Page 769 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 54 Sjögren Syndrome 741

Artificial saliva available as spray or lozenges provides only LYMPHOMa iN SJÖGrEN SYNDrOME
limited relief. Local activation of salivary glands (in patients
with preserved function) with sugar-free sour candies or gums risk Factors
provides some relief of symptoms. • Increase in risk with time: cumulative risk 3.4% at 5 years and 9.8%
Cholinergic agonists, such as pilocarpine and cevimeline, at 15 years after diagnosis of Sjögren syndrome (SS)
provide effective symptom relief in selected patients. Cevimeline • Persistent enlargement of parotid glands
• Splenomegaly and lymphadenopathy
is a more selective muscarinic agonist predominantly affecting • Palpable purpura
M1 and M3 receptors and hence is associated with fewer side • Leg ulcers secondary to vasculitis
effects compared with pilocarpine. 4 • Mixed cryoglobulinemia
The Sjögren’s Syndrome Foundation’s Clinical Practice • Low complement levels
Guidelines Committee recently recommended the use of topical • CD4 lymphocytopenia
fluoride to reduce dental caries in patients with SS who suffer
from dry mouth. 38 Staging and Management (in Collaboration With an Oncologist)
• Computed tomography (CT) of neck, thorax, and abdomen
Immune-Modulating Medications • Laboratory tests: Lactate dehydrogenase (LDH), serum and urine
electrophoresis and immunofixation, human immunodeficiency virus
Cyclosporine eye drops are frequently prescribed to reduce the (HIV), and hepatitis C serology
local immune response involving the conjunctiva and the cornea. • Bone marrow biopsy
Use of topical nonsteroidal antiinflammatory and steroid-based • Localized low-grade mucosa-associated lymphoreticular tissue (MALT)
eye drops provide short-term benefits and should be used lymphoma (most common): careful monitoring required
cautiously. • Multiple extranodal site involvement: single agent chemotherapy
• High-grade transformation or aggressive lymphoma at presentation:
Hydroxychloroquine is commonly prescribed for patients with rituximab and CHOP (cyclophosphamide, hydroxy doxorubicin, Oncovin,
SS, even though some trials have shown significant laboratory and prednisone)
improvement but no beneficial effects on symptoms.
Other immune-modulating agents, such as azathioprine,
cyclosporine, methotrexate, and mycophenolate mofetil, have
shown only limited benefits in treating sicca symptoms and are
used primarily for extraglandular manifestations. 39 their sicca symptoms. Women of child-bearing age with positive
Trials using biological agents, such as infliximab and etanercept, anti-SSA/Ro and anti-SSB/La antibodies should be counseled
failed to show any significant improvement in the primary regarding the risk of congenital heart block in the fetus. Patients
outcomes of treatment for oral and ocular dryness. 39 with loss of smell associated with SS are at an increased risk of
Data on the use of rituximab are controversial, with some injury in the event of gas leakage. Alternative methods should
studies showing only modest benefit. 39 be employed to detect gas leakage in the patient’s environment.
An open-label trial using the anti–B cell–activating factor
(BAFF) monoclonal antibody (mAb) belimumab revealed no TRANSLATIONAL RESEARCH AND
major safety concerns. There were minor improvements in parotid FUTURE DIRECTIONS
gland swelling and lymphadenopathy but no significant improve-
ment in salivary and lacrimal gland function or patient-reported
outcomes. Despite the central role of autoantibodies in the ON THE HOriZON
pathogenesis of SS, targeting of B-cell function has been surpris-
ingly unsuccessful in managing SS. • Whole transcriptome and exome studies will lead to better understand-
ing of genetic risk factors.
Treatment for Lymphoma Associated With SS • Further studies are needed to better understand the interaction between
immune and nonimmune abnormalities leading to Sjögren
As discussed above, lymphoma associated with SS is usually low syndrome.
grade with 5-year survival rates of 86–100%. In a study of patients • Pilot clinical studies are needed to identify potential therapeutic
with SS, overall survival rates of patients with MALT lymphoma candidates for larger efficacy trials.
24
was similar in both the treated and the untreated groups. • There is a pressing need to identify and to validate clinically relevant
biomarkers.
However, patients with disseminated and more aggressive
lymphoma have reduced overall survival. Recently, high levels
of BAFF and Flt3 were shown to be highly predictive of lymphoma SS is the clinical manifestation of a complex interplay between
development in patients with SS. 40 genetic factors and environmental and stochastic events that
involve innate and adaptive immunity, hormonal mechanisms,
PATIENT EDUCATION and the ANS. A better understanding of these elements is necessary
to develop more effective treatments. Two large genome-wide
Because of its significant impact on quality of life, educating patients association studies are currently underway to better delineate
and their families is of utmost importance. Excellent resources the genetic risk factors of SS. Pilot treatment trials targeting key
for patient education are available through focus groups, such as cells (B and T lymphocytes) and mediators (Blyss, lymphotoxin,
the Sjögren’s Syndrome Foundation (http://www.sjogrens.com/) IFN) of autoimmune/inflammatory pathways are expected to
and the British Sjögren’s Syndrome Association. identify the most promising molecule(s) that can be tested in
In general, patients are advised to avoid dry environments, larger efficacy studies. There is a clear and present need to identify
protect the eyes from bright sunlight, maintain good dental and validate biomarkers that can be used in clinical trials as well
hygiene, and be aware of symptoms suggestive of lymphoma. as everyday clinical practice to improve the management of
They should avoid medications and substances that may worsen patients with SS.