J. Pijpe

Treatment of primary Sjögren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment

We previously reported that B cell depletion therapy with rituximab (4 weekly infusions of 375 mg/m2, premedication: 25 mg prednisolone intravenously) in eight patients with early primary Sjogren syndrome (pSS) and seven patients with mucosa-associated lymphatic tissue (MALT)/pSS was effective in reducing subjective and objective symptoms after 12 weeks of follow-up.1 Three patients with early pSS developed serum sickness-like disease, of whom one patient declined to further participate. The MALT component of six of the seven patients with MALT/pSS was initially effectively treated with rituximab, one of these six patients was successfully retreated 9 months after the first treatment and all six patients are …

Progression of salivary gland dysfunction in patients with Sjögren’s syndrome

Background: Salivary gland dysfunction is one of the key manifestations of Sjögren’s syndrome. Objectives: (1) To assess prospectively loss of function of individual salivary glands in patients with primary and secondary Sjögren’s syndrome in relation to disease duration and use of immunomodulatory drugs. (2) To study changes in sialochemical and laboratory values and subjective complaints over time. Methods: 60 patients with Sjögren’s syndrome were included in this study. Whole and gland-specific saliva (parotid and submandibular/sublingual (SM/SL)), samples were collected at baseline and after a mean of 3.6 (SD 2.3) years of follow-up. Disease duration was recorded for all patients. Results: Patients with Sjögren’s syndrome with short disease duration had significantly higher stimulated flow rates at baseline than those with longer disease duration (p<0.05). When compared with healthy controls, the decrease in SM/SL flow rates at baseline was more prominent than that in parotid flow rates (p<0.05). Over time, there was a significant further decrease of stimulated flow rates, especially of the parotid gland, accompanied by increasing problems with swallowing dry food (p<0.05). The decrease was independent of the use of corticosteroids or disease-modifying antirheumatic drugs (DMARDs). Sialochemical variables remained stable. Conclusions: Early Sjögren’s syndrome is characterised by a decreased salivary gland function (parotis>SM/SL), which shows a further decrease over time, regardless of the use of DMARDs or steroids. Patients with Sjögren’s syndrome with longer disease duration are characterised by severely reduced secretions of both the parotid and SM/SL glands. These observations are relevant for identifying patients who would most likely benefit from intervention treatment.

Treatment of Mucosa-associated Lymphoid Tissue Lymphoma in Sjögren’s Syndrome: A Retrospective Clinical Study

Objective. To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjögren’s syndrome (SS). Methods. All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen between January 1997 and January 2009 were analyzed. Clinical course and treatment outcome of SS and MALT lymphoma were evaluated. Results. From a total of 329 patients with SS, 35 MALT-SS patients were identified, with a median followup of 76 months (range 16–153 mo). MALT lymphoma was localized in the parotid gland in all cases. Treatment consisted of “watchful waiting” (n = 10), surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n = 2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6). Complete response was observed in 14 patients, partial response in 1 patient, and stable disease in 20 patients. In 6 of 7 patients with initially high SS disease activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe extraglandular manifestations), MALT lymphoma progressed and/or SS disease activity increased after a median followup of 39 months (range 4–98 mo), necessitating retreatment. Only 1 patient with MALT who had low SS disease activity showed progression of lymphoma when left untreated. Conclusion. An initially high SS disease activity likely constitutes an adverse prognostic factor for progression of lymphoma and/or SS. Such patients may require treatment for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT lymphoma and low SS disease activity, a “watchful waiting” strategy seems justified.

The Future of Biologic Agents in the Treatment of Sjögren’s Syndrome

The gain in knowledge regarding the cellular mechanisms of T and B lymphocyte activity in the pathogenesis of Sjögren’s syndrome (SS) and the current availability of various biological agents (anti-TNF-α, IFN- α, anti-CD20, and anti-CD22) have resulted in new strategies for therapeutic intervention. In SS, various phase I and II studies have been performed to evaluate these new strategies. Currently, B cell-directed therapies seem to be more promising than T cell-related therapies. However, large, randomized, placebo-controlled clinical trials are needed to confirm the promising results of these early studies. When performing these trials, special attention has to be paid to prevent the occasional occurrence of the severe side effects.

The use of botulinum toxin type A in cosmetic facial procedures

Over the past decade, facial cosmetic procedures have become more commonplace in dentistry and oral and maxillofacial surgery. An increasing number of patients seek minimal invasive procedures. One of the most requested procedures is treatment with botulinum toxin type A (BoNTA). Treatment of dynamic rhytids and lines with BoNTA is effective and produces high rates of improvement with rapid onset and long duration of action (longer than 4 months for some patients) compared with placebo. This paper considers the history and pharmacology of this neurotoxin, and focusses on the literature concerning the treatment of different facial areas with BoNTA. It also presents clinical guidelines on the treatment of glabellar lines, the frontalis muscle, peri-orbital lines, gummy smile and masseter muscle hypertrophy. Knowledge about the mechanisms of action and the ability to use BoNTA as an adjunctive treatment are mandatory for those working in the field of cosmetic facial surgery.

Long term stability of mandibular advancement procedures: bilateral sagittal split osteotomy versus distraction osteogenesis.

The aim of this study was to compare the postoperative stability of the mandible after a bilateral lengthening procedure, either by bilateral sagittal split osteotomy (BSSO) or distraction osteogenesis (DOG). All patients who underwent mandibular advancement surgery between March 2001 and June 2004 were evaluated; 26 patients in the BSSO group and 27 patients in the DOG group were included. The decision to use the intraoral distraction or BSSO for mandibular advancement primarily depended on the patients choice. In both groups, standardized cephalometric radiographs were taken preoperatively, postoperatively (BSSO group) or directly post-distraction (DOG group) and during the last study measurement in May 2005. The cephalometric analysis was performed using the following measurements: Sella/Nasion-Mandibular point B and Sella/Nasion-Mandibular Plane. Point B was used to estimate relapse. This study showed no significant difference in relapse between the BSSO and the DOG group measured 10-49 months after advancement of the mandible (p>0.05). There is no postoperative difference in the stability between BSSO and DOG after mandibular advancement after 1 year.

Retention of lipiodol after parotid gland sialography

There is limited information about the retention of lipiodol in the parotid gland after parotid gland sialography. This study assesses the prevalence of lipiodol retention after parotid sialography and determines if retention of lipiodol is related to the sialography technique or the underlying salivary gland pathology. Using the electronic hospital database (1996-2006), 66 out of 565 patients were identified who had additional maxillofacial radiographic examinations after the initial sialography. Additional radiographs up to October 2007 were included; these were orthopantomographic radiographs in all cases. In 28 patients (42%) signs of lipiodol retention were observed (mean radiographic follow-up: 15+/-13 months). Retention was characterized by small radiopaque spots in the periphery of the gland. Lipiodol retention was predominantly associated with a fausse route (n=8) or the presence of salivary gland disease (sialectasia; n=17). In 9 patients with signs of lipiodol retention, a series of radiographs was available. Lipiodol radiodensities decreased in size during 28 months, and could disappear gradually (follow-up 14-57 months). Despite the high frequency of retention of small depots of lipiodol for years after sialography in patients subjected to additional radiographic examinations, no clinically adverse effects were observed.