Comparative Assessment of Hand Joint Ultrasound Findings in Symptomatic Patients with Systemic Lupus Erythematosus and Sjögren's Syndrome: A Pilot Study.

Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) can be associated with inflammatory arthritis, which is underdiagnosed by clinical examination. The aim of this cross-sectional, observational study was to compare, for the first time, the ultrasound (US)-detected joint abnormalities in these two diseases and to define the role of US in patient management. Participants had SLE (n = 18) and SS (n = 23), symptoms of hand joint pain and no previous diagnosis of arthritis. Data on disease activity, duration, damage scores, inflammatory and serologic markers, treatment and clinical and ultrasound parameters (derived from the assessment of 902 joints) were analysed and correlated using descriptive statistics, correlation tests and regression models. Subclinical synovitis/tenosynovitis was detected in 44.4% of SLE patients and 21.7% of SS patients (p = 0.23). There was no significant correlation between either the total Power Doppler score or the total grey-scale score and disease activity scores (British Isles Lupus Assessment Group index and European League Against Rheumatism Sjögren's syndrome disease activity index). Both damage scores (Systemic Lupus International Collaborating Clinics index and Sjögren's syndrome disease damage index) correlated with the total grey-scale synovitis score. Significant proportions of the participants with SLE and SS had erosions (55.6% and 34.8%, respectively, p = 0.184) and osteophytes (61.1% vs. 60.9%, p = 0.98) in at least one joint. The lack of correlation between disease activity scores and US outcome measures indicated their limitations in diagnosing subclinical synovitis in SLE and SS patients. Future research is needed to determine if the development of erosions could be prevented by early diagnosis and prompt treatment of inflammatory arthritis associated with SLE and SS.

Successful use of ofatumumab in two cases of early-onset juvenile SLE with thrombocytopenia caused by a mutation in protein kinase C δ.

BACKGROUND: We previously described an endogamous Pakistani kindred in whom we identified a novel homozygous missense mutation in the PRKCD gene encoding for protein kinase C δ (PKCδ) as a cause of monogenic systemic lupus erythematosus (SLE). PKCδ has a role in the negative regulation of B cells. Given the nature of the disease, a logical targeted therapeutic approach in these patients is B cell depletion. Indeed, the 3 siblings all had a marked clinical response and resolution of symptoms with rituximab, although 2 of the siblings had severe reactions to rituximab thus precluding further treatment with this. We therefore describe the first successful use of ofatumumab for this rare form of monogenic SLE. CASE PRESENTATION: All three affected siblings presented with SLE before the age of 3-years with lethargy, intermittent fever, thrombocytopenia, cutaneous involvement, alopecia, and hepatosplenomegaly. Tubulointerstitial nephritis was also present in 1 of the siblings. Homozygosity mapping followed by whole exome sequencing identified a homozygous missense mutation in PRKCD (p.Gly432Trp), subsequently confirmed by Sanger sequencing to be present in all 3 siblings. All 3 patients were initially treated with rituximab, however 2 of the siblings developed severe infusion-related reactions. For subsequent disease flare in these individuals we therefore used an alternative B cell depleting agent, ofatumumab (300 mg/1.73m2 on day 1; 700 mg/1.73m2 on day 15). This resulted in marked clinical improvement in both patients. To the best of our knowledge, this is the first report describing the successful use of ofatumumab for PKCδ deficiency. CONCLUSIONS: PKCδ deficiency causes a monogenic form of SLE which responds well to B cell depletion. Ofatumumab is also likely to have a therapeutic role for sporadic juvenile SLE (jSLE) patients intolerant of rituximab.