Azacitidine-induced pyoderma gangrenosum at injection sites in a patient with myelodysplastic syndrome.

Pyoderma gangrenosum (pg) is a rare neutrophilic dermatosis characterized by painful necrotic ulceration affecting preferentially the lower extremities. Diagnosis is challenging, and a thorough workup (including biopsy) is required. In this case report, we describe a 67-year-old patient with a diagnosis of myelodysplastic syndrome (mds) who developed fever and pg two days after the first cycle of subcutaneous azacitidine (Vidaza; Celgene Corporation, Summit, NJ, USA). On physical examination, the patient had four erythematous plaques at sites of subcutaneous injections of azacitidine on the arms, as well as three other plaques in proximity. A skin biopsy demonstrated a dense neutrophilic interstitial infiltrate in the dermis. After the diagnosis of pg, prednisone 1 mg/kg was started and the fever subsided rapidly. This was followed by the resolution of the cutaneous lesions. Changing the route of administration of azacitidine from subcutaneous to intravenous and adding a daily dose of prednisone during the treatment allowed the patient to receive a total of 10 cycles of azacitidine. This is the second case reported in the literature. Because azacitidine is frequently used in mds and acute myeloid leukemia, clinicians should be aware of this rare cutaneous adverse event. Our approach can be used to avoid the recurrence of pg when continuing azacitidine treatment.

A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodies at the synovial level in patients with rheumatoid arthritis.

BACKGROUND: Several studies have confirmed that galectin-1 (Gal-1) plays a role in controlling the immune response because of its pro-apoptotic effect. Although studies based on a rheumatoid arthritis (RA) mouse model have suggested a crucial role for Gal-1 in inflammation, clinical data are lacking. We have detected the presence of autoantibodies against galectins in blood, but their physiological meaning remains unknown. OBJECTIVES: To compare plasma and synovial levels of Gal-1 in RA patients and in healthy controls, and correlate them with clinical parameters. METHODS: Plasma and synovial (non-arthritic knee effusion) samples were collected from RA patients and healthy donors. All patients were receiving treatment with steroids and/or disease-modifying anti-rheumatic drugs (DMARDs). A blood sample was taken at a baseline visit to determine plasma anti-cyclic citrullinated peptide (anti-CCP) antibodies, tumour necrosis factor alpha (TNF-α), Gal-1, and anti-Gal-1 autoantibodies. RESULTS: Although plasma levels of Gal-1 were similar in patients and controls, the concentration of Gal-1 was significantly reduced in the synovial fluid of patients with RA. This reduction was not correlated with TNF-α or C-reactive protein (CRP) levels. However, the decrease in synovial Gal-1 correlated with a significant increase in anti-Gal-1 autoantibodies and anti-CCP antibody titres, suggesting a physiological effect of autoantibodies limiting the amount Gal-1 and potentially blocking its biological effect in RA patients. CONCLUSION: Gal-1 levels were significant reduced at the synovial level in RA patients, possibly as a consequence of the increase in anti-Gal-1 autoantibodies.

Percepción de la sexualidad en pacientes con enfermedades reumáticas: estudio piloto de casos y controles / Perception of sexuality in women with rheumatic disease: case-control pilot study

Introducción: Las enfermedades reumáticas se caracterizan por ser problemas inflamatorios crónicos con afección sistémica que frecuentemente se acompañan de limitación funcional y depresión. Su repercusión sobre la respuesta sexual ha sido pobremente estudiada. El objetivo del presente estudio fue evaluar la percepción sexual en mujeres con enfermedad reumática. Pacientes y métodos: Se aplicó un cuestionario que, además de incluir datos generales, aspectos socioeconómicos, características de la enfermedad y marcadores serológicos de inflamación, midió la percepción de la sexualidad por parte de los sujetos, rasgos de depresión y el nivel de autoestima de éstos. Resultados: Se entrevistó a 16 pacientes, 9 de las cuales tenían artritis reumatoide (AR), 6 lupus eritematoso sistémico (LES), 1 artritis psoriásica. Se seleccionó a 25 mujeres sanas como grupo control. Todas las pacientes recibían tratamiento y presentaban una clase funcional que les permitía valerse por sí mismas. Las pacientes presentaron una peor percepción de la sexualidad (p = 0,001), tendiendo a presentar más rasgos de depresión y una menor autoestima que el grupo control. Conclusiones: Los pacientes con enfermedades reumáticas se benefician del tratamiento, al ser éste un adyuvante en su calidad de vida y en su funcionalidad. La percepción de la sexualidad se afecta como parte de la enfermedad inflamatoria crónica, pero es independiente de la clase funcional del paciente(AU)

Introduction: Rheumatic diseases are characterized by chronic inflammation with systemic involvement and are often accompanied by functional limitation and depression. Their effect on sexual response has been little studied. The objective of the present study was to evaluate perception of sexuality in women with rheumatic disease. Patients and methods: We administered a questionnaire that included general data, socioeconomic aspects, disease characteristics, serum markers of inflammation and measured perception of sexuality, depression traits and self-esteem. Results: Sixteen patients were interviewed, of which nine had rheumatoid arthritis, six had systemic lupus erythematosus and one had psoriatic arthritis. Twentyfive women were selected as controls. All patients were receiving treatment and had a functional class that allowed them to be self-dependent. Patients presented a worse perception of sexuality than controls (p = 0.001) with a trend to more depressive traits and lower self-esteem. Conclusions: Patients with rheumatic disease gain benefits from treatment in terms of quality of life and functionality. Perception of sexuality is affected by chronic inflammatory disease but is independent of the patient’s functional class(AU)

[Perception of sexuality in women with rheumatic disease: case-control pilot study]. / Percepción de la sexualidad en pacientes con enfermedades reumáticas: estudio piloto de casos y controles.

INTRODUCTION: Rheumatic diseases are characterized by chronic inflammation with systemic involvement and are often accompanied by functional limitation and depression. Their effect on sexual response has been little studied. The objective of the present study was to evaluate perception of sexuality in women with rheumatic disease. PATIENTS AND METHODS: We administered a questionnaire that included general data, socioeconomic aspects, disease characteristics, serum markers of inflammation and measured perception of sexuality, depression traits and self-esteem. RESULTS: Sixteen patients were interviewed, of which nine had rheumatoid arthritis, six had systemic lupus erythematosus and one had psoriatic arthritis. Twentyfive women were selected as controls. All patients were receiving treatment and had a functional class that allowed them to be self-dependent. Patients presented a worse perception of sexuality than controls (p=0.001) with a trend to more depressive traits and lower self-esteem. CONCLUSIONS: Patients with rheumatic disease gain benefits from treatment in terms of quality of life and functionality. Perception of sexuality is affected by chronic inflammatory disease but is independent of the patient's functional class.

[Interferon beta-1b (Betaferon)therapy in patients with relapsing-remitting multiple sclerosis: findings of a prospective, multi-center study of disease progression]. / Interferon beta-1b (Betaferon) bei Patienten mit schubförmig-remittierender Multipler Sklerose. Ergebnisse einer prospektiven, multizentrischen Verlaufsbeobachtung.

In a survey of disease course, the efficacy and tolerability of 24-month interferon beta-1b therapy for relapsing remitting multiple sclerosis (RRMS) were evaluated in 410 patients. The investigation aimed at obtaining data from general practice and of possibly unknown, unexpected adverse reactions. In the 241 patients still on therapy, efficacy was rated after 24 months as "good" or "very good" in 75% of cases. After 24 months, 36.9% of the patients had no exacerbation (baseline 0.3%). Annual exacerbation rates dropped from 1.5 before treatment to 0.7 in the second treatment year. In the 2 years before treatment, 66.2% had worsened by at least 0.5 points on the extended disability status scale (EDSS). This proportion was reduced to 41.2% after 2 years of treatment. The safety profile corresponded to results from controlled trials. This postmarketing survey supports data from the published controlled interferon beta-1b studies and confirms the main effects of this therapy under routine conditions in general practice.

Production of high affinity autoantibodies in autoimmune New Zealand Black/New Zealand white F1 mice targeted with an anti-DNA heavy chain.

Lupus-prone, anti-DNA, heavy (H) chain "knock-in" mice were obtained by backcrossing C57BL/6 mice, targeted with a rearranged H chain from a VH11(S107)-encoded anti-DNA hybridoma (D42), onto the autoimmune genetic background of New Zealand Black/New Zealand White (NZB/NZW) F1 mice. The targeted female mice developed typical lupus serologic manifestations, with the appearance of transgenic IgM anti-DNA autoantibodies at a young age (2-3 mo) and high affinity, somatically mutated IgM and IgG anti-DNA Abs at a later age (6-7 mo). However, they did not develop clinical, lupus-associated glomerulonephritis and survived to at least 18 mo of age. L chain analysis of transgenic anti-DNA Abs derived from diseased NZB/NZW mouse hybridomas showed a very restricted repertoire of Vkappa utilization, different from that of nonautoimmune (C57BL/6 x BALB/c)F1 transgenic anti-DNA Abs. Strikingly, a single L chain was repetitively selected by most anti-DNA, transgenic NZB/NZW B cells to pair with the targeted H chain. This L chain had the same Vkappa-Jkappa rearrangement as that expressed by the original anti-DNA D42 hybridoma. These findings indicate that the kinetics of the autoimmune serologic manifestations are similar in wild-type and transgenic lupus-prone NZB/NZW F1 mice and suggest that the breakdown of immunologic tolerance in these mice is associated with the preferential expansion and activation of B cell clones expressing high affinity anti-DNA H/L receptor combinations.

B cell deletion, anergy, and receptor editing in "knock in" mice targeted with a germline-encoded or somatically mutated anti-DNA heavy chain.

To study the relative contributions of clonal deletion, clonal anergy, and receptor editing to tolerance induction in autoreactive B cells and their dependence on B cell receptor affinity, we have constructed "knock in" mice in which germline encoded or somatically mutated, rearranged anti-DNA heavy (H) chains were targeted to the H chain locus of the mouse. The targeted H chains were expressed on the vast majority of bone marrow (BM) and splenic B cells and were capable of Ig class switching and the acquisition of somatic mutations. A quantitative analysis of B cell populations in the BM as well as of Jkappa utilization and DNA binding of hybridoma Abs suggested that immature B cell deletion and light (L) chain editing were the major mechanisms affecting tolerance. Unexpectedly, these mechanisms were less effective in targeted mice expressing the somatically mutated, anti-DNA H chain than in mice expressing the germline-encoded H chain, possibly due to the greater abundance of high affinity, anti-DNA immature B cells in the BM. Consequently, autoreactive B cells that showed features of clonal anergy could be recovered in the periphery of these mice. Our results suggest that clonal deletion and receptor editing are interrelated mechanisms that act in concert to eliminate autoreactive B cells from the immune system. Clonal anergy may serve as a back-up mechanism for central tolerance, or it may represent an intermediate step in clonal deletion.

Primary cutaneous pleomorphic small T-cell lymphoma. A review of 11 cases. The French Study Group on Cutaneous Lymphomas.

BACKGROUND AND DESIGN: Cutaneous pleomorphic small T-cell lymphoma is a rare, recently recognized lymphoma, different from mycosis fungoides and Sézary syndrome. Only a few cases have been reported and no treatment modalities have been defined. We reviewed the clinical, histologic, immunohistochemical, molecular biologic, and follow-up data of 11 primary cutaneous pleomorphic small T-cell lymphomas. RESULTS: The lesions presented as red purplish nodules, tumors, or plaques. The infiltrate consisted of small pleomorphic lymphoid cells without epidermotropism in nine patients and with a propensity to infiltrate the dermis and subcutaneous fat. Most cases were CD4+/CD8-. A T-cell clone was detected in the skin lesions of nine patients tested. The mean follow-up was 70.1 months and the median follow-up was 20 months. Ten patients are alive with three having persistent lesions. Interferon alfa-2a induced partial or complete remissions in five patients. Interferon alfa-2a combined with a regimen containing doxorubicin chlorhydrate induced a complete remission in a patient suffering a relapse after cyclophosphamide and interferon alone. CONCLUSIONS: Cutaneous pleomorphic small T-cell lymphoma is a well-defined type of low-grade cutaneous lymphoma with favorable prognosis. Interferon and/or chemotherapy are the treatment of choice in patients with large tumor burden.

Prolidase deficiency: a multisystemic hereditary disorder.

Prolidase deficiency is a rare hereditary disorder with a wide spectrum of clinical manifestations including skin ulcers, eczematous eruptions, characteristic facies, mental retardation, splenomegaly, and susceptibility to infections. We report two new cases of prolidase deficiency. Our patients had the typical manifestations of prolidase deficiency. One also had lupus erythematosus. Prolidase activity was either normal or half-normal in all family members. The skin disease in our patients did not respond to topical glycine/proline ointment or to oral vitamin C.