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A man in his 60s presented with a 6-month history of alternating eye pain, urticarial rash and intermittent arthritis in his small joints. His medical history included latent tuberculosis (TB), plaque psoriasis, hypertension and clinically diagnosed giant cell arteritis (GCA). He received a prolonged course of oral steroids for GCA in 2014 and was treated for latent TB in 2018 with 4 months of rifampicin. The patient’s psoriasis had been treated with topical steroids and calcipotriol but had not required any therapy in the lead up to this presentation. He was currently on amlodipine daily.
His best-corrected vision was 6/12 in both eyes. Intraocular pressure fluctuated between 11 and 40 mm Hg, depending on the degree of inflammation. Ocular examination revealed episcleritis, scleritis, iritis, trabeculitis and papillitis in both eyes over time. Slit lamp examination showed bilateral pigmented stromal deposits in the cornea with a flower-petal distribution that was confirmed by anterior segment optical coherence tomography (figures 1–4). He was phakic in both eyes with mild nuclear sclerotic cataracts. There was no peripheral anterior synechiae on gonioscopy. Erythematous urticated plaques were distributed on the trunk and proximal limbs (figure 5).
Right eye anterior segment photograph, demonstrating flower-petal corneal changes.
Left eye anterior segment photograph, demonstrating flower-petal corneal changes.
Left eye anterior segment optical coherence tomography scan of the corneal changes.
Left eye anterior segment photograph when acutely inflamed.
Clinical photograph of the patient’s urticarial rash on his left shoulder, arm and chest.
Laboratory tests were ordered to investigate for a systemic cause. The full blood count, renal function and liver function were normal. He had a low titre positive antinuclear antibody (ANA) 1:80. Erythrocyte sedimentation rate (ESR) was normal, but C-reactive protein (CRP) was raised at 148 mg/L (reference range: <5 mg/L). Complement C3 was 0.45 (reference range 0.86–1.84 g/L), C4 <0.08 (reference range 0.20–0.59 g/L) and CH50 was 34% (reference range 59–132%). Anti-C1q antibodies were positive. Other tests, including the extractable nuclear antigens (ENA), anti-dsDNA, antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor, HLA-B27, hepatitis B and C serology were negative. Serum angiotensin-converting enzyme (ACE) was normal. The urine microscopy was normal and did not suggest glomerulonephritis. The Quanti-FERON-TB Gold test was repeated but remained positive, despite no active TB symptoms. Skin biopsy showed superficial blood vessels surrounded by tight cuffs of small lymphocytes and neutrophils, with moderate karyorrhexis around capillaries, endothelial swelling and margination of intravascular neutrophils. This was in keeping with urticarial vasculitis, or a phase in the evolution of a leukocytoclastic vasculitis, with granular IgG, IgA and C3 deposition on direct immunofluorescence. No signs of amyloidosis were found. Brain and orbital MRI was unremarkable. Chest imaging revealed multiple, small and partially calcified, mediastinal lymph nodes consistent with prior granulomatous insult and advanced emphysema. It also showed a left lower and right upper lobe lung nodule, which was not intensely avid on positron emission tomography. Bronchoscopy ruled out active TB.
Based on his urticarial rash, hypocomplementaemia, leukocytoclastic vasculitis, arthritis, uveitis and positive anti-C1q antibodies, he fulfilled diagnostic criteria for hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome (table 1).1 2 Although he had a positive ANA, he did not reach the clinical criteria for systemic lupus erythematosus (SLE). McDuffie syndrome is a rare autoimmune disorder, characterised by hypocomplementaemia and chronic urticaria, and a spectrum of systemic manifestations presenting diagnostic and therapeutic challenges.1 2 Previously reported ocular manifestations include scleritis, episcleritis, conjunctivitis and uveitis.3 4 Angioedema and obstructive airways disease have also been associated.5 Most cases of HUVS are idiopathic, but it has been associated with SLE, Sjögren’s syndrome, malignancy and drug sensitivities.6 7 The authors are not aware of any reported association between HUVS and GCA.
Consensus criteria for the diagnosis of HUVS (Schwartz et al)2
The patient’s stromal, pigmentary deposits in the cornea suggested a differential diagnosis of infectious interstitial keratitis such as TB or syphilis, cornea verticillata from drug toxicity, amyloidosis, siderosis or Wilson’s disease. Psoriatic uveitis was also considered; however, it typically causes a chronic anterior uveitis with minimal vasculitis. The flower-petal pattern may have resulted from immune complexes (from anti-C1q antibodies) infiltrating the corneal endothelium, activating the classical complement pathway, and forming membrane attack complexes (MACs).8 These MACs alter membrane integrity, leading to the deposition of pigment/inflammatory debris from intraocular structures into the corneal stroma.8 This pigment may have followed the radial furrows of the iris, creating a characteristic flower-petal appearance.
As he had multiple organ involvement, immunosuppression with high-dose oral steroids was required, in addition to topical eye drops. He was later transitioned to methotrexate as a steroid-sparing agent, and 2 months later, switched to mycophenolate mofetil due to progression of his eye disease.9 He was well controlled on this therapy.
Patient’s perspective
I have been having eye pain that moves from the right eye to the left one, and it comes with a headache which gets worse. The eye starts getting red and then increases in pain. The (steroid) eye drops help clear it but then it swaps to the other one. It goes away after three or four weeks.
Over the last two years, I have lost 80% of my vision in the left eye and 85% in the right eye. The rashes, fevers and sweating are the worst. However, the eyes are the biggest worry. I have lost energy, both mental and physical, to do things. I am still working, as a cleaner, two hours per day. I still go to the shop, drive around but have lost motivation. It is a type of depression. I sleep and stare at nothing.
I get really angry with nothing, upset and frustrated, just during a normal talk. I know I do it, and I will stop. It is affecting the whole family. I will scratch my head, constantly, in cycles. I need to get out and go somewhere. The rashes have gone away but my skin has become really thin. I have lost a lot of weight, maybe 6 or 7 kg. It doesn’t help that I have started smoking again.
Learning points
Flower-petal, granular and stromal corneal deposits, with accompanying inflammatory eye disease and urticarial rash, should raise suspicion of hypocomplementaemic urticarial vasculitis syndrome or McDuffie syndrome.
Systemic immunosuppression with mycophenolate is often required to control ocular inflammation.
Ethics statements
Patient consent for publication
Footnotes
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: JRD, ECW, JAT, EW. The following authors gave final approval of the manuscript: JRD, ECW, JAT, EW. Guarantor: JRD.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.