Table 2.
Evidence of efficacy for the use of NSAIDs, corticosteroids, HCQ and topical treatments in SS with childhood onset
| Treatment | Reference | Acute symptoms/signs associated with SS targeted by treatment | Response | Background medications | Symptoms/signs targeted by background medications | Response |
|---|---|---|---|---|---|---|
| NSAIDs | Kobayashi et al., 1996 [14] | Secondary SS to mixed connective tissue disease, no details of symptoms targeted by treatment | No clear benefit or further details. Liver functions remained abnormal | NA | NA | NA |
| De Souza et al., 2012 [23] | Arthritis, parotitis | Controlled arthritis with no systemic evolution of SS after a 12 month follow-up. No further parotitis episodes | NA | NA | NA | |
| Oral corticosteroids | Schuetz et al., 2010 [13] | Sicca syndrome, fever, abdominal pain, parotid swelling | Good response | NA | NA | NA |
| Houghton et al., 2005 [24] | LIP | Clinical and radiographic improvement | HCQ | Not specified | Not specified | |
| Flaitz et al., 2001 [30] | Parotitis and fever | Cessation of pyrexia, decrease in size of parotid gland swelling and improved appetite. Two months after treatment, there was evidence of improvement in non-specific markers of inflammation but hypergammaglobulinemia persisted | NA | NA | NA | |
| Nathavitharana et al., 1995 [31] | Parotitis | Evidence of clinical improvement after 2 months of treatment | Not specified | Rampant caries | Not specified | |
| Saad-Magalhães et al., 2011 [17] | Recurrent orbital swelling | Prompt response | NA | NA | NA | |
| Yang et al., 2009 [19] | Kidney involvement | Relieved symptoms (non-specific) | NA | NA | NA | |
| Siamopoulou-Mavridou et al., 1989 [32] | Juvenile RA and SS | Evidence of clinical improvement after 2 months | Aspirin 90 mg/kg/day | Not specified | Not specified | |
| Civilibal et al., 2007 [33] | Parotid swelling, arthralgias, local oedema and purpura | Follow-up at 6 months: patient reported only one parotid swelling attack; arthralgias, local oedema and purpura disappeared completely | MTX 10 mg/m2/week | Same symptoms | Improvement, as mentioned | |
| Zhao et al., 2020 [47] | Tubular interstitial damage | Treatment with prednisone (5–10 mg/day) for half a year (for persistent renal glycosuria). At 1.5 years follow-up there was stable renal function | Celebrex (200 mg/day) and HCQ (100 mg/day) for the first week. HCQ (200 mg/day) and SSZ enteric-coated tablets (400 mg/day) for the next 6 months | Joint pain, increased ESR | Complete remission of joint pain, normal complete blood counts and ESR at 2 months follow-up | |
| Kobayashi et al., 1996 [14] | Primary SS. Presented with aseptic meningoencephalitis | Symptoms resolved and condition has been stable on low-dose prednisolone (5 mg/day) | Acetylsalicylic acid, diclofenac | High-grade fever, headache, nausea and skin rash | Symptoms resolved | |
| Methylprednisolone i.v. | Kobayashi et al., 1996 [14] | Primary SS complicated with overt dRTA | Good response to treatment. Patient’s condition and renal function have remained stable during 5 years of follow-up | CYC, sodium citrate | Same symptoms | Good overall response |
| Houghton et al., 2005 [24] | LIP | Clinical and radiographic improvement | 3 daily pulses of i.v. methylprednisolone (1 g/day) followed by prednisone (1 mg/kg/day), additional HCQ | Same symptoms | Clinical and radiographic improvement | |
| Ohtsuka et al., 1995 [38] | CNS involvement: hemiparesis, diffuse swelling of the cervical cord and increased signal intensity on MRI | Resolution of symptoms occurred progressively after i.v. methylprednisolone | Corticosteroids for 28 days; prednisolone (2 mg/kg/day then tapered to 0.2 mg/kg/day), followed by i.v. methylprednisolone 30 mg/kg/day for 3 days | Same symptoms | Four months after being discharged from hospital, patient developed nausea, headache and new-onset left hemiparesis despite being on prednisolone (0.2 mg/kg/day), requiring i.v. methylprednisolone | |
| Gottfried et al., 2011 [49] | Orofacial swelling, facial nerve palsy or stroke-like symptoms | Rapid improvement of diplopia, disequilibrium and ataxia, less prominent ptosis while facial diplegia remain unchanged after i.v. methylprednisolone therapy | Oral prednisolone (2 mg/kg/day) then slowly tapered over the next 3 months following i.v. methylprednisolone for 5 days | Same symptoms | MRI showed full resolution of midbrain lesion at a the 6 month follow-up. Patient continued to improve with full conjugate extraocular movements, minimal ptosis and stable facial diplegia | |
| HCQ | Schuetz et al., 2010 [13] | Not specified | 2/3 (66.6%) clinically stable, 1/3 (33.3%) not specified (patient later diagnosed with SS with overlapping SLE and started on AZA) |
1/3 steroids 1/3 NSAIDs |
Arthritis and “skin eruption,” asthenia, fever, arthritis of toes and forefeet | Good response. Controlled symptoms for 1 year until development of asthenia and jaundice—diagnosed with AIH with underlying diagnosis of SS with overlapping SLE. Responded partially to NSAIDs |
| Moy et al. 2014 [41] | Parotitis | Patient still had recurrent bilateral/unilateral parotid swelling in the subsequent 3 years despite HCQ therapy | Antibiotics | Episodes of parotitis lasting 1 week were treated with antibiotics | Still recurrent symptoms | |
| Hamzaoui et al., 2010 [18] | Inflammatory arthralgia | Good | NA | NA | NA | |
| Ladino et al., 2015 [42] | Joint pain and fatigue | Prednisone and HCQ associated with good response in terms of joint pain and fatigue | Prednisolone (7.5 mg/day), artificial tears, oral mucolytic | Eye dryness, xerostomia | Artificial tears associated with benefit for eye dryness, oral mucolytic treatment beneficial for xerostomia | |
| Thouret et al., 2002 [43] | Parotid swelling | Clinical improvement of bilateral parotid swelling, although no impact on serological markers | NA | NA | NA | |
| Shahi et al., 2011 [44] | Recurrent arthralgia | Stable clinical features and laboratory values at 6 months follow-up. No mention of response to HCQ therapy | A | N/A | NA | |
| Majdoub et al., 2017 [51] | Parotid swelling | HCQ was effective in preventing parotid swelling (at 2 year follow-up, no flares were reported since starting HCQ) | Artificial tears | Dry eyes | Effective | |
| Treatments for dryness-related symptoms | ||||||
| Pilocarpine | Tomiita et al., 2010 [15] | Xerostomia | Improved in 5/5 (100%) patients. Specified as ‘improved’ in 1/5 (20%), ‘slightly improved’ in 4/5 (80%) | NA | NA | NA |
| De Souza et al., 2012 [23] | Dryness | Adequate control of SS symptoms | NA | NA | NA | |
| Bromhexine | Hamzaoui et al., 2010 [18] | Dryness | Not specified | NA | NA | NA |
| Artificial tears | Hamzaoui et al., 2010 [18] | Eye dryness | Not specified | NA | NA | NA |
| Oral balance gel | Nikitakis et al., 2003 [37] | Xerostomia | No new cavities at 10 months follow-up | NA | No systemic symptoms | Stable clinical features and laboratory values with no evidence of connective tissue disease |
| Plaque control, diet modification, regular fluoride application, restorative treatment | Sardenberg et al., 2010 [45] | Xerostomia and dental problems | No complications or new carious lesions at 2 year follow-up | NA | NA | NA |
| Oral hygiene instructions, vulvar moisturizer, 1% hydrocortisone cream for intermittent use | Aburiziza et al. 2020 [48] | Dental problems, vulvar dryness | Patient continued to have new dental caries. Vulvar itchiness and irritation became a prominent clinical problem 2 years after presentation | Short course of oral prednisolone given once with antibiotics | Parotitis | Resolved |
| Artificial saliva, dental treatment | Fidalgo et al., 2016 [50] | Dry mouth, tooth sensibility and dental pain | Artificial saliva: improved hydration of the tissues of the oral cavity, in particular the oral mucosa. Successful endodontic treatment and dental restorations | Corticoid therapy | Additional diagnosis of RA, parotitis | No details |
AIH: autoimmune hepatitis; NA: not available.