Sara Simeoni

In chronic idiopathic urticaria autoantibodies against FcεRII/CD23 induce histamine release via eosinophil activation

Background Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto‐antibodies (Abs) directed against either the α subunit of the high‐affinity IgE receptor or the IgE molecule in nearly half of the patients.

Reactive arthritis following BCG immunotherapy for urinary bladder carcinoma: a systematic review

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is used with efficacy and safety in the treatment of patients with intermediate and high-risk superficial bladder carcinoma. Arthralgia and/or arthritis is one of the rare severe complications following intravesical BCG immunotherapy. We searched MEDLINE in order to analyze the frequency of this clinical complication, its pathogenesis and outcome. The electronic search was conducted using the following key words: “BCG immunotherapy” and “Arthritis, arthralgias and BCG immunotherapy”. At the end of a process of abstract analysis, 48 papers were included in the systematic review. All the selected papers, except one that was a clinical review, described at least one case of arthritis after BCG therapy. The BCG immunotherapy resulted to be safe and efficacious in the treatment of bladder cancer; the development of reactive arthritis is rare and can evolve in a chronic process. The review of the literature highlighted that reactive arthritis following BCG intravesical instillation is a complication usually well controlled with the discontinuation of the immunotherapy and nonsteroidal anti-inflammatory drugs (NSAIDs) treatment. Only a small portion of patients with a particular genetic background will develop a chronic process.

Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: a possible explanation for the lack of efficacy of hrDNase I treatment

The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I <7.79 ng ml(-1) are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.

Endothelin‐1 serum levels correlate with MCP‐1 but not with homocysteine plasma concentration in patients with systemic sclerosis

Objectives: To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin‐1 (ET‐1) and monocyte chemoattractant protein‐1 and ‐3 (MCP‐1, MCP‐3), in patients with systemic sclerosis (SSc). Methods: Eighty‐two patients were enrolled in this study; the control group included 75 age‐ and sex‐matched subjects. Plasma Hcy was determined by high‐performance liquid chromatography; folic acid, and vitamin B12 plasma levels were determined by a chemiluminescence method. ET‐1, MCP‐1, and MCP‐3 were determined by enzyme‐linked immunosorbent assay (ELISA). Analysis of the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme HinfI. Results: Hcy levels were lower in patients whereas ET‐1 was significantly higher in patients and correlated with MCP‐1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET‐1, MCP‐1, and MCP‐3. Patients with diffuse disease presented the highest levels of ET‐1 and MCP‐1. The distribution of the MTHFR genotypes was not different in patients and controls. Conclusions: In SSc, Hcy plasma concentration does not influence ET‐1, MCP‐1, or MCP‐3 levels. On the contrary, ET‐1, a marker of vascular activation, correlates with MCP‐1, a chemokine involved in the fibrotic process of SSc.

Schnitzler's syndrome treated successfully with intravenous pulse cyclophosphamide

Schnitzlers syndrome is a rare clinical condition characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and monoclonal immunoglobulin M (IgM) gammopathy. Here we describe the case of a 48‐year‐old Italian female with a long history of arthralgia, leucocytosis, spiking fever, and chronic urticaria with severe pruritus. The IgM‐κ monoclonal component in the serum and bone densification on conventional X‐ray with hyperfixation on bone technetium scanning at the distal part of the femurs and at the proximal part of the tibias were detected 4 years after the onset of the symptoms. After many ineffective treatments, the use of pulse cyclophosphamide (CPX) resulted in complete remission of the disease that is still lasting after a 2‐year follow‐up.

Reactive arthritis following BCG immunotherapy for bladder carcinoma

Intravesical instillation of bacillus Calmette-Guérin (BCG) is used in the treatment of patients with intermediate and high-risk superficial bladder carcinoma with efficacy and safety. The vast majority of patients do not present any side effects and only 5% of patients have mild and short-lived clinical manifestations such as malaise, low-grade fever, cystitis, and hematuria. Arthralgia and/or arthritis is one of the rare severe complications following intravesical BCG immunotherapy. We report here the case of a patient with reactive arthritis successfully treated with nonsteroidal anti-inflammatory drugs (NSAIDs) after the discontinuation of BCG immunotherapy.

Leprosy initially misdiagnosed as sarcoidosis, adult-onset still disease, or autoinflammatory disease.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. We describe the case of a 20-year-old man from India living in Italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. He also had episodes of high fever, polyarthritis, and episcleritis. Sarcoidosis was suspected on the basis of elevated angiotensin-converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about a year. A flare of the disease occurred each time corticosteroid was tapered or suspended. An autoinflammatory disease was then suspected and treated with immunosuppressant. Only the third deep skin biopsy revealed the presence of M. leprae. The lack of clinical suspicion and the unfamiliarity with the histology of leprosy delayed diagnosis and treatment. Leprosy should be considered in the differential diagnoses of patients presenting with rheumatic and cutaneous manifestations especially when they come from countries where the disease is endemic.

Dermatomyositis complicated with Kaposi sarcoma: A case report

We describe the case of a 75-year-old Italian woman affected by dermatomyositis (DM) treated with steroid, high-dose intravenous immunoglobulins (IVIgs) and cyclophosphamide (CPX), taken orally. After a few months, the patient presented multiple red vascular skin lesions diagnosed as Kaposi sarcoma (KS). Steroid was furtherly reduced, and CPX was stopped. We put the patient on chemotherapy with intravenous infusion of vinblastine and vincristine on alternate weeks obtaining the remission of KS. DM is well controlled by a low-dosage steroid and high-dose IVIgs.