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. 2021 Jul 21;61(3):892–912. doi: 10.1093/rheumatology/keab579

Table 1.

Clinical manifestations and characteristics of patients with SS with childhood onset included in literature reports describing the use of various treatments

Author, year [reference] Level of evidence (Oxford criteria) N (F:M) Patient classification criteria used Age at symptoms onset (years)/age at diagnosis (years) [mean (range) for studies where N > 2] Associated conditions/ comorbidities, n (%) Cumulative signs and symptoms, n (%, where applicable)
Singer et al., 2008 [11] 4 7 (7:0) Not specified NA/14.2 [10–17] JIA, 1/7 (14)
  • Arthralgia, 4/7 (57)

  • Joint swelling, 3/7 (42)

  • Fatigue, 3/7 (42)

  • Purpuric rash, 2/7 (29)

  • Recurrent parotitis, 1/7 (14)

  • RP, 1/7 (14)

  • Headache with hemiplegia, 1/7 (14)

  • Sicca symptoms, 1/7 (14)

  • Mouth ulcers, 1/7 (14)

  • Lower back pain, 1/7 (14)

Cimaz et al., 2003 [12] 4 40 (35:5) Variable classification criteria. Not specified 10.7/12.4 NA
  • Recurrent parotid swelling, 29/40 (75)

  • Dry mouth, 5/40 (12.5)

  • Dry eyes, 5/40 (12.5)

  • Other, 5/40 (12.5)

  • Dry eyes and dry mouth, 4/40 (10)

  • Arthritis/arthralgia, 4/40 (10)

  • Fever, 4/40 (10)

  • Fatigue, 3/40 (7.5)

  • Submandibular swelling, 2/40 (5)

Schuetz et al., 2010 [13] 4 8 (7:1) Not specified (diagnosis based on histological evidence of salivary gland involvement with or without positive autoantibodies) 6.5 [0.5–12]/10.6 [6–15]
  • SLE and AIH, 1/8 (12.5)

  • JIA, 1/8 (12.5)

  • Arthralgia/arthritis, 4/8 (50)

  • Systemic symptoms, 3/8 (37.5)

  • Sicca symptoms, 3/8 (37.5)

  • Parotitis, 3/8 (37.5)

  • Keratitis, 2/8 (25)

  • Renal involvement, 2/8 (25)

  • Rash, 1/8 (12.5)

  • Tendinitis, 1/8 (12.5)

  • Photophobia, 1/8 (12.5)

  • Uveitis, 1/8 (12.5)

  • RP, 1/8 (12.5)

Kobayashi et al., 1996 [14] 4 4 (4:0) Not specified 8.75 [7–10]/10.75 [10–12]
  • SLE, 1/4 (25)

  • MCTD, 1/4 (25)

  • Interstitial nephritis, 2/4 (50)

  • Aseptic meningoencephalitis, 1/4 (25)

  • Thyroiditis, 1/4 (25)

  • Intracranial haemorrhage, 1/4 (25)

  • Parotitis, 4/4 (100)

  • Arthritis, 2/4 (50)

  • Rash, 2/4 (50)

  • KCS, 2/4 (50)

  • Fever, 2/4 (50)

  • Parotitis, 1/4 (25)

  • Sicca symptoms, 1/4 (25)

  • RP, 1/4 (25%)

Tomiita et al., 2010 [15] 3B 5 (5:0) Japanese SS diagnostic criteria (1999) NA/13.6 [9–16]
  • JIA, 1/4 (25)

  • SLE, 1/4 (25)

  • Xerostomia, 4/5 (80)

  • Other symptoms not specified

Franklin et al., 1986 [16] 4 5 (4:1) At least two of the following three criteria: keratoconjunctivitis sicca, histological evidence of salivary gland involvement with SS and association with well-defined connective tissue disorder NA/12.6 [5–17]
  • JRA, 4/5 (80)

  • SLE, 2/5 (40)

  • Proliferative glomerulonephritis, 2/5 (40)

  • Papillary carcinoma of the thyroid gland, 1/5 (20)

  • Xerostomia, 5/5 (100)

  • Xerophthalmia, 5/5 (100)

  • Parotid enlargement, 4/5 (80)

  • Anterior cervical adenopathy, 2/5 (40)

  • Polyarticular arthritis, 4/5 (40)

Saad-Magalhães et al., 2011 [17] 4 8 (6:2) AECG-2002 (only 3/8 patients fulfilled the criteria) 5–13 years/NA NA
  • Ocular symptoms, 5/8 (62.5)

  • Oral symptoms, 3/8 (37.5)

  • RP, 3/8 (37.5)

  • Recurrent parotitis, 3/8 (37.5)

  • Arthritis, 2/8 (25)

  • Tenosynovitis, 2/8 (25)

  • Enlarged lymph nodes, 2/8 (25)

  • Arthralgia, 1/8 (12.5)

  • Myalgia, 1/8 (12.5)

  • Osteomalacia, 1/8 (12.5)

  • Migraine, 1/8 (12.5)

  • Lymphocytic gastritis, 1/8 (12.5)

  • Anaemia, 1/8 (12.5)

  • Dry skin, 1/8 (12.5)

  • Eczema, 1/8 (12.5)

  • Fatigue, 1/8 (12.5)

  • Corneal abrasions, 1/8 (12.5)

  • Swollen parotid glands, 1/8 (12.5)

  • Recurrent orbital swelling, 1/8 (12.5)

Hamzaoui et al., 2010 [18] 4 3 (3:0) AECG 2002 15.66 [15–16]/15.66 [15–16] NA
  • Xerostomia, 3/3 (100)

  • Parotid enlargement, 2/3 (66)

  • Keratitis, 1/3 (33)

  • Dental caries ,1/3 (33)

  • RP, 1/3 (33)

  • Arthralgia, 1/3 (33)

Yang et al., 2009 [19] 4 4 (4:0) Revised International Classification for SS (2002) NA/9–17  years NA
  • Anterior neck and axillary lymph node swellings, 2/4 (50)

  • Haematuria and proteinuria, 2/4 (50)

  • Repeated epistaxis, 2/4 (50)

  • Stunted growth, 2/4 (50)

  • Rampant caries, 2/4 (50)

  • Arthritis, 1/4 (25)

  • Joint swelling, 1/4 (25)

  • Haemoptysis, 1/4 (25)

  • Hypokalaemia, 1/4 (25)

  • Malar rashes, 1/4 (25)

Hammett et al., 2020 [20] 4 4 (4:0) A combination of 2017 ACR/EULAR and expert opinion 16/16 N/A Case 1: abnormal behaviour, tremors, insomnia, polyphagia, polyuria, and suicidal ideation
16/12 Case 2: 4 year history of severe anxiety, OCD, and tic disorder presented with an abrupt and severe worsening of anxiety, OCD and new auditory hallucinations
19/19 (adult- onset) Case 3: progressively altered behaviour, incoherent speech, insomnia, headache, and tangential thoughts
17/17 Case 4: new-onset suicidal ideation, paranoia, confusion and emotional lability
Pessler et al., 2006 [21] 5 2 (2:0) Expert opinion F, 0.7/10 NA Case 1: purpura, polyarthritis, uveitis, RTA, sialadenitis
F, 6/10 NA Case 2: sialadenitis, RTA/GN
Tesher et al., 2019 [22] 5 2 (1:1) Revised International Classification for SS (2002) F, 15/15 NA Case 1: MALT parotid gland
M, 15/15 Case 2: MALT parotid gland, arthritis
De Souza et al., 2012 [23] 5 1 (1:0) Revised International Classification for SS (2002) F, 8/16 NA Dry eyes, dry mouth
Houghton et al., 2005 [24] 5 2 (2:0) Expert opinion F, 14 NA Case 1: parotid swelling, dental caries, keratitis, xerostomia, LIP
F, 14 Case 2: parotid swelling
Berman et al., 1990 [25] 5 1 (1:0) Expert opinion with histological evidence (parotid biopsy) F, 10 NMOSD, hypothyroidism NMOSD (presented with weakness, decreased sensation in right arm, headache, dizziness, vomiting and low-grade fever)
Kornitzer et al., 2016 [26] 5 1 (1:0) Expert opinion with histological evidence (salivary gland biopsy) F, 6/9 NMOSD NMOSD (presented with fever, headache, progressive right-side weakness and altered mental status)
Ostuni et al., 1996 [27]; specific details only given for 2 of 10 patients 4 10 (8:2) Copenhagen criteria 11(4–14)/14.6 (11–17)
  • dRTA, 1/10 (10)

  • Mesangial glomerulonephritis, 1/10 (10)

  • Parotid swelling, 10/10 (100)

  • Xerostomia, 3/10 (30)

  • Several dental caries, 1/10 (10)

  • Rampant caries, 3/10 (30)

  • Recurrent oral candidiasis, 1/10 (10)

  • Other symptoms: arthralgia, fever, rash, fatigue, muscle weakness

Baszis et al., 2011 [28] 4 4 (3:1) Not specified NA/12 [9–17] NA
  • Recurrent bilateral parotitis, 3/4 (75)

  • Unilateral parotitis, 1/4 (25)

  • Fever, 2/4 (50)

  • Rash, 1/4 (25)

  • Headache, 1/4 (25)

  • Polyarthritis, 1/4 (25)

Gmuca et al., 2017 [29] 5 2 (2:0) Expert opinion with histological evidence (lip biopsy) F, 11 NMOSD NMOSD (presented with optic neuritis), sicca symptoms
F, 13 NMOSD (presented with optic neuritis)
Flaitz et al., 2001 [30] 5 1 (1:0) Expert opinion with histological evidence (labial lip biopsy) F, 11/14 NA Bilateral parotid swelling, dental problems
Nathavitharana et al., 1995 [31] 5 1 (0:1) Expert opinion with histological evidence (salivary gland biopsy) M, 5 NA Tooth decay, fever, weight loss, bilateral parotid enlargement
Siamopoulou-Mavridou et al., 1989 [32] 5 2 (1:1) Expert opinion with histological evidence (labial salivary gland and lip biopsy, respectively) M, 8/12 NA Recurrent parotid swelling enlargement, keratoconjunctivitis sicca
F, 3 JRA Arthritis, parotic gland enlargement, dry eyes and dry mouth
Civilibal et al., 2007 [33] 5 1 (1:0) Expert opinion with histological evidence (salivary gland biopsy) F, 9/13 N/A Recurrent bilateral swelling, arthralgia
Pessler et al., 2006 [34] 5 1 (1:0) Expert opinion with histological evidence (salivary gland biopsy) F, 1/11 RTA Purpura, polyarthritis, uveitis, severe dental caries
De Oliveira et al., 2011 [35] 5 1 (1:0) American-European Consensus Group classification criteria for SS F, 2.6 NA Xerostomia, xeropthalmia, bilateral parotic gland enlargement
Ohlsson et al., 2006 [36] 5 1 (1:0) Expert opinion F, 8 dRTA Arthritis
Nikitakis et al., 2003 [37] 5 1 (1:0) Expert opinion with histological evidence (parotid biopsy and labial minor salivary glands biopsy) F, 4 NA Bilateral parotid gland enlargement
Ohtsuka et al., 1995 [38] 5 1 (1:0) Japanese criteria (1980–85) F, 9 CNS manifestations SS with CNS involvement (other symptoms included fever, nausea, xerostomia, parotid gland enlargement)
Zhang et al., 2007 [39] 5 1 (1:0) Expert opinion with histological evidence (minor salivary gland biopsy) F, 6/9 PHTN Recurrent parotid enlargement, xerostomia, purpura, exertional dyspnoea
Skalova et al., 2008 [40] 5 1 (1:0) Expert opinion F, 16 dRTA Rapid-onset muscle weakness, dysphagia, dysphonia, significant wasting
Moy et al., 2014 [41] 5 1 (1:0) Expert opinion with histological evidence (labial gland biopsy) F, 9 NA Recurrent parotid swelling
Ladino et al. 2015 [42] 5 1 (0:1) Expert opinion with histological evidence (salivary gland biopsy) M, 9/12 NA Arthralgia
Thouret et al. 2002 [43] 5 1 (1:0) Expert opinion with histological evidence (labial gland biopsy) F, 9/13 NA Bilateral parotid swelling
Shahi et al., 2011 [44] 5 1 (1:0) Expert opinion with histological evidence (salivary minor gland biopsy) F, 10 NA Recurrent arthralgia, foot swelling
Sardenberg et al., 2010 [45] 5 1 (0:1) Expert opinion M, 10 NA Recurrent parotitis, xerostomia, dental caries
Bogdanovic et al., 2013 [46] 5 1 (1:0) Expert opinion with histological evidence (kidney biopsy) F, 13 TIN (manifested as dRTA) Nephrocalcinosis (incidental finding), parotid gland swelling
Zhao et al., 2020 [47] 5 1 (1:0) 2012 ACR criteria F, 12 TIN Arthritis, glucosuria
Aburiziza et al., 2020 [48] 5 1 (1:0) Expert opinion F, 3/5 NA Bilateral parotid gland enlargement, severe teeth decay, painful micturition
Gottfried et al., 2011 [49] 5 1 (1:0) European Classification Criteria (1996) F, 4/9 CNS involvement Bilateral conjunctival injection and ptosis, lip and cheek swelling, parotid gland enlargement, dry eyes and mouth
Fidalgo et al., 2016 [50] 5 1 (1:0) Expert opinion F, 12 JRA Dry mouth, tooth sensitivity, dental pain, recurrent parotic gland enlargement
Majdoub et al., 2017 [51] 5 1 (1:0) Expert opinion with histological evidence (labial gland biopsy) F, 4/7 NA Recurrent parotid gland swelling
Vermylen et al., 1985 [52] 5 1 (1:0) Expert opinion with histological evidence (parotid gland biopsy) F, 2/2 NA Combination of parotid gland enlargement, hyperglobulinaemia and interstitial infiltrations of chest radiography suggestive of SS
Marino et al., 2017 [53] 5 1 (0:1) Expert opinion and evidence of cystic changes on parotid gland MRI M, 2/1 NMOSD Left vision loss, right hemiparesis and lethargy associated with dry mouth

AECG: American European Consensus Criteria; AIH: autoimmune hepatitis; JRA: juvenile RA; NA: not available.