ORAL PRESENTATIONS 26 September 2019 i7

9. SUCCESSFUL USE OF IL-6 PATHWAY BLOCKADE TO TREAT Careful history and examination are required to differentiate between
AUTOINFLAMMATION OCCURRING IN THE CONTEXT OF A potentially overlapping symptoms of drug reaction, autoinflammation,
NOVEL TNFRS1A GENE MUTATION and infection in patients with systemic autoinflammatory disorders
(SAIDs).Onceahistoryconsistentwith autoinflammatoryflare wasestab-
Bernard Dyke1, Caroline Gordon1, Phillip Hawkins2, and Sofia lished, cautiously rechallenging with an IL-6 pathway inhibitor ensured
Tosounidou1 this effective treatment was not discounted due to concerns over a drug
1
Institute of Inflammation and Ageing, City Hospital, Birmingham, reaction.
United Kingdom, and 2National Amyloidosis Centre, Royal Free With a degree of commonality between the more common conditions in
Hospital, London, United Kingdom the SAID family, a detailed examination of the clinical phenotype is essen-
tial to the interpretation of genetic tests used for the diagnosis of TRAPS
Introduction: Autoinflammatory fever syndromes are rare and present and related disorders.
significant diagnostic and treatment challenges. We present a case Uncontrolled inflammatory disease is associated with pregnancy mor-
which illustrates some key concepts regarding the diagnosis and treat- bidity and very limited information is available about the short and long-
ment of a patient with an autoinflammatory disorder, and also touches on term safety of treatments for autoinflammatory diseases in general.

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the management of active autoinflammation in pregnancy. Current guidelines do not recommend the use of IL-6 inhibitor therapy in
Case description: A 29-year-old woman with a recently identified auto- pregnancy.
inflammatory disorder was referred to the local rheumatology service Conflict of interest: The authors declare no conflicts of interest.
in September 2018. She reported having been symptomatic of fever,
rashes and arthralgia since the age of 10, and TNF receptor 1 associated
periodic syndrome (TRAPS) was suspected on the basis of an N71 dele- 10. DRUG-INDUCED LUPUS AS A TRIGGER FOR
tion on axon 2 of the TNFRS1A gene when tested by a national reference MACROPHAGE ACTIVATION SYNDROME
centre 9 monthspreviously.
At the time of presentation she was 25 weeks into her sixth pregnancy, the Mark Leith1, and Eimear Savage1
first with a new partner. She reported significant pregnancy morbidity 1
Rheumatology, Craigavon Area Hospital, Craigavon, United
having given birth to a daughter with multiple congenital abnormalities Kingdom
who unfortunately died two days after birth. She suffered 4 subsequent
miscarriages at 5-7 weeks gestation with the same partner and under-
went extensive genetic testing. At her initial review in the obstetric clinic, Introduction: Macrophage activation syndrome (MAS) or haemophago-
she was already receiving low-molecular-weight heparin with aspirin. cytic lympohistiocytosis (HLH) is a rare, life threatening cause of fever. It
Colchicine 1 mg tds, did not confer significant symptomatic benefit. can be due to a primary haematological condition, but can also be trig-
One month later, with careful counselling about pregnancy exposure to gered by several rheumatological conditionssuchas Stills disease orsys-
this biological treatment, IL-1 receptor antagonist (anakinra) therapy was temic lupus erythematosus. It can often be misdiagnosed as infection,
instituted but discontinued after three weeks for generalised rash, as well leading to a delayed or even missed diagnosis. Given its life threatening
as lack of efficacy manifesting in raised inflammatory markers. Infection course, we need not only recognise the syndrome, but also identify the
was excluded during asubsequent hospital admission, and prednisolone underlying trigger so that appropriate treatment of the underlying cause
treatment resulted in significant improvement in clinical course and acute can be initiated early. This case is the first reported case of drug-induced
phase response. The patient gave birth to a healthy infant at 37 weeks’ lupus causing MAS.
gestation. Case description: This is a 56-year-old female of Indian origin who ini-
In the postpartum period, a recurrence of symptoms was observed. IL-6 tially presented to rheumatology in January 2018 with a seronegative
receptor antagonist (tocilizumab) treatment was commenced at 12 inflammatory arthritis. ANA was negative at this time and she had no other
weeks postpartum but discontinued owing to reports of sore throat, clinical features of a connective tissue disease. She was intolerant of
cough, headache and fever on the day of the injection. The patient had methotrexate, so switched to sulphasalazine in October 2018.
also discontinued prednisolone on the day of the injection and tocilizu- Unfortunately, sulphasalazine failed to control her disease, and she was
mab was rechallenged with good symptomatic response, normalisation assessed for biologic therapy in March 2019. It was noted she had trav-
of inflammatory markers, and successful reductionin prednisolone dose. elled to India at the start of 2019, but IGRA screening in March returned
Discussion: This case highlights some interesting points with relation to negativeprior to being considered forbiologics.
the treatment of autoinflammatory disorders refractory to IL-1 pathway She was admitted to Daisy Hill Hospital in Newry, Northern Ireland on 22/
blockade, and also, of the management of flares of autoinflammation dur- 3/19 with pyrexia, right sided abdominal pain and leucopenia. She was
ing pregnancy. treated with several courses of broad spectrum antibiotics, but multiple
Firstly, this lady failed to respond to IL-1 receptor antagonist anakinra blood and urine cultures came back negative. CT chest, abdomen and
which has been associated with efficacy in several reports for individuals pelvis found duodenitis, but failed to identify a source of sepsis or evi-
with TRAPS, and has supplanted TNF blockade with agents such as eta- dence of tuberculosis. Echocardiogram was normal. Investigations from
nercept for this condition. Only a handful of case reports describe suc- infectious diseases ruled out HIV, Hepatitis B&C, EBV, CMV, stongy-
cessful IL-6 inhibitor administration for this condition, and this merits loides, leishmaniasis, syphilis and malaria.
further study. This patient’s flare of autoinflammation was treated in the Daily pyrexia persisted, and she developed a progressive pancytopenia,
post-partum period, but the demographic characteristics of the autoin- rash, mucositis and a rising ferritin up to 30000. Skin biopsy was non-spe-
flammatory diseases are such that people of child-bearing age may be cific but showed weak staining for IgM and C3 raising the possibility of
required to receive treatment in order to prevent pregnancy morbidity as vasculitis but was not definitive. Triglycerides were elevated at 3.6 and
a result of uncontrolled inflammation. IL-6 blockade has not to date been fibrinogen 1.2. ANA, which had initially been normal before sulphasala-
associated with adverse pregnancy outcomes, although this data zine, was now positive at 1in40 with an anti-chromatin of 3.5 and ds-DNA
requires extension and validation. 2 cases of renal agenesis have been 18. Complement was normal. CD25 soluble receptor later returned at
reported in children born to mothers with anakinra, but the very small 5370. Anti histone antibody was negative. Bone marrow biopsy con-
numbers of exposed parents warrants further examination of this obser- firmed MAS.
vation and the careful study of ongoing pharmacovigilance data to She was treated with intravenous immunoglobulins, intravenous methyl-
explore this observation. prednisolone for 3 days followed by prednisolone, and anakinra. Her
Secondly, success with IL-6 inhibition has been reported in a series of fevers subsequently settled, ferritin normalised and her blood counts
patients with familial Mediterranean fever, the most common autoinflam- gradually improved. She was commenced on hydroxychloroquine and
matory disorder, but this treatment does not feature in the most recent prednisolone dose weaned.
European guidelines for this condition. IL-6 inhibition is well-established Discussion: Our working diagnosis in this case was that of a drug-
in the treatment of adult-onset Still’s disease (AoSD) however, and this induced lupus secondarytosulphasalazine therapywhich then was com-
lady’s presentation shares important features with that condition. The plicated by MAS. This is the first reported case in the literature of a drug-
existence of TNF-receptor 1 mutations has been reported in patients with induced lupus-driven MAS. We had considered if this could have repre-
AoSD, and it may be that this patient’s presentation is more akin to adult- sented a systemic lupus erythematosus picture from the onset of the
onset Still’s disease and that her TNF receptor mutation is an incidental inflammatory arthritis, however, the initial ANA was normal and only
finding. became positive after treatment with sulphasalazine. Interestingly, this
Key learning points: This report adds to the handful cases in which IL-6 patient’s ANA profile became negative following treatment with steroid/
blockade hasbeen used successfully to treatthe autoinflammatory mani- anakinra and following withdrawal of the drug. It is unusual that comple-
festations of suspected TNF receptor 1 associated periodic syndrome ment would be normal if this was a presentation of systemic lupus, and
(TRAPS) after the failure of IL-1 receptor blockade with anakinra. whilst anti histone antibody negativity perhaps points away from drug
induced lupus, it can benegativein 5% cases of drug induced lupus.
i8 26 September 2019 ORAL PRESENTATIONS

Key learning points: Early recognition of MAS is imperative if we are to treatment with high dose steroid, intravenous immunoglobulin and ana-
improve morbidity and mortality from this condition. It is important to be kinra, as well as withdrawing the causative drug, proved to be very effec-
aware of potential triggers of the syndrome, and this case has highlighted tive in resolving her MAS.
a previously unrecorded cause of MAS in drug induced lupus. In this case, Conflict of interest: The authors declare no conflicts of interest.

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