Zachary Spigelman

A reappraisal of Gaucher disease-diagnosis and disease management algorithms.

Type 1 (non-neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of Type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and nonspecific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease.

Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease

Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.

First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up ☆ ☆☆

BACKGROUND Conventional therapy for pemphigus vulgaris (PV) consists of high-dose systemic corticosteroids (CS) and immunosuppressive agents (ISA). This combination may be ineffective, cause serious adverse events or relapses in some patients. OBJECTIVE To determine if the combination of intravenous immunoglobulin (IVIg) therapy and rituximab (RTX) can be used as first-line therapy in PV patients in whom systemic CS and ISA are contraindicated and evaluate its ability to produce long-term sustained remissions. METHOD This a retrospective study of five male and five female patients (mean age 47.87 years). RTX was administered once weekly for eight consecutive weeks, followed by once monthly for four months (dose 375 mg/m(2)). Since CD20(+) B cells were undetectable, IVIg was infused until they reached normal levels (dose 2 g/kg/cycle). IVIg was then continued according to published protocol. RESULTS Initial clinical response and complete disease resolution occurred in a mean of 3.2 weeks and 7.4 weeks, respectively. Mean duration of rituximab therapy was 6.09 months and 33.7 months for IVIg therapy. Mean duration of follow-up after the last dose of rituximab was 86.08 months, during which all patients remained in complete remission. Mean length of total follow-up was 103.99 months. No relapses, infections, or hospitalizations were reported. CONCLUSIONS When systemic CS and ISA are contraindicated in PV patients, combination RTX and IVIg therapy can produce a prolonged, sustained remission without additional systemic therapy. This positive clinical outcome could be the consequence of pathogenic B cell depletion and restoration of immune regulation.

Long-Term Remissions in Recalcitrant Pemphigus Vulgaris.

In a case series involving 10 patients with recalcitrant recurrent pemphigus vulgaris, a combination of rituximab plus intravenous immune globulin induced complete remission for 10 years or more, with no further therapy.

Corrigendum to “First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up” [Int. Immunopharmacol. (2016) 25–31]

The authors regret Fig. 1, panel B, the photographs printed were that of a patient not described in this study. The preand posttherapy photographs of the patient described in this study are provided below. The photograph on the left represents active disease and the photograph on the right represents the back of the patient at the conclusion of rituximab and intravenous immunoglobulin therapy. The authors would like to apologise for any inconvenience caused.