Clinical practice guideline for Sjögren’s syndrome 2017

Figures & data

Figure 1. Guideline development process. CPG: clinical practice guideline; CQs: clinical questions.

Figure 2. Relationship between algorithm of clinical practice for Sjögren’s syndrome and each clinical question. CQ: clinical question; SS: Sjögren’s syndrome.

Table 1. Setting of clinical questions using the PICO format (clinical question 28 is used here as an example).

	Patients				Interventions/comparisons		Outcomes
Clinical question 28	Gender	Age	Disease	Pathology	Interventions	C	List	Content	Benefit/Harm	Importance	Pros and cons
Is corticosteroid effective for	Not assigned	Not assigned	SS	Glandular	Systemic administration	Placebo	O1	Improvement of salivary secretion	Benefit	8	Yes
glandular involvement?				manifestation	of corticosteroids		O2	Improvement of lacrimation	Benefit	8	Yes
							O3	Improvement of sicca symptom	Benefit	8	Yes
							O4	Increased infection	Harm	7	Yes

PICO: problem, population; C: comparisons, controls, comparators; SS: Sjögren’s syndrome.

Table 2. Summary of clinical questions and recommendations.

Number	Clinical question	Recommendation	Strength of recommendation
1	What oral examination is useful for diagnosis and decision making?	Unstimulated whole saliva, Saxon test, Gum test, and labial salivary gland biopsy are useful for diagnosis and decision making of SS	Strong
2	What are useful ophthalmic tests for diagnosis and determination of treatment policy?	Schirmer test, Tear film break-up time (TFBUT), Rose Bengal test, Lissamine Green test, and Fluorescein test are useful for improvement of diagnosis and evaluation disease condition	Weak
3	Which extra-glandular manifestations influence prognosis?	There is no specific extra-glandular manifestation known to influence prognosis. However, it is suggested that the presence of extra-glandular manifestations should be considered a risk factor for poor prognosis	Weak
4	What are the characteristic cutaneous lesions?	Annular erythema and cutaneous vasculitis are characteristic cutaneous lesions in SS	Weak
5	What are the characteristic renal lesions?	Tubulointerstitial nephritis and renal tubular acidosis are characteristic renal lesions, followed by glomerulonephritis	Weak
6	What are the characteristic peripheral nerve lesions?	Polyneuropathy and cranial neuropathy are characteristic peripheral nerve lesions, followed by mononeuritis multiplex	Weak
7	What are the characteristic central nervous system lesions?	Encephalopathy and aseptic meningitis, followed by cerebral white matter and spinal cord lesions, are characteristic central nervous system lesions, with headache, cognitive disorders, and mood disorders as characteristic symptoms	Weak
8	What are the characteristic pulmonary lesions?	Small airway involvement and interstitial lung disease are characteristic pulmonary lesions	Weak
9	What are the characteristic articular lesions?	Symmetrical polyarthritis with involvement of fewer than five joints and absence of radiographic bone erosions or positive anti-cyclic citrullinated peptide (CCP) antibody are characteristic articular involvement	Weak
10	Which autoantibodies are useful for diagnosis?	Need to evaluate anti-SS-A/Ro and anti-SS-B/La antibodies for diagnosis of SS, in patients with symptoms of dryness	Strong
11	Which hematological tests are useful for diagnosis?	Check for cytopenia and hypergammaglobulinemia	Weak
12	Which imaging tests are useful for evaluation of glandular involvement?	Salivary gland ultrasonography (SGUS), magnetic resonance imaging (MRI), salivary gland scintigraphy, and sialography	Weak
13	To what extent can salivary gland ultrasonography (SGUS) contribute to diagnosis, evaluation of severity, and response to treatment?	SGUS is useful for the diagnosis of glandular involvement and evaluation of severity	Weak
14	To what extent can magnetic resonance imaging (MRI) of salivary glands contribute to diagnosis, evaluation of severity, and response to treatment?	MRI of salivary glands is useful for the diagnosis of glandular involvement and evaluation of severity	Weak
15	To what extent can salivary gland scintigraphy contribute to diagnosis, evaluation of severity, and response to treatment?	Salivary gland scintigraphy is useful for the diagnosis of glandular involvement and evaluation of severity	Weak
16	To what extent can sialography contribute to diagnosis, evaluation of severity, and response to treatment?	Sialography is useful for the diagnosis of glandular involvement and evaluation of severity	Weak
17	Which complications negatively affect prognosis?	Malignant lymphoma affects prognosis, together with hematological malignancies (e.g. multiple myeloma), primary biliary cirrhosis, autoimmune hepatitis, and pulmonary arterial hypertension	Weak
18	What are the clinical manifestations of malignant lymphoma associated with SS?	Malignant lymphoma associated with SS is characterized by high incidence of marginal zone lymphoma (MZL), including mucosa-associated lymphoid tissue (MALT) lymphoma and nodal marginal zone lymphoma (NMZL), which should be noted at diagnosis	Strong
19	What are the risk factors for the development of malignant lymphoma?	Salivary gland swelling, purpura (palpable purpura or cutaneous vasculitis), low serum C3, and C4 levels are risk factors for development of malignant lymphoma	Strong
20	Which clinical features reflect glandular lesions of pediatric patients?	Recurrent parotid swelling improves the diagnostic sensitivity of pediatric patients. Subjective and objective dry symptoms of the oral cavity or eyes are suggestive of pediatric patients	Strong
21	What are the clinical findings that reflect extra-glandular involvements in pediatric patients?	Articular symptoms, skin rash, fatigue, Raynaud’s phenomenon, fever, and lymphadenopathy are symptoms of extra-glandular involvement in pediatric patients. Neurological symptoms, hepatitis, renal tubular acidosis (RTA), and peptic ulceration are uncommon but important complications	Strong
22	Which hematological findings are the useful for the diagnosis of SS in pediatric patients?	Positive ANA and anti SS-A/Ro antibody have high sensitivity for diagnosis of SS in pediatric patients. Rheumatoid factor, hypergammaglobulinemia, and anti-SS-B/La antibody are also useful	Strong
23	Which clinical tests should be used for assessment of glandular lesions in pediatric patients?	(1) Sialography (including MR sialography) and labial salivary gland biopsy can be used with high sensitivity for diagnosis and assessment of glandular lesions in pediatric patients	Strong
		(2) Salivary scintigraphy, Schirmer test, and keratoconjunctive staining test are tests useful for assessment of glandular lesions	Weak
24	What treatments are effective for dry mouth?	Cevimeline hydrochloride and pilocarpine hydrochloride can improve salivary secretion and dry mouth	Strong
25	What treatments are effective for recurrent swelling of salivary glands?	Antimicrobial agents and corticosteroids can improve recurrent swelling of salivary glands. Parotid gland irrigation can improve swelling and prevent recurrence	Weak
26	Do ophthalmic solutions rebamipide, diquafosol sodium and sodium hyaluronate improve corneal conjunctival epithelial disorders, tear fluid volume, and subjective symptoms in dry eye?	(1) Rebamipide ophthalmic solution is the treatment option. It improves corneal conjunctival epithelial disorders and dry eye	Strong
		(2) Diquafosol sodium ophthalmic solution is the treatment option for corneal conjunctival epithelial disorders and dry eye and tends to improve tear fluid volume	Strong
		(3) Sodium hyaluronate ophthalmic solution is the treatment option for corneal conjunctival epithelial disorders and dry eye	Strong
27	Does punctal plug improve tear fluid volume, corneal conjunctival epithelial disorders and subjective symptoms in dry eye?	Punctal plug is a treatment option to improve tear fluid volume, corneal epithelial disorders, and dry eye	Strong
28	Are corticosteroids effective against glandular involvements?	Systemic corticosteroids do not improve salivary or lacrimal secretion	Weak
29	Are corticosteroids effective against extra-glandular involvements?	Systemic corticosteroids can improve articular, muscle, and skin involvements	Weak
30	Are immunosuppressants effective against glandular involvement?	Mizoribine can increase salivary secretion and improve dryness. Methotrexate can improve dryness	Weak
31	Are immunosuppressants effective against extra-glandular involvements?	Systemic cyclophosphamide can improve lung, kidney, and central nervous system involvement	Weak
32	Are biologics effective against glandular involvement?	(1) Rituximab can improve glandular involvements	Weak
		(2) Abatacept can improve glandular involvements	Weak
		(3) Belimumab does not improve glandular involvements	Weak
		(4) Infliximab does not improve glandular involvements	Weak
		(5) Etanercept does not improve glandular involvements	Weak
33	Are biologics effective against extra-glandular	(1) Rituximab can improve extra-glandular involvements	Weak
	involvements?	(2) Abatacept can improve extra-glandular involvements	Weak
		(3) Belimumab can improve extra-glandular involvements	Weak
		(4) Infliximab does not improve extra-glandular involvements	Weak
34	Are systemic corticosteroids effective against glandular and extra-glandular lesions in pediatric patients?	(1) There is no clear evidence that systemic corticosteroids improve glandular lesions in pediatric patients	Weak
		(2) Systemic corticosteroids are effective for some extra-glandular lesions in pediatric patients	Weak
35	Are immunosuppressants effective against glandular/extra-glandular lesions in pediatric patients?	(1) There is no clear evidence that immunosuppressants improve glandular lesions in pediatric patients	Weak
		(2) Immunosuppressants are useful for pediatric patients with severe extra-glandular lesions, intractable lesions with frequent recurrences, and corticosteroid tapering failure	Weak
36	Are biologics effective for glandular/extra-glandular lesions in pediatric patients?	Although the effect of biologics is not clear at present, their use might be considered for severe cases who fail to respond to concomitant use of corticosteroid and immunosuppressants, or for intractable cases with frequent recurrences or corticosteroid tapering failure	Weak
37	Are Kampo medicines, muscarinic receptor agonists, and expectorant effective against glandular and extra-glandular lesions in pediatric patients?	Muscarinic receptor agonist can improve salivary secretion in pediatric patients	Weak
38	What are the important aspects of management of pregnancy and delivery in female patients?	Care should be taken to prevent the development of fetal congenital heart block in pregnant females positive for anti SS-A antibody. There are yet no screening tests, prophylactic treatment, or therapeutic strategy for this complication. Thus, management should be provided by a multidisciplinary team of internists, obstetricians, and pediatricians	Strong