Picture quiz

This 25 year old lady presented with multiple joint swelling, including her elbows, in particular her right. Limited extension clinically with synovitis.

Right elbow

Left elbow for comparison.

What are the radiological findings? 

Asymptomatic but positive autoantibodies, what do you do?

Screening of autoantibodies is becoming routine among the general public. The question is how do you approach patients with positive autoantibodies but is otherwise well.

Today we look into patients with a positive autoantibody to Ro(SSA) antigen. The study below looks at a cohort of patients over 10 years. Interestingly, 65% of patients eventually had some sort of progressive disease. 25% develop into Sjogrens and rheumatoid-like arthritis. It can affect multi systems from lungs, CNS, blood vessels, kidneys and skin. In fact, some actually would eventuallybe diagnosed with lupus.

Also of interest is that 47% of renal patients actually were negative for anti DNA antibodies, ie both to ssDNA and dsDNA.

The lesson is that despite being asymptomatic, presence of autoantibodies does warrant a continuous follow up and vigilance as to the possible systemic effects, so that treatment can be promptly instituted if necessary.

AbstractSend to:
Medicine (Baltimore). 1995 May;74(3):109-30.
One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow-up.
Simmons-O’Brien E1, Chen S, Watson R, Antoni C, Petri M, Hochberg M, Stevens MB, Provost TT.

To explore further the varied clinical expression of anti-Ro(SS-A) antibody positive patients and to determine the outcomes of these patients, we followed 100 anti-Ro(SS-A) antibody positive patients, originally seen at the Johns Hopkins Medical Institutions in 1982 and 1983, over a 10-year period. The results of this study indicate that anti-Ro(SS-A) antibody positive patients have a diverse clinical presentation and that the anti-Ro(SS-A) antibody response generally persists for years. Some of these patients appear to have a static disease process for years. However, 65% (51, including 13 deaths, of 78 patients) of the patients for whom we had follow-up data had a chronic (10 years or greater) progressive disease process. Black patients, in general, have an earlier onset of disease and may have a more severe disease than white patients. At least 25% of our anti-Ro(SS-A) antibody positive patients demonstrated a dynamic change in clinical presentation with the development of Sjögren syndrome and/or a progressive “rheumatoid-like” arthritis. Interstitial pulmonary disease, central nervous system disease, and vasculitic insults occur frequently in these patients. Renal disease occurred in 19 anti-Ro(SS-A) positive patients, and in 47% of these renal disease patients, no anti-DNA antibodies (dsDNA or ssDNA) were detected. Cutaneous manifestations are prominent in anti-Ro(SS-A) antibody positive patients with lupus. Photosensitivity and a malar dermatitis were the most common features. Twenty percent of lupus patients had discoid lesions, and 20% had SCLE lesions. Based on this study, we believe that anti-Ro(SS-A) antibody positive patients should be routinely evaluated for the emergence of systemic features. Since these systemic features are at least in part, if not solely, the result of inflammation, early treatment with steroids and/or immunosuppressive agents may minimize the damage and influence in a positive manner the significant morbidity and mortality observed in some anti-Ro(SS-A) antibody positive patients.
PMID: 7760718 [PubMed – indexed for MEDLINE]

A common referral

Presenting a case that is commonly referred to rheumatology. A concerned patient is worried about her hands and visited her GP. The concerned GP then forwards the patient to rheumatology.


What are your thoughts?

Biologics in Sjogren's Syndrome

Biologics is likely to be the way to go in Sjogren’s syndrome. Understanding the underlying pathology is crucial.

Ann Rheum Dis. 2015 Mar;74(3):526-31. doi: 10.1136/annrheumdis-2013-203991. Epub 2013 Dec 17.
Efficacy and safety of belimumab in primary Sjögren’s syndrome: results of the BELISS open-label phase II study.
Mariette X1, Seror R1, Quartuccio L2, Baron G3, Salvin S2, Fabris M4, Desmoulins F1, Nocturne G1, Ravaud P3, De Vita S2.

Increased expression of B cell activating factor (BAFF or B lymphocyte stimulator) may explain the B cell activation characteristic of primary Sjögren’s syndrome (pSS).
To evaluate the efficacy and safety of belimumab, targeting BAFF, in patients with pSS.
Patients were included in this bi-centric prospective 1-year open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjögren’s syndrome A-positive and had current systemic complications or salivary gland enlargement, or early disease (<5 years), or biomarkers of B cell activation. They received belimumab, 10 mg/kg, at weeks 0, 2 and 4 and then every 4 weeks to week 24. The primary end-point, assessed at week 28, was improvement in two of five items: reduction in ≥30% in dryness score on a visual analogue scale (VAS), ≥30% in fatigue VAS score, ≥30% in VAS pain score, ≥30% in systemic activity VAS assessed by the physician and/or >25% improvement in any B cell activation biomarker values.
Among 30 patients included, the primary end-point was achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p=0.0015) and EULAR) Sjögren’s Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to 4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer’s test did not change.
These encouraging results justify future randomised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment.

Screen Shot 2015-03-28 at 2.35.38 PM
Advances in the Treatment of Ocular Dryness Associated with Sjögren’s Syndrome

Coziana Ciurtin, Anca Ostas, Viorica M. Cojocaru, Stephen B. Walsh, David A. Isenberg
Published Online: June 18, 2015
Publication stage: In Press Accepted Manuscript
DOI: http://dx.doi.org/10.1016/j.semarthrit.2015.06.007


Sjögren´s Syndrome (SS) is an autoimmune rheumatic disease that is characterised by decreased exocrine gland function and frequent ocular symptoms associated with eye dryness. Significantly, dry eyes can lead to corneal abrasions, infection, ulceration, chronic scarring, and in severe cases, perforation. The available conventional therapies have limited efficacy and there are no biologic therapies licensed for use in SS patients.

Materials and methods
A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was performed covering the period from January 1994 to September 2014. Evidence was graded in categories I-IV and a treatment algorithm, comprising first line, second line and rescue therapies for ocular dryness associated with SS was proposed. It is based on the current evidence of efficacy of different therapies and explores their link with the pathogenesis of ocular dryness associated with SS.

Recent developments in the understanding of the pathogenesis of SS provided evidence that the ocular dryness is associated with pathologic infiltration and dysfunction of the lacrimal glands and changes in the tear composition, together with abnormalities involving the neurosecreting circuits. There is good evidence for the efficacy of topical artificial tears, antiinflammatories and Cyclosporine, and oral Pilocarpine and Cevimeline in controlling the symptoms of ocular dryness associated with SS.

Conventional DMARDs are not particularly effective in addressing the symptoms of ocular dryness associated with SS, despite being commonly prescribed for other SS manifestations. Emerging evidence suggests that B cell and co-stimulatory targeted therapy may play a role in the future.

Anxiety predominate in active SLE


Anxiety appears to be a possible ‘marker’ for active lupus. Anxiety could have several causes from valid worries about the disease and the impending escalation of medications to actual organic pathology especially involving the brain. Could there also be subclinical involvement of the brain in these circumstances?



Active disease is independently associated with more severe anxiety rather than depressive symptoms in patients with systemic lupus erythematosus

The inter-correlation between and co-existence of depression and anxiety may engender inconsistency in addressing the relationship between the severity of depression and disease activity of systemic lupus erythematosus (SLE). We aimed at identifying whether lupus disease activity is independently associated with depression and anxiety in lupus patients.


Adult lupus patients were assessed for the severity of depressive and anxiety symptoms and lupus disease activity by using the Hospital Anxiety and Depression Scale (HADS) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), respectively. Age- and gender-matched healthy controls (HCs) were recruited for comparison. Prevalence and severity of depressive and anxiety symptoms were compared between lupus patients and HCs. Independent relationships between the severity of anxiety (HADS-Anxiety) and depressive (HADS-Depression) symptoms, and SLEDAI were studied with regression models.


In total, 110 lupus patients and 110 HCs were studied. Lupus patients had significantly higher HADS scores than HCs (10.82 ± 6.5 vs 7.34 ± 4.9, p < 0.001). Significantly more lupus patients had anxiety (40.9 vs 21.8%, p = 0.002) and depressive symptoms (15.5 vs 6.4%, p = 0.025) than HCs. Multiple linear regression analyses revealed that SLEDAI (β = 0.160, p = 0.016), calcineurin inhibitor non-use (β = –1.929, p = 0.041) and past cyclophosphamide non-use (β = –1.603, p = 0.039) independently predicted HADS-Anxiety amongst lupus patients even after adjusting for HADS-Depression. Conversely, SLEDAI (β = 0.014, p = 0.834) lost its significant univariate correlation with HADS-Depression after controlling for HADS-Anxiety and other covariates.


Anxiety is more common in lupus patients than in HCs, and its severity is independently associated with more active SLE regardless of the presence or absence of concomitant depression.

Eular 2015 – A reflection



Rome, Italy

Traveling to EULAR has always been exciting. European cities tend to have a different charm, where modernity meets its medieval past.

Large conferences has always been a struggle if one happens to do general clinical rheumatology. Without a specific academic interest, there are many sessions that would be of interest running concurrently.

Despite already having the abstracts in the wonderful EULAR mobile app, there is just something missing if you are not in a session. Unfortunately, debates are always kept to the minimum due mainly to time constraints.

This is where the social media shines. Twitter seem to fit the role of keeping people’s thoughts on a session and maintaining a discussion online. It would be great if we could one day tweet a question. I am encouraged that certain sessions are highlighting the area of health informatics, although they have to catch up to ACR on that front.

Overall it was a successful event. The venue had lots of space to stretch and halls are usually large enough, otherwise there is always standing room outside which is a plus point. The ‘Ask Me’ guides all along the main walkway is a great feature!” And should be kept for future conferences. The materials are great and I suspect that in the future we may be able to do away with the thick programme book!!

The downside, although the organizers did do their bit to alleviate it, was the poor access to public transportation. Moving to and fro to the conference area without being bound to certain limited times would be a better idea. Perhaps more regular buses should have been provided for this purpose.

Thank you EULAR for a great conference. We would look forward to future congresses. One final note, there is a hope that a greater collaborative work between EULAR and APLAR can be forged. Getting delegates to APLAR would be a great way to foster a greater partnership.

Signing out! #EULAR2015. Our next event will likely be the #MSRSSR2015.

Vaginal delivery after bilateral hip arthroplasty

A case was presented where a primigravid mother with rheumatoid arthritis, who had a history of bilateral hip arthroplasty, was contemplating normal vaginal delivery. There is still much debate amongst the orthopedic surgeons and obstetrician when it comes to this. Can the mother sustain prolonged periods in a lithotomy position?

J Bone Joint Surg Am. 2001 Oct;83-A(10):1490-4.
Pregnancy after total hip arthroplasty.
McDowell CM1, Lachiewicz PF.

Younger patients are having total hip arthroplasty now, and a woman who has had such a procedure may want to become pregnant. The purposes of this study were to report on a series of women who had completed a pregnancy after a total hip arthroplasty and to determine if pregnancy affects the function and longevity of the prosthesis.
Five women, with a total of seven uncemented total hip replacements, had six successful pregnancies. The mean age at the arthroplasty was twenty-nine years (range, twenty-two to thirty-eight years), and the mean time from the hip arthroplasty to the pregnancy was 2.5 years (range, one to seven years). These patients (Group A) were compared with a matched group of five women with a total of eight uncemented total hip prostheses (Group B) who had not completed a pregnancy. The mean follow-up time was eight years (range, two to thirteen years) for Group A and seven years (range, two to twelve years) for Group B. Patients were clinically evaluated with the Harris hip score. Radiographs were evaluated for component fixation and osteolysis.
The five women completed a total of six successful pregnancies. One patient, with a bilateral total hip arthroplasty, had two successful pregnancies, 2.5 years apart. Three children were delivered vaginally (with the mother in the lithotomy position) and three, by cesarean section. There were no complications related to the total hip arthroplasty after delivery. The mean weight gain during the pregnancy was 13 kg (range, 8 to 14.2 kg). In Group A, the mean Harris hip score was 94 points prior to the pregnancy and 97 points at the time of the most recent follow-up. In group B, the mean Harris hip score was 91 points at one to two years after the arthroplasty and it was unchanged at the time of the most recent follow-up. There were six excellent results and one good result of the hip arthroplasty in Group A and five excellent and three good results in Group B. The mean total arc of hip motion was 217 degrees in Group A before the pregnancy and 241 degrees at the time of the most recent follow-up. The mean total arc of hip motion was 193 degrees in Group B at one to two years postoperatively and 190 degrees at the time of the most recent follow-up. The difference in the total arc of hip motion between the two groups at the latest follow-up evaluation was significant (p = 0.025). There were no reoperations in either group. Radiographs showed osteolysis of the femur in three hips in Group A and three hips in Group B.
It appears that successful pregnancy and normal vaginal delivery can occur safely after total hip arthroplasty. The overall result, function, and radiographic appearance after the total hip arthroplasty was not adversely affected by pregnancy in this small group of patients.

Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial

For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.

Source: Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial

Editorial comment

Cost is an important component in decision making especially involving expensive biologics.

Subcutaneous Methotrexate wins vs Oral

Ann Rheum Dis doi:10.1136/annrheumdis-2014-206504

The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis

  1. Glen S Hazlewood1,2,3,
  2. J Carter Thorne4,
  3. Janet E Pope5,
  4. Daming Lin6,
  5. Diane Tin4,
  6. Gilles Boire7,
  7. Boulos Haraoui8,
  8. Carol A Hitchon9,
  9. Edward C Keystone6,
  10. Shahin Jamal10,
  11. Vivian P Bykerk6,11
  12. for the CATCH Investigators


Objective To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA).

Methods Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)).

Results 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (−0.38 (95% CI −0.64 to −0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75).

Conclusions Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.

Likely the bioavailability of subcutaneous methotrexate will be higher having bypassed the 1st pass effect.
However, injections are always a difficult topic with patients. Not many would like to poke themselves every week.
Moreover, readily available syringes for subcutaneous forms of methotrexate is not available in Malaysia. Therefore patients would not be able to bring these medications home. It is currently reserved for patients willing to make the weekly trip to a doctor and those intolerant to oral forms of Methotrexate.