Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease characterised by urticarial skin rash, intermittent fever, arthralgia, and the frequent development of systemic AA amyloidosis. It is caused by mutations in the gene known as NALP3 or CIAS, which encodes a member of the purine superfamily of death domain fold proteins that are implicated in the regulation of inflammation through activation of nuclear factor κB (NF-κB) and regulation of interleukin 1 (IL1) processing.^1,2 Over recent years, therapeutic trials with the human recombinant IL1 receptor antagonist anakinra have reported encouraging results in patients with various autoinflammatory syndromes.^3,4 We report here the unusual case of acute visual loss in a patient with MWS and its good response to anakinra.

CASE REPORT

A 70 year old woman with a history of a MWS associated with the NALP3 variant R260W was referred to our hospital with loss of vision in one eye that developed within days, accompanied by intermittent flash sensations.

On admission, she had an increased body temperature (38°C) and urticarial rashes as typical signs of a flare of MWS. Residual visual acuity at admission was limited to hand motion perception and light-darkness discrimination. A slit lamp examination showed regular pseudophakia on both eyes with an afferent pupillary defect of the left eye. Ophthalmoloscopy of the left eye showed a pale optic nerve head oedema of 2 diopters. Pattern visual evoked potentials (VEPs) and flash VEPs of the affected eye were without responses. A kinetic visual field examination proved concentric constriction of the visual field of the left eye. Laboratory analysis showed a raised erythrocyte sedimentation rate of 36 mm/1st h and a C reactive protein of 32 mg/l.

Initial treatment with systemic high dose glucocorticoids and one cycle of plasmapheresis had no influence on the visual disturbance. The patient then consented to undergo a therapeutic trial of anakinra (Kineret; Amgen) given by subcutaneous injection at a dose of 100 mg daily, which is the dosage licensed for the treatment of rheumatoid arthritis.

Within 1 day of the first injection the rash and fever disappeared, and the patient reported a profound improvement in general wellbeing. The patient’s sight of the left eye improved from hand movement upon referral to 0.3 within 10 days. In addition, the visual field defect recovered from band shaped to 50 degrees temporal and a vertical expansion of a maximal 20 degrees. The afferent pupillary defect persisted as well as VEP changes. As a serological marker, plasma concentration of serum amyloid A, which was markedly raised before treatment, normalised within 6 days and remained below 2 mg/l (normal <10 mg/l) on frequent testing for 3 weeks (fig 1⇓).

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Figure 1

 Serial measurement of serum amyloid A concentration in one patient with MWS. The arrow indicates when treatment with anakinra began.

DISCUSSION

In this unusual and dramatic manifestation of MWS we observed a remarkable clinical remission, including recovery of the patient’s visual acuity and visual field associated with a profound serological remission using the IL1 receptor antagonist anakinra.

To the best of our knowledge, this is the first description of acute visual loss in MWS. Being aware of the pale and swollen optic disc in our patient, we had to consider an anterior ischaemic optic neuropathy as a possible differential diagnosis. However, the clinical response using anakinra is strongly indicative for an association with an underlying inflammatory condition.

Visual disturbance is reported to be a clinical feature in patients with neonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease that is also related to mutations in the NALP3 gene.⁵ Recent studies suggest that the same NALP3 genetic defect may cause vastly different phenotypes of hereditary fever syndromes.⁶ In this context, visual loss may possibly occur in patients considered to have MWS. The efficacy of anakinra in the treatment of visual disturbance in MWS strongly supports studies for this treatment of patients with NOMID, in which eye involvement is more common.