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Idiopathic Pyoderma Gangrenosum: Successful Resolution with Infliximab Therapy and Pro-inflammatory Cytokines Assessment

of primary idiopathic forms is reached following the exclusion of inflammatory bowel disease (IBD), rheuma-tic disorders, monoclonal gammopathy and solid tumours (1, 2). Treatment is generally based on corticosteroid and immunosuppressive therapy; however, the recent use of biological drugs has shown their effectiveness.CASE REPORT

Systemic lupus erythematosus occurring in a patient with Niemann-Pick type B disease.

Niemann–Pick disease is an inherited lipid storage disorder caused by the deficiency of acid sphingomyelinase, which results in accumulation of sphingomyelin within cells of several organs and consequent tissue damage. The broad clinical spectrum of this disorder may overlap with that of systemic lupus erythematosus, hindering differential diagnosis. Herein, we report the case of a patient affected by Niemann–Pick type B disease intertwined with clinical and serological features of systemic lupus erythematosus. Two novel mutations in the SMPD1 gene were found in compound heterozygosity: p.A36V and IVS2 + 8 T > G.

Systemic reactive (AA) amyloidosis in the course of common variable immunodeficiency.

Patients with primary immunodeficiencies (PID) are currently at low risk for the development of systemic reactive AA amyloidosis. A patient with common variable immunodeficiency and nephrotic syndrome was referred to our Clinic from a Nephrology unit. She had a history of recurrent infections. Monthly intramuscular immunoglobulin substitution treatment was started in 1979, subsequently switched to intravenous route. Between 1984 and 2007, she continued to experience infections and did not have follow-up visits in an Immunology Centre. Replacement therapy was discontinued in 2008 for adverse events related to IVIG infusion; since then she was admitted for recurrent cellulitis, sepsis, and pneumonia. In 2009, the patient developed massive proteinuria and renal failure due to clinically overt reactive systemic AA amyloidosis. Despite the prompt resumption of antibody replacement, adequate IgG levels were not achieved and SAA concentration remained elevated. Delay in diagnosis and inadequate treatment of PIDs results in increased irreversible complications, including AA amyloidosis. Introduction: The primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders that affect the cells and proteins of the immune system. Defects in antibody production are the most common type, comprising about 60% of the primary immunodeficiencies encountered in practice. Patients with predominantly antibody deficiencies, such as common variable immunodeficiency (CVID), are recognized to have immunodeficiency in the second, third, or fourth decade of life, after they have had several bouts of pneumonia; however, children and older adults may be affected. The diagnosis is defined by the severe reduction of at least two immunoglobulin isotypes, a poor response to vaccination, the onset after the second year of life, and the exclusion of defined differential diagnosis [1]. Approximately, 50% of patients have autoimmune manifestations and there is an increased risk of malignancy. In recent years, the first monogenic defects have been identified in ICOS, TACI, CD19, BAFF-R [2]. The mainstay of treatment in CVID is lifelong replacement of antibody, today achieved by either intravenous (IVIG) or subcutaneous (s.c.) route of immunoglobulin (Ig), usually in doses of 0.4–0.6 g/ kg body weight a month. When treated with replacement therapy in appropriate doses there is a significant reduction in incidence of infections. Patients with PIDs are currently at low risk for the development of systemic reactive AA amyloidosis. Methods: A 66-year-old patient with CVID and nephrotic syndrome was referred to our Clinic from a Nephrology unit. She had been diagnosed at the age of 31 years as having severe hypogammaglobulinemia, presenting with a history of recurrent sinupulmonary infections, otitis, and diarrhea due to gastrointestinal infections and giardiasis. At that time, she had no evidence of proteinuria or renal impairment and secondary causes of hypogammaglobulinemia were excluded as well. Monthly intramuscular immunoglobulin substitution treatment was started in 1979. Dose had been increased over the 3 years following and subsequently she was switched from this route of administration to intravenous infusion. Between 1984 and 2007, the patient experienced relapsing infections (mainly of sinuses, lung and bladder) and did not have followup visits in an Immunology Centre. Replacement therapy without accomplishing adequate IgG trough levels was discontinued in 2008 for moderate adverse events (malaise, fever, flushing, and anaphylactoid symptoms) related to IVIG infusion. Since then, she required hospitalization for recurrent cellulitis of lower extremities, sepsis and multiple episodes of pneumonia. In early 2009, patient developed massive proteinuria (exceeding 20 g/24 h) and renal failure due to clinically overt reactive systemic AA amyloidosis. A kidney biopsy was performed on 25 March 2009, and histological examination of specimen revealed eosinophilic material infiltrating the mesangium and vessel walls. This material stained positively with Congo red, and the deposits showed intense apple-green birefringence under polarized light, consistent with the presence of amyloid. On immunohistochemistry, the amyloid deposits were intensively and specifically stained with anti-amyloid A antibody and were negative for other amyloidogenic proteins which are known to target the kidney. On admission to our hospital in July 2009, laboratory data included IgG 0 mg/dl (694–1618), and IgA 1 mg/dl (48–271,) but normal IgM. Total protein was 3.9 g/dl, albumin was 1.68 g/dl (normal 3.2–5.35), and proteinuria 4.3 g/24 h with significant loss of polyclonal IgG on urine immunofixation electrophoresis (Figure 1). Serum amyloid A (SAA) concentration was 45.1 mg/l (normal 56.8). We confirmed diagnosis of CVID complicated by AA amyloidosis and promptly started high-dose IVIG (using premedication with acetaminophen, steroids, and antihistamines) and intravenous antibiotics to treat urinary tract infection and recurrence of 214

SWITCH TO ICATIBANT IN A PATIENT AFFECTED BY HEREDITARY ANGIOEDEMA WITH HIGH DISEASE ACTIVITY: A CASE REPORT

Icatibant, an antagonist of the bradykinin B2 receptor, was approved for the treatment of acute attacks of hereditary angioedema in the EU in 2008. This paper presents the case of a 65-year-old woman affected by frequent acute attacks of hereditary angioedema who benefitted from a change of therapy to icatibant, following years of treatment with C1-inhibitor.