease [R118C] and neuropsychiatric symptoms [A143T]. Conclusion: Misdiagnoses occurred in 64.8% of FD patients, most frequently for rheumatic conditions. Median time for correct diagnosis was 16 years. Rheumatic manifestations are also frequent in subjects with GLA gene R118C and A143T mutations. These results reinforce the need to raise awareness and increase knowledge about Fabry disease among physicians, notably rheumatologists, who definitely have a role in identifying patients and determining disease burden. Decision to start treatment should consider expert opinion and follow local guidelines.

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Section: Discussionsupporting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

Neto¹,

Bento²,

Pereira³

2020

Adv Rheumatol

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“…Moiseev i wsp. [6] podają, że 28/107 pacjentów z FD do czasu prawidłowej diagnozy przez wiele lat rozpoznawano chorobę reumatologiczną [6]. Typowe dla FD zmiany skórne zostały zignorowane przez dermatologów.…”

Section: Omówienieunclassified

Choroba Fabry’ego — długa droga do prawidłowego rozpoznania u 43-letniego chorego „Dr Google” nie zawsze taki zły...

Ciba-Stemplewska

Krzos²,

Wożakowska−Kapłon

2020

Folia Cardiologica

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“…More specifically, in Gaucher disease, bone marrow infiltration with histiocytes causes acute attacks of pain, which may be mistaken for arthritis in the vicinity of a joint [5,8]. In Fabry disease, episodes of neuropathic pain in hands, feet, wrists, ankles (acroparesthesias), often associated with fever, malaise and elevated inflammation markers, can mimic a rheumatic condition, such as an inflammatory arthritis [3,9]. Finally, joint stiffness and contractures are characteristic for some types of MPS, the so called "attenuated" forms like Hurler-Scheie syndrome, which have a less severe presentation and progress silently over the years, making the diagnosis a challenge [3,10,11].…”

Section: Introductionmentioning

confidence: 99%

Beyond the guidelines management of juvenile idiopathic arthritis: a case report of a girl with polyarticular disease refractory to multiple treatment options and Leri Weill syndrome

et al. 2021

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Background The last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities. Case presentation We report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung’s deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome. Conclusions This case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.

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What rheumatologist should know about Fabry disease

Cited by 14 publications

References 4 publications

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients

Choroba Fabry’ego — długa droga do prawidłowego rozpoznania u 43-letniego chorego „Dr Google” nie zawsze taki zły...

Beyond the guidelines management of juvenile idiopathic arthritis: a case report of a girl with polyarticular disease refractory to multiple treatment options and Leri Weill syndrome

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