Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis.

Background: Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis. For this reason, in patients with an initial clinical suspicion of Gaucher disease, we aimed to carry out a parallel screening of acid sphingomyelinase and glucocerebrosidase. Methods: Peripheral blood samples of 627 patients were collected, and enzymatic activity analysis was performed on both glucocerebrosidase and acid sphingomyelinase. The specific gene was studied in samples with null or reduced enzymatic activity. Specific molecular biomarkers helped to achieve the correct diagnosis. Results: In 98.7% of patients, normal values of glucocerebrosidase activity excluded Gaucher disease. In 8 of 627 patients (1.3%), the glucocerebrosidase enzymatic activity assay was below the normal range, so genetic GBA1 analysis confirmed the enzymatic defect. Three patients (0.5%) had normal glucocerebrosidase activity, so they were not affected by Gaucher disease, and showed decreased acid sphingomyelinase activity. SMPD1 gene mutations responsible for Acid Sphingomyelinase Deficiency were found. The levels of specific biomarkers found in these patients further strengthened the genetic data. Conclusions: Our results suggest that in the presence of typical signs and symptoms of Gaucher disease, Acid Sphingomyelinase Deficiency should be considered. For this reason, the presence of hepatosplenomegaly, thrombocytopenia, leukocytopenia, and anemia should alert clinicians to analyze both enzymes by a combined screening. Today, enzyme replacement therapy is available for the treatment of both pathologies; therefore, prompt diagnosis is essential for patients to start accurate treatment and to avoid diagnostic delay.

Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy: paradoxical complication of treatment of bone lesions in multiple myeloma patients.

It has been demonstrated that bisphosphonate-based supportive therapy (pamidronate or zoledronate) reduces skeletal events (onset or progression of osteolytic lesions) both in patients with multiple myeloma (MM) and in cancer patients with bone metastasis. Bisphosphonates (eg, alendronate) are also indicated in the treatment of osteoporosis. Nevertheless, osteonecrosis of the jaw (ONJ) has been reported in some patients being treated with bisphosphonates. We present a series of 9 MM patients who developed ONJ after treatment with bisphosphonates and chemotherapy. All the patients in this case series had undergone tooth extraction for recurrent dental abscesses while taking bisphosphonates. We also review the diagnostic and therapeutic implications of this paradoxical complication associated with treatment of bone lesions in MM.

Mycosis fungoides/Sézary syndrome: a report of three cases treated with Campath-1H as salvage treatment.

We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three patients with advanced mycosis fungoides/Sézary syndrome who had previously been treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42 and 68 yr, respectively, were heavily pretreated (more than three prior therapy regimens, including autologous transplant in case 2) and refractory to conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids. Campath-1H was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of 1080, 223, and 480 mg, respectively. The patients with Sézary syndrome (case 2 and case 3) showed clearance of circulating Sézary cells and clinical improvement of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3) completed the treatment (12 and 6 wk) without significant toxicity, the former achieving a partial response and the latter a clinical complete response. The patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly achieved a clinical improvement of the Sézary syndrome, but he died because of a myocardial infarction after 3 wk of treatment. Our report shows that the treatment with Campath-1H is active even in patients with advanced refractory mycosis fungoides/Sézary syndrome. Further clinical observations on a larger cohort of patients are needed to establish if Campath-1H may have a role as first line therapy in addition to conventional therapy including chemotherapy.