[Show abstract][Hide abstract] ABSTRACT: Objective:
We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study.
In this study, 123 patients with MDS and SIADs were analysed.
Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5).
The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.
[Show abstract][Hide abstract] ABSTRACT: Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15 % and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.
Rheumatology International 10/2014; 35(6). DOI:10.1007/s00296-014-3162-4 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Peripheral cytopenias are common in systemic lupus erythematosus (SLE), but bone marrow involvement is rarely reported. Myelofibrosis is a rare disorder characterized by reticulin fibrosis of the bone marrow, which usually occurs in response to clonal proliferation of hematopoietic stem cells in myeloproliferative disorders. However, bone marrow fibrosis has also been described in association with auto-immune diseases, especially SLE.
We will report here a new case of bone marrow fibrosis associated with SLE. We also reviewed the 27 cases published in the English language literature, and will discuss the clinical presentation, outcome, treatment, and pathophysiology of bone marrow fibrosis occurring in association with SLE.
Over one half of patients were diagnosed concomitantly with bone marrow fibrosis and SLE. Epidemiological, clinical and biological features of lupus were unremarkable. Except for the presence of reticulin fibrosis, the findings from the bone marrow biopsies proved highly variable. Overall mortality was about 14% but corticosteroid-based therapy lead to clinical improvement and reverted bone marrow fibrosis in most cases. Data on the usefulness of other immunomodulatory therapies are inconclusive.
SLE may be complicated by bone marrow involvement, of a likely autoimmune origin. Bone marrow fibrosis occurring with SLE is probably similar to “primary autoimmune myelofibrosis” and may respond to steroid and immunomodulatory therapies. Further studies with standardised proofreading of bone marrow aspirations and biopsies are needed to delineate the clinical and biological features of this rare complication of SLE.
[Show abstract][Hide abstract] ABSTRACT: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by diffuse cartilage involvement, especially those of the respiratory tract, leading to potentially life threatening complications. Corticosteroids remain the first-line empirical therapy. Immunosuppressive drugs such as azathioprine, cyclophosphamide and tumor necrosis factor blockers (anti-TNFα) are commonly used as second-line therapy with varying degrees of success.
We report a 40-year-old man with severe RP for whom conventional therapy and immunosuppressive treatments were ineffective. Prolonged clinical remission was obtained after introduction of the anti-interleukin-6 receptor antibody (tocilizumab), which was perfectly tolerated and allowed to taper steroids and methotrexate to a very low dosage.
Our patient is the fifth published one documenting the efficacy of tocilizumab in severe refractory RP, which strengthens the use of anti-IL-6 in that indication.
La Revue de Médecine Interne 09/2013; 35(3). DOI:10.1016/j.revmed.2013.02.019 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in 1 or more organs. Gastrointestinal manifestations of systemic mastocytosis have been previously studied in small cohorts of patients, and no specific histologic description is available.
We sought to assess the clinical and pathologic features of gastrointestinal manifestations in patients with mastocytosis.
Medical history and gastrointestinal symptoms of patients with mastocytosis (n = 83) were compared with those of matched healthy subjects (n = 83) by means of patient questionnaire. Data were analyzed for epidemiologic, clinical, biological, and genetic factors associated with gastrointestinal symptoms for patients with mastocytosis. A comparative analysis of gastrointestinal histology from patients with mastocytosis (n = 23), control subjects with inflammatory bowel disease (n = 17), and healthy subjects (n = 19) was performed.
The following gastrointestinal symptoms occurred more frequently and were more severe in patients with mastocytosis than in healthy subjects: bloating (33% vs 7.2%, P < .0001), abdominal pain (27.3% vs 4.8%, P < .0001), nausea (23% vs 8.4%, P = .02), and diarrhea (33.85% vs 1.2%, P < .0001). Patients with mastocytosis had a significantly higher incidence of personal history of duodenal ulcer (P = .02). Wild-type (WT) c-Kit was associated with diarrhea (P = .03). Specific histologic lesions were present in patients with mastocytosis but were not correlated with clinical symptoms.
Gastrointestinal manifestations in patients with mastocytosis are highly prevalent and often severe. Clinical symptoms do not correspond to histologic findings, are nonspecific, and can simulate irritable bowel syndrome.
The Journal of allergy and clinical immunology 07/2013; 132(4). DOI:10.1016/j.jaci.2013.05.026 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: TNFRSF1A is involved in an autosomal dominant autoinflammatory disorder called TNFR-associated periodic syndrome (TRAPS). Most TNFRSF1A mutations are missense changes and, apart from those affecting conserved cysteines, their deleterious effect remains often questionable. This is especially true for the frequent R92Q mutation, which might not be responsible for TRAPS per se but represents a susceptibility factor to multifactorial inflammatory disorders. This study investigates TRAPS pathophysiology in a family exceptional by its size (13 members) and compares the consequences of several mutations affecting arginine 92.
TNFRSF1A screening was performed by PCR-sequencing. Comparison of the 3-dimensional structure and electrostatic properties of wild-type and mutated TNFR1 proteins was performed by in silico homology modeling. TNFR1 expression was assessed by FACS analysis, western blotting and ELISA in lysates and supernatants of HEK293T cells transiently expressing wild-type and mutated TNFR1.
A TNFRSF1A heterozygous missense mutation, R92W (c.361C>T), was shown to perfectly segregate with typical TRAPS manifestations within the family investigated (p<5.10(-4)). It was associated with very high disease penetrance (0.9). Prediction of its impact on the protein structure revealed local conformational changes and alterations of the receptor electrostatic properties. R92W also impairs the TNFR1 expression at the cell surface and the levels of soluble receptor. Similar results were obtained with R92P, another mutation previously identified in a very small familial form with incomplete penetrance and variable expressivity. In contrast, TNFR1-R92Q behaves like the wild-type receptor.
These data demonstrate the pathogenicity of a mutation affecting arginine 92, a residue whose involvement in inflammatory disorders is deeply debated. Combined with previous reports on arginine 92 mutations, this study discloses an unusual situation in which different amino acid substitutions at the same position in the protein are associated with a clinical spectrum bridging Mendelian to multifactorial conditions.
PLoS ONE 07/2013; 8(7):e69757. DOI:10.1371/journal.pone.0069757 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.
Medicine 03/2013; 92(2):61-68. DOI:10.1097/MD.0b013e318288925c · 5.72 Impact Factor