Page 767 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 54 Sjögren Syndrome 739

involvement is dry, itchy skin (xerosis) and angular cheilitis.
Other less common nonvasculitic lesions include alopecia, vitiligo, Genitourinary and Renal Involvement
eyelid dermatitis, and erythema nodosum–like lesions. Annular Renal involvement is frequently caused by tubulointerstitial
erythema, a rash similar to subacute cutaneous lupus, has been nephritis often presenting as distal (type1) renal tubular acidosis,
reported in about 10% of patients with SS and is closely associated renal calculi, and hypokalemia. Glomerular disease has been
with the presence of anti-SSA and/or anti-SSB autoantibod- rarely reported and, in most cases, is linked to cryoglobulinemic
ies. However, the rash is less photosensitive and histologically vasculitis. Inflammation of the urinary bladder epithelium can
has deeper perivascular and periappendageal lymphocytic cause interstitial cystitis. Vaginal dryness leading to dyspareunia
infiltrates. has been reported in 40% of women.
Vasculitic lesions include nonpalpable purpura caused by
hypergammaglobulinemia, palpable purpura, and urticarial vas- Clinical Manifestations in Children
19
culitis. Patients with vasculitis have higher prevalence of positive Primary SS is rarely diagnosed in children, but many adult patients
ANA, anti-Ro/SSA antibodies, and rheumatoid factor compared with SS recall the presence of symptoms since childhood. Clinical
with those with nonvasculitic skin involvement. Palpable purpura presentation in children is more insidious with predominant
is histologically characterized by leukocytoclastic vasculitis and recurrent parotitis and, less commonly, sicca symptoms. 26
may indicate presence of underlying cryoglobulinemia. Raynaud
phenomenon (RP) is seen in 30–50% of SS patients and frequently Associated Autoimmune Conditions
precedes the development of sicca symptoms. Autoimmune thyroiditis is seen in more than one-third of patients
with SS. Celiac disease is also increasingly recognized in these
Gastrointestinal Involvement patients, with a prevalence 10 times higher than in the general
Dysphagia is common as a result of dryness of the pharynx and population.
esophageal dysmotility. Nausea, epigastric pain, and constipation
are frequently encountered. Gastrointestinal (GI) tract dysmotility Lymphoma Associated With SS
can be seen as a result of ANS involvement. Pancreatic dysfunction, SS is associated with increased risk of lymphoma, with about
with reduced production of amylase and lipase, is present in 5% of patients developing lymphoma. In a meta-analysis of 20
25% of patients with SS. studies the standardized incidence rate of lymphoma was 18.9%
27
(confidence interval [CI] 9.4–37.9). Most of these are low-grade
Pulmonary Involvement marginal zone lymphomas of the mucosa-associated lympho-
Cough is a common complaint in patients with SS and results reticular tissue (MALT) type. Only 10% of lymphomas in patients
from tracheobronchitis sicca (tracheal and bronchial dryness). with SS evolve into a less differentiated cell (more aggressive)
Clinically significant pulmonary involvement is reported in variety. Risk factors for development of lymphoma include
20
9–12% of SS patients. Pulmonary manifestations include persistent enlargement of the parotid glands, palpable purpura,
large airway disease and small airway disease, bronchial hyper- leg ulcers secondary to vasculitis, mixed cryoglobulinemia, and
responsiveness, recurrent respiratory infections, interstitial lung low C4 levels.
disease, pulmonary hypertension, pleuritis, and pulmonary
amyloidosis. Interstitial lung disease is increasingly recognized DIAGNOSIS AND CLASSIFICATION CRITERIA
as an extraglandular manifestation of SS and can precede the
diagnosis of SS. Patients with SS can present with heterogeneous combinations
Patients with primary SS presenting with unexplained dyspnea of sicca symptoms and extraglandular manifestations. Moreover,
should be evaluated for pulmonary arterial hypertension (PAH); various clinical syndromes and medications can lead to similar
an unexpectedly high prevalence (14%) of pulmonary hyperten- symptoms and mimic SS. The diagnosis of SS is based on the
sion was found in a cohort of 1158 patients. The majority of combination of subjective symptoms of dryness (sicca symptoms),
patients with SS and PAH manifest symptoms early in the disease objective evidence of lachrymal or salivary gland hypofunction,
course. 21,22 and evidence of autoimmunity or salivary gland inflammation.
Classification criteria were proposed by an American–European
Cardiac Involvement consensus group (AECG) in 2002, primarily for classification
28
Clinically significant cardiac involvement is uncommon in primary of patients in clinical studies. These criteria are widely accepted
SS. Patients may develop pericarditis, thickened pericardium, and are frequently used as a guide for clinical diagnosis. Applica-
or left ventricle diastolic dysfunction. Rhythm abnormalities tion of these criteria to classify patients with primary SS has a
resulting from autonomic dysfunction may be encountered. sensitivity of 89.5% and specificity of 95.2%, whereas for second-
28
Placental transfer of anti-SSA/Ro and anti-SSB/La antibodies ary SS, it has a sensitivity of 97.2% and specificity of 90.2%.
from pregnant patients with SS can cause lesions in the cardiac The AECG classification scheme is based on a set of two subjective
conducting system of the fetus. Pregnant women with positive criteria and four objective criteria.
anti-SSA/Ro and anti-SSB/La antibodies have a 2.5% risk of Patients are classified as having primary SS in the absence of
delivering a baby with congenital heart block. any other systemic autoimmune disease, whereas in secondary
Like patients with other chronic inflammatory conditions, SS, sicca manifestations are present in conjunction with other
patients with SS are at an increased risk of premature atheroscle- underlying autoimmune diseases, such as SLE, RA, polymyositis/
rosis and cardiovascular events. Some traditional cardiovascular dermatomyositis, or systemic sclerosis. SS is excluded if patients
risk factors, such as hypertension and hypercholesterolemia, are use anticholinergic medications or have other conditions that
more prevalent in patients with SS. However, disease-specific can mimic SS, such as chronic viral infections, graft-versus-host
factors also contribute to the pathogenesis of premature disease (GvHD), or status post irradiation of the head and neck
atherosclerosis. 23-25 region.